Successful Regression in Patients with Progressive Keratoconus by Corneal Crosslinking

Abstract

Background Since 2019, corneal collagen crosslinking (CXL) is included in the catalog of procedures covered by statutory health insurance in Germany. CXL is an established ophthalmological procedure for the last 20 years. The aim of this investigation was the measurement of progression before and after CXL.

Material und Methods 65 consecutive eyes with progressive keratoconus from 53 patients were included in the retrospective study, which were observed at the University Eye Hospital Tübingen at least two years before and at least two years after CXL. The time of observation took place from October 2009 until March 2018. Parameters of interest had been the best corrected visual acuity (BCVA) and the keratometric values from the elevation maps measured by a Scheimpflug camera.

Results 65 eyes of 53 patients had been documented. The study population included 46 (86.8%) male and 7 (13.2%) female subjects. The mean age was 24 ± 8 years. The averaged observation time between the primary consultation and CXL showed 25 ± 15 months. Preoperatively the mean BCVA pointed out in a significant increase (0.13 ± 0.17 [first visit] vs. 0.23 ± 0.22 [preOP], p < 0.0001) while the mean Kmax resulted in a statistically significant increase (46.34 ± 3.33 dpt [first visit] vs. 48.78 ± 4.17 dpt [preOP], p < 0.0001). The mean thinnest point of the cornea showed a significant decrease (490.48 ± 34.23 µm [first visit] vs. 468.62 ± 29.84 µm [preop], p < 0.0001). Postoperatively the mean BCVA resulted in a significant improvement at the 12th postoperative month in comparison to the preoperative measurement (0.23 ± 0.22 [preOP] vs. 0.16 ± 0.14 [12 months], p = 0.04 respectively 0.17 ± 0.17 [24 months], p = 0.0006). The mean Kmax demonstrated in the 12th postoperative month a significant reduction (48.78 ± 4.17 dpt [preOP] vs. 47.91 ± 3.41 dpt [12 months], p = 0.0009 respectively 48 ± 4.56 dpt [24 months], p = 0.0051). The mean thinnest point of the cornea indicated a decrease at the 12th postoperative month (468.62 ± 29.84 µm [preOP] vs. 459.82 ± 35.88 µm [12 months], p = 0.0078 respectively 453.47 ± 43.39 µm [24 months], p = 0.0227).

Conclusion CXL is a successful procedure for the therapy of progressive keratoconus.

