Pharmacologic alternatives to the standard corneal cross-linking procedure, which avoid the need for epithelial debridement and irradiation and can be used to treat all corneas irrespective of thickness, are currently being investigated.  In vitro studies on porcine eyes have shown that aliphatic β-Nitro alcohols act as both formaldehyde and nitrite donors under physiologic pH and temperature to induce crosslinking [1-2] and are capable of inducing cross-links in the cornea with negligible effects on light transmission [1].  The preliminary results suggest that such compounds could be used as topical stiffening agents for Keratoconus and related disorders [1]. However, their precise mechanism of action is currently unclear and a better understanding of the specific chemistry involved is crucial to enhancing the speed and efficiency of the cross-linking effect.

[1] Paik, D. C. et al. Initial studies using aliphatic beta-nitro alcohols for therapeutic corneal cross-linking. Invest Ophthalmol Vis Sci. 2009;50(3):1098-105.

[2] Paik, D. C. et al. Aliphatic beta-nitro alcohols for therapeutic corneal cross-linking: chemical mechanisms and higher order nitroalcohols. Invest Ophthalmol Vis Sci. 2010;51(2):836-843.