Myocilin protein levels in the aqueous humor of the glaucomas in selected canine breeds.

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.

Aqueous humor myocilin protein levels in normal, genetic carriers, and glaucoma Beagles.

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.

Immunolocalization of myocilin protein in the anterior eye of normal and primary open-angle glaucomatous dogs.

OBJECTIVE: The 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. METHODS: Paraffin- 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. RESULTS: With 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. CONCLUSIONS: Myocilin 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.

Effect of lacrimal punctal occlusion on tear production and tear fluorescein dilution in normal dogs.

OBJECTIVE: To 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 METHODS: Lacrimal 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. RESULTS: Lacrimal 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%). CONCLUSION: Lacrimal 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.

Inheritance of cataract in the Bichon Frise.

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.

Progressive changes in ophthalmic blood velocities in Beagles with primary open angle glaucoma.

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.

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 relationship of cataract maturity to intraocular pressure in dogs.

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.

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.

Evaluation of tear film proteinases in horses with ulcerative keratitis.

Ulcerative keratitis is a common and potentially blinding ocular disease of horses, capable of progressing to corneal perforation in as little as 24 h. This rapid stromal degeneration is mediated in part by exogenous and endogenous proteinases. We measured and compared the concentrations of two matrix metalloproteinases (MMP-2 and MMP-9) and a serine proteinase (neutrophil elastase) present in the precorneal tear film of normal horses and horses with rapidly progressing ulcerative keratitis. Precorneal tear film samples were collected from 23 ulcerated and 21 unaffected eyes of 23 horses with unilateral ulcerative keratitis, and from 33 normal eyes of 17 control horses. MMP-2, MMP-9, and neutrophil elastase were identified by casein and gelatin zymography and quantified by computerized image analysis. Median MMP-9 levels were significantly higher in the precorneal tear film of young control horses vs. older control horses (P = 0.005). Median MMP-2, MMP-9, and neutrophil elastase levels were significantly higher in the precorneal tear film of ulcerated eyes when compared to age-matched normal controls (P = 0.004, P = 0.001, and P = 0.012, respectively). Median MMP-2 levels were also significantly higher in the precorneal tear film of contralateral eyes of affected horses when compared to age-matched normal controls (P = 0.004). No significant differences in median proteinase levels were detected between 'sterile' ulcers and those from which bacteria or mixed infections (bacteria and fungi) were isolated. However, median MMP-2 and neutrophil elastase levels were significantly higher in the precorneal tear film of eyes with 'sterile' ulcers when compared with ulcerated eyes from which fungi were isolated (P < 0.05). The results of this study support the use of topical antiproteinase therapy which targets both MMPs and serine proteinases in progressive equine ulcerative keratitis.

Comparative Doppler imaging of the ophthalmic vasculature in normal Beagles and Beagles with inherited primary open-angle glaucoma.

The objective of this study was to compare orbital and ocular vasculature velocity, measured by Doppler imaging, in normal Beagles and Beagles with inherited primary open-angle glaucoma. Eight normal Beagles and 13 Beagles with different stages of primary open-angle glaucoma were evaluated twice with a 2-4-week period between measurements. Doppler imaging was performed with the dogs anesthetized, and the Doppler transducer applied directly on the corneal surface. The majority of the orbital vasculature (external ethmoidal artery; internal ophthalmic artery and vein; and external ophthalmic artery and vein) and ocular blood vessels (anterior ciliary artery and veins; long posterior ciliary arteries; short posterior ciliary arteries; primary retinal arteries; and the vortex veins) were identified and Doppler blood velocity parameters were determined. The glaucomatous dogs demonstrated significant differences in the Doppler velocity parameters of several orbital vessels (external ethmoidal, external ophthalmic, and internal ophthalmic arteries), and several ocular vessels (anterior ciliary, short posterior ciliary, and long posterior ciliary arteries). These differences included decreased blood velocities, and increased pulsatility and resistive indexes. The Doppler blood flow velocities of the primary retinal arteries were unchanged between the normal and glaucomatous dogs. In the glaucomatous dogs, the Doppler imaging suggests increased vascular resistance downstream in both the orbital and ocular vasculature. These blood velocity parameter changes may be primary or secondary, and may offer therapeutic opportunities to increase perfusion, prolong the retina and optic nerve head function, and maintain vision in the canine glaucomas.

Photoreceptor density of the domestic pig retina.

