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.

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation). Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2) and c.8868C>A (p.Y2956X), were identified in 16 patients and accounted for 57.1% (20/35 alleles) of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing and counseling of RP patients in Japan.

The value of parameters in Hertel’s exophthalmometry was measured by using orbit computerized tomography (CT) in this study. We selected images that revealed the center of the lens, the largest eyeball contour and the optic canal on the axial view of orbit CT. Parameters of exophthalmometry on orbit CT were the distance between the lateral orbital rims of both eyes (A), the shortest distance from the corneal center to line A (B), the B/A ratio, the distance between the lateral orbital rim and the medial orbital rim (C), the length of the line passing through the lens center from the apex to line C (D) and the D/C ratio. To compare the center position of the eye, we measure the axial length (E) and the longest distance between the corneal apex and the posterior pole (F) which is parallel to line B. We also calculated B-F/2 and Hertel-F/2 in order to know if there is a difference between measurements of orbit CT and of Hertel’s exophthalmometer. Subjects were classified into group 1 (aged 8–13 years old) and group 2 (aged 20 years old more). Sixteen subjects were enrolled in group 1 (32 eyes). In group 2, 100 subjects were male (200 eyes) and 35 were female (70 eyes). In group 1, the mean value was 89.94 mm for A, 13.49 mm for B, 35.13 mm for C, 10.64 mm for D, 24.40 mm for E, 24.20 mm for F, 0.15 for the B/A ratio and 0.30 for the D/C ratio. In group 2, the mean value was 100.93 mm for A, 15.03 mm for B, 38.78 mm for C, 12.03 mm for D, 24.62 mm for E, 24.33 mm for F, 0.15 for the B/A ratio and 0.31 for the D/C ratio. There was a statistically significant difference between the two groups for parameters A, B, C and D (p = 0.001), but no significant difference for the B/A (p = 0.239) and D/C ratios (p = 0.803). In the males and females of group 2, there was a statistically significant difference for the B/A ratio (p = 0.028). We suggest that the value of the D/C ratio (0.30–0.31) could be used as the index of protrusion. The normal values of exophthalmometry parameters measured by orbit CT could also be helpful to evaluate the exact protrusion in orbital diseases.

Postoperative OCT revealed that thickening of the macula with loss of the normal foveal contour was more frequent in the ILM peeling group. However, these morphological differences did not result in functional differences in terms of visual outcome.

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