Ophthalmic abnormalities secondary to periocular or ocular snakebite (pit vipers) in dogs--11 cases (2012-2014).

OBJECTIVE: To describe ophthalmic abnormalities secondary to periocular and ocular snakebite in dogs. ANIMAL STUDIED: Retrospective review of medical records from dogs presenting to the Small Animal Hospital at University of Florida following snakebites to the face (2012-2014). Two groups were identified: periocular bites (PB) and ocular bites (OB). RESULTS: Records from eleven dogs matched the search criteria and were included in the study (PB=9, 81.8%; OB=2, 18.2%). Both OB cases involved the cornea. Facial edema, blepharospasm, chemosis, and conjunctival hyperemia occurred in all cases (100%). Hemorrhage from the eyelids occurred in eight cases (72.7%; PB=7, OB=1). Subconjunctival hemorrhage occurred in seven cases (63.6%; PB=6, OB=1). Third eyelid laceration and nictitans gland prolapse occurred in 1 case each (9%; PB=1). Lagophthalmia was present in three cases (27.3%; PB=3), with secondary corneal ulcer in two cases (18.2%; PB=2). Corneal ulcer due to direct corneal bite occurred in two cases (18.2%-partial thickness with melting (1) and full thickness (1) ). Uveitis was present in 6 cases (54.5%; PB=4, OB=2), with flare and miosis in 4 cases (36.4%; PB=2, OB=2). Hyphema, fibrin in anterior chamber, and cataract occurred in one case (9%; OB=1). Vision loss occurred in two cases (18.2%; PB=2), secondary to retinal degeneration (PB=1) and amaurosis (PB=1). Mean follow-up time was 7 weeks (range: 3 days-11 months). Most clinical signs had resolved by last examination. CONCLUSIONS: Periocular symptoms were more commonly observed than ocular alterations, regardless of bite location. Appropriate supportive therapy should be instituted according to clinical signs.

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.

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.

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).

Use of a biosynthetic material to repair the surgical defect following excision of an epibulbar melanoma in a cat.

A limbal melanoma was surgically excised from the OS of a 4-year-old castrated male Domestic Short-haired cat (DSH). The resultant scleral defect was repaired by placement of A-cell bio-scaffold material. The patient responded well in the postoperative period with no apparent discomfort, nor any observable complications. No signs of recurrence have been evident nearly 2.5 years following surgical removal. A-cell appears to be a safe and reasonable option to lend support to corneoscleral defects following removal of neoplastic lesions. It carries with it the advantages of availability, minimal host rejection, and reduced potential for iatrogenic spread of infections agents.

Evaluation of clinical characteristics and bacterial isolates in dogs with bacterial keratitis: 97 cases (1993-2003).

OBJECTIVE: To evaluate clinical characteristics and breeds affected with bacterial keratitis and compare patterns of resistance in bacterial isolates over time in dogs. DESIGN: Retrospective cross-sectional study. ANIMALS: 97 dogs with bacterial keratitis. PROCEDURE: Dogs with bacterial keratitis were identified from teaching hospital medical records at the Universities of Tennessee and Florida during the years 1993 to 2003. Data were collected pertaining to breed, Schirmer tear test results, treatments administered at the time of initial examination, bacterial species isolated, and resistance to selected antimicrobials. RESULTS: 66% of the dogs were brachycephalic, 54% had tear production < 15 mm/min, and 29% were receiving a corticosteroid at the time of initial examination. The most common bacteria isolated were Staphylococcus intermedius (29%), beta-hemolytic Streptococcus spp (17%), and Pseudomonas aeruginosa (21%). Staphylococcus intermedius isolates had limited resistance to certain antimicrobials. More than 80% of beta-hemolytic Streptococcus spp isolates were resistant to neomycin, polymyxin B, and tobramycin. Isolates of P aeruginosa were susceptible to tobramycin and gentamicin and had limited resistance to ciprofloxacin and enrofloxacin. Among bacterial species isolated, there was no evidence of development of antimicrobial resistance over time. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that administration of ciprofloxacin or a combination of a first-generation cephalosporin and tobramycin may be used in the treatment of bacterial keratitis while awaiting results of bacterial culture and susceptibility testing. Evidence suggests that current methods of medical management of bacterial keratitis are not associated with increased antimicrobial resistance.

Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation.

Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in the affected dogs, age-associated scleral stiffening and loss of mechanical damping were still prominent and had a similar rate of change as in the normal dogs.

