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BMC Ophthalmology
Published in: BMC Ophthalmology 1/2015

Open Access 01-12-2015 | Research article

Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus

Authors: Stefan J. Lang, Elisabeth M. Messmer, Gerd Geerling, Marc J. Mackert, Tobias Brunner, Sylvia Dollak, Borislav Kutchoukov, Daniel Böhringer, Thomas Reinhard, Philip Maier

Published in: BMC Ophthalmology | Issue 1/2015

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Abstract

Background

Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy.

Methods

The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model.

Results

A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/−standard deviation) by 0.35 +/− 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/− 0.61 dioptres/year. This difference was statistically significant (p = 0.02).

Conclusions

Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not.

Trial registration

NCT00626717, Date of registration: February 20, 2008.
Literature
1.
Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28:293–322.CrossRefPubMed
2.
Tuft SJ, Hassan H, George S, Frazer DG, Willoughby CE, Liskova P. Keratoconus in 18 pairs of twins. Acta Ophthalmol (Copenh). 2012;90:e482–6.CrossRef
3.
4.
Shapiro MB, France TD. The ocular features of Down’s syndrome. Am J Ophthalmol. 1985;99:659–63.CrossRefPubMed
5.
6.
7.
Bühren J, Bischoff G, Kohnen T. Keratoconus: clinical aspects, diagnosis, therapeutic possibilities. Klin Monbl Augenheilkd. 2011;228:923–40. quiz 941–2.CrossRefPubMed
8.
McMahon TT, Edrington TB, Szczotka-Flynn L, Olafsson HE, Davis LJ, Schechtman KB. Longitudinal changes in corneal curvature in keratoconus. Cornea. 2006;25:296–305.CrossRefPubMed
9.
Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66:97–103.CrossRefPubMed
10.
Spoerl E, Wollensak G, Dittert D-D, Seiler T. Thermomechanical behavior of collagen-cross-linked porcine cornea. Ophthalmologica. 2004;218:136–40.CrossRefPubMed
11.
Wollensak G, Wilsch M, Spoerl E, Seiler T. Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/UVA. Cornea. 2004;23:503–7.CrossRefPubMed
12.
Hayes S, Boote C, Kamma-Lorger CS, Rajan MS, Harris J, Dooley E, et al. Riboflavin/UVA collagen cross-linking-induced changes in normal and keratoconus corneal stroma. PLoS One. 2011;6:e22405.CrossRefPubMedPubMedCentral
13.
Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004;29:35–40.CrossRefPubMed
14.
Vetter JM, Tubic-Grozdanis M, Faust M, Lorenz K, Gericke A, Stoffelns BM. Effect of various compositions of riboflavin eye drops on the intraoperative corneal thickness during UVA-cross-linking in keratoconus eyes. Klin Monbl Augenheilkd. 2011;228:509–14.CrossRefPubMed
15.
Messmer EM, Meyer P, Herwig MC, Loeffler KU, Schirra F, Seitz B, et al. Morphological and immunohistochemical changes after corneal cross-linking. Cornea. 2013;32:111–7.CrossRefPubMed
16.
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–7.CrossRefPubMed
17.
Kampik D, Koch M, Kampik K, Geerling G. Corneal riboflavin/UV-A collagen cross-linking (CXL) in keratoconus: two-year results. Klin Monbl Augenheilkd. 2011;228:525–30.CrossRefPubMed
18.
Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34:796–801.CrossRefPubMed
19.
Saffarian L, Khakshoor H, Zarei-Ghanavati M, Esmaily H. Corneal crosslinking for keratoconus in Iranian patients: Outcomes at 1 year following treatment. Middle East Afr J Ophthalmol. 2010;17:365–8.CrossRefPubMedPubMedCentral
20.
Koller T, Pajic B, Vinciguerra P, Seiler T. Flattening of the cornea after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2011;37:1488–92.CrossRefPubMed
21.
Asri D, Touboul D, Fournié P, Malet F, Garra C, Gallois A, et al. Corneal collagen crosslinking in progressive keratoconus: multicenter results from the French National Reference Center for Keratoconus. J Cataract Refract Surg. 2011;37:2137–43.CrossRefPubMed
22.
