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.

Drug delivery by contact lens in spontaneously glaucomatous dogs.

PURPOSE: The efficacy of ophthalmic drug delivery through contact lenses in animal model was explored to evaluate its potential for serving as an alternative to eye drops, which are inefficient vehicles for delivering ophthalmic drugs. METHODS: The efficacy of timolol delivered via contact lenses was compared to eye drops in beagle dogs that suffer from spontaneous glaucoma. Experiments were conducted with NIGHT & DAY™ silicone hydrogel contact lenses and NIGHT & DAY™ loaded with vitamin E, which was included in the lens to extend the release duration of the drug. Timolol was loaded into contact lenses by soaking in drug/phosphate buffered saline solution, and the drug-loaded lenses were subsequently inserted in one of the eyes, with the other eye serving as control. The lenses were replaced every 24 hours, and the pharmacodynamics of intraocular pressure (IOP) and pupil size were monitored in both eyes. RESULTS: The IOP reduction from baseline by NIGHT & DAY™ (5.02 ± 0.83 mmHg) was comparable with that by eye drops with similar drug dosing (4.64 ± 0.41 mmHg). In addition, lenses with one-third of the drug loading as eye drops resulted in the similar IOP reduction, suggesting higher bioavailability for contact lenses compared to eye drops. Inclusion of vitamin E into the lenses did not improve the IOP reduction. The IOP in the untreated eye also decreased from baseline for eye drops (3.17 ± 0.42 mmHg) but it remained relatively unchanged with treatments based on lenses, suggesting reduction in systemic absorption for delivery of drugs by contact lenses. CONCLUSIONS: Ophthalmic drug delivery through contact lenses increases bioavailability and reduces systemic drug uptake.

Dose response for travoprost® in the glaucomatous beagle.

OBJECTIVE: To evaluate the changes in intraocular pressure (IOP) and pupil size in 12 Beagles with inherited glaucoma after instillations of 0.033, 0.0033, 0.001, 0.00033, and 0.0001% travoprost (Travatan®-Alcon Laboratories, Inc., Ft Worth, TX, USA) in multiple single-dose studies. PROCEDURES: Intraocular pressure and pupil diameter (PD) measurements were obtained at 9 am, 12 pm, 3 pm, and 9 am the following day (24 h) in two groups of six glaucoma dogs. After 7 days, the vehicle or concentration was repeated in the contralateral eye of the same animals. RESULTS: Concentrations of 0.00033, 0.001, and 0.0033% travoprost significantly lowered IOP and PD, but the 0.0001% concentration provided limited IOP changes, although PD changes were still significant. This suggests travoprost is effective in the dog to lower IOP and reduce pupil size at concentrations starting between 0.0001 and 0.00033%. CONCLUSIONS: The dose response for travoprost in the glaucomatous Beagle indicates this model is highly sensitive to this group of drugs, even at concentrations as low as 0.00033% (1/12 the commercially available concentration).

Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma.

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide, with elevated intraocular pressure as an important risk factor. Increased resistance to outflow of aqueous humor through the trabecular meshwork causes elevated intraocular pressure, but the specific mechanisms are unknown. In this study, we used genome-wide SNP arrays to map the disease gene in a colony of Beagle dogs with inherited POAG to within a single 4 Mb locus on canine chromosome 20. The Beagle POAG locus is syntenic to a previously mapped human quantitative trait locus for intraocular pressure on human chromosome 19. Sequence capture and next-generation sequencing of the entire canine POAG locus revealed a total of 2,692 SNPs segregating with disease. Of the disease-segregating SNPs, 54 were within exons, 8 of which result in amino acid substitutions. The strongest candidate variant causes a glycine to arginine substitution in a highly conserved region of the metalloproteinase ADAMTS10. Western blotting revealed ADAMTS10 protein is preferentially expressed in the trabecular meshwork, supporting an effect of the variant specific to aqueous humor outflow. The Gly661Arg variant in ADAMTS10 found in the POAG Beagles suggests that altered processing of extracellular matrix and/or defects in microfibril structure or function may be involved in raising intraocular pressure, offering specific biochemical targets for future research and treatment strategies.

Ocular parameters in a captive colony of fruit bats.

