ORCID Profile
0000-0001-7914-4709
Current Organisations
University of Western Australia
,
Royal Australasian College of Surgeons
,
Royal Australian and New Zealand College of Ophthalmologists
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Microbial Ecology | Biochemistry and Cell Biology | Signal Transduction | Cell Development, Proliferation and Death
Publisher: Swets & Zeitlinger Publishers
Date: 1999
Publisher: Elsevier BV
Date: 02-2010
Publisher: Wiley
Date: 12-2007
DOI: 10.1111/J.1442-9071.2007.01612.X
Abstract: To determine what proportion of primary open angle glaucoma (POAG) in Tasmania, Australia is familial. Between 1994 and 1996 an audit of Tasmanian patients diagnosed with glaucoma was performed. Identified probands along with their family members were invited to participate. Family history of POAG was noted and pedigrees constructed. Each participant underwent a detailed examination, including visual acuity, intraocular pressure measurement, gonioscopy, optic disc assessment and visual field testing. Participants were classified as normal, suspect or POAG. Data from 467 participants in the Twins Eye Study in Tasmania (TEST) were used as a reference for the general population. Of 2062 participants examined, 1700 were classified as POAG. A total of 1014 participants (59.6%) belonged to families in which other members were affected (familial glaucoma). Six hundred and fifty-six of these 1014 familial cases (64.8%) had a first-degree relative affected. The number of affected members in the family groups varied from two to 29. Six hundred and eighty-eight participants had no known family history of POAG (sporadic glaucoma). There were significantly more POAG patients with a family history of POAG compared to the TEST population (chi2 = 161.81, P < 0.0001), and for a person with POAG the odds ratio of having a positive family history was 4.1 (95% confidence interval: 3.2-5.2). Approximately 60% of POAG in Tasmania is familial. This percentage is higher than most previous reports of familial glaucoma and emphasizes the importance of genetics in POAG, with major implications for screening and future research.
Publisher: Springer Science and Business Media LLC
Date: 27-07-2018
DOI: 10.1038/S41588-018-0176-Y
Abstract: Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide
Publisher: Elsevier BV
Date: 08-2021
Publisher: Wiley
Date: 02-2002
DOI: 10.1046/J.1442-9071.2002.00487.X
Abstract: To compare the conventional (Humphrey 24-2) automated visual field testing with the Goldmann standard visual field test for driving, and to predict how many patients with glaucoma may not meet the Australian driving standard with respect to visual fields. Four patients (retinitis pigmentosa, glaucoma or vigabatrin treatment) with marked visual field defects as determined by uniocular static computerized perimetry (conventional testing) were re-evaluated with binocular kinetic Goldmann IV4e target field test (Australian driving standard). A series of 48 consecutive patients seen by the Glaucoma Inheritance Study in Tasmania were assessed with both static computerized perimetry and the Goldmann IV4e target test. The four patients with severe visual field defects (on computerized perimetry) were found to meet the driving standard on the binocular Goldmann IV4e target test. On computerized perimetry, 15 of 48 patients from the Glaucoma Inheritance Study in Tasmania were found to have visual field defects of sufficient severity that they may not meet the driving standard. However, only five of these patients failed the driving standard for visual fields, two of whom were still driving. Patients with severe field defects on conventional uniocular automated perimetry may still meet the Goldmann standard visual field test for driving. Approximately 30% of glaucoma patients would have visual field loss shown on Humphrey 24-2 test of a severity that requires further testing to determine if they meet the driving standard. Ten per cent of glaucoma patients tested did not meet the driving standard for visual fields.
Publisher: AMPCo
Date: 06-2012
DOI: 10.5694/MJA11.11322
Publisher: Cambridge University Press (CUP)
Date: 05-08-2021
DOI: 10.1017/S0022215121002085
Abstract: This study aimed to assess olfactory dysfunction in patients at six months after confirmed coronavirus disease 2019 infection. Coronavirus disease 2019 positive patients were assessed six months following diagnosis. Patient data were recoded as part of the adapted International Severe Acute Respiratory and Emerging Infection Consortium Protocol. Olfactory dysfunction was assessed using the University of Pennsylvania Smell Identification Test. Fifty-six patients were included. At six months after coronavirus disease 2019 diagnosis, 64.3 per cent of patients ( n = 36) were normosmic, 28.6 per cent ( n = 16) had mild to moderate microsmia and 7 per cent ( n = 4) had severe microsmia or anosmia. There was a statistically significant association between older age and olfactory dysfunction. Hospital or intensive care unit admission did not lead to worse olfactory outcomes compared to those managed in the out-patient setting. At six months after coronavirus disease 2019 diagnosis, approximately two-thirds of patients will be normosmic. This study is the first to describe six-month outcomes for post-coronavirus disease 2019 patients in terms of olfactory dysfunction.
Publisher: BMJ
Date: 17-07-2019
DOI: 10.1136/BJOPHTHALMOL-2018-312159
Abstract: To conduct a systematic review and meta-analysis of the association of blood vitamin D (25-hydroxyvitamin D, 25(OH)D) concentration and vitamin D pathway genes with myopia. We searched the MEDLINE and EMBASE databases for studies published up to 29 January 2018. Cross-sectional or cohort studies which evaluated the blood 25(OH)D concentration, blood 25(OH)D3 concentration or vitamin D pathway genes, in relation to risk of myopia or refractive errors were included. Standard mean difference (SMD) of blood 25(OH)D concentrations between the myopia and non-myopia groups was calculated. The associations of blood 25(OH)D concentrations and polymorphisms in vitamin D pathway genes with myopia using summary ORs were evaluated. We summarised seven studies involving 25 008 in iduals in the meta-analysis. The myopia group had lower 25(OH)D concentration than the non-myopia group (SMD=−0.27 nmol/L, p=0.001). In the full analysis, the risk of myopia was inversely associated with blood 25(OH)D concentration after adjusting for sunlight exposure or time spent outdoors (adjusted odds ratio (AOR)=0.92 per 10 nmol/L, p .0001). However, the association was not statistically significant for the years subgroup (AOR=0.91 per 10 nmol/L, p=0.13) and was significant only for 25(OH)D3 (likely to be mainly sunlight derived), but not total 25(OH)D (AOR=0.93 per 10 nmol/L, p=0.00007 AOR=0.91 per 10 nmol/L, p=0.15). We analysed four single nucleotide polymorphisms in the VDR gene from two studies there was no significant association with myopia. Lower 25(OH)D is associated with increased risk of myopia the lack of a genetic association suggests that 25(OH)D level may be acting as a proxy for time outdoors.
Publisher: PeerJ
Date: 10-03-2018
DOI: 10.7287/PEERJ.PREPRINTS.26654V1
Abstract: Background. The institutional affiliations and associated collaborative networks that scientists foster during their research careers are salient in the production of high quality science. The phenomenon of multiple institutional affiliations and its relationship to research output remains relatively unexplored in the literature. Methods . We examined 27,612 scientific articles, modelling the citation counts received against the number of authors and affiliations held. Results. In agreement with previous research, we found that teamwork is an important factor in high impact papers, with average citations received increasing concordant with the number of co-authors listed. For articles with more than five co-authors, we noted an increase in average citations received when authors with more than one institutional affiliation contributed to the research. Discussion . Multiple author affiliations may play a positive role in the production of high-impact science. This ‘polygamous’ behavior, sometimes shunned by institutional board, should instead be viewed as meritorious in the pursuit of scientific discovery.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2018
Publisher: Informa UK Limited
Date: 14-03-2011
DOI: 10.3109/09286586.2010.545933
Abstract: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18(th) century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-l biomicroscopy. We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2007
DOI: 10.1167/IOVS.06-0611
Abstract: Approximately 1 in 30 unselected patients with open-angle glaucoma (OAG) have a mutation in the myocilin gene. The purpose of this study was to describe the morphologic features of the optic nerve head (ONH) in myocilin glaucoma. A case-control design was adopted. Sixty-six patients heterozygous for a range of myocilin mutation (cases) were matched in disease severity to 105 patients with OAG known not to have a myocilin mutation (controls), using visual field findings. Quantifiable analysis of the ONH was undertaken of stereoscopic photographs, by using custom software with a z-screen. Subjective grading of the cup depth, lamina cribrosa pore shape and orientation, and the slope of the neuroretinal rim was performed by an examiner masked to the subject's mutation status. Mutation screening was conducted using either direct sequencing or single-stranded conformation polymorphism analysis. Patients with a myocilin mutation had glaucoma diagnosed earlier (P < 0.001) and had higher maximum recorded intraocular pressures (P 0.05) difference in global disc area, global neuroretinal rim area, alpha-parapapillary atrophy, beta-parapapillary atrophy, slope of neuroretinal rim, or visible lamina cribrosa morphology between myocilin mutation carriers and patients with nonmyocilin glaucoma. Disc hemorrhages were identified more frequently in those without mutations (14/209 vs. 1/129), though this was not significant after correction for multiple hypothesis testing. No major structural or morphologic difference of the ONH was detected in pooled data from subjects who had myocilin mutations compared with data from in iduals with nonmyocilin glaucoma.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-033440
Abstract: Eye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989–1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes. Participants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters. The Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences. ACTRN12617001599369 Active, not recruiting.
Publisher: Springer Science and Business Media LLC
Date: 17-03-2021
DOI: 10.1038/S41598-021-85626-3
Abstract: Inflammation and cigarette smoking predispose to macular diseases, and choroidal and retinal thinning. We explored the choroidal and retinal thicknesses in young adults against their 7-year C-reactive protein (CRP) level trajectory and pack-years smoked. Participants from the Raine study, a longitudinal cohort study, had serum CRP levels analysed at the 14-, 17-, and 20-year follow-ups. Group-based trajectory modelling was used to classify participants according to their 7-year CRP levels. At the 20-year follow-up (at 18–22 years old), participants completed questionnaires on their smoking history, and underwent optical coherence tomography imaging to obtain their choroidal and retinal thicknesses at the macula. Three CRP trajectories were identified: consistently low CRP levels (78% of s le), increasing (11%), or consistently high (11%). 340 and 1035 participants were included in the choroidal and retinal thickness analyses, respectively. Compared to those in the “Low” trajectory group, participants in the “Increasing” and “High” groups had 14–21 μm thinner choroids at most macular regions. Every additional pack-year smoked was linked with a 0.06–0.10 μm thinner retina at the inner and outer macular rings, suggesting a dose-dependent relationship between smoking and thinner retinas. These associations may suggest that an increased risk of future visual impairment or eye disease associated with these risk factors may be present since young adulthood.
Publisher: Wiley
Date: 08-2012
DOI: 10.1111/J.1442-9071.2011.02742.X
Abstract: Glaucoma is a sight-threatening disease affecting 3% of the population over the age of 50. Glaucoma is treatable, and severe vision loss can usually be prevented if diagnosis is made at an early stage. Genetic factors play a major role in the pathogenesis of the condition, and therefore, genetic testing to identify asymptomatic at-risk in iduals is a promising strategy to reduce the prevalence of glaucoma blindness. Furthermore, unravelling genetic risk factors for glaucoma would also allow a better understanding of the pathogenesis of the condition and the development of new treatments. The Australian and New Zealand Registry of Advanced Glaucoma is a prospective study that aims to develop a large cohort of glaucoma cases with severe visual field loss to identify novel genetic risk factors for glaucoma blindness. Clinical information and blood are collected from participants after referral by eye practitioners. S les are collected across Australia and New Zealand using postage kits. Our registry has recruited just over 2000 participants with advanced glaucoma, as well as secondary and developmental glaucomas. A positive family history of glaucoma is present in more than half of the advanced glaucoma cases and the age at diagnosis is significantly younger for participants with affected relatives, which reinforces the involvement of genetic factors in glaucoma. With the collection of glaucoma cases recruited so far, our registry aims to identify novel glaucoma genetic risk factors to establish risk profiling of the population and protocols for genetic testing.
Publisher: American Medical Association (AMA)
Date: 07-2006
DOI: 10.1001/ARCHOPHT.124.7.950
Abstract: To determine whether there is a difference in disease severity between familial and sporadic primary open-angle glaucoma (POAG). A cross-sectional study design compared the distribution of Glaucoma Inheritance Study in Tasmania (GIST) severity scores of patients with genealogically confirmed familial POAG and those with sporadic POAG. The GIST severity scores provide a combined weighting of glaucoma severity based on findings from visual field defects and optic disc analysis, with and without intraocular pressure. A Poisson regression analysis, t test, and chi(2) tests were performed. One thousand twelve (59.5%) of 1700 subjects had familial glaucoma. The mean +/- SD age at examination was greater in the sporadic POAG group compared with the familial group (72.6 +/- 10.3 years vs 70.6 +/- 12.6 years P = .001). The family group was significantly younger at diagnosis than the sporadic group (mean +/- SD, 61.4 +/- 13.0 years vs 64.0 +/- 12.6 years P<.001). The GIST severity scores were significantly skewed toward greater disease severity in the familial group compared with the sporadic group (P<.001). Identifying in iduals at risk of severe POAG will be more successful if screening programs are developed with appropriate weighting toward those with a positive family history of the disease.
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 17-11-2010
Publisher: BMJ
Date: 08-2022
DOI: 10.1136/BMJOPHTH-2022-001064
Abstract: Paediatric (childhood or congenital) cataract is an opacification of the normally clear lens of the eye and has a genetic basis in at least 18% of cases in Australia. This study aimed to replicate clinical gene screening to identify variants likely to be causative of disease in an Australian patient cohort. Sixty-three reported isolated cataract genes were screened for rare coding variants in 37 Australian families using genome sequencing. Disease-causing variants were confirmed in eight families with variant classification as ‘likely pathogenic’. This included novel variants PITX3 p.(Ter303LeuextTer100), BFSP1 p.(Glu375GlyfsTer2), and GJA8 p.(Pro189Ser), as well as, previously described variants identified in genes GJA3, GJA8, CRYAA, BFSP1, PITX3, COL4A1 and HSF4 . Additionally, eight variants of uncertain significance with evidence towards pathogenicity were identified in genes: GJA3, GJA8, LEMD2, PRX, CRYBB1, BFSP2, and MIP . These findings expand the genotype–phenotype correlations of both pathogenic and benign variation in cataract-associated genes. They further emphasise the need to develop additional evidence such as functional assays and variant classification criteria specific to paediatric cataract genes to improve interpretation of variants and molecular diagnosis in patients.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-2009
DOI: 10.1167/IOVS.08-3346
Publisher: Proceedings of the National Academy of Sciences
Date: 06-09-2017
Abstract: Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, pharmacological treatments in these diseases are limited due to the lack of knowledge of underlying disease mechanisms, partly because appropriate human models to study AMD and related MDs are lacking. Furthermore, in the living human eye, the entire retina acts as a functional unit, making it difficult to investigate the specific contribution of a particular retinal cell type in the disease. Here, we established human models of multiple MDs, which demonstrated similar molecular and phenotypic manifestations within these diseases. Furthermore, we showed that dysfunction of an in idual cell type, retinal pigment epithelium cells in the retina, is sufficient for the development of key pathological features in these MDs.
Publisher: Wiley
Date: 08-2019
DOI: 10.1111/CEO.13586
Publisher: Wiley
Date: 03-10-2016
DOI: 10.1002/MGG3.248
Publisher: Springer Science and Business Media LLC
Date: 07-1994
DOI: 10.1038/EYE.1994.102
Abstract: Variations in classic Leber hereditary optic neuropathy (LHON) include recovery of vision and association with other neurological abnormalities. Sixteen multi-generational Australian families originating from the United Kingdom with LHON were studied by the one examiner, using the same protocol. In particular, recovery of vision and other neurological abnormalities were noted. One very large family (Tas2) and one small family (Vic2) were found to have frequent recovery of vision (50% of patients). They both had the 14484 T to C mutation in their mitochondrial DNA (mtDNA). One apparently unique family (Qld1) was found to have frequent juvenile encephalopathy and peripheral neurological signs. They had the 4160 T to C and 14484 T to C mutations. The remaining 13 families rarely showed visual recovery or associated neurological abnormalities. They had the common 11778 G to A or the 3460 G to A mutations. Thus mitochondrial genotypes in LHON are associated with variable phenotypes.
Publisher: Elsevier BV
Date: 11-2004
DOI: 10.1086/425080
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1086/497348
Publisher: Wiley
Date: 04-09-2017
Publisher: Springer Science and Business Media LLC
Date: 29-06-2023
DOI: 10.1038/S41588-023-01428-5
Abstract: Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as the vertical cup-to-disc ratio. Here, since much of glaucoma heritability remains unexplained, we conducted a large-scale multitrait genome-wide association study in participants of European ancestry combining primary open-angle glaucoma and its two associated traits (total s le size over 600,000) to substantially improve genetic discovery power (263 loci). We further increased our power by then employing a multiancestry approach, which increased the number of independent risk loci to 312, with the vast majority replicating in a large independent cohort from 23andMe, Inc. (total s le size over 2.8 million 296 loci replicated at P 0.05, 240 after Bonferroni correction). Leveraging multiomics datasets, we identified many potential druggable genes, including neuro-protection targets likely to act via the optic nerve, a key advance for glaucoma because all existing drugs only target intraocular pressure. We further used Mendelian randomization and genetic correlation-based approaches to identify novel links to other complex traits, including immune-related diseases such as multiple sclerosis and systemic lupus erythematosus.
Publisher: Elsevier BV
Date: 09-2004
Publisher: Elsevier BV
Date: 11-2021
Publisher: Wiley
Date: 07-2006
DOI: 10.1111/J.1442-9071.2006.01268.X
Abstract: Glaucoma, which is a complex heterogeneous disease, presents an ideal case for genetic investigation. Primary open-angle glaucoma (POAG) is the commonest subtype and will be the focus of this review. When detected early, POAG is amenable to therapeutic intervention. Unfortunately, current population-based clinical screening lacks efficacy. If in iduals with a genetic predisposition for developing POAG can be identified, then efficient and cost-effective population-based screening programs could be designed. Although considerable inroads have been made in understanding the natural history of POAG caused by mutations in the myocilin and optineurin genes, other POAG genes accounting for most cases remain to be identified. This review explores the genetic mechanisms that have been unequivocally linked to the glaucomatous process and then discusses potential avenues for future breakthroughs.
Publisher: American Medical Association (AMA)
Date: 06-1991
DOI: 10.1001/ARCHOPHT.1991.01080060093033
Abstract: We studied the clinical appearance and inheritance in five families with X-linked megalocornea. Affected male subjects had corneal diameters between 13.0 and 16.5 mm. Arcus juvenilis, mosaic corneal dystrophy, and cataracts were found only in adult affected male subjects. No carrier female abnormality was identified. The gene locus for the X-linked form is in the region Xq12-q26. This is near the locus described for Aarskog (facial-digital-genital) syndrome, Xq12-13.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-2004
DOI: 10.1167/IOVS.03-1413
Abstract: Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among in iduals with the third CFEOM phenotype, CFEOM3. All pedigrees and sporadic in iduals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic in iduals were screened for mutations in KIF21A and PHOX2A. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic in iduals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic in iduals harbored mutations in PHOX2A. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.EJMG.2017.06.002
Abstract: Knobloch syndrome [OMIM: (KNO1) #267750] is a rare and clinically heterogeneous autosomal recessive disorder caused by mutations in COL18A1. Knobloch syndrome is characterised by abnormalities of the eye and occipital skull defects however the full phenotypic spectrum is yet to be defined. This report describes a family of four affected sisters with polymicrogyria, refractory seizures, and intellectual impairment of varying severity with a Lennox-Gastaut phenotype, and complex eye abnormalities where a syndromic diagnosis was not initially made. Whole exome sequencing of two affected sisters followed by filtering for rare and potentially disease causing variants in all genes identified compound heterozygous variants in NM_030582.3 (COL18A1): c.3690G > A: p.(Trp1230*) and NM_030582.3 (COL18A1): c.4063_4064delCT: p.(Leu1355Valfs*72). The two variants co-segregated with the affected in iduals in the family. Identification of COL18A1 mutations in in iduals with a Lennox-Gastaut phenotype and anterior polymicrogyria but lacking the classical occipital encephalocele expands the COL18A1 clinical spectrum.
Publisher: Springer Science and Business Media LLC
Date: 13-05-2016
DOI: 10.1038/SREP25853
Abstract: Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry s les (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4 P = 6.3E–04).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2017
Publisher: Wiley
Date: 07-2008
DOI: 10.1111/J.1442-9071.2008.001798.X
Abstract: WE Gillies was a major contributor to research in glaucoma, notably pseuodexfoliation (XFS), as well as strabismus, particularly in relation to axial length (AL). The latter work involved breaking down the geometry of the eye to its basic components and using the measured AL to tailor the amount of strabismus surgery required. Similarly, the search for glaucoma genes requires us to break down glaucoma into its component measures and associated risk factors. Over the last 14 years, our data from the Glaucoma Inheritance Study in Tasmania have shown the following: that a family history is present in 60% of glaucoma cases that 27% of members of large glaucoma families were unaware of their family history of glaucoma and that familial glaucoma is more severe than sporadic glaucoma. Myocilin mutations account for 3% of cases of primary open angle glaucoma. Some genotype-phenotype correlations have been identified. Notably, with respect to earlier age of onset, higher maximum recorded intraocular pressure and need for surgery, the Gln368Stop mutation confers mild risk, Thr377Met and Gly252Arg mutations intermediate risk, and the Pro370Leu mutation severe risk. To identify the other genes associated with glaucoma, we have examined normal twins in the Twins Eye Study to determine the heritability of parameters that are abnormal in glaucoma - intraocular pressure and cup-to-disc ratio and confounding factors for glaucoma such as central corneal thickness, disc area, refraction and AL. We have identified high heritabilities for all of these as well as a gene locus associated with AL on chromosome 5. Recently, the LOXL1 gene was associated with XFS. Identification of further genes will improve our understanding of glaucoma and allow cascade genetic screening.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 24-04-0007
DOI: 10.1167/IOVS.11-7258
Publisher: Elsevier BV
Date: 04-2004
DOI: 10.1086/383202
Publisher: Elsevier BV
Date: 05-2015
Publisher: Elsevier BV
Date: 12-2013
Publisher: Informa UK Limited
Date: 02-01-2021
DOI: 10.1111/CXO.13081
Publisher: Springer Science and Business Media LLC
Date: 19-04-2021
DOI: 10.1038/S41431-021-00889-8
Abstract: Inherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of the eye’s crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previously mapped to Xq24. Linkage at Xq24–25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. In addition, two autosomal regions with suggestive evidence of linkage were observed. A segregating 127 kb deletion (chrX:g.118373226_118500408del) in the Xq24–25 linkage region was identified from whole-genome sequencing data. This deletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the protein coding progesterone receptor membrane component 1 ( PGRMC1 ) gene following exon 1. A literature search revealed a report of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguous gene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-induced pgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lens development and cataract formation. We hypothesise that the loss of PGRMC1 causes cataract through disrupted PGRMC1-CYP51A1 protein–protein interactions and altered cholesterol biosynthesis. The cause of paediatric cataract in this family is the truncating deletion of PGRMC1 , which we report as a novel cataract gene.
Publisher: Elsevier BV
Date: 08-2013
Publisher: BMJ
Date: 28-09-2012
Publisher: Elsevier BV
Date: 06-2022
Publisher: Wiley
Date: 10-12-2012
DOI: 10.1111/CEO.12020
Abstract: Inherited retinal disease represents a significant cause of blindness and visual morbidity worldwide. With the development of emerging molecular technologies, accessible and well-governed repositories of data characterising inherited retinal disease patients is becoming increasingly important. This manuscript introduces such a repository. Participants were recruited from the Retina Australia membership, through the Royal Australian and New Zealand College of Ophthalmologists, and by recruitment of suitable patients attending the Sir Charles Gairdner Hospital visual electrophysiology clinic. Four thousand one hundred ninety-three participants were recruited. All participants were members of families in which the proband was diagnosed with an inherited retinal disease (excluding age-related macular degeneration). Clinical and family information was collected by interview with the participant and by examination of medical records. In 2001, we began collecting DNA from Western Australian participants. In 2009 this activity was extended Australia-wide. Genetic analysis results were stored in the register as they were obtained. The main outcome measurement was the number of DNA s les (with associated phenotypic information) collected from Australian inherited retinal disease-affected families. DNA was obtained from 2873 participants. Retinitis pigmentosa, Stargardt disease and Usher syndrome participants comprised 61.0%, 9.9% and 6.4% of the register, respectively. This resource is a valuable tool for investigating the aetiology of inherited retinal diseases. As new molecular technologies are translated into clinical applications, this well-governed repository of clinical and genetic information will become increasingly relevant for tasks such as identifying candidates for gene-specific clinical trials.
Publisher: Rural and Remote Health
Date: 10-04-2018
DOI: 10.22605/RRH4224
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.AJO.2010.06.028
Abstract: To examine the relationship of birth weight with ocular measures in a Caucasian twin population. Cross-sectional study of 1498 twins (308 monozygotic and 441 dizygotic pairs) aged between 5 to 80 years participating in the Australian Twins Eye Study. All participants underwent ophthalmic examination including bilateral cycloplegic autorefraction, keratometry, interpupillary distance (IPD), central corneal thickness, intraocular pressure (IOP), and retinal photography. Birth weight and gestation were obtained from a self-administered questionnaire. A subset of the twins also participated in the Tasmanian Infant Health Study (288) and the Childhood Blood Pressure Study (184), which collected data on birth parameters allowing for verification of data. Linear mixed models were used for the main analysis. Both the within-pair (β(w) 0.27, 95% confidence interval [CI] 0.15, 0.38 mm per kg increase in birth weight, P < .001) and between-pair associations (β(B) 0.22, 95% CI 0.08, 0.35, P = .002) of birth weight with axial length were significant and of similar magnitude (difference in effect, P = .56), after adjusting for relevant confounders. In contrast, birth weight was negatively associated with corneal curvature (β(w) -0.82, 95% CI -1.09, -0.55 diopters per kg increase β(B) -0.69, 95% CI -0.98, -0.41, both P < .001). These associations remained significant within dizygotic and monozygotic pairs. Refraction, anterior chamber depth, IPD, IOP, and optic disc parameters are unrelated to birth weight. Consistent with previous studies in singleton children, lower birth weight is associated with shorter axial length and more curved corneas in this twin study. This also adds new insights into the emmetropization process.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2010
DOI: 10.1007/S00439-009-0729-3
Abstract: Osteogenesis imperfecta (OI) is a rare connective tissue disorder caused by mutations in the type I collagen genes, COL1A1 and COL1A2, and is characterised by low bone mass and bone fragility. In this study, we explored the relationship between type 1 collagen genes and the quantitative trait central corneal thickness (CCT). CCT was measured in a cohort of 28 Australian type I OI patients and mean CCT was found to be significantly lower compared to a normal population (P < 0.001). We then investigated CCT and corneal collagen fibril diameter and density in a mouse model of OI with a col1a2 mutation. Mean CCT was significantly lower in mutant mice (P = 0.002), as was corneal collagen fibril diameter (P = 0.034), whilst collagen fibril density was significantly greater in mutants (P = 0.034). Finally, we conducted a genetic study to determine whether common single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2 are associated with CCT variation in the normal human population. Polymorphism rs2696297 (P = 0.003) in COL1A1 and a three SNP haplotype in COL1A2 (P = 0.007) were all significantly associated with normal CCT variation. These data implicate type 1 collagen in the determination of CCT in both OI patients and normal in iduals. This provides the first evidence of quantitative trait loci that influence CCT in a normal population and has potential implications for investigating genes involved in glaucoma pathogenesis, a common eye disease in which the severity and progression is influenced by CCT.
Publisher: Elsevier BV
Date: 12-1999
Publisher: Wiley
Date: 25-03-2019
DOI: 10.1111/AOS.14086
Abstract: To describe the history of eye injuries and the consequent evolution of eye protection. A comprehensive search of Medline and the grey literature using the terms 'ocular trauma' and 'eye protection' or 'injury prevention' and 'history'. References were used to identify other relevant publications. Publications were classified according to the setting of eye injury: occupational, recreational or combat-related. Eye protection has been described in a wide range of sources, including in literature and art. With advances in eye protection material and design, as well as government and societal promotion of appropriate eye protection usage in the workplace, the epidemiology of ocular trauma has changed over time. In developed countries, the use of eye protection in the workplace has reduced the proportion of occupation-related eye injuries over the last century, with a higher proportion occurring during sports or at home. New protection devices and policies have evolved to meet this change. Vision loss has broad implications for the in idual and for society and despite available prevention strategies, ocular trauma is a significant cause of preventable monocular and bilateral vision loss. The use of appropriate eye protection has reduced the burden of ocular trauma. History provides lessons for informing current eye protection and eye injury prevention strategies.
Publisher: Wiley
Date: 14-06-2011
DOI: 10.1111/J.1442-9071.2011.02579.X
Abstract: We aimed to determine the prevalence and associations of refractive error on Norfolk Island. Population-based study on Norfolk Island, South Pacific. All permanent residents on Norfolk Island aged ≥ 15 years were invited to participate. Patients underwent non-cycloplegic autorefraction, slit-l biomicroscope examination and biometry assessment. Only phakic eyes were analysed. Prevalence and multivariate associations of refractive error and myopia. There were 677 people (645 right phakic eyes, 648 left phakic eyes) aged ≥ 15 years were included in this study. Mean age of participants was 51.1 (standard deviation 15.7 range 15-81). Three hundred and seventy-six people (55.5%) were female. Adjusted to the 2006 Norfolk Island population, prevalence estimates of refractive error were as follows: myopia (mean spherical equivalent ≥ -1.0 D) 10.1%, hypermetropia (mean spherical equivalent ≥ 1.0 D) 36.6%, and astigmatism 17.7%. Significant independent predictors of myopia in the multivariate model were lower age (P < 0.001), longer axial length (P < 0.001), shallower anterior chamber depth (P = 0.031) and increased corneal curvature (P < 0.001). Significant independent predictors of refractive error were increasing age (P < 0.001), male gender (P = 0.009), Pitcairn ancestry (P = 0.041), cataract (P < 0.001), longer axial length (P < 0.001) and decreased corneal curvature (P < 0.001). The prevalence of myopia on Norfolk Island is lower than on mainland Australia, and the Norfolk Island population demonstrates ethnic differences in the prevalence estimates. Given the significant associations between refractive error and several ocular biometry characteristics, Norfolk Island may be a useful population in which to find the genetic basis of refractive error.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-06-2012
DOI: 10.1167/IOVS.11-8596
Abstract: Retinal vessel attenuation is a key finding in the diagnosis of retinitis pigmentosa (RP), but there have been no studies to determine whether quantitative measurement of this retinal sign is useful. We aimed to investigate retinal vessel caliber and its relationship with the severity of RP. This is a cross-sectional study based on 74 patients (145 eyes) with RP who had visual field assessment with Goldmann permeter and good-quality retinal images for vessel size measurements identified by retrospective medial chart review (1973-2007) in the electrophysiology clinic of a tertiary eye hospital in Australia. Retinal vessel calibers were measured using a computer-based program as the central retinal artery and vein equivalent (CRAE and CRVE). Goldmann visual field area for III4e white test light was measured quantitatively using ImageJ software as a clinical parameter to indicate the severity of RP. We used the generalized estimating equation models to estimate the difference in retina vessel calibers accounting for correlation between right and left eyes. Mean CRAE and CRVE were significantly narrower in persons with smaller visual field area. For each 100 cm2 decrease in visual field area, CRAE and CRVE decreased by -15.2 μm (95% confidence interval -20.7, -9.78) and -26.8 μm (-35.1, -18.5), respectively (both P<0.001). In RP patients, the severity of visual field loss is correlated with retinal vessel attenuation. Quantitative retinal vessel caliber measurement may be a useful additional clinical marker for monitoring progression of RP or potential treatment response.
Publisher: Wiley
Date: 27-04-2011
DOI: 10.1111/J.1442-9071.2011.02556.X
Abstract: To develop, implement and evaluate a telemedicine model to reduce glaucoma blindness through the early detection of undiagnosed glaucoma in high-risk in iduals. Prospective study, private ophthalmology practice and public outpatient clinics in Tasmania. One hundred and thirty-three in iduals with primary open-angle glaucoma were invited to enrol their first-degree relatives (FDRs) to undergo an eye examination. Within the study period, 211 FDRs were available for examination. A registered nurse was trained to perform the required assessments. Clinical data were entered into a purpose-built database, converted to a portable document format and graded offsite by an ophthalmologist to determine the presence, absence or risk of developing glaucoma. Participants were notified of the grading result and recommendations for review. Incidence of undiagnosed glaucoma in a high-risk population. Previously undiagnosed glaucoma was identified in 5% of those examined. For every 19 participants screened, one new case of previously undiagnosed case of glaucoma was identified. Additionally 15% of participants showed suspicious signs of glaucoma, and 6% had ocular hypertension. A telemedicine model is an efficient method for screening, grading and notifying participants of examination results. Nurses can be adequately trained to undertake the initial screening examinations, with grading of the results performed offsite by a suitably qualified ophthalmologist. Targeted screening for glaucoma increases the yield of identifying in iduals with undiagnosed glaucoma or those at greatest risk. Cost efficiencies for this model of glaucoma screening should be further explored and implemented to prevent blindness from familial glaucoma.
Publisher: Wiley
Date: 08-2014
DOI: 10.1111/CEO.12394
Publisher: BMJ
Date: 21-01-2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-08-2020
Publisher: Wiley
Date: 04-2014
DOI: 10.1111/CEO.12155
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/AH15071
Abstract: Objective The aim of the present study was to provide a summary of a systematic review of literature reporting benefits and limitations of implementing National Emergency Access Target (NEAT), a target stipulating that a certain proportion of patients presenting to hospital emergency departments are admitted or discharged within 4 h of presentation. Methods A systematic review of published literature using specific search terms, snowballing techniques applied to retrieved references and Google searches was performed. Results are presented as a narrative synthesis given the heterogeneity of included studies. Results Benefits of a time-based target for emergency care are improved timeliness of emergency care and reduced in-hospital mortality for emergency admissions to hospital. Limitations centre on using a process measure (time) alone devoid of any monitoring of patient outcomes, the threshold nature of a time target and the fact that currently NEAT combines the measurement of clinical management of two very different patient cohorts seeking emergency care: less acute patients discharged home and more acute patients admitted to hospital. Conclusions Time-based access targets for emergency presentations are associated with significant improvements in in-hospital mortality for emergency admissions. However, other patient-important outcomes are deserving of attention, choice of targets needs to be validated by empirical evidence of patient benefit and single targets need to be partitioned into separate targets pertaining to admitted and discharged patients. What is known about the topic? Time targets for emergency care originated in the UK. The introduction of NEAT in Australia has been controversial. NEAT directs that a certain proportion of patients will be admitted or discharged from an emergency department (ED) within 4 h. Recent dissolution of the Australian National Partnership Agreement (which provided hospitals with financial incentives for achieving NEAT compliance) has prompted a re-examination of the 4-h rule, the evidence underpinning its introduction and its benefits and risks to patients What does this paper add? This paper is executive summary of key findings from a systematic literature review on the benefits and limitations of NEAT (the 4-h rule) commissioned by the Queensland Clinical Senate to inform future policy and targets. What are the implications for practitioners? There is evidence that a time-based target has been associated with a reduction in in-hospital mortality for emergency admissions to Australian hospitals. Concerns remain regarding a time-based target alone being used to drive redesign efforts at improving access to emergency care. A time-based target should be coupled with close monitoring of patient outcomes of emergency care. Target thresholds need to be evidence based and separate targets should be reported for admitted, discharged and all patients presenting to the ED.
Publisher: Wiley
Date: 09-12-2016
DOI: 10.1111/AOS.12911
Abstract: To identify the causes of sports-related eye and adnexal injuries in children in Perth, Western Australia, to determine which sporting activities pose the highest risk of eye and adnexal injury to children. We performed a 12-year retrospective review of children admitted to hospital from 2002 to 2013 with sports-related ocular and adnexal eye injuries. The main outcome measures were the cause and type of ocular and adnexal injuries, age and gender risk factors. A total of 93 cases of sports-related ocular and adnexal injury were identified in the 12-year time period. A peak in injuries occurred for 12- to 14-year-olds with a second peak in 6- to 8-year-olds the median age was 8.82 years (range = 1.59-16.47). Cycling, football (including soccer and Australian Rules Football), tennis, tr olining, fishing and swimming were the sports responsible for the greatest number of injuries, a total of 63%. More than one-third (35%) of injuries resulted from being struck by a blunt object, and more than a quarter (26%) were as a result of contact with a blunt projectile. Serious ocular and adnexal injuries have occurred in children as a result of participating in sports, with cycling and football being the largest contributors in the 12-year period we assessed. As we continue to encourage children to spend more time participating in sports and recreational activities, identifying associated risk factors will help us develop injury prevention strategies to promote eye safety for children.
Publisher: Wiley
Date: 20-07-2018
DOI: 10.1111/CEO.13007
Publisher: American Medical Association (AMA)
Date: 06-2022
Publisher: Springer Science and Business Media LLC
Date: 16-10-2013
DOI: 10.1038/502303E
Publisher: Wiley
Date: 12-03-2023
DOI: 10.1111/CEO.14216
Publisher: Informa UK Limited
Date: 02-2013
DOI: 10.1586/EOP.12.81
Publisher: Elsevier BV
Date: 11-2021
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/13816810701356676
Abstract: PAX6 is a key regulator of eye development and there are many well recognized ophthalmic sequelae of mutations at this locus. The 14 exon PAX6 gene is well conserved across species and phyla. Coding region mutations manifest in a variety of phenotypes. Predicted premature protein truncations are generally associated with classical aniridia. Missense mutations are often found in cases with variant phenotypes such as ectopia pupillae isolated foveal hypoplasia nystagmus and hyaloid vessel proliferation. The locus has also been implicated, through a genome-wide sib-pair scan, to be important in the normal variation of myopia. We investigated the association between identified PAX6 mutations and refractive error in Australian patients from four pedigrees. Two of eight subjects with a 1410delC PAX6 mutation had a mean spherical equivalence < -9D, whilst a mean spherical equivalence < or = -5D was recorded in two from four subjects with an Arg240Stop PAX6 mutation and one of two subjects with a Glu93Stop mutation. One in idual identified with a Pro346Ala PAX6 mutation had a mean spherical equivalence of +2.8 D. Thus, our observations generally support other incidental findings, that PAX6 mutation, particularly predicted haploinsufficiency, may be associated with extreme refractive error, although the mechanism by which this occurs is not clear.
