Effects of topical application of a 2% solution of dorzolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs

OBJECTIVE: To evaluate effects of topical application of a 2% solution of dorzolamide on intraocular pressure (IOP) and aqueous humor flow rate in clinically normal dogs. ANIMALS: 15 Beagles. PROCEDURE: The IOP was measured in both eyes of all dogs for 3 days to determine baseline values. In a single-dose study, 50 microl of dorzolamide or control solution was applied in both eyes at 7:00 AM, and IOP was measured 7 times/d. In a multiple-dose study, dorzolamide or control solution was applied to both eyes 3 times/d for 6 days, and IOP was measured 4 times/d during treatment and for 5 days after cessation of treatment. Aqueous humor flow rate was measured for all dogs fluorophotometrically prior to treatment and during the multiple-dose study. RESULTS: In the single-dose study, dorzolamide significantly decreased IOP from 30 minutes to 6 hours after treatment. Mean decrease in IOP during this time span was 3.1 mm Hg (18.2%). Maximal decrease was detected 6 hours after treatment (3.8 mm Hg, 22.5%). In the multiple-dose study, dorzolamide decreased IOP at all time points, and maximal decrease was detected 3 hours after treatment (4.1 mm Hg, 24.3%). Mean aqueous humor flow rate decreased from 5.9 to 3.4 microl/min (43%) after treatment in the dorzolamide group. CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of a 2% solution of dorzolamide significantly decreases IOP and aqueous humor flow rate in clinically normal dogs. Therefore, topical administration of dorzolamide should be considered for the medical management of dogs with glaucoma.     

Effect of single- and multiple-dose 0.5% timolol maleate on intraocular pressure and pupil size in female horses

OBJECTIVE: To determine the effect of single and multiple-dose 0.5% timolol maleate on intraocular pressure (IOP) and pupil size between 8 AM and 8 PM. Animals Nine female horses with normotensive eyes. Procedure IOP, horizontal and vertical pupil size were measured on a single day, between 8 AM and 8 PM at hours 0, 0.5, 1, 2, 4, 6, 8, 10, and 12. A single dose of 0.5% timolol maleate was applied to both eyes immediately after the first measurement at 8 AM. IOP and pupil size were measured at 8 AM and 4 PM in a 5-day experiment of twice-daily application of 0.5% timolol maleate. RESULTS: A significant decrease in IOP from 24.9 +/- 4.2 mmHg prior to application of timolol maleate to 20.7 +/- 3.1 mmHg (4.2 mmHg = 17%) was observed 8 h after single-dose application. A significant decrease in horizontal pupil size (2.0 mm = 11%) was present 6 h after single-dose application. In the multiple-dose experiment, a significant decrease in IOP was present on days 4 and 5 as compared to IOP measured prior to application of timolol maleate. A significant decrease in horizontal and vertical pupil size was present throughout the 5-day study as compared to the values obtained prior to treatment. CONCLUSIONS: 0.5% timolol maleate significantly decreased IOP and pupil size in normo-tensive eyes of this group of female horses in both single and multiple twice daily applications.     

Effects of the topically applied calcium-channel blocker flunarizine on intraocular pressure in clinically normal dogs

OBJECTIVE: To determine effects of the topically applied calcium-channel blocker flunarizine on intraocular pressure (IOP) in clinically normal dogs. ANIMALS: 20 dogs. PROCEDURES: Baseline diurnal IOPs were determined by use of a rebound tonometer on 2 consecutive days. Subsequently, 1 randomly chosen eye of each dog was treated topically twice daily for 5 days with 0.5% flunarizine. During this treatment period, diurnal IOPs were measured. In addition, pupillary diameter and mean arterial blood pressure (MAP) were evaluated. Serum flunarizine concentrations were measured on treatment day 5. Intraday fluctuation of IOP was analyzed by use of an ANOVA for repeated measures and a trend test. Changes in IOP from baseline values were assessed and compared with IOPs for the days of treatment. Values were also compared between treated and untreated eyes. RESULTS: A significant intraday fluctuation in baseline IOP was detected, which was highest in the morning (mean +/- SE, 15.8 +/- 0.63 mm Hg) and lowest at night (12.9 +/- 0.61 mm Hg). After 2 days of treatment, there was a significant decrease in IOP from baseline values in treated (0.93 +/- 0.35 mm Hg) and untreated (0.95 +/- 0.34 mm Hg) eyes. There was no significant treatment effect on pupillary diameter or MAP. Flunarizine was detected in serum samples of all dogs (mean +/- SD, 3.89 +/- 6.36 microg/L). CONCLUSIONS AND CLINICAL RELEVANCE: Topically applied flunarizine decreased IOP in dogs after 2 days of twice-daily application. This calcium-channel blocker could be effective in the treatment of dogs with glaucoma.     

