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Aims: To develop and externally test deep learning (DL) models for assessing the image quality of three-dimensional (3D) macular scans from Cirrus and Spectralis optical coherence tomography devices., Methods: We retrospectively collected two data sets including 2277 Cirrus 3D scans and 1557 Spectralis 3D scans, respectively, for training (70%), fine-tuning (10%) and internal validation (20%) from electronic medical and research records at The Chinese University of Hong Kong Eye Centre and the Hong Kong Eye Hospital. Scans with various eye diseases (eg, diabetic macular oedema, age-related macular degeneration, polypoidal choroidal vasculopathy and pathological myopia), and scans of normal eyes from adults and children were included. Two graders labelled each 3D scan as gradable or ungradable, according to standardised criteria. We used a 3D version of the residual network (ResNet)-18 for Cirrus 3D scans and a multiple-instance learning pipline with ResNet-18 for Spectralis 3D scans. Two deep learning (DL) models were further tested via three unseen Cirrus data sets from Singapore and five unseen Spectralis data sets from India, Australia and Hong Kong, respectively., Results: In the internal validation, the models achieved the area under curves (AUCs) of 0.930 (0.885-0.976) and 0.906 (0.863-0.948) for assessing the Cirrus 3D scans and Spectralis 3D scans, respectively. In the external testing, the models showed robust performance with AUCs ranging from 0.832 (0.730-0.934) to 0.930 (0.906-0.953) and 0.891 (0.836-0.945) to 0.962 (0.918-1.000), respectively., Conclusions: Our models could be used for filtering out ungradable 3D scans and further incorporated with a disease-detection DL model, allowing a fully automated eye disease detection workflow., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To assess the association of smoking with age of onset of neovascular age-related macular degeneration (nAMD), visual acuity (VA), central macular thickness (CMT) and the presence of fluid in patients with nAMD., Methods: 547 patients with nAMD were recruited from a tertiary eye clinic during 2012-2015; of these, 490 patients were followed up 12 months later. Clinical diagnosis of nAMD was confirmed by a retinal specialist. Smoking was determined from self-reported history as never, past or current. Age of onset was defined as date of first recorded diagnosis of nAMD in either eye or date of first anti-vascular endothelial growth factor injection. CMT and presence of fluid were recorded from spectral-domain optical coherence tomography images. VA was recorded as number of letters read at 3 m., Results: After multivariable adjustment, current smokers developed nAMD at an average 5.5 years younger age than never smokers and 4.4 years younger age than past smokers (p<0.0001 and p=0.0008, respectively). At baseline, adjusted mean CMT was significantly higher in current compared with past smokers (259.2 µm vs 231.9 µm, respectively, p=0.04). Current smokers versus never smokers had greater odds of presence of subretinal fluid at 12-month follow-up: multivariable-adjusted OR 1.99 (95% CI 1.09 to 3.67). Smoking status was not significantly associated with VA over 12 months., Conclusions: Current smoking was associated with a younger age of nAMD onset and key treatment outcomes such as higher mean CMT and greater odds of subretinal fluid presence. These findings suggest that smoking cessation may benefit patients being treated for nAMD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To report the prevalence of treatable complications (cystoid macular oedema, CME; epiretinal membrane, ERM and cataract) in patients with retinitis pigmentosa (RP)., Methods: Consecutive patients with RP attending a tertiary eye clinic in 2012. Spectral domain-optical coherence tomography was used to determine presence of CME and ERM. Clinic records were reviewed to identify cataract and pseudophakia. Multivariable analyses adjusted for age, gender and other confounders., Results: Data are presented for 338 eyes from 169 patients. CME was present in 58.6% of patients and 50.9% of eyes and was bilateral in 73.7%. ERM, cataract and pseudophakia were present in 22.8%, 23.4% and 11.2% eyes, respectively. In multivariable analyses, CME was associated with younger age (OR 0.81, 95% CI 0.67 to 0.98) but not with gender. Patients with ERM and cataract/pseudophakia were less likely to also have CME (OR 0.19, 95% CI 0.09 to 0.40 and OR 0.37, 95% CI 0.16 to 0.84, respectively). CME was most prevalent in patients with autosomal-dominant inheritance (71.4%), followed by autosomal recessive/sporadic inheritance (58.9%) and least likely in persons with X linked inheritance (12.5%, p<0.001)., Conclusions: The prevalence of treatable RP complications is high and suggests it may be clinically beneficial to screen patients with RP to identify those who may benefit from current or future interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the 5-year progression from unilateral to bilateral age-related macular degeneration (AMD) and associated risk factors., Design: Pooled data analyses of three prospective population-based cohorts, the Blue Mountains Eye Study, Beaver Dam Eye Study and Rotterdam Study., Methods: Retinal photography and interview with comprehensive questionnaires were conducted at