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.     

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.     

The effects of moxifloxacin ophthalmic solution 0.5% or gatifloxacin ophthalmic solution 0.3% treatment on corneal wound healing in pigmented rabbits following anterior keratectomy

Purpose These studies examined corneal healing rates, Type‐IV collagen and zonula occludens membrane‐associated protein (ZO‐1) expression, as well as aqueous PGE₂ and IL‐1β concentrations in pigmented rabbits treated with either moxifloxacin 0.5%, gatifloxacin 0.3% or BSS^® following anterior keratectomy. Methods Anterior keratectomy surgery was followed by topical administration with commercial ophthalmic formulations of either moxifloxacin or gatifloxacin or BSS^® (TID for 96 h). Images of the fluorescein‐stained healing corneas were analyzed for wound area. At 48 or 96 h following surgery, aqueous humor samples were collected and analyzed for the inflammatory mediators PGE₂ and IL‐1β using an ELISA. The corneas were subsequently evaluated using both scanning and transmission electron microscopy. In a second parallel study, corneas were evaluated at both 48 and 96 h for Type‐IV collagen and ZO‐1 expression using immunohistochemistry. Results Fluorescein‐stained corneal images at 96 h postsurgery demonstrated that 90% ± 8% re‐epithelialization for moxifloxacin, 81% ± 14% for gatifloxacin, and 88 ± 6% for BSS^® (P > 0.05). PGE₂ levels in the aqueous humor of fluoroquinolone treated eyes were reduced at 48 h compared to BSS^® treated eyes. IL‐1β was undetectable in all samples. No differences in Type‐IV collagen or ZO‐1 expression were observed between any treatment groups. There were no differences between groups in histological appearance or in ultrastructural healing processes. Conclusions These studies demonstrated that the commercial ophthalmic formulations of moxifloxacin and gatifloxacin were similar to each other in their effects on the levels of aqueous humor PGE₂ and rates of corneal wound re‐epithelialization.     

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

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

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

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

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.     

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

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

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 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.     

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration

Bayesian population pharmacokinetic models of florfenicol in healthy pigs were developed based on retrospective data in pigs either via intravenous (i.v.) or intramuscular (i.m.) administration. Following i.v. administration, the disposition of florfenicol was best described by a two‐compartment open model with the typical values of half‐life at α phase (t _1/2α), half‐life at β phase (t _1/2β), total body clearance (Cl), and volume of distribution (V _d) were 0.132 ± 0.0289, 2.78 ± 0.166 hr, 0.215 ± 0.0102, and 0.841 ± 0.0289 L kg^?1, respectively. The disposition of florfenicol after i.m. administration was best described by a one‐compartment open model. The typical values of maximum concentration of drug in serum (C _max), elimination half‐life (t _1/2Kel), Cl, and Volume (V ) were 5.52 ± 0.605 μg/ml, 9.96 ± 1.12 hr, 0.228 ± 0.0154 L hr^?1 kg^?1, and 3.28 ± 0.402 L/kg, respectively. The between‐subject variabilities of all the parameters after i.m. administration were between 25.1%–92.1%. Florfenicol was well absorbed (94.1%) after i.m. administration. According to Monte Carlo simulation, 8.5 and 6 mg/kg were adequate to exert 90% bactericidal effect against Actinobacillus pleuropneumoniae after i.v. and i.m. administration.     

The effect of low dose rocuronium bromide on eyeball position, muscle relaxation, and ventilation in dogs