OBJECTIVES: To establish normal reference ranges of ocular parameters including phenol read thread, palpebral fissure length, horizontal and vertical corneal diameter, upright and hanging intraocular pressure (IOP) and to report ophthalmic examination findings of the anterior segment and lens, in a population of captive fruit bats. ANIMALS STUDIED: Eyes of 30 bats of three species were included in this study: 10 (5 males, 5 females) Malayan Flying Foxes (Pteropus vampyrus), 10 (5 males, 5 females) Little Golden-mantled Flying Foxes (Pteropus pumilus), and 10 (4 males, 6 females) Island Flying Foxes (Pteropus hypomelanus). RESULTS: The most common ophthalmic examination findings included iris-iris persistent pupillary membranes (83%), nuclear sclerosis (56.7%), prominent arterial circle (40%), iridal hyperpigmented foci (30%), pupillary margin cysts (27%), and third eyelid defects (20%). The mean, among all species for: phenol red thread was 20.23 ± 1.28 mm/15 s both eyes (OU); palpebral fissure length was 13.34 ± 0.33 mm for OU; for horizontal corneal diameter was 10.72 ± 0.32 mm for OU; for vertical corneal diameter was 9.90 ± 0.30 mm for OU; for the hanging intraocular pressures was 19.38 ± 0.77 mmHg for OU; for upright IOP was 13.95 ± 0.60 mmHg for OU. Measurements for the individual species groups and eyes were also calculated. CONCLUSIONS: Results revealed the IOP of bats in a hanging position were significantly higher than the IOP of bats in an upright position. The size of the bat, between the species, affected palpebral fissure length, horizontal corneal diameter, and vertical corneal diameter. Information about the ocular structures and normal ophthalmic parameters for the Pteropus species is crucial for species protection because of dependence on vision for survival.

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.

Prevalence of primary breed-related cataracts in the dog in North America.

The objective of the study was to determine the prevalence of cataracts in dogs presented to veterinary medical teaching hospitals in North America between 1964 and 2003. A retrospective study of all dogs presented with cataracts to veterinary medical teaching hospitals in North America between 1964 and 2003 was conducted to determine cataract prevalence. The different decades, breeds, gender, and age at time of presentation with cataract were compared. The prevalence of dogs presented with cataract varied by decade and ranged from 0.95% (1964-73), 1.88% (1974-83), 2.42% (1994-2003), to 3.5% (1984-93). The total number of dogs presented with cataracts over the 40-year period was 39,229. From 1964 to 2003 the prevalence of cataract formation in this patient population increased by about 255%. Fifty-nine breeds of dogs were affected with cataracts above the baseline prevalence of 1.61% seen in mixed-breed/hybrid dogs. The breeds with the highest cataract prevalence included: Smooth Fox Terrier (11.70%), Havanese (11.57%), Bichon Frise (11.45%), Boston Terrier (11.11%), Miniature Poodle (10.79%), Silky Terrier (10.29%) and Toy Poodle (10.21%). The breeds with the largest number of cataractous dogs during the entire four decades were the Boston Terrier (11.11%), Miniature Poodle (10.79%), American Cocker Spaniel (8.77%), Standard Poodle (7.00%), and Miniature Schnauzer (4.98%). Gender ratios of cataractous dogs seemed to affect limited breeds. Age of presentation with cataract diagnosis varied among several breeds. In the mixed-breed/hybrid baseline population, cataract formation appeared to be age related with a higher frequency of cataract formation in dogs after 4-7 years. Cataract formation is one of the most prevalent eye diseases in the dog population, and in about 60 breeds of dogs the prevalence of cataract exceeds that of the baseline mixed-breed/hybrid group. The prevalence of cataract is also influenced by age in most purebred dogs and affects 16.80% of the 7-15+-year-old mixed-breed/hybrid dog population. Total and age-related cataract prevalence in dogs seems very similar to that in man.

Secondary glaucomas in the dog in North America.

