Although renal disease is the most prominent feature of the
lysosomal storage disease cystinosis, corneal
cystine crystal formation remains a major complication, leading to
photophobia, corneal erosions, and keratopathies. Moreover, the extent of corneal crystal accumulation reflects the course and severity of the disease itself, and the cornea is accessible to direct examination. Therefore, we employed a scoring system, based on a library of
slit-lamp photographs of corneas with increasing crystal densities (0.00-3.00), to assess the degree of crystal accumulation in 170 patients with
nephropathic cystinosis examined at the National Institutes of Health between 1976 and 2000. None of the patients had received topical
cystine-depleting
therapy at the time of the evaluation. In this natural history study, infants in the first year of life had absent or minimal corneal crystals, i.e., a corneal
cystine crystal score (CCCS) of 0 or 0.25. However, the CCCS increased linearly with age, such that every patient had visible crystals by 16 months of age, and plateaued at approximately 3.00 by early adolescence. Longitudinal studies in representative patients support the cross-sectional results. Individuals homozygous for the common 57-kb deletion involving the
cystinosis gene (CTNS) displayed the same course of corneal crystal accumulation as did individuals not bearing the large deletion. Patients with ocular or nonnephropathic
cystinosis had CCCSs that were, in general, half those expected for patients with
nephropathic cystinosis of the same age. Administration of 0.55%
cysteamine eyedrops, given 6 to 12 times per day, dissolved corneal
cystine crystals in 10 representative patients with
nephropathic cystinosis aged 1 to 32 years within 8 to 41 months.