Commercial amniotic membrane extract for treatment of corneal ulcers in adult horses.
Abstract: Amniotic membrane extract enhances the rate of epithelialisation after corneal ulceration in several species but has not been studied in the equine cornea. Objective: To evaluate the effect of amniotic membrane extract on re-epithelialisation of equine corneal ulcers compared with ulcers treated with antibiotic, antifungal and mydriatic medical therapy alone, and to evaluate equine corneal healing after experimentally induced superficial ulceration. Methods: Masked, randomised, controlled experimental trial. Methods: Superficial, 8 mm corneal ulcers were created bilaterally in each horse. One eye was treated with amniotic membrane extract and the opposite was control. Both eyes were treated with medical therapy. Treatment eyes received amniotic membrane extract, and control eyes received the amniotic membrane extract vehicle. Ulcers were stained with fluorescein and photographed in 12-hour increments until completely healed. Ulcer surface area was determined by analysing photographs with ImageJ. A mixed linear model was used to compare ulcer surface area and hours until healing between treatment groups. A regression model was also used to calculate corneal re-epithelialisation rate over time. Results: Regardless of therapy, healing occurred in two phases: an initial rapid phase of 0.88 mm2 /hr (95% CI: 0.81-0.94 mm2 /hr) for approximately 48-54 hours followed by a second, slow phase of 0.07 mm2 /hr (95% CI: 0.04-0.09 mm2 /hr). Most eyes healed within 135.5 ± 48.5 hours. Treatment (amniotic membrane extract vs. control) was not significantly associated with size of ulcers over time (P = .984). Discomfort was minimal to absent in all horses. Conclusions: Results achieved experimental studies may differ from outcomes in the clinical setting. Conclusions: There was no significant difference in healing rate with addition of amniotic membrane extract to medical therapy for equine superficial corneal ulcers. A biphasic corneal healing process was observed, with an initial rapid phase followed by a slow phase. Further study will be needed to determine whether amniotic membrane extract will be helpful for infected or malacic equine corneal ulcers.
© 2020 EVJ Ltd.
Publication Date: 2021-01-19 PubMed ID: 33320369DOI: 10.1111/evj.13399Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
- Veterinary
Summary
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This research explores the effectiveness of amniotic membrane extract on the healing process of surface (or superficial) corneal ulcers in horses. The study found that adding amniotic membrane extract to the standard medical therapy does not significantly increase the healing rate of such ulcers, highlighting the need for further research.
Study Design and Methods
- The researchers conducted a masked, randomised, controlled trial in which they created superficial corneal ulcers, with an 8mm diameter, in both eyes of the involved horses.
- The eye that was treated with both amniotic membrane extract and the standard therapy was termed the ‘treatment eye’ while the other eye, which received only the standard therapy, was called a ‘control eye’.
- The surface area of ulcers was measured by staining them with a substance known as fluorescein and captured in photographs. This was done in 12-hour intervals until the ulcers were completely healed.
- The photographs were analysed using a software program known as ImageJ to determine the ulcer surface area.
- The researchers made statistical comparisons between the size of ulcers and the time it took for them to heal in both the treatment and control groups.
- A regression model was used to calculate how the rate of corneal re-epithelialisation changed over time.
Findings of the Research
- The study found that, regardless of the therapy used, healing of the ulcer occurred in two phases: a fast initial phase that took about 48-54 hours and a slow second phase.
- Metrically, the speed of healing during the first phase was 0.88mm per hour, and during the second phase, it was 0.07mm per hour.
- The study revealed that most of the eyes healed completely within approximately 135.5±48.5 hours.
- The addition of amniotic membrane extract to the standard therapy did not significantly affect the size of ulcers or the time it took for them to heal.
- All horses showed minimal or no discomfort throughout the duration of the study.
Conclusions and Future Implications
- In this experimental setting, there was no significant benefit of using amniotic membrane extract in treating superficial corneal ulcers in horses, as the healing rates did not differ significantly between the treatment and control groups.
- The corneal healing process seemed to follow a biphasic pattern, with an initial rapid healing phase followed by a slow one.
