David Anthony Mackey

Changes in corneal curvature have been reported with low-concentration atropine eyedrops for myopia treatment and have been suggested to play a role in the refractive changes observed during atropine therapy. A case of keratoconus was identified from the Western Australia atropine for the treatment of myopia (WA-ATOM) cohort. We tested the null hypothesis that 0.01% atropine eyedrops produce no change in corneal parameters or ectasia risk compared to placebo. Children with progressive myopia (6–16 years; n = 153) were randomly assigned to receive 0.01% atropine eyedrops or a placebo (2:1 ratio) for 2 years, followed by a 1-year washout. Scheimpflug imaging was performed at baseline, 24-months, and 36-months. Changes in corneal parameters were compared between the treatment and placebo groups using linear mixed models. One child allocated to the treatment group developed keratoconus during the treatment phase. At 24 and 36 months, the atropine group had significantly lower BAD-D values compared to placebo, with reductions of − 0.075 (95% CI − 0.126 to − 0.023, p = 0.027) and − 0.115 (95% CI − 0.168 to − 0.063, p = 0.005) from baseline, respectively ( p = 0.029 and 0.005). At 36 months, a significant steepening of K _max of + 0.301D (95% CI 0.214 to 0.389, p = 0.039) was observed in the atropine group. All other corneal parameters and cylindrical power remained similar between the groups. The case of incidental keratoconus in the treatment group (1 out of 153 children) is compatible with population prevalence rates. No signal suggesting a treatment-related increase in corneal ectatic changes was identified within the limitations of this cohort, and these findings provide reassurance from a safety perspective, but clinicians should be aware of the rare possibility of keratoconus and refer patients with suspicious corneal findings.

The fovea is a specialized central area of the macula, responsible for the sharpest visual acuity.1 Foveal development in humans occurs from 22 weeks’ gestation and reaches maturity at 15 to 45 mon...

Pathogenic variants in the myocilin ( MYOC ) gene are the most common cause of Mendelian open-angle glaucoma. In 2022, the Clinical Genome Resource (ClinGen) Glaucoma Variant Curation Expert Panel (VCEP) published rule specifications for MYOC variant interpretation, including a pilot study of 81 variants. Here, we present the results of curating 271 MYOC variants reported in people with open-angle glaucoma using updated specification rules. Of all the variants, 11 were classified as benign (B), 45 as likely benign (LB), 166 as variants of uncertain significance (VUS), 35 as likely pathogenic (LP), and 14 as pathogenic (P). All LP/P variants were located within the conserved olfactomedin domain encoded by exon 3. The updated variant curation guidelines from the Glaucoma VCEP increased the number of clinically definitive classifications from 28% (74/265) to 39% (105/271), with 95% (41/43) of reclassified variants moving to greater clinical relevance. Functional evidence was lacking for 93% (154/166) of VUS. Additional functional evidence could further enhance classification by halving (85/166) the proportion of those classified as VUS. These findings highlight the role of rule calibration and rigorous functional evidence assessment toward improving variant classification with clinical utility for patients.

Background: Data on myopia prevalence in Australia and associations with common systemic conditions and quality of life are limited. This study aimed to profile Australian adults self-reporting to have myopia, including co-morbidities and quality of life. Methods: This research included participants from the ongoing longitudinal 45 and Up Study. Sex and education data were collected at the baseline survey and additional data from the follow-up Health Compass survey. Responses on self-reported myopia, health and quality of life were analysed with logistic regression to assess the association between myopia and health conditions. Results: Of the 21,384 participant responses, 54.3% self-reported myopia, with higher rates in females and younger individuals. Self-reported myopes were more likely to have achieved higher levels of education, reside in urban and less remote regions and rate their quality of life and overall health worse than non-myopes. Education level was the strongest predictor of self-reported myopia. They were also more likely to report having visual or physical impairment, cardiovascular disease, chronic lung disease, diabetes and cancer. Non-myopic participants were less likely to report any disabilities or impairments and health conditions. Conclusion: The prevalence of self-reported myopia in Australian adults appears high and likely an overestimation. As commonly observed, self-reported myopia was higher in educated urban populations, with a greater propensity in females than males in the younger cohorts. Poorer quality of life and health ratings in self-reported myopes align with previous findings. The higher rates of health conditions in self-reported myopes may reflect shared lifestyle and environmental risk factors.

