Macular Degeneration: Wu IH

Ibarra MS, Hsu J, Mirza N, Wu IH, Ying GS, Mainster MA, Tolentino MJ. · Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15452076 links to  free full text

Abstract: PURPOSE: To study the risk of adverse events in transpupillary thermotherapy (TTT) for age-related macular degeneration by measuring how laser-induced retinal temperature increase is affected experimentally by subretinal blood, choroidal blood flow, and chorioretinal pigmentation. METHODS: An ultrafine thermocouple technique was developed to measure retinal temperature increase during TTT in albino and pigmented rabbit eyes. TTT was performed with 60-second, 0.78-mm spot size, 810-nm infrared diode laser exposures with power settings ranging from 50 to 950 mW. Intraretinal and subretinal temperature increases were measured in pigmented and albino rabbits, with or without subretinal blood and choroidal blood flow. RESULTS: Threshold power settings for visible lesions in albino and pigmented rabbits were 950 and 90 mW, respectively, corresponding to retinal temperature increases of 11.8 degrees C and 5.28 degrees C, respectively. Power settings required to produce threshold lesions in albino rabbits caused retinal temperature increases in pigmented rabbits that were five times higher than in the albino rabbits. Temperature increases in albino rabbits were 1.5 times higher with subretinal blood than without it. Choroidal blood flow generally did not affect measured retinal temperature increases. CONCLUSIONS: The results confirm prior theoretical recommendations that clinicians should consider decreasing TTT power settings in darkly pigmented eyes and proceed with caution in those with subretinal hemorrhage or pigment clumping.

Tolentino MJ, Brucker AJ, Fosnot J, Ying GS, Wu IH, Malik G, Wan S, Reich SJ. · Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA. · Retina. · Pubmed #15076954 No free full text.

Abstract: PURPOSE: To determine the safety and efficacy of small interfering RNA (siRNA) directed against vascular endothelial growth factor (VEGF) in a nonhuman primate model of laser-induced choroidal neovascularization (CNV). METHODS: Each animal received laser rupture of Bruch's membrane to induce CNV in both eyes. Each animal was then randomized to receive 0.05 mL of either vehicle alone or VEGF siRNA at 70 microg, 150 microg, or 350 microg in both eyes by intravitreal injection. Eyes were monitored weekly by ophthalmic examination, color photography, and fluorescein angiography for 36 days after laser injury. Electroretinograms were measured at baseline and at 5 weeks after laser. CNV on fluorescein angiograms were measured for area and graded for clinically significant leakage in a standardized, randomized, and double-masked fashion on days 15, 22, 29, and 36 after laser. RESULTS: VEGF siRNA did not cause any change in electroretinographic, hemorrhage, inflammation, or clinical signs of toxicity. A single administration of VEGF siRNA significantly inhibited growth of CNV and attenuated angiographic leakage in a dose-dependent manner. CONCLUSION: Intravitreal injection of VEGF siRNA is capable of inhibiting the growth and vascular permeability of laser-induced CNV in a nonhuman primate in a dose-dependent manner. This study demonstrates preclinical proof of a principle that supports proceeding to clinical studies of VEGF siRNA in patients with exudative age-related macular degeneration.