Combining CXL and PRK

Simultaneous and separate approaches can both work in treatment of keratoconus

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A John Kanellopoulos MD
Corneal cross-linking (CXL) combined with topography-guided photorefractive keratectomy (partial in refraction PRK) to help normalise the corneal surface is a safe and effective treatment for keratoconus. But should they be performed simultaneously, or CXL first followed by PRK later? Both approaches can be successful according to debaters at the JCRS Symposium at the 38th Congress of the ESCRS, held virtually for the first time. Arguing for combining the two procedures in the approach known as the Athens Protocol, A John Kanellopoulos MD noted that the simultaneous procedure can flatten the corneal ectasia several times more than either procedure can do alone collectively. (We routinely experience 6-12 dioptres of cone flattening). “We started performing CXL first and a normalizing surface ablation later back in 2003-2005. Then the idea of combining the two ensued,” said Dr Kanellopoulos. “You cannot achieve this with cross-linking alone; you cannot achieve this with laser alone with the specific ablation depths used. It is the combination of the two that has a synergistic effect.” Indeed, in a study involving 358 cases comparing almost in half CXL followed by topo-guided PRK six months later vs the Athens protocol (simultaneous combined procedure) in the other half of cases, Dr Kanellopoulos found the greater flattening of the mean keratometry by 3.2D in the Athens protocol cases versus 2.5D for the procedures performed six months separate, and improved uncorrected and corrected vision and central corneal thickness significantly better than in the separate procedure group (Kanellopoulos AJ. J Refract Surg. 2009;25:S812-8). This greater flattening often is needed to normalise keratoconic corneas enough so that patients can achieve acceptable vision with spectacles or soft contacts rather than gas-permeable hard contacts. “In our part of southern Europe, having a lot of sand and particles in the air, hard contact lenses have proven in clinical practice almost impossible to tolerate on a daily basis,” said Dr Kanellopoulos, of the Laservision Clinical & Research Eye Institute, Athens, Greece, and New York University Medical School, New York City, USA. The Athens Protocol, developed by Dr Kanellopoulos, is a four-step procedure designed not to correct refractive error per se but to normalise the corneal surface to correct asymmetric astigmatism. It involves a partial in refraction PRK, followed by PTK to account for epithelial removal, followed by mitomycin C, followed by accelerated CXL at 6mW/cm2 for 15 minutes. He has followed more than 3,000 eyes for topography changes after the combined procedure, the last three years even cases performed in his New York City practice, over 1,000 of those published in detail in dozens of peer-reviewed articles already. Outside the US, a customised partial in refraction surface ablation combined with accelerated CXL has become the treatment of choice by most clinicians for progressive keratoconus. Besides treating each patient, Dr Kanellopoulos evaluates carefully any available family members, as his team’s experience in Greece is that there is almost 100% chance at least one of the two parents will have at least tomographic signs of keratoconus. Important considerations include whether there is enough residual stroma to allow the surface ablation, how well the patient functions with his or her current refractive error and if there is documented progression. He makes sure patients understand that the goal may not be emmetropia and they may still need spectacles or contacts afterward. Careful ocular surface management is required after the procedure, he added, as healing issues may persist for one-to-two weeks. In regard to the refractive outcome with the Athens protocol: “The result is not completely predictable, Dr Kanellopoulos said. “You may get a 6.0D flattening or you may end up with an impressive 15.0D flattening over the tip of the cone.” Dr Kanellopoulos noted that separating the procedures may have significant downsides. “It may prove counterintuitive to go back and remove some of the best biomechanical part of the cornea you have strengthened when performing the surface ablation months after the CXL strengthening.” In a 10-year follow study published recently he found less than 1% over-flattening, and this can be corrected with a hyperopic laser treatment, he added. In general, results are stable after one year with the Athens Protocol, though longer follow-up studies are needed. SEPARATE PROCEDURES This unpredictability of corneal flattening after CXL – along with its effect on both stromal and epithelial corneal remodelling, residual corneal thickness and any adverse events – is a major reason why it makes more sense to wait for the cornea to stabilise after CXL before proceeding with PRK, argued Alanna Nattis DO, FAAO, of SightMD, Babylon, New York, USA. This typically takes 12-to-18 months, but helps ensure a safer and perhaps better refractive outcome, she reasoned. “When you are planning refractive surgery for these patients you want to make sure you are not working on a moving target.” The wide and changing range of CXL procedures, including epi-on, epi-off and various strengths and lengths of UV exposure, further complicates predictability, Dr Nattis said. How CXL affects corneal remodelling remains a significant uncertainty, she noted. “We should be able to see the refractive result of this remodelling before we move on to topography-guided PRK.” Perhaps more importantly, corneal thinning can vary by technique, Dr Nattis said. In a study she conducted involving 62 eyes in 56 patients, 45% of eyes were limited to treatment for topographic irregularities only due to insufficient corneal thickness to support refractive PRK after CXL. Mean time between CXL and PRK was 30.5 months, and 82% overall achieved 20/40 or better corrected vision one year after PRK with no adverse events (Nattis et al. JCRS 2020;46:507-516). In the end, Dr Nattis acknowledged Dr Kanellopoulos’ success with the simultaneous procedures. Techniques vary by the equipment available as well as surgeon preferences and surgeon comfort with the procedures. She also noted that individualised treatment planning is essential, and advocated more research to better understand the biomechanics of corneal remodelling. “We can reshape the cornea; it is just a matter of how.” Dr Kanellopoulos agreed that both the simultaneous combined and separate procedures are effective for treating keratoconus. He sees no problem going with a separate approach for those uncomfortable with the Athens Protocol. Studying carefully “suspicious” young myopic astigmats, teaching to avoid eye rubbing, evaluating family members and early intervention before the cornea thins under 400 microns is far more important.
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