The impact of cross-linking on corneal transplant rates

Before the availability of cross-linking, corneal transplantation was the only treatment for keratoconus, and it was generally deferred until vision had declined significantly. Rates of corneal transplant for keratoconus have declined in recent years around the world. For example, the 2022 Eye Banking Statistical Report revealed a 26% decrease in the number of corneal transplants performed in the US in the first 6 years after the approval of cross-linking.¹ This decrease in transplants—from 3166 procedures in 2017 to 2334 in 2022—was attributed to cross-linking.¹ Similarly, Dutch researchers found a 25% reduction in corneal transplants for keratoconus 5 to 7 years after cross-linking was introduced in the Netherlands vs a 3-year period before the introduction of cross-linking in that country.²

Anecdotally, I have been performing far fewer corneal transplants since iLink corneal cross-linking (Glaukos Corporation) was approved in the US in 2016. I prefer to stabilize the cornea and stop disease progression with cross-linking, and then optimize vision with scleral contact lenses if good vision can’t be obtained with traditional contact lenses or glasses. I almost never perform a keratoplasty procedure for keratoconus anymore unless the patient has already experienced treatment failure with scleral lenses.

Recently, researchers in Norway found that transplant rates continue to decline well beyond the first few years after the introduction of cross-linking. The Oslo University Hospital, which provides corneal transplantation services for approximately half of Norway’s population, reported a 50% decrease in keratoplasties
8 years after cross-linking was approved there, and an 80% reduction after 15 years.³

Researchers at the hospital compared transplant rates during a 2-year period (2005 and 2006) just before the 2007 introduction of cross-linking in Norway, as well as a more recent 2-year period (2021 and 2022). During the 15 years in between the 2 time periods studied, the number of transplants performed for keratoconus declined from 55 to 11 procedures, or 40% of all transplants to just 3% in the later time period. Authors acknowledged that previous studies of the decline in transplant rates after 7 to 8 years were too short of a time frame to ensure cross-linking treatment was offered to all patients with progressive keratoconus.

I agree with that perspective. I would expect we’ll continue to see sharp declines in the US over the next several years. Although surgeons have adopted cross-linking relatively quickly, it still takes time for doctors to gain access to and familiarity with the procedure. I believe that as doctors become more experienced at cross-linking, they gain a better understanding of who is a candidate for the procedure.

We initially thought that factors such as age, severity, and corneal thickness might be contraindications to treatment. It turns out that in most cases, they are not—and our willingness to perform cross-linking in both early- and late-stage disease has increased over time.

In the Oslo study, there was an increase in the mean age of patients undergoing corneal transplant for keratoconus, with only 9% of the transplants (1 of 11) being performed on patients younger than 30 years in 2021-2022 vs nearly 47% of those undergoing keratoplasties (26 of 55) during the earlier time period.3 The vast majority (90.9%) of those undergoing a transplant in the 2021-2022 period were already in the advanced stages of keratoconus.

I believe it is encouraging to see that surgeons are avoiding transplants in young patients and those with milder disease. The ability to avoid or delay transplantation is life-changing, and I think we sometimes underestimate what a big deal a transplant is for a young person. Yes, it can successfully restore their vision, but a transplant also introduces the risk of infection, graft failure, traumatic dislocation of the graft, a greater risk of glaucoma or early cataracts, and a high likelihood of repeat transplants during the patient’s lifetime.

While it is unlikely that corneal transplants for keratoconus will ever drop to 0, I do foresee that transplants will become less common even for advanced keratoconus over time. Take, for example, a case where an older patient with keratoconus who is stable and has stopped progressing but has poor vision in glasses. In almost all cases, we can now correct that patient’s vision effectively with scleral lenses, and that will continue to improve as access to optometrists who fit advanced lenses expands.

Additionally, iLink corneal cross-linking can reduce the time patients spend in advanced stages of keratoconus by up to 28 years, according to a discrete-event microsimulation model.⁴ Ideally, patients will undergo cross-linking to stop progression of keratoconus earlier in the disease course and never reach the advanced stages in the first place.

Kenneth A. Beckman, MD, FACS

P: 614-890-5692

Beckman is director of corneal services at Comprehensive EyeCare of Central Ohio and clinical assistant professor of ophthalmology at The Ohio State University in Columbus.

References

1. Mathews P, Benbow A, Corcoran K, et al. 2022 Eye Banking Statistical Report—executive summary. Eye Bank Corneal Transpl. 2023;2(3):e0008. doi:10.1097/ebct.0000000000000008

2. Godefrooij DA, Gans R, Imhof SM, Wisse RP. Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking. Acta Ophthalmol. 2016;94(7):675-678. doi:10.1111/aos.13095

3. Hagem AM, Thorsrud A, Sæthre M, Sandvik G, Kristianslund O, Drolsum L. Dramatic reduction in corneal transplants for keratoconus 15 years after introduction of corneal crosslinking. Cornea. 2024;43(4):437-442. doi:10.1097/ICO.0000000000003401

4. Lindstrom RL, Berdahl JP, Donnenfeld ED, et al. Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model. J Med Econ. 2021;24(1):410-420. doi:10.1080/13696998.2020.1851556