Publisher: Frontiers Media SA
Date: 07-06-2023
Publisher: BMJ
Date: 05-1993
DOI: 10.1136/BJO.77.5.311
Abstract: In iduals from 33 unrelated Australian families with optic atrophy were screened for 10 different single base alterations in mitochondrial DNA (mtDNA) associated with Leber hereditary optic neuropathy (LHON) using direct polymerase chain reaction lification of blood spots collected on Guthrie cards. This method using blood spots allows easily accessible screening for LHON mtDNA mutations with minimal biohazard risk and reduced expense in the storage and transport of specimens.
Publisher: Wiley
Date: 19-11-2021
DOI: 10.1111/IMJ.15505
Abstract: This document provides consensus‐based recommendations for general physicians and primary care physicians who diagnose and manage patients with mitochondrial diseases (MD). It builds on previous international guidelines, with particular emphasis on clinical management in the Australian setting. This statement was prepared by a working group of medical practitioners, nurses and allied health professionals with clinical expertise and experience in managing Australian patients with MD. As new treatments and management plans emerge, these consensus‐based recommendations will continue to evolve, but current standards of care are summarised in this document.
Publisher: Springer Science and Business Media LLC
Date: 30-03-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-03-2022
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-02-2023
DOI: 10.1167/TVST.12.2.20
Publisher: Springer Science and Business Media LLC
Date: 08-01-2019
DOI: 10.1038/S41467-018-07819-1
Abstract: Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article.
Publisher: Oxford University Press (OUP)
Date: 05-06-2015
DOI: 10.1093/HMG/DDV211
Abstract: Keratoconus is a degenerative eye condition which results from thinning of the cornea and causes vision distortion. Treatments such as ultraviolet (UV) cross-linking have proved effective for management of keratoconus when performed in early stages of the disease. The central corneal thickness (CCT) is a highly heritable endophenotype of keratoconus, and it is estimated that up to 95% of its phenotypic variance is due to genetics. Genome-wide association efforts of CCT have identified common variants (i.e. minor allele frequency (MAF) >5%). However, these studies typically ignore the large set of exonic variants whose MAF is usually low. In this study, we performed a CCT exome-wide association analysis in a s le of 1029 in iduals from a population-based study in Western Australia. We identified a genome-wide significant exonic variant rs121908120 (P = 6.63 × 10(-10)) in WNT10A. This gene is 437 kb from a gene previously associated with CCT (USP37). We showed in a conditional analysis that the WNT10A variant completely accounts for the signal previously seen at USP37. We replicated our finding in independent s les from the Brisbane Adolescent Twin Study, Twin Eye Study in Tasmania and the Rotterdam Study. Further, we genotyped rs121908120 in 621 keratoconus cases and compared the frequency to a s le of 1680 unscreened controls from the Queensland Twin Registry. We found that rs121908120 increases the risk of keratoconus two times (odds ratio 2.03, P = 5.41 × 10(-5)).
Publisher: Springer Science and Business Media LLC
Date: 05-2009
Abstract: Hereditary optic neuropathies are a prominent cause of blindness in both children and adults. The disorders in this group share many overlapping clinical characteristics, including morphological changes that occur at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging when indicated, is essential for optimum management of the relevant optic neuropathy and appropriate counseling of the patient on its natural history. Patient history, visual field assessment, optic disc findings and imaging are the cornerstones of a correct diagnosis. This Review highlights the characteristic optic nerve head features that are common to the various hereditary optic neuropathies, and describes the features that enable the conditions to be differentiated.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-09-2020
DOI: 10.1167/TVST.9.10.9
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-06-2021
DOI: 10.1097/IAE.0000000000003227
Abstract: To establish a mutation-specific age-dependent ultra-widefield fundus autofluorescence (UWF-FAF) trajectory in a large Stargardt disease (STGD1) cohort using total lesion size (TLS) and to develop a clinical method for variant classification. A retrospective study of patients with biallelic ABCA4 mutations that were evaluated with UWF-FAF. Boundaries of TLS, defined by stippled hyper/hypoautofluorescence, were outlined manually. Pathogenicity was assessed according to ACMG/AMP criteria, and mutation severities were classified based on the current literature. Age-dependent trajectories in TLS were examined in patients with nullizygous, mild, and intermediate mutations. Mutations of uncertain severities were classified using a clinical criterion based on age of symptom onset and TLS. Eighty-one patients with STGD1 (mean age = 42 ± 20 years and mean visual acuity = 20/200) were recruited from 65 unrelated families. Patients with biallelic null/severe variants (n = 6) demonstrated an increase in TLS during their second decade reaching a mean ± SD of 796 ± 29 mm 2 by age 40. Those harboring mild mutations c.5882G A or c.5603A T had lesions confined to the posterior pole with a mean ± SD TLS of 30 ± 39 mm 2 . Intermediate mutations c.6079C T or c.[2588G C A T] in trans with a null/severe mutation had a mean ± SD TLS of 397 ± 29 mm 2 . Thirty-two mutations were predicted to cause severe (n = 22), intermediate (n = 6), and mild (n = 5) impairment of ABCA4 function based on age of symptom onset and TLS. Age-dependent TLS showed unique ABCA4 mutation-specific trajectories. Our novel clinical criterion using age of symptom onset and TLS to segregate ABCA4 mutations into three severity groups requires further molecular studies to confirm its validity.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-2009
DOI: 10.1167/IOVS.08-3271
Abstract: Many ocular parameters show strong heritable tendencies. The significance of central corneal thickness (CCT) in the context of glaucoma has been the subject of much debate recently, but its heritability has not been extensively explored. This study was designed to investigate the parent-child heritability of CCT among groups who have CCT considered to be at the extreme ends of the normal range. Index cases were recruited through a tertiary referral center if their CCT was greater than 578 microm (thick) or less than 510 microm (thin), representing +/-1 SD from a previously published meta-analysis mean of 544 microm (34 microm SD). Subsequently, CCT was measured in all available family members of the index cases. Family units were then analyzed to establish the degree of heritability of CCT from parent to child. Thirty-three index cases were included in the analysis (10 >1 SD and 23 <1 SD from the meta-analysis CCT mean). The mean CCT of the children of index cases with a CCT more than 1 SD from the mean (n = 15) and less than 1 SD from the mean (n = 40) was 568 microm (32 microm SD) and 521 microm (22 microm SD), respectively (t = 6.14 P < 0.0001). The parent-child heritability estimate for CCT was h(2) = 0.68 (95% CI, 0.64-0.73). These results indicate that CCT shows strong parent-child heritability, with offspring likely to demonstrate CCT similar to the parental index case.
Publisher: Springer Science and Business Media LLC
Date: 05-2011
DOI: 10.1038/NG.824
Abstract: We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 in iduals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010 rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68 rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-07-2022
DOI: 10.1167/TVST.11.7.8
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-02-2019
Publisher: Informa UK Limited
Date: 05-2015
DOI: 10.1111/CXO.12283
Abstract: The aim was to review the prevalence of spectacle-related ocular trauma and the performance of currently available spectacle materials and to identify the risk factors associated with spectacle-related ocular trauma. A literature review was conducted using Medline, Embase and Google with the keywords 'eyeglasses' OR 'spectacles' AND 'ocular injury' / 'eye injury'/ 'eye trauma' / 'ocular trauma'. Articles published prior to 1975 were excluded from this review because of advances in spectacle lens technology and Food and Drug Administration legislative changes requiring impact resistance of all prescription spectacle lenses in the United States. Six hundred and ninety-five in idual ocular traumas, for which spectacles contributed to or were the main cause of injury, were identified in the literature. Eye injuries occurred when spectacles were worn in sports, in which medium- to high-impact energies were exerted from balls, racquets or bats and/or as a result of a collision with another player. Frame, lens design and product material choice were found to be associated with ocular injury, with polycarbonate lenses cited as the material of choice in the literature. International, regional and national standards for spectacle lenses had a wide range of impact requirements for prescription spectacle lenses, sports eye protection and occupational eye protection. Spectacle-related injury represents a small but preventable cause of ocular injury. With the increasing numbers of spectacle wearers and calls to spend more time outdoors to reduce myopia, spectacle wearers need to be made aware of the potential risks associated with wearing spectacles during medium- to high-risk activities. At particular risk are those prone to falls, the functionally one-eyed, those who have corneal thinning or have had previous eye surgery or injury. With increased understanding of specific risk factors, performance guidelines can be developed for prescription spectacle eye-protection requirements.
Publisher: Springer Science and Business Media LLC
Date: 25-09-2017
Publisher: Elsevier BV
Date: 2022
Publisher: Springer International Publishing
Date: 06-11-2014
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.AJO.2012.04.023
Abstract: To ascertain if single nucleotide polymorphisms (SNPs) involved in the determination of central corneal thickness, optic disc area, and vertical cup-to-disc ratio (VCDR) also are associated with open-angle glaucoma (OAG). Retrospective case-control genetic association study. A total of 16 SNPs associated with central corneal thickness, optic disc area, and VCDR were genotyped in 876 OAG cases and 883 normal controls. To determine if the SNPs were also correlated with OAG severity, the cohort was stratified into advanced OAG (n = 326) and nonadvanced OAG (n = 550). Both the cases and controls were of European descent and were recruited from within Australia. Two VCDR SNPs were found to be significantly associated with OAG after correction for multiple testing. The 2 SNPs were rs10483727, found adjacent to the SIX1 gene (P = 6.2 × 10(-06) odds ratio, 1.38 95% confidence interval, 1.20 to 1.59), and rs1063192, found within the CDKN2B gene (P = 2.2 × 10(-05) odds ratio, 0.74 95% confidence interval, 0.64 to 0.85). The CDKN2B variant rs1063192 also was found to be associated more strongly with advanced OAG. The findings from this study indicate that variants influencing VCDR are also risk alleles for OAG in our Australian cohort of European descent. The identification of SIX1 and CDKN2B as susceptibility loci will assist in understanding the pathologic mechanisms involved in the development of OAG.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2021
DOI: 10.1038/S41598-021-85825-Y
Abstract: Myopia (near-sightedness) is an important public health issue. Spending more time outdoors can prevent myopia but the long-term association between this exposure and myopia has not been well characterised. We investigated the relationship between time spent outdoors in childhood, adolescence and young adulthood and risk of myopia in young adulthood. The Kidskin Young Adult Myopia Study (KYAMS) was a follow-up of the Kidskin Study, a sun exposure-intervention study of 1776 children aged 6–12 years. Myopia status was assessed in 303 (17.6%) KYAMS participants (aged 25–30 years) and several subjective and objective measures of time spent outdoors were collected in childhood (8–12 years) and adulthood. Index measures of total, childhood and recent time spent outdoors were developed using confirmatory factor analysis. Logistic regression was used to assess the association between a 0.1-unit change in the time outdoor indices and risk of myopia after adjusting for sex, education, outdoor occupation, parental myopia, parental education, ancestry and Kidskin Study intervention group. Spending more time outdoors during childhood was associated with reduced risk of myopia in young adulthood (multivariable odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69, 0.98). Spending more time outdoors in later adolescence and young adulthood was associated with reduced risk of late-onset myopia (≥ 15 years of age, multivariable OR 0.79, 95% CI 0.64, 0.98). Spending more time outdoors in both childhood and adolescence was associated with less myopia in young adulthood.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-07-2014
Abstract: To investigate the association between serum vitamin D levels and myopia in young adults. A total of 946 in iduals participating in the 20-year follow-up of the Western Australian Pregnancy Cohort (Raine) Study were included in this study. Ethnicity, parental myopia, and education status were ascertained by self-reported questionnaire. A comprehensive ophthalmic examination was performed, including postcycloplegic autorefraction and conjunctival UV autofluorescence photography. Serum 25-hydroxyvitamin D₃ (25(OH)D₃) concentrations were determined using mass spectrometry. The association between serum 25(OH)D₃ concentrations and prevalent myopia was determined using multivariable logistic regression. Myopia was defined as mean spherical equivalent ≤ -0.5 diopters. Of the 946 participants, 221 (23.4%) had myopia (n = 725 nonmyopic). Myopic subjects had lower serum 25(OH)D₃ concentrations compared to nonmyopic participants (median 67.6 vs. 72.5 nmol, P = 0.003). In univariable analysis, lower serum 25(OH)D₃ concentration was associated with higher risk of having myopia (odds ratio [OR] for <50 vs. ≥50 nmol/L: 2.63 confidence interval [95% CI] 1.71-4.05 P < 0.001). This association persisted after adjustment for potential confounders, including age, sex, ethnicity, parental myopia, education status, and ocular sun-exposure biomarker score (adjusted OR 2.07 95% CI 1.29-3.32 P = 0.002). Myopic participants had significantly lower 25(OH)D₃ concentrations. The prevalence of myopia was significantly higher in in iduals with vitamin D deficiency compared to the in iduals with sufficient levels. Longitudinal studies are warranted to investigate whether higher serum 25(OH)D₃ concentration is protective against myopia or whether it is acting as a proxy for some other biologically effective consequence of sun exposure.
Publisher: Wiley
Date: 30-09-2019
DOI: 10.1111/CEO.13381
Abstract: Artificial intelligence (AI) has emerged as a major frontier in computer science research. Although AI has broad application across many medical fields, it will have particular utility in ophthalmology and will dramatically change the diagnostic and treatment pathways for many eye conditions such as corneal ectasias, glaucoma, age-related macular degeneration and diabetic retinopathy. However, given that AI has primarily been driven as a computer science, its concepts and terminology are unfamiliar to many medical professionals. Important key terms such as machine learning and deep learning are often misunderstood and incorrectly used interchangeably. This article presents an overview of AI and new developments relevant to ophthalmology.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-03-2017
Abstract: Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) with Mendelian inheritance are caused by mutations in at least nine genes. Utilizing whole-exome sequencing, we examined the disease burden accounted for by these known Mendelian glaucoma genes in a cohort of in iduals with advanced early-onset POAG. The cases exhibited advanced POAG with young age of diagnosis. Cases and examined local controls were subjected to whole-exome sequencing. Nine hundred ninety-three previously sequenced exomes of Australian controls were called jointly with our dataset. Qualifying variants were selected based on predicted pathogenicity and rarity in public domain gene variant databases. Case-control mutational burdens were calculated for glaucoma-linked genes. Two hundred eighteen unrelated POAG participants and 103 nonglaucomatous controls were included in addition to 993 unexamined controls. Fifty-eight participants (26.6%) harbored rare potentially pathogenic variants in known glaucoma genes. Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls. After multiple testing correction, only MYOC showed statistically significant enrichment of qualifying variants (odds ratio [OR] = 16.62, P = 6.31×10-16). Rare, potentially disease-causing variants in Mendelian POAG genes that showed enrichment in our dataset were found in 22.9% of advanced early-onset POAG cases. MYOC variants represented the largest monogenic cause in POAG. The association between WDR36 and POAG was not supported, and the majority of POAG cases did not harbor a potentially disease-causing variant in the remaining Mendelian genes.
Publisher: Wiley
Date: 22-08-2017
DOI: 10.1002/MGG3.321
Publisher: Asia Pacific Academy of Ophthalmology
Date: 05-2016
Publisher: Springer Science and Business Media LLC
Date: 11-01-2016
DOI: 10.1038/NG.3482
Publisher: Wiley
Date: 10-2010
Publisher: Elsevier BV
Date: 1998
DOI: 10.1086/301675
Publisher: Elsevier BV
Date: 09-2020
Publisher: Oxford University Press (OUP)
Date: 20-09-2016
DOI: 10.1093/HMG/DDW319
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/13816819309087625
Abstract: STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM, Igα, and Igβ via SEL1L/HRD1-mediated ER-associated degradation (ERAD). B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igα and Syk than those without activated STING. When immunized with T-independent antigens, STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type (WT) mice. We further generated B cell-specific STING
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.PRETEYERES.2009.05.004
Abstract: Morphometrics, a branch of morphology, represents the study of size and shape components of biological form and their variation in the population. Assessment of optic disc morphology is essential in the diagnosis and management of many ophthalmic disorders. Much work has been performed to characterize size-related parameters of the optic disc however, limited information is available on shape variation in the general population. In contrast to optic disc or cup sizes, which are conceptually meaningful variables with a defined unit of measurement, there are few metric constructs by which to quantify, visualize and interpret variation in optic disc or cup shape. This has significance in ophthalmic diseases with a genetic basis as recent evidence has suggested that optic disc shape may be heritable. Conventional optic disc shape measures of 'ovality' and 'form-factor' reduce a complex structure to a single number and eliminate information of potential diagnostic relevance from further analyses. The recent advent of 'geometric morphometrics', a branch of statistics that incorporates tools from geometry, biometrics and computer graphics in the quantitative analysis of biological forms, has enabled spatial relationships in shape data to be retained during analysis. The analytical methods employed in geometric morphometrics can be separated into two distinct groups: landmark-based (e.g. Procrustes analysis, thin-plate splines) and boundary outline techniques (e.g. Fourier analysis). In this review, we summarize current approaches to the study of optic disc morphology, discuss the underlying theory of geometric morphometrics within the context of analytical techniques and then explore the contemporary relevance of the subject matter to several biological fields. Finally we illustrate the potential application of geometric morphometrics to the specific problem of optic disc shape and glaucoma assessment.
Publisher: Hindawi Limited
Date: 24-09-2002
DOI: 10.1002/HUMU.9066
Publisher: Informa UK Limited
Date: 08-02-2010
DOI: 10.3109/13816810903479842
Abstract: In contrast to Autosomal dominant optic atrophy (ADOA), acute loss of vision is normally observed in Leber's hereditary optic neuropathy (LHON) patients. We present a case of a young child with ADOA with a confirmed OPA1 mutation who appeared to have had an acute visual loss in the third year of life. Differentiating between ADOA and LHON requires careful documentation of visual symptoms, family history, clinical examination and genetic testing if available. This clarifies the clinical diagnosis, ensuring appropriate genetic counselling is provided so that affected in iduals are accurately informed on inheritance patterns and implications for family members.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-03-2020
Publisher: Wiley
Date: 12-03-2013
DOI: 10.1111/CEO.12067
Abstract: To determine the incidence and predictors of glaucoma following surgery for congenital and infantile cataract in an Australian population. Retrospective cohort study. Infants (<12 months) having had lens extraction between January 1992 and May 2006, from two tertiary referral centres. Children with uveitis, anterior segment dysgenesis, aniridia, retinopathy of prematurity, and lens subluxation were excluded. Potential predictors of incident glaucoma were examined using Cox proportional hazards regression with adjustment for clustering between eyes. Incidence and predictors of secondary glaucoma. One hundred and forty-seven eyes of 101 patients (46 bilateral cataract 55 unilateral cataract) were included, with median follow-up of 9.9 years (range 1.2-18.9 years). Cumulative incidence of glaucoma was 32.0% for eyes (n = 47) and 30.7% (n = 31) for subjects. Incidence was higher in children with bilateral cataract (38.9 vs. 17.1%, p = 0.004). There were 3.9 cases of glaucoma per 100 person years of follow-up, the incidence rate being highest for surgery performed in the first month of life. Children with glaucoma had longer median follow-up (11.8 vs. 9.3 years, p = 0.005). Risk of glaucoma decreased with increasing months of age at operation: hazard ratio 0.79, 95% confidence interval 0.69-0.91, p = 0.001. Median visual acuity was worse in children with unilateral cataract (p < 0.001). We identified an increased risk of glaucoma when cataract surgery was performed in younger infants, and in those with bilateral cataract. As glaucoma may develop over a decade following lens extraction, life-long surveillance is needed to prevent glaucoma-associated vision loss.
Publisher: Wiley
Date: 18-05-2023
DOI: 10.1111/CEO.14240
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JID.2017.04.026
Abstract: Loss of fine skin patterning is a sign of both aging and photoaging. Studies investigating the genetic contribution to skin patterning offer an opportunity to better understand a trait that influences both physical appearance and risk of keratinocyte skin cancer. We undertook a meta-analysis of genome-wide association studies of a measure of skin pattern (microtopography score) damage in 1,671 twin pairs and 1,745 singletons (N = 5,087) drawn from three independent cohorts. We identified that rs185146 near SLC45A2 is associated with a skin aging trait at genome-wide significance (P = 4.1 × 10
Publisher: Wiley
Date: 13-06-2022
DOI: 10.1111/CEO.14120
Abstract: To investigate the relationship between dietary intake of niacin (water‐soluble form of vitamin B 3 ) and retinal nerve fibre layer (RNFL) thickness in healthy eyes. This cross‐sectional study examined the association between daily niacin intake and RNFL thickness in three large population‐based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data energy‐adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed‐effects models were utilised to examine the association between RNFL thickness and energy‐adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable. In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20 Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64 TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI β: Raine Study Gen 2, −0.174 to 0.074 BHAS, −0.066 to 0.078 TwinsUK −0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts. Dietary intake of niacin from a standard diet does not appear to be associated with age‐related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.
Publisher: Wiley
Date: 07-2009
DOI: 10.1111/J.1442-9071.2009.02058.X
Abstract: The completion of the Human Genome Project heralded a new era in human genetic testing to predict in iduals at risk from many common diseases. DNA markers can also be used to track one's ancestry. Eye diseases such as age-related macular degeneration and glaucoma have been important ex les of the success of genome-wide association studies. Resource-strapped genetic services have been limited in providing DNA testing for many well-established hereditary diseases. Thus, several direct-to-consumer genetic services have arisen to fill the gap. However, there is a major need for research into interpreting the results of such tests of up to one million DNA markers. Studies of population, family and twins sharing common diseases help us clarify the significance of gene-disease associations. However, as identical twins show us, for some conditions our genes do not absolutely determine our destiny and environmental factors interact with our genetic profile.
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.AJO.2004.11.061
Abstract: To investigate the prevalence of the Q368STOP myocilin mutation in a population-based cohort: the Blue Mountains Eye Study (BMES). Population-based study. DNA was extracted from 2,142 in iduals collected through the BMES, including 31 in iduals with glaucoma. All in iduals were screened for the presence of the Q368STOP mutation of myocilin. Genotyping of the microsatellite markers My5, My3, D1S2815, and D1S1619 was also undertaken. None of the 31 open-angle glaucoma-positive in iduals presented with the Q368STOP mutation. However, two in iduals (aged 56 and 72) with no clinical signs of OAG, were identified with this mutation. Allele sharing at the four microsatellite markers defining the Q368STOP disease haplotype for OAG was found in these two in iduals. The Q368STOP myocilin mutation occurs at a low prevalence (0.09%) in a general, older population.
Publisher: Elsevier BV
Date: 04-2021
Publisher: AMPCo
Date: 05-2014
DOI: 10.5694/MJA14.00086
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 21-04-2022
DOI: 10.1167/IOVS.63.4.12
Publisher: Cambridge University Press (CUP)
Date: 10-2009
Abstract: Visual impairment is a leading cause of morbidity and poor quality of life in our community. Unravelling the mechanisms underpinning important blinding diseases could allow preventative or curative steps to be implemented. Twin siblings provide a unique opportunity in biology to discover genes associated with numerous eye diseases and ocular biometry. Twins are particularly useful for quantitative trait analysis through genome-wide association and linkage studies. Although many studies involving twins rely on twin registries, we present our approach to the Twins Eye Study in Tasmania to provide insight into possible recruitment strategies, expected participation rates and potential examination strategies that can be considered by other researchers for similar studies. Five separate avenues for cohort recruitment were adopted: (1) piggy-backing existing studies where twins had been recruited, (2) utilizing the national twin registry, (3) word-of-mouth and local media publicity, (4) directly approaching schools, and finally (5) collaborating with other research groups studying twins.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.SCHRES.2018.06.061
Abstract: Congenital/early blindness is reportedly protective against schizophrenia. Using a whole-population cohort of 467,945 children born in Western Australia between 1980 and 2001, we examined prevalence of schizophrenia and psychotic illness in in iduals with congenital/early blindness. Overall, 1870 children developed schizophrenia (0.4%) while 9120 developed a psychotic illness (1.9%). None of the 66 children with cortical blindness developed schizophrenia or psychotic illness. Eight of the 613 children with peripheral blindness developed a psychotic illness other than schizophrenia and fewer had developed schizophrenia. Our results support findings from small case studies that congenital/early cortical but not peripheral blindness is protective against schizophrenia.
Publisher: BMJ
Date: 08-2004
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2005
DOI: 10.1167/IOVS.04-1497
Abstract: A classic twin study was performed to determine the heritability of central corneal thickness (CCT), an important parameter in glaucoma assessment. The concordance of CCT between monozygotic (MZ) and dizygotic (DZ) twins was compared. A total of 256 twin pairs (131 MZ and 125 DZ) were recruited from three centers: the Twin Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Twins U.K. Adult Registry held at St. Thomas' Hospital in London. As part of an extensive ophthalmic evaluation, CCT was measured by ultrasound pachymetry. Structural equation modeling with the Mx program (Department of Psychiatry, Medical College of Virginia, Richmond, VA) was used to determine the heritability of CCT. The mean age of subjects was 38 years (range, 8-81). The mean CCT of all eyes examined was 544.5 +/- 37.3 mum (SD). The CCT measurements correlated more highly in MZ twins than in DZ twins, with intraclass correlation coefficients of 0.95 and 0.52, respectively, suggesting a strong genetic influence. A model of additive genetic and unique environmental effects provided the best fit, yielding a heritability of 0.95 (95% confidence interval [CI], 0.93-0.96) with the remaining variation being attributable to unique environmental factors. In this study of Australian and U.K. twins, genetic factors were shown to be of major importance in CCT, with a heritability of 0.95.
Publisher: Wiley
Date: 07-03-2018
DOI: 10.1111/CEO.13167
Publisher: Wiley
Date: 16-08-2007
DOI: 10.1111/J.1399-0004.2007.00864.X
Abstract: Analysis of CYP1B1 in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of CYP1B1 mutations in Australian PCG patients. The aim of this study is to determine the frequency of CYP1B1 mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty-seven probands were recruited from South-Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of CYP1B1 analysed by direct sequencing. Sequence analysis identified 10 different CYP1B1 disease-causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for CYP1B1 mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported CYP1B1 R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in CYP1B1 account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG-related genes remain to be identified.
Publisher: AMPCo
Date: 05-2016
DOI: 10.5694/MJA15.01177
Abstract: We explored the relationship between the National Emergency Access Target (NEAT) compliance rate, defined as the proportion of patients admitted or discharged from emergency departments (EDs) within 4 hours of presentation, and the risk-adjusted in-hospital mortality of patients admitted to hospital acutely from EDs. Retrospective observational study of all de-identified episodes of care involving patients who presented acutely to the EDs of 59 Australian hospitals between 1 July 2010 and 30 June 2014. The relationship between the risk-adjusted mortality of inpatients admitted acutely from EDs (the emergency hospital standardised mortality ratio [eHSMR]: the ratio of the numbers of observed to expected deaths) and NEAT compliance rates for all presenting patients (total NEAT) and admitted patients (admitted NEAT). ED and inpatient data were aggregated for 12.5 million ED episodes of care and 11.6 million inpatient episodes of care. A highly significant (P < 0.001) linear, inverse relationship between eHSMR and each of total and admitted NEAT compliance rates was found eHSMR declined to a nadir of 73 as total and admitted NEAT compliance rates rose to about 83% and 65% respectively. Sensitivity analyses found no confounding by the inclusion of palliative care and/or short-stay patients. As NEAT compliance rates increased, in-hospital mortality of emergency admissions declined, although this direct inverse relationship is lost once total and admitted NEAT compliance rates exceed certain levels. This inverse association between NEAT compliance rates and in-hospital mortality should be considered when formulating targets for access to emergency care.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-12-2017
DOI: 10.1167/TVST.6.6.7
Publisher: Oxford University Press (OUP)
Date: 10-04-2015
DOI: 10.1093/HMG/DDV128
Publisher: Springer Science and Business Media LLC
Date: 04-11-2014
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.ORET.2022.04.022
Abstract: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study. Cross-sectional, community-based, prospective cohort study. 5020 Australian adults (2264 men and 2756 women age range, 45-69 years, and median age, 58 years). Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis. Prevalence of toxoplasmic retinochoroiditis. Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021 :3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67% or 1 per 149 persons. Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified.
Publisher: Wiley
Date: 10-2010
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-12-2021
Publisher: Elsevier BV
Date: 11-2014
Publisher: Wiley
Date: 19-06-2012
DOI: 10.1111/J.1442-9071.2012.02804.X
Abstract: To characterize the clinical and genetic abnormalities within two Australian pedigrees with high incidences of retinal detachment and visual disability. Prospective review of two extended Australian pedigrees with high rates of retinal detachment. Twenty-two family members from two extended Australian pedigrees with high rates of retinal detachment were examined. A full ophthalmic history and examination were performed, and DNA was analysed by linkage analysis and mutation screening. Characterization of a causative hereditary gene mutation in each family. All affected family members of one pedigree carried a C192A COL2A1 exon 2 mutation. None of the affected family members had early-onset arthritis, hearing abnormalities, abnormal clefting or facial features characteristic of classical Stickler syndrome. All affected members of the familial exudative vitreoretinopathy pedigree carried a 957delG FZD4 mutation. Patients with retinal detachment and a positive family history should be investigated for heritable conditions associated with retinal detachment such as Stickler syndrome and familial exudative vitreoretinopathy. The absence of non-ocular features of Stickler syndrome should raise the possibility of mutations in exon 2 of COL2A1. Similarly, late-onset familial exudative vitreoretinopathy may appear more like a rhegmatogenous detachment and not be correctly diagnosed. When a causative gene mutation is identified, cascade genetic screening of the family will facilitate genetic counselling and screening of high-risk relatives, allowing targeted management of the pre-detachment changes in affected patients.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2020
DOI: 10.1038/S41439-020-00122-W
Abstract: Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in the CHM gene. Several CHM gene replacement clinical trials are in advanced stages. In this study, we report the molecular confirmation of choroideremia in 14 Australian families sourced from the Australian Inherited Retinal Disease Registry and DNA Bank. Sixteen males (14 symptomatic) and 18 females (4 symptomatic 14 obligate carriers) were identified for analysis. Participants’ DNA was analyzed for disease-causing CHM variants by Sanger sequencing, TaqMan qPCR and targeted NGS. We report phenotypic and genotypic data for the 14 symptomatic males and four females manifesting disease symptoms. A pathogenic or likely pathogenic CHM variant was detected in all families. Eight variants were previously reported, and five were novel. Two de novo variants were identified. We previously reported the molecular confirmation of choroideremia in 11 Australian families. This study expands the CHM genetically confirmed Australian cohort to 32 males and four affected carrier females.
Publisher: Informa UK Limited
Date: 10-2016
DOI: 10.1080/13816810.2016.1232416
Abstract: The Marshall Parks Lecture 2015, entitled "Myopia-The future progression of myopia: Seeing where we are going," was presented by Professor David A. Mackey at the American Academy of Ophthalmology meeting held in Las Vegas in November 2015.
Publisher: American Medical Association (AMA)
Date: 2014
Publisher: Wiley
Date: 11-05-2016
DOI: 10.1111/AOS.13082
Publisher: BMJ
Date: 05-2003
DOI: 10.1136/BJO.87.5.635
Publisher: Informa UK Limited
Date: 03-05-2020
Publisher: BMJ
Date: 09-2005
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.OPHTHA.2015.12.008
Abstract: Corneal dystrophies are a genetically heterogeneous group of disorders. We previously described a family with an autosomal dominant epithelial recurrent erosion dystrophy (ERED). We aimed to identify the underlying genetic cause of ERED in this family and 3 additional ERED families. We sought to characterize the potential function of the candidate genes using the human and zebrafish cornea. Case series study of 4 white families with a similar ERED. An experimental study was performed on human and zebrafish tissue to examine the putative biological function of candidate genes. Four ERED families, including 28 affected and 17 unaffected in iduals. HumanLinkage-12 arrays (Illumina, San Diego, CA) were used to genotype 17 family members. Next-generation exome sequencing was performed on an uncle-niece pair. Segregation of potential causative mutations was confirmed using Sanger sequencing. Protein expression was determined using immunohistochemistry in human and zebrafish cornea. Gene expression in zebrafish was assessed using whole-mount in situ hybridization. Morpholino-induced transient gene knockdown was performed in zebrafish embryos. Linkage microarray, exome analysis, DNA sequence analysis, immunohistochemistry, in situ hybridization, and morpholino-induced genetic knockdown results. Linkage microarray analysis identified a candidate region on chromosome chr10:12,576,562-112,763,135, and exploration of exome sequencing data identified 8 putative pathogenic variants in this linkage region. Two variants segregated in 06NZ-TRB1 with ERED: COL17A1 c.3156C→T and DNAJC9 c.334G→A. The COL17A1 c.3156C→T variant segregated in all 4 ERED families. We showed biologically relevant expression of these proteins in human cornea. Both proteins are expressed in the cornea of zebrafish embryos and adults. Zebrafish lacking Col17a1a and Dnajc9 during development show no gross corneal phenotype. The COL17A1 c.3156C→T variant is the likely causative mutation in our recurrent corneal erosion families, and its presence in 4 independent families suggests that it is prevalent in ERED. This same COL17A1 c.3156C→T variant recently was identified in a separate pedigree with ERED. Our study expands the phenotypic spectrum of COL17A1 disease from autosomal recessive epidermolysis bullosa to autosomal dominant ERED and identifies COL17A1 as a key protein in maintaining integrity of the corneal epithelium.
Publisher: BMJ
Date: 24-07-2008
Abstract: Autosomal dominant optic atrophy (ADOA) is a genetically heterogenous disease. However, a large proportion of this disease is accounted for by mutations in OPA1. The aim of this longitudinal study was to investigate disease progression in Australian ADOA patients with confirmed OPA1 mutations. Probands with characteristic clinical findings of ADOA were screened for OPA1 mutations, and relatives of identified mutation carriers were invited to participate. Disease progression was determined by sequential examination or using historical records over a mean of 9.6 (range 1-42) years. OPA1 mutation carriers (n = 158) were identified in 11 ADOA pedigrees. Sixty-nine mutation carriers were available for longitudinal follow-up. Using the right eye as the default, best-corrected visual acuity (BCVAR) remained unchanged (defined as visual acuity at or within one line of original measurement) in 43 patients (62%). BCVAR worsened by 2 lines in 13 patients (19%). BCVAR deteriorated by more than 2 lines in six patients (9%). Ten per cent of patients had an improvement in visual acuity. Mean time to follow-up was 9.6 years with the mean visual acuity being 6/18 for both the initial and subsequent measurements. There was no statistical significance in the rate of BCVAR loss across different OPA1 mutations (p = 0.55). OPA1-related ADOA generally progresses slowly and functional visual acuity is usually maintained. Longitudinal disease studies are important to enable appropriate counselling of patients. This study enables a better understanding of the natural history of ADOA.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 15-06-2022
DOI: 10.1167/IOVS.63.6.15
Publisher: Wiley
Date: 09-09-2022
DOI: 10.1111/CEO.14148
Abstract: To test the hypothesis that 0.01% atropine eyedrops are a safe and effective myopia‐control approach in Australian children. Children (6–16 years 49% Europeans, 18% East Asian, 22% South Asian, and 12% other/mixed ancestry) with documented myopia progression were enrolled into this single‐centre randomised, parallel, double‐masked, placebo‐controlled trial and randomised to receive 0.01% atropine ( n = 104) or placebo ( n = 49) eyedrops (2:1 ratio) instilled nightly over 24 months (mean index age = 12.2 ± 2.5 and 11.2 ± 2.8 years, respectively). Outcome measures were the changes in spherical equivalent (SE) and axial length (AL) from baseline. At 12 months, the mean SE and AL change from baseline were −0.31D (95% confidence interval [CI] = −0.39 to −0.22) and 0.16 mm (95%CI = 0.13–0.20) in the atropine group and −0.53D (95%CI = −0.66 to −0.40) and 0.25 mm (95%CI = 0.20–0.30) in the placebo group (group difference p ≤ 0.01). At 24 months, the mean SE and AL change from baseline was −0.64D (95%CI = −0.73 to −0.56) and 0.34 mm (95%CI = 0.30–0.37) in the atropine group, and −0.78D (95%CI = −0.91 to −0.65) and 0.38 mm (95%CI = 0.33–0.43) in the placebo group. Group difference at 24 months was not statistically significant ( p = 0.10). At 24 months, the atropine group had reduced accommodative litude and pupillary light response compared to the placebo group. In Australian children, 0.01% atropine eyedrops were safe, well‐tolerated, and had a modest myopia‐control effect, although there was an apparent decrease in efficacy between 18 and 24 months, which is likely driven by a higher dropout rate in the placebo group.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Informa UK Limited
Date: 30-07-2020
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-04-2021
DOI: 10.1167/IOVS.62.5.7
Publisher: BMJ
Date: 09-03-2012
DOI: 10.1136/BJOPHTHALMOL-2011-301255
Abstract: Conjunctival ultraviolet autofluorescence (UVAF) photography was developed to detect and characterise pre-clinical sunlight-induced UV damage. The reliability of this measurement and its relationship to outdoor activity are currently unknown. 599 people aged 16-85 years in the cross-sectional Norfolk Island Eye Study were included in the validation study. 196 UVAF in idual photographs (49 people) and 60 UVAF photographs (15 people) of Norfolk Island Eye Study participants were used for intra- and inter-observer reliability assessment, respectively. Conjunctival UVAF was measured using UV photography. UVAF area was calculated using computerised methods by one grader on two occasions (intra-observer analysis) or two graders (inter-observer analysis). Outdoor activity category, during summer and winter separately, was determined with a UV questionnaire. Total UVAF equalled the area measured in four conjunctival areas (nasal/temporal conjunctiva of right and left eyes). Intra-observer (ρ_c=0.988, 95% CI 0.967 to 0.996, p<0.001), and inter-observer concordance correlation coefficients (ρ_c=0.924, 95% CI 0.870 to 0.956, p<0.001) of total UVAF exceeded 0.900. When grouped according to 10 mm(2) total UVAF increments, intra- and inter-observer reliability was very good (κ=0.81) and good (κ=0.71), respectively. Increasing time outdoors was strongly with increasing total UVAF in summer and winter (p(trend) <0.001). Intra- and inter-observer reliability of conjunctival UVAF is high. In this population, UVAF correlates strongly with the authors' survey-based assessment of time spent outdoors.