- The results of this study imply that the medicinal potential of amniotic membrane extract in treating infected or malacic (softened or degenerated) equine corneal ulcers requires further research.
Cite This Article
APA
Lyons VN, Townsend WM, Moore GE, Liang S.
(2021).
Commercial amniotic membrane extract for treatment of corneal ulcers in adult horses.
Equine Vet J, 53(6), 1268-1276.
https://doi.org/10.1111/evj.13399 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Purdue University, Indiana, USA.
- Department of Veterinary Clinical Sciences, Purdue University, Indiana, USA.
- Department of Comparative Pathobiology, Purdue University, Indiana, USA.
- Department of Statistics, College of Science, Purdue University, Indiana, USA.
MeSH Terms
- Amnion / transplantation
- Animals
- Cornea
- Corneal Ulcer / drug therapy
- Corneal Ulcer / veterinary
- Horse Diseases / drug therapy
- Horses
- Plant Extracts
- Wound Healing
Grant Funding
- Purdue University
- Department of Veterinary Clinical Sciences
- Graduate Student Competitive Research Funds
- Vetrix
- LLC
References
This article includes 47 references
- Tighe S, Moein HR, Chua L, Cheng A, Hamrah P, Tseng SCG. Topical cryopreserved amniotic membrane and umbilical cord eye drops promote re-epithelialization in a murine corneal abrasion model.. Invest Ophthalmol Vis Sci 2017;58(3):1586-93.
- Tseng SC, Espana EM, Kawakita T, Di Pascuale MA, Li W, He H. How does amniotic membrane work?. Ocul Surf 2004;2(3):177-87.
- Liang L, Li W, Ling S, Sheha H, Qiu W, Li C. Amniotic membrane extraction solution for ocular chemical burns.. Clin Exp Ophthalmol 2009;37(9):855-63.
- Murri MS, Moshirfar M, Birdsong OC, Ronquillo YC, Ding Y, Hoopes PC. Amniotic membrane extract and eye drops: a review of literature and clinical application.. Clin Ophthalmol 2018;12:1105-12.
- Baradaran-Rafii A, Asl NS, Ebrahimi M, Jabbehdari S, Bamdad S, Roshandel D. The role of amniotic membrane extract eye drop (AMEED) in in vivo cultivation of limbal stem cells.. Ocul Surf 2018;16(1):146-53.
- Kordić R, Suić SP, Jandroković S, Kalauz M, Kuzman T, Škegro I. Application of the amniotic membrane extract (AMX) for the persistent epithelial defect (PED) of the cornea.. Coll Antropol 2013;37(S1):161-4.
- Guo Q, Hao J, Yang Q, Guan L, Ouyang S, Wang J. A comparison of the effectiveness between amniotic membrane homogenate and transplanted amniotic membrane in healing corneal damage in a rabbit model.. Acta Ophthalmol 2011;89(4):e315-e319.
- Asi NS, Nejat F, Mohammadi P, Nekoukar A, Hesam S, Ebrahimi M. Amniotic membrane extract eye drop promotes limbal stem cell proliferation and corneal epithelium healing.. Cell 2019;20(4):459-68.
- Yang LL, Zhou QJ, Wang Y, Gao Y, Wang YQ. Comparison of the therapeutic effects of extracts from spirulina platensis and amnion membrane on inflammation-associated corneal neovascularization.. Int J Ophthalmol 2012;5(1):32-7.
- Bonci PO, Bonci PA, Lia A. Suspension made with amniotic membrane: clinical trial.. Eur J Ophthalmol 2005;15(4):441-5.
- Shahriari HA, Tokhmehchi F, Reza M, Hashemi NF. Comparison of the effect of amniotic membrane suspension and autologous serum on alkaline corneal epithelial wound healing in the rabbit model.. Cornea 2008;27(10):1148-50.
- Jester JV, Villasenor RA, Schanzlin DJ, Cavanagh HD. Variations in corneal wound healing after radial keratotomy: possible insights into mechanisms of clinical complications and refractive effects.. Cornea 1992;11(3):191-9.
