ORCID Profile
0000-0002-5778-6310
Current Organisations
Lions Eye Institute
,
University of Western Australia
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Publisher: Wiley
Date: 23-04-2020
DOI: 10.1002/MGG3.1259
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-06-2020
DOI: 10.1167/TVST.9.7.19
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-12-2018
Abstract: To compare the phenotype of blue cone monochromacy (BCM) caused by large deletion mutations with those having the C203R missense mutation. BCM patients with large deletion mutations (n = 21 age range, 5-60 years), and with the C203R missense mutation (n = 13 age range, 5-70 years), were studied with optical coherence tomography, visual acuity, and perimetric sensitivity in a retrospective observational case series. Perceptual estimates of spatial resolution driven by rods, S-cones, and L/M-cones were obtained by the choice of chromatic gratings presented on varied adapting conditions with a modified microperimeter. Both genotypes had abnormal foveal photoreceptor structure early in life. Patients with the C203R mutation, however, had decades-longer persistence of foveal photoreceptor outer nuclear layer thickness and a slower rate of development of inner segment/outer segment defects than did patients with large deletion mutations. At late ages, both genotypes had comparably severe losses of central structure. At the rod-rich hot spot, there was no difference in structure between cohorts with age. Grating acuities in all BCM patients were driven by S-cones and rods the foveal structural differences were not reflected in a difference between cohorts in visual sensitivity and spatial resolution. A difference in structural phenotype due to the C203R mutation versus large deletion mutations in BCM was detected as a more prolonged persistence of foveal photoreceptor structure in patients with the missense mutation. This should be taken into account in planning natural history studies, selecting outcomes for clinical trials, and defining the time window for possible therapies.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 16-05-2017
Abstract: To determine efficacy outcome measures for clinical trials of Leber congenital amaurosis (LCA) associated with a common intronic mutation in the CEP290 gene. CEP290-LCA patients (ages 5-48) with the intronic mutation (c.2991+1655A>G) were studied as a retrospective observational case series using clinical methods and with full-field sensitivity testing (FST), optical coherence tomography (OCT), autofluorescence imaging (NIR-RAFI), transient pupillary light reflex (TPLR), oculomotor control and instability (OCI), a mobility course, and a questionnaire (NEI-VFQ). Patients were investigated cross-sectionally but a subset was able to be followed longitudinally. With FST, there was no rod function cone sensitivities had a wide range from not detectable to near normal. OCT analyses indicated retained central photoreceptors with abnormal distal laminae. Based on OCT and FST, most patients had dissociation of structure and function. TPLR was nondetectable in the majority of patients, with responders demonstrating severe losses in light sensitivity. OCI was abnormal in most patients. NEI-VFQ scores had a similar range to those of other severe retinopathies. Mobility scores were consistent with FST sensitivities. In patients examined with FST, OCT, and NIR-RAFI over long-term intervals (7-10 years), there was limited but detectable disease progression. Efficacy would be a quantitative change in foveal cone function and possibly distal laminar structure. FST provides a subjective photoreceptor-based outcome OCT and NIR-RAFI can assess photoreceptor and RPE structure. TPLR and OCI can provide objective measures of postretinal transmission. Minimal change over a decade indicates that there is no practical value in natural history studies.
Publisher: Oxford University Press (OUP)
Date: 25-10-2016
DOI: 10.1093/HMG/DDW361
Publisher: Public Library of Science (PLoS)
Date: 12-09-2013
Publisher: Springer Science and Business Media LLC
Date: 17-12-2018
DOI: 10.1038/S41591-018-0295-0
Abstract: Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) with intravitreal injections of an antisense oligonucleotide to restore correct splicing. There were no serious adverse events, and vision improved at 3 months. The visual acuity of one exceptional responder improved from light perception to 20/400.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Springer Science and Business Media LLC
Date: 27-03-2023
DOI: 10.1186/S12883-023-03149-Y
Abstract: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines. The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target s le is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention. The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated. The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.