Publisher: Informa UK Limited
Date: 23-04-2019
DOI: 10.1080/00140139.2018.1562107
Abstract: This study aimed to describe contemporary technology use, especially smartphones and tablets (mobile touch screen devices), and examine associations with musculoskeletal symptoms and visual health among adolescents in Singapore. A representative s le of 1884 adolescents (50.4% girls) from grades primary 5 to post-secondary (10-18 years old), recruited from 13 schools, completed an online questionnaire in class. Total technology use was high, with smartphone duration being highest (mean = 264 [SD = 243] min/day). Patterns of use, including multitasking and bout length, were influenced by gender, school level, type of device and activities. Musculoskeletal discomfort and visual symptoms were commonly reported. After adjusting for potential confounders, more hours/day of smartphone use was associated with increased risk of neck/shoulders, upper back, arms and wrist/hand discomfort (OR = 1.04[95%CI = 1.01-1.07] to 1.07[1.03-1.10]) and visual symptoms (OR = 1.05[1.02-1.08]), but was associated with decreased odds of myopia (OR = 0.97[0.94-0.99]). No significant associations were found for tablet use.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-2009
DOI: 10.1167/IOVS.08-2781
Publisher: Springer Science and Business Media LLC
Date: 14-11-2018
DOI: 10.1038/S41467-018-06649-5
Abstract: The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 in iduals. We confirm known loci including MTAP , PLA2G6 , and IRF4 , and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1 , PPARGC1B , HDAC4 , FAM208B, DOCK8 , and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk ( KITLG an exception), while many melanoma risk loci do not alter nevus count. For ex le, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
Publisher: Elsevier BV
Date: 2015
Publisher: F1000 Research Ltd
Date: 25-09-2019
DOI: 10.12688/HRBOPENRES.12914.2
Abstract: Background: The Myopia Outcome Study of Atropine in Children (MOSAIC) aims to explore the efficacy, safety, acceptability and mechanisms of action of 0.01% unpreserved atropine for myopia control in a European population. Methods: MOSAIC is an investigator-led, double-masked, placebo-controlled, randomised clinical trial (RCT) investigating the efficacy, safety and mechanisms of action of 0.01% atropine for managing progression of myopia. During Phase 1 of the trial, 250 children aged 6-16 years with progressive myopia instil eye drops once nightly in both eyes from randomisation to month 24. From month 24 to 36 participants are re-randomised in Phase 2 of the trial, into continued 0.01% atropine, and washout, at 1:1 ratio for those participants initially randomised to the intervention arm (n=167), during which any potential rebound effects on cessation of treatment will be monitored. All participants initially assigned to the placebo (n=83) crossover to the intervention arm of the study for Phase 2, and from month 24 to 36, instil 0.01% atropine eye drops in both eyes once nightly. Further treatment and monitoring beyond 36 months is planned (Phase 3) and will be designed dependent on the outcomes of Phase 1. Results: The primary outcome measure is cycloplegic spherical equivalent refractive error progression at 24 months. Secondary outcome measures include axial length change as well as the rebound, safety and acceptability profile of 0.01% atropine. Additional analyses will include the mechanisms of action of 0.01% atropine for myopia control. Conclusions: The generalisability of results from previous clinical trials investigating atropine for myopia control is limited by the predominantly Asian ethnicity of previous study populations. MOSAIC is the first RCT to explore the efficacy, safety and mechanisms of action of unpreserved 0.01% atropine in a predominantly White population.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.OPHTHA.2012.02.004
Abstract: Genetic variation at the 9p21 locus encompassing the CDKN2B-AS1, CDKN2A, and CDKN2B genes has been associated with primary open-angle glaucoma (POAG) in several independent studies. This study aimed to dissect the association further and to determine genotype-phenotype correlations between genetic variation at this locus and a range of glaucoma-related traits in a large cohort of POAG patients. Comparative case series and case-control study. One thousand four hundred thirty-two POAG patients and 595 unaffected controls recruited from 2 population-based and 2 cross-sectional studies. Each patient was genotyped at 9 single nucleotide polymorphisms (SNPs) previously associated with POAG at the 9p21 locus. Each SNP was assessed for association with each outcome measure using linear regression under an additive genetic model. Associated traits were explored further including adjustment for relevant covariates. Highest recorded intraocular pressure (IOP) also was analyzed both with and without correction for central corneal thickness (CCT) and was dichotomized into high-tension glaucoma and normal-tension glaucoma (NTG). Intraocular pressure and vertical cup-to-disc ratio (VCDR). Glaucoma risk alleles at 9p21, particularly, rs7049105 and rs10120688, were associated with the presence of both NTG and advanced POAG. The SNP rs10120688 was associated with greater VCDR after adjustment for covariates (P = 0.003 β = 0.016 standard error, 0.006). In addition, multiple SNPs in the region were associated with reduced IOP, before and after adjustment for CCT. The SNP most significantly associated with IOP was also rs10120688 (P = 0.001 β = -2.135 standard error, 0.634) after adjustment for covariates under an additive model. In a comparison of high-tension versus low-tension glaucoma, this SNP was also the most significantly associated, particularly when IOP was corrected for CCT before classification of the type of glaucoma (P = 0.0009 odds ratio, 0.63 95% confidence interval, 0.48-0.83). Patients with POAG carrying the glaucoma risk alleles at the 9p21 locus have larger VCDR and lower IOP than POAG patients without these alleles. Carriers of these alleles seem to be predisposed to POAG developing at lower IOP levels and exhibit stronger associations with NTG and advanced glaucoma phenotypes. This may be of relevance when setting target pressures in patients carrying these risk alleles.
Publisher: Springer Science and Business Media LLC
Date: 05-06-2012
Publisher: Informa UK Limited
Date: 05-2017
DOI: 10.1111/CXO.12486
Abstract: The aim was to investigate the characteristics and outcomes of ocular and adnexal injuries requiring hospitalisation in children in Perth, Western Australia. This is a hospital-based retrospective review of children admitted to Princess Margaret Hospital for Children with diagnoses of ocular and/or adnexal trauma from 2002-2013. Hospital charts were reviewed for demographic information, injury and management details, follow-up and visual outcome. Final visual acuity was categorised into three groups: 6/12 or better, from 6/12 to 6/60, worse than 6/60. Ordinal logistic regression was used to compute odds ratios and predicted probabilities for each category of final visual outcome. Over the 12-year time period, 482 children were admitted with ocular or adnexal injuries - an average of 40 admissions per year. The mean age of the cohort was 7.1 years (range 0.09 to 16.47 years) with a male to female ratio of 2.6:1.0. There were 185 closed-globe injuries, 72 open-globe injuries and 293 adnexal injuries. Fourteen per cent of the cohort sustained a combined globe and adnexal injury. Children in the up to five-year age group were most susceptible to injury. Eighty-two per cent of the group had a final visual acuity of 6/12 or better. Factors associated with poor visual outcomes included younger age (p < 0.01), open-globe injury (p < 0.01) and lens injury (p < 0.01). Based on the outcomes of our review, paediatric ocular and adnexal trauma are significant causes for hospital attendance in childhood. Identifying associated risk factors will help develop injury prevention strategies to promote eye safety for children.
Publisher: American Medical Association (AMA)
Date: 2007
DOI: 10.1001/ARCHOPHT.125.1.98
Abstract: To determine the phenotype of an Australian pedigree with the myocilin (MYOC) Gly252Arg mutation, comparing it with other pedigrees carrying the same mutation. All recruited subjects underwent a comprehensive clinical examination, including optic disc assessment, applanation tonometry, and visual field measurement. Mutation analysis was performed through direct sequencing. Haplotype analysis was performed using microsatellite markers around the MYOC gene. Eight Gly252Arg mutation carriers with glaucoma were identified from the same pedigree. Carriers' mean +/- SD age at diagnosis was 46.3 +/- 11.4 years (range, 31-60 years). Highest recorded intraocular pressure ranged from 27 to 42 mm Hg (mean +/- SD, 32.4 +/- 5.6 mm Hg). Cup-disc ratios in the worst eye ranged from 0.6 to 0.9. Six of the 8 in iduals had undergone filtration surgery. A common founding haplotype between MY5 and D1S218 was found for Caucasian in iduals tested with this mutation. One subject was compound heterozygotic for the MYOC Gly252Arg mutation and a novel MYOC Gly244Val variant. Although a common founder for Gly252Arg across Caucasian subjects was found, the phenotype from this Australian MYOC mutation-carrying pedigree is less severe than previously described. The severity of glaucoma caused by the Gly252Arg mutation may be similar to the Thr377Met MYOC mutation, yet is more severe than the most common Gln368Stop mutation. Since its implication in glaucoma, much work has been performed investigating the clinical features of MYOC-related glaucoma. Given the strong genotype-phenotype correlations with MYOC disease-causing variants, health care professionals armed with such molecular information are able to accurately counsel patients on their likely disease course. Our work suggests that the disease associated with MYOC Gly252Arg is less severe than previously described in other pedigrees with this specific mutation.
Publisher: F1000 Research Ltd
Date: 23-07-2019
DOI: 10.12688/HRBOPENRES.12914.1
Abstract: Background: The Myopia Outcome Study of Atropine in Children (MOSAIC) aims to explore the efficacy, safety, acceptability and mechanisms of action of 0.01% unpreserved atropine for myopia control in a European population. Methods: MOSAIC is an investigator-led, double-masked, placebo-controlled, randomised clinical trial (RCT) investigating the efficacy, safety and mechanisms of action of 0.01% atropine for managing progression of myopia. During Phase 1 of the trial, 250 children aged 6-16 years with progressive myopia instil eye drops once nightly in both eyes from randomisation to month 24. No treatment is given during Phase 2 from month 24 to 36 (washout period) for those participants initially randomised to the intervention arm (n=167), during which any potential rebound effects on cessation of treatment will be monitored. All participants initially assigned to the placebo (n=83) crossover to the intervention arm of the study for Phase 2, and from month 24 to 36, instil 0.01% atropine eye drops in both eyes once nightly. Further treatment and monitoring beyond 36 months is planned (Phase 3) and will be designed dependent on the outcomes of Phase 1. Results: The primary outcome measure is cycloplegic spherical equivalent refractive error progression at 24 months. Secondary outcome measures include axial length change as well as the rebound, safety and acceptability profile of 0.01% atropine. Additional analyses will include the mechanisms of action of 0.01% atropine for myopia control. Conclusions: The generalisability of results from previous clinical trials investigating atropine for myopia control is limited by the predominantly Asian ethnicity of previous study populations. MOSAIC is the first RCT to explore the efficacy, safety and mechanisms of action of unpreserved 0.01% atropine in a predominantly White population. Trial registration: ISRCTN: ISRCTN36732601 (04/10/2017), EudraCTdatabase 2016-003340-37 (03/07/2018).
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 24-06-2022
DOI: 10.1167/IOVS.63.6.25
Publisher: Springer Science and Business Media LLC
Date: 29-05-2013
DOI: 10.1038/NG0613-712B
Publisher: American Association for the Advancement of Science (AAAS)
Date: 12-03-2021
Abstract: A GWAS including 192,986 European and 1636 Asian participants identifies 50 novel discrete associations with eye color.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2023
DOI: 10.1038/S41588-023-01424-9
Abstract: Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3 . These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2014
Publisher: Springer Science and Business Media LLC
Date: 04-2003
Publisher: Springer Science and Business Media LLC
Date: 21-12-2015
DOI: 10.1038/NG.3448
Publisher: Oxford University Press (OUP)
Date: 06-09-2019
DOI: 10.1093/HMG/DDZ193
Abstract: Optic nerve head morphology is affected by several retinal diseases. We measured the vertical optic disc diameter (DD) of the UK Biobank (UKBB) cohort (N = 67 040) and performed the largest genome-wide association study (GWAS) of DD to date. We identified 81 loci (66 novel) for vertical DD. We then replicated the novel loci in International Glaucoma Genetic Consortium (IGGC, N = 22 504) and European Prospective Investigation into Cancer–Norfolk (N = 6005) in general the concordance in effect sizes was very high (correlation in effect size estimates 0.90): 44 of the 66 novel loci were significant at P & 0.05, with 19 remaining significant after Bonferroni correction. We identified another 26 novel loci in the meta-analysis of UKBB and IGGC data. Gene-based analyses identified an additional 57 genes. Human ocular tissue gene expression analysis showed that most of the identified genes are enriched in optic nerve head tissue. Some of the identified loci exhibited pleiotropic effects with vertical cup-to-disc ratio, intraocular pressure, glaucoma and myopia. These results can enhance our understanding of the genetics of optic disc morphology and shed light on the genetic findings for other ophthalmic disorders such as glaucoma and other optic nerve diseases.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JPEDS.2015.10.048
Abstract: To investigate whether being anesthesia administered at least once in early life influenced 3 main proxies of visual function: visual acuity, refractive error, and optic nerve health in young adulthood. At age 20 years, participants of the Western Australian Pregnancy Cohort Study had comprehensive ocular examinations including visual acuity, postcycloplegic refraction, and multiple scans of the optic disc. We identified in iduals who had at least 1 procedure requiring anesthesia during the first 3 years of life (between 1990 and 1994) and compared their visual outcomes with nonexposed in iduals. We excluded 40 participants with strabismus or other ophthalmic disease or surgery and 136 with non-European background. Of 834 participants, 15.2% (n = 127) were exposed to anesthesia at least once before age 3 years. In both exposed and nonexposed groups, median visual acuity (measured using the logarithm of the minimum angle of resolution [LogMAR] chart) was -0.06 LogMAR in the right eye and -0.08 LogMAR in the left eye (P > .05). Median spherical equivalent refractive error was +0.44 diopters (IQR -0.25, +0.63) and +0.31 diopters (IQR -0.38, +0.63) in the exposed and nonexposed group, respectively (P = .126). No difference was detected in mean global retinal nerve fiber layer thickness of the 2 groups (100.7 vs 100.1 μm, P = .830). We were unable to demonstrate an association of exposure to anesthesia as a child with reduced visual acuity or increased myopia or thinning of retinal nerve fiber layer. These findings support the view that anesthesia is unlikely to impair visual development, but further work is needed to establish whether more subtle defects are present and repeated exposures have any effects.
Publisher: Springer Science and Business Media LLC
Date: 03-2020
DOI: 10.1039/C9PP00240E
Publisher: Hindawi Limited
Date: 05-2009
DOI: 10.1002/HUMU.20995
Abstract: Congenital cataracts (CCs) are clinically and genetically heterogeneous. Mutations in the same gene may lead to CCs differing in inheritance, morphology and severity. Loci for autosomal dominant posterior polar CC and total CC have both been mapped to the chromosomal 1p36 region harboring the EPHA2 receptor tyrosine kinase gene. Here, we report mutations of EPHA2 in three CC families from different ancestral groups. In a Chinese family with posterior polar CC, we identified a missense mutation, c.2819C>T (p.T940I), replacing a critical amino acid that functions at the receptor oligomerization interface. In a British family with posterior polar CC and an Australian family with total CC, we found a frameshift mutation (c.2915_2916delTG) and a splicing mutation (c.2826-9G>A), respectively. These two mutations are predicted to produce novel C-terminal polypeptides with 39 identical amino acids. Yeast two-hybrid analysis showed stronger interaction between the total CC-associated mutant EPHA2 and low molecular weight protein-tyrosine phosphatase, a negative regulator of EPHA2 signaling. Our results implicate the Eph-ephrin signaling system in development of human cataract and provide a novel insight into the molecular mechanism underlying the pathogenesis of human CCs.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 26-05-2022
DOI: 10.1167/IOVS.63.5.34
Publisher: Hindawi Limited
Date: 02-2008
DOI: 10.1002/HUMU.20634
Abstract: Glaucoma, a complex heterogenous disease, is the leading cause for optic nerve-related blindness worldwide. Since 1997, when mutations in the myocilin (MYOC) gene were identified as causing juvenile onset as well as a proportion of primary open-angle glaucoma (POAG), more than 180 variants have been documented. Approximately one in 30 unselected patients with POAG have a disease-causing myocilin mutation and it has been shown that firm genotype-phenotype correlations exist. We have compiled an online catalog of myocilin variants and their associated phenotypes. This locus-specific resource, to which future submissions can be made, is available online (www.myocilin.com last accessed 28 August 2007). The database, constructed using MySQL, contains three related sheets that contain data pertaining to the information source, variant identified, and relevant study data, respectively. The website contains a list of all identified variants and summary statistics as well as background genomic information, such as the annotated sequence and cross-protein/species homology. Phenotypic data such as the mean+/-standard deviation (SD) age at POAG diagnosis, mean+/-SD maximum recorded intraocular pressure, proportion of patients requiring surgical intervention, and age-related penetrance can be viewed by selecting a particular mutation. Approximately 40% of the identified sequence variants have been characterized as disease causing, with the majority ( approximately 85%) of these being missense mutations. Preliminary data generated from this online resource highlight the strong genotype-phenotype correlations associated with specific myocilin mutations. The large-scale assimilation of relevant data allows for accurate comprehensive genetic counseling and the translation of genomic information into the clinic.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Elsevier BV
Date: 06-2020
Publisher: Informa UK Limited
Date: 24-08-2023
Publisher: Elsevier BV
Date: 06-2003
DOI: 10.1086/375537
Abstract: The complete mitochondrial DNA (mtDNA) sequences for 63 Dutch pedigrees with Leber hereditary optic neuropathy (LHON) were determined, 56 of which carried one of the classic LHON mutations at nucleotide (nt) 3460, 11778, or 14484. Analysis of these sequences indicated that there were several instances in which the mtDNAs were either identical or related by descent. The most striking ex le was a haplogroup J mtDNA that carried the 14484 LHON mutation. Four different but related mitochondrial genotypes were identified in seven of the Dutch pedigrees with LHON, including six of those described by van Senus. The control region of the founder sequence for these Dutch pedigrees with LHON matches the control-region sequence that Macmillan and colleagues identified in the founder mtDNA of French Canadian pedigrees with LHON. In addition, we obtained a perfect match between the Dutch 14484 founder sequence and the complete mtDNA sequences of two Canadian pedigrees with LHON. Those results indicate that these Dutch and French Canadian 14484 pedigrees with LHON share a common ancestor, that the single origin of the 14484 mutation in this megalineage occurred before the year 1600, and that there is a 14484/haplogroup J founder effect. We estimate that this lineage--including the 14484 LHON mutation--arose 900-1,800 years ago. Overall, the phylogenetic analyses of these mtDNA sequences conservatively indicate that a LHON mutation has arisen at least 42 times in the Dutch population. Finally, analysis of the mtDNA sequences from those pedigrees that did not carry classic LHON mutations suggested candidate pathogenic mutations at nts 9804, 13051, and 14325.
Publisher: Wiley
Date: 09-09-2011
Publisher: Oxford University Press (OUP)
Date: 15-04-2010
DOI: 10.1093/HMG/DDQ144
Publisher: IEEE
Date: 06-2018
Publisher: Cold Spring Harbor Laboratory
Date: 18-10-2019
DOI: 10.1101/19009183
Abstract: Early diagnosis and intervention is essential to achieve optimal outcomes for most pediatric eye diseases. Educating parents/caregivers to recognize early signs of disease and consult a healthcare professional is critical to achieving this aim. We evaluate the effectiveness of an eye-health information p hlet on parents’ level of concern and their help-seeking intention if they observed leukocoria or strabismus. Pregnant women attending a metropolitan antenatal clinic were recruited to the study. Participants were randomly assigned to receive a p hlet on either pediatric eye health (intervention) or strategies for play (control). The primary outcome measure was a change in the parents’ level of concern if they observed leukocoria or strabismus. The secondary outcome measure was a change in their help-seeking intention if either sign was observed. Of the 518 women enrolled, 382 (73.7%) completed the post-test survey. At follow-up, women who received the intervention were more likely to report a higher level of concern if they observed leukocoria (OR 1.711 [CI: 1.176-2.497] p=0.005]) and were less likely to have a delayed help-seeking intention. (OR 0.560 [CI 0.382-0.817] p =0.003) No change in the level of concern for strabismus was identified between the groups however, at follow-up, women who received the intervention were less likely to delay help-seeking (OR 0.318 [CI 0.125-0.806] p=0.016). Providing parents with relevant, evidence-based information can significantly improve their knowledge and positively influence help-seeking intentions if leukocoria or strabismus are observed. ANZCTR.org.au identifier: ACTRN12617001431314p World Health Organization Universal Trial Number: U1111-1203-0485 This study reports the results of a randomised controlled trial evaluating a novel, evidence-based, theory-informed pediatric eye-health information p hlet for parents. Lack of parental awareness of signs of pediatric eye disease (leukocoria and strabismus) delays consultation with healthcare professionals (help-seeking), contributing to late diagnosis and poor outcomes. Providing parents with relevant health information can improve their child’s health outcomes. Using an RCT to evaluate a novel health intervention, this study demonstrates that providing parents with evidence-based, theory informed pediatric eye-health information can improve their knowledge and help-seeking intentions if leukocoria or strabismus are observed in their child.
Publisher: American Medical Association (AMA)
Date: 20-09-2019
Publisher: Springer Science and Business Media LLC
Date: 02-09-2011
DOI: 10.1007/S00415-011-6230-7
Abstract: The aims of this study are to investigate whether auditory dysfunction is part of the spectrum of neurological abnormalities associated with Leber's hereditary optic neuropathy (LHON) and to determine the perceptual consequences of auditory neuropathy (AN) in affected listeners. Forty-eight subjects confirmed by genetic testing as having one of four mitochondrial mutations associated with LHON (mt11778, mtDNA14484, mtDNA14482 and mtDNA3460) participated. Thirty-two of these had lost vision, and 16 were asymptomatic at the point of data collection. While the majority of in iduals showed normal sound detection, >25% (of both symptomatic and asymptomatic participants) showed electrophysiological evidence of AN with either absent or severely delayed auditory brainstem potentials. Abnormalities were observed for each of the mutations, but subjects with the mtDNA11778 type were the most affected. Auditory perception was also abnormal in both symptomatic and asymptomatic subjects, with >20% of cases showing impaired detection of auditory temporal (timing) cues and >30% showing abnormal speech perception both in quiet and in the presence of background noise. The findings of this study indicate that a relatively high proportion of in iduals with the LHON genetic profile may suffer functional hearing difficulties due to neural abnormality in the central auditory pathways.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 13-02-2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 24-07-2012
DOI: 10.1167/IOVS.11-9047
Abstract: Glaucoma is the leading cause of irreversible blindness worldwide. Primary open angle glaucoma (POAG) is the most common subtype. We recently reported association of genetic variants at chromosomal loci, 1q24 and 9p21, with POAG. In this study, we determined association of the most significantly associated single nucleotide polymorphism (SNP) rs4656461, at 1q24 near the TMCO1 gene, with the clinical parameters related to glaucoma risk and diagnosis, and determined ocular expression and subcellular localization of the human TMCO1 protein to understand the mechanism of its involvement in POAG. Association of SNP rs4656461 with five clinical parameters was assessed in 1420 POAG cases using linear regression. The TMCO1 gene was screened for mutations in 95 cases with a strong family history and advanced disease. Ocular expression and subcellular localization of the TMCO1 protein were determined by immunolabeling and as GFP-fusion. The data suggest that in iduals homozygous for the rs4656461 risk allele (GG) are 4 to 5 years younger at diagnosis than noncarriers of this allele. Our data demonstrate expression of the TMCO1 protein in most tissues in the human eye, including the trabecular meshwork and retina. However, the subcellular localization differs from that reported in other studies. We demonstrate that the endogenous protein localizes to the cytoplasm and nucleus in vivo and ex vivo. In the nucleus, the protein localizes to the nucleoli. This study shows a relationship between genetic variation in and around TMCO1 with age at diagnosis of POAG and provides clues to the potential cellular function/s of this gene.
Publisher: Wiley
Date: 04-2008
Publisher: Wiley
Date: 12-2001
Publisher: BMJ
Date: 06-2002
DOI: 10.1136/BJO.86.6.696
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-01-2023
DOI: 10.1167/IOVS.64.1.3
Publisher: Elsevier BV
Date: 06-2022
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1999
DOI: 10.1097/00055735-199904000-00009
Abstract: The understanding of the genetic basis of the glaucomas has advanced rapidly. Mutations in the myocilin gene (previously known as TIGR) at the GLC1A locus on chromosome 1q21-q31 occur in a subset of patients with juvenile- and adult-onset primary open-angle glaucoma. Five other genetic localizations for primary open-angle glaucoma have now been reported. In patients with primary congenital glaucoma, mutations have been found in the CYP1B1 gene on chromosome 2p21. At least one other locus for primary congenital glaucoma is mapped. In the developmental glaucomas, mutations in the PITX2 gene on chromosome 4q25 have been associated with Rieger syndrome, iris hypoplasia, and iridogoniodysgenesis. A second locus for Rieger syndrome resides on chromosome 13q14. Mutations in the FKHL7 gene on chromosome 6p25 have been described in patients with Axenfeld-Rieger anomaly. A new ocular finding of glaucoma in pedigrees with the nailpatella syndrome has been described, and mutations in the LMX1B gene on chromosome 9q34 are now known to underlie nail-patella syndrome. Two loci for the pigment dispersion syndrome have been mapped. This paper provides an overview of recent literature, summarizes developments in glaucoma genetics, and addresses their potential relevance to the clinical management of glaucoma.
Publisher: Elsevier BV
Date: 07-2019
Publisher: Springer Science and Business Media LLC
Date: 31-05-2016
DOI: 10.1038/SREP26885
Abstract: Primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD) are leading causes of irreversible blindness. Several loci have been mapped using genome-wide association studies. Until very recently, there was no recognized overlap in the genetic contribution to AMD and POAG. At genome-wide significance level, only ABCA1 harbors associations to both diseases. Here, we investigated the genetic architecture of POAG and AMD using genome-wide array data. We estimated the heritability for POAG (h 2 g = 0.42 ± 0.09) and AMD (h 2 g = 0.71 ± 0.08). Removing known loci for POAG and AMD decreased the h 2 g estimates to 0.36 and 0.24, respectively. There was evidence for a positive genetic correlation between POAG and AMD (r g = 0.47 ± 0.25) which remained after removing known loci (r g = 0.64 ± 0.31). We also found that the genetic correlation between sexes for POAG was likely to be less than 1 (r g = 0.33 ± 0.24), suggesting that differences of prevalence among genders may be partly due to heritable factors.
Publisher: American Medical Association (AMA)
Date: 04-2015
Publisher: Springer Science and Business Media LLC
Date: 27-07-2020
DOI: 10.1038/S41598-020-69524-8
Abstract: SIX1/SIX6 polymorphism has been shown to be associated with glaucoma. Studies have also found that, in older adults, retinal nerve fibre layer (RNFL) thickness is significantly thinned with each copy of the risk allele in SIX1/SIX6 . However, it is not known whether these genetic variants exert their effects in younger in iduals. Comparing a healthy young adult with an older adult cohort (mean age 20 vs 63 years), both of Northern European descent, we found that there was no significant RNFL thinning in each copy of the risk alleles in SIX1/SIX6 in the eyes of younger in iduals. The older cohort showed an unexpectedly thicker RNFL in the nasal sector with each copy of the risk allele for both the SIX1 (rs10483727) and SIX6 (rs33912345) variants. In the temporal sector, thinner RNFL was found with each copy of the risk allele in rs33912345 with a decrease trend observed in rs10483727. Our results suggest that SIX1/SIX6 gene variants exert their influence later in adult life.
Publisher: Elsevier BV
Date: 09-2001
DOI: 10.1016/S0161-6420(01)00654-6
Abstract: To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the most common Myocilin mutation (Gln368STOP). Cross-sectional genetic study. Eight pedigrees carrying the Gln368STOP mutation were ascertained from 1730 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Gln368STOP mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. From the eight pedigrees, 29 Gln368STOP mutation-carrying in iduals with either ocular hypertension (OHT) or POAG were found, with a mean age at diagnosis of 52.4 +/- 12.9 years and a mean peak intraocular pressure (IOP) of 28.4 +/- 4.7 mmHg. A further 11 mutation carriers older than 40 years have been studied, who as yet show no signs of OHT or POAG. Within the 8 pedigrees, a further 31 in iduals with OHT or POAG were identified who did not carry the Gln368STOP mutation. For these in iduals the mean age at diagnosis was higher (62.3 +/- 13.7 years, P < 0.01), and the mean peak IOP was lower (25.4 +/- 6.4 mmHg, P = 0.01). For Gln368STOP carriers, age-related penetrance for OHT or POAG was 72% at age 40 years and 82% at age 65 years. A positive family history of POAG was present in all index cases. Five of the eight pedigrees had a positive family history on both maternal and paternal sides. Seven of the eight pedigrees had one or more in iduals with POAG who did not carry the mutation. Eight of the 29 Gln368STOP carriers with OHT or POAG had undergone trabeculectomy. The GLC1A Gln368STOP mutation is associated with POAG, which in the pedigrees studied is of a younger age of onset and higher peak IOP than non-mutation glaucoma cases. In addition, Gln368STOP mutation glaucoma cases were more likely to have undergone glaucoma drainage surgery. We have not observed simple autosomal dominant inheritance patterns for POAG in these pedigrees. Other factors, as yet uncharacterized, are involved in expression of the POAG phenotype in Gln368STOP pedigrees.
Publisher: American Society for Microbiology
Date: 07-01-2021
DOI: 10.1128/MRA.01213-20
Abstract: Nannizziopsis barbata is an emerging fungal pathogen capable of causing contagious dermatomycosis in reptiles. Here, we report a 31.54-Mb draft genome sequence of an isolate originating from an infected eastern water dragon in Brisbane, Australia.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2009
DOI: 10.1038/EYE.2009.37
Abstract: The aim of this study was to investigate the causes of mortality in in iduals with open-angle glaucoma (OAG). All-cause mortality data from the Registry of Births, Deaths and Marriages for the Australian state of Tasmania, for all people who were at least 40 years of age at the time of death, were classified using International Classification of Diseases-10 guidelines. This information was cross-referenced to identify participants in the Glaucoma Inheritance Study in Tasmania (GIST) who had died. Contingency tables were used for crude analysis and then models were constructed, adjusting for age at death as well as gender. Between 1996 and 2005, a total of 33 879 deaths were recorded. Data were unavailable for 4868 (14.4%) people. The mean age at death for the study s le was 78.4+/-11.5 (range 41-109) years. Of those cases known to have OAG by their participation in GIST (n=2409), full mortality data were available for 741 (92.0%). Following adjustment for the age at death and male gender, the odds ratio for death due to ischaemic heart disease in people with OAG compared to the general population not known to have OAG was significant (OR=1.30, 95% CI: 1.08-1.56 P=0.006). Crude analysis revealed that there were significantly fewer people with OAG who died due to metastatic cancer (P<0.001) however, this did not remain significant following adjustment for age and gender. The pathoaetiological relationship between OAG and ischaemic heart disease is unclear and requires further investigation. Increased awareness of the association between cardiovascular disease and OAG is warranted.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2018
DOI: 10.1038/S41598-018-20435-9
Abstract: Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis s le size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1 , LINC02052 and CRYGS , LMX1B , and LMO7 using single variant tests, one additional locus ( C9 ) using gene-based tests, and two genetic pathways - “response to fluid shear stress” and “abnormal retina morphology” - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.
Publisher: BMJ
Date: 25-10-2019
DOI: 10.1136/BJOPHTHALMOL-2019-314819
Abstract: To report the protocol of a trial designed to evaluate the efficacy, safety and mechanism of action of low-dose atropine (0.01%) eye-drops for reducing progression of myopia in UK children. Multicentre, double-masked, superiority, placebo-controlled, randomised trial. We will enrol children aged 6–12 years with myopia of −0.50 dioptres or worse in both eyes. We will recruit 289 participants with an allocation ratio of 2:1 (193 atropine 96 placebo) from five centres. Participants will instil one drop in each eye every day for 2 years and attend a research centre every 6 months. The vehicle and preservative will be the same in both study arms. The primary outcome is SER of both eyes measured by autorefractor under cycloplegia at 2 years (adjusted for baseline). Secondary outcomes include axial length, best corrected distance visual acuity, near visual acuity, reading speed, pupil diameter, accommodation, adverse event rates and allergic reactions, quality of life (EQ-5D-Y) and tolerability at 2 years. Mechanistic evaluations will include: peripheral axial length, peripheral retinal defocus, anterior chamber depth, iris colour, height and weight, activities questionnaire, ciliary body biometry and chorioretinal thickness. Endpoints from both eyes will be pooled in combined analysis using generalised estimating equations to allow for the correlation between eyes within participant. Three years after cessation of treatment, we will also evaluate refractive error and adverse events. The Childhood Atropine for Myopia Progression in the UK study will be the first randomised trial reporting outcomes of low-dose atropine eye-drops for children with myopia in a UK population. ISRCTN99883695 , NCT03690089 .
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 15-02-2018
DOI: 10.1167/TVST.7.1.18
Publisher: American Medical Association (AMA)
Date: 07-2015
DOI: 10.1001/JAMAOPHTHALMOL.2015.0980
Abstract: Juvenile open-angle glaucoma (JOAG) is a severe neurodegenerative eye disorder in which most of the genetic contribution remains unexplained. To assess the prevalence of pathogenic CYP1B1 sequence variants in an Australian cohort of patients with JOAG and severe visual field loss. For this cohort study, we recruited 160 patients with JOAG classified as advanced (n = 118) and nonadvanced (n = 42) through the Australian and New Zealand Registry of Advanced Glaucoma from January 1, 2007, through April 1, 2014. Eighty in iduals with no evidence of glaucoma served as a control group. We defined JOAG as diagnosis before age 40 years and advanced JOAG as visual field loss in 2 of the 4 central fixation squares on a reliable visual field test result. We performed direct sequencing of the entire coding region of CYP1B1. Data analysis was performed in October 2014. Identification and characterization of CYP1B1 sequence variants. We identified 7 different pathogenic variants among 8 of 118 patients with advanced JOAG (6.8%) but none among the patients with nonadvanced JOAG. Three patients were homozygous or compound heterozygous for CYP1B1 pathogenic variants, which provided a likely basis for their disease. Five patients were heterozygous. The allele frequency among the patients with advanced JOAG (11 in 236 [4.7%]) was higher than among our controls (1 in 160 [0.6%] P = .02 odds ratio, 7.8 [95% CI, 0.02-1.0]) or among the control population from the Exome Aggregation Consortium database (2946 of 122 960 [2.4%] P = .02 odds ratio, 2.0 [95% CI, 0.3-0.9]). In iduals with CYP1B1 pathogenic variants, whether heterozygous or homozygous, had worse mean (SD) deviation on visual fields (-24.5 [5.1] [95% CI, -31.8 to -17.2] vs -15.6 [10.0] [95% CI, -17.1 to -13.6] dB F1,126 = 5.90 P = .02 partial ηp2 = 0.05) and were younger at diagnosis (mean [SD] age, 23.1 [8.4] [95% CI, 17.2-29.1] vs 31.5 [8.0] [95% CI, 30.1-33.0] years F1,122 = 7.18 P = .008 ηp2 = 0.06) than patients without CYP1B1 pathogenic variants. Patients with advanced JOAG based on visual field loss had enrichment of CYP1B1 pathogenic variants and a more severe phenotype compared with unaffected controls and patients with nonadvanced JOAG.
Publisher: Springer Science and Business Media LLC
Date: 20-05-2005
DOI: 10.1007/S00439-005-1296-X
Abstract: Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the world. It is a clinically variable group of diseases with the majority of cases presenting as the late onset adult type. Several chromosomal loci have been implicated in disease aetiology, but causal mutations have only been identified in a small proportion of glaucoma. We have previously described a large six-generation Tasmanian family with POAG exhibiting genetic heterogeneity. In this family, approximately one third of affected in iduals presented with a glutamine-368-STOP (Q368STOP) mutation in the myocilin gene. We now use a Markov Chain Monte Carlo (MCMC) method to identify a second disease region in this family on the short arm of chromosome 3. This disease locus was initially mapped to the marker D3S1298 and a subsequent minimum disease region of 9 cM between markers D3S1298 and D3S1289 was identified through additional mapping. The region did not overlap with any previously described locus for POAG. Using a multiplicative relative risk model, we identified a positive association between this region and the Q368STOP mutation of myocilin on chromosome 1 in affected in iduals. These findings provide evidence of a new autosomal dominant glaucoma locus on the short arm of chromosome 3.
Publisher: Wiley
Date: 02-2004
DOI: 10.1046/J.1442-9071.2004.00750.X
Abstract: Primary infantile glaucoma presents rarely, but can be responsible for significant visual morbidity. There is little information on the clinical features and visual outcome of a pure population of primary infantile glaucoma, as opposed to a mixed population of primary and secondary glaucoma or combined group of those with trabeculodysgenesis and iridotrabeculodysgenesis. We conducted a retrospective review of children with primary infantile glaucoma seen in south-eastern Australia between 1980 and 2000, using The Royal Children's Hospital ophthalmic diagnostic coding database. Fifty-one patients with primary infantile glaucoma were identified (83 eyes). This equates to an estimated incidence of approximately 1 in 30,000 births. The mean +/- SD age at presentation was 135 +/- 84 days. 'Burnt-out' disease (megalocornea without raised intraocular pressure) was diagnosed in 10.8%. Goniotomy was the most commonly performed surgical procedure (69.4% of 72 eyes). Surgical success with one or two goniotomies was achieved in 74% of eyes. Visual outcomes at final review were generally good with 61.8% reading 6/12 or better. There were a disproportionately high number of children having a final recorded acuity of <6/60 in the group diagnosed in the first 3 months of life. Primary infantile glaucoma is a rare ocular condition in this population that presents at a mean age of 4.4 months. Surgical and visual outcomes are generally favourable.
Publisher: American Medical Association (AMA)
Date: 06-2021
Publisher: Informa UK Limited
Date: 03-2015
DOI: 10.1111/CXO.12209
Abstract: The aim was to determine whether latitudinal (Queensland versus Tasmania) variation in reported disease frequency in Australia may be biased by differences in population. A retrospective analysis was conducted from data of two large Australian twin studies (n = 1,835) having undertaken ophthalmic examination, namely, Twins Eye Study in Tasmania (TEST) and the Brisbane Adolescent Twins Study (BATS). Ordinal logistic regression was used to compute odds ratios and predicted probabilities for each category of eye colour by state. Tasmanian residence was associated with lower odds of darker iris colour (odds ratio 0.77, 95% CI [0.63-0.95]) signifying that participants living in Tasmania (TAS) are less likely to have darker-coloured irides than those residing in Queensland (QLD). For in iduals living in Tasmania the predicted probability (TAS versus QLD) of having light blue eyes was greater (16.7 versus 13.3 per cent), approximately the same for green eyes and less for brown/dark brown-coloured eyes (6.2 versus 7.9 per cent). We found a general trend of in iduals living in the southern states (TAS/VIC) of Australia having lighter-coloured irides compared to those living in the north (QLD). This finding has potential implications for all epidemiological research conducted to explore differences in UV-associated disease frequency in Australia, as population heterogeneity may confound the estimates obtained.
