Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations.

The effect of topically applied 2% pilocarpine and 0.25% demecarium bromide on aqueous humor flare was evaluated while treating normal eyes of dogs 3 times daily for 8 days. Fifteen clinically normal Beagles were allotted to 2 drug treatment groups, and flare was measured, using laser flaremetry. Pilocarpine caused an increase of flare to 167 photon counts (pc)/ms at 7 hours, compared with the nontreated control eye mean value 3.7 pc/ms. By 31 hours, flare had decreased to 70 pc/ms with 3 daily topical treatments. By 55 hours, the flare measurement was in the normal range. Intraocular pressure (IOP) decreased in the treated eyes, compared with the nontreated eyes, and maximal decrease in IOP was observed at the same time as maximal flare. Demecarium induced a similar increase in flare and decrease in IOP, with peak effect seen at 31 hours. At that time, the flaremetry result was 28 pc/ms, compared with 3.4 pc/ms in the nontreated control eyes. After 8 days of 3 times daily treatment, flare values had returned to normal in eyes of dogs in both treatment groups. The transient increase in aqueous humor protein concentration did not result in ocular or visual damage, and long-term changes were not seen. The amount of flare increase attributable to topical application of pilocarpine was greater than the increase in human eyes when measured by use of laser flaremetry.

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.

Topically administered tissue plasminogen activator (tPA) was evaluated for its penetration into aqueous humor of clinically normal dogs. Two concentrations of tPA (5 mg/ml and 10 mg/ml) were evaluated in a single-dose study, and a concentration of 5 mg of tPA/ml was used for a multiple-dose study. The contralateral eye served as a nontreated control. Enzyme substrate analysis of aqueous humor was used to determine tPA activity. The activity of tPA in aqueous humor was significantly (P < 0.05) greater in treated eyes of all dogs, compared with that in control eyes. Significant differences in activity of tPA were not detected at different doses in treated eyes.

The effect that topical administration of cyclosporine would have on the number and type of microorganisms isolated from the corneal surface of dogs with keratoconjunctivitis sicca was studied. Schirmer tear tests were performed on and corneal swab specimens were collected from 61 eyes of 31 dogs with keratoconjunctivitis sicca prior to and after 3, 6, and 12 months of treatment with cyclosporine. In eyes that responded to cyclosporine treatment (Schirmer tear test value increased by greater than or equal to 5 mm/min, compared with pretreatment value), the percentage of eyes from which bacteria were isolated after 3, 6, and 12 months of treatment was significantly (P < 0.001) less than the percentage from which bacteria were isolated prior to treatment. However, among eyes that did not respond to treatment, we did not detect a significant change over time in prevalence of bacteria or type of bacteria isolated. The percentage of eyes from which fungi were isolated decreased during treatment; however, the small number of eyes in which fungal culture results were initially positive precluded demonstration of a significant change. For all eyes, we did not detect any significant differences over time in the frequency with which specific bacterial genera were isolated, with the exception of beta-hemolytic Streptococcus spp. Opportunistic corneal infections were not detected even though none of the dogs received antibiotics. An increase in production of tears, which contain anti-infection proteins, was believed to be the primary factor responsible for the decrease in the percentage of eyes from which microorganisms could be isolated.