Retinal Toxicity of Intravitreal Melphalan in Albino Rabbits

Abstract

Background: Intravitreal melphalan injections have been used for treating retinoblastoma with vitreous seeds. The aim of this study was to evaluate the safety margins for intravitreal melphalan, using clinical observations, electrophysiological testing and morphological observations. Methods: In this experimental study, 18 albino rabbits, were treated with intravitreal injection of 0.1 ml melphalan solution to the right, experimental eye, and were divided into 4 dose groups: 5 μg (N=4); 15 μg (N=4); 30 μg (N=5); 60 μg (N=5). The left, control eye, of each rabbit was injected with 0.1 ml saline. Clinical examination, electroretinography (ERG) and visual evoked potentials (VEP) were conducted at baseline and periodically throughout the 4-week follow-up. The eyes were then enucleated and the retinas were prepared for histology and glial fibrillary acidic protein (GFAP) immunocytochemistry. Results: No clinical, ERG, or histologic damage were found in rabbits treated with 5 μg melphalan. However, expression of glial fibrillary acidic protein was detected in retinal Muller cells of the experimental eyes and not in the control eyes. With all other doses of melphalan, dose-dependent funduscopic changes, ERG amplitude, histological damage and GFAP expression were found. VEP responses were similar between the experimental eyes and control eyes of all rabbits regardless of melphalan dose injected into the eye, indicating no change in retinal output. Conclusions: These findings indicate that intravitreal melphalan dose of 5 μg in rabbits, approximately equivalent to 10 μg in human, appears to be safe, but induce a mild stress to the retina. However, higher doses are toxic, and their utilization should be executed with caution, particularly if visual potential exists.