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Corneal Collagen Cross Linking pp 189–223Cite as

Clinical Results of Corneal Collagen Cross-linking

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Abstract

We report on clinical results of corneal collagen cross-linking (CXL), analyzing intraoperative results, results in postrefractive surgery ectasia, results by iontophoresis, and results analyzed according to age of the patient.

Intraoperative Results. In eyes with progressive advanced keratoconus (KC) undergoing standard CXL, we evaluated uncorrected (UDVA) and corrected (CDVA) distance visual acuities, sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count at baseline and follow-up at 1, 3, 6, 12, and 24 months after treatment. Topography was also recorded intraoperatively, and corneal biomechanics during CXL was studied with the Ocular Response Analyzer (ORA).

Intraoperative topography obtained after epithelial removal showed a dramatic change in corneal power with an increase in the steepest meridian keratometry, simulated cylinder, and apical keratometry immediately after epithelial abrasion. Two years postoperatively, mean baseline UDVA and CDVA improved significantly and mean spherical equivalent manifest refraction (MRSE) decreased significantly. Mean baseline flattest and steepest meridians on simulated keratometry, simulated keratometry average, mean average pupillary power, and apical keratometry all decreased significantly. Mean 12-month baseline pupil center pachymetry and total corneal volume also decreased significantly. Endothelial cell counts did not change significantly.

Our intraoperative findings indicate that the epithelium acts as a smoothing agent that reduces corneal power, astigmatism, and irregularity of keratoconic corneas. Intraoperatively, we observed corneal thickness reduction apparently due to the dehydrating effect of T-dextran, which is part of the riboflavin solution.

Two years postoperatively, CXL appeared to be effective in improving UDVA and CDVA in eyes with progressive KC by significantly reducing corneal average pupillary power, keratometry, and total corneal wavefront aberrations. Our findings indicate that keratoconic corneas with very low pachymetry are more likely to improve, thus we suggest treating advanced KC. In case of corneal thickness below 400 μm, this can be attained safely by using swelling solutions.

Pertaining corneal biomechanics, corneal hysteresis (CH), and corneal resistance factor (CRF) showed similar behavior during and after CXL. Corneal epithelium removal did not affect CH and CRF. However, riboflavin impregnation and Ultraviolet-A (UVA) irradiation increased both parameters significantly. After the procedure, CH and CRF remained statistically significantly higher than the preoperative values only at 1-month follow-up. At 6 and 12 months postoperatively, no statistically significant changes were noted in CH and CRF. Our results indicate that corneal epithelium does not seem to affect the structural stability of the cornea, that the dehydrated cornea was more resistant and stiff, and that CXL did not induce any effect on intraocular pressure (IOP), as measured with the ORA.

Ectasia Results. One of the most dreadful long-term complications of excimer laser refractive surgery is ectasia. We present the results of 78 post-LASIK/PRK ectatic eyes that underwent CXL treatment and were followed for up to 5 years. The Dresden protocol was adopted. Corneas thinner than 400 μm could be treated after appropriate swelling. At 6 months and beyond, UDVA and CDVA improved, and mean sphere and astigmatism values were significantly reduced (P < 0.05). Klyce indices CVP, SDP, LogMAR, SRC showed significant decrease (P < 0.05) at 3 months. At 6 months postoperatively, the Ambrosio index IVA had significantly increased, and the KCI index had significantly decreased (P < 0.05). Corneal pachymetry decreased, endothelial cell count variations were unremarkable, and no ocular or systemic adverse events were observed. CXL appeared to stabilize as well as improve CDVA in these iatrogenic ectatic eyes.

Iontophoresis Results. Corneal epithelium may block UV penetration and riboflavin penetration, and this may be important for understanding the reduced effect of transepithelial (epithelium-on; Epi-On) CXL. Sparing the epithelium is important in order to reduce CXL-associated complications, discomfort, and length of procedure. A novel approach to enhance riboflavin penetration into the corneal stroma is based on iontophoresis, a noninvasive system aimed to enhance the delivery of charged molecules into tissues, using a small electric current.