Purpose: To determine whether ocular dominance is associated with systematic interocular asymmetry in spherical equivalent refraction (SER) and axial length (AL) across childhood and early adulthood, and assess whether such asymmetry exceeds laterality effects. Methods: Data were analysed from three population-based cohorts: 728 children (6–7-year-olds) and 898 adolescents (12–13-year-olds) from Ireland and 303 young adults (25–30-year-olds) from Western Australia. Ocular dominance was assessed using sighting tests. SER was measured by cycloplegic autorefraction and AL by optical biometry. Interocular differences were evaluated using paired comparisons, concordance correlation coefficients (CCC), Deming regression, Bland–Altman analyses and mediation modelling. Analyses were stratified by refractive status and anisometropia. Results: Across all age groups, right–left differences in SER and AL were minimal (mean differences p < 0.05). Deming regression and Bland–Altman analyses confirmed systematic deviation from interocular symmetry, most pronounced in childhood. Mediation analyses indicated that ocular dominance statistically explained over 85% of the observed interocular asymmetry, independent of laterality. Dominance-related asymmetry was most evident in non-myopes (SER −0.09 to −0.36 D; AL 0.03–0.06 mm), attenuated in myopia and amplified in anisometropia (SER up to −1.09 D; AL up to 0.42 mm), particularly in younger cohorts. Conclusion: In this cross-sectional analysis, ocular dominance was associated with small but systematic interocular asymmetry in SER and AL across childhood and early adulthood, which exceeds laterality effects. Dominance-related asymmetry was attenuated in myopia and amplified in anisometropia. Ocular dominance should be considered when analysing interocular refractive and biometric data in research and clinical contexts.

Objectives: To evaluate the efficacy and safety of low concentration atropine eye drops for reducing progression of myopia in children in the UK. Design: Multicentre, double masked, superiority, placebo controlled, randomised trial. Setting: National Health Service hospital eye services and academic institutions at five UK centres. Participants: 289 children aged 6-12 years with myopia between −0.50 and −10.0 dioptres (D). Participants were allocated in ratio of 2:1 to atropine or placebo. Interventions: One eye drop of preserved atropine 0.01% or placebo daily for two years. Main outcome measures: The primary outcome was spherical equivalent refractive error of both eyes measured by autorefractor under cycloplegia after two years. Secondary outcomes included change in axial length, best corrected distance and near visual acuity, reading speed, pupil diameter, spectacle correction, adverse event rates, quality of life, and tolerability. Outcomes were collected every six months. An electronic monitoring system was used to assess adherence. Results: 192 participants were included in the atropine group and 97 in the placebo group, with an average age of 9.3 years (standard deviation (SD) 1.7 years). 207 (72%) reported white ethnicity, 161 (56%) were girls, and the mean level of myopia was −2.87 D (SD 1.71 D). A total of 235 (81%) participants completed the study, with primary outcome data available for 230 (80%) participants: 151 (79%) in the atropine group and 79 (81%) in the placebo group. Atropine eye drops were more effective than placebo in reducing myopia progression (mean difference 0.33 D, 95% confidence interval (CI) 0.17 to 0.49 D, P<0.001). Prespecified subgroup analyses did not show differences according to age, ethnicity, sex, or severity of myopia. Changes in central axial length were significantly less in the atropine group versus placebo group: mean difference 0.14 mm (95% CI 0.07 to 0.21, P<0.001). There were no differences in other secondary outcomes, except pupil diameter, which was greater in the atropine group (0.36 mm, 95% CI 0.17, 0.55, P<0.001), and no differences in frequency of adverse events or in tolerability measures. No serious adverse events were related to the trial drugs. Conclusions: Low concentration atropine (0.01%) eye drops significantly reduced progression of myopia and were well tolerated compared with placebo in children in the UK. Trial registration: ISRCTN registry ISRCTN99883695 , ClinicalTrials.gov NCT03690089 .

The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.