A RANDOMIZED CLINICAL-TRIAL OF TOPICAL CYSTEAMINE DISULFIDE (CYSTAMINE) VERSUS FREE THIOL (CYSTEAMINE) IN THE TREATMENT OF CORNEAL CYSTINE CRYSTALS IN CYSTINOSIS

In nephropathic cystinosis, corneal cystine crystals cause severe phot ophobia and corneal erosions. Topical cysteamine dissolves these cryst als, but cannot be marketed because it rapidly oxidizes to the disulfi de form, cystamine, at room temperature. Since cystamine itself could be used commercially, we compared the efficacy of cystamine and cystea mine with respect to cystine crystal dissolution in a randomized, doub le-masked clinical trial. One eye each of 14 patients with cystinosis was randomized to either cystamine or cysteamine, 0.5%, with 0.01% ben zalkonium chloride; the companion eye was treated with the alternate p reparation. Corneal crystals were photographed and a density score was assigned to each slide based on 13 standard slides. After 8-20 months , 6 patients showed significant reduction of the corneal crystal score in only one eye. In each case, the improved eye was the cysteamine-tr eated eye. Theoretically, cysteamine should dissolve both intracellula r and extracellular crystals, whereas cystamine should dissolve only i ntracellular crystals because it must first be reduced to the free thi ol by the cytoplasmic-reducing environment. Hence, the lack of efficac y of the disulfide cystamine suggests that some corneal cystine crysta ls in cystinosis patients are extracellular, and that another form of stable, topical cysteamine must be developed for cystinosis patients, (C) 1998 Academic Press.