BackgroundLittle information describing the biologic behaviour and therapies for corneal lymphoma exist.ObjectivesTo characterise histologically confirmed equine corneal lymphoma considering breed, age or sex predisposition, histologic and immunologic features, therapies and outcomes.Study designRetrospective case series.MethodsA multicentre retrospective medical record review was used to identify horses that presented with corneal disease confirmed morphologically as corneal lymphoma from 2012 to 2022.ResultsMean age at diagnosis was 10.5 years. Males represented 18/26 cases. Warmblood (14) and Thoroughbred (6) breeds were most commonly represented. 25/26 had unilateral ocular involvement. No cases had evidence of multicentric lymphoma. Most eyes (77.7%) had a history of suspected immune-mediated keratitis (IMMK) or eosinophilic keratitis. Morphological diagnosis confirming lymphoma was available for all cases. B-cell lymphoma was diagnosed in 19/24 eyes for which immunohistochemistry was performed, with intermediate to large B-cell lymphoma being most common. Fifteen of 27 eyes received at least one form of adjunctive therapy following keratectomy. Four eyes, which did not receive adjunctive therapy following keratectomy, experienced recurrence. No horses treated with adjunctive therapy following keratectomy experienced recurrence. Malignant transformation of IMMK to lymphoma was morphologically documented in one eye and suspected in three others based on recurrence of clinical signs. All globes were retained and visualised at the last follow-up.Main limitationsIncomplete medical records, owner subjectivity concerning onset of disease and cases being lost to follow-up.ConclusionsMalignant transformation of IMMK to corneal lymphoma likely occurs in horses. Lymphoma should be a differential for nonulcerative keratitis in horses. Keratectomy and histopathology may be considered in progressive or refractory cases of IMMK to rule out neoplastic disease. Recurrence of corneal lymphoma is unlikely following excision and adjunctive therapy. Cases with large corneal surface area or deep stromal involvement may have a likelihood for recurrence.
Recurrent uveitis (RU) is a leading cause of ocular decrement in both humans and horses, which can lead to blindness. Equine recurrent uveitis (ERU) serves as the only spontaneous model for human RU as the eye destruction in both diseases is guided by a dysregulated cytokine milieu mediated by T lymphocytes. We have recently shown that the topical administration of a peptide (SOCS1-KIR), which mimics a natural regulator of cytokine signaling, was correlated with a reduction in clinical pathology when applied to the eye of horses with ERU. This administration was without any observed toxicity. The purpose of this study is to establish the intraocular presence of topical SOCS1-KIR treatment. As such, we administered SOCS1-KIR to the eye of experimental horses (lacking ocular pathology) to evaluate peptide localization and detection of a biological signature. SOCS1-KIR peptide, that was intravitreally-injected, was readily detectable within the retina by immunofluorescence. Although we were unable to detect topically administered SOCS1-KIR by immunofluorescence, topical administration reduced levels of TNFa and IL-10 in the aqueous humor of treated eyes. Additionally, we found that SOCS1-KIR modulated TNFa, IL-6, IL-10, RANTES, and IL-8 levels within activated healthy equine PBMC. Together these results suggest a novel biological signature that is mediated by topical SOCS1-KIR administration to the equine eye that has implications for translation to the clinical setting. This work was supported by the Grayson Jockey Club grant
AbstractBackgroundPain recognition in hospitalized horses is challenging, and the utility of pain scoring systems in horses with ocular disease has not been well‐described.Hypothesis/ObjectivesEvaluate the horse grimace scale (HGS) and behavior pain score (BPS) in hospitalized horses with ocular disease. We hypothesized that HGS and BPS would be associated with different clinical progressions.AnimalsPrivately owned horses hospitalized for ocular disease between September 2018 and September 2020.MethodsRetrospective observational study. The HGS and BPS were recorded daily throughout hospitalization. Clinical progressions were categorized as: (a) discharge from hospital after medical treatment, (b) ophthalmic surgery (eg, keratectomy, conjunctival flap, amniotic membrane transplantation, corneal transplant), or (c) enucleation. Temporal trends in HGS and BPS were assessed using linear regression. Correlations among slope, intercept, and progression were determined using the Kruskal‐Wallis test.ResultsOf 65 horses that met inclusion criteria, 29 (45%) were discharged after exclusively medical management, 28 (43%) underwent ophthalmic surgery, and 8 (12%) underwent enucleation. Two horses (3%) had 2 ophthalmic surgeries performed. The BPS scores at admission were higher in horses that were managed medically than in those that underwent enucleation (P = .01). Horses requiring enucleation had higher increases in HGS (P = .02) and BPS (P = .01) during hospitalization than horses that were medically managed and a higher increase in BPS (P = .04) than horses that required ophthalmic surgery.Conclusions and Clinical ImportancePain scoring may represent a useful tool for monitoring progression and response to treatment in hospitalized horses with ocular disease.
