BLOG: Unapproved cross-linking failure leads to vision loss
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I recently performed epi-off cross-linking on a 23-year-old male patient whose keratoconus was still progressing despite two prior cross-linking procedures.
Both of the previous procedures, which were ineffective in halting progression, were performed elsewhere with an unapproved device and drugs when the patient was approximately age 19 and 21 years old, respectively.
When I first saw this patient, he was becoming more myopic. His refraction was –5.00 +2.25 × 180. Although he was still able to be corrected in glasses, he had lost a line of best corrected vision. Given that he had already undergone two treatments, I initially followed him closely to be sure that he was truly progressing, but it became clear that progression was occurring (Figure 1). His maximum keratometry (Kmax) had increased from 45.48 D after his first epi-on procedure to 45.61 D after the second cross-linking procedure and now, 2 years after that second cross-linking procedure, to 48.21 D.
The standard epi-off Dresden protocol, performed with the only FDA-approved device (iLink system, Glaukos) and drugs (Photrexa Viscous [riboflavin 5’-phosphate in 20% dextran ophthalmic solution] and Photrexa [riboflavin 5’-phosphate ophthalmic solution], Glaukos), has been shown to be highly effective at halting progression in studies that have followed patients for up to 10 years. Of course, we know this protocol is not failsafe, either. Over long-term follow-up, up to 8% of patients may progress even after treatment. However, there is stronger evidence to support the use of epi-off cross-linking as compared to alternatives. Epithelial removal ensures efficient penetration of riboflavin, UV and oxygen into the corneal stroma; additionally, using approved (and highly regulated) technologies means that one has the assurance of high standards for manufacturing quality and product consistency.
The patient is now only about 2 months out from re-treatment but is doing well so far.
In the U.S., there currently are no cross-linking devices or drugs approved for epi-on cross-linking. When nonapproved procedures are performed, we currently don’t know the efficacy, and patients don’t get the benefit of insurance coverage for this otherwise covered, medically necessary procedure.
There have been some positive recent clinical trial findings of novel epi-on treatments. For example, in early 2021, Glaukos reported meeting the primary endpoint (a difference of 1.0 D or greater mean change in Kmax between treatment and control arms from baseline to month 6) in its phase 3 clinical trial of the iLink system for epi-on cross-linking. There are also other epi-on protocols under investigation.
If an epi-on platform is eventually approved in the U.S., we will have to decide based on the evidence available at that time whether epi-on is a better option for some or all of our patients. It is important that we continue to use validated and approved technology and make treatment decisions based on the scientific evidence of which procedures have the best chance of protecting our patients from continued progression and preserving their vision for the future.
- References:
- Choi M, et al. Cornea. 2017;doi:10.1097/ICO.0000000000001165.
- Glaukos announces positive phase 3 trial results for iLink epi-on investigational therapy that met the primary efficacy endpoint. https://investors.glaukos.com/investors/news/news-details/2021/Glaukos-Announces-Positive-Phase-3-Trial-Results-for-iLink-Epi-on-Investigational-Therapy-That-Met-the-Primary-Efficacy-Endpoint/default.aspx. Published Feb. 25, 2021.
- Kobashi H, et al. J Cataract Refract Surg. 2018;doi:10.1016/j.jcrs.2018.08.021.
- Koller T, et al. J Cataract Refract Surg. 2009;doi:10.1016/j.jcrs.2009.03.035.
- Mazzotta C, et al. Cornea. 2018;doi:10.1097/ICO.0000000000001505.
- Raiskup F, et al. J Cataract Refract Surg. 2015;doi:10.1016/j.jcrs.2014.09.033.
- Rush SW, et al. Br J Ophthalmol. 2017;doi:10.1136/bjophthalmol-2016-308914.
- Vinciguerra R, et al. J Refract Surg. 2020;doi:10.3928/1081597X-20201021-01.
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