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.     

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.     

Effects of topical administration of 1% brinzolamide on intraocular pressure in clinically normal horses

Reasons for performing study: Only few drugs with limited efficacy are available for topical treatment of equine glaucoma. Objective: To evaluate the effect of topical administration of 1% brinzolamide on intraocular pressure (IOP) in clinically normal horses. Methods: Healthy mature horses (n = 20) with normal ocular findings, were studied. The IOP was measured 5 times daily (07.00, 11.00, 15.00, 19.00 and 23.00 h) over 10 days. On Days 1 and 2, baseline values were established. On Days 3–5 one eye of each horse was treated with one drop of 1% brinzolamide every 24 h immediately following the 07.00 h measurement. On Days 6–8 the same eye was treated with 1% brinzolamide every 12 h (07.00 and 19.00 h). Measurements on Days 9 and 10 documented the return of IOP to baseline values. Statistical analysis of the data was performed. Results: In the treated eye a significant decrease in IOP compared to baseline values was noted during both the 24 and 12 h dosing periods (P<0.001). During the once‐daily treatment protocol an IOP reduction of 3.1 ±1.3 mmHg (14%) from baseline was recorded. During the twice‐daily protocol a total IOP reduction of 5.0 ± 1.5 mmHg (21%) was achieved. Conclusion: Intraocular pressure was significantly decreased by 1% brinzolamide in a once‐daily and a twice‐daily treatment protocol in normotensive eyes. These findings suggest that brinzolamide might also be effective in horses with an elevated IOP. Potential relevance: This drug may be useful for treatment of equine glaucoma.     

Effects of topical 0.5% tropicamide on intraocular pressure in normal cats

The objective of the study was to determine the effect of topical 0.5% tropicamide on intraocular pressure (IOP) in normotensive feline eyes. IOP was measured bilaterally in 70 clinically healthy cats and gonioscopy (and goniophotography) was performed. Thereafter, 50 cats were treated unilaterally with one drop of 0.5% tropicamide. The contralateral, left eye served as a control. In the placebo group consisting of 20 cats, one drop of physiologic saline solution was administered to the right eye. In all cats, IOP of both eyes was measured 30, 60 and 90 min after topical administration. After unilateral tropicamide application, IOP increased significantly both in the right and in the left eye. Maximum average IOP increase was observed at the control measurement performed 90 min after treatment, with an elevation of 3.8 +/- 4.2 mmHg in the right eye and 3.5 +/- 3.6 mmHg in the left eye. Maximum IOP increase after treatment was 18.0 mmHg in the treated eye and 17.0 mmHg in the left eye. Measurements made at 60 min after treatment revealed a significantly higher increase in IOP in the right eye as compared to the left eye (P60 < 0.05), whereas the differences between right and left eye in IOP increase were not significant at 30 and 90 min after mydriatic application (P30 = 0.123; P90 = 0.305). Although tropicamide-induced mydriasis was observed in the treated eye, the contralateral eye did not show any changes in pupillary function at any time. With increasing age of the cats, IOP increase was found to be more moderate, whereas the gender of the cats did not have any significant influence on IOP changes. In the 20 cats in the placebo group, no significant changes in IOP were observed. We conclude that topical 0.5% tropicamide causes a significant elevation of IOP in the treated and untreated eye in normal cats.     

The effect of a single dose of topical 0.005% latanoprost and 2% dorzolamide/0.5% timolol combination on the blood-aqueous barrier in dogs: a pilot study

Objective To determine the effects of 0.005% latanoprost and 2% dorzolamide/0.5% timolol on the blood‐aqueous barrier (BAB) in normal dogs. Animals studied Eight mixed‐breed and pure‐breed dogs. Procedures Baseline anterior chamber fluorophotometry was performed on eight normal dogs. Sodium fluorescein was injected and the dogs were scanned 60–90 min post‐injection. Seventy‐two hours following the baseline scan, one eye received one drop of latanoprost. Fluorophotometry was repeated 4 h after drug administration. Following a washout period, the identical procedure was performed 4 h after the administration of dorzolamide/timolol. The degree of BAB breakdown was determined by comparing the concentrations of fluorescein within the anterior chamber before and after drug administration. BAB breakdown was expressed as a percentage increase in the post‐treatment fluorescein concentration over the baseline concentration: %INC [Fl] = {([Fl]_post – [Fl]_baseline)/[Fl]_baseline} × 100. The percentage increase in fluorescein concentration in the treated eye was compared to that in the nontreated eye using a paired t‐test with significance set at P ≤ 0.05. Results Following administration of latanoprost, the fluorescein in the treated eyes increased 49% (± 58%) from baseline compared to 10% (± 31%) in the untreated eyes (P = 0.016). Following administration of dorzolamide/timolol, the fluorescein concentration increased 38% (± 54%) compared to baseline vs. 24% (± 38%) in the untreated eyes (P = 0.22). Conclusions The results of this study show that topical latanoprost may cause BAB disruption in normal dogs while topical dorzolamide/timolol may have no effect on the BAB 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 twice daily application of 2% dorzolamide on intraocular pressure in normal cats