each visit of three studies. AMD was assessed following the modified Wisconsin AMD grading protocol. Progression to bilateral any (early and late) or late AMD was assessed among participants with unilateral involvement only. Factors associated with the progression were assessed using logistic regression models while simultaneously adjusting for other significant risk factors., Results: In any 5-year duration, 19-28% of unilateral any AMD cases became bilateral and 27-68% of unilateral late AMD became bilateral. Factors associated with the progression to bilateral involvement of any AMD were age (per year increase, adjusted OR 1.07), carrying risk alleles of the complement factor H and age-related maculopathy susceptibility 2 genes (compared with none, OR 1.76 for 1 risk allele and OR 3.34 for 2+ risk alleles), smoking (compared with non-smokers, OR 1.64 for past and OR 1.67 for current smokers), and the presence of large drusen area or retinal pigmentary abnormalities in the first eye., Conclusion: One in four to one in five unilateral any AMD cases, and up to one in two unilateral late AMD cases, progressed to bilateral in 5 years. Known AMD risk factors, including smoking, are significantly associated with the progression to bilateral involvement., Competing Interests: Competing interests: There are no financial disclosures for all authors except for PM and CCWK, who have provided consultancy to Bayer (PM, CCWK), Novartis (PM, CCWK) and Allergan (PM) and received payment and travel/accommodations from these companies for lectures., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Knowledge of the risk factor profile of patients presenting with late-stage age-related macular degeneration (AMD) could help identify the most frequent modifiable AMD precursors among people who are referred for treatment. We aimed to assess dietary behaviours by comparing adjusted mean intakes of micronutrients and major food groups (fruits, vegetables, fish) among patients with AMD and a sample of age-sex-matched controls., Methods: Cross-sectional analysis of 480 late AMD cases and 518 population-based age-sex-matched controls with no AMD signs. AMD cases (aged 60+ years) were those presenting for treatment to a hospital eye clinic in Sydney, Australia, during 2012-2015. The comparator group were obtained from a cohort study (Blue Mountains Eye Study; Sydney, Australia) during 2002-2009. Dietary intake was assessed using a semiquantitative food-frequency questionnaire. AMD lesions were assessed from retinal photographs., Results: After multivariable adjustment, patients with late-stage AMD compared with controls had significantly lower intakes of vitamin E (7.4 vs 9.8 mg/day; p<0.0001), beta-carotene (6232 vs 7738 μg/day; p<0.0001), vitamin C (161 vs 184 mg/day; p=0.0002) and folate (498.3 vs 602 μg/day; p<0.0001); but had higher intakes of zinc (13.0 vs 11.9 mg/day; p<0.0001). A significantly lower proportion of patients with late AMD met the recommended intake of vegetables than controls: 52.9% versus 64.5%; p=0.0002., Conclusions: This study showed significant differences in intakes of vitamins C and E, beta-carotene, folate and vegetables between patients with late-stage AMD and healthy controls, and thus has provided a better understanding of the nutritional intake of patients presenting with advanced AMD., Competing Interests: Competing interests: None., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: To investigate the independent associations between metabolic syndrome and retinal vessel calibre in a high cardiovascular risk cohort, and to determine whether these associations also exist in patients without diabetes, hypertension or coronary artery disease (CAD)., Methods: The Australian Heart Eye Study is an observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Metabolic syndrome was defined according to the Third Report of the National Cholesterol Education Program. Retinal arteriolar calibre narrowing and retinal venular calibre widening were measured from retinal photographs. CAD was quantified using severity (Gensini) and extent scores. Diabetes and hypertension were defined from clinical investigation (fasting plasma glucose >7.0 mmol/L and blood pressure >130/85 mm Hg) or from self-reported clinical diagnosis, including the use of medications., Results: A total of 979 participants had complete information on metabolic syndrome components and were included in cross-sectional analyses. After adjusting for age, sex, smoking status and fellow vessel calibre, persons with metabolic syndrome (compared with persons without metabolic syndrome) had narrower retinal arteriolar calibre (mean difference 4.3 µm, p<0.0001). No significant difference in venular calibre was observed (p=0.05). This association persisted in persons without diabetes (mean arteriolar calibre difference 4.4 µm, p=0.0006) but not in participants without CAD and those without hypertension., Conclusions: Metabolic syndrome is independently associated with narrower retinal arterioles but not wider retinal venules among those at high risk of CAD. The association between metabolic syndrome and narrower retinal arterioles is likely due to the presence of CAD or hypertension in individuals with this syndrome, as the association is not significant in individuals without hypertension or without CAD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: