Corneal cross-linking in 9 horses with ulcerative keratitis

BMC Veterinary Research

Björn Ekesten²  Jes Mortensen³  Karim Makdoumi³  Anna Hellander-Edman¹ 

[1] Department of Animal Environment & Health, Swedish University of Agricultural Sciences, PO Box 234, SE-532 24 Skara, Sweden;Department of Clinical Sciences, Swedish University of Agricultural Sciences, PO Box 7054, SE-750 07 Uppsala, Sweden;Department of Ophthalmology, Örebro University Hospital, SE-701 85 Örebro, Sweden

关键词: Stromal melting;    Riboflavin;    UVA;    CXL;    Collagen;    Cross linking;    Cross-linking;    Corneal ulceration;    Keratitis;    Horse;    Equine;   

Others  :  1119510
DOI  :  10.1186/1746-6148-9-128

 received in 2012-10-08, accepted in 2013-06-13,  发布年份 2013

【 摘 要 】

Background

Corneal ulcers are one of the most common eye problems in the horse and can cause varying degrees of visual impairment. Secondary infection and protease activity causing melting of the corneal stroma are always concerns in patients with corneal ulcers. Corneal collagen cross-linking (CXL), induced by illumination of the corneal stroma with ultraviolet light (UVA) after instillation of riboflavin (vitamin B2) eye drops, introduces crosslinks which stabilize melting corneas, and has been used to successfully treat infectious ulcerative keratitis in human patients. Therefore we decided to study if CXL can be performed in sedated, standing horses with ulcerative keratitis with or without stromal melting.

Results

Nine horses, aged 1 month to 16 years (median 5 years) were treated with a combination of CXL and medical therapy. Two horses were diagnosed with mycotic, 5 with bacterial and 2 with aseptic ulcerative keratitis. A modified Dresden-protocol for CXL could readily be performed in all 9 horses after sedation. Stromal melting, diagnosed in 4 horses, stopped within 24 h. Eight of nine eyes became fluorescein negative in 13.5 days (median time; range 4–26 days) days after CXL. One horse developed a bacterial conjunctivitis the day after CXL, which was successfully treated with topical antibiotics. One horse with fungal ulcerative keratitis and severe uveitis was enucleated 4 days after treatment due to panophthalmitis.

Conclusions

CXL can be performed in standing, sedated horses. We did not observe any deleterious effects attributed to riboflavin or UVA irradiation per se during the follow-up, neither in horses with infectious nor aseptic ulcerative keratitis. These data support that CXL can be performed in the standing horse, but further studies are required to compare CXL to conventional medical treatment in equine keratitis and to optimize the CXL protocol in this species.

