Comparing Standard, Accelerated Corneal Crosslinking in Pediatric Keratoconus

Researchers compared 5 years worth of follow up from patients who underwent 2 styles of corneal collagen crosslinking.

While both standard corneal collagen crosslinking (epi-off CXL) and accelerated transepithelial CXL (epi-on CXL) halt the progression of pediatric keratoconus, epi-off CXL is safer and more effective, according to research published in Cornea.

Researchers conducted a prospective cohort study of 78 eyes from 65 consecutive pediatric patients (55.38% male) who underwent either standard epi-on CXL or accelerated epi-off CXL for progressive keratoconus between 2008 and 2014. Inclusion criteria included age below 18 years (range, 8 years to 17 years), a clear central cornea, minimum pachymetry of 400 µm at the thinnest point, and documented progression defined by an increase in steep keratometry of 1 D or greater on 2 tests conducted at least 2 months apart. 

The accelerated epi-on CXL group included 32 eyes and the epi-off group included 46 eyes. Mean patient age was approximately 13.2 years and 14.6 years in each group, respectively. No statistically significant difference in uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), sphere, cylinder, keratometry, or pachymetry during preoperative evaluations. At 5 years follow-up, 46 eyes and 31 eyes from each group were evaluated. 

Both groups showed no significant changes UCVA were noted at either 12- or 60-month follow-up. In the epi-off CXL group, BCVA improvement at 12- and 60-month follow-up was 0.03±0.13 and 0.09±0.13 logarithm of the minimum angle, respectively (P =.097 and <.001). In the accelerated epi-on CXL group, mean improvement was 0.09±0.17 and 0.06±0.19 in the same time frame. This was statistically significant in both follow-up periods (P =.042 and =.037, respectively). 

In the epi-off CXL group, a significant cylinder decrease was noted at both follow-up points (0.66±1.37 D and 0.89+2.39 D; P =.04 for both) with no significant changes in sphere. Flat, steep, and maximum keratometry did not have significant changes at 12 months; however, by 60 months, all measures reached significant flattening (0.77±1.41, 1.02+1.85 D, and 1.67±2.22 D; P <.001, P =.023, and P <.001, respectively). Mean keratometry reached significant flattening at both time points (2.45±5.22 D and 3.18±5.17 D). 

No significant changes in cylinder or sphere were found in the accelerated epi-on CXL group. Also in this group, flat, steep, maximum, and mean keratometry were not associated with significant changes at either postoperative time point. 

The epi-off CXL group also experienced a significant decrease in pachymetry (24.40±28.87 µm and 16.67±26.20 µm at 12 and 60 months; P <.001 for both), no significant changes in anterior elevation values at 12 months but a significant decrease at 60 months (4.42±5.42 µm; P <.001) and had 29 and 17 centered and decentered cones. Comparatively, the accelerated epi-on CXL group had no significant changes in pachymetry at the thinnest point at 12 months but a significant increase at 60 months (7.33±11.78 µm; P =.044), no significant changes in corneal elevation value, and 16 of each centered and decentered cones.

In the accelerated epi-on CXL group, 3 participants experienced disease progression throughout the follow-up period. 

One noted study limitation was the lack of randomized studies comparing these procedures in children.

“Our results show that epi-off CXL was safer and more effective in halting the progression of [keratoconus] in children at 5 years of follow-up compared with [accelerated] epi-on CXL,” the researchers concluded.  


Henriquez MA, Hernandez-Sahaugn G, Camargo J, Izquierdo Jr. L. Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in pediatric patients: five years of follow-up. Cornea. 2020;39(12):1493-1498.