The spatial distribution and densities of photoreceptors in seven whole-mounted porcine retinas were studied and maps illustrating photoreceptor topography were constructed. Total photoreceptor densities ranged from to 83 000 to 200 000 cells/mm2, with a mean of 138 500 cells/mm2. Cone densities ranged from 39 000 (area centralis) to 8500 cones/mm2 (peripherally), with a mean of 16 400 cones/mm2. Rod:cone ratios ranged from 3:1 centrally to 16:1 peripherally, with a mean ratio of 8:1. Averaged photoreceptor densities are greatest (166 000 cells/mm2) within the central inferior retina, and regional differences in rod:cone ratios were found. Cone densities are increased in a broad region dorsal to the optic disk, extending both nasally and temporally. This region is believed to represent the area centralis. Cone densities gradually decrease and taper towards the periphery and inferior retina as rod:cone ratios increase. In addition to the many anatomic and ultrastructural similarities to the human eye, this study illustrates similarities within the photoreceptor mosaic of these two species and supports the use of the pig retina as a model for human/animal research.

The ocular hypertensive effects of topical 0.1% dexamethasone in beagles with inherited glaucoma.

Topical 0.1% dexamethasone(50 microl) instilled QID in glaucomatous Beagles increased intraocular pressure (IOP) by about 5 mm Hg within the first seven to ten days in a four week test. The elevated levels of IOP persisted until drug instillations ceased. Both drug eye and placebo eye IOP levels were increased significantly over the predrug (control) IOPs. Comparisons of the IOP changes associated with topical dexamethasone in beagles bred for glaucoma and less than seven months of age to older glaucomatous Beagles did not detect any significant differences. The magnitude of elevation in IOP in both age groups was about 4.8 mmHg. During the week after cessation of the topical dexamethasone instillations, IOPs of both the drug and placebo eyes declined toward predrug levels. Primary open angle glaucoma in the Beagle exhibits a significant and rapid elevation in IOP following unilateral or bilateral 0.1% dexamethasone instilled QID.

Distribution of intraocular pressure in dogs.

Intraocular pressure (IOP) was measured by four different applanation tonometers in normal dogs. By MacKay-Marg tonometry in 391 dogs (772 eyes) the mean +/- SD IOP was 18.8 +/- 5.5 mmHg (range 8-52 mmHg). Using Tono-Pen XL tonometry in 421 dogs (823 eyes) the mean IOP was 19.2 +/- 5.9 mmHg, and the range was 4.42 mmHg. With MMAC-II tonometry in 80 dogs (158 eyes), the mean IOP was 15.7 +/- 2.8 mmHg with a range of 10-30 mmHg. By pneumatonograph tonometry in 135 dogs (255 eyes), the mean IOP was 22.9 +/- 6.1 mmHg and the range was 10-47 mmHg. In this study 53 breeds were represented. Of those breeds with six animals or more, no significant differences were detected in IOP between breeds (P > 0.353) or sex (P > 0.270). There was a significant decline of 2-4 mmHg (P > 0.0001) in IOP as age increased from less than 2 years to greater than 6 years of age. This trend was present with all of the four tonometers. There were no significant differences between the MacKay-Marg and TonoPen-XL tonometers (P > 0.198), but significant differences with the MMAC-II (P > 0.001) and pneumatonograph (P > 0.001) tonometers existed compared to the first two instruments. Based on this study and the literature, the mean IOP for the normal dog is 19.0 mmHg with a range of 11 (5%) and 29 (95%) mmHg.

Intraocular pressure in normal dairy cattle.

Intraocular pressure (IOP) was measured in normal dairy cows by applanation tonometry. In the first study of 15 Holstein and 17 Jersey cows the mean IOP by Mackay-Marg tonometry was 27.5 +/- 4.8 mmHg (range 16-39 mmHg); no significant differences (P < 0.92) were observed between the Holstein and Jersey breeds. In the second study of 15 Holstein and 12 Jersey cows, the mean IOPs by Mackay-Marg and TonoPen-XL tonometry were 28.2 +/- 4.6 mmHg (range 19-39 mmHg) and 26.9 +/- 6.7 mmHg (range 16-42 mmHg), respectively. Comparisons of the Mackay-Marg and TonoPen tonometers indicated no significant differences (P < 0.16). The mean and range of IOP in normal dairy cows within 2 SD (95% of the population) is 27 mmHg with a range of 16-36 mmHg.

In vitro flow characteristics of the Ahmed and self-constructed anterior chamber shunts.

