Purpose: To compare the safety and efficacy of a 100 microgram subconjunctival injection of liposome-encapsulated sirolimus (SCJS) to cyclosporine (CsA) or tacrolimus (CsA/T) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: Dogs with signs and symptoms of KCS were block-randomized to one of two treatment groups: Biweekly SCJS or conventional treatment (CsA/T). Schirmer tear test 1 (STT-1) scores, conjunctival hyperemia (CH) scores, corneal opacity (CO) scores, and clinical evaluation of potential side effects were recorded every 2 weeks for 14 weeks for both groups. Differences between groups were analyzed using the mixed results ANOVA and U-Mann Whitney tests (p < .05 was considered significant). Results: A total of 30 eyes were included in the study, of which 20 eyes completed follow-up. There was no statistically significant interaction between the treatment group and time on STT-1 score (p = .165), and median CH and CO scores showed no statistically significant differences between groups (p = .353 and p = .393, respectively). There were no clinically significant side effects present in any subject at any time. Conclusion: In this trial, a 1 mg/mL (100 micrograms) SCJS every 2 weeks showed similar safety and efficacy profiles as daily CsA/T in dogs with KS after 14 weeks of treatment. Larger studies should be performed to further assess SCJS as an alternative treatment for KCS.

OBJECTIVE:To report a case of idiopathic lipid keratopathy in a normolipemic cat.ANIMAL STUDIED:A 10-year-old neutered female European domestic cat.RESULTS:A cat was evaluated for bilateral white corneal deposits. Slit-lamp examination revealed multiple, well-defined, round, stromal, cream-colored deposits of different sizes associated with generalized superficial corneal vascularization. Blood lipids were normal, and no history of travel to tropical locations or ocular trauma was present. Topical betamethasone/gentamicin 0.1% suspension q 12 hours did not result in any improvement of clinical appearance after one week. Tomography following the initial therapy revealed dense, hyperreflective deposits with posterior shadowing in the anterior and mid stroma of both corneas. A four-week course of itraconazole 0.01% ophthalmic cream was prescribed q 12 hours with no improvement. Four months after the initial examination, a diagnostic superficial keratectomy and amniotic membrane implantation were performed. Histopathological analysis showed membrane bound vacuoles with infiltration of foamy macrophages suggesting a diagnosis of primary lipidosis. The post-surgical period was unremarkable, and ten days later, the patient was re-examined. Opacification from a corneal leukoma was observed in the excision site with mild fibrotic tissue. Two months post-keratectomy, no further changes were detected in the cornea, and the patient was managed only with topical lubricant.CONCLUSIONS:To our knowledge, this is the first report of idiopathic corneal lipidosis in a cat and may be considered as a differential diagnosis of corneal disease in felines.

A wild Agassiz's desert tortoise, Gopherus agassizii, with bilateral eyelid reduction and plaques of tissue covering the superior surface of both corneas was examined in the field and subsequently submitted to the University of Florida for diagnostics. Polymerase chain reaction (PCR), from a swab of both corneas, was positive for Mycoplasma agassizii. Two months later, the tortoise was euthanatized and necropsied. There was increased bulbar exposure associated with dermal excoriation of periocular scales in both superior and inferior palpebra resulting in an increased palpebral fissure opening. Concurrently, there was bilateral conjunctivitis of the nictitating membranes and squamous metaplasia of the bulbar conjunctiva. Using PCR, Mycoplasma testudineum, another pathogen of tortoises, was identified in both nasal cavities, and the upper respiratory tract histopathological findings were consistent with those described for M. testudineum in Agassiz's desert tortoises. Although eye disease has been reported in desert and gopher (Gopherus polyphemus) tortoises with mycoplasmosis, widespread loss of palpebral tissue, conjunctivitis of the nictitans, and squamous metaplasia of the bulbar conjunctiva have not been reported in tortoises.

