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Purpose To investigate the difference in intraocular vascular endothelial growth factor (VEGF) concentration between pachychoroid neovasculopathy and neovascular age-related macular degeneration (nAMD) and its associations with responses to three monthly anti-VEGF injections as an initial treatment for the two conditions. Methods This study included nine eyes with treatment-naive pachychoroid neovasculopathy and 21 eyes with treatment-naive nAMD. Before the initial intravitreal anti-VEGF injection, aqueous humor samples were collected and the concentration of VEGF was measured using enzyme-linked immunosorbent assay. The concentration was compared between the two conditions, and its associations with responses to anti-VEGF therapy were investigated. Results The mean VEGF concentration in pachychoroid neovasculopathy was significantly lower than that in nAMD (63.4 ± 17.8 pg/ml and 89.8 ± 45.0 pg/ml, respectively; P = 0.035). The VEGF concentration was associated with the presence or absence of drusen (β = 0.503, P = 0.004). After anti-VEGF therapy, 6 (66.7%) of 9 eyes with pachychoroid neovasculopathy and 17 (81.0%) of 21 eyes with nAMD achieved dry macula (P = 0.640). Dry macula at 3 months and 12 months was significantly associated with a low VEGF concentration in pachychoroid neovasculopathy (P = 0.013 and P = 0.042, respectively), but not in nAMD (P = 0.108 and P = 0.219). Conclusions The mean VEGF concentration in pachychoroid neovasculopathy was lower than that in nAMD, suggesting that the way in which VEGF is involved in angiogenesis may differ between pachychoroid neovasculopathy and nAMD.

PURPOSE To assess photoreceptor structure in macular microholes by using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and spectral-domain optical coherence tomography (SD-OCT) and compare with visual acuity. METHODS Fourteen eyes from 12 patients with macular microholes underwent a full ophthalmologic examination and imaging with a fundus camera, SD-OCT, and an original prototype AO-SLO system at each visit. RESULTS All eyes had a cone outer segment tip line disruption and a normal retinal pigment epithelium line on SD-OCT images. Adaptive optics scanning laser ophthalmoscopy revealed foveal cone disruption (13 eyes, round or oval; 1 eye, T-shaped) in all eyes. Cone disruption area (mean = 14,805 ± 9120 μm(2); range, 3495-35,901 μm(2)) positively correlated with logMAR visual acuity at the first visit (P = 0.015, rs = 0.679). During the follow-up period, cone disruption area increased in two eyes, was stable in seven eyes, and decreased in five eyes. At the last visit, cone disruption area (mean = 8717 ± 7432 μm(2); range, 0-25,746 μm(2)) also positively correlated with logMAR visual acuity (P = 0.035, rs = 0.610). In one patient with bilateral microholes and no apparent vitreous traction, lesion size gradually increased. Cone disruption area decreased and visual acuity improved following oral prednisone therapy. CONCLUSIONS Cone disruption occurs in eyes with macular microholes and a larger cone disruption area translates into a poorer visual acuity. Macular microholes, which are commonly observed as foveal cone inner and outer segment disruptions, may occur in eyes with or without vitreofoveal traction.

PURPOSE To integrate parameters on spectral-domain optical coherence tomography (SD-OCT) in diabetic retinopathy (DR) based on the self-organizing map and objectively describe the macular morphologic patterns. METHODS A total of 336 consecutive eyes of 216 patients with DR for whom clear SD-OCT images were available were retrospectively reviewed. Eleven OCT parameters and the logarithm of the minimal angle of resolution (logMAR) were measured. These multidimensional data were analyzed based on the self-organizing map on which similar cases were near each other according to the degree of their similarities, followed by the objective clustering. RESULTS Self-organizing maps indicated that eyes with greater retinal thickness in the central subfield had greater thicknesses in the superior and temporal subfields. Eyes with foveal serous retinal detachment (SRD) had greater thickness in the nasal or inferior subfield. Eyes with foveal cystoid spaces were arranged to the left upper corner on the two-dimensional map; eyes with foveal SRD to the left lower corner; eyes with thickened retinal parenchyma to the lower area. The following objective clustering demonstrated the unsupervised pattern recognition of macular morphologies in diabetic macular edema (DME) as well as the higher-resolution discrimination of DME per se. Multiple regression analyses showed better association of logMAR with retinal thickness in the inferior subfield in eyes with SRD and with external limiting membrane disruption in eyes with foveal cystoid spaces or thickened retinal parenchyma. CONCLUSIONS The self-organizing map facilitates integrative understanding of the macular morphologic patterns and the structural/functional relationship in DR.

PURPOSE To investigate the relationship between the cystoid spaces in the outer plexiform layer (OPL) and the characteristics of the photoreceptors beneath the cystoid spaces in patients with diabetic macular edema (DME). METHODS In this observational cross-sectional study, 123 eyes of 96 consecutive patients with clinically significant macular edema were retrospectively reviewed. The characteristics of the photoreceptors on optical coherence tomography (OCT) images represented by the external limiting membrane (ELM) and the junction between inner and outer segments (IS/OS), and their association with the overlying cystoid spaces were investigated. RESULTS The areas beneath the cystoid spaces in the OPL had a longer transverse length of disrupted or faint IS/OS and disrupted ELM lines than those without cystoid spaces (P < 0.001, P < 0.001, and P = 0.009). The IS/OS lines beneath the cystoid spaces had higher reflectivity than those in areas without cystoid spaces (P < 0.001). Enlarged cystoid spaces extending from the inner nuclear layer to the OPL were associated with disrupted IS/OS or ELM but not faint IS/OS (P < 0.001, P < 0.001, and P = 0.467). The transverse length of disrupted IS/OS at the fovea was correlated with the logarithm of the minimum angle of resolution (logMAR) more than the association between foveal thickness and logMAR (r = 0.49, P < 0.001 vs. r = 0.28, P = 0.002). The ELM descended to the RPE more frequently in eyes with single-lobulated fluorescein pooling in the foveal avascular zone than those with multi-lobulated pooling (P < 0.001). CONCLUSIONS OCT showed that the cystoid spaces in the OPL were accompanied by photoreceptor damage beneath the cystoid spaces in DME.