ORCID Profile
0000-0002-9441-4356
Current Organisations
Johannes Gutenberg Universität Mainz
,
University of Melbourne
,
Centre for Eye Research Australia
,
Royal Australian and New Zealand College of Ophthalmologists
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Publisher: Springer Science and Business Media LLC
Date: 15-09-2013
DOI: 10.1038/NG.2758
Publisher: Springer Science and Business Media LLC
Date: 13-07-2016
DOI: 10.1007/S00401-016-1596-3
Abstract: Sporadic Alzheimer's disease (AD) is characterised by the deposition and accumulation of specific protein aggregates. Failure of clearance could underlie this process, and recent genetic association studies point towards involvement of the phagocytosis and autophagy pathways. We developed a real-time tri-color flow cytometry method to quantitate the phagocytic function of human peripheral blood monocyte subsets including non-classic CD14(dim)CD16(+), intermediate CD14(+)CD16(+) and classic CD14(+)CD16(-) monocytes. Using this method, we have measured the phagocytic ability of fresh monocytes in a study of preclinical, prodromal and clinical AD, matched with cognitively normal healthy control subjects. Basal levels of phagocytosis in all three subsets of monocytes were similar between healthy controls and AD patients, while a significant increase of basal phagocytosis was found in subjects with high Aβ-amyloid burden as assessed by PET scans. Pre-treating cells with Copaxone (CPX, to stimulate phagocytosis) or ATP (an inhibitor of P2X7-mediated phagocytosis) showed a differential response depending on clinical or Aβ-burden status, indicating a relative functional deficit. Overall the results are consistent with a perturbation of basal and stimulated innate phagocytosis in sporadic AD.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2022
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S1350-9462(98)00012-3
Abstract: Age-related macular disease is a major and growing public health burden in developed Caucasian societies, accounting for about 50% of blind registration. Evidence exists that this is an emerging problem in Eastern Asia, although the phenotype appears to differ from that seen in Western society. It is likely that several genes are involved, and that the genes or allelic variants conferring are common. Environment plays a major role in its pathogenesis, and it is believed that genetic susceptibility becomes apparent only if there are sufficient environmental pressures. There is no therapy currently available that will have an impact on the prevalence of blindness from age-related macular disease. It has been shown that visual loss occurs as a reaction to ageing changes in Bruch's membrane, which is interposed between the choriocapillaris and the retinal pigment epithelium. The age changes in all three structures have been partly characterised, and as a consequence, multiple putative pathogenic mechanisms have been proposed. Cross-sectional studies of populations with different genetic background and life styles would serve to prove the importance of inheritance and environment. Molecular genetic analysis of blood from affected sibling pairs from these sources may indicate the relevant genes, the prevalence of which may differ in different communities. Enquiries as to life styles may determine important environmental influences. Examination of donor eyes from these communities may reveal distinctive features that may reflect the variation in genetic predisposition and environmental pressures. It is hoped that the findings from such studies will lead to novel and potentially successful management strategies.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.OPHTHA.2016.12.002
Abstract: To summarize the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (AMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials. Systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings. A panel of retina specialists. During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases. A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular AMD was held. Advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced AMD trials. Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus autofluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution optical coherence tomography volume scans. These images should be acquired at regular intervals throughout the study. In studies of non-neovascular AMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit. Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study. Indocyanine-green angiography (ICG-A) may be considered at baseline under certain conditions. For studies in patients with neovascular AMD, increased need for visualization of the vasculature must be taken into account. Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions. A multimodal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features. Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future.
Publisher: Wiley
Date: 14-06-2016
DOI: 10.1111/ANS.13616
Publisher: Impact Journals, LLC
Date: 02-2017
Publisher: Wiley
Date: 07-2006
DOI: 10.1111/J.1442-9071.2006.01256.X
Abstract: We report a single case study of concordant bilateral Duane's Retraction Syndrome (DRS) (type 1) in female monozygotic (MZ) twins aged 47 years. The twin pair were recruited through the Australian Twin Registry as part of a twin study on myopia. This twin pair were full term and had a similar birth weight: 2.27 kg and 1.81 kg in twin 1 and twin 2, respectively. There was no report of any other childhood medical conditions in either twin. Both twins had an equal amount of restriction in right and left abduction. Narrowing of the palpebral fissures and globe retraction in right and left adduction was also observed in both twins. To our knowledge this is the first case to report concordant bilateral DRS (type 1) in female MZ twins. The concordance for the presence of DRS and associated clinical signs observed in this MZ twin pair supports a genetic origin to DRS.
Publisher: Springer Science and Business Media LLC
Date: 29-06-2012
DOI: 10.1038/EYE.2012.98
Publisher: Elsevier BV
Date: 12-2010
Publisher: Springer Science and Business Media LLC
Date: 06-06-2023
DOI: 10.1038/S41433-023-02540-W
Abstract: With a growing aging population, the prevalence of age-related eye disease and associated eye care is expected to increase. The anticipated growth in demand, coupled with recent medical advances that have transformed eye care for people living with retinal diseases, particularly neovascular age-related macular degeneration (nAMD) and diabetic eye disease, has presented an opportunity for health systems to proactively manage the expected burden of these diseases. To do so, we must take collective action to address existing and anticipated capacity limitations by designing and implementing sustainable strategies that enable health systems to provide an optimal standard of care. Sufficient capacity will enable us to streamline and personalize the patient experience, reduce treatment burden, enable more equitable access to care and ensure optimal health outcomes. Through a multi-modal approach that gathered unbiased perspectives from clinical experts and patient advocates from eight high-income countries, substantiated perspectives with evidence from the published literature and validated findings with the broader eye care community, we have exposed capacity challenges that are motivating the community to take action and advocate for change. Herein, we propose a collective call-to-action for the future management of retinal diseases and potential strategies to achieve better health outcomes for in iduals at-risk of, or living with, retinal disease.
Publisher: Wiley
Date: 11-11-2013
DOI: 10.1111/CEO.12247
Abstract: A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration (AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported. Prospective non-randomised, pilot intervention study. Subjects with bilateral intermediate AMD (n = 50, aged 50-75 years). Ultra-low energy laser pulses applied in 12 spots around the macula of one eye (0.15-0.45 mJ), using 400 μm diameter spot, 3 nanosecond pulse length, 532 nm wavelength and energy titrated to each patient. Best corrected visual acuity, drusen area and macular sensitivity (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser. Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3° was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect >15 dB), seven improved sufficiently to be taken out of this high-risk category. A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD.
Publisher: Wiley
Date: 30-07-2009
DOI: 10.1111/J.1442-9071.2009.02095.X
Abstract: To investigate if cataract surgery causes progression, from high-risk early age-related macular degeneration (AMD) to choroidal neovascularization (CNV), in the postoperative period. Randomized controlled trial. Patients, with visually significant cataract and fundus features of early AMD at high risk of progression to CNV, were randomized into two groups and were evaluated at baseline and 6 months. The study patients (n = 27) underwent immediate cataract surgery. The control group (n = 29) comprised patients who had cataract surgery deferred until after the 6-month visit. Assessment included visual acuity, quality of life (QoL) and fundus fluorescein angiography (FFA). Of 68 eligible eyes, 60 participated and 56 completed the study. Three referred eyes (3.2%) were ineligible on the basis of a pre-existing, unsuspected occult CNV that was detected by baseline FFA. All three cases had end-stage exudative AMD in the fellow eye. Of the study eyes in the immediate surgery arm (n = 27), one (3.7%) developed CNV compared with none (0/29) in the deferred arm (chi(2) P = 1.0) at 6 months. In the operated group, there was a 2.8-line improvement in logMAR visual acuity and 2.1-fold average gain in QoL at 6 months. No increased short-term risk of progression of AMD to CNV in high-risk fundi following uncomplicated phacoemulsification surgery was found. A low threshold for performing preoperative imaging in patients with AMD, especially in those with exudative AMD in the fellow eye, to exclude undetected CNV is recommended. Provided there is no CNV, there are distinct benefits of cataract surgery in people with early AMD.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2019
Publisher: Wiley
Date: 12-09-2017
DOI: 10.1111/CEO.12804
Abstract: Late neovascular age-related macular degeneration (nvAMD) is very common and causes irreversible severe visual loss unless treated swiftly with vascular endothelial growth factor (VEGF) inhibitors. Although publicly subsidized access to treatment may be inequitable, which is why we assessed treatment provision across Australia. Secondary analysis of Australian data. All Pharmaceutical Benefits Scheme (including Repatriation PBS) beneficiaries. Treatment and incidence data were obtained from Medicare Australia, the Royal Australian and New Zealand College of Ophthalmologists, Optometry Australia, the Blue Mountains Eye Study and the Australian Bureau of Statistics. Data were mapped using geographical information software, and factors associated with treatment provision were assessed using multiple linear regression models. Unmet need (%) for anti-VEGF treatment for nvAMD. On average, we estimated 7316 incident cases of nvAMD not to be treated per year from 2010 to 2014 (50.1% of total). Number of ophthalmologists and optometrists (per 1000, β = -0.024 95% confidence interval [CI] -0.041, -0.007) and being located in remote regions (β = 0.186 95% CI 0.110, 0.262) were associated with percentage of untreated cases. A higher proportion of the population speaking a language other than English at home was associated in univariate analyses only (β = 0.0015 95% CI -0.0004, 0.0027 P = 0.007). A large proportion of incident nvAMD is not treated with anti-VEGF. Not receiving treatment is more likely in regional or remote areas and areas with fewer service providers. Not speaking English at home may further limit access. Service delivery models for more equitable service provision are needed.
Publisher: Wiley
Date: 27-11-2003
DOI: 10.1046/J.1442-9071.2003.00711.X
Abstract: To investigate the relationship between iris colour, ethnic origin and the progression of age-related macular degeneration (AMD). Participants were recruited from the population-based Melbourne Visual Impairment Project or the prospective, randomized, double-masked Vitamin E, Cataract and Age-Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992-1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants' iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo-Saxon or non-Anglo-Saxon, according to the participants' grandparents' country of birth. In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age-adjusted and multivariate-adjusted associations were not significant (both P = 0.13). Age-adjusted and multivariate comparisons of Anglo-Saxon ethnic origin to non-Anglo-Saxon ethnic origin showed a noticeable but non-significant association with progression of AMD (P= 0.22 and P= 0.14, respectively). In iduals with light iris colour or of Anglo-Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger s le is required to confirm these clinically important, but statistically non-significant, associations.
Publisher: Future Medicine Ltd
Date: 08-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1097/OPX.0000000000000891
Abstract: This study aimed to determine the feasibility of an assessment of vision-related orientation and mobility (O& M) tasks in persons with severe vision loss. These tasks may be used for future low vision rehabilitation clinical assessments or as outcome measures in vision restoration trials. Forty legally blind persons (mean visual acuity logMAR 2.3, or hand movements) with advanced retinitis pigmentosa participated in the Orientation & Mobility—Very Low Vision (O& M-VLV) subtests from the Low Vision Assessment of Daily Activities (LoVADA) protocol. Four categories of tasks were evaluated: route travel in three indoor hospital environments, a room orientation task (the “cafe”), a visual exploration task (the “gallery”), and a modified version of the Timed Up and Go (TUG) test, which assesses re-orientation and route travel. Spatial cognition was assessed using the Stuart Tactile Maps test. Visual acuity and visual fields were measured. A generalized linear regression model showed that a number of measures in the O& M-VLV tasks were related to residual visual function. The percentage of preferred walking speed without an aid on three travel routes was associated with visual field (p 0.01 for all routes) whereas the number of contacts with obstacles during route travel was associated with acuity (p = 0.001). TUG-LV task time was associated with acuity (p = 0.003), as was the cafe time and distance traveled (p = 0.006 and p 0.001, respectively). The gallery score was the only measure that was significantly associated with both residual acuity and fields (p 0.001 and p = 0.001, respectively). The O& M-VLV was designed to capture key elements of O& M performance in persons with severe vision loss, which is a population not often studied previously. Performance on these tasks was associated with both binocular visual acuity and visual field. This new protocol includes assessments of orientation, which may be of benefit in vision restoration clinical trials.
Publisher: Elsevier BV
Date: 02-2017
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-04-2011
DOI: 10.1167/IOVS.10-6568
Abstract: To determine the longitudinal impact of idiopathic macular telangiectasia (MacTel) type 2 on vision-specific quality of life (QoL). Participants with MacTel type 2 and controls with no vision impairment were recruited at baseline. All underwent a full ophthalmic examination and the interview-administered 28-item Impact of Vision Impairment (IVI) questionnaire at baseline, to gather information on sociodemographic factors and vision-specific QoL. The MacTel patients were reassessed at 24 months. For the MacTel participants (n = 22), the median (range) age and visual acuity were 64 years (45-87) and 20/32 (20/13-20/63) in the better eye, respectively. The corresponding median values in the control group (n = 38) were 57 years (41-68) and 20/25 or better in both eyes, respectively. Rasch analysis showed that the IVI and its three subscales had sufficient psychometric validity and possessed interval level estimates. The control group had almost twice the level of vision-specific QoL than did the MacTel group at baseline on all IVI scores (P < 0.001 for all). At 24 months, we found no significant change in any of the IVI scores in the MacTel group. Similarly, there was no significant difference in visual acuity in the better or worse eyes in that group after 2 years. Persons with MacTel type 2 had poorer overall vision-related QoL than did healthy controls. Several aspects of vision-related QoL and distance visual acuity did not significantly change after 24 months. Longer follow-up assessment periods are needed to determine the longitudinal impact of this condition on vision-related QoL.
Publisher: Informa UK Limited
Date: 2004
Publisher: Wiley
Date: 12-11-2014
DOI: 10.1096/FJ.14-262444
Abstract: Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.SURVOPHTHAL.2013.03.009
Abstract: Currently available evidence on predictors of anti-vascular endothelial growth factor (VEGF) treatment response in neovascular age-related macular degeneration was reviewed. No meta-analysis of results is possible because of a lack of controlled and randomized trials, varying treatment regimes and outcome measures used, as well as suboptimal reporting. For genetic factors, most evidence to date has been generated for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH gene and 15% of the SNPs assessed in the VEGF gene were found to be associated with visual outcomes or the number of injections required during follow-up. Some evidence suggests association of worse treatment outcomes as well as a younger age at treatment onset with an increasing number of risk alleles in known risk genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical factors such as higher age, a better visual acuity (VA), a larger choroidal neovascularization (CNV) lesion at baseline, and a delay between symptom onset and initiation of treatment of more than 3 weeks also impact outcomes. Conversely, a worse acuity at baseline predicted more gain in vision. Overall, patients presenting with good acuity at baseline were more likely to have good VA at follow up, but the gain afforded by treatment was impacted by a ceiling effect. Most available evidence suggests a strong association of clinical factors such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes. No behavioral factors such as smoking influence treatment outcomes. Based on the studies conducted so far, the evidence suggests that underlying genotype of known AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas presenting clinical factors appear to be more important in determining treatment outcomes.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-03-2014
Abstract: Vision restoration is a fast-approaching reality for some people with profound vision loss. In order to reliably determine treatment efficacy, accurate assessment of baseline residual visual function is critical. The purpose of this study was to compare residual function as detected on Goldman visual field (GVF) and full-field ERG (ffERG), and correlate with the remaining photoreceptor layer as determined by spectral-domain optical coherence tomography (SD-OCT), in subjects with severe vision loss. Fifty-four subjects with advanced retinitis pigmentosa and no discernible signal on ffERG were included. Trace residual function was assessed using discrete Fourier transform (DFT) analysis of the 30-Hz flicker ffERG and the percentage of remaining GVF. The horizontal extent of the outer nuclear layer (ONL) on SD-OCT was assessed. Thirty percent of the study eyes had a 30-Hz flicker response after DFT analysis of the ffERG, and 57% had a measurable GVF. Thirty-five percent had a visible ONL on SD-OCT. There was no significant correlation between the magnitude of the 30-Hz flicker response and the percentage of remaining GVF (r = 0.172, P = 0.213) or the extent of remaining central photoreceptors (r = 0.258, P = 0.06). Only 17% of the eyes had all three parameters detected. Discrete Fourier transform analysis of the 30Hz-flicker ffERG response and GVF can detect trace residual function. Evidence of this residual function is not always supported by the structural correlate of a measurable ONL. Our findings highlight the importance of completing a multimodal assessment to accurately define the important parameters of retinal structure and function in people with profound vision loss.
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: Springer Science and Business Media LLC
Date: 2008
Publisher: Proceedings of the National Academy of Sciences
Date: 23-04-2018
Abstract: Genetic variation of the complement factor H ( CFH ) gene family is associated with several complex diseases. Here, we have performed both long- and short-read sequencing of multiple humans and nonhuman primates in an effort to understand its complex evolutionary history. We find that this locus has evolved predominantly through incomplete segmental duplication and identify recurrent reuse of donor and acceptor duplications leading to CFHR fusion genes with erse functions. Investigation of a large cohort of patients with age-related macular degeneration revealed multiple structural variation breakpoints and mutational burdens that cluster in specific domains of the CFH protein. These domains overlap sites showing signatures of natural selection, providing strong evidence for the shared role of selective pressure on ersity and disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2018
DOI: 10.1097/IAE.0000000000001496
Abstract: To report 24-month outcomes of a treat and extend (T& E) regimen using aflibercept in eyes with neovascular age-related macular degeneration. This was a database observational study that included treatment-naive eyes with neovascular age-related macular degeneration tracked by the Fight Retinal Blindness! outcome registry completing 24 months of sole monotherapy with aflibercept treatment under a T& E regimen between November 1, 2012 and January 31, 2014. Locally weighted scatterplot smoothing curves were used to display visual acuity outcomes. Main outcome measures were change in visual acuity at 24 months and number of injections and visits during the study period. The study population, identified by reviewing the database, consisted of 136 eyes from 123 patients completing 24 months of follow-up on aflibercept. Mean (SD) age was 77.2 (7.0) years, 59% were female. Mean visual acuity increased from 61.4 (∼20/60 SD 17.4) letters at baseline to 67.4 (∼20/45 SD 17.7) letters at 24 months (+6.0 letters [95% confidence interval: 3.3–8.5] P 0.001). From baseline to 24 months, the proportion of eyes with visual acuity ≥70 letters (20/40) increased (40%–58%, P 0.001) and the proportion of eyes with visual acuity ≤35 letters (20/200) remained the same (10% P = 0.547). Ninety-eight per cent of eyes starting with visual acuity ≥70 letters (20/40) were able to maintain this up to 24 months. From the first to the second year of treatment, the mean number of injections (7.8 [2.1] vs. 5.7 [2.6] P 0.001) and visits (8.7 [1.7] vs. 6.5 [2.4] P 0.001) decreased for eyes completing 24 months of treatment. When data from 60 eligible eyes that did not complete 2 years follow-up, along with 14 eyes that switched to ranibizumab, were included using last observation carried forward, the mean change in visual acuity from baseline was +5.6 letters (95% confidence interval: 3.3–7.7). These data indicate that eyes treated with aflibercept, as a sole therapy, in routine clinical practice with a T& E regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.
Publisher: Wiley
Date: 03-2007
Publisher: Elsevier BV
Date: 2018
Publisher: Informa UK Limited
Date: 31-01-2017
DOI: 10.1080/09286586.2016.1259422
Abstract: Age-related macular degeneration (AMD) is the leading cause of severe, irreversible vision loss in older adults. Evidence for an association between AMD and mortality remains inconclusive despite evidence for an association with cardiovascular and inflammatory diseases. We aim to compare all-cause, cardiovascular and cancer mortality between those with early or late AMD and control study participants. A protocol was registered at PROSPERO (CRD42015020622). A systematic search of Medline (Ovid), PubMed, and Embase (Ovid) was conducted on 6 June 2015. Reference lists from identified studies and four clinical trial registries were searched for additional studies. Participants were required to be over the age of 40 years, and AMD status must have been objectively assessed. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. Random-effects meta-analyses were performed. A total of 12 reports from 10 studies were included in the meta-analysis. Late AMD was associated with elevated rates of all-cause (nine studies, hazard ratio (HR) 1.20, 95% confidence interval, CI, 1.02-1.41) and cardiovascular mortality (six studies, HR 1.46, 95% CI 1.13-1.98), but early AMD was not (all-cause mortality, 10 studies, HR 1.06, 95% CI 0.98-1.14 cardiovascular mortality, five studies, HR 1.12, 95% CI 0.96-1.31). There was no evidence of an association between early or late AMD and cancer mortality (early AMD, three studies, HR 1.17, 95% CI 0.78-1.75 late AMD, three studies, HR 1.01, 95% CI 0.77-1.33). Late AMD is associated with increased rates of all-cause and cardiovascular mortality, suggesting shared pathways between late AMD and systemic disease.
Publisher: Informa UK Limited
Date: 02-2009
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.AJO.2018.03.012
Abstract: To evaluate outcomes and predictive factors of visual acuity (VA) change after cataract surgery in patients being treated for neovascular age-related macular degeneration (nAMD). Retrospective, matched case-control study. We studied eyes undergoing cataract surgery that had been tracked since they first started treatment for nAMD. These eyes were compared with a cohort of unoperated phakic eyes being treated for nAMD (3 per case) matched for treatment duration before cataract surgery, baseline VA, age, and length of follow-up. We included 124 patients that had cataract surgery and 372 matched controls. The mean (95% confidence interval) VA gained was 10.6 letters (7.8, 13.2 P < .001) 12 months after surgery 26.0% had gained ≥3 lines and 1.6% had lost ≥3 lines of VA. Visual acuity (mean [standard deviation]) 12 months after surgery was higher in eyes that had cataract extraction compared with controls (65.8 [17.1] vs 61.3 [20.8] letters, respectively, P = .018). The proportion of visits where the choroidal neovascular (CNV) lesion was graded active and the mean number of injections were similar before and after surgery (P = .506 and P = .316, respectively), whereas both decreased in the control group, suggesting that surgery modestly increased the level of activity of the CNV lesion. Mean [SD] VA prior to surgery was lower in eyes that gained ≥15 letters compared with eyes that gained 0-14 letters (40.2 [21.4] vs 62.1 [15.1], P < .001). Patients undergoing cataract surgery within the first 6 months of anti-VEGF therapy were more likely to lose rather than gain vision (20.8% lost vision vs 12.8% and 4.4% gaining ≥15 or 0-14 letters respectively, P = .023). Age, receiving an injection at least 2 weeks before surgery, and the CNV lesion type had no discernible association with VA outcomes. We found evidence of a modest effect of cataract surgery on CNV lesion activity in eyes being treated for nAMD. Despite this, visual outcomes were reassuringly good. Cataract surgery within 6 months of starting treatment for nAMD should be avoided if possible.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.OPHTHA.2010.12.019
Abstract: To evaluate the safety and efficacy of in idualized ranibizumab treatment in patients with neovascular age-related macular degeneration. Twelve-month, phase III, multicenter, open-label, single-arm study. A total of 513 ranibizumab-naïve SUSTAIN patients. Three initial monthly injections of ranibizumab (0.3 mg) and thereafter pro re nata (PRN) retreatment for 9 months based on prespecified retreatment criteria. Patients switched to 0.5 mg ranibizumab after approval in Europe. Frequency of adverse events (AEs), monthly change of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline, the time to first re-treatment, and the number of treatments were assessed. A total of 249 patients (48.5%) reported ocular AEs, and 8 (1.5%) deaths, 5 (1.2%) patients with ocular serious AEs of the study eye (retinal hemorrhage, cataract, retinal pigment epithelial tear, reduced visual acuity [VA], vitreous hemorrhage), and 19 (3.7%) patients with arteriothromboembolic events were observed. Most frequent AEs in the study eye were reduced VA (18.5%), retinal hemorrhage (7.2%), increased intraocular pressure (7.0%), and conjunctival hemorrhage (5.5%). The average number of re-treatments from months 3 to 11 was 2.7. Mean best-corrected visual acuity increased steadily from baseline to month 3 to reach +5.8 letters, decreased slightly from month 3 to 6, and remained stable from month 6 to 12, reaching +3.6 at month 12. Mean change in CRT was -101.1 μm from baseline to month 3 and -91.5 μm from baseline to month 12. The safety results are comparable to the favorable tolerability profile of ranibizumab observed in previous pivotal clinical studies in idualized treatment with less than monthly re-treatments shows a similar safety profile as observed in previous randomized clinical trials with monthly ranibizumab treatment. Efficacy outcomes were achieved with a low average number of re-treatments. Visual acuity in SUSTAIN patients with in idualized re-treatment based on VA/optical coherence tomography assessment reached on average a maximum after the first 3 monthly injections, decreased slightly under PRN during the next 2 to 3 months, and was then sustained throughout the treatment period.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-04-2017
Abstract: Reduction of the ellipsoid zone (EZ) intensity has been reported in eyes with age-related macular degeneration (AMD). This study determined whether overall EZ intensity, in retinal locations undisturbed by pathologic features, is associated with the presence of clinical features, which are known important phenotypic risk factors for disease progression, large drusen, reticular pseudodrusen (RPD), and pigmentary abnormalities. A horizontal B-scan through the foveola on spectral-domain optical coherence tomography (SD-OCT) was performed in both eyes of 75 participants with bilateral intermediate AMD and 10 age-similar control participants. Eyes with AMD were classified as per the presence of large drusen, RPD, and hyperpigmentary changes. The relative EZ intensity profile, up to an eccentricity of 3400 μm, was averaged over seven 1000-μm retinal segments. The association between relative EZ intensity profile over seven retinal segments and AMD pathologic features was analyzed. The average relative EZ intensities were significantly reduced in eyes with intermediate AMD compared to normal eyes (P ≤ 0.025) and with increasing age (P ≤ 0.020). On multivariate analyses, only the presence of hyperpigmentary changes and increasing age were significantly associated with reduced overall relative intensities (P ≤ 0.024), but not the presence of large drusen or RPD (P ≥ 0.115). The presence of hyperpigmentary change in the macula in association with large drusen, not large drusen alone, nor large drusen with RPD, was significantly associated with a generalised reduction in EZ intensity. Quantitative assessment of the relative EZ intensity may serve as an effective biomarker of disease severity and progression.