Summary A 5‐year‐old Belgian Warmblood gelding presented for evaluation of increased opacity in both eyes. Initial ophthalmic examination revealed bilateral mild blepharospasm, multifocal axial and dorsal anterior stromal corneal opacities with mild axial mid‐stromal haze and oedema, and superficial, branching corneal vascularisation. A presumptive diagnosis of bilateral immune‐mediated keratitis (IMMK) was made. The lesions progressed despite 2 years of exhaustive options for medical management. Surgical intervention in the left eye with lamellar keratectomy and ocular surface reconstruction with amnion membrane transplantation was elected. The keratectomy specimen was submitted for histopathology and was consistent with immune‐mediated keratitis. When surgical intervention in the right eye was performed, histopathology revealed sheets of atypical round cells with a high mitotic index. Immunohistochemistry from both the left and right specimens had immunoreactivity to CD3 antibodies. An amended diagnosis of bilateral T cell lymphoma was made. The patient recovered well from surgery, and there have been no signs of recurrence or systemic involvement following surgical intervention. This is a unique case of primary corneal T cell lymphoma in a horse. Prior to electing surgical management, the patient received topical immunomodulating medications including cyclosporine and tacrolimus for significant lengths of time. Both chronic inflammation and chronic administration of immunosuppressive agents are associated with neoplastic transformation. Surgical intervention provides both a diagnostic sample and therapeutic relief.

The aim of this study was to evaluate the effect of topical 1% tetracaine hydrochloride on the intraocular pressure (IOP) in ophthalmologically normal horses. Thirty eyes of 15 clinically normal horses were used for this study. The animals were randomly assigned to two groups (treatment and control). Prior to the instillation of 1% tetracaine or placebo, the baseline IOPs (T0) of each animal were recorded in both groups. Then one drop of tetracaine was instilled randomly into one eye of each horse in the treatment group (8 horses). In the control group (7 horses), one drop of artificial tear was instilled in one randomly selected eye. The measurements were repeated at 2 minutes (T2), 5 minutes (T5), 15 minutes (T15), and 30 minutes (T30) post instillation via a rebound tonometer. There was no significant difference in the treatment group (P = .3). The peak IOP measured at T2 returned to the baseline value at T30. No significant difference was found in the mean IOP values between the treatment and the control groups, or between the males and females on any of the occasions (P > .05). The Results of this study revealed a nonsignificant increase of the IOP 2 minutes post instillation of 1% tetracaine in horses.

BACKGROUNDUlcerative keratitis with peripheral furrow formation is a poorly-described condition which has been associated with a grave prognosis due to rapid necrosis of the cornea.OBJECTIVETo describe the infectious aetiologies associated with furrow-forming ulcerative keratitis, its overall clinical course and the efficacy of medical and surgical intervention in horses.STUDY DESIGNRetrospective clinical case series.METHODSMedical records of 72 horses which presented with furrow-forming ulcerative keratitis at the University of Florida between 1987 and 2015 were reviewed.RESULTSSeventy-two horses (72 eyes) with furrow-forming ulcerative keratitis were treated at the University of Florida between 1987 and 2015. Of these, a definitive aetiologic diagnosis was available for 37 eyes. Ten of 37 eyes (27%) were diagnosed with fungal keratitis based on cytology of corneal scraping, culture, histopathology and/or fungal PCR. Fourteen of 37 eyes (38%) were diagnosed with a mixed fungal and bacterial keratitis. Thirteen of 37 eyes (35%) were diagnosed with bacterial keratitis. Overall, 26 of 72 total eyes were treated with medical therapy alone (36%). Forty-six of 72 eyes were treated medically and surgically (64%). Of the 26 eyes which received medical therapy, 20 healed with a positive visual outcome (77%) and 6 eyes were non-visual (23%). Of the 46 eyes which received surgical intervention, 40 healed with a positive visual outcome (87%), while six eyes were non-visual (13%). Altogether, 60 of 72 eyes healed with a positive visual outcome following medical or surgical treatment of furrow-forming ulcerative keratitis (83%). Twelve of 72 eyes failed treatment (17%), with six eyes requiring enucleation and six globes becoming phthisical after treatment.MAIN LIMITATIONSInconsistencies in available medical record data due to the large span of time (1987-2015) are inherent in this retrospective study, along with gradual evolution of corneal surgical techniques and medical therapies over the decades.CONCLUSIONSFurrow-forming ulcerative keratitis was associated with a positive visual outcome in 83% of horses treated at the University of Florida between the years 1987 and 2015. Furrow formation may be associated with either fungal or bacterial infection.

