Optimizing riboflavin/ultraviolet-a corneal collagen cross-linking for the treatment of progressive keratoconus
Sylvestre, Daniel Joseph
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Patients with keratoconus exhibit a biomechanically weakened cornea which loses its proper shape and thereby loses its refractive power. It is usually progressive, beginning with poor visual acuity and eventually necessitating corneal transplant. The cause is likely multifactorial, but involves the weakening of the collagen structure of the corneal stroma, resulting in characteristic thinning and conical distortion. Collagen cross-linking is the first treatment to demonstrate efficacy in halting the progression of the disease. UVA radiation is used to activate riboflavin and photochemically induce cross-linking reactions among collagen and proteoglycans within the stroma, thereby stiffening and strengthening the tissue, and preventing further loss of shape. The current standard treatment, which gained FDA approval less than one year ago, has proven to be efficacious, but has been modified very little since pioneering experiments. Optimization aims to maximize clinical effect while maintaining safety and reducing total treatment time. Major procedural modifications involve increasing light intensity over a reduced exposure duration, and varying the method of delivering riboflavin to the stroma. Theoretical modeling, informed by and scaled to experimental results, has the potential to predict clinical effect as a function of treatment parameters, enabling tailoring of individual treatments to the specific needs of each patient.