Publisher: Public Library of Science (PLoS)
Date: 24-07-2015
Publisher: BMJ
Date: 08-10-2007
Publisher: Springer Science and Business Media LLC
Date: 04-05-2012
DOI: 10.1038/EYE.2012.72
Publisher: Springer Science and Business Media LLC
Date: 20-09-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Informa UK Limited
Date: 02-2013
DOI: 10.1586/EOP.12.71
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1993
DOI: 10.1097/00007890-199301000-00008
Abstract: Urocanic acid (UCA) was investigated for its activity as an immunosuppressive agent in murine heterotopic allotransplantation. Mice grafted with cornea, pancreas, and skin under the renal capsule were given either intravenous, subcutaneous, or topical cis-UCA in the peritransplant period. Grafts were performed across complete and minor MHC barriers. Peritransplant immunosuppression with cis-UCA prolonged survival of these grafts, but no route of administration was clearly superior to another. Survival of cornea was prolonged more than survival of skin or pancreas in all MHC disparate combinations. cis-UCA was also used to assess its effect on stimulator cells, derived from mice that had received UCA, in mixed lymphocyte responses. cis-UCA adversely affected the ability of stimulator cells to provoke T cell proliferation in an allogeneic MLR. These findings suggest that cis-UCA may be a potentially useful immunosuppressive agent.
Publisher: Wiley
Date: 2007
DOI: 10.1111/J.1442-9071.2006.01392.X
Abstract: The role of inflammation in the aetiology of age-related macular degeneration (AMD) has become very topical as the discovery that genetic variation in complement pathway genes influences the risk of developing AMD. Complement factor H gene, an inhibitor of the alternative complement activation pathway along with other complement pathway genes factor F (BF) and C2 show significant contribution to the risk of AMD. The alternative complement pathway is activated by a trigger, which is often microbial in nature. One current model of AMD aetiology implicates aberrant regulation of the alternative pathway of complement, in combination with some unknown infectious agents. Chlamydia pneumoniae could be one such potential trigger of the alternative complement pathway and several investigations have linked C. pneumoniae to AMD. However, there are only a few studies to date and numbers in most studies are small. Also there are many difficulties in verifying laboratory techniques for the detection of C. pneumoniae chronic infection. As such we need to be cautious not to over interpret the current results. However, the findings certainly give impetus for further work on C. pneumoniae and AMD. This paper provides an overview of work in this area.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.OPHTHA.2015.10.029
Abstract: To determine the prevalence of reticular pseudodrusen (RPD) and its association with age-related macular degeneration (AMD) and AMD risk factors in a large s le. Community-based cohort study in Melbourne, Victoria, Australia. A total of 21,130 participants 48 to 86 years of age available for ophthalmic assessment at follow-up from 2003 through 2007. Lifestyle, diet, and anthropometric measurements were obtained at baseline and follow-up. At follow-up, digital macular color photographs were graded for early, intermediate, and late AMD as well as the presence of RPD. Data were analyzed using multinomial logistic regression controlling for age, gender, smoking, country of birth, and diet. Detection of RPD based on color fundus photographs. Prevalence of RPD was 0.41% (87 of 21,130 participants), with 51% having bilateral RPD. Patients with RPD were older compared with patients with large drusen (>125 μm 76±4 vs. 68±9 years P 125 μm) were associated with a higher prevalence of RPD. Presence of geographic atrophy (GA) was associated with the highest odds of having RPD (odds ratio [OR], 153 95% confidence interval [CI], 53-442), followed by choroidal neovascularization (CNV OR, 90 95% CI, 26-310), intermediate AMD (OR, 33 95% CI, 14-77), and early AMD (OR, 12 95% CI, 5-31) compared with those with no AMD. The ARMS2 single nucleotide polymorphism (SNP) rs10490924, HTRA1 SNPs rs11200638 and rs3793917, and CFH SNPs rs393955, rs1061170, and rs2274700 were associated with increased prevalence of RPD (all P < 0.05). Reticular pseudodrusen are highly concurrent with AMD and have similar associations with known AMD risk factors such as age, gender, smoking, and genetic risk factors. Reticular pseudodrusen are associated more strongly with GA than with CNV. Although RPD are not specific to AMD, they are likely to be a strong risk factor for progression to late-stage AMD, similar to focal pigmentary abnormalities and large drusen.
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.SURVOPHTHAL.2004.12.002
Abstract: Age-related macular degeneration is a progressive late onset disease affecting central vision. It is the leading cause of irreversible blindness in developed countries, and with the aging population the problem is increasing. Current treatment options are limited to the late stage of the disease when central vision is already under great threat, and even new treatments make little impact on the rate of blindness. Intervention earlier in the disease may prove more rewarding, but to date little progress has been made with this approach. Epidemiologic, genetic, and pathological evidence continues to accumulate, suggesting a possible link between risk factors for cardiovascular diseases and age-related macular degeneration. This article reviews the evidence and discusses the rationale behind the recent suggestions that cholesterol-lowering agents may be useful in the treatment of early age-related macular degeneration. The cholesterol-lowering family of drugs called statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) inhibitors with pleiotropic actions. Their therapeutic effects in cardiovascular disease and dyslipidaemia have been well proven. In this review we will outline the known actions of statins and discuss possible ways that they may impact on age-related macular degeneration.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-2006
DOI: 10.1167/IOVS.06-0270
Abstract: A classic twin study was undertaken to assess the contribution of genes and environment to the development of refractive errors and ocular biometrics in a twin population. A total of 1224 twins (345 monozygotic [MZ] and 267 dizygotic [DZ] twin pairs) aged between 18 and 88 years were examined. All twins completed a questionnaire consisting of a medical history, education, and zygosity. Objective refraction was measured in all twins, and biometric measurements were obtained using partial coherence interferometry. Intrapair correlations for spherical equivalent and ocular biometrics were significantly higher in the MZ than in the DZ twin pairs (P < 0.05), when refraction was considered as a continuous variable. A significant gender difference in the variation of spherical equivalent and ocular biometrics was found (P < 0.05). A genetic model specifying an additive, dominant, and unique environmental factor that was sex limited was the best fit for all measured variables. Heritability of spherical equivalents of 88% and 75% were found in the men and women, respectively, whereas, that of axial length was 94% and 92%, respectively. Additive genetic effects accounted for a greater proportion of the variance in spherical equivalent, whereas the variance in ocular biometrics, particularly axial length was explained mostly by dominant genetic effects. Genetic factors, both additive and dominant, play a significant role in refractive error (myopia and hypermetropia) as well as in ocular biometrics, particularly axial length. The sex limitation ADE model (additive genetic, nonadditive genetic, and environmental components) provided the best-fit genetic model for all parameters.
Publisher: Elsevier BV
Date: 09-2015
Publisher: Elsevier BV
Date: 10-2023
Publisher: Wiley
Date: 07-2007
Publisher: Wiley
Date: 30-10-2013
DOI: 10.1111/J.1442-9071.2012.02867.X
Abstract: Little quantitative information exists regarding the effect that retinitis pigmentosa (RP) has on the choroid. The aim of this study was to determine choroidal thickness profiles in patients with RP. Prospective. Forty-two RP and 22 control subjects participated in the study. RP patients had mild to severe disease, with a visual acuity range of logMAR 0.1 to no light perception. Images of the retina and choroid were obtained using the enhanced depth-imaging method and optical coherence tomography (OCT). Choroidal thickness measures were determined via manual segmentation of the OCT image. The thickness profiles of the normal and RP groups were compared. The associations between choroidal thickness, visual acuity and duration of RP were determined. The choroid was thickest in the control eyes at the subfoveal location (336.60 ± 70.42 μm), and the thickness gradually decreased towards the peripheral retina (temporal 8° = 295.55 ± 60.52 μm nasal 8° = 251.68 ± 49.93 μm). In RP, the mean thickness was also greater at the fovea (215.60 ± 94.91 μm) than the temporal (191.66 ± 72.42 μm) and nasal (149.91 ± 57.42 μm) retina, but all values were significantly lower than those of the controls (P ≤ 0.001). Subfoveal choroidal thickness was significantly correlated with visual acuity (r = -0.46, P < 0.001) and duration of disease (r = -0.4, P = 0.001). Patients with RP have a thinner choroid than controls. Patients with poorer visual acuity or longer duration of symptoms tended to have thinner choroids. Knowledge of choroidal thickness profile in RP is important for the field of restorative vision research and the development of suprachoroidal retinal prostheses.
Publisher: Wiley
Date: 11-07-2013
DOI: 10.1111/AOS.12114
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.SCITOTENV.2021.151462
Abstract: Wildfires are becoming an increasing threat to many communities worldwide. There has been substantial progress towards understanding the proximal causes of increased fire activity in recent years at regional and national scales. However, subcontinental scale examinations of the commonalities and differences in the drivers of fire activity across different regions are rare in the Mediterranean zone of the European Union (EUMed). Here, we first develop a new classification of EUMed pyroregions, based on grouping different ecoregions with similar seasonal patterns of burned area. We then examine the thresholds associated with fire activity in response to different drivers related to fuel moisture, surface meteorology and atmospheric stability. We document an overarching role for variation in dead fuel moisture content (FM
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000209667
Abstract: i Aims: /i We intended to investigate the relative genetic contribution in wavefront aberrations using a sub-group of twins recruited in the Genes in Myopia twin study, and subsequently provide direction for future studies into the aetiology of mono-chromatic aberrations. To our knowledge, the Genes in Myopia twin study is the first study to explore the role of genetic factors in both lower- and higher-order aberrations in a Caucasian population. i Methods: /i Each in idual completed a general questionnaire and underwent a comprehensive eye examination. Higher-order wavefront aberrations were calculated with Zernike coefficients up to the fourth order. i Results: /i A total of 46 twin pairs with a mean age of 65.3 years were included in the analysis. Monozygotic intra-pair correlations were significantly higher compared to those in dizygotic twin pairs for defocus aberrations (p 0.05). A trend for a genetic component was identified for higher-order aberrations. i Conclusion: /i Genetic studies into refraction typically explore the genetic effects of lower-order aberrations such as myopia and hypermetropia however, there is little to no research into the genetic basis of higher-order aberrations. The Genes in Myopia twin study indicates a potential genetic role for higher-order aberrations and provides useful insights into the aetiology of refractive error.
Publisher: Springer Science and Business Media LLC
Date: 08-2023
Publisher: Wiley
Date: 06-2004
Publisher: Springer Science and Business Media LLC
Date: 12-2008
Publisher: Elsevier
Date: 2011
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.OPHTHA.2017.09.028
Abstract: To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Consensus meeting. Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. A consensus classification system for atrophy and OCT-based criteria to identify atrophy. OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.
Publisher: Wiley
Date: 11-01-2018
DOI: 10.1111/CEO.13131
Abstract: Reticular pseudodrusen (RPD) is strongly associated with late age-related macular degeneration (AMD) but their aetiology remains unknown. RPD have been associated with reduced choroidal thickness (ChT) but most studies are limited by small s le size and varying severity of AMD. To investigate the relationship between choroidal thickness and RPD in eyes with intermediate AMD (iAMD), controlling for variables known to influence ChT. Retrospective cohort study. Participants were recruited from Centre for Eye Research Australia. Colour fundus photographs, fundus auto fluorescence, near-infrared and spectral-domain ocular coherence tomography (OCT) were graded for RPD. ChT was measured from enhanced-depth imaging OCT scans at the centre of fovea, 1500 and 3000 μm nasal, temporal, superior and inferior from centre of fovea. ChT between RPD and non-RPD group. A total of 297 eyes from 152 subjects were included. A total of 84 (28%) had RPD and were older than non-RPD group (75.1 ± 5.4 years and 68.7 ± 6.9 years, respectively P < 0.001). In unadjusted analysis, the RPD group was significantly associated with thinner choroids across all measured locations (P ≤ 0.022). After adjustment for variables, the presence of RPD was no longer associated with ChT (P ≥ 0.132 for all locations) but age (P < 0.001) and refractive error (P = 0.002) remained significantly associated with ChT. Age and refractive error, rather than RPD, was significantly associated with reduced ChT in eyes with iAMD. Choroidal insufficiency may be a less important variable in RPD aetiology than previously considered.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-2004
DOI: 10.1167/IOVS.04-0253
Publisher: Wiley
Date: 07-02-2014
DOI: 10.1111/CEO.12287
Publisher: Elsevier BV
Date: 06-2013
Publisher: Future Medicine Ltd
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 11-11-2022
DOI: 10.1038/S41433-022-02269-Y
Abstract: This systematic review and meta-analysis investigated the impact of anti-vascular endothelial growth factor (VEGF) treatment in management of eyes with non-proliferative diabetic retinopathy (NPDR) without centre involving diabetic macular oedema (CI-DMO). We searched multiple databases for all randomised clinical trials (RCTs) that evaluated anti-VEGF treatment versus observation in eyes with NPDR without CI-DMO. Data was collected for six outcomes (best corrected visual acuity (BCVA) improvement, diabetic retinopathy severity score (DRSS), central subfield thickness, progression to vision threatening complications (VTCs), ocular adverse events and quality of life measures). Risk of bias was assessed using Cochrane risk-of-bias tool for randomised trials (RoB 2) and certainty of evidence was assessed using Grade of Recommendations, Assessment, Development and Evaluation (GRADE). We identified a total of 2 unique RCTs that compared aflibercept and sham to treat a total of 811 eyes. For BCVA change, there was a small, clinically insignificant benefit for aflibercept treatment at year 2 (MD 0.70, 95% CI 0.02-1.38, GRADE rating: MODERATE). DRSS demonstrated a statistically significant improvement with aflibercept use at year 2 (RR 3.76, 95% CI 2.75-5.13, GRADE rating: MODERATE). VTCs were significantly less in aflibercept arm at year 2 (RR 0.30, 95% CI 0.23-0.40, GRADE rating: MODERATE). In conclusion, aflibercept treatment versus observation in eyes with NPDR without CI-DMO can result in reduced risk of development of VTCs and regression of DRSS score over 2 years. Future trials are needed to increase the precision of the treatment effect and to provide data on quality-of-life metrics.PROSPERO Registration: CRD42021288608.
Publisher: Elsevier BV
Date: 11-2012
Publisher: Wiley
Date: 05-2006
Publisher: Springer Science and Business Media LLC
Date: 08-08-2008
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.OPHTHA.2016.07.012
Abstract: To present the treatment patterns, disease activity, and visual outcomes of eyes in the maintenance phase of a treat-and-extend regimen for neovascular age-related macular degeneration (nAMD). To compare the maintenance phase behavior of eyes with a shorter induction phase (≤3 injections) with those requiring a longer induction phase (>3 injections). Database observational study. Eyes with nAMD receiving anti-vascular endothelial growth factor (VEGF) treatment using a treat-and-extend protocol. Persistently active eyes were excluded, as were eyes with 0 letters and ≥15 letters). The mean change in visual acuity during the maintenance phase was +1.0 letters at 12 months -0.6 letters at 24 months and -1.5 at 36 months. Median treatment interval increased from 35 days at study entry to 63 days at 12 months and was 60 days at 36 months. 38.5% of eyes remained inactive at all observed visits during the maintenance phase (minimum 1 year follow-up, mean 945 days). The most common treatment interval at first reactivation was 8 weeks. Treatment intervals beyond 12 weeks seemed to be associated with increased risk of disease reactivation, with risk of reactivation reaching 37.4% at treatment intervals of ≥20 weeks. Eyes with a longer induction phase had worse visual outcomes in the maintenance phase, and earlier and more-frequent disease reactivation, although they received injections less frequently. The detailed behavior of eyes in the maintenance phase of treat-and-extend management for nAMD is presented. Visual acuity was well maintained during the study period. The most common interval at which reactivation first occurred was 8 weeks. Longer duration of induction phase was associated with worse visual acuity outcomes and earlier disease reactivation, perhaps because of undertreatment.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 07-08-2012
DOI: 10.1167/IOVS.11-8958
Abstract: The aim of this study was to investigate the relationship between clinical macular changes and retinal function in age-related macular degeneration (AMD). We recruited 357 participants with visual acuity of better than 20/60 in the study eye, including 64 in iduals with normal fundi and 293 AMD participants classified into 12 subgroups based upon the International Classification and Grading System. Visual function in the study eye was assessed using two steady-state tests (achromatic 14 Hz flicker [F14Hz] and isoluminant blue color [BCT]) and two adaptation measurements (cone photo-stress recovery rate [CRR] and rod dark adaptation recovery rate [RRR]). The groups were compared on their average psychophysical measurements and ranked according to functional deficiency. Both adaptation parameters were significantly abnormal when only hard and/or intermediate drusen were evident (compared to controls, P < 0.023) and yielded considerably worse outcomes in cases with more advanced fundus changes (P < 0.001), but provided limited ability to discriminate between these cases (linear trend, CRR t = 0.68, P = 0.50 and RRR t = 1.76, P = 0.08). Steady-state measurements, however, declined gradually along the entire hierarchy of fundus changes (linear trend, F14Hz t = 10.16, P < 0.001 and BCT t = 11.19, P < 0.001) with F14Hz being able to detect significant functional change as early as in the intermediate drusen group, when compared to controls (P = 0.003). Steady state thresholds (F14Hz and BCT) and clinical signs showed significant concordance across the spectrum of early AMD fundus changes. This suggests that these tests may be an effective tool for monitoring progression of AMD to supplement clinical grading.
Publisher: BMJ
Date: 06-08-2015
DOI: 10.1136/BJOPHTHALMOL-2015-306621
Abstract: To determine the relationship between self-reported visual difficulties under low luminance conditions (night vision symptoms) and visual function measures in intermediate age-related macular degeneration (AMD). One hundred participants with bilateral intermediate AMD were examined in a prospective cross-sectional study with visual function measures including best-corrected visual acuity (BCVA), low luminance visual acuity (LLVA) and microperimetry in both eyes. A 10-item Night Vision Questionnaire (NVQ-10) was then used to determine the degree of self-reported night vision symptoms experienced by each participant. For analyses, low luminance deficit (LLD) was derived as the difference between LLVA and BCVA, and microperimetric mean sensitivity (MS all points) and central sensitivity (CS points within the central 1°) were determined. Rasch analysis was used to estimate the person measure of night vision symptoms, and its relationship with visual function parameters was determined. NVQ-10 person measures were significantly associated with LLD (β coefficient=0.067, 95% CI 0.005 to 0.130, p=0.034), but not BCVA, LLVA, microperimetric MS or CS (p≥0.090). Participants with the highest degree of self-reported night vision symptoms (fourth quartile of person measure) had significantly worse LLD than those with the least difficulty (first quartile of person measure p=0.019). In in iduals with bilateral intermediate AMD, LLD was associated with self-reported night vision symptoms, suggesting that this measure may better capture the visual difficulties experienced by these in iduals under low luminance conditions than the conventional measure of photopic visual acuity.
Publisher: Elsevier BV
Date: 12-2011
DOI: 10.1016/J.YGENO.2011.08.002
Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It has been proposed that the polymorphism encoding Y402H (T1277C) in the complement factor H gene (CFH) is one of the main determinants of disease. We genotyped the polymorphism at a number of loci in the region encompassing the Regulators of Complement Activation (RCA) on chromosome 1, including T1277C SNP, in 187 patients and 146 controls. Haplotypes have been classified as protective (P) or susceptible (S) with respect to AMD. This included the identification of an S haplotype with a T at 1277. The results show that no single locus should be assumed to be directly responsible for AMD, but rather argue for the existence of RCA haplotypes, which can be assigned meaningful predictive values for AMD. We conclude that the critical sequences are within a region 450 kb centromeric to 128 kb telomeric of CFH.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 30-06-2015
DOI: 10.1167/TVST.4.3.13
Publisher: Springer Science and Business Media LLC
Date: 21-02-2020
DOI: 10.1186/S12890-020-1081-6
Abstract: Asthma is one of the chronic diseases which affects the airway, and inhalers are the preferred medications to treat this problem. Improper inhalational technique leads to decreased efficacy of the medication by reducing its deposition in the lungs. The aim of this study was to assess the barriers to and competency with the use of Metered Dose Inhaler (MDI) and its impact on disease control among adult asthmatic patients. A prospective cross-sectional study was conducted in University of Gondar comprehensive specialized hospital outpatient department (OPD) chronic follow up from 12-March-2018 to 15-May- 2018. Patients were interviewed face to face with questions which determined their competency, asthma control level and barriers for inhaler use. Overall, 307 asthmatic patients were included in the study. More than half of participants were females, 170 (55.4%) and lived in urban area 185 (60.3%). The mean age of the respondents was 51.77 years with a standard deviation of ±15.40. The cost of medication, 282 (91.9%) and the perception that medication should be used in response to symptoms but not on a regular basis 277 (90.2%) were the most identified barriers. Only 56 (18.2%) were competent for Metered Dose Inhaler use (MDIU) and 17 (5.5%) patients had well controlled asthma. Being not competent AOR 0.168[0.41–0.687] was one of the factors decreasing asthma control. Generally from this study, cost of the medication and the perception that medication should be used only for symptoms were the major identified barriers that affect the MDI use among asthmatic patients. Patients show very poor competence to their MDI which in turn led to poor asthma control. So, patients need to be taught the correct inhaler technique in the hospital and pharmacy while they came for follow up every time.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2010
Publisher: Public Library of Science (PLoS)
Date: 04-06-2018
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-06-2017
Abstract: With a retinal prosthesis connected to a head-mounted camera, subjects can perform low vision tasks using a combination of electrode discrimination and head-directed localization. The objective of the present study was to investigate the contribution of retinotopic electrode discrimination (perception corresponding to the arrangement of the implanted electrodes with respect to their position beneath the retina) to visual performance for three recipients of a 24-channel suprachoroidal retinal implant. Proficiency in retinotopic discrimination may allow good performance with smaller head movements, and identification of this ability would be useful for targeted rehabilitation. Three participants with retinitis pigmentosa performed localization and grating acuity assessments using a suprachoroidal retinal prosthesis. We compared retinotopic and nonretinotopic electrode mapping and hypothesized that participants with measurable acuity in a normal retinotopic condition would be negatively impacted by the nonretinotopic condition. We also expected that participants without measurable acuity would preferentially use head movement over retinotopic information. Only one participant was able to complete the grating acuity task. In the localization task, this participant exhibited significantly greater head movements and significantly lower localization scores when using the nonretinotopic electrode mapping. There was no significant difference in localization performance or head movement for the remaining two subjects when comparing retinotopic to nonretinotopic electrode mapping. Successful discrimination of retinotopic information is possible with a suprachoroidal retinal prosthesis. Head movement behavior during a localization task can be modified using a nonretinotopic mapping. Behavioral comparisons using retinotopic and nonretinotopic electrode mapping may be able to highlight deficiencies in retinotopic discrimination, with a view to address these deficiencies in a rehabilitation environment. (ClinicalTrials.gov number, NCT01603576).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1994
DOI: 10.1097/00007890-199404270-00019
Abstract: A model of murine heterotopic allogeneic transplantation was used to study the rejection characteristics of three tissues--adult cornea, fetal pancreas, and fetal skin--for attributes that might explain their variation in rejection rates and help define the determinants of graft immunogenicity. Under identical conditions, tissues were transplanted to the renal subcapsular space and their base-line rejection rates compared. The expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1), was determined for each tissue, as was their ability to produce interleukin-6, IL-3, interferon-gamma, and granulocyte-macrophage colony-stimulating factor in vitro. These studies were performed under basal conditions and after stimulation with concanavalin A-stimulated spleen cell supernatant (CAS) or INF gamma. Corneal grafts had a slow rejection rate compared with pancreas and skin. While all three tissues had low basal expression of MHC class II, both fetal skin and pancreas, but not adult cornea, were able to increase this under our experimental conditions. Pancreas and skin produced IL-6 under basal conditions and could be stimulated to increase production 2-3-fold but the cornea did not basally produce IL-6 and showed minimal upregulation. We postulate that delayed corneal rejection, compared with pancreas and skin, results from two compounding deficiencies: the relative lack of class II MHC-positive APC and the inability to overcome this deficiency by upregulating class II expression and producing accessory molecules for antigen presentation.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 29-11-2012
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.OPHTHA.2017.07.005
Abstract: To assess the incidence, cumulative rate, and long-term outcomes of infectious and noninfectious endophthalmitis after intravitreal injections (IVTs) of anti-vascular endothelial growth factor (VEGF) agents. Database study, prospectively designed. Treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) tracked by the Fight Retinal Blindness! (FRB!) registry that commenced anti-VEGF therapy between January 1, 2006, and November 30, 2016. Cumulative rate of endophthalmitis and survival curves were measured using Cox-proportional hazards models. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA). Incidence and cumulative rate of endophthalmitis, and change in VA 12 months after endophthalmitis. Infectious endophthalmitis developed in 18 of 88 150 injections (1/4897 injections [0.020%] 95% confidence interval [CI], 0.012-0.032) with no difference found between types of anti-VEGF medications (P = 0.896). The cumulative rate of infectious endophthalmitis per patient was 0.055%, 0.183%, 0.360%, 0.360%, 0.555%, and 0.843% after 10, 20, 30, 40, 50, and 60 IVTs, respectively. However, the "risk" of infectious endophthalmitis did not increase with each successive injection (P = 0.202). Noninfectious endophthalmitis developed in 11 of 88 150 injections (1/8013 injections [0.012%] 95% CI, 0.006-0.022). The cumulative rate of noninfectious endophthalmitis per patient was 0.087% and 0.228% after 10 and 20 IVTs, respectively, and then remained stable up to 60 IVTs. The incidence of noninfectious endophthalmitis was higher for bevacizumab (8/9931, 0.081%) compared with ranibizumab (3/54 776, 0.005% P = 0.005) and aflibercept (0/23 425 P = 0.016), and no differences were observed between ranibizumab and aflibercept (P = 1.0). The 12-month VA in infectious and noninfectious endophthalmitis was within ±2 lines of before endophthalmitis in 53% and 75% of eyes, respectively a loss >2 lines was observed in 31% and 25% of eyes, respectively. The incidences of infectious and noninfectious endophthalmitis after IVT were low, and the risk did not increase with each successive injection. We found higher rates of noninfectious endophthalmitis with bevacizumab compared with ranibizumab or aflibercept. Three quarters of cases with infectious and two thirds of cases with noninfectious endophthalmitis retained vision within 10 letters of the pre-endophthalmitis level.
