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Anterior Ocular Toxicity of Intravitreous Melphalan for Retinoblastoma. IMPORTANCE: Intravitreous injections of melphalan hydrochloride are increasingly used in the treatment of vitreous seeding of retinoblastoma. Although this technique can save eyes otherwise destined for enucleation, ocular salvage may be accompanied by local toxic effects. Posterior segment toxic effects in this context are well established. This report describes the toxic effects on the anterior segment following intravitreous administration of melphalan. OBSERVATIONS: Our clinic cohort included 76 patients who received intravitreous injections of melphalan at Memorial Sloan Kettering Cancer Center from September 12, 2012, through April 15, 2015; data analysis was performed from April 15 through May 15, 2015. We report a series of 5 patients from this cohort who developed anterior segment toxic effects. These abnormalities were found at the injection site or within the meridian of the injection and included a traumatic cataract following an injection at an outside hospital, iris depigmentation and thinning, iris recession with retinal necrosis and hypotony, a filtering conjunctival bleb, and focal scleromalacia with localized pigmentation. CONCLUSIONS AND RELEVANCE: Intravitreous injection of melphalan may result in toxic effects on the anterior segment of the eye, in addition to retinal abnormalities, and appears to be more common in the meridian of the injection where the drug concentration is highest.