Objective To compare aqueous humor myocilin protein levels in dogs with the primary glaucomas to those with the secondary glaucomas, primary cataracts, and diabetic cataracts.Materials and methods Four groups were selected, based on diagnosis by the attending veterinary ophthalmologists and included: primary glaucoma (primary open-angle glaucoma (POAG) and primary closed angle glaucoma (PCAG); n = 155); secondary glaucoma (n = 94); primary (presumed inherited) cataract (n = 142), and diabetic cataract (n = 83). A total of 474 samples (187 males, 263 females, 24 unreported) with average ages of 117 months for the males and 101 months for the females were analyzed. Myocilin protein was measured using the Coomassie staining and Western blot methods relative to a myocilin control.Results Differences were seen between nonglaucomatous (cataractous) and glaucomatous dogs with myocilin levels in glaucomatous eyes being many times higher than those in the cataractous dogs. Primary glaucomatous dogs were found to have an aqueous humor myocilin protein level of 17.30 +/- 1.03 units. Secondary glaucomas had the highest level of myocilin in the aqueous humor with 19.27 +/- 1.41 units. Diabetic cataractous dogs had the lowest levels of myocilin reported with 6.60 +/- 0.88 (mean +/- SEM) units. Normal (cataractous) dogs had a myocilin level in the aqueous humor of 8.05 +/- 0.86 units.Conclusion Aqueous humor protein levels were elevated, relative to the myocilin control, in both the primary and secondary glaucoma groups compared to the cataract and diabetic cataract groups. Like in the Beagle POAG, aqueous humor myocilin protein levels are increased. Further studies are indicated to investigate the exact role of the aqueous humor myocilin protein in the genesis in increased IOP in these primary glaucomatous breeds.

OBJECTIVE The gene (myocilin: MYOC) has been attributed to be involved in over 6% of inherited types of human glaucoma, the highest correlation for any gene to date. This study determines myocilin protein levels in the aqueous humor (AH) of normal laboratory quality, genetic carrier (offspring of normal laboratory quality and POAG Beagles), and primary open angle glaucoma (POAG) Beagles. MATERIALS AND METHODS Eighteen dogs were used and classified as either normal, carrier or having mild, moderate or advanced POAG. A 0.1 mL sample of AH was drawn from the anterior chamber of each dog in the study and frozen on dry ice. A modified Coomassie stain and Western blot, using a polyclonal rabbit antihuman myocilin antibody (Santa Cruz Biotechnologies, Santa Cruz, CA), was run on each sample to compare the myocilin levels. A purified human trabecular meshwork excreted myocilin protein sample was used as a control (Alcon Research Laboratories, Fort Worth, TX) and its band/densitometry measurement was defined as one unit of myocilin for comparisons. RESULTS Comparisons of AH myocilin levels differed among normal laboratory quality, genetic carrier, and POAG Beagles at different stages of the disease. In the normal laboratory, Beagles the AH myocilin measured 0.817 +/- 0.075 units (mean +/- SEM); in the carrier Beagles the AH myocilin was 3.117 +/- 0.290 units. As POAG progressed, myocilin protein levels also increased to 6.097 +/- 0.810, 8.844 +/- 1.079, and 17.228 +/- 1.198 units in the early, moderate, and advanced forms, respectively. Overall comparisons between normal, carrier and all POAG Beagles combined showed significant differences (P < 0.0010). Individual comparisons between normal and carrier eyes showed significant differences (P < 0.0193). Comparisons between normal and all POAG eyes also showed significant differences (P < 0.0426). CONCLUSION This study shows myocilin protein is present in normal Beagles, markedly increased in POAG Beagles, and mildly increased in genetic carrier Beagles. There is a strong correlation between amounts of AH myocilin protein and the presence and severity of POAG. The exact role of AH myocilin levels in the genesis of ocular hypertension remains unresolved, but myocilin may adversely affect AH outflow.