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/13816810490498323
Abstract: To evaluate the clinical overlap of families with Duane syndrome and infantile esotropia to determine whether the identification of genes for Duane syndrome may explain some cases of infantile esotropia. Three separate groups of patients were evaluated. 1) Families with features of infantile esotropia were identified through the Strabismus Inheritance Study Tasmania (SIST). Clinical details of participants and their families were reviewed for any cases of Duane syndrome. 2) Cases of Duane syndrome were identified through the clinical diagnostic database at the Royal Children's Hospital, Melbourne, and private ophthalmology clinics in Melbourne and Tasmania. Previous medical notes were reviewed and family history of strabismus noted. All affected in iduals were invited for re-examination in cases where a positive family history of strabismus was reported siblings, parents, and other family members, where appropriate, were invited to be examined for signs of Duane syndrome or infantile esotropia. 3) Cases of mosaic trisomy 8, which has been associated with Duane syndrome and infantile esotropia, were reviewed for signs of strabismus. A total of 133 families from the SIST were reviewed, but no 'pure' families of Duane syndrome were identified. Two families with infantile esotropia had several members affected with Duane syndrome. Of the 40 index cases with Duane syndrome whose families agreed to be involved in the study, 21 had a family history of ocular motility disorders, but only two of these families had multiple cases of Duane syndrome. From 24 cases with mosaic trisomy 8, one in idual case had Duane syndrome and another had mild congenital cataracts and infantile esotropia. There is clinical overlap in families with Duane syndrome and infantile esotropia. We confirmed the previous association of mosaic trisomy 8 with both Duane syndrome and infantile esotropia. These data suggest that the two conditions may be allelic and may be due to a gene on chromosome 8.
Publisher: Elsevier BV
Date: 2009
Publisher: BMJ
Date: 27-01-2011
Publisher: Wiley
Date: 16-03-2022
DOI: 10.1111/CEO.14071
Abstract: There is a growing body of literature on the effects of sleep disorders, in particular obstructive sleep apnoea (OSA), on ocular health, with consistent evidence of an increased risk of floppy eyelid syndrome, non‐arteritic anterior ischaemic optic neuropathy, diabetic macular oedema, and other retinal vasculature changes in in iduals with OSA. However, reports on OSA's associations with glaucoma, papilloedema, diabetic retinopathy, central serous chorioretinopathy, and keratoconus have been conflicting, while links between OSA and age‐related macular degeneration have only been described fairly recently. Despite numerous suggestions that OSA treatment may reduce risk of these eye diseases, well‐designed studies to support these claims are lacking. In particular, the ocular hypertensive effects of continuous positive airway pressure (CPAP) therapy for OSA requires further investigation into its potential impact on glaucoma risk and management. Reports of ocular surface complications secondary to leaking CPAP masks highlights the importance of ensuring good mask fit. Poor sleep habits have also been linked with increased myopia risk however, the evidence on this association remains weak.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 26-10-2021
Publisher: IEEE
Date: 11-2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-10-2012
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-06-2017
Abstract: To evaluate the impact of image magnification correction on superficial retinal vessel density (SRVD) and foveal avascular zone area (FAZA) measurements using optical coherence tomography angiography (OCTA). Participants with healthy retinas were recruited for ocular biometry, refraction, and RTVue XR Avanti OCTA imaging with the 3 × 3-mm protocol. The foveal and parafoveal SRVD and FAZA were quantified with custom software before and after correction for magnification error using the Littman and the modified Bennett formulae. Relative changes between corrected and uncorrected SRVD and FAZA were calculated. Forty subjects were enrolled and the median (range) age of the participants was 30 (18-74) years. The mean (range) spherical equivalent refractive error was -1.65 (-8.00 to +4.88) diopters and mean (range) axial length was 24.42 mm (21.27-28.85). Images from 13 eyes were excluded due to poor image quality leaving 67 for analysis. Relative changes in foveal and parafoveal SRVD and FAZA after correction ranged from -20% to +10%, -3% to +2%, and -20% to +51%, respectively. Image size correction in measurements of foveal SRVD and FAZA was greater than 5% in 51% and 74% of eyes, respectively. In contrast, 100% of eyes had less than 5% correction in measurements of parafoveal SRVD. Ocular biometry should be performed with OCTA to correct image magnification error induced by axial length variation. We advise caution when interpreting interocular and interin idual comparisons of SRVD and FAZA derived from OCTA without image size correction.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2002
DOI: 10.1097/00041327-200212000-00002
Abstract: To report the clinical and mitochondrial genetic analyses of two families, each of which carries both the 11778 and 14484 Leber hereditary optic neuropathy (LHON) mutations in mitochondrial DNA. In addition to detailed clinical histories, the complete sequence of the mitochondrial DNA (mtDNA) from each family was determined. A small Australian LHON family (Vic20) and a family from the United States carry the 11778 and 14484 LHON mutations. In addition to the optic neuropathy, one branch of the Baltimore LHON pedigree had a high incidence of a fatal infantile encephalopathy. In both families, the 14484 LHON mutation was homoplasmic, whereas the 11778 LHON mutation was heteroplasmic. There are no additional mtDNA sequence changes that explain the encephalopathy in the Baltimore LHON family, and a nuclear gene involvement is an alternative explanation that is supported by the available data. The ophthalmological characteristics and penetrance in the 11778 and 14484 "two-mutation" LHON families are not markedly more severe than those of classic LHON families who carry a single mtDNA mutation.
Publisher: American Medical Association (AMA)
Date: 12-2018
Publisher: Springer Science and Business Media LLC
Date: 26-11-2011
DOI: 10.1038/EYE.2010.180
Publisher: Springer Science and Business Media LLC
Date: 08-2022
DOI: 10.1186/S40662-022-00299-X
Abstract: To generate and validate a method to estimate axial length estimated (AL est ) from spherical equivalent (SE) and corneal curvature [keratometry (K)], and to determine if this AL est can replace actual axial length (AL act ) for correcting transverse magnification error in optical coherence tomography angiography (OCTA) images using the Littmann-Bennett formula. Data from 1301 participants of the Raine Study Gen2-20 year follow-up were ided into two datasets to generate (n = 650) and validate (n = 651) a relationship between AL, SE, and K. The developed formula was then applied to a separate dataset of 46 participants with AL, SE, and K measurements and OCTA images to estimate and compare the performance of AL est against AL act in correcting transverse magnification error in OCTA images when measuring the foveal avascular zone area (FAZA). The formula for AL est yielded the equation: AL est = 2.102K − 0.4125SE + 7.268, R 2 = 0.794. There was good agreement between AL est and AL act for both study cohorts. The mean difference [standard deviation (SD)] between FAZA corrected with AL est and AL act was 0.002 (0.015) mm 2 with the 95% limits of agreement (LoA) of − 0.027 to 0.031 mm 2 . In comparison, mean difference (SD) between FAZA uncorrected and corrected with AL act was − 0.005 (0.030) mm 2 , with 95% LoA of − 0.064 to 0.054 mm 2 . AL act is more accurate than AL est and hence should be used preferentially in magnification error correction in the clinical setting. FAZA corrected with AL est is comparable to FAZA corrected with AL act , while FAZA measurements using images corrected with AL est have a greater accuracy than measurements on uncorrected images. Hence, in the absence of AL act , clinicians should use AL est to correct for magnification error as this provides for more accurate measurements of fundus parameters than uncorrected images.
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1086/301719
Publisher: BMJ
Date: 04-2003
DOI: 10.1136/BJO.87.4.500
Publisher: Wiley
Date: 22-07-0012
DOI: 10.1111/WVN.12014
Publisher: Springer Science and Business Media LLC
Date: 10-02-2013
DOI: 10.1038/NG.2554
Publisher: BMJ
Date: 07-08-2012
Publisher: American Medical Association (AMA)
Date: 09-2021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 21-03-2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 30-10-2017
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2006
DOI: 10.1167/IOVS.05-0631
Abstract: POAG is a complex disease therefore, families in which a glaucoma gene has been mapped may carry additional POAG genes. The goal of this study was to determine whether mutations in the myocilin (MYOC) gene on chromosome 1 are present in two POAG families, which have previously been mapped to the GLC1C locus on chromosome 3. The three exons of MYOC were screened by denaturing (d)HPLC. S les with heteroduplex peaks were sequenced. Clinical findings were compared with genotype status in all available family members over the age of 20 years. A T377M coding sequence change in MYOC was identified in family members of the Greek GLC1C family but not in the Oregon GLC1C family. In iduals carrying both the MYOC T377M variant and the GLC1C haplotype were more severely affected at an earlier age than in iduals with just one of the POAG genes, suggesting that these two genes interact or that both contribute to the POAG phenotype in a cumulative way.
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.AJO.2006.12.038
Abstract: We identified families with autosomal dominant optic atrophy (ADOA), determined the number and type of OPA1 mutations, and investigated the phenotypic variation and penetrance in ADOA Australian pedigrees. Cross-sectional genetics study. Probands were identified on the basis of characteristic clinical features of ADOA. We screened the OPA1 gene using single-strand conformational polymorphism, heteroduplex analysis (SSCP/HA), or by direct sequencing. Penetrance for pedigrees in which a mutation of OPA1 had been identified was calculated initially using all recruited in iduals, and subanalysis was performed using only those families for which there was total recruitment of siblings. A total of 406 patients from 17 pedigrees were recruited, and OPA1 mutations were identified in 11/17 (65%) of these. The mean age at clinical examination was 38.2 +/- 19.9 years (median age, 35 years range, four to 83 years). The median best-corrected visual acuity in OPA1-mutation carriers was 20/70 (range, 20/16 to hand movements [HM]). The penetrance in Australian ADOA pedigrees in the families with complete sibling recruitment was 82.5%. On the other hand, overall penetrance for all in iduals harboring an OPA1 mutation was 88%. OPA1 mutations were identified in 11/17 (65%) of the ADOA pedigrees in this study. The penetrance in our cohort was lower than originally described (82.5% vs 98%) but higher than some recent studies since the availability of genotyping. It is anticipated that this figure would be even lower as more asymptomatic in iduals are identified. There are likely to be other genetic and environmental modifiers influencing disease penetrance.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Springer Science and Business Media LLC
Date: 16-04-2018
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.AJO.2016.03.008
Abstract: To characterize and quantify Bruch membrane opening (BMO)-based optic nerve head (ONH) parameters in a large, young and healthy, predominantly white population. Cross-sectional study and reliability analysis. The ONH of 1344 predominantly white subjects were imaged with spectral-domain optical coherence tomography (SD-OCT). A customized script, coded in Matlab, was used to manually segment and measure multiple BMO-based parameters of the ONH. Measurements were compared to those obtained with confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph HRT). Regression analysis was performed to assess the relationship between BMO parameters and other ocular and demographic variables. Mean BMO disc and neuroretinal rim (NRR) areas ranged from 0.94 to 4.06 mm(2) (mean 1.77 ± 0.38 mm(2)) and 0.94 to 3.99 mm(2) (mean 1.56 ± 0.31 mm(2)), respectively. When compared to the equivalent HRT measurements, SD-OCT-derived measures differed significantly for all comparable ONH parameters (P < .001). The limits of agreement computed from Bland-Altman plots comparing SD-OCT and HRT measurements showed suboptimal agreement between the techniques. Linear regression analysis demonstrated an effect of ethnicity, axial length, and refractive error on BMO-based parameters. We have quantified BMO-based parameters in a large cohort of young adults using SD-OCT. These data will be informative in constructing normative profiles for clinical and research purposes in glaucoma diagnosis and management.
Publisher: Asia Pacific Academy of Ophthalmology
Date: 2016
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.PHARMTHERA.2016.06.004
Abstract: Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function.
Publisher: Informa UK Limited
Date: 12-2015
DOI: 10.2147/OPTH.S92018
Publisher: Wiley
Date: 19-03-2014
DOI: 10.1111/AOS.12388
Abstract: To investigate the age range for which cycloplegia provides additional information compared with non-cycloplegic refraction in teenagers and young adults. Data for 1295 subjects (704 female 591 male) from the Twins Eye Study in Tasmania (TEST) and the Brisbane Adolescent Twin Study (mean age: 19.65 ± 3.56, range: 13-26 years) were included. For all participants, cycloplegia was induced by instillation of either one drop of 1% cyclopentolate (13-14 years) or one drop of 1% tropicamide (15-26 years). Pre- and postcycloplegic refractive errors for both eyes were measured using a Humphrey-598 automated refractor and spherical equivalents of refractive error were calculated. Generalized Estimating Equations (GEE) were used to model the spherical equivalent refraction (SER) for each eye against age (by year) and axial length (in the given eye). The mean group difference between pre- and postcycloplegic SER (post minus pre) was 0.17 ± 0.52 D and 0.12 ± 0.51 D for the right and left eyes, respectively, indicating that postcycloplegic refraction was generally more hyperopic/less myopic. The mean difference between pre- and postcycloplegic SER decreased from 0.36 ± 0.41 D in the 13-year-olds to 0.06 ± 0.50 D in people aged 25 years. After adjusting for family-relatedness, the difference between pre- and postcycloplegia SER was significant in all age groups up until the age of 20 years. Non-cycloplegic autorefraction can result in group mean SER differences of greater myopia than cycloplegic autorefraction and occurs in teenagers (13-19 years of age), but not in adults 20-26 years. These data suggest that cycloplegia is not required in population estimates of refractive error for young adults once they reach approximately 20 years of age.
Publisher: Springer Science and Business Media LLC
Date: 12-02-2010
DOI: 10.1038/EYE.2010.11
Abstract: The purpose of this study was to compare the reliability of the 'gold standard' Goldmann applanation tonometer (GAT), with that of the ocular response analyser (ORA), and the dynamic contour tonometer (DCT). A total of 694 subjects were recruited to participate from the TwinsUK (UK Adult Twin Registry) at St Thomas' Hospital, London. Intraocular pressure (IOP) was measured using GAT, ORA, and the DCT. The agreement between the three methods was assessed using the Bland-Altman method. Repeatability coefficients and coefficient of variation between first and second readings of the same eye were used to assess reliability. Mean age was 57.5 years (SD, 13.1 range, 16.1-88.5). The mean IOPs, calculated using the mean of two readings from the right eye were as follows: Goldmann (GAT), 14.1+/-2.8 mm Hg IOPg (ORA), 15.9+/-3.2 mm Hg IOPcc (ORA), 16.6+/-3.2 mm Hg and DCT, 16.9+/-2.7 mm Hg. The 95% limits of agreement were for ORA (IOPcc): GAT, -2.07 to 7.18 mm Hg for DCT: GAT, -0.49 to 6.21 mm Hg and for DCT: ORA (IOPcc), -3.01 to 4.85 mm Hg. Coefficients of variation for the three tonometers were GAT, 8.3% ORA, 8.2% DCT, 6.3%. The repeatability coefficients were 3.4 mm Hg for GAT, 3.57 mm Hg for ORA and 3.09 mm Hg for DCT. GAT and ORA (IOPg) readings showed a positive correlation with central corneal thickness (P<0.005). This study found similar reliability in all three tonometers. Bland-Altman plots showed the three instruments to have 95% limits of agreement outside the generally accepted limits, which means they are not interchangeable. GAT measurements were found to be significantly lower than the two newer instruments.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 24-02-2021
DOI: 10.1038/S41467-020-20851-4
Abstract: Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638 , CLIC5, SLC2A12, YAP1, MXRA5 , and SMAD6 . Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Publisher: Elsevier BV
Date: 06-1992
DOI: 10.1016/0140-6736(92)91257-9
Abstract: 1. Innervated adult skeletal muscle is sensitive to acetylcholine at the end-plate region only. After denervation the entire muscle membrane becomes chemosensitive. The period of greatest increase in sensitivity in rat soleus muscles following section of the sciatic nerve in the thigh is between 48 and 72 hr post-operatively.2. Direct electrical stimulation was found to prevent the onset of the development of denervation hypersensitivity during the first 2-3 days after nerve section. Thereafter, electrical stimulation only reduced the sensitivity of denervated muscles to acetylcholine (ACh).3. The period of greatest increase in sensitivity follows loss of transmission and degeneration of the nerve terminals. Once this degeneration is under way, electrical stimulation is no longer as effective in preventing the development of denervation hypersensitivity.4. Hypersensitivity is also seen in muscles on which a small piece of thread or degenerating nerve has been placed. Hypersensitivity following these procedures declines within a few days, unlike denervation hypersensitivity which persists until innervation is restored.5. The present results suggest that activity alone cannot prevent the development of hypersensitivity in the presence of degenerating nerve fibres, or muscle damage. Activity does however counteract increased sensitivity. It is suggested that two factors interact to produce denervation hypersensitivity the presence of degenerating nerve tissue and concomitant cellular changes bring about changes in the muscle fibre membrane causing it to become hypersensitive and the loss of muscle activity, resulting in the persistence of hypersensitivity until innervation is restored.
Publisher: Wiley
Date: 10-2004
DOI: 10.1111/J.1442-9071.2004.00886.X
Abstract: The optineurin (OPTN) gene has been reported to possess both causal as well as risk-associated alleles for open-angle glaucoma. However, these findings have so far only been reported in family and clinic based studies. The aim of this study was to investigate the spectrum of mutations and gene variants in OPTN that might be present in people with glaucoma from a population-based study, the Blue Mountains Eye Study (BMES). A total of 108 subjects of Caucasian origin were identified at baseline in the BMES as having open-angle glaucoma. Blood s les were available from 27 of these, of whom 18 had high-tension glaucoma and the remaining nine had normal-tension glaucoma. Ninety-four control subjects were chosen at random from the BMES, who satisfied the criteria of not having glaucoma at baseline and were over age 70 years. The 13 coding exons (exons 4-16 inclusive) and their intron-exon boundaries of OPTN were screened by the use of single-strand conformation polymorphism. S les exhibiting mobility shifts were di-deoxy nucleotide sequenced. The M98K polymorphism was additionally screened using the restriction enzyme Stu1 in all cases and controls in this study. The M98K risk-associated alteration was identified in 2/18 (11%) subjects with high-tension glaucoma, 0/9 subjects (0%) with normal-tension glaucoma and 3/94 (3.2%) controls. However, association of this variant with disease was not significant (P = 0.2 for each phenotype) for either high-tension glaucoma or normal-tension glaucoma. A novel variant (P556P in exon 16) was found in one subject with open-angle glaucoma and a previously described variant (exon 7) was found in a further subject with open-angle glaucoma and in one control. No other OPTN variants were identified in this study cohort. Cross-sectional analysis from baseline observations of the BMES suggested that the M98K risk-associated allele appeared at a higher prevalence in high-tension glaucoma compared with controls, although this finding was not statistically significant.
Publisher: Elsevier BV
Date: 03-2023
DOI: 10.1016/J.OPHTHA.2022.09.015
Abstract: Observational studies suggest that higher serum 25-hydroxyvitamin D concentration may be associated with lower risk of cataract. However, no randomized controlled trials (RCTs) have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery. We conducted an ancillary study of D-Health Trial, a randomized, double-masked, placebo-controlled trial of monthly vitamin D for the prevention of all-cause mortality conducted from 2014 to 2020 within the Australian general population. We invited 421,207 men and women aged 60-84 years to participate including an additional 1,896 volunteers, 40,824 expressed interest. Those with hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia or sarcoidosis, or who were taking >500 international units (IU) supplemental vitamin D per day were excluded. 21,315 people were randomized. 1,390 participants did not fulfil the eligibility criteria for this analysis (linked data available, no cataract within first 6 months) leaving 19,925 included. The median follow-up was 5 years. . 60,000 IU of vitamin D The primary outcome for this analysis was the first surgical treatment for cataract, ascertained through linkage to universal health insurance records and hospital data. Among 19,925 participants eligible for the analysis of incident cataract (mean age 69.3 years, 46% women) 3,668 (18.4%) underwent cataract surgery during follow-up (n=1,841 (18.5%) of the vitamin D group and n=1,827 (18.3%) of the placebo group). The incidence of cataract surgery was similar between the two groups (incidence rate 41.6 and 41.1 per 1,000 person-years in the vitamin D and placebo groups, respectively hazard ratio 1.02 95% CI 0.95 to 1.09). In pre-specified subgroup analyses, the effect of vitamin D supplementation on the incidence of cataract surgery was not modified by age, sex, body mass index, predicted serum 25-hydroxyvitamin D concentration, or ambient ultraviolet radiation. Routinely supplementing older adults who live in an area with a low prevalence of vitamin D deficiency with high-dose vitamin D is unlikely to reduce the need for cataract surgery.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2010
Abstract: Acquired optic neuropathies are a common cause of blindness in adults, and are associated with characteristic morphological changes at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging where appropriate, is essential to optimize management of the optic neuropathy and to counsel the patient appropriately on its natural history. History taking, optic disc findings, visual field assessment and imaging of the nerve head and surrounding retinal nerve fiber layer are all paramount to achieving the correct diagnosis. This Review highlights the optic nerve head features that are common to the acquired optic neuropathies, and describes the features that can be used to differentiate these various conditions.
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.AJO.2005.04.043
Abstract: To ascertain whether there is a common disease haplotype for the Q368STOP mutation of the myocilin gene in Australian and Canadian families with primary open-angle glaucoma (POAG). Family pedigree study. A disease haplotype for the Q368STOP mutation of the myocilin gene has previously been identified in 15 Tasmanian families with POAG. The four microsatellite markers that constitute this 0.14-megabase (Mb) disease haplotype were genotyped in in iduals from a large French Canadian family with POAG (family CT) and two unrelated French Canadian in iduals with ocular hypertension. The Tasmanian Q368STOP disease haplotype was identified in affected in iduals from family CT, and the same alleles were shared at the four microsatellite markers in the two unrelated French Canadian in iduals. The same disease haplotype for the Q368STOP mutation of the myocilin gene was found in both the Tasmanian and French Canadian populations, supporting the view that this mutation arose from a common Caucasian founder.
Publisher: Springer Science and Business Media LLC
Date: 07-05-2020
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-12-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
DOI: 10.1161/HYPERTENSIONAHA.108.125914
Abstract: Recent studies reported an association between smaller birth size and narrower retinal vascular caliber, but it remains unclear whether this association is attributed to confounding by shared environment or genetic factors. At a mean age of 9.3 years, 266 twins (49 monozygotic and 84 dizygotic pairs) in the Twins Eye Study in Tasmania underwent an ophthalmic examination including retinal photography. Retinal vascular caliber was measured using a validated protocol. The majority of these twins were also in the Tasmanian Infant Health Study, which prospectively collected data on birth parameters and antenatal maternal factors. We conducted the main analysis using linear mixed models, accounting for birth set clustering. Both the within-pair (−9.73 95% CI: −14.68 to −4.77 μm per 5-cm decrease in birth length) and between-pair associations (−7.15 95% CI: −11.54 to −3.01) with retinal arteriolar caliber were significant and of similar magnitude (difference in effect, P =0.61), after adjusting for age, sex, maternal smoking, mean arterial blood pressure, and other confounders. These associations remained within dizygotic and monozygotic pairs. Analyses of head circumference and retinal arteriolar caliber were similar to those of birth length (within-pair regression coefficient: −2.41 95% CI: −5.09 to 0.28 between-pair regression coefficient: −2.60 95% CI: −5.00 to −0.19). For birth weight, only a between-pair association was evident (−7.28 95% CI: −13.07 to −1.48). This study demonstrates a consistent association between smaller birth size and narrower retinal arterioles in twins. The independent effect of shorter birth length on retinal arteriolar caliber supports a role for twin-specific supply line factors affecting fetal growth on vascular structure.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1038/S42003-019-0634-9
Abstract: A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG) intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is h ered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.
Publisher: Public Library of Science (PLoS)
Date: 27-08-2013
Publisher: BMJ
Date: 03-2021
DOI: 10.1136/BMJOPHTH-2021-000728
Abstract: To evaluate the functional benefits (best corrected visual acuity (BCVA), central subfield thickness, injection loads, central venous pressure (CVP)) of a laser-induced chorioretinal anastomosis (L-CRA) in patients with central retinal vein occlusion (CRVO) treated with ranibizumab compared with ranibizumab monotherapy. This is a post-hoc analysis of the 2-year randomised ranibizumab plus L-CRA for CRVO trial. Twenty-four patients (82.5%) developed a functioning or successful L-CRA outcome effects were monitored in the monthly as-needed ranibizumab phase from months 7 to 24 and compared with the ranibizumab monotherapy group (n=29). From months 7 to 24, the mean (95% CI) injection load for the functioning L-CRA group was 2.18 (1.57 to 2.78) compared with 7.07 (6.08 to 8.06) for the control group (p .0001). The mean BCVA was averaged across all timepoints between the control and functioning L-CRA groups (average difference=11.46 (3.16 to 19.75) letters, p=0.01). At 2 years, there was an 82.5% reduction in the odds of high CVP (greater or equal to central retinal artery diastolic pressure) for those with a successful L-CRA compared with controls (p .0001). For patients with CRVO, adding L-CRA as a causal-based treatment to conventional therapy reduced CVP and injection loads and offered improved BCVA. Trial registration number ACTRN12612000004864.
Publisher: AMPCo
Date: 02-2015
DOI: 10.5694/MJA14.01104
Publisher: Informa UK Limited
Date: 03-2015
DOI: 10.1111/CXO.12217
Abstract: The aim was to compare the power of spectacles donated to a recycled spectacle program to the custom-made spectacle refractive prescriptions dispensed in a developing country. Two hundred consecutive prescriptions were audited in an optical dispensary in Timor-Leste, a developing nation. These refractions were compared against measurements of 2,075 wearable donated spectacles. We determined how many of the 200 prescriptions could be matched to a donated spectacle measurement, how many donated spectacles could be tried for each prescription and how long it would take to find the matched spectacles. There were 1,854 donated spectacles identified as being suitable for comparison with the 200 refractive prescriptions. Twenty-nine out of 200 prescriptions (14.5 per cent) were matched to at least one pair of donated spectacles. Recycling all spectacles is not cost-effective in a developing country that has the ability to make custom-made spectacles and dispense ready-made spectacles.
Publisher: American Medical Association (AMA)
Date: 12-2003
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2001
DOI: 10.1097/00043426-200112000-00004
Abstract: The purpose of this study was to examine the clinical and radiologic response to carboplatin by children with progressive optic/thalamic gliomas. Between July 1997 and July 1999, 12 consecutive children were treated with monthly carboplatin for progressive optic/thalamic gliomas. Five children have completed 12 cycles of carboplatin and five children are currently receiving treatment. Two children had progressive disease noted both clinically and radiologically. Nine children have stable radiologic disease and one child has had a partial radiologic response to chemotherapy. Eight children have had regular visual assessments. Four children (three with stable radiology and one with a partial radiologic response) have had improvement in their vision. Three children with radiologically stable disease have had no change in vision. One child has had deterioration in vision despite radiologically stable disease. The results suggest that the clinical response of optic/thalamic gliomas to carboplatin, as measured by visual acuity and visual fields, may be better than predicted by radiologic assessment. These data suggest that a prospective clinical study is warranted of the role of carboplatin in children with progressive optic/thalamic gliomas and visual impairment.
Publisher: MDPI AG
Date: 10-05-2023
Abstract: Mutations in the RCBTB1 gene cause inherited retinal disease however, the pathogenic mechanisms associated with RCBTB1 deficiency remain poorly understood. Here, we investigated the effect of RCBTB1 deficiency on mitochondria and oxidative stress responses in induced pluripotent stem cell (iPSC)-derived retinal pigment epithelial (RPE) cells from control subjects and a patient with RCBTB1-associated retinopathy. Oxidative stress was induced with tert-butyl hydroperoxide (tBHP). RPE cells were characterized by immunostaining, transmission electron microscopy (TEM), CellROX assay, MitoTracker assay, quantitative PCR and immunoprecipitation assay. Patient-derived RPE cells displayed abnormal mitochondrial ultrastructure and reduced MitoTracker fluorescence compared with controls. Patient RPE cells displayed increased levels of reactive oxygen species (ROS) and were more sensitive to tBHP-induced ROS generation than control RPE. Control RPE upregulated RCBTB1 and NFE2L2 expression in response to tBHP treatment however, this response was highly attenuated in patient RPE. RCBTB1 was co-immunoprecipitated from control RPE protein lysates by antibodies for either UBE2E3 or CUL3. Together, these results demonstrate that RCBTB1 deficiency in patient-derived RPE cells is associated with mitochondrial damage, increased oxidative stress and an attenuated oxidative stress response.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/13816810701503715
Abstract: To report the presence of dense and abnormal iris processes in the unaffected parents and sibling of a non consanguineous family where 3 children out of 4 suffer from primary infantile glaucoma (PIG). A descriptive case report. All family members were clinically characterized. Candidate gene screening and chromosome analysis were also performed. The 3 children with PIG displayed a spectrum of anterior chamber angle anomalies with the absence of posterior embryotoxon and iridotrabeculodysgenesis abnormalities. Unaffected family members had dense and abnormal iris processes but no features of glaucoma. Candidate gene screening and chromosome analysis were normal. Iris processes indicate angle maldevelopment and may signify carrier status of an autosomal recessive glaucoma gene. Identification of iris processes in relatives of PIG children is a useful clinical sign that may be of benefit for genetic counseling and risk stratification purposes.
Publisher: Public Library of Science (PLoS)
Date: 06-05-2010
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-02-2011
DOI: 10.1167/IOVS.10-5927
Publisher: Wiley
Date: 11-09-2023
DOI: 10.1111/AOS.15761
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-10-2022
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.AJO.2006.02.041
Abstract: To investigate in Australian patients with glaucoma and normal controls the prevalence and associated phenotype of the WDR36 D658G mutation, which has previously been suggested to be a disease-causing mutation in pedigrees with primary open-angle glaucoma (POAG). Case-control study. Two hundred forty-nine in iduals with POAG and 217 age-matched control subjects were recruited through the Glaucoma Inheritance Study in Tasmania, Australia. Genomic DNA was lified by polymerase chain reaction by intronic primers. The presence of the D658G variant was detected by BglI restriction enzyme digestion. The D658G variant was identified in four POAG cases (1.6%) and four control subjects (1.8%) (chi(2) = 0.04, P = .84). No control subject with the variant had a family history of glaucoma. The WDR36 D658G is a neutral variant in the Australian population. Further populations should be carefully assessed for this variant before concluding that WDR36 is a glaucoma gene.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-02-2016
DOI: 10.1167/TVST.5.1.3
Publisher: Oxford University Press (OUP)
Date: 12-04-2018
DOI: 10.1093/HMG/DDY121
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/13816810590918398
Abstract: To present a case of congenital glaucoma with an unbalanced translocation trisomy 8q22-qter/monosomy 9p23-pter, resulting in trisomy of the GLC1D locus. To perform a literature review of chromosomal abnormalities associated with glaucoma. A case report of a family with balanced translocation without glaucoma and unbalanced translocation with congenital glaucoma. PubMed and OMIM databases were searched for reports of chromosomal abnormalities and glaucoma. Other case reports of congenital glaucoma with chromosomal abnormalities in this region were identified. A review of cytogenetics in southeastern Australia found nine cases involving the loss of 9p23 and 10 cases involving mosaicism for trisomy 8, but none had congenital glaucoma. A review of the literature identified reports of glaucoma and chromosomal abnormalities in regions with glaucoma loci mapped by conventional linkage analysis. These include the loci GLC1B, GLC1C, GLC1D, GLC1F, GPDS1, and RIEG2. The study of patients with glaucoma and chromosomal abnormalities may help to identify new glaucoma genes. Ophthalmologists can assist with this by requesting cytogenetic studies on congenital and developmental glaucoma cases and interacting with ophthalmic genetics researchers.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-1995
DOI: 10.1097/00055735-199512000-00008
Abstract: Recent advances in genetics tend to center on the discoveries of molecular biology. A disease is first linked to a region on a chromosome, a gene is later cloned, or a candidate gene identified, point mutations described, phenotype-genotype correlations made, and rationales for treatment proposed. Several neuro-ophthalmological diseases have recently been studied in this way including Leber's hereditary optic neuropathy and other mitochondrial diseases, autosomal dominant (Kjer) optic atrophy, Wolfram syndrome, or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), Usher syndrome, neurofibromatosis types I and II, and two disorders of the paired box genes: aniridia and Waardenburg's syndrome. Apart from molecular biology there are still some new disease entities being described and new inheritance patterns identified for some syndromes, such as periodic alternating nystagmus.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-09-2018
Publisher: Wiley
Date: 30-07-2009
Publisher: Public Library of Science (PLoS)
Date: 07-07-2009
Publisher: Wiley
Date: 28-01-2015
DOI: 10.1002/GEPI.21886
Publisher: Springer Science and Business Media LLC
Date: 06-01-2013
DOI: 10.1038/NG.2506
Publisher: Hindawi Limited
Date: 19-10-2022
DOI: 10.1002/HUMU.24482
Abstract: The standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene-specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC and determined 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewing functional assays. The rules were piloted on 81 variants and led to a change in classification in 40% of those that were classified in ClinVar, with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1016/S0896-1549(03)00066-X
Abstract: As new genes and common mutations are identified, DNA testing can be offered. Like clinical testing used in glaucoma, such as IOP, tonography, disc measurements, nerve fiber layer analysis, and the various methods of visual field analysis, well-designed studies are needed to be able to interpret clearly the meaning of abnormal results. To use DNA testing to identify in iduals at high risk for glaucoma, it is necessary to have solid evidence with sensitivity and specificity parameters, genotype-phenotype correlations, and information on prevalence and penetrance. These data will have to be replicated in several studies using large, population-matched control groups. Mass screening of glaucoma patients for Myocilin mutations may be worthwhile if 3% to 5% of glaucoma patients will be positive. For comparison, screening all cases of colon cancer for gene mutations involved in hereditary nonpolyposis colorectal cancer is considered feasible and desirable with a yield of only 3%. Recent research has shown the value of early treatment of glaucoma. The cost effectiveness of genetics screening will need to be weighed against the cost of conventional screening and the benefits of early treatment considered. Within glaucoma pedigrees with known mutations, DNA mutation-positive in iduals will need more frequent clinical screening, whereas DNA mutation-negative in iduals will need less frequent follow-up. It is likely that, for every positive-mutation glaucoma case identified, there will be on average two siblings and two children to test. In addition to the laboratory costs, the costs of counseling, and, in particular, the availability of suitably trained in iduals who can correctly interpret these test results, must be considered. The risk and benefits of these measures must be calculated and then balanced with the long-term visual outcome of such a strategy. How could genetic testing alter management in glaucoma? If a family member in a Myocilin pedigree with a severe mutation is negative for the mutation, that in idual's risk changes from 50% to that of the general population (ie, -2%), and the frequency of clinical screening can be reduced. There are ethical issues involved in testing, particularly in children, but testing would seem justified in congenital, developmental, and juvenile glaucoma. Issues related to insurance may affect the decision making of some patients. A further consideration, which may regrettably become important in the future, is that of intellectual property and patent issues pertaining to glaucoma gene discovery. In addition to clinical evidence of the value of predictive DNA testing, it is incumbent on those working in the field to evaluate the acceptability of testing to patients and their family members. The authors' experience to date is that predictive DNA testing in glaucoma is well supported in suitable families. As with predictive DNA screening in other ophthalmic conditions, issues relating to insurance, ethics, and confidentiality need to be taken into consideration. Although many of the more recently described genetic associations of POAG require more thorough evaluation, Myocilin gene testing can and should be offered for young-onset severe glaucoma cases with a positive family history.
Publisher: BMJ
Date: 07-2002
DOI: 10.1136/BJO.86.7.782
Abstract: Paediatric cataract is a major cause of childhood blindness. Several genes associated with congenital and paediatric cataracts have been identified. The aim was to determine the incidence of cataract in a population, the proportion of hereditary cataracts, the mode of inheritance, and the clinical presentation. The Royal Children's Hospital and the Royal Victorian Eye and Ear Hospital have a referral base for almost all paediatric patients with cataracts in south eastern Australia. The database contains cases seen over the past 25 years. The medical histories of these patients were reviewed. 421 patients with paediatric cataract were identified, which gives an estimated incidence of 2.2 per 10,000 births. Of the 342 affected in iduals with a negative family history, 50% were diagnosed during the first year of life, and 56/342 (16%) were associated with a recognised systemic disease or syndrome. Unilateral cataract was identified in 178/342 (52%) of sporadic cases. 79 children (from 54 nuclear families) had a positive family history. Of these 54 families, 45 were recruited for clinical examination and DNA collection. Ten nuclear families were subsequently found to be related, resulting in four larger pedigrees. Thus, 39 families have been studied. The mode of inheritance was autosomal dominant in 30 families, X linked in four, autosomal recessive in two, and uncertain in three. In total, 178 affected family members were examined of these 8% presented with unilateral cataracts and 43% were diagnosed within the first year of life. In the paediatric cataract population examined, approximately half of the patients were diagnosed in the first year of life. More than 18% had a positive family history of cataracts. Of patients with hereditary cataracts 8% presented with unilateral involvement. Identification of the genes that cause paediatric and congenital cataract should help clarify the aetiology of some sporadic and unilateral cataracts.
Publisher: American Diabetes Association
Date: 11-09-2020
DOI: 10.2337/DB20-0070
Abstract: Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 in iduals of erse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in in iduals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10−16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.INJURY.2019.07.019
Abstract: Registries are integral to monitoring, surveying, treating, preventing and prognosticating trauma. The quantity and quality of data must justify a change or intervention in treatment and/or preventive strategies and must be collected while balancing the cost and time invested in the registry. This review documents the quality, completeness and operational and funding models for ocular trauma registries worldwide. The databases CENTRAL, MEDLINE, EMBASE and Informit Health Collection were searched using key word and mesh terms for: "Eye injury, "Ocular trauma", "Eye injury prevention", "Eye protection", "Registry". To find relevant unpublished articles and theses, clinicaltrials.gov, Trip, MedNar and Google Scholar were searched using the key words "eye injury" OR "ocular trauma" AND "registry*". No date or language restrictions were applied. The quality of registry data was assessed against published measures including design, operation and data quality. The electronic search retrieved 528 distinct published articles 61 articles were assessed for eligibility. Of the 61 articles identified, 28 were eligible to be included in the review, with cross-referencing identifying a further 7 articles. The source of most articles on ocular trauma registries was the United States, followed by Germany and China. Patient follow-up was conducted in 31 studies, with 6 months being the most frequently reported period. Issues with data quality included incomplete data such as presence or absence of eye protection and initial visual acuity. Attrition bias was controlled by the United States Eye Injury Register with follow-up. Patients without follow-up data were removed for some studies and this may have introduced bias. National, state and hospital-based ocular trauma registries have contributed significantly to our understanding of ocular trauma. The United States has the most frequently cited and well-resourced ocular trauma registries. It is anticipated that this review will guide the development of future registries for ocular trauma in order to inform evidence-based prevention strategies and, ultimately, improve visual outcomes. We recommend the development of a consensus guidelines for international ocular trauma registry that includes mechanism and context of injury and visual outcomes, to permit international comparison that can be implemented at low cost with secure data capture.