Publisher: Elsevier BV
Date: 06-2014
Publisher: Wiley
Date: 26-09-2003
DOI: 10.1046/J.1442-9071.2003.00683.X
Abstract: Age-related macular degeneration (AMD) is the leading cause of legal blindness in in iduals 50 years and older in the developed world. Choroidal neovascularization (CNV) in exudative AMD is responsible for the majority of severe vision loss. Until recently, laser photocoagulation was the only well-established and widely accepted treatment for CNV. However, it is beneficial only for a small subset of patients, has a high rate of CNV persistence and recurrence and results in iatrogenic, collateral damage to the overlying retina. These issues make it difficult to recommend in the case of subfoveal lesions. Consequently, numerous experimental therapeutic interventions are under investigation with the common objective of destroying the CNV but leaving the foveal neurosensory retina intact. Treatment modalities can be grouped into five major categories: photodynamic therapy radiotherapy transpupillary thermotherapy anti-angiogenic and angiostatic agents and surgical intervention. The present review aims to explain the rationale behind these new treatments, analyse the evidence for their safety and efficacy, determine their stage of development and indicate in which patients they are potentially useful.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.OPHTHA.2013.12.032
Abstract: To assess the impact of anti-vascular endothelial growth factor (VEGF) treatment in routine medical practice on vision-related quality of life (VRQoL) in neovascular age-related macular degeneration (AMD). Prospective case series. A total of 169 patients with neovascular AMD undergoing anti-VEGF treatment. The VRQoL interviews at baseline (n = 169), 6 months (n = 138), and 12 months (n = 120), routine anti-VEGF treatment with up to monthly follow-ups, and re-treatment as indicated. The Impact of Vision Impairment (IVI) questionnaire was subjected to Rasch analysis to assess its measurement performance and generate interval-level estimates of VRQoL at all time points, anchoring the instrument to its baseline measurement characteristics. Factors associated with a change in reported VRQoL were assessed using generalized linear regression models. The VRQoL as measured by the IVI using its 3 subscales: Accessing Information, Mobility, and Emotional Well-being. The mean age was 70 years (±6 years standard deviation [SD]) 56% were female. Visual acuity (VA) improved by a mean of 8 letters (±17 SD), and mean retinal thickness decreased by 87 (±89.7) μm with an average of 6.5 (±2.6) injections over 12 months. Those who lost >2 lines (n = 13, 11%) reported worse VRQoL at 12 months on the Accessing Information and Mobility subscales (P = 0.007 and P = 0.050, respectively). Conversely, those who gained >2 lines (n = 29, 24%) reported better VRQoL on the Accessing Information and Emotional Well-being subscales (P = 0.009 and P = 0.008, respectively). Patients who did not experience a change in VA reported no change in their VRQoL. In multivariate analyses, only a change in VA but not whether the better or worse eye was treated predicted a change in VRQoL on the Accessing Information (P = 0.004) and the Emotional Well-being (P = 0.008) subscales. We confirmed that anti-VEGF treatment for neovascular AMD improves patients' VRQoL in those who gain vision and maintains VRQoL in those who maintain VA in their treated eye, irrespective of whether the worse or better eye is treated. Against this background, the best possible outcomes should be aimed for even if the worse eye is treated because a loss of VA in the worse eye will adversely affect patients' VRQoL.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-11-2013
Abstract: To determine the intrasession test-retest variability of microperimetry in participants with age-related macular degeneration (AMD). This study consisted of two separate groups of subjects who had not performed microperimetry previously. In group 1, 30 AMD and 14 control participants performed three microperimetry examinations of a selected eye within one session (test 1 and 2, first pair test 2 and 3, second pair). Follow-up examination at 6 months was available in 20 AMD participants in group 1, who performed two microperimetry examinations. In group 2, 71 AMD participants performed a short practice examination, then two microperimetry examinations of the right eye (test 1 and 2, first pair) and two of the left eye (test 3 and 4, second pair). There was a significant improvement in average point-wise sensitivity (PWS) between the first pair of examination in both groups (P < 0.001), but not in the subsequent pair (P ≥ 0.774). This improvement was not observed at the follow-up visit in the subset of AMD participants in group 1 (P = 0.433). The PWS coefficient of repeatability (CoR) for the second pair of examinations was ± 4.12 dB and ± 4.37 dB for AMD participants for group 1 and 2 respectively. A significant increase in sensitivity between the first and second test, but not in the subsequent tests, was found for participants who had not performed microperimetry previously. Intrasession test-retest variability can therefore be minimized by discarding the first examination to avoid the influence of a learning effect.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2018
DOI: 10.1167/TVST.7.3.3
Publisher: Springer Science and Business Media LLC
Date: 07-2003
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.OPHTHA.2015.05.010
Abstract: To analyze the long-term outcomes of eyes with neovascular age-related macular degeneration (AMD) starting treatment with vascular endothelial growth factor (VEGF) inhibitors at least 5 years earlier. Database observational study. Treatment-naïve eyes with neovascular AMD tracked by the Fight Retinal Blindness outcome registry that received at least 1 anti-VEGF injection. Locally weighted scatterplot smoothing curves were used to display visual acuity (VA) results. Change in mean VA and number of injections and visits from baseline up to 7 years after initiating treatment. The mean follow-up time of all 1212 identified eyes was 53.5 months, and 549 (45%) continued attending after 60 months. Mean VA improved from 55.1 to 61.4 letters after 6 months and remained above the mean presenting VA for approximately 6 years. After 7 years, mean VA was 2.6 letters lower than baseline for the 131 eyes still being followed 40% had VA ≥70 (20/40) letters, and 18% had VA ≤35 letters (20/200). Of those with 20/40 VA before treatment, 40% had lost it after 7 years. Geographic atrophy affecting the fovea was thought to be the cause of a ≥10-letter loss after 6.5 years in 37% of a subset of such eyes that were retrospectively analyzed. A median of 6 injections and 9 visits were recorded over the first 12 months, and then 5 treatments and 7 to 9 visits per annum thereafter through 7 years. Treatment was discontinued for 663 eyes (53%) within the first 5 years. Despite initial gains in vision, the mean VA of these eyes had deteriorated to baseline or worse around the time treatment was discontinued. The rate of serious adverse events was low. Good long-term outcomes of VEGF inhibition for neovascular AMD were found in this study. These results may be better than other reports because more injections were given to our patients, possibly associated with a greater incentive for the physician to treat. Further studies to determine how to maximize the proportion of eyes that retain the initial VA gains of anti-VEGF are warranted.
Publisher: Wiley
Date: 04-08-2020
DOI: 10.1111/CEO.13823
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.BBALIP.2018.04.007
Abstract: The human retina is a complex structure of organised layers of specialised cells that support the transmission of light signals to the visual cortex. The outermost layer of the retina, the retinal pigment epithelium (RPE), forms part of the blood retina barrier and is implicated in many retinal diseases. Lysophosphatidic acid (LPA) is a bioactive lipid exerting pleiotropic effects in various cell types, during development, normal physiology and disease. Its producing enzyme, AUTOTAXIN (ATX), is highly expressed by the pigmented epithelia of the human eye, including the RPE. Using human pluripotent stem cell (hPSC)-derived retinal cells, we interrogated the role of LPA in the human RPE and photoreceptors. hPSC-derived RPE cells express and synthesize functional ATX, which is predominantly secreted apically of the RPE, suggesting it acts in a paracrine manner to regulate photoreceptor function. In RPE cells, LPA regulates tight junctions, in a receptor-dependent mechanism, with an increase in OCCLUDIN and ZONULA OCCLUDENS (ZO)-1 expression at the cell membrane, accompanied by an increase in the transepithelial resistance of the epithelium. High concentration of LPA decreases phagocytosis of photoreceptor outer segments by the RPE. In hPSC-derived photoreceptors, LPA induces morphological rearrangements by modulating the actin myosin cytoskeleton, as evidenced by Myosin Light Chain l membrane relocation. Collectively, our data suggests an important role of LPA in the integrity and functionality of the healthy retina and blood retina barrier.
Publisher: Springer Science and Business Media LLC
Date: 07-03-2015
DOI: 10.1007/S00417-015-2970-X
Abstract: To investigate the plasma levels of amyloid beta (Aβ) and select inflammatory mediators in patients with various stages of AMD compared to that of age-matched controls, and discern a relationship to disease severity. Plasma s les were obtained from AMD subjects at various stages of disease-early (drusen only), geographic atrophy (GA), neovascular AMD (CNV)-and from controls of similar age without AMD. S les were analyzed using a commercially available ELISA kit (sixteen cytokines) or LC/MS/MS (Aβ isotypes). Descriptive statistics were compiled on all analytes. Analysis of covariance (ANCOVA) was conducted to compare each analyte across AMD groups while adjusting for sex and age of the patients, and in comparison to the control group. Receiver operating characteristics plots were generated for the strongest predictor variables. Levels of alternative spliced CC3 proteins were significantly different between controls and CNV groups (p < 0.05), with median levels almost twice higher in CNV than in controls. There was an increasing trend for plasma levels of Αβ isotypes across AMD progressive stages (p values ranged from 0.052 to 0.0012) (ANCOVA). When adjusted for multiple comparisons analysis, plasma Aβ 1-42 levels, and its ratio with Aβ 1-40 were the most significantly associated with late AMD stages. Consistently with the ANCOVA results for Αβ isotypes, the ROC curve showed a moderate prediction (AUC = - ~ 0.78) of AMD vs control using the Aβ 1-42 isotype. Plasma Aβ 1-42 may have utility as a systemic biomarker for AMD.
Publisher: Public Library of Science (PLoS)
Date: 05-12-2013
Publisher: Wiley
Date: 2012
DOI: 10.1111/J.1442-9071.2011.02581.X
Abstract: The last decade has produced pivotal change in our understanding of the molecular mechanisms underlying age-related macular degeneration (AMD), a leading cause of global blindness. In this time, the complement system has featured as a unifying theme for several elements of new evidence: initially, the discovery of complement proteins within drusen and subsequently, the association between AMD and mutations in various complement pathway genes, most notably complement factor H. Increasingly, a wealth of data are pointing towards a role for chronic local inflammation and complement activation in the patho-aetiology of AMD. These findings have paved the way for the exploration of a new paradigm of therapy in AMD management targeting of specific molecular constituents in the complement pathway thus producing d ening or inhibition of the inflammatory response. Such an approach has the potential to intervene earlier in the disease process and ideally before vision is compromised. In this review we discuss the role of the complement system in AMD, novel therapies in preclinical evaluation and clinical trial, and whether these have a part to play in reducing the burden of disease.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-08-2013
Abstract: We report the 12-month outcomes of 1140 treatment-naïve eyes with exudative age-related macular degeneration (wet AMD) who were treated for 12 months with intravitreal anti-VEGF drugs in routine clinical practice. Index visit characteristics, such as lesion type and size, visual acuity (VA, in Logarithm of the Minimal Angle of Resolution [logMAR] letters), as well as treatments, outcomes (VA, lesion activity status) and ocular adverse events were recorded in a prospectively designed electronic database. Index visit characteristics associated with the 12-month VA outcome were identified using mixed effects linear regression. Mean change in VA in the cohort after 12 months was +4.7 logMAR letters (95% confidence interval [CI], 3.4-6.1) with a mean of 7.0 injections. No significant difference was found in change in VA, or number of injections by type or size of the lesion. Median time to inactivation of lesions was 194 days. VA at the index visit was the strongest predictor for the 12-month outcomes. Infectious endophthalmitis occurred in 2 cases, and retinal detachment occurred in 1 case from a total of 9162 injections. These findings indicate that VEGF inhibitors can achieve reasonably good outcomes for wet AMD when used in routine clinical practice.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Asia Pacific Academy of Ophthalmology
Date: 2017
DOI: 10.22608/APO.2017262
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2006
DOI: 10.1167/IOVS.05-0599
Abstract: To examine whether genetic factors significantly influence macular thickness in healthy older subjects. A classic twin study was performed to compare the correlation of macular thickness between monozygotic (MZ) and dizygotic (DZ) twins in a s le of population-based volunteer twins. The study included 109 white twin pairs from 50 to 80 years of age without evidence of manifest eye disease and corrected visual acuity better than 6/7.5. Dilated macular optical coherence tomography (OCT), fundus photography, clinical examination, ocular biometry, a health-dietary questionnaire, and subjective autorefraction were performed on all subjects. Correlation of retinal thickness was significantly greater between MZ twin pairs than DZ pairs in all macular regions. The MZ-to-DZ correlation was 0.88:0.44 for the foveal region, 0.79:0.47 for the inner macular region, and 0.81:0.50 for the outer macular region. With adjustment for significant covariates and model fitting, final heritability estimates of 85%, 81%, and 81%, respectively, were obtained. A significant correlation between foveal thickness and gender was present, with the men having significantly thicker foveae. There was a significant negative correlation between outer macular thickness and axial length. This study confirms that macular thickness in older healthy subjects, as measured by OCT, may be affected by genetic factors. Factors such as axial length, gender and age, warrant further examination in larger population-based studies, as variables that may influence macular thickness. This finding suggests an inherited basis of macular thickness and may help in the understanding of the factors that govern macular structure and function.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 23-01-2014
Abstract: To determine the effect of a statin (simvastatin) on the ultrastructure and function of the RPE, Bruch's membrane (BM), and photoreceptor interface in a high-fat atherogenic mouse model of thickened BM. Wild-type C57BL/6 mice (6-weeks old) were ided into three study groups according to their diet and treatment given Group 1, normal chow diet-fed mice Group 2, high fat diet (HFD) fed mice and Group 3, HFD-fed mice treated with simvastatin daily for 30 weeks. All mice were followed-up for 30 weeks. The retinal morphology and function was examined in vivo using fundus imaging and electroretinography at 15- and 30-weeks follow-up. At the end of the study, at 36 weeks of age, eye tissues were collected and retinal sections were examined using light microscopy and transmission electron microscopy. Fundus images of the HFD-fed mice showed the presence of discrete, multiple white spots, which was significantly reduced by approximately 73% in the simvastatin-treated animals. In the HFD-fed mice, there was an increase in the empty cytoplasmic vacuoles of the RPE, presence of lipid droplets in the BM, thickening and fragmentation of the elastic lamina of the BM, and a reduction in retinal function these ultrastructural and functional changes were significantly improved in the simvastatin-treated group. Chronic administration of simvastatin significantly improves the ultrastructure and function of the RPE, BM, and photoreceptor in a high-fat atherogenic mouse model of thickened BM.
Publisher: Oxford University Press (OUP)
Date: 19-01-2009
DOI: 10.1093/AJE/KWN393
Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness among older people, and diet has been postulated to alter risk of AMD. To evaluate associations between red meat and chicken intake and AMD, the authors conducted a cohort study of 6,734 persons aged 58-69 years in 1990-1994 in Melbourne, Australia. Meat intake was estimated from a food frequency questionnaire at baseline. At follow-up (2003-2006), bilateral digital macular photographs were taken and evaluated for AMD (1,680 cases of early AMD, 77 cases of late AMD). Logistic regression was used to estimate odds ratios, adjusted for age, smoking, and other potential confounders. Higher red meat intake was positively associated with early AMD the odds ratio for consumption of red meat > or =10 times/week versus <5 times/week was 1.47 (95% confidence interval: 1.21, 1.79 P-trend or =3.5 times/week versus <1.5 times/week was inversely associated with late AMD (odds ratio = 0.43, 95% confidence interval: 0.20, 0.91 P-trend = 0.007). These results suggest that different meats may differently affect AMD risk and may be a target for lifestyle modification.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Informa UK Limited
Date: 09-2005
DOI: 10.1111/J.1444-0938.2005.TB06716.X
Abstract: Age-related macular degeneration (AMD) is the greatest cause of legal blindness in the western world. Established treatments include argon laser photocoagulation of extrafoveal choroidal neovascularisation (CNV) and photodynamic therapy of selected sub-foveal CNV. Newer approaches are targeting the angiogenic pathway in CNV development. Currently, other treatment modalities, such as radiotherapy and transpupillary thermotherapy do not have a clear role to play. Surgical options are experimental and only available in some centres for selected patients. Prevention of AMD remains elusive. Dietary supplements may have a role, while statins and prophylactic laser photocoagulation of drusen remain experimental. This paper explains the principles behind these approaches.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.OPHTHA.2010.09.004
Abstract: To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study. Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions. Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection). Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs). In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 μm in 0.3 mg quarterly, -105.6 μm in 0.5 mg quarterly, and -105.3 μm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths 1 death was suspected to be study related (cerebral hemorrhage 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low. After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies.
Publisher: Wiley
Date: 04-10-2018
DOI: 10.1111/CEO.13038
Abstract: Identifying variables that influence presenting visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) is important because it is a strong predictor of long-term outcomes. To assess the clinical and social characteristics associated with low presenting VA in nAMD patients. The present study is a cross-sectional analysis from a prospective, observational database. We identified 3242 treatment-naïve patients from 54 Australian practices in the Fight Retinal Blindness! registry. Age, gender, ethnicity and VA were recorded at the baseline visit. Socio-economic status was determined using the Australian Bureau of Statistics socio-economic indexes for areas. Association between clinical and socio-economic characteristics with presenting VA was identified. Poor VA (≤35 letters) in the presenting eye was associated with older age (adjusted odds ratio [AOR]: 1.33 for patients aged ≥80 years vs. <80 years [95% confidence interval, CI: 1.04, 1.71]), treatment at a public practice (AOR: 1.91 for public vs. private practices [95% CI: 1.46, 2.50]) and intermediate (36-69 letters) VA in the fellow eye (AOR: 0.67 [95% CI: 0.47, 0.95] and 0.64 [95% CI: 0.48, 0.85] for poor [≤35 letters] and good [≥70 letters] VA vs. intermediate VA in the fellow eye). Gender, ethnicity and socio-economic status were not independently associated with VA at presentation. Poor presenting vision is detrimental to the long-term outcomes of nAMD. Poor presentation of nAMD in Australia may not be related to socio-economic circumstances, but due to systems of care. Further research is warranted to determine why patients at public practices present with worse vision compared with private practices in Australia.
Publisher: Springer Science and Business Media LLC
Date: 26-05-2006
Abstract: To determine the risk of age-related macular degeneration (AMD) progression posed by the presence of each early AMD characteristic. A prospective cohort study of 254 participants aged 50 years and older, all with early AMD features at their baseline visit followed for an average of 7 years. Stereoscopic colour fundus photographs were graded for early AMD features using the International Classification System. AMD status was stratified into six exclusive levels along a continuum of disease severity according to drusen type, pigmentary abnormalities, or late AMD. Progression was assessed according to three definitions: a change between or within a severity level, or by side by side grading. The progression rate of early AMD ranged between 3.4 and 4.67% per annum depending upon the definition used. In total, 15 (6%) cases progressed from early AMD to the late complication of AMD. After controlling for age and smoking, cases with soft indistinct drusen at baseline were at a greater risk of progressing from early to late AMD than were cases without this characteristic (OR=3.72, 95%CI 1.20-11.54 P=0.02). Our proposed definitions of AMD progression give rates that are consistent with current knowledge of progression and its determinants. Each early AMD characteristic conveys its own risk of progression to an eye, with soft indistinct drusen carrying the greater risk. An international consensus on what defines AMD progression would greatly help the research community when trying to assess the importance of new risk factors and the effectiveness of novel interventions.
Publisher: Wiley
Date: 09-2020
DOI: 10.1111/CEO.13837
Publisher: Elsevier BV
Date: 07-2023
Publisher: Mary Ann Liebert Inc
Date: 2016
Abstract: Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (β2GPI) in the plasma of in iduals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of β2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H(2)O(2))-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate β2GPI in the retina and choroid of patients with AMD. Free thiol β2GPI is shown to protect the immortalized human RPE cell line against H(2)O(2)-induced cell death, whereas the oxidized form of β2GPI and free thiol bovine serum albumin were not protective. Free thiol β2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol β2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.
Publisher: Informa UK Limited
Date: 05-2016
DOI: 10.2147/EB.S70822
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2003
DOI: 10.1167/IOVS.02-0769
Abstract: To evaluate cone visual function of subjects with age-related maculopathy (ARM). Cone thresholds in 16 patients with ARM and 14 age-matched control subjects were compared. All subjects had visual acuity of 6/12 or better in the studied eye. A range of contrast thresholds were measured to evaluate erse aspects of cone visual function under steady state conditions (spatiotemporal, color and luminance, and photopic sensitivity) or after bleaching (adaptation dynamics). ARM produced a diffuse loss across all cone steady state visual functions in 31% to 44% of subjects. The adaptation time constant of cone recovery was significantly prolonged in most (69%) ARM eyes. A cross-correlational analysis found adaptational kinetics to be independent of other steady state losses, with cone photopigment regeneration being the most affected visual function in ARM (chi(2) = 4.03, P < 0.05). The results show that cone-adaptational kinetics are affected in ARM more so than are steady state thresholds. Given that cone recovery is easy to examine in a clinical setting, this test may provide a useful index of photopic function in patients with ARM.
Publisher: American Medical Association (AMA)
Date: 06-2012
DOI: 10.1001/ARCHOPHTHALMOL.2012.277
Abstract: To investigate the longitudinal changes in flicker perimetry in patients with age-related macular degeneration (AMD) as the condition progresses from early AMD to geographic atrophy (GA) or choroidal neovascularization (CNV). Patients with AMD and control subjects were recruited from a longitudinal study of retinal function in early AMD consisting of 187 participants. Only those who completed at least 4 consecutive, 6-monthly flicker perimetry tests were selected for this study. Study groups consisted of everyone who went on to develop GA (n = 16) or CNV (n = 5), controls (n = 24), and the high-risk, early- AMD participants whose eyes did not progress to GA or CNV (drusen >125 μm n = 18). The flicker sensitivity was determined, and its rate of change during the 18 months before the clinical detection of late AMD was calculated. Eyes that went on to develop GA or CNV had a significantly reduced mean (SD) flicker sensitivity in the months before clinical detection of GA (15.8 [5.6] dB) or CNV (19.1 [3.8] dB) compared with control eyes (22.9 [3.0] dB) (P < .001) and with eyes that did not progress to GA or CNV (21.4 [3.4] dB) (P < .001). The rate of change in flicker sensitivity was significantly increased in GA eyes (-0.07 dB/mo) (P < .001) but not in CNV eyes (0.006 dB/mo) (P = .56) compared with the control eyes (-0.003 dB/mo). Flicker sensitivity is reduced in eyes that go on to develop late AMD. The rate of change in flicker sensitivities over time was particularly useful in predicting eyes and areas within the eye that subsequently develop GA.