【 授权许可】

   
2013 Hellander-Edman et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Brooks DE, Matthews AG: Equine ophthalmology. In Veterinary ophthalmology. Volume II. 4th edition. Edited by Gelatt KN. Ames, IA, USA: Blackwell Publishing Professional; 2007:1192-1211.
• [2]Wada S, Hobo S, Niwa H: Ulcerative keratitis in thoroughbred racehorses in Japan from 1997 to 2008. Vet Ophthalmol 2010, 13(2):99-105.
• [3]Johns IC, Baxter K, Booler H, Hicks C, Menzies-Gow N: Conjunctival bacterial and fungal flora in healthy horses in the UK. Vet Ophthalmol 2011, 14(3):195-199.
• [4]Clode AC, Matthews AG: Diseases and surgery of the cornea. In Equine ophthalmology. 2nd edition. Edited by Gilger BC. Maryland Heights, MO, USA: Elsevier Saunders; 2011:181-215.
• [5]Moore CP, Collins BK, Fales WH: Antibacterial susceptibility patterns for microbial isolates associated with infectious keratitis in horses - 63 cases (1986–1994). J Am Vet Med Assoc 1995, 207(7):928-933.
• [6]Sauer P, Andrew SE, Lassaline M, Gelatt KN, Denis HM: Changes in antibiotic resistance in equine bacterial ulcerative keratitis (1991–2000): 65 horses. Vet Ophthalmol 2003, 6(4):309-313.
• [7]Cannon DJ, Davison PF: Aging, and crosslinking in mammalian collagen. Exp Aging Res 1977, 3(2):87-105.
• [8]Malik NS, Moss SJ, Ahmed N, Furth AJ, Wall RS, Meek KM: Ageing of the human corneal stroma: structural and biochemical changes. Biochim Biophys Acta 1992, 1138(3):222-228.
• [9]Baier J, Maisch T, Maier M, Engel E, Landthaler M, Bäumler W: Singlet oxygen generation by UVA light exposure of endogenous photosensitizers. Biophys J 2006, 91(4):1452-1459.
• [10]McCall AS, Kraft S, Edelhauser HF, Kidder GW, Lundquist RR, Bradshaw HE, Dedeic Z, Dionne MJC, Clement EM, Conrad GW: Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA). Invest Ophthalmol Vis Sci 2010, 51(1):129-138.
• [11]Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE: Biomechanical evidence of the distribution of cross-links in corneastreated with riboflavin and ultraviolet A light. J Cat Ref Surg 2006, 32(2):279-283.
• [12]Spoerl E, Huhle M, Seiler T: Induction of cross-links in corneal tissue. Exp Eye Res 1998, 66(1):97-103.
• [13]Spörl E, Huhle M, Kasper M, Seiler T: Erhöhung der Festigkeit der Hornhaut durch Vernetzung. Ophthtalmologe 1997, 94(12):902-906.
• [14]Wollensak G, Spoerl E, Seiler T: Stress–strain measurements of human and porcine corneas after riboflavin–ultraviolet-A-induced cross-linking. J Cat Ref Surg 2003, 29(9):1780-1785.
• [15]Spoerl E, Wollensak G, Seiler T: Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res 2004, 29(1):35-40.
• [16]Snibson GR: Collagen cross-linking: a new treatment paradigm in corneal disease - a review. Clin Experiment Ophthalmol 2010, 38(2):141-153.
• [17]Muller L, Thiel MA, Kipfer-Kauer AI, Kaufmann C: Corneales Crosslinking als zusätzliche Therapieoption bei einschmelzender Hornhaut: eine Fall-Serie [Corneal cross-linking as supplementary treatment option in melting keratitis: a case series]. Klin Monatsbl Augenh 2012, 229(4):411-415.
• [18]Corbin F: Pathogen inactivation of blood components: current status and introduction of an approach using riboflavin as a photosensitizer. Int J Hematol 2002, 76:253-257.
• [19]Douki T, Cadet J: Modification of DNA bases by photosensitized one-electron oxidation. Int J Radiat Biol 1999, 75(5):571-581.
• [20]Tsugita A, Okada Y, Uehara K: Photosensitized inactivation of ribonucleic acids in the presence of riboflavin. Biochim Biophys Acta 1965, 103(2):360-363.
• [21]Makdoumi K, Bäckman A, Mortensen J, Crafoord S: Evaluation of antibacterial efficacy of photo-activated riboflavin using ultraviolet light (UVA). Graefes Arch Clin Exp Ophthalmol 2010, 248(2):207-212.
• [22]Martins SAR, 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, 49(8):3402-3408.
• [23]Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T: Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea 2008, 27(5):590-594.
• [24]Morén H, Malmsjö M, Mortensen J, Öhrström A: Riboflavin and ultraviolet A collagen crosslinking of the cornea for the treatment of keratitis. Cornea 2010, 29(1):102-104.
