New treatment options revise the prognosis for keratoconus

Take-home message: Understanding of keratoconus and the resulting dramatic changes in management in recent years have given rise to treatment paradigms that would have been unrecognizable to ophthalmologists a generation ago. The new landscape features a wider range of treatment options, better diagnostic and monitoring tools, and better understanding of the underlying pathology of the disease.

By Nancy Groves; Reviewed by Charles McGhee, MD, PhD, FRCS

Auckland, New Zealand ‒ The management of keratoconus has transformed more in the past 10 to 15 years than at any time since the disease was first described in the literature nearly 300 years ago. Recent changes, as well as those currently being tested in the lab, will continue to alter treatment paradigms into the future, said Charles McGhee, MD, PhD, FRCS, Chair of Ophthalmology, University of Auckland, Auckland, New Zealand

Until recently, there were only two treatments. The first-line approach was to prescribe contact lenses; when the lenses could no longer be worn, a corneal transplant was performed.

“That was it. It was pretty straightforward, and there were not really any other interventions,” said Dr. McGhee.

Fortunately, the situation has changed dramatically.

Now, doctors can perform multiple types of corneal transplants, including deep anterior lamellar keratoplasty (DALK). DALK has emerged as the preferred transplant approach for keratoconus in most countries, although penetrating keratoplasty (PK) remains more popular in the United States.

One of the perceived advantages of DALK is that there is no risk of endothelial rejection, which should result in a higher likelihood of long-term allograft survival.

“That’s a big sea change in transplantation,” Dr. McGhee said, adding however that published evidence has not yet conclusively demonstrated the superiority of DALK and that PK remains a viable treatment option.

Another sweeping development in the treatment of keratoconus is corneal collagen crosslinking (CXL). Although there is a degree of “hyperbole” surrounding the potential advantages of CXL, the procedure appears to stabilize the disease and stop progression in the majority of patients, Dr. McGhee said.

“For a few patients it makes vision better and reverses the disease process a little,” he added. But for most, the likely result is stabilization, which may last for a lifetime.

Other newer approaches include advanced tomographic techniques to detect progression, therapies to reduce eye rubbing, intracorneal ring segments, surface-based keratorefractive laser procedures post-CXL, phakic IOLs, and cataract extraction with toric IOLs.

Improved screening

Dr. McGhee advocated renewed emphasis in screening for early signs of disease in families with a history of the condition.

“In New Zealand, for instance, we see keratoconus in kids who are 12 years of age, and we see really severe keratoconus that might need a transplant before they’re 20. What we want to do is pick up these children at 10, 11, 12 years of age, and, if there is good evidence that their disease is progressing, we should be doing crosslinking probably before they’re 14 years of age, or certainly in the mid-teens and not in the mid-20s,” he said.

“The ideal is to identify disease as early as possible so that a minimum intervention will prevent progression, so as a worst-case, scenario the patient will end up wearing a contact lens, which is much preferable to having a corneal graft.”

“The big challenge facing us is identifying key indicators of progression, key indicators of diagnosis, then finding those teenagers who should be treated. We could, in theory, eliminate the need for corneal transplants,” he continued.

Screening in the general population is impractical, since the incidence of keratoconus is about 1 in 2,000 and the condition is not life-threatening. Therefore, targeted screening of family members would be more useful.

Screening should investigate both genetic predisposition and the environment, Dr. McGhee recommended.

“In some countries in the Middle East, keratoconus is very common because of consanguinity, so the genetic element prevails. But in most countries, it’s a combination of genetics and the environment,” he said.

Environmental factors related to keratoconus include excessive eye rubbing. Until recently, any association between the two was considered anecdotal, but increasing evidence points to the role of recurrent microtrauma to the eye in individuals who have a genetic predisposition.

“It would appear that the cells in the keratoconic cornea are susceptible to apoptosis under the stimulus of mild trauma, and rubbing your eyes is enough to cause that,” Dr. McGhee said.

Understanding the pathology

Discussing another aspect of keratoconus that has evolved, he also observed that the understanding of its pathology has changed.

Dr. McGhee and others have demonstrated that the total number of cells in all layers of the cornea is less in keratoconic eyes, suggesting that the cornea is predisposed to apoptosis.

“Anything we can do at the moment only stops the disease from getting worse, but the big question would be is there something we could do to reverse the disease? Could we alter the cells in the cornea genetically, or could we transplant new cells into the cornea?” Dr. McGhee asked. The latter possibility is simpler and more direct, especially if the disease is detected early.

Researchers are investigating the insertion of new keratocytes grown from donor corneas; in theory, the new, healthy cells would repopulate the cornea, making it resistant to keratoconus.

“This is very much in the early stages, but it’s quite exciting,” he said, adding that although the technique has been demonstrated in the laboratory, clinical trials are 5 to 10 years away.

Between new approaches such as this and the ongoing development of new or modified treatment strategies and diagnostic techniques, Dr. McGhee is optimistic about the future of keratoconus management.

“I believe that the visually debilitating effects of keratoconus will be reduced more significantly in the next decade than they have been in the last 150 years,” he said.

Charles McGhee, MD, PhD, FRCS

P: +64 95 22 2125

E: c.mcghee@auckland.ac.nz

Dr. McGhee presented a keynote lecture on new treatment paradigms in keratoconus at the World Cornea Congress VII. A related paper by McGhee, Kim, and Wilson was published in Cornea (June 24, 2015). Dr. McGhee did not report any relevant financial interests.