Publisher: American Medical Association (AMA)
Date: 20-11-0200
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.OPHTHA.2012.10.006
Abstract: To determine the association of genetic variants of the VEGFA gene with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD). A prospective cohort study. We included 201 consecutive patients receiving anti-VEGF injections for neovascular AMD. Patients were followed over 12 months. They were treated with 3 initial monthly ranibizumab or bevacizumab injections. Thereafter, the decision to retreat was made by clinicians at each follow-up visit on the basis of retreatment criteria. Seven tagged single nucleotide polymorphisms (tSNPs) in the VEGFA gene were selected and examined. Multivariate data analysis was used to determine the role of each tSNP in treatment outcome. The influence of selected VEGFA tSNPs on visual acuity (VA) outcome at 6 months. Mean baseline VA was 51±17 Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Overall, the mean change in VA from baseline was +6.5±12, +4.4±13.4, and +2.3±14.6 letters at 3, 6, and 12 months, respectively. The tSNP rs3025000 was the only SNP significantly associated (P<1 × 10(-4)) with visual outcome at 6 months with multiple correction. The presence of the T allele (TC or TT genotypes) at this tSNP predicted a better outcome of +7 letters at 6 months compared with the CC genotype. In a subgroup analysis, presence of the T allele predicted a significantly higher chance of the patients belonging to the responder group (gain of ≥5 letters from baseline) after 3, 6, and 12 months treatment (odds ratio, 2.7, 3.5, and 2.4 95% confidence interval, 1.46-5.07, 1.82-6.71, and 1.27-4.57, respectively) than any other outcome group. Pharmacogenetic association with anti-VEGF treatments may influence the visual outcomes in neovascular AMD. In patients with the T allele in tSNP rs3025000, there was a significantly better visual outcome at 6 months and a greater chance of the patients belonging to the responder group with anti-VEGF treatment at 3, 6, and 12 months. The VA outcomes of patients harboring the T allele at SNP rs3025000 were comparable with those of the pivotal clinical trials but with fewer injections, making the treatment perhaps more cost effective in certain subgroups of patients. The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Publisher: American Medical Association (AMA)
Date: 05-2001
DOI: 10.1001/ARCHOPHT.119.5.745
Abstract: To investigate the role of 2 specific alleles of the Stargardt disease gene (ABCA4) in the pathogenesis of age-related macular degeneration (AMD). Secondary objectives were to investigate differences in frequency of the G1961E allele in selected ethnic groups as well as to examine the segregation of both G1961E and D2177N alleles in 5 multiplex families with AMD. Five hundred forty-four patients with AMD and 689 controls were ascertained from 3 continents. Blood s les from 62 normal in iduals of Somalian ancestry were also obtained. Participants were screened for the presence of these ABCA4 alleles with a combination of restriction digestion and single-strand conformation polymorphism analysis of polymerase chain reaction lification products. Detected alleles were confirmed by DNA sequencing. The number of subjects exhibiting the G1961E or D2177N variants were compared between AMD and control groups using a 2-tailed Fisher exact test. There was no significant difference (P >.1) in the frequency of the G1961E and D2177N alleles in patients with AMD (2.2%) vs controls (1.0%). In contrast, there was a significant difference (P< .001) in the frequency of the G1961E alleles between normal in iduals of Somali ancestry (11.3%) and normal in iduals from other populations (0.4%). There was no evidence of cosegregation of these alleles and the AMD phenotype in the 5 multiplex families with AMD examined. These two ABCA4 alleles were slightly more frequent in patients with AMD with choroidal neovascularization (2.7%) than those without this complication (2.5%). Somali ancestry is more than 100 times more strongly associated with presence of the G1961E allele than the AMD phenotype. This study did not find any statistically significant evidence for involvement of the G1961E or D2177N alleles of the ABCA4 gene in AMD. The ABCA4 gene is definitively involved in the pathogenesis of Stargardt disease and some cases of photoreceptor degeneration. However, it does not seem to be involved in a statistically significant fraction of AMD cases.
Publisher: Wiley
Date: 06-1999
DOI: 10.1046/J.1440-1606.1999.00193.X
Abstract: Purpose: Data is reported from an ongoing trial considering functional losses in patients with high‐risk drusen. We evaluate the temporal processing in 12 subjects: four patients with high‐risk drusen, four age‐matched controls and four young observers aged 22–30. Methods: Subjects were tested using frequency‐doubling technology, macula static and flicker fields on a Medmont perimeter and foveal temporal contrast sensitivity at 2, 5, 10 and 24 Hz. Results: Eyes with high‐risk drusen had good visual acuity (6/9.5 –2 or better). All control eyes had normal fields for static, flicker and frequency‐doubling perimetry. All high‐risk drusen eyes had normal static perimetry in the presence of abnormal flicker and frequency‐doubling perimetry. High‐risk drusen eyes showed a generalized loss of temporal sensitivity across all frequencies. Conclusions: We conclude that eyes with high‐risk drusen show losses to temporal stimuli in the presence of near‐normal acuity and static thresholds. We suggest that flickering stimuli might be useful for detecting and monitoring such patients.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.OPHTHA.2013.01.014
Abstract: To determine the association of genetic variants in known age-related macular degeneration (AMD) risk-associated genes with outcome of anti-vascular endothelial growth factor (VEGF) treatment in neovascular AMD. Prospective cohort study. We enrolled 224 consecutive patients with neovascular AMD at the Royal Victorian Eye and Ear Hospital, Australia. Patients were treated with 3 initial monthly ranibizumab or bevacizumab injections followed by 9 months of "as required" injections based on clinician's decision at each follow-up visit according to retreatment criteria. Seventeen single nucleotide polymorphisms (SNPs) in known AMD risk-associated genes including CFH (rs800292, rs3766404, rs1061170, rs2274700 and rs393955), HTRA1 (rs11200638), CFHR1-5 (rs10922153, rs16840639, rs6667243, and rs1853883), LOC387715/ARMS2 (rs3793917 and rs10490924), C3 (rs2230199 and rs1047286), C2 (rs547154), CFB (rs641153) and F13B (rs6003) were examined. Multivariate analysis was used to determine the role of each SNP in treatment outcome. The influence of selected SNPs on mean change in visual acuity (VA) at 12 months. Mean baseline VA was 51 ± 16.8 Early Treatment Diabetic Retinopathy Study letters. Overall, the mean change in VA from baseline was +3.2 ± 14.9 letters at 12 months. The AA (homozygote risk) genotype at rs11200638 - HTRA1 promoter SNP (P = 0.001) and GG (homozygote risk) genotype at rs10490924 (A69S) in LOC387715/ARMS2 (P = 0.002) were each significantly associated with poorer VA outcome at 12 months after multiple correction. Mean ± standard deviation change in VA from baseline in patients with AA genotype at rs11200638 was -2.9 ± 15.2 letters after 12 months compared with +5.1 ± 14.1 letters in patients with AG or GG genotypes at this SNP. Patients with either of these genotypes were also significantly more likely to lose >15 letters after 12 months. SNPs rs11200638 and rs10490924 were in high linkage disequilibrium (r(2) = 0.92). None of the other examined SNPs was associated with outcome. The HTRA1 promoter SNP (rs11200638) and A69S at LOC387715/ARMS2 were associated with a poorer visual outcome for ranibizumab or bevacizumab treatment in neovascular AMD, suggesting strong pharmacogenetic associations with anti-VEGF treatment. This finding could aid in applying more in idualized treatment regimens based on patients' genotype to achieve optimal treatment response in AMD. The authors have no proprietary or commercial interest in any materials discussed in this article.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-06-2011
DOI: 10.1167/IOVS.10-6550
Publisher: Wiley
Date: 14-07-2021
DOI: 10.1111/CEO.13962
Abstract: We assessed the proportion of eyes with neovascular age‐related macular degeneration (nAMD) in routine clinical practice that reach ≥14 week treatment intervals and their outcomes. We analysed data from the Fight Retinal Blindness! (FRB!) Project database, a prospectively designed registry of ‘real‐world’ outcomes. Treatment‐naive eyes starting vascular endothelial growth factor (VEGF) inhibitors for nAMD from 1st January 2006 were included. Eyes were defined to have reached the ≥14 week treatment interval if they received ≥2 consecutive injections at treatment intervals of ≥14 week but not exceeding 26 weeks. Outcomes were reported in a subgroup of eyes that had 12 months of follow‐up from reaching this interval. Of the 3907 treatment‐naïve eyes that started treatment during the identified periods on a treat‐and‐extend regimen and received at least 8 injections over the first 2 years, 402 (10%) eyes received at least 2 consecutive injections at an interval of ≥14 week during their follow‐up. Fifty‐two percent of these eyes maintained vision to 12 months, however only 40% stayed at this interval and 25% of the lesions reactivated. We found that only 10% of eyes with nAMD were extended beyond a 13‐week injection interval and that over half had returned to a shorter interval by 12 months. Eyes that stayed at this extended treatment interval maintained stable vision. More data on the outcomes of eyes treated with intervals longer than 3 months are required to establish whether emerging VEGF inhibitors provide a more sustained effect than the currently available drugs.
Publisher: Wiley
Date: 24-10-2022
DOI: 10.1111/CEO.14018
Abstract: Subthreshold nanosecond laser (SNL) treatment has been studied as a potential intervention in intermediate age‐related macular degeneration (iAMD). This study investigated the effect of 100 SNL treatment spots on retinal structure and function. A prospective single‐arm interventional pilot study. SNL treatment was delivered as 100 spots around the retinal vascular arcades of the study eye (worst visual acuity) in a single session in subjects with iAMD. Multimodal retinal imaging and dark‐adapted chromatic perimetry were performed at baseline and at 0.5, 3, 6 and 12 months post treatment. Post treatment changes in best corrected visual acuity (BCVA), retinal thickness, relative ellipsoid zone reflectivity (rEZR) and rod‐mediated functional parameters were compared to baseline. Twenty‐one subjects with iAMD were recruited. SNL treatment was associated with an increase in retinal thickness ( p = 0.008) and decrease in rEZR ( p 0.001) at 2 weeks post laser. Recovery of retinal thickness and rEZR was observed at the 3‐month post laser visit. A gradual improvement in BCVA was observed after laser treatment. The mean change in BCVA between baseline and 12‐month visit was +1.9 ± 3.3 letters for the SNL treated eyes, compared to −0.4 ± 3.0 letters for the fellow eyes ( p = 0.027). Rod‐mediated function improved at 3 months post laser ( p 0.001) and returned to the baseline levels at 12 months post treatment. A single treatment with 100 SNL spots causes a short‐term change in retinal structure and improvement in retinal function that are apparent at 3 months post treatment.
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/09286580801939338
Abstract: The genes in myopia twin study were established to assess the relative genetic contribution of spherical equivalent using a classical twin model. This manuscript will provide a detailed outline of the methodological design, twin recruitment, and the prevalence of myopia in the genes in myopia twin study. All Victorian-based twins registered with the Australian Twin Registry aged 18 years or older were invited to participate genes in myopia twin study. Each subject underwent a general questionnaire, comprehensive eye examination, and a blood s le was collected. Myopia was defined as worse than or equal to -0.50 diopters sphere (in at least one eye). A total of 627 twin pairs out of 4,158 twin pairs consented to participate in the genes in myopia twin study. A total of 345 monozygotic and 267 dizygotic twin pairs aged between 18 and 86 years were examined. The response rate for monozygotic twins (19.8%) was almost double that of dizygotic twins (11.7%). The overall prevalence of myopia was 29.7% for all twins. The genes in myopia twin study is the first Australian-based twin study to assess refraction in an adult twin population and the largest of its kind in the world. The comprehensive testing protocol used in the in the genes in myopia twin study has provided an extensive twin database for genetic analysis. Participation rate was found to vary according to zygosity, gender, and age.
Publisher: Wiley
Date: 09-01-2013
DOI: 10.1096/FJ.12-215368
Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness in Western countries and is diagnosed by the clinical appearance of yellow subretinal deposits called drusen. Genetic changes in immune components are clearly implicated in the pathology of this disease. We have previously shown that the purinergic receptor P2X7 can act as a scavenger receptor, mediating phagocytosis of apoptotic cells and insoluble debris. We performed a genetic association study of functional polymorphisms in the P2RX7 and P2RX4 genes in a cohort of 744 patients with AMD and 557 age-matched Caucasian control subjects. The P2X4 Tyr315Cys variant was 2-fold more frequent in patients with AMD compared to control subjects, with the minor allele predicting susceptibility to disease. Pairwise linkage disequilibrium was observed between Tyr315Cys in the P2RX4 gene and Gly150Arg in the P2RX7 gene, and these two minor alleles formed a rare haplotype that was overrepresented in patients with AMD (n=17) compared with control subjects (n=3) (odds ratio 4.05, P=0.026). Expression of P2X7 (wild type or variant 150Arg) in HEK293 cells conferred robust phagocytosis toward latex beads, whereas coexpression of the P2X7 150Arg with P2X4 315Cys variants almost completely inhibited phagocytic capacity. Fresh human monocytes harboring this heterozygous 150Arg-315Cys haplotype showed 40% reduction in bead phagocytosis. In the primate eye, immunohistochemistry indicated that P2X7 and P2X4 receptors were coexpressed on microglia and macrophages, but neither receptor was seen on retinal pigment epithelial cells. These results demonstrate that a haplotype including two rare variants in P2RX7 and P2RX4 confers a functional interaction between these two variant receptors that impairs the normal scavenger function of macrophages and microglia. Failure of this P2X7-mediated phagocytic pathway may impair removal of subretinal deposits and predispose in iduals toward AMD.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-10-2016
Abstract: We determine the feasibility of using a dark-adapted chromatic (DAC) perimeter to obtain dark-adapted static and dynamic rod function at multiple retinal locations, and compare these functional parameters between subjects with intermediate age-related macular degeneration (AMD) and normal controls. Perimetric dark-adapted retinal sensitivities for the 505 and 620 nm stimuli across 7 retinal locations within the central 12° were repeatedly measured after exposing to a single photobleach in 22 intermediate AMD subjects and 8 controls. The sensitivities for each stimulus at 20 minutes after bleach and the sensitivity difference between the stimuli were used to determine static rod function. Sensitivities for the 505 nm stimulus at various times within the initial 20 minutes after bleach were used to estimate the rod criterion time to determine rod function dynamics. The static and dynamic rod functional parameters were compared between AMD and control eyes. Compared to the control eyes, AMD eyes had a reduction in retinal sensitivities for the 505 nm (P < 0.001) and 620 nm (P < 0.001) stimuli, a reduction in sensitivity difference (P < 0.001), and an increased in rod criterion time (P < 0.001). Region within the central 6° appeared to be the most defective and AMD eyes with reticular pseudodrusen (RPD) seemed to have worse function than eyes without RPD. It is feasible to use a DAC perimeter to study dark-adapted static and dynamic rod-mediated function at multiple retinal loci. Static and dynamic rod function were abnormal in intermediate AMD and more so in eyes with RPD, particularly within the central 6° retina.
Publisher: Informa UK Limited
Date: 26-08-2021
Publisher: American Medical Association (AMA)
Date: 11-05-2009
DOI: 10.1001/ARCHOPHTHALMOL.2009.60
Abstract: To evaluate associations between past dietary fat intake and the prevalence of age-related macular degeneration (AMD). Six thousand seven hundred thirty-four participants aged 58 to 69 years in 1990-1994 took part in this cohort study. Participants' nutrient intakes were estimated from a food frequency questionnaire at baseline. At follow-up from 2003 to 2006, digital macula photographs of both eyes were evaluated for early and late AMD signs. Logistic regression was used to estimate odds ratios, with adjustment for age, smoking, and other potential confounders. Higher trans-unsaturated fat intake was associated with an increased prevalence of late AMD the odds ratio comparing the highest with the lowest quartile of trans fat was 1.76 (95% confidence interval, 0.92-3.37 P = .02). Higher omega-3 fatty acid intake (highest quartile vs lowest quartile) was inversely associated with early AMD (odds ratio, 0.85 95% confidence interval, 0.71-1.02 P = .03). Olive oil intake (> or =100 mL/week vs <1 mL/week) was associated with decreased prevalence of late AMD (odds ratio, 0.48 95% confidence interval, 0.22-1.04 P = .03). No significant associations with AMD were observed for intakes of fish, total fat, butter, or margarine. A diet low in trans-unsaturated fat and rich in omega-3 fatty acids and olive oil may reduce the risk of AMD.
Publisher: Frontiers Media SA
Date: 29-04-2016
Publisher: Elsevier BV
Date: 10-2004
DOI: 10.1016/J.AJO.2004.04.053
Abstract: To investigate the reported association of the two single-nucleotide polymorphisms (SNPs) of the paraoxonase gene (PON1), Met-Leu 55 (M55L) and Gln-Arg 192 (Q192R), in in iduals of Anglo-Celtic descent who have age-related macular degeneration (AMD). Case-control association study. Sixty-two in iduals with late (end-stage) AMD and 115 control subjects (without AMD) were included in this study. The M55L and Q192R SNPs were lified by polymerase chain reaction and genotyped, and statistical analysis was undertaken. No association of either SNP was detected in persons of Anglo-Celtic descent who had AMD, although there was a significant difference in SNP allele frequency between Anglo-Celtic and Japanese in iduals. The M55L and Q192R SNPs of the PON1 gene do not appear to be associated with late AMD in in iduals of Anglo-Celtic descent.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 26-04-2018
Abstract: Although impairment of rod function in the early stages of age-related macular degeneration (AMD) has been well recognized, data on longitudinal changes in rod function at multiple retinal locations remain limited. This study investigated the longitudinal changes in retinotopic rod function in eyes with intermediate AMD (iAMD). Complete ophthalmic examination, multimodal imaging, and scotopic perimetry were performed at baseline and at 12-month follow-up. Perimetric scotopic retinal sensitivities for the 505-nm stimulus were repeatedly measured for 20 minutes after exposing to a single photobleach (∼30%). The rod intercept time (RIT) and retinal sensitivity at seven retinal loci within the central 12° were ascertained. Using the 95% limit of measurement variability derived from the control eyes as a reference, the proportion of test points with a significant change in retinal sensitivity or RIT at follow-up was determined. Twenty iAMD and 6 control eyes were included. Decline in rod function was detected at 12-month follow-up in eyes with iAMD, but not in control eyes. Approximately 25% of test points in iAMD eyes showed a significant increase in RIT compared to 6% of test points with a decrease in RIT over the 12-month period (P < 0.001). Similarly, 40% of test points demonstrated a reduction in retinal sensitivity compared to the 7% of test points with an increase in retinal sensitivity at follow-up (P < 0.001). There are detectable retinotopic changes in rod function over 12 months in iAMD eyes, indicating an ongoing disease progression in rod impairment or loss with time.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 17-04-2013
Abstract: The second hyper-reflective on spectral domain optical coherence tomography (SD-OCT) has been suggested to correlate with the photoreceptor inner segment ellipsoids (ISe). The purpose of our study was to determine the relationship between the intensity of the ISe band and retinal function measured by multifocal electroretinography (mfERG) in patients with early age-related macular degeneration (AMD). A high-resolution horizontal line scan through the fovea on SD-OCT and an mfERG recording were performed in one eye of 29 early AMD and 31 control participants. The relative intensity of the ISe band within 1000 μm of the fovea was quantified using ImageJ. The relationships between the relative intensity of the ISe band and the mfERG response parameters (P1 litude and implicit time) within the three central hexagons along the horizontal axis were determined. In normal participants, the relative intensity of the ISe band was significantly correlated with age (r = -0.634, P < 0.001) and also exhibited a topographic variation. On average, the relative intensity of the ISe band was significantly lower in patients with early AMD (1.77 ± 0.26) compared to control subjects (1.95 ± 0.27, P < 0.001) of a similar age range. The relative intensity of the ISe band was correlated significantly with the mfERG P1 implicit time (r = -0.745, P < 0.001), but not P1 litude (r = 0.144, P = 0.281). The relative intensity of the ISe band reduced with age and further in early AMD. The relative intensity was significantly correlated with mfERG P1 implicit time.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2009
DOI: 10.1167/IOVS.08-2423
Abstract: Several single-nucleotide polymorphisms (SNPs) in the C2 and BF genes have been associated with age-related macular degeneration (AMD) in Caucasian populations from the United States. The study was conducted to evaluate whether these SNPs are also associated with AMD in persons of Anglo-Celtic ethnicity in an Australian population. Included in the study were 565 persons with AMD and 204 ethnically matched control subjects. All participants completed a standard health questionnaire, were given a fundus examination, and provided a blood s le for DNA extraction. Alleles were determined by a matrix-assisted desorption ionization-time of flight (MALDI-TOF)-based approach followed by statistical analysis. The C2 and BF genes indicated significant association with AMD of only two SNPs rs547154 (IVS10) in the C2 gene (P=9.1 x 10(-5)) and rs641153 (R32Q) in the BF gene (P=7.0 x 10(-5)). No association with AMD was found for SNP rs9332739 (E318D) in the C2 gene or for rs4151667 (L9H), rs1048709 (R150R), rs4151659 (K565E), or rs2072633 (IVS17) in the BF gene. A protective haplotype of variants IVS10 and R32Q was associated with AMD (OR 0.29, 95% CI 0.20-0.42). In this study, the association of the IVS10 and R32Q variants in the C2 and BF genes in AMD was replicated. Haplotype analysis indicated association of these variants with AMD in an Australian population. Both IVS10 and R32Q variants were in strong linkage disequilibrium with each other (r(2)=0.96). Although the E318D and L9H variants have shown association with AMD in previous studies, the findings were not in agreement. This demonstrates a refined pattern of association of these rare variants with AMD.
Publisher: Springer-Verlag
Date: 2005
Publisher: Informa UK Limited
Date: 13-03-2017
DOI: 10.1080/09286586.2016.1276934
Abstract: We illustrate the effect of survival bias when investigating risk factors for eye disease in elderly populations for whom death is a competing risk. Our investigation focuses on the relationship between smoking and late age-related macular degeneration (AMD) in an observational study impacted by censoring due to death. Statistical methodology to calculate the survivor average causal effect (SACE) as a sensitivity analysis is described, including ex le statistical computing code for Stata and R. To demonstrate this method, we examine the causal effect of smoking history at baseline (1990-1994) on the presence of late AMD at the third study wave (2003-2007) using data from the Melbourne Collaborative Cohort Study. Of the 40,506 participants eligible for inclusion, 38,092 (94%) survived until the start of the third study wave, 20,752 (51%) were graded for AMD (60% female, aged 47-85 years, mean 65 ± 8.7 years). Late AMD was detected in 122 participants. Logistic regression showed strong evidence of an increased risk of late AMD for current smokers compared to non-smokers (adjusted naïve odds ratio 2.99, 95% confidence interval, CI, 1.74-5.13). Among participants expected to be alive at the start of follow-up regardless of their smoking status, the estimated SACE odds ratio comparing current smokers to non-smokers was at least 3.42 (95% CI 1.57-5.15). Survival bias can attenuate associations between harmful exposures and diseases of aging. Estimation of the SACE using a sensitivity analysis approach should be considered when conducting epidemiological research within elderly populations.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 29-11-2011
DOI: 10.1167/IOVS.11-8517
Abstract: To determine the retinal function in early age-related macular degeneration (AMD) assessed by the multifocal electroretinogram (mfERG) and flicker perimetry and to seek a relationship between local objective mfERG parameters and subjective flicker perimetry thresholds. mfERG and flicker perimetry were performed in 15 patients (15 eyes) with early AMD and 14 controls (14 eyes) of similar age. The mfERG P1 response litude density (nV/deg²) and P1 implicit time of the first-order kernel and the flicker thresholds of each concentric ring were analyzed. The relationship between in idual mfERG responses and the corresponding in idual flicker sensitivity outcomes was determined. The mfERG response litude of the central ring (ring 1) was significantly reduced in early AMD eyes compared with the controls (P = 0.009). No significant difference in mfERG litude between early AMD and control eyes was detected in the other rings. The mfERG implicit time was significantly increased in the early AMD eyes but only within the central four rings of 12°. A significant reduction in flicker sensitivity was also detected in early AMD eyes but only within the central 6°. There was a significant, moderate correlation (r = -0.477 P < 0.001) between local mfERG latency and flicker sensitivity from the same tested locations within the central 6°. There was a weak correlation (r = 0.200 P = 0.014) between mfERG litude and flicker sensitivity. Both mfERG and flicker perimetry show abnormal retinal function, but only in the very central macula, in early AMD. A novel relationship between mfERG and flicker sensitivity should enhance the clinical monitoring of disease progression.
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.OPHTHA.2014.02.005
Abstract: To compare the effectiveness of low-luminance visual acuity (LLVA) and microperimetry as functional measures in early stages of age-related macular degeneration (AMD). Prospective cross-sectional study. One hundred seventy-nine participants with a clinical spectrum of non-neovascular AMD and 26 control participants. Best-corrected visual acuity (BVCA), LLVA, and microperimetric retinal sensitivity were measured on 1 eye of all participants. Low-luminance deficit (LLD) was calculated as the difference between LLVA and BCVA. The functional parameters were compared between 6 clinical severity groups (from controls to non-foveal geographic atrophy [GA]), and the relationships and magnitude of these parameters were determined and compared. Visual acuity parameters (BCVA, LLVA, and LLD) and central retinal sensitivity. Best-corrected visual acuity, LLVA, and central retinal sensitivity were reduced significantly for all AMD clinical severity groups when compared with control participants (P ≤ 0.002), except for those with drusen between 63 and 125 μm (P ≥ 0.107). However, LLD was not significantly different from control participants in all groups (P ≥ 0.073), except in the non-foveal GA group (P = 0.008). A significant positive relationship between central retinal sensitivity and LLD (R = 0.613 P < 0.001), but not BCVA, suggests that there is a trend for LLVA to detect a greater extent of functional deficit than BCVA in eyes with increasingly poorer retinal sensitivity. However, the results of the linear regression models estimated central retinal sensitivity to be 6.1, 3.7, and 5.1 standard deviations (SDs) less than normal by the time BCVA, LLVA, and LLD, respectively, were 2 SDs less than normal. In early stages of AMD, LLVA did not detect a greater extent of functional deficit than BCVA when compared with control participants. Although there was a trend for LLVA to be more effective at detecting foveal deficits than BCVA in eyes with increasingly poorer retinal sensitivity, both visual acuity measures were much less sensitive compared with microperimetry.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.OPHTHA.2016.02.009
Abstract: To determine the histologic and cellular correlates in the retina and retinal pigment epithelium (RPE) with the presence of optical coherence tomography-defined reticular pseudodrusen (RPD). Observation case using immunocytochemistry of an exenterated eye with immediate fixation after removal. Two patients, one with confirmed RPD and the other with mid-peripheral drusen, underwent multimethod imaging before exenteration and immediate fixation of the posterior eyecup for high-resolution immunocytochemical analysis. Optical coherence tomography (OCT) was compared with high-resolution immunocytochemistry using a range of cellular markers to determine changes in the RPE, photoreceptors, and gliosis. Correlations of the appearance of reticular pseudodrusen on OCT and immunocytochemical analysis. Reticular pseudodrusen were deposits juxtaposed to photoreceptor outer segments extending through the outer nuclear layer and even beyond the outer limiting membrane. Deposits were rich in vitronectin, photoreceptor-associated proteins, and Iba1-immunoreactive immune cells. In contrast to conventional drusen the lipid stain Oil Red O failed to stain RPD. Cellular analysis revealed that RPD were associated with photoreceptor disruption and loss and localized gliosis. In addition, anomalies in the RPE were observed. Reticular pseudodrusen represent subretinal deposits that extend through the outer nuclear layer, affect photoreceptor integrity, and are associated with retinal gliosis and RPE damage.