Publisher: Wiley
Date: 13-06-2022
DOI: 10.1111/CEO.14120
Abstract: To investigate the relationship between dietary intake of niacin (water‐soluble form of vitamin B 3 ) and retinal nerve fibre layer (RNFL) thickness in healthy eyes. This cross‐sectional study examined the association between daily niacin intake and RNFL thickness in three large population‐based cohorts with varied age differences. RNFL thickness was extracted from optical coherence tomography data energy‐adjusted niacin intake was estimated from food frequency questionnaires. Linear mixed‐effects models were utilised to examine the association between RNFL thickness and energy‐adjusted niacin intake. Three separate analyses were conducted, with niacin treated as a continuous, a categorical (quartiles) or a dichotomous (above/below Australian recommended daily intake) variable. In total, 4937 subjects were included in the study [Raine Study Gen2, n = 1204, median age 20 Busselton Healthy Ageing Study (BHAS), n = 1791, median age 64 TwinsUK, n = 1942, median age 64). When analysed as a continuous variable, there was no association between RNFL thickness and niacin intake in any of the three cohorts (95% CI β: Raine Study Gen 2, −0.174 to 0.074 BHAS, −0.066 to 0.078 TwinsUK −0.435 to 0.350). Similar findings were observed with quartiles of niacin intake and for niacin intakes above or below Australian recommended daily intake levels in all three cohorts. Dietary intake of niacin from a standard diet does not appear to be associated with age‐related RNFL thinning in healthy eyes. Supraphysiological doses of niacin may be required for therapeutic effect in the retina.
Publisher: Wiley
Date: 04-2020
DOI: 10.1111/CEO.13736
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-09-2020
DOI: 10.1167/TVST.9.10.9
Publisher: Informa UK Limited
Date: 27-09-2021
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.AJO.2017.02.003
Abstract: To determine outcome measures for a clinical trial of Leber congenital amaurosis (LCA) associated with mutations in the GUCY2D gene. Retrospective observational case series. Twenty-eight patients with GUCY2D-LCA (aged 2-59 years) were studied clinically and with chromatic full-field sensitivity testing (FST), optical coherence tomography (OCT), pupillometry, and the NEI Visual Function Questionnaire (VFQ). FST permitted quantitation of cone and rod sensitivity in these patients with severe visual impairment. For most patients, the degree of rod and cone sensitivity losses showed a relationship, thereby providing an opportunity to ide patients into cohorts by severity of rod and cone dysfunction. OCT analyses indicated that retinal structure could be used not only as an objective safety measure but also as an exploratory efficacy outcome. A foveal bulge was not present in 67% of patients. The intensity of inner segment/outer segment (ellipsoid zone line) reflectivity was reduced significantly at the fovea and in the rod-dense superior retina. Based on OCT and FST parameters, most patients had dissociation of structure and function. Abnormal pupillometry sensitivity in the majority of GUCY2D-LCA patients provided another objective efficacy outcome. NEI VFQ scores showed a similar range of findings to those of other severe retinal diseases. Conventional outcome measures, such as visual acuity and the NEI VFQ, will need to be complemented by methods more specific to this GUCY2D-LCA population. Any therapeutic strategy should determine if there is an effect on rod as well as cone function and structure. FST provides a photoreceptor-based subjective outcome and OCT in 2 retinal regions, fovea and superior retina, can assess photoreceptor structure. A change in the relationship of structure and function away from baseline becomes evidence of efficacy.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.PHARMTHERA.2017.02.009
Abstract: The retina is an easily accessible out-pouching of the central nervous system (CNS) and thus lends itself to being a biomarker of the brain. More specifically, the presence of neuronal, vascular and blood-neural barrier parallels in the eye and brain coupled with fast and inexpensive methods to quantify retinal changes make ocular biomarkers an attractive option. This includes its utility as a biomarker for a number of cerebrovascular diseases as well as a drug pharmacology and safety biomarker for the CNS. It is a rapidly emerging field, with some areas well established, such as stroke risk and multiple sclerosis, whereas others are still in development (Alzheimer's, Parkinson's, psychological disease and cortical diabetic dysfunction). The current applications and future potential of retinal biomarkers, including potential ways to improve their sensitivity and specificity are discussed. This review summarises the existing literature and provides a perspective on the strength of current retinal biomarkers and their future potential.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/5801826
Abstract: Objective . To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods . Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results . Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions . Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings.
