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Comparison of corneal keratocytes before and after corneal collagen cross-linking in keratoconus patients

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Abstract

Keratoconus is a bilateral and asymmetric corneal ectasia. Cross-linking uses ultra-violate rays to enhance corneal tissue. The purpose of this study was to use in vivo confocal microscopy to quantitatively analyze microstructural changes over time, after corneal collagen cross-linking (CXL) in keratoconus patients. In this before-and-after study, a total of 45 keratoconic eyes were selected for cross-linking among patients referred to Al-Zahra ophthalmology clinic during 2013–2014. All patients underwent complete ophthalmologic examinations. Keratocytes and the present of activated keratocytes were calculated preoperatively and at 1, 3, 6, and 12 months postoperatively using confocal microscopy. One year after CXL, best corrected and best uncorrected visual acuity was increased significantly (p < 0.001). Spherical equivalent and spherical refractive errors reduced significantly (p < 0.001). The reduction in density of anterior and mid-stromal keratocytes was significant initially (p < 0.001). During follow-up, the density of keratocytes increased significantly in all layers reaching near normal values by 12 months. The percentage of activated keratocytes showed a significant increase 1 month after cross-linking (p < 0.001) albeit this percent reduced as the corneal healing proceeded by month 12. The endothelial cells showed no significant reduction during the follow-up. Collagen cross-linking-induced significant reduction in keratocyte density. The percent of activated keratocytes increased significantly after cross-linking which showed reduction with improvement of corneal healing. After collagen cross-linking, hyper-reflective structures were observed consistent with the stromal collagen structures. Further studies are needed to assess possible changes on corneal biomechanics. The consistency in corneal endothelium numbers proves the safety of this technique.

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References

  1. Rabinowitz YS (1998) Keratoconus. Surv Ophthalmol 42:297–319

    Article  CAS  PubMed  Google Scholar 

  2. Dhaliwal JS, Kaufman SC (2009) Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas. Cornea 28:62–67

    Article  PubMed  Google Scholar 

  3. Wagner H, Barr JT, Zadnik K (2007) Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Group. Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study: methods and findings to date. Contact Lens Anterior Eye 30:223–232

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Jankov MR II, Jovanovic V, Nikolic L, Lake JC, Kymionis G, Koskunseven E (2010) Corneal collagen cross-linking. Mid East Afr J Ophthalmol 17(1):21–27

    Google Scholar 

  5. Jordan C, Patel DV, Abeysekera N, McGhee CN (2014) In vivo confocal microscopy analyses of corneal microstructural changes in a prospective study of collagen cross-linking in keratoconus. Ophthalmology 121(2):469–474

    Article  PubMed  Google Scholar 

  6. Wollensak G, Spoerl E, Seiler T (2003) Riboflavin/ultraviolet A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 135:620–627

    Article  CAS  PubMed  Google Scholar 

  7. Henriquez MA, Izquierdo L Jr, Bernilla C, Zakrzewski PA, Mannis M (2011) Riboflavin/ultraviolet a corneal collagen cross-linking for the treatment of keratoconus: visual outcomes and Scheimpflug analysis. Cornea 30:281–286

    Article  PubMed  Google Scholar 

  8. Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE (2006) Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg 32:279–283

    Article  PubMed  Google Scholar 

  9. Abdelghaffar W, Hantera M, Elsabagh H (2010) Corneal collagen cross-linking: promises and problems. Br J Ophthalmol 94:1559–1560

    Article  PubMed  Google Scholar 

  10. Koller T, Iseli HP, Hafezi F, Vinciguerra P, Seiler T (2009) Scheimpflug imaging of corneas after collagen cross-linking. Cornea 28:510–515

    Article  PubMed  Google Scholar 

  11. Chaidaroon W (2007) Confocal microscopy of the human cornea. Chiang Mai Med J 46(2):83–91

    Google Scholar 

  12. Holladay JT (2004) Visual acuity measurements. J Cataract Refract Surg 30:287–290

    Article  PubMed  Google Scholar 

  13. Spoerl E, Huhle M, Seiler T (1998) Induction of cross-links in corneal tissue. Exp Eye Res 66(1):97–103

    Article  CAS  PubMed  Google Scholar 

  14. Mazzotta C, Traversi C, Baiocchi S, Caporossi O, Bovone C, Sparano MC et al (2008) Corneal healing after riboflavin ultraviolet-A collagen cross-linking determined by confocal laser scanning microscopy in vivo: early and late modifications. Am J Opthalmol 146:527–533