- Matsuda M, Ubels JL, Edelhauser HF. A larger corneal epithelial wound closes at a faster rate.. Invest Ophthalmol Vis Sci 1985;26(6):897-900.
- Burling K, Seguin MA, Marsh P, Brinkman K, Madigan J, Thurmond M. Effect of topical administration of epidermal growth factor on healing of corneal epithelial defects in horses.. Am J Vet Res 2000;61(9):1150-5.
- Kingsley RE, Marfurt CF. Topical substance P and corneal epithelial wound closure in the rabbit.. Invest Ophthalmol Vis Sci 1997;38(2):388-95.
- Newton C, Hatchell DL, Klintworth GK, Brown CF. Topical fibronectin and corneal epithelial wound healing in the rabbit.. Arch Ophthalmol 1988;106:1277-9.
- Kwok LS, Madigan M. A new analysis of wound closure kinematics in the cat and rabbit corneal epithelium.. Clin Exp Optom 1986;69(1):4-12.
- Giuliano EA, Maggs DJ, Moore CP, Boland LA, Champagne ES, Galle LE. Inferomedial placement of a single-entry subpalpebral lavage tube for treatment of equine eye disease.. Vet Ophthalmol 2000;3(2-3):153-6.
- Hidaka S, Kobayashi M, Ando K, Fujii Y. Efficacy and safety of lomefloxacin on bacterial extraocular disease in the horse.. J Vet Med Sci 2015;77(7):829-35.
- Wada S, Hobo S, Niwa H. Ulcerative keratitis in thoroughbred racehorses in Japan from 1997 to 2008.. Vet Ophthalmol 2010;12(2):99-105.
- Matsumoto SS, Stern ME, Oda RM, Ghosn CR, Cheng JW, Gelber TA. Effect of ofloxacin on corneal epithelial wound healing evaluated by in vitro and in vivo methods.. Clin Drug Investig 1993;6:96-103.
- Betbeze CM, Wu CC, Krohne SG, Stiles J. In vitro fungistatic and fungicidal activities of silver sulfadiazine and natamycin on pathogenic fungi isolated from horses with keratomycosis.. Am J Vet Res 2006;67(10):1788-93.
- Mohan M, Gupta SK, Kalra VK, Vajpayee RB, Sachdev M. Topical silver sulphadiazine - a new drug for ocular keratomycosis.. Br J Ophthalmol 1998;72:192-5.
- Gronkiewicz KM, Giuliano EA, Sharma A, Mohan RR. Effects of topical hyaluronic acid on corneal wound healing in dogs: a pilot study.. Vet Ophthalmol 2017;20(2):123-30.
- Ollivier FJ, Kallberg ME, Plummer CE, Barrie KP, O'Reilly S, Taylor DP. Amniotic membrane transplantation for corneal surface reconstruction after excision of corneolimbal squamous cell carcinomas in nine horses.. Vet Ophthalmol 2006;9(6):404-13.
- Plummer CE, Ollivier F, Kallberg M, Brooks D, Barrie K, Utter M. The use of amniotic membrane transplantation for ocular surface reconstruction: a review and series of 58 equine clinical cases (2002-2008).. Vet Ophthalmol 2009;12(S1):17-24.
- Lassaline ME, Brooks DE, Ollivier FJ, Komaromy AM, Kallberg ME, Gelatt KN. Equine amniotic membrane transplantation for corneal ulceration and keratomalacia in three horses.. Vet Ophthalmol 2005;8(5):311-7.
- Kim JY, Choi YM, Jeong SW, Williams DL. Effect of bovine freeze-dried amniotic membrane (Amnisite-BATM) on uncomplicated canine corneal erosion.. Vet Ophthalmol 2009;12(1):36-42.
- Colio S, Bodor M, Dregalla R. Amniotic and umbilical cord products, alpha-2 macroglobulin, and interleukin-1 receptor antagonist protein.. In: Malanga GA, Ibrahim V, editors. Regenerative Treatments In Sports And Orthopedic Medicine. 1st ed. New York City, NY: Springer Publishing Company; 2018. p. 149-62.
