E Q What we’ve been doing at UINE VETERINARY EDUCATION/American Edition equine American Edition | November 2019 veterinary KindredBio is cool, and we education can’t wait to show you.

V olume 31 Number 11

N in this issue: ovember 2019 Position statement on wild horse and burro management released The official journal of the KindredBio.com American Association of The outcomes of epidural anaesthesia in horses with perineal and tail melanomas: Equine Practitioners, produced Complications associated with ataxia and the risks of rope recovery in partnership with BEVA. Transmaxillary anchored silicon embedded gauze plug in the post-operative treatment of a large oromaxillary fistula caused by a supernumerary cheek tooth ©2019 Kindred Biosciences, Inc., Burlingame, CA 94010. All rights reserved. US-CORP-1900163 AUG-19 What’s your vision for the future of your practice?

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NVA has over 700 partnerships in the US, Canada, Australia and New Zealand. Our veterinarians provide a full range of medical and surgical services, and our passionate, visionary local hospital and pet resort leaders embody NVA’s unique entrepreneurial spirit. We’d be more than happy to talk through your questions and concerns. You can reach us at 888.767.7755 | [email protected]. Fast, affordable, and accurate equine testing. You no longer have to compromise.

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© 2017 IDEXX Laboratories, Inc. All rights reserved. • 108866-01 • All ®/TM marks are owned by IDEXX Laboratories, Inc. or its affi liates in the United States and/or other countries. The IDEXX Privacy Policy is available at idexx.com. equine veterinary education American Edition NOVEMBER 2019 • VolumE 31 • NumBER 11

AAEP NEWS In this issue contents Position statement on wild horse and burro management released...... III

Invest in patient and personal wellbeing at #AAEPDenver...... VI

Practitioner empowering remote veterinarians to improve horse health across Mongolia...... XI

Highlights of Recent Clinically Relevant Papers S. WRIGHT...... 562

Editorial A problem-based approach to the ‘red eye’ C. DAWSON...... 564

Case Reports The outcomes of epidural anaesthesia in horses with perineal and tail melanomas: Complications associated with ataxia and the risks of rope recovery A. R. BIRD, S. J. MORLEY, C. E. SHERLOCK and T. S. MAIR...... 567

Two cases of hepatopathy and hyperferraemia managed with deferoxamine and phlebotomy L. GUMMERY, P. E. J. JOHNSTON, D. G. M. SUTTON and A. G. RAFTERY...... 575

Transmaxillary anchored silicon embedded gauze plug in the post-operative treatment of a large oromaxillary fistula caused by a supernumerary cheek tooth A. T. HEVESI, D. UTO, N. TAKACS, V. LORINCZ and H. SIMHOFER...... 582

A standing pararectal approach to treat small colon obstruction by a pedunculated lipoma E. DURKET, V. ALBANESE, S. K. STEWARD and D. E. FREEMAN...... 594

Clinical Commentaries Orosinuidal and oronasal fistulas: The search for an adequate treatment M. STOLL...... 588

Surgical approaches to the equine abdomen F. TÓTH and J. SCHUMACHER...... 599

Original Article Equine retrobulbar disease: Diagnoses and outcomes of 15 horses with exophthalmos (1988–2017) K. E. KNICKELBEIN, B. J. HOLMBERG and M. E. LASSALINE...... 601

Review Article Equine eosinophilic keratitis: An emergent ocular condition? S. GONZÁLEZ-MEDINA...... 609

Marketplace ...... 616C-F

Advertisers’ Index...... 616

Cover photo by Dr. Rocio Espinoza. American Association of Equine veterinary education Equine Practitioners American Edition 4033 Iron Works Parkway Lexington, KY 40511 NOVEMBER 2019 • Volume 31 • Number 11 TEL (800) 443-0177 • (859) 233-0147 FAX (859) 233-1968 EMAIL [email protected] Editor (UK) Assistant Editors aaep.org T. S. Mair, BVSc, PhD, DEIM, DESTS, F. Andrews S. Love D. Archer M.L. Macpherson To access our website, go to aaep.org, select DipECEIM, MRCVS LOGIN, then enter your email and password. If you F.T. Bain M.J. Martinelli have difficulty logging in or have forgotten your Editors (USA) A.R.S. Barr I.G. Mayhew password, please call or email the office. N. A. White II, DVM A. Blikslager M. Mazan W. D. Wilson, MRCVS M. Bowen C.W. McIlwraith AAEP Officers N. Cohen B. McKenzie Jeff Berk, VMD, President Deputy Editors V. Coudry R. Moore Y. Elce A. Dart M. Oosterlinck David Frisbie, DVM, President-Elect P.R. Morresey J.-M. Denoix A. Parks Scott Hay, DVM, Vice President P.A. Wilkins T. Divers S. Puchalski Lisa Metcalf, DVM, Treasurer P. Dixon C. Riggs Margo Macpherson, DVM, Immediate Past President Management Group W. Duckett H. Schott D. Foley B. Dunkel J. Schumacher AAEP Staff T. S. Mair S. Dyson S. Semevelos David Foley, CAE, Executive Director N. A. White T. Fischer J. Slater D. Freeman B. Sponseller [email protected] W. D. Wilson T. Greet C. Sweeney Lori Rawls, Director of Finance & Operations J. L. N. Wood [email protected] R. Hanson H. Tremaine P. Harris K. Wareham Sally J. Baker, APR, Director of Marketing Management Board & Public Relations • [email protected] M. Hillyer S. Weese A. R. S. Barr P. Smith Keith Kleine, Director of Industry Relations M. Holmes R. Weller [email protected] D. Foley N. A. White (US Editor) N. Hudson C. Yao D. Mountford S. White Nick Altwies, Director of Membership P. Johnson [email protected] T. S. Mair (Editor) W. D. Wilson (US Editor) P.T. Khambatta Ex-officio S. E. Palmer J. L. N. Wood (Chairman) J.-P. Lavoie J. Cooney Kevin Hinchman, Director of Information Technology [email protected]

Karen Pautz, Director of Education Equine Veterinary Education is a refereed educational journal designed to keep the practicing veterinarian up to [email protected] date with developments in equine medicine and surgery. Submitted case reports are accompanied by invited reviews Sadie Boschert, Student Programs Coordinator of the subject (satellite articles) and clinical quizzes. Tutorial articles, both invited and submitted, provide in-depth [email protected] coverage of issues in equine practice.

John Cooney, Publications Coordinator Equine Veterinary Education (American Edition ISSN 1525-8769) is published monthly by the American [email protected] Association of Equine Practitioners, an international membership organization of equine veterinarians. Office of Giulia Garcia, Communications Coordinator publication is 4033 Iron Works Parkway, Lexington, KY 40511. Periodicals Postage paid at Lexington, KY and [email protected] additional mailing office. POSTMASTER: Send address changes to: Equine Veterinary Education, 4033 Iron Works Parkway, Lexington, KY 40511. Megan Gray, Member Concierge [email protected] Communications regarding editorial matters should be addressed to: The Editor, Equine Veterinary Education, Dana Kirkland, Sponsorship & Advertising Mulberry House, 31 Market Street, Fordham, Ely, Cambridgeshire CB7 5LQ, UK. Telephone: 44 (0) 1638 720250, Coordinator • [email protected] Fax: 44 (0) 1638 721868, Email: [email protected]. Katie McDaniel, EDCC Communication Manager All manuscript submissions for the journal should be submitted online at http://mc.manuscriptcentral.com/eve. Full [email protected] instructions and support are available on the site and a user ID and password can be obtained on the first visit. If you Deborah Miles, CMP, Trade Show Coordinator require assistance, click the Get Help Now link that appears at the top right of every ScholarOne Manuscripts page. [email protected] All subscription inquiries should be addressed to: Subscriptions Department, AAEP, 4033 Iron Works Parkway, Jayson Page, Office Manager Lexington, KY 40511, Telephone: (859) 233-0147, Email: [email protected]. Subscription rates: AAEP annual [email protected] membership dues include $40 for a subscription to Equine Veterinary Education. Other subscriptions at $151.80. Single copies $37.50. Paul Ransdell, Senior Development Officer [email protected] Canadian Subscriptions: Canada Post Corporation Number 40965005. Send change address information and Carey Ross, Scientific Publications Coordinator blocks of undeliverable copies to IBC, 7485 Bath Road, Mississauga, ON L4T 4C1, Canada. [email protected] © World copyright by Equine Veterinary Journal Ltd 2019. Pam Shook, Foundation Programs Coordinator [email protected] The authors, editors and publishers do not accept responsibility for any loss or damage arising from actions or Sue Stivers, Executive Assistant decisions based or relying on information contained in this publication. Responsibility for the treatment of horses [email protected] under medical or surgical care and interpretation of published material lies with the veterinarian. This is an aca- demic publication and should not be used or interpreted as a source of practical advice or instruction. Amity Wahl, Communications & Technology Coordinator The American Association of Equine Practitioners cannot accept responsibility for the quality of products or ser- [email protected] vices advertised in this journal or any claim made in relation thereto. Every reasonable precaution is taken before Kristin Walker, Membership & Event advertisements are accepted, but such acceptance does not imply any form of recommendation or approval. Services Coordinator [email protected] All companies wishing to advertise in Equine Veterinary Education, American edition, must be current AAEP exhibitors. AAEP retains the right, in its sole discretion, to determine the circumstances under which an exhibitor may advertise in this Elaine Young, Convention & Meetings Coordinator journal. While all advertisers must comply with applicable legal guidelines, Compounding Pharmacies are specifically [email protected] directed to limit themselves to pharmacy practices as dictated by the FDA Center for Veterinarian Medicine, Compliance Policy Guideline (www.fda.gov/ora/compliance_ref/cpg/cpgvet/cpg608-400.html). Advertising any complete or partial Published monthly. Deadlines are the mimicry of drugs and dosage forms of FDA approved formulations will not be accepted. Compounding Pharmacies, or any seventh of the preceding month. other exhibitors/advertisers who violate this rule in any fashion, will render their advertising contract null and void. Address advertising inquiries to Dana Kirkland (859) 233-0147 / [email protected] As a private organization, the AAEP reserves the right to exclude any company from advertising in Equine Veterinary Education, American edition, for any reason. The signing and delivery of the advertising contract shall AAEP Mission Statement: To improve the health and constitute an offer subject to acceptance by the AAEP. In its sole and absolute discretion, the AAEP may revoke its welfare of the horse, to further the professional acceptance of the advertising contract or may terminate any contract by delivery of written notice, in which event development of its members, and to provide resources the AAEP shall have no liability to the advertiser for damages for any other remedy. and leadership for the benefit of the equine industry. Printed by: Cenveo Publisher Services, Lancaster Division, Lancaster, PA. Association AAEP News November 2019 III

Position statement on wild horse and burro management released

The AAEP board of directors recently approved the position statement, Management of Bureau of

Land Management Wild Horses and Dr. Tom Lenz Burros. The position, developed by the Wild Horse Subcommittee of the AAEP’s Welfare & Public Policy Advisory Council, also has been adopted by the AVMA.

AAEP Position on Management of Bureau of Land Management Wild Horses and Burros The wild free-roaming horses and burros on lands managed by the Bureau of Land Management (BLM) The AAEP and AVMA endorses the E. Unrestricted sale, which was in the Western United States are a humane management of the wild incorporated into the Wild Free- unique population of animals horse and burro population through Roaming Horses and Burro Act protected by the 1971 Wild Free- a combination of the following by amendment in the Omnibus Roaming Horses and Burros Act strategies: Appropriations Act of 2005, (Public Law 92-195). This act and should also be an available subsequent amendments provide for A. Ongoing development and use management strategy for horses the necessary management, of long-lasting, effective contra- in holding that are over the age protection and control of these ceptives in herds where feasible. of 10 years or have been offered animals on public lands. B. Use of permanent sterilization for adoption unsuccessfully methods such as spaying or three times. At present time, the number of castration in selected herds wild horses and burros on the range where repeated capture or Additionally, the AAEP and AVMA is three times greater than the darting with contraceptive supports the BLM’s existing policy appropriate management level vaccines is not feasible. The that allows for the humane determined by the BLM. Historically, AAEP and AVMA encourages euthanasia of wild horses and burros herd population numbers have research into other methods of for reasons related to health and increased at the rate of 15-20% per permanent sterilization to welfare, including animals that are year. Overpopulation has created prevent pregnancy. seriously ill or injured with a poor welfare risks such as starvation and prognosis for improvement; irrevers- dehydration due to scarce food and C. Continued removal of animals ibly lame; starved with a poor water supplies in some management from areas where the range prognosis for recovery; or dangerous. areas. Current population control cannot support a growing methods employed by the BLM, population because of the While safe and effective long-lasting including the removal of excess danger of starvation or dehydra- contraceptive methods are under horses from the range, adoption of tion or where the population development, it will be years before gathered horses by private individu- numbers threaten limited they are fully tested and available. als, sex-ratio adjustments and con- rangeland resources and wildlife. The AAEP and AVMA believes traceptive vaccines, have not been D. Continued development of new short-term and permanent steriliza- successful in achieving manageable adoption and sales strategies for tion methods combined with greater population numbers. animals removed from the private-sale and adoption options range. Strategies may include will best serve the Bureau of Land The AAEP and AVMA believes collaboration with private enter- Management’s mission to protect the multiple strategies are necessary for prises within the horse industry health and welfare of wild horses the wild horse and burro population as well as public sector and non- and burros. to reach the desired level that governmental organizations so Resource: optimizes the health of the animals that the animals may be utilized American Veterinary Medical Association. AVMA Guidelines on the range, while reducing welfare for recreation, companionship on Euthanasia. Available at: https://www.avma.org/KB/ impacts caused by overpopulation in or placement in privately funded Policies/Documents/euthanasia.pdf. areas of limited resources. sanctuaries. IV AAEP News November 2019 Association

AAEP establishes position statement on use of MPA in competition horses

At the recommendation of the Performance Horse Committee, the AAEP board of directors recently approved the position statement, Use of Medroxyprogesterone Acetate in Competition Horses. The complete text of the position follows. It is also accessible at https://tinyurl.com/aaepmpa.

AAEP Statement on the Use of Medroxyprogesterone Acetate in Competition Horses

Medroxyprogesterone acetate (MPA) is a synthetic progestin hormone administered to mares off-label in an benefit that goes beyond this behavior modification. attempt to suppress behavioral estrus. However, a Therefore, the AAEP recommends that MPA should not be controlled research study found that MPA was not administered to horses in competition. effective at suppression of behavioral estrus.1 Many veteri- Reference: narians believe MPA modifies behavior by producing a 1 Gee EK, C DeLuca, JL Stylski, PM McCue. Efficacy of medroxyprogesterone acetate in calming effect in the horse and does not have a therapeutic suppression of estrus in cycling mares. J Equine Vet Sci 2009;29:140-145.

Texas A&M discontinues document retrieval service

Texas A&M University has discontinued its Get It For Me document retrieval service, which had been a popular benefit among many AAEP members for two decades. The service provided institutional support for accessing veterinary literature through complimentary database search and document delivery services.

The AAEP is examining ways to reinstitute this type of service in some format and will notify the membership of any developments.

Stay informed of disease risk with new EDCC app

The Equine Disease Communication Center (EDCC), which provides real-time alerts for risk assessment of infectious diseases for all parts of the horse industry by county or municipality in the United States and Canada, has launched a mobile app version of its online information system.

The EDCC Disease Alerts app connects directly to the disease alerts page, making it easy to filter information by disease, state and date. Users have quick access to the disease risk information necessary to make decisions about travel and biosecurity. The app also provides access to disease fact sheets with helpful information about diagnosis and treatment.

“The EDCC is a reliable source for not only quickly assessing disease threats, but also defining progression of disease events,” said E.S. “Rusty” Ford, equine operations consultant, Kentucky Office of State Veterinarian. “The greatest benefit is reliability of the information posted… enabling us and others opportunity to develop and implement disease-mitigating strategies.”

Protect the health of your clients’ horses by downloading the EDCC Disease Alerts app and encouraging your clients to do likewise. Search “EDCC Disease Alerts” at the App Store or Google Play to download. Association AAEP News November 2019 V

5 things to know about AAEP this month

1. Read the new AAEP position 2. Download the Equine 3. Save $100 by registering 4. Soak in sun, sand and 5. Read the inaugural report statement on the Use of Disease Communication for the AAEP’s 65th Annual science at the Resort from the Equine Welfare Medroxyprogesterone Center’s new EDCC Convention in Denver in Symposium in Aruba, Data Collective, funded Acetate in Competition Disease Alerts app by advance of the meeting at Jan. 23–25, 2020. in part by the AAEP Horses at https://tinyurl. searching “EDCC Disease convention.aaep.org. Learn more and register Foundation, at com/aaepmpa. Alerts” at the App Store or at aaep.org/meetings/ unitedhorsecoalition.org/ewdc. Google Play. resort-symposium.

On air: Listen to new EVE podcast

A new Equine Veterinary Education podcast After Diagnostic Analgesia: Reduction in Behaviour episode offers a deeper look into a pair of Scores”; and Dr. Stephen Purdy discusses the article “Small papers recently published in the journal. Herd Behaviour in Domestic Donkeys.”

In the most recent episode, Dr. Sue Dyson Listen to the 35-minute episode, view the articles and discusses the article “Application of a Ridden Horse subscribe to future episodes at equineveterinaryeducation. Ethogram to Video Recordings of 21 Horses Before and podbean.com.

Touch Point: Don’t overlook young horse owners for practice growth

Young horse owners (18–40 years) may present an overlooked oppor- tunity for veterinarians seeking to grow their practices, according to AAEP market research. Not only do these young owners provide the most long-term opportunity for business, but their above- average involvement in the horse industry adds to their prospective customer value.

Compared with older horse owners, those aged 18–40 are more involved in the horse industry and their horses see an equine veterinarian more frequently. These owners also put as much or more emphasis on relationship-oriented attributes as they do on their veterinarian’s knowledge and experience. Demonstrating compassion, taking time with the horse, explaining diagnoses and having a pleasant demeanor are characteristics that the younger owner places a higher importance on than older owners. To obtain more information about the preferences of this important client group, read the complete Touch research With lower incomes than older owners, the 18–40 segment report at touch.aaep.org. Log in to the Touch website is the most cost-sensitive but also the most likely to using the same username and password that you use to increase their already frequent usage of veterinarians. access aaep.org. Young owners are the most likely to expect to increase their usage of veterinarian services over the next few years The bottom line: young horse owners can contribute to (8% vs. 5% for those aged 41+), pointing to stricter regu- your practice’s bottom line if you take the time to lations at horse shows and plans to do more preventive understand the attributes they most value in veterinary care and breeding in the future. relationships and services. VI AAEP News November 2019

If you are unable to join your colleagues in Denver, you can follow along through email and social media. Check your inbox each evening for news, recaps and more in the Convention Daily; “like” the convention on Facebook at facebook.com/AAEPConvention; and join the discussion on Twitter and view photos on Instagram by following @AAEPHorseDocs and using the hashtag #AAEPDenver.

Take your next step at Career Fair In between jobs? Looking for a new opportunity? Leave Denver with new knowledge and a new opportunity by Invest in patient and personal participating in the virtual Career Fair. wellbeing at #AAEPDenver AAEP will help get your resume in front of practices Ascend new heights professionally and personally at the attending the convention and looking to fill open AAEP’s 65th Annual Convention in Denver, Colo., Dec. positions. You’ll meet employers and recruiters face to 7–11. You’ll acquire the latest science-backed solutions face to discuss your skill set and qualifications for their for patients, establish beneficial connections with job openings. Here’s how: colleagues and veterinary suppliers, and acquire tips and resources to strengthen your emotional resilience so you 1. Create or log in to your AAEP Career Center account can live your best life. at jobs.aaep.org.

You may still register online at the reduced rate of $675 2. Upload your resume if you haven’t done so already. through Dec. 6; after this date, the rate increases $100. 3. Indicate on your account page that you’ll be On-site registration at the Colorado Convention Center attending the Career Fair at the convention, which begins Dec. 6 at 3:00 p.m. At check-in, you’ll receive the will flag your resume for participating employers to 2019 Proceedings book containing all the papers being review and contact you (confidentially if you prefer). presented at the meeting that otherwise is mailed to AAEP members in January. You’ll also be able to view a list of participating employers and create email job alerts to be notified of Register and view the educational program and schedule new Career Fair listings. Contact Megan Gray, member of social and networking events at convention.aaep.org. concierge, at [email protected] with any questions.

Steer the conversation

Help drive the conversation at this year’s Table Topic sessions without saying a word.

A new audience response feature integrated into the AAEP Convention App enables you to submit questions (anonymously if you wish) to the moderators, see questions posed by others, and upvote questions that are most important or applicable to you. The most popular questions will rise to the top and provide moderators with insight into the questions that are most pertinent to the group.

Within the app, click the Schedule icon, locate and select the relevant Table Topic session, and then click the “Q&A/Polling” button.

If you will be attending the convention but do not have the AAEP Convention app installed on your device, search “AAEP Education” at the App Store or Google Play to download. American Association of Equine Practitioners

22nd AnnuAl ResoRt symposium ARuBA January 23-25, 2020 The Ritz-Carlton | Palm Beach, Aruba

At the AAEP’s 22nd Annual Resort Symposium, you’ll lower your stress amid Aruba’s natural splendor and raise the level of care you provide to client horses during practical half-day sessions devoted to:

Field procedures and emergencies with Dr. Stephanie Caston Effective sedation and restraint techniques with Dr. John Hubbell Preventative medicine and biosecurity strategies with Dr. Tracy Norman

RACE-approved CE credits: 15

Sponsored by

Register by Jan. 10 at aaep.org/meetings VIII AAEP News November 2019 CONtINUING EDUCATION

Share your research and knowledge at the 66th Annual Convention in Las Vegas Deadline to submit an educational paper is March 16, 2020, 3:00 p.m. ET

AAEP members and others are invited to submit papers for consideration for presentation during the AAEP’s 66th Annual Convention in Las Vegas, Nev., Dec. 5-9, 2020. Eligible for consideration are scientific papers, “how-to” papers, review papers, 250-word abstracts and The Business of Practice papers.

Submitting your paper • All papers must be submitted by March 16, 2020, 3:00 p.m. ET at https://s3.goeshow.com/aaep/ annual/2020/AAEP_paper_submission.cfm. The system will shut down after this time. • Be sure to familiarize yourself with the submission process well in advance of the deadline. You can set up your profile with paper and author information in advance and then upload your paper when it is Programs Committee to material with practical content complete. or new information. • Since the review process is blinded, make sure your How-to papers should describe and explain a technique paper does not include author or institution names. or procedure used in veterinary medicine or the equine industry. The technique should be relatively new or not A few key points widely understood or used in practice. There is no word • Products and equipment must be identified by limit for how-to papers. chemical or generic names or descriptions and footnoted. Review papers should update the membership on a new • Due to the length and complexity of the process, all subject or gather information that may be conflicting. deadlines are strictly enforced. Although a review paper does not necessarily contain • Submission of a paper represents a commitment to original data, it is anticipated that the presenter will have present this paper at the meeting if it is selected. considerable experience in the field. • Selected papers will be printed in the 2020 AAEP Abstracts ≤ 250 words may be submitted by authors who Proceedings and presented at the 2020 Annual intend to publish in a refereed journal. An abstract Convention. The presenting author will receive conforming to the AAEP guidelines to authors must also complimentary registration and a travel allowance. be submitted (for review purposes only) to allow the reviewers to assess the experimental design, materials and Ethical Considerations methods, statistical analyses, and results (with graphs, • Authors are expected to disclose the nature of any tables, charts, etc.) and to discuss the results as they financial interests they have with companies that pertain to interpretation and conclusions. manufacture or sell products that figure prominently in the submitted paper or with companies that manu- The Business of Practice papers may cover any business facture or sell competing products. management topic that can help the practitioner and their • If your presentation references the use of a practice achieve more success and improve profitability. compounded pharmaceutical, ensure that you are The theme for 2020 is “The Healthy Practice.” familiar with the FDA guidelines on the use of compounded pharmaceuticals and that the product Need help submitting a paper? you reference is in compliance. As an aid to private practitioners, first-time authors or members seeking guidance with their submission, AAEP • All AAEP abstracts submitted for presentation should offers a mentorship program in which experienced cite levels of evidence-based medicine. presenters are available to provide advice and direction. However, mentors are not responsible for rewriting or Types of papers accepted selecting material. All paper presentations are limited to 15 minutes plus 5 minutes for Q&A. Contact Carey Ross, scientific publications coordinator, at [email protected] for a list of available mentors or with Scientific papers should be a minimum of 600 words. questions concerning the annual convention and educa- Special attention will be given by the Educational tional paper submission. FOUNDation AAEP News November 2019 IX

Equine Welfare Data Collective releases inaugural report

The Equine Welfare Data Collective (EWDC), whose funding partners include the AAEP Foundation, has released its inaugural report assessing data from 2017 and the first half of 2018 of at-risk and transitioning equines and the organizations assisting them.

The EWDC analyzed responses from 253 nonprofit, 501(c)(3), and municipal organizations across the United States and Puerto Rico, which represented 27.59% of the total population of those organizations that take legal custody of at-risk equines and those in transition.

The data analysis is reported on a national and regional level. Respondents varied widely, from small capacity organizations capable of caring for fewer than 10 equines at any one time, to larger organizations with capacity for over 100 equines.

Organizations most commonly obtained custody of “This data report is a steppingstone to understanding the at-risk and transitioning equines through owner demographics of at-risk equines and those in transition, surrenders or assisting law enforcement seizures. the needs of the organizations taking custody of them, Adoptions represented 79.95% of all reported outcomes and the opportunities for growth within the community,” for the first half of 2018. said American Horse Council President Julie Broadway.

Presently, it is out of the scope of the EWDC survey to View the full report at unitedhorsecoalition.org/ewdc. The make national projections based on the sample size. EWDC hopes to continue to measure progress and However, it is promising to note that the respondents, identify trends through continued data collection and representing one quarter of all welfare organizations, reporting. All rescues, shelters, and sanctuaries are reported a total capacity of over 13,000 equines at any encouraged to assist in the effort to collect this much- one time. needed data. X AAEP News November 2019 MEMBERSHIP

Benefit: Profit from pre-owned practice equipment

Whether you’re in the early stages of your career and looking for pre-owned veterinary equipment to grow your practice prudently, or you’ve recently upgraded and are looking to sell your used equipment, the AAEP’s online Equipment Marketplace connects members on both sides of the commerce equation.

As of Oct. 30, over 50 practices had more than $500,000 worth of inventory listed.

“I have converted thousands of dollars of underused equipment into cash through the AAEP’s Equipment Marketplace,” said Dr. Susan Moreland of Farmington, units to vet boxes and dental tools, you’ll find it all at N.M. aaep.org/dashboard/equipmentmarketplace.

Creating a listing as a seller is easy; and buyers can use If you have questions about the Equipment Marketplace, search capabilities to narrow results to specific categories please contact Megan Gray, member concierge, at mgray@ of equipment. From ultrasound machines and radiograph aaep.org.

Members in the News

Dr. Nicholas Meittinis joins TRF board Dr. Nicholas Meittinis, founder of Maryland Veterinary Group LLC in Laurel, Md., has been appointed to the Thoroughbred Retirement Foundation board of directors. TRF is the oldest and largest Thoroughbred aftercare organization in the United States.

A 1989 graduate of Cornell University, Dr. Meittinis established his current practice in 1995 after working as a solo practitioner at Pimlico and Laurel racetracks. He serves on the Maryland Racing Commission’s Medication Committee and previously served on the AAEP’s Racing Committee.

Dr. Nicholas Meittinis

Three honored by The Right Horse Initiative Drs. Bruce Connally, James Fukuda and Wayne Marteney are the Veterinary Professional recipients of The Right Horse Initiative’s inaugural Good People for Good Horses Awards, which recognize outstanding contributions to equine adoption and welfare efforts.

Dr. Connally, a 1979 graduate of Colorado State University, was recognized in the Central region for his work with Colorado Horse Rescue in Longmont, Colo. Dr. Fukuda, a Dr. Bruce Connally Dr. James Fukuda Dr. Wayne Marteney 2011 graduate of Kansas State University, was recognized in the East region for his work with Florida Thoroughbred Retirement and Adoptive Care. Dr. Marteney, an Honor Roll member who received his veterinary degree from the University of California, Davis in 1974, was honored in the West region category for his work with Love This Horse Equine Rescue in Acton, Calif.

Additional information about each of the award winners and their contributions to adoption efforts is available at therighthorse.org/2019-good-people-for-good-horses-awards. MEMBERSHIP AAEP News November 2019 XI

Practitioner empowering remote veterinarians to improve horse health across Mongolia

A desire to Accompanied by Dr. John Haffner of volunteer while Murfreesboro, Tenn., the expedition visiting the began as a two-week mission Christian composed of a three-day workshop of Veterinary Mission classroom and wet lab instruction on booth at the 1999 diagnostics and treatments for AAEP Annual common ailments such as lameness, Convention in colic and respiratory disease; and Albuquerque, on-site care at the races, which helped N.M., quickly build trust by showing the effective- accelerated into an ness of modern medicine in a region annual pilgrimage to Mongolia for where many treatment protocols were Dr. Tom Juergens, who for the past established 800 years earlier by 20 years has introduced modern Genghis Khan. veterinary medicine to remote veteri- A remote veterinarian performs a narians and herdspeople to improve The mission has since expanded to nasogastric intubation with an assist the health and wellbeing of the five weeks in the summer; following from Dr. Juergens. country’s horses. the three-day seminar attended by up to 60 veterinarians, Dr. Juergens To date, the mission has trained Dr. Juergens, the retired founder of travels the countryside in a Russian approximately 700 veterinarians in Anoka Equine in Anoka, Minn., and four-wheel drive van to provide every province of Mongolia; some the September honoree of the AAEP’s practical training and mentorship in now teach at the country’s veterinary Good Works, embarked on his the field while living with remote vet- school, elevating the level of Mongolian service in 2000. His goal erinarians and herdspeople. Following education for the next generation of was to train veterinarians in modern training sessions, Dr. Juergens uses the Mongolian veterinarians. These medicine and techniques as well as relationships and trust established to trained veterinarians can also acquire provide much needed veterinary share his Christian faith. Western medicines from a Mongolian- support at the races, which draw up owned and -run pharmacy started by to 3,000 horses competing across the “When we first got there, we didn’t Drs. Juergens and Haffner to aid in countryside under child jockeys at know what to expect,” said Dr. the treatment of horses. distances between 15 and 50 Juergens. “There were going to be kilometers. times when our treatment and “Johnny and I have committed education would be scoffed at, so that ourselves to this group of veterinari- was difficult; and we didn’t know if ans and the care of their horses,” said we’d be allowed to come back a Dr. Juergens. “We’ve been there second time. enough that we’re able to make our training and education culturally “But we came back the second year relevant. We know what their capabil- and then the third year, giving them ities are and then we teach within education and access to quality those capabilities.” medication. Then they really started believing what we were talking about. “They love their horses, which are an And when we’d go out and mentor important part of their culture, and them—whether in the Gobi Desert, we’re seeing the quality of vet care up in the mountains or on the improve not only for these horses but Siberian border—we were so other species as well because of welcomed and appreciated.” lessons taught on the horse.”