The effect of the topical carbonic anhydrase inhibitor, dorzolamide, on intraocular pressure in cats was studied. The intraocular pressure of both eyes of eight healthy cats was measured using applanation tonometery (Tono-Pen) during two phases: control and treatment. Both eyes were treated with 2% dorzolamide twice a day during the treatment phase. Application of dorzolamide resulted in a significant decrease of intraocular pressure over the treatment phase. By the fourth and fifth day of treatment, the mean intraocular pressure (+/- standard deviation) was 9.7 (+/- 1.5) mmHg, whereas the mean (+/- standard deviation) for the last 2 days of the control period was 12.2 (+/- 2.0) mmHg. Based on this study, dorzolamide is a potentially effective treatment for glaucoma in cats, significantly lowering intraocular pressure.     

Effect of topical ophthalmic latanoprost on intraocular pressure in normal horses

The ocular effects of latanoprost ophthalmic solution were evaluated in two studies, with eight horses in each study. One eye of each horse was treated with latanoprost ophthalmic solution once daily for 5 days, and the opposite eye received a control solution of sterile eyewash. Intraocular pressure and pupillary diameter were measured daily for 5 days after treatment. Latanoprost had no significant effect on intraocular pressure or pupillary diameter in normal horse eyes compared with control eyes in these studies. Placement of an eyelid nerve block resulted in significantly lower intraocular pressure.     

Effects of topical nipradilol and timolol maleate on intraocular pressure, facility of outflow, arterial blood pressure and pulse rate in dogs

Nipradilol is an alpha(1), beta-blocker with milder side effects than other beta-blockers used in humans. In this study the effects of nipradilol were compared with those of timolol maleate in dogs. Twelve clinically normal dogs (nine mongrels, two beagles, and one Akita) were used. We applied 0.25% nipradilol or 0.5% timolol maleate drops for a period of 28 days. Intraocular pressure (IOP) was measured before and after administration on the 2nd, 4th, 7th, 14th, 21st and 28th day. Blood pressure, pulse rate and coefficient of aqueous outflow (C-value) were also measured before and after administration on the 7th, 14th, 21st and 28th day. Both nipradilol and timolol maleate significantly lowered IOP from the 2nd day to the end of the study period. Nipradilol lowered IOP to an equivalent degree to timolol maleate. There was no significant change in blood pressure and pulse rate throughout the study period with administration of nipradilol. C-value showed a significant rise from the 14th day with administration of nipradilol, while it did not show any significant change during the study period with administration of timolol maleate. The reduction of IOP by nipradilol was similar to that by an existing beta-adrenergic antagonist, timolol maleate, but nipradilol was associated with fewer systemic side effects in dogs. Nipradilol appears to be a useful drug for treatment of glaucoma in dogs.     

Effects of topical 0.5% levobunolol alone or in association with 2% dorzolamide compared with a fixed combination of 0.5% timolol and 2% dorzolamide on intraocular pressure and heart rate in dogs without glaucoma

The goal of glaucoma management is to reduce intraocular pressure (IOP) and maintain it at a level compatible with the health of the optic nerve. New therapies are constantly being sought. Topical instillation of levobunolol 0.5%, alone or with dorzolamide 2%, has a hypotensive effect on the IOP in healthy dogs, and levobunolol combined with dorzolamide produces a stronger hypotensive effect than the combination of timolol and dorzolamide. All animals tolerate these topical medications well with no signs of discomfort, and no ocular side effects have been observed. Levobunolol, alone or in combination with dorzolamide, induces bradycardia, as does timolol with dorzolamide.     

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.     

The effect of dorzolamide 2% on circadian intraocular pressure in cats with primary congenital glaucoma