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.
OBJECTIVEThis study served to compare the degree of adrenocortical suppression following a 2-week administration of loteprednol etabonate (LE) and prednisolone acetate (PA) ophthalmic drops.PROCEDURESIn this prospective double-masked triple-crossover study, 21 clinically healthy dogs were randomized to receive loteprednol etabonate ophthalmic suspension 0.5%, prednisolone acetate ophthalmic suspension 1%, or artificial tears (AT). Each group (LE, PA, and AT) received one drop in each eye every 12 h for 2 weeks, followed by a 3-week washout period between treatment blocks. ACTH stimulation tests were performed before and after each treatment block. Serum cortisol samples were drawn before and 60 min after administration of 1 μg/kg cosyntropin IV. Repeated-measurement ANOVA followed by a Tukey's multiple comparisons test (or a Friedman test followed by a Dunn's multiple comparisons test) were used to compare pre- and post-treatment cortisol values between each group. A p-value of ≤.05 was considered significant.RESULTSA total of 18 dogs completed the study. Prestimulation cortisol values were lower in the PA group compared to the LE (p = .0106), but not AT (p = .0589) groups, and post-stimulation cortisol values were lower in the PA group than either LE (p = .0005) or AT (p = .0002) groups. There was no significant difference detected in pre- or post-stimulation cortisol values after the treatment periods between LE and AT.CONCLUSIONSBased on the reduced suppression of cortisol values, LE caused significantly less hypothalamic-pituitary-adrenal axis suppression than PA. A topical steroid with minimal adrenocortical suppression, such as LE, may be favorable in patients where systemic glucocorticoid effects should be avoided.
Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness. Notably, suppressor of cytokine signaling 1 (SOCS1), which naturally limits the activation of Jak2 through binding interactions, is often deficient in autoimmune disease patients. Significantly, we previously showed that topical administration of a SOCS1 peptide mimic (SOCS1-KIR) mitigated induced rodent uveitis. In this pilot study, we test the potential to translate the therapeutic efficacy observed in experimental rodent uveitis to equine patient disease. Through bioinformatics and peptide binding assays we demonstrate putative binding of the SOCS1-KIR peptide to equine Jak2. We also show that topical, or intravitreal injection of SOCS1-KIR was well tolerated within the equine eye through physical and ophthalmic examinations. Finally, we show that topical SOCS1-KIR administration was associated with significant clinical ERU improvement. Together, these results provide a scientific rationale, and supporting experimental evidence for the therapeutic use of a SOCS1 mimetic peptide in RU.
PURPOSE:To examine the relationship between Minimum Inhibitory Concentration (MICs) and response to therapy of 6 Fusarium spp. and 5 Aspergillus fumigatus isolated from equine ulcerative keratitis cases.PROCEDURE:Fungi were identified by morphology and Internal Transcribed Spacer (ITS) polymerase chain reaction (PCR) with sequencing and evaluated at the University of Texas Fungal Testing Laboratory for susceptibility to three azole antifungals (miconazole, voriconazole, posaconazole), natamycin, and two echinocandins (anidulafungin, caspofungin). A Mann-Whitney rank sum test was used for the comparison of time to heal between infections of different fungal genera and in vitro susceptibility to the drug administered.RESULTS:Fusarium spp. were resistant to azole antifungals in 6/6 cases (100%). Fusarium spp. were susceptible to echinocandins and natamycin in all cases. A. fumigatus was resistant to anidulafungin in 1/5 cases (20%) and posaconazole in 1/5 cases (20%) The remainder of A. fumigatus isolates were susceptible to all antifungal agents tested. Fusarium isolates were treated with antifungals to which they were not susceptible; however, all cases of A. fumigatus were treated with antifungals to which they were susceptible. All Fusarium cases and A. fumigatus cases experienced clinical resolution, regardless of surgical intervention. There was no statistical correlation between fungal genus and time to heal (p < .082).CONCLUSIONS:The in vitro susceptibility indicated that all cases of Fusarium spp. were resistant to azole antifungal drugs which were used as treatment. Clinical outcomes, however, showed that all cases healed despite resistance to antifungals.
Although rare, embryonal tumors (previously called primitive neuroectodermal tumors) should be considered in the differential diagnosis of retrobulbar tumors in dogs regardless of the age of the patient, and ancillary tests are required for definitive diagnosis.