• [25]Schnitzler E, Spörl E, Seiler T: [Irradiation of cornea with ultraviolet light and riboflavin administration as a new treatment for erosive corneal processes, preliminary results in four patients]. Klin Monatsbl Augenh 2000, 217(3):190-193.
• [26]Makdoumi K, Mortensen J, Sorkhabi O, Malmvall B-E, Crafoord S: UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study. Graefes Arch Clin Exp Ophthalmol 2012, 250(1):95-102.
• [27]Makdoumi K: Ultraviolet light (UVA) photoactivation of riboflavin as a potential therapy for infectious keratitis. PhD. Örebro: Örebro University; 2011.
• [28]Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T: Safety of UVA-riboflavin cross-linking of the cornea. Cornea 2007, 26(4):385-389.
• [29]Dhaliwal JS, Kaufman SC: Corneal collagen cross-linking: a confocal, electron, and light microscopy study of eye bank corneas. Cornea 2009, 28(1):62-67.
• [30]Wollensak G, Spoerl E, Reber F, Seiler T: Keratocyte cytotoxicity of riboflavin//UVA-treatment in vitro. Eye 2004, 18(7):718-722.
• [31]Wollensak G, Spoerl E, Wilsch M, Seiler T: Keratocyte apoptosis after corneal collagen cross-linking using riboflavin/UVA treatment. Cornea 2004, 23(1):43-49.
• [32]Wollensak G, Spoerl E, Wilsch M, Seiler T: Endothelial cell damage after riboflavin–ultraviolet-A treatment in the rabbit. J Cat Ref Surg 2003, 29(9):1786-1790.
• [33]Wollensak G, Spoerl E, Seiler T: Riboflavin/ultraviolet-a–induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003, 135(5):620-627.
• [34]Wollensak G, Iomdina E, Dittert D-D, Herbst H: Wound healing in the rabbit cornea after corneal collagen cross-linking with riboflavin and UVA. Cornea 2007, 26(5):600-605.
• [35]Mazzotta C, Traversi C, Baiocchi S, Caporossi O, Bovone C, Sparano MC, Balestrazzi A, Caporossi A: Corneal healing after riboflavin ultraviolet-A collagen cross-linking determined by confocal laser scanning microscopy in vivo: early and late modifications. Am J Ophthalmol 2008, 146(4):527-533. e521
• [36]Pot S, Florin M, Spiess B, Hafezi F: Treatment of "melting" ulcers in dogs and cats with UV-A/riboflavin cross-linking of corneal collagen (CXL): a pilot study. Vet Ophthalmol 2011, 14(4):281.
• [37]Berman MB: Collagenase inhibitors: rationale for their Use in treating corneal ulceration. Int Ophthalmol Clin 1975, 15(4):49-66.
• [38]Brooks DE: Ophthalmology for the equine practitioner. Jackson, WY, USA: Teton NewMedia; 2002.
• [39]Brooks DE, Andrew SE, Biros DJ, Denis HM, Cutler TJ, Strubbe DT, Gelatt KN: Ulcerative keratitis caused by beta-hemolytic Streptococcus equi in 11 horses. Vet Ophthalmol 2000, 3(2–3):121-125.
• [40]Andrew SE, Brooks DE, Smith PJ, Gelatt KN, Chmielewski NT, Whittaker CJG: Equine ulcerative keratomycosis: visual outcome and ocular survival in 39 cases (1987–1996). Equine Vet J 1998, 30(2):109-116.
• [41]Barnett KC, Crispin SM, Lavach JD, Matthews AG: Equine ophthalmology: an atlas & text. 2nd edition. Oxford, UK: Elsevier Ltd; 2004:98-125.
• [42]Wollensak G, Spörl E, Reber F, Pillunat L, Funk R: Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro. Ophthalmic Res 2003, 35(6):324-328.
• [43]Kurtin WE, Song P-S: Photochemistry of the model phototropic system involving flavins and indoles - I. Fluorescence polarization and MO calculations of the direction of the electronic transition moments in flavins. Photochem Photobiol 1968, 7(3):263-273.
• [44]Goldich Y, Marcovich AL, Barkana Y, Avni I, Zadok D: Safety of corneal collagen cross-linking with UV-a and riboflavin in progressive keratoconus. Cornea 2010, 29(4):409-411.
• [45]Hovakimyan M, Guthoff RF, Stachs O: Collagen cross-linking: current status and future directions. J Ophthalmol 2012., article ID 406850
• [46]Koppen C, Vryghem JC, Gobin L, Tassignon M-J: Keratitis and corneal scarring after UVA/riboflavin cross-linking for keratoconus. J Refract Surg 2009, 25(9):S819-S823.
• [47]Koller T, Mrochen M, Seiler T: Complication and failure rates after corneal crosslinking. J Cat Ref Surg 2009, 35(8):1358-1362.
• [48]Burns FR, Gray RD, Paterson CA: Inhibition of alkali-induced corneal ulceration and perforation by a thiol peptide. Invest Ophthalmol Vis Sci 1990, 31(1):107-114.
• [49]Köhler A: Ein neues Beleuchtungsverfahren fur mikrophotographische Zwecke. Zeitschrift fur wissenschaftliche Mikroskopie und fur Microscopische Technik 1893, 10(4):433-440.