Throughout 2019, the AAEP’s Good Works for Horses Campaign has spotlighted AAEP-member practitioners whose volunteer efforts are Dr. Juergens teaches anatomy inside the improving the health and welfare of horses. To discover the Good Works tent of a remote veterinarian in the of AAEP veterinarians, visit aaep.org/horse-owners/good-works-horses. mountains near Kazakstan. XII AAEP News November 2019 MEMBERSHIP

Welcome new members, and congratulations recent graduates

New Members: Thomas Anderson Ponder, DVM, Greeley, CO C. Scott Bailey, DVM, Paris, KY Carly Louise Ross, DVM, Ames, IA Lori Lynn Bohenko, DVM, Wheeling, WV Margaux Tillinghast, DVM, Chester, NY Charlie Buchanan, DVM, Stephenville, TX Kathleen M. Weatherall, VMD, Auburn, AL Ricardo Ceballos, MVZ, Merida, Yucatan OR, Mexico Federica Zacchia, DVM, Langhirano, Parma, Italy Rose Digianantonio, DVM, Canon City, CO Kristie Dixon, DVM, Laramie, WY Recent Graduates: Shawn N. Dixon, DVM, Wellington, CO Emily Barton, DVM, Old Fort, NC Ana Carolina Do Amaral, DVM, Sorocaba, PA, Brazil Amanda Jo Calvird, DVM, Cumming, GA Shane Fouhy, MVB MRCVS, Hampshire, United Kingdom Evan Crisman, VMD, Conestoga, PA Richard Thomas Geary, DVM, Saint Anthony, ID Cosette Marie Faivre, DVM, Ames, IA Hanna Haardt, DVM, Rocky View County, AB, Canada Rudy Hermosillo, DVM, Los Angeles, CA Anna Hailey, DVM, Tioga, TX Emily Kotelnicki, DVM, PhD, Bozeman, MT Robin Knight, DVM, Nampa, ID Olivia Jean Lattanzi, DVM, Hillsboro, NH Jordan Elizabeth Koivu, BSc, DVM, cVMA, Dartmouth, NS, Molly Lesser, DVM, Newman Lake, WA Canada Hannah Lynaugh, DVM, Keuka Park, NY Laurel B. Marley, DVM, Warrenton, VA Kathleen Meyers, DVM, Ravena, NY Martha Mellish, DVM, Mount Stewart, PE, Canada Merete Moller-Jensen, DVM, Rocky View County, AB, Canada Mitja Miklavcic, DVM, Lexington, KY Giulia Pera, DVM, Bogota, Colombia Armando Moya, DVM, Houston, TX Taylor Rietveld, DVM, West Lafayette, IN Etienne Palerme, DVM, Gatineau, QC, Canada Jodi Leigh Smith, DVM, Gettysburg, SD Hunmin Park, DVM, Gwacheon-Si, Gyeonggi-Do, Republic of Holly Webb, DVM, South Lebanon, OH Korea Zach Young, DVM, Larimore, ND

INDUSTRY

Educational Partner Profile: Zoetis

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Advancing the Veterinary Profession As a longtime supporter of the AAEP, Zoetis sponsors the AAEP Foundation Scholarship for students and matches donations to the AAEP Equine Memorial Giving program. Additionally, Zoetis is proud to sponsor the American Association of Equine Veterinary Technicians and Assistants. The company’s support of the AAEP and AAEVT is part of the Zoetis Commitment to Veterinarians™ program that supports professionals in the industry through continuing education, veterinary wellness, research and development, and philanthropy.

Making a Difference Committed to making a difference in the equine community, Zoetis also contributes to the American Veterinary Medical Foundation, The Right Horse Initiative, the American Horse Council, the American Quarter Horse Association Foundation, the Morris Animal Foundation and many other educational and equine research programs.

For more information on how Zoetis supports the equine veterinary industry and works to help horses live long, healthy lives, visit ZoetisUS.com. E Q UINE VETERINARY EDUCATION/American Edition equine American Edition | December 2018 veterinary education Volume 30 Number 12 B:11.125” T:10.875” S:10”

Don’t leave your horse exposed. New CORE EQ INNOVATOR™ December 2018 in this issue: is the first and only vaccine to help protect against all potentially fatal core equine diseases in one injection. From the President: The magic of the AAEP Annual Convention Intestinal adenocarcinoma in ponies: Clinical and pathological findings CoreEQInnovator.com The official journal of the Pyrimethamine toxicosis in horses given a compounded medication American Association of Equine Practitioners, produced All trademarks are the property of Zoetis Services LLC or a related company or a licensor unless otherwise noted. © 2018 Zoetis Services LLC. All rights reserved. COR-00038 in partnership with BEVA. 562 EQUINE VETERINARY EDUCATION Equine vet. Educ. (2019) 31 (11) 562-563 doi: 10.1111/eve.13193

Highlights of recent clinically relevant papers

Hypoxaemia and general anaesthesia in 25/26 instances. The polarity of the QRS complex was similar on the ECGs acquired simultaneously by both systems. This prospective study by David Bardell and colleagues in the Heart rates calculated from ECG pairs were within one beat UK investigated changes in arterial oxygen tension (PaO )in 2 of each other. horses during recovery from general anaesthesia. The smartphone-acquired ECG accurately identified This study included 102 systemically healthy horses cardiac rhythm and heart rate in most horses. In one case, undergoing general anaesthesia for elective surgery. Arterial small size of the complexes precluded identification of P blood samples were obtained prior to the administration of waves on smartphone-acquired ECGs, resulting in a pre-anaesthetic medication (baseline), at the end of misdiagnosis. The smartphone-acquired ECG device might anaesthesia, when placed in recovery, at 10-min intervals allow veterinarians to evaluate and monitor cardiac whilst in lateral recumbency, immediately upon achieving arrhythmias relatively inexpensively in field or hospital settings. sternal recumbency, at 10-min intervals until standing and 1 h after standing (STAND+1). Pre-anaesthetic medication consisted of acepromazine, Skin antisepsis using an alcohol-based rub an alpha-2 adrenoreceptor agonist and a l-receptor agonist In this study, Aimie Doyle and colleagues in Canada aimed opioid. Induction was achieved with thiopental or ketamine to determine whether an alcohol-based antiseptic is effective plus a benzodiazepine, and anaesthesia was maintained with at reducing bacterial counts on equine skin and the isoflurane or sevoflurane. Forty horses received controlled appropriate contact time without producing any adverse skin mandatory ventilation (CMV) throughout anaesthesia, 47 reactions. breathed spontaneously (SV), and 15 breathed Samples were collected before and after preparation spontaneously before CMV was commenced (S-CMV). from clipped sites over both jugular veins of horses and were Overall, PaO alveolar-to-arterial oxygen tension difference 2 plated on 3M Petrifilm Aerobic Count Plates in duplicate. Trial (P(A-a)O ) and arterial carbon dioxide tension (PaCO ) 2 2 1 tested an alcohol-based product (ET-80% ethanol) against remained significantly lower than baseline at the STAND+1 time a control of sterile saline at a contact time of 180 s. Trial 2 point. The only group in which these values had returned to tested two different contact times of ET-90 and 180 s. All baseline values at STAND+1 was S-CMV. CMV resulted in higher samples were assessed for colony-forming unit counts using PaO at the end of anaesthesia and during early recovery 2 an automated 3M Petrifilm reader. Data were analysed by than SV. Highest PaO values associated with CMV were also 2 Kruskal-Wallis test. The results determined that ET had a mean associated with early recovery apnoea. Oxygen supple- of 2.95 log reduction from prepreparation to mentation in recovery resulted in higher mean PaO than 10 2 post-preparation colony-forming unit counts. A significant horses receiving no additional oxygen. High PaO values did 2 difference in log reduction between ET and control was not appear to adversely affect outcome. observed. There was no difference in log reduction These results indicate that controlled mandatory 10 between the two contact times. Mild urticaria was the only ventilation during general anaesthesia may result in better skin reaction observed and was often present in both ET and pulmonary function in horses. control groups. These findings demonstrate that ET is effective at reducing Smartphone-based electrocardiography bacterial counts on equine skin at a contact time of 90 s In this study, Marc Kraus and colleagues in the USA evaluated without producing significant adverse skin reaction. the accuracy and utility of a smartphone-based electrocardiogram (ECG) device compared with a standard Morphological variations in the caudal cervical base-apex ECG in the horse. spine ECGs were acquired from 28 client-owned horses at two equine referral hospitals. Twenty-five pairs of 30-s ECG This case–control study by Stefanie Veraa and colleagues in recordings were acquired simultaneously from 23 horses with the Netherlands and Belgium investigated the clinical a smartphone ECG device (a bipolar single lead recorder relevance of radiographically visible morphological variations coupled to a smartphone with an ECG application) and with in the caudal cervical vertebrae of Warmbloods. a standard base-apex lead ECG; two horses provided two Cervical radiographic examinations of all Warmblood pairs of simultaneously acquired ECGs. In one horse, the horses (with and without clinical signs) performed between ECGs pairs were recorded immediately sequentially. Seven January 2011 and December 2013 were reviewed by a further smartphone ECGs were recorded from five horses board-certified radiologist. Morphological variations recorded without contemporaneous reference ECGs. Three observers included absence of a ventral laminar part of the transverse evaluated all ECGs without knowledge of ECG pairing. process in combination with a ventral protuberance at Inter- and intraobserver agreement between the two ECG another transverse process and the presence or absence of modalities was evaluated for rhythm diagnosis and QRS degenerative joint disease of the articular facet joint of C6 polarity. Heart rate agreement was also evaluated. and C7. Clinical signs considered relevant included spinal Intraobserver agreement for rhythm assessment was very ataxia, restricted flexion of the neck, cervical pain on high; one observer diagnosed the same cardiac rhythm on palpation, abnormal behaviour (e.g. head-shaking and both recordings in 24/26 instances; and two observers agreed bolting), cervical muscle atrophy, presumed thoracic

© 2019 EVJ Ltd EQUINE VETERINARY EDUCATION / AE / NOVEMBER 2019 563

neurological lameness and hypermetric gait. Univariable direction (28/42; 67%). Rarely (1/42; 2%) was IPL desmopathy Pearson’s Chi-square and multivariable logistic regression the only ultrasonographic abnormality detected. Recheck were used to compare the cases (245 horses with clinical ultrasound examination was performed on 13 horses, the signs) and controls (132 horses with no clinical signs). majority (11/42; 85%) either did not improve or worsened Morphological variation at C6 and C7 was significantly ultrasonographically. Despite this, of 25 horses with a less frequent in horses with clinical signs (23.7%) compared long-term follow-up, 23 (92%) returned to work, 16 at the with the control group (38%). Age, sex, breed and same level or higher. A variety of treatments were used. degenerative joint disease were not associated with the The clinical significance of IPL desmopathy is difficult to presence of clinical signs. determine because it is usually found in conjunction with Radiographic morphological variations in the caudal other stifle abnormalities. Although IPL desmopathy rarely cervical spine are more common in horses without relevant shows ultrasonographic improvement over time, prognosis clinical signs and so should be interpreted with care. can be good for return to work.

Faecal output and colic after standing sedation Superficial digital flexor tendinopathy bandaging In this retrospective study, Christopher Thibault and In this knowledge summary, Rafael Alzola and Sarah Freeman colleagues in the USA aimed to determine time to first address the PICO question ‘In horses with superficial digital passage of faeces, total faecal piles and incidence of colic flexor tendonitis is bandaging and rest compared to rest in the first 24-h post-procedure in 246 horses undergoing alone more effective at promoting healing?’ standing sedation with detomidine, or general anaesthesia There is currently a lack of scientific evidence to suggest with or without detomidine. that bandaging promotes effective tendon healing following Records of all horses that underwent standing sedation or injury. However, rigid bandages significantly limit lesion general anaesthesia between December 2012 and March propagation in equine superficial digital flexor (SDF) 2016 were reviewed. Patient signalment, fasting duration, tendinopathies. The result of this PICO question suggests that procedure performed, drugs administered, time to first a short period (10 days) of cast immobilisation during the faeces, number of faecal piles during 24-h post-procedure initial inflammatory phase of the injury improves prognosis by and mention of colic were recorded. Chi-square, Fisher’s limiting lesion propagation. The level of confidence in the exact and Tukey’s post hoc comparison tests were used. outcomes from the body of evidence in the four studies In total, 116 and 57 horses underwent general identified is moderate. anaesthesia without detomidine (group GA) and with detomidine (group GA-D), respectively, and 73 horses S. WRIGHT underwent standing sedation with detomidine (group S-D). EVE EDITORIAL OFFICE Detomidine dose was significantly higher in group S-D than in group GA-D. Time to first faeces was longer (7.1 4.2 h), and group S-D horses passed one fewer faecal pile (6.3 2.4) References than group GA horses. There was no interaction between detomidine treatment and preprocedure food withholding Alzola, R. and Freeman, S.L. (2019) Comparing rest alone to fi fl and the time to first faeces or the number of faecal piles in bandaging and rest in horses with super cial digital exor tendinopathy. Veterinary Evidence 4,3. the first 24-h post-procedure. Overall, seven horses (2.8%) showed signs of colic (5 GA, 1 GA-D and 1 S-D). Bardell, D., Mosing, M. and Cripps, P.J. (2019) Restoration of arterial oxygen tension in horses recovering from general anaesthesia. The authors concluded that detomidine administration, as Equine Vet. J. Epub ahead of print; https://onlinelibrary.wiley.com/ part of an anaesthetic protocol or for standing sedation doi/10.1111/evj.13142 procedures, should not be expected to contribute to Doyle, A.J., Saab, M.E., Lewis, K. and McClure, J.T. (2019) Equine skin post-procedural colic. antisepsis using an alcohol-based rub. J. Equine. Vet. Sci. 80, 61-63. Hoaglund, E.L., Barrett, M.F., Daglish, J. and Contino, E.K. (2019) Intermediate patellar ligament desmopathy often occurs in Intermediate patellar ligament desmopathy conjunction with other stifle abnormalities. Vet. Radiol. Ultrasound. 60, 416-422. This retrospective descriptive study by Elizabeth Hoaglund and colleagues in the USA aimed to describe the clinical and Kraus, M.S., Rishniw, M., Divers, T.J., Reef, V.B. and Gelzer, A.R. (2019) Utility and accuracy of a smartphone-based electrocardiogram ultrasonographic features of intermediate patellar ligament device as compared to a standard base-apex electrocardiogram (IPL) desmopathy, its association with other injuries of the stifle in the horse. Res. Vet. Sci. 125, 141-147. and outcome for return to work following injury. Thibault, C.J., Wilson, D.V., Robertson, S.A., Sharma, D. and Kinsley, This study included 42 stifles with an ultrasound diagnosis M.A. (2019) A retrospective study of fecal output and of IPL desmopathy over a 5-year time period. Data regarding postprocedure colic in 246 horses undergoing standing sedation signalment, clinical presentation, diagnostic imaging findings, with detomidine, or general anesthesia with or without detomidine. Vet Anaesth. Analg. 46, 458-465. treatment and outcome were described. Intermediate patellar ligament desmopathy occurred most commonly in Veraa, S., de Graaf, K., Wijnberg, I.D., Back, W., Vernooij, H., Nielen, M. and Belt, A.J.M. (2019) Caudal cervical vertebral morphological the midbody (35/42; 83%) of the ligament, and lesions were variation is not associated with clinical signs in Warmblood horses. predominantly hypoechoic discrete tears (31/42; 74%) that Equine Vet. J. Epub ahead of print; https://onlinelibrary.wiley.c were obliquely oriented in a craniolateral to caudomedial om/doi/10.1111/evj.13140

© 2019 EVJ Ltd 564 EQUINE VETERINARY EDUCATION Equine vet. Educ. (2019) 31 (11) 564-566 doi: 10.1111/eve.13179

Editorial A problem-based approach to the ‘red eye’

We are pleased to announce the publication of an online identify where the redness is, what structures are red and to virtual issue of EVE on the subject of equine ophthalmology. It theorise how they became red, for example bleeding vs. encompasses some relevant ophthalmology articles that inflamed (Where? What? How?). have been published in EVE over the past 10 years, and we ! hope you enjoy it Clinical reasoning

Trying to reduce panic – what tools do you Working out where exactly the redness is, what structures are have? in close proximity and if this is normal or abnormal can really help with narrowing down causes and treatments for No matter in what type of equine practice you work, it is common eye conditions. Once you have identified what is important to know what equipment you have available to you red, trying to work out if this is a primary redness of that and how to use it. From prepurchase examination (Matthews structure or if it is secondarily red due to being in contact 2016) to being able to reach a diagnosis in a clinical patient, with the affected tissue will narrow the differentials further. For examination in the field has its challenges and you need to example, differentiating conjunctival hyperaemia (vessels are know how to get the most out of your surroundings. Ideally, it is short and branching over the sclera) from episcleral best to be able to watch the patient a little in its environment congestion (long, thick and meandering vessels over the first. This will help you to gain an appreciation of vision, comfort sclera) will focus the practitioner’s choice of diagnostic tests levels and general behaviour/husbandry information before (Fig 2). If conjunctival hyperaemia is present, this is more starting a hands-on examination (Seruca and Lowe 2016). You consistent with an ocular surface disease, conjunctivitis/ will gain the most out of your examination by being in a corneal ulceration/eyelid abnormality and diagnostic tests darkened environment (e.g. a stable or examination room), if such as Schirmer tear testing and fluorescein staining may be possible. Being able to see the eye close up (sedation and more helpful. If episcleral congestion is more evident, then peripheral nerve blocks in un-cooperative patients will aid this) intraocular disease may be more likely, meaning tonometry from different angles and having a light source will help the could be more helpful for these cases. Similar distinctions with examiner to gain the most amount of information. Lastly, being iris hyperaemia or hyphema can be made: Is it unilateral or able to take photographs to track clinical progress or to ask for bilateral? A history of trauma? Is this a primary ocular help is also very handy when those complex cases come up. problem or secondary to an underlying systemic disease?

Prioritised problem list Prioritised differentials Having a scheme to follow when presented with a ‘red eye’ Eyelid/third eyelid is helpful (Fig 1). It reminds the practitioner to perform all Redness of the eyelids and third eyelid can result from aspects of the ophthalmic examination. It also helps to blepharitis (traumatic, bacteria, fungal, immune mediated,

‘Red Eye’

Where? What? How?

Adnexa/Ocular Intraocular surface

Eyelids and third Subconjunctival Conjunctival Episcleral Iris hyperaemia Hyphema eyelid hemorrhage hyperemia congestion

Primary ocular Primary ocular Intraocular disease Primary ocular Primary ocular surface

Secondary to Systemic disease Systemic disease Systemic disease intraocular disease

Fig 1: Flow diagram.

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Conjunctival hyperaemia Episcleral congestion

Fig 2: Conjunctival hyperaemia vs. episcleral congestion. etc.), neoplasia (Montgomery 2014), orbital disease leading Initial diagnostic plan or treatment to exophthalmos and eyelid swelling (Pucket 2017). It has also been seen with trauma and traumatic lacerations of the By following the problem-based approach and being able to eyelids. Additionally, traumatic orbital disease has been clinically reason as to which part of the eye is red, along with reported with brain injury leading to optic neuropathy and theorising why that structure is red, will stand the practitioner blindness (Brooks et al. 2014). in a good position to be able to implement an appropriate diagnostic and treatment plan for that patient. Subconjunctival haemorrhage Conclusion Overt haemorrhage underneath the conjunctiva, obscuring visualisation of the underlying sclera, is not common; It is key for the veterinary clinician to follow a logical however, in horses it is mostly seen in association with trauma. approach to equine ophthalmic cases. This starts with a It has also been linked to underlying systemic disease systematic and detailed examination, remembering anatomy processes, for example, clotting abnormalities. and physiology to help locate where the abnormality is within the eye. Understanding the principals of examination and Conjunctival hyperaemia pathophysiology will help the practitioner to arrive at a Redness of the conjunctiva is a common and non-specific prioritised problem list, likely differential diagnoses, and ocular sign. However, when not in combination with therefore a diagnostic and therapeutic approach to the episcleral congestion, it is more likely linked to ocular surface case in front of them. diseases, for example, conjunctivitis (Brooks 2010), C. DAWSON keratomycosis (Brooks 2009a,b; Utter et al. 2010; Henriksen Royal Veterinary College, Hatfield, Hertfordshire, UK et al. 2013), corneal ulcerative disease (Gilger 2012; Gonzalez-Medina 2015; Greenberg 2019; Ledbetter 2019) and eosinophilic keratitis (Gonzalez-Medina 2019). The conjunctiva References is also a location for administration of drugs for the treatment of ophthalmic diseases (Martins and Brooks 2012). Allbaugh, R.A. (2017) Equine recurrent uveitis: a review of clinical assessment and management. Equine Vet. Educ. 29, 279-288. Episcleral congestion Brooks, D.E. (2009a) Extirpation of the horse globe: a commentary on Engorgement of the episcleral vessels is also a common and equine enucleation. Equine Vet. Educ. 21, 608-609. non-specific ocular sign. However, when this sign is more Brooks, D.E. (2009b) Equine keratomycosis: an international problem. Equine Vet. Educ. 21, 243-246. obvious than the frequently concurrent conjunctival hyperaemia, it is more likely linked to intraocular diseases, for Brooks, D.E. (2010) Equine conjunctival disease: a commentary. Equine Vet. Educ. 22, 382-386. example, cataracts (Townsend 2016) and glaucoma (Ollivier et al. 2009; Thomasy and Lassaline 2015). Brooks, D.E., Plummer, C.E., Craft, S.L.M. and Struthers, J.D. (2014) Traumatic brain injury manifested as optic neuropathy in the horse: a commentary and clinical case. Equine Vet. Educ. 26, 527-531. Iris hyperaemia Gilger, B.C. (2012) The search for causes of nonhealing or recurrent Iris hyperaemia is seen commonly in uveitis. Uveitis can be a ulcerative keratitis in horses. Equine Vet. Educ. 24, 561-562. single one-off event in horses, or more frequently Gilger, B.C. (2018) Association of acute leptospirosis with systemic encountered is equine recurrent uveitis (Allbaugh 2017; Gilger disease and uveitis in horses. Equine Vet. Educ. 30, 137-138. 2018; Malalana 2018). Gonzalez-Medina, S. (2015) The role of equine herpesviruses in ocular disease: an incidental finding or a pathogen? Equine Vet. Educ. Hyphema 27, 623-626. Intraocular haemorrhage can occur for many different Gonzalez-Medina, S. (2019) Equine eosinophilic keratitis: an emergent reasons. However, in horses it is mostly seen in association ocular condition? Equine Vet. Educ. 31, 609-616. with trauma, severe uveitis, corneal perforation/globe rupture Greenberg, S. (2019) Ulcerative keratitis and keratomalacia in horses: and retinal detachment. It has also been linked to underlying medical management and surgical considerations. Equine Vet. systemic disease processes, for example, clotting Educ. 31, 179-182. abnormalities. With such severe ocular pathology and the Henriksen, M.D.L., Andersen, P.H., Plummer, C.E., Mangan, B. and amount of trauma often associated with these cases, Brooks, D.E. (2013) Equine corneal stromal abscess: an evolution in the understanding of pathogenesis and treatment during the past enucleation is a treatment option if the eye is blind and 30 years. Equine Vet. Educ. 25, 315-323. painful (Simoens et al. 1996; Brooks 2009a,2009b). Continued on page 581

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Case Report The outcomes of epidural anaesthesia in horses with perineal and tail melanomas: Complications associated with ataxia and the risks of rope recovery A. R. Bird†* , S. J. Morley‡, C. E. Sherlock‡ and T. S. Mair‡ †Department of Veterinary Medicine, University of Cambridge, Cambridge; and ‡Bell Equine Veterinary Clinic, Mereworth, Kent, UK *Corresponding author email: [email protected]

Keywords: horse; melanoma; epidural; ataxia; xylazine; mepivacaine; lidocaine; rope recovery

Summary are limited publications, however, comparing the different Melanoma is a common neoplasm in horses, with a high rate protocols, either in terms of their efficacy or side effects (Fikes of incidence in the perineum and ventral tail. Surgical et al. 1989; Grubb et al. 1992; Wittern et al. 1998). excision is often recommended to remove such masses and This report summarises epidural anaesthesia injections can be achieved in the standing horse either via local administered to horses with tail and/or perineal melanomas, infiltration of local anaesthetic, or via epidural administration at a single hospital over a 7-year period. Associated of a local anaesthetic and/or an adrenergic a2 receptor complications are described. agonist. The clinical records of all horses with tail and/or perineal melanomas that received epidural anaesthesia at a Cases single equine hospital, over a 7-year period, were reviewed to determine the drugs administered and complications The clinical records of horses with tail and/or perineal associated with the epidural injection. Twenty-five cases were melanomas which received epidural anaesthesia at Bell identified, five of which received epidural anaesthesia on two Equine Veterinary Clinic between 2011 and 2017 were occasions. Epidural anaesthesia was insufficient to allow reviewed. Twenty-five horses were identified, five of which surgical melanoma excision in two horses; repeated epidural had received epidural anaesthesia on two occasions. All injection allowed sufficient loss of sensation in one of these horses, with the exception of Cases 3 and 19, received horses and additional regional infiltration of local anaesthetic epidural anaesthesia to allow standing surgical removal of allowed completion of surgery in the other. Three horses their melanomas. Case 3 received epidural anaesthesia to developed significant ataxia associated with epidural allow a peri-rectal biopsy, while Case 19 received epidural anaesthesia, two of which became recumbent. Both anaesthesia to allow partial tail amputation, following a recumbent horses were placed under general anaesthesia, severe laceration and associated tail fracture. Extensive and in one of these, rope-assisted anaesthetic recovery melanomas involving the tail in Case 19 prevented laceration resulted in additional complications associated with facial repair and were suspected to have contributed to the nerve paresis, fractured ribs and a fracture of the first associated fracture. The signalment of the horses, reasons for coccygeal vertebra, with associated neurological dysfunction epidural anaesthesia, drugs administered and associated of the rectum, anus, tail and surrounding skin. complications are summarised in Table 1. Epidural injections were performed at the inter-coccygeal fi Introduction space between the rst and second coccygeal vertebrae. All horses were sedated with romifidine hydrochloride Melanoma is a common neoplasm in horses (Cotchin 1977; (Sedivet, 0.03–0.05 mg/kg bwt)1 or detomidine hydrochloride Moore et al. 2013; Knowles et al. 2015), most frequently (Domosedan, 0.01–0.012 mg/kg bwt)2, butorphanol tartrate occurring in the dermis (Foy et al. 2002; Pilsworth and (Torbugesic, 0.01 mg/kg bwt)3 intravenously (i.v.) prior to Knottenbelt 2006). Since early surgical removal is not epidural injection. The skin over the site for injection was associated with an increased incidence of re-growth or clipped and aseptically prepared before 20–40 mg (total invasiveness (Rowe and Sullins 2004; Pilsworth and Knottenbelt volume 1–2 mL) of mepivacaine (Intra-Epicaine)4 was locally 2006), removal is often recommended (Groom and Sullins infiltrated intradermally and subcutaneously. The injectate 2018). (Table 1) was drawn up in a sterile manner without an air Surgical excision of melanomas from the perineum and pocket in the syringe. An 18 gauge 3.5-inch spinal needle5 tail while standing is possible, following either infiltration of was advanced perpendicularly to the skin, in the midline over local anaesthetic or epidural anaesthesia (Grosenbaugh the identified space in a sterile manner. Correct placement et al. 1999), thereby removing the risks associated with of the spinal needle was presumed following a positive general anaesthesia (Johnston et al. 2002; Dugdale et al. hanging drop response (Grosenbaugh et al. 1999) and lack 2016). Injection of a variety of drugs at varying doses into the of resistance to injection. The injectate was administered over epidural space between coccygeal vertebrae one and two 5–10 s. Surgery commenced 20–30 min later, with the have been reported (Doherty and Valverde 2006; Skarda exception of Case 5, where the epidural was repeated 1 h et al. 2009; Dugdale 2010; Carpenter and Byron 2015). There after it was initially performed. Adequate anaesthesia of the

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08EJLtd EVJ 2018 TABLE 1: Summary of all horses with tail and/or perineal melanomas, which received epidural anaesthesia at Bell Equine Veterinary Clinic, between 2011 and 2017

Total Additional local epidural anaesthetic Height volume required to (Hands. Age Reason Drugs administered in epidural injected perform No. Breed Inches) (years) Sex for epidural injection (mL) procedure Complications

1a Connemara 14.0 11 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None vulva and perineum sterile water for injection9 1b Connemara 14.0 12 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 2 Connemara 14.2 11 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 3 Connemara 13.2 10 Gelding Peri-rectal melanoma 100 mg xylazine hydrochloride6 + 5 None None biopsy sterile water for injection9 4 Welsh pony 12.2 16 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 3 None None cross tail 40 mg mepivacaine4 5 Irish Draught cross 16.1 24 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 Epidural repeated None Thoroughbred perineum sterile water for injection9 after 1 h due to insufficient block 6 Cross breed 14.0 19 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None anus sterile water for injection9 7 Welsh section A 14 Gelding Laser melanoma removal 50 mg xylazine hydrochloride6 + 5.5 None None tail and perineum 0.9% NaCl4

8 Irish Sport Horse 11 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None EQUINE VETERINARY EDUCATION /AENOVEMBER tail and perineum sterile water for injection9 9a Eriskay 14.2 32 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 9b Eriskay 14.2 32 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum 20 mg mepivacaine4 + 0.9% NaCl4 10 Connemara cross 14.2 20 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 11 None Ataxia resulting in Thoroughbred tail and perineum 50 mg mepivacaine4 + 0.9% recumbency NaCl4 11 16.2 13 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 8 None None tail and perineum 0.9% NaCl4 12a Thoroughbred 17 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 12b Thoroughbred 17 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 4 None None tail and perineum 40 mg mepivacaine4 + sterile water for injection9 13 Warmblood 16.2 10 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 14a Irish Sport Horse 16.3 17 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 14b Irish Sport Horse 16.3 17 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None perineum sterile water for injection9 15 Connemara 14.0 9 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None 4

tail and perineum 0.9% NaCl 2019 EQUINE VETERINARY EDUCATION /AENOVEMBER

TABLE 1: Continued

Total Additional local epidural anaesthetic Height volume required to (Hands. Age Reason Drugs administered in epidural injected perform No. Breed Inches) (years) Sex for epidural injection (mL) procedure Complications

