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Long-term Follow-up of Corneal Collagen Cross-linking for Keratoconus—The Cretan Study

Kymionis, George D. MD, PhD*,†; Grentzelos, Michael A. MD*; Liakopoulos, Dimitrios A. MD, MSc*; Paraskevopoulos, Theodoros A. MD*; Klados, Nektarios E. MD*; Tsoulnaras, Konstantinos I. MD*; Kankariya, Vardhaman P. MD*; Pallikaris, Ioannis G. MD, PhD*

doi: 10.1097/ICO.0000000000000248
Clinical Science

Purpose: The aim of this study was to present the long-term results of corneal collagen cross-linking (CXL) in patients with keratoconus.

Methods: In this prospective, interventional case series, patients with progressive keratoconus underwent CXL treatment according to the Dresden protocol. Visual, refractive, and topographic outcomes along with endothelial cell density were evaluated preoperatively and at 1, 2, 3, 4, and 5 years postoperatively.

Results: Twenty-one patients (25 eyes) were enrolled. The mean follow-up was 43.7 ± 12.2 (range, 24–60) months. Logarithm of the minimum angle of resolution (logMAR) mean uncorrected visual acuity and the mean best spectacle-corrected visual acuity improved significantly from 0.92 ± 0.54 and 0.29 ± 0.21 preoperatively to 0.63 ± 0.41 (P = 0.010) and 0.18 ± 0.18 (P = 0.011), respectively, at the last follow-up. Mean steep and mean flat keratometry readings reduced significantly from 52.53 ± 6.95 diopters (D) and 48.11 ± 5.98 D preoperatively to 49.10 ± 4.50 D (P < 0.001) and 45.58 ± 3.81 D (P = 0.001), respectively, at the last follow-up. The mean endothelial cell density was 2708 ± 302 cells per square millimeter preoperatively and did not change significantly (P > 0.05) at any postoperative interval (2593 ± 258 cells/mm2 at the last follow-up; P = 0.149).

Conclusions: CXL seems to be effective and safe in halting progression of keratoconus over a long-term follow-up period up to 5 years postoperatively.

*Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, Heraklion, Greece; and

Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL.

Reprints: George D. Kymionis, MD, PhD, Vardinoyiannion Eye Institute of Crete (VEIC), Faculty of Medicine, University of Crete, 71003 Heraklion, Crete, Greece (e-mail:

Supported in part by the special research account of the University of Crete.

The authors have no conflicts of interest to disclose.

Received May 07, 2014

Received in revised form July 11, 2014

Accepted July 17, 2014

© 2014 by Lippincott Williams & Wilkins.