Keratoconus Crosslinking Associated With Early Complications

Caroline Helwick

November 13, 2012

CHICAGO, Illinois — In the treatment of keratoconus, ocular surface healing disorders may be more common than expected after corneal collagen crosslinking (CXL), according to a 5-year retrospective analysis presented at the American Academy of Ophthalmology (AAO) and Asia-Pacific Academy of Ophthalmology 2012 Joint Meeting.

"Physicians often fail to look for these complications after CXL, but it is important for these patients to be followed closely," said Denise Wajnsztajn, MD, from the Department of Ophthalmology, Hadassah-Hebrew University, Jerusalem, Israel.

CXL can halt the progression of corneal ectasia by promoting biomechanical stabilization and increasing corneal stiffness. The procedure is still experimental in the United States but is widely used in many other countries. Long-term complications have been reported, but early complications may also occur and have not been sufficiently described, she said.

Dr. Wajnsztajn and her colleagues conducted a retrospective review of ocular complications occurring within the first month of CXL in 206 eyes of 180 patients treated between 2007 and 2012. Patients were treated according to the Dresden protocol.

They observed 28 ocular complications in 23 eyes (11.2%) of 22 patients (12 males, 10 females) whose mean age was 24 years. These included delay of epithelial healing (up to 30 days) in 4 eyes, hypertrophic epithelial healing in 4 eyes, marked superficial punctuate keratopathies (greater than 30 days) in 11 eyes, corneal sterile infiltrates in 4 eyes, microbial keratitis in 4 eyes (culture-positive in 2), and marked corneal edema with scarring in 1 eye, Dr. Wajnsztajn reported.

Complications More Common in More Severe Subset

"In the group experiencing complications, we observed that the corneas were thinner (P =.002) and steeper (P < .023)," she added.

When the crosslinked corneas were divided into 2 groups according to corneal thickness, 174 eyes had corneas thicker than 400 µm and 32 had thinner corneas. The latter had higher pretreatment corneal maximum keratometry (Kmax) than those with thicker corneas, and early complications were 3 times more common in this group (28.13%) compared with those with thicker corneas (8.64%) (P = .0018).

Among the patients who experienced complications, prior to CXL 12 eyes (56.5%) presented with floppy eyelids, 10 eyes (43.5%) had superficial punctuate keratopathy, 2 eyes (8.7%) had corneal scars, and 3 eyes (13%) had a history of allergic conjunctivitis. In 11 cases (47.8%) patients wore contact lens. In 12 cases (52.2%) patients wore eyeglasses and 3 of them (4 eyes, 17.4%) had limited tolerance to contact lens.

"We saw more complications in eyes with advanced disease. Those eyes had pre-existing conditions and often an inflammatory environment," Dr. Wajnsztajn explained.

Summarizing the problem, she pointed to 3 main groups of ocular surface-related complications that were seen soon after CXL: healing disorders, corneal infiltrates, and severe stromal edema with a delay of epithelialization.

The researchers further showed that abnormal wound healing may compromise final visual acuity and CXL outcomes. One eye (4.3%) lost 3 lines, 2 eyes (8.7%) lost 2 lines, and 3 eyes (13%) lost 1 line of best corrected visual acuity (BCVA) compared with pre-CXL measurements. Eight eyes (34.8%) maintained the BCVA and 9 eyes (39.1%) gained 1 line or more of BCVA, Dr. Wajnsztajn reported.

Selected as Best Scientific Poster at AOA

Elaborating on the findings, senior investigator Joseph Frucht-Pery, MD, head of the Cornea and Refractive Surgery Service at Hadassah-Hebrew University, explained that theirs is a major academic referral center and, as such, they see many difficult cases and rigorously follow patients. He believes this at least partly explains their higher than expected early complication rate.

"Physicians are not aware, and I am worried about this," he told Medscape Medical News. "I know that eventually when there is an 'open field' on this procedure and it is done by ophthalmologists who are not cornea specialists, there will be problems. My point is that if you are going to do CXL, be aware of the possibility of early complications and keep in mind that you may need a cornea specialist."

Albert Jun, MD PhD, of The Wilmer Eye Institute of The Johns Hopkins School of Medicine, Baltimore, Maryland, commented that the incidence of complications is considerably higher than what he has observed in his own practice and than rates reported from larger studies "where I think the data collection may be more rigorous.

"But it does raise awareness that complications can occur with crosslinking," he agreed. "I would be interested to know if there were differences in post-op care of patient characteristics that may have led to this. It's provocative and a good starting point for more research."

Robert Schultze, MD, of Cornea Consultants and the Albany Medical College, Albany, New York, added, "We have a lot of papers touting the benefits and stability of outcomes with crosslinking but we seldom see reports that focus on complications, which is probably why this paper raised an eyebrow and was selected as a 'Best Scientific Poster' at the meeting. It's a counterpoint to the concept of 'how great' crosslinking is."

Dr. Wajnsztajn, Dr. Frucht-Pery, Dr. Jun and Dr. Schultze have disclosed no relevant financial relationships.

American Academy of Ophthalmology (AAO) and Asia-Pacific Academy of Ophthalmology 2012 Joint Meeting. Abstract PO367. Presented November 12, 2012.