Objective To determine the extent of fluctuation in circadian intraocular pressure (IOP) and the efficacy of topical dorzolamide 2% q 8 h in lowering IOP and blunting circadian fluctuation in IOP in glaucomatous cats. Animals studied Seven adult cats with primary congenital glaucoma (PCG). Procedures Measurements of IOP and pupil diameter were obtained for both eyes (OU) of each cat q 4 h for 12 days. Cats were housed in a laboratory animal facility with a 12‐h light:dark cycle. Baseline values were established for 2 days. For the next 5 days, placebo (1.4% polyvinyl alcohol) was administered OU q 8 h. Dorzolamide 2% was then administered OU q 8 h for a further 5 days. A multivariate mixed linear model was fitted to the data, with parameters estimated from a Bayesian perspective. The 4 am time point was selected as the reference for the purposes of comparisons. Results Estimated mean IOP for the reference time point pre‐treatment was symmetric (about 33 mmHg OU). In all cats, IOP was significantly lower during the diurnal phase, relative to the 4 am measurements, with highest IOP observed 2–6 h after the onset of the dark phase. Circadian fluctuations in IOP were dampened during the treatment period. There was a significant decrease in IOP in all cats during the dorzolamide treatment period (estimated mean for the treatment period reference = 17.9 mmHg OU). Conclusions Topical dorzolamide 2% q 8 h is effective in reducing IOP and IOP fluctuation in cats with PCG.     

Effects of systemic administration of 0.5% tropicamide on intraocular pressure, pupillary diameter, blood pressure, and heart rate in normal cats

OBJECTIVE: The objective of the study was to determine the effects of systemic 0.5% tropicamide on intraocular pressure (IOP), pupillary diameter (PD), blood pressure, and heart rate (HR) in normal felines with normotensive eyes. PROCEDURES: Intraocular pressure, PD, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), and HR were measured in 18 clinically healthy cats. Each of the previously mentioned parameters was measured every 30 min during the trial period. At T(60), each cat was treated with one to two drops of 0.5% tropicamide ophthalmic solution placed on the dorsal aspect of the tongue. Changes in SBP, DBP, MBP, and HR were evaluated using one-way repeated measures analysis of variance, with time as the repeated factor. IOP and PD were evaluated using two-way repeated measures analysis of variance, with time and side (OD vs. OS) as the repeated factors. P values less than or equal to 0.05 were considered statistically significant. RESULTS: After lingual tropicamide administration, the mean PD at T(60) was 3.53 mm OD and 3.53 mm OS. The mean PD at T(90) was 6.36 mm OD and 6.31 mm OS. The mean PD at T(120) was 8.25 mm OD and 8.19 mm OS. This change in PD from T(60), T(90), and T(120) was statistically significant, demonstrating a linear increase in PD over time after tropicamide application on the tongue (P<0.0001). There was no statistically significant difference in PD when comparing the right to the left pupils (P=0.10). The mean IOP at T(60) was 14 mmHg OD and 12.94 mmHg OS. The mean IOP at T(90) was 14.5 mmHg OD and 14.23 mmHg OS. The mean IOP at T(120) was 14.94 mmHg OD and 14.89 mmHg OS. This change in IOP from T(60), T(90), and T(120) was statistically significant, demonstrating a linear increase in IOP over time after tropicamide application on the tongue (P=0.034). There was no statistically significant difference in IOP when comparing the right eye to the left eye (P=0.28). There were no statistically significant differences in SBP, DBP, MBP, and HR values over time for the duration of the study. CONCLUSIONS: We conclude that although lingual application of tropicamide appears to result in systemic absorption, causing significant pupillary dilation and elevations in IOP, systemic effects on SBP, DBP, MBP, and HR were not observed.     

Effects of unilateral topical administration of 0.5% tropicamide on anterior segment morphology and intraocular pressure in normal cats and cats with primary congenital glaucoma

Objective To determine the effects of topical 0.5% tropicamide on anterior segment morphology (ASM) and intraocular pressure (IOP) in normal and glaucomatous cats. Animals used Normal cats and cats with inherited primary congenital glaucoma (PCG). Procedures Control IOP curves were performed in untreated normal and PCG cats. In the first experiment, tropicamide was applied OD in eight normal and nine PCG cats. IOP and pupillary diameter (PD) were measured at 0, 30, and 60 min, then hourly until 8 h post‐treatment. In a second experiment, six normal and seven PCG cats received tropicamide OD. High‐resolution ultrasound images were obtained at 0, 1, 5, and 10 h post‐treatment to measure ASM changes. IOP and PD were measured OD at 0, 1, 2, 3, 5, 7, and 9 h. Results In untreated normal cats IOP OU decreased throughout the day. In PCG cats IOP OU had wide fluctuations over time. In normal cats IOP response varied in the treated eye but did not change significantly in untreated eyes. IOP significantly increased from baseline in both eyes of all treated PCG cats. Increases in IOP were associated with some ASM changes. Cats with PCG had a significantly smaller angle recess areas, diminished ciliary clefts and decreased iris‐lens contact. ASM changes were not strongly correlated with IOP in all cats. Conclusions The ASM of PCG cats is markedly different from normal cats, and clinically significant increases in IOP OU occur in cats with PCG after tropicamide treatment. The mechanism for this increase remains unclear.