CASE DESCRIPTION:A yearling Thoroughbred stallion and an 8-year-old Saddlebred mare were evaluated for persistent mucoid ocular discharge.CLINICAL FINDINGS:Examination of both horses revealed copious yellow-tan mucoid ocular discharge with a negative Jones I test, absent nasal punctum, and unsuccessful anterograde nasolacrimal duct (NLD) irrigation. Clinical abnormalities were present on the right side only in one horse and bilaterally in the other. Computed tomography (CT) with contrast confirmed nasolacrimal duct atresia in both horses.TREATMENT AND OUTCOME:Under general anesthesia, the affected NLD was catheterized anterograde and contrast injected. Using fluoroscopic guidance, retrograde access to the distal NLD was obtained for through-and-through wire access. Over the wire, the stoma was dilated and a temporary stent placed for 4-8 weeks. After the procedure, both horses were comfortable and free of ocular discharge at the minimum time of last follow-up, 9 months postoperatively.CLINICAL RELEVANCE:Fluoroscopically guided neocanalization is a viable alternative to traditional surgical approaches for NLD atresia, especially when access to the site of obstruction is limited.

SummaryLymphoma is a relatively uncommon neoplasm in the horse; however, it is considered the most common neoplasia of the equine haemolymphatic system. Limited reports of adnexal lymphoma have been documented in the literature, with no known reports of recurrence nearly a decade after mass excision. The objective is to describe a case of recurrent adnexal lymphoma in a 20‐year‐old Quarter Horse gelding presented to the Ophthalmology service at the University of Florida Veterinary Hospital (UFVH) for evaluation of a solitary subconjunctival mass of the right eye (OD). A focal, pink, fleshy mass associated with the dorsomedial bulbar conjunctiva was noted. An excisional biopsy was performed. Histopathology revealed lymphoma with clean margins. The client declined staging and further therapy at the initial visit. Approximately 8 years later, the horse began to exhibit intermittent mild to moderate diffuse swelling of the conjunctiva OD. Six months after onset, the swelling worsened acutely and was accompanied by severe swelling of the left conjunctiva (OS). The horse then returned to UFVH and was diagnosed with diffuse, bilateral conjunctival lymphoma. Humane euthanasia was elected. T cell lymphoma was confirmed with immunohistochemistry performed post‐mortem. At necropsy, neoplastic tissue was observed throughout the adnexal and ocular tissues of both eyes and in the submandibular lymph nodes. Adnexal lymphoma is an uncommon neoplasm in the horse. To the authors’ knowledge, this is the first documentation of a nodular adnexal lymphoma that involved an 8‐year period without recurrence followed by development of diffuse, bilateral disease. Typically, surgical excision of the nodular form of lymphoma involving the extraocular tissues yields an improved prognosis compared with the diffuse form of the disease. Further investigation is necessary to determine if nodular forms of adnexal lymphoma represent early stages of diffuse extraocular or systemic disease.

Objective:The aim of this study was to evaluate the therapeutic utility of sirolimus liposomes (prepared by two different techniques at two different doses) by sub conjunctival injection, and tacrolimus ophthalmic solution at 0.03% in canine patients diagnosed with Kerato Conjunctivitis Sicca (KCS) non-responsive to conventional treatment.Procedures: 20 privately owned pet dogs with clinically confirmed non-responsive KCS were randomized into 5 groups.Patients were administered with 0.15 ml of placebo or product respectively every 2 weeks for 60 days.Also, all patients received topically tacrolimus 0.03% solution 3 times a day for 90 days.Each animal was given a full ophthalmic examination prior and during the evaluation.Results: During the evaluation, no adverse effects were observed.For a 0.16 mg/ml dose of sirolimus, the heating method provided liposomes with enhanced immunomodulating activity in contrast to the ethanol injection method.On the other hand, the improvement in lacrimal production achieved by a 0.4 mg/ml sirolimus dose was independent of the preparation technique.HM4 and EI16 formulations showed important decrease in secondary pigmentary keratitis.Also, the use of sirolimus liposomes exhibited reduction in corneal vascularization and conjunctival discharge.Conclusions: The 0.4 mg/ml dose provided greater improvement of lacrimal production and minimization of ocular irritation indicators with no influence of the preparation technique used.The heating method generated liposomal dispersions with enhanced immunomodulating activity at a lower dose of 0.16 mg/ml.Besides lacrimal production improvement, the treatment significantly improved patient vision clarity.

