Effects of oral administration of methazolamide on intraocular pressure and aqueous humor flow rate in clinically normal dogs

OBJECTIVE: To determine magnitude and duration of the effect of oral administration of methazolamide at 2 dosages on intraocular pressure (IOP) in dogs in single-dose and multiple-dose trials and to determine aqueous humor flow rate (AHFR) by use of anterior segment fluorophotometry before and during treatment. ANIMALS: 25 healthy adult Beagles. PROCEDURE: Baseline IOPs and AHFRs were determined on days 0 and 1, respectively. On day 2, the single-dose trial was initiated with oral administration of 25 or 50 mg of methazolamide at 7 AM to 2 groups of 10 dogs each. Five dogs served as controls. In the multiple-dose trial, the same dogs received 25 or 50 mg of methazolamide at 7 AM and at 3 and 11 PM on days 3 through 9. RESULTS: Intraocular pressures varied diurnally with highest IOPs in the morning. In the single-dose trial, IOP decreased significantly at 3 to 6 hours after treatment and then increased significantly at later time points, compared with baseline values. In the multiple-dose trial, dogs in both treatment groups had significantly lower IOPs during the treatment period at 10 AM and 1 PM but not at 6 and 9 PM, compared with baseline values. In both treatment groups morning IOPs had returned to baseline values by the first day after treatment. Evening IOPs were significantly increased by 2 to 3 days after treatment, compared with baseline values. The AHFRs in both treatment groups were significantly lower than pretreatment AHFRs. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of methazolamide decreases IOPs and AHFRs in clinically normal dogs, with effectiveness diminishing in the evening.     

Fluorophotometric determination of aqueous humor flow rate in clinically normal dogs

OBJECTIVE: To determine aqueous humor flow rate in clinically normal dogs, using fluorophotometry. ANIMALS: 20 clinically normal Beagles. PROCEDURE: A study was performed on 5 dogs to establish an optimal protocol for fluorophotometric determination of aqueous humor flow rate. This protocol then was used to measure aqueous humor flow rate in 15 dogs. Corneas were loaded with fluorescein by topical application, and corneal and aqueous humor fluorescein concentrations were measured 5, 6.5, and 8 hours after application. Concentration-versus-time plots were generated, and slopes and ratios of the fluorescein concentration in the cornea and aqueous humor from these graphs were used to calculate flow rates. Calculations were performed by use of automated software provided with the fluorophotometer and by manual computation, and the 2 calculation methods were compared. RESULTS: The protocol established for the 5 dogs resulted in semilogarithmic and parallel decay of corneal and aqueous humor concentrations. Manually calculated mean +/- SD aqueous humor flow rates for left, right, and both eyes were 5.58 +/- 2.42, 4.86 +/- 2.49, and 5.22 +/- 1.87 microl/min, respectively, whereas corresponding flow rates calculated by use of the automated software were 4.54 +/- 3.08, 4.54 +/- 3.10, and 4.54 +/- 2.57 microl/min, respectively. Values for the left eye were significantly different between the 2 computation methods. CONCLUSIONS AND CLINICAL RELEVANCE: Aqueous humor flow rates can be determined in dogs, using fluorophotometry. This technique can be used to assess pathologic states and medical and surgical treatments that alter aqueous humor dynamics.     

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.     

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.     

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.     

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.     

Evaluation of a topically administered carbonic anhydrase inhibitor (MK-927) in normotensive and glaucomatous beagles.

A new topically administered anhydrase inhibitor, MK-927, was evaluated for its ocular hypotensive activity in normotensive and glaucomatous Beagles. Single- and multiple-dose studies were performed. Six concentrations of the drug were evaluated in the single-dose study and the 2% solution was used for multiple-dose evaluation. The decrease in intraocular pressure (IOP) was greater in glaucomatous Beagles at the higher concentrations of the drug. The 2 and 4% solutions of MK-927 significantly lowered IOP (mean, 5 mm of Hg; SEM +/- 1.6 and SEM +/- 1.2, respectively) in normotensive and glaucomatous Beagles. In the multiple-dose study, IOP was significantly decreased in the normotensive (mean, 4 mm of Hg; SEM +/- 0.74) and glaucomatous Beagles (mean, 9 mm of Hg; SEM +/- 1.2). The maximal effect was observed by day 4. A contralateral effect was found in glaucomatous Beagles, with the maximal effect on day 4.     