Key words

corneal crosslinking - cornea - keratoconus - regression - keratometry

Publication History

Received: 24 March 2020

Accepted: 08 September 2020

Article published online:
19 February 2021

• References/Literatur

• 1 Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998; 42: 297-319 doi:10.1016/s0039-6257(97)00119-7
• 2 Gordon-Shaag A, Millodot M, Shneor E. et al. The genetic and environmental factors for keratoconus. Biomed Res Int 2015; 2015: 795738 doi:10.1155/2015/795738
• 3 Fournié P, Touboul D, Arné JL. et al. [Keratoconus]. J Fr Ophtalmol 2013; 36: 618-626 doi:10.1016/j.jfo.2013.05.004
• 4 Romero-Jimenez M, Santodomingo-Rubido J, Wolffsohn JS. Keratoconus: a review. Cont Lens Anterior Eye 2010; 33: 157-166 quiz 205 doi:10.1016/j.clae.2010.04.006
• 5 Müller PL, Loeffler KU, Messmer E. et al. Histological Corneal Alterations in Keratoconus After Crosslinking-Expansion of Findings. Cornea 2020; 39: 333-341 doi:10.1097/ICO.0000000000002144
• 6 Sharif R, Bak-Nielsen S, Hjortdal J. et al. Pathogenesis of keratoconus: The intriguing therapeutic potential of prolactin-inducible protein. Prog Retin Eye Res 2018; 67: 150-167 doi:10.1016/j.preteyeres.2018.05.002
• 7 Priyadarsini S, Hjortdal J, Sarker-Nag A. et al. Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease. PLoS One 2014; 9: e113310 doi:10.1371/journal.pone.0113310
• 8 Maier P, Reinhard T. [Riboflavin UVA crosslinking in progressive keratoconus]. Ophthalmologe 2017; 114: 571-586 doi:10.1007/s00347-017-0500-4
• 9 Parker JS, van Dijk K, Melles GR. Treatment options for advanced keratoconus: A review. Surv Ophthalmol 2015; 60: 459-480 doi:10.1016/j.survophthal.2015.02.004
• 10 Spörl E, Huhle M, Kasper M. et al. [Increased rigidity of the cornea caused by intrastromal cross-linking]. Ophthalmologe 1997; 94: 902-906
• 11 Lang SJ, Reinhard T. [Crosslinking in Keratoconus]. Klin Monbl Augenheilkd 2016; 233: 713-716 doi:10.1055/s-0042-103494
• 12 Goebels S, Seitz B, Langenbucher A. Diagnostik und stadiengerechte Therapie des Keratokonus. Ophthalmologe 2013; 110: 808-809 doi:10.1007/s00347-013-2917-8
• 13 Jouve L, Borderie V, Temstet C. et al. [Corneal collagen crosslinking in keratoconus]. J Fr Ophtalmol 2015; 38: 445-462 doi:10.1016/j.jfo.2014.12.003
• 14 Röck T, Bartz-Schmidt KU, Röck D. Trends in corneal transplantation at the University Eye Hospital in Tübingen, Germany over the last 12 years: 2004–2015. PLoS One 2018; 13: e0198793 doi:10.1371/journal.pone.0198793
• 15 Lang SJ, Bischoff M, Böhringer D. et al. Analysis of the changes in keratoplasty indications and preferred techniques. PLoS One 2014; 9: e112696 doi:10.1371/journal.pone.0112696
• 16 Konrad EM, Röck D, Blumenstock G. et al. [Long-term experiences with corneal crosslinking in patients with progressive keratoconus at the University Eye Hospital in Tübingen, Germany]. Ophthalmologe 2020; 117: 538-545 doi:10.1007/s00347-019-00982-w
• 17 Raiskup-Wolf F, Hoyer A, Spoerl E. et al. Collagen crosslinking with riboflavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg 2008; 34: 796-801 doi:10.1016/j.jcrs.2007.12.039
• 18 Iqbal M, Elmassry A, Badawi AE. et al. Visual and refractive long-term outcomes following standard cross-linking in progressive keratoconus management. Clin Ophthalmol 2019; 13: 2477-2488 doi:10.2147/OPTH.S232954
• 19 Duncan JK, Belin MW, Borgstrom M. Assessing progression of keratoconus: novel tomographic determinants. Eye Vis (Lond) 2016; 3: 6 doi:10.1186/s40662-016-0038-6
• 20 Imbornoni LM, McGhee CNJ, Belin MW. Evolution of Keratoconus: From Diagnosis to Therapeutics. Klin Monbl Augenheilkd 2018; 235: 680-688 doi:10.1055/s-0044-100617