Publisher: Bentham Science Publishers Ltd.
Date: 19-10-2016
DOI: 10.2174/1567205013666160603003800
Abstract: This study investigated signs of age related macular degeneration (AMD) in Alzheimer's disease (AD). These age-related diseases primarily affect different parts of the central nervous system but are substantially similar in terms of abnormal extracellular deposits, metabolic and oxidative stress, neuroinflammation and microvascular abnormalities. While AMD is a retinal disease, AD is reported to affect not only the brain but also the retina, with Aβ deposits, neurodegeneration and vascular changes. Large population based studies have provided conflicting results regarding the comorbidity of AD and AMD. This study investigated signs of AMD in a small but well characterized cohort from the Australian Imaging Biomarkers and Lifestyle study of aging (AIBL). The cohort consisted of 22 AD patients (age 70.2 ± 9.0 yrs, 13 male, 9 female) and 101 cognitively normal (CN) participants (age 71.3 ± 6.0 yrs, 40 male, 61 female). In comparison with the CN group, the AD group had a greater proportion of participants with early AMD (p < 0.0001, odds ratio 18.67, 95% CI 4.42 - 78.80). A logistic model for early AMD found a significant association with AD diagnosis (p < 0.0001), after adjusting for confounders (age, smoking, hypertension, high and low density lipoproteins, cataract surgery and APOE ε4 carrier status). The results of this study are consistent with an increased risk of AMD in AD. While the pathophysiology of these diseases are unclear, understanding the shared features between them may provide further knowledge about their pathogenesis and could lead to accelerated development of therapies for both diseases.
Publisher: Informa UK Limited
Date: 07-08-2015
DOI: 10.1586/17512433.2015.1075879
Abstract: Age-related macular degeneration (AMD) is a progressive, degenerative disease of the retina that occurs with increasing incidence with age and ranks third among the global causes of visual impairment. VEGF has been implicated in the development and progression of neovascular AMD. Drugs that block VEGF, leading to regression of the abnormal blood vessels, are the mainstay of treatment of neovascular AMD, particularly for subfoveal neovascular lesions. Anti-VEGF agents currently in use in neovascular AMD are pegaptanib (Macugen(®)), ranibizumab (Lucentis(®)), bevacizumab (Avastin(®)) and a soluble VEGF receptor decoy aflibercept (Eylea(®)). Recently, China Food and Drug Administration have approved conbercept for the treatment of neovascular AMD in China. Conbercept appears to offer yet another anti-VEGF drug for use in neovascular AMD. However, there is still a need for large, well-designed, randomized clinical trials to ensure its safety and efficacy.
Publisher: American Medical Association (AMA)
Date: 04-2015
DOI: 10.1001/JAMAOPHTHALMOL.2014.5963
Abstract: There is a need for more sensitive measures of disease in intermediate age-related macular degeneration (AMD) to evaluate novel interventions more effectively and expediently. To determine if microperimetry and low luminance visual acuity can detect functional changes over a short duration of follow-up. Prospective longitudinal examination of 49 participants with consecutive AMD and 10 healthy participants in a research clinic from May 1, 2012, to December 31, 2013. Forty-one participants had intermediate AMD, 8 had nonfoveal geographic atrophy due to AMD. Participants underwent microperimetry examinations in 1 eye during a 12-month period at 6-month intervals for participants with AMD and at baseline and 12 months for control participants low luminance visual acuity was performed at baseline and at 12 months for all participants. Changes in pathological features of intermediate AMD eyes were determined using side-by-side comparisons of color fundus photographs from the initial and final visit as remaining stable, progressed, or improved. Microperimetric sensitivity and low luminance visual acuity. A reduction in mean (SE) microperimetric pointwise sensitivity was identified at 12 months compared with the baseline for intermediate AMD eyes graded as stable (-0.31 dB [0.10 dB] P = .003) or worsened (-0.42 dB [0.12 dB] P < .001) and an improvement in mean (SE) pointwise sensitivity was identified in eyes graded as improved (1.13 dB [0.23 dB] P < .001). A reduction in mean (SE) pointwise sensitivity was identified in eyes with nonfoveal geographic atrophy at both 6 months (-1.41 dB [0.22 dB] P < .001) and 12 months compared with the baseline (-2.56 dB [0.22 dB] P < .001) while a change in mean (SE) pointwise sensitivity was not identified over the 12-month period for control participants (-0.11 dB [0.11 dB] P = .34). No changes in best-corrected visual acuity or low luminance visual acuity were identified in all groups over the 12-month period (P ≥ .07). Microperimetry detected subtle changes in visual function over a 12-month period in eyes with intermediate AMD but visual acuity measures did not identify any such changes. These findings suggest that microperimetry is worth exploring as a method for assessing the efficacy of novel interventions for intermediate AMD potentially requiring a shorter duration of follow-up.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 21-03-2016
Abstract: To determine the prevalence of reticular pseudodrusen (RPD) and their detection using multimodal imaging in patients with bilateral large drusen, and examine their clinical, demographic, environmental, and genetic associations. Three hundred participants with bilateral large drusen (>125 μm) underwent color fundus photography (CFP), near-infrared reflectance (NIR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging. Demographic information, smoking, and medical history were recorded, and a blood s le was obtained and genotyped to identify the risk alleles of the CFH and ARMS2 genes. Reticular pseudodrusen were detected in 28.2% eyes of 29.0% participants using NIR and SD-OCT combined, but CFP and FAF detected only 42% and 89%, respectively, of these eyes with RPD. Participants with RPD were significantly older than those without (P 0.173). However, the minor allele frequency of the ARMS2 gene was significantly higher in participants with RPD (P = 0.002). The presence of RPD was also independently associated with the presence of atrophic changes (including nascent geographic atrophy and drusen-associated atrophy detected on SD-OCT P = 0.043). Reticular pseudodrusen were detected on NIR and SD-OCT in more than a quarter of participants with bilateral large drusen, being often overlooked with CFP. Those with RPD had a higher frequency of the ARMS2 risk variant, and eyes with RPD were more likely to have atrophic changes. These findings are important to consider when managing patients with intermediate AMD.
Publisher: Wiley
Date: 29-10-2009
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2018
Abstract: Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD) however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice. Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15-0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR. Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch's membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium-derived factor, an antiangiogenic factor, was upregulated. In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch's membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner.
Publisher: Hindawi Limited
Date: 2006
DOI: 10.1002/HUMU.20288
Abstract: Progression of age-related macular degeneration (AMD), the leading cause of blindness in the elderly, was followed in a cohort of 238 in iduals from a single center. In iduals with an epsilon (epsilon)2 genotype (c.526C>T of reference sequence NM_000041.2) of the apolipoprotein (APOE) gene were found to be strongly associated with disease with a significant 4.8-fold increased relative risk compared to in iduals with an epsilon4 genotype (c.388T>C of reference sequence NM_000041.2) (odds ratio [OR], 4.8 95% confidence interval [CI], 1.19-19.09) and a nearly significant three-fold increased relative risk compared to in iduals with an epsilon3 genotype (reference sequence NM_000041.2) (OR, 2.8 95% CI, 0.96-19.09). This finding was present only in females who progressed with AMD, which suggests that there may be a gender-specific role in progression of AMD in in iduals with an epsilon2 allele. A gender-related factor is therefore implicated either directly or indirectly in the AMD disease process.
Publisher: BMJ
Date: 2001
DOI: 10.1136/BJO.85.1.40
Abstract: To identify if laser photocoagulation induces morphological changes specifically related to the choroidal capillary endothelial processes that protrude into Bruch's membrane. Two human eyes and one adult macaque monkey eye received retinal laser photocoagulation that was just suprathreshold, before enucleation or exenteration. They were examined by electron microscopy to determine the length of the endothelial processes emanating from the choroidal capillaries in the region around the laser burn. One human and two monkey untreated eyes were used for comparison. In human eyes, there was no increase in the number of processes 15 hours after laser treatment but at 5 days the processes were more numerous and longer within 400-500 microm of the burn than in the untreated half of the same eye. The processes were longer 9 days after photocoagulation in the monkey, when compared with untreated monkeys, and some breached the elastic lamina, a phenomenon not seen in the untreated eyes. Qualitative differences were also noted in the endothelial cell processes following photocoagulation. Neovascularisation was not observed. Protrusion of choroidal endothelial cell processes into Bruch's membrane is a normal anatomical feature but the number, length, and morphology of the processes change following mild photocoagulation. It is plausible that these processes may play a part in the clearance of debris from Bruch's membrane, and represent an early stage of angiogenesis. If the latter is true prophylactic laser photocoagulation at just suprathreshold levels may carry a risk of inducing choroidal neovascularisation.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.AJO.2018.05.026
Abstract: To assess outcomes of the treat-and-extend (T&E) injection regimen for neovascular age-related macular degeneration (AMD) as compared to either a monthly or a pro re nata (PRN) treatment strategy. Systematic review and meta-analysis. Studies that compared the T&E regimen with either monthly or PRN dosing for treatment-naïve AMD were included. Trial eligibility, data extraction, and risk of bias were assessed according to Cochrane review methods. Estimates were pooled using random-effects meta-analysis. Four eligible studies were identified, all using ranibizumab (total N = 940 eyes), including 2 randomized controlled trials comparing T&E to monthly and 2 retrospective reviews comparing T&E to PRN. No studies evaluating aflibercept were identified. Improvements in vision and central retinal thickness were similar between T&E and monthly at 12 months, with a mean difference of -1.79 letters (95% confidence interval [CI]: 3.70, 0.13) and 3.76 μm (95% CI: -13.78, 21.30) in favor of monthly injections. In contrast, visual gains were higher in the T&E compared to the PRN group (difference of +6.18 letters, 95% CI: 3.28, 9.08). Fewer injections were required using the T&E regimen when compared to monthly (mean of -1.6 and -6.9 injections at 12 and 24 months, respectively). A mean of 1.44 more injections was required for the T&E compared to PRN regimen at 12 months however, this was achieved with fewer visits. Despite the growing preference for the T&E regimen, there is limited head-to-head evidence comparing dosing strategies. The evidence available, however, suggests that at 12 months, T&E is comparable to monthly and superior to PRN dosing for both efficacy and safety outcomes when using ranibizumab.
Publisher: Elsevier BV
Date: 11-2012
Publisher: Wiley
Date: 23-12-2011
DOI: 10.1111/J.1442-9071.2011.02719.X
Abstract: To investigate the efficacy of ranibizumab therapy for choroidal neovascular (CNV) membranes secondary to conditions other than macular degeneration. Prospective case series conducted at the Royal Victorian Eye and Ear Hospital. Twelve-month follow-up data for 41 patients with CNV recruited from the outpatient clinic from May 2008 to April 2010 is presented. Fifteen patients had myopia, seven had multifocal choroiditis, and eight had other primary causes. All patients had visual acuity, fluorescein angiogram and optical coherence tomography performed at the initial visit (baseline). Ranibizumab was injected with a standard sterile technique. Patients were reviewed after 1 month, and further injections were given at the treating doctors' discretion. Change in visual acuity and central macular thickness at 12 months was compared with baseline for each of the groups. Local and systemic adverse outcomes were recorded. Analysis was stratified by primary pathology. On average, 40%, 43% and 25% of patients with myopia, multifocal choroiditis and 'other' pathologies, respectively, experienced a three or more line improvement in vision. The average number of injections in 12 months was 4.2 for the entire group. Central macular thickness significantly decreased in the 12-month period for the combined group (P = 0.03). No patient had an adverse systemic side-effect however, there was one case of endophthalmitis. Ranibizumab is an effective treatment for CNV secondary to non-age-related macular degeneration causes, with most patients gaining an improvement in the first 2 months following injection.
Publisher: Wiley
Date: 26-10-2015
DOI: 10.1111/CEO.12658
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2006
DOI: 10.1167/IOVS.05-1285
Abstract: Recent studies in U.S. populations have indicated that the Y402H variant of the complement factor H (CFH) gene contains a major risk susceptibility allele for age-related macular degeneration (AMD). This study was conducted to ascertain whether this is also true in a non-U.S. population and also whether the at-risk allele is associated with the clinical phenotype of disease and the age at diagnosis. Two hundred thirty-six unrelated in iduals with AMD and 144 unrelated but ethnically matched control subjects were recruited and examined. All subjects completed a standard questionnaire, were given a fundus examination, and provided a blood s le for DNA extraction. Alleles of Y402H in the CFH gene were determined by use of a MALDI-TOF-based approach followed by statistical analysis. In iduals with AMD who had at least one copy of the C allele of Y402H had an increased risk of disease (odds ratio [OR] 2.98 95% confidence interval [CI] 1.81-4.93) compared with cases with the T allele. On subgroup analysis, this risk was found to be most significant in in iduals with neovascular disease (OR 4.34 95% CI 1.94, 9.71). In addition, in iduals with neovascular disease who were homozygous CC presented with a significant 7.0-year earlier age at diagnosis relative to those in iduals who were homozygous TT. The population-attributable risk for the C allele ranged between 47% to 69%, depending on the AMD disease subtype. The C allele of Y402H represents a significant risk factor in in iduals with AMD, and this effect is most pronounced in in iduals with neovascular disease.
Publisher: Wiley
Date: 18-08-2012
DOI: 10.1111/J.1442-9071.2011.02613.X
Abstract: To describe the changes in retinal vascular calibre in response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration. Prospective interventional case series. Treatment naïve patients with neovascular age-related macular degeneration were recruited over a 1-year period. Each patient received three monthly intravitreal injections according to a 'loading dose'. Retinal arteriolar and venular calibre was measured from digital fundus photographs and summarized as central retinal artery equivalent and central retinal vein equivalent at baseline and 3 months. Central retinal artery equivalent and central retinal vein equivalent changes from baseline to 3 months. Seventy-four eyes of 71 patients had good quality images for grading vessel calibre at baseline and at 3 months in treated (study) eyes and 51 eyes of 51 patients had good quality images in fellow (control) eyes. Over 3 months, in study eyes treated with ranibizumab, there was a significant increase in central retinal vein equivalent over baseline (+6.20 µm, P = 0.005), but no significant change in central retinal artery equivalent (+0.86 µm, P = 0.55). In control eyes, there was no change in central retinal vein equivalent (-0.82 µm, P = 0.70) or central retinal artery equivalent (0.34 µm, P = 0.75). Intravitreal ranibizumab has a significant vasodilational effect on retinal venular calibre in eyes treated for neovascular age-related macular degeneration. The reason for this change is unclear, but may relate to changes in blood flow or inflammatory changes within the retina.
Publisher: Wiley
Date: 12-07-2006
DOI: 10.1111/J.1442-9071.2006.01264.X
Abstract: Photodynamic therapy with verteporfin for choroidal neovascularization (CNV) secondary to macular disease received an Australian government grant in 2002 to fund treatment for 3 years. Funding was restricted to subfoveal predominantly classic CNV where visual acuity was at least 6/60. Access to this funding was via review of angiograms by an expert panel, the Angiogram Review Panel (ARP), managed by the Royal Australian and New Zealand College of Ophthalmologists. De-identified data from the ARP were obtained for the period June 2002 to April 2005 inclusive and the panel's outcomes were analysed. Health Insurance Commission and Department of Veteran Affairs data for photodynamic therapy for the same interval were also retrieved. A total of 7198 submissions to the ARP were received for 5867 in iduals in this period. Overall 86.6% eyes submitted were accepted for initial funding (treatments 2-4). There was no change over time in the percentage rejected during this period. The first reviewer accepted 77.2%. And the second reviewer accepted a further 7.7%. An additional 1.6% were accepted on appeal. It was estimated that 29.2% of this initial cohort received five or more treatments. The ARP data indicate an incidence of subfoveal predominantly classic CNV secondary to macular disease in Australia of about 2000 eyes per annum. Only one quarter of patients received five or more treatments. The panel provided a unique opportunity to estimate the 'whole of nation' incidence of predominantly classic subfoveal CNV secondary to macular disease and thus provides a firm foundation upon which to plan public health spending as new treatments become available.
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.OPHTHA.2010.02.003
Abstract: To determine the effect of elevated level of C-reactive protein (CRP) and its joint effect with the complement factor H (CFH) polymorphism on prevalent age-related macular degeneration (AMD) and its progression. Two-arm case-control study: (a) Study on prevalent AMD cases and population-based controls (b) longitudinal study on AMD progression, comparing those in whom AMD progressed with those with no progression. (a) A cross-sectional s le of 544 participants, of whom 312 had features of early or late AMD and 232 were controls (b) a s le of 254 early AMD cases, followed for 7 years. The study was conducted in Melbourne, Australia. Macular stereo photographs were graded for AMD according to the International Classification and Grading System. High-sensitivity CRP was measured in fresh serum, and genotyping was performed through the Australian Genome Research Facility. The association of CRP with outcomes was tested using multivariate logistic regression analysis adjusted for age, smoking, anti-inflammatory medications, and the CC genotype of the CFH gene. Risk factor interaction was explored using an additive model. Prevalent early AMD, prevalent late AMD, progressed AMD, and measures of risk factor interaction. Elevated CRP levels were associated with late AMD: odds ratio (OR), 3.12 95% confidence interval (CI), 1.38-7.07. An association of elevated CRP with AMD progression was weaker: OR, 1.90 (95% CI, 0.88-4.10). A combination of elevated CRP and the CC (Y402H) genotype resulted in a super-additivity of the risks, with odds ratios of 19.3 (95% CI, 2.8-134) for late AMD, and 6.8 (95% CI, 1.2-38.8) for AMD progression, with the attributable proportion of risk owing to CRP-CFH interaction calculated at 26% for prevalent late AMD and 22% for AMD progression. Synergistic influence of CRP levels and the at risk genotype of the CFH gene resulted in a super-additive risk for prevalent late AMD and AMD progression. Testing for the combination of these 2 risk factors to predict a high risk of AMD and its progression would allow for targeted trials of new intervention strategies.
Publisher: Elsevier BV
Date: 06-1999
DOI: 10.1016/S0002-9394(99)00043-4
Abstract: Initial studies suggest that drusen associated with age-related maculopathy resolve in response to laser photocoagulation there are conflicting reports regarding whether this treatment might prevent neovascular complications and blindness. The goal of the Drusen Laser Study is to maintain good visual acuity in eyes at the highest risk for neovascular complications of age-related maculopathy. In this report, we alert the ophthalmic community to possible laser-induced complications in patients treated within the context of this clinical trial. A double-masked, randomized, controlled clinical trial of prophylactic macular photocoagulation for high-risk age-related maculopathy is in progress. Patients randomly assigned to treatment received a ring-type distribution of 12 light spots of argon laser photocoagulation. Drusen were treated directly only if they were present at the protocol treatment locations. Fluorescein angiography was performed in all patients at yearly review, and at nonprotocol visits if symptoms or clinical examination were suggestive of choroidal neovascularization. Fluorescein angiographic abnormalities suggestive of choroidal neovascularization have been seen in treated eyes only: one patient in the pilot study and six patients in the Drusen Laser Study. No fluorescein angiographic abnormalities were seen in eyes of control subjects. Laser photocoagulation in high-risk age-related maculopathy may induce choroidal neovascularization and, therefore, is not recommended outside the context of a randomized, controlled clinical trial.
Publisher: Springer Science and Business Media LLC
Date: 21-12-2015
DOI: 10.1038/NG.3448
Publisher: Informa UK Limited
Date: 08-2009
Publisher: IEEE
Date: 09-2013
Publisher: Springer Science and Business Media LLC
Date: 18-08-2017
DOI: 10.1038/EYE.2017.139
Publisher: Elsevier
Date: 2006
Publisher: American Medical Association (AMA)
Date: 06-2015
DOI: 10.1001/JAMAOPHTHALMOL.2015.0325
Abstract: Topical phenylephrine hydrochloride is routinely administered with few safety precautions, but evidence regarding its systemic safety to date is controversial. As even short-term variations in 24-hour blood pressure (BP) and heart rate (HR) can adversely affect cardiovascular health, better evidence on phenylephrine's effects on HR and BP is required. To perform a meta-analysis of available evidence regarding cardiovascular adverse effects of topical phenylephrine. PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews and Clinical Trials were searched for relevant literature from January 1, 1970, to January 1, 2014, using a combination of the following search terms: topical, ocular, ophthalmic, phenylephrine, tropicamide, cardiovascular effect, side effect, blood pressure, heart rate, mydriatic, and eye drops. A total of 70 articles related to the topic were identified and all full texts were retrieved. Randomized clinical trials reporting change in BP and HR for adults were included in this review. All studies reporting results for neonates or infants, not reporting standard deviations, or not specifying the time of measurement or the concentration of phenylephrine used were excluded. Data from randomized clinical trials that reported BP and/or HR as well as the time following administration of topical phenylephrine at which measurements were obtained by concentration of phenylephrine as a mean change and its standard deviation were extracted. Data were synthesized by concentration of phenylephrine and time of measurement following topical application using random-effects models with inverse variance weighting to account for heterogeneity across studies. Difference in BP and HR after topical administration of phenylephrine. Eight RCTs with a total of 916 participants were included. Data were available for phenylephrine, 2.5%, at 20 to 30 minutes and 60 minutes or longer after administration, and neither BP nor HR changed at either time. Following application of phenylephrine, 10%, BP increased at 5 and 10 minutes (mean difference for both, +15 mm Hg 95% CI, 11.94-18.54 P < .001) but decreased at 20 to 30 minutes and 60 minutes or longer with no changes detected against baseline. A mean increase in HR by 4.48 beats/min (95% CI, 1.09-7.88 P = .01) was present at 20 to 30 minutes following application of phenylephrine, 10%, and HR decreased by 60 minutes or longer with no changes detected compared with baseline. Phenylephrine, 2.5%, leads to no clinically relevant change in BP or HR, and the changes in BP and HR seen with phenylephrine, 10%, are short lived. Thus, phenylephrine, 2.5%, is safe to use in clinical routine.
