CORNEAL CROSS-LINKING

KERATOCONUS

Keratoconus is a non-inflammatory disease, characterized by a progressive thinning and deformation of the cornea, which becomes curved and asymmetrical in the center (ectasia), assuming a cone shape.

The causes of the disease are still unclear, but it has been demonstrated that keratoconus involves collagen fibers degradation, which leads to the loss of intramolecular bonds. These phenomena of thinning and deformation have a faster evolution at a young age and may progress for the entire life. In advanced keratoconus stages, the apex of the corneal cone can become opaque and, rarely, perforate. Corneal deformation can cause irregular astigmatism, usually myopic, with progressive and invalidating visual loss, which can hardly be corrected by glasses or contact lenses.

CORNEAL CROSS-LINKING TREATMENT (CXL)

Corneal Cross-linking (CXL) is a para-surgical technique developed in Dresden in 1998. It consists of a photodynamical polymerization of the corneal stroma, aimed at increasing its strength by multiplying collagen fibers, thereby stabilizing the cornea and halting keratoconus’ progression. CXL is performed using a riboflavin (vitamin B2) based solution combined with an ultraviolet light source (UV-A).

Cross-linking increases and strengthens collagen fibers bonds, stiffening corneal tissues, and halting the ectasia progression. Many clinical and experimental studies demonstrated a significant increase in corneal stiffness after CXL. The technique can be performed with (CXL EPI-OFF) or without corneal epithelium removal (CXL EPI-ON).

BIBLIOGRAPHY

1. Carmine Ostacolo, Ciro Caruso, Diana Tronino, Salvatore Troisi, Sonia Laneri, Luigi Pacente, Antonio Del Prete, Antonia Sacchi “Increasing of corneal permeation of riboflavin-5′-phosphate through enhancers: A promising approach in corneal trans-epithelial cross-linking treatment” Inter J Pharm 440 (2013) 148– 153. [PDF]

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2. Ciro Caruso, Carmine Ostacolo, Robert L. Epstein, Gaetano Barbaro, Salvatore Troisi, Decio Capobianco: “Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes” Cornea 2016;35:145–150. [PDF]

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3. Ciro Caruso, Gaetano Barbaro, Robert L. Epstein, Diana Tronino, Carmine Ostacolo, Antonia Sacchi, Luigi Pacente, Antonio Del Prete, Marina Sala, Salvatore Troisi: “Corneal Cross-Linking: Evaluating the Potential for a Lower Power, Shorter Duration Treatment” Cornea 2016;35:659–662. [PDF]

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4. Ciro Caruso, Robert L. Epstein, Carmine Ostacolo, Luigi Pacente, Salvatore Troisi, Gaetano Barbaro. “Customized Corneal Cross-linking – A Mathematical Model” Cornea 2017; 36:600–604. [PDF]

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5. Roy S. Rubinfeld, Ciro Caruso, Carmine Ostacolo “Corneal Cross-Linking - The Science Beyond the Myths and Misconceptions” Cornea 2019 Jun;38(6):780-790. [Pdf]

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6. Ciro Caruso, Robert L. Epstein, Pasquale Troiano, Carmine Ostacolo, Gaetano Barbaro, Luigi Pacente, Silvia Bartollino, Ciro Costagliola “Topography and Pachymetry Guided, Rapid Epi-on Corneal Cross-Linking for Keratoconus: 7-year Study Results” Cornea 2020;39:56–62. [PDF]
   

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7. Ciro Caruso, Ciro Costagliola, Salvatore Troisi, Robert L. Epstein “Compaction of very thin corneas from ultraviolet A riboflavin-vitamin E transepithelial cross-linking” Experimental Eye Research 205 (2021) 108484.[PDF]

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8. Ciro Caruso, Robert L. Epstein, Pasquale Troiano, Francesco Napolitano, Fabio Scarinci, Ciro Costagliola “Topo-pachimetric accelerated EPI-ON cross-linking compared to the Dresden protocol using riboflavin with Vitamin E TPGS: results of a 2-year randomized study” J. Clin. Med. 2021, 10, 3799.[PDF]

PRESENTATIONS

1. Ciro Caruso, Salvatore Troisi, Antonio Del Prete, Luigi Pacente, Gaetano Barbaro, Carmine Ostacolo, Salvatore Del Prete “Evaluation of the penetration through human cornea of riboflavin 0.1% in solution with other molecules after trans-epithelial application”. 1st EuCornea Congress, June 17-19 2010, Venice, Italy [PDF]

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2. Robert L. Epstein, Salvatore Del Prete, Ciro Caruso, Salvatore Troisi, Carmine Ostacolo, Luigi Pacente, Antonio Del Prete, Gaetano Barbaro “Thickness and ultra-structural changes in keratoconus-affected human corneas after transepithelial cross-linking” American Academy of Ophthalmology Annual Meeting, October 2010, Chicago (P0073). [PDF]

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3. Robert L. Epstein, Ciro Caruso, Carmine Ostacolo, Salvatore Troisi, Luigi Pacente, Gaetano Barbaro, Antonio Del Prete, Antonia Sacchi: “A new riboflavin solution for trans-epithelial cross-linking: a study of corneal pharmacokinetic” American Academy of Ophthalmology Annual Meeting, October 2010, Chicago (P0073). [PDF]

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4. Salvatore Del Prete, Ciro Caruso, Luigi Pacente, Salvatore Troisi, Antonio Del Prete, Gaetano Barbaro “Effects of UV-A rays on the corneal epithelial surface after topical application of riboflavin solutions: an electron microscope study”. American Academy of Ophthalmology Annual Meeting, October 2010, Chicago (P0073) [PDF]

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5. Gaetano Barbaro, Ciro Caruso, Salvatore Troisi, Antonio Del Prete, Luigi Pacente “A Mathematical Model of Corneal UV-A Absorption After Soaking With a Riboflavin Solution During Trans-epithelial Cross-linking”. 1st Refractive Online and SICSSO Joint International Congress, July 7-9, 2011, Grosseto, Italy (Best paper, podium presentation) [PDF]

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6. Ciro Caruso, Salvatore Troisi, Gaetano Barbaro, Carmine Ostacolo, Antonio Del Prete, Luigi Pacente “UV-A rays absorption in human corneas before and after trans-epithelial riboflavin application: an experimental study”. 2nd Refractive Online and SICSSO Joint International Congress, June 28-30, 2012, Rome, Italy (Podium presentation) [PDF]

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7. Ciro Caruso, Salvatore Troisi, Antonio Del Prete, Luigi Pacente, Gaetano Barbaro “Trans-epithelial cross-linking with riboflavin solution: one-year clinical results”. 1st Refractive Online and SICSSO Joint International Congress, July 7-9, 2011, Grosseto, Italy (Podium presentation) [PDF]

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8. Ciro Caruso, Luigi Pacente, Robert L. Epstein, Salvatore Troisi, Gaetano Barbaro, Antonio Del Prete: “Trans-epithelial cross-linking with riboflavin solution: two-year clinical results” 2nd joint International Congress Refractive Online & SICSSO, Rome 2012 (podium presentation). [PDF]

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9. Marco Fantozzi: “Safety ed Efficacy di due diversi protocolli di cross-linking nella SMILE Xtra  -   Follow-Up di 12 mesi” 13th AIMO Congress, Rome 2022. [PDF]