Objective To measure intraocular pressure (IOP) in horses during hoisting after induction of anesthesia. Study design Prospective nonrandomized clinical study. Animals Eighteen healthy adult horses aged [mean +/- standard deviation (SD)] 10 +/- 4.2 years and weighing 491 +/- 110 kg anesthetized for elective procedures. Methods IOP was measured in the superior eye of each horse based on planned recumbency after induction of anesthesia. Measurements were taken directly after premedication with xylazine or detomidine with butorphanol, after induction with diazepameketamine, after intubation, when suspended by the hoist and on the operating table. During hoisting, the head was supported and the eyeeheart height was measured to account for variations in head positioning among patients. IOPs were compared across time points using repeated-measures analysis of variance. Regression was used to compare IOP outcome with potential cofactors. Results Compared with measurements after premedication (17.5 +/- 2.5 mmHg) (mean +/- SD), hoisting significantly increased IOP (32.4 +/- 15.3 mmHg) (p < 0.01). The highest recorded IOP in the hoist was 80.0 (range, 16.0-80.0) mmHg. The difference in IOP between premedication and hoisting was 15.0 +/- 16.2 range, -1.0 to 68.0) mmHg. Body weight had a significant effect on absolute IOP and change in IOP in the hoist (p < 0.01). Conclusions and clinical relevance Hoist IOP was significantly higher than post-premedication IOP with heavier horses having higher hoist IOPs and greater increases in IOP. The clinician should take this relationship into account when anesthetizing and hoisting larger horses where an increase in IOP could be detrimental.

The objective of this paper is to describe clinical behavior, histopathologic features, and immunohistochemical staining of two-related horses with intraocular teratoid medulloepithelioma. Two-related Quarter Horses with similar intraocular masses presented to the UF-CVM Comparative Ophthalmology Service for evaluation and treatment. The first horse, a 3-year-old gelding, had glaucoma and a cyst-like mass in the anterior chamber. Enucleation was performed. Histopathology revealed a teratoid medulloepithelioma. The tumor was considered to be completely excised. Fifteen months later, the gelding presented with swelling of the enucleated orbit and local lymph nodes with deformation of the skull. Cytology revealed neuroectodermal neoplastic cells. Necropsy confirmed tumor metastasis. Six weeks later, a 9-year-old mare, a full sibling to the gelding, presented for examination. An infiltrative mass of the iris and ciliary body was found that extended into the anterior, posterior, and vitreal chambers. Uveitis was present, but secondary glaucoma was not noted. Enucleation was performed and the histopathologic diagnosis was also teratoid medulloepithelioma. The mare has had no recurrence to date, 2 years following enucleation. Metastasis of intraocular teratoid medulloepithelioma is possible. Staging is recommended in cases where the diagnosis of teratoid medulloepithelioma is confirmed. Surveillance of full siblings is recommended until more information regarding etiology is known.

Purpose: To develop a novel ex vivo extended culture model of canine corneal epithelial cell wound healing.Materials and Methods: Canine corneoscleral rims (CSR) were obtained and, after preparation for culture, were placed on a nutating scaffold and incubated in physiological conditions. In experiment 1, eight CSR in a serum-containing antimicrobial-fortified medium were monitored for epithelial integrity and bacterial infection up to 28 days in culture. CSR were assessed histologically at the end of the culture period end points 0, 7, 14, and 28 days with accompanying scanning electron microscopic (SEM) and transmission electron microscopic (TEM) evaluation. Samples for microbial culture were obtained at days 0, 3, 7, 14, and 28. In experiment 2, uniform 8-mm-diameter superficial corneal epithelial wounds were created and monitored for re-epithelialization in the same culture conditions or in a serum-free protein equivalent medium, with four CSR per group. Standardized digital images were obtained with cobalt filter at the time of fluorescein staining and media change every six hours. Image J imaging software was used to measure the area of fluorescein retention. Re-epithelialization rates were calculated and CSR then fixed for immunohistochemistry (IHC).Results: All corneas survived to end points as described in experiment 1 with no evidence of contamination or compromised epithelial integrity. Histologically, a multilayered epithelium was maintained and corneal edema was not appreciated until day 14. SEM examination revealed epithelial cell layer confluence and migrating epithelial cells of normal cellular morphology with normal cell-cell interactions on TEM. In experiment 2, all eight corneas healed with a healing rate of 0.702 0.130 mm(2)/h (1.25 mm/day epithelial cell migration rate) and were positive in IHC evaluation for markers of corneal fibrosis.Conclusion: This ex vivo canine corneal wound healing model is an appropriate and clinically relevant tool for assessment and modulation of epithelial wound healing.