Long-term effect of retinal ganglion cell axotomy on the histomorphometry of other cells in the porcine retina.

PURPOSE: To determine the effect of retinal ganglion cell axotomy on the thickness of inner plexiform, inner nuclear, and outer plexiform layers, as well as the densities of short- and middle-to-long-wavelength cones, in the porcine retina. METHODS: Unilateral retinal ganglion cell axotomy was performed in seven domestic pigs by either surgical optic nerve section or peripapillary argon laser photocoagulation. Damage to the retinal vasculature was ruled out with fluorescein angiography. Histologic examination of the retinal tissue was performed nine months later. Cone densities were determined immunohistochemically with the anti-visual pigment antibodies COS-1 and OS-2. Image analysis of semithin retinal cross sections was used to measure the thickness of the retinal layers. The effect of axotomy was quantified by optic nerve axon counts and estimations of retinal ganglion cell counts. The data were compared between the eyes with axotomy and the contralateral normal eye using the nonparametric Wilcoxon rank sum test. RESULTS: Treatment of the peripapillary retina with the argon laser resulted in a median decrease in axon counts and retinal ganglion cell density estimates of 31%. No optic nerve axons and cells resembling retinal ganglion cells were found in the eyes with transected optic nerves. There was no significant difference in either the thickness of any retinal layers or cone densities between axotomized and normal control eyes. CONCLUSION: No signs of retrograde transsynaptic degeneration were observed in porcine retinas nine months after retinal ganglion cell axotomy.

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.

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.

Treatment of equine glaucoma by transscleral neodymium:yttrium aluminum garnet laser cyclophotocoagulation: a retrospective study of 23 eyes of 16 horses.

Contact neodymium:yttrium aluminum garnet (Nd:YAG) laser transscleral cyclophotocoagulation (TSCP) was performed on 23 eyes of 16 horses for treatment of glaucoma. The mean highest preoperative IOP was 51 +/- 17 mmHg. Follow-up evaluation was available for 19 eyes 1 day after surgery, 14 eyes from 1 to 2 weeks, 16 eyes from 4 to 6 weeks, 9 eyes from 12 to 16 weeks, and 10 eyes greater than 20 weeks after laser treatment. The mean intraocular pressure (IOP) the day following surgery was 34 +/- 13 mmHg. The mean IOP for each follow-up period was: one to two weeks postoperative, 23 +/- 9 mmHg; four to six weeks, 24 +/- 7 mmHg; 12-16 weeks, 28 +/- 10 mmHg; and >/= 20 weeks, 22 +/- 9 mmHg. IOP measurements were significantly different from pretreatment values for all follow-up intervals except for weeks 12-16 (P < 0.05). Treatment success was defined as maintenance of IOP < 30 mmHg. Treatment success was achieved in 93%, 88%, 78%, and 70% of the treated eyes at the 1-2 weeks, 4-6 weeks, 12-16 weeks, and the >/= 20 weeks re-evaluation, respectively. No significant difference was found between the number of eyes visual at presentation (52.2%) and visual at 20 weeks (60%). The most common laser complications were conjunctival hyperemia (21.7%) and corneal ulcers (13.0%). Results of this study indicate that Nd:YAG TSCP is an effective method of controlling IOP and preserving vision in horses with glaucoma. An effective Nd:YAG laser protocol for TSCP in the equine glaucomatous eye is a power setting of 11 W, duration of 0.4 s, applied 5 mm posterior to the limbus at 60 sites, resulting in a total energy dose of 264 J.

Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis.

OBJECTIVE: To examine in vitro effects of various antiproteolytic compounds on activity of matrix metalloproteinase (MMP)-2 and -9 in the tear film of horses with active corneal ulcers. SAMPLE POPULATION: Samples of tear film obtained from the eyes of 34 horses with active ulcerative keratitis. PROCEDURE: Horses were sedated, and tear samples were collected from the lower fornix of 34 ulcerated eyes by use of capillary tubes. The protease inhibitors 0.2% EDTA, 0.1% doxycycline, 10% N-acetylcysteine (NAC), 0.1% solution of a modified dipeptide that contains hydroxamic acid (ie, ilomostat), 0.1% alpha1-proteinase inhibitor (PI), 0.5% alpha1-PI, and 100% fresh equine serum (ES) were used to treat pooled samples. Amount of latent and active MMP-2 and -9 was measured by optical density scanning of gelatin zymograms of treated and untreated tear samples. RESULTS: Pooled tear samples obtained from ulcerated eyes contained the latent and active forms of MMP-2 and -9. Compared with MMP activity in untreated samples, total MMP activity (sum of all bands detected) observed on the gelatin zymogram gels was reduced by 99.4% by EDTA, 96.3% by doxycycline, 98.8% by NAC, 98.9% by ilomostat, 52.4% by 0.1% alpha1-PI, 93.6% by 0.5% alpha1-PI, and 90.0% by ES. CONCLUSIONS AND CLINICAL RELEVANCE: We documented that EDTA, doxycycline, NAC, ilomostat, alpha1PI, and ES inhibited MMP activity in vitro. Because these compounds use different mechanisms to inhibit various families of proteases in the tear film of horses, a combination of these protease inhibitors may be beneficial for treatment of corneal ulcers in horses.