Combined cycloablation and gonioimplantation for treatment of glaucoma in dogs: 18 cases (1992-1998)

OBJECTIVE: To evaluate a combined cycloablative and gonioimplantation technique for treatment of glaucoma in dogs. DESIGN: Retrospective study. ANIMALS: 18 adult dogs with glaucoma. PROCEDURE: Medical records of dogs that received a valved gonioimplant and a cyclodestructive procedure (cyclocryoablation or diode laser cyclophotocoagulation) during a 6-year period were reviewed. Retention of vision and intraocular pressure control were assessed, as well as number and nature of complications. RESULTS: 19 eyes of 18 dogs received a valved gonioimplant and either cyclocryoablation (n = 12) or diode laser cyclophotocoagulation (7). At > or = 1 year after surgery, 11 of 19 eyes had vision and 14 of 19 eyes had intraocular pressure < 25 mm Hg. Two dogs (2 eyes) were lost to follow-up 3 and 6 months after surgery. Despite the alternative route for aqueous humor flow created by the gonioimplant, 7 eyes had increased intraocular pressure (27 to 61 mm Hg) < 24 hours after surgery. Other complications included excessive intraocular fibrin, focal retinal detachment, corneal ulcer, retinal hemorrhage, cataract, and implant migration. CONCLUSIONS AND CLINICAL RELEVANCE: Combined cycloablation and gonioimplantation appears to be a promising technique for retention of vision and control of intraocular pressure in dogs with glaucoma.     

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.     

Evaluation of a rebound tonometer for measuring intraocular pressure in dogs and horses

OBJECTIVE: To compare intraocular pressure (IOP) measurements obtained with a rebound tonometer in dogs and horses with values obtained by means of applanation tonometry and direct manometry. DESIGN: Prospective study. ANIMALS: 100 dogs and 35 horses with clinically normal eyes, 10 enucleated eyes from 5 dogs, and 6 enucleated eyes from 3 horses. PROCEDURES: In the enucleated eyes, IOP measured by means of direct manometry was sequentially increased from 5 to 80 mm Hg, and IOP was measured with the rebound tonometer. In the dogs and horses, results of rebound tonometry were compared with results of applanation tonometry. RESULTS: For the enucleated dog and horse eyes, there was a strong (r2 = 0.99) linear relationship between pressures obtained by means of direct manometry and those obtained by means of rebound tonometry. Mean +/- SD IOPs obtained with the rebound tonometer were 10.8 +/- 3.1 mm Hg (range, 5 to 17 mm Hg) and 22.1 +/- 5.9 mm Hg (range, 10 to 34 mm Hg) for the dogs and horses, respectively. Mean IOPs obtained with the applanation tonometer were 12.9 +/- 2.7 mm Hg (range, 8 to 18 mm Hg) and 21.0 +/- 5.9 mm Hg (range, 9 to 33 mm Hg), respectively. Values obtained with the rebound tonometer were, on average, 2 mm Hg lower in the dogs and 1 mm Hg higher in the horses, compared with values obtained with the applanation tonometer. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the rebound tonometer provides accurate estimates of IOP in clinically normal eyes in dogs and horses.     

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.     

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.     

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.     

