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Application of optical coherence tomography and optical path length method for monitoring corneal thickness and refractive index change during corneal cross-linking.

Corneal cross-linking (CXL) using UVA irradiation with a riboflavin photosensitizer has emerged as a new treatment paradigm for corneal ectatic disorders. The thickness threshold for protection of intraocular structures has often been challenged with ongoing developments, and corneal thinning becomes an important safety concern, especially for patients with thin corneas. In this study with an ex vivo bovine eye model, we monitored corneal thinning and corneal refractive index changes using optical coherence tomography (OCT) integrated with an adaptation of the optical path length method. CXL experiments were performed based on the standard protocol that includes removal of the corneal epithelium to facilitate diffusion of riboflavin into the stroma. The corneal stromal thickness and group refractive index were measured by a 1310 nm Fourier-domain OCT imaging system at three critical points of the procedure: immediately after epithelial removal, after 30 min riboflavin instillation, and after 30 min UVA irradiation with continuing instillation. We found that the refractive index of the bovine cornea changed significantly from epithelial removal to riboflavin instillation and UVA irradiation, increasing from 1.377±0.005 (mean±standard deviation) after de-epithelization to 1.387±0.003 after 30 min instillation and 1.388±0.008 after subsequent irradiation. The corneas also underwent a considerable decrease (10%-20%) in stromal thickness with thinning of 95±29  μm (mean±standard deviation) after riboflavin instillation and a further decrease (∼5%) with thinning of 42±19  μm after UVA irradiation. Our study highlights the importance of corneal thickness monitoring during CXL, especially after riboflavin instillation when the decrease is the largest, to avoid delivering endothelial cytotoxic doses. An increase in refractive index heightens the concern for corneal thinning and the need for careful monitoring as a safety precaution.