Pro-inflammatory cytokines in aqueous humor from dogs with anterior uveitis and post-operative ocular hypertension following phacoemulsification, primary glaucoma, and normal healthy eyes.

BACKGROUND: The aim of this study was to evaluate the levels of pro-inflammatory cytokines in aqueous humor (AH) from dogs with anterior uveitis and post-operative ocular hypertension (POH) following phacoemulsification, in AH from dogs with primary glaucoma, and in normal healthy eyes with no signs of anterior uveitis or other ocular diseases. METHODS: An exploratory study including 21 samples of AH collected from 15 dogs; post-phacoemulsification with anterior uveitis and POH ('POH group', n = 10 samples), primary glaucoma ('glaucoma group', n = 6 samples), and normal ('normal group', n = 5 samples). Target mass spectrometry via multiple reaction monitoring (MRM-MS) with the Canine Cytokine SpikeMix™ as internal standard was used to measure the pro-inflammatory cytokine levels. RESULTS: The MRM-MS method measured 15 pro-inflammatory cytokines. Tumor-necrosis-factor-alpha (TNFα) and interleukin-18 (IL-18) levels in AH were different between all three groups (glaucoma>POH>normal) (p = .05, p = .02, respectively). Additionally, IL-6 was higher in the 'POH group' compared to the 'glaucoma group' (p = .04) and IL-4 was higher in the 'POH group' compared to the 'normal group' (p = .04). Intraocular pressure (IOP) was positively associated with increased AH levels of IL-18 (Spearman correlation = .64, p = .03). CONCLUSIONS: MRM-MS using the Canine Cytokine SpikeMix™ as an internal standard was established as a method to detect pro-inflammatory cytokine levels in canine AH. The study demonstrated increased levels of IL-4, IL-6, IL-18, and TNFα in AH from canines with POH following phacoemulsification. Primary glaucomatous eyes had the highest levels of IL-18 and TNFα which may indicate that inflammation plays a role in the pathogenesis of primary glaucoma in dogs.

Acidic chemical corneal ulceration secondary to nail polish spill in a puppy.

PURPOSE: To describe the treatment of an acidic chemical corneal ulceration in a puppy secondary to nail polish spilling on and adhering to the cornea. CASE SUMMARY: A 12-week-old neutered male Australian Shepherd mix dog was presented to Colorado State University Veterinary Teaching Hospital's (CSU-VTH) Emergency and Urgent Care service acutely after exposure to nail polish spilling on the left eye (OS). Initial ophthalmic examination revealed nail polish adhered to approximately 80% of the cornea with moderate diffuse corneal edema and chemosis, and green nail polish adhered to the skin and fur of the periocular area. Copious flushing with eye wash was performed, but no areas of reduced nail polish adherence were noted. The patient was treated with 1 drop of topical ofloxacin 0.3% ophthalmic solution OS and hospitalized overnight, receiving hyaluronic acid ophthalmic lubrication every hour OS. The treatment plan was carried out for 6 h until time of transfer. In the morning, CSU-VTH's Ophthalmology service removed a nonadhered nail polish plaque in 1 piece using Bishop-Harmon tissue forceps. Following removal, a superficial ulcer secondary to an acidic chemical burn covering 100% of the corneal surface was noted, as well as moderate diffuse corneal edema. Following topical treatment for 8 days, the superficial ulcer healed completely, with no significant long-term consequences. UNIQUE INFORMATION PROVIDED: This is the first report of management of an acidic chemical corneal ulceration secondary to nail polish spill in a puppy. Early assessment and vigilance in treatment was essential for a good prognosis and outcome.

Cataracts and phacoemulsification in the Siberian Husky: A retrospective and multicentric study (2008-2018).

