Vet Med - Czech, 2022, 67(4):190-198 | DOI: 10.17221/46/2021-VETMED

Riboflavin/UV-A corneal phototherapy as stand-alone management of ulcerative keratitis in dogsOriginal Paper

A Marchegiani ORCID...1, R Gialletti2, MP Cassarani1, M Cerquetella1, AR Attili1, G Lombardo3,4, M Lombardo4,5, A Spaterna1, R Arcelli2
1 School of Biosciences and Veterinary Medicine, University of Camerino, Matelica (Macerata), Italy
2 Department of Veterinary Medicine, University of Perugia, Perugia, Italy
3 CNR-IPCF, Istituto per i Processi Chimico-Fisici, Messina, Italy
4 Vision Engineering Italy srl, Rome, Italy
5 Studio Italiano di Oftalmologia, Rome, Italy

Corneal ulcers are one of the most common ocular disorders in veterinary ophthalmology and several factors can negatively influence the efficacy of the currently available therapeutic options, leading to a loss of corneal transparency and, thus, vision. Twenty-five dogs with clinical signs of corneal ulcers were randomised to receive either corneal phototherapy (16 dogs; study group) or topical standard medical therapy (9 dogs; control group). The riboflavin/UV-A corneal phototherapy (PACK-CXL) consisted in the application of a riboflavin ophthalmic solution (Visioflavin®; Vision Engineering Italy srl, Rome, Italy) onto the cornea for 20 min followed by 30 mW/cm2 UV-A irradiance for 3 min using a point-of-care UV-A device (Vetuvir®; Vision Engineering Italy srl, Rome, Italy). The complete healing of the ulcerative lesion was defined as the complete restoration of the corneal epithelial integrity with negative fluorescein staining. The corneal phototherapy achieved complete corneal healing in all the dogs by 20.5 ± 7.8 days. In the control group, only two dogs achieved complete healing by 21.5 ± 15.6 days. This intervention may represent a valid option to hasten corneal wound healing and a clinical resolution of ulcerative keratitis in dogs.

Keywords: corneal melting; corneal ulcer; cross-linking; keratitis; riboflavin; UV-A

Received: March 25, 2021; Accepted: December 13, 2021; Prepublished online: February 9, 2022; Published: April 15, 2022  Show citation

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Marchegiani A, Gialletti R, Cassarani M, Cerquetella M, Attili A, Lombardo G, et al.. Riboflavin/UV-A corneal phototherapy as stand-alone management of ulcerative keratitis in dogs. Vet Med-Czech. 2022;67(4):190-198. doi: 10.17221/46/2021-VETMED.
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    References