A central eyeball position is often required during sedation or anaesthesia to facilitate examination of the eye. However, use of neuromuscular blockade to produce a central eye position may result in depressed ventilation. This study evaluated the eyeball position, muscle relaxation and changes in ventilation during general anaesthesia after the IV administration of 0.1 mg kg^?1 rocuronium. With client consent, 12 dogs of different breeds, body mass 27.2 ± 11.8 kg, aged 5.6 ± 2.8 years (mean ± SD) were anaesthetized for ocular examination. Pre‐anaesthetic medication was 0.01 mg kg^?1 medetomidine and 0.2 mg kg^?1 butorphanol IV. Anaesthesia was induced with propofol to effect and maintained with 10 mg kg^?1 hour^?1 propofol by infusion. The dogs were placed in left lateral recumbency, their trachea intubated and connected to a circle breathing system (Fi O₂ = 1.0). All dogs breathed spontaneously. The superficial peroneal nerve of the right hind leg was stimulated every 15 seconds with a train‐of‐four (TOF) stimulation pattern and neuromuscular function was assessed with an acceleromyograph (TOF‐Guard). Adequacy of ventilation was measured with the Ventrak 1550. After 10 minutes of anaesthesia to allow stabilisation of baseline values, 0.1 mg kg^?1 rocuronium was administered IV. Minute volume (Vm ), tidal volume (Vt ), respiratory rate (RR), Pe ′CO₂ and maximal depression of T1 and TOF ratio were measured. Data were analysed using a paired t‐test. The changes in the eyeball position were recorded. A total of 100 ± 33 seconds after the injection of rocuronium, T1 was maximally depressed to 62 ± 21% and the TOF ratio to 42 ± 18% of baseline values. Both variables returned to baseline after 366 ± 132 seconds (T1) and 478 ± 111 seconds (TOF). There was no significant reduction in Vm (2.32 ± 1.1 L minute^?1), Vt (124.1 ± 69.3 mL) and RR (10 ± 3.8 breaths minute^?1) and no increase in Pe ′CO₂ (6.5 ± 2.1 kPa (48.8 ± 16.1 mm Hg)) throughout the procedure. The eyeball rotated to a central position 35 ± 7 seconds after rocuronium IV and remained there for a minimum of 20 ± 7 minutes in all dogs. We conclude that rocuronium at a dose of 0.1 mg kg^?1 can be administered to dogs IV with minimal changes in ventilatory variables. The eyeball is fixed in a central position for at least 20 minutes, which greatly facilitates clinical examination.     

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 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.     

A comparison between the effect of topical tafluprost and latanoprost on intraocular pressure in healthy male guinea pigs

This study was aimed to evaluate the effect of 0.0015% preservative-free tafluprost (Zioptan®) and 0.005% preservative containing latanoprost ophthalmic solutions (Lataprost®) on intraocular pressure (IOP) in healthy male guinea pigs (Cavia porcellus). A total of 16 male guinea pigs were randomly assigned to receive one drop of tafluprost or one drop of latanoprost in the right eye. The contralateral eye served as control. IOP was measured using a rebound tonometer at time 0(baseline), after 30 minutes and every 60 minutes for the next three hours and then every three hours for the next 21 hours. Administration of tafluprost and latanoprost was not associated with changes in IOP in the treated eyes. The maximum IOP-lowering effect of the ophthalmic solutions was observed 30 minutes post-instillation in the treated eyes (-1.25 ± 1.50 mmHg, P-value = 0.194 in group A and -1.50 ± 1.29 mmHg, P-value = 0.103 in group B) and returned to normal after 9 and 12 hours in group A and B, respectively. There was no significant difference between the IOP measurements of the right and left eyes in neither groups during the study (repeated measure test and Generalized Linear Mixed Model). The administration of one drop of tafluprost and latanoprost had no significant effect on the IOP of healthy guinea pigs. Further studies are needed in guinea pigs affected by glaucoma to explore the effectiveness of these drugs.     

Effect of topical tropicamide on tear production as measured by Schirmer's tear test in normal dogs and cats