The effect of intravenous mannitol or oral glycerol on intraocular pressure in dogs

The effect of IV mannitol (1.5 gm/kg) or oral glycerol (1.4 and 2.0 gm/kg) on intraocular pressure (IOP) and serum osmolality (SOSM) was investigated in 24 normal dogs. Mean IOPs were significantly decreased from baseline values from 0.5 through 5.5 hours following mannitol administration with a mean maximum depression of 8.7 +/- 1.8 mm Hg whereas mean SOSM was significantly increased from baseline values. Mean IOPs were significantly decreased from baseline values from 1.0 through 10 hours following oral administration of 1.4 gm/kg glycerol with a mean maximal depression of 5.4 +/- 2.7 mm Hg. Mean SOSM increased initially followed by a significant decrease. The change in IOP following mannitol administration showed less variation (smaller standard deviations) than glycerol (1.4 gm/kg). Five of the 6 dogs that received the 2.0 gm/kg glycerol vomited; the mean IOP and SOSM values were not significantly altered from baseline values in these dogs. Four of 5 dogs given cooled (10C) 2.0 gm/kg glycerol vomited. The incidence of vomiting appeared to be dose related. Both mannitol and glycerol (1.4 gm/kg) are effective for decreasing IOP in normal dogs.     

Effect of topical administration of 2% dorzlamide hydrochloride or 2% dorzlamide hydrochloride-0.5% timolol maleate on intraocular pressure in clinically normal horses

OBJECTIVE: To evaluate the effect of topical administration of 2% dorzolamide hydrochloride or 2% dorzolamide hydrochloride-0.5% timolol maleate on intraocular pressure (IOP) in clinically normal horses. ANIMALS: 18 healthy adult horses without ocular abnormalities. PROCEDURE: The IOP was measured at 5 time points (7 AM, 9 AM, 11 AM, 3 PM, 7 PM) over 11 days. On days 1 and 2, baseline values were established. On days 3 through 5, horses received 2% dorzolamide HCI (group D, n = 9) or 2% dorzolamide HCl-0.5% timolol maleate (group DT, 9) in 1 randomly assigned eye every 24 hours immediately following each daily 7 AM IOP measurement. On days 6 through 9, each drug was given every 12 hours (7 AM and 7 PM) in the treated eye. Measurements on days 10 and 11 assessed return to baseline. Mixed linear regression models compared mean IOP difference for each drug at each time period. RESULTS: Mean IOP decreased significantly in all eyes during the 2 dose/d period, compared with the baseline, 1 dose/d, and follow-up periods. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of either drug every 24 hours for short-term treatment does not reduce IOP significantly. Administering either drug every 12 hours induced a significant reduction of IOP; however, controlling for all variables, the reduction was less than 2 mm Hg.     

Effects of travoprost 0.004% compared with latanoprost 0.005% on the intraocular pressure of normal dogs

PURPOSE: To compare the effects of travoprost 0.004% and latanoprost 0.005% on the intraocular pressure (IOP) of normal dogs. METHODS: Twenty mixed breed dogs were randomized to two groups: latanoprost was used in group A and travoprost in group B. The drugs were instilled in the right eye of the dogs, whereas the left eye received placebo. Both drugs were instilled once a day at 8 am during 5 days. IOP measurements were made at 8 am, 10 am, 2 pm and 8 pm during the 5 days of treatment, the 3 days that preceded treatment, and 3 days following treatment. Presence of blepharospasm, miosis, anterior chamber flare, and conjunctival hyperemia were evaluated during the study. RESULTS: Mean IOP was significantly reduced in the eyes treated with both latanoprost and travoprost, when compared with the eyes treated with placebo (P<0.05). There was no statistically significant difference between the mean IOPs of eyes treated with latanoprost and travoprost at all time intervals during baseline, treatment, and recovery (P>0.05). On the fifth day of treatment and on the first day of the recovery period, a severe ocular hypotension was noted with both drugs, resulting in imprecise readings with the tonometer. Miosis and conjunctival hyperemia were observed in the treated eyes of both groups, whereas flare was noticed in one latanoprost-treated eye. CONCLUSION: Travoprost 0.004% significantly reduces the IOP in normal dogs. The hypotensive effect obtained with travoprost 0.004% is comparable to that obtained with latanoprost 0.005%.     

