CLINICAL SCIENCE A Retrospective Study of Corneal Endothelial Dystrophy in Dogs (1991–2014) Brian C. Leonard, DVM, PhD,* Celine S. Kermanian, DVM,* Sarah R. Michalak, BS,* Philip H. Kass, DVM, MPVM, MS, PhD,† Steven R. Hollingsworth, DVM,* Kathryn L. Good, DVM,* 09/29/2020 on BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3z4CBEZThIGwS//mXtwHgAUe8Vzqgd6BeWXfu+ncecuU= by https://journals.lww.com/corneajrnl from Downloaded David J. Maggs, BVSc,* and Sara M. Thomasy, DVM, PhD*‡ Downloaded model for studying genetic predispositions and development of from Purpose: To retrospectively evaluate the clinical data, diagnostic novel therapeutics for Fuchs endothelial corneal dystrophy. https://journals.lww.com/corneajrnl tests, treatments, and outcomes for dogs with corneal endothelial dystrophy (CED) and determine risk factors for CED when Key Words: dog, corneal endothelium, Fuchs endothelial corneal compared with a canine reference population. dystrophy, corneal endothelial dystrophy – Methods: Medical records of 99 dogs (1991–2014) diagnosed with (Cornea 2020;00:1 6) CED at the University of California Davis Veterinary Medical by Teaching Hospital were reviewed and compared with 458,680 dogs BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3z4CBEZThIGwS//mXtwHgAUe8Vzqgd6BeWXfu+ncecuU= comprising the general hospital population during the study period. uchs endothelial corneal dystrophy (FECD) is characterized Retrieved data included signalment, examination findings, diagno- Fby progressive corneal endothelial cell loss, and affects ses, treatments, and outcomes associated with CED. The exact approximately 4% of humans over 40 years of age in the United Pearson x2 test or exact Kruskal–Wallis test was used to compare States.1 Corneal endothelial cells have a limited capacity to parameters between the groups. Progression of corneal edema was regenerate, and once a critically low number is reached in assessed using 3 independent Kaplan–Meier curves, identifying patients with FECD, corneal edema can occur concomitantly clinically significant changes in corneal opacity. with loss of vision. The 2016 Eye Banking Statistical Report identified FECD as the most frequent indication for corneal Results: Boston terriers, German wirehaired pointers, and Dachs- transplantation in the United States. Although several factors hunds were overrepresented in the CED-affected group, whereas have been implicated in the pathogenesis of FECD, including Labradors were underrepresented. Dogs older than 11 years were damage from oxidative stress,2 RNA toxicity,3 unfolded protein overrepresented in the CED-affected group, whereas intact dogs response,4 abnormal extracellular matrix deposition,5 and were underrepresented. Surgical intervention was performed (n = 11) genetic mutations,6 the fundamental mechanisms responsible based on the severity of disease and secondary complications from for this disease remain poorly understood. CED. Median time to progression of corneal edema was 1) 368 days A similar condition to FECD termed corneal endothe- when an at-risk eye initially without edema developed edema at a lial dystrophy (CED) occurs in dogs. This is a bilateral, subsequent visit, 2) 701 days when there was progression from mild primary degenerative process of corneal endothelial cells in to marked corneal edema, and 3) 340 days when there was progression from focal to diffuse corneal edema. which affected dogs subsequently develop corneal edema. With chronicity, both FECD and CED can result in bullous Conclusions: Many CED-affected dogs progress over months to keratopathy and ulcerative and/or infectious keratitis, which years without surgical intervention, making dogs with CED a useful severely compromise vision and comfort in affected patients.7 It has been suggested that several canine breeds are predis- 8 on posed to CED, including Boston Terriers (BTs), Chihua- 09/29/2020 Received for publication April 23, 2020; revision received June 17, 2020; 9 10 accepted June 25, 2020. huas, Dachshunds, German Shorthaired Pointers From the *Departments of Surgical and Radiological Sciences, School of Veterinary (GSHPs),11 and German Wirehaired Pointers (GWHPs),11 Medicine, University of California, Davis, Davis, CA; and †Department of but there are no studies directly comparing the prevalence of Population Health and Reproduction, School of Veterinary Medicine, University CED in affected individuals against a reference population. of California, Davis, Davis, CA; and ‡Department of Ophthalmology & Vision Science, School of Medicine, University of California, Davis, Davis, CA. Furthermore, neither a prospective nor retrospective evalua- Supported by the National Institutes of Health K08EY028199 (BCL), tion