To describe the prevalence of idiopathic and secondary epiretinal membranes (ERM) in a clinical cohort (Australian Heart Eye Study, AHES) and compare to the Blue Mountains Eye Study, and to determine whether associations exist between idiopathic ERM and the extent and severity of coronary artery disease (CAD)., Methods: The AHES is an observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Severity and extent of CAD was assessed using three scoring systems: (1) segment/vessel scores, (2) Gensini and (3) extent scores. Two types of ERM were identified: a more severe form, termed 'preretinal macular fibrosis' (PMF) in which retinal folds were identified; and a less severe form termed 'cellophane macular reflex' (CMR), without visible retinal folds., Results: Overall prevalence of ERM was 7.0% (n=115), with CMR and PMF each 3.5%. 72.7% of ERM cases were idiopathic (no secondary cause identified). Prevalence of PMF, but not CMR, was significantly higher than the corresponding age-standardised prevalence in the baseline Blue Mountains Eye Study (p<0.001). There was no significant association between extent and severity of CAD and idiopathic ERM., Conclusions: This study suggests that cardiovascular disease (specifically severity and extent of CAD) is not associated with ERM. However, there may be a greater prevalence of severe ERM (PMF) in a high cardiovascular risk cohort relative to a population-based cohort., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: To assess the association between visual impairment (VI) and subsequent presence of depressive symptoms among older persons., Methods: Of the 3654 baseline participants (aged over 49 years) of the Blue Mountains Eye Study, 2334, 1952 and 1149 were re-examined after 5, 10 and 15 years, respectively. VI was defined as best-corrected visual acuity <6/12 in either or both eyes. Presence of depressive symptoms was defined if mental health index (MHI) scores <59 or incident use of antidepressant medications. Persons with VI detected at the 5-year or 10-year follow-up visits were assessed for depressive symptoms in 5 years. Persons with VI detected at baseline or the 5-year follow-up were assessed for depressive symptoms over 10 years. Controls were persons without VI over the corresponding period. Discrete logistic regression models with time-dependent study and outcome variables were used, adjusting for potential confounders., Results: Of 1568 participants who had the MHI assessed at two consecutive visits, 226 had bilateral or unilateral VI detected 5 years earlier and 120 had VI detected over 10 years earlier. Depressive symptoms were reported in 27% and 31.6% of cases with VI detected 5 and over 10 years earlier, respectively, compared with 10.8%-11.5% of controls. There was a significantly greater odds of presenting depressive symptoms among VI cases detected 5 years earlier (OR, 3.06, 95% CI 1.72 to 5.44), but this was non-significant for cases detected over 10 years earlier (OR 1.29, 95% CI 0.84 to 1.98)., Conclusions: VI was associated with subsequently presenting depressive symptoms over 5 years among older persons., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background/aims: To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy., Methods: Multicentre national nAMD database study on patients treated 3-5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections., Results: The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12-6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001-0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12., Conclusions: All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients' funding., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background/aims: To describe the prevalence of early, late and any age-related macular degeneration (AMD) in a clinical cohort (Australian Heart Eye Study, AHES) and to determine whether associations exist between extent and severity of coronary artery disease (CAD) and AMD, independent of traditional cardiovascular risk factors., Methods: The AHES is an observational study that surveyed 1680 participants between 2009 and 2012 who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Severity and extent of CAD was assessed using three scoring systems: (1) segment/vessel scores, (2) Gensini and (3) extent scores., Results: Prevalence of early and late AMD was 5.8% (n=86) and 1.4% (n=21), respectively. After multivariable adjustment, patients with stenosis >50% in any coronary artery segment (vessel score) had approximately twofold higher odds of early AMD, OR 1.95 (95% CI 1.07 to 3.57). Patients with obstructive coronary stenosis in all three main coronary arteries (segment score) had greater than twofold higher likelihood of early AMD, OR 2.67 (95% CI 1.24 to 5.78). Participants in the highest versus lowest tertile of Gensini scores were also twice as likely to have early AMD, multivariable-adjusted OR 2.27 (95% CI 1.12 to 4.58). Extent scores were not associated with AMD. There was no significant association between CAD and late AMD., Conclusions: Severity of coronary stenosis and the presence of stenotic lesions were independently associated with early AMD. These findings could have potential clinical significance as they suggest that individuals with evidence of CAD may be screened for early AMD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)