[Long-term outcome of radiation therapy for exudative age-related macular degeneration in Japan].

PURPOSE: To evaluate the long-term outcome of radiation therapy in eyes with exudative age-related macular degeneration (AMD). METHODS: Eighty eyes of 80 patients (54 men and 26 women) with exudative AMD, which underwent radiation therapy with a photon beam of 20 Gy (2 Gy per day for 10 days) between 1998 and 2003, were retrospectively reviewed. Average age was 69 +/- 8.1 and follow-up period was 66 months. Best-corrected visual acuity (BCVA), additional therapies and complications were assessed. RESULTS: Mean duration till the best value of postoperative BCVA could be reached was 10 months. The best BCVA was improved in 20 eyes (25.0%), stabilized in 56 eyes (70.0%), and deteriorated in 4 eyes (5.0%). On the final visit visual improvement was observed in 9 (11.3%), stabilization in 25 (31.3%), and deterioration in 46 eyes (57.5%). Additional therapies for exudative AMD were performed in 24 eyes (30.0%). Severe subretinal hemorrhage was observed in 9 eyes (11.3%), which resulted in severe vision loss despite additional vitrectomy. CONCLUSIONS: Low-dose radiation therapy for exudative AMD achieved short-term efficacy but seemed less effective in the long-term.

Suppression of laser-induced choroidal neovascularization by a CCR3 antagonist.

PURPOSE: To evaluate the efficacy of a novel CCR3 antagonist for laser injury-induced choroidal neovascularization (CNV) in mice. METHODS: We evaluated YM-344031, a novel and selective small-molecule CCR3 antagonist. CNV was induced by laser injury in C57BL/6J mice, and its volume was measured after 7 days by confocal microscopy. Leakage from the CNV was also measured after 7 days by fluorescein angiography. The CCR3 antagonist was administered by gavage at 1 hour before and 1 day after the laser injury, or intravitreous injection immediately after the laser injury. After the laser injury, ELISA, Western blot analysis, and real-time RT-PCR for VEGF-A expression in the RPE/choroid, and immunohistochemistry for CCR3, CCL11, Ki67, and Rac1 was performed. RESULTS: Both oral administration and intravitreous injection of YM-344031 significantly suppressed the CNV volume (P < 0.0001 and P < 0.01, respectively). Pathologically significant leakage was significantly less common in YM-344031-injected mice (P < 0.0001). The mean VEGF protein level was significantly increased in vehicle-injected eyes after the laser injury (P < 0.05). Although the YM-344031-injected eyes did not show VEGF-A suppression after the laser injury, VEGF164 mRNA upregulation was significantly suppressed in YM-344031-injected mice (P < 0.05), and intravitreous injection of YM-344031 appeared to suppress CCR3, CCL11 (eotaxin), Ki67, and Rac1 expression after the laser injury. CONCLUSIONS: The present data suggest that the CCR3 antagonist YM-344031 can suppress CNV, via suppression of the upregulation of VEGF164 mRNA in VEGF isoform after the laser injury. Although our findings may warrant further investigation, YM-344031 may have potential as a new therapy for age-related macular degeneration.

Suppression of laser-induced choroidal neovascularization by nontargeted siRNA.

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.

Copper foreign body in the lens without damage of iris and lens capsule.

PURPOSE: The objective is to report a rare case of asymptomatic penetrating injury with a copper foreign body found during an examination for cataract surgery. METHOD: A case report. RESULTS: A 73-year-old woman had vision loss. Examination by pupil dilation disclosed a dark-brown metallic mass located under the anterior capsule of the lens, as well as nuclear sclerosis of the lens. Although no history of traumatic injury was reported by the patient, careful examination revealed a dot corneal opacity. This finding, and the past history of the patient that she had worked in the fabrication of copper wire, suggested previous penetrating injury. The iris had no scar. No inflammatory reaction was observed in the posterior segment of the eye. Phacoemulsification and implantation of an intraocular lens were performed. After continuous curvilinear capsulorrhexis (CCC), the foreign body was extracted with a microforceps. The anterior capsule overlying the foreign body was intact, with normal light reflex. Qualitative analysis showed that the foreign body extracted contained pure copper at the center. Nevertheless, visual acuity of the right eye improved from 20/50 to 20/20 without any copper-related retinal damage. CONCLUSION: In this case, copper localized under the anterior capsule of the lens had been able to stay in the eye without causing severe inflammatory reaction.