- Mahbod M, Shahhoseini S, Khabazkhoob M, Beheshtnejad AH, Bakhshandeh H, Atyabi F. Amniotic membrane extract preparation: what is the best method?. J Ophthalmic Vis Res 2014;9(3):314-9.
- . Amniograft.. Biotissue.com/amniograft. Biotissue, 2020. Accessed May 18, 2020.
- Neaderland MH, Riis RC, Rebhun WC, Erb HN. Healing of experimentally induced corneal ulcers in horses.. Am J Vet Res 1987;48(3):427-30.
- Ljubimov AV, Saghizadeh M. Progress in corneal wound healing.. Prog Retin Eye Res 2015;49:17-45.
- Crosson CE, Klyce SD, Beuerman RW. Epithelial wound closure in the rabbit cornea: a biphasic process.. Invest Ophthalmol Vis Sci 1986;27(4):464-73.
- Strubbe DT, Brooks DE, Schultz GS, Willis-Goulet H, Gelatt KN, Andrew SE. Evaluation of tear film proteinases in horses with ulcerative keratitis.. Vet Ophthalmol 2000;3(2-3):111-9.
- Khodadoust AA, Silverstein AM, Kenyon KR, Dowling JE. Adhesion of regenerating corneal epithelium: the role of basement membrane.. Am J Ophthalmol 1968;65(3):339-48.
- Moses RA, Parkinson G, Schuchardt R. A standard large wound of the corneal epithelium in the rabbit.. Invest Ophthalmol Vis Sci 1979;18(1):103-6.
- Jumblatt MM, Fogle JA, Neufeld AH. Cholera toxin stimulates adenosin 3’5’-minophosophate synthesis and epithelial wound closure in the rabbit cornea.. Invest Ophthalmol Vis Sci 1980;19(11):1321-7.
- Pal-Ghosh S, Pajoohesh-Ganji A, Tadvalkar G, Stepp MA. Removal of the basement membrane enhances corneal wound healing.. Exp Eye Res 2011;93(6):927-36.
- Chinnery HR, McLenachan S, Binz N, Sun Y, Forrester JV, Degli-Esposti MA. TLR9 ligand CpG-ODN applied to the injured mouse cornea elicits retinal inflammation.. Am J Pathol 2012;180(1):209-20.
- Ferrington DA, Roehrich H, Chang AA, Huang CW, Maldonado M, Bratten W. Corneal wound healing is compromised by immunoproteasome deficiency.. PLoS One 2013;8(1):e54347.
- Terai K, Call MK, Liu H, Saika S, Liu CY, Hayashi Y. Crosstalk between TGF-beta and MAPK signaling during corneal wound healing.. Invest Ophthalmol Vis Sci 2011;52(11):8208-15.
- Yang Y, Yang H, Wang Z, Varadaraj K, Kumari SS, Mergler S. Cannabinoid receptor 1 suppresses transient receptor potential vanilloid 1-induced inflammatory responses to corneal injury.. Cell Signal 2013;25(2):501-11.
- Stepp MA, Zieske JD, Trinkaus-Randall V, Kyne BM, Pal-Ghosh S, Tadvalkar G. Wounding the corneal to learn how it heals.. Exp Eye Res 2014;121:178-93.
- da Silva EG, Powell CC, Gionfriddo JR, Ehrhart EJ, Hill AE. Histologic evaluation of the immediate effects of diamond burr debridement in experimental superficial corneal wounds in dogs.. Vet Ophthalmol 2011;14(5):285-91.
- BenEzra D. Possible mediation of vasculogenesis by products of the immune system.. In: Silverstein AM, O’Connor GR, editors. Immunology and Immunopathology of the Eye. 1st ed. NY: Masson Publishing USA, Inc, 1978; 315.
- Brooks DE, Matthews A, Clode AB. Diseases of the cornea.. In: Gilger B, editor. Equine Ophthalmology, 2nd ed. Maryland Heights, MO: Elsevier Saunders; 2017. p. 252-368.
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