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.OPHTHA.2007.08.013
Abstract: To estimate heritability and locate quantitative trait loci influencing axial length. Classic twin study of monozygotic and dizygotic twins reared together. Eight hundred ninety-three in iduals from 460 families were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) and had ocular axial length measured. Structural equation modeling on the entire s le was used to estimate genetic and environmental components of variation in axial length. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 in iduals from 142 BATS families. Ocular axial length. The heritability estimate for axial length, adjusted for age and sex, in the full s le was 0.81. The highest multipoint logarithm of the odds (LOD) score observed was 3.40 (genomewide P = 0.0004), on chromosome 5q (at 98 centimorgans [cM]). Additional regions with suggestive multipoint LOD scores were also identified on chromosome 6 (LOD scores, 2.13 at 76 cM and 2.05 at 83 cM), chromosome 10 (LOD score, 2.03 at 131 cM), and chromosome 14 (LOD score, 2.84 at 97 cM). Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.
Publisher: MDPI AG
Date: 09-2017
Publisher: Massachusetts Medical Society
Date: 09-04-1998
DOI: 10.1056/NEJM199804093381503
Abstract: The increasing global burden of obesity especially in low-and-middle-income countries (LMICs) accentuates the need for critical action. In the absence of evidence-based approaches to mitigate recent obesity trends, the likelihood of reaching global obesity targets will be almost zero. This study examined the obesity prevalence in Sub-Sahara Africa and observed transitions on the burden of obesity prevalence over time. Data from the Demographic and Health Survey which is based on cross sessional design was used. Most recent surveys carried out in 16 sub-Saharan Africa (SSA) between 2000 and 2018 were included in the analysis. Equiplot by the International Centre for Equity was used to display the inequities by the following socioeconomic measures: wealth index, education, and place of residence. Age-standardized prevalence was measured across these socioeconomic measures using the WHO standard population age distribution, examined changing trends and finally assessed transition in obesity prevalence by percentage point difference of highest and lowest prevalence within each of the three socioeconomic measures. A total of 496,482 women were included in the analysis. Obesity prevalence among women varied substantially, from 2% in Chad to 27% in Lesotho. Variation in obesity prevalence was observed across countries and by socioeconomic status measures. Among women in all the countries except Comoros, the burden was concentrated among the wealthiest. Out of the 16 countries included, the prevalence of obesity was concentrated among women with no education in eight countries (Benin, Burundi, Chad, Cote d'Ivoire, Guinea, Mali, Niger, Comoros) while it was concentrated in those with primary education in Congo and Lesotho and among those with secondary school education in DR Congo, Gabon, Namibia, Nigeria, and Zimbabwe. The burden of obesity was more concentrated in the urban across the 16 countries except in Comoros and Lesotho where they were higher in the rural (8.9 [7.2, 11.1] and 15.1 [13.0, 17.5] respectively) than in urban (6.6 [5.0, 8.8] and 6.8 [5.2, 8.8] respectively). Finally, the trend analysis with five countries indicated that the prevalence and gap in obesity among women increased between previous and most recent surveys except in Zimbabwe where it reduces across the three socioeconomic measures between 2011 and 2018. This study examined transition in obesity prevalence among women across three socioeconomic measures in selected sub-Saharan African countries. Increasing prevalence of obesity was found in SSA but transition to women in lower socioeconomic status is already taking place in some countries.
Publisher: Wiley
Date: 16-12-2013
DOI: 10.1111/J.1755-3768.2011.02314.X
Abstract: To investigate the association between conjunctival ultraviolet autofluorescence (UVAF), a biomarker of ocular ultraviolet radiation (UVR) exposure, and prevalent pterygium. We conducted a cross-sectional study on Norfolk Island, South Pacific. All permanent residents aged ≥15 were invited to participate. Participants completed a sun exposure questionnaire and underwent autorefraction and slit l biomicroscope examination. Area of conjunctival UVAF (sum of temporal/nasal area in right and left eyes) was determined using computerized methods. Multivariate logistic and linear regression models were used to estimate the associations with pterygia and UVAF, respectively. Of 641 participants, 70 people (10.9%) had pterygium in one or both eyes, and prevalence was higher in males (15.0% versus 7.7%, p = 0.003). Significant independent associations with pterygium in any eye were UVAF (per 10 mm(2)) [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.16-1.28, p = 0.002], tanning skin phenotype (OR 2.17, 1.20-3.92, p = 0.010) and spending more than three-quarters of the day outside (OR 2.22, 1.20-4.09, p = 0.011). Increasing quartile of UVAF was associated with increased risk of pterygium following adjustment of age, sex and time outdoors (p(Trend) = 0.002). Independent associations with increasing UVAF (per 10 mm(2)) were decreasing age, time outdoors, skin type and male gender (all p < 0.001). UVAF area correlated well with the duration of outdoor activity (p(Trend) < 0.001). Pterygium occurs in approximately one-tenth of Norfolk Islanders. Increasing conjunctival UVAF is associated with prevalent pterygia, confirming earlier epidemiological, laboratory and ray-tracing studies that pterygia are associated with UVR. Protection from the sun should be encouraged to reduce the prevalence of pterygium in the community.
Publisher: AMPCo
Date: 12-2012
DOI: 10.5694/MJA12.10698
Publisher: Wiley
Date: 09-09-2016
DOI: 10.1002/GEPI.21999
Abstract: Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 in iduals aged 25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated and in adults 20 loci were associated. Association with GRS increased with age β = 0.0016 per risk allele (P = 2 × 10
Publisher: BMJ
Date: 2004
DOI: 10.1136/BJO.88.1.79
Abstract: Mutations of seven crystallin genes have been shown to cause familial cataract. The authors aimed to identify disease causing crystallin mutations in paediatric cataract families from south eastern Australia. 38 families with autosomal dominant or recessive paediatric cataract were examined. Three large families were studied by linkage analysis. Candidate genes at regions providing significant LOD scores were sequenced. Single stranded conformational polymorphism (SSCP) analysis was used to screen five crystallin genes in the probands, followed by direct sequencing of observed electrophoretic shifts. Mutations predicted to affect the coding sequence were subsequently investigated in the entire pedigree. A LOD score of 3.72 was obtained at the gamma-crystallin locus in one pedigree. Sequencing revealed a P23T mutation of CRYGD, found to segregate with disease. A splice site mutation at the first base of intron 3 of the CRYBA1/A3 gene segregating with disease was identified by SSCP in another large family. Five polymorphisms were also detected. Although mutations in the five crystallin genes comprehensively screened in this study account for 38% of paediatric cataract mutations in the literature, only two causative mutations were detected in 38 pedigrees, suggesting that crystallin mutations are a relatively rare cause of the cataract phenotype in this population.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-05-2020
DOI: 10.1167/TVST.9.6.29
Publisher: PeerJ
Date: 24-09-2018
DOI: 10.7717/PEERJ.5664
Abstract: The institutional affiliations and associated collaborative networks that scientists foster during their research careers are salient in the production of high-quality science. The phenomenon of multiple institutional affiliations and its relationship to research output remains relatively unexplored in the literature. We examined 27,612 scientific articles, modelling the normalized citation counts received against the number of authors and affiliations held. In agreement with previous research, we found that teamwork is an important factor in high impact papers, with average citations received increasing concordant with the number of co-authors listed. For articles with more than five co-authors, we noted an increase in average citations received when authors with more than one institutional affiliation contributed to the research. Multiple author affiliations may play a positive role in the production of high-impact science. This increased researcher mobility should be viewed by institutional boards as meritorious in the pursuit of scientific discovery.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2005
DOI: 10.1167/IOVS.05-0312
Abstract: The purpose of this study was to identify genetic contributions to primary open-angle glaucoma (POAG) through investigations of two quantitative components of the POAG phenotype. Genome-wide multipoint variance-components linkage analyses of maximum recorded intraocular pressure (IOP) and maximum vertical cup-to-disc ratio were conducted on data from a single, large Australian POAG pedigree that has been found to segregate the myocilin Q368X mutation in some in iduals. Multipoint linkage analysis of maximum recorded IOP produced a peak LOD score of 3.3 (P = 0.00015) near marker D10S537 on 10q22, whereas the maximum cup-to-disc ratio produced a peak LOD score of 2.3 (P = 0.00056) near markers D1S197 to D1S220 on 1p32. Inclusion of the myocilin Q368X mutation as a covariate provided evidence of an interaction between this mutation and the IOP and cup-to-disc ratio loci. Significant linkage has been identified for maximum IOP and suggestive linkage for vertical cup-to-disc ratio. Identification of genes contributing to the variance of these traits will enhance understanding of the pathophysiology of POAG as a whole.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2003
DOI: 10.1097/00061198-200306000-00010
Abstract: To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography. Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography. Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant. Carriers of the myocilin Thr377Met mutation have reduced outflow facility, which may be detected prior to developing glaucoma. Tonography was not seen to be clinically useful in predicting progression towards glaucoma.
Publisher: Public Library of Science (PLoS)
Date: 22-06-2011
Publisher: Springer Science and Business Media LLC
Date: 11-05-2021
DOI: 10.1186/S12916-021-01973-Y
Abstract: Sleep apnoea, a common sleep-disordered breathing condition, is characterised by upper airway collapse during sleep resulting in transient hypoxia, hypoperfusion of the optic nerve, and spike in intracranial pressure. Previous studies have reported conflicting findings on the association of sleep apnoea with glaucoma, and there are limited reports on the link between sleep apnoea and age-related macular degeneration (AMD). Middle-aged and older participants from the longitudinal United Kingdom (UK) Biobank ( n = 502,505) and the Canadian Longitudinal Study on Aging (CLSA n = 24,073) were included in this analysis. Participants in the UK Biobank and the CLSA were followed for 8 and 3 years, respectively. Participants with diagnosed glaucoma or AMD at baseline were excluded from the analysis. In the UK Biobank, sleep apnoea and incident cases of glaucoma and AMD were identified through hospital inpatient admission, primary care records, and self-reported data. Multivariable Cox proportional hazards models were used to explore associations of sleep apnoea with incidence of glaucoma or AMD. During the 8-year follow-up in the UK Biobank, glaucoma incidence rates per 1000 person-years were 2.46 and 1.59 for participants with and without sleep apnoea, and the AMD incidence rates per 1000 person-years were 2.27 and 1.42 for participants with and without sleep apnoea, respectively. Multivariable adjusted hazard ratios of glaucoma and AMD risk for sleep apnoea were 1.33 (95% confidence interval [CI] 1.10–1.60, P = 0.003) and 1.39 (95% CI 1.15–1.68, P 0.001) relative to participants without sleep apnoea. In the CLSA cohort, disease information was collected through in-person interview questionnaires. During the 3-year follow-up, glaucoma incidence rates per 1000 person-years for those with and without sleep apnoea were 9.31 and 6.97, and the AMD incidence rates per 1000 person-years were 8.44 and 6.67, respectively. In the CLSA, similar associations were identified, with glaucoma and AMD odds ratios of 1.43 (95% CI 1.13–1.79) and 1.39 (95% CI 1.08–1.77), respectively, in participants with sleep apnoea compared to those without sleep apnoea (both P 0.001). In two large-scale prospective cohort studies, sleep apnoea is associated with a higher risk of both glaucoma and AMD. These findings indicate that patients with sleep apnoea might benefit from regular ophthalmologic examinations.
Publisher: Informa UK Limited
Date: 03-07-2018
Publisher: Informa UK Limited
Date: 19-01-2017
DOI: 10.1080/09286586.2016.1255975
Abstract: To outline and detail the importance of conditional probability in clinical decision making and discuss the various diagnostic measures eye care practitioners should be aware of in order to improve the scope of their clinical practice. We conducted a review of the importance of conditional probability in diagnostic testing for the eye care practitioner. Eye care practitioners use diagnostic tests on a daily basis to assist in clinical decision making and optimizing patient care and management. These tests provide probabilistic information that can enable the clinician to increase (or decrease) their level of certainty about the presence of a particular condition. While an understanding of the characteristics of diagnostic tests are essential to facilitate proper interpretation of test results and disease risk, many practitioners either confuse or misinterpret these measures. In the interests of their patients, practitioners should be aware of the basic concepts associated with diagnostic testing and the simple mathematical rule that underpins them. Importantly, the practitioner needs to recognize that the prevalence of a disease in the population greatly determines the clinical value of a diagnostic test.
Publisher: Public Library of Science (PLoS)
Date: 13-05-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
DOI: 10.1097/APO.0000000000000415
Abstract: Report the age-standardized annual incidence of blindness registration due to age-related macular degeneration (AMD) in Australia in patients aged 50 years and older. Frequencies of photodynamic therapy (PDT) and intravitreal therapy (IVT) were examined. Retrospective observational study. Registry of the Association for the Blind of Western Australia with best-corrected visual acuity worse than 20/200 in the better-seeing eye. Registering as blind aged 50 years or over. Annual age-standardized incidence of blindness over 3 time periods: 1996–2001 (pre-PDT), 2002–2007 (PDT era) and 2008–2016 (IVT era). The rates of PDT and IVT usage were assessed. Age-standardized annual incidence of blindness rose during the PDT era, reaching 72.5 cases per 100,000 person-years in 2004. The incidence declined from 2007 onwards, reaching 8.2 cases per 100,000 person-years in 2016 (IVT era). The age at AMD blindness registration increased from 82.7 to 84.9 and 83.7 to 86.0 years from the PDT era to the IVT era in both male and females ( P 0.001) respectively. Over the same time period, PDT usage increased in 2002 and declined in 2006, whereas IVT usage increased from 2009 by 3745 per year. The increase in new blindness registrations due to AMD coincided with public funding of verteporfin for PDT, whereas the subsequent decline occurred when bevacizumab was used off-label and ranibizumab and aflibercept were publicly funded. An understanding of the effect of retinal therapy on public health measures may inform improvements in the allocation of limited resources.
Publisher: BMJ
Date: 07-05-2009
Abstract: Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are estimated to cause up to 20% of all Caucasian retinitis pigmentosa and up to 75% of cases of X-Linked RP (XLRP). Exon open reading frame 15 (ORF15) is a purine-rich mutation hotspot. Mutations in RPGR ORF15 have also been documented to cause X linked cone-rod dystrophy (XLCORD) and atrophic macular degeneration at an unknown frequency. From a hospital clinic population, probands with probable XLRP and XLCORD were screened for RPGR ORF15 mutations and fully phenotyped. Four different RPGR ORF15 mutations were found in four probands. All mutations in the ORF15 exon resulted in premature truncation of the RPGR protein. Three were nonsense mutations: c.507G>T (p.E169stop), c.867G>T (p.G289stop), c.897G>T (p.E299stop) and the fourth a single nucleotide insertion c.1558-1559insA (p.S522fs 525stop). One family exhibited typical XLRP, two XLCORD and one a combination of the phenotypes. RPGR ORF15 mutations produce intrafamilial and interfamilial clinical variability with varying degrees of cone degeneration. In an Australian clinic population RPGR ORF15 mutations cause XLCORD in addition to XLRP.
Publisher: Springer Science and Business Media LLC
Date: 22-09-2014
DOI: 10.1038/NCOMMS5883
Abstract: Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 in iduals of European ancestry and 6,784 in iduals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.
Publisher: American Society for Clinical Investigation
Date: 06-06-2016
DOI: 10.1172/JCI85830
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-04-2021
Publisher: American Medical Association (AMA)
Date: 2019
Publisher: Public Library of Science (PLoS)
Date: 13-04-2022
DOI: 10.1371/JOURNAL.PONE.0266909
Abstract: Changes in retinal thickness are common in various ocular diseases. Transverse magnification due to differing ocular biometrics, in particular axial length, affects measurement of retinal thickness in different regions. This study evaluated the effect of axial length and refractive error on measured macular thickness in two community-based cohorts of healthy young adults. A total of 2160 eyes of 1247 community-based participants (18–30 years 23.4% myopes, mean axial length = 23.6mm) were included in this analysis. Macular thickness measurements were obtained using a spectral-domain optical coherence tomography (which assumes an axial length of 24.385mm). Using a custom program, retinal thickness data were extracted at the 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) regions with and without correction for transverse magnificent effects, with the corrected measurements adjusting according to the participant’s axial length. Linear mixed models were used to analyse the effect of correction and its interaction with axial length or refractive group on retinal thickness. The raw measures (uncorrected for axial length) underestimated the true retinal thickness at the central macula, while overestimating at most non-central macular regions. There was an axial length by correction interaction effect in all but the nasal regions (all p .05). For each 1mm increase in axial length, the central macular thickness is overestimated by 2.7–2.9μm while thicknesses at other regions were underestimated by 0.2–4.1μm. Based on the raw thickness measurements, myopes have thinner retinas than non-myopes at most non-central macular. However, this difference was no longer significant when the corrected data was used. In a community-based s le, the raw measurements underestimate the retinal thickness at the central macula and overestimate the retinal thickness at non-central regions of the ETDRS grid. The effect of axial length and refractive error on retinal thickness is reduced after correcting for transverse magnification effects resulting from axial length differences.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.AJO.2005.08.073
Abstract: To describe the phenotype of an in idual homozygous for the common Gln368STOP myocilin mutation and to discuss the other family members. Cascade screening was performed for Australian families that had been identified as having the myocilin Gln368STOP mutation. Recruited subjects underwent comprehensive clinical examination and mutation analysis for the Gln368STOP myocilin mutation by direct sequencing. One 49-year-old woman was found to be homozygous for the mutation. Her maximal recorded intraocular pressure was 17 mm Hg. Bilateral optic disk examination revealed small, healthy optic discs. Automated perimetry testing was normal. Neither the in idual homozygous for the Gln368STOP myocilin mutation nor her younger heterozygous siblings displayed any signs suggestive of glaucoma. One of the two heterozygous parents did manifest glaucoma. Although there is the possibility of the homozygous in idual developing glaucoma in the future, she does not manifest a phenotype that is more severe than usual.
Publisher: BMJ
Date: 27-06-2012
Publisher: Springer Science and Business Media LLC
Date: 24-05-2020
DOI: 10.1186/S12874-020-00996-Y
Abstract: Recent changes in communication technologies, including increased reliance on mobile phones and the internet, may present challenges and/or opportunities to re-engaging inactive study cohorts. We evaluate our ability to recruit participants for the Kidskin Young Adult Myopia Study (KYAMS), a follow-up of the Kidskin Study. KYAMS participants were recruited from the Kidskin Study, a sun exposure-intervention study for 5–6 year-olds running from 1995 to 1999 with most recent follow-up in 2005. From 2015 to 2019, the KYAMS used mail-outs, phone calls and social media to contact Kidskin Study participants. Multivariable logistic regression was used to identify variables associated with successful contact of a Kidskin Study participant or family member and KYAMS participation. Of 1695 eligible participants, 599 (35.5%) participants (or a family member) were contacted and 303 (17.9%) participated in the KYAMS. KYAMS participation was more likely in those who participated in the 2005 follow-up (odds ratio [OR] = 5.09, 95% confidence interval [CI]: 3.67–7.06) and had a mobile phone number on record (OR = 2.25, CI: 1.57–3.23). Of those contacted, participants who were the first point of contact (OR = 4.84, CI: 2.89–8.10) and who were contacted by letter in the first (OR = 6.53, CI: 3.35–12.75) or second (OR = 5.77, CI: 2.85–11.67) round were more likely to participate in the KYAMS, compared to contact by landline phone. We recruited approximately one-fifth of Kidskin Study participants for the KYAMS. Participants were more likely to participate in the KYAMS if they were contacted directly, rather than through a family member, and if they were contacted by invitation letter. ACTRN12617000812392 .
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-06-2020
DOI: 10.1167/TVST.9.7.19
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-09-2011
DOI: 10.1167/IOVS.11-7872
Abstract: To identify the defective gene in the sex-linked, recessively inherited retinal dysplasia and degeneration (rdd) chicken and to search for the human equivalent disease. Microsatellites from chicken chromosome Z were genotyped in 77 progeny of a carrier male (rdd/+) and an affected female (rdd/W), and candidate genes were sequenced. Retinal cross-sections from rdd and wild-type birds were analyzed by immunohistology. The human orthologous gene was screened in a panel of archival DNAs from 276 patients with retinitis pigmentosa (RP) or Leber congenital amaurosis (LCA) using melting curve analysis and DNA sequencing. The rdd locus was refined to an approximately 3-Mb region on chromosome Z. Sequence analysis identified a C→T change in the mpdz gene that created a premature stop codon (c.1372C→T, p.R458X), which segregated with the disease phenotype. As expected, the full-length mpdz protein was absent in rdd retinas, but in wild-type birds, it localized to the retinal outer limiting membrane, where it may have a role in the interactions between photoreceptors and Müller glia cells. The screen to identify the human equivalent disease found 10 heterozygous variants in the orthologous gene in patients with RP (three missense and two null alleles) and LCA (four missense and one null allele). These findings reveal that MPDZ is essential for normal development of the retina and may have a role in maintaining photoreceptor integrity. The identification of human mutations suggests that MPDZ plays a role in human retinal disease, but the precise nature of this role remains to be determined.
Publisher: Oxford University Press (OUP)
Date: 06-06-2017
DOI: 10.1093/IJE/DYX068
Publisher: Wiley
Date: 24-02-2006
DOI: 10.1111/J.1442-9071.2006.01194.X
Abstract: On the 65th anniversary of Gregg's observation "Congenital cataract following German measles in the mother", rubella has retired as the leading cause of congenital cataract, from 87% of Gregg's cohort to less than 3% over the last 25 years and almost zero now in Australia and other developed countries. However, people must keep vigilance in maintaining immunization rates and encourage immunization in developing countries. At least one-fifth of congenital cataract is familial. Understanding the genetics of familial cataract will lead to better treatment of congenital as well as age-related cataract.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-2007
DOI: 10.1167/IOVS.06-1470
Abstract: Numerous genetic diseases and environmental stimuli affect optic nerve morphology. The purpose of this study was to identify the principal heritable components of visible optic nerve head structures in a population-based s le of twins. Fifteen optic nerve specialists viewed stereoscopic optic nerve head photographs (Stereo Viewer-II Pentax Corp., Tokyo, Japan) from 50 randomly selected monozygotic or dizygotic twin pairs. Before viewing, each expert was questioned about which optic nerve head traits they believed were inherited. After viewing a standardized teaching set, the experts indicated which twin pairs they thought were monozygotic. Participants were then questioned about how their decisions were reached. A rank-ordered Rasch analysis was used to determine the relative weighting and value applied to specific optic nerve head traits. The proportion of twin pairs for which zygosity was correctly identified ranged from 74% to 90% (median, 82%) across the panel. Experts who correctly identified the zygosity in more than 85% of cases placed most weighting on shape and size of the optic disc and cup, whereas experts with the lowest scores placed greater weighting on the optic nerve head vasculature in reaching their decisions. In determining the genetic components of the optic nerve head, the results of this study suggest that the shape and size of the optic disc and cup are more heritable and should receive a greater priority for quantification than should vascular features.
Publisher: Informa UK Limited
Date: 17-08-2022
DOI: 10.1080/08164622.2021.1964921
Abstract: Eye injuries, both accidental and non-accidental, are a significant cause of long-term visual impairment in children. An understanding of when and how such injuries occur is key to development of adequate prevention strategies. To evaluate accidental and non-accidental eye injuries in children presenting to the major tertiary emergency department and outpatient ophthalmology clinic in Western Australia during the nationwide COVID-19 lockdown and to determine whether the frequency or nature of these injuries differed from pre-pandemic presentations. Retrospective review of the medical records of paediatric patients presenting to the emergency department and specialist ophthalmology clinic with an ocular injury and those presenting to the hospital Child Protection Unit with physical injuries during March-August 2020 and the same period in 2019. There was no significant difference in the total number of accidental eye injury presentations during the lockdown period despite a significant decrease in emergency department attendance overall. Closed-globe injuries were the most common accidental eye injury presentation during lockdown (70/110, 64%), followed by adnexal injuries (39/110, 35%) and open-globe injuries (1/110, 1%). In contrast, referrals to the hospital Child Protection Unit for suspicious injuries declined during lockdown. Although eye injury presentations have changed in other parts of the world since the start of the pandemic, during COVID-19 lockdown in Western Australia, accidental paediatric ocular and adnexal trauma sustained at home continues to be a significant cause for hospital attendance. Public education regarding in-home eye injury prevention must be ongoing.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.OPHTHA.2008.02.011
Abstract: To examine the roles of genetic and environmental factors in corneal hysteresis and ocular pulse litude by performing a classic twin study. Cross-sectional twin study. Two hundred sixty-four twin pairs: 135 monozygotic (MZ) and 129 dizygotic (DZ). Corneal hysteresis was measured using the Reichert Ocular Response Analyzer (ORA Reichert, Buffalo, NY), and ocular pulse litude was measured using the Pascal Dynamic Contour Tonometer (DCT Swiss Microtechnology AG, Port, Switzerland). Contribution of genetic and environmental effects on corneal hysteresis and OPA among MZ and DZ twins. The mean corneal hysteresis was 10.24+/-1.54 mmHg and the mean ocular pulse litude was 2.88+/-0.97 mmHg. The MZ correlations were higher than DZ for both corneal hysteresis and ocular pulse litude (correlation coefficients, 0.75:0.42 and 0.59:0.32 for MZ:DZ twins, respectively). Modeling suggested heritability of corneal hysteresis of 0.77 (95% confidence interval [CI], 0.70-0.82), with the remaining proportion of variance because of in idual environmental effects of 0.23 (95% CI, 0.18-0.30). For ocular pulse litude, the heritability was 0.62 (95% CI, 0.51-0.70), with the remaining proportion of variance the result of in idual environmental effects of 0.38 (95% CI, 0.30-0.49). This study demonstrated that additive genetic influences explained most of the in idual differences in corneal hysteresis and ocular pulse litude among these twins.
Publisher: Hindawi Limited
Date: 09-06-2017
DOI: 10.1002/HUMU.23247
Abstract: Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10
Publisher: ACM
Date: 20-01-2020
Publisher: Springer Science and Business Media LLC
Date: 15-04-2011
DOI: 10.1038/EYE.2011.83
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.OPHTHA.2019.04.041
Abstract: Obstructive sleep apnea (OSA) is linked to increased glaucoma risk in middle-aged and older adults. However, little is known about associations between OSA and glaucoma-related optic disc parameters in young adults. We explored associations between overnight polysomnography-derived measures of OSA and the optic disc in young adults. Cross-sectional cohort study. Eight hundred forty-eight adults 19 to 22 years of age. Participants underwent an ophthalmic examination that included OCT imaging of the optic disc and measurements of intraocular pressure, axial length, and refractive error. Participants then underwent an overnight polysomnography study that obtained measurements of apnea-hypopnea index (AHI), peripheral oxygen saturation level, and number of cortical arousals from sleep. Based on the AHI results, participants were grouped into no OSA (AHI < 5 events/hour), mild OSA (AHI ≥ 5 and <15 events/hour), moderate OSA (AHI ≥ 15 and <30 events/hour), or severe OSA (AHI ≥ 30 events/hour). Neuroretinal rim area, horizontal and vertical widths, and peripapillary retinal nerve fiber layer (RNFL) thickness. The median AHI result across the study cohort was 2.2 events per hour (interquartile range, 1.0-4.4 events/hour). Based on the AHI results, 178 participants (21.0%) demonstrated OSA: 150 with mild OSA, 26 with moderate OSA, and 2 with severe OSA. In the unadjusted analyses, participants with OSA on average showed thinner peripapillary RNFL at the inferotemporal (P = 0.026) and superotemporal (P = 0.008) segments compared with those without OSA. Additionally, higher AHI results were associated with thinner RNFL superotemporally (P = 0.007). These findings remained significant after adjusting for gender, body mass index, ethnicity, and potential ocular confounders. There were no significant differences in optic disc measures between groups of OSA severity. Obstructive sleep apnea may be associated with preclinical thinning of the peripapillary RNFL in young adults. This suggests that an increased glaucoma risk already may be present in in iduals with OSA since young adulthood. Long-term follow-up of this cohort will allow further optic disc changes in relationship to polysomnography parameters to be documented and associations with future glaucoma diagnosis to be explored.
Publisher: BMJ
Date: 08-2023
DOI: 10.1136/BMJOPEN-2022-068811
Abstract: Glaucoma, a major cause of irreversible blindness, is a highly heritable human disease. Currently, the majority of the risk genes for glaucoma are unknown. We established the Genetics of Glaucoma Study (GOGS) to identify disease genes and improve genetic prediction of glaucoma risk and response to treatment. More than 5700 participants with glaucoma or a family history of glaucoma were recruited through a media c aign and the Australian Government healthcare service provider, Services Australia, making GOGS one of the largest genetic studies of glaucoma globally. The mean age of the participants was 65.30±9.36 years, and 62% were female. Participants completed a questionnaire obtaining information about their glaucoma-related medical history such as family history, glaucoma status and subtypes, surgical procedures, and prescriptions. The questionnaire also obtained information about other eye and systemic diseases. Approximately 80% of the participants provided a DNA s le and ~70% consented to data linkage to their Australian Government Medicare and Pharmaceutical Benefits Scheme schedules. 4336 GOGS participants reported that an optometrist or ophthalmologist has diagnosed them with glaucoma and 3639 participants reported having a family history of glaucoma. The vast majority of the participants (N=4393) had used at least one glaucoma-related medication latanoprost was the most commonly prescribed drug (54% of the participants who had a glaucoma prescription). A subset of the participants reported a surgical treatment for glaucoma including a laser surgery in 2008 participants and a non-laser operation in 803 participants. Several comorbid eye and systemic diseases were also observed the most common reports were ocular hypertension (53% of the participants), cataract (48%), hypertension (40%), nearsightedness (31%), astigmatism (22%), farsightedness (16%), diabetes (12%), sleep apnoea (11%) and migraines (10%). GOGS will contribute to the global gene-mapping efforts as one of the largest genetic studies for glaucoma. We will also use GOGS to develop or validate genetic risk prediction models to stratify glaucoma risk, particularly in in iduals with a family history of glaucoma, and to predict clinical outcomes (eg, which medication works better for an in idual and whether glaucoma surgery is required). GOGS will also help us answer various research questions about genetic overlap and causal relationships between glaucoma and its comorbidities.
Publisher: BMJ
Date: 09-09-2015
DOI: 10.1136/BJOPHTHALMOL-2014-305498
Abstract: Previous studies have demonstrated a small but significant transient increase in intraocular pressure (IOP) in in iduals wearing certain types of swimming goggles. These findings suggested that wearing goggles could represent a significant risk factor for developing and/or worsening of glaucoma in people who swim regularly. The aim of this study was to determine if glaucoma prevalence is increased among adult swimmers. A comprehensive ocular examination was performed on 231 members of local swimming clubs and 118 non-swimmers. IOP was measured using iCARE tonometry and visual field testing was performed using Humphrey SITA fast 24-2. Retinal nerve fibre layer thickness was assessed using spectral domain optical coherence tomography. Based on measurements of IOP and visual fields, we did not detect any new cases of glaucoma in our cohort of frequent swimmers. Similarly, we found no difference in the thickness of the retinal nerve fibre layer between swimmers and non-swimmers the mean right global thickness (GT) was 94.0 μm (IQR 88.0, 100.3) vs 93.0 μm (IQR 89.0, 101.0), respectively (p=0.976), and the median left GT was 93.7 μm (IQR 88.0, 101) in both groups (p=0.799). These findings suggest that frequently wearing swim goggles does not lead to an increased risk of glaucoma over time in adults.
Publisher: Wiley
Date: 09-2006
DOI: 10.1111/J.1442-9071.2006.01314.X
Abstract: To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity (ROP). A dataset comprising 13 Norrie-FEVR, one Coat's disease, 31 ROP patients and 90 ex-premature babies of <32 weeks' gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high-performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high-performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing. Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14-bp deletion located in the 5' unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex-premature girl. Only two of the 13 Norrie-FEVR index cases had the full features of Norrie disease with deafness and mental retardation. Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.
Publisher: Wiley
Date: 22-10-2022
DOI: 10.1111/OPO.12905
Abstract: Cross‐sectional studies have variably reported that poor sleep quality may be associated with myopia in children. Longitudinal data, collected over the ages when myopia develops and progresses, could provide new insights into the sleep‐myopia paradigm. This study tested the hypothesis that 12‐year trajectories of sleep behaviour from childhood to adolescence is associated with myopia during young adulthood. At the 5‐, 8‐, 10‐, 14‐ and 17‐year follow‐ups of the longitudinal Raine Study, which has been following a cohort since their birth in 1989–1992, participants' parents/guardians completed the Child Behaviour Checklist questionnaire (CBCL), which collected information on their child's sleep behaviour and quality. The CBCL includes six questions measuring sleep behaviour, which parents rated as 0 = not true, 1 = somewhat/sometimes true, or 2 = very/often true. Scores were summed at each follow‐up to form a composite “sleep behaviour score”. Latent Class Growth Analysis (LCGA) was used to classify participants according to their 12‐year trajectory of sleep behaviour. At the 20‐year follow‐up, an eye examination was performed which included cycloplegic autorefraction and axial length measurement. The LCGA identified three clusters of participants based on their trajectory of sleep behaviour: those with minimal' (43.6% of the total Raine Study s le), ‘declining’ (48.9%), or ‘persistent’ (7.5%) sleep problems. A total of 1194 participants had ophthalmic data and longitudinal sleep data available for analysis (47.2% female, 85.6% Caucasian). No significant differences were observed in regards to age, sex, ethnicity or ocular parameters between trajectory groups. Unadjusted and fully adjusted analyses demonstrated that sleep problem behaviour was not significantly associated with changes in refractive error, axial length or corneal radius. Our findings do not support the hypothesis that there is an association between sleep behaviour and myopia. Future longitudinal studies should explore sleep trajectory data pre‐ and post‐myopia diagnosis to confirm our results.
Publisher: Asia Pacific Academy of Ophthalmology
Date: 2019
DOI: 10.22608/APO.2018329
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2009
DOI: 10.1161/HYPERTENSIONAHA.109.132902
Abstract: Research into the genetic effects and specific genes associated with retinal vascular caliber, a risk marker of cardiovascular diseases, may provide new insights into the genetic contribution of early microvascular disease. A combined 374 monozygotic and 536 dizygotic twin pairs and 322 siblings from the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study underwent complete ophthalmic examinations, including retinal photography, and bilateral retinal vascular caliber was measured. Structural equation modeling was used to estimate the heritability. Genome-wide linkage analysis was conducted on 836 in iduals from 381 Brisbane Adolescent Twin Study families, with adjustments for age, sex, and other covariates. The heritabilities for the retinal arteriolar caliber were 59.4% (95% CI: 53.2% to 64.7%) and 56.5% (95% CI: 50.1% to 61.9%) in the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study, respectively, and for venular caliber they were 61.7% (95% CI: 55.6% to 67.0%) and 64.2% (95% CI: 58.7% to 68.8%), respectively, after adjusting for age, sex, and body mass index. Two multipoint peaks detected on chromosomes 3p12.3 and 8p23.1 for retinal arteriolar caliber had suggestive linkage, with the highest multipoint peak logarithm of odds score of 2.24 on chromosome 8p23.1 (genome-wide P =7.0×10 −4 ). Two suggestive logarithm of odds scores for venular caliber were identified on chromosomes 2p14 and 9q21.13. The largest multipoint logarithm of odds score was 2.69 on chromosome 2p14 (genome-wide P =2.0×10 −4 ). In this large twin population, genetic factors appear to play a significant role in the variation of retinal vascular caliber. Several putative loci were identified for the retinal vascular caliber.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2018
DOI: 10.1038/S10038-017-0374-Y
Abstract: Primary open-angle glaucoma (POAG) is influenced by both genetic and environmental factors. Despite significant progress in identifying genetic variants associated with POAG, there remains a substantial amount of unexplained heritability. Study design features that may enhance knowledge of the genetic architecture include focusing on multiple quantitative traits related to ocular disorders (i.e. endophenotypes), targeting genetic variants that directly influence gene expression (i.e. cis-eQTLs) and utilising genetically isolated populations to reduce genetic and environmental noise and thus enhance association signals. In this study we performed heritability and blood-based eQTL association analysis of five key POAG endophenotypes in 330 in iduals from the Norfolk Island (NI) isolate. Results showed evidence of heritability for all five traits, with H
Publisher: MDPI AG
Date: 19-12-2014
DOI: 10.3390/JCM3041511
Publisher: Springer Science and Business Media LLC
Date: 05-10-2020
DOI: 10.1038/S41598-020-73339-Y
Abstract: Stargardt disease is one of the most common forms of inherited retinal disease and leads to permanent vision loss. A diagnostic feature of the disease is retinal flecks, which appear hyperautofluorescent in fundus autofluorescence (FAF) imaging. The size and number of these flecks increase with disease progression. Manual segmentation of flecks allows monitoring of disease, but is time-consuming. Herein, we have developed and validated a deep learning approach for segmenting these Stargardt flecks (1750 training and 100 validation FAF patches from 37 eyes with Stargardt disease). Testing was done in 10 separate Stargardt FAF images and we observed a good overall agreement between manual and deep learning in both fleck count and fleck area. Longitudinal data were available in both eyes from 6 patients (average total follow-up time 4.2 years), with both manual and deep learning segmentation performed on all (n = 82) images. Both methods detected a similar upward trend in fleck number and area over time. In conclusion, we demonstrated the feasibility of utilizing deep learning to segment and quantify FAF lesions, laying the foundation for future studies using fleck parameters as a trial endpoint.
