Subconjunctival liposomal sirolimus vs. cyclosporine or tacrolimus as treatment of keratoconjunctivitis sicca in dogs: A double-blind, randomized study.

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.

Bilateral palpebral reduction and concurrent mycoplasmosis in a wild Agassiz's desert tortoise (Gopherus agassizii).

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.

Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults.

BACKGROUND: AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab). METHODS: This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated AZD7442 administered intramuscularly (300 mg) or intravenously (300, 1000, or 3000 mg) in healthy adults (aged 18-55 years). The primary end point was safety and tolerability. Secondary end points included pharmacokinetics and antidrug antibodies. RESULTS: Between 18 August and 16 October 2020, a total of 60 participants were enrolled; 50 received AZD7442, and 10 received placebo. Adverse events (all of mild or moderate intensity) occurred in 26 participants (52.0%) in the AZD7442 groups and 8 (80.0%) in the placebo group. No infusion or injection site or hypersensitivity reactions occurred. Tixagevimab and cilgavimab had mean half-lives of approximately 90 days (range, 87.0-95.3 days for tixagevimab and 79.8--91.1 days for cilgavimab) and similar pharmacokinetic profiles over the 361-day study period. SARS-CoV-2-specific neutralizing antibody titers provided by AZD7442 were maintained above those in plasma from convalescent patients with coronavirus disease 2019 (COVID-19). CONCLUSIONS: AZD7442 was well tolerated in healthy adults, showing a favorable safety profile across all doses. Depending on the SARS-CoV-2 variant, pharmacokinetic analyses suggest the AZD7442 could offer protection for ≥6 months against symptomatic COVID-19 after a single 300-mg intramuscular administration. CLINICAL TRIALS REGISTRATION: NCT04507256.

Antibodies are proteins produced by the body in response to infections caused by microbes, including viruses. AZD7442 is a combination of 2 human antibodies, with an extended duration of effect, sourced from people who had recovered from coronavirus disease 2019 (COVID-19). These antibodies recognize a specific part (spike protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and prevent the virus from infecting cells in the body. The current study evaluated the safety of AZD7442 in healthy volunteers. Sixty adults were given AZD7442 or placebo (salt solution) as injections into the muscle (300-mg dose) or infusions into a vein (300­3000-mg doses). The study did not find any safety issues with AZD7442, including at the highest dose. AZD7442 was measured in the blood 12 months after dosing, suggesting a long duration of protection. Following this study, AZD7442 was tested in larger clinical trials to investigate its potential in preventing and treating COVID-19. AZD7442 is currently authorized as treatment for outpatients with COVID-19 and as a preventive drug in people who may not respond well to COVID-19 vaccines and need additional protection (eg, those taking medications that dampen the immune system).

Disseminated idiopathic lipid keratopathy in a normolipemic cat.

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.

Cardiovascular disease in women: A review of spontaneous coronary artery dissection.

Research has demonstrated the disproportionate quality of care for women with cardiovascular disease. These findings have prompted a renewed focus on cardiovascular disease awareness and disease prevention in women. Spontaneous coronary artery dissection (SCAD) is a significant cause of myocardial infarction (MI) and sudden death that primarily affects women. ongoing research has led to improved diagnostic capabilities and changes in approaches to initial and long-term management most importantly this research has provided evidence that SCAD is more common than previously thought and must be evaluated and treated differently from atherosclerotic MI. The difference between SCAD and atherosclerotic MI is highlighted in high rates of recurrent disease, gender distribution, association with exogenous hormones, pregnancy, migraine, physical and emotional stress triggers, concurrent systemic arteriopathies, and connective tissue disease. In this review, we provide updated insights and a summary of the epidemiology, risk factors, clinical presentation, diagnosis, treatment options, prognosis, and recurrence prevention of SCAD. We aim to provide a review of SCAD as a focus on cardiovascular disease awareness and disease prevention in women.

Pharmacokinetics of Sirolimus in a Novel Liposome Delivery System in Selected Ocular Tissues and Plasma Following a Single Subconjunctival Injection in Dutch Belted Rabbits.