Chapter 7 Diseases of the cornea Dennis E. Brooks, Dennis E. BrooksSearch for more papers by this authorAndrew Matthews, Andrew MatthewsSearch for more papers by this authorAlison B. Clode, Alison B. ClodeSearch for more papers by this author Dennis E. Brooks, Dennis E. BrooksSearch for more papers by this authorAndrew Matthews, Andrew MatthewsSearch for more papers by this authorAlison B. Clode, Alison B. ClodeSearch for more papers by this author Book Editor(s):Brian C. Gilger, Brian C. Gilger North Carolina State UniversitySearch for more papers by this author First published: 09 December 2016 https://doi.org/10.1002/9781119047919.ch7Citations: 12 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onFacebookTwitterLinked InRedditWechat Summary Corneal abnormalities are the most common ocular disease in horses and a very important part of veterinary practice. In this chapter, a review of the anatomy and physiology of the equine cornea is followed by descriptions of congenital and acquired corneal diseases. Extensive information on the treatment and surgery of corneal diseases is also discussed. Multiple photographs of corneal disease accompany descriptions of these conditions in the text. Citing Literature Equine Ophthalmology, Third Edition RelatedInformation

This study was conducted to determine the effects of intravenous detomidine on Schirmer tear test (STT) results in clinically normal horses. Eighteen adult horses were randomly divided into two groups of nine horses each. The treatment group was sedated with intravenous detomidine alone (20 mu g/kg), and the control group received only intravenous saline (0.2 mL/100 kg). Schirmer tear test was performed just before intravenous administration of detomidine or saline in treatment and control groups, respectively. Schirmer tear tests were repeated 5, 20, 60, and 120 minutes later. Horses enrolled in this study consisted of nine males and nine females. Breeds were Arabian and Hanoverian, ranging from 3 to 6 years in age. In the treatment group, the pretreatment and subsequent post-treatment mean standard deviation values were 17.0 +/- 6.9 (0 minutes), 11.8 +/- 2.9 (5 minutes), 12.1 +/- 2.0 (20 minutes), 12.1 +/- 3.1 (60 minutes), and 15.0 +/- 2.8 (120 minutes) mm wetting/min. In this group of horses, a significant reduction was observed in SIT values at 5, 20, and 60 minutes after treatment with detomidine hydrochloride in comparison to the pretreatment values (analysis of variance with post hoc testing; P-5 = 0.004, P-20 = 0.007, P-60 = 0.006). There was no significant difference between baseline values and posttreatment values in the control saline group (P >= .08). We conclude that intravenous detomidine causes a significant reduction in STT values in clinically normal horses. In horses, practitioners should measure STT values before intravenous administration of detomidine to accurately assess the results. (C) 2016 Elsevier Inc. All rights reserved.

