OBJECTIVE To evaluate the effectiveness of a novel fluorescence tracer agent, MB-102, for conducting ocular angiography in dogs. ANIMALS 10 ophthalmologically normal dogs (2 to 4 years old) and 10 dogs with retinal degeneration or primary open-angle glaucoma (< 6 years old). PROCEDURES While anesthetized, all dogs received sodium fluorescein (20 mg/kg, IV) or MB-102 (20 or 40 mg/kg, IV) first and then the other dye in a second treatment session 2 days later in a randomized crossover design. Anterior fluorescence angiography was performed on one eye and posterior fluorescence angiography on the other. Imaging was performed with a full-spectrum camera and camera adaptor system. Filter sets that were tailored to match the excitation and emission characteristics of each angiographic fluorescent agent were used. RESULTS All phases and phase intervals during anterior and posterior segment angiography were identified, regardless of the dye used. However, agent fluorescence and visualization of the iridal blood vessels were hindered in some dogs, irrespective of agent, owing to the degree of iridal pigmentation present. No significant difference was noted between the 2 dyes in any phase or phase interval, and slight improvement in image contrast was observed with MB-102 during the venous phases owing to a reduction of vessel wall staining in both normal and diseased eyes. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that MB-102 would be useful for conducting ocular angiography in dogs.

OBJECTIVE: To assess changes in pupil size and intraocular pressure (IOP) following topical application of a 0.5% tropicamide solution in the eyes of healthy butorphanol-sedated dogs. ANIMALS: 12 healthy adult Beagles. PROCEDURES: In a randomized crossover study consisting of 2 treatment periods with a 1-week washout between periods, dogs received an IM injection of butorphanol (0.2 mg/kg) or an equal volume of sterile saline (0.9% NaCl) solution. For each dog, 1 drop of 0.5% tropicamide ophthalmic solution was topically instilled in one eye and 1 drop of artificial tear solution was topically instilled in the other eye 10 minutes after the IM injection and again 5 minutes later. Extent of sedation, pupil size, and IOP were evaluated from 20 minutes before to 80 minutes after the IM injection and compared among treatment combinations. RESULTS: Butorphanol induced mild (n = 9) or moderate (3) sedation in all dogs and slightly delayed the onset of, but did not prevent, tropicamide-induced mydriasis. Butorphanol caused a significant increase in IOP, which was not exacerbated by tropicamide-induced mydriasis; however, that increase was generally not sufficient to exceed the upper limit of the IOP reference range. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that butorphanol did not prevent tropicamide-induced mydriasis but did increase the IOP in ophthalmologically normal Beagles. Although the butorphanol-induced increase in IOP did not appear clinically relevant for the dogs of this study, that may not be true for dogs with glaucoma, and care should be taken when butorphanol is administered to such dogs.

OBJECTIVE To evaluate the coding regions of ADAMTS17 for potential mutations in Chinese Shar-Pei with a diagnosis of primary open-angle glaucoma (POAG), primary lens luxation (PLL), or both. ANIMALS 63 Shar-Pei and 96 dogs of other breeds. PROCEDURES ADAMTS17 exon resequencing was performed on buccal mucosal DNA from 10 Shar-Pei with a diagnosis of POAG, PLL, or both (affected dogs). A candidate causal variant sequence was identified, and additional dogs (53 Shar-Pei [11 affected and 42 unaffected] and 95 dogs of other breeds) were genotyped for the variant sequence by amplified fragment length polymorphism analysis. Total RNA was extracted from ocular tissues of 1 affected Shar-Pei and 1 ophthalmologically normal Golden Retriever; ADAMTS17 cDNA was reverse transcribed and sequenced, and ADAMTS17 expression was evaluated by quantitative reverse-transcription PCR assay. RESULTS All affected Shar-Pei were homozygous for a 6-bp deletion in exon 22 of ADAMTS17 predicted to affect the resultant protein. All unaffected Shar-Pei were heterozygous or homozygous for the wild-type allele. The variant sequence was significantly associated with affected status (diagnosis of POAG, PLL, or both). All dogs of other breeds were homozygous for the wild-type allele. The cDNA sequencing confirmed presence of the expected variant mRNA sequence in ocular tissue from the affected dog only. Gene expression analysis revealed a 4.24-fold decrease in the expression of ADAMTS17 in ocular tissue from the affected dog. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that the phenotype (diagnosis of POAG, PLL, or both) is an autosomal recessive trait in Shar-Pei significantly associated with the identified mutation in ADAMTS17.