Objective To evaluate the effect of a single dose of topical 1% tropicamide on tear production as measured by the Schirmer tear test (STT) in the normal dog and cat. Material and methods Twenty‐eight dogs and 32 cats received 50 µl : l of 1% tropicamide in one eye and the opposite eye served as the control. STTs were performed immediately before instillation of tropicamide and then at 1, 4, 8 and 24 h post drug instillation. STT results were compared between the control and treated eyes at the different times. Results Aqueous tear production in dogs, measured by STT, was not significantly reduced. The mean ± SEM STTs for the baseline time for control and tropicamide‐treated eyes were 19.9 ± 0.8 and 20.3 ± 0.8 mm wetting/min, respectively. For the control eyes, the subsequent mean ± SEM STT levels were 20.3 ± 0.9 (1 h), 21.1 ± 0.8 (4 h), 20.1 ± 0.9 (8 h), and 18.7 ± 0.7 (24 h). For the tropicamide‐treated eyes, the subsequent mean ± SEM STT levels were 19.4 ± 0.9 (1 h), 19.3 ± 0.9 (4 h), 20.0 ± 0.9 (8 h), and 18.4 ± 0.8 (24 h). Aqueous tear production of both eyes was significantly reduced in cats at 1 h but returned to baseline by 4 h post tropicamide instillation. The mean ± SEM STT levels for the baseline time in cats for control and tropicamide‐treated eyes were 14.9 ± 0.8 and 14.7 ± 0.8 mm wetting/min, respectively. Subsequent mean ± SEM STT levels for the control eyes were 6.4 ± 1.1 (1 h), 11.9 ± 1.0 (4 h), 13.9 ± 0.8 (8 h), and 16.4 ± 1.0 (24 h). For the tropicamide‐treated eyes, the subsequent mean ± SEM STT levels were 5.3 ± 0.8 (1 h), 10.2 ± 0.8 (4 h), 14.7 ± 1.0 (8 h), and 16.6 ± 1.0 (24 h). Conclusion Single dose 1% tropicamide does not significantly lower tear production rates, as measured by the STT, in normal dogs. However, in normal cats single doses of 1% tropicamide in one eye cause significant reductions in tear production of both eyes at 1 h that recovered to baseline levels by 4 h.     

Cardiovascular effects of topical ophthalmic 10% phenylephrine in dogs

Objective To evaluate the effect of topical ophthalmic 10% phenylephrine on systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), pulse rate (PR) and electrocardiogram (ECG) in dogs. Animals studied Nine clinically normal dogs. Procedure Arterial catheters were placed in the dorsal pedal artery of awake dogs and ECG leads were attached. After a 15‐min acclimatization period, baseline PR, SAP, DAP and MAP were recorded every 5 min for 20 min. Two treatment groups (eight dogs each) were studied. Group I: one drop of phenylephrine was placed in each eye once. Group II: one drop of phenylephrine was placed in each eye three times at 5‐min intervals. Following treatment, PR, SAP, DAP and MAP were recorded every 5 min for 90 min. The mixed procedure of the SAS system was used to perform a repeated measures analysis of variance to test for linear and quadratic trends across time. Results Group I: There was a significant quadratic decrease in PR across time (P = 0.0051). Systolic arterial pressure increased linearly with time (P = 0.0002), MAP increased linearly with time (P = 0.0131), and DAP increased linearly with time (P = 0.0001). Group II: There was a significant quadratic decrease in PR across time (P = 0.0023). There was a significant quadratic increase in SAP (P = 0.0324), MAP (P = 0.0103) and DAP (P = 0.0131) across time. Conclusions Topical ophthalmic application of 10% phenylephrine in normal dogs results in elevation of arterial blood pressure and reflex bradycardia.     

The pharmacokinetics of midazolam after intravenous,intramuscular, and rectal administration in healthy dogs

Intravenous benzodiazepines are utilized as first‐line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3‐way crossover design with a 3‐day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high‐pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 μg/mL (C₀) and 0.20 ± 0.06 μg/mL (C_max), following IV and IM administration, respectively. Time to peak concentration (T_max) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.     

Time-specific intraocular pressure curves in Rhesus macaques (Macaca mulatta) with laser-induced ocular hypertension