OBJECTIVETo perform retrospective analysis of captive pteropodid bats presented to the University of Florida for ocular or adnexal disease from 2003-2020.ANIMALS STUDIEDTwenty-four individuals from seven species were included.PROCEDURESRecords were analyzed for disease process, methods of treatment, and surgical techniques and complications.RESULTSThe most frequently reported abnormality was corneal disease (79%), followed by cataracts (54%), and uveitis (42%). Corneal disease was primarily attributed to either trauma or exposure keratitis secondary to buphthalmia. The majority of uveitis appeared to be lens-induced. Five cases (21%) of glaucoma were reported, all of which accompanied lens luxation. Of the seven enucleations performed, six had post-operative complications (85.7%), including swelling at the surgical site, seroma formation, and bacterial infection. There was no significant relationship between age and trauma, age and cataract formation, sex and trauma, or species and cataract formation.CONCLUSIONSThe most common underlying cause of ocular pathology in these cases was trauma. While the bats tolerated topical and systemic treatment well, individual temperament must be taken into account when developing treatment plans, and prevention of injury is the most effective management strategy.
OBJECTIVE To describe a novel, minimally invasive method for re-establishing aqueous humor outflow in dogs with refractory glaucoma after fibrous encapsulation of their Ahmed drainage implants. PROCEDURE Three dogs (4 eyes) underwent trans-capsular implantation of an Alcon EX-PRESS® glaucoma filtration device under sedation (2 dogs) or general anesthesia (1 dog). After rotating the eye downwards, a 2 mm incision was made in the conjunctiva/Tenon's capsule overlying the encapsulated Ahmed plate, and later closed with absorbable suture. All eyes received subconjunctival mitomycin-C 0.02 mg. RESULTS Mean post-operative follow-up was 341 days (range: 77-530). All eyes were hypertensive pre-operatively (mean IOP: 31.25 ± 7.14 mmHg) despite receiving topical latanoprost (4/4), timolol (4/4), carbonic anhydrase inhibitors (4/4), and demecarium bromide (2/4). Two eyes (dogs 1 and 2) were visual pre-operatively, while 2 eyes (dog 3) displayed equivocal or no vision. Post-operatively, all eyes received timolol and a carbonic anhydrase inhibitor. Other anti-hypertensive medications were discontinued. Immediately following surgery, all eyes were mildly hypotensive (mean IOP: 5.75 ± 1.71 mm Hg). Two of 4 eyes were normotensive and visual until days 90 (dog 2) and 530 (dog 1) (IOP range: 10-16 mm Hg). One eye (dog 3) was normotensive for approximately 150 days, and then hypertension returned. One eye (dog 3) from the start displayed severe uveitis, hypertensive episodes, and was phthisical by the end of follow-up. CONCLUSIONS Trans-capsular EX-PRESS® implantation is a minimally invasive procedure for treatment of refractory glaucoma in dogs with encapsulated Ahmed drainage implants, and further investigation is warranted.
OBJECTIVETo describe common bacterial organisms cultured from retrobulbar cellulitis and abscess lesions, in vitro susceptibility patterns, common diagnostic techniques utilized, etiologies encountered, and prevalence of blindness.ANIMALS STUDIEDThirty-eight dogs diagnosed with retrobulbar cellulitis or abscessation from 2007 to 2017.PROCEDUREFor cases of orbital cellulitis or abscess, signalment, orbital imaging, cytology, histopathology, bacterial culture and susceptibility testing, presence of vision at the initial examination and resolution, and presumed cellulitis/abscess etiology were recorded.RESULTSMost cases were medically (78.9%) versus surgically managed (18.4%). Most common form of orbital imaging was computed tomography (48.5%) followed by ocular ultrasound (18.2%). Fifteen of eighteen cultures (83.3%) showed growth of aerobic bacterial organisms, anaerobic bacterial organisms, or both. Most common aerobic bacteria were gram-negative bacilli (40.0%) followed by Corynebacterium sp. (26.7%) and α-hemolytic Streptococci sp. (26.7%) but Micrococcus and Bacillus spp. were also identified. Most common anaerobic bacteria were gram-negative bacilli (40.0%). Antibiotics with highest susceptibility patterns included gentamicin, followed equally by amoxicillin/clavulanic acid, cephalothin, chloramphenicol, and imipenem. No bacteria were susceptible to cefovecin. Six cases presented with vision loss due to retrobulbar disease (15.8%). Idiopathic (50%) disease and tooth root abscessation (23.7%) were most commonly diagnosed cause of orbital disease.CONCLUSIONRetrobulbar cellulitis/abscess is a serious and vision-threatening process, which can be effectively managed by broad-spectrum antibiotics such as gentamicin or amoxicillin/clavulanic acid, but not cefovecin. This study identified three organisms that have not been previously reported to be associated with orbital cellulitis (Corynebacterium sp., Bacillus sp. and Micrococcus sp.).
