Nephropathic cystinosis is an autosomal, recessively inherited storage disease in which nonprotein cystine accumulates within cellular lysosomes due to a defect in lysosomal cystine transport. Ocular manifestations include photophobia, crystal deposits in the cornea, conjunctiva, and iris, and depigmentation of the retina. Systemic complications include the Fanconi syndrome and renal failure. Nine years ago cysteamine, a free thiol that depletes cystine from cells, was introduced in the therapy of cystinotic patients. Although patients had improved growth and stabilized renal function, there was no noticeable effect on the accumulation of corneal crystals. Recent studies showed that corneal cells in tissue culture are readily depleted of cystine by the introduction of cysteamine, making feasible the use of topical ophthalmic cysteamine to circumvent the humoral route. After appropriate animal studies to test for complications revealed none, we began a double-masked clinical trial to test the efficacy of topical cysteamine (0.1%) in humans. Fourteen patients of ages less than 3 years were enrolled and randomized to 0.1% cysteamine. Five patients showed a significant decrease in crystals in the cysteamine-treated eyes. In order to test the effects of increasing the concentration of cysteamine eye drops in humans, a toxicity study was performed in rabbits, showing no adverse reactions. The results permitted an increase in the concentration to 0.5% for human use, and all patients receiving 0.1% cysteamine were switched to 0.5%. An additional 5 young patients showed a significant decrease in treated eyes. Thus, of 18 young patients, 10 successfully had the code broken; of the remaining 8, 2 died, 3 discontinued medication, and 3 are still in the trial. Due to the success in the younger patients, this study was expanded to include older patients, 3-31 years of age. The findings have been most exciting: seven patients have shown a significant decrease in crystals in treated eyes as well as improvements in comfort, i.e, relief of pain and photophobia. This study has resulted in significantly improved quality of life for the successfully treated patients.