Publisher: Informa Healthcare
Date: 29-04-2014
DOI: 10.1517/14740338.2014.914169
Abstract: This commentary on the review by Christen and Chew discusses the controversy surrounding aspirin use and its association with age-related macular degeneration (AMD). We address the strength of evidence between low-dose aspirin use and AMD and also discuss the risks and benefits of aspirin use in primary versus secondary prevention of cardiovascular diseases in these cases. We also highlight an ongoing randomized controlled trial in this area.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.AJPATH.2017.04.016
Abstract: Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2008
Publisher: Oxford University Press (OUP)
Date: 18-10-2006
DOI: 10.1093/NDT/GFL607
Abstract: Alport syndrome is an inherited disease resulting in kidney failure, hearing loss and ocular abnormalities. Alport syndrome is however often unrecognized, and the aim of this study was to characterize the associated but rarely described peripheral retinopathy and determine whether its demonstration was diagnostically helpful. Index cases were diagnosed with Alport syndrome on renal biopsy in themselves or a family member. Inheritance and affected status were determined using microsatellite markers at the COL4A5 and COL4A3/COL4A4 loci, respectively. Participants' eyes were dilated, and examined with direct and indirect ophthalmoscopy, and slit l biomicroscopy by an expert ophthalmologist who was unaware of the patients' disease status. Ten males and nine females with X-linked Alport syndrome and seven with autosomal recessive disease were studied. Of the 26 patients, 16 had central retinopathy (62%), and 19 patients had peripheral retinopathy (74%). The peripheral changes occurred in both males and females with X-linked and autosomal recessive Alport syndrome, and were more common when renal failure, hearing loss, lenticonus and the central changes were present, but were also noted in 3 X-linked carriers with normal renal function. The peripheral retinopathy occurs in X-linked and autosomal recessive Alport syndrome even when the central retinopathy is absent. Careful retinal examination and photography that includes the periphery is a safe and inexpensive method that may help in the diagnosis of Alport syndrome especially in carriers of X-linked disease.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.PRETEYERES.2021.101017
Abstract: Reticular pseudodrusen (RPD), or subretinal drusenoid deposits (SDD), refer to distinct lesions that occur in the subretinal space. Over the past three decades, their presence in association with age-related macular degeneration (AMD) has become increasingly recognized, especially as RPD have become more easily distinguished with newer clinical imaging modalities. There is also an increasing appreciation that RPD appear to be a critical AMD phenotype, where understanding their pathogenesis will provide further insights into the processes driving vision loss in AMD. However, key barriers to understanding the current evidence related to the independent impact of RPD include the heterogeneity in defining their presence, and failure to account for the confounding impact of the concurrent presence and severity of AMD pathology. This review thus critically discusses the current evidence on the prevalence and clinical significance of RPD and proposes a clinical imaging definition of RPD that will help move the field forward in gathering further key knowledge about this critical phenotype. It also proposes a putative mechanism for RPD formation and how they may drive progression to vision loss in AMD, through examining current evidence and presenting novel findings from preclinical and clinical studies.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.OPHTHA.2008.05.007
Abstract: Bevacizumab is an inhibitor of vascular endothelial growth factor widely used as an "off-label" treatment of neovascular age-related macular degeneration (AMD), despite the lack of clinical trial data on efficacy or safety of this drug. We describe acute intraocular inflammation after intravitreous injection of bevacizumab for the treatment of neovascular AMD. A retrospective case series. Patients with neovascular AMD treated with intravitreous injection of bevacizumab from clinical practices in 2 states (Victoria and South Australia) in Australia. We retrospectively reviewed cases of acute intraocular inflammation after intravitreous injection of bevacizumab for the treatment of neovascular AMD. The detection and description of inflammation in a large cohort of patients. There were 14 cases (11 women and 3 men), from a total of 1278 injections given. The mean age of patients was 83.7 years (range, 74-98). The majority had a prior injection of bevacizumab, with a mean number of injections of 2.7 (range, 1-6). Most patients presented within 24 hours of intravitreous injection, with rapid reduction in vision, but minimal discomfort. There were associated signs of ocular inflammation in the anterior and posterior segments of the eye. Visual acuity at presentation was substantially reduced compared with the preinjection acuity, although the vision rapidly improved with treatment over a period of 7-25 days toward preinjection visual acuity. Intravitreous injection of bevacizumab for the treatment of neovascular AMD may be associated with acute intraocular inflammation. Differentiation from infectious endophthalmitis is important for appropriate management of this condition.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2021
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.OPHTHA.2014.10.001
Abstract: To characterize in more detail routine treatment patterns of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD), we analyzed the length of time and the number of injections required until lesions with choroidal neovascularization (CNV) were first graded inactive. Database observational study. Treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice that were tracked in the Fight Retinal Blindness! observational registry. Eyes treated with ranibizumab were followed until CNV was first reported to be "inactive" (i.e., absence of intraretinal fluid and hemorrhages). The length of time until lesion inactivation occurred and the number of injections required. A total of 1096 eyes (65.8% from women) were included in the study. The median number of weeks until a lesion was graded as inactive after beginning treatment was 15 weeks. One to 3 injections were sufficient to inactivate the lesion in 61.1% of eyes. A mean change in visual acuity of +5.5 logarithm of the minimum angle of resolution letters (95% confidence interval, 4.8-6.3) was found from treatment initiation to the time that eyes were reported as inactive. In eyes with a mean treatment frequency less than every 5.3 weeks, a median of only 3 injections (mean=3.7) were required before lesions with CNV were graded as inactive, but if the mean treatment interval extended beyond 5.3 weeks, the median number of injections required increased sharply to 6 injections (mean, 7 injections). Occult lesions became inactive more slowly than classic lesions. Most lesions with CNV became inactive with 3 injections of ranibizumab, but a small proportion remained active for more than 12 months. Injection frequency and lesion type were the main factors that predicted the time and number of injections required to render lesions inactive.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2022
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2004
DOI: 10.1167/IOVS.03-1121
Abstract: To date, of all the genes studied in relation to age-related macular degeneration (AMD), the alleles of the apolipoprotein (apoE) gene have been the most consistently associated with disease. However, not all apoE studies have found an association, and among these the associations differ. The current study was conducted to investigate further the association of this gene in AMD. Three hundred twenty-two unrelated in iduals with diagnosed AMD and 123 unrelated but ethnically matched control subjects were analyzed. All subjects completed a standard questionnaire and were given a fundus examination. A blood s le was collected for DNA extraction. The common allelic variants of apoE were screened through the use of polymerase chain reaction (PCR) and restriction enzyme digestion followed by statistical analysis. In iduals with the epsilon3 epsilon4 genotype of apoE had an approximate halving of disease risk for late (end-stage) AMD (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.34-0.98) relative to the epsilon3 epsilon3 genotype at age of ascertainment. Stratification of late AMD into atrophic and neovascular disease revealed that the greatest protective effect for the epsilon3 epsilon4 genotype was in in iduals with atrophic disease (OR 0.35, 95% CI 0.13-0.92). Men with the epsilon3 epsilon4 genotype also showed almost a threefold reduction in risk of disease in late AMD (OR 0.36, 95% CI 0.16-0.82). However, in iduals with late AMD and the epsilon2 epsilon3 genotype had a significantly earlier mean age of diagnosis of disease (3.4 years, P = 0.015) compared with those with the epsilon3 epsilon3 genotype, and this was most evident in women (3.9 years, P = 0.011) and in in iduals with neovascular disease (4.7 years, P = 0.003). The alleles of apoE appear to have a role in the etiology of AMD, with the epsilon4 allele being protective, or at the very least, delaying the age of diagnosis of disease, whereas the epsilon2 allele appears to have a modifier effect by bringing forward the mean age of disease diagnosis.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 24-05-2013
Abstract: The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. The pattern of change in sensitivity and percentage of abnormal eyes for static perimetry across all AMD severity groups were similar to flicker perimetry. Eyes with drusen > 125 μm (P[static] = 0.018, P[flicker] = 0.024), drusenoid epithelial detachment (P[static and flicker] < 0.001) and noncentral geographic atrophy (GA P[static and flicker] 125 μm are present, but before the development of late AMD.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-10-2014
Abstract: To correlate and compare retinal function measured using multifocal electroretinography (mfERG) with microperimetry in intermediate age-related macular degeneration (AMD). Sixty AMD participants underwent multifocal electroretinography (mfERG) and microperimetry testing in one eye, and 44 control participants were included to provide normative values for each test. Thirteen hexagons in the central three rings of a 103-hexagon stimulus grid for mfERG and retinotopically matched points on microperimetry were chosen and converted into standard deviations (SDs) away from that of normal participants (Z-score) to represent the magnitude of measured functional deficit and to allow a comparison of the two measures. For the average of all points on mfERG and microperimetry, mfERG N1 to P1 response litude and microperimetric retinal sensitivity was significantly lower (P = 0.013 and P < 0.001, respectively) and mfERG P1 implicit time was significantly increased (P < 0.001) in the AMD participants compared to those in the control participants. Considering retinotopically matched points, there was no significant correlation between the average Z-scores of the microperimetric retinal sensitivity and mfERG implicit time (correlation coefficient, R = 0.254, P = 0.051), nor response litudes (R = 0.006, P = 0.965), and the measured functional deficit with microperimetry was consistently greater than both mfERG parameters (P < 0.001). The measured functional deficit with microperimetry was greater than mfERG parameters in eyes with intermediate AMD. The absence of correlations between these two measures suggests that mfERG may be capturing unique aspects of retinal dysfunction. These findings are important when considering the use of these functional measures in intermediate AMD.
Publisher: The Optical Society
Date: 27-04-2017
DOI: 10.1364/BOE.8.002732
Publisher: Public Library of Science (PLoS)
Date: 10-09-2015
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 29-04-2015
Abstract: The purpose of this study was to examine the test-retest repeatability of microperimetric sensitivity at the border of deep scotomas. Thirty normal participants underwent two examinations, each on the Macular Integrity Assessment (MAIA) microperimeter and on the MP-1 microperimeter (four examinations in total). A customized stimulus pattern allowed microperimetric sensitivity to be measured at the border of the optic nerve head (ONH), which acted as a model for the border of a deep scotoma-and also at the macular and peripapillary region. There were no significant changes in average point-wise sensitivity (PWS) values between the two examinations for all three regions using the MAIA microperimeter (P ≥ 0.262). The PWS coefficient of repeatability (CoR) was ±12.99 dB at the border of the ONH, which was significantly larger than points in the macular and peripapillary regions (P > 0.001). A significant decrease in average PWS, using the MP-1 microperimeter at the macular and peripapillary region (P < 0.001), meant that the PWS CoR could not be determined in these regions. No significant changes in average PWS were observed at the border of the ONH (P = 0.223), and the PWS CoR was ±7.52 dB in this region. Microperimetric test-retest repeatability at the border of a deep scotoma was worse than at other areas of normal retina, and this highlights the limitation of applying a single estimate of test-retest repeatability to determine whether significant functional decline has occurred at the border of a deep scotoma.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 16-12-2014
Abstract: To determine the microperimetric retinal sensitivity in areas with nascent geographic atrophy (nGA) compared with other pathological features in eyes with intermediate AMD. Participants with bilateral intermediate AMD underwent microperimetry examinations and high-resolution spectral-domain optical coherence tomography (SD-OCT) scans in a prospective study. Twenty-two participants (24 eyes) identified as having a microperimetric stimulus s ling an atrophic area (nGA or drusen-associated atrophy detected on SD-OCT) in an eye were analyzed, using three neighboring nonatrophic regions (with or without AMD-associated features) in the same eye as reference areas. On average, the mean microperimetric retinal sensitivity was worse in areas with nGA than nonatrophic reference areas (P ≤ 0.008), but better than areas with drusen-associated atrophy (P = 0.008). Considering all the microperimetry points in an eye, there were only 6 out of 16 eyes (37.5%) where the retinal sensitivity over nGA was the worst performing point in the eye, while all eight out of eight eyes (100.0%) with an area of drusen-associated atrophy detected on SD-OCT had the worst-performing point over that area. Areas of nGA were characterized by worse microperimetric retinal sensitivity compared with nonatrophic areas in eyes with intermediate AMD, but better retinal sensitivity compared with areas of drusen-associated atrophy detected on SD-OCT. Areas of nGA were also not always the worst performing point in an eye. These findings further our understanding of the functional changes occurring in novel SD-OCT identified pathological changes in intermediate AMD.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 25-11-2014
Abstract: To develop and characterize a feline model of retinal degeneration induced by intravitreal injection of adenosine triphosphate (ATP). Nineteen normally sighted adult cats received 100 μL intravitreal injections of ATP with a final concentration of 11, 22, or 55 mM at the retina. Four animals were euthanized 30 hours after injection and retinal sections examined for apoptosis using a TUNEL cell death assay. In the remaining animals, structural and functional changes were characterized over a 3-month period using a combination of electroretinography (ERG) and optical coherence tomography (OCT). Using a TUNEL cell death assay, we detected widespread photoreceptor death 30 hours after injection with 55 mM intravitreal ATP. All concentrations of ATP caused loss of retinal function and gross changes in retinal structure within 2 weeks of injection. Intravitreal injection of ATP led to a rapid loss of rod photoreceptor function and a gradual loss of cone photoreceptor function within 3 months. Outer nuclear layer thickness was globally reduced by 3 months, with the inner nuclear layer including the retinal nerve fiber layer remaining intact. Structural abnormalities were observed, including focal retinal detachment with evidence of both intravitreal and intraretinal inflammation in some eyes. Development of an ATP-induced feline model of retinal degeneration provides a rapid and effective large-eyed animal model for research into vision restoration.
Publisher: Therapeutic Guidelines Limited
Date: 10-2002
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-03-2018
DOI: 10.1167/TVST.7.2.2
Publisher: Informa Healthcare
Date: 17-11-2006
DOI: 10.1517/14656566.7.17.2355
Abstract: Age-related macular degeneration (AMD) is the leading cause of legal blindness in people > 50 years of age in the developed world. AMD is both a debilitating and costly disease for the in idual and the community. Greater understanding of the mechanisms and pathways involved in causing the visual loss in AMD has resulted in the advent of several newer and more effective treatment options, making it an exciting time in the management of AMD. This paper will examine the principles behind the existing drug therapies available, as well as those being developed in the management or prophylaxis of AMD and its vision-threatening complications.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.TIG.2022.01.003
Abstract: Reticular pseudodrusen (RPD) are subretinal deposits that, when observed with age-related macular degeneration (AMD), form a distinct phenotype, often associated with late-stage disease. To date, RPD genetic risk associations overlap six well-established AMD-risk regions. Determining RPD-specific underlying genetic causes by using adequate imaging methods should improve our understanding of the pathophysiology of RPD.
Publisher: American Medical Association (AMA)
Date: 09-06-2008
DOI: 10.1001/ARCHOPHT.126.6.826
Abstract: To systematically review the evidence on dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration (AMD). Seven databases were systematically searched with no limits on publication year or language using standardized criteria. Randomized controlled trials and prospective cohort, case-control, and cross-sectional studies were included. Of 2754 abstracts identified, 3 prospective cohort, 3 case-control, and 3 cross-sectional studies met the criteria. Measures of associations were pooled quantitatively using meta-analytic methods. Nine studies provided data on a total s le of 88 974 people, including 3203 AMD cases. A high dietary intake of omega-3 fatty acids was associated with a 38% reduction in the risk of late AMD (pooled odds ratio [OR], 0.62 95% confidence interval [CI], 0.48-0.82). Fish intake at least twice a week was associated with a reduced risk of both early AMD (pooled OR, 0.76 95% CI, 0.64-0.90) and late AMD (pooled OR, 0.67 95% CI, 0.53-0.85). Although this meta-analysis suggests that consumption of fish and foods rich in omega-3 fatty acids may be associated with a lower risk of AMD, there is insufficient evidence from the current literature, with few prospective studies and no randomized clinical trials, to support their routine consumption for AMD prevention.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-12-2011
DOI: 10.1167/IOVS.10-7043
Abstract: To evaluate the potential of psychophysical assessments of retinal function to provide diagnostic biomarkers of early age-related macular degeneration (AMD). Unilateral visual function was assessed in 221 participants (72.86 ± 9.94 years 67% women) with early AMD (visual acuity better than 20/60) and 109 controls (73.07 ± 10.32 years 65% women). Psychophysical assessment included steady state thresholds (4- and 14-Hz flicker and red and blue color) and dynamic tests (photostress recovery [PSR] and dark adaptation [DA]). All test parameters were compared in terms of their diagnostic capacity (sensitivity and specificity), reproducibility, and clinical applicability (test duration and participant's perception of test difficulty). AMD status was determined by digital photography, according to the International Classification and Grading System. All functional measurements were significantly worse, on average, in the AMD group than in the control group (P < 0.001). Static and dynamic parameters showed weak correlations (range, 0.003-0.225). Rod recovery in DA and cone recovery in PSR had the best diagnostic capacity (area under curve [AUC], receiver operating characteristic [ROC] analysis, 0.93 ± 0.016 and 0.85 ± 0.021, respectively). Considering diagnostic capacity together with test reproducibility and clinical applicability, the 14-Hz flicker gave the best outcome, followed by PSR. Combination of these two tests detected 71% of abnormal early AMD cases. All the visual function tests had good diagnostic capacity. Combination of the 14-Hz flicker thresholds and dynamics of the PSR test provided optimal quantitative assessment of retinal function in early AMD, suggesting that this set is a potentially useful clinical tool for following progression of early AMD and assessing the efficacy of interventions.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.SURVOPHTHAL.2017.09.008
Abstract: Because of complications and side effects, conventional laser therapy has taken a back seat to drugs in the treatment of macular diseases. Despite this, research on new laser modalities remains active. In particular, various approaches are being pursued to preserve and improve retinal structure and function. These include micropulsing, various exposure titration algorithms, and real-time temperature feedback control of short-pulse continuous wave lasers, and ultra-short-pulse nanosecond lasers. Some of these approaches are at the preclinical stage of development, whereas others are available for clinical use. Cell biology is providing important insights into the mechanisms of action of retinal laser treatment. We outline the technological bases of current laser platforms, their basic science, therapeutic concepts, clinical experience, and future directions for retinal laser treatment.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.OPHTHA.2015.08.014
Abstract: To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52). Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials. Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients. Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks. Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits. After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96. These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation.
Publisher: Springer Science and Business Media LLC
Date: 25-06-2004
Publisher: BMJ
Date: 19-11-2009
Abstract: X linked Alport syndrome is characterised by renal failure, hearing loss, lenticonus, and a central and peripheral dot-and-fleck retinopathy. complement factor H (CFH) gene variants are strongly associated with retinal drusen in macular degeneration and mesangiocapillary glomerulonephritis, and this study examines their role in the development of the Alport retinopathy. Twenty-three males and 27 females from 27 unrelated families were examined and their DNA tested for the CFH risk allele (1277 T>C, h1, Y402H) and protective haplotypes (h2 and h4) using a MALDI-TOF-based method. The prevalence of the CFH risk allele was not increased in males with a central or peripheral retinopathy. Three of the nine (33%) with the central retinopathy had at least one copy of the risk allele, and five of the 14 (36%) without the retinopathy did (NS, OR 0.900, CI 0.154 to 5.259). Four of the 12 (33%) with either retinopathy had the risk allele, and two of the six (33%) with none did (NS OR 1.0, CI 0.125 to 7.996). The pathogenesis of the retinal dots and flecks in Alport syndrome is independent of CFH-dependent mechanisms and, like other clinical features, may depend on the nature of the underlying COL4A5 mutations.
Publisher: Springer Science and Business Media LLC
Date: 09-03-2018
Publisher: Springer Science and Business Media LLC
Date: 03-03-2013
DOI: 10.1038/NG.2578
Publisher: Wiley
Date: 04-2009
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.OPHTHA.2008.09.009
Abstract: To examine the relationship of retinal vascular caliber to macular telangiectasia (MT) type 2. Case-control study. Patients with MT aged 18 years and older were identified from Australian sites of the multicenter Macular Telangiectasia Project. Three controls per case were selected from participants of the Australian Diabetes, Obesity and Lifestyle study, matched according to age and diabetes status. Baseline ophthalmic examinations of cases included assessment of best corrected visual acuity, fluorescein angiography, autofluorescence imaging, optical coherence tomography, and retinal photography. Retinal vascular caliber of cases and controls were measured from optic disc-centered digital retinal images by a computer-assisted method. MT, central retinal arteriolar, and venular caliber. There were 55 cases and 170 controls. After controlling for diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglycerides, hypertension, fasting plasma glucose, and glycosylated hemoglobin, each standard deviation (SD) increase in retinal arteriolar caliber was associated with a 2-fold higher odds of MT (odds ratio [OR] 2.18 95% confidence interval [CI], 1.50-3.18). Similarly, each SD increase in retinal venular caliber was associated with increased odds of having MT (OR 1.87 95% CI, 1.31-2.67). This study shows that MT is associated with wider arteriolar and venular caliber, measured outside of the foveal area. Generalized changes in retinal vascular caliber may reflect underlying dysfunction in retinal pericytes or glial cells, and may provide a means to monitor progression of disease. Proprietary or commercial disclosure may be found after the references.
Publisher: Oxford University Press (OUP)
Date: 15-04-2011
DOI: 10.1093/AJE/KWR015
Publisher: Wiley
Date: 20-09-2022
DOI: 10.1111/ANS.18038
Abstract: Many autosomal dominant polycystic kidney disease (ADPKD) patients undergo nephrectomy and subsequent renal transplantation. We report our outcomes after hand-assisted laparoscopic nephrectomy (HALN) where a Rutherford-Morrison incision is used as a hand-port site and kidney extraction site, as well the future incision site for staged transplantation. A retrospective review was performed on all adult nephrectomies for ADPKD by the Transplant Surgery department at Westmead Hospital between June 2011 and June 2021. Outcomes were compared between HALN, laparoscopic nephrectomy (LN) and open nephrectomy (ON) including operation time, hospital length of stay (LOS), post-operative complications, subsequent transplantation and post-transplantation wound complications. Twenty-two HALN, 8 LN and 5 ON were performed during the study period. Median kidney weights for HALN, LN and ON were significantly different (1575, 403, 3420 g respectively, P = 0.001). There was a significant difference in LOS between the HALN and ON (5.8 versus 9.8 days, P = 0.04), but not between HALN and LN (5.8 versus 5.1, P = 0.06). There was no significant difference for operation time (P = 0.34) and major complication rates (P = 0.58). There were 8 HALN, 5 LN and 2 ON who have had subsequent renal transplantation with one wound complication, an incisional hernia in the HALN group. Our HALN is associated with a shorter LOS and similar complication rate to ON and can be efficiently performed for significantly larger kidneys than LN without a significant difference in operation time or LOS. The same Rutherford-Morrison incision site can be used for transplantation.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.AJO.2022.03.007
Abstract: To examine the association between reticular pseudodrusen (RPD) and progression to late age-related macular degeneration (AMD) in in iduals with intermediate AMD. Prospective cohort study. Two hundred eighty eyes from 140 participants with bilateral large drusen underwent multimodal imaging (MMI), including optical coherence tomography (OCT), near-infrared reflectance (NIR), fundus autofluorescence, and color fundus photography (CFP), at 6-monthly intervals up over a 36-month follow-up period. The presence of RPD per eye was determined based on either a combined MMI criterion, or each in idual imaging modality, and their extent measured on combined OCT and NIR imaging. The association between the presence of RPD on different imaging modalities, and their extent, with the development of late AMD (including OCT-defined atrophy) was evaluated. The presence of RPD on MMI, or any of its in idual modalities, at baseline was not significantly associated with an increased rate of developing late AMD, with or without adjusting for risk factors for AMD progression (age, drusen volume on OCT, and pigmentary abnormalities on CFP all P ≥ 0.205). The extent of RPD present was also not significantly associated with an increased rate of developing late AMD, with or without adjustment for risk factors for AMD progression (both P ≥ 0.522). In this cohort with bilateral large drusen, the presence of RPD was not significantly associated with an increased risk of developing late AMD. Additional longitudinal studies in all stages of AMD are needed to understand the implications of RPD on vision loss in this condition.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2014
Abstract: To design and evaluate an instrument appropriate for assessing vision-related quality of life (VRQoL) in persons with severe vision loss. A total of 603 legally blind persons (better eye visual acuity of <20/200) were interviewed using an item pool based on the original Impact of Vision Impairment (IVI) questionnaire, augmented by items appropriate for persons with severe vision loss. Refinement and item reduction was done in three steps using factor and Rasch analysis to assess psychometric properties, exploring key indices, such as response category functioning (floor and ceiling effects), instrument unidimensionality, discriminant ability, and targeting of item difficulty to patient ability. A final pool of 28 items was selected that grouped into two subscales of the IVI-VLV: activities of daily living, mobility, and safety (ADLMS 16 items) and emotional well-being (EWB 12 items). Both subscales are unidimensional, able to differentiate reliably between at least three different levels of VRQoL, and item difficulty was adequate for the assessed s le. Using generalized linear models and controlling for age, we found that only poor general health (P = 0.005 and P = 0.007) and concurrent depression and anxiety (P = 0.019 and P < 0.001) were associated with a lower ADLMS and EWB subscale score, respectively. The IVI-VLV is a valid and reliable VRQoL measure in persons with severe vision loss, and its measurement is almost unaffected by participants' self-perceived general or mental health. The IVI-VLV can be used as an outcome measure in trials attempting sight restoration.
Publisher: Elsevier BV
Date: 10-2014
Publisher: BMJ
Date: 18-03-2016
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 25-11-2014
Abstract: To determine the validity, reliability, and measurement characteristics using factor and Rasch analysis of the Very Low Vision Instrumental Activities of Daily Living (IADL-VLV) in persons with severe vision loss. From an initial pool of 296 tasks, 25 were shortlisted after conducting a Delphi survey with persons designated legally blind. Using further input from occupational therapy and low-vision professionals, 11 activities were chosen to be pilot tested. Forty legally blind participants (better eye visual acuity < 20/200) underwent clinical assessments and functional tests as well as the 53 IADL tasks related to the 11 activities. The task pool was refined and condensed using factor and Rasch analysis. Based on iterative principal component analyses, tasks were grouped together into the following domains: reading signs/information access, signature placement, clothes sorting, shelf search, gesture recognition, clock reading, and table search. A final selection of 23 tasks yielded satisfactory measurement characteristics, differentiated between at least four different levels of IADL performance (person separation of 3.8), and had adequate task difficulty for the tested s le (person mean -0.61). In multivariate analyses, only visual acuity (VA) and percent of remaining visual field (VF) were associated with IADL performance. Using a large item pool, participant, and expert input, as well as factor and Rasch analysis, we designed a valid and reliable assessment to measure vision-related IADL performance in persons with severe vision loss. This assessment tool can be used in clinical sight restoration trials.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 2024
Publisher: Wiley
Date: 18-12-2017
DOI: 10.1111/CEO.13097
Abstract: Improved vision self-monitoring tools are required for people at risk of neovascular complications from age related macular degeneration (AMD). to report the self-monitoring habits of participants with intermediate AMD using the Amsler grid chart, and the use of personal electronic devices and gameplay in this over 50 year old cohort. single-centre descriptive study carried out at the Centre for Eye Research (CERA), Melbourne, Australia. 140 participants over 50 years of age, with a diagnosis of intermediate AMD and best-corrected visual acuity (BCVA) of ≥6/12 in each eye. structured questionnaire survey of participants who were enrolled in natural history of AMD studies at CERA. frequency of vision self-monitoring using the Amsler grid chart, and frequency of general use of personal electronic devices and gameplay. Of 140 participants with mean age of 70.5 years, 83.6% used an Amsler grid chart, but only 39.3% used it once per week. Most participants (91.4%) used one or more personal electronic devices. Of these, over half (54.7%) played games on them, among whom 39% played games once a day. Of participants aged 50-69 years, 92% (95%CI 85.1-98.9) were willing to play a game to monitor their vision, compared to 78% (95%CI 69.0-87.0) of those aged 70 years and older (P < 0.05). a large proportion of AMD patients already use personal electronic devices. Gamification techniques are likely to increase compliance with self-monitoring, leading to earlier detection in the next generation of patients with neovascular AMD.
Publisher: AMPCo
Date: 03-2013
DOI: 10.5694/MJA12.11295
Publisher: Wiley
Date: 07-2006
DOI: 10.1111/J.1442-9071.2006.01250.X
Abstract: Cardiovascular disease and age-related macular degeneration (AMD) may share common risk factors in their causal pathways. Decades of research from the cardiovascular sciences on fats have led investigators to focus on specific types of fats rather than total fat as a whole. They have established that saturated and trans-unsaturated fats (trans fats) are damaging to cardiovascular health while polyunsaturated fats, particularly the marine omega 3 fatty acids appear protective. This has led to a number of studies investigating the associations of fat and AMD. Though the causal relationship between fats and AMD remain unproven, some studies suggest that an association may be present. To be able to understand and interpret the study results and their implications, an understanding of the fats in the diet is important. This review aims to give an overview of fatty acids, particularly the trans-unsaturated fatty acids, and the relevant food groups.
