Theranostic‐guided corneal cross‐linking: Preclinical evidence on a new treatment paradigm for keratoconus

• Published in: Journal of biophotonics Vol. 15; no. 12; pp. e202200218 - n/a
• Main Authors: Lombardo, Giuseppe, Bernava, Giuseppe Massimo, Serrao, Sebastiano, Lombardo, Marco
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 01.12.2022; Wiley Subscription Services, Inc
• Subjects: Biomechanics; Cornea; Cornea - diagnostic imaging; Corneal Cross-Linking; Cross-Linking Reagents; Human performance; Humans; Irradiance; Keratoconus; Keratoconus - diagnostic imaging; Keratoconus - drug therapy; Photosensitizing Agents - pharmacology; Photosensitizing Agents - therapeutic use; Precision Medicine; Riboflavin; Riboflavin - pharmacology; Riboflavin - therapeutic use; Stiffening; Stiffness; theranostics; Therapy; Ultraviolet Rays; Viscoelasticity; Vitamin B; theranostics; keratoconus; riboflavin; corneal cross-linking
• ISSN: 1864-063X; 1864-0648
• DOI: 10.1002/jbio.202200218

Theranostics is an emerging therapeutic paradigm of personalized medicine; the term refers to the simultaneous integration of therapy and diagnostics. In this work, theranostic‐guided corneal cross‐linking was performed on 10 human sclero‐corneal tissues. The samples were soaked with 0.22% riboflavin formulation and underwent 9 minutes UV‐A irradiance at 10 mW/cm2 using theranostic device, which provided both a measure of corneal riboflavin concentration and a theranostic score estimating treatment efficacy in real time. A three‐element viscoelastic model was developed to fit the deformation response of the cornea to air‐puff excitation of dynamic tonometry and to calculate the mean corneal stiffness parameter before and after treatment. Significant correlation was found between the theranostic score and the increase in mean corneal stiffness (R = 0.80; P < .001). Accuracy and precision of the theranostic score in predicting the induced corneal tissue stiffening were both 90%. The riboflavin concentration prior to starting the UV‐A photo‐therapy phase was the most important variable to allow corneal cross‐linking to be effective. Theranostic UV‐A light mediated imaging and therapy enables the operator to adopt a precise approach for achieving highly predictable biomechanical strengthening on individual corneas. Theranostics is an emerging therapeutic paradigm of personalized and precision medicine that performs therapy guided by molecular diagnostic imaging. The technology was implemented in a UV‐A medical device and showed to efficiently drive the operator in performing personalized riboflavin/UV‐A corneal cross‐linking for treatment of corneal disorders with high accuracy and precision through light activated image‐guided drug therapy.