benzoporphyrin-d and Retinal-Neovascularization

Conventional photocoagulation of subretinal membranes induces a non-selective thermal necrosis of retinal and choroidal layers with extensive collateral damage. Hence, this modality is of limited value for the treatment of lesions close to or underneath the fovea. Photodynamic therapy uses systemic administration of a primarily non-toxic photosensitizer with localized light activation of the dye by subthermal light intensities. It provides intraluminal vascular occlusion by means of localized endothelial damage. Enhanced selectivity for neovascularization is achieved by the use of carrier molecules with increased receptor density on proliferating endothelial cells, e.g. low-density lipoproteins (LDL). Benzoporphyrin derivative (BPD), currently in phase I clinical trials, was complexed with LDL. BPD-LDL was used for photodynamic occlusion of the choriocapillary layer in the rabbit model. Subretinal photothrombosis and collateral damage to neural retina, retinal pigment epithelium, Bruch's membrane and large choroidal vessels were documented by ophthalmoscopy, angiography and light and electron microscopic histology. Homogenous vascular occlusion without retinal destruction was induced with light doses as low as 10 J/cm2. Selective neovascular occlusion by photodynamic therapy may allow occlusion of subretinal membranes while preserving retinal integrity and visual function.

Topics: Animals; Microscopy, Electron; Ophthalmoscopy; Photochemotherapy; Porphyrins; Rabbits; Radiation-Sensitizing Agents; Retinal Neovascularization; Retinal Vessels

To evaluate the potential of photodynamic therapy (PDT) using benzoporphyrin derivative (BPD) for occlusion of subretinal neovascular membranes, the authors studied efficiency and collateral damage of PDT-induced photothrombosis in the rabbit choriocapillary layer.. Benzoporphyrin derivative, a new photosensitizer, currently in clinical trials for tumor therapy, was used. Low-density lipoprotein served as a carrier to enhance selective targeting of vascular endothelial cells.. Complete choriocapillary occlusion was achieved at a BPD dose of 2 mg/kg and a radiant exposure as low as 10 J/cm2. When PDT was performed 3 hours after BPD application, damage to the neural retina was minimal. Only inner photoreceptor segments showed mitochondrial swelling probably secondary to choroidal ischemia. Bruch's membrane remained intact. Retinal pigment epithelium was invariably damaged as seen with other photosensitizers.. Compared with photocoagulation BPD-PDT allows endothelial-bound intraluminal photothrombosis, sparing important structures such as neural retina and Bruch's membrane. It may thus provide a more selective treatment of juxtafoveal and subfoveal neovascular membranes.

Topics: Animals; Bruch Membrane; Choroid; Drug Carriers; Endothelium, Vascular; Lipoproteins, LDL; Photochemotherapy; Photoreceptor Cells; Pigment Epithelium of Eye; Porphyrins; Rabbits; Radiation-Sensitizing Agents; Retinal Neovascularization; Retinal Vessels