Publisher: Public Library of Science (PLoS)
Date: 12-05-2021
DOI: 10.1371/JOURNAL.PGEN.1009497
Abstract: Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 17-11-2011
DOI: 10.1167/IOVS.11-7602
Abstract: To investigate the effect of old age (3 vs. 18 months) on the retinal function of albino (Sprague-Dawley [SD]) and pigmented (Long-Evans [LE]) rats. Electroretinograms (ERG) were recorded in both albino (SD 3 months old n = 16, 18 months old n = 16) and pigmented (LE 3 months n = 16, 18 months n = 5) rats. Data are analyzed for photoreceptor, ON-bipolar, and retinal ganglion cell (RCG) litudes as well as photoreceptor and ON-bipolar cell sensitivities. In the pigmented strain, senescence results in decreased photoreceptor output, but ON-bipolar and retinal ganglion cell litudes were preserved, due to a relative increase in ON-bipolar cell sensitivity. In the albino rats, although ageing decreased both photoreceptor and ON-bipolar cell litudes, increased photoreceptor sensitivity produced a relative sparing of retinal ganglion cell litude. Both strains show evidence of retinal plasticity with senescence, albeit at different retinal levels. The exact mechanisms underlying sensitivity changes require further investigation. Nevertheless, given the findings of previous human studies, pigmented rats appear to be a more appropriate model for human ageing. Future work using animals to study the effect of ageing need careful consideration in strain selection.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 12-09-2018
Abstract: To determine the progression rate and the variability of rod and cone sensitivities in patients with X-linked retinitis pigmentosa (XLRP) caused by mutations in ORF15-RPGR. ORF15-RPGR-XLRP patients (n = 15) were studied prospectively over 2 years with static perimetry s ling the visual field under dark-adapted and light-adapted conditions on a 12° square grid covering 168° width and 84° height. Natural history of rod and cone sensitivity loss and test-retest variability were estimated. Data were analyzed pointwise as well as averaged across small regions of neighboring loci of approximately 80 mm2 (900 deg2) in size representing the likely extent of localized gene therapy injections. Retinal loci with mild to moderate loss of sensitivity tended to be in the mid- to far-peripheral retina in most patients. When averaged across small regions, dark-adapted rod vision progressed at an average of 2 dB per year with a coefficient of repeatability (CR) of 6.3 dB, and light-adapted cone vision with white stimulus progressed at an average of 0.9 dB per year with a CR of 3.8 dB. For an average patient enrolled in an early-phase clinical trial, significant (α = 0.05) progression would be predicted to occur with 80% power in 4.5 years for rod vision and 6.1 years for cone vision. Localization of regions in the temporal hemifield and grouping of results from multiple patients would permit trial designs of shorter duration. Measurement of rod sensitivity under dark-adapted conditions averaged across a small region showed the greatest potential for detectability of progression in the shortest period.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-033440
Abstract: Eye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989–1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes. Participants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters. The Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences. ACTRN12617001599369 Active, not recruiting.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 16-06-2016
Publisher: Informa UK Limited
Date: 23-08-2022
DOI: 10.1080/08164622.2022.2111201
Abstract: Deep learning (DL) represents a paradigm-shifting, burgeoning field of research with emerging clinical applications in optometry. Unlike traditional programming, which relies on human-set specific rules, DL works by exposing the algorithm to a large amount of annotated data and allowing the software to develop its own set of rules (i.e. learn) by adjusting the parameters inside the model (network) during a training process in order to complete the task on its own. One major limitation of traditional programming is that, with complex tasks, it may require an extensive set of rules to accurately complete the assignment. Additionally, traditional programming can be susceptible to human bias from programmer experience. With the dramatic increase in the amount and the complexity of clinical data, DL has been utilised to automate data analysis and thus to assist clinicians in patient management. This review will present the latest advances in DL, for managing posterior eye diseases as well as DL-based solutions for patients with vision loss.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.AJO.2018.06.017
