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.

PurposeTo investigate fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy (PCV).MethodsThis phase IV, prospective, single-arm, interventional case series was conducted in eight centers. Forty treatment-naïve PCV patients were administered three monthly doses of intravitreal aflibercept (2.0 mg) and an injection every 2 months thereafter. Best-corrected visual acuity (BCVA) and central subfield macular thickness (CSMT) were measured at each visit. Fluorescein and indocyanine green angiography (ICGA) were performed at baseline, 3 and 12 months. The primary outcome measure was the proportion of patients who maintained BCVA (<15 letters loss) at 12 months. Changes in BCVA, macular appearance, and polypoidal lesion appearance were also examined.ResultsThirty-five eyes (87.5 %) had maintained BCVA at 12 months. Average BCVA was significantly higher at 12 months (20/53, 64.2 letters) than at baseline (20/80, 55.1 letters, 9-letter gain; P < .001). Mean CSMT was significantly lower at 12 months (253.6 μm) than at baseline (365.2 μm, P < .001). The macula was dry in 32 (76.2 %), 27 (64.3 %), and 24 eyes (60.0 %) at 3, 6, and 12 months respectively. Fourteen eyes (33.3 %) had a fluid recurrence or increase at 6 months, and they had a significantly lower vision gain (P = .005) than other patients at 12 months. Complete polyp regression occurred in 26 eyes (66.7 %) at 12 months.ConclusionsFixed-dosing aflibercept showed favorable outcomes in PCV patients at 12 months. However, some patients had worse outcomes because of fluid recurrence during maintenance dosing, and these patients would require additional treatments.

The macula was displaced centripetally, nasally, and slightly inferiorly after surgical closure of idiopathic macular hole. Hole closure, contraction of the nerve fiber layer, and gravity are the suggested mechanisms of macular displacement caused by internal limiting membrane peeling.