Objective-To investigate whether differences existed between clinically normal dogs and dogs with goniodysgenesis-related glaucoma (GDRG) in serum autoantibodies against optic nerve antigens. Animals-16 dogs with GDRG, 17 healthy dogs with unremarkable pectinate ligament and iridocorneal angle morphology, and 13 euthanized dogs with no major ocular abnormalities or underlying diseases. Procedures-Western blotting was performed with optic nerve extracts from the euthanized dogs as an antigen source and serum from clinically normal dogs and dogs with GDRG as a primary antibody (autoantibody) source. Blots were evaluated for presence and density of bands. Results-Multiple bands were identified on western blots from all dogs with GDRG and all clinically normal dogs, with a high degree of variability among individual dogs. Dogs with GDRG were significantly more likely than healthy dogs to have bands present at 38, 40, and 68 kDa. Dogs with GDRG had significant increases in autoreactivity at 40 and 53 kDa and a significant decrease in autoreactivity at 48 kDa. Conclusions and Clinical Relevance-Significant differences in serum autoantibodies against optic nerve antigens were found in dogs with versus without GDRG. Although it remains unclear whether these differences were part of the pathogenesis of disease or were sequelae to glaucomatous changes, these findings provide support for the hypothesis that immune-mediated mechanisms play a role in the development or progression of GDRG. However, the high degree of variability among individual dogs and the considerable overlap between groups suggest that the clinical usefulness of this technique for distinguishing dogs with GDRG from clinically normal dogs is likely limited.

Objective: To determine the effects of topically applied 2% delta-9-tetrahydrocannabinol (THC) ophthalmic solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in clinically normal dogs. Animals: 21 clinically normal dogs. Procedures: A randomized longitudinal crossover design was used. Following acquisition of baseline IOP (morning and evening) and AHFR (afternoon only) data, dogs were randomly assigned to 2 treatment groups and received 1 drop of either 2% THC solution or a control treatment (olive oil vehicle) to 1 randomly selected eye every 12 hours for 9 doses. The IOPs and AHFRs were reassessed after the final treatment. Following a washout period of ≥ 7 days, dogs were administered the alternate treatment in the same eye, and measurements were repeated. Results: Mean ± SD IOPs in the morning were 15.86 ± 2.48 mm Hg at baseline, 12.54 ± 3.18 mm Hg after THC treatment, and 13.88 ± 3.28 mm Hg after control treatment. Mean ± SD IOPs in the evening were 13.69 ± 3.36 mm Hg at baseline, 11.69 ± 3.94 mm Hg after THC treatment, and 12.13 ± 2.99 mm Hg after control treatment. Mean IOPs were significantly decreased from baseline after administration of THC solution but not the control treatment. Changes in IOP varied substantially among individual dogs. Mean ± SD AHFRs were not significantly different from baseline for either treatment. Conclusions and Clinical Relevance: Topical application of 2% THC ophthalmic solution resulted in moderate reduction of mean IOP in clinically normal dogs. Further research is needed to determine efficacy in dogs with glaucoma.

Objective: To evaluate the effects of oral administration of diphenhydramine on pupil diameter, intraocular pressure (IOP), tear production, tear film quality, corneal sensitivity, and conjunctival goblet cell density (GCD) in clinically normal adult dogs. Animals: 12 healthy adult dogs. Procedures: All dogs received diphenhydramine (2.2 mg/kg, PO, q 12 h) for 21 days. Conjunctival biopsy samples were obtained immediately before (day 1) and after (day 21) treatment with diphenhydramine and conjunctival GCDs were determined. Gross ophthalmic examinations and fluorescein staining of corneas were performed, and pupil diameter, corneal sensitivity, IOP, tear production, and tear film breakup time were determined prior to administration of diphenhydramine on days 1 through 5 and on day 21; pupil diameter and IOP measurements were repeated on each of those days at 20 and 40 minutes and 1, 3, 6, and 8 hours after administration of diphenhydramine. Data were analyzed to detect differences among values for dogs. Results: Clinically important increases in pupil diameter were not detected after administration of diphenhydramine to dogs. Day 1 corneal sensitivity and tear film breakup time for dogs were significantly higher than day 21 values for those variables. Conclusions and Clinical Relevance: Results of this study suggested that oral administration of diphenhydramine to healthy adult dogs was not likely to acutely induce glaucoma or keratoconjunctivitis sicca. However, effects of diphenhydramine in dogs with keratoconjunctivitis sicca or primary glaucoma or dogs genetically predisposed to development of those conditions were not determined. Administration of diphenhydramine to dogs decreased corneal sensitivity and tear film breakup time, although these effects were not clinically important.