Publisher: Oxford University Press (OUP)
Date: 16-11-2008
DOI: 10.1093/HMG/DDM342
Abstract: Pseudoexfoliation syndrome is a generalized disorder of the extracellular matrix, characterized by the pathological accumulation of abnormal fibrillar material in the anterior segment of the eye predisposing to glaucomatous optic neuropathy. We investigated the role of lysyl oxidase-like 1(LOXL1) sequence variation in a Caucasian Australian population-based cohort of 2508 in iduals, 86 (3.4%) of whom were diagnosed with pseudoexfoliation syndrome. Two non-synonymous variants in exon 1 of LOXL1 (Arg141Leu Gly153Asp) were found to be strongly associated with pseudoexfoliation. Two copies of the high risk haplotype at these single-nucleotide polymorphisms conferred a risk of 7.20 (95%CI: 3.04-20.75) compared with no copies of the high risk haplotype. Each of the disease-associated alleles is by far commoner in the normal population, and examination of cross-species homology reveals that the two disease-associated coding variants belong to the ancestral version of the gene. LOXL1 was found to be expressed by reverse transcription-polymerase chain reaction in all ocular tissues examined except retina. The presence of LOXL1 protein in ocular tissues of interest was demonstrated by western blotting. Specific bands of approximately 130 and 80 kDa, representing polymerized protein forms, were detected in the cornea, iris, ciliary body, lens capsule and optic nerve. The 42 kDa mature form of LOXL1 was detected in the iris and ciliary body. Our Caucasian population has a 9-fold lower lifetime incidence of pseudoexfoliation syndrome compared with Nordic populations despite having similar allelic architecture at the LOXL1 locus. This strongly suggests that as yet unidentified genetic or environmental factors independent of LOXL1 strongly influence the phenotypic expression of the syndrome.
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/AH14242
Abstract: Objective The aim of the present study was to identify patient and non-patient factors associated with reduced mortality among patients admitted from the emergency department (ED) to in-patient wards in a major tertiary hospital that had previously reported a near halving in mortality in association with a doubling in National Emergency Access Target (NEAT) compliance over a 2-year period from 2012 to 2014. Methods We retrospectively analysed routinely collected data from the Emergency Department Information System (EDIS) and hospital discharge abstracts on all emergency admissions during calendar years 2011 (pre-NEAT interventions) and 2013 (post-NEAT interventions). Patients admitted to short-stay wards and then discharged home, as well as patients dying in the ED, were excluded. Patients included in the study were categorised according to age, time and day of arrival to the ED, mode of transport to the ED, emergency triage category, type of clinical presentation and major diagnostic codes. Results The in-patient mortality rate for emergency admissions decreased from 1.9% (320/17 022) in 2011 to 1.2% (202/17 162) in 2013 (P 0.001). There was no change from 2011 to 2013 in the percentage of deaths in the ED (0.19% vs 0.17%) or those coded as in-patient palliative care (17.9% vs 22.2%). Although deaths were not associated with age by itself, the mortality rate of older patients admitted to medical wards decreased significantly from 3.5% to 1.7% (P = 0.011). A higher mortality rate was seen among patients presenting to ED triage between midnight and 12 noon than at other times in 2011 (2.5% vs 1.5% P 0.001), but this difference disappeared by 2013 (1.3% vs 1.1% P = 0.150). A similar pattern was seen among patients presenting on weekends versus weekdays: 2.2% versus 1.7% (P = 0.038) in 2011 and 1.3% versus 1.1% (P = 0.150) in 2013. Fewer deaths were noted among patients with acute cardiovascular or respiratory disease in 2013 than in 2011 (1.7% vs 3.6% and 1.5% vs 3.4%, respectively P 0.001 for both comparisons). Mode of transport to the ED or triage category was not associated with changes in mortality. These analyses took account of any possible confounding resulting from differences over time in emergency admission rates. Conclusions Improved NEAT compliance as a result of clinical redesign is associated with improved in-patient mortality among particular subgroups of emergency admissions, namely older patients with complex medical conditions, those presenting after hours and on weekends and those presenting with time-sensitive acute cardiorespiratory conditions. What is known about the topic? Clinical redesign aimed at improving compliance with NEAT and reducing time spent within the ED of acutely admitted patients has been associated with reduced mortality. To date, no study has attempted to identify subgroups of patients who potentially derive the greatest benefit from improved NEAT compliance in terms of reduced risk of in-patient death. It also remains unclear as to what extent non-patient factors (e.g. admission practices and differences in coding of palliative care patients) affect or confound this reduced risk. What does this paper add? The present study is the first to reveal that enhanced NEAT compliance is associated with lower mortality among particular subgroups of emergency patients admitted to in-patient wards. These include older patients with complex medical conditions, those presenting after hours or on weekends or those with time-sensitive acute cardiorespiratory conditions. These results took account of any possible confounding resulting from differences over time in emergency admission rates, deaths in the ED, numbers of short-stay ward admissions and coding of palliative care deaths. What are the implications for practitioners? Efforts aimed at improving NEAT compliance and efficiencies at the ED–in-patient interface appear to be worthwhile in reducing in-patient mortality among particular subgroups of emergency admissions at high risk. More research is urgently needed in identifying patient- and system-level factors that predispose to higher mortality rates in such populations, but are potentially amenable to focused interventions aimed at optimising transitions of care at the ED–in-patient interface and increasing NEAT compliance for patients admitted to in-patient wards from the ED.
Publisher: Wiley
Date: 20-02-2012
DOI: 10.1111/J.1399-0004.2012.01851.X
Abstract: Fraser syndrome (FS) and microphthalmia syndromic 9 (MCOPS9) are autosomal recessive conditions with distinct, and some overlapping features affecting the ocular, respiratory and cardiac systems. Mutations in FRAS1 and FREM2 occur in FS, and mutations in STRA6 occur in MCOPS9. We report two sibships, in the same family, where four deceased offspring had ocular, respiratory and cardiac abnormalities. Two sibs with microphthalmia had syndactyly and laryngeal stenosis, suggesting a clinical diagnosis of FS. Our results indicate that they were compound heterozygotes for novel FRAS1 mutations, p.Cys729Phe and p.Leu3813Pro. The other two sibs, first cousins to the first sib pair, had anophthalmia, lung hypoplasia and cardiac anomalies, suggesting a retrospective diagnosis of MCOPS9. Our results indicate compound heterozygous STRA6 mutations, a novel frameshift leading to p.Tyr18* and a p.Thr644Met mutation. The one surviving in idual from these sibships is heterozygous for the p.Tyr18*STRA6 mutation and has bilateral ocular colobomata and microphthalmia. This work emphasises the need for careful phenotypic characterisation to determine genes for assessment in ocular syndromic conditions. It also indicates that heterozygous STRA6 mutations may rarely contribute to microphthalmia and coloboma.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-08-2018
Publisher: Public Library of Science (PLoS)
Date: 06-03-2017
Publisher: Oxford University Press (OUP)
Date: 14-02-2018
DOI: 10.1093/HMG/DDY053
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-09-2019
Publisher: Springer Science and Business Media LLC
Date: 23-07-2018
Publisher: Elsevier BV
Date: 02-2001
DOI: 10.1086/318183
Publisher: Wiley
Date: 02-1996
DOI: 10.1111/J.1442-9071.1996.TB01545.X
Abstract: Leber hereditary optic neuropathy (LHON) is one of the more common forms of hereditary optic neuropathy and one of the few mitochondrial neuropathies. Prior to the advent of molecular DNA testing, the diagnosis depended on the recognition of typical fundal changes, as well as a family history of maternal transmission. Sporadic cases were therefore diagnosed with a level of uncertainty. The aim of this study is to identify the proportion of patients with idiopathic bilateral optic neuropathy/atrophy who are suffering from LHON. Requests were sent to all ophthalmologists and neurologist in Australia and New Zealand for blood or hair follicle s les of patients with diagnosis of bilateral optic neuropathy/atrophy of uncertain aetiology for DNA testing by restriction endonuclease analysis. One hundred and forty-four s les were received, of which 96 were sporadic cases of idiopathic optic atrophy. Eleven of these sporadic patients were found to harbour pathogenetic mitochondrial point mutations associated with LHON. Our results indicated that 11% of patients with bilateral optic neuropathy/atrophy of uncertain aetiology are suffering from LHON. Comparing this data with all the known familial cases of LHON, we report that at least 8% of all LHON cases in Australia are sporadic. We concluded that mtDNA testing for LHON in patients with idiopathic optic atrophy should be included in the initial laboratory work-up.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-06-2016
Abstract: Many genome-wide association studies have identified common single nucleotide polymorphisms (SNPs) at the 9p21 glaucoma locus (CDKN2B/CDKN2B-AS1) to be significantly associated with primary open-angle glaucoma (POAG), with association being stronger in normal tension glaucoma (NTG) and advanced glaucoma. We aimed to determine whether any observed differences in genetic association at the 9p21 locus are influenced by sex. Sex was assessed as a risk factor for POAG for 2241 glaucoma participants from the Australian and New Zealand Registry of Advanced Glaucoma, the Glaucoma Inheritance Study in Tasmania, and the Flinders Medical Centre. A total of 3176 controls were drawn from the Blue Mountains Eye Study and South Australia: 1523 advanced POAG and 718 nonadvanced POAG cases were genotyped along with 3176 controls. We selected 13 SNPs at the 9p21 locus, and association results were subanalyszd by sex for high-tension glaucoma (HTG) and NTG. Odds ratios (ORs) between sexes were compared. A sex bias was present within advanced NTG cases (57.1% female versus 42.9% male, P = 0.0026). In all POAG cases, the strongest associated SNP at 9p21 was rs1063192 (OR, 1.43 P = 4 × 10-18). This association was stronger in females (OR, 1.5 P = 5 × 10-13) than in males (OR, 1.35 P = 7 × 10-7), with a statistically significant difference in female to male OR comparison (P = 1.0 × 10-2). An NTG to HTG subanalysis yielded statistically significant results only in females (OR, 1.63 P = 1.5 × 10-4) but not in males (OR, 1.15 P = 2.8 × 10-1), with a statistically significant difference in female to male OR comparison (P = 1.4 × 10-4). This study demonstrated that female sex is a risk factor for developing advanced NTG. The stronger genetic signals at the 9p21 locus among females may contribute at least in part to the observed sex bias for NTG.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2013
Publisher: Springer Science and Business Media LLC
Date: 05-2000
DOI: 10.1038/EYE.2000.83
Abstract: Vigabatrin (Sabril), a drug that blocks GABA transaminase, has been used in the treatment of epilepsy since 1989. There have been reports of irreversible constriction of the visual field in adult patients related to vigabatrin (VGB) therapy, resulting in reduced VGB usage in adults. Although used as a second or third line agent in adults, in children it is often considered as a first line treatment for several subgroups of seizures in spite of there being no way, in the majority of cases, to monitor visual fields. Some of these children have a pre-existing visual field defect as part of their primary disorder. We aimed to identify whether visual field loss due to VGB was occurring in our hospital. We have studied the results of ophthalmic examination in 14 children on VGB at Great Ormond Street Hospital who were able to perform Goldmann visual fields. Ten of the 14 patients had constriction of their visual fields attributed to VGB. In addition there were 2 patients with suspicious visual field defects thought to be due to VGB. There was pre-existing visual pathway damage in 4 cases and in 2 of these optic disc pallor increased in association with constricted visual fields. However, the optic discs were normal in 7 patients in spite of visual field constriction. Visual acuity was generally normal in spite of gross visual field constriction. We believe that VGB should be used with great caution where there is pre-existing visual pathway damage. In other cases the benefits should be considered in relation to the risks, which include irreversible visual field damage. At present visual fields can only be monitored by perimetry, which is often not possible in children with epilepsy.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.OPHTHA.2012.04.020
Abstract: To summarize relevant evidence investigating the association between time spent outdoors and myopia in children and adolescents (up to 20 years). Systematic review and meta-analysis. Results from 7 cross-sectional studies were pooled in a meta-analysis. A further 16 studies (8 cross-sectional not meeting criteria for meta-analysis 7 prospective cohort studies 1 randomized, controlled trial [RCT]) were reported in the systematic review. The literature search included 4 databases (Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials [CENTRAL]), and reference lists of retrieved studies. Estimates of association were pooled using random effects meta-analysis. We summarized data examining the association between time spent outdoors and prevalent myopia, incident myopia, and myopic progression. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for myopia for each additional hour spent outdoors per week from a meta-analysis. The pooled OR for myopia indicated a 2% reduced odds of myopia per additional hour of time spent outdoors per week, after adjustment for covariates (OR, 0.981 95% CI, 0.973-0.990 P<0.001 I(2), 44.3%). This is equivalent to an OR of 0.87 for an additional hour of time spent outdoors each day. Three prospective cohort studies provided estimates of risk of incident myopia according to time spent outdoors, adjusted for possible confounders, although estimates could not be pooled, and the quality of studies and length of follow-up times varied. Three studies (2 prospective cohort and 1 RCT) investigated time spent outdoors and myopic progression and found increasing time spent outdoors significantly reduced myopic progression. The overall findings indicate that increasing time spent outdoors may be a simple strategy by which to reduce the risk of developing myopia and its progression in children and adolescents. Therefore, further RCTs are warranted to investigate the efficacy of increasing time outdoors as a possible intervention to prevent myopia and its progression.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-2010
DOI: 10.1167/IOVS.09-4786
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-2009
DOI: 10.1167/IOVS.09-3577
Publisher: Springer Science and Business Media LLC
Date: 13-12-2022
Publisher: Wiley
Date: 29-07-2003
Publisher: Public Library of Science (PLoS)
Date: 23-09-2014
Publisher: Oxford University Press (OUP)
Date: 10-05-2006
DOI: 10.1093/HMG/DDL120
Abstract: Nance-Horan syndrome, characterized by congenital cataracts, craniofacial, dental abnormalities and mental disturbances, is an X-linked disorder with significant phenotypic heterogeneity. Affected in iduals have mutations in the NHS (Nance-Horan syndrome) gene typically resulting in premature truncation of the protein. This report underlines the complexity of the regulation of the NHS gene that transcribes several isoforms. We demonstrate the differential expression of the two NHS isoforms, NHS-A and NHS-1A, and differences in the subcellular localization of the proteins encoded by these isoforms. This may in part explain the pleiotropic features of the syndrome. We show that the endogenous and exogenous NHS-A isoform localizes to the cell membrane of mammalian cells in a cell-type-dependent manner and that it co-localizes with the tight junction (TJ) protein ZO-1 in the apical aspect of cell membrane in epithelial cells. We also show that the NHS-1A isoform is a cytoplasmic protein. In the developing mammalian lens, we found continuous expression of NHS that became restricted to the lens epithelium in pre- and postnatal lens. Consistent with the in vitro findings, the NHS-A isoform associates with the apical cell membrane in the lens epithelium. This study suggests that disturbances in intercellular contacts underlie cataractogenesis in the Nance-Horan syndrome. NHS is the first gene localized at TJs that has been implicated in congenital cataracts.
Publisher: Informa UK Limited
Date: 20-04-2017
DOI: 10.3109/13816810.2016.1164195
Abstract: Hereditary hyperferritinemia-cataract syndrome (HHCS) is an autosomal dominant Mendelian disorder characterized by early onset cataracts and elevated levels of serum ferritin in the absence of iron overload. Numerous mutations associated with the development of HHCS have been reported in the 5' non-coding region of the ferritin light chain (FTL) gene in family studies. We present an FTL mutation in an Australian family with 10 HHCS-affected members spanning three generations. Blood and saliva s les were collected from affected and unaffected family members and DNA was extracted using commercially available kits (Qiagen). The complete sequencing of the iron-responsive element (IRE) of the FTL gene was analyzed using bi-directional genomic sequencing. A heterozygous single nucleotide substitution (c.-167 C>T) was identified in the proband and five affected family members (logarithm of the odds score [Z] = 3.61, recombination distance [θ = 0]). All affected in iduals had previously been found to have high ferritin levels and early onset cataracts. This is the first Australian report of the c.-167 C>T mutation in a large family with multiple affected in iduals. This finding raises the possibility that identification of HHCS mutations may be an effective means of disease detection and may aid in facilitating appropriate genetic counseling.
Publisher: Springer Science and Business Media LLC
Date: 06-04-2016
DOI: 10.1038/NCOMMS11008
Abstract: Myopia is the most common human eye disorder and it results from complex genetic and environmental causes. The rapidly increasing prevalence of myopia poses a major public health challenge. Here, the CREAM consortium performs a joint meta-analysis to test single-nucleotide polymorphism (SNP) main effects and SNP × education interaction effects on refractive error in 40,036 adults from 25 studies of European ancestry and 10,315 adults from 9 studies of Asian ancestry. In European ancestry in iduals, we identify six novel loci ( FAM150B-ACP1 , LINC00340 , FBN1 , DIS3L-MAP2K1 , ARID2-SNAT1 and SLC14A2 ) associated with refractive error. In Asian populations, three genome-wide significant loci AREG , GABRR1 and PDE10A also exhibit strong interactions with education ( P .5 × 10 −5 ), whereas the interactions are less evident in Europeans. The discovery of these loci represents an important advance in understanding how gene and environment interactions contribute to the heterogeneity of myopia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2011
Publisher: Wiley
Date: 26-03-2003
DOI: 10.1002/AJMG.A.20135
Abstract: The penetrance in Leber's hereditary optic neuropathy (LHON) pedigrees is determined primarily by a mutation in the mitochondrial genome (mtDNA), but secondary factors are also necessary for manifestation of the disorder. It has been proposed that mtDNA polymorphisms affect penetrance in LHON pedigrees. In particular, it has been postulated that one or more polymorphisms associated with European haplogroup J mtDNAs substantially increase the penetrance of the primary LHON mutation at nucleotide 14484. We report here a haplogroup H matrilineal pedigree (VIC14) in which the single affected member carries the 14484 LHON mutation, but who manifested a milder and atypical optic nerve disorder. In addition, during a population screen, we identified an in idual who carried the 14484 mutation but who had normal vision. Finally, the 14484 mutation is under-represented among haplogroup H mtDNAs that carry a LHON mutation. These results, in conjunction with other studies that are reviewed, indicate that 14484 LHON mutations have a low penetrance when they arise in a haplogroup H mtDNA background.
Publisher: Springer Science and Business Media LLC
Date: 24-11-2017
DOI: 10.1038/S41467-017-00837-5
Abstract: Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1 , that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically erse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.
Publisher: Springer Science and Business Media LLC
Date: 28-05-2018
Publisher: Wiley
Date: 18-08-2011
DOI: 10.1111/J.1442-9071.2011.02626.X
Abstract: Ophthalmic population-based studies have been used to establish the frequency of eye disease and the associated environmental and genetic factors that cause vision impairment and blindness. Most of these studies have concentrated on the diseases of ageing: cataract, age-related macular degeneration, glaucoma and diabetic retinopathy. Other studies have identified eye diseases in children but few studies of young adult eye disease exist. We conducted a systematic review of the ophthalmic literature to identify potential population-based eye studies and then note the age of participants in the studies. We then summarized the disease specific to young adults to show there is a need for further research to identify eye disease in this important and often-neglected group in the community. Eighty-four large population-based studies have been conducted worldwide: 9 in North America, 2 in South America, 17 in Africa, 35 in Asia, 11 in Australia and the Pacific, 6 in Europe, 4 in the Middle East and 1 that covered 3 continents. No studies specifically examined young adults. Twenty-six per cent of studies included young adults as part of all ages examined but none of these examined a large number of young adults.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.OPHTHA.2010.09.002
Abstract: Optic nerve morphology is affected by genetic and acquired disease. Glaucoma is the most common optic neuropathy autosomal-dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON) are the most prevalent hereditary optic neuropathies. These 3 entities can exhibit similar topographical changes at the optic nerve head. Both ADOA and LHON have been reported to be misdiagnosed as glaucoma. Our aim was to determine whether glaucoma subspecialists and neuro-ophthalmologists can distinguish these diagnoses on optic disc assessment alone. Observational study. Twenty-three optic nerve experts. We randomized and masked 60 high-resolution stereoscopic optic disc photographs (15 ADOA images, 15 LHON, 15 glaucoma, and 15 normal controls). Experts were asked to assess the discs on 12 conventional topographic features and assign a presumptive diagnosis. Intra- and interanalysis was performed using the index of qualitative variation and absolute deviation. Can glaucoma specialists and neuro-ophthalmologists distinguish among the disease entities by optic nerve head phenotype. The correct diagnosis was identified in 85%, 75%, 27%, and 16% of the normal, glaucoma, ADOA, and LHON disc groups, respectively. The proportion of correct diagnoses within the ADOA and LHON groups was significantly lower than both normal and glaucomatous (P<0.001). Where glaucoma was chosen as the most likely diagnosis, 61% were glaucomatous, 34% were pathologic but nonglaucomatous discs, and 5% were normal. There was greater agreement for in idual parameters assessed within the normal disc set when compared with pathologic discs (P<0.05). The only parameter to have a significantly greater agreement within the glaucomatous disc set when compared with ADOA or LHON disc sets was pallor, whereby experts agreed on is absence in the glaucomatous discs but were not in agreement on its presence or its absence in the ADOA and LHON discs (P<0.01). Optic neuropathies can result in similar topographic changes at the optic disc, particularly in late-stage disease, making it difficult to differentiate ADOA and LHON from glaucoma based on disc assessment alone. Other clinical parameters such as acuity, color vision, history of visual loss, and family history are required to make an accurate diagnosis.
Publisher: Springer Science and Business Media LLC
Date: 23-08-2022
DOI: 10.1038/S41433-021-01749-X
Abstract: Eye colour and colour perception are excellent ex les to use when teaching genetics as they encompass not simply the basic Mendelian genetics of dominant, recessive and X-linked disorders, but also many of the new concepts such as non-allelic diseases, polygenic disease, phenocopies, genome-wide association study (GWAS), founder effects, gene-environment interaction, evolutionary drivers for variations, copy number variation, insertions deletions, methylation and gene inactivation. Beyond genetics, colour perception touches on concepts involving optics, physics, physiology and psychology and can capture the imagination of the population, as we saw with social media trend of “#the dress”. Television shows such as Game of Thrones focused attention on the eye colour of characters, as well as their Dire-wolves and Dragons. These themes in popular culture can be leveraged as tools to teach and engage everyone in genetics, which is now a key component in all eye diseases. As the explosion of data from genomics, big data and artificial intelligence transforms medicine, ophthalmologists need to be genetically literate. Genetics is relevant, not just for Inherited Retinal Diseases and congenital abnormalities but also for the leading causes of blindness: age-related macular degeneration, glaucoma, myopia, diabetic retinopathy and cataract. Genetics should be part of the armamentarium of every practicing ophthalmologist. We need to ask every patient about their family history. In the near future, patients will attend eye clinics with genetic results showing they are at high risk of certain eye diseases and ophthalmologists will need to know how to screen, follow and treat these patients.
Publisher: Springer Science and Business Media LLC
Date: 19-03-2020
DOI: 10.1038/S42003-020-0802-Y
Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 in iduals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11 / FBLN2 rs2630445, RBP3 rs11204213) others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.
Publisher: Wiley
Date: 2016
DOI: 10.1111/CEO.12629
Abstract: Our aim is to compare retinal sensitivity measurements obtained on two microperimeters: the CenterVue MAIA and the Nidek MP-1. A prospective study was conducted in a private ophthalmology clinic. Seventeen in iduals with a range of stable macular function were recruited as participants. Microperimetry in one eye with identical test strategy in both devices, with randomized testing order, is used. The main outcome measures include differences in mean sensitivity (MS), point-wise sensitivity (PWS) and duration. Limits of agreement (LoA) in MS and pooled PWS were calculated. Concordance in scotoma assessment was analysed by kappa (κ) agreement of local defect classification (LDC), LoA in number of scotomatous loci detected and congruence in scotoma localization (CSL). Median (interquartile range) MS of the MP-1 and MAIA was 13.3 (5.6-18.1) and 21.2 (14.5-27.0) dB, (P MP-1). Median (interquartile range) duration for the MP-1 and MAIA was 10'28″ (7'17″-11'53″) and 8'46″ (8'30″-9'06″), (P = 0.21). LoA for MS and pooled PWS was 1.4 to 13.3 dB and -3.9 to 18.5 dB. There was moderate agreement between the devices for LDC (weighted κ = 0.55, P < 0.05). LoA in number of scotomatous loci detected was -13 to 18. CSL varied from 0 to 100% and correlated strongly with increasing scotoma size. The large LoA and variation in scotoma mapping concordance suggest that the same microperimeter should be used for follow-up examination. We recommend caution in comparing results derived from different types of microperimeters.
Publisher: Wiley
Date: 27-04-2015
DOI: 10.1111/CEO.12508
Abstract: The sequencing of the human genome has seen the emergence of the direct-to-consumer (DTC) genetic-testing market, which allows in iduals to obtain information about their genetic profile and its many health and lifestyle implications. Genetics play an important role in the development of many eye diseases, however, little information is available describing the influence of the DTC industry in ophthalmology. In this review, we examined DTC companies providing genetic test products for eye disease. Of all eye conditions, the majority of DTC companies provided susceptibility testing or risk assessment for age-related macular degeneration (AMD). For the 15 companies noted to offer products, we found considerable variation in the cost, scope and clarity of informational content of DTC genetic testing for ophthalmic conditions. The clinical utility of these tests remains in question, and the American Academy of Ophthalmology recommendations against routine testing for many conditions probably still apply.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-2004
DOI: 10.1167/IOVS.03-1044
Abstract: Mutations in the frizzled-4 gene (FZD4) have recently been associated with autosomal dominant familial exudative vitreoretinopathy (FEVR) in families linking to the EVR1 locus on the long arm of chromosome 11. The purpose of this study was to screen FZD4 in a panel of 40 patients with FEVR to identify the types and location of mutations and to calculate what proportion of this heterogeneous condition is attributable to FZD4 mutations. PCR products were generated from genomic DNA with primers designed to lify the coding sequence of FZD4. The PCR products were screened for mutations by single-strand conformational polymorphism-heteroduplex analysis (SSCP-HA) and by direct sequencing. In total, eight mutations were identified, seven of which were novel. Three were deletions (c957delG, c1498delA, and c1501-1502delCT), one was a nonsense mutation (Q505X), and four were missense mutations (G36D, M105T, M157V, and S497F). Eight mutations have been identified in the FZD4 gene in a cohort of 40 unrelated patients with FEVR. This result indicates that FZD4 mutations are responsible for only 20% of FEVR index cases and suggests that the other FEVR loci may account for more cases than previously anticipated.
Publisher: Impact Journals, LLC
Date: 29-04-2017
Publisher: Swets & Zeitlinger Publishers
Date: 2001
DOI: 10.1076/OPGE.22.1.49.2240
Abstract: DNA s les are the fundamental research substrate in genetics. Although methodology and cost-effectiveness in molecular biology have improved dramatically, collecting biological s les and extracting DNA continue to be expensive and time-consuming steps of genetic research. This article reviews the issues surrounding the choice of biological s les for methods of DNA extraction as well as the storage and transport of biological and DNA s les for genetic studies.
Publisher: SPIE-Intl Soc Optical Eng
Date: 05-08-2016
Publisher: BMJ
Date: 2019
DOI: 10.1136/BMJOPHTH-2018-000215
Abstract: This study aims to evaluate the presenting characteristics, management, outcomes and complications for paediatric traumatic hyphaema in Western Australia. A retrospective review of medical records was conducted for consecutive patients ≤16 years of age admitted for traumatic hyphaema to Princess Margaret Hospital for Children (Perth, Australia) between January 2002 and December 2013 (n=82). From this s le, a cohort whose injury occurred ≥5 years prior attended a prospective ocular examination (n=16). Hospital records were reviewed for patient demographics, injury details, management, visual outcomes and complications. The prospective cohort underwent examination for visual and structural outcomes. Most injuries (72%) resulted from projectile objects. Angle recession was present in 53% and was associated with projectiles (p=0.002). Most eyes (81%) achieved a final visual acuity of 0.3 logarithm of the minimum angle of resolution (logMAR) (20/40) or better. Age ≤5 years and posterior segment injury were significant predictors of final visual acuity poorer than 0.3 logMAR. At ≥5 years post-trauma, injured eyes had greater intraocular pressure (IOP) (p=0.024) and anterior chamber depth (ACD) (p=0.022) compared with sound eyes. IOP asymmetry was associated with angle recession (p=0.008) and ACD asymmetry (p=0.012). Poorer visual outcomes are associated with younger age at injury and posterior segment injury. Angle recession and ACD asymmetry are associated with IOP asymmetry 5–12 years after injury.
Publisher: American Medical Association (AMA)
Date: 02-2020
Publisher: American Medical Association (AMA)
Date: 04-2019
Publisher: Wiley
Date: 11-09-2020
DOI: 10.1111/CEO.13844
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
DOI: 10.1016/J.JCRS.2013.07.055
Abstract: To compare the monochromatic aberrations in a large cohort of 20-year-old Australians with differing levels of visual acuity and explore the relationship between these aberrations and refractive error. Lions Eye Institute, Perth, Western Australia, Australia. Cross-sectional analysis of a population-based cohort. Monochromatic aberrations were measured using a Zywave II wavefront aberrometer with natural pupils in a dark room. The logMAR corrected distance visual acuity (CDVA) was measured monocularly under normal illumination. Cycloplegic autorefraction was also performed. The study enrolled 2039 eyes of 1040 participants. Data from 1007 right eyes were analyzed. The median CDVA and spherical equivalent were -0.06 logMAR (interquartile range [IQR], -0.10 to 0.00) and +0.25 diopters (D) (IQR, -0.38 to 0.63), respectively. The median 6.0 mm higher-order aberration (HOA) was 0.58 μm (IQR, 0.44 to 0.79). Coma-like aberrations and 3rd-, 4th-, and 5th-order HOAs were significantly different between subjects with a CDVA of -0.10 logMAR or better and those with a CDVA worse than -0.10 logMAR. Fourth-order aberrations Z(4,-4) (P=.024) and Z(4,-2) (P=.029) and 2nd-order aberration Z(2,0) (P<.001) differed significantly between myopic eyes, emmetropic eyes, and hyperopic eyes. Subjects with higher myopia had slightly higher total HOAs. The HOAs in this population were marginally higher than previously reported values. The findings confirm there is a difference in monochromatic aberrations between different vision and refractive groups. Results in this study will benefit decision-making processes in the clinical setting.
Publisher: Wiley
Date: 26-10-2016
DOI: 10.1002/GEPI.21936
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.SURVOPHTHAL.2015.05.003
Abstract: Eye injury remains the leading cause of monocular blindness in children despite 90% of injuries being potentially preventable. Children interact with animals in a variety of situations, and the associated dangers may be underestimated. Animals are capable of causing ocular and adnexal injuries that are cosmetically and visually devastating. We examine the current literature regarding the nature and severity of animal-inflicted ocular and adnexal injuries in children.
Publisher: Springer Science and Business Media LLC
Date: 14-06-2016
DOI: 10.1007/S10561-016-9563-8
Abstract: The ability to generate human induced pluripotent stem cells (iPSCs) has opened new avenues for human disease modelling and therapy. The aim of our study was to determine research participants' understanding of the information given when donating skin biopsies for the generation of patient-specific iPSCs. A customised 35-item questionnaire based on previous iPSC consent guidelines was sent to participants who had previously donated s les for iPSC research. The questionnaire asked pertinent demographic details, participants' motivation to take part in iPSC research and their attitudes towards related ethical issues. 234 participants were contacted with 141 (60.3 %) complete responses received. The median duration between recruitment and follow-up questioning was 313 days (range 10-573 days). The majority of participants (n = 129, 91.5 %) believed they understood what a stem cell was however, only 22 (16.1 %) correctly answered questions related to basic stem cell properties. We found no statistically significant difference in responses from participants with different levels of education, or those with a health sciences background. The poor understanding amongst participants of iPSC research is unlikely to be unique to our study and may impact future research if not improved. As such, there is a need to develop an easily understood yet comprehensive consent process to ensure ongoing ethical progress of iPSC biobanking.
Publisher: Wiley
Date: 16-03-2011
DOI: 10.1111/J.1442-9071.2010.02487.X
Abstract: Eye colour or, more accurately, iris colour is one of the most obvious physical characteristics of a person. European parents frequently ask the colour of their newborn's eyes, only to see the iris change dramatically during their child's first year of life. Genetic and epidemiological findings have uncovered further details about the basis for iris colour, which may have important implications for further research and treatment of some eye diseases and ocular characteristics. Surprisingly there is no widely recognized classification system for eye colour. An added difficulty when trying to devise an international system is that subtle differences in colour description exist between languages (e.g. hazel vs. auburn). We reviewed the recent and very early literature pertaining to eye colour classification. Recent genetic investigations of eye colour have tended to either use simple (three-category grading systems) or more complex digital colour grading. We present a nine-category grading system. Categories in this novel schema include: (i) light blue (ii) darker blue (iii) blue with brown peripupillary ring (iv) green (v) green with brown iris ring (vi) peripheral green central brown (vii) brown with some peripheral green (viii) brown and (ix) dark brown. Although different observers may categorize a person's eye colour differently, it is generally only by an adjacent category. We also describe a continuum of iris pigmentation from a small ring of brown around the pupil to almost complete brown with small peripheral flecks. Digital publishing and assessment of iris colour will result in more standardized classification of iris colour and investigation of its role in eye disease.
Publisher: Springer Science and Business Media LLC
Date: 07-2010
Publisher: Cold Spring Harbor Laboratory
Date: 22-10-2021
DOI: 10.1101/2021.10.19.21264544
Abstract: Integrating polygenic risk scores (PRS) into healthcare has the potential to stratify an in idual’s risk of glaucoma across a broad population. Glaucoma is the most common cause of irreversible blindness worldwide, therefore effective screening for glaucoma endorsed by the population is highly important. This study assessed the attitude of unaffected in iduals towards PRS testing for glaucoma, and sought to identify factors associated with interest in testing. We surveyed 418 unaffected in iduals including those with a first-degree relative with glaucoma (n=193), those who had a recent eye examination (n=117), and general members of the community (n=108). Overall, 71.3% indicated an interest in taking a polygenic risk test for glaucoma. Interest was more likely in those who believed glaucoma to be a severe medical condition (OR 14.58, 95%CI (1.15-185.50), p=0.039), those concerned about developing glaucoma (OR 4.37, 95%CI (2.32-8.25), p .001), those with an intention to take appropriate measures regarding eye health (OR 2.39, 95%CI (1.16-4.95), p=0.019), and those preferring to know if considered to be at-risk or not (OR 4.52, 95%CI (2.32-8.83), p .001). These findings represent a valuable assessment of general public interest in glaucoma polygenic risk testing, which will be integral to the implementation and uptake of novel PRS based tests into clinical practice.
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/09286580590964784
Abstract: To demonstrate that use of a mydriatic agent remains a significant confounder in autorefraction of the presbyopic population. The pre- and post-cycloplegic autorefraction results of 37 subjects over 50 years of age were measured using a Humphrey-598 autorefractor. The results of both eyes were included in a multivariate regression analysis. The average age of the patient s le was 63.4 years. The mean spherical equivalent (SEQ) shifts for the hyperopic, myopic, pseudophakic, and emmetropic eyes were -0.53 D (95% CI -0.77 D to -0.39 D p < 0.001), -0.38 D (95%CI -0.81 D to +0.04 D p = 0.077), -0.49 D (95% CI -0.78 D to -0.20 D p = 0.001), and -0.35 D (95% CI -0.59 D to -0.11 D p = 0.004), respectively. Cyclopleged autorefraction in the presbyopic population is associated with a myopic shift that can potentially lead to overestimation of myopic prevalence. This is an important factor in comparing population studies where cyclogleged autorefraction is used in contrast to non-cyclopleged autorefraction and subjective refraction.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-2010
DOI: 10.1167/IOVS.10-5527
Publisher: Informa UK Limited
Date: 10-01-2013
DOI: 10.3109/13816810.2012.755632
Abstract: The Raine Eye Health Study (REHS) was conceived to determine the prevalence of and risk factors for eye disease in young adults, and to characterize ocular biometric parameters in a young adult cohort. This article summarizes the rationale and study design of REHS and outlines the baseline prevalence of ophthalmic disease in this population. The Western Australian Pregnancy Cohort (Raine) Study originated as a randomized-controlled trial of 2900 women recruited from the state's largest maternity hospital. Their offspring (N = 2868) have been followed at birth, ages 1, 2, 3, 5, 8, 10, 14, 17 and 20 years of age in a prospective cohort study. DNA has been collected from participants for genome-wide association studies. At the 20-year follow-up participants completed a comprehensive eye assessment that included visual acuity, orthoptic assessment and cycloplegic autorefraction, as well as several ocular biometric variables and multiple ophthalmic photographs of the anterior and posterior segments. A total of 1344 participants (51.3% male) were assessed over a 24-month period. For the majority of examined participants (85.5%) both parents were Caucasian, 63.3% had completed school year 12 or equivalent, 5.5% had myopia (spherical equivalent ≤-3 diopters) and 15 participants (1.2%) had unilateral or bilateral pterygia. Keratoconus, cataract, keratitis and uveitis were rare. The REHS design and methodology allow comparison with other population-based studies of eye disease. The study established the prevalence of eye disorders in a large s le of predominantly Caucasian young Australian adults.
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/CEO.13736
Publisher: Wiley
Date: 13-01-2015
DOI: 10.1111/AOS.12644
Abstract: Astigmatism is a common cause of refractive error and is known to vary in prevalence with age. Although the search for genes associated with spherical refractive errors (especially myopia) has met with limited success, current efforts to identify genetic variants implicated in astigmatism development have been less rewarding. We aimed to assess the association between astigmatism and age to identify appropriate age cut‐offs for maximizing power in genetic studies of astigmatism. We performed a cross‐sectional analysis of right eye astigmatism data from four Australian‐based eye studies comprising 3841 participants aged 5–90 years. Measurements were performed under cycloplegia using an autorefractor, and in iduals with a history of cataract, refractive surgery or corneal pathology were excluded from the analysis. In addition to the magnitude and type (against‐the‐rule, with‐the‐rule, and oblique) of astigmatism, we calculated the vector components (J 0 , J 45 ) and evaluated the association of these outcome measures with age. The magnitude of refractive astigmatism ( RA ) remained relatively stable [mean ± SD (−0.44 D ± 0.50)] until in iduals reached the age of 50, thereafter increasing in average magnitude by approximately 1.00 D for those subjects aged 90. In contrast, corneal astigmatism ( CA ) remained relatively stable from childhood until the age of 80 (−0.76 D ± 0.61). The prevalence of clinically significant RA (≥1.00 D) increased with age and was highest in those aged years [55.1% (47.2–62.7%)]. Age was significantly associated with RA in adults [odds ratio ( OR ) = 1.04 per 1 year, p 0.001]. A weaker relationship was observed between CA and age ( OR = 1.007 per 1 year, p = 0.02). We have confirmed the previously documented association between RA and age. Our results indicate that most of the observed change occurs after the age of 50, providing a recommended cut‐off for participants in genetic studies of this refractive condition.
