Monitor keratoconus progression after cross-linking treatment

A 35-year-old man with keratoconus (KC) was referred to Midwestern University Eye Institute in Glendale, Arizona, in September 2018 for a scleral lens fit in both eyes. Both eyes had recently undergone epithelial (epi)-on corneal collagen cross-linking at another clinic with an unapproved riboflavin solution and unapproved cross-linking device.

Although the patient, who is a pharmacist, was aware an FDA-approved cross-linking procedure was available, he had chosen what he believed would be a more comfortable procedure. However, he experienced significant pain and discomfort from the epi-on procedure.

By February 2020, we determined his condition was still progressing despite the unapproved experimental cross-linking treatment and recommended epi-off cross-linking treatment. However, because of the pain he experienced during the epi-on procedure, he was reluctant to undergo cross-linking again. He declined to proceed and was scheduled for a follow-up appointment 6 months later. Unfortunately, he didn’t return until nearly 1 year later.

Figure 1

By January 2021, there was topographic steepening and a concerning amount of KC progression in the right eye (Figure 1). Although the patient could still see with visual acuity of 20/20-3 through the scleral lens, he was having trouble reading the fine print on medicine bottles.

Concern about his ability to continue working as a pharmacist made him more willing to consider cross-linking. We expressed the importance of halting further progression and reassured him that any discomfort could be managed.

In May 2021, he underwent the FDA-approved iLink epi-off cross-linking procedure on the right eye. This technology has been proven safe and effective in clinical trials^1,2 and real-world settings.³

After the procedure, he was given comfort drops of 0.25% proparacaine every 15 minutes as needed for pain for the first 48 hours and autologous serum tears to accelerate healing. Although patient comfort is touted as an advantage of the epi-on procedure, recent contralateral eye study results found it is less comfortable than epi-off treatment.4 That was the case for this patient as well, because he reported minimal pain after undergoing the epi-off treatment.

Figure 2

Two months after the patient received treatment with iLink, there was some additional steepening (Figure 2). This is an expected change in the early postoperative phase following the procedure; changes in keratometry, pachymetry, and vision in the early postprocedure period should not be mistaken as progression.

As the cornea stabilizes and the epithelium undergoes remodeling during the initial months, changes are common and not an indication of treatment failure. This is the reason why the measurements taken 1 year after cross-linking become the new baseline.

Figure 3

This patient was able to return to his habitual scleral lens 1 week after treatment, providing him with immediate functional vision. Minor adjustments to the fit were made several weeks after that. One year after the procedure, the patient was very happy, reporting his vision as “10 out of 10” with scleral lenses. The changes that occurred between 2018 and 2021 could not be reversed, but corneal stability seems to have been achieved at 1 year (Figure 3).

Lessons learned

Continued KC progression in patients in their mid- to late 30s—especially after cross-linking—is less common than in patients in their teens and 20s, but it does occur.5 In fact, we have treated patients aged 65 years with documented KC progression. It is impossible to know whether the progression in the case described here occurred because the original epi-on procedure provided insufficient corneal stability or whether the condition would have progressed even with an epi-off procedure, as it does for a small percentage of patients.

Most study findings have shown results of current epi-on protocols are inferior to those achieved with the epi-off or Dresden protocol approved in the United States.6-8 In any case, it is important to continue to monitor patients for KC progression after cross-linking, regardless of age.

Vision rehabilitation with a skilled contact lens specialist after the procedure is also very important. Surgeons tend to focus on the cross-linking itself, but for patients who are school aged or working, visual function is an essential part of a successful outcome.

Our typical protocol is that established scleral lens wearers can resume wear 1 week after cross-linking. A scleral lens will vault over the cornea and help protect it during healing. Those patients who wear soft or gas-permeable lenses that touch the cornea should wait longer before reinitiating habitual lens wear. Patients may need a new contact lens fit as early as 1 to 3 months after the procedure, when the cornea has fully stabilized, because their vision and/or fit may have changed.

Finally, management of KC and cross-linking presents excellent opportunities for interdisciplinary and collaborative care. The corneal specialist and contact lens specialist each bring specific knowledge and skills to help patients achieve the best possible clinical outcomes.

Contemporary scleral lenses work so well that stable vision in them cannot necessarily be taken as a sign that KC progression has stopped. Determination of KC progression requires advanced imaging. There are many different types, sizes, and fitting approaches with scleral lenses, and these must be carefully tailored to the patient for optimal results. With ongoing collaboration and open lines of communication, it is possible to halt progression and help patients achieve good visual function.

Florencia Yeh, OD, FAAO, FSLS

E: fyeh@midwestern.edu

Yeh is an associate professor at Midwestern University Arizona College of Optometry and contact lens clinical care coordinator at Midwestern University Eye Institute, both in Glendale.

Robert Fintelmann, MD, FACS

E: rfinte@midwestern.edu

Fintelmann is an associate professor at Midwestern University Arizona College of Optometry and is in practice at Midwestern University Eye Institute, both in Glendale.

References

1. Photorexa Viscous and Photrexa ISI. Glaukos. Accessed September 22, 2022. https://www.glaukos.com/important-safety-information/photrexa-viscous-and-photrexa-isi/

2. Belin MW, Lim L, Rajpal RK, Hafezi F, Gomes JAP, Cochener B. Corneal cross-linking: current USA status report: from the Cornea Society. Cornea. 2018;37(10):1218-1225.doi:10.1097/ICO.0000000000001707

3. Ansah DO, Wang J, Lu K, Jabbour S, Bower KS, Soiberman US. Post-FDA approval results of epithelium-off, full-fluence, Dresden protocol corneal collagen crosslinking in the USA. Ophthalmol Ther. 2022;9(4):1023-1040. doi:10.1007/s40123-020-00306-1

4. Yuksel E, Cubuk MO, Yalcin NG. Accelerated epithelium-on or accelerated epithelium-off corneal collagen cross-linking: contralateral comparison study. Taiwan J Ophthalmol. 2020;10(1):37-44. doi:10.4103/tjo.tjo_11_19

5. Gokul A, Patel DV, Watters GA, McGhee CNJ. The natural history of corneal topographic progression of keratoconus after age 30 years in non-contact lens wearers. Br J Ophthalmol. 2017;101(6):839-844. doi:10.1136/bjophthalmol-2016-308682

6. Rush SW, Rush RB. Epithelium-off versus transepithelial corneal collagen crosslinking for progressive corneal ectasia: a randomised and controlled trial. Br J Ophthalmol. 2017;101(4):503-508. doi:10.1136/bjophthalmol-2016-308914

7. Choi M, Kim J, Kim EK, Seo KY, Kim TI. Comparison of the conventional Dresden protocol and accelerated protocol with higher ultraviolet intensity in corneal collagen cross-linking for keratoconus. Cornea. 2017;36(5):523-529. doi:10.1097/ICO.0000000000001165

8. Kobashi H, Rong SS, Ciolino JB. Transepithelial versus epithelium-off corneal crosslinking for corneal ectasia. J Cataract Refract Surg. 2018;44(12):1507-1516. doi:10.1016/j.jcrs.2018.08.021