Quantifying Corneal Crystal Deposition Patterns In Ocular Cystinosis Using Densitometry

Cystinosis is a genetic, multisystem metabolic disease presenting in infancy, characterised by the accumulation of cystine crystals in the corneal stroma, causing severe, persistent photophobia. Topical cysteamine remains the only treatment for reducing corneal crystals, but its administration, up to 10 times daily, poses compliance issues. Monitoring corneal crystals is therefore essential, yet currently only possible with subjective scoring systems. Corneal densitometry is an objective, well-tolerated imaging modality quantifying corneal transparency. This study evaluates the utility of corneal densitometry for measuring corneal cystinosis progression, focusing on age-related changes across different corneal regions compared to controls.

Royal Manchester Eye Hospital, United Kingdom. This is a tertiary eye hospital with a specialist cystinosis service.

This retrospective cohort-control study analysed corneal densitometry readings obtained using the Pentacam device. Densitometry values were recorded for the anterior, central, and posterior layers and for the 0-2mm (central), 2-6mm (mid-peripheral), and 6-10mm (peripheral) zones in all cystinosis patients, as well as from age-matched controls. Statistics were performed using IBM SPSS Statistics (Version 31.0.1.0), with a significance level set at p<0.05. A linear mixed model (LMM), accounting for repeated measures, included a three-way interaction of disease status (patient or control), age, and corneal region.

252 scans from 52 patients (age range: 5–48), and 146 scans from 73 controls (age range: 10-50) were included. LMM revealed that patients exhibited a significantly higher increase in corneal densitometry compared to controls (0.335 vs 0.072 GSU/year; p<0.01). A significant three-way interaction was observed (p<0.05), indicating that age-related changes in densitometry differed by anatomical zone between groups. While patients demonstrated a higher baseline densitometry in the periphery, this region did not significantly diverge further over time (p=0.7). In contrast, the most pronounced age-related divergence occurred in the anterior (p=0.01) and central 0–2mm (p=0.03) zones, whereas the posterior zone remained statistically stable (p=0.8).

This is the largest cohort of cystinosis adult and paediatric patients in whom corneal densitometry has been performed. Densitometry reflects established regional patterns of corneal crystal deposition in ocular cystinosis, with greater involvement of the peripheral, anterior and central cornea, with relatively sparing of the posterior region. Age-related changes in densitometry significantly differ between patients and controls in a region-specific manner, emphasising the importance of anatomical localisation when interpreting disease burden. Limited studies have evaluated corneal densitometry in cystinosis; this study offers further validation of this objective tool for monitoring ocular cystinosis progression and treatment adherence.