Time to Drop the Debate

Dr. Rubinfeld

Dr. Rubinfeld

It shouldn’t be about epi-on or epi-o CXL...The focus should be on what’s best for patients.

By Roy Rubinfeld, Clinical Associate Professor at MedStar Georgetown University/Washington Hospital Center, and Medical Director of Re:Vision, Rockville, MD and Fairfax, VA, USA

(This article was excerpted from the full article that appeared in The Ophthalmologist, November, 2017.)

Back in 2010, during Cornea Day at the AAO annual meeting, I was nearly booed off stage. A few years ago, at a prestigious dinner for cornea specialists, I was accused of malpractice, and of selling “snake oil.” Why? Because I was discussing epithelium-on (epi-on) corneal crosslinking (CXL) and presenting results that suggested success. 

The history of CXL began with Theo Seiler, Michael Mrochen and colleagues in Dresden, Germany. But why [in these early studies in 2003] was the epithelium removed? According to personal communications with Michael Mrochen and others, despite a preference to leave the epithelium intact, making CXL a noninvasive procedure, it was primarily because there was no formulation or technology available to adequately load riboavin into the stroma through the epithelium.

Traditional epi-off CXL is a typically safe and effective procedure, but there are well-documented complications including corneal edema, infectious keratitis, delayed epithelial healing, corneal haze, stromal scars and even corneal perforation - nearly all of which derive from the surgical removal of the epithelium. Additionally, removal of the epithelium is painful for patients, and re-epithelialization can take at least a week during which they may require opioids for pain management. Recovery of pre-operative vision can take at least one month or longer. Would most patients prefer to have their epithelium removed, suffer worsened vision, be in substantial pain and at risk of complications such as infection, perforation, scarring and haze, and effectively ‘out of commission’ for weeks per eye - or undergo an equally effective non-invasive procedure that consists essentially of ‘eyedrops and sunlight,’ returning to work the next day?

When the epi-on approach first came around, everyone was excited about it - all the while hoping that a less-disruptive, safer approach might be forthcoming. When people use the term ‘epi-on,’ do they mean the 10 approaches that haven’t worked or the one approach with scientifically validated potential? That’s why I refer to the “epi-on versus epi-off ” as the great non-debate; this discussion is a red herring leading nowhere. We should be open to scientifically evaluating my approach that achieves the best outcomes for patients. Previous epi-on approaches may not have worked well, but we have developed a new approach - and we are seeing extremely promising long-term study results. Through much communication between our investigators and many procedures, we have developed a new way to perform epi-on CXL: the CXLUSA methodology.

Earlier this year at the American Society of Cataract and Refractive Surgeons (ASCRS) annual meeting, we presented results from 592 eyes with keratoconus (n=512) and ectasia (n=80) that received our procedure between October 7, 2013 and April 26, 2016 (7). The results are promising: at 12 and 24 months after surgery, we saw improvements in five parameters (corrected distance visual acuity, uncorrected visual acuity, Kmax, higher order aberrations and coma), and we saw no progression, even among the 48 pediatric eyes (≤18 years) (7).

In conclusion, we believe that our novel approach works - and we’re thrilled with the results we’re achieving because it means we’re able to perform a safer and more comfortable procedure for our patients. We have submitted our findings for publication, and our next goal is to proceed through the regulatory process so that more patients in the future might be able to benefit from an effective epi-on CXL approach. It hasn’t been easy to reach where we are now after eight years of research - there have been many hurdles, not least the ongoing skepticism. However, I believe the tide is slowly turning and that more people in the field are willing to accept the idea of an epi-on CXL approach once they see the scientific in vitro and clinical study data. The fact that there are many other groups investigating transepithelial CXL is testament to this. I think it is time to ‘drop the debate,’ because it is not about epi-on or epi-off; it is about what is best for our patients and which approach works best with the least discomfort and risks.