Assessment of the Predictive Ability of Theranostics for Corneal Cross-linking in Treating Keratoconus: A Randomized Clinical Trial.

Abstract

To validate the ability of theranostic imaging biomarkers in assessing corneal cross-linking (CXL) efficacy in flattening the maximum keratometry (K_max) index. Prospective, randomized, multicenter, masked clinical trial (ClinicalTrails.gov identifier, NCT05457647). Fifty patients with progressive keratoconus. Participants were stratified to undergo epithelium-off (25 eyes) and epithelium-on (25 eyes) CXL protocols using an ultraviolet A (UV-A) medical device with theranostic software. The device controlled UV-A light both for performing CXL and assessing the corneal riboflavin concentration (riboflavin score) and treatment effect (theranostic score). A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epithelium-off and epithelium-on protocols, respectively. All eyes underwent 9 minutes of UV-A irradiance at 10 mW/cm². The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to classify eyes correctly and predict a K_max flattening at 1 year after CXL. Other outcome measures included change in K_max, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction and central corneal thickness 1 year after CXL. Accuracy and precision of the theranostic imaging biomarkers in predicting eyes that had >0.1 diopter (D) of K_max flattening at 1 year were 91% and 95%, respectively. The K_max value significantly flattened by a median of -1.3 D (IQR, -2.11 to -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 logarithm of the minimum angle of resolution (logMAR; IQR, -0.3 to 0.0 logMAR [P < 0.001] and -0.2 to 0.0 logMAR [P < 0.001], respectively). No significant changes in endothelial cell density (P = 0.33) or central corneal thickness (P = 0.07) were noted 1 year after surgery. The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epithelium-off and epithelium-on CXL protocols. Concentration of riboflavin and its UV-A light mediated photoactivation in the cornea are the primary factors determining CXL efficacy. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.