Sample storage conditions are an important factor in fecal microbiota analyses in general. The objective of this study was to investigate the effect of sample storage at room temperature on the equine fecal microbiota composition. Fecal samples were collected from 11 healthy horses. Each sample was divided into 7 sealed aliquots. One aliquot was immediately frozen at −80 °C; the remaining aliquots were stored at room temperature (21 to 22 °C) with one transferred to the freezer at each of the following time points: 6, 12, 24, 48, 72 and 96 h. The Illumina MiSeq sequencer was used for high-throughput sequencing of the V4 region of the 16S rRNA gene. Fibrobacteraceae (Fibrobacter) and Ruminococcaceae (Ruminococcus) were enriched in samples from 0 h and 6 h, whereas taxa from the families Bacillaceae, Planococcaceae, Enterobacteriaceae and Moraxellaceae were enriched in samples stored at room temperature for 24 h or greater. Samples frozen within the first 12 h after collection shared similar community membership. The community structure was similar for samples collected at 0 h and 6 h, but it was significantly different between samples frozen at 0 h and 12 h or greater. In conclusion, storage of equine fecal samples at ambient temperature for up to 6 h before freezing following sample collection had minimal effect on the microbial composition. Longer-term storage at ambient temperature resulted in alterations in alpha-diversity, community membership and structure and the enrichment of different taxa when compared to fecal samples immediately frozen at −80 °C.
OBJECTIVE To report ophthalmic examination, biometry, phenol red thread test (PRTT), intraocular pressure (IOP), and histologic findings from a private collection of inland bearded dragons (Pogona vitticeps). ANIMALS STUDIED Fourteen inland bearded dragons. PROCEDURES Complete ophthalmic examinations were performed on all animals, including slit-lamp biomicroscopy, indirect ophthalmoscopy, fluorescein stain, phenol red thread test, and rebound tonometry. B-mode ultrasonography was used to measure anterior chamber depth, axial lens thickness, vitreal chamber depth, and axial globe length. Horizontal corneal diameter was estimated using ImageJ software. Histologic assessment was obtained for one of the bearded dragons that died following the study period. RESULTS The median PRTT value was 7.27 mm/15 seconds. Mean IOP was 6.29 ± 1.60 mm Hg and 2.14 ± 1.37 mm Hg using the dog and undefined calibration settings, respectively. Median axial globe length was 11.75 mm. Mean anterior chamber depth and mean lens thickness were 2.06 ± 0.35 mm and 3.38 ± 0.45 mm, respectively. Median vitreal chamber depth was 6.79 mm. Mean horizontal corneal diameter was 5.138 ± 0.346 mm. Two distinct ocular phenotypes were observed, with two of the bearded dragons having corneal globosa, deep anterior chambers, and tufts of iridal vessels and fibrillar material extending into the anterior chamber. CONCLUSIONS The ultrasound biometry, PRTT, and rebound tonometry results may serve as a guideline for ophthalmic parameters in healthy bearded dragons. Examination and testing of greater numbers of animals are necessary to establish true reference ranges and determine if the observed ocular phenotypes represent normal variants or pathologic changes.
BACKGROUND Creeping Indigo (Indigofera spicata) toxicosis is an emerging problem among horses in Florida and bordering states. OBJECTIVES To quantify the putative toxins l-indospicine (IND) and 3-nitropropionic acid (NPA) in creeping indigo collected from multiple sites and to measure plasma toxin concentrations in ponies fed creeping indigo and horses with presumptive creeping indigo toxicosis. STUDY DESIGN Experimental descriptive study with descriptive observational field investigation. METHODS Air-dried creeping indigo was assayed for IND and NPA content. Five ponies were fed chopped creeping indigo containing 1 mg/kg/day of IND and trace amounts of NPA for 5 days, then observed for 28 days. Blood samples from these ponies and from horses involved in a presumptive creeping indigo toxicosis were assayed for IND and NPA. RESULTS IND in creeping indigo plants was 0.4 to 3.5 mg/g dry matter whereas NPA was <0.01 to 0.03 mg/g. During creeping indigo feeding, clinical and laboratory signs were unchanged except for significant weight loss (median 6%, range 2-9%; p = 0.04) and significant increase from baseline plasma protein concentration (median 16 g/L, range 8-25 g/L; p <0.001). These changes could not definitively be ascribed to creeping indigo ingestion. Plasma IND rose to 3.9 ± 0.52 mg/L on day 6. Pharmacokinetic modeling indicated an elimination half-life of 25 days and a steady state plasma concentration of 22 mg/L. Plasma IND concentration in sick horses during an incident of creeping indigo toxicosis was approximately twice that of clinically normal pasture-mates. Plasma NPA was <0.05 mg/L in all samples. MAIN LIMITATIONS Creeping indigo used in the feeding trial may not be representative of plants involved in creeping indigo toxicosis. There was no control group without creeping indigo in the feeding trial. CONCLUSIONS Indospicine can be detected in blood of horses consuming creeping indigo and the toxin accumulates in tissues and clears slowly. The role of NPA in the neurological signs of this syndrome is unclear.
