Emerging data suggest a potential role for corneal collagen crosslinking (CXL) in the management of infectious keratitis.
Nevertheless, right now there are more questions than answers about the mechanism, efficacy and safety of this technique,
said Dr A. John Kanellopoulos, during Cornea Subspecialty Day at the annual meeting of the American Academy of Ophthalmology.
"There are a handful of studies1–5 in the current literature reporting on CXL for treating infectious keratitis, and surprisingly enough, one is a comparative
study in which one group was treated with CXL and no antibiotics," said Dr Kanellopoulos, clinical professor of ophthalmology,
New York University Medical School,York, USA, and director, Laser Vision GR Institute, Athens, Greece.
"The findings from these papers are interesting in suggesting that CXL works as a disinfecting and perhaps a sterilizing method
within the infected cornea," he said. "That concept is supported by our own experience that includes CXL treatment of a consecutive
series of 412 keratoconic eyes without a single infection, although antibiotic prophylaxis was also used. However, for now,
ideas about how CXL works in infectious keratitis, modifications to improve its activity, and potential risks are mainly theoretical
so that much more research is needed."
Mechanism of action
Discussing potential mechanisms by which CXL may be an effective treatment for infectious keratitis, Dr Kanellopoulos noted
that UVA light with riboflavin is known to have a sterilizing effect. He explained that originally, the photochemical reaction
of CXL was attributed to oxygen radical generation (type I) from the interaction of UV light and riboflavin. Recently, an
additional mechanism has been theorized involving creation of a riboflavin radical.
"Both the oxygen radicals and possibly energized riboflavin may be directly cytotoxic to microbes," Dr Kanellopoulos said.
A second mechanism, by which CXL might benefit the treatment of infectious keratitis, may be through biomechanical strengthening
of the cornea.
"After crosslinking, human corneal tissue has been shown to be much more resistant to enzyme degradation," Dr Kanellopoulos
said. "In addition, the procedure may also directly reduce the activity of proteolytic enzymes. Both of these mechanisms may
reduce the cornea's susceptibility to infectionrelated melt and the consequent spread of infection within the cornea."
He added that with those latter concepts in mind, he has been performing CXL as a prophylactic treatment in cases of Boston
(Dohlman) keratoprosthesis implantation over the past 5 years.
"In these procedures, the vehicle cornea transplanted along with the prosthesis is often susceptible to melts and infectious
keratitis due to severe preexisting external disease," Dr Kanellopoulos explained. "With preemptive crosslinking of the vehicle
cornea to the prosthesis, we have found a significant reduction of melts and potential infections associated with this very
He also said that CXL may be helpful in treating infectious keratitis by potentially reducing postinfection scarring, recognizing
reports that the crosslinked corneal stroma is denuded of keratocytes for 3 to 6 months. In addition, he presented a case
demonstrating how CXL might be used with topographicguided normalization of the cornea as a tool for treating postinfection