OBJECTIVE: To determine the prevalence of secondary glaucomas in dogs associated with cataract formation, lens luxation or displacement, cataract surgery, uveitis, hyphema and intraocular neoplasia. METHODS: Information was obtained from the Veterinary Medical Data Base (VMDB) from all veterinary medical teaching hospitals in North America from March 1964 to March 2003. Secondary glaucomas were diagnosed at the same examination or after the primary diagnosis was made, and included those associated with cataract formation, lens luxation, cataract surgery, uveitis of unknown cause, hyphema of unknown cause, and intraocular neoplasia. The data were evaluated by decade, breed, gender and age of presentation. RESULTS: A total of 1 592 831 dogs were presented, and 9695 canine secondary glaucomas. Secondary glaucoma associated with cataract formation represented 81% of all the canine secondary glaucomas. Breeds (n = 7890 dogs) predisposed to secondary glaucoma and cataracts had an overall prevalence of 0.5%, but nearly 20% of all the cataractous dogs developed secondary glaucoma in at least one eye. For the years 1994-2003, these breeds included the American Cocker Spaniel; Boston Terrier; Toy, Miniature and Standard Poodle; English Springer Spaniel; Bichon Frise; and Labrador Retriever. The other forms of secondary glaucoma occurred less frequently, and included those glaucomas with lens luxation or displacement (779 dogs; 12.0%), postcataract surgery (528 dogs; 5.1%), with uveitis from unknown cause (399 dogs; 7.1%), with hyphema from unknown cause (117 dogs; 7.3%), and with intraocular neoplasia (19 dogs; 3.5%). The risk of the secondary glaucomas from 1984 to 2002 was highest after the intracapsular lens extraction (ICLE), less in the extracapsular technique (ECLE), and lowest for the phacoemulsification/phacofragmentation method. CONCLUSION: Prevalence of the canine secondary glaucomas ranges from 0.25% (1964-1973), 0.46% (1974-1983), 0.79% (1984-1993), to 0.80% (1994-2003) and are as frequent as the primary or breed-related glaucomas during these same time periods.

Prevalence of the breed-related glaucomas in pure-bred dogs in North America.

OBJECTIVE: To determine the prevalence of the breed-related glaucomas in pure-bred dogs presented to the veterinary medical teaching hospitals in North America that participate in the Veterinary Medical Data Base (VMDB). MATERIALS AND METHODS: In this retrospective study, age of first diagnosis, breed, and gender data for all breeds of dogs were collected from the VMDB with the clinical diagnosis of primary glaucoma (glaucoma-NOS) at 5-10 year intervals from 1964 to 2002. The prevalence for each breed (affected dogs compared to all dogs of each breed), any changes over the 38 years, and any gender differences for these glaucomas were determined. RESULTS: The prevalence of the primary breed-related glaucomas has gradually increased from 0.29% (1964-1973); 0.46% (1974-1983); 0.76% (1984-1993); to 0.89% (1994-2002). Breeds that consistently featured among the highest 10 for glaucoma prevalence from four different periods (1964 to 2002) included American Cocker Spaniel, Basset Hound, Wire Fox Terrier, and Boston Terrier. During the last observation period (1994-2002), 22 different breeds had 1% or higher prevalence of the glaucomas. The highest prevalence of glaucomas in 1994-2002 by breed included: American Cocker Spaniel (5.52%); Basset Hound (5.44%); Chow Chow (4.70%); Shar-Pei (4.40%); Boston Terrier (2.88%); Wire Fox Terrier (2.28%); Norwegian ElkHound (1.98%); Siberian Husky (1.88%); Cairn Terrier (1.82%); and Miniature Poodle (1.68%). A predominance of females with glaucoma occurred in the American Cocker Spaniel, Basset Hound, Cairn Terrier, Chow Chow, English Cocker Spaniel, Samoyed, and perhaps the Siberian Husky, and a predominance of males in the Australian Cattle dog and St Bernard. Age affected the time for first presentation of the glaucomas in the pure-bred dog. In the majority of breeds the glaucomas were presented for initial diagnosis in dogs between 4 and 10 years of age. CONCLUSION: Breed-related glaucomas in pure-bred dogs are frequently presented to the veterinary medical teaching hospitals in North America. The prevalence of the breed-related glaucomas in the dog appears similar to humans, and in some breeds exceeds that in humans. In many breeds the high prevalence of the glaucomas suggests a genetic basis.

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.

Effect of different dose schedules of 0.15% unoprostone isopropyl on intraocular pressure and pupil size in the glaucomatous beagle.