PURPOSE: To compare cataract characteristics and complications related to cataracts and phacoemulsification in the Siberian Husky (Huskies) versus other canine breeds (non-Huskies). ANIMALS: A total of 50 Huskies (92 eyes) and 96 non-Huskies (182 eyes) were evaluated. METHODS: Medical records of Huskies (at four university veterinary hospitals, 2008-2018) and non-Huskies (Colorado State University, 2017-2018) diagnosed with cataracts were reviewed. Age of dog, cataract stage at presentation, and pre- and post-operative complications were recorded and analyzed. RESULTS: Mean (±standard deviation) age at presentation was significantly lower in Huskies (3.5 ± 3.3 years) compared to non-Huskies (9.5 ± 2.9 years) (p < .0001). Huskies more commonly presented with hereditary cataracts than non-Huskies (84% versus 52%) and a significantly higher percentage of non-Huskies presented with diabetic cataracts than Huskies (48% versus 16%; p = .0001). Cataract stage at presentation did not differ between Huskies and non-Huskies. Phacoemulsification was performed in 40% (20 out of 50 dogs, 39 out of 92 eyes) of Huskies and 42% (40 out of 96 dogs, 74 out of 182 eyes) of non-Huskies. Pre-operative and post-operative retinal detachment were more common in Huskies than non-Huskies (13% versus 2% and 10% versus 1%, respectively) but the difference was not significant. Other post-operative complications occurred with similar frequency in both groups (p ≥ .17). CONCLUSIONS: Huskies evaluated for cataracts were younger and less likely to present with diabetic cataracts than other canine breeds and, although not statistically significant, had a clinically important increased risk of retinal detachment pre- and post-phacoemulsification.

Investigation of Schirmer tear test-1 for measurement of tear production in cats in various environmental settings and with different test durations.

OBJECTIVE: To assess reliability of the Schirmer tear test-1 (STT-1) for measurement of tear production in cats in various environments, investigate whether sympathetic stimulation impacts measurements, and determine whether meaningful conclusions regarding lacrimation in cats can be drawn from STT-1 measurements obtained with STT strip placement for < 1 minute. ANIMALS: 176 cats examined in a private practice (n = 100), a feral cat clinic (56), or a veterinary teaching hospital (20). PROCEDURES: The STT-1 was performed in both eyes of each cat. Measurements were recorded at 10- or 30-second intervals for 1 minute. Cats at the teaching hospital were tested once in a quiet examination room (unstimulated conditions) and once in the same room with loud prerecorded noises (stimulated conditions), with a 30-minute interval between tests and evaluation of cats' heart rates before and after STT-1. Data were analyzed with parametric statistical tools and a nonlinear mixed-effect model. RESULTS: 30- and 60-second STT-1 measurements were significantly correlated (r = 0.94). The STT-1 measurements did not differ under nonstimulated versus stimulated conditions, despite significant changes in heart rates that indicated sympathetic stimulation. A hyperbolic model of STT-1 kinetics was validated, allowing for extrapolation of measurements obtained in < 60 seconds and generation of reference values (95% predictive intervals) for various test durations. Median (95% predictive interval) 30- and 60-second STT-1 measurements were 9.1 mm (4.8 to 15.6 mm) and 14.3 mm (8.2 to 22.3 mm), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The STT-1 was a reliable diagnostic test in all settings; results were not affected by sympathetic stimulation, and a shorter duration of testing could be considered in selected cases.

Fluorophotometric Assessment of Tear Volume and Turnover Rate in Healthy Dogs and Cats.

Purpose: The study establishes normative data of tear volume (TV) and tear turnover rate (TTR) in healthy dogs and cats, 2 species commonly used for translational research in ophthalmology. Methods: Thirty-six dogs and 24 cats were enrolled, encompassing a variety of breeds with diverse skull conformations (brachycephalic, mesocephalic, and dolichocephalic). Two microliters of 10% fluorescein were instilled onto the upper bulbar conjunctiva of both eyes, followed by tear collection with 2-µL capillary tubes at 0, 2, 4, 6, 10, 15, and 20 min. Fluorescein concentrations were measured with a computerized scanning ocular fluorophotometer. The TV and TTR were estimated based upon nonlinear mixed-effects analysis of fluorescein decay curves. Results: In dogs, median (interquartile range) TV, basal TTR (bTTR), and reflex TTR (rTTR) were 65.3 µL (42.3-87.9), 12.2%/min (3.7-22.1), and 50.0%/min (25.9-172.3), respectively. In cats, median (interquartile range) TV, bTTR, and rTTR were 32.1 µL (29.5-39.9), 10.9%/min (3.0-23.7), and 50.0%/min (28.4-89.4), respectively. Body weight (r = 0.44) and age (r = 0.30) were positively correlated (P ≤ 0.019) with TV in dogs. Age was negatively correlated (P ≤ 0.018) with TTR in dogs (r = -0.33) and cats (r = -0.24). However, TV and TTR were not associated with skull conformation in either species. Conclusions: Dogs have greater TV than cats but similar basal and rTTR. Tear parameters were impacted by body weight and age, but not by skull conformation. In both clinical and research settings, successive lacrimal tests should be spaced by ≥10 min to provide sufficient time for the tear film to replenish, as bTTR is ∼11%/min-12%/min in both species.

