Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis

PRÉCIS: Cystinosis is a lysosomal storage disease leading to an accumulation of cystine crystals in several organs. We aim to comprehensively describe chorioretinal cystine crystals via spectral domain optical coherence tomography (SD-OCT) and elaborate a new biomarker for systemic disease control. BACKGROUND/AIMS: Cystinosis is a rare lysosomal storage disease leading to an accumulation of cystine crystals in several organs. This study aims to describe the deposition of retinochoroidal crystals in infantile nephropathic cystinosis and to elucidate their potential value as an objective biomarker for systemic disease control. METHODS: This cross-sectional study was carried out by the University Eye Hospital of the Ludwig-Maximilian University (Munich, Germany) in collaboration with the German Cystinosis Study Group. A complete ophthalmologic examination was performed, along with posterior segment SD-OCT (Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany). Retinochoroidal crystals were graded by employing a novel semiquantitative grading system—the retinochoroidal cystine crystal score (RCCCS). To quantify quality of vision, patients completed a specific questionnaire. A total of 85 eyes of 43 patients with cystinosis were included (mean age 22.3±8.8 years, range 6–39; male:female ratio=23:20). RESULTS: Cystine crystals were detectable in all neuroretinal layers and the choroid, most frequently in the choriocapillaris. The RCCCS was negatively correlated with cysteamine intake (r=0.533, p=0.001) and positively with cystatin C, a stable parameter of renal function (r=0.496, p=0.016). Moreover, the value of the RCCCS affected subjective quality of vision. Genetic analysis indicated pronounced crystal deposition in patients with heterozygous mutations containing the 57-kb-deletion allele of the CTNS gene. CONCLUSION: Ocular cystinosis leads to retinochoroidal crystal accumulation in every stage of the disease. Crystal deposition may be markedly influenced by oral cysteamine therapy. Therefore, the presented SD-OCT based grading system might serve as an objective biomarker for systemic disease control.