Changes in intraocular pressure associated with topical dorzolamide and oral methazolamide in glaucomatous dogs

Objective To compare the reduction in intraocular pressure (IOP) by topical 2% dorzolamide to oral methazolamide (5 mg/kg) in dogs, and determine if the combination of both drugs would reduce IOP more than either drug administered alone. Animals studied Thirteen glaucomatous beagles. Procedures Measurements, including applanation tonometry, pupil size and heart rate, were obtained at 8 am, 12 noon, and 5 pm on days 1, 3 and 5. The 5‐day drug studies included placebo (0.5% methylcellulose); 2% dorzolamide administered in one eye twice daily (8 am and 5 pm), and repeated again in one eye three times (8 am, 12 noon and 5 pm) daily; methazolamide (5 mg/kg per os administered at 8 am and 5 pm); 2% dorzolamide instilled twice daily (5 days) combined with oral methazolamide on the last 3 days, and methazolamide (5 days) combined with 2% dorzolamide on the last 3 days and instilled twice daily. Statistical comparisons between drug groups included control (nondrug) eye and treated (placebo/drug) eyes for days 1, day 3 and 5. Results Topical 2% dorzolamide, administered twice and three times daily, significantly decreased IOP (mean ± SEM) in glaucomatous dogs on the first day (twice daily 7.6 ± 2.4 mmHg, and three times daily 16.4 ± 3.6 mmHg) that was even greater by day 5 (twice daily 10.4 ± 2.0 mmHg, and three times daily 13.9 ± 2.7). Oral methazolamide also significantly lowered IOP in both eyes. Oral methazolamide (administered from day 1 through to day 5) combined with 2% topical dorzolamide (instilled in the drug eye for day 3 through to day 5) also significantly lowered IOP of both eyes for all days, and for day 5 the mean ± SEM IOP was decreased by 7.9 ± 1.7 mmHg (methazolamide plus dorzolamide) and 7.5 ± 2.6 mmHg (methazolamide only). Topical dorzolamide (instilled in the drug eye for day 1 through to day 5) combined with oral methazolamide (administered from day 3 through to day 5) significantly lowered IOP in the drug eye on day 1 (5 pm: 9.6 ± 1.9 mmHg), for day 3 (11 am and 5 pm) and for all of day 5 for both eyes (5 pm: control eye 9.5 ± 1.8 mmHg; drug eye 9.2 ± 1.9 mmHg). Topical dorzolamide (2%) instilled three times daily produces similar IOP declines compared to the combination of oral methazolamide and 2% dorzolamide administered twice daily. Conclusions Dorzolamide (2%) instilled twice or three times daily causes significant decreases in IOP in glaucomatous dogs. Twice daily instillations caused progressive declines in IOP from day 1 to day 5. Dorzolamide (2%) combined with oral methazolamide (5 mg/kg per os twice daily) produces similar but not additional declines in IOP.     

Effects of ketamine, diazepam, and their combination on intraocular pressures in clinically normal dogs