The effects of bimatoprost and unoprostone isopropyl on the intraocular pressure of normal cats

OBJECTIVE: To evaluate the effects on intraocular pressure (IOP), pupillary diameter (PD), blepharospasm score, conjunctival injection score, and aqueous humor flare score when either 0.03% bimatoprost solution is applied once daily or 0.15% unoprostone isopropyl solution is applied twice daily topically to the eyes of normal cats. MATERIALS AND METHODS: The aforementioned parameters were evaluated daily in each of 12 cats throughout the entirety of the study. During an initial 10-day treatment phase a single eye of six of the cats was treated with 0.03% bimatoprost solution while a single eye of the remaining six cats was treated with buffered saline solution (BSS) once daily. During a second 10-day treatment phase a single eye of six of the cats was treated with 0.15% unoprostone isopropyl solution while a single eye of the remaining six cats was treated with BSS twice daily. Contralateral eyes of all cats remained untreated at all time points. RESULTS: Blepharospasm score, conjunctival injection score, and aqueous humor flare score never rose from a value of 0, for any eye of any cat during the study. The mean +/- SD of IOP for eyes treated with 0.03% bimatoprost solution and BSS were 16.55 +/- 3.06 mmHg and 18.02 +/- 3.52 mmHg, respectively. The mean +/- of PD for eyes treated with 0.03% bimatoprost solution and BSS were 5.7 +/- 1.57 mm and 6.39 +/- 1.78 mm, respectively. The mean +/- SD of IOP for eyes treated with 0.15% unoprostone isopropyl solution and BSS were 15.7 +/- 2.91 mmHg and 17.2 +/- 2.9 mmHg, respectively. The mean +/- SD of PD for eyes treated with 0.15% unoprostone isopropyl solution and BSS were 5.8 +/- 1.43 mm and 6.9 +/- 1.37 mm, respectively. There was no significant difference (P > or = 0.05) in IOP or PD between eyes treated with 0.03% bimatoprost solution vs. eyes treated with BSS. Similarly, there was no significant difference (P > or = 0.05) in IOP or PD between eyes treated with 0.15% unoprostone isopropyl solution vs. eyes treated with BSS. CONCLUSION: Neither once daily topical administration of 0.03% bimatoprost solution nor twice daily topical administration of 0.15% unoprostone isopropyl solution significantly affect the IOP of normal cats. Both 0.03% bimatoprost solution and 0.15% unoprostone isopropyl solution induced no significant ocular side effects in normal cats when dosed over a 10-day treatment period.     

The effect of 0.12% unoprostone isopropyl (rescula) on intraocular pressure in normotensive dogs

Rescula (0.12% unoprostone isopropyl) is the first docosanoid compound approved for treatment of glaucoma in humans. It is commercially available in Japan, and is undergoing clinical testing elsewhere. The aim of this study was to evaluate the effect of Rescula on intraocular pressure (IOP) in normotensive dogs. After establishing a baseline diurnal IOP curve, six dogs were unilaterally treated with Rescula while the contralateral eye was treated with a placebo. Applanation tonometry was performed in both eyes, and pupil size was evaluated, 30 min after treatment, and at 1-hr intervals for the next 9 hr. Rescula caused a significant (p=0.014) and long-lasting decrease in IOP, from 20.49+/-2.02 mm Hg in control eyes to 15.49+/-0.69 mm Hg in treated eyes. These results suggest that Rescula is potentially efficacious in treatment of canine glaucoma.     

Effects of topical administration of 2.0% pilocarpine on intraocular pressure and pupil size in cats

Effects of topical administration of a single dose of 2% pilocarpine on intraocular pressure (IOP) and pupil diameter were evaluated in 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 found to be 10.1 (+/- 0.5) mm. Topical treatment with pilocarpine resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 4 hours after treatment. Mean reduction of IOP was 15.2% in the treated eye and 9.3% 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 in pupil diameter was 28.5% in the treated eye and 14.2% in the nontreated eye. Topically administered pilocarpine results in reduction of IOP and pupil diameter in treated and contralateral eyes, which supports the use of pilocarpine for treatment of glaucoma in cats.     

Intraocular pressure measurements obtained as part of a comprehensive geriatric health examination from cats seven years of age or older.