Abstract: To determine the change in vision and retinal structure in patients with the common c.2299delG mutation in the USH2A gene in anticipation of clinical trials of therapy. Retrospective observational case series. Eighteen patients, homozygotes or compound heterozygotes with the c.2299delG mutation in USH2A, were studied with regard to visual acuity, kinetic perimetry, dark- and light-adapted static perimetry, optical coherence tomography (OCT), and autofluorescence (AF) imaging. Serial data were available for at least half of the patients, depending on the parameter analyzed. The kinetics of disease progression in this specific molecular form of USH2A differed between the measured parameters. Visual acuity could remain normal for decades. Kinetic and light-adapted static perimetry across the entire visual field had similar rates of decline that were slower than those of rod-based perimetry. Horizontal OCT scans through the macula showed that inner segment/outer segment line width had a similar rate of constriction as co-localized AF imaging and cone-based light-adapted sensitivity extent. The rate of constriction of rod-based sensitivity extent across this same region was twice as rapid as that of cones. In patients with the c.2299delG mutation in USH2A, rod photoreceptors are the cells that express disease early and more aggressively than cones. Rod-based vision measurements in central or extracentral-peripheral retinal regions warrant monitoring in order to complete a clinical trial in a timely manner.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2020
DOI: 10.1038/S41598-020-73339-Y
Abstract: Stargardt disease is one of the most common forms of inherited retinal disease and leads to permanent vision loss. A diagnostic feature of the disease is retinal flecks, which appear hyperautofluorescent in fundus autofluorescence (FAF) imaging. The size and number of these flecks increase with disease progression. Manual segmentation of flecks allows monitoring of disease, but is time-consuming. Herein, we have developed and validated a deep learning approach for segmenting these Stargardt flecks (1750 training and 100 validation FAF patches from 37 eyes with Stargardt disease). Testing was done in 10 separate Stargardt FAF images and we observed a good overall agreement between manual and deep learning in both fleck count and fleck area. Longitudinal data were available in both eyes from 6 patients (average total follow-up time 4.2 years), with both manual and deep learning segmentation performed on all (n = 82) images. Both methods detected a similar upward trend in fleck number and area over time. In conclusion, we demonstrated the feasibility of utilizing deep learning to segment and quantify FAF lesions, laying the foundation for future studies using fleck parameters as a trial endpoint.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-2017
Publisher: Elsevier BV
Date: 09-2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 10-03-2021
DOI: 10.1167/TVST.10.3.8
Publisher: Springer Science and Business Media LLC
Date: 07-02-2022
DOI: 10.1007/S00417-022-05570-4
Abstract: To investigate retinal sensitivity changes in eyes with pure cuticular drusen. Multimodal imaging and microperimetry (37-loci grid) data were examined retrospectively to evaluate functional changes in eyes with pure cuticular drusen. Mean sensitivity in the cuticular drusen cohort was compared to age-matched normals. An age- and loci-specific normative reference was created to analyse localised sensitivity deviation. The mean number loci with relative scotoma in the cuticular drusen cohort ( n = 27, mean [SD] age: 48.5 [12.4] years) referenced to normal eyes ( n = 80, 53.5 [14.6] years) was 5.5 (95% confidence interval 3.0 to 8.1). However, mean sensitivity was not statistically different to the age-matched normal cohort (95% CI, − 2.3 to + 3.4 dB). The 37-loci grid was stratified into three rings of the approximately same number of loci, and the percentage of cuticular drusen eyes with pointwise deviation was significantly lower in the inner compared to the middle ring (12.3 [5.3]% vs. 17.3 [5.1]%, p 0.05). Eyes with cuticular drusen demonstrated relative scotoma, but mean sensitivity was not affected. Pointwise sensitivity provides a more robust measure of retinal sensitivity than mean sensitivity in cuticular drusen and should be assessed both in the clinic and in future clinical trials.
