Retinal Toxicity of Intravitreal Polyethylene Glycol 400.

Purpose: Polyethylene glycol (PEG)-400 is a clear, colorless viscous liquid that readily dissolves many hydrophobic drugs. It is a widely used commercial solvent and vehicle for many pharmaceutical and cosmetic products. The purpose of this study is to investigate the intravitreal safety of PEG-400 to determine its suitability as a potential vehicle for intraocular drug delivery. Methods: Six healthy, male, Dutch Belted rabbits, weighing between 2.0 and 3.0kg, were used for this experiment. The left eye of each animal received a single 0.1mL intravitreal injection of PEG-400. Complete eye exams and dark- and light-adapted electroretinograms (ERG) were obtained at baseline and at 1 and 4 weeks after injection. After the 4-week ERG was completed, animals were euthanized, eyes were enucleated, and histology and transmission electron microscopy (TEM) were performed. Results: Ophthalmic examinations demonstrated diffuse signs of retinal degeneration and cataract formation in all 6 eyes injected with PEG-400, which was apparent at 1 week, but more evident by 4 weeks. Photopic and scotopic ERG studies demonstrated significant reduction in amplitudes at 1 and 4 weeks after injection compared to baseline. Histopathological and TEM analysis of eyes demonstrated both inner and outer retinal atrophy. Conclusion: Intravitreal injection of PEG-400 resulted in severe ocular toxicity.