High-Fluence Accelerated Epithelium-Off Corneal Cross-Linking Protocol Provides Dresden Protocol–Like Corneal Strengthening

PURPOSE: To assess whether optimized technical settings for accelerated epithelium-off corneal cross-linking may lead to increases in biomechanical stiffness similar to the benchmark 30-minute epithelium-off Dresden protocol. METHODS: Three-hundred porcine eyes were divided equally into six groups for analysis. All samples underwent epithelial debridement and soaking with 0.1% iso-osmolar riboflavin solution for 20 minutes. Corneal cross-linking (CXL) was performed using epithelium-off protocols varying in acceleration and total fluence (intensity in mW/cm² * time in minutes, total fluence in J/cm²): standard (S)-CXL (3*30, 5.4), accelerated (A)-CXL (9*10, 5.4), A-CXL (9*13′20″, 7.2), A-CXL (18*6′40″, 7.2), and A-CXL (18*9′15″, 10). Control corneas were not irradiated. The elastic modulus of 5-mm wide corneal strips was measured as an indicator of corneal stiffness. RESULTS: All irradiated groups had significantly higher elastic modulus than controls (P < 0.05), with a stiffening effect of 133% S-CXL (3*30, 5.4), 122% A-CXL (9*10, 5.4), 120% A-CXL (9*13′20″, 7.2), 114% A-CXL (18*6′40″, 7.2) and 149% A-CXL (18*9′15″, 10). The high-fluence accelerated epithelium-off protocol (18*9′15″, 10) showed the highest stiffening effect. Elastic modulus at 5% strain (1%–5% strain) showed significant differences between A-CXL (18*9′15″, 7.2) and three other accelerated protocols: A-CXL (9*10, 5.4; P = 0.01), A-CXL (9*13′20″, 7.2; P = 0.003), and A-CXL (18*6′40″, 10; P = 0.0001). CONCLUSIONS: An accelerated high-fluence epithelium-off CXL protocol (18 mW/cm² for 9′15″) was identified to provide a significantly greater stiffening effect than any other accelerated protocols and is indistinguishable from the Dresden protocol, with accelerating irradiation times ranging from 30 to 9 minutes; by combining gentle acceleration with higher fluence, such a protocol does not require supplemental oxygen. TRANSLATIONAL RELEVANCE: This A-CXL (18*9′15″, 10) protocol has the potential to become a new standard in epithelium-off CXL, delivering Dresden protocol–like strengthening over a shorter period.