Abstract
Purpose: :
Retinal photocoagulation is a proven therapy for proliferative retinopathies and macular edema, but often produces detrimental side effects associated with retinal scarring. We studied changes in retinal structure and function following photocoagulation to elaborate the time course and mechanisms of the retinal healing response, including anatomical restoration and scarring.
Methods: :
Photocoagulation lesions of "Barely Visible", "Mild" and "Moderate" clinical grades were produced in rabbits with a 532-nm laser, using beam diameters of 250 and 400 microns. Lesion size and retinal structural changes were characterized using histology and immunohistochemistry from 1 hour to 4 months. Functional properties were assessed electrophysiologically in-vitro using a multielectrode array.
Results: :
Width of the lesions increased with clinical grade, with histological damage confined to the photoreceptor layer. Enhanced GFAP-immunoreactivity in Muller cells occurred within and around all lesion types from 3 days until 2 months. Significant cellular proliferation was detected in the RPE and choroid, but not in the neurosensory retina. During this time, the acellular zone within smaller, lighter lesions was gradually replaced by photoreceptors, while both larger and more intense lesions exhibited more permanent scarring with incomplete photoreceptor recovery. Initial destruction of photoreceptors was confirmed by the absence of light sensitivity 1 day after treatment. At 1 week these defects significantly decreased in size, and completely disappeared after 2 months in the smaller lesions, while larger lesions retained central scotomata even at 2 months.
Conclusions: :
Retinal photocoagulation with barely visible lesions results in an initial destruction of photoreceptors similar to the more intense standard of care, and thus may offer comparable therapeutic benefit. However, unlike the standard treatment, retinal continuity is restored by apparent shifting of photoreceptors, accompanied by recovery of light response. In smaller lesions this recovery is virtually complete, thus avoiding common detrimental side effects such as microscotomata and scarring. Since damage in all studied lesions was limited to the photoreceptor layer, the difference in healing dynamics is likely related to lesion size. To maintain clinical efficacy by coagulating the same total treatment area, a larger number of smaller-sized lesions would likely be required.
Keywords: retinal connections, networks, circuitry • photoreceptors • laser