OBJECTIVE To evaluate effects of topical ophthalmic administration of diclofenac on intraocular pressure (IOP) when applied at 4 frequencies to eyes of Beagles. ANIMALS 8 ophthalmologically normal Beagles. PROCEDURES The study involved four 5-day experimental periods each separated by a 16-day washout period. During each period, 1 drop of 0.1% diclofenac sodium ophthalmic solution was administered to the right eye at 4 treatment frequencies (1, 2, 3, or 4 times/d); 1 drop of eyewash was administered to the left eye as a control treatment. A complete ophthalmic examination was performed on days 0 (day before first treatment) and 5 of each experimental period. Gonioscopy was performed on day 0 of the first period. The IOPs were measured at 7 am and 7 pm on days 1 through 5. RESULTS No abnormalities were detected during neuro-ophthalmic and ophthalmic examinations on day 0 of each experimental period. No adverse reactions to administration of diclofenac or eyewash were observed at any time point. No abnormalities were detected during ophthalmic examinations performed on day 5, and IOPs remained < 25 mm Hg in all 4 periods. No significant differences were identified between the treated and control eyes or among the 4 treatment frequencies. CONCLUSIONS AND CLINICAL RELEVANCE Topical ophthalmic administration of diclofenac up to 4 times/d in dogs with no ophthalmic abnormalities did not significantly increase the IOP. Additional research is needed to evaluate the effect of topical ophthalmic administration of diclofenac on IOP in dogs with anterior uveitis.

OBJECTIVE To determine the effects of orally administered raltegravir in cats with experimentally induced ocular and respiratory feline herpesvirus-1 (FHV-1) infection. ANIMALS 14 healthy 6-month-old unvaccinated specific pathogen–free cats. PROCEDURES On day 0, all cats were experimentally inoculated by topical application of 0.1 mL of a solution containing 106 plaque-forming units of FHV-1 strain FH2CS to the inferior conjunctival fornix of each eye. Cats were randomly assigned to receive either raltegravir (80 mg; n = 7) or lactose (250 mg; vehicle; 7), PO, every 12 hours for 14 days beginning on day 1. Cats were assigned clinical ocular and respiratory disease scores every other day from days 0 to 30. Conjunctival swab specimens were collected for detection of FHV-1 by virus isolation and real-time PCR assay at 3-day intervals from days 0 to 30. Confocal microscopy was performed on days 0 and 10 to assess corneal epithelial leukocyte infiltration. The assessed variables and duration of FHV-1 shedding were compared between the 2 treatment groups. RESULTS Cats in both groups developed moderate to severe conjunctivitis and ulcerative keratitis characteristic of FHV-1 infection. Median duration of FHV-1 shedding was shorter and signs of ocular and respiratory disease were less severe for raltegravir-treated cats than for vehicle-treated cats. However, the mean conjunctival FHV-1 titer and corneal epithelial leukocyte count did not differ between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested orally administered raltegravir might be effective for alleviation of ocular and respiratory signs of FHV-1 infection in cats.

OBJECTIVE To determine the plasma pharmacokinetics and safety of 1% diclofenac sodium cream applied topically to neonatal foals every 12 hours for 7 days. ANIMALS Twelve 2- to 14-day old healthy Arabian and Arabian-pony cross neonatal foals. PROCEDURES A 1.27-cm strip of cream containing 7.3 mg of diclofenac sodium (n = 6 foals) or an equivalent amount of placebo cream (6 foals) was applied topically to a 5-cm square of shaved skin over the anterolateral aspect of the left tarsometatarsal region every 12 hours for 7 days. Physical examination, CBC, serum biochemistry, urinalysis, gastric endoscopy, and ultrasonographic examination of the kidneys and right dorsal colon were performed before and after cream application. Venous blood samples were collected at predefined intervals following application of the diclofenac cream, and plasma diclofenac concentrations were determined by liquid chromatography–mass spectrometry. RESULTS No foal developed any adverse effects attributed to diclofenac application, and no significant differences in values of evaluated variables were identified between treatment groups. Plasma diclofenac concentrations peaked rapidly following application of the diclofenac cream, reaching a maximum of < 1 ng/mL within 2 hours, and declined rapidly after application ceased. CONCLUSIONS AND CLINICAL RELEVANCE Topical application of the 1% diclofenac sodium cream to foals as described appeared safe, and low plasma concentrations of diclofenac suggested minimal systemic absorption. Practitioners may consider use of this medication to treat focal areas of pain and inflammation in neonatal foals.