    1. Brejchova K, Liskova P, Cejkova J, Jirsova K. Role of matrix metalloproteinases in recurrent corneal melting. Exp Eye Res. 2010 May;90(5):583-90. Go to original source... Go to PubMed...
    2. De Briyne N, Atkinson J, Pokludova L, Borriello SP. Antibiotics used most commonly to treat animals in Europe. Vet Rec. 2014 Oct 4;175(13):325. Go to original source... Go to PubMed...
    3. Brooks DE, Ollivier FJ. Matrix metalloproteinase inhibition in corneal ulceration. Vet Clin North Am Small Anim Pract. 2004 May;34(3):611-22. Go to original source... Go to PubMed...
    4. Cain CL. Antimicrobial resistance in staphylococci in small animals. Vet Clin North Am Small Anim Pract. 2013 Jan; 43(1):19-40. Go to original source... Go to PubMed...
    5. Famose F. Assessment of the use of spectral domain optical coherence tomography (SD-OCT) for evaluation of the healthy and pathological cornea in dogs and cats. Vet Ophthalmol. 2014a Jan;17(1):12-22. Go to original source... Go to PubMed...
    6. Famose F. Evaluation of accelerated collagen cross-linking for the treatment of melting keratitis in eight dogs. Vet Ophthalmol. 2014b Sep;17(5):358-67. Go to original source... Go to PubMed...
    7. Famose F. Evaluation of accelerated collagen cross-linking for the treatment of melting keratitis in ten cats. Vet Ophthalmol. 2015 Mar;18(2):95-104. Go to original source... Go to PubMed...
    8. Famose F. Evaluation of accelerated corneal collagen crosslinking for the treatment of bullous keratopathy in eight dogs (10 eyes). Vet Ophthalmol. 2016 May;19(3):250-5. Go to original source... Go to PubMed...
    9. Fini ME, Cook JR, Mohan R. Proteolytic mechanisms in corneal ulceration and repair. Arch Dermatol Res. 1998 Jul; 290(Suppl):S12-23. Go to original source... Go to PubMed...
    10. Gallhoefer NS, Spiess BM, Guscetti F, Hilbe M, Hartnack S, Hafezi F, Pot SA. Penetration depth of corneal cross-linking with riboflavin and UV-A (CXL) in horses and rabbits. Vet Ophthalmol. 2016 Jul;19(4):275-84. Go to original source... Go to PubMed...
    11. Goulle F. Use of porcine small intestinal submucosa for corneal reconstruction in dogs and cats: 106 cases. J Small Anim Pract. 2012 Jan;53(1):34-43. Go to original source... Go to PubMed...
    12. Hayes S, Kamma-Lorger CS, Boote C, Young RD, Quantock AJ, Rost A, Khatib Y, Harris J, Yagi N, Terrill N, Meek KM. The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma. PLoS One. 2013;8(1):e52860. Go to original source... Go to PubMed...
    13. Hellander-Edman A, Makdoumi K, Mortensen J, Ekesten B. Corneal cross-linking in 9 horses with ulcerative keratitis. BMC Vet Res. 2013 Jun 26;9:128. Go to original source... Go to PubMed...
    14. Hollingsworth SR. Corneal surgical techniques. Clin Tech Small Anim Pract. 2003 Aug;18(3):161-7. Go to original source... Go to PubMed...
    15. Ion L, Ionascu I, Birtoiu A. Melting keratitis in dogs and cats. Agric Agric Sci Procedia. 2015;6:342-9. Go to original source...
    16. Kamaev P, Friedman MD, Sherr E, Muller D. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci. 2012 Apr 30;53(4):2360-7. Go to original source... Go to PubMed...
    17. Kim J, Ji DB, Takiyama N, Bae J, Kim MS. Corneal collagen cross-linking following superficial keratectomy as treatment for corneal endothelial cell dystrophy in dogs: Preliminary clinical study. Vet Ophthalmol. 2019 Jul;22(4): 440-7. Go to original source... Go to PubMed...
    18. Kumar V, Lockerbie O, Keil SD, Ruane PH, Platz MS, Martin CB, Ravanat JL, Cadet J, Goodrich RP. Riboflavin and UV-light based pathogen reduction: Extent and consequence of DNA damage at the molecular level. Photochem Photobiol. 2004 Jul-Aug;80:15-21. Go to original source... Go to PubMed...
    19. Ledbetter EC, Dubovi EJ, Kim SG, Maggs DJ, Bicalho RC. Experimental primary ocular canine herpesvirus-1 infection in adult dogs. Am J Vet Res. 2009 Apr;70(4):513-21. Erratum in: Am J Vet Res. 2009 Jun;70(6):740. Go to original source... Go to PubMed...
    20. Lombardo M, Lombardo G. Noninvasive real-time assessment of riboflavin consumption in standard and accelerated corneal crosslinking. J Cataract Refract Surg. 2019 Jan;45(1):80-6. Go to original source... Go to PubMed...
    21. Lombardo M, Pucci G, Barberi R, Lombardo G. Interaction of ultraviolet light with the cornea: Clinical implications for corneal crosslinking. J Cataract Refract Surg. 2015 Feb;41(2):446-59. Go to original source... Go to PubMed...
    22. Lombardo G, Micali NL, Villari V, Serrao S, Lombardo M. All-optical method to assess stromal concentration of riboflavin in conventional and accelerated UV-A irradiation of the human cornea. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):476-83. Go to original source... Go to PubMed...
