Although effective in the management of keratoconus, the standard riboflavin/UVA collagen cross-linking procedure has several drawbacks associated with the use of a prolonged exposure to UVA exposure. For example, UVA irradiation is harmful to the keratocytes (cells) within the tissue, and a corneal thickness of less than 400µm is a contraindication for the standard (epithelium-off) procedure due to the risk of endothelial cell damage from the UVA [1-3]. There have also been rare reports of side-effects such as corneal haze, keratitis and corneal scarring after riboflavin/UVA treatment [4]. As a result, researchers have also been investigating the potential of alternative corneal stiffening treatments that do not require UVA exposure.

One possibility is photochemical corneal stiffening by topical application of a novel photosensitizer referred to as WST11 followed by exposure to non-hazardous, near infrared (NIR, 755nm) light [5]. WST11, or palladium bacteriochlorin 130-(2-sulfoethyl) amide dipotassium salt, is a synthesized chemical derivative of a photosynthetic pigment that generates oxygen radicals after illumination with NIR [6,7]. One role of these photogenerated radicals is thought to be the promotion of protein cross-linking [8].

Laboratory studies have shown that a 20-minute topical application of WST11 in 20% dextran T-500 (WST-D), followed by a 30-minute illumination with NIR produces a significant and lasting stiffening effect in rabbit corneas [9], that is comparable in magnitude to that achieved with standard riboflavin/UVA cross-linking [5]. However, similarly to riboflavin/UVA cross-linking, WST-D/NIR cross-linking also causes post-operative keratocyte apoptosis within the anterior 1/3 of the stroma [5].

Ultrastructural examination of WST-D/NIR treated corneas using x-ray scattering techniques revealed no evidence of large-scale changes in the average size and spacing of the stromal collagen fibrils [10]. Since corneal transparency is largely dependent on the regular spacing of uniformally thin collagen fibrils within the stroma, the absence of any changes in these parameters, along with the absence of any damage to the endothelium and deeper ocular structures [5], highlights the clinical potential of this novel cross-linking therapy as a means of safely stiffening diseased or surgically weakened corneas of any thickness.

1. Wollensak G. et al. Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye. 2004;18: 718–722.
2. Wollensak G., et al. Endothelial cell damage after riboflavin-ultraviolet-A treatment in the rabbit. J. Cataract. Refract. Surg. 2003; 29: 1786-1790.
3. Spoerl E., et al. Safety of UVA-Riboflavin Cross-Linking of the Cornea. Cornea. 2007; 26.
4. Hersh P., et al. United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment.” Ophthalmology. 2017; 124: 1259-1270.
5. Marcovich A. et al. Stiffening of rabbit corneas by the bacteriochlorophyll derivative WST11 using near infrared light. Invest Ophthalmol Vis Sci. 2012; 53: 6378-88.
6. Ashur I., et al. Photocatalytic generation of oxygen radicals by the water-soluble bacteriochlorophyll derivative WST11, noncovalently bound to serum albumin. J Phys Chem. 2009; 113: 8027–8037.
7. Mazor O., et al. WST11, a novel watersoluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution, and vascular targeted photodynamic activity against melanoma tumors. Photochem Photobiol. 2005; 81: 342–345.
8. Liu K., et al. Superoxide, hydrogen peroxide and hydroxyl radical in D1/D2/cytochrome b-559 Photosystem II reaction center complex. Photosynth Res. 2004; 81: 41–47.
9. Brekelmans, J. et al. Long-term biomechanical and histologic results of WST-D/NIR corneal stiffening in rabbits, up to 8 months follow-up. Invest Ophthalmol Vis Sci. 2017; 58: 4089-4095.
10. Hayes S., et al. The effect of bacteriochlorophyll derivative WST-D and near infrared light on the molecular and fibrillar architecture of the corneal stroma. Scientific Reports 2020; 10: 9836.

Last updated: March 2021