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Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: Long-term results
Frederik Raiskup-Wolf, MD, Anne Hoyer, MD, Eberhard Spoerl, PhD, Lutz E. Pillunat, MD

PURPOSE: To prove the long-term dampening effect of riboflavin- and ultraviolet-A-induced collagen crosslinking on progressive keratoconus. SETTING: Department of Ophthalmology, C.G. Carus UniversityHospital, Dresden, Germany. METHODS: Four hundred eighty eyes of 272 patients with progressive keratoconus were included in this long-term retrospective study. The maximum follow-up was 6 years. At the first and all followup examinations, refraction, best corrected visual acuity (BCVA), corneal topography, corneal thickness, and intraocular pressure were recorded. RESULTS: The analysis included 241eyes with a minimum follow-up of 6 months. The steepening decreased significantly by 2.68 diopters (D) in the first year, 2.21 D in the second year, and 4.84 D in the third year. The BCVA improved significantly (R1 line) in 53% of 142 eyes in the first year, 57% of 66 eyes in the second year, and 58% of 33 eyes in the first year or remained stable (no lines lost) in 20%, 24%, and 29%,respectively. Two patients had continuous progression of keratoconus and had repeat crosslinking procedures. CONCLUSIONS: Despite the low number of patients with a follow-up longer than 3 years, results indicate long-term stabilization and improvement after collagen crosslinking. Thus, collagen crosslinking is an effective therapeutical option for progressive keratoconus. J Cataract Refract Surg 2008;34:796–801 Q 2008 ASCRS and ESCRS

Keratoconus is a corneal degeneration characterized by bilateral conical protrusion and corneal thinning.1 The average age of appearance of keratoconus is the second decade of life.2 The course of the disease varies from slight irregular astigmatism to severe visual impairment due to increasing protrusion and subepithelial scarring. Because of the young age of thepatients, keratoconus often has a significant negative effect on quality of life.3 Results of currently available treatment options are not encouraging because the treatments do

Accepted for publication December 27, 2007. From the Department of Ophthalmology, C.G. Carus University Hospital, Dresden, Germany. No author has a financial or proprietary interest in any material or method mentioned.Corresponding author: Frederik Raiskup-Wolf, MD, Department of Ophthalmology, C.G. Carus University Hospital, Dresden, Germany. E-mail:

not stop the progression of keratoconus. Thus, because of its progressive nature, keratoconus was the most frequent reason for keratoplasty in the past 3 decades.4 Keratoconus leads to biomechanical alterations, and itsspecific cause is not known. The biomechanical characteristics of the cornea result from the collagen scaffold and collagen compound and their bonding with the collagen fibrils. The 3-dimensional configuration of the collagen lamella fundamentally codetermines the cornea’s resistance. Biochemical and immunohistochemical studies of the matrix’s proteoglycans show differences between normal andkeratoconic corneas.5–8 Enzymatic alterations with an increased expression of lysosomal and proteolytic enzymes,6,9–11 decreased concentration of protease inhibitors9,12 decreased thickness,6 and modified configuration of the stromal collagen lamella13–15 have been observed. A photooxidative collagen crosslinking technique using riboflavin and ultraviolet-A (UVA) light was developed to counteract theprogressive corneal thinning, and thus the progression, of keratoconus. With crosslinking, additional covalent binding between
0886-3350/08/$dsee front matter doi:10.1016/j.jcrs.2007.12.039


Q 2008 ASCRS and ESCRS Published by Elsevier Inc.



collagen molecules can be achieved, which stabilizes the collagen scaffold and changes several...
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