Aggressive Keratoconus May Not Respond to Accelerated Crosslinking Treatment

Younger patients with high maximum corneal curvatures and pronounced optical aberrations responded most poorly, the study shows.

Patients with progressive keratoconus who did not respond to accelerated crosslinking (A-CXL) treatment were younger and tended to have more aggressive cases, higher maximum corneal curvature, and the more pronounced optical aberrations, according to research results published in Journal Français d’Ophtalmologie

These patients should be informed of their high risk of nonresponse and the potential for additional treatment, the researchers advise. 

The investigators compared clinical and corneal topographic parameters both before and after an accelerated-crosslinking procedure in patients with keratoconus spanning a 2-year period. 

All A-CXL procedures were conducted between 2014 and 2016, with a minimum follow-up duration of 24 months. Patient inclusion criteria included the presence of progressive keratoconus and minimal pachymetry higher than 400 µm. Following the A-CXL procedures, patients received oral painkillers, artificial tears (acetylcysteine 5%), and topical antibiotics (azithromycin 1.5%). 

The total cohort included 82 eyes from 60 patients (33% women). Overall, 76% of the A-CXL procedures were performed with isotonic riboflavin. 

At baseline, the mean best spectacle-corrected visual acuity (BSCVA) was 0.32±0.19 logMAR; this improved to 0.31±0.21 logMAR at 6 months, 0.22±0.17 logMAR at 1 year; and 0.20±0.17 logMAR at 2 years. BSCVA was stable in 52.8% of treated eyes, while 41.5% had improved BSCVA at year 2. Decrease in BSCVA higher than 0.1 logMAR was seen in 5.3% of cases, or 3 eyes. 

All eyes demonstrated an initial decrease in pachymetry at 6 months after A-CXL(462±33 µm to 429±47 µm; 7.1% decrease). Mean corneal thickness increased gradually to 438±39 µm and to 444±48 µm at 1 and 2 years, respectively. 

Mean maximum anterior keratometry (Kmax) demonstrated an increase during the first 6 months; a gradual decrease then began and continued through 2 years (57.34±6.69 D at baseline vs 56.75±6.53 D at 2 years). Only 12.5% of eyes had a Kmax increase of more than 1 diopter at 2 years. 

Investigators found that baseline mean corneal topographic cylinder was -2.99±1.82 D, which stayed stable over the 2-year follow-up period. In 12.5% of eyes, Kmax increase was above 1.0 D at 2 years post-procedure, while 5.3% of eyes had an increase in BSCVA of more than 0.1 logMAR. 

No correlation was identified between mean pachymetry evolution and other parameters. At 6 months, a weak positive correlation was noted between variation in cylinder and Kmax (correlation rate, r=0.28). At 1 year, another weak negative correlation between Kmax variation and BSCVA evolution was noted. 

One patient experienced severe corneal scarring after A-CXL treatment. 

Eyes that did not respond to A-CXL treatment were typically younger (mean age, 20±5 vs 25±7 years in responders). These patients also have a higher risk for keratoconus progression. Additionally, researchers found that nonresponder eyes had more higher-order optical aberrations. 

“In our study, eyes with progressive keratoconus which did not respond to A-CXL were the most severe cases and belonged to the youngest patients,” the research concludes. 


Sot M, Gan G, François J, et al. Risk factors for keratoconus progression after treatment by accelerated cross-linking (A-CXL): A prospective 24-month study. J Fr Ophthalmol. 2021;44(6):863-872. doi:10.1016/j.jfo.2020.08.040