Publisher: Public Library of Science (PLoS)
Date: 25-04-2012
Publisher: Wiley
Date: 11-02-2016
DOI: 10.1111/CEO.12685
Abstract: Emergence of the high-resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. However, some anatomical correlates still remain contentious, such as the second hyper-reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 07-2017
Publisher: Informa UK Limited
Date: 24-01-2022
DOI: 10.1080/08164622.2021.2022961
Abstract: In recent years, there has been intense development of artificial intelligence (AI) techniques, which have the potential to improve the clinical management of age-related macular degeneration (AMD) and facilitate the prevention of irreversible vision loss from this condition. Such AI techniques could be used as clinical decision support tools to: (i) improve the detection of AMD by community eye health practitioners, (ii) enhance risk stratification to enable personalised monitoring strategies for those with the early stages of AMD, and (iii) enable early detection of signs indicative of possible choroidal neovascularisation allowing triaging of patients requiring urgent review. This review discusses the latest developments in AI techniques that show promise for these tasks, as well as how they may help in the management of patients being treated for choroidal neovascularisation and in accelerating the discovery of new treatments in AMD.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-2004
DOI: 10.1167/IOVS.03-0913
Abstract: To describe the cytoarchitecture of the choroidal capillary endothelial cells, especially as it relates to cellular processes that protrude through the basal lamina into Bruch's membrane (BM). Human donor eyes and monkey and hamster eyes were examined by transmission electron microscopy and freeze-fracture replication. The number of endothelial cell processes and the characteristics of the processes and surrounding structures were determined in the maculae of human eyes and correlated with age-related changes in neighboring structures. Endothelial cell processes were observed in eyes of all species examined and at all ages. They typically occurred at sites of focally thickened, nonfenestrated regions of the endothelial cells. The basal lamina adjacent to the processes was often hypertrophic and associated deposits of long-spacing collagen (LSC) were observed frequently. In humans, there was no correlation between the number of processes per 100 micro m of the BM with age, sex, cause of death, postmortem time, RPE autofluorescence, or RPE residual body content. There was a weak linear association with the thickness of the BM. The finding of cellular processes of choroidal capillary endothelial cells penetrating their basal laminae is normal. These processes may serve to stabilize choroidal endothelial cells physically and play an important structural role in the maintenance of patency of the choriocapillaris. It is also possible that they have additional functions, as suggested for similar processes in other tissues. They are not necessarily the harbinger of choroidal neovascularization, although growth of new vessels may result from distortion of this normal attribute.
Publisher: Elsevier BV
Date: 04-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 25-05-2010
DOI: 10.1007/S10792-010-9374-Z
Abstract: Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case-control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA s les from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P=0.43) or the Ala114Val SNP (P=0.85), or for any combinations however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2 however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.OPHTHA.2008.09.002
Abstract: To elucidate the contribution of environmental versus genetic factors to the significant losses in visual function associated with normal aging. A classical twin study. Forty-two twin pairs (21 monozygotic and 21 dizygotic age 57-75 years) with normal visual acuity recruited through the Australian Twin Registry. Cone function was evaluated by establishing absolute cone contrast thresholds to flicker (4 and 14 Hz) and isoluminant red and blue colors under steady state adaptation. Adaptation dynamics were determined for both cones and rods. Bootstrap res ling was used to return robust intrapair correlations for each parameter. Psychophysical thresholds and adaptational time constants. The intrapair correlations for all color and flicker thresholds, as well as cone absolute threshold, were significantly higher in monozygotic compared with dizygotic twin pairs (P<0.05). Rod absolute thresholds (P = 0.28) and rod and cone recovery rate (P = 0.83 P = 0.79, respectively) did not show significant differences between monozygotic and dizygotic twins in their intrapair correlations, indicating that steady-state cone thresholds and flicker thresholds have a marked genetic contribution, in contrast with rod thresholds and adaptive processes, which are influenced more by environmental factors over a lifetime. Genes and the environment contribute differently to important neuronal processes in the retina and the role they may play in the decline in visual function as we age. Consequently, retinal structures involved in rod thresholds and adaptive processes may be responsive to appropriate environmental manipulation. Because the functions tested are commonly impaired in the early stages of age-related macular degeneration, which is known to have a multifactorial etiology, this study supports the view that pathogenic pathways early in the disease may be altered by appropriate environmental intervention. The authors have no proprietary or commercial interest in any materials discussed in this article.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.OPHTHA.2012.07.026
Abstract: To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Twenty-four-month, open-label, multicenter, phase IV extension study. Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8% 1 event related to study drug), cataract (11.5% 1 event related to treatment procedure), and increased intraocular pressure (6.4% 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment. Proprietary or commercial disclosure may be found after the references.
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.AJO.2007.12.005
Abstract: To review systematically the evidence currently available on alcohol consumption and the risk of age-related macular degeneration (AMD). Systematic review and meta-analysis of observational studies. Seven databases were searched systematically with no limits on the year or language of publication for prospective cohort studies. References identified from pertinent reviews and articles also were retrieved. Two reviewers independently searched the above databases and selected the studies using prespecified standardized criteria. These criteria included appropriate adjustment for age and smoking in the analysis. Of the 441 studies identified initially, five cohort studies met the selection criteria. Data extraction and study quality evaluation were performed independently by two reviewers and results were pooled quantitatively using meta-analytic methods. The five cohort studies included 136,946 people, among whom AMD developed in 1923 (1,513 early and 410 late). Pooled results showed that heavy alcohol consumption was associated with an increased risk of early AMD (pooled odds ratio, 1.47 95% confidence interval, 1.10 to 1.95), whereas the association between heavy alcohol consumption and risk of late AMD was inconclusive. There were insufficient data to evaluate a dose-response association between alcohol consumption and AMD or the association between moderate alcohol consumption and AMD. Heavy alcohol consumption (more than three standard drinks per day) is associated with an increased risk of early AMD. Although this association seems to be independent of smoking, residual confounding effects from smoking cannot be excluded completely.
Publisher: Hindawi Limited
Date: 12-09-2011
DOI: 10.1002/HUMU.21577
Publisher: American Medical Association (AMA)
Date: 07-2006
Publisher: Oxford University Press (OUP)
Date: 04-2013
DOI: 10.1093/AJE/KWS332
Abstract: In this study, we examined the relationship between exposure to siblings and 1) the risk of age-related macular degeneration (AMD) and 2) C-reactive protein levels. We retrospectively analyzed pooled cross-sectional data from 2 studies: the Cardiovascular Health and Age-Related Maculopathy Study (2001-2002) and the Age-Related Maculopathy Statin Study (2004-2006). Associations between number of siblings and AMD were assessed by using multinomial logistic regression. Associations between number of siblings and C-reactive protein levels were examined by using a generalized linear model for γ distribution. A higher number of younger siblings was associated with significantly lower odds of early AMD in those with a family history of AMD (odds ratio = 0.2, 95% confidence interval: 0.1, 0.8) (P = 0.022) but was unrelated to AMD for those who had no family history of the disease (odds ratio = 1.0, 95% confidence interval: 0.9, 1.2) (P = 0.874). A higher number of younger siblings correlated with lower C-reactive protein levels (β = -0.19, 95% confidence interval: -0.38, -0.01) (P = 0.036). This supports the theory that immune modulation contributes to AMD pathogenesis and suggests that exposure to younger siblings might be protective when there is a family history of AMD.
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.AJO.2005.08.019
Abstract: The Drusen Laser Study evaluated macular laser to prevent choroidal neovascularization (CNV) and vision loss in high-risk age-related maculopathy (ARM). Prospective, interventional, randomized, controlled clinical trial in five hospital centers. Patients in the unilateral group had neovascular ARM and drusen in the study eye. Study eyes were randomized to laser-treated or no-laser groups. For patients in the bilateral drusen group, eyes were randomized to right eye, laser or no laser and left eye, alternative. Laser treatment comprised 12 argon spots. Outcome was best-corrected visual acuity and CNV signs, which were monitored for 3 years. In the unilateral group, vision loss occurred in 21 (28.8%) of 73 patients in laser vs 13 (19.7%) of 66 no-laser patients (P=.214). Incidence of CNV was 27 (29.7%) of 91 in laser vs 15 (17.65%) of 85 no-laser patients (P=.061). CNV onset was approximately 6 months earlier in laser-treated compared with no-laser patients (P=.05). In the bilateral group, vision loss occurred in six (8.3%) of 72 laser-treated vs 10 (13.9%) of 72 fellow eyes (P=.3877). CNV incidence was 12 (11.6%) of 103 in laser-treated vs seven (6.8%) of 103 fellow eyes (P=.225). There was no difference in onset of CNV. Results do not support prophylactic laser of the fellow eye of patients with neovascular ARM. Its role in patients with bilateral drusen remains unclear.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.OPHTHA.2014.01.002
Abstract: To evaluate the association between dietary patterns and age-related macular degeneration (AMD). Food frequency data were collected from Melbourne Collaborative Cohort Study (MCCS) participants at the baseline study in 1990-1994. During follow-up in 2003-2007, retinal photographs were taken and evaluated for AMD. At baseline, 41514 participants aged 40 to 70 years and born in Australia or New Zealand (69%), or who had migrated from the United Kingdom, Italy, Greece, or Malta (31%) were recruited. Of these, 21132 were assessed for AMD prevalence at follow-up. Principal component analysis was used to identify dietary patterns (Factors F1-6) among the food items. Logistic regression was used to assess associations of dietary patterns with AMD. Odds ratios (ORs) for early stages and advanced AMD in association with dietary patterns. A total of 2508 participants (12.8%) had early stages of AMD, and 108 participants (0.6%) had advanced AMD. Six factors characterized by predominant intakes of fruits (F1) vegetables (F2) grains, fish, steamed or boiled chicken, vegetables, and nuts (F3) red meat (F4) processed foods comprising cakes, sweet biscuits, and desserts (F5) and salad (F6) were identified. Higher F3 scores were associated with a lower prevalence of advanced AMD (fourth vs. first quartile) (OR, 0.49 95% confidence interval [CI], 0.28-0.87), whereas F4 scores greater than the median were associated with a higher prevalence of advanced AMD (OR, 1.46 95% CI, 1.0-2.17). Rather than specific in idual food items, these factors represent a broader picture of food consumption. A dietary pattern high in fruits, vegetables, chicken, and nuts and a pattern low in red meat seems to be associated with a lower prevalence of advanced AMD. No particular food pattern seemed to be associated with the prevalence of the earliest stages of AMD.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2016
Publisher: Elsevier BV
Date: 07-1998
DOI: 10.1016/S0002-9394(98)00061-0
Abstract: To evaluate prophylactic laser treatment of the macula in reducing the risk of visual loss in the fellow eye of patients with a retinal pigment epithelial tear caused by age-related macular degeneration in the first eye. In a prospective study, 12 patients with a retinal pigment epithelial tear in one eye caused by age-related macular degeneration and drusen in the fellow eye received prophylactic laser treatment of the retina in their fellow eyes and were followed up for 2 years or more after prophylactic treatment. In 12 fellow eyes that received prophylactic laser treatment, a reduction in best-corrected visual acuity to 20/80 or worse occurred in one (8%) of 12 eyes in the first year and two (18%) of the remaining 11 eyes in the second year after treatment. The cumulative risk of visual loss in the treated fellow eye was 25% in 2 years. In historical control subjects in a natural history study of patients with retinal pigment epithelial tear in one eye, central visual loss occurred in 16 (37%) of 43 eyes in the first year and in seven (30%) of 23 eyes in the second year for a cumulative loss of 59% in the first 2 years. Compared with these historical control subjects, our findings suggest that visual loss in the fellow eyes of patients with a retinal pigment epithelial tear in the first eye is reduced by prophylactic low intensity laser photocoagulation of the macula.
Publisher: Oxford University Press (OUP)
Date: 15-07-2009
DOI: 10.1093/AJE/KWP184
Publisher: Springer Science and Business Media LLC
Date: 26-11-2011
DOI: 10.1038/EYE.2010.180
Publisher: Wiley
Date: 24-10-2013
DOI: 10.1111/CEO.12212
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-10-2016
Abstract: Retinal prostheses have emerged as a promising technology to restore vision in patients with severe photoreceptor degeneration. To better understand how neural degeneration affects the efficacy of electronic implants, we investigated the function of a suprachoroidal retinal implant in a feline model. Unilateral retinal degeneration was induced in four adult felines by intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post injection, animals received suprachoroidal electrode array implants in each eye, and responses to electrical stimulation were obtained using multiunit recordings from the visual cortex. Histologic measurements of neural and glial changes in the retina at the implant site were correlated with cortical thresholds from in idual stimulating electrodes. Adenosine triphosphate-injected eyes displayed changes consistent with mid-to-late stage retinal degeneration and remodeling. A significant increase in electrical charge was required to induce a cortical response from stimulation of the degenerated retina compared to that in the fellow control eye. Spatial and temporal characteristics of the electrically evoked cortical responses were no different between eyes. In idual electrode thresholds varied in both the control and the ATP-injected eyes and were correlated with ganglion cell density. In ATP-injected eyes, cortical threshold was also independently correlated with an increase in the extent of retinal gliosis. These data suggest that even when ganglion cell density remains unaffected, glial changes in the retina following degeneration can influence the efficacy of suprachoroidal electrical stimulation. A better understanding of how glial change impacts retinal prosthesis function may help to further the optimization of retinal implants.
Publisher: Therapeutic Guidelines Limited
Date: 06-2012
Publisher: Wiley
Date: 14-11-2002
DOI: 10.1046/J.1442-9071.2002.00572.X
Abstract: A single base change within the EFEMP1 gene has been associated with malattia leventinese and Doyne honeycomb retinal dystrophy, two dominantly inherited macular diseases with early onset drusen. The aim of this study was to determine whether the same disease allele was also associated with other forms of early onset drusen or familial cases of age-related macular degeneration. Thirteen index cases of early onset drusen together with 15 other family members were examined. In addition, 54 familial cases of age-related macular degeneration were examined. Blood was taken for DNA analysis and screened for the Arg345Trp disease-associated allele of the EFEMP1 gene. Twenty-four cases of malattia leventinese or Doyne honeycomb retinal dystrophy were also screened as positive controls. Another 150 ethnicity- and age-matched in iduals acted as controls. The Arg345Trp disease-associated allele in the EFEMP1 gene was confirmed in in iduals with malattia leventinese and Doyne honeycomb retinal dystrophy. However, involvement of this allele was not evident in either early onset drusen or familial age-related macular degeneration. The Arg345Trp disease-associated allele of the EFEMP1 gene does not appear to be associated with cases of early onset drusen that fall outside the diagnosis of malattia leventinese or Doyne honeycomb retinal dystrophy, nor does it appear to play a role in familial age-related macular degeneration. These findings do not exclude the involvement of other alleles of the EFEMP1 gene in either phenotype. The genetic mechanisms involved in the heterogeneous group of early onset drusen remain to be elucidated but should lead to insights into the genetic causes of macular diseases.
Publisher: BMJ
Date: 19-01-2016
DOI: 10.1136/BJOPHTHALMOL-2015-307663
Abstract: To assess the association between past physical activity and early, intermediate and late age-related macular degeneration (AMD) in a community-based cohort study in Melbourne, Australia. Diet and lifestyle information was recorded at baseline (1990-1994) and total recreational activity was derived from walking, vigorous and non-vigorous exercise. At follow-up (2003-2007), digital macular photographs were graded for early, intermediate and late AMD. Data were analysed using multinomial logistic regression controlling for age, sex, smoking, region of descent, diet and alcohol. Effect modification by sex was investigated. Out of 20 816 participants, early, intermediate and late AMD were detected at follow-up in 4244 (21%), 2661 (13%) and 122 (0.6%) participants, respectively. No association was detected between past total recreational physical activity and early, intermediate or late AMD. Frequent (≥3 times/week) and less frequent (1-2 times/week) vigorous exercise were associated with lower odds of intermediate and late AMD in univariable models. After controlling for confounders, there was evidence of effect modification by sex and frequent vigorous exercise was associated with a 22% decrease in the odds of intermediate AMD (95% CI 4% to 36%) in women, but no association was found for men. Past frequent vigorous exercise may be inversely related to the presence of intermediate AMD in women. Further studies are needed to confirm whether physical activity and exercise have a protective effect for AMD.
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.3129/I07-116
Abstract: To estimate the effect of dietary intake of lutein and zeaxanthin (L/Z) and fats on the progression of age-related macular degeneration (AMD). Two hundred and fifty-four subjects identified with early age-related macular degeneration (AMD) were re-examined to determine 7-year AMD progression. Intakes of L/Z and fatty acids were estimated from food frequency questionnaires. Progression was defined by 3 different definitions, 2 quantitative and 1 qualitative, which varied in the stringency of the change required for the AMD to be deemed to have progressed. Covariates included age, smoking, AMD family history, source study, and follow-up duration. Energy-adjusted L/Z intake as a continuous variable was associated with AMD progression in the worse affected eye when defined by the most stringent criterion (odds ratio [OR] = 2.65, 95% confidence interval [CI] 1.13-6.22, p = 0.02). Similar associations were observed for the 2 other progression definitions (p = 0.18 and p = 0.13). Energy-adjusted omega-3 fatty acid intake modelled as a quintile median was associated with AMD progression only in the side-by-side assessment (OR = 2.56, 95% CI 1.11-5.91, p = 0.03), with borderline significance in the other 2 definitions (p = 0.05 and p = 0.08). No association of AMD progression was observed with the intake of either total fat or other subgroups: saturated, polyunsaturated, or monounsaturated fats trans fatty acids or omega-6 fatty acids. The findings of the study are counterintuitive, suggesting that increased intakes of dietary L/Z and omega-3 fatty acids are associated with progression of AMD. These results may indicate that too much of a good thing might be harmful. It is possible that in this study participants adopted a more healthy diet, having been aware of their AMD status at the beginning of the study. This healthy diet was then reflected in the dietary questionnaire completed at the end of study. However, this explanation may not adequately explain why those whose AMD had progressed, on the basis of fundus signs and not symptoms such as visual acuity decline, adopted a healthier lifestyle more aggressively than those without progression.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
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: Future Medicine Ltd
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 12-10-2005
DOI: 10.1007/S00417-005-0121-5
Abstract: We develop the logic for a stimulus that can evaluate cone-dependent spatial summation and detail the modelling and interpretation of thresholds obtained with this stimulus. Fifteen observers participated, including two young normals tested extensively in control experiments, and a clinical trial based on four observers with age-related macular degeneration (AMD), four age-similar controls and five young observers. Monocular spatial summation functions were measured with contrast-modulated Gabor targets that approximated the optimal visual contrast detector. Thresholds were returned from a yes/no adaptive psychophysical algorithm. By fine titration along the size domain it was demonstrated that the spatial summation of normal observers can be adequately described by a two-component model. A reduced set of variables are proposed for clinical applications and the model was applied to data derived using these variables in persons with AMD and age-similar controls. We do not find a significant age-related loss of contrast sensitivity in our normal group. On the other hand, persons with early AMD exhibited a 0.41 log unit loss of sensitivity (P=0.04) from age-similar controls, without any change in their maximum summation area (A(max)). The nature of the spatial summation is consistent with the interpretation that early AMD produces a decrease in cone input to post-receptoral mechanisms in the absence of neural remodelling.
Publisher: Elsevier BV
Date: 10-2007
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.LAB.2006.01.005
Abstract: Whole blood provides one of the most common sources of both high-quality DNA and high-quantity DNA for molecular biological purposes. Typically, blood storage at 4 degrees C is short term, which ranges from a few days to a few weeks. However, long-term storage usually involves blood being frozen, with a resultant loss in DNA yield. The authors examined the effects of long-term storage at 4 degrees C. Duplicate blood s les were collected from 301 participants (aged 20-98 years) enrolled as part of ongoing studies. S les were stored at 4 degrees C for between 11 days and 922 days, and DNA was subsequently extracted using a phenol/chloroform procedure. A negative correlation of the number of storage days existed at 4 degrees C with DNA yield. The main determinant on DNA yield was the age of the participant in the study, with older persons having a lower DNA yield. Long-term storage of blood at 4 degrees C does have a detrimental effect on DNA yield, but this effect seemed less significant than the age of a person. The impact of age of a person or storage time has a minimal impact on DNA quality. Therefore, storage of blood at 4 degrees C offers an acceptable alternative to frozen storage.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2010
DOI: 10.1167/IOVS.09-5114
Abstract: There is still a debate as to whether the LOC387715 or HTRA1 genes represent the key significant association identified with age-related macular degeneration (AMD) on the long arm of chromosome 10, region 26. An Australian patient cohort was genotyped by using tagged single nucleotide polymorphisms (tSNPs) to identify a causal SNP within this region. Multiple tSNPs across the region showed association with AMD with the tSNP rs3793917 (odds ratio [OR], 3.45 95% confidence interval [CI], 2.36-5.05, P = 2.8 × 10(-13)) having the highest association with AMD. This tSNP occurred in the intergenic region between the LOC387715 and HTRA1 genes. A second tSNP rs2672587 (OR, 2.92 95% CI, 2.04-4.17 P = 7.7 × 10(-11)) located in intron 1 of the HTRA1 gene had the second highest association with AMD. After logistic regression analysis, the only tSNP to survive covariate testing was rs3793917, which occurred in the same LD block as the HTRA1 promoter SNP rs11200638 (r(2) = 0.88, D' = 0.97). The findings indicate that the intergenic region between the tSNP rs3793917 and the SNP rs11200638 in the HTRA1 gene is the most likely site explaining the significant association with AMD.
Publisher: Wiley
Date: 10-2004
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.OPHTHA.2014.06.034
Abstract: To characterize the pathological changes preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). Longitudinal and cross-sectional retrospective observational study. A total of 181 participants with intermediate AMD in at least 1 eye (141 unilateral, 40 bilateral) were assessed longitudinally. A total of 230 participants with bilateral intermediate AMD (40 longitudinal participants with an additional 190 participants) were analyzed cross-sectionally. Spectral-domain OCT, color fundus photography (CFP), near-infrared reflectance, and fundus autofluorescence imaging were performed in all participants at cross-section and every 3 months for up to 30 months in the longitudinal study. Spectral-domain OCT volume scans were examined for features that portend the development of drusen-associated atrophy, and the topography, prevalence, and risk factors of these features were determined through cross-sectional analysis. The pathological features on SD-OCT preceding the development of drusen-associated atrophy and the characteristics of these features. Twenty areas from 16 eyes of 16 participants developed drusen-associated atrophy after an average of 20 months (range, 8-30 months). Spectral-domain OCT features unique in these areas included: subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), and development of a hyporeflective wedge-shaped band within the limits of the OPL. These characteristics were termed "nascent geographic atrophy" (nGA), describing features that portend the development of drusen-associated atrophy. Cross-sectional examination of participants with bilateral intermediate AMD revealed that independent risk factors for the presence of nGA included the presence of pigmentary changes (odds ratio [OR], 16.84 95% confidence interval [CI], 2.42-117.24) and nGA in the fellow eye (OR, 4.15 95% CI, 1.12-15.34) nGA was present in 21.9% of participants with drusen >125 μm and pigmentary changes in both eyes. This study identified pathological changes occurring before the development of drusen-associated atrophy using SD-OCT, which we defined as nGA. Although nGA is undetectable on CFP, it is important for determining the risk of future vision loss in AMD and could be used as an earlier surrogate end point in interventional trials targeting the early stages of AMD.
Publisher: Springer Science and Business Media LLC
Date: 31-07-2009
DOI: 10.1038/EYE.2009.175
Abstract: Although randomized clinical trials (ANCHOR and MARINA) have shown excellent results of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD), it is unclear whether such an outcome is achievable in daily practice. We evaluated the results of ranibizumab treatment for neovascular AMD in clinical practice in Australia. A retrospective chart review of patients in four practices injected with ranibizumab in 2006 for AMD. Patients who had been diagnosed with subfoveal choroidal neovascular membrane in the preceding 6 months and had completed at least 6 months follow-up were enrolled. No standard treatment protocols were required. The main outcome measure was visual acuity (VA) at 6 and 12 months. A total of 158 patients fulfilled the entry criteria. The mean baseline VA (decimal) was 0.35+/-0.21 (Snellen equivalent 6/17). At 6 months, the mean VA improved to 0.46+/-0.27 (6/13) and remained stable until month 12 (0.48+/-0.30). The improvement in VA between baseline and months 6 and 12 was statistically significant (P<0.0001). Both the mean and the median number of injections were four in the first 6 months and nine at 12 months. VA results were comparable with those of the ANCHOR and MARINA trials, and were achieved with a lower number of injections (P<0.0001). VA results achieved in daily clinical practice using ranibizumab for neovascular AMD are similar to large prospective randomized trials.