Publisher: Informa UK Limited
Date: 13-10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: Informa UK Limited
Date: 02-11-2019
Publisher: Springer Science and Business Media LLC
Date: 08-2022
DOI: 10.1186/S40662-022-00299-X
Abstract: To generate and validate a method to estimate axial length estimated (AL est ) from spherical equivalent (SE) and corneal curvature [keratometry (K)], and to determine if this AL est can replace actual axial length (AL act ) for correcting transverse magnification error in optical coherence tomography angiography (OCTA) images using the Littmann-Bennett formula. Data from 1301 participants of the Raine Study Gen2-20 year follow-up were ided into two datasets to generate (n = 650) and validate (n = 651) a relationship between AL, SE, and K. The developed formula was then applied to a separate dataset of 46 participants with AL, SE, and K measurements and OCTA images to estimate and compare the performance of AL est against AL act in correcting transverse magnification error in OCTA images when measuring the foveal avascular zone area (FAZA). The formula for AL est yielded the equation: AL est = 2.102K − 0.4125SE + 7.268, R 2 = 0.794. There was good agreement between AL est and AL act for both study cohorts. The mean difference [standard deviation (SD)] between FAZA corrected with AL est and AL act was 0.002 (0.015) mm 2 with the 95% limits of agreement (LoA) of − 0.027 to 0.031 mm 2 . In comparison, mean difference (SD) between FAZA uncorrected and corrected with AL act was − 0.005 (0.030) mm 2 , with 95% LoA of − 0.064 to 0.054 mm 2 . AL act is more accurate than AL est and hence should be used preferentially in magnification error correction in the clinical setting. FAZA corrected with AL est is comparable to FAZA corrected with AL act , while FAZA measurements using images corrected with AL est have a greater accuracy than measurements on uncorrected images. Hence, in the absence of AL act , clinicians should use AL est to correct for magnification error as this provides for more accurate measurements of fundus parameters than uncorrected images.
Publisher: MyJove Corporation
Date: 29-06-2016
DOI: 10.3791/54160
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 28-06-2017
Publisher: Elsevier BV
Date: 05-2021
Publisher: Wiley
Date: 26-05-2021
DOI: 10.1111/CEO.13940
Abstract: To describe ocular adverse events and retinal changes during fibroblast growth factor receptor (FGFR) inhibitor (AZD4547) anticancer therapy. This is a sub‐study examining ocular adverse effects from AZD4547 therapy (single‐centre, open‐label, single arm phase II clinical trial). Comprehensive ocular examinations were performed 3 weekly in 24 patients. Macular optical coherence tomography (OCT) scan (30 0 × 25 0 ) was obtained at each visit and OCT parameters [central 1 mm retinal thickness (CRT) and total macular volume in central 6 mm] extracted. OCT scans were sub ided into outer (ELM to RPE) and inner (ELM to ILM) layers to compare outer and inner retinal changes. In 24 patients, AZD4547 was associated with eyelash elongation ( n = 5, 21%) and punctate corneal erosion ( n = 2, 8%). One patient developed clinically significant posterior capsular opacification during the study. OCT data were available in 23 patients, retinal changes ranged from an asymptomatic increased visibility of the interdigitation zone (IDZ) ( n = 10, 43%) to multilobular subretinal fluid pockets ( n = 5, 22%), which was associated with mild visual acuity loss. In a subset of patients ( n = 9) with pre‐AZD4547 dosing OCT baseline, CRT increased by mean ( SD ) of 9 (4) μm in those with IDZ change only compared with 64 (38) μm in those with other retinal changes. Retinal changes tended to be bilateral, self‐limiting and improved over time without medical intervention. The ocular signs and symptoms did not result in dose cessation. Posteriorly, FGFR inhibition leads to outer retinal changes ranging from increased visibility of IDZ to distinct, multiple fluid pockets.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 18-08-2023
DOI: 10.1167/TVST.12.8.14
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.ORET.2022.04.022
