Purpose: To investigate the possible roles of various cytokines or growth factors in the pathogenesis of exudative age-related macular degeneration (AMD) by comparing aqueous humor levels of 14 cytokines between eyes with polypoidal choroidal vasculopathy (PCV) and those with neovascular AMD. Methods: Forty eyes from 40 patients with treatment-naïve exudative AMD consisting of 18 eyes with neovascular AMD and 22 eyes with PCV were studied. Twenty eyes from 20 patients with no retinal pathology who underwent cataract surgery served as controls. Aqueous humor samples were collected just before intravitreal ranibizumab injection in 40 eyes with exudative AMD and before cataract surgery in 20 control eyes. Concentrations of 14 cytokines were determined by chemiluminescence-based ELISA: interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein 1, interferon-γ-inducible protein (IP)-10 and C-reactive protein (CRP). Results: After adjusting for gender, age and axial length, concentrations of CRP and IP-10 were significantly higher in eyes with neovascular AMD or PCV compared with control eyes (p < 0.05), and IP-10 levels were strongly associated with lesion size (p = 0.002). None of the 14 cytokines, including VEGF, were significantly different between eyes with neovascular AMD and those with PCV. Conclusion: Aqueous humor concentrations of CRP and IP-10 were elevated in eyes with PCV or neovascular AMD. IP-10 could be associated with the pathogenesis of neovascular AMD and PCV. © 2014 S. Karger AG, Basel

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13,029 controls, identified two novel CSC susceptibility loci: TNFRSF10A-LOC389641 and near GATA5 (rs13278062, odds ratio = 1.35, P = 1.26 × 10−13; rs6061548, odds ratio = 1.63, P = 5.36 × 10−15). A T allele at TNFRSF10A-LOC389641 rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD.

We investigated the clinical and genetic characteristics of patients with unilateral exudative age-related macular degeneration (AMD), including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation, in whom pachydrusen was seen. Patients with unilateral exudative AMD with at least a 12-month follow-up period were included. According to the fellow eye condition, 327 consecutive patients were classified into 4 groups: Group 0: no drusen (42.8%), Group 1: pachydrusen (12.2%), Group 2: soft drusen (30.3%), Group 3: pseudodrusen with or without soft drusen (14.7%). Development of exudative AMD in the fellow eye was retrospectively studied for a 60-month period and this inter-group comparisons were performed. Genotyping was performed for ARMS2 A69S and CFH I62V. The thickness of the choroid in the fellow eyes increased significantly in Group 1 than in other groups (all P < 1.0 × 10 −7 ). The development of exudative AMD in the fellow eye was significantly less frequent in Group 1 than in Groups 2 or 3 (P = 0.022 and 0.0015, respectively). Risk allele frequency of ARMS2 A69S was significantly lower in Group 1 than in Group 2 and 3 (all P < 1.0 × 10 −4 ). Patients with pachydrusen have genetic and clinical characteristics distinct from those of soft drusen and pseudodrusen.

Diabetes mellitus and end-stage renal disease are more prevalent in patients with nAMD than in those with PCV. Specific systemic conditions might be associated with the development of nAMD.