AIMTo examine the use of prophylactic anti-glaucoma medications in the normotensive fellow eye in dogs with unilateral overt primary glaucoma by veterinary ophthalmology clinicians.METHODSA survey of veterinary ophthalmology clinicians was distributed over two international list serves servicing veterinary ophthalmologists, trainees, and individuals whose practice consisted primarily of ophthalmic patients. The survey was developed following analysis of historical and currently available medical options for control of intraocular pressure and for neuroprotection.RESULTSResponses from 199 veterinary ophthalmology clinicians were evaluated. While a large variety of topical anti-hypertensive drugs and protocols were used, the most commonly used medications were aqueous humor production suppressors such as dorzolamide 2.0% ophthalmic solution, timolol 0.5% ophthalmic solution, and a combination product containing both drugs. Latanoprost 0.005% ophthalmic solution was used infrequently for prophylaxis by comparison. The majority of respondents do not use concurrent anti-inflammatory medications (61.22%), although a sizeable minority used prednisolone acetate, dexamethasone, or ketorolac as prophylactic treatment. Systemically administered ocular anti-hypertensive agents were rarely used. Only 40% of respondents used neuroprotectant agents; the most commonly prescribed were the calcium channel blocker amlodipine and the nutraceutical Ocu-Glo™. Recommended intervals between re-examination by the clinician ranged from one month to one year, with most re-evaluations occurring every 3 to 6 months. The majority of respondents recommended more frequent assessments of IOP at intervals between once monthly and once every 3 months.CONCLUSIONSData analysis of medical therapy for the normotensive fellow eye of dogs previously diagnosed with primary glaucoma suggests that there is a great need for well-designed, prospective, controlled, multi-center studies to determine which protocols have the greatest efficacy in delaying an overt attack in the previously normotensive eye in dogs with a genetic predisposition to glaucoma. Prospective studies utilizing a carbonic anhydrase inhibitor such as dorzolamide and a prostaglandin analogue such as latanoprost would be reasonable as these two drugs are widely used in the treatment of overt glaucoma and would allow for an exploration of the impact of different mechanisms of action of lowering IOP on the pathophysiology of primary glaucoma.
Abstract Recurrent Uveitis (RU), is a relapsing/remitting disease that accounts for more than 10% of severe visual handicaps in US patients per year, despite treatments that often include steroids. Even when effective, prolonged steroid use is accompanied by significant negative side effects. As such, there is a critical need for the development of novel therapeutic strategies to treat RU. Notably, equine recurrent uveitis (ERU) is the only spontaneous model of human recurrent uveitis, and is also a leading cause of equine blindness. RU is driven by aberrant inflammation from the immune system. Notably, the body naturally generates a family of intracellular proteins, known as suppressors of cytokine signaling (SOCS), which prevent excessive inflammatory responses. We have previously shown that topical application of an eye drop, containing a cell-penetrating peptide that mimics SOCS1 (SOCS1-KIR), could mitigate experimental uveitis in mice. In order to evaluate the ability to translate our preclinical findings we conducted a first in equine, open label study in which we evaluated the safety and efficacy of topical SOCS1 peptide administration in ERU patients. We found that topical SOCS1-KIR administration was well tolerated in equine patients. Moreover, topical administration of SOCS1-KIR peptide twice a day was associated with reductions in ocular discomfort, hyperemia, and aqueous flare. Additionally, biochemical analyses of SOCS1-KIR revealed an enrichment strategy that could potentially be utilized to optimize ocular peptide dosing. Together, these results prove justification for conducting larger additional treatment studies in horses, and exploring SOCS1-KIR use in humans.