OBJECTIVE To determine whether 2- or 3-times-daily application of topical ophthalmic 0.005% latanoprost solution is more effective at lowering intraocular pressure (IOP) in clinically normal dogs. ANIMALS 9 clinically normal dogs. PROCEDURES For each dog, I drop of latanoprost 0.005% solution was applied to 1 eye every 8 or 12 hours each day for 5 days; the contralateral eye received topical ophthalmic treatment with 1 drop of saline (0.9% NaCl) solution at the times of latanoprost application. Ocular examinations of both eyes were performed every 6 hours starting 48 hours prior to and ending 42 hours after the treatment period. Following a 5-week washout interval, the procedures were repeated but the previously latanoprost-treated eye of each dog received latanoprost application at the alternate frequency. RESULTS Mean ± SD IOP reduction in the latanoprost-treated eyes was 31 ± 6.9% with 2-times-daily application and 33 ± 8.2% with 3-times-daily application. A 2-way repeated-measures ANOVA revealed significant differences in IOP with contributions by treatment (2 or 3 times daily), time of day (diurnal variation), and individual dog. The maximum mean daily IOP reduction in latanoprost-treated eyes was detected on day 3 of latanoprost treatment in each group. Eyes treated 3 times daily had significantly smaller pupil diameter and greater conjunctival hyperemia than eyes treated 2 times daily. CONCLUSIONS AND CLINICAL RELEVANCE The clinical importance of the ocular hypotensive effects of 3-times-daily topical ophthalmic application of 0.005% latanoprost solution in dogs with glaucoma warrants investigation.

Objective: To evaluate agents used for delivery of small interfering RNAs (siRNAs) into feline corneal cells, toxicity of the delivery agents, and functionality of anti-feline herpesvirus 1 (FHV-1)–specific siRNA combinations. Sample: Feline primary corneal cells and 19 six-month-old colony-bred cats. Procedures: siRNA delivery into corneal cells via various delivery agents was evaluated via flow cytometric detection of labeled siRNAs. Cellular toxicity was evaluated with a proliferation assay. Functionality was tested via quantitative reverse transcriptase PCR assay, plaque assay, and flow cytometry. In vivo safety was evaluated with an ocular scoring method following topical application of delivery agents containing siRNAs into eyes. Corneal biopsy specimens were used to assess safety and uptake of siRNAs into corneal cells. Results: Use of 3 delivery agents resulted in > 95% transfection of primary corneal cells. Use of a peptide for ocular delivery yielded approximately 82% transfection of cells in vitro. In cultured corneal cells, use of the siRNA combinations resulted in approximately 76% to 89% reduction in FHV-1–specific mRNA, 63% to 67% reduction of FHV-1–specific proteins in treated cells, and 97% to 98% reduction in FHV-1 replication. The agents were nonirritating in eyes, caused no substantial clinical ocular signs, and were nontoxic. Histologically, corneal epithelium and stroma were normal in treated cats. However, none of the agents were effective in delivering siRNAs into the corneal cells in vivo. Conclusions and Clinical Relevance: The tested anti–FHV-1–specific siRNAs could potentially be used as a treatment for FHV-1 if a successful means of in vivo delivery can be achieved.