Screening ADAMTS10 in dog populations supports Gly661Arg as the glaucoma-causing variant in beagles.

PURPOSE: Previously, we mapped the disease locus in the beagle model of autosomal recessive primary open angle glaucoma (POAG) to a 4-Mb interval on chromosome 20, and identified a Gly661Arg variant in ADAMTS10 as the candidate disease-causing variant. The purpose of this study was to test the hypothesis that the Gly661Arg variant of ADAMTS10 causes glaucoma by genotyping dogs of various breeds affected and unaffected by primary glaucoma. METHODS: Dogs of various breeds, affected or unaffected with primary glaucoma, were genotyped for the Gly661Arg variant of ADAMTS10, as well as 7 other nonsynonymous single nucleotide polymorphisms (SNPs) in other genes in the beagle POAG locus that segregate with disease. Alternate allele frequencies were calculated with 95% confidence intervals and comparisons made to expected allele frequency relative to disease prevalence or between cases and controls. RESULTS: For the nonsynonymous SNPs other than the ADAMTS10 variant, control dogs were identified that were homozygous for the alternative alleles, ruling out those variants as causative. None of the nonsynonymous SNPs were found associated with primary glaucoma in American cocker spaniels. The Gly661Arg variant of ADAMTS10 was the only variant with minor allele frequency consistent with the prevalence of primary glaucoma in the general beagle population. The only dog found homozygous for the Gly661Arg variant of ADAMTS10 was an affected beagle, unrelated to the POAG colony. CONCLUSIONS: These findings support the Gly661Arg mutation of ADAMTS10 as the likely cause of POAG in beagles.

Angiopoietin-like 7 secretion is induced by glaucoma stimuli and its concentration is elevated in glaucomatous aqueous humor.

PURPOSE: To investigate the possibility that Angiopoietin-like 7 (ANGPTL7) protein is involved in the pathogenesis of glaucoma. METHODS: Primary human trabecular meshwork (TM) cells and corneoscleral explants were stimulated with either dexamethasone (DEX) or transforming growth factor beta (TGFbeta), and ANGPTL7 protein secreted into culture medium was determined by Western blot analysis. The effect of stable overexpression of ANGPTL7 in transfected immortalized TM cell lines on collagen expression was investigated by immunocytochemistry. Localization of ANGPTL7 protein in human eyes was determined by immunohistochemistry. The concentration of ANGPTL7 protein in aqueous humor (AH) from patients with glaucoma and control patients was compared by Western blot analysis. The beagle model of primary open-angle glaucoma (POAG) was used to correlate ANGPTL7 protein levels in canine AH with disease progression. RESULTS: TGFbeta and DEX stimulated secretion of ANGPTL7 protein by TM cells and corneoscleral explants. Overexpression of ANGPTL7 by immortalized TM cell lines increased expression of type I collagen. Expression of ANGPTL7 protein was located in the corneal stroma, near the limbus, and throughout the sclera, with lower expression in the TM. In the lamina cribrosa, ANGPTL7 expression was associated with the cribriform plates. The concentration of ANGPTL7 protein was elevated in AH from patients with glaucoma and increased as disease progressed in POAG beagle dogs. CONCLUSIONS: Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. Since overexpression of ANGPTL7 increases collagen expression, a potential disease mechanism, ANGPTL7 could have a pathogenic role in glaucoma, and may serve as a potential therapeutic target.

Ocular manifestations of endocrine disease.

