Potential uses for collagen crosslinking

Boston-Collagen crosslinking (CXL) is currently used to treat keratoconus, pellucid marginal degeneration, and post-LASIK ectasia, although it has not yet received FDA approval. Thomas John, MD, discussed the potential of the technology to treat corneal infections.

“Photochemical reaction using riboflavin and ultraviolet (UV) A has been successfully used in transfusion medicine to inactivate various microorganisms in blood products,” said Dr. John, Loyola University, Chicago. “This led to explorations of the potential benefits of collagen CXL in microbial keratitis. The first in vitro study in 2008 showed that riboflavin and UVA inhibited growth of drug-sensitive and drug-resistant bacteria, but had no effect on the fungus Candida albicans.

"Other studies showed very mixed results, i.e., with some successfully inhibiting microorganisms, and others showing no effectiveness against keratitis," he continued.

The clinical studies of the effectiveness of collagen CXL were generally very limited in that they were small cases series or case reports. For example, all but one were retrospective with varying doses and durations of exposure to treatment, and case selection seemed arbitrary with some reporting presumed infections without confirmation, and others relying only on confocal microscopy. Interpretation of results was difficult regarding the effectiveness of collagen crosslinking, Dr. John said.

Collagen CXL may be an option for treating keratitis, but it cannot now be conclusively determine that it is efficacious. The standard of care must be continued before that conclusion can be reached, he explained.

Regarding pseudophakic bullous keratopathy, one clinical study indicated that collagen CXL resulted in no long-term improvement in the best-corrected visual acuity in 50 treated eyes, although pain was temporarily reduced.

Recombinant human collagen was crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide as a substitute for corneal tissue and tested in humans. The implants, tested in a phase I human study, were found to promote corneal tissue growth and regeneration. 

 “Collagen crosslinking appears promising and has a good future,” Dr. John concluded.

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