    23. Marchegiani A, Magagnini M, Cerquetella M, Troiano P, Franchini I, Franchini A, Scapagnini G, Spaterna A. Preoperative topical liposomal ozone dispersion to reduce bacterial colonization in conjunctival sac and periocular skin: Preliminary study in dogs. Exp Eye Res. 2019 Dec; 189:107848. Go to original source... Go to PubMed...
    24. Martins SA, Combs JC, Noguera G, Camacho W, Wittmann P, Walther R, Cano M, Dick J, Behrens A. 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 Aug;49(8):3402-8. Go to original source... Go to PubMed...
    25. Murphy JM, Lavach JD, Severin GA. Survey of conjunctival flora in dogs with clinical signs of external eye disease. J Am Vet Med Assoc. 1978 Jan 1;172(1):66-8.
    26. Ollivier FJ. Bacterial corneal diseases in dogs and cats. Clin Tech Small Anim Pract. 2003 Aug;18(3):193-8. Go to original source... Go to PubMed...
    27. Ollivier FJ, Brooks DE, Kallberg ME, Komaromy AM, Lassaline ME, Andrew SE, Gelatt KN, Stevens GR, Blalock TD, van Setten GB, Schultz GS. Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis. Am J Vet Res. 2003 Sep;64(9):1081-7. Go to original source... Go to PubMed...
    28. Ollivier FJ, Gilger BC, Barrie KP, Kallberg ME, Plummer CE, O'Reilly S, Gelatt KN, Brooks DE. Proteinases of the cornea and preocular tear film. Vet Ophthalmol. 2007 Jul-Aug;10(4):199-206. Go to original source... Go to PubMed...
    29. Perazzi A, Peruffo A, Gomiero C, Contin R, Corain L, Grisan E, Lombardo M, Lombardo G, Salvalaio G, Patruno M, Iacopetti I, Martinello T. Assessment of uv-a/riboflavin corneal cross-linking efficacy for the treatment of experimentally induced. International CXL experts meeting, Switzerland; 2018. p. 2014-5.
    30. Perazzi A, Gomiero C, Corain L, Iacopetti I, Grisan E, Lombardo M, Lombardo G, Salvalaio G, Contin R, Patruno M, Martinello T, Peruffo A. An assay system to evaluate riboflavin/UV-A corneal phototherapy efficacy in a porcine corneal organ culture model. Animals (Basel). 2020 Apr 23;10(4):730. Go to original source... Go to PubMed...
    31. Pot SA, Gallhofer NS, Matheis FL, Voelter-Ratson K, Hafezi F, Spiess BM. Corneal collagen cross-linking as treatment for infectious and noninfectious corneal melting in cats and dogs: Results of a prospective, nonrandomized, controlled trial. Vet Ophthalmol. 2014 Jul;17(4):250-60. Go to original source... Go to PubMed...
    32. Pot SA, Gallhofer NS, Walser-Reinhardt L, Hafezi F, Spiess BM. Treatment of bullous keratopathy with corneal collagen cross-linking in two dogs. Vet Ophthalmol. 2015 Mar;18(2):168-73. Go to original source... Go to PubMed...
    33. Sondergaard AP, Ivarsen A, Hjortdal J. Reduction of stromal swelling pressure after UVA-riboflavin cross-linking. Invest Ophthalmol Vis Sci. 2013 Mar 5;54(3):1625-34. Go to original source... Go to PubMed...
    34. Spadea L, Tonti E, Spaterna A, Marchegiani A. Use of ozonebased eye drops: A series of cases in veterinary and human spontaneous ocular pathologies. Case Rep Ophthalmol. 2018;9(2):287-8. Go to original source... Go to PubMed...
    35. Spiess BM, Pot SA, Florin M, Hafezi F. Corneal collagen cross-linking (CXL) for the treatment of melting keratitis in cats and dogs: A pilot study. Vet Ophthalmol. 2014 Jan;17(1):1-11. Go to original source... Go to PubMed...
    36. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004 Jul;29(1):35-40. Go to original source... Go to PubMed...
    37. Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVA-riboflavin cross-linking of the cornea. Cornea. 2007 May;26(4):385-9. Go to original source... Go to PubMed...
    38. Tabibian D, Mazzotta C, Hafezi F. PACK-CXL: Corneal cross-linking in infectious keratitis. Eye Vis (Lond). 2016 Apr 19;3:11. Go to original source... Go to PubMed...
    39. Varges R, Penna B, Martins G, Martins R, Lilenbaum W. Antimicrobial susceptibility of Staphylococci isolated from naturally occurring canine external ocular diseases. Vet Ophthalmol. 2009 Jul-Aug;12(4):216-20. Go to original source... Go to PubMed...
    40. Wang L, Pan Q, Zhang L, Xue Q, Cui J, Qi C. Investigation of bacterial microorganisms in the conjunctival sac of clinically normal dogs and dogs with ulcerative keratitis in Beijing, China. Vet Ophthalmol. 2008 May-Jun;11(3): 145-9. Go to original source... Go to PubMed...
    41. Wollensak G, Spoerl E, Reber F, Seiler T. Keratocyte cytotoxicity of riboflavin/UVA-treatment in vitro. Eye (Lond). 2004 Jul;18(7):718-22. Go to original source... Go to PubMed...

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