16 Andalusian 16.2 16 Stallion Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 Local infiltration None tail and perineum sterile water for injection9 of mepivicaine4 due to extensive resection beyond area epidural was expected to block 17 Connemara 14.2 11 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail sterile water for injection9 18 Thoroughbred 16.1 15 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 19 Spanish 16.0 26 Stallion Partial tail amputation 80 mg mepivacaine4 4 None None

due to laceration and 2019 fracture 20 Irish Sport 16.0 20 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None Horse cross tail and perineum 20 mg mepivacaine4 + sterile water for injection9 21 Highland 12.2 21 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 5 None None cross Shetland tail and perineum sterile water for injection9 22 Connemara 14.2 12 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 23 Sport Horse 9 Mare Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 24 Spanish 15.3 10 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 6 None Severe ataxia tail and perineum 70 mg mepivacaine4 + sterile water for injection9 25a Thoroughbred 16.1 18 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 10 None None tail and perineum sterile water for injection9 25b Thoroughbred 16.1 20 Gelding Laser melanoma removal 100 mg xylazine hydrochloride6 + 4 None Ataxia resulting tail and perineum 40 mg mepivacaine4 + in recumbency sterile water for injection9 © 08EJLtd EVJ 2018 569 570 EQUINE VETERINARY EDUCATION / AE / NOVEMBER 2019

surgical site was confirmed by loss of anal tone and lack of hindlimb weakness were present. The horse’s mentation response to artery forceps applied to the perineum. Lack of appeared normal, suggesting recovery from the sedation movement of the horse in response to commencement of given at the time of epidural. The horse was walked slowly to surgery was also used to confirm adequate anaesthesia of a stable with traction applied to the tail as he was moved. the surgical site. All cases received phenylbutazone Normal hindlimb function returned over the following 3 h and (Equipalazone, 4.4 mg/kg bwt)4 i.v. at time of surgery. no further complications were noted. The horse was In two horses, epidural anaesthesia failed to block discharged the following day. sensation of the surgical site sufficiently. In one horse (Case 5), anal tone and response to artery forceps placement on Case 25b the perineum persisted. The epidural was repeated 1 h after the initial injection and anaesthesia was deemed to be A 20-year-old gelding, approximately 500 kg, presented for successful. In the second horse (Case 16), the area for multiple melanoma removal. Tail and perianal melanomas had resection was extensive and additional local infiltration of been removed under epidural anaesthesia (100 mg xylazine mepivacaine4 was required to allow resection of the masses hydrochloride6) 2 years previously (Case 25a) with no at their most cranio-lateral margins. complications. Detomidine hydrochloride2 (6 mg) and butorphanol tartrate3 (6 mg) were administered i.v. and 100 mg 6 4 Complications xylazine hydrochloride and 40 mg mepivacaine , diluted to 4 mL with sterile water for injection9, were administered Moderate to severe ataxia (>grade 4/5 based on the grading epidurally. Approximately 15 min following epidural injection, system of Mayhew et al. 1978) occurred in three horses the horse became mildly ataxic on his hindlimbs but remained (Cases 10, 24 and 25b). In two of these horses (Cases 10 and standing. Laser excision of tail and perineal masses commenced 25b) the ataxia resulted in recumbency, and in one case approximately30 minpostepidural. (Case 25b), further complications occurred secondary to the Following completion of surgery, 45 min post epidural, an subsequent recovery. attempt was made to walk the horse from the stocks. Severe hindlimb weakness was apparent and he became partially 6 Case 10 recumbent in a dog sitting position. Xylazine hydrochloride (40 mg) was administered i.v. and general anaesthesia A 20-year-old mare, weighing approximately 450 kg, presented induced with 1.6 g ketamine2. A rescue glide was used to for melanoma removal. Sedation was achieved with 20 mg move the horse to a recovery box for a rope-assisted romifidine hydrochloride1 i.v., before caudal epidural anaesthesia recovery from anaesthesia (Hubbell 1999). was performed with 100 mg xylazine hydrochloride (Chanazine Forty minutes following induction of anaesthesia, the horse 10%)6 and 50 mg mepivacaine4, diluted to a total volume of attempted to stand. Marked hindlimb ataxia and generalised 11 mL with 0.9% NaCl (Vetivex 1)4. weakness were observed and the horse fell heavily into Approximately 25 min after epidural injection, the mare lateral recumbency on several occasions. He was re-sedated became severely ataxic on her hind legs, progressing to with 30 mg romifidine hydrochloride1 and general bilateral hindlimb paralysis and recumbency. Further sedation anaesthesia re-induced with 1.7 g ketamine2. Based on the (25 mg romifidine hydrochloride1) was administered i.v. and experience with Case 10, the horse was kept anaesthetised general anaesthesia induced with 1.2 g ketamine (300 mg ketamine2 every 10–15 min) until 3 h 15 min after (Narketan)2 and 10 mg diazepam (Diazepam injection)7 i.v. epidural administration, at which time he was once again The mare was placed onto a rescue glide and transferred to allowed to recover from anaesthesia. Multiple further a padded anaesthesia recovery box. Surgical removal of the attempts to stand were made. On one occasion, after melanomas was performed and the mare allowed to recover standing successfully, the tail rope was locked into a rope spontaneously from anaesthesia. Recovery of full hindlimb clutch10 to provide continuous tail support. The horse function took 3 h, during which time the mare was kept subsequently fell again resulting in a period of several recumbent with sedation and given supportive care. An seconds of suspension via the tail rope, before the AnimaRescue and Carriage Sling8 was placed and once the mechanism could be freed. Successful recovery to standing mare stood on a second attempt the sling remained in place occurred 4 h 15 min after epidural administration. to provide support for a further 2 h. After this time (7 h after Clinical examination of the horse once standing revealed the epidural was placed) the mare returned to her stable tachypnoea (peak respiratory rate 120 breaths/min; and was discharged the following day with no further Supplementary Item 1), tachycardia (heart rate 56 beats/min) complications. and hyperthermia (39.5°C). Oxygen was supplied at 10 L/min via a nasal tube and 250 mg flunixin meglumine (Flunixin9) ’ Case 24 administered i.v. Over the following 2 h the horse s ataxia and hyperthermia resolved and his respiratory rate and heart A 10-year-old gelding, approximately 500 kg, presented for rate reduced to 24 breaths/min and 48 beats/min. The horse perineal melanoma removal. Following sedation with 5 mg remained in the recovery box overnight and following a 20 L detomidine hydrochloride2 and 5 mg butorphanol tartrate3, bolus of compound sodium lactate4, i.v. crystalloid was epidural administration of 100 mg xylazine hydrochloride6 and supplied at 4 mL/kg bwt/h. 70 mg mepivacaine4, diluted to a volume of 6 mL with sterile water (Water for injections)9 was performed. Surgery Post recovery management and further complications commenced 30 min later. During surgery, the horse leant on of Case 25b one side of the stocks, and when walked from the stocks 1 h As a result of the prolonged recumbency and falls during following epidural injection, severe ataxia (grade 4/5) and anaesthesia the horse had a prolonged period of

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hospitalisation and drug therapy. Facial nerve paralysis was apparent on standing but resolved over the following 2 weeks. Multiple rib fractures were present (Fig 1) resulting in a mild pneumothorax and effusion which resolved over 5 days without specific therapy. The most important complication was that of tail fracture and associated loss of neurological function. Paralysis of the tail was noted after standing, with absence of skin and deep pain sensation to this area. In addition, skin sensation was absent from a 10-cm diameter region dorsal to the tail, although a response to deep pain, albeit reduced, was present. Reduced anal tone and skin sensation around the anal ring and perineum were also present. Radiographs the following morning (Fig 2) revealed a displaced caudal vertebral body fracture of the first coccygeal vertebra, with ventral displacement of the caudal fracture fragment. Gas opacity adjacent to the fractured vertebra was present (suspected to be the result of air entrapment during epidural placement). Neurological Fig 1: Case 25b. Left ventral to right dorsal oblique thoracic radiograph showing displaced fractures of ribs 8–13 (rib 7 was assessment of hindlimb function was normal but the horse also fractured but not included in this field of view). developed a rectal impaction which required extensive medical treatment over 6 weeks. Seven weeks post epidural the horse was discharged home. At this time, marked muscle atrophy of the tail head was present, and repeat radiographs showed that further fracture and displacement of the first coccygeal vertebra had occurred (Fig 3). With the exception of the tail, which remained paralysed with lack of deep pain sensation, perineal skin sensation and anal tone had returned to normal. On re-examination, 4 months following discharge, complete paralysis of the tail remained, but anal tone and perineal sensation were normal. The horse was in good bodily condition, and reported to be defaecating normally, apart from faecal staining of the tail and perineum.

Discussion Fig 2: Case 25b. Lateral-lateral radiograph of the tail base Epidural anaesthesia provided sufficient loss of nociception to showing displaced fracture of the caudal vertebral body of the allow surgery in all but two cases. Following the initial epidural first coccygeal vertebra with ventral displacement of the caudal administration of xylazine hydrochloride to Case 5, no loss of fragment and tail. There is also gas opacity in the soft tissues sensation was detected during the hour post epidural and adjacent to the fractured vertebra. anal tone remained normal. Had part, or all of the initial injectate been successfully placed in the epidural space, but the continued sensation been due to delayed onset, early cases. While the weights of the majority of the horses were repeated epidural injection may have increased cranial not recorded, based on height and breed, it is estimated spread of the injectate, and increased the risk of ataxia. Due that most horses received 0.17–0.25 mg/kg bwt xylazine to reported onset times of anaesthesia from xylazine being hydrochloride (100 mg xylazine hydrochloride given to a approximately 30 min (LeBlanc et al. 1988), it was felt that 400–600 kg horse). The lack of specific drug dose calculations continued sensation after 1 h was sufficient to conclude based on kg bwt, however, makes it difficult to draw misplacement. In Case 16, the area of melanoma resection conclusions over the effect of dose (mg/kg bwt) on was large, and while epidural xylazine hydrochloride reduced subsequent ataxia. It is worth noting, however, that the cases sensation, it was insufficient to allow full resection. This may which developed ataxic complications were not the smallest have been because the masses for resection extended of the horses presented. One case (Case 4) was a 127 cm outside the area anaesthetised by epidural anaesthesia pony, and, if 250–300 kg, would have received 0.34–0.4 mg/ (Grosenbaugh et al. 1999), or that, in this horse, the epidural kg bwt xylazine hydrochloride. No ataxia was observed in this failed to completely block nociception in an area that would pony, despite being given an epidural dose of xylazine normally be expected to be anaesthetised. In either case, hydrochloride above that where ataxia began to become the authors recommend while using epidural anaesthesia for apparent in initial studies by LeBlanc et al. (1988). standing melanoma removal, that local anaesthetic be The recommended drugs and doses administered by available for local infiltration, should it be required. epidural injection to provide anaesthesia vary (Grosenbaugh For all other cases, a single epidural injection produced et al. 1999; Robinson and Natalini 2002; Doherty and sufficient loss of sensation to allow completion of the planned Valverde 2006; Natalini and Driessen 2007; Skarda et al. 2009; procedure, with no complications in 25 of the 28 remaining Dugdale 2010; Michou and Leece 2012; Carpenter and Byron

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only mepivacaine, at 0.15–0.16 mg/kg bwt (assuming 500–550 kg) and also showed no complications. The observed ataxia may have been due to the use of mepivacaine as the choice of local anaesthetic. While there are recommended doses in the literature, no reports of its clinical use could be found. Epidural administration of lidocaine has been reported, and therefore may have been a better local anaesthetic choice, but ataxia has been reported with lidocaine when used alone at doses of 0.22–0.45 mg/kg bwt (LeBlanc et al. 1988; Fikes et al. 1989; Grubb et al. 1992). The volume of local anaesthetic administered may also be an important factor in determining the likelihood of subsequent ataxia, particularly if any reduction in the epidural space is present. Hendrickson et al. (1998) demonstrated a relationship between cranial spread of methylene blue injected into the epidural space of horses and the volume used. In women, a nonlinear relationship between the injected Fig 3: Case 25b. Lateral-lateral radiograph of the tail base volume of mepivacaine and the number of dermatomes showing the displaced fracture of the caudal vertebral body of anaesthetised has also been shown (Kaneko and Iwama the first coccygeal vertebra with increased ventral displacement 1999). Administering smaller total volumes epidurally, when of the caudal fragment and tail. There has been further fracture of local anaesthetics are used, would therefore be expected to fi the mid body of the vertebral body of the rst coccygeal reduce the risk of subsequent ataxia. In Case 25b, however, vertebrae. There is sclerosis of the fracture line through the only 4 mL total volume was administered, lower than vertebral body and a smooth osseous fragment protruding recommended volumes (Grosenbaugh et al. 1999; Robinson ventrally and cranially from the ventral aspect of the fracture line. The ventrally displaced fracture fragment of the caudal body and and Natalini 2002; Doherty and Valverde 2006; Natalini and endplate is poorly defined and has become more lucent Driessen 2007; Skarda et al. 2009; Dugdale 2010; Michou and consistent with osseous resorption. The gas opacity in the soft Leece 2012), although these recommendations are for tissues adjacent to the fractured vertebra has resolved. mepivacaine alone. One additional factor contributing to the ataxia in the three horses described here may be the presenting complaint 2015). The majority of cases we report received only xylazine of melanomas. Increased cranial spread of epidural injections hydrochloride, diluted to a volume of 10 mL with 0.9% NaCl or has been suggested to occur in obese horses due to a sterile water for injection. LeBlanc et al. (1988) reported that narrowing of the epidural space (Robinson and Natalini 2002), 0.17 mg/kg bwt xylazine hydrochloride diluted to 10 mL with and presence of melanomas close to the spinal cord might 0.9% NaCl induced 2.5 h of local analgesia without side have a similar effect. Since discharge, however, neither Case effects. This dose has subsequently been repeatedly 10 nor 24 have developed neurological deficits suggestive of recommended (Robinson and Natalini 2002; Doherty and spinal cord pathology, and the deficits present at discharge Valverde 2006; Skarda et al. 2009; Dugdale 2010; Carpenter in Case 25b have not deteriorated. a and Byron 2015). There are suggestions that adrenergic 2 If signs of ataxia or hindlimb weakness are noted following agonists alone produce patchy and variable results (Robinson epidural anaesthesia, support on the tail, by means of a tied and Natalini 2002) and that the addition of local anaesthetic rope has been recommended (Robinson and Natalini 2002; provides more reliability. The recommended doses of local Natalini and Driessen 2007; Skarda et al. 2009). However, anaesthetic vary, however, as shown in Table 2. While our securing the tail in this way, without the availability for cases do not support the necessity in most horses for addition immediate release, can result in severe morbidity as fi of local anaesthetic to provide suf cient local anaesthesia for described in Case 25b. Different variations in the design and tail and perineal surgery, lidocaine has been shown to use of rope assistance have been reported (Kastner€ 2010), provide a faster onset of block compared with xylazine with no clear consensus as to the best method. One report of hydrochloride (Fikes et al. 1989; Grubb et al. 1992). almost 18,000 horses (Bidwell et al. 2007), where rope The three horses (Cases 10, 24 and 25b) which developed assistance was used for the majority of cases, reported a limb ataxia all received a combination of xylazine hydrochloride fracture rate of 0.04% (8 horses), lower than the 0.2% (84 of and mepivacaine via epidural injection, whereas none of the 41,824 horses) reported by the CEPEF study (Johnston et al. horses that received xylazine hydrochloride alone developed 2002). The link between rope recovery and this improved fi signi cant ataxia. Based on the approximated weights of fracture rate is not proven, however, and many other factors, these horses, the doses equated to 0.22 mg/kg bwt xylazine such as length of surgery, may contribute to the difference. A + hydrochloride 0.11 mg/kg bwt mepivacaine, 0.2 mg/kg bwt comparison of 200 horses undergoing emergency abdominal + xylazine hydrochloride 0.14 mg/kg bwt mepivacaine and surgery (Ruegg€ et al. 2016), half of which were recovered + 0.2 mg/kg bwt xylazine hydrochloride 0.08 mg/kg bwt with head and tail ropes, found no reduction in fatalities or mepivacaine respectively. These doses of mepivacaine are improvement in recovery scores with the use of ropes. lower than those recommended in the literature (Table 2). Evidence for the unequivocal benefit of rope recovery is Four other horses received xylazine hydrochloride and currently lacking (Dugdale and Taylor 2016), with an almost mepivacaine combinations, however, and did not show any 50:50 split in the use of rope recovery or free recovery as signs of ataxia (Cases 4, 9a, 12b and 20). Case 19 received standard procedure by diplomates of the American and

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TABLE 2: Recommended doses for epidural administration of mepivacaine, lidocaine and a combination of lidocaine and xylazine hydrochloride

Epidural drug(s)

Lidocaine + Xylazine Reference Mepivacaine Lidocaine hydrochloride

Grosenbaugh et al. (1999) 0.14–0.25 mg/kg bwt 0.16–0.45 mg/kg bwt 0.22 mg/kg bwt lidocaine + 0.17 mg/kg bwt xylazine hydrochloride Robinson and Natalini (2002) For a 450 kg horse 5–7mL For a 450 kg horse 5–8mL2% 0.22 mg/kg bwt 2% (0.22–0.31 mg/kg bwt) (0.22–0.35 mg/kg bwt) lidocaine + 0.17 mg/kg bwt xylazine hydrochloride Doherty and Valverde (2006) 1–1.25 mL/100 kg bwt 2% 1–1.25 mL/100 kg bwt 2% (0.2–0.25 mg/kg bwt) (0.2–0.25 mg/kg bwt) Can increase volume with 0.9% Can increase volume with 0.9% NaCl but not more than 10 mL NaCl but not more than 10 mL in a 500 kg horse in a 500 kg horse Natalini and Driessen (2007) 5–8mL2% 5–8mLof1–2% 5–8 mL total of lidocaine 2% + xylazine hydrochloride 0.17 mg/ kg bwt Skarda et al. (2009) For a 450 kg horse 5–7mL2% For a 450 kg horse 6–8mL2% (0.22–0.31 mg/kg bwt) (0.26–0.35 mg/kg bwt) Dugdale (2010) For a 500 kg horse 5 mL 2% For a 500 kg horse 5–10 mL 2% (0.2 mg/kg bwt) (0.2–0.4 mg/kg bwt) Michou and Leece (2012) 1–1.5 mL/100 kg bwt 2% 1–1. 5 mL/100 kg bwt 2% 0.14 mg/kg bwt (0.2–0.3 mg/kg bwt) (0.2–0.3 mg/kg bwt) lidocaine + 0.17 mg/kg bwt xylazine hydrochloride Carpenter and Byron (2015) For a 450 kg horse 6–8mL2% (0.26–0.35 mg/kg bwt)

European colleges of veterinary anaesthesia (Kastner€ 2010). It beneficial, but again, the concern that excitation might is unclear in Case 25b whether the complications would have increase the risk of falling prevented its use. been reduced if the horse had been allowed to recover In conclusion, a2 agonists and local anaesthetics without assistance, or with a manually controlled tail rope administered epidurally in conscious horses have the potential without a locking mechanism. The presence of the head to cause hindlimb ataxia, postural instability and recumbency collar during recovery may have contributed to the (LeBlanc et al. 1988; Chopin and Wright 1995; Wittern et al. subsequent facial paralysis, although whether the head 1998), and veterinarians should be prepared to deal with these collar, or direct trauma from falling was the cause of the untoward effects should they arise (such as facilities to induce, nerve damage is uncertain. Rope recovery is only used by maintain and recover from general anaesthesia). While rope the clinic reporting these cases for ‘high-risk’ cases. Greater assistance can provide support to ataxic horses, care should familiarity with the equipment and experience with the set up be taken when using this technique in horses which have may have reduced the likelihood of the complications hindlimb weakness post epidural. The three horses in this series reported, although complications have been reported by that developed severe ataxia all received epidural injections clinics using rope recovery as standard (Bidwell et al. 2007). of a combination of xylazine hydrochloride and mepivacaine; Administration of i.v. yohimbine (0.05 mg/kg bwt) to mares in view of the small number of cases it is impossible to ascertain following epidural detomidine hydrochloride reversed many of whether this combination of drugs increases the risk of ataxia the side effects of the epidural, including perineal analgesia compared to either drug alone. and changes in pelvic limb position (Skarda and Muir 1999). Yohimbine administration to horses with ataxia following Authors declaration of interests epidural administration of a combination drugs including an adrenergic a2 agonist may therefore be beneficial, by No conflicts of interest have been declared. reversing any synergistic action that the a2 agonist has on the local anaesthetic action. It should be noted, however, that Ethical animal research yohimbine has been associated with excitation in horses (Zeiler 2015). This concern prevented its use in Cases 10 and 25b, as it Not applicable. was felt that complications associated with attempts to stand may have increased if excitation did occur, but hindlimb Source of funding weakness was not fully reversed due to continued action of the mepivacaine. Administration to Case 24 may have been None.

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Acknowledgements Hendrickson, D.A., Southwood, L.L., Lopez, M.J., Johnson, R. and Kruse- Elliott, K.T. (1998) Cranial migration of different volumes of new- The authors wish to thank the staff at Bell Equine Veterinary methylene blue after caudal epidural injection in the horse. Equine Clinic for their help with the care of the horses described in Pract. 20, 12-14. this report. Hubbell, J.A.E. (1999) Recovery from anaesthesia in horses. Equine Vet. Educ. 11, 160-167. Johnston, G.M., Eastment, J.K., Wood, J.L.N. and Taylor, P.M. (2002) Authorship The confidential enquiry into perioperative equine fatalities (CEPEF): mortality results of Phases 1 and 2. Vet Anaesth. Analg. All three cases outlined in detail were managed by T. Mair 29, 159-170. and/or C. Sherlock. These authors contributed to the Kaneko, T. and Iwama, H. (1999) The association between injected information detailed in the report regarding these cases. S. volume of local anesthetic and spread of epidural anesthesia: a Morley assisted with the care of Case 25b and contributed to hypothesis. Reg. Anesth. Pain Med. 24, 153-157. the details of the management of this case. A. Bird prepared Kastner,€ S.B.R. (2010) How to manage recovery from anaesthesia in the case series, with editorial input from all authors. All authors the horse – to assist or not to assist? Pferdeheilkunde 26, 1-5. approved the final manuscript. Knowles, E.J., Tremaine, W.H., Pearson, G.R. and Mair, T.S. (2015) A database survey of equine tumours in the United Kingdom. Equine Vet. J. 48, 280-284. Manufacturers' addresses LeBlanc, P.H., Caron, J.P., Patterson, J.S., Brown, M. and Matta, M.A. 1Boehringer Ingelheim Ltd, Bracknell, Berkshire, UK. (1988) Epidural injection of xylazine for perineal analgesia in horses. 2Vetoquinol UK Ltd, Buckingham, Buckinghamshire, UK. J. Am. Vet. Med. Assoc. 193, 1405-1408. 3 Zoetis UK Ltd, London, UK. Mayhew, I.G., deLahunta, A., Whitlock, R.H., Krook, L. and Tasker, J.B. 4 Dechra Ltd, Skipton, North Yorkshire, UK. (1978)Spinalcorddiseaseinthehorse. Cornell.Vet.68,Suppl.6,1-207. 5Becton Dickinson Ltd, Oxford, UK. 6Chanelle Animal Health Ltd, Liverpool, UK. Michou, J. and Leece, E. (2012) Sedation and analgesia in the 7Hameln Pharmaceuticals Ltd, Gloucester, Gloucestershire, UK. standing horse 2. Local anaesthesia and analgesia techniques. In 8Grosstier-Rettungsdienst CH/FL, Embrach, Switzerland. Pract. 34, 578-587. 9Norbrook Laboratories Ltd, Corby, Northamptonshire, UK. Moore, J.S., Shaw, C., Buechner-Maxwell, V., Scarratt, W.K., Crisman, 10Petzl, Crooes, France. M., Furr, M. and Robertson, J. (2013) Melanoma in horses: current perspectives. Equine Vet. Educ. 25, 144-151. Natalini, C.C. and Driessen, B. (2007) Epidural and spinal anesthesia References and analgesia in the equine. Clin. Tech. Equine Pract. 6, 145-153. Bidwell, L.A., Bramlage, L.R. and Rood, W.A. (2007) Equine Pilsworth, R. and Knottenbelt, D. (Eds) (2006) Melanoma. In: Common perioperative fatalities associated with general anaesthesia at a Equine Skin Diseases, Equine Veterinary Journal Ltd., Suffolk. pp private practice – a retrospective case series. Vet Anaesth. Analg. 42-44. 34, 23-30. Robinson, E.P. and Natalini, C.C. (2002) Epidural anesthesia and Carpenter, R.E. and Byron, C.R. (2015) Equine local anesthetic and analgesia in horses. Vet. Clin. North Am. Equine Pract. 18, 61-82. analgesic techniques. In: Veterinary Anesthesia and Analgesia, 5th Rowe, E.L. and Sullins, K.E. (2004) Excision as treatment of dermal edn., Eds: K.A. Grimm, John Wiley and Sons, Iowa. pp 886-911. melanomatosis in horses: 11 cases (1994-2000). J. Am. Vet. Med. Chopin, J.B. and Wright, J.D. (1995) Complication after the use of a Assoc. 225, 94-96. combination of lignocaine and xylazine for epidural anaesthesia in Ruegg,€ M., Bettschart-Wolfensberger, R., Hartnack, S., Junge, H.K., a mare. Aust. Vet. J. 72, 354-355. Theiss, F. and Ringer, S.K. (2016) Comparison of non-assisted versus Cotchin, E. (1977) A general survey of tumours in the horse. Equine head and tail rope-assisted recovery after emergency abdominal Vet. J. 9, 16-21. surgery in horses. Pferdeheilkunde 32, 469-478. Doherty, T. and Valverde, A. (Eds) (2006) Epidural analgesia and Skarda, R.T. and Muir, W.W. (1999) Effects of intravenously anaesthesia. In: Manual of Equine Anesthesia and Analgesia, administered yohimbine on antinociceptive, cardiorespiratory, and Blackwell Publishing, Oxford. pp 275-281. postural changes induced by epidural administration of Dugdale, A. (Ed) (2010) Local anaesthetic techniques: horses. In: detomidine hydrochloride solution to healthy mares. Am. J. Vet. Veterinary Anaesthesia Principles to Practice, Blackwell Publishing, Res. 60, 1262-1270. Oxford. pp 135-140. Skarda, R.T., Muir, W.W. and Hubbell, J.A.E. (2009) Local anesthetic Dugdale, A.H. and Taylor, P.M. (2016) Equine anaesthesia-associated drugs and techniques. In: Equine Anaesthesia Monitoring and mortality: Where are we now? Vet. Anaesth. Analg. 43, 242-255. Emergency Therapy, 2nd edn. Eds: W.W. Muir and J.A.E. Hubbell, Saunders Elsevier, Missouri. pp 210-242. Dugdale, A.H., Obhrai, J. and Cripps, P.J. (2016) Twenty years later: a single-centre, repeat retrospective analysis of equine perioperative Wittern, C., Hendrickson, D.A., Trumble, T. and Wagner, A. (1998) mortality and investigation of recovery quality. Vet. Anaesth. Complications associated with administration of detomidine into Analg. 43, 171-178. the caudal epidural space in a horse. J. Am. Vet. Med. Assoc. 213, 516-518. Fikes, L.W., Lin, H.C. and Thurmon, H.C. (1989) A preliminary comparison of lidocaine and xylazine as epidural analgesics in Zeiler, G.E. (2015) A review of clinical approaches to antagonism of ponies. Vet. Surg. 18, 85-86. alpha2-adrenoreceptor agonists in the horse. Equine Vet. Educ. 27, 48-54. Foy, J.M., Rashmir-Raven, A.M. and Brashier, M.K. (2002) Common equine skin tumors. Compend. Contin. Educ. Pract. Vet. 24, 242-254. Groom, L. and Sullins, K. (2018) Surgical excision of large melanocytic Supporting information tumours in grey horses: 38 cases (2001–2013), Equine Vet. Educ. Epub ahead of print. 30, 438-443. Additional Supporting Information may be found in the online ’ Grosenbaugh, D.A., Skarda, R.T. and Muir, W.W. (1999) Caudal version of this article at the publisher s website: regional anaesthesia in horses. Equine Vet. Educ. 11, 98-105. Supplementary Item 1: Case 25b. Tachypnoea following Grubb, T.L., Riebold, D.W. and Huber, M.J. (1992) Comparison of recovery from anaesthesia. Paroxysmal movement of the lidocaine, xylazine, and xylazine/lidocaine for caudal epidural analgesia in horses. J. Am. Vet. Med. Assoc. 201, 1187-1190. right hemithorax associated with fractured ribs.