OBJECTIVE: To evaluate the effects of ketamine, diazepam, and the combination of ketamine and diazepam on intraocular pressures (IOPs) in clinically normal dogs in which premedication was not administered. ANIMALS: 50 dogs. PROCEDURES: Dogs were randomly allocated to 1 of 5 groups. Dogs received ketamine alone (5 mg/kg [KET5] or 10 mg/kg [KET10], IV), ketamine (10 mg/kg) with diazepam (0.5 mg/kg, IV; KETVAL), diazepam alone (0.5 mg/kg, IV; VAL), or saline (0.9% NaCl) solution (0.1 mL/kg, IV; SAL). Intraocular pressures were measured immediately before and after injection and at 5, 10, 15, and 20 minutes after injection. RESULTS: IOP was increased over baseline values immediately after injection and at 5 and 10 minutes in the KET5 group and immediately after injection in the KETVAL group. Compared with the SAL group, the mean change in IOP was greater immediately after injection and at 5 and 10 minutes in the KET5 group. The mean IOP increased to 5.7, 3.2, 3.1, 0.8, and 0.8 mm Hg over mean baseline values in the KET5, KET10, KETVAL, SAL, and VAL groups, respectively. All dogs in the KET5 and most dogs in the KETVAL and KET10 groups had an overall increase in IOP over baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with baseline values and values obtained from dogs in the SAL group, ketamine administered at a dose of 5 mg/kg, IV, caused a significant and clinically important increase in IOP in dogs in which premedication was not administered. Ketamine should not be used in dogs with corneal trauma or glaucoma or in those undergoing intraocular surgery.     

Effects of topical administration of timolol maleate on intraocular pressure and pupil size in dogs

Effects of topical administration of a single dose of timolol maleate on intraocular pressure (IOP) and pupil diameter were evaluated in normotensive eyes of 11 clinically normal dogs over 12 hours (7:00 AM to 7:00 PM). Mean (+/- SEM) normal IOP was 15.5 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the morning. Mean normal pupil diameter was 8.5 (+/- 0.3) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in the treated and nontreated eyes. Mean reduction of IOP in the treated eye was 2.5 mm of Hg, a reduction of 16.1%, with maximal reduction of 3.7 mm of Hg. Mean reduction of IOP in the nontreated eye was 1.4 mm of Hg, a reduction of 9.0%. The treated eye had reduced pupil diameter at 30 minutes after treatment, which persisted throughout the 12 hours of the study. Mean reduction of pupil diameter in the treated eye was 2.9 mm, a reduction of 34.1%. In addition, a contralateral effect on pupil diameter was seen in the nontreated eye, with mean reduction of 1.2 mm, a reduction of 14.1%. Topical administration of timolol maleate resulted in reduction of IOP and pupil diameter in treated and contralateral eyes, thus supporting the use of timolol for treatment of glaucoma in dogs. Miosis indicates possible beta-adrenergic inhibition or alpha-adrenergic activation of the sphincter muscle. beta-Adrenergic blockade would then result in miosis.     

Effects of cyclophotocoagulation with a neodymium:yttrium-aluminum-garnet laser on corneal sensitivity,intraocular pressure,aqueous tear production,and corneal nerve morphology in eyes of dogs

OBJECTIVE: To determine effects of cyclophotocoagulation via administration of 100 J with a neodymium:yttrium aluminum garnet (Nd:YAG) laser on corneal touch threshold (CTT), intraocular pressure (IOP), aqueous tear production, and corneal nerve morphology in eyes of dogs. ANIMALS: 15 dogs. PROCEDURE: Noncontact Nd:YAG laser was transsclerally applied (10 applications; 25 W for 0.1 seconds for each application to each of 4 quadrants) to the ciliary body of the left eye of 15 dogs; the right eye was the control eye. Corneal integrity, CTT, tear production as measured by the Schirmer tear test (STT), and IOP were evaluated for 14 days following laser treatment. On day 14, dogs were euthanatized, eyes harvested, and corneas stained with gold chloride. Major nerve bundles were analyzed by use of a drawing tube attached to a light microscope, and maximum diameters were measured by use of image analysis software. RESULTS: All laser-treated eyes had significantly higher CTT values, compared with control eyes. Six of 15 laser-treated eyes developed ulcerative keratitis. On most days, IOP was significantly lower in laser-treated eyes in both morning and evening. Laser-treated eyes had a significant decrease of approximately 1 nerve bundle/corneal quadrant. Values for STT or nerve bundle diameters did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of 100 J with a Nd:YAG laser effectively reduced IOP while increasing CTT and caused a significant decrease in number, but not diameter, of major corneal nerve bundles. Nerve damage and corneal hypoesthesia are etiologic factors in ulcerative keratitis following Nd:YAG cyclophotocoagulation.     

