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.     

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 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 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.     

Ocular effects of topical 0.03% bimatoprost solution in normotensive feline eyes

OBJECTIVE: The current study was undertaken to evaluate the effects of topically applied bimatoprost, an ocular hypotensive lipid, on intraocular pressure (IOP) and pupil size (PS) in healthy cats. ANIMAL STUDIED: Nine European Shorthair cats free from clinically relevant ocular abnormalities were used in the study. PROCEDURES: Pretreatment baseline measurements of IOP and PS were obtained bilaterally at 8 am, 2 pm, and 8 pm for five consecutive days (days 1 to 5). Then the cats received one drop twice daily (10 am and 6 pm) of bimatoprost ophthalmic solution 0.03% (Lumigantrade mark, Allergan Inc., Irvine, CA USA), in one randomly selected eye and one drop of artificial tears in the fellow eye (control eye) for 5 days (days 6 to 10). Values for IOP and PS were obtained under the same conditions as in the pretreatment phase. The potential for ocular irritation following bimatoprost application was also evaluated. RESULTS: During the pretreatment period, the mean IOP and mean PS were not significantly different between the eyes subsequently treated with bimatoprost and those subsequently determined as controls. During the treatment period, the mean IOP in bimatoprost-treated eyes was not significantly lower than in control eyes (14.2+/-2.3 vs. 14.5+/-2.8 mmHg). Mean IOP in control eyes was not significantly changed at any time during the study period. A marked reduction of PS was seen in all bimatoprost-treated eyes, but no other clinically relevant side effects were observed. CONCLUSION: Twice daily topical applications of bimatoprost produced miosis but had no significant effect on IOP in healthy cats.     

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.     

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.     

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

Objective To evaluate changes in intraocular pressure and pupil size in glaucomatous dogs after instillation of 0.004% travoprost once in the morning, or once in the evening, or twice daily in 5‐day multiple dose studies. Materials and methods Applanation tonometry (IOP) and pupil size (PS) measurements were obtained at 8 a.m., 10 a.m., 12 noon, 2 p.m. and 4 p.m. in eight glaucoma dogs. Methylcellulose (0.5% as placebo) was instilled in the control eye, and 0.004% travoprost was instilled in the opposite drug eye. Methylcellulose (0.5%) and 0.004% travoprost were instilled on the 2nd through to the 5th day with instillations in the morning (8.30 a.m.), or evening (8 p.m.), or twice daily (8.30 a.m. and 8 p.m.). Results The mean ± SEM diurnal changes from baseline IOP in the control and placebo eyes in all three studies ranged from 1.2 ± 0.3 mmHg to 3.2 ± 0.9 mmHg. The mean ± SEM diurnal changes from the baseline IOP after 0.004% travoprost at 8 a.m. once daily for the next 4 days were 19.0 ± 2.7 mmHg, 24.7 ± 2.7 mmHg, 24.9 ± 3.1 mmHg, and 24.7 ± 3.1 mmHg, respectively, and were significantly different from the control eye. After travoprost was instilled at 8 p.m., the mean ± SEM baseline changes from the baseline IOP in the drug eyes were 23.5 ± 2.2 mmHg, 24.2 ± 2.2 mmHg, 24.5 ± 2.3 mmHg, and 24.2 ± 2.3 mmHg, respectively. When 0.004% travoprost was instilled twice daily, the mean ± SEM baseline IOP changes were 27.7 ± 2.1 mmHg, 28.1 ± 2.1 mmHg, 28.4 ± 2.2 mmHg, and 28.5 ± 2.2 mmHg, respectively, and were significantly different from the control eyes. Miosis of varying duration was frequent during the three studies. Conclusion Travoprost instilled once daily (a.m. or p.m.) as well as twice daily produces significant decreases in IOP and PS in the glaucomatous Beagle.     

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.     

Diurnal variations of central corneal thickness and intraocular pressure in dogs from 8:00 am to 8:00 pm

Diurnal variations in central corneal thickness (CCT) and intraocular pressure (IOP) and their relationships were studied in healthy dogs. Central corneal thickness was measured by ultrasonic pachymetry and IOP by applanation tonometry in 16 beagle dogs. Measurements were taken every 90 min over 12 h (08:00 am to 08:00 pm). The mean CCT and IOP values obtained during the sampling period were 545.6 ± 21.7 μm (range: 471 to 595 μm) and 15 ± 2.2 mmHg (range: 10 to 19 mmHg), respectively. The CCT and IOP showed statistically significant decreases at 6:30 pm and 5:00 pm, respectively (P < 0.001). Central corneal thickness and IOP values were lower in the afternoon/evening than in the morning and were positively correlated. Both findings are important for the diagnostic interpretation of IOP values in dogs.     

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.     

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%.     