Publisher: Informa UK Limited
Date: 03-05-2021
Publisher: Informa UK Limited
Date: 27-09-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2004
DOI: 10.1097/00061198-200408000-00008
Abstract: Glaucoma is a major cause of visual impairment and blindness in developed countries. Half of those with glaucoma are unaware that they have the disease. Mutations in the myocilin (MYOC) gene are responsible for 3 to 5% of primary open angle glaucoma, thus predictive DNA testing in family members of some glaucoma pedigrees is possible. We wished to determine the attitudes of affected and unaffected family members to the use of predictive DNA testing in glaucoma. We surveyed the attitudes of family members from one such pedigree to determine the acceptability of predictive DNA testing. We studied 72 members of a large family in which the MYOC mutation, THR377MET, segregates. Family members were examined over an 8-year period as part of research initiated to identify the gene. Once the mutation was identified, we offered participants the result of their DNA test after a genetic counseling session. Family members were subsequently given a questionnaire about the counseling and DNA result. Most wished to know their result after counseling 26 of 27 (96%) felt the genetic counseling session was necessary, but participants' attitudes varied as to whether they preferred this in person, by phone, or letter. Forty three patients were resurveyed 5 years after their initial counseling session. No adverse problems relating to the predictive testing were reported, though two had been asked about DNA testing by insurance companies 5 of 24 (21%) in iduals who had been informed they did not carry the mutation were unsure if they carried the mutation 5 years after counseling, while all 19 mutation carriers (who were being examined annually) correctly recalled their mutation status. This study suggests that predictive glaucoma testing in appropriate circumstances is acceptable to patients and their families.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.SURVOPHTHAL.2010.07.003
Abstract: Heritability is the proportion of phenotypic variation in a population that is attributable to genetic variation among in iduals. Many ophthalmic disorders and biometric traits are known to have a genetic basis and consequently much work has been published in the literature estimating the heritability of various ocular parameters. We collated and summarized the findings of heritability studies conducted in the field of ophthalmology. We grouped the various studies broadly by phenotype as follows: refraction, primary open-angle glaucoma, age-related macular degeneration (AMD), cataract, diabetic retinopathy, and others. A total of 82 articles were retrieved from the literature relating to estimation of heritability for an ocular disease or biometric trait of these, 37 papers were concerned with glaucoma, 28 with refraction, 4 with AMD, 5 with diabetic retinopathy, and 4 with cataract. The highest reported heritability for an ophthalmic trait is 0.99 for the phenotype ≥ 20 small hard drusen, indicating that observed variation in this parameter is largely governed by genetic factors. Over 60% of the studies employed a twin study design and a similar percentage utilized variance components methods and structural equation modeling (SEM) to derive their heritability values. Using modern SEM techniques, heritability estimates derived from twin subjects were generally higher than those from family data. Many of the estimates are in the moderate to high range, but to date the majority of genetic variants accounting for these findings have not been uncovered, hence much work remains to be undertaken to elucidate fully their molecular etiology.
Publisher: American Medical Association (AMA)
Date: 02-2022
Publisher: Springer Science and Business Media LLC
Date: 23-03-2002
DOI: 10.1007/S00439-002-0707-5
Abstract: The diagnosis of congenital fibrosis of the extraocular muscles (CFEOM) encompasses several different inherited strabismus syndromes characterized by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. The OMIM database (www.ncbi.nlm.nih.gov/Omim/) currently contains four familial CFEOM phenotypes: CFEOM1-3, which map to the FEOM1-3 loci (MIM 135600, 602078, 604361), respectively, and congenital fibrosis of the vertically acting extraocular muscles (MIM 600638), reported in a single family without a corresponding genotype. We have had the opportunity to study the reported family with this fourth phenotype and now demonstrate that their phenotype can be reclassified as CFEOM3 and that it maps to FEOM3, flanked by D16S498 to 16qter, with a maximum lod score of 6.0.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.OPHTHA.2012.11.029
Abstract: To determine the proportion of all Myocilin coding mutations responsible for advanced primary open-angle glaucoma (POAG) in early-age-at-onset in iduals and to investigate the prevalence of exon 3 Myocilin mutations in advanced POAG at any age at onset in a large Australasian cohort. Cross-sectional study using a national disease registry. One thousand sixty in iduals with advanced POAG (103 with age at onset of 40 years or younger) and 320 with nonadvanced POAG all recruited by the Australian and New Zealand Registry of Advanced Glaucoma. Participants were examined and referred by their eye practitioner, and Myocilin genetic testing was performed by direct sequencing. Cascade genetic testing was made available for relatives of participants found to carry a Myocilin mutation. Advanced glaucoma diagnosis based on strict visual field entry criteria. Prevalence and spectrum of Myocilin mutations in in iduals with advanced and nonadvanced POAG. This is the first study to report Myocilin mutations in an advanced POAG cohort. No pathogenic Myocilin mutations were identified in exons 1 and 2 in early-age-at-onset advanced POAG cases. Exon 3 Myocilin mutations were identified in 45 advanced POAG patients (4.2%), which is significantly higher (P = 0.02) compared with nonadvanced POAG patients (1.6%). A novel mutation (Trp373X) and a new variant of uncertain pathogenicity (Ala447Thr) also were reported. The prevalence of Myocilin mutations rose from 16% to 40% in selected advanced POAG subgroups based on different thresholds of maximum recorded intraocular pressure, age at diagnosis, and the presence and strength of positive family history. Twenty-six in iduals with Myocilin mutations were identified through cascade genetic testing of first-degree relatives of affected mutation carriers. The prevalence of Myocilin mutations in glaucoma cases with severe visual field loss is significantly greater than in nonadvanced glaucoma patients. Myocilin screening in phenotypically selected cases can have a much higher yield than in previous unselected series. Identifying in iduals who have Myocilin mutations provides an opportunity to screen at-risk clinically unaffected relatives and to reduce glaucoma blindness through early management and intervention. The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Publisher: Springer Science and Business Media LLC
Date: 11-08-2021
DOI: 10.1186/S12889-021-11578-Y
Abstract: Chronic medical conditions accumulate within in iduals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive in idual phenotyping in a general population of Australian middle-aged adults. Participants ( n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. The in idual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0–13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence 1.5% and O/E 1.5. Of the triplets, arthritis ( 50%), bowel disease ( 33%) and depression-anxiety ( 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) “Healthy” (70%) with average of 1.95 conditions 2) “Respiratory and Atopy” (11%, 3.65 conditions) 3) “Non-cardiometabolic” (14%, 4.77 conditions), and 4) “Cardiometabolic” (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in in iduals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.
Publisher: Oxford University Press (OUP)
Date: 05-1999
DOI: 10.1093/HMG/8.5.899
Abstract: A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.
Publisher: Oxford University Press (OUP)
Date: 11-02-2014
DOI: 10.1093/HMG/DDU050
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-2008
DOI: 10.1167/IOVS.07-1397
Abstract: To estimate the heritability of the iridotrabecular angle width measured by anterior segment optical coherence tomography (ASOCT) in a classic twin study. Twins aged 8 to 16 years were identified from the Guangzhou Twin Registry. ASOCT was used to obtain one horizontal scan, and the images were analyzed with custom software. Angle width was represented by the angle opening distance (AOD) at the 500-microm anterior-to-scleral spur, as well as the angle recess area (ARA) and trabecular-iris space area (TISA) located 750 microm anterior to the scleral spur. Zygosity was confirmed by genotyping with 16 polymorphic markers in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling after adjustment for age and sex, with the Mx program. The mean age of the participants was 11.7 +/- 2.6 years in 305 monozygotic (MZ) and 11.8 +/- 2.4 years in 157 dizygotic (DZ) pairs. The intraclass correlation coefficients for the AOD, ARA, and TISA were 0.70, 0.75, and 0.72 in the MZ pairs and 0.34, 0.32, and 0.33 in the DZ pairs, respectively. A model with additive genetic (69.7% 95% CI: 63.9%-74.6%) and unique environmental effects (30.3% 95% CI: 25.4%-36.1%) was the most parsimonious for AOD. Similar results were identified for ARA and TISA. The variance in drainage angle width in Chinese children appears to be largely attributable to genetic effects, with a heritability of approximately 70%.
Publisher: Wiley
Date: 19-08-2021
DOI: 10.1111/CEO.13980
Abstract: The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle‐aged Australian adults over approximately a 20‐year period. Two contemporary Western Australian studies (conducted in mid‐late 2010s): the coastal‐regional Busselton Healthy Ageing Study (BHAS) and the urban Gen1 of the Raine Study (G1RS) were compared to two earlier studies (early‐mid 1990s) in Australia: the urban Blue Mountains Eye Study (BMES) and urban/regional Melbourne Visual Impairment Project (MVIP). Refractive error was measured by autorefraction, vertometry, or subjective refraction. Participants (49–70 years) of European descent without self‐reported/diagnosed cataract, corneal disease, or refractive or corneal surgery were included. After exclusions, data were available from 2217, 1760, 700, 2987 and 756 participants from BMES, urban MVIP, regional MVIP, BHAS, and G1RS, respectively. The mean age ranged from 57.1 ± 4.6 years in the G1RS to 60.1 ± 6.0 years in the BMES 44–48% of participants were male. When stratified by location, the contemporary urban G1RS cohort had a higher age‐standardised myopia prevalence than the urban MVIP and BMES cohorts (29.2%, 16.4%, and 23.9%, p 0.001). The contemporary coastal‐regional BHAS had a higher age‐standardised myopia prevalence than the regional MVIP cohort (19.4% vs. 13.8%, p = 0.001). We report an increase in myopia prevalence in older adults in Australia born after World War ll compared to cohorts born before, accounting for urban/regional location. The prevalence of myopia remains relatively low in middle‐aged Australian adults.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.MATURITAS.2022.05.002
Abstract: Worldwide, glaucoma affects about 3% of the population over the age of 50 years and is a leading cause of irreversible visual impairment among older people. Because glaucoma is asymptomatic in its early stages and can be challenging to diagnose clinically, it often remains undiagnosed until substantial vision loss has occurred. Efficient methods of glaucoma screening are therefore warranted for early detection of disease. Identification of risk factors for glaucoma - family history of glaucoma, older age, African or Asian ethnicities, raised intraocular pressure, and thin corneas - have helped inform guidelines on the recommended age at commencement and frequency of glaucoma screenings. A genetic predisposition or family history of glaucoma is one of the most important risk factors for the disease. However, an accurate family history cannot always be ascertained. Genetic testing for genes such as myocilin could help to identify high-risk in iduals and, with further research, could even provide insight into in idual patients' response to treatment. With the ongoing discovery of glaucoma-associated genes and the advent of polygenic risk scores to identify in iduals at high risk of glaucoma, gene-based screening for glaucoma is becoming closer to realisation. In the meantime, regularly screening family members of people with existing glaucoma is an efficient way of detecting early glaucoma. Raising public awareness of glaucoma is also necessary to educate the general public on the key role of routine eye examinations and early disease detection. Future studies should be undertaken to explore efficient public health c aign methods for improving glaucoma awareness.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-01-2018
DOI: 10.1167/TVST.7.1.6
Publisher: Oxford University Press (OUP)
Date: 30-01-2015
DOI: 10.1093/HMG/DDV027
Abstract: Primary open-angle glaucoma (POAG) is a blinding disease. Two important risk factors for this disease are a positive family history and elevated intraocular pressure (IOP), which is also highly heritable. Genes found to date associated with IOP and POAG are ABCA1, CAV1/CAV2, GAS7 and TMCO1. However, these genes explain only a small part of the heritability of IOP and POAG. We performed a genome-wide association study of IOP in the population-based Rotterdam Study I and Rotterdam Study II using single nucleotide polymorphisms (SNPs) imputed to 1000 Genomes. In this discovery cohort (n = 8105), we identified a new locus associated with IOP. The most significantly associated SNP was rs58073046 (β = 0.44, P-value = 1.87 × 10(-8), minor allele frequency = 0.12), within the gene ARHGEF12. Independent replication in five population-based studies (n = 7471) resulted in an effect size in the same direction that was significantly associated (β = 0.16, P-value = 0.04). The SNP was also significantly associated with POAG in two independent case-control studies [n = 1225 cases and n = 4117 controls odds ratio (OR) = 1.53, P-value = 1.99 × 10(-8)], especially with high-tension glaucoma (OR = 1.66, P-value = 2.81 × 10(-9) for normal-tension glaucoma OR = 1.29, P-value = 4.23 × 10(-2)). ARHGEF12 plays an important role in the RhoA/RhoA kinase pathway, which has been implicated in IOP regulation. Furthermore, it binds to ABCA1 and links the ABCA1, CAV1/CAV2 and GAS7 pathway to Mendelian POAG genes (MYOC, OPTN, WDR36). In conclusion, this study identified a novel association between IOP and ARHGEF12.
Publisher: Wiley
Date: 26-10-2020
DOI: 10.1111/CEO.13866
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.SURVOPHTHAL.2008.10.003
Abstract: Quantitative studies of retinal vascular caliber using new computer-assisted retinal imaging systems have allowed physicians and researchers to understand the influence of systemic, environmental, and genetic factors on retinal vascular caliber. Retinal vascular caliber changes reflect cumulative response to aging, cardiovascular risk factors, inflammation, nitric oxide-dependent endothelial dysfunction, and other processes. Recent epidemiological studies have shown that changes in retinal arteriolar and venular caliber size may reflect the differential effects of a range of systemic, environmental, and genetic risk factors. Narrower retinal arteriolar caliber and smaller arteriovenous ratio are associated with older age higher levels of past, current, and future blood pressure and obesity and predict the incidence of diabetes and coronary heart disease. Wider retinal venular caliber, in contrast, is associated with younger age impaired fasting glucose and diabetes dyslipidemia obesity systemic marker of inflammation, endothelial dysfunction, and cigarette smoking and predicts the risk of stroke and coronary heart disease. New data from family and twin studies indicate a significant genetic contribution to retinal vascular caliber, an area that is under investigation. Elucidating the complete range of systemic, environmental, and genetic factors linked with retinal vascular caliber changes may provide critical insight into the etiology, pathogenesis, and natural history of early vascular disease not only in the eye but elsewhere in the body.
Publisher: Wiley
Date: 10-01-2021
DOI: 10.1111/AOS.14709
Abstract: To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25‐hydroxyvitamin D [25(OH)D] concentration as a biomarker of time spent outdoors. Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6‐, 14‐, 17‐ and 20‐year follow‐ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent −0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age‐specific 25(OH)D concentrations. Linear mixed‐effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years. After adjusting for sex, race, parental myopia, body mass index and studying status, myopia at 20 years was associated with lower 25(OH)D concentration at 20 years (per 10 nmol/L decrease, odds ratio (aOR)=1.10, 95% CI: 1.02, 1.18) and a low vitamin D status [25(OH)D 50 nmol/L] at 17 years (aOR = 1.71, 95% CI: 1.06, 2.76) and 20 years (aOR = 1.71, 95% CI: 1.14, 2.56), compared to those without low vitamin D status. There were no associations between 25(OH)D at younger ages and myopia. In iduals who were myopic at 20 years had a 25(OH)D concentration trajectory that declined, relative to non‐myopic peers, with increasing age. Differences in 25(OH)D trajectory between in iduals with and without myopia were greater among non‐Caucasians compared to Caucasians. Myopia in young adulthood was most strongly associated with recent 25(OH)D concentrations, a marker of time spent outdoors.
Publisher: Wiley
Date: 16-03-2020
DOI: 10.1111/CEO.13741
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 12-2019
Publisher: Wiley
Date: 08-1992
DOI: 10.1111/J.1442-9071.1992.TB00937.X
Abstract: Leber hereditary optic neuropathy (LHON) presents with sudden onset of visual loss mainly in young adult males. LHON is not uncommon in Australia, accounting for 2% of invalid blind pensions. We have identified 20 unrelated families carrying mitochondrial DNA mutations associated with LHON and 135 of 291 in iduals with documented LHON are currently alive in Australia. The mean age of onset of visual loss for males was 26 years and for females 27 years, with a range from six to 65 years. The mean risk of visual loss was 20% for males and 4% for females. There are over 1750 male and female carriers living in Australia who have not yet lost vision 600 carriers are under 24 years of age. The expected number of new cases of blindness from LHON is three to four per year.
Publisher: Springer Science and Business Media LLC
Date: 02-2017
DOI: 10.1038/NATURE21039
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1086/302049
Publisher: Elsevier BV
Date: 05-2009
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 24-05-2013
Publisher: Wiley
Date: 11-2007
Publisher: BMJ
Date: 17-08-2006
Publisher: Informa UK Limited
Date: 2007
Publisher: Springer Science and Business Media LLC
Date: 05-08-2016
DOI: 10.1007/S00417-016-3434-7
Abstract: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis, primarily affecting medium-large arteries. It has a predilection for the aorta and its major branches, including the carotid and vertebral arteries. Ophthalmic artery involvement frequently leads to irreversible visual loss, and therefore GCA is one of the few true ophthalmic emergencies. GCA, although classified as a large vessel vasculitis, is known to affect smaller-sized vessels, resulting in a multiplicity of signs in the eye, some of which are often missed. We set out to highlight some of the less frequently observed clinical signs, which may provide clues to clinically diagnosing GCA in patients presenting with non-classical features and inconclusive inflammatory markers. We review the literature and describe the erse ocular features and some of the systemic findings that can be associated with GCA. Although the most common ocular manifestation of GCA is anterior ischaemic optic neuropathy, the clinical presentation of GCA can vary dramatically. In the absence of obvious ocular involvement, more subtle ophthalmic signs of anterior segment ischaemia, such as hypotony and anisocoria, may be present at the time of initial clinical examination. There are no specific biomarkers for disease to date therefore, pertinent history and clinical examination can guide towards diagnosis in the acute setting. The diagnostic process is not always straightforward, yet appropriate and prompt diagnosis is critical to enable timely intervention and prevent significant morbidity.
Publisher: Public Library of Science (PLoS)
Date: 03-05-2012
Publisher: BMJ
Date: 13-11-2020
DOI: 10.1136/BJOPHTHALMOL-2019-314675
Abstract: Myopia is an increasingly common condition that is associated with significant costs to in iduals and society. Moreover, myopia is associated with increased risk of glaucoma, retinal detachment and myopic maculopathy, which in turn can lead to blindness. It is now well established that spending more time outdoors during childhood lowers the risk of developing myopia and may delay progression of myopia. There has been great interest in further exploring this relationship and exploiting it as a public health intervention aimed at preventing myopia in children. However, spending more time outdoors can have detrimental effects, such as increased risk of melanoma, cataract and pterygium. Understanding how spending more time outdoors prevents myopia could advance development of more targeted interventions for myopia. We reviewed the evidence for and against eight facets of spending time outdoors that may protect against myopia: brighter light, reduced peripheral defocus, higher vitamin D levels, differing chromatic spectrum of light, higher physical activity, entrained circadian rhythms, less near work and greater high spatial frequency (SF) energies. There is solid evidence that exposure to brighter light can reduce risk of myopia. Peripheral defocus is able to regulate eye growth but whether spending time outdoors substantially changes peripheral defocus patterns and how this could affect myopia risk is unclear. Spectrum of light, circadian rhythms and SF characteristics are plausible factors, but there is a lack of solid evidence from human studies. Vitamin D, physical activity and near work appear unlikely to mediate the relationship between time spent outdoors and myopia.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.OPHTHA.2016.11.011
Abstract: To assess the difference in severity of disease in primary open-angle glaucoma (POAG) patients with a Myocilin (MYOC) disease-causing variant who presented through normal clinical pathways (Clinical cases) versus those who were examined following genetic testing (Genetic cases). Retrospective clinical and molecular study. Seventy-three MYOC mutation carriers identified through the Australian and New Zealand Registry of Advanced Glaucoma. In iduals were classified based on how they first presented to an ophthalmologist: Clinical cases were referred by their general practitioner or optometrist, and Genetic cases were referred following positive results from genetic testing for the previously identified familial MYOC variant (cascade genetic testing). All cases were then sub-classified into 4 groups (unaffected, glaucoma suspect, glaucoma, advanced glaucoma) according to the severity of disease at the time of their first examination by an ophthalmologist. Glaucoma clinical parameters and age at presentation. At their first examination, 83% of Genetic cases were unaffected and 17% were glaucoma suspect, whereas among Clinical cases 44% were glaucoma suspect, 28% had glaucoma, and 28% had advanced glaucoma. Genetic cases were significantly younger at presentation than Clinical cases (40.6±12.5 vs. 47.5±16.7 years P = 0.018). The mean highest intraocular pressure (32.2±9.7 vs. 17.6±3.6 mmHg P < 0.001), cup-to-disc ratio (0.65±0.27 vs. 0.48±0.13 P = 0.006), and mean deviation on visual field testing (-10.0±10.3 vs. -1.2±1.2 P < 0.001) were all significantly worse in Clinical cases compared with Genetic cases. In iduals with common MYOC p.Gln368Ter variant were further analyzed separately to account for the phenotypic variability of different disease-causing variants. All findings remained significant after adjusting for the common MYOC p.Gln368Ter variant. Our findings demonstrated that MYOC cascade genetic testing for POAG allows identification of at-risk in iduals at an early stage or even before signs of glaucoma are present. To our knowledge, this is the first study to demonstrate the clinical utility of predictive genetic testing for MYOC glaucoma.
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/13816810802334341
Abstract: In recent years, noteworthy gains have been made in unravelling the genetic contribution to some complex ocular diseases, principally age-related macular degeneration. Yet, a relatively poor understanding of the genetic aetiology for many other heritable blinding diseases, such as glaucoma, keratoconus and myopia, remains. Genetic isolates, populations with varying degrees of geographical or cultural seclusion, provide an effective means for investigating the molecular mechanisms involved in human diseases. This is particularly true for rare diseases in which founded alleles can be rapidly driven to a high frequency due to restriction of gene flow in the population. Recent success in complex gene mapping has resulted from the widened linkage disequilibrium (LD) in the genome of genetically isolated populations. An improved understanding of the predisposing genetic risk factors allows for enhanced screening modalities and paves the foundations for the translation of genomic technology into the clinic. This review focuses on the role population isolates have had in the investigation of genes underlying complex eye diseases and discusses their likely usefulness given the expansion of large-scale case-control association studies.
Publisher: Wiley
Date: 19-06-2015
DOI: 10.1111/CEO.12541
Abstract: X-linked retinoschisis (XLRS) is a leading cause of juvenile macular degeneration associated with mutations in the RS1 gene. XLRS has a variable expressivity in males and shows no clinical phenotype in carrier females. Clinical and molecular characterization of male and female in iduals affected with XLRS in a consanguineous family. Consanguineous Eastern European-Australian family Four clinically affected and nine unaffected family members were genetically and clinically characterized. Deoxyribonucleic acid (DNA) analysis was conducted by the Australian Inherited Retinal Disease Register and DNA Bank. Clinical and molecular characterization of the causative mutation in a consanguineous family with XLRS. By direct sequencing of the RS1 gene, one pathogenic variant, NM_000330.3: c.304C > T, p. R102W, was identified in all clinically diagnosed in iduals analysed. The two females were homozygous for the variant, and the males were hemizygous. Clinical and genetic characterization of affected homozygous females in XLRS affords the rare opportunity to explore the molecular mechanisms of XLRS and the manifestation of these mutations as disease in humans.
Publisher: Optica Publishing Group
Date: 14-05-2010
DOI: 10.1364/OE.18.011347
Publisher: Elsevier BV
Date: 04-1993
Publisher: Public Library of Science (PLoS)
Date: 12-05-2021
DOI: 10.1371/JOURNAL.PGEN.1009497
Abstract: Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
Publisher: Informa UK Limited
Date: 2006
DOI: 10.1080/13816810600870843
Abstract: Primary infantile glaucoma (PIG) is predominantly inherited as a recessive disease, whereas anterior segment dysgenesis (ASD) is usually dominantly inherited. The purpose of this study was to determine the likelihood of a person who has infantile glaucoma to produce a child who also manifests the disease. A retrospective cross-sectional design was utilized. The pedigrees of probands from south-eastern Australia diagnosed with infantile glaucoma since 1980 were reviewed. Cases were sub ided into two groups according to the presence or absence of ASD. Exclusion criteria included incomplete pedigree phenotype information or aphakic glaucoma following congenital cataract surgery. Fisher's exact test was used to compare the parent-offspring phenotype transmission between ASD-associated infantile glaucoma and PIG. A total of 67 probands were identified however, three pedigrees were excluded due to incomplete phenotype information. Direct parent-offspring transmission of phenotype was statistically significantly more common in ASD-associated infantile glaucoma (2/8) than in PIG (1/56) pedigrees (p = 0.039). Although this study reveals that Australian patients with ASD-associated infantile glaucoma are at greater risk of having children with infantile glaucoma than patients with PIG, the number of ASD pedigrees with direct transmission of infantile glaucoma is lower than expected. Based on our population frequency analysis and the results of our study, the risk of PIG, if one parent is affected by PIG and the other is normal, is less than 2%.
Publisher: S. Karger AG
Date: 21-12-2005
DOI: 10.1159/000089271
Abstract: Primary open-angle glaucoma (POAG) is genetically heterogeneous, with 6 named POAG loci GLC1A-F mapped and genes myocilin i (MYOC) /i and optineurin i (OPTN) /i identified at 2 of the loci. Using penetrance-model-free methods, we screened the POAG loci GLC1A-F in an extended Australian pedigree, using 3–5 markers within each locus. p values of less than 0.05 were obtained empirically using SimWalk2 and exactly using Genehunter for 2 markers within the GLC1B region on chromosome 2. Fine mapping of this region produced pvalues of 0.01 or less at 5 markers flanked by D2S1897 and D2S2269. The 9 cM haplotype of interest overlaps the original GLC1B region. These results provide supportive evidence for the GLC1B locus on chromosome 2cen-q13 and verify the existence of POAG susceptibility gene in this region, increasing the likelihood of gene identification.
Publisher: Springer Science and Business Media LLC
Date: 14-05-2018
DOI: 10.1038/S41467-018-03646-6
Abstract: Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, % of the CCT-loci are near or within Mendelian disorder genes. These included FBN1 , ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus ( r = −0.62, P = 5.30 × 10 −5 ) but not between CCT and primary open-angle glaucoma ( r = −0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.
Publisher: Springer Science and Business Media LLC
Date: 07-2015
DOI: 10.1038/NATURE14618
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-2010
DOI: 10.1167/IOVS.09-4912
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.OGLA.2021.11.002
Abstract: Glaucoma is the leading cause of irreversible blindness worldwide however, vision loss resulting from glaucoma generally can be prevented through early identification and timely implementation of treatment. Recently, polygenic risk scores (PRSs) have shown promise in stratifying in idual risk and prognostication for primary open-angle glaucoma (POAG) to reduce disease burden. Integrating PRS testing into clinical practice is becoming increasingly realistic however, little is known about the attitudes of patients toward such testing. Cross-sectional, questionnaire-based study. Among the participants in the Australian and New Zealand Registry of Advanced Glaucoma, 2369 were invited to participate who fit the inclusion criteria of adults with a diagnosis of POAG who had not received genetic results that explain their condition, were not known to be deceased, resided in Australia, and had agreed to receive correspondence. One thousand one hundred sixty-nine in iduals (response rate, 49%) with POAG completed the survey evaluating their attitudes towards polygenic risk testing for glaucoma. Sociodemographic, health, perception, and emotional factors were examined to assess associations with interest in PRS testing. Interest in PRS testing was evaluated through assessing likelihood to take the test to predict personal risk of disease and disease severity, and whether the in idual would recommend the test to family members or others. Our results show strong interest in the test, with 69.4% of in iduals (798 of 1150) indicating a keenness in testing before diagnosis, had it been available. In particular, interest was seen in those from an urban area (odds ratio [OR], 1.70 95% confidence interval [CI], 1.15-2.49 P = 0.007), those who perceived their risk of developing glaucoma as higher (OR, 2.05 95% CI, 1.28-3.29 P = 0.003), and those who were worried about developing glaucoma (OR, 2.07 95% CI, 1.27-3.37 P = 0.004). People who were interested in testing were more likely to change their eye health-seeking intentions and to recommend testing to family members and others, as well as to undergo testing for prognostication. These findings will help to facilitate the clinical implementation of PRS testing for glaucoma to reduce irreversible vision loss.
Publisher: BMJ
Date: 26-08-2018
DOI: 10.1136/BJOPHTHALMOL-2017-310686
Abstract: To investigate whether pterygium is an indicator of an increased risk of cutaneous melanoma (CM). A matched-cohort study, using linked health administrative data sets to identify all hospital-treated pterygium in Western Australia (WA) between 1979 and 2014. We identified pterygium cases from hospital diagnosis and/or procedure International Classification of Diseases 9th revision (ICD-9) and 10th revision (ICD-10) codes and matched cases by age, sex and residential postcode to WA Electoral Roll controls with no known history of pterygium. Both cohorts were linked to the WA Cancer Registry and the WA Deaths Registry. 23 625 people had pterygium treatment (64% male) in WA hospitals. The median age for pterygium diagnosis and/or treatment was 49 years (range 14–96). There were significantly more CM cases in the pterygium cohort compared with the control cohort (1083 vs 874 p .001). In a logistic regression analysis, there was a 24% increase in the odds of developing a CM in the pterygium cohort, compared with controls, after controlling for other predictors (OR 1.24, 95% CI 1.1 to 1.4). The incident rate ratio (IRR) of a malignant CM diagnosis was 20% greater in people who had treatment for a pterygium compared with controls (IRR 1.2, 95% CI 1.0 to 1.4). The presence of a pterygium indicates a significantly increased risk of developing a CM. Eye care providers who see patients with developing pterygia should advise these patients of this increased risk and recommend regular skin surveillance.
Publisher: BMJ
Date: 07-2005
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2008
DOI: 10.1167/IOVS.07-1052
Abstract: To assess the heritability of anterior chamber depth (ACD) and relative anterior chamber depth (ACD/axial length, rACD) in Chinese in a classic twin study. Twins aged 7 to 15 years living in two local districts were recruited from the Guangzhou Twin Registry. Anterior chamber depth and axial length were measured by partial coherence laser interferometry. Zygosity in all same-sex twin pairs was confirmed by genotyping with 16 polymorphic markers. The phenotypes of the right eyes were used in analysis. Heritability was assessed by structural variance component genetic modeling. In total, 1126 twin participants were available for analysis, including 357 monozygotic (MZ) and 206 dizygotic (DZ) twin pairs. ACD increased with age (0.036 mm per year, P < 0.001) and 0.09 mm shallower in the girls than in the boys (P < 0.001). Age- and sex-adjusted intraclass correlation coefficients (ICCs) for ACD were 0.92 for the MZ and 0.50 for the DZ twins those for rACD were 0.89 for the MZ and 0.52 for the DZ twins. The best-fitting model yielded 90.1% (95% CI: 88.2%-91.7%) of additive genetic and 9.9% (95% CI: 8.3%-11.8%) of unique environmental effects for ACD and 89.2% (95% CI: 87.1%-90.9%) of additive genetic and 10.8% (95% CI: 9.1%-12.9%) of unique environmental effects for rACD. Additive genetic effects appear to be the major contributor to the variation of ACD and rACD in Chinese population. High heritability remained even when the data were corrected for the influence of myopia.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.EXER.2010.06.014
Abstract: The morphologic appearance of the optic disc is of interest in glaucoma. In contrast to descriptive classification systems that are currently used, a quantitative approach to the analysis of optic disc morphology is required. Our goal was to determine the optimal method for quantifying optic cup shape by comparing traditional (ovality, form-factor and neuroretinal rim (NRR) width ratio) and geometric morphometric approaches. Left optic disc stereophotographs of 160 (80 normal and 80 glaucomatous (stratified by severity)) subjects were examined. The optic cup margins were stereoscopically delineated with a custom tracing system and saved as a series of discrete points. The geometric morphometric methods of elliptic Fourier analysis (EFA) and sliding semi-landmark analysis (SSLA) were used to eliminate variation unrelated to shape (e.g. size) and yield a series of shape variables. Differences in optic cup shape between normal and glaucoma groups were investigated. Discriminant functions were computed and the sensitivity and specificity of each technique determined. Receiver operator characteristic (ROC) curves were calculated for all methods and evaluated in their potential to discriminate between normal and glaucomatous eyes based on the shape variables. All geometric morphometric methods revealed differences between normal and glaucomatous eyes in optic cup shape, in addition to the traditional parameters of ovality, form-factor and NRR width ratio (p<0.0005). SSLA (minimum bending energy criterion--18 points) had the best sensitivity (83%) and area under the curve (AUC) (0.91). EFA (72 points) performed similarly well (74%, 0.89) as did the set of traditional shape-based variables (76%, 0.86). This study demonstrated that a geometric morphometric approach for discriminating between normal and glaucomatous eyes in optic cup shape is superior to that provided by traditional single parameter shape measures. Such analytical techniques could be incorporated into future automated optic disc screening modalities.
Publisher: Wiley
Date: 08-2014
DOI: 10.1002/UOG.13399
Abstract: Through comprehensive ophthalmic examination of adult offspring we sought to determine the impact of multiple prenatal ultrasound scans on ocular development. 2743 pregnant women recruited to the Western Australian Pregnancy (Raine) Cohort study during 1989-1991 were randomized to receive at King Edward Memorial Hospital, Western Australia either multiple prenatal ultrasound scans and Doppler flow studies (intensive group) or a single ultrasound scan at 18 weeks' gestation. Neonatal birth weight of the offspring and other physical measurements were collected prospectively. At age 20 years, participants underwent a comprehensive ophthalmic examination including measurement of ocular biometry and visual acuity. Complete data were available for 1134 adult offspring participants. The mothers of 563 of these had been randomized to receive multiple prenatal ultrasound scans. The mean age of participants at follow-up was 20.0 years. There was no statistically significant difference between the two groups with regard to ocular biometric or visual outcomes, except for slightly higher intraocular pressure identified in in iduals exposed to multiple ultrasound scans (P = 0.034). Although infants in the intensive-ultrasound arm were more likely to have birth weights in the lower quartiles, this was not reflected in adult eye development. Axial length, lens thickness, corneal curvature and thickness and optic cup to disc ratio (a risk factor for glaucomatous optic neuropathy) were not significantly influenced by the more frequent ultrasound protocol. Prior to this study, there was a paucity of safety data for ultrasound with regard to eye development. We found that frequent in-utero exposure to ultrasound, including B-mode imaging and the use of spectral Doppler mode from 18 weeks' gestation, had no significant impact on visual outcomes or ocular biometry.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2012
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.EXER.2019.107806
Abstract: Age-related cataract is the major cause of blindness worldwide. Both genetic and environmental factors contribute to the disease. Genetic variation in the Ephrin type-A receptor 2 (EPHA2) gene is associated with the risk of age-related cataract in multiple populations, and exposure to ultraviolet-B (UV-B) radiation is a well-established risk factor for the disease. Epha2 knockout and UV-B radiation independently lead to cataract in mice, and UV-B radiation reportedly alters EPHA2 expression in cultured cells. We hypothesised that an interaction between UV-B radiation exposure and Epha2 signalling may influence cataract development. To test this hypothesis, 5-week-old Epha2
Publisher: BMJ
Date: 2018
DOI: 10.1136/BMJOPEN-2017-020868
Abstract: Excessive and insufficient sun exposure during childhood have been linked to serious diseases in later life for ex le, insufficient sun exposure during childhood may increase the risk of developing myopia. The Kidskin-Young Adult Myopia Study (K-YAMS) is a follow-up of participants in the Kidskin Study, a non-randomised controlled trial that evaluated the effect of a 4-year educational intervention on sun-protection behaviours among primary school children in the late 1990s. Children who received the Kidskin intervention had lower levels of sun exposure compared with peers in the control group after 2 and 4 years of the intervention, but this was not maintained 2 years after the intervention had ceased. Thus, a follow-up of Kidskin Study participants provides a novel opportunity to investigate the associations between a childhood sun-exposure intervention and potentially related conditions in adulthood. The K-YAMS contacts Kidskin Study participants and invites them to participate using a variety of methods, such as prior contact details, the Australian Electoral Roll and social media. Self-reported and objective measures of sun-exposure and sun-protection behaviours are collected as well as a number of eye measurements including cycloplegic autorefraction and ocular biometry. Data will be analysed to investigate a possible association between myopic refractive error and Kidskin intervention group or measured sun exposure. The K-YAMS is approved by the Human Research Ethics Committee of the University of Western Australia (RA/4/1/6807). Findings will be disseminated via scientific journals and conferences. ACTRN12616000812392 Pre-results .
Publisher: Elsevier BV
Date: 05-2021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-08-2023
DOI: 10.1167/TVST.12.8.14
Publisher: Frontiers Media SA
Date: 27-04-2022
DOI: 10.3389/FPUBH.2022.861044
Abstract: Myopia tends to develop and progress fastest during childhood, and the age of stabilization has been reported to be 15–16 years old. Thus, most studies on myopia have centered on children. Data on the refractive error profile in young adulthood — a time in life when myopia is thought to have stabilized and refractive error is unaffected by age-related pathology such as cataract — are limited. The Raine Study has been following a community-based cohort of young adults representative of the general Western Australia population since their prenatal periods in 1989–1991, with eye examinations performed when participants were 20 and 28 years old. At 20 years old, prevalence of myopia in the cohort was 25.8%. Using long-term trajectory of serum vitamin D levels and conjunctival ultraviolet autofluorescence (CUVAF) area to objectively quantify sun exposure, the Raine Study confirmed a negative relationship between time spent outdoors and myopia prevalence. However, prospective studies are required to determine the amount of CUVAF area or serum vitamin D levels associated with time duration. Combining data from the Raine Study and several other cohorts, Mendelian randomization studies have confirmed a link between myopia and a genetic predisposition toward higher education. Several novel potential associations of myopia or ocular biometry were investigated, including fetal growth trajectory, which was found to be significantly associated with corneal curvature at 20 years. By age 28, myopia prevalence had increased to 33.2%. Between 20 and 28 years old, myopia progressed and axial length elongated, on average, by −0.041D/year and 0.02 mm/year, respectively. Smaller CUVAF area at follow-up, female sex, and parental myopia were significant risk factors for myopia incidence and progression between 20 and 28 years. Given the limited research in young adults, further investigations are warranted to confirm the Raine Study findings, as well as identify novel genetic or environmental factors of myopia incidence and progression in this age group.
