Crosslinking for keratitis

This patient’s pre- and post-collagen crosslinking topography shows stabilization and some reduction in cone steepness
Source: A. John Kanellopoulos, M.D.

Collagen crosslinking of the cornea has traditionally been focused on weakened corneal states like keratoconus, but new research is looking at its usage for a much different problem: keratitis.
The latest case describing the successful usage of riboflavin and ultraviolet A for the treatment of infectious keratitis was reported online in August 2009 in the journal Cornea. “After riboflavin and UV collagen crosslinking therapy, there was a rapid decrease of pain and necrotic material,” according to lead author H. Morén, M.D., Department of Ophthalmology, Regional Hospital of Vasteras, Vasteras, Sweden.
The article was later recalled—not for scientific reasons but because an administrative error led to its publication earlier than intended. The full report is therefore no longer available online as of publication, but its abstract, which remains available online, is unequivocal in the potential importance of this research.
“This case illustrates the positive effects of riboflavin and UV [ultraviolet] collagen crosslinking on presumed infectious keratitis with a satisfactory final visual outcome,” the researchers reported. “This may be a promising new treatment for keratitis.”
Earlier case research also points to this same promising possibility, even though crosslinking itself has been found to lead to infection in a few isolated cases.

A new battle against keratitis

Dr. Morén’s case involved a 25-year-old contact lens user with unilateral severe keratitis. Clinical investigation suggested Acanthamoeba was the causative agent.
“A 4-mm diameter, annular, semi-opaque infiltrate was found on the paracentral parts of the cornea in the left eye (OS),” Dr. Morén reported. “Laboratory examinations for bacteria, herpes simplex, and Acanthamoeba were performed, but no specific pathogen could be detected.”
The case was clearly dire, as best-corrected visual acuity (BCVA) was only 20/1000 at presentation. Antibiotics weren’t working. “Treatment was initialized with broad-spectrum antibiotics also covering acanthamoeba,” Dr. Morén reported. “During the first month of treatment the keratitis progressed and the corneal thickness diminished.”
After collagen crosslinking was initiated, healing began. “Re-epithelialization of the cornea started within a few days and was complete within a month,” Dr. Morén reported. “After 2 months, the wound had healed completely.”
Treatment was so successful that BCVA returned to 20/30, according to the nine-month follow-up visit.
Dr. Morén cautioned against widespread use of the technique at this time, however. “Until more data are available this treatment should only be considered in therapy-refractive keratitis or ulceration and not in the first line of defense since it may have cytotoxic side effects,” Dr. Morén noted.

Additional research

Another report surfaced in the March-April 2009 European Journal of Ophthalmology in which a case of Escherichia coli keratitis was successfully treated with ultraviolet A (UVA)-riboflavin corneal crosslinking.
Though not mainstream, the technique is proving effective in these case reports. “The case that we reported shows that in a patient not responding to maximal therapy for corneal ulceration, the use of UVA/riboflavin corneal crosslinking led to the healing of the lesion, with a remarkable and rapid improvement in symptoms,” according to lead study author Tommaso Micelli Ferrari, M.D., U.O.C. Oculistica, Ospedale Generale Regionale F. Miulli, Acquaviva delle Fonti, Bari, Italy. “One month after the treatment, corneal edema was almost completely resolved, corneal ulceration was healed, and the painful symptoms of the patient had disappeared.”
Dr. Ferrari explained the mechanism of action as twofold. First, UVA light can actually damage the bacterial DNA. Second, riboflavin, activated by UV light chemically alters functional groups of nucleic acids in the bacteria, making replication impossible.
Other researchers have “reported five cases of infectious keratitis not responding to systemic and topical antibiotic therapy treated with corneal crosslinking; in all cases, the progression of corneal melting was halted after corneal crosslinking treatment.”
Karl G. Stonecipher, M.D., medical director, TLC, Greensboro, N.C., and Raleigh, N.C., suggested that corneal crosslinking is promising in this area especially because corneal perforation is so troublesome to deal with.
“Crosslinking is a last resort before a perforating injury,” Dr. Stonecipher said. “Corneal perforation is nearly impossible to treat. If crosslinking of the cornea occurred before that point, I don’t see a downside because it’s a last resort prior to a transplant.”
Dr. Stonecipher said crosslinking would add to the biomechanical stability of the cornea, hence preventing corneal perforation. He suggested preliminary results with crosslinking are good.
Surgeons should note, however, that crosslinking has also been linked to infection in some patients. The June 2009 issue of the Journal of Cataract & Refractive Surgery described a case in which a 29-year-old woman had corneal collagen crosslinking with riboflavin and UVA for keratoconus and subsequently was found to have Staphylococcus epidermidis keratitis. Researchers suggested that epithelial removal linked to the crosslinking technique could have been the predisposing factor for bacterial keratitis.

Editors’ note: Dr. Ferrari has no financial interests related to his research. Dr. Stonecipher has no financial interests related to his comments.

Contact information

Ferrari: tommasomicelliferrari@alice.it
Stonecipher: 336-288-8523, stonenc@aol.com