Clinical features of cats with aqueous tear deficiency: a retrospective case series of 10 patients (17 eyes).

OBJECTIVES: The aim of this study was to describe the clinical findings, diagnostic test results and response to therapy of cats with Schirmer tear test 1 (STT-1) values below the reference interval. METHODS: The medical records of three institutions were searched for cats with ocular surface disease and STT-1 values <9 mm/min, confirmed at two or more separate visits. RESULTS: Ten cats (17 eyes) were included. The mean ± SD (range) age and STT-1 values in affected eye(s) were 6.1 ± 5.7 (0.2-16) years and 2.4 ± 3.1 (0-8) mm/min, respectively. Concurrent ocular surface disease was bilateral in 5/10 cats. Clinical signs included conjunctivitis (14/17 eyes), corneal ulceration (6/17 eyes), non-ulcerative keratitis (4/17 eyes), symblepharon (4/17 eyes), eosinophilic keratitis (3/17 eyes), corneal sequestrum (3/17 eyes), corneal fibrosis (2/17 eyes) and meibomitis (2/17 eyes). Management included: topically applied lacrimomimetics, antiviral drugs, corticosteroids or immunomodulatory drugs; orally administered famciclovir; or surgical procedures, in various combinations. Response to therapy (defined as an increase in STT-1 value of ⩾5 mm/min) was transient (seen at a single reassessment) in 65% of eyes and sustained (seen at ⩾2 consecutive reassessments) in 18% of eyes. CONCLUSIONS AND RELEVANCE: Clinical features seen in cats with low STT-1 values are described, although the association between aqueous deficiency and the reported ocular changes is unknown at this time. We encourage clinicians to assess the tear film in cats with ocular surface disease, and initiate therapy with lacrimomimetics if STT-1 values are repeatedly below normal. Such information will further define aqueous tear deficiency in cats, providing a better understanding of disease prevalence, pathogenesis and treatment.

Pharmacokinetics, efficacy and safety of aleglitazar for the treatment of type 2 diabetes with high cardiovascular risk.

INTRODUCTION: In preliminary clinical studies, aleglitazar, a new dual PPAR-α-γ agonist, has been demonstrated to improve hyperglycemia and dyslipidemia in patients with type 2 diabetes mellitus. This review will provide up-to-date information on the clinical safety and efficacy of aleglitazar, which is currently under Phase III clinical investigation for reduction of cardiovascular events in patients with type 2 diabetes and recent acute coronary syndrome. AREAS COVERED: A PubMed literature search (January 1950 to February 2011) was conducted using the following search terms: aleglitazar, PPAR, PPAR α agonist, PPAR γ agonist and PPAR α/γ agonist. Additional articles were gathered using reference lists from sources obtained from the original literature search. This review summarizes available information pertaining to pharmacodynamics, pharmacokinetics, clinical studies and safety/tolerability of aleglitazar. The effects of this new drug are compared and contrasted with those of fibrates (PPAR-α agonists), thiazolidinediones (PPAR-γ agonists) and other dual PPAR-α-γ agonists. EXPERT OPINION: Preliminary evidence from clinical studies with aleglitazar is promising, with reported improvements in glycemia, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, apolipoprotein B and blood pressure. However, PPAR-α- and -γ-associated side effects have been observed and additional large-scale, long-term clinical studies are necessary to better understand the clinical implications of these effects.