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.

ABSTRACT.Purpose: To determine the distribution of choroidal thickness (CT) and ocular factors associated with CT in high myopic eyes in comparison with emmetropic eyes of young healthy adults. Methods: A case-control study of 648 young, male subjects, including 520 high myopes and 128 emmetropes. Choroidal imaging was performed using enhanced depth imaging spectral domain optical coherence tomography. Images were postprocessed using adaptive compensation for quality enhancement. CT was measured at nine locations, including subfovea and 1.5 and 3 mm nasal, temporal, superior and inferior to fovea. Results: The CT at the subfovea was significantly thinner (mean AE standard error: 225.87 AE 5.51 lm) for high myopes compared to emmetropes (375.15 AE 6.58 lm, p < 0.001). Likewise, CT in high myopic group was significantly thinner than emmetropic control group at all locations (p for trend <0.001 for all locations). Distribution of CT showed a markedly different pattern in high myopic eyes (thickest superiorly at 3 mm, 265.97 AE 5.97 lm) and emmetropic eyes (thickest subfoveally, 375.15 AE 6.58 lm). Choroid was thinnest at nasal 3 mm location in both the myopic (108.85 AE 3.97 lm) and emmetropic (238.25 AE 6.72 lm) groups. Among the ocular factors studied, axial length, posterior staphyloma and chorioretinal atrophy were the significant predictors of CT. Conclusions: Highly myopic eyes have significantly thinner choroid and showed different distribution pattern, compared to emmetropes. Axial length, posterior staphyloma and chorio-retinal atrophy are the strongest determinants of CT.

Hypertension has profound effects on various parts of the eye. Classically, elevated blood pressure results in a series of retinal microvascular changes called hypertensive retinopathy, comprising of generalized and focal retinal arteriolar narrowing, arteriovenous nicking, retinal hemorrhages, microaneurysms and, in severe cases, optic disc and macular edema. Studies have shown that mild hypertensive retinopathy signs are common and seen in nearly 10% of the general adult non-diabetic population. Hypertensive retinopathy signs are associated with other indicators of end-organ damage (for example, left ventricular hypertrophy, renal impairment) and may be a risk marker of future clinical events, such as stroke, congestive heart failure and cardiovascular mortality. Furthermore, hypertension is one of the major risk factors for development and progression of diabetic retinopathy, and control of blood pressure has been shown in large clinical trials to prevent visual loss from diabetic retinopathy. In addition, several retinal diseases such as retinal vascular occlusion (artery and vein occlusion), retinal arteriolar emboli, macroaneurysm, ischemic optic neuropathy and age-related macular degeneration may also be related to hypertension; however, there is as yet no evidence that treatment of hypertension prevents vision loss from these conditions. In management of patients with hypertension, physicians should be aware of the full spectrum of the relationship of blood pressure and the eye.

Highly myopic eyes have significantly thinner peripapillary choroid and showed different distribution of thickness, compared with emmetropes. Axial length, IOP, and presence of posterior staphyloma and chorioretinal atrophy significantly influence PPCT and should be taken into consideration during clinical interpretation of PPCT measurement.

This study will provide in-depth longitudinal data of the evolution of clinical features, risk factors, natural history and treatment pattern and response of Asian AMD and polypoidal choroidovasculopathy, allowing unique insights into pathogenesis and the design of new treatment strategies.

White without pressure (WWOP) and LD were the commonest peripheral retinal changes. One-third of high myopes with LD had more than one area in the same eye. Increasing AL was associated with LD and retinal holes. Studies in older adults should be conducted to develop clinical guidelines for the management of high myopes.

Purpose. To identify systemic factors that may influence the response to anti-VEGF therapy in patients with diabetic macular edema (DME). Methods. 35 patients undergoing anti-VEGF injections for centre-involving DME were studied in this prospective observational study. The primary outcome was change in macular thickness one month after treatment, measured using spectral-domain optical coherence tomography (OCT). At baseline, information on various systemic factors was collected including glycosylated hemoglobin (HbA1c), serum VEGF levels, lipid profile and markers of renal function, and blood pressure. Thirty-three of the 35 patients were included in this study. Nonparametric statistical tests were used for the analysis of the data in view of the nonnormal distribution of the outcome variables. Multivariate analysis was performed using logistic regression. Stata 12.1 software was used for the analysis. Main Outcome Measures. Reduction in macular central subfield thickness (on spectral-domain OCT) and change in logMAR visual acuity at one month after injection. Results. Lower HbA1c levels (7% or less) were significantly associated with greater reduction in central macular subfield thickness at one month after injection of bevacizumab or ranibizumab on both univariate analysis (p=0.012) and multivariate analysis (p=0.042). Conclusions. Better glycemic control is associated with a greater reduction in central macular thickness after the first injection of bevacizumab or ranibizumab in diabetic macular edema. Patients with high levels of HbA1c and poor response to anti-VEGF may benefit from strict control of their blood glucose.

ABSTRACT.Purpose: To describe prevalence and risk factors for retinopathy in an Asian Indian population without diabetes. Methods: A population-based cross-sectional study of 3400 Indians aged 40-80 years residing in Singapore was conducted. Retinopathy was assessed from retinal photographs by trained graders using modified Airlie House Classification System. Risk factors were assessed from standardized interviews, clinical examinations and laboratory investigations. Diabetes mellitus was defined as glycosylated haemoglobin ≥6.5%, use of diabetic medication or physician diagnosis of diabetes. Results: Among the 1900 individuals without diabetes, mean HbA1c was 5.7% and mean systolic blood pressure was 132.4 mmHg. Age-standardized prevalence of retinopathy was 5.05% (n = 98; 95% confidence interval [CI], 4.07-6.21), with no significant difference in retinopathy prevalence between males (6.15%) and females (4.13%). Among non-diabetic persons with retinopathy, 96.9% (n = 95) had signs of minimal-to-mild retinopathy while 3.06% (n = 3) had moderate-tosevere retinopathy. After adjusting for multiple covariables, retinopathy signs were associated with higher levels of HbA1c (odds ratio [OR], 2.4; 95% CI, 1.3-4.5; per % increase), systolic blood pressure (OR, 1.02; 95% CI, 1.01-1.03; per mmHg increase) and serum creatinine (OR, 1.005; 95% CI, 1.002-1.009; per mM increase), but not C-reactive protein, cigarette smoking or lipid levels. Conclusion: One in 20 Asian Indian persons without diabetes had retinopathy signs. Risk factors for these signs include higher glycosylated haemoglobin, systolic blood pressure and serum creatinine.