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Case Report Two cases of hepatopathy and hyperferraemia managed with deferoxamine and phlebotomy L. Gummery* , P. E. J. Johnston, D. G. M. Sutton and A. G. Raftery Weipers Centre Equine Hospital, School of Veterinary Medicine, University of Glasgow, Glasgow, UK *Corresponding author email: [email protected]

Keywords: horse; iron; deferoxamine; phlebotomy; hepatic; environmental

Summary indication of hepatic failure. Environmental testing of shared The following case report documents the investigation and pasture revealed high levels of iron in groundwater. progression of two cases of hepatic failure and Treatment with phlebotomy and a chelation agent hyperferraemia in Shetland ponies in Scotland exposed to (deferoxamine) was instigated in an attempt to reduce total high environmental levels of iron in groundwater, and to the body iron and associated haemosiderosis. These cases authors’ knowledge describes the first use of deferoxamine in highlight the potential importance of iron in hepatic adult ponies. The importance of consideration of serum iron pathology, indicating a requirement for further research to levels in cases of equine hepatic disease is highlighted and it identify whether hyperferraemia is inciting or exacerbating is suggested that reduction in serum iron by phlebotomy or hepatic disease in horses, or whether accumulation is simply treatment with deferoxamine may be beneficial in cases a secondary marker of hepatic dysfunction. displaying hyperferraemia. Case 1 Introduction Case history Liver disease in horses is relatively common with ponies being A 6-year-old Shetland pony gelding was referred to the at greater risk of severe types of disease than large riding Weipers Centre Equine Hospital for investigation and horses (Smith et al. 2003). Despite the evolution of more treatment of inappetance and lethargy of 7 days’ duration. sensitive diagnostic techniques such as liver biopsy the The pony had been in the owner’s possession for 2 years and primary aetiological agent remains unspecified in many was cograzed on several small areas of pasture with one cases of equine hepatopathy (Smith et al. 2003). Recent other pony. Prior to referral the pony had been investigated publications have focused on identification of novel for signs of respiratory disease (mucopurulent bilateral nasal pathogens such as equine hepacivirus (Lyons et al. 2012; discharge and pyrexia) of 1 month’s duration. Respiratory Pfaender et al. 2015). signs had resolved following treatment with doxycycline and The association between hyperferraemia and equine suxibuzone, however, 1 week prior to referral the pony had hepatopathy has been explored. Although most reports are become inappetent. associated with acute overload (post-transfusion in neonatal isoerythrolysis or excessive oral supplementation [Edens et al. Clinical findings 1993; Elfenbein et al. 2010]), one case series from the On presentation the pony was dull with a low head carriage, Netherlands implicates chronic iron intoxication due to high and was in good body condition (2.5/5 [Carroll and groundwater iron levels as a cause of hepatopathy in 11 Huntington 1988]; 138 kg). The pony was tachycardic (60 horses (Theelen et al. 2015). beats/min) and tachypnoeic (24 breaths/min), but Hepatic iron accumulation in people is reported to be normothermic (37.1°C). Mucous membranes were congested due to genetic causes (haemochromatosis, thallasaemia) or with a prolonged capillary refill time (4 s). Distal extremities toxic, metabolic or viral hepatic disease (Franchini et al. 2008; were cool to palpate. Borborygmi were reduced and the Abu Rajab et al. 2014). Iron depletion therapy in humans with abdomen was mildly distended. Abdominal ultrasonography hereditary haemochromatosis is reported to result in a identified fluid ingesta in the right ventral colon and caecum. decreased risk of hepatocellular carcinoma and cirrhosis The liver was heterogeneous in appearance. Evaluation of (Beaton and Adams 2006; Kanwar and Kowdley 2013). In the respiratory system (ultrasound, endoscopy and tracheal horses data to support the specific role of iron in hepatic wash cytology) confirmed resolution of the previous disease are limited although haemosiderin accumulation is respiratory infection. noted in advanced liver disease and carries a poor prognosis for survival (Dunkel et al. 2015). Clinical pathology In this report, two unrelated cograzing Shetland ponies A complete blood count revealed haemoconcentration with no history of iron supplementation exhibited signs of (PCV 48%) and a regenerative neutrophilia with evidence of hepatic failure. Extensive hepatic fibrosis and marked mild toxic change (Table 1). Significant findings on serum haemosiderosis were found in the most severe case; biochemistry were markedly increased hepatobiliary enzymes concurrent hyperferraemia was detected in both ponies. A and bile acids (55.8 lmol/L, rr <15 lmol/L) consistent with marked elevation in serum iron also was detected in a mule hepatic failure. The pony was also markedly hyperlipaemic cohabiting with the ponies with no clinical or biochemical (triglycerides 18.76 mmol/L, rr <0.8 mmol/L) and azotaemic

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TABLE 1: Haematological and biochemical parameters in Case 1 over the period of treatment. (*denotes first treatment with phlebotomy)

Day (0 = presentation)

Variable Ref. range 023579* 14 22 63

Bile acids (lmol/L) <15.0 55.8 46.6 23.8 20.5 22.4 14.7 7.2 5.4 Triglycerides (mmol/L) <0.8 18.8 3.5 n/a 2.1 1.7 n/a 2.6 0.4 0.3 Alk phos (U/L) <280 2398 2530 n/a 3410 1979 n/a 998 588 173 AST (U/L) <240 1010 1073 1012 807 612 516 367 240 243 GGT (U/L) <40 1094 1441 1713 1798 1350 1022 730 444 125 Total protein (g/L) 60–83 86 69 66 73 66 72 69 70 71 Albumin (g/L) 26–35 30 26 21 30 29 29 32 32 33 Globulin (g/L) 30–55 56 43 45 43 37 43 37 38 38 Haematocrit (%) 32–53 48.6 42.2 36.8 42.1 35.7 31.5 20.9 24.8 34 RBC (91012/L) 6.8–12.9 9.7 8.9 7.5 8.8 7.4 6.5 4.2 4.9 6.8 Hb (g/dL) 11.0–19.0 16.6 15.5 13.8 15 12.7 11.3 8.2 8.7 12.3 MCH (pg) 12.3–19.7 17.2 17.3 18.5 17.1 17.2 17.4 19.4 17.6 18.0 WBC (9109/L) 5.4–14.3 10.5 12.0 9.3 18.0 17.8 16.3 12.6 12.2 7.3 Neutrophils (9109/L) 2.7–6.8 8.3 9.9 7.4 15.1 15.7 13.7 10.4 9.6 3.3 Lymphocytes (9109/L) 1.5–5.5 1.7 1.4 1.7 2.0 1.4 2.3 1.9 2.1 3.3

(urea 13.0 mmol/L, rr 6.8 mmol/L, creatinine 386 lmol/L, rr and biochemistry were re-evaluated. A mild leucopenia was 62–140 lmol/L). Blood ammonia was within the normal detected and serum biochemistry revealed elevated hepatic reference range (17 mmol/L, rr <90 mmol/L). enzymes (Table 2) with moderately increased bile acid concentration (23 lmol/L, rr <15 lmol/L). The mare was treated Initial stabilisation supportively with silibinin (milk thistle, 10 g q. 8 h) and Vitamin E A catheter was placed aseptically into the left jugular vein. (Nano Eâ4, 1250 IU per os q. 12 then q. 24 h). Fluid resuscitation was initiated with 20 mL/kg of isotonic fluids 1 (Vetivex No 11) administered as a bolus. Continued rate was Further investigations guided by sequential clinical re-assessment including PCV/TP. The fluids were supplemented with glucose (2.5%)1 and insulin In an attempt to identify common risk factors for hepatic was administered (initial dose 0.1 IU/kg i.m. q. 8 h, then failure in the two animals, further investigations were titrated to effect) to address the hyperlipaemia. commenced. As the pony was inappetent, enteral feeding via a nasogastric tube (fibre gruel administered q. 4 h) was Clinicopathological testing introduced to correct the negative energy balance. This was A faecal sample was submitted from Case 1 for a modified discontinued after 3 days as even transient presence of the fluke egg sedimentation test and was negative for fluke eggs nasogastric tube was causing the pony to aspirate saliva. As (Antonia et al. 2002). Serum iron levels (Day 7 after inappetence persisted despite regular tempting with a range presentation) were found to be significantly elevated in both of feeds, total parenteral nutrition (1 L 50% glucose [Steriflexâ]; animals, with a transferrin saturation of 71.4% in Case 1 (rr 1 L 20% lipid [Intralipidâ]; 1 L amino acid solution [Aminovenâ <40%), 98.8% in Case 2 and markedly increased total serum 25] in combination)2 was commenced and continued for iron levels of 61.4 lmol/L (rr 18–35 lmol/L) and 100.8 lmol/L, 6 days until serum triglycerides normalised and the pony’s respectively (Table 3, Fig 1). appetite started to improve. During hospitalisation the pony Abdominal ultrasound and ultrasound-guided liver biopsy also received supportive therapy in the form of lactulose3 were performed on Case 2. A small hepatic window on the (0.65 mg/kg bwt per os q. 12 h) to reduce the risk of right side of the abdomen suggested reduced total liver size. hyperammonaemia and silibinin (milk thistle, 10 g q. 8 h) and Samples were obtained from the left and right sides using a Vitamin E (Nano Eâ)4 (1250 IU per os q. 12 then q. 24 h) to biopsy needle (Temno EvolutionTM Biopsy Device)7. ameliorate ongoing liver damage. Sucralfate (Sucrabestâ)5 Histopathology revealed marked hepatocellular (20 mg/kg bwt per os q. 8 h) and omeprazole (Gastrogardâ)6 degeneration with bridging and internodular fibrosis, biliary (4 mg/kg bwt per os q. 24 h) were administered whilst hyperplasia and iron accumulation (haemosiderosis) in inappetent to reduce the risk of gastric ulceration. macrophages and almost all hepatocytes (Fig 2) with a cumulative score of 10/14 (Durham et al. 2003). Liver biopsy Case 2 was not performed initially on Case 1 due to concern regarding the risk of hepatic lipidosis and subsequent capsule Clinical findings rupture. The 17-year-old Shetland pony mare companion (Case 2) was in good body condition (BCS 3/5) with regional adiposity and a Cograzing equines (CG 1 and 2) history of laminitis consistent with an equine metabolic Clinical examination and serum biochemistry and iron syndrome (EMS) phenotype. General clinical examination was measurements were performed on the two remaining animals otherwise unremarkable, however, the mare had historical grazed on the same property, a 7-year-old Cob gelding (CG 1), records of raised hepatic enzymes and therefore haematology recently introduced to the farm, and a 42-year-old female

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TABLE 2: Haematological and biochemical parameters in Case 2 instigated in both ponies to attempt to reduce total body over the period of treatment iron levels. Therapeutic phlebotomy was carried out on the ponies Day compared with presentation (Day 9; 8% of calculated blood volume). Packed cell volume (Day 0 = presentation) Reference remained low (22% in both animals) 1 week following Variable range 319 2 5 22 63 therapy, but was increasing on subsequent samples (25% 2 weeks following therapy). Phlebotomy was repeated once Bile acids 15 23 33.9 41.9 47 in Case 1 (after which values normalised) and four further (lmol/L) times in Case 2 over the following 4 months due to Alk phos (U/L) 280 312 509 276 291 AST (U/L) 240 376 509 459 536 481 persistently elevated serum iron levels. The mule (CG 2) was GGT (U/L) 40 129 647 560 673 482 not treated due to apparent lack of hepatic involvement or Total 60–83 81 83 80 86 86 clinical or biochemical abnormalities associated with protein (g/L) hyperferraemia. Treatment with an iron chelating agent Albumin (g/L) 26–35 31 31 31 31 28 (deferoxamine; Desferalâ)8 (20 mg/kg s.q. q. 12 h as a Globulin (g/L) 30–55 50 52 49 55 58 100 mg/mL solution) was commenced in Cases 1 and 2 9 WBC (910 /L) 5.4–14.3 5.1 4.3 4.0 6.6 4.4 1 week after phlebotomy, and continued for 2 weeks. – Neutrophils 2.7 6.4 2.6 1.8 1.2 3.0 1.9 Phlebotomy was not repeated during the treatment period. (9109/L) The sites of injection were varied; some transient mild Lymphocytes 1.5–5.5 2.3 2.2 2.4 3.1 2.4 oedema and localised sensitivity at the sites of injection were (9109/L) noted (the owner described increased urine production), otherwise no adverse effects were recognised. mule (CG 2), which had spent over 30 years grazing on the property. Clinical and biochemistry profiles were unremarkable in both cases, except the serum iron levels and transferrin Case progression saturation were increased in the mule (Table 3), with no Case 1 demonstrated clinical and clinicopathological concurrent evidence of liver disease. improvement with normalisation of bile acids (7.2 lmol/L, rr 0–15 lmol/L) and marked improvement in serum iron levels Environmental testing (Tables 1 and 3). Liver biopsy was carried out 8 weeks after Testing of the mains, trough and ground water iron levels, and admission, after resolution of hyperlipaemia, in order to fi the soil and forage iron content was carried out. This identi ed provide the owner with prognostic information. increased groundwater iron (10 mg/L, recommended range in Histopathology identified marked cloudy swelling and water 0.5 mg/L (M.J.P. Theelen 2016, personal communication) cytoplasmic granularity consistent with reversible toxic to 3 mg/L (WHO 2003). Soil and forage iron levels were hepatopathy, occasional individual hepatic necrosis, mild to acceptable (NRC 2007). Soil pH was recorded as 5.4 and 5.3 moderate portal fibrosis with occasional intralobular fibrosis fi from the eld and grazing near the house (Fig 3C). Evaluation of and mild accumulation of haemosiderin in peri-portal the pasture did not identify any poisonous plants (e.g. genera macrophages (liver score 2/14 [Durham et al. 2003]). Senecio containing pyrrolizidine alkaloids) on the property. Sequential sampling from Case 2 in contrast showed increasing bile acids and hepatic enzymes (Table 2)and Further targeted treatment increasing serum iron levels (Fig 1) although the mare remained clinically stable. Both ponies were prevented from grazing area Corticosteroids were contraindicated in both ponies due to C where high levels of groundwater iron had been identified. historical laminitis. Given the increased serum iron levels Repeat serum samples 8 weeks after admission indicated serum present in both animals and the degree of haemosiderosis iron levels were comparable (Table 3), and repeat liver in biopsy samples (Case 2) targeted treatment was histopathology was similar with a liver score of 11/14 (Durham et al. 2003). The case was re-examined and remains clinically 50 ^ 140 stable 12 months after admission. 45 120 40 Diagnoses Case 1: Histopathological findings and response to treatment

100 iron (μmol/L)

35 Total serum consistent with reversible acute hepatopathy (suspected 30 80 hepatic lipidosis secondary to marked hyperlipaemia), with 25 concurrent or secondary hyperferraemia. 60

(μmol/L) 20 fi

Bile acids Case 2: Histopathological ndings consistent with a severe 15 40 chronic hepatopathy of unknown aetiology with concurrent Bile acids case 2 10 iron accumulation and toxicity of either primary or secondary 20 Total iron case 2 5 Total iron case 1 origin. 0 0 Bile acids case 1 CG 2: Hyperferraemia with no concurrent evidence of 9* 19 29 39 hepatic disease. Days Fig 1: Line graph documenting progression of bile acids (rr Discussion <15 lmol/L and total iron (rr 18–35 lmol/L in Case 1 and Case 2 over the initial treatment period. * denotes first treatment with In this report, serum iron concentrations were significantly phlebotomy; ^ denotes period of treatment with deferoxamine. elevated in three of four unrelated animals grazed on the

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a) c)

400 μm 40 μm

b) d)

400 μm 100 μm Fig 2: Hepatopathy, liver, pony. a) Marked bridging fibrosis and fine intranodular fibrosis. Masson’s Trichrome. b) Haemosiderin accumulation within the hepatocellular nodule and within the strands of fibrous connective tissue. Perl’s Prussian blue. c) Fine intranodular fibrosis, often isolating individual hepatocytes, haemosiderin granules visible within hepatocytes. Masson’s Trichrome. d) Haemosiderin accumulation within most hepatocytes and high numbers of periportal haemosiderophages. Perl’s Prussian Blue. same property. Environmental testing identified increased regulated by feedback mechanisms and so leads to hepatic groundwater iron and an acidic soil pH which may promote accumulation (Wheby and Jones 1963; Craven et al. 1987; iron uptake by pasture (Fageria and Baliger 2003). There is no Chua et al. 2003; Cheng et al. 2012). NTBI can catalyse the physiological mechanism in mammals for the excretion of formation of oxyradicals (‘Fenton reaction’) which cause lipid iron (Kohgo et al. 2008), and in the absence of other obvious peroxidation and impairment of the membrane dependent sources of iron, it is hypothesised that grazing these areas functions of mitochondria and lysosomes, resulting in DNA over a period of time could predispose to iron accumulation. damage (Britton et al. 2002; Brissot et al. 2012). Since ferritin, The contribution of iron to hepatic failure in the two cases transferrin and hepcidin are all metabolised by the liver, described is difficult to quantify. Gastrointestinal iron determination of the precise interaction between liver absorption is regulated by hepcidin (Nemeth and Ganz dysfunction and iron overload is complicated (Zhao et al. 2009), a hormone synthesised by the liver, and excessive iron 2013; Milic et al. 2016). Regardless of this interaction, absorption may occur if hepcidin production is reduced, as is monitoring and regulating serum iron levels may be beneficial known to occur in chronic liver disease. The majority of iron in in horses with hepatopathy. Quantification of hepcidin mammals (approximately 80%) is bound to heme in concentrations may further clarify pathophysiology of disease erythrocytes, and the remaining variable portion mainly to (Girelli et al. 2016). transferrin in blood or ferritin or haemosiderin intracellularly In humans an association has been reported between (Kohgo et al. 2008). Iron accumulation results in high obesity or metabolic syndrome and altered iron homeostasis, transferrin saturation and unbound plasma iron (also although a causal link has not been confirmed (Rajpathak described as non-transferrin bound iron [NTBI]). Rodent et al. 2009; Cheng et al. 2012; Datz et al. 2013). Whilst both models suggest that if transferrin capacity is overwhelmed Shetland ponies had a phenotypical diagnosis of EMS the liver, rather than erythrocytes will take up NTBI in (Morgan et al. 2015) the temporal correlation of serum iron preference to transferrin bound iron; this process is not with hepatic parameters without a change in body condition

TABLE 3: Serum iron levels in Cases 1 and 2 and cograzing animals. Reference ranges provided by laboratory (APHA, Shrewsbury, UK), corroborated by breed specific published reference (Osbaldiston and Griffith 1972)

Case Ref. range Case 1 Case 2 CG 1 CG 2

Day from admission 7 22 63 7 22 63 Fe total (lmol/L) 18–35 61.4 42.6 40.8 100.8 115.3 116 35.1 56.9 Fe TIBC (lmol/L) 51–103 86 85.4 70.3 102 117.8 78.9 59.0 Transferrin saturation (%) <40 71.4 49.9 58 98.8 97.9 44.5 96.4 UIBC (lmol/L) 24.6 42.8 29.5 1.2 2.5 43.8 2.1

TIBC, total iron binding capacity; UIBC, unsaturated iron binding capacity; CG, Cograzer.

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within normal limits (Loreal et al. 2000), caution should be practiced in cases with concurrent coagulopathies or disseminated intra-vascular coagulation. In this case 8% of B the blood volume was taken (over 15% of blood volume is likely to require fluid replacement [Mudge 2014]), this was repeated as necessary following recovery of the PCV. Humans have a variable response to phlebotomy as ‘iron A recycling’ causes increases in unbound plasma iron. This may be the cause for the iron levels increasing in Case 2 post- phlebotomy (Loreal et al. 2000). Phlebotomy in Case 1 may have contributed to the rapid reduction in total serum iron and speed of recovery from liver failure. Longevity in Case 2 has exceeded expectations with the pony remaining clinically stable 12 months after admission (likelihood of 86% mortality at 6 months based on reported histopathological score of 10–11/14 [Durham et al. 2003]), although the BARN D histopathological score demonstrated no improvement on C repeat biopsy and bile acids have remained elevated. Deferoxamine inhibits cell iron uptake by binding to intra- and extra-cellular NTBI which is then excreted in bile or urine E (Britton et al. 2002; Chua et al. 2003). Treatment with Fig 3: Satellite view of farm with areas A–E used for grazing. deferoxamine has been reported to have other beneficial Elevation 107.1 m above sea level. Soil samples taken from areas effects in hepatopathy including attenuation of lipid most commonly grazed by Cases 1 and 2 (A and C), ground peroxidation and the reduction of hepatic stellate cell water taken from area C. activation and fibrogenesis (Britton et al. 2002; Mohammed et al. 2016). Treatment was used concurrently with phlebotomy in the two reported cases to reduce total iron score suggests it is an unlikely confounding factor in these stores and encourage mobilisation, and the relative cases. Viral hepatotrophic disease could not be excluded contribution of each to this process could not be (Pfaender et al. 2015); viral PCR was not commercially distinguished. The owner noted a significant increase in available and was not performed. urination whilst the ponies were treated with deferoxamine Although hyperferraemia was a common feature of the which may have resulted from increased urinary iron cases there were significant differences between the degree excretion (Elfenbein et al. 2010). Mild sensitivity and swelling of hepatic disease and response to treatment. Acute was noted at the sites of injection. No other significant side reversible histopathological changes (Case 1) were effects were documented. Both phlebotomy and associated with a positive response to treatment and deferoxamine may provide safe and useful adjunctive resolution of hepatic disease and hyperferraemia. Chronic treatment for equids with high serum iron levels and irreversible histopathological changes (Case 2) were suspected hepatic haemosiderosis. associated with persistent hyperferraemia and hepatopathy. This report describes the first use of deferoxamine The mule (CG 2) exhibited hyperferraemia with no alongside phlebotomy to treat iron accumulation in adult clinicopathological evidence of hepatic disease (although ponies and documents hyperferraemia and concurrent liver biopsy was not performed). These differences may be hepatic failure in equids in Scotland, highlighting the due to differences in body mass, concurrent disease potential importance of serum iron levels in hepatic disease. processes, the chronicity of hepatic disease or iron One subject (Case 1) from a property with excessive ground accumulation, the ongoing effect of hepatic fibrosis on water iron content exhibited a severe but acute iron absorption and homeostasis, or genetic differences in hepatopathy with concurrent hyperferraemia, both of which iron homeostasis. Genetic heterogeneity has been reported features proved reversible with intensive management, in transferrin in horses (Stratil et al. 1984). The unresolved phlebotomy and deferoxamine. In a cograzing individual with questions presented by these cases indicate the requirement chronic fibrosing hepatopathy, iron homeostasis and hepatic for further research in this area. parameters did not normalise, but prolongation of residual Irrespective of the primary contribution of iron to hepatic hepatic function may have resulted from attempted disease in these cases, hepatic accumulation of iron management of the hyperferraemia. A third cograzing (haemosiderosis of greater than 50% hepatocytes as seen in individual was found to be affected by elevation of plasma Case 2) has been described as an independent predictor of iron concentration, but did not have clinicopathological non-survival in liver disease (Durham et al. 2003; Dunkel et al. evidence of concurrent hepatopathy. This may reflect both 2015). Phlebotomy and chelation therapy have been duration of exposure to excessive environmental iron or reported to result in clinical improvement in people with individual variation in propensity to hepatic iron increased hepatic iron concentration (Britton et al. 2002; accumulation. The authors suggest that further investigation Dongiovanni et al. 2011). Phlebotomy represents a cost- of the inter-relationship between equine hepatopathy and effective method of decreasing total body iron. Phlebotomy iron homeostasis is required. As a starting point, consideration or venesection is often performed in people to reduce total should be given to assessment of iron plasma concentrations body iron, removing approximately 4% of blood volume and attempted medical management to normalise weekly until total body iron and transferrin saturation are hyperferraemia in cases of equine hepatopathy.

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Authors’ declaration of interests Cheng, H.L., Bryant, C., Cook, R., O’Connor, H., Rooney, K. and Steinbeck, K. (2012) The relationship between obesity and No conflicts of interests have been declared. hypoferraemia in adults: a systematic review. Obes. Rev. 13, 150-161. Chua, A.C.G., Ingram, H.A., Raymond, K.N. and Baker, E. (2003) Multidentate pyridinones inhibit the metabolism of nontransferrin- Ethical animal research bound iron by hepatocytes and hepatoma cells. Eur. J. Biochem. 270, 1689-1698. Informed consent obtained from owner. Craven, C.M., Alexander, J., Eldridge, M., Kushner, J.P., Bernstein, S. and Kaplan, J. (1987) Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: a Source of funding rodent model for hemochromatosis. Proc. Natl Acad. Sci. USA 84, 3457-3461. None. Datz, C., Felder, T.K., Niederseer, D. and Aigner, E. (2013) Iron homeostasis in the Metabolic Syndrome. Eur. J. Clin. Invest. 43, 215-224. Acknowledgements Dongiovanni, P., Fracanzani, A.L., Fargion, S. and Valenti, L. (2011) Iron in fatty liver and in the metabolic syndrome: a promising Full informed client consent was received for the use of this therapeutic target. J. Hepatol. 55, 920-932. material in the publication. The authors gratefully Dunkel, B., Jones, S.A., Pinilla, M.J. and Foote, A.K. (2015) Serum bile acknowledge the owners of the animals for their full co- acid concentrations, histopathological features, and short-, and operation during investigation and treatment as well as Sarah long-term survival in horses with hepatic disease. J. Vet. Intern. Voss, Dr. Hayley Haining, Ronnie Barron and Jennifer Hollyer Med. 29, 644-650. for their involvement in these cases. Durham, A.E., Smith, K.C., Newton, J.R., Hillyer, M.H., Hillyer, L.L., Smith, Testing Laboratories: VDS, University of Glasgow. M.R.W. and Marr, C.M. 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Ledbetter, E.C. (2019) Clinical diagnosis and management of atypical Seruca, C. and Lowe, R. (2016) Equine ophthalmic examination: infectious keratitis in the horse. Equine Vet. Educ. 31, 31-313. routine diagnostic techniques. Equine Vet. Educ. 28, 455-469. Malalana, F. (2018) Does leptospirosis cause uveitis in the UK? Equine Simoens, P., Muylle, S. and Lauwers, H. (1996) Anatomy of the ocular Vet. Educ. 30, 139-140. arteries in the horse. Equine Vet. J. 28, 360-367. Martins, B.C. and Brooks, D.E. (2012) Subconjunctival drug Thomasy, S.M. and Lassaline, M. (2015) Equine glaucoma: where are administration in horses. Equine Vet. Educ. 24, 493-495. we now? Equine Vet. Educ. 27, 420-429. Matthews, A.G. (2016) Eye examination as part of the equine Townsend, W.M. (2016) Cataracts: clinical presentations, diagnosis prepurchase examination. Equine Vet. Educ. 28, 566-591. and management. Equine Vet. Educ. 28, 705-711. Montgomery, K.W. (2014) Equine ocular neoplasia: a review. Equine Utter, M.E., Wotman, K.L., Armour, M. and Bagel, J. (2010) Clinical Vet. Educ. 26, 372-380. findings and outcomes of ulcerative keratomycosis in 30 horses in Ollivier, F.J., Sanchez, R.F. and Monclin, S.J. (2009) Equine glaucomas: the mid-Atlantic United States (2006-2007). Equine Vet. Educ. 22, 31-39. a review. Equine Vet. Educ. 21, 232-235. Pucket, J.D. (2017) Equine orbital disease: a review. Equine Vet. Educ. 29, 452-458.

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Case Report Transmaxillary anchored silicon embedded gauze plug in the post-operative treatment of a large oromaxillary fistula caused by a supernumerary cheek tooth A. T. Hevesi†* , D. Uto†, N. Takacs†, V. Lorincz‡ and H. Simhofer‡ †Hungarian Equine Rehabilitation and Health Service Ltd., Kaposvar, Hungary; and ‡Equine University Clinic, University of Veterinary Medicine Vienna, Vienna, Austria *Corresponding author email: [email protected]

Keywords: horse; equine dentistry; oromaxillary fistula; silicon plugging; supernumerary cheek tooth

Summary This case report describes the successful treatment of a A 9-year-old Hungarian sport horse gelding was presented to horse with two large oromaxillary fistulae, caused by the clinic in poor condition displaying malodorous bilateral supernumerary cheek teeth diastemata, treated with an purulent nasal discharge. Oral examination revealed the anchored silicon plug following cheek teeth extractions presence of supernumerary 111 and 211. Bilateral diastema adjacent to the oromaxillary fistulae. formation between the third maxillary molars and the supernumerary teeth with deep periodontal pockets and Case history massive food impactions were diagnosed endoscopically. Radiography revealed inhomogenous sinus opacities in the left A 9-year-old Hungarian sport horse gelding (396 kg) used for and right paranasal sinuses. Following bilateral oral extractions general riding was presented to the clinic in poor body of the supernumerary cheek teeth and third maxillary molars, condition displaying bilateral purulent nasal discharge. bilateral oromaxillary fistula formations were diagnosed (about According to the owner, the horse started displaying 17 mm diameter on the right side). Bilateral frontal and clear mucoid bilateral nasal discharge and periodical right-sided maxillary trephinations and resection of the right coughing at the age of 6 years. It was further reported that bulla of the maxillary septum were performed. Massive food the horse had repeatedly been treated with dexamethasone, impactions of the left and right paranasal sinuses were removed NSAIDs and penicillin by local veterinarians. When the under endoscopic control. Repeated trans-endoscopic sinus bilateral nasal discharge turned purulent at the age of lavage was performed post-operatively. After 2.5 months, the 8.5 years, the owner called a veterinary service to re-examine large right-sided oromaxillary communication was temporarily the horse. This examination revealed bilateral sinusitis and closed with a transmaxillary anchored, gauze-cored silicon bilateral supernumerary 111 and 211 maxillary cheek teeth on plug on an outpatient basis. Follow-up examination after the distal aspects of both maxillary cheek teeth rows. fi 187 days revealed complete closure of the oromaxillary fistula Subsequently, the rst and second left maxillary molars (209 and absence of sinusitis. In a 1.5-year follow-up control, no and 210) were extracted orally and a left-sided maxillary fl pathological conditions were found. bone ap was performed to access the left maxillary sinus. During the procedure, small amounts of decaying hay were encountered in the sinus. As healing was not satisfactory, a fl Introduction frontonasal bone ap with dorsal bullectomy was made by the same surgeons a couple of weeks later. Again Oromaxillary fistulae develop in 7–33% of horses following inspissated, decaying food was found in the left caudal repulsion of caudal maxillary cheek teeth (Orsini et al. 1992; maxillary sinus. When the bilateral nasal discharge severely Prichard et al. 1992). In contrast, oromaxillary fistula formation increased about 3 weeks after surgery and the horse not associated with cheek tooth repulsion (Hawkes et al. additionally displayed a lethargic demeanour, substantial 2008) but with supernumerary cheek teeth has rarely been weight loss, poor mastication, quidding and halitosis, the reported in horses (Quinn et al. 2005). Extraction of a cheek owner decided to present the animal at our clinic. tooth on one side of the fistula has been advised to treat this condition (Dixon et al. 2000, 2005; Hawkes et al. 2008). Clinical findings and diagnosis Oromaxillary and oronasal fistulae following dental repulsion have been treated successfully using sliding mucoperiosteal On presentation, the gelding’s vital parameters were within flaps (Barakzai and Dixon 2005), by transposition of the normal limits although the horse was in poor body condition levator nasalabialis muscle (Orsini et al. 1992) or the levator displaying malodorous bilateral purulent nasal discharge. At labii superioris muscle (Brink 2006). Oromaxillary fistulae might the areas of the left maxillary and frontonasal bone flaps, signs also be treated by alveolar curettage, removal of inspissated of wound infection including suture dehiscence with purulent food and exudate and sealing of the oral aspect of the exudate emanating between the former stitches and defect with polymethylmethacrylate (PMMA) (Tremaine subcutaneous frontal/maxillary bone sequestration were 2006). In contrast, silicon-based transmaxillary anchored present. The horse was sedated with detomidine-hydrochloride packing of the alveolus to our knowledge has not been (Detonervin1; 0.01 mg/kg bwt, i.v.) and butorphanol reported in literature. (Butomidor2; 0.01 mg/kg bwt, i.v.). Oral examination revealed

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the presence of supernumerary distal maxillary molars (s111, of the third maxillary molars and the supernumerary teeth s211) in both maxillary quadrants. Bilateral diastema formation were diagnosed (Fig 1). between the third maxillary molars and the supernumerary teeth with deep periodontal pockets and massive food Treatment impactions were diagnosed endoscopically. Complete healing of the alveoli of the formerly extracted It was decided to orally extract the last molar (211) and the 209 and 210 was observed. On radiographs, inhomogenous supernumerary 211 cheek tooth in the left maxillary quadrant opacities were detected bilaterally in the paranasal sinuses with forceps. Following sedation with detomidine-hydrocloride (Fig 1). Missing 209 and 210 teeth, wide and deep diastema (0.01 mg/kg bwt, i.v.) and butorphanol (0.01 mg/kg bwt, i.v.) formations between the third maxillary molars and the (bolus and constant rate i.v. infusion), a left maxillary nerve supernumerary 111 and 211 with severe periodontal disease block in the pterigopalatine fossa (Staszyk et al. 2008) was performed with 10 mL, 2% lidocaine with 0.01% adrenalin. Prior to treatment, the horse also received flunixin-meglumine (Flunidol3; 1.1 mg/kg bwt, i.v.) and a long acting penicillin a) combination. The oral extractions were completed in a short period of time due to significant loss of periodontal attachment of both teeth. After completion of the dental extractions, an oromaxillary fistula of 4 mm diameter was encountered between the distal apex of 211 and the mesial apex of the supernumerary 211 cheek tooth. The 111 s111 subcutaneous sequestrae of the frontal/maxillary bones at the left cheek were surgically removed. A frontal trephination (39 mm diameter) was performed to allow endoscopic b) access to the left paranasal sinuses with a 5.3 mm flexible endoscope (Olympus4; BF type 1T20D) using trans-endoscopic foreign body forceps through the working channel and a variety of blunt dissectors with varying curvatures to clean the left sinus compartments (rostral and caudal maxillary-, c) conchofrontal-, sphenopalatine- and ventral conchal sinuses). Local anaesthesia of the sensitive and inflamed respiratory epithelium was performed by topical application s211 211 of 2% lidocaine spray prior to foreign body removal. Cleaning the sinuses of the copious amounts of inspissated and decaying feed material, inspissated pus and debris was time- d) consuming (6 h). Two handfuls of foreign material and pus concrements were eliminated from the sinuses (Fig 2). At the end of the procedure, the sinus lining appeared severely inflamed and oedematous. All accessible sinus compartments were rinsed thoroughly under endoscopic control with lukewarm (37°C) saline solution; chlorhexidine solution (0.2%) was used at the end of the rinsing procedure 110 as a final flush. The alveoli were packed with gauze soaked in 0.2% chlorhexidine solution. A 6 mm silicon catheter was placed into the maxillary sinus through a stab incision in the centre of the skin flap covering the trephination portal. The Fig 1: a) Lateral oblique (35°) radiographic view of the right skin incision was closed in single interrupted vertical mattress maxillary cheek teeth and sinuses. The presence of a pattern with polyamide USP 1, 4 metric (Supramid5). supernumerary maxillary molar (s111), diastema formation Surgical treatment of the right side commenced on Day between 111 and the supernumerary 111, severe periodontal and 3. The supernumerary right maxillary cheek tooth (s111) and apical changes of the cheek teeth adjacent to the diastema, and opacities of the right paranasal sinuses can be seen. b) the right maxillary molar 111 were extracted orally and a right Lateral oblique (30°) radiographic view of the left maxillary cheek 39 mm conchofrontal trephination was performed. Resection teeth and sinuses. Two molars (209 and 210) had been extracted of the dorsal portion of the bulla of the maxillary septum previously. Presence of a supernumerary molar (s211), diastema (bullectomy) was performed via the frontal approach using formation between 211 and the supernumerary 211, severe slightly curved uterus forceps. Similar to the left side, large periodontal and apical changes of the cheek teeth adjacent to quantities of decaying, impacted food and inspissated pus the diastema, marked sclerosis (red arrows) of the maxillary bone were eliminated from the sinuses. A right oromaxillary fistula in the affected region and opacities of the left paranasal sinuses with a diameter of 17 mm was encountered in the same are clearly visible. c) Intraoral view of the wide diastema position as described on the left side. Sinus lavage, catheter between 211 and supernumerary 211. d) Lateral oblique (35°) radiographic view of the right maxillary cheek teeth and sinuses. positioning and alveolar closures were performed as The two vertically placed 18G needles indicate the position of the previously described. Contralateral changes of the alveolar maxillary trephine hole (black arrows). The long slightly curved, gauze packing and sinus lavage were also performed. blunt tester indicates the location of the oromaxillary fistula (white Antimicrobial and antiphlogistic medication was arrow). continued for 6 days. Ongoing granulation tissue formation in