Publisher: Oxford University Press (OUP)
Date: 10-06-2011
DOI: 10.1093/HMG/DDR270
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2007
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-07-2016
Abstract: To determine whether longitudinal changes in mesopic visual function on microperimetry occurred independent of its associations with microstructural parameters on spectral-domain optical coherence tomography (SD-OCT) in the early stages of AMD. Forty-one AMD eyes underwent microperimetry testing and SD-OCT scans over a 12-month period at 6-month intervals. Microstructural parameters analyzed include the retinal pigment epithelium-drusen complex (RPEDC) layer thickness, number of hyperreflective foci (HF) and their inner retinal migration (represented by a weighted axial distribution score AxD), and the number of atrophic areas. Microperimetric sensitivity was 0.29 dB (95% confidence interval [CI] = -0.38 to -0.20 dB, P < 0.001) and 0.13 dB (95% CI = -0.22 to -0.03 dB, P = 0.008) lower in each sector for every 10-μm higher RPEDC layer thickness and 1-HF present, but was not associated with the AxD score or the number of atrophic areas present (P ≤ 0.464). However, each 10-μm greater RPEDC layer thickness and 1-HF present was not independently associated with a further decline in sensitivity (-0.08 dB/year, 95% CI = -0.24 to 0.07 dB/year, P = 0.288 and 0.09 dB/year, 95% CI = -0.06 to 0.24 dB/year, P = 0.242, respectively) over time when accounting for the association between RPEDC layer thickness and number of HF with microperimetric sensitivity. Longitudinal changes in mesopic visual function measured on microperimetry paralleled changes in the microstructural changes over a 12-month time frame, without any changes occurring independent of the associations between structure and function alone.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-02-2015
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 31-03-2015
Abstract: To examine the influence of reticular pseudodrusen (RPD) on retinal and visual function in intermediate AMD using multifocal electroretinography (mfERG) and microperimetry. In a prospective cross-sectional study, microperimetry and mfERG testing, followed by color fundus photography, near-infrared reflectance imaging and spectral-domain optical coherence tomography (SD-OCT) scans were performed in 120 eyes from 60 participants with bilateral intermediate AMD. The number of subfields with pigmentary changes and RPD within the central 3-mm diameter of the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and drusen cube root volume within the central 3-mm diameter was determined. The influence of these pathological features on microperimetry and mfERG in this region were examined. Microperimetric sensitivity was not significantly associated with the presence and extent of RPD (P = 0.068), but with drusen volume and extent of pigmentary changes (P < 0.001 for both). However, the presence and extent of RPD was independently and significantly associated with mfERG implicit time, along with drusen volume and the extent of pigmentary changes (P ≤ 0.023). The mfERG response litude was not significantly associated with the presence and extent of RPD (P = 0.130). The presence and extent of RPD was associated with functional changes on mfERG implicit time, but not mfERG response litude or microperimetry. These findings suggest that the presence of RPD in eyes with intermediate AMD has a significant influence on cone-mediated neuroretinal function, without a significant influence on mesopic visual function as determined on microperimetry.
Publisher: Wiley
Date: 29-05-2018
DOI: 10.1111/CEO.13317
Publisher: Elsevier BV
Date: 12-2023
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.AJO.2017.05.016
Abstract: To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD. Systematic review and meta-analysis. Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015. Reference lists of published articles were hand searched and study authors were contacted to provide additional data. Those in the lowest category of activity in each study were compared with all other participants to assess the association between physical activity and both early and late AMD using random-effects meta-analysis. Nine studies (subject age range 30-97 years) were included in the meta-analysis. Physical activity was found to have a protective association with both early AMD (8 studies, n = 38 112, odds ratio (OR) 0.92, 95% confidence interval [CI] 0.86-0.98) and late AMD (7 studies, n = 28 854, OR 0.59, 95% CI 0.49-0.72). Physical activity is associated with lower odds of early and late AMD in white populations. These findings have important implications, reinforcing the public health message of staying active throughout life. However, further longitudinal studies are required to confirm and further characterize a protective effect of physical activity on the onset and/or progression of AMD.
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Informa UK Limited
Date: 07-2001
DOI: 10.1111/J.1444-0938.2001.TB05023.X
Abstract: AIM: To review the genetics of age-related macular degeneration (AMD). The pathogenesis of AMD, the leading cause of severe visual disability and blindness in our community, remains unknown. However, AMD is regarded as a genetic disease where family history of AMD is a significant risk factor for the disease. Understanding the genetic factors associated with AMD offers the greatest chance for understanding the underlying disease processes. METHODS: Through a review of the literature and the use of original research findings, the current knowledge of the genetics of AMD is explored. CONCLUSION: AMD is increasing in prevalence and remains a major challenge for eye heath providers. Finding the genes that are associated with AMD offers the greatest chance for the development of preventative strategies and treatments.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2020
DOI: 10.1038/S41598-020-69164-Y
Abstract: Macular Telangiectasia type 2 (MacTel) is an uncommon bilateral retinal disease, in which glial cell and photoreceptor degeneration leads to central vision loss. The causative disease mechanism is largely unknown, and no treatment is currently available. A previous study found variants in genes associated with glycine–serine metabolism ( PSPH , PHGDH and CPS1 ) to be associated with MacTel, and showed low levels of glycine and serine in the serum of MacTel patients. Recently, a causative role of deoxysphingolipids in MacTel disease has been established. However, little is known about possible other metabolic dysregulation. Here we used a global metabolomics platform in a case–control study to comprehensively profile serum from 60 MacTel patients and 58 controls. Analysis of the data, using innovative computational approaches, revealed a detailed, disease-associated metabolic profile with broad changes in multiple metabolic pathways. This included alterations in the levels of several metabolites that are directly or indirectly linked to glycine–serine metabolism, further validating our previous genetic findings. We also found changes unrelated to PSPH, PHGDH and CPS1 activity. Most pronounced, levels of several lipid groups were altered, with increased phosphatidylethanolamines being the most affected lipid group. Assessing correlations between different metabolites across our s les revealed putative functional connections. Correlations between phosphatidylethanolamines and sphingomyelin, and glycine–serine and sphingomyelin, observed in controls, were reduced in MacTel patients, suggesting metabolic re-wiring of sphingomyelin metabolism in MacTel patients. Our findings provide novel insights into metabolic changes associated with MacTel and implicate altered lipid metabolism as a contributor to this retinal neurodegenerative disease.
Publisher: Wiley
Date: 27-11-2003
DOI: 10.1046/J.1442-9071.2003.00714.X
Abstract: To review the 12-month results of the first 136 eyes treated with photodynamic therapy (PDT) with verteporfin at a single institution, and to determine if this treatment when used in the broader community could reproduce the results achieved in the Treatment of Age-related Macular Degeneration (AMD) with PDT (TAP) study. A record of all patients who first received PDT with verteporfin at The Royal Victorian Eye and Ear Hospital between the time of its introduction in February 2000 and February 2001 was prospectively maintained. The medical charts of these cases were reviewed and fluorescein angiograms were graded. Eyes with AMD were classified into three groups: TAP comparable if they had predominantly classic subfoveal choroidal neovascularization (CNV) and visual acuity between 6/12 and 6/60 VIP comparable if they had occult but no classic subfoveal CNV and visual acuity better than 6/36 and PDT ineligible if they fell outside recommended eligibility guidelines of the TAP/VIP studies. The main outcome measure was visual acuity change, with total number of treatments a secondary outcome variable. A total of 136 eyes of 130 patients began PDT during this period. The baseline angiogram and clinical data were available for 123 eyes (90%), and these were reviewed. Fourteen eyes had non-AMD related CNV, while 109 eyes of 105 patients had AMD. Of the 109 AMD related lesions, 72 (66%) were TAP comparable, six (5.5%) were VIP comparable and 31 (28%) were PDT ineligible. At the 12-month visit the proportion of TAP comparable eyes with same or better vision was 36/72 (50%), compared to 13/31 (42%) of the PDT ineligible eyes (P = 0.45). Only 30/72 (42%) of the TAP comparable eyes were still undergoing regular angiographic and clinical assessment (similar to the TAP protocol) at the time of the 12 month visit. The number of these who had same or better vision at 12 months was 17/30 (57%) compared to 19/42 (44%) TAP comparable eyes without regular angiographic follow up to 12 months (P = 0.37). CONCLUSDIONS When used according to the guidelines established by the TAP study, the visual acuity results with PDT approached those achieved in the TAP study. When eyes were either enrolled outside the TAP study eligibility guidelines, or were not actively followed up over the 12-month period as per TAP study guidelines, the visual outcome was similar to natural history of CNV secondary to AMD.
Publisher: BMJ
Date: 23-09-2015
DOI: 10.1136/BJOPHTHALMOL-2014-305514
Abstract: To describe outcomes of eyes with wet age-related macular degeneration (AMD) sub ided by lesion activity in a large multicentre cohort study. Treatment-naive eyes with subfoveal choroidal neovascularisation receiving antivascular endothelial growth factor therapy enrolled in the Fight Retinal Blindness observational study were included. Lesions were graded at each visit as active if there was intraretinal or subretinal fluid attributable to leak from choroidal neovascularisation lesion or fresh haemorrhage. Eyes were ided into four groups based on the proportion of visits, each eye was graded as active during the first 12 months of treatment (persistent, high, moderate and low activity). 655 eyes were included. Similar mean visual acuity changes compared with baseline were observed in all four groups at 12 months (+6.8, +8.3, +6.2 and +5.5 letters for the low, moderate, high and persistent groups, respectively p<0.001 for each group). The mean number of injections given increased only modestly in groups with more active lesions (7.6, 7.9, 8.4 and 8.3, respectively, p=0.015). Occult and minimally classic lesions were more frequent in the more active groups (p=0.024). Persistent activity of neovascular lesions during 12 months after starting intravitreal therapy was not associated with worse visual outcomes in this observational study of AMD.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-01-2012
DOI: 10.1167/IOVS.11-7689
Abstract: To examine whether baseline retinal vascular caliber predicts visual response to intravitreal ranibizumab injections in patients with neovascular age-related macular degeneration (AMD). In this prospective cohort study, patients with neovascular AMD received three monthly intravitreal injections of ranibizumab, followed by as needed dosing up to 1 year. Retinal vascular caliber was measured from digital fundus photographs at baseline and summarized as central retinal artery equivalent (CRAE) and venular equivalent (CRVE), representing average caliber of arterioles and venules, respectively. Visual outcome at 12 months was assessed and the relation to baseline retinal vascular caliber was determined. A total of 88 eyes were analyzed at baseline. After accounting for age, sex, size of choroidal neovascularization, and number of injections, patients who deteriorated in visual acuity at 12 months had significantly larger baseline CRVE, 243.10 μm (95% confidence interval [CI], 227.01-259.19), compared with those who were stable, 214.30 μm (95% CI, 205.79-222.81) and those who improved, 215.26 μm (95% CI, 204.69-225.84 P = 0.007). Baseline CRAE did not differ significantly from eyes whose vision deteriorated, 150.12 μm (95% CI, 140.67-159.57), compared with those remaining stable, 143.64 μm (95% CI, 138.64-148.63), or gaining vision 142.92 μm (95% CI, 136.71-149.13 P = 0.69). In eyes with neovascular AMD treated with intravitreal ranibizumab, larger baseline retinal venular caliber was significantly associated with a poorer response to treatment, possibly reflecting increased disease severity.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 2008
DOI: 10.1167/IOVS.06-1048
Abstract: A cathode-ray-tube (CRT) monitor-based technique was used to isolate clinically significant components of dark adaptation. The utility of the technique in identifying adaptation abnormalities in eyes with age-related maculopathy (ARM) is described. A CRT dark adaptometer was developed to assess cone and rod recovery after photopigment bleach. The following measures were obtained: cone recovery rate (R(c) in decades per minute) and absolute threshold (Tf(c) log candelas per square meter), rod recovery rate (R(r) decades per minute), and rod-cone transition (rod-cone break [RCB], in minutes). These components were isolated by appropriately selecting stimulus size, stimulus location, pigment bleach, and test duration and by coupling the CRT with judiciously selected neutral-density (ND) filters. The protocol was developed by using 5 young observers and was tested on 27 subjects with ARM in the study eye and 22 age-matched control subjects. The parameters necessary for effective isolation of cone and early phase rod dark adaptation were a 2.6 ND filter (for a standard CRT monitor, 0.08-80 cd . m(-2) luminance output) a 4 degrees foveated, 200-ms, achromatic spot approximately 30% pigment bleaching and a 30-minute test duration. These settings returned obvious rod and cone recovery curves in control and ARM eyes that were compatible with conventional test methods and identified 93% of participants with ARM as having delayed dynamics in at least one of the parameters. Cone recovery dynamics were significantly slower in the ARM group when compared with age-matched control subjects (R(c), 0.99 +/- 0.35 vs. 2.63 +/- 0.61 decades . min(-1), P < 0.0001). Three of the 27 eyes with ARM did not achieve RCB during the allowed duration (30 minutes). The remaining eyes with ARM (n = 24) exhibited a significant delay in rod recovery (R(r)(,) ARM, 0.16 +/- 0.03 vs. controls, 0.22 +/- 0.02 decades . min(-1), P < 0.0001) and the average time to RCB (+/-SD) in the ARM group was significantly longer than in the control subjects (19.12 +/- 5.17 minutes vs. 10.40 +/- 2.49 minutes, P < 0.0001). The CRT dark-adaptation technique described in this article is an effective test for identifying abnormalities in cone and rod recovery. Slowed cone and rod recovery and a delayed RCB were evident in the eyes with ARM. The test method is potentially useful for clinical intervention trials in which ARM progression is monitored.
Publisher: Oxford University Press (OUP)
Date: 18-01-2008
DOI: 10.1093/HMG/DDN018
Abstract: A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 in iduals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and in iduals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07-5.49] as was smoking (OR 2.28, 95% CI 1.26-4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1-65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment-interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.
Publisher: Public Library of Science (PLoS)
Date: 31-12-2013
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2017
Publisher: Elsevier BV
Date: 02-2002
DOI: 10.1016/S0042-6989(01)00232-2
Abstract: We used the chemical mutagen, N-ethyl-N-nitrosourea, to induce random point mutations in the germline of the mouse strain C57BL/6 in order to generate models of retinal diseases. 1163 mutagenised first generation mice produced using this approach were examined for eye abnormalities. Approximately one-third (412) presented with some form of ocular abnormality. Most changes were unilateral and confined to the anterior segment of the eye. Less than 10% (44) of identified changes affected the posterior segment of the eye. 21 mice with varying ocular abnormalities, including 17 with retinal changes, were bred to produce second generation mice to confirm genetic inheritance. Genetic inheritance was confirmed in several of these lines including three with retinal changes.
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.OPHTHA.2014.01.025
Abstract: To determine the relationship between structural parameters of the outer retina on spectral-domain optical coherence tomography (SD-OCT) and microperimetric retinal sensitivity in early stages of age-related macular degeneration (AMD). Prospective, observational study. Seventy-five eyes of 75 participants with early stages of AMD (drusen ≥ 125 μm, with/without pigmentary abnormalities) and 25 control participants of a similar age. Participants underwent microperimetry testing and high-resolution SD-OCT scans. Structural parameters at 5 central points (0°, 1°, and 2.33° nasal and temporal to the fovea along the horizontal axis) corresponding to areas tested by microperimetry were compared. Structural parameters included outer segment (OS) length, thickness and elevation of the retinal pigment epithelium (RPE) band, grading of the inner-segment ellipsoid (ISe) band integrity, and presence of hyperreflective foci (HF). Relationship between structural parameters and retinal sensitivity. Retinal sensitivity was significantly correlated with RPE elevation (P<0.001), ISe grading (P<0.001), and presence of HF (P ≤ 0.018) at all test points, but not with OS length (P ≥ 0.093) or RPE thickness (P ≥ 0.125). However, multiple linear regression analyses revealed that only ISe grading (P ≤ 0.011) and RPE elevation (P ≤ 0.030) remained significantly associated with retinal sensitivity at all points. By using a simple linear model incorporating ISe grading and RPE elevation to predict values of retinal sensitivity, the 95% limits of agreement between the predicted and the actual value was ± 3.83 dB. The integrity of the ISe band and drusen-associated RPE elevation are significant independent predictors of microperimetric retinal sensitivity. Our findings imply that these 2 structural parameters may be surrogate markers of retinal function in the early stages of AMD.
Publisher: American Medical Association (AMA)
Date: 05-1997
DOI: 10.1001/ARCHOPHT.1997.01100150597004
Abstract: To verify that a few laser lesions in the posterior pole can cause drusen to resolve in patients with age-related macular degeneration, and to document central retinal sensitivity as drusen resolve. In a pilot study, 12 patients considered to be at high risk for sight-threatening complications from age-related macular degeneration were treated with 12 argon laser lesions in the posterior pole, with review for 12 to 24 months. Choroidal neovascularization developed in 1 patient 8 months after treatment, with consequent loss of central vision. In 9 of the remaining 11 patients, high-risk characteristics of drusen were reduced. Four patients had retinal pigment epithelial depigmentation, and all maintained 20/40 visual acuity at 12 months. One patient lost 3 lines of vision due to geographic atrophy after 12 months. Scotopic retinal threshold was elevated before treatment in 8 patients, compared with an age-matched comparison group. Of these, 4 patients underwent retesting 3 to 6 months after treatment, and all had improved thresholds, but only 1 patient sustained the improvement at 12 months. At 12 months, 3 of the 8 patients showed an improvement in their mean retinal threshold. Of those in whom the mean retinal threshold worsened, the mean elevation in threshold was not more than 0.6 log units. A few laser lesions in the posterior pole leads to resolution of drusen. There does not appear to be an increased risk for choroidal neovascularization. Retinal threshold measurements show no indication of geographic atrophy at 1 year, but cannot be excluded as a late outcome. Laser treatment may reduce the risk for profound sight-threatening lesions in age-related macular degeneration.
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.SURVOPHTHAL.2006.08.003
Abstract: In most of the Western world, age-related macular degeneration (AMD) remains the largest single cause of severe visual impairment, and its prevalence continues to increase. It is considered to be a complex disease, in which multiple genes and environment play a role in pathogenesis. Several environmental insults are implicated with smoking, serum cholesterol, hypertension, sunlight exposure, and many other factors being variously associated with disease pathogenesis. Until recently, there have been relatively few breakthroughs to further our understanding of the genetics of AMD, despite remarkable progress in molecular genetic techniques over the last 20 years, and the fact that many rare inherited macular diseases have had their causative genes mapped. Development of new tools such as high-density single-nucleotide polymorphism chips and microarrays have changed the face of genetic research, but have yet to directly translate into improved clinical outcomes in ophthalmology. However with the recent finding of the Tyr402His polymorphism in the complement factor H gene being implicated in AMD, we are about to witness a new wave of research in this disease. Not only does the identification of a biologically plausible gene identify a new pathway, but it also identifies new biological mechanisms for disease, avenues to pursue treatment, and a better understanding of how the environment interacts with the genetic background to create disease. This article aims to review the process of gene discovery in complex disease, why the search for genes remains difficult, how to translate laboratory findings to a clinical setting, and how these findings will impact on disease treatment and public health issues.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-06-2011
DOI: 10.1167/IOVS.10-7120
Abstract: Age-related macular degeneration (AMD) can be considered as a chronic low-grade systemic inflammatory disease. This study was undertaken to test the associations of AMD with the urinary proinflammatory cytokines transforming growth factor (TGF)-β1, macrophage chemoattractant protein (MCP)-1 and C3a-desArg, as potential noninvasive biomarkers for monitoring AMD. A cross-sectional study of 103 AMD cases, comprising early AMD (n = 51), geographic atrophy (GA n = 19), or choroidal neovascularization (CNV 33), and 54 unrelated controls, aged 73 ± 9 years, who attended the Royal Victorian Eye and Ear Hospital and private practice in Victoria, Australia. AMD status was determined from the bilateral retinal digital photographs and through angiography and optical coherence tomography images when confirmation of CNV was needed. Serum and urine cytokine levels were measured by immunoassay and the rs1061170 (Y402H) single-nucleotide polymorphism of the complement factor H (CFH) gene was determined. Multivariate logistic regression analyses demonstrated significant associations of urinary TGF-β1 levels (odds ratio [95% confidence interval]: OR = 1.24 [1.02-1.50] P < 0.031) and MCP-1 levels (OR = 1.07 [1.02-1.12] P < 0.008), in early AMD, and also MCP-1 levels with GA (OR = 1.10 [1.03-1.17] P < 0.003). There was no correlation between urinary and serum cytokine levels. In iduals with one or more copies of the C allele (Y402H) were 2.5 times more likely to have urinary MCP-1 above median levels (P < 0.040). This study demonstrates a novel finding of an association between elevated urinary cytokines TGF-β1 and MCP-1 and AMD. Further development of a urinary biomarker profile could provide a practical tool for detection of early AMD, progression monitoring, and assessment of treatment efficacy.
Publisher: Wiley
Date: 03-2004
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2016
Publisher: Springer Science and Business Media LLC
Date: 18-04-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2016
Publisher: Elsevier BV
Date: 03-2201
DOI: 10.1016/J.OPHTHA.2013.09.050
Abstract: To compare outcomes of intravitreal therapy from an observational study cohort with those of participants receiving treatment in the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab (MARINA) for the treatment of neovascular age-related macular degeneration (wet AMD). Database observational study. Participants in the observational cohort were chosen to match demographic features and entry criteria of the treatment group from MARINA. Outcomes over 12 months were compared. Eight hundred twenty-one anti-vascular endothelial growth factor (anti-VEGF)-naïve eyes treated with ranibizumab with 12 months or more of follow-up were included in the total Fight Retinal Blindness! (FRB-All) cohort, whereas a subset of this cohort of 401 eyes who were matched to the MARINA treatment group were included as the FRB-MARINA cohort. Intravitreal ranibizumab therapy of 0.5 mg for wet AMD. Visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters and treatments given were recorded continuously and anonymously in an electronic database for 12 months. Locally weighted scatterplot smoothing (LOESS) regression was used to plot change in visual acuity data over the course of 12 months for both the FRB-All cohort and the FRB-MARINA cohort, whereas results from the MARINA trial were taken from the published study report. Change in VA in logMAR letters over 12 months, treatment, and visit intensity. Mean visual acuity improvement after 12 months in FRB-MARINA (+5.5 letters) was similar to that of the 0.5-mg group from MARINA (+7.2 letters). Improvement in FRB-ALL was slightly less (+4.9 letters). Mean treatment effect compared with the MARINA control group was similar for the MARINA treated group (+17.6 letters) and the FRB-MARINA cohort (+15.9 letters). A mean of 7.3 injections in 12 months was received by the observational cohorts. Similarity of mean VA improvement in the matched observational cohort with that of the phase 3 clinical trial suggests that these results can be achieved in real-world clinical practice with a modified treatment regimen.
Publisher: Wiley
Date: 04-2006
DOI: 10.1111/J.1442-9071.2006.01208.X
Abstract: Female monozygotic twins aged 54 years discordant for myopia are reported. One twin presented with bilateral high myopia (right eye = -6.00/+0.50 x 5 degrees , left eye = -6.00/+0.50 x 45 degrees ) and her identical twin had no significant refractive error (right eye = -0.50 lano, left eye = -0.50/+0.75 x 40 degrees ). An explanation for the striking refractive discordance seen in this case report is yet to be determined.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.OPHTHA.2015.02.009
Abstract: To report 24-month outcomes of anti-vascular endothelial growth factor (VEGF) therapy for treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) using a treat and extend treatment regimen in routine clinical practice. Database observational study. We included treatment-naïve eyes receiving predominantly ranibizumab for nAMD in routine clinical practice treated using a treat and extend regimen that were tracked in the Fight Retinal Blindness observational registry. A cohort of eyes treated by practitioners using exclusively a treat and extend regimen was extracted from the Fight Retinal Blindness observational registry. Change in visual acuity (VA) over 2 years and number of injections and visits. Data from 1198 eyes from 1011 patients receiving anti-VEGF therapy using a treat and extend regimen for treatment-naïve nAMD between January 2007 and December 2012 and with 24-month follow-up were included in the analysis. Mean VA increased by +5.3 logarithm of the minimum angle of resolution letters from 56.5 letters (20/80+1) at initial visit to 61.8 (20/60+2) letters at 24 months. Mean VA gains improved and number of injections increased with successive years from +2.7 letters for eyes commencing in 2007 after a mean of 9.7 injections in 2 years, to +7.8 letters for eyes commencing in 2012 after a mean of 14.2 injections over 2 years. The proportion of eyes with VA >20/40 increased from 27% when starting treatment to 45% after 24 months the proportion with vision of <20/200 remained unchanged (13% initial, 11% at 24 months). Of the included eyes, 90.5% avoided a vision loss of ≥15 letters. There was an overall mean of 13.0 injections over the 24 months, 7.5 injections in the first year and 5.5 in the second year, with a mean of 14.8 clinic visits. These data indicate that eyes managed in routine clinical practice with a treat and extend regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.
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: Wiley
Date: 04-2014
DOI: 10.1111/AOR.12287
Abstract: Retinitis pigmentosa affects over 1.5 million people worldwide and is a leading cause of vision loss and blindness. While retinal prostheses have shown some success in restoring basic levels of vision, only generic, "one-size-fits-all" devices are currently being implanted. In this study, we used optical coherence tomography scans of the degenerated retina from 88 patients with retinitis pigmentosa to generate models of retinal thickness and curvature for the design of customized implants. We found the average retinal thickness at the fovea to be 152.9 ± 61.3 μm, increasing to a maximum retinal thickness of 250.9 ± 57.5 μm at a nasal eccentricity of 5°. These measures could be used to assist the development of custom-made penetrating electrodes to enhance and optimize epiretinal prostheses. From the retinal thickness measurements, we determined that the optimal length of penetrating electrodes to selectively stimulate retinal ganglion cell bodies and interneuron axons in the ganglion cell layer should be 30-100 μm, and to preferentially stimulate interneurons in the inner nuclear layer, electrodes should be 100-200 μm long. Electrodes greater than 200 μm long had the potential to penetrate through the retina into the choroid, which could cause devastating complications to the eye and should be avoided. The two- and three-dimensional models of retinal thickness developed in this study can be used to design patient-specific epiretinal implants that will help with safety and to optimize the efficacy of neuronal stimulation, ensuring the best functional performance of the device for patients.
Location: Spain
Location: Australia
No related grants have been discovered for Robyn Guymer.