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Aims-To clarify the developmental mechanism and critical period for the uncommon complex of Peters' anomaly and persistent hyperplastic primary vitreous (PHPV). Methods-Two eyes with Peters' anomaly and PHPV were histologically examined by serial section. One eye was enucleated at age 7 months (case 1) and the other at age 4 months (case 2) owing to severe anterior staphyloma. Results-In both eyes, defects in the endothelium, Descemet's membrane, and posterior stroma were observed in the central cornea, and the degenerative lens adhered to the posterior surface of the defective corneal stroma. Also, in both eyes, the anterior chamber space was not formed and the undiVerentiated iris stroma adhered to the posterior surface of the peripheral cornea. Mesenchymal tissue containing melanocytes was observed behind the degenerative lens, and the pigment epithelium was absent at the lower nasal side of the ciliary body in case 1. In case 2, mesenchymal tissue containing scattered melanocytes in the vitreous cavity was seen on the posterior retina. Based on the histological findings, both cases were diagnosed as Peters' anomaly caused by the faulty separation of the lens vesicle, PHPV, maldevelopment of the iris and ciliary body, and goniodysgenesis. Conclusion-Migratory disorders of neural crest cells from 4 to 7 weeks of gestation may be responsible for various ocular anomalies including Peters' anomaly and PHPV, as observed in these cases.

Peters' anomaly accompanying corneolenticular adhesion and/or other ocular anomalies should be evaluated for the presence of systemic anomalies.

PURPOSE. To investigate the effect of nontargeted siRNAs on vascular leakage and vascular endothelial growth factor (VEGF)-A expression in the development of choroidal neovascularization (CNV). METHODS. Nontargeted siRNAs were 21-nt (nucleotides) siRNA-Luc (Luciferase) or 16-nt siRNA-Luc. Targeted 21-nt siRNA-Vegfa or phosphate-buffered saline (PBS) was used for comparison. Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice; 7 days later, vascular leakage was determined by fluorescein angiography, and CNV volumes were measured by confocal microscopy. Expression of VEGF-A in the retinal pigment epithelium (RPE)/choroid was quantified by ELISA 3 days after photocoagulation. RESULTS. Pathologically significant leakage developed in most of the 16nt-siRNA-Luc- or PBS-injected mice but in significantly fewer 21nt-siRNA-Luc- and 21nt-siRNA-Vegfa-injected mice (P = 0.0004, P = 0.0001, respectively). CNV volume in 21-nt siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes was significantly lower than in PBS-injected eyes (P = 0.0124, P = 0.0040, respectively). CNV volume was not suppressed by 16-nt siRNA-Luc injection (P = 0.7700). The mean VEGF protein level decreased significantly in the 21nt-siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes compared with PBS-injected eyes 3 days after laser photocoagulation (P = 0.0011, P = 0.0063, respectively). The 16nt-siRNA-Luc-injected eyes did not show VEGF-A suppression 3 days after laser photocoagulation (P = 0.3177). Between 21-nt siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes, there were no significant differences in CNV volume, the VEGF-A level, or pathologic leakage detected by fluorescein. CONCLUSIONS. These data suggest that nontarget 21nt-siRNA can suppress laser-induced choroidal neovascularization anatomically and functionally through VEGF suppression.

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Purpose Abnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD. Methods Sixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as “within,” “close,” and “distant,” based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated. Results In Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF. Conclusion In Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

Aims: The purpose of this study was to evaluate the effect of pulse duration on the expression of inflammatory cytokines in the murine retina after laser photocoagulation treatment with a PASCAL® pattern scan laser photocoagulator and conventional laser treatment. Methods: Retinal scatter laser photocoagulation was performed on C57BL/6J mice using a short pulse (10 ms) with a PASCAL laser or conventional settings (100 ms) with a multicolor laser. Eyes were enucleated before treatment (control) and 1 day, 3 days and 7 days after treatment. The levels of inflammatory cytokines (i.e., VEGF, MCP-1, RANTES and IL-6) in the retina/choroid were quantified by an ELISA. The expression patterns of VEGF and macrophages (i.e., F4/80) in the retina/choroid were evaluated by immunohistochemistry. Results: The levels of RANTES, IL-6 and MCP-1 after PASCAL and conventional laser treatments were significantly elevated compared with controls (p < 0.05). Conventional laser treatment, but not PASCAL treatment, resulted in the up-regulation of VEGF. RANTES and IL-6 levels on day 1 and MCP-1 levels on day 3 in the sensory retina were also significantly up-regulated with conventional laser treatment compared with PASCAL treatment (p < 0.05). Immunohistochemical analysis showed that PASCAL treatment was associated with lower VEGF and F4/80 expression levels compared with conventional laser treatment. Conclusions: Our data suggested that the short pulse duration induced fewer inflammatory cytokines in the sensory retina compared with the conventional pulse duration. Short pulse laser photocoagulation with the PASCAL may prevent macular edema after panretinal photocoagulation.

To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). Methods Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline