One new development in collagen cross-linking technology is a method that uses green light to activate rose bengal, a well-known diagnostic agent for ocular surface damage. This technology has already proven useful in sealing cornea wounds, bonding amniotic membrane to the corneal surface, and for applications in many other tissues [1-6]. Photochemical cross-linking of the corneal stroma using rose bengal and green light (a process referred to as RGX) has been shown to produce a similar increase in rabbit corneal stiffness to that achieved with riboflavin/UVA cross-linking. However, in contrast to riboflavin/UVA cross-linking which causes apoptotic cell death at depths up to 350 µm, RGX is limited to the anterior 100 µm of the tissue and is non-toxic to stromal keratocytes [7, 8].  Reconstructed bio-mechanical parameters from numerical finite element simulations show that the cross-linked layer of the cornea is actually stiffer after RGX than after riboflavin/UVA cross-linking. However, the cross-linked layer is substantially thinner after RGX and air puff deformation imaging of rabbit eyes indicate that the overall corneal stiffening effect achieved with RGX does not match that of riboflavin/UVA cross-linking [9].

Preliminary studies on rabbit corneas indicate that RGX has the potential to offer a rapid (less than 15 min), safe and effective treatment for ectatic diseases but further studies are needed to assess its safety in terms of the retina and iris.

[1] Gu, C. et al. Photochemical tissue bonding: a potential strategy for treating limbal stem cell deficiency. Lasers Surg Med. 2011 43(5):433-42.

[2] Henry, F. P. et al. Real-time in vivo assessment of the nerve microenvironment with coherent anti-Stokes Raman scattering microscopy. Plast Reconstr Surg. 2009;123(2 Suppl):123S-30S.

[3] O’Neill, A. C. et al. Microvascular anastomosis using a photochemical tissue bonding technique. Lasers Surg Med. 2007;39(9):716-22.

[4] Proaño, C. E. et al. Photochemical keratodesmos for bonding corneal incisions.Invest Ophthalmol Vis Sci. 2004;45(7):2177-81.

[5] Tsao, S. et al. Light-activated tissue bonding for excisional wound closure: a split-lesion clinical trial. Br J Dermatol. 2012;166(3):555-63.

[6] Verter, E. E. et al. Light-initiated bonding of amniotic membrane to cornea. Invest Ophthalmol Vis Sci. 2011;52(13):9470-7.

[7] Cherfan, D. et al. Collagen cross-linking using rose bengal and green light to increase corneal stiffness. Invest Ophthalmol Vis Sci. 2013;54(5):3426-33.

[8] Zhu, H. et al. Corneal crosslinking with rose Bengal and green light: efficacy and safety evaluation. Cornea. 2016. Epub ahead of print.

[9] Bekesi, N et al. Corneal biomechanical response following collagen cross-linking with rose bengal-green light and riboflavin-UVA. Invest Ophthalmol Vis Sci. 2016;57(5):992-1001.