Effect of Coherin™ on intraocular pressure,pupil size and heart rate in the glaucomatous Beagle: a pilot study

Objective To evaluate effects of Coherin? on intraocular pressure (IOP), pupil size (PS), and heart rate (HR) in glaucomatous Beagles in single‐dose studies in a pilot study. Materials and methods Intraocular pressure, PS, and HR were measured in eight glaucomatous Beagles. One randomly chosen eye received single 50 μL doses of differing concentrations of Coherin? (treated eye) or vehicle (placebo‐treated eye), and the fellow eye served as the untreated control. After the first measurements, a single dose of either Coherin? or sterile water vehicle was instilled in the drug and placebo eyes, respectively. Results The mean ± SEM diurnal changes in IOP after 0.005%, 0.01%, 0.2%, 0.284%, 1%, 2%, and 4% topical Coherin? once daily were 7.6 ± 3.2 mmHg, 15.5 ± 5.3 mmHg, 11.2 ± 4.4 mmHg, 11.8 ± 4.4 mmHg, 19.1 ± 3.8 mmHg, 5.0 ± 1.8 mmHg, and 8.8 ± 2.8 mmHg, respectively. The declines in IOP were significantly different (P < 0.05) from the untreated control eyes with the 0.2% and 0.284% Coherin?‐treated eyes and suggestive for 1% Coherin? concentrations. No signs of irritation, significant PS, and HR changes were detected in the Coherin?‐treated eyes. Conclusion Of seven different concentrations, 2% and 0.248% Coherin? produced significant declines in IOP in the glaucomatous beagle in single‐dose studies when compared to both untreated control and placebo‐treated eyes. One percent Coherin? solution produced significant IOP decreases compared with the placebo‐treated eye but not the untreated control eyes. No local ocular irritation, PS and HR changes were observed in Coherin?‐treated eyes. This pilot study suggests that topical Coherin? has potential as an ocular hypotensive agent.     

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.     

Effects of atracurium on intraocular pressure, eye position, and blood pressure in eucapnic and hypocapnic isoflurane-anesthetized dogs

OBJECTIVE: To determine effects of atracurium on intraocular pressure (IOP), eye position, and arterial blood pressure in eucapnic and hypocapnic dogs anesthetized with isoflurane. ANIMALS: 16 dogs. PROCEDURE: Ventilation during anesthesia was controlled to maintain Paco2 at 38 to 44 mm Hg in group- I dogs (n = 8) and 26 to 32 mm Hg in group-II dogs (8). Baseline measurements for IOP, systolic, diastolic, and mean arterial blood pressure, central venous pressure (CVP), and heart rate (HR) were recorded. Responses to peroneal nerve stimulation were monitored by use of a force-displacement transducer. Atracurium (0.2 mg/kg) was administered i.v. and measurements were repeated at 1, 2, 3, and 5 minutes and at 5-minute intervals thereafter for 60 minutes. RESULTS: Atracurium did not affect IOP, HR, or CVP Group II had higher CVP than group I, but IOP was not different. There was no immediate effect of atracurium on arterial blood pressure. Arterial blood pressure increased gradually over time in both groups. Thirty seconds after administration of atracurium, the eye rotated from a ventromedial position to a central position and remained centrally positioned until 100% recovery of a train-of-four twitch response. The time to 100% recovery was 53.1 +/- 5.3 minutes for group I and 46.3 +/- 9.2 minutes for group II. CONCLUSIONS AND CLINICAL RELEVANCE: Atracurium did not affect IOP or arterial blood pressure in isoflurane-anesthetized dogs. Hyperventilation did not affect IOP or the duration of effect of atracurium.     

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.     

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 mydriatics on intraocular pressure and pupil size in the normal feline eye

OBJECTIVE: To determine the effect of various mydriatics (1% atropine, 1% cyclopentolate, 0.5% tropicamide, 10% phenylephrine) on intraocular pressure (IOP) and pupil size (PS) in normal cats. ANIMALS STUDIED: The mydriatics were tested in 10 adult ophthalmoscopically normal European Domestic Short-haired cats. Procedure Single-dose drug studies were divided into placebo (vehicle of phenylephrine), 10% phenylephrine, 0.5% tropicamide, 1% cyclopentolate and 1% atropine. After measurement of IOP and pupil size (PS) at 8 a.m. on the first day, one drop of the tested drug was applied to one randomly selected eye. The IOP and PS were measured for a minimum of 36 h until the pupil returned to pretest size. RESULTS: Ten per cent phenylephrine had no significant effect on IOP, and the effect on the pupil size was minimal (相似文献   

Comparison of the effect of hypertonic hydroxyethyl starch and mannitol on the intraocular pressure in healthy normotensive dogs and the effect of hypertonic hydroxyethyl starch on the intraocular pressure in dogs with primary glaucoma