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a) a)

b)

b) Fig 3: The fistulous tract was debrided with a diode laser (12 W, continuous wave) to improve granulation and prevent epithelisation. a) Before and b) after treatment.

strands were tied under gentle tension around a 5 mL syringe positioned at the right maxillary trephination site (Fig 4a). The first plug protruded too deep into the fistula tract impeding healing. Consequently, the plug was changed on Day 66 to a smaller and shorter one. The next silicon plug was placed into the healing alveolus on Day 89. Gentle curettage of the fistula tract was performed via the maxillary trephination portal during each plug change. Incisions in the centres of the conchofrontal soft tissue flaps were kept Fig 2: a) Cleaning the sinuses of copious amounts of inspissated patent by inserting strips of polyurethane wound dressing and decaying feed material, inspissated pus and debris. b) Two (Ligasanoâ7) to facilitate continuing sinus lavages (Fig 4a). handfuls of foreign material and pus concrements were eliminated from the sinuses. During the whole period of hospitalisation, the horse was fed oats, grass pellets and grass hay. Upon discharge on Day 92, the anchored plug was firmly in place, the horse had a body weight of 463 kg and showed no signs of halitosis or the alveoli of the extracted teeth on both sides resulted in nasal discharge but clean sinus compartments. closure of the left oromaxillary fistula on Day 21. Alveolar packing was terminated on Day 45 on the left side. Healing Outcome of the larger right oromaxillary communication progressed as well. On Day 58, the tract had a diameter of 5–8mm (Fig Prior to returning the horse to its remote home stable where 5b). Its conical shape rendered further closure with gauze local veterinary support was not available, the owner was difficult and insecure (Fig 5a). To prevent spontaneous loss of trained how to perform sinus lavage through the frontal port, packing material and resulting food contamination of the wound management and tighten the anchor in case of sinuses, the alveolus was closed with an anchored silicone loosening. Further follow-up examinations were performed on plug moulded around a gauze core. an outpatient basis. On Day 112 minimal yellowish, right Just before completing the alveolar packing, the fistulous sided nasal discharge was detected. The plug placed on tract was debrided with a diode laser to improve granulation Day 89 had been displaced orally by newly formed and prevent epithelisation (Fig 3). A small piece of cotton granulation tissue. The plug was shaped to fit with a surgical gauze was rolled and tied with supramid (USP 6, 8 metric) blade and replaced following alveolar curettage and (Fig 4b), leaving two 70 cm long double strands of suture lavage. The diameter of the fistula was about 3–4 mm at this material. The thread ends were guided into the oral cavity, time. On Day 154 a new, smaller silicon plug was formed to grabbed with haemostats inserted through the right maxillary occlude the healing alveolus and oromaxillary fistula. trephination portal and pulled through the right fistulous tract Supramide (USP 1, 4 metric) was used to anchor the plug as and the right caudal maxillary sinus. The gauze core was described. On Day 187, the silicon plug was missing and the centrally embedded in freshly mixed, malleable dental granulation completed. Using a measuring tape, the body silicone (Bisico S16)(Fig 4b,d). Exerting gentle traction, the weight of the horse was estimated to be 500–520 kg. The construct was inserted into the fistulous tract. Subsequently, owner was advised to present the horse at 6 month intervals the occlusal surface of the silicone plug was carefully for control examinations. The last control was performed moulded to the oral mucosa to produce a tight oral seal about 1.5 years after the horse was discharged from our (Fig 4c). Following the setting of the silicone, both supramid clinic revealing complete resolution of sinusitis, healing of the

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a) a)

b)

c)

b) c)

d)

Fig 5: a) The conical shape of the fistulous tract rendered further closure with gauze difficult and insecure. b) Endoscopic view of the right oromaxillary fistula on Day 58. The tract had a diameter of 5–8 mm. c) Control about 1 year after the horse was â7 Fig 4: a) Strips of polyurethane wound dressing (Ligasano ) discharged from our clinic revealing perfect healing of the (black arrow) were inserted into the central incision of the flap to alveolus. facilitate continuing sinus lavages. A 5 mL syringe (white arrow) positioned like an anchor at the right maxillary trephination site to hold the strands keeping the silicone plug tight. b) and d) A small piece of cotton gauze was rolled and tied with supramid. The Casey 2013). Between the caudal maxillary cheek teeth, gauze core was centrally embedded in freshly mixed, malleable severe lesions may erode through the alveolar bone and dental silicone. c) The occlusal surface of the silicone plug was cause oromaxillary fistulation with subsequent sinusitis (Dixon carefully moulded to the oral mucosa to produce a tight oral et al. 1999; Hawkes et al. 2008). Reportedly, the horse seal. displayed bilateral nasal discharge at the age of 6 years (2 years prior to treatment) which, over time, became increasingly viscous and yellowish. Supernumerary cheek alveoli (Fig 5c) and absence of nasal discharge and odour teeth may not erupt until horses are over 5 years old (Dixon on both sides. and Dacre 2005). The distal molars are exposed to the greatest forces during mastication (Huthmann et al. 2009). Discussion Repetitive masticatory forces and pressure exerted by inspissated feed material in the diastemata in conjunction Diastemata commonly occur between supernumerary or with the fact that the distal supernumerary molars (s111/s211) dysplastic cheek teeth and their neighbours (Dixon and were only partly opposed by their mandibular antagonists, Dacre 2005; Quinn et al. 2005; Casey and Tremaine 2010; weak periodontal support and missing of interdental alveolar

© 2018 EVJ Ltd 586 EQUINE VETERINARY EDUCATION / AE / NOVEMBER 2019

septae between the third maxillary molars and the technique precluded periodic examinations of the progress supernumerary teeth might have contributed to diastema of fistula healing. formation and aggravation of periodontal disease over time. Finally, it was decided to pack the alveoli with gauze As a result, increasing amounts of feed particles were forced until increasing granulation precluded a secure fitofthe into the diastemata and pressed in an apical direction. The gauze packing. At this point, dental silicone of moderate resulting periodontal disease progressed apically which might rigidity- (Bisico S1) was used to tightly seal the deep but have caused low-grade sinusitis long before the narrow and conoid-shaped alveolus on the right side. The development of oro-sinusoidal communication occurred. gauze-cored, transmaxillary anchored silicon plug Recurrent nasal discharge was already present 2 years effectively sealed the oral cavity towards the sinus. This before treatment was initiated, and might have been technique to pack the alveolus and seal off the misinterpreted as a sign of lower airway disease instead of oro-sinusoidal communication had the advantage of a early stage sinusitis. Accurate oral inspection with a mirror or long-term use of the same plug. Its tight fitcouldbe an oral camera is of importance, especially in cases with checked from the outside and tightening of the anchor nasal discharge (Dixon and Dacre 2005) and might have could also be performed by the owner without the need helped in diagnosing the underlying disease earlier in this for sedation or special equipment, if needed. Furthermore, case. the material was easy to mould when soft but could also Considering the extent of sinus pathology in this case, be easily shaped and shortened with a knife after setting. surgical approaches via bilateral frontal trephinations It resisted the physical and chemical stresses in the oral appeared to be ideally suited for accessing the frontal-, cavity well and did not cause damage to the soft tissues dorsal conchal-, caudal maxillary-, and the entrance to the of the oral cavity. ethmoidal- and sphenopalatine sinuses (Barakzai and Dixon 2014). Inserting a small diameter endoscope through the trephination portals facilitated sinoscopy of the rostral Conclusion maxillary sinus and the ventral conchal sinuses following Gauze-cored anchored silicon plugs were successfully used fenestration and removal of the bulla of the maxillary septum. in the post-operative treatment of large oromaxillary fistula. Maintaining small openings in the centre of the skin flaps by â The technique proved to be inexpensive and easy to apply inserting strips of polyurethane wound dressing (Ligasano ) although an extensive length of time - approximately fl facilitated prolonged sinus ushing and sinoscopic 6 months - was needed for complete healing. Control of the examination of the paranasal sinuses and the oromaxillary correct fit was straightforward without the need for sedation. fi stulae. Following oral dental extractions, diagnosis of the Despite an initially guarded prognosis, uncompromised fi large oromaxillary stula and the extent of sinus healing could be achieved. contamination, the question of how to resolve this pathological condition most effectively was raised and different techniques of fistula repair were discussed. Financial Authors’ declaration of interests constraints of the owner and the long distance between the 0 No conflicts of interest have been declared. clinic and the owner s home were also considered. In horses, two facial muscles, the temporal (Waldridge et al. 1997) and levator labii superioris (Campbell and Peyton 1984) muscles, Ethical animal research have been used for correction of sinocutaneous fistulae. The levator nasolabialis muscle has been used for prevention of No ethical review was required. Consent was provided by the orosinus fistulae (Orsini et al. 1992; Hahn and Kohler 2002) and owner for all diagnostic and therapeutic procedures. for reconstruction of maxillary sinus defects (Dart et al. 1994). Transposition of the levator nasolabialis muscle to obliterate an oromaxillary sinus fistula is complicated because the Source of funding muscle is difficult to mobilise, and its flat configuration can None. result in a poor fit in the dorsal aspect of an oromaxillary sinus fistula (Brink 2006). In contrast, the levator labii superioris muscle is ellipsoid in its transverse plane (Brink 2006). Authorship Transposition of the levator labii superioris muscle was A.T. Hevesi contributed to study design, study execution, data successfully used for treatment of oromaxillary fistulae of the analysis and interpretation. H. Simhofer contributed to data 8th and 10th maxillary cheek teeth alveoli in three horses analysis and interpretation. D. Uto, N. Takacs, V. Lorincz (Brink 2006). The need for general anaesthesia to perform this contributed to study execution. All authors contributed to the procedure, the limited length of the muscle, the distal preparation of the manuscript and gave their final approval position and large size of the right-sided fistula and the of the manuscript. owner0s financial limitations rendered this technique less suitable. As the fistulae were located in the distal aspect of the oral cavity, a mucoperiosteal flap (Barakzai and Manufacturers' addresses Dixon 2005) was also excluded. The application of 1Produlab Pharma B.V., SJ Raamsdonksveer, Netherlands. 2 polymethylmethacrylate (PMMA) alveolar packing was Richter Pharma AG, Wels, Austria. 3 considered a feasible technique (Tremaine 2006; Hawkes CP-Pharma GmbH, Burgdorf, Germany. 4Olympus Optical Co.LTD, Japan. et al. 2008). However, this technique was also excluded 5Luxsutures, Weiswampach, Luxembourg. because of the inability to mould the PMMA to neighbouring 6Bielefelder Dentalsilicone Gmbh, Bielefeld, Germany. teeth, the rigidity of the material and the fact that this 7Ligamed Medikal Produkte Gmbh, Cadolzburg, Germany. Continued on page 593

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Clinical Commentary Orosinuidal and oronasal fistulas: The search for an adequate treatment M. Stoll Equine Dental Clinic, Hohenstein, Germany Corresponding author email: [email protected]

Periapical resorption and bacterial destruction of the alveolar tooth is, in many cases, not perfectly closed; this facilitates bone are common findings in apically infected cheek teeth. food impression into the apical area. The alveolar bone is a In particular, diastemata with food impression and thin border between the maxillary molar teeth and the sinus periodontitis often show infected interdental sites and, in system. The described periodontal and periapical infection severe cases, infected periapical alveolar bones. Between can lead to huge fistulas in the sinus system. Radiographs regular and supernumerary teeth, there is often no interdental with contrast medium (barium sulfate suspension) injected bone. The interproximal space to an adjacent supernumerary into the interdental space often demonstrate connections of

a)

b)

Fig 1: a) Diastema 111/s111 b) contrast medium (barium sulfate) shows communication with the sinus.

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a)

b)

Fig 2: Several diastemas and fistulas in a donkey.

Fig 4: Gauze fixed with PDS suture. a) post-operative b) two weeks post-operative.

the presented defect. If the alveolar bone is necrotic or missing in some areas, there is still a chance that the border to the sinus is partly intact with only sinus mucosa. The alveolus is routinely packed with gauze to prevent food accumulation. To increase the growth of the granulation Fig 3: Several diastemas and fistulas in a donkey. tissue from the apical area of the alveolus, it can be an advantage to use healing substances in the apical area of the alveolus covered with gauze. For example, crystallised the interproximal space to the sinus (Fig 1). Only after honey can be applied into the apical part of the alveolus. extraction of the infected teeth, the complete damage to This prevents the gauze being inserted too deeply into the the alveolar bone can be seen. alveolus which would inhibit granulation. Also, honey and As described in the Case Report by Hevesi et al. (2019), sugar are chemoattractants for tissue macrophages and routine therapy in these cases consists of alveolar flushing and enhance fibroplasia (Tonks et al. 2003; Theoret 2006; Molan debridement to remove necrotic tissue and food material 2008). after extracting the supernumerary and, if indicated, the The alveolar packing has to be renewed within an interval adjacent tooth (Quinn et al. 2005). Debridement should not of a few days to a maximum of 10 days, depending on the be too aggressive to prevent unnecessary enlargement of situation.

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Fig 5: Insufficient granulation and epithelisation of huge fistulas.

Fig 6: Auricular cartilage graft placement.

Similar to the described case by Hevesi et al. (2019), the trephination of the frontal sinus is the most efficient related sinus compartments are often filled with inspissated approach to clean the caudal sinus compartments. After pus and food material. As a consequence of the chronic resection of the dorsal portion of the bulla of the maxillary infection, leucopenia and weight loss can be observed septum, access to the rostral maxillary sinus and the ventral frequently in cases with a long medical history. Because of conchal sinus is easily achieved. Maxillary bone flaps and the inspissated material in the sinus compartments, frontonasal bone flaps are also described for this purpose. A

© 2018 EVJ Ltd EQUINE VETERINARY EDUCATION / AE / NOVEMBER 2019 591

Fig 7: Buccal flap along the left upper arcade.

and bone necrosis is not an issue; skin closure usually leads to good cosmetic results, especially if the periosteum and skin layers are sutured in separate layers. The trauma to the region of the trephination or the bone flap may later sporadically lead to nasofrontal suture line periostitis (Dixon

2014). As in the described case, antimicrobial treatment should be started prior to surgery to achieve tissue levels above MIC when the procedure begins. Because treatment of an urgent case cannot wait for the result of a bacterial culture, a broad-spectrum antimicrobial is often used. Because anaerobic bacteria can be expected in dental and dental-related sinus infections (Bienert-Zeit et al. 2017), the chosen antimicrobials should be effective against anaerobic bacteria (metronidazole, penicillin). In the case described by Hevesi et al. (2019), the alveolar healing led to the closure of the smaller fistula in the left arcade (211/s211). Granulation in the alveolus 111/s111 decreased the diameter of the fistula but did not close it. Because granulation tissue has reduced the depth of the alveolus and adjacent teeth are missing in the described case, the fixation of any material to cover the fistula is extremely difficult. The challenge can be to seal the fistula and to induce a healing process in this stage of stopped healing and chronic inflammation. In cases where it is possible to cover the fistula, it is a routine treatment to mechanically debride the fistula to induce bleeding and to achieve blood clot formation. Hevesi et al. (2019) have used a diode laser to debride the fistula, which can be used to destroy the epithelium layer in the fistula and seems to induce a healing process if the setting is low enough to Fig 8: Dehiscence of the buccal flap but epithelisation of the prevent underlying tissue from becoming necrotic due to the cartilage. heat production (Moritz 2006). Debridement is extremely important because when the orosinuidal communication fails to close spontaneously, it remains patent and gets starting point from a frontal trephination or frontonasal bone epithelialised. The epithelised fistula usually has no flap gives a better chance to obtain access to both the tendency to heal spontaneously. The blood clot formed in the rostral and the caudal sinus systems, compared with the fistula after mechanical debridement should be protected maxillary bone flap (Easley and Freeman 2013). Similar to against dislodgement. In human dentistry, primary closure or the case described by Hevesi et al. (2019), bone flaps can the use of tissue flaps of well-vascularised tissue are become necrotic because of the likely bacterial performed to protect the alveolus. The shape of an alveolus contamination and the reduced blood perfusion. The bone and the rigid tissue around the alveolus impede these of the 39-mm frontal bone trephination is therefore removed methods and make them almost impossible in the distal site

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of an arcade. Most techniques of tissue grafts, such as the use possible to use mucosa flaps along the complete arcade of a mucoperiosteal flap (Barakzai and Dixon 2005) and (Fig 7). Although partial suture dehiscence of the buccal an alveolar bone flap (Easley and Freeman 2016), are flap occurred (Fig 8), the transplanted cartilage did not described in the mesial aspect of the maxillary arcade. become necrotic in any of the three locations, resulting in The transposition of a facial muscle such as the levator the healing of the fistulas (Fig 9). nasolabialis (Orsini et al. 1992) or the levator labii superioris As an alternative to auricular cartilage graft, a collagen (Brink 2006) is a more realistic approach in the molar membrane made of equine macerated tendons, coated region. with fibrinogen and thrombin, is commercially available Although some methods have been described to (Tachosil1). increase the healing process and to obturate fistulas (Orsini To provide good healing conditions, the area of the fistula et al. 1992; Barakzai and Dixon 2005; Brink 2006; Hawkes et al. should fulfil the following criteria: 2008); one of the difficulties is to find and harvest tissue for tissue grafts or for transposition and to fix the tissue to close • Epithelium has to be removed. the defect. • Blood clot has to be protected from dislocation. In humans and small animals, auricular cartilage is used to • Sinus must be free of infection, with adequate nasal close comparable defects and fistulas; such an approach is drainage. used to close oroantral fistulas in human subjects and cats • All necrotic soft tissue and necrotic bone must be (Cox et al. 2007; Van de Wetering et al. 2010; Khandelwal removed. and Hajira 2018). Also, a case report of the treatment of • Closure in case of a flap must be tension-free. orosinuidal fistulas in a donkey with auricular cartilage graft • If flap surgery is performed, the tissue must be well- shows the effectiveness of this technique in equids (Stoll vascularised. 2017). Auricular cartilage is biocompatible, highly resistant to • Obturation has to be strong enough to resist air pressure infections, easy to harvest and nonresorbable. This graft does differences between the connected cavities (during not require vascularisation for the integration to the recipient breathing and sneezing). site. Also, in this technique, the challenge is to fix and protect the area of the fistula and to cover the cartilage. Reports The technique described by Hevesi et al. (2019) to from small animals show that the cartilage does not become obturate the fistula with a gauze-cored silicone plug fulfils necrotic, even if it is unprotected in the oral cavity. the criteria above and was successful in this case. However, Compared with small animals, it is considerably more difficult the authors reported that in the beginning, the silicone plug to feed horses with only liquid food over the healing period. was inserted too deeply into the fistula, which impeded the Also, fixation with sutures is more difficult, so protection seems healing process. Because there are almost no dental to be a good support for the healing process. materials available licensed for equine dentistry, often The donkey that was presented with auricular cartilage human dental materials or even technical materials are graft also had severe periodontitis and diastema with one rededicated for equine use. An in vitro study with equine oronasal and two orosinuidal fistulas (Figs 2 and 3). The periodontal fibroblasts showed that a similar dental A- fistulas were protected with gauze after extraction of all silicone material had severe cytotoxic effects (Ringeisen cheek teeth in the left maxillary arcade and fixated with et al. 2017). This information encourages further clinical single interrupted sutures of PDS (metric 4) to the gum and studies to show which materials are well tolerated by the cheek mucosa (Fig 4). Because granulation over a periodontal tissue or granulation tissue if placed into the oral period of 4 weeks was insufficient to close the fistulas cavity for a longer period. Until any data are available, it (Fig 5), an auricular cartilage graft was transplanted into might be a good idea to use a membrane, such as the the fistula after debridement and covered with a buccal equine collagen membrane, between the silicone and the mucosal flap (Figs 6 and 7). This case shows that it is granulation tissue.

Fig 9: Onset of granulation and fistula closure after auricular cartilage graft.

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1 Data on fi le. 2 Adequan® i.m. Package Insert, Rev 1/19. 3 Burba DJ, Collier MA, DeBault LE, Hanson-Painton O, Thompson HC, Holder CL: In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fl uid compartments and articular cartilage in an osteochondral defect model. J Equine Vet Sci 1993; 13: 696-703. 4 Kim DY, Taylor HW, Moore RM, Paulsen DB, Cho DY. Articular chondrocyte apoptosis in equine osteoarthritis. The Veterinary Journal 2003; 166: 52-57. 5 McIlwraith CW, Frisbie DD, Kawcak CE, van Weeren PR. Joint Disease in the Horse.St. Louis, MO: Elsevier, 2016; 33-48.

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Author’s declaration of interests Hawkes, C.S., Easley, J., Barakzai, S.Z. and Dixon, P.M. (2008) Treatment of oromaxillary fistulae in nine standing horses (2002–2006). Equine No conflicts of interest have been declared. Vet. J. 40, 546-551. Hevesi, A.T., Uto, D., Takacs, N., Lorincz, V. and Simhofer, H. (2019) Transmaxillary anchored silicon embedded gauze plug in the Ethical animal research post-operative treatment of a large oromaxillary fistula caused Not applicable. by a supernumerary cheek tooth. Equine Vet. Educ. 31, 582- 587. Khandelwal, P. and Hajira, N. (2018) Management of oro-antral Source of funding communication and fistula: various surgical options. World J. Plast. Surg. 6, 3-8. None. Molan, P.C. (2008) The role of honey in the management of wounds. J. Wound Care 8, 415-418. Manufacturer's address Moritz, A. (2006) Oral Laser Application, Quintessenz Verlags-GmbH, Berlin. 1Takeda Austria GmbH, Linz, Austria. Orsini, P.G., Ross, M.W. and Hamir, A.N. (1992) Levator nasolabialis muscle transposition to prevent an oro-maxillary sinus fistula after References tooth extraction in horses. Vet. Surg. 21, 150-156. Quinn, G.C., Tremaine, W.H. and Lane, J.G. (2005) Supernumerary Barakzai, S.Z. and Dixon, P.M. (2005) Sliding mucoperiosteal hard cheek teeth (n = 24): clinical features, diagnosis, treatment and fl fi palate ap for treatment of a persistent oronasal stula. Equine outcome in 15 horses. Equine Vet. J. 37, 505-509. Vet. Educ. 17, 287-292. Ringeisen, H., Poschke,€ A., Krahling,€ B., Schrock,€ C., Stoll, M., Bienert-Zeit, A., Verwilghen, D. and Feige, K. (2017) Antibiotische Vogelsberg, J., Failing, K. and Staszyk, C. (2017) Influence of Therapie bei Zahn- und Sinuserkrankungen des Pferdes. Der dental materials on cells of the equine periodontium. Equine Praktische Tierarzt 98, 1048-1057. Vet. J. 50, 363-369. Brink, P. (2006) Levator labii superioris muscle transposition to treat Stoll, M. (2017) Orosinuidal and oronasal fistulas after tooth extraction, fi oromaxillary sinus stula in three horses. Vet. Surg. 35, 596-600. ear cartilage transplantation in a donkey and comparison to other Cox, C.L., Hunt, G.B. and Cadier, M.M. (2007) Repair of oronasal fistulae fistula treatments. Proc. Eur. Vet. Dent. Forum 26, 154. fi using auricular cartilage grafts in ve cats. Vet. Surg. 36, 164-169. Theoret, C.L. (2006) What’s new and innovative in wound Dixon, P.M. (2014) A review of swellings of the frontal region of the management: problems and solutions. Proc. Am. Ass. Equine equine head. Equine Vet. Educ. 26, 365-371. Practnrs. 52, 265-269. Easley, J.T. and Freeman, D.E. (2013) New ways to diagnose and treat Tonks, A.J., Cooper, R.A., Jones, K.P., Blair, S., Parton, J. and Tonk, A. equine dental-related sinus disease. Vet. Clin. North Am. Equine (2003) Honey stimulates inflammatory cytokine production from Pract. 29, 467-485. monocytes. Cytokine 21, 242-247. Easley, J.T. and Freeman, D.E. (2016) Surgical repair of a chronic, Van de Wetering, A., Caldwell, L., Loman, S. and Reid, T.K. (2010) oronasal fistula in a horse using an alveolar bone flap. Equine Vet. Repair of palatal defect using an auricular cartilage graft in small Educ. 28, 550-555. animals. J. Vet. Dent. 27, 128.

Continued from page 586 References Dixon, P.M., Easley, K.J. and Eckman, A. (2005) Supernumerary teeth in the horse. Clin. Tech. Equine Pract. 4, 155-161. Barakzai, S.Z. and Dixon, P.M. (2005) Sliding mucoperiosteal hard Hahn, P. and Kohler, L. (2002) Removal of upper cheek teeth of the palate flap for treatment of persistant oronasal fistula. Equine Vet. horse using bone flap technique, muscle transposition and alveolar Educ. 17, 287-292. closure. Tierarztl. Prax. 30, 39-45. Barakzai, S.Z. and Dixon, P.M. (2014) Standing equine sinus surgery. Hawkes, C.S., Easley, J., Barakzai, S.Z. and Dixon, P.M. (2008) Treatment Vet. Clin. Equine 30, 45-62. of oromaxillary fistulae in nine standing horses (2002-2006). Equine Brink, P. (2006) Levator labii superioris muscle transposition to treat Vet. J. 40, 546-551. oromaxillary sinus fistula in three horses. Vet. Surg. 35, 596-600. Huthmann, S., Staszyk, C., Jacob, H.G. and Gasse, H. (2009) Campbell, M.L. and Peyton, L.C. (1984) Muscle flap closure of a Biomechanical evaluation of the equine masticatory action: frontocutaneous fistula in a horse. Vet. Surg. 13, 185-188. calculation of the masticatory forces occurring on the cheek tooth Casey, M. (2013) A new understanding of oral and dental pathology battery. J. Biomech. 42, 67-70. of the equine cheek teeth. Vet. Clin. Equine 29, 301-324. Orsini, P.G., Ross, M.W. and Hamir, A.N. (1992) Levator nasolabialis fi Casey, M.B. and Tremaine, W.H. (2010) Dental diastemata and muscle transposition to prevent an orosinus stula after tooth periodontal disease secondary to axially rotated maxillary cheek extraction in horses. Vet. Surg. 21, 150-156. teeth in three horses. Equine Vet. Educ. 22, 439-444. Prichard, M.A., Hackett, R.P. and Erb, H.N. (1992) Long-term outcome Dart, A., Best, P. and Peatfield, J. (1994) Reconstruction of a maxillary of tooth repulsion in horses. A retrospective study of 61 cases. Vet. sinus defect in a horse using a levator nasolabialis muscle flap. Surg. 21, 145-149. Aust. Vet. J. 71, 379-380. Quinn, G.C., Tremaine, W.H. and Lane, J.G. (2005) Supernumerary = Dixon, P.M. and Dacre, I. (2005) A review of equine dental disorders. cheek teeth (n 24): clinical features, diagnosis, treatment and Vet. J. 169, 165-187. outcome in 15 horses. Equine Vet. J. 37, 505-509. € Dixon, P.M., Tremaine, W.H., Pickles, K., Kuhns, L., Hawe, C., McCann, Staszyk, C., Bienert, A., Baumer, W., Feige, K. and Gasse, H. (2008) J., McGorum, B.C., Railton, D.I. and Brammer, S. (1999) Equine Simulation of local anaesthetic nerve block of the infraorbital dental disease part 2: a long-term study of 400 cases: disorders of nerve within the pterygopalatine fossa: anatomical landmarks fi development and eruption and variations in position of the cheek de ned by computed tomography. Res. Vet. Sci. 85, 399-406. teeth. Equine Vet. J. 31, 519-528. Tremaine, W.H. (2006) Complications associated with dental and Dixon, P.M., Tremaine, W.H., Pickles, K., Kuhns, L., Hawe, C., paranasal sinus surgery. In: Proceedings of the AAEP Focus McCann, J., McGorum, B.C., Railton, D.I. and Brammer, S. Meeting, Indianapolis. pp 141-147. (2000) Equine dental disease Part 4: a long term study of 400 Waldridge, B.M., Bradley, D.M., Scardino, M.S. and Schumacher, J. cases: apical infections of the cheek teeth. Equine Vet. J. 32, (1997) Repair of a sinocutaneous fistula in a horse using a mucosal- 182-194. lined myocutaneous transposition flap. Equine Pract. 19, 7-11. © 2018 EVJ Ltd 594 EQUINE VETERINARY EDUCATION Equine vet. Educ. (2019) 31 (11) 594-598 doi: 10.1111/eve.12898

Case Report A standing pararectal approach to treat small colon obstruction by a pedunculated lipoma E. Durket†1, V. Albanese†2, S. K. Steward†3 and D. E. Freeman†* †Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA *Corresponding author email: freemand@ufl.edu Present addresses: 1Lloyd Veterinary Medical Center, College of Veterinary Medicine, Ames, Iowa, USA; 2Tierarztliche€ Klinik fur€ Pferde Großwallstadt, Großwallstadt, Germany; 3University of Pennsylvania, Kennett Square, Pennsylvania, USA

Keywords: horse; lipoma; colic; small colon

Summary approach for cystotomy has been described for urolith In an 18-year-old Paso Fino mare presented with mild colic of removal in standing horses (Abuja et al. 2010), and was used 36 h duration, a luminal obstruction was found on rectal in this report to create a narrow path of dissection to the palpation in the most oral part of the rectum, and this obstruction. appeared to be caused by a tight band on the left side. A standing procedure was used that involved pararectal Case details dissection with long-handled instruments to the level of the constricting band, guided by a hand in the rectum. A hooked Case history bistoury designed for treating entrapped epiglottis was used An 18-year-old Paso Fino mare was presented to the University to transect the band, which immediately released the of Florida College of Veterinary Medicine with a history of mild obstruction and allowed manual evacuation of the aboral colic of approximately 36 h duration. Predominant signs were end of the small colon. The band was most likely the pedicle recumbency, sweating, decreased faecal production and of a pedunculated lipoma that had encircled the oral end of anorexia. She was treated with flunixin meglumine (1.1 mg/kg the rectum. The mare made a complete recovery. bwt per os) 24 h before admission, but continued to have mild to moderate signs of abdominal pain. When examined by the referring veterinarian 4 h before presentation, the mare was Introduction treated with flunixin meglumine (1.1 mg/kg bwt i.v.). The mare Small colon obstructions that require surgical intervention are had been used for pleasure riding and had never been bred. rare, with a prevalence of 3.5–4.2% of horses that had colic surgery in two large studies (Edwards 1992; Mair and Smith Clinical findings 2005). They are classified as congenital diseases, simple On presentation to the University of Florida, the mare was obstructions, vascular lesions and strangulating obstructions mildly painful, quiet, and dull, and she had a body score of (Edwards 1997a,b). Strangulating lesions can be caused by 5–6 on the Henneke scale of 1–9 (Henneke et al. 1983). Her vascular events, volvulus, hernias, intussusceptions and initial physical examination revealed a temperature of 37.9°C pedunculated lipomas (Edwards 1997a,b; Schumacher and (100.3°F), heart rate of 60 beats/min and respiratory rate of 40 Mair 2002). The most common lesions that require surgery in breaths/min. Mucous membranes were pale pink and the the small colon are impaction, followed by pedunculated capillary refill time was 2 s. Intestinal sounds were within lipoma (Mair and Smith 2005; de Bont et al. 2012), and the normal limits. Ultrasound examination did not reveal any latter is the disease most likely to require resection and abnormalities. Palpation per rectum revealed a anastomosis in this organ (Prange et al. 2010). Typically, pneumorectum extending caudally from a rectal constriction these are seen in horses of the same age group as in small about 43 cm from the anus (at the finger tips with the elbow intestinal cases (Garcia-Seco et al. 2005). However, the at the anus). The constriction reduced the lumen to distribution of a strangulating lipoma in the small colon can approximately 4 cm in diameter and dry impacted faeces be 4–10% of all horses with this disease, compared with 89– could be palpated at the finger tips oral to the constriction. 96% in the small intestine (Edwards 1997b; Garcia-Seco et al. The most likely diagnosis was a lipoma with a stalk that 2005). encircled the aboral end of the small colon, close to the A lipoma can encircle the aboral part of the small colon peritoneal reflection. Treatment options discussed with the and occlude it at the peritoneal reflection, thereby creating owner included midline exploratory celiotomy, flank laparotomy a tight luminal constriction that prevents palpation beyond and flank laparoscopy. Because of financial constraints, these that point (Mason 1978; Edwards 1992). In one such case, the options could not be considered. Vaginal access to the site of lipoma was removed through a dorsolateral incision in the obstruction was also considered (Mason 1978), but even a small cranial end of the vagina (Mason 1978). In this case report, hand encountered considerable resistance to insertion of the we describe a pararectal approach to relieve a small colon finger tips at the vestibule. Therefore, a pararectal approach obstruction attributed to a pedunculated lipoma at the (Abuja et al. 2010) was used to relieve the small colon approximate level of the peritoneal reflection. A pararectal obstruction and associated impaction.