The changes in intraocular pressure (IOP) and pupil size (PS) after instillations of 0.15% unoprostone isopropyl (Rescula, Novartis Ophthalmics, Duluth, GA) were investigated in the spontaneous glaucoma Beagle model. From the first-day baseline IOP of 27.3+/-3.2 mmHg placebo eye and 32.8+/-5.1 mmHg control eye, the mean+/-standard error of the mean (SEM) diurnal changes after 0.15% unoprostone, at 8 AM once-daily for the next 4 days, were 15.5+/-1.3 mmHg, 14.7+/-1.9 mmHg, 16.1+/-1.1 mmHg, and 17.0+/-1.5 mmHg, respectively, and were significantly different from the control eye. After 0.15% unoprostone was instilled at 8 PM, the mean+/-SEM baseline changes from the baseline IOP (insert drug eye 9 AM) in the drug eyes were 5.9+/-2.5 mmHg, 5.2+/-4.1 mmHg, 9.7+/-2.5 mmHg, and 3.6+/-3.6 mmHg, respectively. When 0.15% unoprostone was instilled twice-daily, the mean+/-SEM baseline IOP (insert drug eye 9 AM) changes were 13.6+/-0.7 mmHg, 13.9+/-1.4 mmHg, 11.3+/-1.0 mmHg, and 9.3+/-1.4 mmHg, respectively, and were significantly different from the control eyes. Miosis occurred within 2 hours and lasted several hours. Unoprostone isopropyl instilled once-daily (AM or PM), as well as twice-daily, produces significant decreases in IOP and PS in the glaucomatous Beagle.

Cataracts in the Bichon Frise.

PURPOSE: To determine the clinical characteristics of possible inherited cataract in the Bichon Frise breed. These characteristics include the relative frequency, gender effects, site of first cataract formation, age of onset, relationship of age to cataract maturity, and other concurrent pre- and postoperative ophthalmic diseases. METHODS: Four different populations of Bichon Frise were examined. They included: (1) referred patients of the University of Florida (VMTH; 1990-2000); (2) patients from other universities and large institutions (VMDB; 1970-2000); (3) patients from the Canine Eye Registry Foundation (CERF; 1970-2000); and (4) special patients recruited from eye clinics and ACVO specialty practices (1995-2001). Blood samples were obtained from many patients for future DNA analyzes. Statistical comparisons between groups were by general linear and anova analyzes, and P < 0.05 was considered significant. RESULTS: The four populations of cataractous and total Bichon Frise dogs included: (1) UF-VMTH: 57 cataractous dogs; (2) VMDB: 406 dogs (28%) with cataracts; total dogs--1407; (3) CERF: 505 cataractous dogs (6%); total dogs--8222; and (4) ACVO: 223 cataractous dogs (57%); total dogs--391. In each population group, gender did not affect cataract distribution. Dogs between 2 and 8 years of age were most frequently affected, and initial cataract involvement affected equally the anterior and posterior cortices. Immature cataracts occurred more often in younger dogs, and hypermature cataracts were more frequently diagnosed in older dogs. Dogs with early cataracts were encountered more frequently in the CERF population. Pre- and postoperative retinal detachments (RD) were not infrequently diagnosed in the UF-VMTH and VMDB groups. RD in the UF-VMTH and VMDB groups occurred in 33% and 13% of the patients, respectively. CONCLUSIONS: Cataracts were first encountered in CERF and VMDB data between 1975 and 1979 and have increased since this time. As expected, both similarities and differences between the four different populations of Bichon Frise were encountered. Both sexes of dogs are equally affected. The anterior and posterior cortical areas of the lens were first involved and dogs 2-8 years of age are most frequently affected. Cataracts affected younger dogs in the CERF group and older cataractous dogs in the other populations. Cataract formation appears to be inherited in the Bichon Frise dog. The frequency of pre- and postoperative retinal detachments present higher risks for cataract surgery in this breed.

Effect of single and multiple doses of 0.2% brimonidine tartrate in the glaucomatous Beagle.

