A new gel formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis: The Cystadrops OCT-1 study.

Abstract

Purpose: To establish the safety and efficacy of a new gel formulation of cysteamine hydrochloride (CH) eye drops, for the treatment of corneal complications of nephropathic cystinosis.

Methods: Eight patients with infantile nephropathic cystinosis treated with CH 0.1% eye drops were enrolled in this open label dose response study. Patients were treated, in both eyes, with the control CH 0.1% eye drops formulation 4 times daily for one month and then switched to Cystadrops® at the same dose frequency. Based on clinical ocular findings, the dose regimen was adapted at D30 and D90 in order to decrease the frequency of instillation. After D90, this dose frequency was maintained, except in cases of crystal density worsening. Patients had a follow up visit every 6 months during 48 months. Safety assessment consisted of adverse events and serious adverse events monitoring and recording at each visit. For the efficacy study, the primary endpoint was the corneal cystine crystal density measured with an in vivo confocal microscopy (IVCM) score.

Results: All patients completed the study. During the 4-year study period, neither serious adverse events nor significant adverse events related to the study drug were reported. After switching for Cystadrops®, the IVCM total score decreased from baseline to D90 by a mean of 28.6 ± 17.5 % (p<0.001). From D90 to M48, IVCM total score remained stable and significantly decreased as compared to D1 despite a reduced dose regimen from D90. At M48, mean IVCM total score was 8.13 ± 4.15, decreased by a mean 29.9 ± 26.29% from D1 (p=0.001), with a reduced number of instillations compared to D1. IVCM total score and photophobia were significantly correlated (p=0.04).

Conclusions: This study provides evidence that Cystadrops® gel has a good safety profile over a long follow-up period and may be superior to the CH 0.1% formulation in terms of efficacy.

Keywords: 479 cornea: clinical science • 550 imaging/image analysis: clinical • 503 drug toxicity/drug effects