Effects of 0.005% latanoprost solution on intraocular pressure in healthy dogs and cats

OBJECTIVE: To evaluate effects of daily topical ocular administration of latanoprost solution on intraocular pressure (IOP) in healthy cats and dogs. ANIMALS: 9 domestic shorthair cats and 14 dogs. PROCEDURE: Latanoprost solution (0.005%) was administered topically to 1 eye (treated) and vehicle to the other eye (control) of all animals once daily in the morning for 8 days. Intraocular pressure was measured twice daily for the 5 days preceding treatment, and IOP, pupillary diameter, conjunctival hyperemia, and blepharospasm were measured 0, 1, 6, and 12 hours after the first 4 treatments and 0 and 12 hours after the final 4 treatments. Measurements continued twice a day for 5 days after treatment was discontinued. Aqueous flare was measured once daily during and for 5 days after the treatment period. RESULTS: Intraocular pressure and pupillary diameter were significantly decreased in the treated eye of dogs, compared with the control eye. Mild conjunctival hyperemia was also detected, but severity did not differ significantly between eyes. Blepharospasm and aqueous flare were not detected in either eye. Intraocular pressure in cats was not significantly affected by treatment with latanoprost. However, pupillary diameter was significantly decreased in the treated eye, compared with the control eye. Conjunctival hyperemia, aqueous flare, and blepharospasm were not detected in either eye. CONCLUSIONS AND CLINICAL RELEVANCE: Once-daily topical ocular administration of latanoprost solution (0.005%) reduced IOP in healthy dogs without inducing adverse effects but did not affect IOP in healthy cats. Latanoprost may be useful for treating glaucoma in dogs.     

Effects of topical administration of 0.005% latanoprost solution on eyes of clinically normal horses.

OBJECTIVE: To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration. ANIMALS: 20 adult clinically normal horses. PROCEDURE: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora, blepharospasm, blepharedema, and aqueous flare were recorded prior to IOP measurement. RESULTS: IOP was reduced from baseline by a mean value of 1.03 mm Hg (5%) in males and 3.01 mm Hg (17%) in females during the treatment period. Miosis developed in all treated eyes and was moderate to marked in 77% of horses, with the peak effect observed 4 to 8 hours after drug administration. Conjunctival hyperemia, epiphora, blepharospasm, and blepharedema were present in 100, 57, 42, and 12% of treated eyes, respectively, 2 to 24 hours following drug administration. Aqueous flare was not observed at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Although IOP was reduced with every 24-hour dosing of latanoprost, the frequency of prostaglandin-induced adverse events was high. Because recurrent uveitis appears to be a risk factor for glaucoma in horses, topical administration of latanoprost may potentiate prostaglandin-mediated inflammatory disease in affected horses.     

Plasma concentrations of praziquantel after oral administration of single and multiple doses in loggerhead sea turtles (Caretta caretta)

OBJECTIVE: To determine the pharmacokinetics of praziquantel following single and multiple oral dosing in loggerhead sea turtles. ANIMALS: 12 healthy juvenile loggerhead sea turtles. PROCEDURE: Praziquantel was administered orally as a single dose (25 and 50 mg/kg) to 2 groups of turtles; a multiple-dose study was then performed in which 6 turtles received 3 doses of praziquantel (25 mg/kg, PO) at 3-hour intervals. Blood samples were collected from all turtles before and at intervals after drug administration for assessment of plasma praziquantel concentrations. Pharmacokinetic analyses included maximum observed plasma concentration (Cmax), time to maximum concentration (Tmax), area under the plasma praziquantel concentration-time curve, and mean residence time (MRTt). RESULTS: Large interanimal variability in plasma praziquantel concentrations was observed for all dosages. One turtle that received 50 mg of praziquantel/kg developed skin lesions within 48 hours of administration. After administration of 25 or 50 mg of praziquantel/kg, mean plasma concentrations were below the limit of quantification after 24 hours. In the multiple-dose group of turtles, mean plasma concentration was 90 ng/mL at the last sampling time-point (48 hours after the first of 3 doses). In the single-dose study, mean Cmax and Tmax with dose were not significantly different between doses. After administration of multiple doses of praziquantel, only MRTt was significantly increased, compared with values after administration of a single 25-mg dose. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of 25 mg of praziquantel/kg 3 times at 3-hour intervals may be appropriate for treatment of loggerhead sea turtles with spirorchidiasis.     