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Surgical approach a) The mare was restrained in stocks, an i.v. catheter (14 gauge mila catheter) was placed in the left jugular vein and she was given xylazine (0.4 mg/kg bwt i.v.) and butorphanol tartrate (0.01 mg/kg bwt i.v.). A continuous rate infusion of detomidine (25 mg added to 500 mL 0.9% sodium chloride) was given for a mean dose of 0.03 mg/kg bwt/h throughout the procedure, with the rate adjusted based on the response 1 cm to surgical stimulation. A caudal epidural was given into the first intercoccygeal space with 6 mL of 2% lidocaine hydrochloride. A tail wrap was placed and the tail was held away from the surgical field throughout the procedure. The perineum, rectum and vulva were cleaned with cotton, soap b) and water, followed by a surgical scrub of the perineal region with povidone-iodine scrub and isosopryl alcohol rinse. To ensure desensitisation of the left pararectal space lateral to the anus, 15 mL 2% lidocaine hydrochloride was injected in the skin and subcutaneous tissues. Aseptic preparation with povidone-iodine scrub and isosopryl alcohol was completed after the local anaesthetic agent had been injected. A left- sided approach was chosen because the constricting band could be felt on that side of the rectum. A 10-cm vertical skin incision was made with a No. 10 scalpel blade between the anus and the left semimembranosus muscle and was continued through subcutaneous tissues with the scalpel blade. Digital dissection 1 cm was continued to establish a natural plane of division between the semimembranosus muscle and the external anal sphincter. Care was taken to avoid damage to the internal pudendal artery and vein and end branches, including the caudal rectal artery, and the pudendal and caudal rectal Fig 1: Curved bistoury used to transect the pedicle of the lipoma nerves. Metzenbaum scissors, long-handled Metzenbaum through a pararectal approach. a) Tip of the hook with blade on scissors and laparoscopic scissors were used in that order as the concave side. b) Handle designed to allow manipulation of dissection progressed further cranially. The right hand of the the instrument and to maintain orientation of the hooked end surgeon was inserted in the rectum throughout the procedure during use. to ensure that dissection did not progress too far axially and perforate the rectal wall. As dissection progressed cranially, the mare became uncomfortable, so that approximately 40 mL of 2% lidocaine was infused at progressive increments handfuls of alfalfa hay every 4 h overnight. She remained into the side port of the laparoscopic scissors to anaesthetise comfortable and passed many piles of soft but formed tissues at its tip. Once the tip of the scissors was palpated at faeces. At 12 h after surgery, she was given 230 g the band, it was replaced with a hooked bistoury (Fig 1) used magnesium sulfate in 5 L water using a nasogastric tube, and for axial division of entrapped epiglottis (77 cm long, 11 mm then 18 h after surgery, she was given 4 L of mineral oil by a wide gap between tip and blade)1. The hook was advanced nasogastric tube. At 12 h after surgery, a rectal examination in a vertical orientation along the dissected plane along the revealed no abnormalities; however, a clear straw-coloured rectum until it passed beyond and lateral to the constricting fluid was expressed from the perineal incision when faeces band. The relationship of the handle orientation relative to the were removed. The mare was given 2 g of phenylbutazone plane of the hook was used to direct the position of the hook orally once daily for 3 days and then 1 g of phenylbutazone as needed (Fig 2). Once the hook passed the band, it was orally once daily for 3 days. The mare was discharged from then turned with the pointed tip against the rectal wall so that the hospital 24 h after admission. it engaged the band (Fig 2). The hook was drawn caudally Her aftercare included monitoring of faecal output and with a short and sharp movement until the surgeon could feel her incision site. She was given 7 days of stall rest and then the band release. Instant release of the small colon turned out in a paddock. When stalled, she was fed pelleted constriction followed, and faecal balls could be manually mashes with salt and small amount of alfalfa throughout the evacuated from the point of accumulation proximal to the day and then hand walked to graze. At 14 days after level of obstruction. The colonic mucosa was palpated surgery, the owner expressed concern about the persistent carefully and determined to be intact, and frank blood was purulent discharge from the incision and a slight odour not observed on the surgeon’s rectal sleeve. The pararectal associated with it. The mare was behaving normally, with an incision was left open to heal by second intention. excellent appetite and attitude, but had intermittent bouts of fever. The referring veterinarian examined the mare and Post-operative management found no obvious abnormalities on palpation per rectum, an The mare was given 4 L of mineral oil using a nasogastric absence of any swelling along the line of dissection and a tube post-operatively. She was fed a pelleted mash and normal rectal temperature. The incision appeared to be

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injury; however, the subsequent clinical course would suggest that such tissue damage was unlikely. Although the owner was offered a ventral midline Lipoma Small colon celiotomy, flank laparoscopy or an open flank approach, the method used was the only one affordable. A possible advantage of the other options was improved access to Lipoma the peritoneal reflection at the most oral end of the pedicle rectum, which might have allowed assessment of serosal injury and possibly repair of more complicated lesions. However, access to the pelvic part of the abdomen would have been difficult by any of these methods with the possible exception of standing laparoscopy (Freeman 2012). A ventral midline approach would also have allowed more complete exploration and could have allowed correction of any concurrent lesions. A standing flank approach would Hooked Rectum have allowed manual access to the site of intestinal bistoury constriction, but with poor visual guidance and limited opportunity for exteriorising the distal part of the small colon. This approach would have more than doubled the cost over that incurred by our approach, because it would have required draping, gowning, perioperative antimicrobial drugs, suture material, longer hospitalisation, a higher procedure classification, and a risk of incisional swelling and DEF dehiscence (Graham and Freeman 2014). Similar concerns would have applied to laparoscopy. Potential complications of the method used were rectal laceration that could have led to septic peritonitis and/or evisceration. This was avoided by dissecting lateral to the rectal wall so that the full thickness of all rectal layers was preserved. Although the owner reported a concern about discharge from the incision and an associated odour, the attending veterinarian did not detect an odour and Fig 2: Dorsal view to show the epiglottis hook engaging the considered the discharge to be within normal limits at that pedicle of the lipoma through a pararectal approach before stage post-operatively. Antimicrobial drugs were not given transection. Arrow indicates direction of traction to transect the fi lipoma. Note that while the surgeon’s left hand manipulates the at that time because the attending veterinarian did not nd instrument, the right hand guides placement and protects the any evidence of a surgical site infection, including a fever. rectal wall during the procedure. These drugs were also not used perioperatively because of owner’s concerns about cost and because the surgeons assessed the potential benefits as insufficient for a healing well and he did not detect an odour. The incision procedure classified as clean-contaminated (Ahern and continued to heal from that time, the mare made a full Richardson 2012). Although the fluid discharged from the recovery, and was alive and doing well at 20 months after incision on palpation per rectum on the first post-operative surgery. day was either a seroma or peritoneal fluid, ultrasound examination was not used to assess peritoneal fluid Discussion accumulation in the abdomen. This decision was partly determined by cost and also by the absence of clinical This is the first case to the authors’ knowledge of a small signs of peritonitis. colon obstruction relieved by the method described. The Other possible complications of the method used most likely cause of the obstruction was a pedunculated include anal sphincter damage, laceration of a major lipoma with a pedicle that encircled the small colon or mesenteric vessel, bleeding from the internal pudendal vein rectum, presumably from the right side of the mesentery as (Abuja et al. 2010), and failure to relieve the obstruction. the lipoma passed under the colon to become entrapped Possibly disruption of the pedicle could tear the mesocolon, on the left side. Other causes are possible, such as an which could subsequently entrap intestine. Because the adhesion, an anomalous band or lipomatosis (Riley et al. lipoma was probably encircling the intraperitoneal portion 2007), but these would seem less common than a lipoma of the small colon or rectum, the peritoneal lining was likely (Edwards 1997a; Mair and Smith 2005; Freeman 2012; de Bont breached by the surgical procedure; however, this did not et al. 2013). The pedicle in this case did not produce a appear to cause long-term complications. Although all complete constriction as the surgeon could introduce two the other approaches offered would have allowed finger tips through the rectal lumen, so the possibility of complete removal of the lipoma, a lipoma ‘lost’ in the vascular occlusion in the rectal wall was low. An abdomen would seem unlikely to create a problem abdominocentesis was not performed preoperatively, which (Shoemaker et al. 2004) and appeared to be well tolerated would have provided a means of assessing mural vascular in this case.

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A curved bistoury (Fig 1) was used in this case to sever Acknowledgement the pedicle. The hooked blade of the bistoury could engage the rostral edge of the band after manual The authors thank Dr Steve Murphy for case referral and guidance into that position (Fig 2) without inclusion of other follow-up. structures beyond it. The tips of laparoscopic scissors could not be inserted between the rectum and band, whereas Authors’ declaration of interests the tip of the hook could be in this case. The risk with the fl hook was laceration of the rectal wall, especially as the No con icts of interest have been declared. pointed tip was directed towards the rectum (Fig 2). Directing the hook in the opposite direction would have Ethical animal research allowed the tip to engage the perirectal tissues, which might have prevented a clean transection. Also, this This article describes a procedure performed on a client direction of placement was impossible because of owned animal with owner consent. insufficient space between the band and the rectal wall to allow the hook to pass cranial to the constriction. The tip Source of funding was easily directed around the pedicle by a hand in the rectum, and was maintained outside the rectal wall at all None. times (Fig 2). Dissection to the level of the strangulation was deep and required repeated blunt dissection with scissors Antimicrobial stewardship policy and great care to maintain a safe and consistent plane of dissection, away from the rectal wall. Also, the dissection There was no use of any antimicrobial agents in this case. was deep enough to require repeated infiltration of local anaesthetic through the injection port of the laparoscopic Authorship scissors as the cranial limits of the original blocks were exceeded. All authors made substantial contributions to the surgery and In a previous report of a similar case, also in a mare to case management. All authors participated in preparation (Mason 1978), a lipoma encircling the rectum/small colon of the manuscript and gave final approval of the submitted was removed through a colpotomy in the proximal end of version of this case report. the vagina and directly over the point of strangulation. Once located, the lipoma was then twisted off its pedicle to release the obstruction (Mason 1978). The colpotomy was Manufacturer's address closed in that mare with Backhaus towel clamps (Mason 1Sontec Instruments, Centennial, Colorado, USA. 1978). It was not possible to insert a hand into the vagina of the mare in this report for reasons that were not apparent and not obviously related to her small size. In the previous References report, the mare was part Thoroughbred, and therefore of a Abuja, G.A., Garcıa-Lopez, J.M., Doran, R. and Kirker-Head, C.A. size that could facilitate vaginal insertion of a hand (Mason (2010) Pararectal cystotomy for urolith removal in nine horses. Vet. 1978). In retrospect, the lipoma in the mare of this report Surg. 39, 654-659. might have contributed to partial vaginal occlusion by Ahern, B.J. and Richardson, D.W. (2012) Surgical site infection and the compressing the vagina or by including it within its pedicle. use of antimicrobials. In: Equine Surgery, 4th edn. Eds: J.A. Auer However, the point of narrowing in the vagina seemed too and J.A. Stick, Elsevier, St. Louis. pp 68-84. far caudal to the site of obstruction in the rectum to support de Bont, M.P., Proudman, C.J. and Archer, D.C. (2013) Surgical lesions this explanation, and was closer to the level expected for a of the small colon and post operative survival in a UK hospital population. Equine Vet. J. 45, 460-464. partially persistent hymen. Unfortunately, the vagina was not examined after the strangulation was released to assess any Edwards, G.B. (1992) A review of 38 cases of small colon obstruction in the horse. Equine Vet. J. 24, Suppl.13, 42-50. effect the lipoma or its pedicle had on the vaginal lumen. Edwards, G.B. (1997a) Diseases and surgery of the small colon. Vet. The serendipitous result of failure to use the vaginal Clin. N. Am.: Equine Pract. 13, 359-375. approach was the development of a method that would Edwards, G.B. (1997b) Neoplasia in digestive pathology. Proceedings be applicable to a stallion or gelding. A potential limiting 5th Geneva Congress of Equine Medicine and Surgery, factor in completing this procedure would be a horse too Switzerland, Geneva. pp 67-72. ’ small to accommodate the surgeon s hand and arm in the Freeman, D.E. (2012) Rectum and anus. In: Equine Surgery, 4th edn. rectum. Eds: J.A. Auer and J.A. Stick, Elsevier, St. Louis. pp 494-505. This report underscores the observation that a tight luminal Garcia-Seco, E., Wilson, D.A., Kramer, J., Keegan, K.G., Branson, K.R., occlusion in the most oral part of the rectum that restricts Johnson, P.J. and Tyler, J.W. (2005) Prevalence and risk factors palpation beyond that point and causes acute colic in an old associated with outcome of surgical removal of pedunculated horse is probably caused by a pedunculated lipoma (Mason lipomas in horses: 102 cases (1987-2002). J. Am. Vet. Med. Assoc. 226, 1529-1537. 1978; Edwards 1992). In these cases, a standing procedure like that described in this report would allow transection of the Graham, S. and Freeman, D. (2014) Standing diagnostic and therapeutic equine abdominal surgery. Vet. Clin. Equine 30, 143- pedicle with long-handled instruments, such as the hooked 168. bistoury or laparoscopy scissors. The cost to the owner should Henneke, D.R., Potter, G.D., Kreider, J.L. and Yeates, B.F. (1983) be reasonable with this approach, especially if more Relationship between condition score, physical measurements and expensive procedures are not affordable. body fat percentage in mares. Equine Vet. J. 15, 371-372. Continued on page 600

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Clinical Commentary Surgical approaches to the equine abdomen F. Toth †* and J. Schumacher‡ †College of Veterinary Medicine, The University of Minnesota, St Paul, Minnesota; and ‡College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee, USA *Corresponding author email: [email protected]

Keywords: horse; celiotomy; pararectal; colpotomy; flank

Summary 1987; Hooper et al. 1993). The ability to explore even the Factors to consider when deciding on a surgical approach to caudalmost aspect of the abdomen of a horse through a explore the abdomen of a horse include facilities and pararectal approach was not determined by the authors of equipment available, experience of the surgeon, the accompanying article, because they were able to temperament of the horse and the necessity for cosmesis. An relieve the rectal constriction by inserting only the tip of a approach performed with the horse standing may be bistoury into the abdomen of the horse (Durket et al. 2019). necessary when anaesthesia or recovery from anaesthesia is Previously, the use of pararectal incision has been limited to considered risky or when the owner imposes a financial accessing the retroperitoneal portion of the bladder in limitation that does not allow surgery to be performed with standing, sedated horses to remove cystic calculi (Van the horse anaesthetised. Approaches performed with the Dongen and Plenderleith 1994; Abuja et al. 2010) and horse standing include the flank and colpotomy approaches. perirectal melanomas obstructing passage of faeces Each approach has benefits and risks inherent to it. (authors’ experience). The necessity for cosmesis or rapid return to function also influences the choice of the surgical approach. The scar Surgical approaches to the abdominal cavity of the horse resulting from a flank approach may be apparent, even include the vaginal, pararectal, flank, ventral midline, when the abdomen is explored using laparoscopic paramedian and diagonal paramedian celiotomies. The technique, especially if the wound fails to heal by first vaginal celiotomy is often referred to as a colpotomy. The intention. Exploring the abdomen through a vaginal pararectal approach described in the accompanying article approach avoids a cutaneous scar and provides rapid return (Durket et al. 2019) is a modification of the Gokel€ ’s approach to function. The scar left by a pararectal, paramedian, to the retroperitoneal portion of the bladder, described for oblique paramedian or ventral midline approach is removing a cystic calculus. The abdomen can also be inconspicuous, but with the exception of the pararectal explored using laparoscopic techniques, with the approach, the time between surgery and the horse’s return laparoscope and instruments inserted at the flank or ventral to function is much longer than when the abdomen is aspect of the abdomen. Abdominal exploration can be accessed using a vaginal approach. Colpotomy and performed with the horse anaesthetised, using any of the pararectal incisions are typically left unsutured, saving the above approaches, or with the horse standing, through a time and expense associated with primary closure. vaginal or flank celiotomy. The accompanying article is the Each approach to the abdomen can be accompanied first, to our knowledge, to describe a pararectal approach to by complications, some of which are inherent to the the abdomen. Although the approach, as described in the approach. The circumflex iliac artery may accidently be article, was inadequate to allow exploration of the transected, for example, when the abdomen is approached abdomen, it enabled the pedicle of a mass, suspected to be through the flank during conventional or laparoscopic a pedunculated lipoma, obstructing the rectum to be surgery. Inadvertent penetration of an abdominal viscus, such transected (Durket et al. 2019). as the large or small colon or bladder, and damage to the Facilities and equipment available for performing surgery cervix are reported complications of vaginal celiotomy (Moll with the horse anaesthetised and the financial limitation and Slone 1997). Another complication of this approach is imposed by the owner are important considerations when fatal haemorrhage, which can occur if the surgeon selecting an approach to the abdomen. Procedures perforates the vaginal branch of the uterine artery while performed with the horse standing avoid the inherent risks penetrating the fornix of the vagina to enter the abdomen. and cost associated with general anaesthesia. The The mare is at slight risk of evisceration after vaginal temperament of the horse, location and nature of the celiotomy, because the celiotomy is usually left unsutured. suspected lesion and the experience of the surgeon are also Adhesion of a viscus to the site of celiotomy, though factors that influence the decision whether exploration of the frequent, is seldom troublesome (Colbern and Reagan 1987). abdomen should be attempted with the horse standing. The The pararectal approach also has its inherent abdomen of a fractious horse is best explored with the horse complications and drawbacks. Anatomical structures located anaesthetised to protect the safety of the horse and the in the path of dissection include the internal pudendal artery surgeon. The colpotomy approach, usually performed with and vein, along with their branches, the ventral perineal and the horse standing and sedated, limits surgical exploration to caudal rectal arteries and veins. Preserving the pudendal the caudalmost aspect of the abdomen, making it unsuitable nerve and its branches is critical to maintain innervation of for addressing cranially located lesions (Colbern and Reagan the perineum and the anal sphincter, making pararectal

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dissection less straightforward than other approaches. An quicker, with the additional benefit of direct inspection of incision into the abdomen using the pararectal approach the lesion, by using laparoscopic technique. By using might also put the horse at risk of evisceration, if the incision is reusable laparoscopic equipment available in most referral large enough to allow introduction of a hand and arm into centres and by foregoing draping, the cost of disposable the abdomen. A factor unique to the pararectal approach is materials used during the surgery would have been minimal. that its difficulty is greatly influenced by the handedness of To make laparoscopic surgery economically feasible for an the surgeon and the location of the lesion. To facilitate economically disadvantaged owner, however, the careful dissection so that the lumen of the rectum is not veterinarian or hospital director must be willing to waive the entered, the surgeon ideally keeps his/her nondominant hand fee assigned to the use of the laparoscope. in the rectum while using the dominant hand to make the pararectal approach. Thus, if the lesion is located in the left Authors’ declaration of interests side of the abdominal cavity, as was the case in the study fl reported here (Durket et al. 2019), a right-handed surgeon No con icts of interest have been declared. may experience difficulty operating unwieldy, long-handled instruments necessary to complete dissection on the left side Ethical animal research of the rectum. In the study reported here (Durket et al. 2019), financial Not applicable. limitations posed by the client appear to be the primary factor driving the selection of the pararectal approach to resolve a Source of funding lesion constricting the peritoneal portion of the rectum. An approach through colpotomy was also considered, but None. apparent inability of the surgeon to insert his/her hand into the mare’s vagina eliminated this option. The authors also mention Authorship that approaching the lesion through a flank celiotomy was also considered but ultimately not selected, because the cost Both authors contributed equally to preparation of the fi associated with this procedure was perceived to be higher manuscript and both approve the nal version of the than the cost incurred using a pararectal approach. We manuscript. argue, however, that a celiotomy through a flank not only provides access to a larger portion of the abdomen, which in References this case turned out to be unnecessary, it also can be Abuja, G.A., Garcia-Lopez, J.M., Doran, R. and Kirker-Head, C.A. performed more quickly than a pararectal approach, and the (2010) Pararectal cystotomy for urolith removal in nine horses. Vet. difference in speed could offset the cost of draping and Surg. 39, 654-659. fl primary closure associated with the ank approach. Using a Colbern, G.T. and Reagan, W.J. (1987) Ovariectomy by colpotomy in modified grid technique to approach the abdomen through mares. Compend. Contin. Educ. Vet. 9, 1035-1038. fl the ank allows expeditious closure of the celiotomy, which is Durket, E., Albanese, V., Steward, S.K. and Freeman, D.E. (2019) A limited to apposing the external abdominal oblique muscle, standing pararectal approach to treat small colon obstruction by subcutaneous tissues and skin. We also contend that a flank a pedunculated lipoma. Equine Vet. Educ. 31, 594-598. celiotomy can be performed cleanly, with the horse standing, Hooper, R.N., Taylor, T.S., Varner, D.D. and Blanchard, T.L. (1993) Effects without draping the surgical site, provided a large area of the of bilateral ovariectomy via colpotomy in mares - 23 cases (1984- flank is prepared for aseptic surgery. Indeed, we believe that 1990). J. Am. Vet. Med. Assoc. 203, 1043-1046. the abdomen can be approached through a nondraped Moll, H. and Slone, D. (1997) Surgery of the ovaries. In: Large Animal flank incision at least as cleanly as approaching the abdomen Urogential Surgery, Eds: D. Wolfe and H. Moll. Williams & Wilkins, Baltimore. pp 137-141. through a nondraped pararectal incision. Van Dongen, P. and Plenderleith, R. (1994) Equine urolithiasis: surgical Releasing the constricting band around the peritoneal treatment by Gokels pararectal cystotomy. Equine Vet. Educ. 6, portion of the rectum likely could have been accomplished 186-188.

Continued from page 597

Mair, T.S. and Smith, L.J. (2005) Survival and complication rates in 300 Riley, E., Martindale, A., Maran, B., Mochal, C., Cooley, J., Linford, R., horses undergoing surgical treatment of colic. Part 1: short-term Read, R. and Rashmir-Raven, A. (2007) Small colon lipomatosis survival following a single laparotomy. Equine Vet. J. 37, 296-302. resulting in refractory small colon impaction in a Tennessee walking horse. Equine Vet. Educ. 19, 484-487. Mason, T.A. (1978) Strangulation of the rectum of a horse by the pedicle of a mesenteric lipoma. Equine Vet. J. 10, 269. Schumacher, J. and Mair, T.S. (2002) Small colon obstructions in the mature horse. Equine Vet. Educ. 14, 19-28. Prange, T., Holcombe, S.J., Brown, J.A., Dechant, J.E., Fubini, S.L., Embertson, R.M., Peroni, J., Rakestraw, P.C. and Hauptman, J.G. Shoemaker, R.W., Read, E.K., Duke, T. and Wilson, D.G. (2004) In situ (2010) Resection and anastomosis of the descending colon in 43 coagulation and transection of the ovarian pedicle: an alternative to horses. Vet. Surg. 39, 748-753. laparoscopic ovariectomy in juvenile horses. Can. J. Vet. Res. 68, 27-32.

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northamerica.covetrus.com | Toll-Free: 855.724.3461 Equine Dedicated: 855.472.4371 EQUINE VETERINARY EDUCATION 601 Equine vet. Educ. (2019) 31 (11) 601-608 doi: 10.1111/eve.13050

Original Article Equine retrobulbar disease: Diagnoses and outcomes of 15 horses with exophthalmos (1988–2017) K. E. Knickelbein† , B. J. Holmberg‡ and M. E. Lassaline*§ †Veterinary Medical Teaching Hospital, University of California, Davis, California; ‡Animal Eye Center of New Jersey, Little Falls, New Jersey; and §Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, USA *Corresponding author email: [email protected]

Keywords: horse; orbit; neuroendocrine tumour; cyst; aspergillosis; exenteration

Summary The current literature documenting equine exophthalmos Retrobulbar disease, while rare in horses, can pose a clinical is limited to individual case reports, short case series, and two challenge due to the advanced diagnostic procedures review articles. Thirty-eight cases of primary orbital disease necessary to determine the underlying aetiology and extent have been described and include 33 cases of neoplasia of disease. The goal of this study was to explore definitive (Bistner et al. 1983; Sweeney and Beech 1983; Bolton et al. causes of exophthalmos within a hospital population and 1990; Van Maanen et al. 1996; Basher et al. 1997; Goodhead investigate prognoses for the various aetiologies. et al. 1997; Rebhun and Del Piero 1998; Dixon and Head Retrospective medical record review was used to identify 15 1999; Hong et al. 1999; Baptiste and Grahn 2000; Colitz et al. horses diagnosed with a definitive cause of exophthalmos. 2000; Matiasek et al. 2007; Bischofberger et al. 2008; Miesner Patient signalment, disease duration, eye affected, diagnostic et al. 2009; Naylor et al. 2010), four cases of infectious and procedures, therapies, and histopathological diagnosis were inflammatory processes (Walde and Prosl 1976; Hubert et al. ~ evaluated. Geldings (12/15, or 80%) were over-represented 1996; Pearce et al. 2001), and one cystic process (Munoz (P = 0.014). Mean age at presentation (14 6.7 years) was et al. 2007). Twenty cases of orbital disease as an extension not significantly different for horses with (14 8.5 years) and of sinonasal disease have been published: 12 with neoplasia without (15 4.4 years) a diagnosis of neoplasia. Diagnosis of (Hill et al. 1989; Dixon and Head 1999; Davis et al. 2002; € a neoplastic process was made in 8/15 horses (53.3%) with Scotty et al. 2004; Dopke et al. 2005; Schaaf et al. 2007), five neuroendocrine tumour being most common. Eight of the 15 with infectious/inflammatory disease (Scott et al. 1974; cases were classified as primary orbital disease, and seven Roberts et al. 1981; Step et al. 1991; Kanda et al. 2007), two represented extension from paranasal sinus disease. Two with cystic disease (Barnett et al. 1988; Annear et al. 2008) novel diagnoses were identified: cystic hamartoma arising and one with a haematoma (Kafarnik et al. 2014). It is difficult from the lacrimal gland and orbital aspergillosis secondary to to make predictions about prognosis for survival for specific sinonasal disease. In total, eight of 12 horses for which follow- retrobulbar disease processes in horses when only data from up was available were euthanised due to orbital disease, two individual cases and small case series are available. immediately following computed tomography of the skull and The goals of this study were to (1) identify definitive six due to disease progression. One horse was euthanised causes of exophthalmos in horses, (2) determine whether following a peri-anaesthetic complication. Three horses were there was an association between age at presentation lost to follow-up. Of the 12 horses for which follow-up was or disease duration and prognosis for survival in horses available, only four (33.3%) were alive 21 months post- with exophthalmos; and (3) identify associations between diagnosis. Considering only patients for whom a definitive disease aetiology, treatment and outcome in horses with diagnosis was obtained, retrobulbar disease was associated exophthalmos. Understanding these relationships may help with a poor prognosis for life. guide predictions about prognosis for disease resolution and for survival, and thereby guide treatment decisions. Introduction Method Equine retrobulbar disease occurs rarely but can have significant impact, potentially affecting vision, use, and The electronic medical record system at the UC Davis William survival of the horse (Pucket 2017). Retrobulbar disease in R. Pritchard Veterinary Medical Teaching Hospital was horses presents a clinical challenge as a definitive diagnosis searched for horses who met three inclusion criteria: (1) (aetiology and location) requires advanced imaging having been presented during the years 1988–2017; (2) (computed tomography or magnetic resonance imaging) having had a clinical diagnosis of exophthalmos made; and followed by sampling or surgical techniques, which may be (3) having had a definitive histopathological diagnosis made. viewed as costly and invasive. Horses may maintain vision or Variables extracted from the medical record included perceived comfort until advanced stages of disease, and this patient age, sex, breed, duration of disease prior to may make veterinarians and owners more inclined to monitor presentation, as well as which eye was affected, ophthalmic disease progression, making delayed intervention unlikely to examination findings, diagnostic technique utilised, be curative and worsening prognosis for vision and possibly therapeutic interventions, and histopathological diagnosis. for life. Outcome was determined either from the medical record in

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cases of known euthanasia or via communication with the cystic glandular hamartoma (n = 1) and wooden foreign owner via phone or email, and survival time was calculated material (n = 1) comprised the non-neoplastic diagnoses. as the time between presentation and last known follow-up Aetiologies of the seven cases of secondary orbital disease, or euthanasia. For each included patient, disease was which in each case was an extension of paranasal sinus characterised as being either primary orbital or secondary disease, included neoplasia (n = 3), infection/inflammation (n (extension). Sex distribution and laterality of disease were = 2) and cyst (n = 2). Tumour types included lymphosarcoma analysed using binomial distribution, assuming an equal (n = 1), spindle cell sarcoma (n = 1), and undifferentiated number of males and females and an equal number of right carcinoma (n = 1). Aspergillus granulomas were diagnosed in and left eyes in the horse population in general. Descriptive two horses (one case of Aspergillus fumigatus was diagnosed statistics included means and standard deviations for via polymerase chain reaction and one case of Aspergillus normally distributed interval-scaled data, and medians and (Emericella) nidulans was diagnosed via fungal culture), and ranges for data that are not normally distributed. Differences paranasal sinus cysts were diagnosed in two horses. The between means were inferred using a t-test, and differences mean age of presentation for horses diagnosed with between medians were inferred using a Mann–Whitney U neoplasia (14 8.5) and for horses with non-neoplastic test. Significance was set at P<0.05. All statistics were diagnoses (15 4.4) were not significantly different performed using GraphPad Prism v7.04. (P = 0.077).