OBJECTIVEThe presence of myocilin was investigated in a colony of Beagles, a canine model for inherited primary open-angle glaucoma (POAG). The myocilin protein was localized in the normal and glaucomatous canine eyes by immunohistochemistry and immunocytochemistry.METHODSParaffin- and plastic-embedded specimens from the anterior uveas of 10 Beagles with inherited glaucoma (3 months to 13 years old) and 6 age-matched normal dogs were sectioned, and were then incubated with primary antibody, rabbit polyclonal antihuman MYOC IgG, overnight at 4 degrees C. Specimens were incubated with secondary antibody with one of the following: biotinylated link followed by peroxidase-labeled streptavidin and then by substrate-chromogen for light microscopy; fluorescent marker Texas red; or 18 nm colloidal gold-labeled goat antirabbit IgG for transmission electron microscopy.RESULTSWith normal, pre- and early glaucomatous canine specimens, cell membranes of smooth muscle cells of the iris and ciliary body stained positively, as well as most resident stromal and vascular endothelial cells. The cytoplasm of cells within the nonpigmented ciliary epithelium of the ciliary body processes stained intensely, being weaker along the pars plana. Trabecular meshwork (TM) cells and surrounding extracellular matrix labeled, as well as the sclera adjacent to the angular aqueous plexus. In specimens with moderate and advanced glaucoma, greater intensity of staining was observed within TM cells and adjacent sclera, and portions of the nonpigmented epithelium of the ciliary processes. Fibrinous material labeled intensely within the posterior chamber.CONCLUSIONSMyocilin in the normal and glaucomatous canine eye was successfully immunolocalized. These findings with regard to the normal eye are nearly identical to those previously reported in humans, and support the original hypothesis that there is an increase in both accumulation and localization of myocilin in glaucomatous canine eyes. It also supports the possibility that changes in the activity of myocilin within the aqueous humor outflow pathway of individuals with spontaneous glaucoma are associated with the rise of intraocular pressure and subsequent development of this disease, but may not be the primary event in the initial raise in intraocular pressure in POAG in the Beagle.

OBJECTIVETo evaluate effects of lacrimal punctal plugs positioned in either the upper, lower, or combination of upper and lower lacrimal canaliculi on plug retention and tolerance; tear production, as measured by the Schirmer tear test; and the dilution of fluorescein within the tear film in normal dogs.MATERIAL AND METHODSLacrimal punctal plugs were positioned in the lower, upper, or combination of lower and upper plugs in six laboratory-quality Beagles under topical anesthesia. Retention of plugs was evaluated daily from 8 to 23 days by visual inspection and slit-lamp biomicroscopy. Schirmer tear tests (STT 1 without topical anesthesia) were performed at 48-h intervals. Dilution of fluorescein was determined at 5- and 45-min post-fluorescein instillations once weekly.RESULTSLacrimal punctal plugs of 0.4 and 0.6 mm in diameter were retained for 14 (lower plugs: 100%) and 23 days (75%), and for the upper plugs at 8 days less often (75%), and were infrequently locally nonirritating. Combination of lower and upper plugs seemed to adversely affect retention of either plug. When loss of the plugs occurred, a next larger size plug was necessary suggesting some stretching of the lacrimal canaliculi occurred. Pre- and postplug placement STT results indicated no change with lower and combination lacrimal punctal plugs, but decreased levels following upper lacrimal punctal plugs. Tear fluorescein levels at 5 and 45 min in control eye (no punctum plugs) were 3.39% and 0.14%, respectively. With lower, upper, and the combination of lower and upper lacrimal puncta plugs, tear fluorescein levels at 45 min were higher than the controls (lower: 0.76%; upper: 0.45%, and combination 0.56%).CONCLUSIONLacrimal punctal silicone plugs are retained for 8-23 days in the lower, upper, and combined lower and upper canaliculi at high rates. Effects on STT levels appear limited. Fluorescein within the tear film persists longer with all different positioned lacrimal punctum plugs than in the control eyes.

Journal Article Myocilin Localization in the Canine Eye by Light, Confocal and Electron Microscopy Get access D A Samuelson, D A Samuelson University of Florida Search for other works by this author on: Oxford Academic Google Scholar H Tajwar, H Tajwar University of Florida Search for other works by this author on: Oxford Academic Google Scholar H Hart, H Hart University of Florida Search for other works by this author on: Oxford Academic Google Scholar P A Lewis, P A Lewis University of Florida Search for other works by this author on: Oxford Academic Google Scholar E O MacKay, E O MacKay University of Florida Search for other works by this author on: Oxford Academic Google Scholar K N Gelatt K N Gelatt University of Florida Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 11, Issue S02, 1 August 2005, Pages 992–993, https://doi.org/10.1017/S1431927605502174 Published: 01 August 2005

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.

Objective To determine the mode of inheritance of cataract formation in the Bichon Frise.Materials Thirty-six closely related Bichon Frise dogs in a pedigree of 61 dogs were examined using slit-lamp biomicroscopy and indirect ophthalmoscopy over a period of 10 years.Results Of the 61 related dogs, 36 were examined repeatedly. Twelve cataractous dogs were diagnosed (three males and nine females). Cataractous dogs resulted from matings between unaffected parents, and when one parent was cataractous and the other parent was unaffected. Age at onset of cataract formation ranged from 18 to 160 months. Available information suggests that the cataracts are inherited as an autosomal recessive trait.Conclusion Cataracts appear inherited in the Bichon Frise as an autosomal recessive trait. Additional cataract x cataract matings are necessary to confirm the autosomal recessive heredity.