Effects of medetomidine and xylazine on intraocular pressure and pupil size in healthy Beagle dogs

ObjectiveTo determine the effects of intramuscular (IM) administration of medetomidine and xylazine on intraocular pressure (IOP) and pupil size in normal dogs.Study designProspective, randomized, experimental, crossover trial.AnimalsFive healthy, purpose-bred Beagle dogs.MethodsEach dog was administered 11 IM injections of, respectively: physiological saline; medetomidine at doses of 5, 10, 20, 40 and 80 μg kg⁻¹, and xylazine at doses of 0.5, 1.0, 2.0, 4.0 and 8.0 mg kg⁻¹. Injections were administered at least 1 week apart. IOP and pupil size were measured at baseline (before treatment) and at 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours post-injection.ResultsA significant decrease in IOP was observed at 6 hours after 80 μg kg⁻¹ medetomidine compared with values at 0.25 and 0.50 hours, although there were no significant changes in IOP from baseline. In dogs treated with 8.0 mg kg⁻¹ xylazine, significant reductions in IOP were observed at 4 and 5 hours compared with that at 0.25 hours after administration. In dogs treated with 5, 10, 20 and 40 μg kg⁻¹ medetomidine and 0.5, 1.0 and 2.0 mg kg⁻¹ xylazine, there were no significant changes in IOP. Pupil size did not change significantly after any of the medetomidine or xylazine treatments compared with the baseline value.Conclusions and clinical relevanceLow or moderate doses of medetomidine or xylazine did not induce significant changes in IOP or pupil size. In contrast, high doses of medetomidine or xylazine induced significant changes up to 8 hours after treatment, but values remained within the normal canine physiological range. The results of this study suggest a lack of significant change in IOP and pupil size in healthy dogs administered low or moderate doses of xylazine or medetomidine.     

Effect of oral administration of carprofen on intraocular pressure in normal dogs

The aim of this study was to determine the effect of oral administration of carprofen on intraocular pressure in normal dogs. Twelve young adult beagle dogs were randomly assigned to treatment (n = 6) or control (n = 6) groups. After an 11‐day acclimation period, the treatment group received approximately 2.2 mg/kg carprofen per os every 12 h for 7 days, and the control group received a placebo gel capsule containing no drug per os every 12 h for 7 days. Intraocular pressure (IOP) was measured by a rebound tonometer at three time points per day (8 am, 2 pm, and 8 pm) during the acclimation (days 1–11) and treatment (days 12–18) phases and for 48 h (days 19–20) after the completion of treatment. There was no statistically significant change in IOP for either eye in the dogs receiving oral carprofen during the treatment phase (days 12–18). After day 4, no significant daily IOP changes were seen in control group dogs. Carprofen administered orally every 12 h for 7 days had no effect on IOP in normal beagle dogs. An acclimation period to frequent IOP measurements of at least 5 days is necessary to establish baseline IOP values and minimize possible anxiety‐related effects on IOP measurements.     

Effect of single and multiple doses of 0.2% brimonidine tartrate in the glaucomatous Beagle