Objective To detect and categorize time‐specific variations in daytime intraocular pressure (IOP) found in Rhesus monkeys with laser‐induced ocular hypertension. Procedures Ten male monkeys with argon laser‐induced ocular hypertension in one eye were anesthetized with ketamine hydrochloride, and the IOP measured in both eyes at 7 a.m., 7.30 a.m., and then hourly until 1 p.m. with a Tonopen? XL applanation tonometer. Intraocular pressure time profiles for both eyes in each animal were developed. The means ± SD of the IOPs for both eyes were calculated for the whole 6‐h study period, and the values compared statistically. The difference between the lasered eye mean IOP standard deviation and the normal eye mean IOP standard deviation for each animal during the 6‐h follow‐up was also calculated and compared. Results Mean IOP (± SD) in the glaucoma and normal eyes for the 10 animals during the 6‐h study was 32.6 ± 2.5 and 14.9 ± 2.5 mmHg, respectively. The IOP was significantly higher in the experimental eye than in the normal eye (P = 0.0008). The mean IOP in the lasered eye did not significantly change during the study period, whereas a slight but significant increase in IOP of the normal eye over the study period was recorded (P = 0.003). The variance in IOP in the hypertensive eyes was considerably greater than that in the untreated control eyes. From 7 a.m. to 1 p.m. the IOP declined in five eyes and increased in the other five eyes with laser‐induced ocular hypertension. Conclusions The time‐specific IOP variation pattern in the daytime in the laser treated eyes is significantly greater than the variation in the normotensive eyes. This shows that in order to detect statistical differences between IOP variations induced by an IOP‐reducing drug, and the exaggerated spontaneous IOP variations present in the laser‐induced hypertensive eye, sufficient animals should be included in any study. Understanding the time‐specific IOP variation present in a group of monkeys with laser‐induced ocular hypertension is essential prior to using the model for the evaluation of IOP‐reducing drugs.     

The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs

Objective To assess the effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase (AChE) levels in normal dogs. Animals Nine adult mixed breed dogs weighing between 18 and 27 kg. Procedures Fifty µL of 0.25% demecarium bromide were applied to one eye of each dog every 8 h for 6 days. Blood was analyzed for AChE levels prior to commencement of eye drops, and at 45 min, 1 h 45 min, 4 h 45 min, 1 day, 3 days, and 7 days following commencement of eye drops using a 5,5′‐dithiobis‐(2‐nitrobenzoic acid) (DTNB) reaction. Results Acetylcholinesterase levels declined over the first 24 h following commencement of demecarium administration in most dogs. This decline was highly variable and was statistically significant by 24 h. In some individuals AChE levels were suppressed to levels approaching clinical toxicity. By day 3 AChE levels had risen to levels above baseline in most dogs. Conclusions Topical ocular application of demecarium causes transient suppression of systemic acetylcholinesterase levels in most dogs. Acetylcholinesterase levels generally do not fall to toxic levels, but may do so in certain individuals. Demecarium bromide eye drops generally do not cause AChE toxicity, but dogs receiving such therapy should be monitored for signs of AChE toxicity, and concomitant use of other AChE inhibitors should be avoided.     

Ophthalmic examination findings in a colony of Screech owls (Megascops asio)

Objective To report ophthalmic findings in the Screech owl (Megascops asio). Sample population Twenty‐three, apparently healthy adult captive Screech owls in Maryland. Procedures OU of all owls underwent complete ophthalmic examination. One randomly assigned eye of each bird was measured by phenol red thread tear test (PRT), and the other eye by Schirmer tear test (STT). TonoVet^® rebound tonometry and TonoPen‐XL^® applanation tonometry were performed in each eye to measure IOP. Conjunctival swabs were cultured from one eye of 10 birds, corneal diameter was measured in OU of eight birds, and streak retinoscopy was performed on OU of seven birds. Ten birds were anesthetized, and A‐scan ultrasonography using a 15‐MHz probe was performed to obtain axial intraocular measurements. Results Ophthalmic abnormalities were noted in 24/46 (52%) of eyes. Median STT result was ≤ 2 mm/min, ranging ≤ 2–6 mm/min, and mean ± SD PRT was 15 ± 4.3 mm/15 s. Mean ± SD IOP were 9 ± 1.8 mmHg TonoVet^®‐P, 14 ± 2.4 mmHg TonoVet^®‐D, and 11 ± 1.9 mmHg TonoPen‐XL^®. Coagulase negative staphylococcal organisms were cultured from all conjunctival swabs. Mean ± SD corneal dimensions were 14.5 ± 0.5 mm vertically and 15.25 ± 0.5 mm horizontally. All refracted birds were within one diopter of emmetropia. Mean ± SD axial distance from the cornea to the anterior lens capsule was 4.03 ± 0.3 mm, from cornea to the posterior lens capsule was 10.8 ± 0.5 mm, and from cornea to sclera was 20.33 ± 0.6 mm. Conclusions This study reports ophthalmic examination findings in Screech owls, and provide means and ranges for various ocular measurements. This is the first report of rebound tonometry and PRT in owls.