Problems with and pitfalls of photodynamic therapy

Objective: To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. Design: Experimental animal study. Animals: Pigmented and nonpigmented rabb its; rhesus monkeys. Intervention: The hydrophilic photosensitizer, mono L-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injec tion into pigmented and nonpigmented rabbits and rhesus monkeys. Laser ligh t was supplied by a red diode laser coupled to a modified slit-lamp biomicr oscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effect s of fundus pigmentation, intraocular pressure, spot focus and defocus, reg ion of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. Main Outcome Measures: Slit-lamp biomicroscopy, fluorescein angiography, li ght and transmission electron microscopy. Results: Fundus pigmentation appeared to be a factor only at the lowest flu ence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in al bino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic ne rve (>60 mmHg). For laser spots either focused or defocused, there were 6 o f 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography, The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 sec onds. Areas of retreatment in rabbits demonstrated more thinning of the neu rosensory retina and loss of photoreceptor outer segments and nuclei than c orresponding areas receiving one treatment. Conclusions: Photodynamic therapy results varied, depending On intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer, Retreatment resulted in progressive th inning of the neurosensory retina with loss of photoreceptor: Outer segment s and nuclei in the rabbit eye. Ophthalmology 2000;107:29-35 (C) 2000 by th e American Academy of Ophthalmology.