The objective of this study was to evaluate the changes in intraocular pressure (IOP) in glaucomatous dogs after instillations of 0.2% brimonidine once, twice and three times daily in single day studies, and after twice and three times daily for 4 days in multiple dose studies. We studied eight Beagles with inherited primary open angle glaucoma. Applanation tonometry (IOP), pupil size (PS) and heart rate (HR) measurements were obtained at 8 am, 10 am, 1 pm, 3 pm and 5 pm. The studies were divided into: eight glaucoma dogs and five of the eight dogs that demonstrated greater response to 0.2% brimonidine. Single-dose drug studies are divided into placebo (0.5% methylcellulose), 0.2% brimonidine administered once daily (8 am); twice daily (8 am and noon); and three times daily (8 am, noon and 5 pm). The 5-day multiple-dose studies included: day 1, no drug; and 4 days, 0.2% brimonidine instillations either twice daily (8 am and 2 pm) or three times daily (8 am, 2 pm and 9 pm). Statistical comparisons between drug groups included control (nondrug) and treated (placebo/0.2% brimonidine) eyes for both single- and multiple-dose studies. The mean +/- SEM diurnal decrease in IOP in the eight glaucomatous Beagles for the control and placebo eyes were 3.4 +/- 4.7 and 5.4 +/- 2.8 mmHg, respectively. The mean +/- SEM diurnal decrease in IOP after 0.2% brimonidine once, twice and three times daily was 6.4 +/- 3.5, 8.0 +/- 6.1 and 9.8 +/- 8.1 mmHg, respectively; this trend was not significant statistically. Significant miosis occurred starting 2 h postinstillations, and the resultant mean +/- SD pupil size was 2.7 +/- 0.3 mm. A significant decrease in heart rate also occurred (12%). In the five most responsive dogs the changes in PS and HR during these studies were similar to the larger group, but significant decreases in IOP occurred at most measurement times. In the multiple-dose study with 0.2% brimonidine twice daily the mean +/- SEM decrease in IOP for day 1 to day 4 was 5.0 +/- 1.3, 5.7 +/- 1.3, 1.4 +/- 3.3 and 4.9 +/- 1.3 mmHg, respectively. When 0.2% brimonidine was instilled three times daily the mean +/- SEM diurnal IOP decrease was from day 1 to day 4 and was 0.75 +/- 1.3, 2.4 +/- 1.5, 1.2 +/- 2.7 and 1.4 +/- 1.8 mmHg, respectively. The mean change in pupil diameter was 1.3 +/- 0.5 mm. Decrease in HR averaged 22%. In the same single-dose studies with the five most responsive dogs, PS and HR were similar, but the decreases in IOP were significant at more measurement intervals. We conclude that 0.2% brimonidine produces a decrease in IOP in dogs, a statistically significant miosis, and a reduced heart rate (12-22%). However, because of the limited drug-induced ocular hypotension, brimonidine should be combined with other drugs when used for the glaucomas in the dog.     

Effect of oral administration of prednisolone on thyroid function in dogs

To determine the effect of oral administration of prednisolone on thyroid function, 12 healthy Beagles were given 1.1 mg of prednisolone/kg of body weight every 12 hours for 22 days after 8 days of diagnostic testing of the dogs before treatment with prednisolone. Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) response tests were performed before treatment (days 1 and 8 of the study) and during treatment (days 21 and 28 of the study). Blood samples were collected daily at 8 AM and 2 and 8 PM to rule out normal daily hormone fluctuations as the cause of a potential decrease in serum triiodothyronine (T3), thyroxine (T4), and free T4 (fT4) concentrations. Serum T3, T4, and fT4 concentrations before treatment and 1 day and 21 days after the first prednisolone dose were compared by analyses of variance. Post-TSH and -TRH serum T3 and T4 concentrations before and during treatment were compared, using the Student t test for paired data. Oral administration of prednisolone significantly (P less than 0.005) decreased serum T3, T4, and fT4 concentrations in the 8 AM and 2 and 8 PM samples obtained 1 day and 21 days after the first prednisolone dose. Serum T4 and fT4 concentrations in 8 AM and 2 PM samples were significantly (P less than 0.05) lower 21 days after the first prednisolone dose than they were at 1 day after the first dose. Before treatment, serum T4 concentration in the 2 PM samples was significantly (P less than 0.05) higher than serum T4 concentration in 8 AM and 8 PM samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of ketamine‐midazolam anesthesia on intraocular pressure in clinically normal dogs

Objective To determine the effects of intravenous ketamine‐midazolam anesthesia on intraocular pressure (IOP) in ocular normotensive dogs. Animals Thirteen adult mixed‐breed dogs. Procedures Dogs were randomly assigned to treatment (n = 7) and control (n = 6) groups. Dogs in the treatment group received intravenous ketamine 15 mg/kg and midazolam 0.2 mg/kg and dogs in the control group received intravenous saline. The time of intravenous drug injection was recorded (T₀). Measurements of IOP were then repeated 5 min (T₅) and 20 min (T₂₀) following the intravenous administration of ketamine‐midazolam combination and saline in both groups. Results Measurements showed normal IOP values in both groups. The mean ± SD baseline IOP values for treatment and control groups were 13.00 ± 1.47 and 10.33 ± 2.20, respectively. For baseline IOP values, there was no significant difference between treatment and control groups (P = 0.162). In the treatment group, the subsequent post‐treatment mean ± SD values were 15.64 ± 2.17 (5 min), and 14.92 ± 1.98 (20 min). There was no evidence of statistical difference between baseline values and post‐treatment values after treatment with ketamine‐midazolam (P₅ = 0.139; P₂₀ = 0.442). In control eyes, the mean ± SD values at 5 and 20 min were 10.41 ± 2.01 and 10.16 ± 1.69, respectively. There was no significant difference between baseline values and post‐treatment values in control group (P₅ = 1.000; P₂₀ = 1.000). Conclusion Ketamine‐midazolam combination has no clinically significant effect on IOP in the dog.     