Therapies and outcomes Results Eleven of the 15 cases were approached surgically. Four horses Population statistics underwent exenteration, four underwent sinusotomy, and one Thirty-one horses met inclusion criteria of being presented underwent a globe-sparing mass excision via the supraorbital between the years of 1988 and 2017 with a clinical fossa. Foreign body removal and molar extractions were diagnosis of exophthalmos, however, only 15 (48.4%) met performed in one horse each. Follow-up information was the third criterion of having a histological diagnosis, and available for 12 horses. The horse diagnosed with a cystic therefore only 15 patients were included. The mean age at glandular hamartoma underwent globe-sparing mass excision presentation was 14 6.7 years. There were significantly (Figs 1 and 2) and was alive with a visual and apparently more males (n = 12) than females (n = 3) in the study comfortable affected globe 12 years post-operatively. One sample (P = 0.014), which was not representative of the horse diagnosed with a neuroendocrine tumour was alive general hospital population for the same time period (50.5% without clinical evidence of regrowth or metastasis 21 months geldings, 10.7% stallions, and 38.7% mares). Of the additional post-exenteration. The horse diagnosed with extraocular 16 cases presented for exophthalmos for which a definitive myopathy was euthanised 11 years post-exenteration due to histological diagnosis was not reached, 10 (62.5%) were colic and showed no evidence of recurrence of orbital disease. male, 3 (18.8%) were female, and sex was not listed for The horse diagnosed with haemangiosarcoma was euthanised three horses. Affected breeds included the Quarter Horse following luxation of the carpus during recovery from (4), Thoroughbred (3), American Paint Horse (2), and one anaesthesia. Two horses were euthanised while anaesthetised each of Appaloosa, Morgan Horse, Warmblood, Rocky for computed tomographic scanning which revealed Mountain Horse, Shetland Pony and Welsh Pony breeds. The inoperable disease due to invasion of the calvaria. The breed distribution for the study population was similar to that histological diagnosis for one horse was neuroendocrine tumour of the general hospital population. Duration of clinical signs and for the other horse was Aspergillus granuloma. The prior to presentation was reported for 12 horses, for which remaining six horses were euthanised at varying time points due the median was 90 days (range 3–1080 days). The right to progression of disease. The horses diagnosed with squamous globe was affected in nine horses, and the left globe was cell carcinoma and spindle cell carcinoma were euthanised affected in six horses (P = 0.15). Visual status of the affected within 1 week of diagnosis. The horse diagnosed with an globe was reported for 11 cases. Five globes were undifferentiated sinonasal carcinoma was euthanised 1 month evaluated as being visual, one had decreased vision and post-clinical diagnosis of exophthalmos and definitive diagnosis five were non-visual. was made on necropsy. The second case of paranasal sinus aspergillosis with orbital extension was euthanised 6 months Diagnostic procedures and histological diagnoses following histological diagnosis which was obtained via All but one of the horses underwent at least one modality of sinusotomy. One horse diagnosed with a paranasal sinus cyst diagnostic imaging, with many undergoing multiple modalities. was euthanised 7 years post-diagnosis due to extrusion of an Skull radiographs were performed in nine cases, orbital implant which was placed following sinusotomy to aid in closure ultrasonography was performed in nine cases, and computed of the deformed frontal bone. Follow-up was unavailable for the tomography was performed in five cases. Other commonly horse diagnosed with lymphosarcoma, and the remaining horses performed diagnostic procedures included complete blood diagnosed with paranasal sinus cyst (n = 1), and neuroendocrine count (12 horses), and oral examination accompanied by tumour (n = 1). Of the 12 horses for which follow-up was available, nasal or paranasal sinus endoscopy (five horses). only four (33.3%; one neoplastic, three non-neoplastic) survived Orbital disease was classified as primary in eight horses to 21 months post-diagnosis. Summaries of the included cases and secondary to sinonasal disease in seven horses. are provided in Tables 1 and 2. Aetiologies of primary orbital disease included neoplasia (n = fl 5), in ammation (n = 1), cyst (n = 1) and foreign material (n = Discussion 1). Tumour types identified included neuroendocrine tumour (n = 3), haemangiosarcoma (n = 1) and squamous cell The horse has a complete bony orbital rim composed of carcinoma (n = 1). Extraocular muscle myopathy (n = 1), the lacrimal, zygomatic, temporal and frontal bones. The

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a) b)

*

RL

c) d)

Fig 1: a) Clinical photograph of a 12-year-old Quarter Horse gelding with right-sided exophthalmos. Note the anterior displacement of the right globe and filling of the right supraorbital fossa. b) Transverse 5 mm CT image of the skull of the horse depicted in a). A cystic soft tissue mass (*) extends posterior to the right globe and results in bony deformation into the frontal sinus. c) Fluid obtained via US- guided fine needle aspiration of the cystic structure within the right orbit of the 12-year-old Quarter Horse gelding. d) Cyst following globe-sparing excision via the right supraorbital fossa. The histopathological diagnosis was a cystic hamartoma of lacrimal gland origin. medial wall of the orbit is also composed of bone, as the outside of the orbit with extension to the orbit either via local palatine and sphenoid bones provide separation of the invasion or metastasis. The frontal and lacrimal bones orbit from the calvarium (Hartley and Grundon 2017). In separate the equine orbit from the frontal sinus, and this close addition to a complete bony orbit, the horse possesses one association of the paranasal sinuses to the orbit is important of the largest globes of all mammals (Hartley and Grundon as exophthalmos can be a manifestation of sinonasal disease 2017). As such, any expansile space occupying lesion within (Hartley and Grundon 2017). Therapy for retrobulbar disease is the orbit will result first in a decreased ability to retropulse dependent upon definitive diagnosis and extent of orbital/ the globe, followed by displacement of the globe. extraorbital involvement, as well as visual status and Strabismus, which describes deviation of the visual axis from perceived comfort level. Therapy may range from medical the expected position, and exophthalmos, which describes therapy with systemically administered antimicrobial and/or anterior displacement of the globe within the orbit, are the anti-inflammatory drugs to sinusotomy, mass excision via the common clinical presentations of retrobulbar disease in supraorbital fossa, or exenteration. horses (Hartley and Grundon 2017). Vision loss may occur. In this study, 15 horses with orbital disease for which a Exophthalmos must be differentiated from buphthalmos, definitive histological diagnosis was reached are described. which describes an enlarged globe resulting from The significantly higher number of geldings (n = 12) than glaucoma. This determination can be made based on a mares (n = 3) may indicate that geldings are predisposed to comparison of the limbus to limbus horizontal corneal the development of orbital disease, although in previously diameter between the two eyes in a horse with a normal published cases of equine retrobulbar disease, sex was more contralateral globe. evenly distributed among cases with approximately 60% Retrobulbar disease is classified as primary if the tissue of being male and 40% being female (Scott et al. 1974; Walde origin is within the retrobulbar space, or secondary if arising and Prosl 1976; Roberts et al. 1981; Bistner et al. 1983;

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a) diagnosis diagnosis day) unrelated) at (unrelated) at (1 years) months) (12 (21 years- (11 Euthanised Euthanised NA Euthanised Euthanised Alive Alive Euthanised Outcome only. eye removal Orbitotomy None None Exenteration None FB Exenteration Exenteration Therapy affected ects CT CT CT fl re skull skull skull US US US, US, US US, US status radiographs, orbital radiographs, orbital Visual Orbital Orbital None Orbital Orbital Skull Skull/thoracic Orbital Imaging ultrasound.

b) vision Visual Visual Visual Blind Blind Blind Decreased Visual Visual status US, disease eye; eye left orbital OS, OD OD OS OS OS OD OD OD Affected eye; primary with right OD, Horse Horse Mountain horses Pony for Quarter Rocky Paint Welsh Thoroughbred Warmblood Thoroughbred Quarter Breed available; not outcome G G G G G G G G Sex NA, and 6 6 12 25 14 24 11 16 Age (years) gelding; diagnosis G, years months body; months months day months therapy, 2 3 NA NA 3 < 1 16 Duration 9 foreign ndings, fi

Fig 2: Post-operative photographs of a 12-year-old Quarter Horse FB, gelding 6 months following orbital cystic hamartoma excision via body, the right supraorbital fossa (same horse as Fig 1). a) Note the muscle cell gland) resolution of exophthalmos and return to normal anatomic clinical foreign position of the right globe. b) Note the return to a normal myositis, concavity of the right supraorbital fossa. hamartoma tomography; (lacrimal carcinoma tumour myopathy septic meningitis tumour tumour Cystic Squamous Haemangiosarcoma Neuroendocrine Extraocular Neuroendocrine Wooden Diagnosis Neuroendocrine

Sweeney and Beech 1983; Barnett et al. 1988; Hill et al. 1989; Signalment, 1: 6 5 4 3 7 2 8 Bolton et al. 1990; Step et al. 1991; Hubert et al. 1996; Van 1

Maanen et al. 1996; Basher et al. 1997; Goodhead et al. computed 1997; Rebhun and Del Piero 1998; Dixon and Head 1999; Case Case Case Case CT, TABLE Case Case Case Case

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Hong et al. 1999; Baptiste and Grahn 2000; Colitz et al. 2000; Pearce et al. 2001; Davis et al. 2002; Scotty et al. 2004; Dopke€ et al. 2005; Kanda et al. 2007; Matiasek et al. 2007; Munoz~ et al. 2007; Schaaf et al. 2007; Annear et al. 2008; Bischofberger et al. 2008; Miesner et al. 2009; Naylor et al. 2010; Kafarnik et al. 2014). The cases of the present study were divided nearly evenly between primary orbital (8/15) and secondary to Euthanised (3 days) Euthanised at diagnosis Euthanised (6 months) Euthanised (7 years) NA Outcome Euthanised (1 month) paranasal sinus disease (7/15), confirming the need for a thorough diagnostic evaluation of the entire skull with particular attention to the paranasal sinuses when evaluating horses with exophthalmos. Neoplasia comprised over half of the diagnoses, with the most prevalent tumour type in this population being a neuroendocrine tumour. This supports previous documentation of this tumour type as a common primary orbital neoplasm in the horse reconstruction intranasal cisplatin Sinusotomy Sinusotomy, facial Sinusotomy Therapy (Matiasek et al. 2007; Pucket 2017). This tumour can be invasive and result in bony destruction through the calvarium. Metastasis has been reported in only one case, ects affected eye only. fl with neoplastic tissue identified in the lung in addition to the orbit (Basher et al. 1997). The duration of exophthalmos prior to presentation for the horses of this study with neuroendocrine tumours treated by exenteration was 3 and 9 months, and for the case that was euthanised was orbital US skull CT nasal endoscopy 16 months, suggesting that delay in diagnosis and therapy worsens prognosis for life. Previous reports suggest that if surgical intervention via exenteration is implemented, recurrence is unlikely and overall prognosis may be good Visual status Imaging (Miesner et al. 2009). For cases in which osteolysis consistent with bony invasion is present, excisional surgery is unlikely to change survival time of the horse, and thus may not be indicated. OD Blind Orbital US, skull CT None OD NA Skull radiographs, Affected eye However, in the presence of refractory exposure keratitis, enucleation may be required to provide comfort and prevent progression of disease to globe rupture. Expulsive haemorrhage has been reported as a complication of exenteration as treatment of orbital neuroendocrine tumours (Miesner et al. 2009), and it was also the clinical impression of the surgeons of the cases presented in this study that there was significant blood loss, although no complications associated with systemic hypotension or hypoperfusion were observed. For the neoplastic diagnoses other than neuroendocrine tumour, survival time, even with treatment was less than 1 month from diagnosis. Two novel aetiologies of equine orbital disease are Age (years) Sex Breed 9 F Thoroughbred OD Blind Skull radiographs Exenteration, reported here and include one case of a cystic hamartoma of lacrimal gland origin and two cases of orbital aspergillosis as an extension of paranasal sinus infection. There are three previous reports of cystic disease-causing exophthalmos in horses which include a primary orbital dermoid cyst, and Duration > 2 weeks 15 G Paint 6 months 12 F Shetland Pony OS Visual Skull radiographs, NA < 15 months 27 G Thoroughbred OS NA Skull radiographs Molar extractionssecondary NA extension of hydatid and paranasal sinus cysts to the orbit (Barnett et al. 1988; Munoz~ et al. 2007; Annear ndings, therapy, diagnosis, and outcome for horses with orbital disease secondary to sinonasal disease

fi et al. 2008). The National Cancer Institute defines hamartoma as a benign growth made up of an abnormal mixture of cells and tissues normally found in the area of the body where the growth occurs. As these are thought to be developmental lesions, the slowly progressive nature of this mass was attributed to enlargement of the cyst over time carcinoma due to continued secretions, rather than growth of the Aspergillus fumigatus Diagnosis Aspergillus nidulans disorganised tissue. The affected horse remained alive and visual 12 years post-cyst excision, and this information combined with the good outcome of the horse diagnosed ~ Case 6 ParanasalCase sinus 7 cyst Paranasal sinus cyst 3 yearsCT, computed tomography; F, mare; G, 2 gelding; weeks NA, not available; OD, right 14 eye; OS, left eye; US, ultrasound. 15 Visual status re G F Quarter Horse Morgan OS NA Skull radiographs, Case 1 Undifferentiated Case 2Case 3 Lymphosarcoma Case 4 Spindle cell sarcoma 4 weeks 6 G Appaloosa OD NA Skull radiographs Sinusotomy TABLE 2: Signalment, clinical Case 5 with a primary orbital dermoid cyst (Munoz et al. 2007)

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Orbital disease caused by fungal organisms is uncommon a) in the horse, though Cryptococcus granulomas have been reported to invade the orbit via extension from the nasal cavity and paranasal sinuses (Scott et al. 1974; Roberts et al. 1981). Osteolysis and turbinate destruction associated with these infections is reported (Roberts et al. 1981). Aspergillus infection of the nasal cavity and guttural pouches has been reported, although reports of orbital aspergillosis are lacking in the horse (Cook et al. 1968; Greet 1981). Exophthalmos secondary to extension of sinonasal Aspergillus infection has been reported in cats and humans (Hora 1965; Hamilton et al. 2000; Barachetti et al. 2009). While aspergillosis isolated to the equine sinonasal region may have a good outcome with topical antifungal therapy (Greet 1981), the cases presented here, one of which was euthanised upon recognition of invasion of the calvarium via computed tomography and one which was euthanised due to the development of neurological signs 6 months following diagnosis, had poor b) outcomes. Only two cases of equine sinonasal fungal disease with orbital involvement are available in the literature. One horse was euthanised upon diagnosis of cryptococcosis via * cytology of a nasal swab and biopsy via the frontal sinus (Scott et al. 1974). A second case of orbital cryptococcosis had initial nasal signs with no orbital involvement and survived 26 months, at which time the horse was euthanised and early orbital RLinvolvement was diagnosed on necropsy (Roberts et al. 1981). Together, these cases suggest that mycotic sinonasal disease that has extended to involve the orbit carries a poor prognosis for survival in the horse. That the majority of cases (11/15) in this report were treated surgically was a direct reflection of the inclusion criterion of a definitive histological diagnosis, which necessitated either surgical biopsy or necropsy, and thus selected for cases that underwent a surgical treatment method. A definitive diagnosis was a requirement for inclusion c) in the study as one of the aims was to correlate diagnosis with treatment modality and outcome. However, it is important to consider the number of horses who were evaluated for exophthalmos for whom a definitive histological diagnosis was not reached. Within the defined time period (1988–2015), in addition to the 15 horses for whom a histological diagnosis was available, there were 16 horses with RLa clinical diagnosis of exophthalmos for whom a definitive histological diagnosis was not reached. These 16 horses underwent varying degrees of diagnostic work-up including complete blood count (6/16), chemistry profile (4/16), skull radiographs (8/16), nasal endoscopy (4/16), ocular/orbital ultrasonography (11/16), and computed tomography of the skull (6/16), however, a definitive histological diagnosis was not determined (Fig 3). Thus, for the 31 horses presented for Fig 3: a) Clinical photograph of a 17-year-old Quarter Horse gelding evaluation of exophthalmos during the study period, 48.4% fi with left-sided exophthalmos. Note that the left globe protrudes more received a de nitive diagnosis. anteriorly from the orbit compared to the right. b) and c) Transverse By adding the 15 cases of this study to those previously 2.5 mm CT images of the skull of the horse depicted in a). b) An described in the literature, conclusions based on aetiology extensive soft tissue mass (*) involving the left caudal maxillary sinus, of orbital disease may be proposed regarding prognosis for retrobulbar space, frontal sinus, sphenopalatine sinus, and survival. Regarding neoplasia within the orbit, early excision nasopharynx is seen. The left ethmoid turbinates are effaced. c) of neuroendocrine tumours (prior to invasion of bone) may Extension through the cribiform plate precluded surgical intervention. grant a good prognosis for life. Fluid resuscitation and whole A histopathological diagnosis was not obtained. blood transfusion should be available for these horses intra- and post-operatively due to the propensity for significant suggests that cystic causes of primary orbital disease in haemorrhage to occur during surgery. Other neoplastic horses may be granted a good prognosis for retention of lesions within the orbit, whether they arise from within or vision and survival of the horse if cyst excision is elected. spread there, likely carry a poorer prognosis for life. Fungal

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disease within the orbit appears to carry a poor prognosis the orbit, cerebrum, and multiple cranial nerves in a horse. J. Am. for life due to its propensity to induce osteolysis and invade Vet. Med. Assoc. 221, 1460-1463. the calvarium. With excision, primary orbital cystic lesions Dixon, P.M. and Head, K.W. (1999) Equine nasal and paranasal sinus may carry a good prognosis for maintenance of vision and tumours: part 2: a contribution of 28 case reports. Vet. J. 157, 279- 294. for life. Dopke,€ C., Grone,€ A., Borstel, M.V., Oppen, T.V., Boeve, M.H. and Baumgartner,€ W. (2005) Metastatic esthesioneuroblastoma in a Authors’ declaration of interest horse. J. Comp. Pathol. 132, 218-222. Goodhead, A.D., Venter, I.J. and Nesbit, J.W. (1997) Retrobulbar extra- fl No con icts of interest have been declared. adrenal paraganglioma in a horse and its surgical removal by orbitotomy. Vet. Comp. Ophthalmol. 7, 96-100. Ethical animal research Greet, T.R. (1981) Nasal aspergillosis in three horses. Vet. Rec. 109, 487- 489. No experimental animals were included in this study. Hamilton, H.L., Whitley, R.D. and McLaughlin, S.A. (2000) Exophthalmos secondary to aspergillosis in a cat. J. Am. Anim. Hosp. Assoc. 36, 343-347. Sources of funding Hartley, C. and Grundon, R.A. (2017) Diseases and surgery of the None. globe and orbit. In: Equine Ophthalmology, 3rd edn., Ed: B. Gilger. John Wiley & Sons Inc, Hoboken, New Jersey. pp 151-196. Hill, F.W., Moulton, J.E. and Schiff, P.H. (1989) Exophthalmos in a horse Acknowledgements resulting from an adenocarcinoma of the frontal sinus. J. S. Afr. Vet. Assoc. 60, 104-105. The authors acknowledge K. Tomo Wiggans, DVM, MEng, Hong, C.B., Van Meter, P.W. and Latimer, C. (1999) Malignant DACVO for their contributions of clinical images. The authors rhabdoid tumour in the orbit of a horse. J. Comp. Pathol. 121, 197- also acknowledge the UC Davis Veterinary Medical Teaching 201. Hospital’s Anatomic Pathology Service for their analyses of Hora, J.F. (1965) Primary aspergillosis of the paranal sinuses and the cases as well as the Diagnostic Imaging Services, Equine associated areas. Laryngoscope 75, 768-773. Surgery Service, and Comparative Ophthalmology Service for Hubert, J., Williams, J., Hamilton, H.L., McClure, J.J. and Partington, B.P. their clinical management of the cases. (1996) What is your diagnosis? Chronic retrobulbar abscess in a horse. J. Am. Vet. Med. Assoc. 209, 1703-1704. Kafarnik, C., Donaldson, D., Payne, R. and Holloway, A. (2014) Authorship Intradiploic hematoma of the frontal bone with secondary exophthalmos in a mare. Vet. Ophthalmol. 17, 168-173. K.E. Knickelbein, B. Holmberg and M.E. Lassaline participated in the study design, study execution, data analysis and Kanda, T., Hikasa, Y., Naota, M., Morita, T., Shimada, A. and Amaya, T. (2007) Exophthalmos caused by chronic sinusitis in a horse: a case interpretation, and preparation of the manuscript. of exophthalmos caused by sinusitis. J. Equine. Vet. Sci. 27, 539- 541. References Matiasek, K., Cronau, M., Schmahl, W. and Gerhards, H. (2007) Imaging features and decision making in retrobulbar Annear, M.J., Gemensky-Metzler, A.J., Elce, Y.A. and Stone, S.G. (2008) neuroendocrine tumors in horses - case report and review of Exophthalmos secondary to a sinonasal cyst in a horse. J. Am. Vet. literature. Transbound. Emerg. Dis. 54, 302-306. Med. Assoc. 233, 285-288. Miesner, T., Wilkie, D., Gemensky-Metzler, A., Weisbrode, S. and Colitz, Baptiste, K.E. and Grahn, B.H. (2000) Equine orbital neoplasia: a review C. (2009) Extra-adrenal paraganglioma of the equine orbit: six of 10 cases (1983-1998). Can. Vet. J. 41, 291-295. cases. Vet. Ophthalmol. 12, 263-268. Barachetti, L., Mortellaro, C.M., Di Giancamillo, M., Giudice, C., Munoz,~ E., Leiva, M., Naranjo, C. and Pena,~ T. (2007) Retrobulbar Martino, P., Travetti, O. and Miller, P.E. (2009) Bilateral orbital and dermoid cyst in a horse: a case report. Vet. Ophthalmol. 10, 394-397. nasal aspergillosis in a cat. Vet. Ophthalmol. 12, 176-182. Naylor, R.J., Dunkel, B., Dyson, S., Paz-Penuelas, M.P. and Dobson, J. Barnett, K.C., Cottrell, B.D. and Rest, J.R. (1988) Retrobulbar hydatid (2010) A retrobulbar meningioma as a cause of unilateral cyst in the horse. Equine Vet. J. 20, 136-138. exophthalmos and blindness in a horse. Equine Vet. Educ. 22, 503- 510. Basher, A.W., Severin, G.A., Chavkin, M.J. and Frank, A.A. (1997) Orbital neuroendrocrine tumors in three horses. J. Am. Vet. Med. Pearce, S.G., Boure, L.P., Taylor, J.A. and Peregrine, A.S. (2001) Assoc. 210, 668-671. Treatment of a granuloma caused by Halicephalobus gingivalis in a horse. J. Am. Vet. Med. Assoc. 219, 1735-1738. Bischofberger, A.S., Konar, M., Posthaus, H., Pekarkova, M., Grzybowski, M. and Brehm, W. (2008) Ocular angiosarcoma in a pony - MRI Pucket, J.D. (2017) Equine orbital disease: a review. Equine Vet. Educ. and histopathological appearance. Equine Vet. Educ. 20, 340-347. 29, 452-458. Bistner, S., Campbell, R.J., Shaw, D., Leininger, J.R. and Ghobrial, H.K. Rebhun, W.C. and Del Piero, F. (1998) Ocular lesions in horses with (1983) Neuroepithelial tumor of the optic nerve in a horse. Cornell. lymphosarcoma: 21 cases (1977-1997). J. Am. Vet. Med. Assoc. Vet. 73, 30-40. 212, 852-854. Bolton, J.R., Lees, M.J., Robinson, W.F., Thomas, J.B. and Klein, K.T. Roberts, M.C., Sutton, R.H. and Lovell, D.K. (1981) A protracted case of (1990) Ocular neoplasms of vascular origin in the horse. Equine cryptococcal nasal granuloma in a stallion. Aust. Vet. J. 57, 287-291. Vet. J. 22, Suppl. 10, 73-75. Schaaf, K.L., Kannegieter, N.J. and Lovell, D.K. (2007) Calcified Colitz, C.M.H., Gilger, B.C. and Davidson, M.G. (2000) Orbital fibroma tumours of the paranasal sinuses in three horses. Aust. Vet. J. 85, in a horse. Vet. Ophthalmol. 3, 213-216. 454-458. Cook, W.R., Campbell, R.S.F. and Dawson, C.O. (1968) The pathology Scott, E.A., Duncan, J.R. and McCormack, J.E. (1974) Cryptococcosis and aetiology of guttural pouch mycosis in the horse. Vet. Rec. 83, invovling the postorbital area and frontal sinus in a horse. J. Am. 422-428. Vet. Med. Assoc. 165, 626-627. Davis, J.L., Gilger, B.C., Spaulding, K., Robertson, I.D. and Jones, S.L. Scotty, N.C., Ford, M., Williams, F. III, Loiacono, C., Johnson, P.J., (2002) Nasal adenocarcinoma with diffuse metastases involving Messer, N.T. IV, Turnquist, S.E. and Essman, S. (2004) Exophthalmia Continued on page 616

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Review Article Equine eosinophilic keratitis: An emergent ocular condition? S. Gonzalez-Medina Comparative Neuromuscular Laboratory, Royal Veterinary College, London, UK Corresponding author email: [email protected]

Summary 2008; Dean and Meunier 2013). In humans, vernal Eosinophilic keratitis (EK) is considered an immune mediated keratoconjunctivitis has a gender and age predisposition, disorder associated with an underlying type I or IV with young males most commonly affected (Bonini et al. hypersensitivity reaction to parasitic or environment allergens. 2000). Prevalence is higher in dry hot climates with marked It is believed that the persistency of inflammatory mediators seasonal presentation (Leonardi 2002; Kumar 2009). One third and recruitment of eosinophils into the conjunctival tissue of affected patients have concurrently multiple atopic have detrimental effects on the corneal surface. Epithelial diseases, with asthma being the most common (Tuft et al. cells are consequently damaged, particularly by eosinophilic 1998; Bonini et al. 2000). In horses, the disease has been toxic proteins, which determine the lack of epithelial healing increasingly recognised in the last 10 years, with several and plaque formation. Although some clinical signs are studies looking into clinical presentation, treatment response common to other corneal diseases, the location of the lesion, and epidemiological factors (Utter et al. 2014; Edwards et al. presence of corneal plaques and time of the year, may help 2015; Gonzalez-Medina et al., unpublished data). There is no practitioners to identify EK. Topical therapy with steroids or sex, breed or age predisposition, although in the latest case immune-modulators seems to be the most effective treatment series by Edwards et al. (2015), mares were most frequently in small, localised lesions while large epithelial defects will affected. A clear seasonal component is present in horses, benefit from a thorough debridement and/or early with summer being the most prevalent (Utter et al. 2014; keratectomy, before secondary microbial infection may Edwards et al. 2015). Urticaria was anecdotally described in occur. three horses but the link with EK in those cases remains unclear (Utter et al. 2014). Generally, affected horses are in Introduction good health, correctly vaccinated, wormed and they have followed an appropriate diet when the diagnosis was made Eosinophilic keratitis (EK) and/or keratoconjuctivitis was first (Utter et al. 2014; Edwards et al. 2015) (Fig 1). documented in horses as such in 1994 in the USA (Ramsey et al. 1994). However, earlier reports of ocular onchocerciasis Eosinophils and immunity: insights on EK in the 1970s might refer to the same condition (Schmidt et al. pathophysiology 1982; Munger 1983) although the presence of microfilariae in cytological samples is an inconsistent finding nowadays. EK is Eosinophils comprise about 1–6% of the total white blood cells considered an immune mediated disorder associated with an pool and they are easy to recognise in cytological and underlying type I or IV hypersensitivity reaction to parasitic or histological samples for their fine and pink granulated environment allergens (Brooks 2004; Utter et al. 2013). The cytoplasm. They reside naturally in the brain, bowel, female complex immunological network established between reproductive system and lymphoid tissue and they are conjunctiva and cornea seems to play a central role in considered pathologic when found in other tissues (Davoine perpetuation and exacerbation of the inflammatory process and Lacy 2014). with sometimes catastrophic consequences for corneal tissue Eosinophils develop from myeloid precursor cells located (Solomon et al. 2004). Perhaps EK should be considered an in the bone marrow under TH2 cytokines influence, particularly ocular syndrome rather than a true disease, as it is possible IL-5 (Mould et al. 1997). They have a limited life span in the that several aetiological factors might contribute to circulation around 8–18 h, which is extended to 3–4 days in eosinophil migration in this tissue. tissues (Davoine and Lacy 2014). Similar to neutrophils, they are Eosinophilic keratitis has been described in several animal terminally end-differentiated cells programmed to undergo species (Chisholm 1989; Yamagata et al. 1996; Andrew 2001; apoptosis after cessation of triggering stimuli. Its persistence in Naisse et al. 1998; De Geyer and Raymond-Letro 2009; the tissues is enhanced by the presence of cytokines that Grinninger et al. 2012), but extensively studied in humans and prolong eosinophil survival by inhibiting apoptosis (Walsh 2013). cats. Feline eosinophilic keratitis does not have age, breed or The understanding of the immunological role of these sex predilection, although it has been reported most eosinophils has continuously evolved in the past decades, from frequently in young castrated males (Paulsen et al. 1987; primarily a homeostatic role in the defence against helminth Morgan et al. 1996) and no seasonal occurrence seems to parasitic infections to an effective modulator of type I exist. Initial presentation, in the majority of cases, is unilateral hypersensitivity reactions (allergy). Currently, emerging roles in although it eventually becomes bilateral (Paulsen et al. 1987; cancer and antiviral host defence immunomodulation Morgan et al. 1996; Dean and Meunier 2013) and the highlight the complexity of the biological contribution of potential link with feline herpesvirus remains unclear (Nasisse eosinophils to the immune response (Jacobsen et al. 2012; et al. 1998; Townsend et al. 2004; Stiles and Pogranichniy Davoine and Lacy 2014).

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a) b)

Fig 1: Notice the similarity in clinical presentation of both species, cat on the left and horse on the right. Raised white/pinkish plaques are often seen in eosinophilic keratitis as well as devitalised and loose epithelium. (Images are courtesy of P. McElroy (A) and D. Donaldson (B)).

Eosinophils produce and release in targeted tissues to exacerbate tissue destruction by releasing chemokines and different toxic substances and effectors such as granule further activating neutrophils, which adversely interfere with proteins, enzymes, reactive oxygen species, and eicosanoids. the anchoring of regenerating corneal epithelial cells (Gleich Among them, eosinophil major basic protein, eosinophilic et al. 1979; Trocme et al. 1997). Chronic deposition of this cationic protein and matrix metalloproteinase (MMP-9) are protein over the denuded epithelium, sometimes reaching the the most important implicated in corneal disease (Gleich epithelial basement membrane, is known to prompt the et al. 1979; Trocme et al. 1993; Kumagai et al. 2000). The first formation of dense plaques that will feedback and encourage two named proteins exert direct epithelial cytotoxicity on the the release of more inflammatory mediators, hence corneal surface (Trocme et al. 1993; Trocme and Aldave perpetuating the corneal damage. 1994) while the latter degrades components of the corneal Microbial infection may complicate the initial aseptic basement membrane and stroma (Kumagai et al. 2000). ulcer and aggravate corneal damage as a result of delayed The sequence of events that trigger eosinophilic keratitis is, re-epithelialisation (Kerr and Stern 1992; Sridhar et al. 2003). relatively, well-understood in human medicine where In horses, approximately 35% presented with concurrent conjunctival inflammation seems to play a pivotal role in infection, by bacteria and/or fungi (Utter et al. 2014; Edwards subsequent corneal injury (Fukuda and Nishida 2010; Solomon et al. 2015) while in humans this figure is significantly lower, et al. 2004). Mast cells are the key cellular component for around 10% (Reddy et al. 2013). initiating the inflammatory cascade in the conjunctiva In equids, environmental factors have been suggested to facilitating the accumulation and activation of eosinophils in play a major role in the development of the disease, however, this tissue by releasing heparin that stabilises eotaxins, and IL-3 no strong evidence is currently available. In one case series, and 5 that lengthen eosinophil survival in tissues. Conjunctival the use of fly masks and/or fly repellents led to resolution of spill over of cells and mediators in the tear film facilitate the clinical signs (Utter et al. 2010). Other authors have suggested exposure of the corneal surface to eosinophilic proteins, which the release of Onchocerca larvae following deworming as a damage corneal epithelium (Leonardi 2002). The persistence potential trigger (Gilger 2013) or linked the presence of of eosinophil major basic protein on the corneal surface seems eosinophils in external ocular structures to Thelezia spp.,

Macroerosions with Conjunctivitis Punctate erosions Elevated plaques Coarse lesions translucent base, ± yellow/whitish deposits Fig 2: Proposed mechanism for the progression of eosinophilic keratitis based on human studies. The conjunctival tissue is stimulated; some of the suggested triggers are represented in the figure (pollens, microfilariae, insects or viruses). The presence of inflammatory mediators and recruitment of inflammatory cells in the conjunctival tissue affects directly corneal epithelial cells creating small defects. The persistency of toxic proteins on corneal surface determines the extensive damage of epithelial cells and the progression towards stromal layers ending by formation of inflammatory deposits and elevated plaques.