The objective of this study was to evaluate the changes in intraocular pressure (IOP) in glaucomatous dogs after instillations of 0.2% brimonidine once, twice and three times daily in single day studies, and after twice and three times daily for 4 days in multiple dose studies. We studied eight Beagles with inherited primary open angle glaucoma. Applanation tonometry (IOP), pupil size (PS) and heart rate (HR) measurements were obtained at 8 am, 10 am, 1 pm, 3 pm and 5 pm. The studies were divided into: eight glaucoma dogs and five of the eight dogs that demonstrated greater response to 0.2% brimonidine. Single-dose drug studies are divided into placebo (0.5% methylcellulose), 0.2% brimonidine administered once daily (8 am); twice daily (8 am and noon); and three times daily (8 am, noon and 5 pm). The 5-day multiple-dose studies included: day 1, no drug; and 4 days, 0.2% brimonidine instillations either twice daily (8 am and 2 pm) or three times daily (8 am, 2 pm and 9 pm). Statistical comparisons between drug groups included control (nondrug) and treated (placebo/0.2% brimonidine) eyes for both single- and multiple-dose studies. The mean +/- SEM diurnal decrease in IOP in the eight glaucomatous Beagles for the control and placebo eyes were 3.4 +/- 4.7 and 5.4 +/- 2.8 mmHg, respectively. The mean +/- SEM diurnal decrease in IOP after 0.2% brimonidine once, twice and three times daily was 6.4 +/- 3.5, 8.0 +/- 6.1 and 9.8 +/- 8.1 mmHg, respectively; this trend was not significant statistically. Significant miosis occurred starting 2 h postinstillations, and the resultant mean +/- SD pupil size was 2.7 +/- 0.3 mm. A significant decrease in heart rate also occurred (12%). In the five most responsive dogs the changes in PS and HR during these studies were similar to the larger group, but significant decreases in IOP occurred at most measurement times. In the multiple-dose study with 0.2% brimonidine twice daily the mean +/- SEM decrease in IOP for day 1 to day 4 was 5.0 +/- 1.3, 5.7 +/- 1.3, 1.4 +/- 3.3 and 4.9 +/- 1.3 mmHg, respectively. When 0.2% brimonidine was instilled three times daily the mean +/- SEM diurnal IOP decrease was from day 1 to day 4 and was 0.75 +/- 1.3, 2.4 +/- 1.5, 1.2 +/- 2.7 and 1.4 +/- 1.8 mmHg, respectively. The mean change in pupil diameter was 1.3 +/- 0.5 mm. Decrease in HR averaged 22%. In the same single-dose studies with the five most responsive dogs, PS and HR were similar, but the decreases in IOP were significant at more measurement intervals. We conclude that 0.2% brimonidine produces a decrease in IOP in dogs, a statistically significant miosis, and a reduced heart rate (12-22%). However, because of the limited drug-induced ocular hypotension, brimonidine should be combined with other drugs when used for the glaucomas in the dog.

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

The changes in intraocular pressure and pupil size in glaucomatous dogs were evaluated after instillations of 0.03% bimatoprost (Lumigan, Allergan, Irvine, CA USA) once in the morning, or once in the evening, or twice daily in five day multiple dose studies. Applanation tonometry (IOP) and pupil size (PS) measurements were obtained at 8 am, 10 am, 12 noon, 2 pm, and 4 pm in 8 glaucoma dogs. Methylcellulose (0.5% as placebo) was instilled in the control eye, and 0.03% bimatoprost was instilled in the opposite drug eye. Methylcellulose (0.5%) and 0.03% bimatoprost 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). The mean +/- SEM diurnal changes in IOP from baseline values after 0.03% bimatoprost at 8 am once daily for the next four days were 25.0 +/- 3.2 mm Hg, 25.6 +/- 2.9 mm Hg, 25.5 +/- 3.0 mm Hg, and 26.0 +/- 3.2 mm Hg respectively, and were significantly different from the control eye. After bimatoprost was instilled at 8 pm, the mean +/- SEM changes in IOP from baseline values in the drug eyes were 27.3 +/- 2.4 mm Hg, 26.6 +/- 2.2 mm Hg, 27.2 +/- 2.5 mm Hg, and 27.3 +/- 2.6 mm Hg respectively. When 0.03% bimatoprost was instilled twice daily, the mean +/- SEM changes in IOP from baseline values were 39.1 +/- 2.3 mm Hg, 39.9 +/- 2.2 mm Hg, 39.9 +/- 2.3 mm Hg, and 39.6 +/- 2.1 mm Hg respectively, and were significantly different from the control eyes. Miosis of varying duration was frequent during the three studies. Bimatoprost instilled once daily (am or pm) as well as twice daily produces significant decreases in IOP and PS in the glaucomatous Beagle.