We report the results of basic research studies on iontophoresis-assisted CXL as well as the initial clinical results that compare the efficacy of standard, epithelium-off (Epi-Off) CXL vs. Epi-On and iontophoresis techniques.

Results According to Age. We evaluated the 4-year outcomes of CXL for progressive KC in a population of different age groups. Four hundred consecutive eyes, treated with CXL for progressive KC from 04/2006 to 04/2010, were considered. The consolidated Epi-Off technique was used: epithelial removal, corneal irrigation for 30 min with a solution of 0.1 % riboflavin and 20 % dextran, followed by irradiation with UVA light of 3 mW/cm2 for 30 min.

Functional (CDVA and aberrometry, sphere, and cylinder refraction) and structural (corneal topography, Scheimpflug tomography) analysis was performed at baseline and at 1, 6, 12, 24, 36, 48 months after CXL treatment. Data were stratified according to age (Group A under 18; Group B 18–29 years; Group C 30–39 years and Group D over 40 years). Comparative analysis included 400 eyes of 301 patients. Functional results showed a significant increase in CDVA in Group A by a mean reduction of −0.11 LogMAR after 12 months, in Group B by a mean reduction of −0.31 after 36 months, in Group C by a mean reduction of −0.33 after 36 months, and in Group D by a mean reduction of −0.26 after 36 months. Morphological results showed an analogous regularization of corneal shape with a significant reduction of Opposite Sector Index (OSI) by a mean value of −0.53 at 12 months in Group A, of −1.14 at 36 months in Group B, of −1.10 at 36 months in Group C, and of −0.55 at 12 months for Group D. Optical quality improvement was demonstrated by a mean significant reduction of coma of −1.52 μm after 12 months in Group A, of −1.58 μm after 24 months in Group B, of −2.57 μm after 36 months for Group C, and of −0.25 μm after 36 months in Group D.

Outcomes stratified by age indicate that CXL is efficacious in stabilizing the progression of ectatic disease in all age groups and in improving the functional and morphological parameters in selected groups. Results indicated better functional and morphological results in the population between 18 and 39 years of age.

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Authors and Affiliations

  1. Department of Ophthalmology, Humanitas Research Hospital, Via Ripamonti, 205, Rozzano, Milan, 20100, Italy

    Paolo Vinciguerra MD & Fabrizio I. Camesasca MD

  2. Department of Medicine and Science of Aging, Ophthalmic Clinic, G d’Annunzio University, Chieti-Pescara, Chieti, Italy

    Leonardo Mastropasqua MD & Manuela Lanzini PhD

  3. Eye Clinic, Instituto Clinico Humanitas, Rozzano, Milan, Italy

    Elena Albè MD

  4. Department of Neuroscience, University of Naples Federico II, Naples, Italy

    Mario R. Romano MD, PhD

  5. Department of Ophthalmology, St. Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, UK

    Vito Romano MD

  6. Department of Ophthalmology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Silvia Trazza (Orthoptist)

  7. Department of Surgical and Morphological Sciences, University of Insubria, Circolo Hospital, Varese, Varese, Italy

    Riccardo Vinciguerra MD

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  1. Paolo Vinciguerra MD
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  2. Fabrizio I. Camesasca MD
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  8. Manuela Lanzini PhD
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  9. Riccardo Vinciguerra MD
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Correspondence to Paolo Vinciguerra MD .

Editor information

Editors and Affiliations

  1. Ophthalmology Department, Damascus University, Damascus, Saudi Arabia

    Mazen M. Sinjab

  2. Wellington Eye Clinic, Dublin, Ireland

    Arthur B. Cummings

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Vinciguerra, P. et al. (2017). Clinical Results of Corneal Collagen Cross-linking. In: Sinjab, M., Cummings, A. (eds) Corneal Collagen Cross Linking. Springer, Cham. https://doi.org/10.1007/978-3-319-39775-7_6

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  • DOI: https://doi.org/10.1007/978-3-319-39775-7_6

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