Initial Studies Using Aliphatic β-Nitro Alcohols for Therapeutic Corneal Cross-Linking

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Abstract
Purpose. Corneal collagen cross-linking through UVA-riboflavin photochemistry (UVAR) has been shown to be an effective treatment for keratoconus and related keratectasias. In recent studies using sclera, the authors observed that short-chain aliphatic β-nitro alcohols can cross-link collagenous tissue under physiologic conditions. Thus, this study was undertaken to evaluate these agents as potential pharmacologic alternatives to UVAR. methods. Porcine corneal strips (8 × 4 mm) and corneoscleral complexes were cross-linked using 1 to 100 mM 2-nitroethanol (2ne), 2-nitro-1-propanol (2nprop), and 3-nitro-2-pentanol (3n2pent) at pH 7.4, 34°C. Cross-linking by UVAR was carried out for comparison. Thermal shrinkage temperature analysis was used to evaluate cross-linking effects, and changes in corneal light transmission were determined with a fiber-optic spectrophotometer. results. At 10 and 100 mM for 96 hours, initial shrinkage temperature (Ti) was shifted by 3.3°C (P < 0.001) and 9.8°C (P < 0.001) for 2ne, 2.9°C (P = 0.008) and 4.9°C (P < 0.001) for 2nprop, and 3.8°C (P = 0.003) and 4.9°C (P < 0.001) for 3n2pent. Reacting at 1 mM through daily exchange of fluid over 7 days shifted Ti by 3.8°C (P < 0.001), 4.4°C (P = 0.002), and 3.2°C (P = 0.005), for 2ne, 2nprop, and 3n2pent, respectively. These shifts were greater than cross-linking using UVAR (Ti = 1.9°C; P = 0.012). In the blue light region (400–500 nm), transmission was decreased by 5.6% (P = 0.003), 2.1% (P = 0.260), and 0% (P = 0.428) for 2ne, 2nprop, and 3n2pent, respectively. conclusions. β-Nitro alcohols can induce corneal cross-linking in vitro better than the UVAR technique and can induce negligible effects on light transmission. These early results suggest that such compounds could be used as topical stiffening agents for keratoconus and related disorders.