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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.

Eyes of patients with DM showed decreased CVI with no corresponding change in choroidal thickness. Image binarization may be potentially useful as a tool to assess choroidal structures and vasculature.

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Dengue-associated ocular inflammation is an emerging ophthalmic condition and often involves the posterior segment. Prognosis is variable. Patients usually regain good vision but may retain persistent scotomata even at 2 years despite clinical resolution of the disease. Optical coherence tomography patterns in dengue maculopathy are useful for characterization, monitoring, and prognostication of the visual defect.

The understanding of polypoidal choroidal vasculopathy has evolved rapidly in the past three decades. The hallmark of the disease is the presence of typical hyperfluorescent nodules in the early phase of indocyanine green angiography. Although the classical clinical presentation is recurrent serosanguinous detachment of the retinal pigment epithelium, it may present with clinical features indistinguishable from exudative age-related macular degeneration secondary to choroidal neovascularization. Some cases may present initially with submacular haemorrhage, but later with features of exudative age-related macular degeneration. Studying the associated network of vessels using confocal scanning laser ophthalmoscopy indocyanine green dynamic angiography revealed in many cases feeder vessels, branching pattern, and leakage similar to choroidal neovascularization. Owing to the overlap of clinical and angiographic features, it may be considered as a vascular subtype of exudative age-related macular degeneration. However, having seemingly better natural history, better response to photodynamic therapy, and incomplete response to antivascular endothelial growth factor therapy suggests that it should be studied as a separate entity from choroidal neovascularization. Combining angio-occlusion of the polyps using photodynamic therapy and antipermeability effect of anti-vascular endothelial growth factor therapy on the branching vascular network may provide a synergistic effect. We await the result of EVEREST trial, a multi-centre randomized controlled trial comparing photodynamic therapy, with or without ranibizumab, with ranibizumab monotherapy.

BackgroundDyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results.MethodsWe investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits.ResultsA 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07–1.29) in Europeans (P = 6.88 × 10–4) and of 1.58 (1.24–2.00) in Asians (P = 2.92 × 10–4) in Model 3. The corresponding OR estimates were 1.30 (1.09–1.55) in Europeans (P = 3.18 × 10–3) and 1.42 (1.11—1.80) in Asians (P = 4.42 × 10–3) in Model 1, and 1.21 (1.11–1.31) in Europeans (P = 3.12 × 10–5) and 1.51 (1.20–1.91) in Asians (P = 7.61 × 10–4) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels.ConclusionsOur study shows that high levels of plasma HDL-C are causally associated with an increased risk for advanced AMD in European and Asian populations, implying that strategies reducing HDL-C levels may be useful to prevent and treat AMD.