OBJECTIVE: To determine intraocular pressure (IOP) in cats > or = 7 years of age undergoing a routine comprehensive geriatric health examination. DESIGN: Prospective study. ANIMALS: 538 cats (1,068 eyes). PROCEDURE: IOP was measured by applanation tonometry following instillation of 0.5% proparacaine. RESULTS: Mean +/- SD IOP for all eyes was 12.3 +/- 4.0 mm Hg (range, 4 to 31 mm Hg). Mean age was 12.3 +/- 2.9 years. Intraocular pressure did not vary significantly cross-sectionally with age. However, in 78 cats, IOP was measured more than once, and follow-up measurements were significantly less than initial measurements (mean time between measurements, 9.4 +/- 3.0 months). The most useful tonometric criteria for identifying ocular abnormalities on the basis of IOP was an IOP > or = 25 mm Hg (mean + 3 SD) or a difference in IOP between eyes > or = 12 mm Hg. Eight cats met these criteria, and 5 of these cats had ophthalmic abnormalities. Low IOP was a nonspecific indicator of the presence of ocular abnormalities, as 111 cats had an IOP < or = 8 mm Hg, but only 2 had uveitis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IOP measurements can be a useful addition to a comprehensive geriatric health examination in cats > or = 7 years of age, especially when combined with an ophthalmic examination. Cats without ocular abnormalities that have lOP > or = 25 mm Hg or a > or = 12 mm Hg difference in IOP between eyes should have tonometry repeated or be referred to an ophthalmologist for further evaluation before beginning antiglaucoma treatment.     

Comparison of applanation tonometers in dogs and horses.

Two Mackay-Marg tonometers and 2 Tono-Pen tonometers were evaluated in eyes in which intraocular pressure (IOP) had been altered and measured by use of a manometer. Eyes of anesthetized dogs and enucleated horse eyes were used. Compared with the manometer, none of the tonometers accurately measured IOP over the range between 0 and 100 mm of Hg. However at manometer measurements from 0 to 30 mm of Hg, several of the tonometers accurately measured IOP. In addition, significant differences were observed when the measurement accuracy of one tonometer was compared with that of another, especially at high IOP. Coefficient of determination (r2) values for a linear model ranged from 0.979 to 0.991 in dogs, and from 0.982 to 0.996 in horse eyes.     

Population pharmacokinetics of marbofloxacin in aqueous humor after intravenous administration in dogs

OBJECTIVE: To evaluate, by use of population pharmacokinetics, the disposition of marbofloxacin in the aqueous humor after IV administration in dogs and identify its potential usefulness in the prophylaxis and treatment of intraocular infection. ANIMALS: 63 dogs. METHODS: Dogs received a single dose of marbofloxacin (2 mg x kg(-1), IV) at various time intervals before cataract surgery. Aqueous humor and blood samples were collected at the beginning of surgery. Marbofloxacin concentrations were measured by high-pressure liquid chromatography. Data were analyzed with a nonlinear mixed-effect model and, by use of population pharmacokinetic parameters, the time course of aqueous humor concentration was simulated for single doses of 3, 4, and 5.5 mg x kg(-1) IV. Pharmacodynamic surrogate markers and measured aqueous humor concentrations were used to predict in vivo antimicrobial activity. RESULTS: A maximum marbofloxacin concentration of 0.41 +/- 0.17 microg x mL(-1) was reached in the aqueous humor 3.5 hours after IV administration. In the post-distributive phase, marbofloxacin disappeared from aqueous humor with a half-life of 780 minutes. The percentage penetration into the aqueous humor was 38%. Predictors of antimicrobial effects of marbofloxacin (2 mg x kg(-1), IV) indicated that growth of the enterobacteriaceae and certain staphylococcal species would be inhibited in the aqueous humor. Marbofloxacin administered IV at a dose of 5.5 mg x kg(-1) would be predicted to inhibit growth of Pseudomonas aeruginosa and all strains of staphylococci but would not eradicate streptococcal infections. CONCLUSIONS AND CLINICAL RELEVANCE: Marbofloxacin administered IV can penetrate the aqueous humor of canine eyes and may be suitable for prophylaxis or treatment of certain anterior chamber infections.     

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.