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Comparison of 2 protocols for accelerated corneal crosslinking in pediatric keratoconus

Budhiraja, Gunjan MBBS, DNB, DO, FICO; Gour, Abha MBBS, DO; Sabherwal, Shalinder MBBS, MD, FRCS, MPHEC

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Journal of Cataract & Refractive Surgery: October 2020 - Volume 46 - Issue 10 - p 1453
doi: 10.1097/j.jcrs.0000000000000385
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We read with great interest the article by Ağca et al.1 This study is commendable in comparing 2 different protocols with analysis of 5-year follow-up after intervention in the pediatric population. We feel that there are few points requiring further clarity in this article.

There is a disparity in description of both groups at 3 different points in the article. In the Abstract, it is mentioned that they divided the patients into 2 groups and that Group 1 received 4 minutes illumination at 30 mW/cm2 and Group 2 received 5 minutes illumination at 18 mW/cm2. However, in the Methods section, it is stated that Group 1 received 5 minutes illumination at 18 mW/cm2 and Group 2 received 4 minutes illumination at 30 mW/cm2. The surgical technique description of 2 groups was that Group 1 received 30 mW/cm2 and Group 2 received 18 mW/cm2 irradiances at 5 minutes each with no difference in the amount of time taken in the technique.

We found a disparity in the mention of study designs in the Abstract and the Methods. The Abstract states the study design was a retrospective case–control study, and the Methods section states it was a retrospective interventional case series. We feel the study design would be a retrospective nonrandomized interventional case series because there are no well-defined cases and controls in the study.

Although this study reported that keratometric progression rates were similar over the 3-year and 5-year follow-up period, 23.3% vs 16.8% in Groups 1 and 2, respectively (P = .411), there is no mention of the use of anterior segment optical coherence tomography to look for the demarcation line to assess the effectiveness of the crosslinking (CXL) procedure in both groups. So, it is difficult to prove whether the CXL procedure alone could explain this effect. There are several confounders related to the progression of keratoconus significant in the pediatric population, for example, history of allergy or atopy and the stage of keratoconus when the intervention was performed, which have not been mentioned by the authors.2

The authors reported that there were no complications, but the endothelial cell density was not documented at any visit. This parameter is important considering the long-term effects of CXL with higher irradiances. Cingü et al. found significant endothelial cell changes in both density and morphology (coefficient of variation and 6A) after accelerated CXL (18 mW/cm2 for 5 minutes), which returned to baseline at 6 months.3 Bhandari et al. used more intensive ultraviolet A irradiance (30 mW/cm2 for 3 minutes) and reported endothelial changes that did not return to baseline.4

As mentioned by the authors as one of the study limitations, we also feel that the unequal distribution of children in the 2 groups could also influence the comparative results.


1. Ağca A, Tülü B, Yaşa D, Kepez Yıldız B, Sucu M, Genç S, Fazıl K, Yıldırım Y. Accelerated corneal crosslinking in children with keratoconus: 5-year results and comparison of 2 protocols. J Cataract Refractive Surg 2020;46:517–523
2. Leoni-Mesplie S, Mortemousque B, Mesplie N, Touboul D, Praud D, Malet F, Colin J. Epidemiologcal aspects of keratoconus in children. Fr J Ophthalmol 2012;35:776–785
3. Cingü AK, Sogutlu-Sari E, Cınar Y, Sahin M, Türkçü FM, Yüksel H, Sahin A, Caça I. Transient corneal endothelial changes following accelerated collagen cross-linking for the treatment of progressive keratoconus. Cutan Ocul Toxicol 2014;33:127–1231
4. Bhandari V, Lohia M, Reddy JK. Haritha effect of accelerated corneal collagen cross linking (CXL) on corneal endothelium. Adv Ophthalmol Vis Syst 2015;3:00074
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