Objective-To evaluate the righting reflex after topical application of a sevoflurane jelly in cane toads (Bufo marinus). Animals-8 cane toads. Procedures-Toads were 6 to 8 months of age and weighed (mean +/- SD) 142.0 +/- 25.2 g. Sevoflurane jelly was applied to the dorsum of each toad at a dose of 25 μL/g in trial 1 and 37.5 μL/g in trial 2. Toads were placed in dorsal recumbency every 30 seconds until loss of the righting reflex. Jelly was then removed by rinsing the toads with tap water. Toads were then left undisturbed in dorsal recumbency until return of the righting reflex. Chamber sevoflurane concentration was measured to determine vaporization. Results-6 of 8 toads in trial 1 and 8 of 8 toads in trial 2 lost the righting reflex. Mean +/- SD time to loss of the reflex was 8.2 +/- 1.3 minutes for trial 1 and 8.3 +/- 0.9 minutes for trial 2; this difference was not significant. Mean +/- SD time to return of the reflex was 25.6 +/- 26.2 minutes for trial 1 and 84.4 +/- 47.2 minutes for trial 2; this difference was significant. Chamber sevoflurane concentration did not change significantly, compared with baseline (time 0) concentration, at any time in trial 1; however, there was a significant change in chamber sevoflurane concentration from baseline (time 0) concentration in trial 2. Chamber sevoflurane concentrations were not significantly different between trial 1 and trial 2 at any time. Mean +/- SD chamber sevoflurane concentration was 0.46 +/- 0.2% for trial 1 and 0.57 +/- 0.28% for trial 2. Conclusions and Clinical Relevance-Sevoflurane jelly applied topically at a dose of 37.5 μL/g induced a more reliable loss of righting reflex and longer recovery time than when applied at a dose of 25 μL/g in cane toads

The mydriatic effect of 3 curare-like neuromuscular blocking agents was tested in European kestrels (Falco tinnunculus) after topical application. Alcuronium chloride (5 mg/ml) was found to be effective at a dose of 1 drop (20 drops = 1 ml) administered twice at a 15-minute interval. Mydriasis was achieved at t = 26 +/- 11 minutes, maximal effect was reached at t = 60 +/- 39 minutes, and sufficient mydriasis ended at t = 364 +/- 134 minutes. Nevertheless, side effects, including temporary full paralysis in 1 bird, indicated that this drug should not be used. Pancuronium bromide (2 mg/ml) had an inconsistent effect on each bird at a dose of 2 drops administered twice at 15-minute intervals, and total mydriasis was not reached in 5 of 8 birds. Mydriasis was achieved at t = 34 +/- 11 minutes, maximal effect was reduced and reached at t = 43 +/- 13 minutes, and sufficient mydriasis ended at t = 90 +/- 39 minutes. Vecuronium bromide (4 mg/ml) was administered at a dose of 2 drops, 3 times, at 15-minute intervals. Mydriasis was achieved at t = 23 +/- 8 minutes, maximal effect was reached at t = 65 +/- 12 minutes, and sufficient mydriasis ended at t = 253 +/- 65 minutes. Side effects were not detected. Vecuronium bromide should be used in raptorial birds whenever retinal examination requires fundoscopy.

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.

Full-thickness skin wounds were created on the dorsum of both metacarpi in 8 horses. Three topical treatment regimens were studied. All wounds were bandaged with a nonadherent dressing, which was held in place with a snug elastic wrap. Group-A wounds were treated with a proprietary topical wound medication that consisted of a spray and an ointment. Group-B wounds were treated with the same regimen, except the putative active ingredients in the ointment were omitted. Group-C wounds were treated with a dry nonadherent bandage only. Wound dressings were changed every day and the limbs were photographed every other day until the wounds were healed. Specimens of normal skin and biopsy specimens of healed wounds were examined histologically and were assayed for hydroxyproline content. Wound healing measurements quantitated for each wound were number of days to healing, maximal wound size attained, day wound contraction commenced, day epithelium first noticed, rate of wound contraction, final wound size, and fraction of the wound that healed by contraction. The cosmetic appearance of the healed wounds was also graded. Significant differences were not noticed in hydroxyproline content, histologic appearance, or any of the wound healing measurements between treatment groups. The cosmetic appearance of healed group-A and -B wounds was significantly better than the appearance of group-C wounds. The topical treatment regimens studied neither enhanced nor inhibited wound healing in this study.

Aqueous outflow from cannulated canine eyes was determined, using a constant-pressure perfusion technique. The effect of topically applied flurbiprofen, a cyclo-oxygenase inhibitor, on outflow in eyes with or without neodymium:yttrium aluminum garnet laser-induced inflammation was measured. Flurbiprofen caused decrease in aqueous outflow that was more marked in the inflamed eyes.