CYSTEAMINE EYEDROPS DISSOLVE CORNEAL CRYSTALS IN YOUNG PATIENTS WITH NEPHROPAT11IC CYSTINOSIS

Abstract

In nephropathic cystinosis, corneal cyatine crystals are present by one year of age and increase in density with time. The crystals are blamed for the photophobia and corneal erosions which plague older patients. He studied the safety and efficacy of eyedrops containing cysteamine, a cystine-depleting agent, in dissolving corneal crystals. First, cystinotic corneal stromal cells, cultured from a penetrating keratoplasty specimen, were depleted of 82% of their cystine by 1 mM cysteamine within 30 min. Second, rabbits treated for 8h per day for 3 weeks with 50 mM cysteamine eyedrops in a placebo-controlled, masked study exhibited no toxicity. Third, two cystinotic children (<2 years old) received cysteamine eyedrops (10 mM, hourly while awake) in a double-masked, placebo controlled trial. Normal saline was put in the opposite eye. In both children, biomicroscopic examination and silt lamp photography documented : a) Bilateral increase of crystals in the cornea between the start of oral cysteamine and the start of the eyedrop protocol; b) Nearly complete clearing of crystals from the cysteamine-treated corneas after 4-5 months of eyedrops; c) Progression or lack of regression in the corneas not treated with cysteamine. No toxicity was observed, and we are now treating the placebo eyes with cysteamine and enrolling older patients. This represents the first in vivo demonstration of crystal dissolution by cysteamine in cystinosis, and suggests that oral cysteamine, if adequately delivered to target tissues, might dissolve crystals in other cystinotic organs also.