PURPOSE: The purpose of this study was to determine if intravenous hypertonic hydroxyethyl starch (7.5%/6%) (HES) could decrease the intraocular pressure (IOP) in healthy normotensive dogs, and compare its effect with that of mannitol (20%) (experimental study). In addition, the potential IOP-lowering effect of hypertonic HES was evaluated in six dogs with primary glaucoma (clinical study). MATERIAL AND METHODS: Experimental study: eight male ophthalmoscopically and clinically healthy Beagles were included in this study. The IOP of each dog was measured by applanation tonometry in both eyes to obtain control values at 10:00, 10:15, 10:30, 10:45, 11:00 a.m., and then every hour until 6:00 p.m. prior to the first treatment (control period). Each dog received, with at least 2-week intervals and in a random order, an intravenous (IV) infusion of 4 mL/kg hypertonic HES (1.2 g/kg NaCl; 0.96 g/kg HES) and 4 mL/kg mannitol 20% (1 g/kg) over a period of 15 min starting at 10:00 a.m. IOP was measured oculus uterque (OU) at the same time intervals as in the control study. The differences in IOP between the treatment groups and the baseline IOP (before the start of infusion), between oculus sinister (OS) and oculus dexter (OD) and between the same time points of all groups were determined with a Student's t-test for paired samples (P = 0.05). Clinical study: six dogs with primary glaucoma (representing seven eyes) received an IV infusion of 4 mL/kg hypertonic HES over a period of 15 min. IOP was measured before and 15 and 30 min after starting the infusion. RESULTS: Experimental study: no significant difference between IOP of both eyes was found. A significant decrease in IOP from baseline value was recorded at 15, 30, 45, and 60 min after the start of mannitol infusion (mean amplitude in IOP decrease 3.21 mmHg; P < 0.05) and at 15 and 30 min in dogs treated with HES (mean amplitude in IOP decrease 2.43 mmHg; P < 0.05). At 120 and 180 min there was a significantly higher IOP (P < 0.05) in HES treatment group compared to the values of the control group. Clinical study: in 5/7 eyes diagnosed with primary glaucoma a maximum decrease in IOP of an average of 24% from the baseline value (IOP before start of the infusion) was observed (range of decrease 2-21 mmHg). In three of these five cases the maximum decrease was reached at 15 min and in two cases at 30 min. In one case an increase in IOP of 35% (+ 18 mmHg) was seen after 15 min and 26% (+ 13 mmHg) after 30 min. Case 4 showed an increase in IOP of 5% (+ 3 mmHg) after 15 min and a decrease of 6% (- 4 mmHg) after 30 min. CONCLUSIONS: Intravenous hypertonic HES is comparable to intravenous mannitol 20% in lowering the intraocular pressure in healthy normotensive dogs. But this effect lasted half an hour longer after mannitol. In 6/7 eyes with primary glaucoma, hypertonic HES decreased IOP.     

Normal values and incidence of cardiorespiratory complications in dogs during general anaesthesia. A review of 1281 cases

This paper describes the cardiorespiratory variables and the incidence of anaesthetic complications in dogs. For this, a retrospective study of 1281 anaesthesias was performed. Heart rate (HR), non-invasive mean arterial (MAP), systolic (SP) and diastolic pressures (DP), invasive mean arterial (IMAP), systolic (ISP) and diastolic pressures (IDP), central venous pressure (CVP), respiratory rate (RR), tidal volume (V(T)), minute volume (V(M)), end-tidal CO(2) (EtCO(2)), arterial oxygen saturation (SpO(2)), temperature (T) and death are reported. Data were described both globally and separately for each ASA (American Society of Anaesthesiologists classification) status. An ANOVA and a Tukey's test were used for comparing the different ASA status' values (alpha=0.05). During anaesthetic maintenance, the mean +/- SD of the studied variables were: HR: 91+/-27 bpm. MAP: 86+/-24 mmHg. IMAP: 80+/-22 mmHg. SP: 114+/-25 mmHg. ISP: 109+/-26 mmHg. DP: 67+/-23 mmHg. IDP: 66+/-22 mmHg. CVP: 5+/-3 mmHg. RR: 19+/-11 rpm. V(T): 14+/-7 ml/kg. V(M): 191+/-93 ml/kg/min. EtCO(2): 40+/-8 mmHg. T: 37.1+/-1.7 degrees C. ASA III and ASA IV patients, compared with those with ASA I, showed higher values of HR, RR, V(T) and V(M) and lower in IMAP, CVP, EtCO(2), SpO(2) and T. The most frequent complications were bradycardia (36.3% of the patients), hypotension (37.9%), hypoventilation (63.4%), hypoxia (16.4%), hypothermia (4.8%) and death (0.9%). Cardiorespiratory complications frequently occur in dogs during general anaesthesia.