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.

OBJECTIVETo 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 METHODSIn 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.RESULTSThe 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.CONCLUSIONBreed-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.

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.

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.

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.

OBJECTIVE:To measure changes in the ocular and orbital blood flow velocities by color Doppler imaging (CDI) in beagles with primary open angle glaucoma as the disease progressed from early to advanced stages.METHODS:CDI measurements were performed periodically on 13 glaucomatous Beagles during the nontreated mild, moderate and advanced stages of POAG over the course of 4 years. CDI was performed with the dogs lightly anesthetized (butorphanol 0.1 mg/kg IV, acepromazine maleate 0.02 mg/kg IV, and atropine sulfate 0.05 mg/kg) while the CD transducer was placed directly on the cornea anesthetized with 0.5% tetracaine hydrochloride. Intraocular pressure (IOP) by pneumatonography or TonoPen XL, heart rate and mean arterial blood pressure were measured at the beginning, middle and end of each study. The ophthalmic vessels examined included: external ophthalmic arteries and veins, long and short posterior ciliary arteries, anterior ciliary arteries and veins, primary retinal arteries, and vortex veins. Recordings of each vessel included peak systolic velocity (PSV), end diastolic velocity (EDV) and time averaged velocity (TAV), and when possible the resistive index (RI) and pulsatility index (PI) were computed.RESULTS:CDI abnormalities were present before intraocular pressure exceeded the normal range. As the animals aged, and the glaucoma progressed with higher levels of IOP, significant changes occurred in nearly all vessels, and generally included a major increase in RI (P < 0.001) and an increase in the PI (P < 0.001). Mean arterial blood pressure (105 +/- 18 mmHg) and heart rate (118 +/- 33/min) remained reasonably constant. The IOP gradually increased as the disease progressed (early and normotensive: 19.4 +/- 3.9 mmHg; moderate: 29.7 +/- 2 mmHg; and advanced: 44.5 +/- 6 mmHg). The ocular veins seemed most influenced early on in the disease. Late in the disease, ocular venous blood flow could not be consistently demonstrated. An increase in the PI of ocular veins occurred in the moderately and severely affected glaucomatous Beagles. As the IOP increased, there were trends of increasing resistive index and pulsatility index in most arteries, and periods of marked decreased velocities of the vortex and external ophthalmic veins in severe cases.CONCLUSION:CDI measurements in Beagles with primary open angle glaucoma during the course of 4 years indicate easily measurable and repeatable progressive blood flow abnormalities before the elevation of IOP and, thereafter, with gradually increased levels of IOP.

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.

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.

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.

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.

OBJECTIVE:To determine the distribution of intraocular pressure, as measured by applanation tonometry, in dogs with cataracts, and compare these tonometric results to the different stages of cataract formation (incipient, immature, mature, and hypermature). Animals studied Retrospection study of canine clinical patients (86 dogs).PROCEDURES:All records of dogs presented from 1991 to 1996 to the university veterinary medical teaching hospital for diagnosis of cataracts and evaluation for cataract surgery were reviewed. The tonometric measurements from the initial ophthalmic examination were selected in cataractous and nonglaucomatous eyes either receiving no topical or no systemic medications. The stage of cataracts was based on the degree of opacification, tapetal reflection, clinical vision, and visibility of the ocular fundus by indirect ophthalmoscopy. The distribution of tonometric results were grouped by the cataract maturity, and compared by anova and Tukey's general linear tests.RESULTS:Intraocular pressure with incipient cataracts ranged from 9 to 17 mmHg (mean 12.7 +/- 1.2 mmHg). Intraocular pressure with immature cataracts ranged from 3 to 27 mmHg (mean 13.6 +/- 0.6 mmHg). For the mature cataracts, IOP ranged from 5 to 22 mmHg (mean 11.9 +/- 0.7 mmHg). For the hypermature cataract group, IOP ranged from 4 to 23 mmHg (mean 10.8 +/- 0.6 mmHg). Comparison of the tonometric results among the different stages of cataract formation indicated a significant difference (P = 0.0086) between only the immature and hypermature groups.CONCLUSIONS:Intraocular pressure in lens-induced uveitis (LIU) is lowered but the relationship to the stage of cataract maturity is less clear. Significant tonometric differences were present between the immature and hypermature cataract groups, but these differences are too small to be clinically useful. Decreased intraocular pressure of dogs with all stages of cataract formation suggests concurrent LIU during all stages of cataract formation, especially with the mature and hypermature stages. The average tonometric measurements in dogs with these cataracts were about two standard deviations below the mean IOP reported in normal dogs.