Derakhshan A, Shandiz JH, Ahadi M, Daneshvar R, Esmaily H. Short-term outcomes of collagen crosslinking for early keratoconus. J Ophthalmic Vis Res. 2011;6:155–9.PubMedPubMedCentral
23.
Viswanathan D, Males J. Prospective longitudinal study of corneal collagen crosslinking in progressive keratoconus. Clin Experiment Ophthalmol. 2013;41:531–6.CrossRefPubMed
24.
Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg. 2008;24:S720–5.PubMed
25.
Wittig-Silva C, Chan E, Islam FMA, Wu T, Whiting M, Snibson GR. A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: Three-year results. Ophthalmology. 2014;121:812–21.CrossRefPubMed
26.
Hersh PS, Greenstein SA, Fry KL. Corneal collagen crosslinking for keratoconus and corneal ectasia: One-year results. J Cataract Refract Surg. 2011;37:149–60.CrossRefPubMed
27.
Greenstein SA, Fry KL, Hersh PS. Corneal topography indices after corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg. 2011;37:1282–90.CrossRefPubMed
28.
O’Brart DPS, Chan E, Samaras K, Patel P, Shah SP. A randomised, prospective study to investigate the efficacy of riboflavin/ultraviolet A (370 nm) corneal collagen cross-linkage to halt the progression of keratoconus. Br J Ophthalmol. 2011;95:1519–24.CrossRefPubMed
29.
Sharma N, Suri K, Sehra SV, Titiyal JS, Sinha R, Tandon R, Vajpayee RB. Collagen cross-linking in keratoconus in Asian eyes: visual, refractive and confocal microscopy outcomes in a prospective randomized controlled trial. Int Ophthalmol. Feb 2015 [Epub ahead of print].
30.
Pérez-Santonja JJ, Artola A, Javaloy J, Alió JL, Abad JL. Microbial keratitis after corneal collagen crosslinking. J Cataract Refract Surg. 2009;35:1138–40.CrossRefPubMed
31.
Eberwein P, Auw-Hädrich C, Birnbaum F, Maier PC, Reinhard T. Corneal melting after cross-linking and deep lamellar keratoplasty in a keratoconus patient. Klin Monbl Augenheilkd. 2008;225:96–8.CrossRefPubMed
32.
Greenstein SA, Fry KL, Bhatt J, Hersh PS. Natural history of corneal haze after collagen crosslinking for keratoconus and corneal ectasia: Scheimpflug and biomicroscopic analysis. J Cataract Refract Surg. 2010;36:2105–14.CrossRefPubMed
33.
Lange C, Böhringer D, Reinhard T. Corneal endothelial loss after crosslinking with riboflavin and ultraviolet-A. Graefes Arch Clin Exp Ophthalmol. 2012;250:1689–91.CrossRefPubMed
34.
Wollensak G, Hammer T, Herrmann CIA. Haze or calcific band keratopathy after crosslinking treatment? Ophthalmologe. 2008;105:864–5.CrossRefPubMed
35.
Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35:1358–62.CrossRefPubMed
36.
Maier P, Reinhard T. Riboflavin UVA cross-linking for keratoconus. Ophthalmologe. 2013;110:818–22.CrossRefPubMed
37.
Wagner H, Barr JT, Zadnik K. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: methods and findings to date. Cont Lens Anterior Eye. 2007;30:223–32.CrossRefPubMedPubMedCentral
38.
39.
Vianna LMM, Muñoz B, Hwang FS, Gupta A, Jun AS. Variability in Oculus Pentacam tomographer measurements in patients with keratoconus. Cornea. 2015;34:285–9.CrossRefPubMed
40.
Hashemi K, Guber I, Bergin C, Majo F. Reduced precision of the Pentacam HR in eyes with mild to moderate keratoconus. Ophthalmology. 2015;122:211–2.CrossRefPubMed
41.
Szalai E, Berta A, Hassan Z, Módis L. Reliability and repeatability of swept-source Fourier-domain optical coherence tomography and Scheimpflug imaging in keratoconus. J Cataract Refract Surg. 2012;38:485–94.CrossRefPubMed
42.
Gomes JAP, Tan D, Rapuano CJ, Belin MW, Ambrósio R, Guell JL, et al. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34:359–69.CrossRefPubMed
Metadata
Title
Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus
Authors
Stefan J. Lang
Elisabeth M. Messmer
Gerd Geerling
Marc J. Mackert
Tobias Brunner
Sylvia Dollak
Borislav Kutchoukov
Daniel Böhringer
Thomas Reinhard
Philip Maier
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2015
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-015-0070-7

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