Abstract: Toxoplasmic retinochoroiditis is the most common clinical manifestation of an infection with the protozoan parasite, Toxoplasma gondii. Up to 50% of the human population is estimated to be infected with T. gondii however, the epidemiology of toxoplasmic retinochoroiditis has not been widely reported. We sought to estimate the prevalence of toxoplasmic retinochoroiditis in Australia using data that were collected as part of the Busselton Healthy Ageing Study. Cross-sectional, community-based, prospective cohort study. 5020 Australian adults (2264 men and 2756 women age range, 45-69 years, and median age, 58 years). Retinal color photographs, centered on the optic disc and macula, were captured using a digital retinal camera after the dilation of the pupils. Three uveitis-subspecialized ophthalmologists assessed each pigmented retinal lesion, and complete concordance of opinion was required to assign a toxoplasmic etiology. Serum T. gondii immunoglobulin (Ig)G levels were measured for those participants with retinal lesions judged to be toxoplasmic retinochoroiditis. Prevalence of toxoplasmic retinochoroiditis. Eight participants (0.16%) had retinal lesions that were considered to have the characteristic appearance of toxoplasmic retinochoroiditis, plus detectable serum T. gondii IgG, consistent with the diagnosis of toxoplasmic retinochoroiditis. On the assumption that 23.81% of retinal lesions occur at the posterior pole, as reported in a community-based survey conducted in Brazil (Sci Rep. 2021 :3420), the prevalence of toxoplasmic retinochoroiditis was estimated to be 0.67% or 1 per 149 persons. Toxoplasmic retinochoroiditis is common in Australian adults. Efforts to quantify and address risk factors for human infection with T. gondii are justified.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 06-01-2023
DOI: 10.1167/IOVS.64.1.3
Publisher: BMJ
Date: 23-11-2021
DOI: 10.1136/BJOPHTHALMOL-2021-320284
Abstract: Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting conjunctival damage related to ultraviolet radiation exposure. In cross-sectional studies, CUVAF area is positively associated with self-reported time spent outdoors and pterygium and negatively associated with myopia however, longitudinal studies are scarce. To use a novel deep learning-based tool to assess 8-year change in CUVAF area in young adults, investigate factors associated with this change and identify the number of new onset pterygia. A deep learning-based CUVAF tool was developed to measure CUVAF area. CUVAF area and pterygium status were assessed at three study visits: baseline (participants were approximately 20 years old) and at 7-year and 8-year follow-ups. Participants self-reported sun protection behaviours and ocular history. CUVAF data were available for 1497 participants from at least one study visit 633 (43%) participants had complete CUVAF data. Mean CUVAF areas at baseline and the 7-year and 8-year follow-ups were 48.4, 39.3 and 37.7 mm 2 , respectively. There was a decrease in mean CUVAF area over time (change in total CUVAF area=−0.96 mm 2 per year (95% CI: −1.07 to –0.86)). For participants who wore sunglasses ≥1/2 of the time, CUVAF area decreased by an additional −0.42 mm 2 per year (95% CI: −0.72 to –0.12) on average. Fourteen (1.5%) participants developed a pterygium. In this young adult cohort, CUVAF area declined over an 8-year period. Wearing sunglasses was associated with a faster reduction in CUVAF area. Deep learning-based models can assist in accurate and efficient measurement of CUVAF area.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Informa UK Limited
Date: 24-02-2021
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 14-12-2021
Publisher: Springer Science and Business Media LLC
Date: 27-07-2020
DOI: 10.1038/S41598-020-69524-8
Abstract: SIX1/SIX6 polymorphism has been shown to be associated with glaucoma. Studies have also found that, in older adults, retinal nerve fibre layer (RNFL) thickness is significantly thinned with each copy of the risk allele in SIX1/SIX6 . However, it is not known whether these genetic variants exert their effects in younger in iduals. Comparing a healthy young adult with an older adult cohort (mean age 20 vs 63 years), both of Northern European descent, we found that there was no significant RNFL thinning in each copy of the risk alleles in SIX1/SIX6 in the eyes of younger in iduals. The older cohort showed an unexpectedly thicker RNFL in the nasal sector with each copy of the risk allele for both the SIX1 (rs10483727) and SIX6 (rs33912345) variants. In the temporal sector, thinner RNFL was found with each copy of the risk allele in rs33912345 with a decrease trend observed in rs10483727. Our results suggest that SIX1/SIX6 gene variants exert their influence later in adult life.
No related grants have been discovered for Jason Charng.