• 21 Belin MW, Duncan JK. Keratoconus: The ABCD Grading System. Klin Monbl Augenheilkd 2016; 233: 701-707 doi:10.1055/s-0042-100626
• 22 Wang YM, Chan TAO, Yu MCY. et al. Comparative evaluation of progression rate in keratoconus before and after collagen crosslinking. Br J Ophthalmol 2018; 102: 1109-1113 doi:10.1136/bjophthalmol-2017-311017
• 23 Golan O, Hwang ES, Lang P. et al. Differences in posterior corneal features between normal corneas and subclinical keratoconus. J Refract Surg 2018; 34: 664-670 doi:10.3928/1081597X-20180823-02
• 24 Jordan C, Patel DV, Abeysekera N. et al. In vivo confocal microscopy analyses of corneal microstructural changes in a prospective study of collagen cross-linking in keratoconus. Ophthalmology 2014; 121: 469-474 doi:10.1016/j.ophtha.2013.09.014
• 25 Mazzotta C, Balestrazzi A, Baiocchi S. et al. Stromal haze after combined riboflavin-UVA corneal collagen cross-linking in keratoconus: in vivo confocal microscopic evaluation. Clin Exp Ophthalmol 2007; 35: 580-582 doi:10.1111/j.1442-9071.2007.01536.x
• 26 Hersh PS, Stulting RD, Muller D. et al. United States multicenter clinical trial of corneal collagen crosslinking for keratoconus treatment. Ophthalmology 2017; 124: 1259-1270 doi:10.1016/j.ophtha.2017.03.052
• 27 El-Husseiny M, Tsintarakis T, Eppig T. et al. [Intacsintracorneal ring segments in keratoconus]. Ophthalmologe 2013; 110: 823-826 828–829 doi:10.1007/s00347-013-2821-2
• 28 Daxer A, Ettl A, Horantner R. Long-term results of MyoRing treatment of keratoconus. J Optom 2017; 10: 123-129 doi:10.1016/j.optom.2016.01.002
• 29 Bromley JG, Randleman JB. Treatment strategies for corneal ectasia. Curr Opin Ophthalmol 2010; 21: 255-258 doi:10.1097/ICU.0b013e32833a8bfe
• 30 DeParis SW, Zhu AY, Majumdar S. et al. Effects of collagen crosslinking on porcine and human tarsal plate. BMC Ophthalmol 2019; 19: 255 doi:10.1186/s12886-019-1254-3
• 31 Idowu OO, Ashraf DC, Vagefi MR. et al. Floppy eyelid syndrome: ocular and systemic associations. Curr Opin Ophthalmol 2019; 30: 513-524 doi:10.1097/ICU.0000000000000617
• 32 Polat N, Gunduz A, Gunduz A. et al. The Influence of Corneal Collagen Crosslinking on Conjunctival Flora. Curr Eye Res 2017; 42: 364-367 doi:10.1080/02713683.2016.1196710
• 33 Su GY, Zheng PP, Su YD. et al. [Therapeutic efficacy of ultraviolet combined with riboflavin for the rabbit bacterial keratitis]. Zhonghua Yan Ke Za Zhi 2018; 54: 902-910 doi:10.3760/cma.j.issn.0412-4081.2018.12.007
• 34 Martins SA, Combs JC, Noguera G. et al. Antimicrobial efficacy of riboflavin/UVA combination (365 nm) in vitro for bacterial and fungal isolates: a potential new treatment for infectious keratitis. Invest Ophthalmol Vis Sci 2008; 49: 3402-3408 doi:10.1167/iovs.07-1592
• 35 Kashiwabuchi RT, Carvalho FR, Khan YA. et al. Assessment of fungal viability after long-wave ultraviolet light irradiation combined with riboflavin administration. Graefes Arch Clin Exp Ophthalmol 2013; 251: 521-527 doi:10.1007/s00417-012-2209-z
• 36 Martinez JD, Arboleda A, Naranjo A. et al. Long-term outcomes of riboflavin photodynamic antimicrobial therapy as a treatment for infectious keratitis. Am J Ophthalmol Case Rep 2019; 15: 100481 doi:10.1016/j.ajoc.2019.100481
• 37 Ramona BI, Catalina C, Andrei M. et al. Collagen crosslinking in the management of microbial keratitis. Rom J Ophthalmol 2016; 60: 28-30
• 38 Hafezi F, Kanellopoulos J, Wiltfang R. et al. Corneal collagen crosslinking with riboflavin and ultraviolet A to treat induced keratectasia after laser in situ keratomileusis. J Cataract Refract Surg 2007; 33: 2035-2040 doi:10.1016/j.jcrs.2007.07.028
• 39 Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135: 620-627 doi:10.1016/s0002-9394(02)02220-1