Publisher: American Medical Association (AMA)
Date: 04-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-12-2023
Publisher: Informa UK Limited
Date: 26-06-2014
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1442-9071.2009.02002.X
Abstract: Primary open angle glaucoma (POAG) is a complex heterogeneous disease. The aim of this study was to describe the POAG phenotype in in iduals who harbour the novel GLC1L disease-associated haplotype in a large pedigree where the Myocilin Gln368STOP mutation also segregates. The clinical findings from 24 subjects with POAG from the GTAS02 family recruited as part of the Glaucoma Inheritance Study of Tasmania (GIST) were compared relative to genotype status. The previously identified GLC1L disease haplotype encompasses a chromosomal region of 8.3 centimorgans bounded by the markers D3S3521 and D3S1289 on 3p21-22. In subjects with the GLC1L disease haplotype (with or without Gln368STOP), the POAG phenotype was characterized by a mean age at diagnosis of 54.3 years, and mean maximum recorded intraocular pressure (IOP) of 23.9 mmHg. The mean maximum recorded IOP was lower in subjects with the predicted disease haplotype and no Gln368STOP mutation, compared with subjects with the predicted disease haplotype and presence of the Gln368STOP mutation (P = 0.02). Presence of the Gln368STOP mutation was significantly more common in those with the predicted disease haplotype than those without (P = 0.04). In the four subjects carrying the GLC1L disease-associated haplotype without the Gln368STOP mutation, a normotensive glaucoma (mean maximum recorded IOP 15 mmHg, range 13-17 mmHg) was present. The GLC1L locus may be associated with glaucoma in the absence of elevated IOP. Discovery of the specific gene within the GLC1L locus on 3p21-22 would provide a useful addition to our ability to offer genetic testing and counselling to POAG in iduals and their families.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2019
DOI: 10.1038/S41467-018-08078-W
Abstract: The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
Publisher: BMJ
Date: 24-07-2008
Abstract: To estimate the heritability of intraocular pressure (IOP) by performing a classical twin study and to determine whether the use of different instruments influences calculation of eye IOP heritability. Twin pairs were recruited to participate from the TwinsUK Adult Twin Registry at St. Thomas' Hospital London. IOP was measured using Goldmann applanation tonometry (GAT). A subset of twins also had their IOP measured using the Ocular Response Analyser (ORA Reichert, Buffalo, NY) and the Dynamic Contour Tonometer (DCT, Pascal Swiss Microtechnology AG, Port, Switzerland). We compared the covariance of IOP within monozygotic (MZ) and dizygotic (DZ) pairs using genetic modelling techniques to determine the relative contribution of genes and environment to the variation in IOP seen in this population. Data for 422 twin pairs (211 MZ 211 DZ) were analysed. The mean IOP for GAT was 15.4 (SD 2.7) mm Hg (range: 8.7-26.2 mm Hg). The MZ correlations were significantly higher than DZ for IOP measured by GAT, DCT and ORA (correlation coefficients: GAT: 0.57:0.39, DCT: 0.62:0.36, Goldmann-correlated ORA (IOPg) 0.73:0.47, for MZ:DZ twins, respectively). Modelling suggested heritability for GAT IOP of 0.62, with in idual environmental factors accounting for 0.38 of the variation. This study demonstrated that genetic effects are important in determining IOP in this twin population. IOP readings differed depending upon the instrument used, and this resulted in different heritability values genetic factors explained 62%, 63% and 74% of the variation in IOP using GAT, DCT and ORA IOPg, respectively. Environmental factors determined the remainder of the variation.
Publisher: Wiley
Date: 13-05-2020
DOI: 10.1111/CEO.13772
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 03-08-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-05-2021
Publisher: American Medical Association (AMA)
Date: 08-2003
Publisher: Public Library of Science (PLoS)
Date: 26-09-2012
Publisher: Cambridge University Press (CUP)
Date: 27-02-2013
DOI: 10.1017/THG.2013.5
Abstract: Twin studies are extremely useful for investigating hypotheses of genetic influence on a range of behavioral and physical traits in humans. Studies of physical traits, however, are usually limited to size-related biological characteristics because it is inherently difficult to quantify the morphological counterpart – shape. In recent years, the development of geometry-preserving analytical techniques built upon multivariate statistical methodologies has produced a new discipline in biological shape analysis known as geometric morphometrics. In this study of hand shape analysis, we introduce the reader already familiar with the field of twin research to the potential utility of geometric morphometrics and demonstrate the cross-discipline applicability of methods. We also investigate and compare the efficacy of the 2D:4D ratio, a commonly used marker of sexual dimorphism, to the fully multivariate approach of shape analysis in discriminating between male and female sex. Studies of biological shape variation utilizing geometric morphometric techniques may be completed with software freely available on the Internet and time invested to master the small learning curve in concepts and theory.
Publisher: Informa UK Limited
Date: 2007
Publisher: Elsevier BV
Date: 11-2003
DOI: 10.1016/S0002-9394(03)00577-4
Abstract: To investigate the association of sequence variations in the optineurin (OPTN) gene in patients with open-angle glaucoma. Prospective case control study. The OPTN gene was screened for sequence variations using a combination of single-strand conformational polymorphism analysis and automated DNA sequencing. A total of 1,299 subjects (1048 glaucoma patients and 251 controls) were screened for variations in the four portions of the gene that had been previously associated with glaucoma. A subset of these subjects (376 patients and 176 controls) was screened for variations in the entire coding sequence. Twenty-four percent of the patients and 35% of the controls were Japanese, whereas the remainder were predominantly Caucasian. Allele frequencies were compared with the Fisher exact test. The OPTN sequence variations were not significantly associated with any form of high-tension open-angle glaucoma. One proband with familial normal-tension glaucoma was found to harbor the previously reported Glu50Lys variation. Another previously reported change, Met98Lys, was associated with normal-tension glaucoma in Japanese but not in Caucasian patients. This study provides some additional evidence for the association of the Glu50Lys OPTN sequence variation with familial normal tension glaucoma. However, because familial normal-tension glaucoma is so rare, this change seems to be responsible for less than 0.1% of all open-angle glaucoma. The Arg545Gln variation is likely to be a nondisease-causing polymorphism. The Met98Lys change may be associated with a fraction of normal-tension glaucoma in patients of Japanese ethnicity.
Publisher: Springer Science and Business Media LLC
Date: 28-03-2002
DOI: 10.1007/S00439-002-0705-7
Abstract: The minimum physical distance surrounding a candidate gene has been determined in founder populations by studying allele sharing and then mapping historical recombination events. In this study, we developed a novel minimalistic approach by using the genetically isolated population of Tasmania, Australia, to identify candidate gene loci in a small number of in iduals of unknown genetic relationship affected by a dominant disorder. Keratoconus, an inheritable non-inflammatory progressive degeneration of the cornea, is present at a five-fold increased incidence in Burnie, a coastal town on the island of Tasmania. Based on the fundamental assumption that in iduals with keratoconus from this town are likely to be related through a founder effect, a 10-cM interval genome scan was conducted on six patients of undefined genetic relationship and one affected sib-pair to identify commonly shared chromosomal segments for the elucidation of candidate gene loci. Analysis of allele sharing revealed four markers on three chromosomes where all eight in iduals shared a common allele on at least one chromosome, and thirteen markers where all but one patient shared common alleles. No excess of allele sharing was observed at any marker tested on chromosome 21, a suggested candidate chromosome for keratoconus. Further analysis of positive loci revealed suggestive association at 20q12, where significant deviation in allele frequency D20S119 ( P=2.1 x 10(-5)) is observed when additional Tasmanian keratoconus s les are genotyped. Identification of a conserved minimal chromosomal haplotype around D20S119 in related Tasmanian patients suggests association with this locus, however association with the nearby candidate gene MMP-9 has been excluded.
Publisher: Oxford University Press (OUP)
Date: 08-2001
Publisher: Informa UK Limited
Date: 23-08-2022
DOI: 10.1080/08164622.2022.2111201
Abstract: Deep learning (DL) represents a paradigm-shifting, burgeoning field of research with emerging clinical applications in optometry. Unlike traditional programming, which relies on human-set specific rules, DL works by exposing the algorithm to a large amount of annotated data and allowing the software to develop its own set of rules (i.e. learn) by adjusting the parameters inside the model (network) during a training process in order to complete the task on its own. One major limitation of traditional programming is that, with complex tasks, it may require an extensive set of rules to accurately complete the assignment. Additionally, traditional programming can be susceptible to human bias from programmer experience. With the dramatic increase in the amount and the complexity of clinical data, DL has been utilised to automate data analysis and thus to assist clinicians in patient management. This review will present the latest advances in DL, for managing posterior eye diseases as well as DL-based solutions for patients with vision loss.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Wiley
Date: 07-2010
Publisher: Springer Science and Business Media LLC
Date: 12-09-2010
DOI: 10.1038/NG.661
Publisher: Springer Science and Business Media LLC
Date: 12-09-2010
DOI: 10.1038/NG.664
Publisher: Elsevier BV
Date: 02-2012
Publisher: Springer Science and Business Media LLC
Date: 12-09-2010
DOI: 10.1038/NG.663
Publisher: Wiley
Date: 27-07-2016
DOI: 10.1111/CEO.12570
Abstract: P values associated with null hypothesis significance testing (NHST) are almost universal in the ophthalmic literature. A P value < 0.05 is traditionally considered 'significant'. This concept may deflect further thought about the veracity of the results. P values influence the publishability of the data and have flow-on effects for funding success and the direction of future research. Despite their importance, the problems inherent in P values have been recognized since their inception, and in more recent years have been increasingly highlighted in some scientific fields. In this review, we aim to bring the problems associated with P values and NHST to the attention of the ophthalmic research community. We do not offer a universal solution to the problem of determining the veracity of a scientific claim however, we demonstrate the need for caution in interpreting 'significant' P values by performing a Bayesian re-analysis of t-tests in the ophthalmic literature.
Publisher: MDPI AG
Date: 14-06-2021
Abstract: PRPF31-associated retinopathy (RP11) is a common form of autosomal dominant retinitis pigmentosa (adRP) that exhibits wide variation in phenotype ranging from non-penetrance to early-onset RP. Herein, we report inter-familial and intra-familial variation in the natural history of RP11 using multimodal imaging and microperimetry. Patients were recruited prospectively. The age of symptom onset, best-corrected visual acuity, microperimetry mean sensitivity (MS), residual ellipsoid zone span and hyperautofluorescent ring area were recorded. Genotyping was performed using targeted next-generation and Sanger sequencing and copy number variant analysis. PRPF31 mutations were found in 14 in iduals from seven unrelated families. Four disease patterns were observed: (A) childhood onset with rapid progression (N = 4), (B) adult-onset with rapid progression (N = 4), (C) adult-onset with slow progression (N = 4) and (D) non-penetrance (N = 2). Four different patterns were observed in a family harbouring c.267del patterns B, C and D were observed in a family with c.772_773delins16 and patterns A, B and C were observed in 3 unrelated in iduals with large deletions. Our findings suggest that the RP11 phenotype may be related to the wild-type PRPF31 allele rather than the type of mutation. Further studies that correlate in vitro wild-type PRPF31 allele expression level with the disease patterns are required to investigate this association.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-04-2020
Publisher: Elsevier BV
Date: 08-2011
Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-01-1997
DOI: 10.1126/SCIENCE.275.5300.668
Abstract: Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma ( GLC1A ) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein ( TIGR ) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control in idual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.
Publisher: Oxford University Press (OUP)
Date: 10-01-2017
DOI: 10.1093/HMG/DDW399
Publisher: Wiley
Date: 06-2015
DOI: 10.1111/AOS.12732
Publisher: Wiley
Date: 04-2010
DOI: 10.1111/J.1442-9071.2010.02236.X
Abstract: To review visual acuity outcomes from paediatric traumatic cataract and examine the mechanisms by which they occur. A retrospective review of paediatric patients (aged less than 18 years) who underwent lens surgery following ocular trauma, between 1992 and 2006 at the Royal Children's Hospital and Royal Victorian Eye and Ear Hospital in Melbourne. Data collected included gender, mechanism of injury, wound type, age at injury, age at surgery, refractive rehabilitation, complications and visual acuity outcome. A total of 74 patients (75% male) were identified over the 15-year period, representing an incidence of 4.9 cases per year. The mean age at injury was 7.5 years. Sixty-five cataracts (88%) followed a penetrating eye injury, whereas only nine patients (12%) developed cataract after known blunt trauma. Fourteen patients (19%) underwent lensectomy at the time of primary wound repair and 45 patients (61%) underwent primary intraocular lens (IOL) implantation. Visual acuity outcomes ranged from 6/5 to no perception of light. Twenty-five patients (34%) achieved 6/12 or better in the injured eye, 23 patients (31%) achieved between 6/15 and 6/60, and 14 patients (19%) had visual acuity of less than 6/60. Twelve patients (16%) were lost to follow-up. In a paediatric population, cataract formation as a result of trauma requiring lensectomy is not uncommon. Males are more likely to suffer from such injury. A variety of sharp and blunt objects are the primary mechanism by which the injury is sustained with variable visual outcomes.
Publisher: Springer Science and Business Media LLC
Date: 31-08-2014
DOI: 10.1038/NG.3087
Publisher: Wiley
Date: 14-11-2018
DOI: 10.1111/CEO.13423
Abstract: Excessive ocular sun exposure is linked to various eye pathologies. Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting sun-related conjunctival damage however, the custom-built camera system required is not readily available. We investigated whether blue laser autofluorescence (BAF) on a commonly used confocal scanning laser ophthalmoscope (cSLO) can be utilized to measure CUVAF area. Cross-sectional evaluation of a diagnostic technology at a medical research institute. Sixty-four participants recruited from three on-going observational eye studies in Western Australia. All participants had four images, two of each eye, captured using the CUVAF camera and BAF on the same day. Participants with pterygium or poor quality images were excluded from the analysis. Two graders measured CUVAF area in each image twice. CUVAF area measured by BAF was then compared to measurements determined with the conventional camera system. CUVAF area. After exclusions, 50 participants' images were analysed. Intra- and inter-observer repeatability were similar between the two systems. When comparing CUVAF area measured by BAF to the camera measurement, grader 1 had a mean difference of +1.00 mm BAF on a commercially available cSLO is a valid method for measuring CUVAF area. This finding provides broader opportunity for identifying, monitoring and educating patients with sun-exposure-related ocular conditions and for researching the ocular impacts of sun exposure.
Publisher: Wiley
Date: 07-11-2015
DOI: 10.1111/CEO.12455
Abstract: Sun exposure is associated with several ophthalmic diseases, including pterygium which may develop in adolescence. This study reports the prevalence of pterygium and its associations in a large cohort of young Australian adults. Conjunctival ultraviolet autofluorescence, a biomarker of ocular sun exposure, has recently been characterized in some Australian populations. Cross-sectional population-based study. One thousand three hundred forty-four subjects aged 18-22 years in the Western Australian Pregnancy Cohort (Raine) Study. Standardized colour and ultraviolet autofluorescence photographs of the nasal and temporal conjunctiva were taken, and assessed for presence of pterygium and area of autofluorescence. Sun exposure and protective factors were assessed by structured questionnaire. Area of conjunctival ultraviolet autofluorescence in square millimetre (mm(2)) and presence of pterygium. Median total conjunctival autofluorescence was 44.2 mm(2) (interquartile range 20.2-69.8 mm(2)). Median conjunctival autofluorescence was higher in nasal than in temporal quadrants (23.8 mm(2) vs. 18.9 mm(2), P < 0.001), but did not differ according to age or gender. Higher body mass index was associated with lower levels of autofluorescence. Total autofluorescence increased with increasing time spent outdoors. Prevalence of pterygium was 1.2% (95% confidence interval 0.6-1.8%), and was associated with male gender (odds ratio 6.71, P = 0.012). Participants with pterygium had significantly more conjunctival autofluorescence than those without (median 73.4 mm(2) vs. 44.0 mm(2), P = 0.001). Conjunctival ultraviolet autofluorescence is associated with increased time spent outdoors, and increased prevalence of pterygium. The association of this biomarker with other ophthalmohelioses, including cataract, ocular surface squamous neoplasia and eyelid malignancy, has yet to be determined.
Publisher: Informa UK Limited
Date: 05-09-2022
DOI: 10.1080/09286586.2021.1968005
Abstract: In 1989-1991, pregnant women completed questionnaires on their current smoking and alcohol drinking patterns. Following the birth of their offspring, information on household smokers was obtained between the 1- and 13-year follow-ups. At the 20-year follow-up, these offspring underwent an eye examination including optical coherence tomography imaging of the RNFL. Participants (n = 1,287) were 19-22 years old at time of eye examination. Most participants (77%) had no
Publisher: BMJ
Date: 23-11-2021
DOI: 10.1136/BJOPHTHALMOL-2021-320284
Abstract: Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting conjunctival damage related to ultraviolet radiation exposure. In cross-sectional studies, CUVAF area is positively associated with self-reported time spent outdoors and pterygium and negatively associated with myopia however, longitudinal studies are scarce. To use a novel deep learning-based tool to assess 8-year change in CUVAF area in young adults, investigate factors associated with this change and identify the number of new onset pterygia. A deep learning-based CUVAF tool was developed to measure CUVAF area. CUVAF area and pterygium status were assessed at three study visits: baseline (participants were approximately 20 years old) and at 7-year and 8-year follow-ups. Participants self-reported sun protection behaviours and ocular history. CUVAF data were available for 1497 participants from at least one study visit 633 (43%) participants had complete CUVAF data. Mean CUVAF areas at baseline and the 7-year and 8-year follow-ups were 48.4, 39.3 and 37.7 mm 2 , respectively. There was a decrease in mean CUVAF area over time (change in total CUVAF area=−0.96 mm 2 per year (95% CI: −1.07 to –0.86)). For participants who wore sunglasses ≥1/2 of the time, CUVAF area decreased by an additional −0.42 mm 2 per year (95% CI: −0.72 to –0.12) on average. Fourteen (1.5%) participants developed a pterygium. In this young adult cohort, CUVAF area declined over an 8-year period. Wearing sunglasses was associated with a faster reduction in CUVAF area. Deep learning-based models can assist in accurate and efficient measurement of CUVAF area.
Publisher: Springer Science and Business Media LLC
Date: 10-2009
Publisher: Elsevier BV
Date: 04-2001
DOI: 10.1016/S0002-9394(00)00812-6
Abstract: To identify a rapid and reliable method to detect the Glutamine 368 STOP (Q368STOP) disease-predisposing allele of the myocilin gene associated with adult onset, primary, open-angle glaucoma. In iduals with the Q368STOP mutation of the myocilin gene were identified from a cohort of primary open-angle glaucoma patients from Tasmania and subjected to Taa1 restriction digestion. In the Tasmanian family presented, screening with the Taa1 restriction enzyme successfully confirmed identification of all in iduals with the Q368STOP mutation. The use of the Taa1 restriction enzyme offers a relatively simple, rapid, and reproducible technique that could be applied to detect the Q368STOP mutation of the myocilin gene.
Publisher: Springer Science and Business Media LLC
Date: 06-1999
DOI: 10.1038/9722
Abstract: Malattia Leventinese (ML) and Doyne honeycomb retinal dystrophy (DHRD) refer to two autosomal dominant diseases characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium (RPE). Both loci were mapped to chromosome 2p16-21 (refs 5,6) and this genetic interval has been subsequently narrowed. The importance of these diseases is due in large part to their close phenotypic similarity to age-related macular degeneration (AMD), a disorder with a strong genetic component that accounts for approximately 50% of registered blindness in the Western world. Just as in ML and DHRD, the early hallmark of AMD is the presence of drusen. Here we use a combination of positional and candidate gene methods to identify a single non-conservative mutation (Arg345Trp) in the gene EFEMP1 (for EGF-containing fibrillin-like extracellular matrix protein 1) in all families studied. This change was not present in 477 control in iduals or in 494 patients with age-related macular degeneration. Identification of this mutation may aid in the development of an animal model for drusen, as well as in the identification of other genes involved in human macular degeneration.
Publisher: Wiley
Date: 19-08-2022
DOI: 10.1002/MGG3.2023
Abstract: Corneal dystrophies describe a clinically and genetically heterogeneous group of inherited disorders. The International Classification of Corneal Dystrophies (IC3D) lists 22 types of corneal dystrophy, 17 of which have been demonstrated to result from pathogenic variants in 19 identified genes. In this study, we investigated the diagnostic yield of genetic testing in a well‐characterised cohort of 58 in iduals from 44 families with different types of corneal dystrophy. In iduals diagnosed solely with Fuchs endothelial corneal dystrophy were excluded. Clinical details were obtained from the treating ophthalmologist. Participants and their family members were tested using a gene candidate and exome sequencing approach. We identified a likely molecular diagnosis in 70.5% families (31/44). The detection rate was significantly higher among probands with a family history of corneal dystrophy (15/16, 93.8%) than those without (16/28, 57.1%, p = .015), and among those who had undergone corneal graft surgery (9/9, 100.0%) compared to those who had not (22/35, 62.9%, p = .041). We identified eight novel variants in five genes and identified five families with syndromes associated with corneal dystrophies. Our findings highlight the genetic heterogeneity of corneal dystrophies and the clinical utility of genetic testing in reaching an accurate clinical diagnosis.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2017
DOI: 10.1038/EJHG.2017.59
Publisher: BMJ
Date: 11-2006
Publisher: Oxford University Press (OUP)
Date: 10-2017
Abstract: Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric cataract genes in 33 affected in iduals with a family history (cases with previously known or published mutations were excluded) using the Ion Torrent Personal Genome Machine. Variants were prioritized for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency & % in public databases. Confirmed mutations were assessed for segregation with the phenotype in all available family members. All identified novel or previously reported cataract-causing mutations were screened in 326 unrelated Australian controls. We detected 11 novel mutations in GJA3, GJA8, CRYAA, CRYBB2, CRYGS, CRYGA, GCNT2, CRYGA, and MIP and three previously reported cataract-causing mutations in GJA8, CRYAA, and CRYBB2. The most commonly mutated genes were those coding for gap junctions and crystallin proteins. Including previous reports of pediatric cataract-associated mutations in our Australian cohort, known genes account for & % of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.
Publisher: American Medical Association (AMA)
Date: 2007
DOI: 10.1001/ARCHOPHT.125.1.112
Abstract: To investigate whether structural differences of the optic nerve head are evident in young people who do not have manifest glaucoma but are known to carry myocilin mutations. A case-control design was adopted. Subjects from Australian pedigrees known to have either the Gln368STOP myocilin mutation (cutoff age, <40 years) or the Thr377Met myocilin mutation (cutoff age, <30 years) were examined for signs of glaucoma. Stereoscopic disc photographs were digitalized. Analysis of the optic disc area, optic cup area, and neuroretinal rim area was performed using digital stereoscopy with a Z-screen. Mutation analysis was conducted using direct sequencing. The t test, corrected for multiple comparison testing, was used in analysis. A total of 29 myocilin mutation-carrying (case) and 33 mutation-free (control) in iduals were reviewed. The mean +/- SD ages were 19.9 +/- 9.0 and 22.1 +/- 9.5 years in the mutation and mutation-free groups, respectively (P = .35). There was no significant difference in intraocular pressure between mutation carriers and noncarriers (P = .44). There were no statistically significant differences in the mean disc, neuroretinal rim, and cup areas between the groups. The mean +/- SD neuroretinal rim area was 1.24 +/- 0.24 mm(2) in the noncarrier group and 1.25 +/- 0.23 mm(2) in the mutation group (P = .46). No notch, nerve fiber layer defect, or neuroretinal rim hemorrhage was noted in any eye examined. Although confounded by penetrance and expressivity, no quantified structural difference in the optic nerve head was observed in in iduals who had a myocilin mutation prior to the diagnosis of glaucoma.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/01658100701486467
Abstract: To investigate the association between maternal smoking in pregnancy, early-life environment and childhood vision. Twin and triplet children enrolled in the Twins Eye Study in Tasmania underwent a comprehensive ophthalmic examination and their parents/guardians retrospectively answered a questionnaire regarding crawling, walking and other measures. A subset of these twins was also in the Tasmanian Infant Health Survey, which prospectively collected data on antenatal smoking, gestation, birth weight and other factors. The mean age of the 346 in iduals (172 multiple birth sets) at the time of examination was 9.25+/-2.4 years. Mean unaided visual acuity was 0.0 (6/6). The mean spherical equivalent was +0.87D, and decreased with increasing child age (p ) than 100'', p=0.05) and Lang test (p=0.001) and also with the presence of esotropia (p=0.02). These associations persisted after adjustment for infant postnatal smoke exposure at one month of age. Poor stereoacuity on Titmus stereo test circles was associated with late age of first crawling (RR=1.23 (1.06, 1.42) p=0.005 per month) and late age of first walking (RR 1.18 (1.05, 1.22) p=0.001 per month). Antenatal smoking was independently associated with poor stereovision and the presence of esotropia. Poor stereoacuity may be associated with delayed age at first crawling or walking.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 20-01-2022
DOI: 10.1167/IOVS.63.1.25
Publisher: Springer Science and Business Media LLC
Date: 31-08-2014
DOI: 10.1038/NG.3079
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-07-2012
DOI: 10.1167/IOVS.11-8677
Abstract: We sought to determine whether conjunctival ultraviolet autofluorescence (UVAF), a biomarker of outdoor light exposure, is associated with myopia. We performed a cross-sectional study on Norfolk Island and recruited in iduals aged ≥ 15 years. Participants completed a sun-exposure questionnaire and underwent non-cycloplegic autorefraction. Conjunctival UVAF used a specially adapted electronic flash system fitted with UV-transmission filters (transmittance range 300-400 nm, peak 365 nm) as the excitation source. Temporal and nasal conjunctival UVAF was measured in both eyes using computerized photographic analysis with the sum referred to as "total UVAF." In 636 participants, prevalence of myopia decreased with an increasing quartile of total UVAF (P(trend) = 0.002). Median total UVAF was lower in subjects with myopia (spherical equivalent [SE] ≤ -1.0 diopter [D]) than participants without myopia: 16.6 mm(2) versus 28.6 mm(2), P = 0.001. In the multivariable model that adjusted for age, sex, smoking, cataract, height and weight, UVAF was independently associated with myopia (SE ≤ -1.0 D): odds ratio (OR) for total UVAF (per 10 mm(2)) was 0.81, 95% confidence interval (CI) 0.69 to 0.94, P = 0.007. UVAF was also significantly associated with myopia when analysis was restricted to subjects <50 years, and in moderate-severe myopia (SE ≤ -3.0 D). Prevalence of myopia decreased with increasing time outdoors (P(trend) = 0.03), but time outdoors was not associated with myopia on multivariable analysis. Study authors identified a protective association between increasing UVAF and myopia. The protective association of higher UVAF against myopia was stronger than that of increased levels of time spent outdoors as measured by this study's questionnaire. Future studies should investigate the association between UVAF and incident myopia, and its relationship to myopic progression.
Publisher: Cambridge University Press (CUP)
Date: 02-2011
DOI: 10.1375/TWIN.14.1.42
Abstract: Aim: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were in iduals descended from the English Bounty mutineers and their Polynesian wives. Methods: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 in iduals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. Results: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg ( P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. Conclusion: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.
Publisher: Public Library of Science (PLoS)
Date: 23-10-2015
Publisher: Hindawi Limited
Date: 15-03-2010
DOI: 10.1002/HUMU.21236
Abstract: PRPF8-retinitis pigmentosa is said to be severe but there has been no overview of phenotype across different mutations. We screened RP patients for PRPF8 mutations and identified three new missense mutations, including the first documented mutation outside exon 42 and the first de novo mutation. This brings the known RP-causing mutations in PRPF8 to nineteen. We then collated clinical data from new and published cases to determine an accurate prognosis for PRPF8-RP. Clinical data for 75 PRPF8-RP patients were compared, revealing that while the effect on peripheral retinal function is severe, patients generally retain good visual acuity in at least one eye until the fifth or sixth decade. We also noted that prognosis for PRPF8-RP differs with different mutations, with p.H2309P or p.H2309R having a worse prognosis than p.R2310K. This correlates with the observed difference in growth defect severity in yeast lines carrying the equivalent mutations, though such correlation remains tentative given the limited number of mutations for which information is available. The yeast phenotype is caused by lack of mature spliceosomes in the nucleus, leading to reduced RNA splicing function. Correlation between yeast and human phenotypes suggests that splicing factor RP may also result from an underlying splicing deficit.
Publisher: Cambridge University Press (CUP)
Date: 13-06-2012
DOI: 10.1017/THG.2012.22
Abstract: Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent (‘phoria’) and manifest (‘tropia’) strabismus using cover–uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) ( r = 0.65) compared to dizygotic (DZ) twin pairs ( r = 0.33), suggesting a genetic role ( p = .003). There was no significant difference in polychoric correlation between MZ ( r = 0.55) and DZ twin pairs ( r = 0.53) for exo-deviation ( p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50–0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and unravel their mechanisms of action.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-03-2021
DOI: 10.1167/TVST.10.3.8
Publisher: Asia Pacific Academy of Ophthalmology
Date: 2017
DOI: 10.22608/APO.201698
Publisher: Wiley
Date: 23-12-2011
DOI: 10.1111/J.1442-9071.2011.02728.X
Abstract: Although considerable recent work on hereditary eye diseases in Tasmanian families has been published, much of this depended on a century of meticulous pedigree collection by earlier clinical researchers. This article reviews some of the historical papers and the importance they have played in gene discovery and understanding of ophthalmic genetics. Tasmanian families have contributed to the identification of genes for X-linked megalocornea, Leber's hereditary optic neuropathy, retinitis pigmentosa, congenital cataract, ptosis, keratoconus, glaucoma and myopia. The true value of the Tasmanian pedigrees will be realized with the translation of genetic discoveries into early diagnosis and treatment for these eye diseases.
Publisher: Trans Tech Publications Ltd.
Date: 15-01-2006
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 22-01-2019
DOI: 10.1167/TVST.8.1.13
Publisher: Elsevier BV
Date: 03-2003
DOI: 10.1086/368264
Publisher: American Association for Cancer Research (AACR)
Date: 07-2017
DOI: 10.1158/1055-9965.EPI-16-0846
Abstract: Background: Conjunctival ultraviolet autofluorescence (CUVAF) area detected from UVAF photographs is a recently developed potential marker for past sun exposure, but its relationship with sun-related factors has not been fully investigated. Methods: The study included 339 healthy children ages 5 to 15 years in Melbourne, Australia. Data were collected by questionnaire and examination at school. CUVAF area was measured using a computer program and analyzed as a continuous and dichotomous outcome (any/none). Results: Fifty-three children (15.6%) had detectable CUVAF, and the youngest age at which a child showed sun damage was 8 years. Compared with silicone skin cast score, there was good inter-grader agreement on CUVAF grading, with Cohen kappa 0.85 [95% confidence interval (CI), 0.65–1.00] for total CUVAF area using both eye photographs. Perfect intra-grader agreement was achieved. Fairer pigmentation, including medium/fair skin color [adjusted odds ratio (AOR), 3.42 95% CI, 1.02–11.48 vs. dark/olive] and blue/gray eye color (AOR, 4.07 95% CI, 1.73–9.55 vs. brown) was associated with increased odds of CUVAF. Increasing lifetime sunburn number (e.g., AOR, 2.89 95% CI, 1.14–7.35 and 4.29 1.04–17.76 for sunburns 2 to 4 and ≥ 5 times, respectively, vs. no sunburns, trend P = 0.004) and freckling by the end of last summer were associated with increased odds of CUVAF. Conclusions: CUVAF area can be an a priori objective measure of past sun exposure in pediatric populations for future research. Impact: To our knowledge, this is the first pediatric study that evaluated associations of sun-related risk factors with CUVAF. Cancer Epidemiol Biomarkers Prev 26(7) 1146–53. ©2017 AACR.
Publisher: Public Library of Science (PLoS)
Date: 25-01-2018
Publisher: Informa UK Limited
Date: 02-11-2019
Publisher: Springer Science and Business Media LLC
Date: 03-01-2023
DOI: 10.1038/S42003-022-04323-7
Abstract: Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. In iduals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP , the circadian rhythm gene PER3 , and P4HTM , which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.
Publisher: Wiley
Date: 28-01-2010
DOI: 10.1111/J.1755-3768.2009.01786.X
Abstract: This aim of this study was to compare the prevalence of various disease-associated and potentially modifiable risk factors between people with familial and sporadic forms of primary open angle glaucoma (OAG). A cross-sectional, retrospective study design was utilized. A detailed questionnaire enquiring about knowledge of family history, demographic data, current medications, and medical history of systemic disorders was administered. Where possible, living relatives were examined for signs of OAG. A total of 3,800 potential patients with OAG were identified, of whom 2062 were examined. One thousand twelve (59.5%) subjects were found to have familial OAG, and 688 (40.5%) subjects had no known or identified relative with OAG (sporadic glaucoma). One thousand forty-two unaffected family members examined. A past history of migraine was found more often with familial OAG (OR: 1.67 95% CI: 1.15-2.42). This effect was primarily driven by patients who had a first-degree relative also affected by OAG. Following adjustment for male gender and the age at review, the presence of atherosclerosis was also found to be more common in patients with familial glaucoma than in people with sporadic disease (OR: 1.42 95% CI: 1.05-1.92). No significant difference in the prevalence of hypertension, Raynaud's phenomenon, diabetes mellitus or thyroid disease was identified. Patients with a known relative affected by OAG were statistically significantly more likely to have a past history for migraine or presence of atherosclerosis compared to people with no known affected relative. An understanding of such differences and systemic comorbidities will be useful for further work investigating the underlying molecular mechanisms of this disease.
Publisher: Wiley
Date: 18-12-2019
DOI: 10.1111/CEO.13446
Publisher: Elsevier BV
Date: 04-2023
Publisher: Wiley
Date: 31-05-2005
DOI: 10.1111/J.1442-9071.2005.01018.X
Abstract: X-linked retinoschisis (XLRS), an X-linked recessive inherited degenerative retinopathy, is characterized by splitting in the nerve fibre layer and is caused by alterations in the RS1 gene. The aim of the present study was to review both the phenotypic features of XLRS and the mutation spectrum of the RS1 gene in an Australian cohort. Patients were recruited from ophthalmic and paediatric hospitals as well as private ophthalmic clinics across Australia. A cohort of 18 presumably unrelated families was identified. Twenty-two affected patients underwent clinical examination. Following DNA extraction all six exons of the RS1 gene were sequenced. The median age at diagnosis was 8 years (range 1-43 years) the median age at review was 14 years (range 5-63 years). The median best-corrected visual acuity upon review was 6/24 (range 6/6-1/36). Typical foveal schisis was found in 90.1% eyes examined (39/43) while peripheral schisis was present in 30% of eyes (13/43). The scotopic blue b-wave litude ranged between 2% and 82% of the mean normal litude. Five novel mutations (61G-->T, Gly21X 103C-->T, Gln35X 327-329del, Cys110del 527T-->C, Phe176Ser 573Gdel, Pro192fs) and six previously identified missense mutations (304C-->T, Arg102Trp 305G-->A, Arg102Gln 336G-->C, Trp112Cys 418G-->A, Gln140Arg 598C-->T, Arg200Cys 625C-->T, Arg209Cys) were found. The mutations present in codons 21 and 102 were each identified in two presumably unrelated pedigrees. One previously described point deletion (416Adel) was identified. Two pedigrees contained affected in iduals where exons 2 or 3, respectively, were unable to be lified, indicating the likely presence of a significant deletion. No mutation was found in the RS1 gene in two affected in iduals from different pedigrees. Population genetic studies of XLRS have not previously been conducted in Australia. The phenotype associated with these mutations varied. The identification of each pedigree's specific mutation allows future determination of female carrier status for genetic counselling purposes. Further study into the refinement of the XLRS phenotype as well as the degree of intrafamilial phenotypic variation is required.
Publisher: Elsevier BV
Date: 11-2003
DOI: 10.1086/379381
Abstract: Nance-Horan syndrome (NHS) is an X-linked disorder characterized by congenital cataracts, dental anomalies, dysmorphic features, and, in some cases, mental retardation. NHS has been mapped to a 1.3-Mb interval on Xp22.13. We have confirmed the same localization in the original, extended Australian family with NHS and have identified protein-truncating mutations in a novel gene, which we have called "NHS," in five families. The NHS gene encompasses approximately 650 kb of genomic DNA, coding for a 1,630-amino acid putative nuclear protein. NHS orthologs were found in other vertebrates, but no sequence similarity to known genes was identified. The murine developmental expression profile of the NHS gene was studied using in situ hybridization and a mouse line containing a lacZ reporter-gene insertion in the Nhs locus. We found a complex pattern of temporally and spatially regulated expression, which, together with the pleiotropic features of NHS, suggests that this gene has key functions in the regulation of eye, tooth, brain, and craniofacial development.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2022
DOI: 10.1038/S41467-022-31707-4
Abstract: There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies are needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with geographic atrophy and healthy in iduals were differentiated to retinal pigment epithelium. Integrating transcriptional profiles of 127,659 retinal pigment epithelium cells generated from 43 in iduals with geographic atrophy and 36 controls with genotype data, we identify 445 expression quantitative trait loci in cis that are asssociated with disease status and specific to retinal pigment epithelium subpopulations. Transcriptomics and proteomics approaches identify molecular pathways significantly upregulated in geographic atrophy, including in mitochondrial functions, metabolic pathways and extracellular cellular matrix reorganization. Five significant protein quantitative trait loci that regulate protein expression in the retinal pigment epithelium and in geographic atrophy are identified - two of which share variants with cis- expression quantitative trait loci, including proteins involved in mitochondrial biology and neurodegeneration. Investigation of mitochondrial metabolism confirms mitochondrial dysfunction as a core constitutive difference of the retinal pigment epithelium from patients with geographic atrophy. This study uncovers important differences in retinal pigment epithelium homeostasis associated with geographic atrophy.
Publisher: American Medical Association (AMA)
Date: 03-2007
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Start Date: 2009
End Date: 2012
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2004
End Date: 2006
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2013
End Date: 2015
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2023
End Date: 2025
Funder: Glaucoma Australia
View Funded ActivityStart Date: 2023
End Date: 2024
Funder: Mito Foundation
View Funded ActivityStart Date: 2014
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2019
End Date: 2023
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2017
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2022
End Date: 2024
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2021
End Date: 2021
Funder: Ophthalmic Research Institute of Australia
View Funded ActivityStart Date: 2018
End Date: 2018
Funder: The Ophthalmic Research Institute of Australia
View Funded ActivityStart Date: 2019
End Date: 2023
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2018
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2015
End Date: 2019
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2000
End Date: 2002
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2013
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2009
End Date: 2011
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2010
End Date: 2012
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2021
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2015
End Date: 12-2015
Amount: $440,000.00
Funder: Australian Research Council
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