Small animal patients with endocrinopathies are at risk of developing many ophthalmic conditions resulting from endocrine hormone imbalances. Diabetic animals frequently develop cataracts but can also have numerous other ocular problems, including uveitis, keratopathy, retinopathy, and the effects of lipid derangements and systemic hypertension. Cushing's patients can develop complications from hyperlipidemia and hypertension and sometimes present with corneal disease. Acute blindness from sudden acquired retinal degeneration has been associated with disease of the pituitary-adrenal axis. Growth hormone disturbances can result in the secondary ocular effects of hypertension or of thyroid deficiency (e.g., corneal infiltrates, decreased tear production, neurologic dysfunction). Hyperthyroid animals can present with the ocular manifestations of systemic hypertension. Disorders of calcium homeostasis are unusual, typically manifesting as cataracts in hypocalcemic patients or as metastatic calcification of the ocular tissues.

Immunocytochemical localization of smooth muscle actin-containing cells in the trabecular meshwork of glaucomatous and nonglaucomatous dogs.

PURPOSE: It has been recently demonstrated that trabecular meshwork (TM) cells within the canine iridocorneal angle (ICA) contain smooth muscle actin (smA) and possess contractile abilities that probably alter aqueous outflow. As the number of trabecular meshwork cells in glaucomatous canine eyes have been found to be less than those in age-matched nonglaucomatous eyes, we hypothesize that the sub-population of TM cells that contain smooth muscle actin will also decline with age. We also hypothesize that a greater loss of these cells will be observed in glaucomatous eyes than in nonglaucomatous eyes of the same age. In the present study the ICA of 17 glaucomatous and eight nonglaucomatous eyes were examined for the presence of smA-containing TM cells. MATERIAL AND METHODS: Five-micron sagittal sections of each whole globe were immunolocalized for smooth muscle actin. Positive and negative controls were performed concomitantly. RESULTS: Labeling was observed in the meshwork of 10 out of the 17 glaucomatous eyes, distributed across all of the age groups represented, including eyes with primary and secondary glaucoma. Smooth muscle actin labeling was observed in the TM of 7 out of 14 eyes with closed-angle glaucoma. Positive immunoreaction was observed in 3/3 eyes with open ICAs. Labeling of smooth muscle actin was observed in the anterior part of the meshwork in only 4 of the 17 glaucomatous eyes, each having had secondary glaucoma. There were no eyes in which label was observed exclusively in the anterior portion of the meshwork. Labeling was most consistently observed in the outer, posterior uveal TM and the inner, posterior corneoscleral TM. All of the eight nonglaucomatous eyes showed greater labeling in both area and intensity than the glaucomatous eyes of the same age. CONCLUSION: It was concluded that smooth muscle actin-cell loss is associated with age in canine eyes and that this loss is more severe in glaucomatous eyes.

Endothelin-1, nitric oxide, and glutamate in the normal and glaucomatous dog eye.

PURPOSE: To document differences in the levels of the endothelin-1 peptide, nitric oxide, and glutamate in aqueous humor and vitreous in the dog eye with spontaneous glaucoma compared to the normal dog eye. METHODS: Samples of aqueous humor and vitreous from enucleated normal eyes (n = 21) of 14 dogs and glaucomatous eyes (n = 8) of eight dogs were collected. Levels of endothelin-1, nitric oxide, and glutamate were measured by enzyme immunoassay. RESULTS: Endothelin-1 aqueous humor levels (mean +/- SD) increased significantly from 3.05 (+/- 1.66) pg/mL for the normal eyes to 6.22 (+/- 2.83) pg/mL for the glaucomatous eyes (P = 0.0054). The increase in vitreous from 1.83 (+/- 1.66) pg/mL for the normal eyes to 2.86 (+/- 1.31) pg/mL for the glaucomatous eyes was not significant (P = 0.0840). Nitric oxide levels (mean +/- SD) increased significantly in aqueous humor from 4.12 (+/- 2.64) microM for the normal eyes to 12.95 (+/- 14.42) microM for the glaucomatous eyes (P = 0.0141). The vitreous levels increased from 4.86 (+/- 3.92) microM for the normal eyes to 15.33 (+/- 16.22) microM for the glaucomatous eyes (P = 0.0179). Glutamate levels (mean +/- SD) decreased nonsignificantly in aqueous humor from 2.35 (+/- 3.84) microM for the normal eyes to 1.61 (+/- 0.74) microM for the glaucomatous eyes (P = 0.9377) and in vitreous from 1.37 (+/- 1.89) microM for the normal eyes to 1.02 (+/- 1.11) microM for the glaucomatous eyes (P = 0.3303). CONCLUSION: Endothelin-1 and nitric oxide increased in aqueous humor and vitreous of dogs with spontaneous glaucoma while the changes in glutamate varied.

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.