of a large population of dogs with CED has been K08EY021142 (SMT), R01EY01634 (SMT), P30EY12576, and start- performed to evaluate progression of this disease. up funds from the School of Veterinary Medicine, University of Thus, this study sought to 1) retrospectively evaluate California, Davis (SMT). The authors have no conflicts of interest to disclose. the clinical data, diagnostic test results, treatments, and B. C. Leonard and C. S. Kermanian contributed equally to this work. outcomes for dogs with CED and 2) determine risk factors Correspondence: Sara M. Thomasy, DVM, PhD, Department of for CED when compared with a reference population. The Surgical and Radiological Sciences, School of Veterinary Medicine, results from this study will help inform subsequent analyses University of California, Davis, 1 Shields Avenue, Davis, CA 95616 (e-mail: [email protected]). designed to determine additional genetic loci associated with Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. CED in the dog and thereby provide additional potential Cornea Volume 00, Number 00, Month 2020 www.corneajrnl.com | 1 Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Leonard et al Cornea Volume 00, Number 00, Month 2020 targets for investigation in humans with FECD and for whom ficial keratectomy and conjunctival advancement hood flap a genetic cause has not yet been identified. (SKCAHF)] were excluded from this analysis. Progression criteria were defined as follows: Criterion 1: Eyes recorded as having clear (nonedem- MATERIALS AND METHODS atous) corneas during the first visit, but showed signs of CED in the contralateral globe, subsequently progressing to any Retrospective Study degree of corneal edema in the unaffected globe at later visits. Medical records were electronically searched for dogs Criterion 2: Eyes recorded as having mild corneal diagnosed with CED at the University of California Davis edema during the first visit and subsequently progressing to Veterinary Medical Teaching Hospital (UCD-VMTH) between severe corneal edema at later visits. August 22, 1991 and October 23, 2014. The earlier cutoff date Criterion 3: Eyes recorded as having focal corneal corresponds to the establishment of electronic records at UCD- edema during the first visit and subsequently progressing to VMTH, and the later cutoff date reflects the beginning of clinical diffuse corneal edema in later visits. trials where CED patients were specifically recruited to the Kaplan–Meier curves were generated to demonstrate UCD-VMTH to study their disease process. Each record was time to edema progression, defined as time from initial carefullyreviewedtoensureitmet the inclusion criteria: 1) a examination to each progression criterion. clinical diagnosis of CED/degeneration by a board-certified veterinary ophthalmologist or resident in training, 2) a support- ing description of corneal edema as part of the ophthalmic Statistical Analysis examination, and/or 3) in vivo confocal microscopy results All dogs presented to the UCD-VMTH for any reason supporting the diagnosis. Patients with a history of intraocular during the same period formed a reference population against surgery, chronic anterior uveitis, diabetes mellitus, anterior lens which the study population was compared. Proportions of dogs luxation, and/or glaucoma were excluded. For all dogs meeting by breed and sex were each compared between the study and the inclusion criteria, the signalment (age at presentation, gender, x2 fi reference populations using an exact Pearson test. To and breed), ophthalmic examination ndings, concurrent sys- compare sex status between populations, dogs were assigned to temic disease, treatments before presentation, results of all fl one of the following 4 groups: intact male, neutered male, diagnostic testing performed including uorescein stain to assess intact female, and spayed female dogs. To compare age among for corneal ulceration, and medical treatments instituted were populations, dogs were assigned to one of the following 5 recorded. Vision and light perception were assessed by the groups: ,1, 1 to 5, 6 to 10, 11 to 15, and .15 years. The exact presence of a menace response (an elicited blink, retraction of Kruskal–Wallis test was then used to compare age distributions globe, or head turn when a threatening hand motion was made at fl between the study and reference populations. For all analyses, asingleeye)andadazzlere ex (a partial or complete eyelid a P value of ,0.05 was considered significant. blink as a reflex to a very bright light shone in the eye), respectively.12,13 Central corneal thickness (CCT) was measured using ultrasound pachymetry (USP, Pachette 3; DGH Technol- RESULTS ogy, Inc, Exton, PA) on 6 CED-affected dogs.8