Comparison of the effects of topical administration of a fixed combination of dorzolamide-timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs

OBJECTIVE: To determine whether the combination multiple-dose dorzolamide-timolol administered topically has any greater effects on the reduction of intraocular pressure, pupil size, and heart rate in dogs with glaucoma than do either timolol or dorzolamide alone. PROCEDURE: Applanation tonometry, pupil size, and heart rate measurements were made at 7 a.m., 1 p.m., and 7 p.m. daily of 12 laboratory Beagles with inherited primary open-angle glaucoma during each active phase of this study. Timolol 0.5% was administered first twice daily for 4 consecutive days. Dorzolamide 2.0% was administered next three times daily for 4 consecutive days. The fixed combination of the two (timolol 0.5% and dorzolamide 2.0%) was administered twice daily for 4 consecutive days during the final week of the study. Between administration of each drug, a withdrawal period of at least 10 days was instituted. Statistical comparisons between the effects of the three drugs were performed. RESULTS: Intraocular pressure (IOP) was decreased with the administration of all three drugs: timolol alone, dorzolamide alone, and the combination of the two decreased IOP after 1 day of treatment 2.83 +/- 0.70 mmHg, 6.47 +/- 0.32 mmHg, and 6.56 +/- 0.37 mmHg, respectively. After 4 days of treatment, the IOP decreased even further: timolol alone, dorzolamide alone, and the combination of the two decreased IOP 3.75 +/- 0.88 mmHg, 7.50 +/- 0.29 mmHg, and 8.42 +/- 0.58 mmHg, respectively. Heart rate was significantly decreased with timolol (-11.9 +/- 2.0 bpm) and the combination preparation (-8.6 + 2.4 bpm), but not with dorzolamide (-3.7 +/- 1.8 bpm) alone. Pupil size was significantly decreased with timolol (-1.42 + 0.40 mm) and the combination preparation (-1.3 + 0.33 mm), but not with dorzolamide (0.97 +/- 0.36 mm) alone. CONCLUSIONS: The combination dorzolamide-timolol appears to be more effective at reducing intraocular pressure in glaucomatous dogs than is either timolol or dorzolamide alone.     

Effect of topical 1% atropine sulfate on intraocular pressure in normal horses

OBJECTIVE: To determine the effect of topical 1% ophthalmic atropine sulfate on intraocular pressure (IOP) in ocular normotensive horses. Animals Studied Eleven clinically healthy horses. Procedures IOP was measured bilaterally twice daily, at 8 AM and 4 PM, for 5 days. No medication was applied for the first 2 days of the study. Thereafter, one eye of each horse was treated with 0.1 mL of topical 1% atropine sulfate ointment twice daily (7 AM and 7 PM) for 3 days. The contralateral eye served as a control. In eight of the horses, an additional IOP reading was taken 3 days following cessation of the atropine treatment. RESULTS: There was no significant difference in the IOP of control vs. treatment eyes in the pretreatment period, days 1 and 2 (P = 0.97 and 0.55, respectively). During the treatment period, treated eyes of 10 of the horses had significantly lower IOP than control eyes (P = 0.03). The mean IOP reduction in treated eyes, relative to untreated eyes, was 11.2%. One horse had a significant rise in IOP in the treated eye compared to the remaining study animals. The IOP of control eyes did not vary significantly over the observation period (P = 0.27). There was no significant variation in IOP between the 8 AM and 4 PM measurement (P = 0.9). CONCLUSIONS: Topical 1% atropine sulfate causes a small, but significant decline in IOP in most ocular normotensive horses. Because topical atropine may elevate IOP in some horses, it should be used with caution in the treatment of glaucoma in this species.