Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 × 10⁻⁵) and showed a greater subfoveal choroidal thickness (p = 3.4 × 10⁻¹⁴). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10⁻³). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies.

Purpose.: To investigate the relationship between subfoveal choroidal thickness, choroidal vascular hyperpermeability, and complement factor H (CFH) gene polymorphism in typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods.: Fifty-eight patients with typical AMD and 63 patients with PCV underwent fluorescein angiography, indocyanine green angiography (IA), and spectral-domain optical coherence tomography (OCT) using enhanced depth imaging (EDI). Subfoveal choroidal thickness was measured using EDI-OCT images, and choroidal hyperpermeability was evaluated using late-phase IA images. The major AMD-associated single-nucleotide polymorphisms were genotyped in 86 patients. Results.: Mean subfoveal choroidal thickness was significantly lower in eyes with typical AMD than that in eyes with PCV (P = 0.025). Subfoveal choroidal thickness was greater in eyes with choroidal hyperpermeability than that in eyes without it in typical AMD (P < 0.001) and PCV (P = 0.020), and in the fellow eyes of typical AMD (P < 0.001) and PCV (P = 0.027). In eyes without choroidal hyperpermeability, the mean subfoveal choroidal thickness was greater in PCV than that in typical AMD (P = 0.001). Choroidal thickness decreased after photodynamic therapy combined with intravitreal ranibizumab in typical AMD (P = 0.016) and PCV (P = 0.036). In eyes with PCV, the I62V polymorphism in the CFH gene contributed to choroidal thickness (P = 0.043). Conclusions.: Choroidal thickness is related to the AMD subtypes, choroidal hyperpermeability, and I62V CFH gene polymorphism. In eyes without choroidal hyperpermeability, EDI-OCT is useful as an auxiliary measure for differentiating typical AMD and PCV.

Purpose.: Retinitis pigmentosa (RP), a major cause of blindness in developed countries, has multiple causative genes; its prevalence differs by ethnicity. Usher syndrome is the most common form of syndromic RP and is accompanied by hearing impairment. Although molecular diagnosis is challenging, recent technological advances such as targeted high-throughput resequencing are efficient screening tools. Methods.: We performed comprehensive molecular testing in 329 Japanese RP and Usher syndrome patients by using a custom capture panel that covered the coding exons and exon/intron boundaries of all 193 known inherited eye disease genes combined with Illumina HiSequation 2500. Candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed according to the frequency of the variants in normal populations, in silico prediction tools, and compatibility with known phenotypes or inheritance patterns. Results.: Molecular diagnoses were made in 115/317 RP patients (36.3%) and 6/12 Usher syndrome patients (50%). We identified 104 distinct mutations, including 66 novel mutations. EYS, USH2A, and RHO were common causative genes. In particular, mutations in EYS accounted for 15.0% of the autosomal recessive/simplex RP patients or 10.7% of the entire RP cohort. Among the 189 previously reported mutations detected in the current study, 55 (29.1%) were found commonly in Japanese or other public databases and were excluded from molecular diagnoses. Conclusions.: By screening a large cohort of patients, this study catalogued the genetic variations involved in RP and Usher syndrome in a Japanese population and highlighted the different distribution of causative genes among populations.