Binkhorst Lecture: Predicting, treating keratoconus in 2016

New Orleans-The Binkhorst Lecture and Medal have been conferred since 1975 on “an individual whose career has made significant contributions to the science and practice of ophthalmology and established that person among the world’s most prominent ophthalmologists.”

Doyle Stulting, MD-this year’s recipient-is considered “a primary force in the surgical management of complex cataracts, corneal disease, and intraocular lens complications.”

With more than 200 authored papers and 10 years at the helm of Cornea, Dr. Stulting has also served on the board of directors for the American Society of Cataract and Refractive Surgery (ASCRS), has been awarded the American Academy of Ophthalmology’s Senior Honor award, and has received the Paton Award from the Eye Bank of America.

More recently, however, Dr. Stulting was the principal investigator for a physician-sponsored clinical trial of riboflavin-ultraviolet A corneal collagen crosslinking, the first of its kind in the United States.

A history of ectasia

In 1998, Theo Seiler, MD, brought ophthalmology’s attention to post-LASIK-induced ectasia, Dr. Stulting said. He and colleagues began retrospectively evaluating the risk factors that might contribute to the complication, and developed an ectasia risk score system in 2008.

“Preoperative refraction, pachymetry, forme fruste keratoconus (FFKC), and residual stromal bed (RSB) were all predictors of post-LASIK keratectasia,” he said. “Of those, FFKC was by far the largest risk factor.”

The group also determined age played a factor, with younger patients more affected than older patients, he said.

An analysis of an additional 171 cases found a “significant association with younger age, preoperative manifest refraction, pachymetry and abnormal topography, but we wanted to address the criticisms we’d heard about our strict criteria,” he said.

William Trattler, MD, provided another population of patients, “and we found the same consistent risk factors,” Dr. Stulting said. “Patients often have multiple risk factors.”

Dr. Stulting’s scoring system “has a 9% false positive and a 9% false negative rate, though. Wouldn’t it be great if it worked perfectly?”

A consistent dilemma for surgeons is classifying the corneal topography maps, especially when the patient is on the cusp.

“Even the best of us have a hard time judging these images,” he said.

Over the years, however, Dr. Stulting said the sensitivity has fallen, “but why is our risk system failing today? RSB is increasing, but FFKC is decreasing. Corneal thickness is also increasing. The mean patient age is decreasing-We’re still operating on young patients and the elimination of other risk factors are making age a much more relevant factor.”

Moving forward and the role of CXL

Moving forward and the role of CXL

New analyses “will not identify new risk factors that currently prevent patients from being treated. We cannot forget what we already know,” he said. “We should be using a two-step process, where we use the original scoring system and newly derived screening methods.”

The lower incidence of post-LASIK ectasia, while a good thing, is making it a challenge to develop some newer screening methods, he said.

Dr. Seiler introduced the concept of corneal crosslinking in the 1990s as a means to delay and/or improve naturally occurring cornea ectasia.

“Riboflavin is excited by ultraviolet A, which in turn stiffens the cornea and reduces the steepening,” he said.

Dr. Seiler reported a regression of keratoconus after crosslinking, and Dr. Stulting first used the Dresden Protocol to treat patients starting in 2008.

“We immediately saw a flattening in the treatment group and a progression in the control group,” he said. “We expanded our one center study to a multicenter clinical trial and started seeing a slight improvement in best spectacle corrected visual acuity."

But the early results were not without potential complications, including non-healing epithelial defects, corneal haze, sterile infiltrates, and Acanthoemeba. Early attempts to increase absorption with a preservative (BAK) decreased the results so that only one in five patients achieved the desired outcomes.

“But that was with the epithelial-off (epi-off) procedure,” he said. “Why try epi-on? It was being heralded as a much safer procedure. I was an initial detractor of epi-on, and insisted epi-off would be better. Then I joined CXLUSA.”

CXLUSA Study Group

CXLUSA Study Group

That investigator-led study uses a novel riboflavin formulation, with physician verification and saturation as needed. There is no riboflavin during UVA exposure, and pulsed UVA is used to allow oxygen to enter the cornea.

Outside the United States, researchers report somewhere between 19% and 23% progression rates.

“We saw demarcation lines that were deep,” Dr. Stulting said. “We performed lab studies to see what the differences might be. We found a denser fluorescence in the CXLUSA formulation.”

The CXLUSA formula had a 4.3-fold greater concentration.

Current enrollment in the CXLUSA study is 569 eyes. At 12 months the average visual gain was about 1.5 lines, Dr. Stulting said. Kmax decreased, “but not as much as in some of the epi-off studies.”

With 2-year results now starting to come in, Dr. Stulting said the mean visual improvement is hovering around 1.5 lines, and topography is continuing to improve but still is not meeting the levels of the epi-off studies.

“So why are our patients seeing better if the Ks aren’t changing as much?” he asked. Patients enrolled in the CXLUSA study also had a 37% reduction in total higher-order aberrations and in coma.

In short, Dr. Stulting said, “after 1 to 2 years, the epi-on technique achieves visual results better than some of the epi-off procedures. There is decreased noticeable higher-order aberrations. There is much less risk compared to the classic epi-off procedure, and re-treatment is possible if necessary.”

Dr. Stulting said new technologies also means treating ectasia in the future will be different, as there will be better screening for abnormal topography, and he believes it is possible that surgeons will use riboflavin to penetrate the cornea, but then have the patient expose themselves to natural UVA light (sunlight) to activate the crosslinking.

Finally, he said, a study from Norway showed a 53% reduction in keratoconus and post-LASIK ectasia once crosslinking had been introduced. He hopes the same may happen in the United States now that Avedro has received regulatory approval for its device and technique.

Dr. Stulting dedicated the lecture to his daughters, and with some emotion apologized to them for “the time spent working instead of being with you.”