Accelerated versus Conventional Corneal Collagen Cross-Linking for Progressive Keratoconus

Farshad OSTADIAN, Mahmoud-Reza PANAHI-BAZAZ, Seyed Mohsen MOOSAZADEH, Saeed HESAM


We aimed to compare the effect of accelerated and conventional corneal collagen cross-linking (CXL) on visual, refractive, and topographic parameters in patients with progressive keratoconus. Between December 2014 and February 2016, at Imam Khomeini Hospital, Ahvaz Jundishapur University of Medical Sciences, Iran, we compared 37 eyes of 21 patients treated by conventional CXL (CCXL; 3 mW/cm2 in 30 minutes) with 34 eyes of 18 patients treated by accelerated CXL (ACXL; 18 mW/cm2 in 5 minutes) based on generalizing estimation equation analysis in terms of corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), corneal endothelial cell indices, and topographic parameters before and at 3, 6 and 12 months after the operation. The mean UDVA and spherical equivalent changes were similar in the two groups, but an improvement in CDVA was only observed in the CCXL group (P = 0.003). Keratometry (minimum and maximum) was significantly decreased in the CCXL group (P = 0.043 and P = 0.008, respectively). Indices of keratoconus progression—surface asymmetry index (SAI), keratoconus prediction index (KPI), and keratoconus index (KCI)—were significantly lower in the CCXL group than in the ACXL group (P = 0.002, P < 0.001, and P < 0.001, respectively). The thinnest corneal thickness (TCT) was not significantly different between the two groups (P = 0.15). The reduction of corneal endothelial cell density was also similar between the two groups; however, polymorphism and polymegethism were significantly lower in the ACXL group than in the CCXL group. In conclusion, we showed that although ACXL at 18 mW/cm2 slowed keratoconus progression safely during a 1-year follow-up, CCXL at 3 mW/cm2 may be superior in the prevention of keratoconus progression.


Tuori AJ, Virtanen I, Aine E, Kalluri R, Miner JH, Uusitalo HM. The immunohistochemical composition of corneal basement membrane in keratoconus. Curr Eye Res. 1997;16(8):792-801. pmid: 9255508

Cheng EL, Maruyama I, SundarRaj N, Sugar J, Feder RS, Yue BY. Expression of type XII collagen and hemidesmosome-associated proteins in keratoconus corneas. Curr Eye Res. 2001;22(5):333-40. pmid: 11600933

Radner W, Zehetmayer M, Skorpik C, Mallinger R. Altered organization of collagen in the apex of keratoconus corneas. Ophthalmic Res. 1998;30(5):327-32. doi: 10.1159/000055492 pmid: 9704337

Andreassen TT, Simonsen AH, Oxlund H. Biomechanical properties of keratoconus and normal corneas. Exp Eye Res. 1980;31(4):435-41. pmid: 7449878

Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297-319. doi: 10.1016/s0039-6257(97)001 19-7

Garcia-Lledo M, Feinbaum C, Alio JL. Contact lens fitting in keratoconus. Compr Ophthalmol Update. 2006;7(2):47-52. pmid: 16709339

Wollensak G, Sporl E, Seiler T. [Treatment of keratoconus by collagen cross linking]. Ophthalmologe. 2003;100(1):44-9. doi: 10.1007/s003 47-002-0700-3 pmid: 12557025

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(5):796-801. doi: 10.1016/j.jcrs.2007.12 .039 pmid: 18471635

Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1 pmid: 12719068

Raiskup F, Hoyer A, Spoerl E. Permanent corneal haze after riboflavin-UVA-induced cross-linking in keratoconus. J Refract Surg. 2009;25(9):S824-8. doi: 10.3928/1081597X-20090813-12 pmid: 19772259

Kymionis GD, Portaliou DM, Bouzoukis DI, Suh LH, Pallikaris AI, Markomanolakis M, et al. Herpetic keratitis with iritis after corneal crosslinking with riboflavin and ultraviolet A for keratoconus. J Cataract Refract Surg. 2007;33(11):1982-4. doi: 10.1016/j.jcrs. 2007.06.036 pmid: 17964410

Wollensak G, Hammer T, Herrmann CI. [Haze or calcific band keratopathy after crosslinking treatment?]. Ophthalmologe. 2008;105(9):864-5. doi: 10.1007/s00 347-008-1831-y pmid: 18791720

Wernli J, Schumacher S, Spoerl E, Mrochen M. The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time. Invest Ophthalmol Vis Sci. 2013;54(2):1176-80. doi: 10.1167/iovs.12-11409 pmid: 23299484

Mrochen M. Current status of accelerated corneal cross-linking. Indian J Ophthalmol. 2013;61(8):428-9. doi: 10.4103/0301-4738.116075 pmid: 23925330

