Elsevier

Ophthalmology

Volume 121, Issue 4, April 2014, Pages 812-821
Ophthalmology

Original article
A Randomized, Controlled Trial of Corneal Collagen Cross-Linking in Progressive Keratoconus: Three-Year Results

Presented at: American Society of Cataract and Refractive Surgery Symposium on Cataract, IOL and Refractive Surgery, April 2013, San Francisco, California; and European Society of Cataract and Refractive Surgeons Congress, October 2013, Amsterdam, The Netherlands. Copyright approval has been obtained from the American Society of Cataract and Refractive Surgery. The European Society of Cataract and Refractive Surgeons does not retain copyright for any presentation at the European Society of Cataract and Refractive Surgeons Congress.
https://doi.org/10.1016/j.ophtha.2013.10.028Get rights and content

Purpose

To report the refractive, topographic, and clinical outcomes 3 years after corneal collagen cross-linking (CXL) in eyes with progressive keratoconus.

Design

Prospective, randomized controlled trial.

Participants

One hundred eyes with progressive keratoconus were randomized into the CXL treatment or control groups.

Methods

Cross-linking was performed by instilling riboflavin 0.1% solution containing 20% dextran for 15 minutes before and during the 30 minutes of ultraviolet A irradiation (3 mW/cm2). Follow-up examinations were arranged at 3, 6, 12, 24, and 36 months.

Main Outcome Measures

The primary outcome measure was the maximum simulated keratometry value (Kmax). Other outcome measures were uncorrected visual acuity (UCVA; measured in logarithm of the minimum angle of resolution [logMAR] units), best spectacle-corrected visual acuity (BSCVA; measured in logMAR units), sphere and cylinder on subjective refraction, spherical equivalent, minimum simulated keratometry value, corneal thickness at the thinnest point, endothelial cell density, and intraocular pressure.

Results

The results from 48 control and 46 treated eyes are reported. In control eyes, Kmax increased by a mean of 1.20±0.28 diopters (D), 1.70±0.36 D, and 1.75±0.38 D at 12, 24, and 36 months, respectively (all P <0.001). In treated eyes, Kmax flattened by −0.72±0.15 D, −0.96±0.16 D, and −1.03±0.19 D at 12, 24, and 36 months, respectively (all P <0.001). The mean change in UCVA in the control group was +0.10±0.04 logMAR (P = 0.034) at 36 months. In the treatment group, both UCVA (−0.15±0.06 logMAR; P = 0.009) and BSCVA (−0.09±0.03 logMAR; P = 0.006) improved at 36 months. There was a significant reduction in corneal thickness measured using computerized videokeratography in both groups at 36 months (control group: −17.01±3.63 μm, P <0.001; treatment group: −19.52±5.06 μm, P <0.001) that was not observed in the treatment group using the manual pachymeter (treatment group: +5.86±4.30 μm, P = 0.181). The manifest cylinder increased by 1.17±0.49 D (P = 0.020) in the control group at 36 months. There were 2 eyes with minor complications that did not affect the final visual acuity.

Conclusions

At 36 months, there was a sustained improvement in Kmax, UCVA, and BSCVA after CXL, whereas eyes in the control group demonstrated further progression.

Section snippets

Study Design

This was a prospective, unmasked, randomized controlled trial conducted at the Royal Victorian Eye & Ear Hospital and the Centre for Eye Research Australia, Melbourne, Australia, commencing in 2006. The aim of the study was to assess the efficacy and safety of CXL in the treatment of progressive keratoconus. Approval was obtained from the hospital's Human Research and Ethics Committee, and the conduct of this study adhered to the tenets of the Declaration of Helsinki. The trial is registered

Results

Recruitment for the trial was completed in 2009 with 100 eyes randomized to control (50 eyes) and treatment (50 eyes) groups. Six eyes were excluded from analysis: 4 eyes (3 in the treatment group, 1 in the control group) withdrew from the trial before any follow-up data were obtained; 1 patient was pregnant at the time of her 3-year follow-up appointment, and 1 eye had a delay in treatment date, with only 2-year follow-up data available at the time of preparation of this manuscript.

This

Discussion

Corneal collagen cross-linking is often described as the most promising innovation in the treatment of progressive keratoconus in recent years. The growing interest in CXL is reflected in the rapid increase in publications since the first report by Spoerl et al4 in 1998. A keyword search using PubMed (http://www.ncbi.nlm.nih.gov/pubmed) accessed on September 6, 2013, using the terms collagen cross-linking and keratoconus yielded 323 citations, 90% of which were published in the past 4 years.

Acknowledgments

The authors thank Mario Constantinou for his orthoptic work, patient management, and administrative support during the conduct of the trial.

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Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Supported by the Royal Victorian Eye and Ear Hospital Research Committee, Melbourne, Australia; Eye Research Australia Foundation, Melbourne, Australia; and Keratoconus Australia, Melbourne, Australia. Dr. Wittig-Silva is supported by a scholarship from the Faculty of Medicine, University of Melbourne, Melbourne, Australia, and the Contact Lens Society of Australia, Sydney, Australia. None of the funding organizations had any role in the design or conduct of this research. The UV-X device is on loan from the Institute of Refractive and Ophthalmic Surgery. The Centre for Eye Research Australia receives operational infrastructure support from the Victorian government.

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