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a) b)

c)

Fig 3: a) Sites for nerve blocks used to perform minor procedures in the eye. b) Collection of cytology sample with a cytobrush. c) Microphotography of eosinophils found in a corneal cytology of a horse affected by EK. 603 oil immersion. Notice the granules contained within the cytoplasm. Sometimes these granules may be visualised loose among other inflammatory cells. How to perform corneal cytology: (i) Sedate the horse according to its behaviour. (ii) Perform local nerve blocks: auriculo-palpebral (motor), frontal nerve (sensitive upper lid) with 2% mepivacaine, 0.3 mL per site. Wait 5 min (a). (iii) Apply 2-4 drops of Proxymethacaine tetracaine hydrochloride 0.5% eye-drops in the area to sample and wait 1-2 min before sampling. Remember that if you are also taking samples for culture and sensitivity, you should take them before applying topical anaesthesia. (iv) Prepare and label 1-2 microscope slides. (v) Use a cytobrush for a better yield of cells in your sample; gently roll the brush on the sampling area (b). The blunt side of a scalpel blade or a Kimura spatula can also be used. Avoid cotton buds as the quality of the samples tends to be poor. (vi) Apply the cytobrush to the microscope slide by rolling it over the length of the side. (vii) Let the sample air dry. (viii) Protect the microscope slide(s) in a plastic case. (ix) Diff-quick or Wright Giemsa are the preferred methods for cytology staining (c). (x) Use a microscope with 20-403 magnification, which will allow to easily identify the granules of the eosinophils. Be patient, usually few eosinophils are present, so examine the slide thoroughly. If you do not feel confident, send the slides to a specialised laboratory. [Correction added on 20 Jun 2018, after first online publication: Part of the Figure 3 legend was previously omitted and has been rectified in this version]

Habronema spp., and Ochocerca spp. (Schmidt et al. 1982; only recorded in around 25% of cases (Utter et al. 2014; Ramsey et al. 1994; Munger 1983). Recently, Edwards et al. Edwards et al. 2015). Giant papillae in the tarsal/limbal (2015) tried to correlate climatological conditions, such as solar conjunctiva is a cardinal sign in humans, but it has only been radiation and humidity, with the development of EK without described anecdotally in equids (Jennings 2007; Wolfe et al. success. Despite the high incidence of herpes virus infection in 2010). Any aseptic nonhealing ulcer should be assessed horses, the role that these viruses may play in ocular conditions cytologically in order to rule out EK. Unfortunately, false is still controversial. In cats between 33 and 76% of eyes negatives can occur, as eosinophils are more likely to migrate presenting with EK tested also positive for Feline Herpes virus I into stroma layers in chronic cases (Trocme et al. 1993), from (Morgan et al. 1996; Nasisse et al. 1998), but again, whether where they keep releasing chemotoxic molecules that that reflects a trigger factor or the opportunistic reactivation of prevent epithelial healing. These cases can be challenging to a latent infection is on debate. Likewise, the evidence diagnose by cytology, and almost inevitably necessitate supporting the involvement of viruses in equine EK is very slim. keratectomy for histological confirmation. Clinical signs and Bovine papillomaviruses types 1 and 2 DNA and oncogene E5 the presence of eosinophils in corneal scrapes therefore, transcript were identified in a mare affected by EK (Kainzbauer support diagnosis of the condition (Fig 3). Lack of et al. 2008), but its real link with the condition remains unclear. standardised diagnostic criteria has been suggested to be The use of more sophisticated tools in laboratory diagnosis may detrimental for early diagnosis and successful treatment in help to unravel the aetiology of many idiopathic conditions humans (Kumar 2009). Clinical grading seems to be of help for but the results should be interpreted with care (Fig 2). physicians when treating the condition in human patients (Cameron 1995; Bonini et al. 2000) but it has received little Clinical signs interest in veterinary medicine. Common locations in horses include ventral-medial (under the third eyelid) and ventral- The clinical signs displayed depend on the stage of the lateral (Gilger 2013). Recent work in the UK evidenced two disease and perhaps the trigger factor. Main clinical signs distinctive and frequent clinical presentations in horses include blepharospasm, epiphora, conjunctival hyperaemia (Gonzalez-Medina et al., unpublished data): and corneal ulceration, although all of those are nonspecific. Localised nonprogressive (Fig 4): Characterised by Caseous yellow discharge, yellow/whitish infiltrative deposits minimal corneal involvement and ocular pain, usually lesions and/or corneal plaques are probably pathognomonic but are located around the third eyelid margin and they are

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a) b)

c) d)

Fig 4: Localised lesions. Notice the well-circumscribed corneal injury with either irregular borders and a translucent base or small- elevated plaques. Although often found around the third eyelid margin, other perilimbal locations can be seen. (Images courtesy of the Animal Health Trust, with special thanks to referring veterinarians: Mr. N.M. Wilson (a), Dr. F. Malalana (b), Mrs. H. Shearcroft (c) and Mr. R. Demsen (d). Figure c was also included in ‘Eosinophilic keratitis’ in Equine Health [2015] 26, pp. 20-21).

a) b)

c) d)

Fig 5: Progressive extensive presentation. Notice the large lesions that present with moderate oedema, loose epithelium and can be either superficial or deeper affecting the stroma or forming thick plaques that usually reach the epithelial basement membrane. (Images courtesy of the Animal Health Trust, with special thanks to referring veterinarian Mr. T. Sainty (d). Image b was also included in ‘Eosinophilic keratitis’ in Equine Health [2015] 26, pp. 20-21).

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concentrations might only affect epithelial migration (Trocme et al. 1993).

Treatment options Effective treatment is still debatable in horses due to the lack of firm evidence, and usually relies on personal experience and preference of the clinician. Topical steroids seem to be beneficial in the early stages despite corneal ulceration, but superficial keratectomy to remove plaques and/or inflammatory debris is known to obtain the best results in terms of shorter recovery period, not only in horses (Yamagata et al. 1996; Brooks 2004; Kafarnik 2010) but also in humans (Reddy et al. 2013). This success may be explained by the removal of eosinophil granule major basic protein lodged in the ulcer, which has a major impact in ulcer healing. Additionally, diamond burr debridement has also been suggested to enhance epithelial healing in horses with Fig 6: Multifocal presentation. Notice the small caseous foci refractory healing ulcers (Utter et al. 2014) and it could be a spread over the nasal perilimbar region on this cornea, marked corneal oedema and conjunctival hyperaemia (Image courtesy less invasive option for shallow ulcers. Generally, topical of the Animal Health Trust. This figure was also included in immunosupresive therapy, either corticosteroids and/or ‘Eosinophilic keratitis’ in Equine Health [2015] 26, pp. 20-21). immunomodulators (cyclosporine A, tacrolimus) is used as a first line therapy, but resolution could be prolonged for several weeks (Pucci et al. 2005; Lambiase et al. 2011; Fukushima reported as chronic/long standing non-healing ulcers. In et al. 2014); averaged time with topical therapy in horses is some cases, a small, white/cream plaque that quickly 4 months (Utter et al. 2013; Edwards et al. 2015). Topical detaches from the corneal bed can be seen. steroids are naturally the most effective therapy as they help Progressive extensive (Fig 5): Characterised by marked to restore the corneal damage induced by epithelial toxic ocular pain with extensive lesions that progress rapidly axially, mediators produced by eosinophils and neutrophils (Bonini generally from the periphery towards the central cornea. et al. 2004). However, its use should be limited to aseptic These lesions are more likely to form corneal plaques and get ulcers and carefully monitored. Ocular preparations that complicated with microbial infections, perhaps due to the contain both, a steroid and broad antibiotic, may be a safer extension of the epithelial impairment. Involvement of the option if the veterinarian is in doubt of concurrent microbial stromal layers is possible and should be considered in infection. Cyclosporine A and/or calcineurin inhibitors refractory cases. (Tacrolimus, Picrolimus) are a valid alternative to steroids and Additionally, another form presented infrequently is the they have shown remarkable success in allergic and immune- superficial multifocal (Fig 6), in which multiple caseous foci mediated ocular diseases in humans (Secchi et al. 1990; are spread over the corneal surface, although with Leonardi et al. 1998; Miyazaki et al. 2008), cats (Spiess et al. preference for perilimbar locations. Corneal oedema usually 2009), dogs (Read 1995; Berdoulay et al. 2005; Hendrix et al. occurs from moderate to severe. 2011) and horses (Graztek et al. 1995; Gilger et al. 2005; Disparity in tissue response due to eosinophilic presence Matthews and Gilger 2009). Some topical nonsteroidal drugs, has been previously reported, however, the mechanisms such as ketorolac, diclophenac or indomethacin, behind are unknown (Dixon et al. 2006; Walsh 2013). demonstrated positive effects in reducing itching and Differences in eosinophil recruitment are most likely expression of inflammatory mediators in the tear film in linked to different concentrations of eosinophil granule humans (Gupta et al. 1999; Sharma et al. 1997; D’Angelo major basic protein; high concentrations inhibit both et al. 2003). However, they have been suggested to epithelial migration and protein synthesis, whereas low enhance eosinophilic disease in the horse (McEwan 1990;

a) b)

Fig 7: Notice the deep pigmentation surrounded by moderate fibrosis in both cases. (Images courtesy of the Animal Health Trust with special thanks to referring veterinarian Mr. A. McGladdery (A).

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Brooks et al. 2016). Mast cell stabilisers, which have an Conclusion antieosinophilic effect, such as NAAGA and Iodoxamine, help to control the progression of clinical signs and relieve Eosinophilic keratitis has become relatively common in symptomatology in humans at an early stage, but they have horses, particularly in the summer months. Practitioners been used unfrequently in veterinary medicine. should consider it when raised plaques or deposits are Some oral medications seem to improve clinical signs present on the cornea as well as in chronic nonhealing and/or re-occurrence. Aspirin is consistently reported in the ulcers. Treatment with topical medication can be lengthy fi literature as the most effective NSAIDs treatment in humans but successful; however, super cial keratectomy should be (Abelson et al. 1983; Chaudhary 1990). Megestrol acetate is discussed with horse owners early on the course of the known to effectively control eosinophilic keratitis in cats, disease. although it is only used in refractory cases due to its numerous side effects (Paulsen et al. 1987; Plumb 2008; Spiess References et al. 2009). In horses, a short course of systemic steroids Abelson, M.B., Butrus, S.I. and Weston, J.H. (1983) Aspirin therapy in seemed to shorten resolution time in one study (Utter et al. vernal conjunctivitis. Am. J. Ophthalmol. 95, 502-505. 2013), however, this was still lengthy (average 2 months), and Andrew, S.E. (2001) Ocular manifestations of feline herpesvirus. J. the variable dosing regimen precludes establishment of a Feline Med. Surg. 3, 9-16. therapetical protocol at the moment. Ceterizine is an H1- Berdoulay, A., English, R.V. and Nadelstein, B. (2005) Effect of topical fi receptor antagonist that reduces tissue in ltration with 0.02% tacrolimus aqueous suspension on tear production in dogs eosinophils, but had little effect in severely affected patients with keratoconjunctivitis sicca. Vet. Ophthalmol. 8, 225-232. (Leonardi 2002). Despite good bioavailability after oral Bonini, S., Bonini, S., Lambiase, A., Marchi, S., Pasqualetti, P., Zuccaro, administration in horses (Olsen et al. 2007), this medication O., Rama, P., Magrini, L., Juhas, T. and Bucci, M.G. (2000) Vernal failed to reduce the signs associated with insect-bite keratoconjunctivitis revisited. A case series of 195 patients with long-term follow up. Ophthalmology 107, 1157-1163. hypersensitivity in one study (Olsen et al. 2011) but Utter et al. (2013) showed that this drug reduced significantly the re- Bonini, S., Coassin, M., Aronni, S. and Lambiase, A. (2004) Vernal keratoconjunctivitis. Eye 18, 345e51. occurrence of eosinophilic keratitis in horses although it did fl not shorten recovery time. Brooks, D.E. (2004) In ammatory stromal keratopathies: medical management of stromal keratomalacia, stromal abscess, In human medicine, treatment choice depends on eosinophilic keratitis, and band keratopathy in the horse. Vet. Clin. clinical grading of the lesion (Cameron 1995; Lin et al. 2013). North Am. Equine Pract. 20, 345-360. For ulcers with a transparent base medical treatment allows Brooks, D.E., Matthews, A. and Clode, A.B. (2016) Diseases of the rapid re-epithelialisation. In contrast, more advanced lesions cornea. Equine ophthalmology. In: Equine Ophthalmology. 3rd benefit from an early keratectomy. The downside of ed., Ed: B.C. Gilger. John Wiley & Sons Inc, Ames, IO. pp. 252-292. keratectomy is the corneal defect created that would Cameron, J.A. (1995) Shield ulcers and plaques of the cornea in require topical therapy for several days/weeks, depending on vernal keratoconjunctivitis. Ophthalmology 102, 985-993. lesion size, in order to avoid microbial infections. Nevertheless, Chaudhary, K.P. (1990) Evaluation of combined systemic aspirin and healing time usually ranges from 1 week to 10 days post cromolyn sodium in intractable vernal catarrh. Ann. Ophthalmol. 22, 314-318. surgery. Amniotic grafting is recommended in large corneal defects and/or those that involve the resection of epithelial Chisholm, W.H. (1989) Feline eosinophilic keratitis. Can. Vet. J. 30, 438. basement membrane. This grafting will serve as a basement D’Angelo, G., Lambiase, A., Cortes, M., Sgrulletta, R., Pasqualetti, R., membrane, facilitating migration of epithelial cells and Lamagna, A. and Bonini, S. (2003) Preservative-free diclofenacsodium 0.1% for vernal keratoconjunctivitis. Graefes promoting adhesion of basal cells (Lee and Tseng 1997; Lin Arch. Clin. Exp. Ophthalmol. 241, 192-195. et al. 2013). In the author’s experience topical therapy is most Davoine, F. and Lacy, P. (2014) Eosinophil cytokines, chemokines, and “ ” effective in the previously called localised-nonprogressive growth factors: emerging roles in immunity. Front Immunol. 5, 570. clinical presentation, particularly topical steroids and/or De Geyer, G. and Raymond-Letro, I. (2009) Canine chronic keratitis cyclosporine administered as ointment. Superficial with eosinophilic infiltrate: a retrospective study of 28 cases (2004– debridement of the ulcer’s bed prior to initiating topical 2007). Abstracts: 40th Annual Meeting of the American College of therapy can also reduce significantly the resolution time. The Veterinary Ophthalmologists. Vet. Ophthalmol. 12, 390-409. debridement can be performed either with the blunt end of Dean, E. and Meunier, V. (2013) Feline eosinophilic a scalpel or more effectively with a diamond blur device. keratoconjunctivitis: a retrospective study of 45 cases (56 eyes). J. Feline Med. Surg. 15, 661-666. Dixon, H., Blanchard, C., deSchoolmeester, M.L., Yuill, N.C., Christie, Reoccurrence and sequelae J.W., Rothenberg, M.E. and Else, K.J. (2006) The role of Th2 cytokines, chemokines and parasite products in eosinophil Reoccurrence is relatively frequent in horses, with around recruitment to the gastrointestinal mucosa during helminth 33% affected horses presenting a further episode within a infection. Eur. J. Immunol. 36, 1753-1763. year (Utter et al. 2013). However, it is difficult to know if Edwards, S., Clode, A.B. and Gilger, B.C. (2015) Equine eosinophilic those numbers are reflecting an incomplete resolution keratitis in horses: 28 cases (2003–2013). Clin. Case Rep. 3, 1000-1006. rather than a true reoccurrence. Likewise in humans Fukuda, K. and Nishida, T. (2010) Reciprocal interaction of the (Saboo et al. 2013; Reddy et al. 2013), the most common conjunctiva and cornea in ocular allergy. J. Allergy Clin. Immunol. sequelae is mild to moderate scarring (Ramsey et al. 1994; 125, 493-496. Utter et al. 2013). Pigmentation/melanosis is frequently Fukushima, A., Ohashi, Y., Ebihara, N., Uchio, N.E., Okamoto, S., present during healing and it can be prominent for the Kamagai, N., Shoji, J., Takamura, E., Nakagawa, Y., Namba, K., Fujishima, H. and Miyazaki, D. (2014) Therapeutic effects of 0.1% fi rst couple of months, regressing steadily afterwards. Rarely tacrolimus eye drops for refractory allergic ocular diseases with the lesions remains pigmented for longer than 6 months proliferative lesion or corneal involvement. Br. J. Ophthalmol. 98, (Fig 7). 1023-1027.

© 2018 EVJ Ltd OSPHOS® (clodronate injection) Bisphosphonate. For use in horses only. Brief Summary (For Full Prescribing Information, see package insert) CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTION: Clodronate disodium is a non-amino, chloro- containing bisphosphonate. Chemically, clodronate disodium is (dichloromethylene) diphosphonic acid disodium salt and is manufactured from the tetrahydrate form. INDICATION: For the control of clinical signs associated with navicular syndrome in horses. CONTRAINDICATIONS: Horses with hypersensitivity to clodronate disodium should not receive OSPHOS. Do not use in horses with impaired renal function or with a history of renal disease. WARNINGS: Do not use in horses intended for human consumption. HUMAN WARNINGS: Not for human use. Keep this and all drugs out of the reach of children. Consult a physician in case of accidental human exposure. PRECAUTIONS: OSPHOS has been associated with renal toxicity. Concurrent administration of other potentially nephrotoxic drugs should be approached with caution and renal function should be monitored. Use of bisphosphonates in patients with conditions or diseases affecting renal function is not recommended. Horses should be well-hydrated prior to and after the administration of OSPHOS due to the potential for adverse renal events. Water intake and urine output should be monitored for 3-5 days post-treatment and any changes from baseline should elicit further evaluation. As a class, bisphosphonates may be associated with gastrointestinal and renal toxicity. Sensitivity to drug associated adverse reactions varies with the individual patient. Renal and gastrointestinal adverse reactions may be associated with plasma concentrations of the drug. Bisphosphonates are excreted by the kidney; therefore, conditions causing renal impairment may increase plasma bisphos- phonate concentrations resulting in an increased risk for adverse reactions. Concurrent administration of other potentially nephrotoxic drugs should be approached with caution and renal function should be monitored. Use of bisphosphonates in patients with conditions or diseases affecting renal function is not recommended. Administration of bisphosphonates has been associated with abdominal pain (colic), discomfort, and agitation in horses. Clinical E signs usually occur shortly after drug administration and may be associated with alterations in intestinal motility. In horses treated with OSPHOS these clinical signs usually began within 2 hours of N treatment. Horses should be monitored for at least 2 hours following I administration of OSPHOS. Bisphosphonates affect plasma concentrations of some minerals and electrolytes such as calcium, magnesium and potassium, L immediately post-treatment, with effects lasting up to several hours. Caution should be used when administering bisphosphonates to horses with conditions affecting mineral or electrolyte homeostasis P (e.g. hyperkalemic periodic paralysis, hypocalcemia, etc.). I The safe use of OSPHOS has not been evaluated in horses less than 4 years of age. The effect of bisphosphonates on the skeleton of growing horses has not been studied; however, bisphosphonates C inhibit osteoclast activity which impacts bone turnover and may affect bone growth. S Bisphosphonates should not be used in pregnant or lactating mares, I or mares intended for breeding. The safe use of OSPHOS has not been evaluated in breeding horses or pregnant or lactating mares. Bisphosphonates are incorporated into the bone matrix, from where D they are gradually released over periods of months to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, E is directly related to the total dose and duration of bisphospho- nate use. Bisphosphonates have been shown to cause fetal N developmental abnormalities in laboratory animals. The uptake of I bisphosphonates into fetal bone may be greater than into maternal bone creating a possible risk for skeletal or other abnormalities in U the fetus. Many drugs, including bisphosphonates, may be excreted F Q in milk and may be absorbed by nursing animals. O E Increased bone fragility has been observed in animals treated with R E RY bisphosphonates at high doses or for long periods of time. Bisphos- VE phonates inhibit bone resorption and decrease bone turnover which may lead to an inability to repair micro damage within the bone. In humans, atypical femur fractures have been reported in patients on long term bisphosphonate therapy; however, a causal relationship has not been established. ADVERSE REACTIONS: The most common adverse reactions reported in the field study were clinical signs of discomfort or ner- vousness, colic and/or pawing. Other signs reported were lip licking, The intramuscular yawning, head shaking, injection site swelling, and hives/pruritus. POST-APPROVAL EXPERIENCE (December 2018): The following adverse events are based on post-approval adverse drug experience reporting. Not all adverse events are reported to FDA/ bisphosphonate injection CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. for control of clinical signs The following adverse events are listed in decreasing order of reporting frequency: renal failure, polyuria, polydipsia, abdominal Learn more online pain, anorexia, lethargy, hypercalcemia, behavioral disorder, associated with Navicular Syndrome discomfort, hyperkalemia, hyperactivity, recumbency, hyperthermia, www.dechra-us.com injection site reactions, muscle tremor, urticaria, hyperglycemia, and in horses 4 years of age and older fracture. In some cases, death has been reported as an outcome of www.osphos.com the adverse events listed above. INFORMATION FOR HORSE OWNERS: Owners should be advised to: • NOT administer NSAIDs. As with all drugs, side effects may occur. In field studies and post-approval experience the most common side effects reported were signs • Ensure horses have access to adequate water before and of discomfort, nervousness, and colic. Other signs reported were: renal insufficiency/failure, anorexia, lethargy, hypercalcemia, behavioral after administration of OSPHOS. disorders, hyperkalemia, hyperactivity, recumbency, hyperthermia, injection site reactions, muscle tremor, urticaria, hyperglycemia, and fracture. • Observe their horse for at least 2 hours post-treatment for In some cases, death has been reported as an outcome of these adverse events. The safe use of OSPHOS has not been evaluated in signs of colic, agitation, and/or abnormal behavior. horses less than 4 years of age or breeding horses. OSPHOS should not be used in pregnant or lactating mares, or mares intended for breeding. • If a horse appears uncomfortable, nervous, or experiences NSAIDs should not be used concurrently with OSPHOS. Concurrent use of NSAIDs with OSPHOS may increase the risk of renal toxicity cramping post-treatment, hand walk the horse for 15 minutes. If signs do not resolve contact the veterinarian. and acute renal failure. Use of OSPHOS in patients with conditions affecting renal function or mineral or electrolyte homeostasis is not • Monitor water intake and urine output for 3-5 days post- recommended. Refer to the prescribing information for complete details or visit www.dechra-us.com. treatment. • Contact their veterinarian if the horse displays abnormal clinical signs such as changes in drinking and urination, CAUTION: Federal law restricts this drug to use by or on the order of licensed veterinarian. appetite, and attitude. Manufactured for: Dechra Veterinary Products * Freedom of Information Summary, Original New Animal Drug Application, approved by FDA under NADA # 141-427, for OSPHOS. April 28, 2014. 7015 College Blvd., Suite 525, Overland Park, KS 66211 866-933-2472 Dechra Veterinary Products US and the Dechra D logo are registered trademarks of Dechra Pharmaceuticals PLC. © 2019 Dechra Ltd. © 2019 Dechra Ltd. OSPHOS is a registered trademark of Dechra Ltd. All rights reserved. Approved by FDA under NADA # 141-427 We understand both the risks and rewards of today’s equine practice. For over 60 years, the AVMA Trust has delivered the most complete and supportive professional, business and personal insurance programs available to equine practitioners.

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Gilger, B.C. (2013). Equine ophthalmology. In: Veterinary Morgan, R.V., Abrams, K.L. and Kern, T.J. (1996) Feline eosinophilic Ophthalmology. 5th ed., Ed: K.N. Gelatt. John Wiley & Sons Inc, keratitis: a retrospective study of 54 Cases (1989–1994). Vet. Comp. Ames, IO. pp. 1584-1585. Ophthalmol. 6, 131-134. Gilger, D.C., Michau, T.M. and Salmon, J.H. (2005) Immune-mediated Mould, A.W., Matthaei, K.I., Young, I.G. and Foster, P.S. (1997) keratitis in horses: 19 cases (1998-2004). Vet. Ophthalmol. 8, 233- Relationship between interleukin-5 and eotaxin in regulating blood 239. and tissue eosinophilia in mice. J. Clin. Invest. 99, 1064-1071. Gleich, G.J., Frigas, E., Loegering, D.A., Wasson, D.L. and Steinmuller, Munger, R.J. (1983) Equine onchocercal keratoconjuctivitis. Equine D. (1979) Cytotoxic properties of the eosinophil major basic Vet. J. 2, 65-70. protein. J. Immunol. 123, 2925-2927. Nasisse, M.P., Glover, T.L., Moore, C.P. and Weigler, B.J. (1998) Graztek, A.T., Kaswan, R.L., Martin, C.L., Champagne, E.S. and White, Detection of Feline Herpesvirus 1 DNA in corneas of cats with S.L. (1995) Ophthalmic cyclosporine in equine keratitis and eosinophilic keratitis or corneal sequestration. Am. J. Vet. Res. 59, keratouveitis: 11 cases. Equine Vet. J. 27, 327-333. 856-858. Grinninger, P., Sanchez, R., Kraijer-Huver, I.M., Kitslaar, W.J., Olsen, L., Bondesson, U., Brostrom, H., Olsson, U., Mazogi, B., Sudqvist, Schoemaker, N.J., Grinwis, G.C. and Boeve, M.H. (2012) M., Tjalve, H. and Ingvast-Larsson, C. (2011) Pharmacokinetics and Eosinophilic keratoconjunctivitis in two rabbits. Vet. Ophthalmol. 15, effects of cetirizine in horses with insect bite hypersensitivity. Vet. J. 59-65. 187, 347-351. Gupta, A., Sharma, A., Mohan, K. and Gupta, A. (1999) Mycotic Olsen, L., Ingvast-Larsson, C., Bondesson, U., Brostrom,€ H., Tjalve,€ H. keratitis in nonsteroid exposed vernal keratoconjunctivitis. Acta and Larsson, P. (2007) Cetirizine in horses: pharmacokinetics Ophthalmol. Scand. 77, 229-231. and effect of ivermectin pretreatment. J. Vet. Pharmacol. Ther. 30, 194-200. Hendrix, D.V., Adkins, E.A., Ward, D.A., Stuffle, J. and Skorobohach, B. (2011) An investigation comparing the efficacy of topical ocular Paulsen, M.E., Lavach, J.D., Severin, G.A. and Eichenbaum, J.D. (1987) application of tacrolimus and cyclosporine in dogs. Vet. Med. Feline eosinophilic keratitis: a review of 15 clinical cases. J. Am. Intern. 2011, 487-592. Anim. Hosp. Assoc. 23, 63-69. Jacobsen, E.A., Helmers, R.A., Lee, J.J. and Lee, N.A. (2012) The Pucci, N., Novembre, E., Lombardi, E., Massai, C., Bernardini, R., expanding role(s) of eosinophils in health and disease. Blood 120, Caputo, R., Campa, L., de Libero, C. and Vierucci, A. (2005) Long 3882-3890. eyelashes in a case series of 93 children with vernal keratoconjunctivitis. Pediatrics 115, 86-91. Jennings, A.F. (2007) Eosinophilic keratoconjunctivitis in a donkey. British Association of Veterinary Ophthalmology Annual Plumb, D.C. Ed. (2008) Veterinary Drug Handbook, 6th edn., Blackwell, Conference, Hilton Head. Ames. Kafarnik, C. (2010) Equine eosinophilic keratitis. Comp. Anim. 15, 4-6. Ramsey, D.T., Whiteley, H.E., Gerding, P.A. Jr and Valdez, R.A. (1994) Eosinophilic keratoconjunctivitis in a horse. J. Am. Vet. Med. Assoc. Kainzbauer, C., Steinborn, R., Mair-Scorpio, G., Benz, P., Brandt, S. and 205, 1308-1311. Nell, B. (2008) PCR-mediated detection of bovine papillomavirus E5 and L1 DNA in equine eosinophilic conjunctivitis/keratitis. 39th Read, R.A. (1995) Treatment of canine nictitans plasmacytic Annual Meeting of the American College of Veterinary conjunctivitis with 0.2% cyclosporin ointment (1995). J. Small Anim. Ophthalmologists. Vet. Ophthalmol. 11: 413-429. Pract. 36, 50-56. Kumagai, N., Fukuda, K., Ishimura, Y. and Nishida, T. (2000) Synergistic Reddy, J.C., Basu, S., Saboo, U.S., Murthy, S.I., Vaddavalli, P.K. and induction of eotaxin expression in human keratocytes by TNF-a Sangwan, S. (2013) Management, clinical outcomes, and and IL-4 or IL-13. Invest. Ophthalmol. Vis. Sci. 41, 1448-1453. complications of shield ulcers in vernal conjunctivitis. Am. J. Ophthalmol. 155, 550-559. Kumar, S. (2009) Vernal keratoconjunctivitis: a major review. Acta Ophthalmol. 87, 133-147. Saboo, U.S., Manish, J., Jagadesh, R. and Sangwan Virender, S. (2013) Demographic and clinical profile of vernal Kerr, N. and Stern, G.A. (1992) Bacterial keratitis associated with vernal keratoconjunctivitis at a tertiary eye care center in India. Indian keratoconjunctivitis. Cornea 11, 355-359. J. Ophthalmol. 61, 486-489. Lambiase, A., Leonardi, A., Sacchetti, M., Deligianni, V., Sposato, S. Schmidt, G., Krehbiel, J.D., Coley, S.C. and Leid, R.W. (1982) Equine and Bonini, S. 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associated with paranasal sinus osteoma in a Quarterhorse mare. Van Maanen, C., Klein, W.R., Dik, K.J. and Van den Ingh, T.S.G.A.M. J. Vet. Diagn. Invest. 16, 155-160. (1996) Three cases of carcinoid in the equine nasal cavity and Step, D.L., Divers, T.J., Cooper, B., Kallfelz, F.A., Karcher, L.F. and maxillary sinuses: histologic and immunohistochemical features. Vet. Pathol. 33, 92-95. Rebhun, W.C. (1991) Severe masseter myonecrosis in a horse. J. Am. Vet. Med. Assoc. 198, 117-119. Walde, I. and Prosl, H. (1976) Strongylus edentatus as the cause of subconjunctival phlegmon and granuloma formation in the horse. Sweeney, C.R. and Beech, J. (1983) Retrobulbar melanoma in a horse. Equine Vet. J. 15, Suppl. 2, 123-124. Tierarzti Praxis. 4, 493-496.

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