Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10−22). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l−1 (P=5.82 × 10−21) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10−18), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10−11) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10−8). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40–80 years between 2004–2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better-seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional-hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25–1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24–2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all-cause (HR 1.70; 95% CI, 1.25–2.36) and CVD mortality (HR 1.57; 95% CI, 1.05–2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26–7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality.

In this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings suggest that screening for diabetes is successful, while screening for DR is currently inadequate in our population. Public health strategies to aid early diagnosis of DR in Singapore are urgently warranted to reduce blindness due to diabetes.