Effect of different dose schedules of latanoprost on intraocular pressure and pupil size in the glaucomatous Beagle

Objective To evaluate the changes in intraocular pressure and pupil size in glaucomatous dogs after instillation of 0.005% latanoprost (Xalatan, Pharmacia and Upjohn, Kalamazoo, MI, USA) once in the morning, or once in the evening, or twice daily in five‐day multiple‐dose studies. Animals studied Eight Beagles with the moderate stage of inherited primary open‐angle glaucoma. Procedures Applanation tonometry (IOP) and pupil size (PS) measurements were obtained at 8 am, 10 am, 12 noon, 2 pm, and 4 pm in eight glaucoma dogs. Methylcellulose (0.5% as placebo) was instilled in the control eye, and 0.005% latanoprost was instilled in the opposite drug eye. Control and drug eyes were selected using a random table. For these three studies, 0.5% methylcellulose and 0.005% latanoprost were instilled the second through the fifth days with instillations in the morning (8.30 am), or evening (8 pm), or twice daily (8.30 am and 8 pm). Statistical comparisons between drug groups included control, placebo, and treated (0.005% latanoprost) eyes for three multiple‐dose studies. Results In the 8‐am latanoprost study, the mean ± SEM diurnal declines in IOP for the placebo and drug eyes for the first day were 6.5 ± 3.6 mmHg and 8.4 ± 4.0 mmHg, respectively. The mean ± SEM diurnal changes in IOP after 0.005% latanoprost at 8 am once daily for the next four days were 23.3 ± 5.0 mmHg, 25.4 ± 2.1 mmHg, 25.7 ± 1.7 mmHg, and 26.1 ± 1.7 mmHg, respectively, and were significantly different from the control eye. A significant miosis also occurred starting 2 h postdrug instillation, and the resultant mean ± SD pupil size was 1.0 ± 0.1 mm. In the first day of the second latanoprost study, the mean ± SEM diurnal changes in the placebo and drug eye IOPs were 11.6 ± 3.8 mmHg, and 12.0 ± 4.4 mmHg, respectively. For the following four days with latanoprost instilled at 8 pm, the mean ± SEM diurnal changes in IOP in the drug eyes were 24.9 ± 2.1 mmHg, 22.4 ± 1.8 mmHg, 21.6 ± 1.9 mmHg, and 26.6 ± 2.2 mmHg, respectively. Compared to the fellow placebo eyes, the diurnal changes in IOP were significantly different. Significant changes in pupil size were similar to the IOP changes, with miosis throughout the day and return to baseline pupil size the following morning before drug instillation. In the last study, the mean ± SEM diurnal changes in IOP for the placebo and drug eyes for the first day were 6.6 ± 2.1 mmHg and 9.4 ± 2.8 mmHg, respectively. For the four subsequent days with latanoprost instilled twice daily, the mean ± SEM diurnal IOP changes were 19.6 ± 1.5 mmHg, 19.1 ± 1.4 mmHg, 19.9 ± 1.7 mmHg, and 20.3 ± 0.7 mmHg, respectively, and were significantly different from the placebo eyes. The mean changes in PS were 3.1 ± 0.7 mm. Conclusion 0.005% latanoprost instilled once daily (am or pm) as well as twice daily produces significant decreases in IOP and PS in the glaucomatous Beagle. The evening instillation of 0.005% latanoprost produced less daily fluctuations in IOP than when the drug was instilled in the morning. 0.005% latanoprost instilled twice daily produced the greatest decline in IOP with the least daily fluctuations, but longer duration miosis.     

Effect of three treatment protocols on acute ocular hypertension after phacoemulsification and aspiration of cataracts in dogs

Objective  To compare the effect of topical latanoprost, intracameral carbachol, or no adjunctive medical therapy on the development of acute postoperative hypertension (POH) and inflammation after routine phacoemulsification and aspiration (PA) of cataracts in dogs.
Design  Retrospective study.
Procedures  Dogs received either one drop of topical 0.005% latanoprost (21 dogs, 39 eyes), an intracameral injection of 0.3 mL of 0.01% carbachol (15 dogs, 30 eyes), or no adjunctive therapy (46 dogs, 90 eyes) immediately following PA of cataract(s). Intraocular pressure (IOP) was measured in all dogs 2 and 4 h after surgery. IOP was measured and aqueous flare assessed at 8 am the day after surgery.
Results  Carbachol-treated dogs had significantly higher mean IOP (33.2 ± SD 20.8 mmHg) 2 h after surgery than dogs receiving no adjunctive therapy (22.0 ± SD 14.1 mmHg) ( P  =  0 .049). There were no significant differences in IOP among groups at any other time point. There were no significant differences in number of POH episodes between dogs treated with carbachol (47%), latanoprost (29%), or dogs that received no adjunctive therapy (33%). There were no significant differences in mean aqueous flare grade between eyes treated with latanoprost (1.7 ± SD 0.4) or carbachol (1.4 ± SD 0.6), and eyes that received no adjunctive therapy (1.7 ± SD 0.4).
Conclusions  Topical 0.005% latanoprost or intracameral injection of 0.3 mL of 0.01% carbachol after PA in dogs did not reduce POH or increase intraocular inflammation compared to dogs not receiving adjunctive therapy after PA of cataracts.     

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 0.03% flurbiprofen and 0.005% latanoprost, alone and in combination, on normal canine eyes

Objective Evaluate the influence of topically applied flurbiprofen 0.03% and latanoprost 0.005%, alone or in combination, in normal canines. Animals studied 10 Normal Beagles. Procedures Intraocular pressure (IOP), pupil size, aqueous flare, conjunctival hyperemia, and blepharospasm were evaluated bilaterally five times daily (8 am , 11 am , 2 pm , 5 pm, and 8 pm ). The study consisted of a training and acclimation period, followed by 3, 1‐week experiment periods. A 2‐week washout period occurred between each experiment period. During period 1, all dogs received flurbiprofen (three doses 6‐h apart) in the treated eye, whereas in period 2, all dogs received latanoprost (one dose 24‐h apart). During period 3, both latanoprost (one dose 24‐h apart) and flurbiprofen (three doses 6‐h apart) were administered in the treated eye. Results Flurbiprofen resulted in a mean IOP elevation of 1.1 mmHg (8.65%) in the treated eye, as compared with the control eye. No effect on pupil size, conjunctival hyperemia, or aqueous flare was noted. Latanoprost resulted in a mean IOP reduction of 3.4 mmHg (30.19%). Combined latanoprost and flurbiprofen resulted in a mean IOP reduction of 2.7 mmHg (24.56%). Miosis was noted in the treated eyes during both latanoprost periods, with maximal pupil constriction 3‐h post‐dose. This was followed by relative mydriasis 24‐h post‐dose, persisting 48 h after the last dose. The degree of conjunctival hyperemia varied between individuals. Neither blepharospasm nor aqueous flare was noted at any time point. Conclusion Concurrent administration of latanoprost and flurbiprofen resulted in a 20.41% reduction in the ocular hypotensive effect relative to latanoprost therapy alone.     

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%.