Purpose: To determine the pharmacokinetics of a proprietary liposomal sirolimus (LS) formulation in ocular tissues and plasma following a single subconjunctival (SCJ) injection in Dutch belted rabbits (DBR). Analytical methods for detection of LS in plasma, aqueous humor (AH), vitreous humor (VH), retina, combined retina/choroid/retinal pigment epithelium, sclera, and iris/ciliary body were developed to examine samples. Methods: Thirty male DBR were subconjunctivally injected in both eyes with 0.1 mL of LS of 1,000 µg/mL. At selected times post-injection, ocular tissues and whole blood samples were obtained. Sirolimus concentrations were measured using liquid chromatography/tandem mass spectrometry. Results: No LS was detected in serum or AH at any time. All other examined ocular tissues had quantifiable amounts of LS at all times. LS levels were highest in sclera and lowest in VH, suggesting LS followed the supraciliary and suprachoroidal spaces to reach the posterior segment. Vitreous peak of sirolimus levels occurred at 2 h, and the sclera adjacent to the injection peaked at both 2 and 96 h. LS levels in remaining ocular tissues peaked at 6 h and decreased with time, persisting at presumed therapeutic levels on day 22. Conclusions: LS can quickly diffuse into posterior intraocular tissues after SCJ injection without reaching quantifiable levels in AH or serum in DBR. Peak levels occurred in posterior intraocular tissues at 6 h and persisted in all tissues after 3 weeks. SCJ LS in DBR is safe, has a stable pharmacokinetic profile, and should be considered for further study in human trials for autoimmune ophthalmopathies.

Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Early intramuscular administration of SARS-CoV-2-neutralising monoclonal antibody combination, tixagevimab-cilgavimab, to non-hospitalised adults with mild to moderate COVID-19 has potential to prevent disease progression. We aimed to evaluate the safety and efficacy of tixagevimab-cilgavimab in preventing progression to severe COVID-19 or death. METHODS: TACKLE is an ongoing, phase 3, randomised, double-blind, placebo-controlled study conducted at 95 sites in the USA, Latin America, Europe, and Japan. Eligible participants were non-hospitalised adults aged 18 years or older with a laboratory-confirmed SARS-CoV-2 infection (determined by RT-PCR or an antigen test) from any respiratory tract specimen collected 3 days or less before enrolment and who had not received a COVID-19 vaccination. A WHO Clinical Progression Scale score from more than 1 to less than 4 was required for inclusion and participants had to receive the study drug 7 days or less from self-reported onset of mild to moderate COVID-19 symptoms or measured fever. Participants were randomly assigned (1:1) to receive either a single tixagevimab-cilgavimab 600 mg dose (two consecutive 3 mL intramuscular injections, one each of 300 mg tixagevimab and 300 mg cilgavimab) or placebo. Randomisation was stratified (using central blocked randomisation with randomly varying block sizes) by time from symptom onset, and high-risk versus low-risk of progression to severe COVID-19. Participants, investigators, and sponsor staff involved in the treatment or clinical evaluation and monitoring of the participants were masked to treatment-group assignments. The primary endpoints were severe COVID-19 or death from any cause through to day 29, and safety. This study is registered with ClinicalTrials.gov, NCT04723394. FINDINGS: Between Jan 28, 2021, and July 22, 2021, 1014 participants were enrolled, of whom 910 were randomly assigned to a treatment group (456 to receive tixagevimab-cilgavimab and 454 to receive placebo). The mean age of participants was 46·1 years (SD 15·2). Severe COVID-19 or death occurred in 18 (4%) of 407 participants in the tixagevimab-cilgavimab group versus 37 (9%) of 415 participants in the placebo group (relative risk reduction 50·5% [95% CI 14·6-71·3]; p=0·0096). The absolute risk reduction was 4·5% (95% CI 1·1-8·0; p<0·0001). Adverse events occurred in 132 (29%) of 452 participants in the tixagevimab-cilgavimab group and 163 (36%) of 451 participants in the placebo group, and were mostly of mild or moderate severity. There were three COVID-19-reported deaths in the tixagevimab-cilgavimab group and six in the placebo group. INTERPRETATION: A single intramuscular tixagevimab-cilgavimab dose provided statistically and clinically significant protection against progression to severe COVID-19 or death versus placebo in unvaccinated individuals and safety was favourable. Treating mild to moderate COVID-19 earlier in the disease course with tixagevimab-cilgavimab might lead to more favourable outcomes. FUNDING: AstraZeneca.

Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. METHODS: We randomly assigned, in a 2:1 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection. RESULTS: A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P<0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; 95% CI, -8.6 to 86.8; P = 0.07). Among infants with data available to day 361, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group. Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo. CONCLUSIONS: A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection. (Funded by MedImmune/AstraZeneca and Sanofi; MELODY ClinicalTrials.gov number, NCT03979313.).

Effect of Topical 1% Tetracaine Hydrochloride on Intraocular Pressure in Ophthalmologically Normal Horses; a Pilot Study.

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.

Studies of human twins reveal genetic variation that affects dietary fat perception.

To learn more about the mechanisms of human dietary fat perception, 398 human twins rated fattiness and liking for six types of potato chips that differed in triglyceride content (2.5, 5, 10, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness and liking for the potato chips were reliable (r = 0.31-0.62, p < 0.05) and heritable (up to h2 = 0.29, p < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, p < 1×10-5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was (a) negatively affected by the addition of a saturated fatty acid and (b) related to inborn genetic variants. These data suggest liking for dietary fat is not due solely to fatty acid content and highlight new candidate genes and proteins within this sensory pathway.

Fluoroscopically guided neocanalization for treatment of nasolacrimal atresia in two horses.

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.

Measurement of intraocular pressure in healthy anesthetized horses during hoisting.

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 diazepam-ketamine, after intubation, when suspended by the hoist and on the operating table. During hoisting, the head was supported and the eye-heart 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.

Development and Assessment of a Novel Canine Ex Vivo Corneal Model.

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 mm2/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.

Clinical behavior of intraocular teratoid medulloepithelioma in two-related Quarter Horses.

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.

Preformulation Studies of a Liposomal Formulation Containing Sirolimus for the Treatment of Dry Eye Disease.

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.

A retrospective analysis of environmental risk factors for the diagnosis of deep stromal abscess in 390 horses in North Central Florida from 1991 to 2013.

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.

Ophthalmic abnormalities secondary to periocular or ocular snakebite (pit vipers) in dogs--11 cases (2012-2014).

OBJECTIVE: To describe ophthalmic abnormalities secondary to periocular and ocular snakebite in dogs. ANIMAL STUDIED: Retrospective 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). RESULTS: Records 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. CONCLUSIONS: Periocular symptoms were more commonly observed than ocular alterations, regardless of bite location. Appropriate supportive therapy should be instituted according to clinical signs.

Proteomic analysis of equine amniotic membrane: characterization of proteins.

INTRODUCTION: Human amniotic membrane (AM) has been used as a biomaterial for surgical wound skin and ocular surface reconstruction for several years. Currently, equine AM has been used for corneal reconstruction in several animal species, and appears to have the same properties as human AM. Despite the observed positive healing abilities of this tissue in horses with ulcerative keratitis the proteins of equine AM have not been described. OBJECTIVE: To identify proteins known to be associated with corneal healing from frozen equine AM. PROCEDURES: Placentas were acquired from healthy live foal births from a local Thoroughbred breeding farm. The amnion was removed from the chorion by blunt dissection, washed with phosphate-buffered saline (PBS), and treated with 0.05% trypsin and 0.02% ethylene diaminetetraacetic acid in PBS. Amnion was attached to nitrocellulose paper (epithelial side up), and cut into 4 × 4 cm pieces. The sheets were frozen at -80 °C. The protein samples were solubilized, and analyzed by 2D gel electrophoresis and shotgun proteomics. RESULTS: A reference identification map of the equine AM proteins was produced and 149 different proteins were identified. From gel-based proteomics, 49 spots were excised and 43 proteins identified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Shotgun proteomics identified 116 proteins with an overlap of 10 proteins in both analyses. CONCLUSIONS: We have described a reference map for equine AM proteins that may provide a background to explain the positive results found in horses with ulcerative keratopathies using this biomaterial.

Standing ophthalmic surgeries in horses.

Standing ophthalmic surgery without general anesthesia allows for several routine ophthalmic procedures including eyelid lacerations and enucleations to be performed in the horse, but does contain increased risk of causing tissue damage arising from the inability to eliminate eye and head movements. Heavy sedation and local nerve blocks of the involved motor and sensory nerves are essential in achieving a good outcome from ophthalmic surgery in the nonanesthetized horse. The inability to use an operating microscope in standing surgery in horses prevents performing precise corneal and intraocular microsurgeries.