Long-term results of corneal crosslinking



VSOrnamental collagen crosslinking was approved in the United States in 2016 following successful phase 3 clinical trials in patients with progressive keratoconus and ectasia after refractive surgery.1.2 The patients treated in these pivotal trials are now 10 years away from their crosslinking treatments. Clinicians at our treatment center began the process of evaluating the long-term outcomes of patients treated at our center where the director and founder of our center served as the medical monitor and principal investigator of the 2 aforementioned multicenter clinical trials.

Our preliminary single-center analysis of 26 eyes (20 treated eyes, 6 other untreated eyes) from 16 patients from the pivotal trials shows that most reticulated eyes remained stable 10 years after treatment without significant adverse events or safety concerns. For this study, progression was defined as> 2.00 D or more of maximal keratometry or> 2 or more logMAR lines of uncorrected and eyeglass-corrected visual acuity loss. Data collection and analysis is ongoing.

This is important information for eye care professionals and patients. Although crosslinking has been performed internationally since 1997 and there is substantial evidence of efficacy and safety up to 6, 7 or 10 years in Europe,3-5 studies outside of the United States included a variety of technologies and treatment protocols.

In contrast, the patients we evaluated were treated with the standard epithelium-free protocol using the clinical study light source, Photrexa Viscous (riboflavin 5′-phosphate in 20% dextran ophthalmic solution; Glaukos) and Photrexa (riboflavin 5′-phosphate ophthalmic solution; Glaukos). The clinical study light source output specifications are identical to those of the FDA approved KXL system used in the Glaukos iLink procedure, so the results of this study are directly applicable to US clinical experience.


In eyes treated with keratoconus, no statistically significant difference was observed between corneal topography at 1 year and 10 years, pachymetry and visual acuity results, indicating the stability of the treatment effect. Looking at the results by percentage of eyes stable, about 90% of these keratoconus patients had stable corneal topography a decade after undergoing crosslinking, which is consistent with European data.

Contrary to this stability, untreated eyes experienced a significant increase in peak keratometry (Kmax), thinning of the finest pachymetry (Pthin), and worsening of uncorrected visual acuity and visual acuity. best corrected, respectively.

This long-term stability has had a positive effect on the quality of life of patients and the cost of care. Recent economic analysis has shown that keratoconus patients who have had crosslinking are less likely to undergo penetrating keratoplasty and will spend almost 28 years younger in the advanced stages of the disease. Over their lifetime, the model suggests that they will have more years of quality of life and savings of $ 43,759 per patient.6


A smaller subset of patients underwent crosslinking for post-refractive surgery ectasia. More variability and progression was seen in some of these eyes. The treated eyes still functioned significantly better than the other untreated eyes. This indicates that patients with ectasia required closer and longer-term follow-up, even after crosslinking treatment.

A number of possible reasons exist for different results in the ectasia group. Ectasia may simply be a less predictable or more aggressive condition. Or it may be that further improvements are needed in the current approach to crosslinking for ectasia. In pivotal clinical trials, keratoconus eyes achieved greater Kmax flattening (1.6 D) than ectasia eyes (0.70 D) at 1 year.1.2 Currently, crosslinking treatments target the central 9.0mm of the cornea. In eyes with post-refractive ectasia, the ectatic region may be more peripheral and therefore less effectively treated.7 Future innovations could allow topography-guided personalized treatments or other modifications that could provide more focal crosslinking treatment to the weakened area of ​​the peripheral inferior cornea.

Follow-up after crosslinking

Interestingly, many patients in our study were lost to follow-up after the clinical trial and did not return to the office for the 10-year examination until after persistent and repeated efforts.

Thus, a clear message emerging from our data is that regular monitoring of patients, whether they have undergone crosslinking or not, is essential and should be discussed with all patients undergoing crosslinking.

Ten years after treatment, in the remaining untreated eyes, a progression of approximately 10.00 D was observed in patients with ectasia and 5.00 D in patients with keratoconus. These other eyes initially had subclinical disease or only mild disease, but they were still at high risk for progression. Had these patients been examined at the recommended intervals over the past decade, the other eyes could have been treated equally and possibly avoided the same degree of progression.

In addition, age has not proven to be protective, especially with ectasia. Patients with ectasia (and especially their untreated eyes) continued to progress well into their fifties and sixties. As noted, ectasia may be a less stable condition and it is important to have this conversation with these patients, especially because there may be a greater possibility of needing a second treatment over time. time.

When monitoring postcrosslinking patients or those at risk for ectatic disease, it is also important to be aware of the influence that wearing contact lenses can have on topographic accuracy. For this 10-year review, we asked patients to stop wearing contact lenses before the exam. While it is difficult for patients to stop wearing contact lenses, it is essential for accurate corneal maps.


Preliminary 10-year follow-up data demonstrated that iLink corneal collagen crosslinking is effective in stabilizing corneal topography (Figure 1) and long-term visual acuity in patients with keratoconus or progressive ectasia after refractive surgery. The final results of the study will be released later this year. Clinicians should be aware that a small percentage of treated eyes can continue to progress. Although the cornea has become more stable after crosslinking, postoperative monitoring is still necessary, especially in patients with post-refractive corneal ectasia.

The references

1. Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK; American Study Group on Crosslinking. Multicenter clinical trial in the United States of corneal collagen crosslinking for the treatment of keratoconus. Ophthalmology. 2017; 124 (9): 1259-1270. doi: 10.1016 / d. ophta.2017.03.052

2. Hersh PS, Stulting RD, Muller D, Durrie DS, Rajpal RK; American Study Group on Crosslinking. American multicenter clinical trial on corneal collagen crosslinking for the treatment of corneal ectasia after refractive surgery. Ophthalmology. 2017; 124 (10): 1475-1484. doi: 10.1016 / j.ophtha.2017.05.036

3. Poli M, Lefevre A, Auxenfans C, Burillon C. Crosslinking of corneal collagen for the treatment of progressive corneal ectasia: prospective result at 6 years in a French population. Am J Ophthalmol. 2015; 160 (4): 654-662e1. doi: 10.1016 / d. ajo.2015.06.027

4. O’Brart DP, Patel P, Lascaratos G, et al. Corneal cross-linking to stop the progression of keratoconus and corneal ectasia: seven-year follow-up. Am J Ophthalmol. 2015; 160 (6): 1154-1163. doi: 10.1016 / j.ajo.2015.08.023

5. Raiskup F, Theuring A, Pillunat LE, Spoerl E. Crosslinking of corneal collagen with riboflavin and ultraviolet-A light in progressive keratoconus: results at ten years. Cataract refraction surgery J. 2015; 41 (1): 41-46. doi: 10.1016 / j.jcrs.2014.09.033

6. Lindstrom RL, Berdahl JP, Donnenfeld ED, et al. Corneal cross-linking versus conventional treatment of keratoconus: an economic model for life. J Med Econ. 2021; 24 (1): 410-420. doi: 10. 1080 / 13696998.2020.1851556

7. Greenstein SA, Fry KL, Hersh PS. Effect of topographic location of the cone on corneal collagen crosslinking outcomes for keratoconus and corneal ectasia. J Refract Surg. 2012; 28 (6): 397- 405. doi: 10.3928 / 1081597X-20120518-02


Leave A Reply

Your email address will not be published.