    Article  CAS  Google Scholar 

  15. Wollensak G, Spoerl E, Wilsch M, Seiler T (2004) Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA treatment. Cornea 23(1):43–49

    Article  PubMed  Google Scholar 

  16. Ramírez M, Hernández-Quintela E, Naranjo-Tackman R (2013) Early confocal microscopy findings after cross-linking treatment. Arch Soc Esp Oftalmol 88(5):179–183

    Article  PubMed  Google Scholar 

  17. Mazzotta C, Balestrazzi A, Traversi C, Baiocchi S, Caporossi T, Tommasi C et al (2007) Treatment of progressive keratoconus by riboflavin-UVA-induced crosslinking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans. Cornea 26:390–397

    Article  PubMed  Google Scholar 

  18. Kaya V, Utine CA, Yilmaz OF (2011) Efficacy of corneal collagen cross-linking using a custom epithelial debridement technique in thin corneas: a confocal microscopy study. J Refract Surg 27:444–450

    Article  PubMed  Google Scholar 

  19. Helena MC, Baerveldt F, Kim WJ, Wilson SE (1998) Keratocyte apoptosis after corneal surgery. Investig Ophthalmol Vis Sci 39:276–283

    CAS  Google Scholar 

  20. Salomão MQ, Chaurasia SS, Sinha-Roy A, Ambrósio R Jr, Esposito A, Sepulveda R et al (2011) Corneal wound healing after ultraviolet-A/riboflavin collagen crosslinking: a rabbit study. J Refract Surg 27:401–407

    Article  PubMed  Google Scholar 

  21. Mastropasqua L, Nubile M, Lanzini M, Calienno R, Mastropasqua R, Agnifili L et al (2013) Morphological modification of the cornea after standard and transepithelial corneal cross-linking as imaged by anterior segment optical coherence tomography and laser scanning in vivo confocal microscopy. Cornea 32(6):855–861

    Article  PubMed  Google Scholar 

  22. Knappe S, Stachs O, Zhivov A, Hovakimyan M, Guthoff R (2011) Results of confocal microscopy examinations after collagen cross-linking with riboflavin and UVA light in patients with progressive keratoconus. Ophthalmologica 225:95–104

    Article  CAS  PubMed  Google Scholar 

  23. Touboul D, Efron N, Smadja D, Praud D, Malet F, Colin J (2012) Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus. J Refract Surg 28:769–776

    Article  PubMed  Google Scholar 

  24. Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR (2008) A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg 24:S720–S725

    PubMed  Google Scholar 

  25. Croxatto JO, Tytiun AE, Argento CJ (2010) Sequential in vivo confocal microscopy study of corneal wound healing after cross-linking in patients with keratoconus. J Refract Surg 26:638–645

    Article  PubMed  Google Scholar 

  26. Kymionis GD, Portaliou DM, Diakonis VF, Kontadakis GA, Krasia MS, Papadiamantis AG et al (2010) Posterior linear stromal haze formation after simultaneous photorefractive keratectomy followed by corneal collagen crosslinking. Investig Ophthalmol Vis Sci 51:5030–5033

    Article  Google Scholar 

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Authors and Affiliations

  1. Al-Zahra Eye Hospital, Zahedan University of Medical Sciences, Motahari Blvd., Zahedan, Iran

    Mohammad-Naeim Aminifard & Hoda Khallaghi

  2. Faculty of health, Zahedan University of Medical Sciences, Dr. Hesabi square, Zahedan, Iran

    Mahdi Mohammadi

  3. Khatam-al-Anbia hospital, Zahedan University of Medical Sciences, Jamejam Blvd., Zahedan, Iran

    Reza Jafarzadeh

Authors
  1. Mohammad-Naeim Aminifard
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  2. Hoda Khallaghi
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  3. Mahdi Mohammadi
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  4. Reza Jafarzadeh
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Correspondence to Hoda Khallaghi.

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Aminifard, MN., Khallaghi, H., Mohammadi, M. et al. Comparison of corneal keratocytes before and after corneal collagen cross-linking in keratoconus patients. Int Ophthalmol 35, 785–792 (2015). https://doi.org/10.1007/s10792-015-0041-2

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  • DOI: https://doi.org/10.1007/s10792-015-0041-2

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