OBJECTIVE: To compare in vitro opening pressures (OP) and closing pressures (CP) of the Ahmed VS-1 and VS-2 glaucoma valves with those of several self-constructed valve 'prototypes,' and to assess their ability to maintain perfusion pressures between 6 and 21 mm of Hg. SAMPLE POPULATION: Ahmed VS-1 (n = 6), 2 groups of Ahmed VS-2 (group 1: n = 12; group 2: n = 14), and self-constructed valves with linear incisions in the long axis of the tube wall (n = 6) or X-shaped incisions in the tube walls (n = 2). PROCEDURE: Valves were perfused with deionized water, lactated Ringer's solution (LRS), Dulbecco's modified Eagle's medium (DMEM), DMEM plus 50% equine serum (ES), and 100% ES. Flow rates of 2.85, 4.2, 6.0, 9.0, and 12.0 microliter/min were used for each perfusate. Valves were tested 3 times for reproducibility, and OP/CP were compared for each system. RESULTS: OP/CP of the VS-1, VS-2 (group 1), VS-2 (group 2), and linear 1.0-cm incisional valves with thick tubing consistently increased with increasing perfusion rate. Linear 0.5-cm (thick tubing) and 1.0-cm (thin tubing) incisional valves had increasing OP/CP with increasing perfusion rate in all but a few instances. Mean OP/CP decreased with increasing perfusate osmolarity for all perfusates except LRS, using the VS-1 and V-2 (group 2) valves. Mean OP/CP were consistently lower for VS-1 than VS-2 (group 1) valves at any given flow rate and for any given perfusate. Mean OP/CP were consistently lower for VS-2 (group 1) than VS-2 (group 2) valves at any given flow rate and for any given perfusate. The linear 0.5-cm incisional valves with thick and thin tubing induced the highest mean OP/CP, maximizing at > 30 mm of Hg. CONCLUSIONS: Only the VS-2 (group 2) valves consistently had mean OP/CP between 6 and 21 mm of Hg for all perfusates and at all flow rates. CLINICAL RELEVANCE: Anterior chamber shunts, although imperfect, appear to offer a physiologically sound alternative for glaucoma management.

Effects on intraocular pressure and pupil size in glaucomatous beagles after topical pilocarpine instilled with standard (pH 5) and buffer-tip (pH 7) droptainers.

Single doses (50 microliters) of 1% and 2% pilocarpine, instilled by a buffer-tip droptainer resulting in an approximate pH 7.0 solution, and 1, 2, and 4% pilocarpine, instilled by the standard droptainer, resulting a pH 5.0 solution, were evaluated in the glaucomatous Beagle model. Pupil size and intraocular pressure measurements were performed at 0, 1/4, 1/2, 3/4, 1, 2, 4, 6, and 8 hours. Signs of topical irritation (blepharospasm, conjunctival hyperemia and chemosis, and any corneal changes) were also monitored. Both solutions produced similar onset and duration of miosis and ocular hypotension, but the pH 5.0 solutions produced a brief elevation in intraocular pressure during the first hour post-drug instillation. Moderate blepharospasm, conjunctival hyperemia, and chemosis occurred with only the pilocarpine solutions with pH 5.0.

Evaluation of multiple doses of 4 and 6% timolol, and timolol combined with 2% pilocarpine in clinically normal beagles and beagles with glaucoma.

Topically applied 4% timolol, 4% timolol combined with 2% pilocarpine, 6% timolol, and 6% timolol combined with 2% pilocarpine were evaluated in clinically normal Beagles and Beagles with glaucoma. The drugs were instilled twice daily for 5 days. Changes in intraocular pressure (IOP), pupil size, and heart rate were recorded on days 1, 3, and 5 at 0, 2, 5, and 8 hours, starting at 8:30 AM. In clinically normal dogs, 4 and 6% topically administered timolol did not cause consistent reductions in IOP; however, with addition of 2% pilocarpine, IOP was consistently lower. In the Beagles with glaucoma, 4 and 6% timolol and, to a greater extent, 4 and 6% timolol combined with 2% pilocarpine lowered IOP. The combinations lowered IOP and reduced pupil size consistently. In all test groups, either 4 or 6% topically applied timolol caused approximately 10% decrease in mean heart rate.

Intraocular pressure variation associated with body length in young American alligators (Alligator mississippiensis).

Using an applanation tonometer, 5 replicate intraocular pressure (IOP) measurements were obtained from each eye of 12 young clinically normal, American alligators. Alligator length ranged from 46 to 117 cm, measured from snout to tail tip. All IOP were recorded by a single observer at an ambient temperature of approximately 25 C, and ranged from 5 to 35 mm of Hg. Observer reliability was excellent (intraclass r = 0.93), and IOP did not change over the ordered sequence of 5 replicate measurements/eye. Replicate IOP) measurements were, therefore, averaged in each eye for comparison between eyes of the same alligator. Left and right eve IOP were highly correlated within individual alligators (r = 0.92), whereas the mean within animal difference between left and right eye IOP was not statistically significant (95% confidence interval [CI] for the left eye-right eye mean difference, - 1.9 to 1.3 min of Hg). Mean IOP determined for 5 confirmed females and 3 confirmed males did not differ significantly between the sexes (95% CI for the male-female difference in means, -2.1 to 3.7 mm of Hg). Mean +/- SEM IOP of 23.7 + 2.1 mm of Hg determined for 4 alligators < -50 cm long was significantly (P = 0.009) greater than mean IOP of 11.6 + 0.5 mm of Hg determined for 8 alligators > 50 cm long (95% CI for the difference in means, 8.5 to 15.7 mm of Hg). In young alligators, the relation between body length and IOP appears to be nonlinear, possibly with a negative exponent.