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 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.

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.

The effects of mitomycin-C on intraocular pressure (IOP), facility of outflow (C), and Tenon's capsule fibrosis were studied over 60 days in 10 clinically normal dogs. A 1-piece, silicone glaucoma implant was surgically implanted into both eyes; the filtration site of one eye was treated with a single, 5-minute intraoperative application of mitomycin (0.5 mg/ml), and the fellow eye was treated in a similar manner with balanced salt solution. There were no significant differences in preoperative IOP or C-values between treatment groups. Mean IOP in eyes of both groups initially decreased from the preoperative value, but returned to the baseline value by day 21. Mean facility of aqueous outflow (C-value) increased in all eyes during the first 14 days (mitomycin-C-value = 2.26 +/- 0.72; control C-value = 2.38 +/- 0.81), then reached a plateau that was significantly higher than the baseline value in mitomycin (P = 0.039) and control (P = 0.041) eyes. Histologic evaluation revealed all implants surrounded by a connective tissue capsule composed of regular dense collagen and fibroblasts that was significantly (P = 0.003) thinner in the mitomycin-treated (scleral side = 167 +/- 62 micrometer; conjunctival side = 122 +/- 41 micrometer) than the control (scleral side = 261 +/- 92 micrometer; conjunctival side = 180 +/- 48 micrometer) group. There were, however, no significant differences in IOP or C-values between groups at any postoperative time interval. Results of this study indicate that intraoperative treatment with mitomycin suppresses, but does not prevent fibrosis around silicone filtering implants.

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.

Topically applied 4% timolol, 4% timolol combined with 2% pilocarpine, 6% timolol, and 6% timolol combined with 2% pilocarpine were evaluated in clinically normal Beagles and Beagles with glaucoma. The drugs were instilled twice daily for 5 days. Changes in intraocular pressure (IOP), pupil size, and heart rate were recorded on days 1, 3, and 5 at 0, 2, 5, and 8 hours, starting at 8:30 AM. In clinically normal dogs, 4 and 6% topically administered timolol did not cause consistent reductions in IOP; however, with addition of 2% pilocarpine, IOP was consistently lower. In the Beagles with glaucoma, 4 and 6% timolol and, to a greater extent, 4 and 6% timolol combined with 2% pilocarpine lowered IOP. The combinations lowered IOP and reduced pupil size consistently. In all test groups, either 4 or 6% topically applied timolol caused approximately 10% decrease in mean heart rate.