Kymionis GD, Tsoulnaras KI, Grentzelos MA, Liakopoulos DA, Tsakalis NG, Blazaki SV, et al. Evaluation of corneal stromal demarcation line depth following standard and a modified-accelerated collagen cross-linking protocol. Am J Ophthalmol. 2014;158(4):671-5 e1. doi: 10.1016/j.ajo.2014.07.005 pmid: 25034113

Hammer A, Richoz O, Arba Mosquera S, Tabibian D, Hoogewoud F, Hafezi F. Corneal biomechanical properties at different corneal cross-linking (CXL) irradiances. Invest Ophthalmol Vis Sci. 2014;55(5):2881-4. doi: 10.1167/iovs.13-13748 pmid: 24677109

Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-A-induced cross-linking. J Cataract Refract Surg. 2003;29(9):1780-5. doi: 10.1016/s0886-3350(03)00407-3 pmid: 14522301

Cinar Y, Cingu AK, Turkcu FM, Yuksel H, Sahin A, Yildirim A, et al. Accelerated corneal collagen cross-linking for progressive keratoconus. Cutan Ocul Toxicol. 2014;33(2):168-71. doi: 10.3109/15569527.2013.816724 pmid: 23879803

Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007;26(4):385-9. doi: 10.1097/ICO.0b013e3180334f 78 pmid: 17457183

Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006;17(4):356-60. doi: 10.1097/ 4.86723.25 pmid: 16900027

Vinciguerra P, Albe E, Trazza S, Rosetta P, Vinciguerra R, Seiler T, et al. Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. Ophthalmology. 2009;116(3):369-78. doi: 10.1016/j.ophtha.2008.09. 048 pmid: 19167087

Martin JW, Chin JW, Nguyen T. Reciprocity law experiments in polymeric photodegradation: a critical review. Progr Organ Coat. 2003;47(3-4):292-311. doi: 10.1016/j.porgcoat.2003.08.002

Cinar Y, Cingu AK, Turkcu FM, Cinar T, Yuksel H, Ozkurt ZG, et al. Comparison of accelerated and conventional corneal collagen cross-linking for progressive keratoconus. Cutan Ocul Toxicol. 2014;33(3):218-22. doi: 10.3109/15569527.2013.834497 pmid: 24147938

Cingu AK, Sogutlu-Sari E, Cinar Y, Sahin M, Turkcu FM, Yuksel H, et al. Transient corneal endothelial changes following accelerated collagen cross-linking for the treatment of progressive keratoconus. Cutan Ocul Toxicol. 2014;33(2):127-31. doi: 10.3109/15569527.20 13.812107 pmid: 23859485

Caporossi A, Mazzotta C, Baiocchi S, Caporossi T, Denaro R, Balestrazzi A. Riboflavin-UVA-induced corneal collagen cross-linking in pediatric patients. Cornea. 2012;31(3):227-31. doi: 10.1097/ICO.0b01 3e31822159f6 pmid: 22420024

Sherif AM. Accelerated versus conventional corneal collagen cross-linking in the treatment of mild keratoconus: a comparative study. Clin Ophthalmol. 2014;8:1435-40. doi: 10.2147/OPTH.S59840 pmid: 25120349

Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg. 2014;40(6):1013-20. doi: 10.1016/j.jcrs. 2013.12.012 pmid: 24857442

Hashemi H, Miraftab M, Seyedian MA, Hafezi F, Bahrmandy H, Heidarian S, et al. Long-term Results of an Accelerated Corneal Cross-linking Protocol (18 mW/cm2) for the Treatment of Progressive Keratoconus. Am J Ophthalmol. 2015;160(6):1164-70 e1. doi: 10.1016/j.ajo.2015.08.027 pmid: 26314662

Shetty R, Pahuja NK, Nuijts RM, Ajani A, Jayadev C, Sharma C, et al. Current Protocols of Corneal Collagen Cross-Linking: Visual, Refractive, and Tomographic Outcomes. Am J Ophthalmol. 2015;160(2):243-9. doi: 10.1016/j.ajo.2015.05.019 pmid: 26008626

MacGregor C, Tsatsos M, Hossain P. Is accelerated corneal collagen cross-linking for keratoconus the way forward? No. Eye (Lond). 2014;28(7):786-7. doi: 10.1038/eye.2014.98 pmid: 24788014

Greenstein SA, Shah VP, Fry KL, Hersh PS. Corneal thickness changes after corneal collagen crosslinking for keratoconus and corneal ectasia: one-year results. J Cataract Refract Surg. 2011;37(4):691-700. doi: 10.1016/j.jcrs.2010.10.052 pmid: 21420594

Hafezi F. High-fluence CXL: laboratory results and clinical outcomes. .III Joint International Congress Refractive. Siena, Italy: On-line and SICSSO; 2013.

Caporossi A, Mazzotta C, Baiocchi S, Caporossi T. Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol. 2010;149(4):585-93. doi: 10.1016/j.ajo.2009.10.021 pmid: 20138607.

Full Text: Full Text PDF

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.