Long term effect of Photodynamic Therapy (PDT) using liposomal Benzoporphyrin Derivative (BPD ) on experimental Choroidal Neovascularization (CNV) and normal retina and choroid

Purpose: PDT using BPD has been shown to be effective and selective treatment of CNV. We investigated the long term effect of PDT; including damage to normal retina and choroid and closure of experimental CNV. Methods: CNV was induced in five cynomolgus monkey retinas using Argon laser injury. Liposomal BPD (0.375 mg/kg) was given in (ravenously, either as a bolus injection or as a slow or fast infusion, with timed irradiation after dye injection using laser light at 689 or 692 nm, with 600 mW/cm² irradiance and 150 J/cm² fluence. Normal retina and choroid in two monkeys, was irradiated with the same parameters. Follow up was done weekly with fundus photography and fluorescein angiography (FA) for 4-7 weeks after PDT and tissue was examined by light and electron microscopy. Results: 4 weeks after PDT, 16 of the 23 CNV showed closure by FA. Histopathology showed proliferated RPE overlying the CNV which was composed primarily of RPE derived cells with a few open capillaries. Areas of normal retina and choroid at 6-7 weeks after PDT showed mottled fluorescence on FA without leakage. Histopathology showed normal appearing inner retina, minimal loss in outer nuclear layer with prominent but disorganized outer segments. The RPE repopulated the treatment area with a single layer of variably pigmented RPE cells showing sparse and poorly organized basal infolding. Macrophages with phagolysosomes and pigment granules persisted in the RPE layer. The choriocapillaris and choroid appeared normal. Conclusion: CNV treated with PDT appeared to remain closed out to 4 weeks. Normal retina and choroid demonstrated recovery following PDT. The effect on visual function and long term efficacy in patients, can only be addressed in a clinical trial.