OBJECTIVETo describe ophthalmic abnormalities secondary to periocular and ocular snakebite in dogs.ANIMAL STUDIEDRetrospective review of medical records from dogs presenting to the Small Animal Hospital at University of Florida following snakebites to the face (2012-2014). Two groups were identified: periocular bites (PB) and ocular bites (OB).RESULTSRecords from eleven dogs matched the search criteria and were included in the study (PB=9, 81.8%; OB=2, 18.2%). Both OB cases involved the cornea. Facial edema, blepharospasm, chemosis, and conjunctival hyperemia occurred in all cases (100%). Hemorrhage from the eyelids occurred in eight cases (72.7%; PB=7, OB=1). Subconjunctival hemorrhage occurred in seven cases (63.6%; PB=6, OB=1). Third eyelid laceration and nictitans gland prolapse occurred in 1 case each (9%; PB=1). Lagophthalmia was present in three cases (27.3%; PB=3), with secondary corneal ulcer in two cases (18.2%; PB=2). Corneal ulcer due to direct corneal bite occurred in two cases (18.2%-partial thickness with melting (1) and full thickness (1) ). Uveitis was present in 6 cases (54.5%; PB=4, OB=2), with flare and miosis in 4 cases (36.4%; PB=2, OB=2). Hyphema, fibrin in anterior chamber, and cataract occurred in one case (9%; OB=1). Vision loss occurred in two cases (18.2%; PB=2), secondary to retinal degeneration (PB=1) and amaurosis (PB=1). Mean follow-up time was 7 weeks (range: 3 days-11 months). Most clinical signs had resolved by last examination.CONCLUSIONSPeriocular symptoms were more commonly observed than ocular alterations, regardless of bite location. Appropriate supportive therapy should be instituted according to clinical signs.

PURPOSE:The purpose of this investigation was to identify potential environmental risk factors for the diagnosis of equine deep stromal abscesses (DSA) in the subtropical climate at the University of Florida Veterinary Medical Center (UFVMC).METHODS:Cases included were selected from the UFVMC medical record and imaging database, and included all cases of equine DSA diagnosed during the period from December 1991 to December 2013 in patients residing in north central Florida. Patient date of diagnosis and atmospheric data was obtained for north central Florida for the corresponding time period. Univariate and multivariate general linear models were generated testing effects and interactions between environmental conditions.RESULTS:When year, sulfur dioxide (SO2 ) and wind were analyzed in the presence of each other, a one-mile per hour increase in wind (P = 0.005) significantly increased the number of DSA cases by 1.63 cases per year. When the influence of temperature was evaluated in conjunction with year and nitrogen dioxide (NO2 ), the number of cases decreased by 0.1534 per year for every degree increase in temperature (°C) (P = 0.039).CONCLUSIONS:Wind speed is the first significant atmospheric risk factor to be identified for DSA formation in the horse. The importance of environmental variance in the incidence of DSA indicates that the pathogenesis of DSA formation may be multifactorial, interdependent and provides support in some horses for the micropuncture hypothesis of DSA formation related to the involvement of environmental conditions causing precorneal tear film and epithelial damage.

Abstract Objective: To describe clinical findings and visual outcomes of the fungal plaque form of equine keratomycosis. Design: Retrospective medical records study. Animals studied: Medical

PURPOSE:The aim of this study was to develop and characterize a liposomal product containing sirolimus to be administered subconjunctivally for the treatment of nonresponsive keratoconjunctivitis sicca (KCS) or dry eye.METHODS:Formulations were prepared using an ethanol injection method and an adaptation of the heating method in pursuance of the most suitable methodology for future industrial production. Liposomes were loaded with either a high dose of 1 mg/mL of sirolimus or a less toxic dose of 0.4 mg/mL. The effects of critical process and formulation parameters were investigated. Liposomes were characterized in terms of size, zeta potential, polydispersity, differential scanning calorimetry, morphology, entrapment efficiency, phospholipid content, thermal stability, and sterility. The formulation was evaluated clinically in dogs with spontaneous KCS.RESULTS:Sterile liposomal dispersions with sizes ranging from 140 to 211 nm, were successfully obtained. High entrapment efficiency of 93%-98% was achieved. The heating method allowed an easier production of liposomes with high entrapment efficiency, to significantly shorten production time and the elimination of the use of alcohol. The poor stability of the obtained liposomes in aqueous dispersion made the inclusion of a lyophilization step necessary to the manufacturing process. In vivo testing of the liposomal sirolimus formulations in the spontaneous KCS dog model have produced promising results, particularly with a sirolimus dose of 1 mg/mL, indicating the need for further development and study of proposed formulations in the treatment of canine KCS. Clinical improvement in tear production in dogs with spontaneous KCS treated with the 1 mg/mL dose product was observed.CONCLUSIONS:The heating method allowed easier production of high entrapment efficiency liposomes to significantly shorten production time and the elimination of the use of alcohol. Tear production was increased in dogs administered with the formulation.