Jurriaan Brekelmans1,2, Alexandra Goz2,3, Mor M Dickman1, Alexander Brandis4, Xiaomeng Sui5, H Daniel Wagner5, Rudy M M A Nuijts1, Avigdor Scherz2, Arie L Marcovich2,3. 1. University Eye Clinic Maastricht, Maastricht, The Netherlands. 2. Department of Plant Sciences and Environmental Health, the Weizmann Institute of Science, Rehovot, Israel. 3. Department of Ophthalmology Kaplan Medical Center, Rehovot, Israel. 4. Department of Biological Services, the Weizmann Institute of Science, Rehovot, Israel. 5. Department of Materials and Interfaces, the Weizmann Institute of Science, Rehovot, Israel.
Abstract
Purpose: To determine the long-term safety and efficacy of WST-D/near-infrared (NIR) corneal stiffening. Methods: One eye of 23 New Zealand White rabbits was de-epithelialized mechanically followed by topical application of 2.5 mg/mL WST11, combined with dextran-500 (WST-D) for 20 minutes. Subsequently, samples were irradiated with a NIR (755 nm) laser at 10 mW/cm2 for 30 minutes. Untreated fellow eyes served as controls. One week (n = 4), 1 month (n = 6), 4 months (n = 9), or 8 months (n = 4) after treatment rabbits were euthanized. Corneal strips were cut in superior-inferior direction for extensiometry testing (1, 4, and 8 months), and histologic sections were prepared for evaluation of keratocyte distribution (1 week and 8 months). Results: Elastic modulus after treatment was significantly higher than in paired controls (16.0 ± 2.3 MPa versus 9.6 ± 3.6 MPa [P = 0.008], 18.1 ± 4.5 MPa versus 12.6 ± 2.3 MPa [P = 0.003], and 18.6 ± 3.6 MPa versus 14.2 ± 3.6 MPa [P = 0.010], at 1, 4, and 8 months, respectively). A significant decrease in keratocyte count at the anterior stroma was observed directly after treatment (1.5 ± 1.7 vs. 19.0 ± 4.1 [P = 0.002]). At 8 months keratocyte repopulation appeared completed, with similar distribution in treated and untreated corneas (15.9 ± 1.1 vs. 14.5 ± 2.5 [P = 0.562]). Corneal thickness was comparable between treated and untreated corneas at all time points. Conclusions: WST-D/NIR treatment resulted in significant and persistent long-term increase in corneal stiffness. Initial keratocyte apoptosis in the anterior stroma is followed by repopulation to normal level at 8 months after treatment. The safe nature of NIR light allows treatment of corneas of any thickness without endangering corneal endothelium or deeper ocular structures, potentially benefiting patients deemed unsuitable for riboflavin/UV-A cross-linking.
Purpose: To determine the long-term safety and efficacy of WST-D/near-infrared (NIR) corneal stiffening. Methods: One eye of 23 New Zealand White rabbits was de-epithelialized mechanically followed by topical application of 2.5 mg/mL WST11, combined with dextran-500 (WST-D) for 20 minutes. Subsequently, samples were irradiated with a NIR (755 nm) laser at 10 mW/cm2 for 30 minutes. Untreated fellow eyes served as controls. One week (n = 4), 1 month (n = 6), 4 months (n = 9), or 8 months (n = 4) after treatment rabbits were euthanized. Corneal strips were cut in superior-inferior direction for extensiometry testing (1, 4, and 8 months), and histologic sections were prepared for evaluation of keratocyte distribution (1 week and 8 months). Results: Elastic modulus after treatment was significantly higher than in paired controls (16.0 ± 2.3 MPa versus 9.6 ± 3.6 MPa [P = 0.008], 18.1 ± 4.5 MPa versus 12.6 ± 2.3 MPa [P = 0.003], and 18.6 ± 3.6 MPa versus 14.2 ± 3.6 MPa [P = 0.010], at 1, 4, and 8 months, respectively). A significant decrease in keratocyte count at the anterior stroma was observed directly after treatment (1.5 ± 1.7 vs. 19.0 ± 4.1 [P = 0.002]). At 8 months keratocyte repopulation appeared completed, with similar distribution in treated and untreated corneas (15.9 ± 1.1 vs. 14.5 ± 2.5 [P = 0.562]). Corneal thickness was comparable between treated and untreated corneas at all time points. Conclusions: WST-D/NIR treatment resulted in significant and persistent long-term increase in corneal stiffness. Initial keratocyte apoptosis in the anterior stroma is followed by repopulation to normal level at 8 months after treatment. The safe nature of NIR light allows treatment of corneas of any thickness without endangering corneal endothelium or deeper ocular structures, potentially benefiting patients deemed unsuitable for riboflavin/UV-A cross-linking.
Authors: Jurriaan Brekelmans; Mor M Dickman; Shwetabh Verma; Samuel Arba-Mosquera; Ruth Goldschmidt; Alexandra Goz; Alexander Brandis; Tos T J M Berendschot; Isabelle E Y Saelens; Arie L Marcovich; Avigdor Scherz; Rudy M M A Nuijts Journal: Acta Ophthalmol Date: 2021-09-17 Impact factor: 3.988
Authors: S Hayes; N Aldahlawi; A L Marcovich; J Brekelmans; A Goz; A Scherz; R D Young; J S Bell; D P O'Brart; R M M A Nuijts; K M Meek Journal: Sci Rep Date: 2020-06-17 Impact factor: 4.379
Authors: Jurriaan Brekelmans; Judith Veugen; Koen Rieff; Mor M Dickman; Alexa Goz; Petra Wolffs; Alexander Brandis; Tos T J M Berendschot; Rudy M M A Nuijts; Avigdor Scherz; Arie L Marcovich Journal: Transl Vis Sci Technol Date: 2020-09-03 Impact factor: 3.283