A new topically administered anhydrase inhibitor, MK-927, evaluated for its ocular hypotensive activity in normotensive and glaucomatous Beagles. Single- and multiple-dose studies were performed. Six concentrations of the drug were evaluated in the single-dose study and the 2% solution was used for multiple-dose evaluation. The decrease in intraocular pressure (IOP) was greater in glaucomatous Beagles at the higher concentrations of the drug. The 2 and 4% solutions of MK-927 significantly lowered IOP (mean, 5 mm of Hg; SEM +/- 1.6 and SEM +/- 1.2, respectively) in normotensive and glaucomatous Beagles. In the multiple-dose study, IOP was significantly decreased in the normotensive (mean, 4 mm of Hg; SEM +/- 0.74) and glaucomatous Beagles (mean, 9 mm of Hg; SEM +/- 1.2). The maximal effect was observed by day 4. A contralateral effect was found in glaucomatous Beagles, with the maximal effect on day 4.

Numbers of mast cells in the cornea, sclera, choroid, ciliary body, iris, and retina of sections of globes from 35 clinically normal dogs and 34 dogs with secondary glaucoma was determined. Fixed globes were trimmed along a vertical midsagittal plane and embedded in paraffin. Tissue sections, approximately 6 micrometer thick, were stained with toluidine blue for identification of mast cells. In normal globes, most of the mast cells were observed in the anterior portion of the uvea, and fewer mast cells were seen in the choroid and sclera. Mast cells were not observed in the retina and were seldom observed in the cornea of dogs with or without glaucoma. In sections of glaucomatous globes, mast cells were distributed evenly in the uvea and sclera, and fewer mast cells were present than in normal globes, regardless of the cause of glaucoma.

Ultrastructural examination of optic nerve capillaries in the canine lamina cribrosa revealed many spherical, membrane-bound, electron-dense inclusions that closely resembled Weibel-Palade bodies, in pericytes and endothelial cells of preglaucomatous, early, moderately, and advanced affected Beagles with hereditary primary open-angle glaucoma. This ultrastructural difference between the laminar capillary endothelial cells of normal and glaucomatous Beagles could represent a functional vascular disorder, because Weibel-Palade bodies are associated with microcirculatory abnormalities.

OBJECTIVE To determine whether 2- or 3-times-daily application of topical ophthalmic 0.005% latanoprost solution is more effective at lowering intraocular pressure (IOP) in clinically normal dogs. ANIMALS 9 clinically normal dogs. PROCEDURES For each dog, I drop of latanoprost 0.005% solution was applied to 1 eye every 8 or 12 hours each day for 5 days; the contralateral eye received topical ophthalmic treatment with 1 drop of saline (0.9% NaCl) solution at the times of latanoprost application. Ocular examinations of both eyes were performed every 6 hours starting 48 hours prior to and ending 42 hours after the treatment period. Following a 5-week washout interval, the procedures were repeated but the previously latanoprost-treated eye of each dog received latanoprost application at the alternate frequency. RESULTS Mean ± SD IOP reduction in the latanoprost-treated eyes was 31 ± 6.9% with 2-times-daily application and 33 ± 8.2% with 3-times-daily application. A 2-way repeated-measures ANOVA revealed significant differences in IOP with contributions by treatment (2 or 3 times daily), time of day (diurnal variation), and individual dog. The maximum mean daily IOP reduction in latanoprost-treated eyes was detected on day 3 of latanoprost treatment in each group. Eyes treated 3 times daily had significantly smaller pupil diameter and greater conjunctival hyperemia than eyes treated 2 times daily. CONCLUSIONS AND CLINICAL RELEVANCE The clinical importance of the ocular hypotensive effects of 3-times-daily topical ophthalmic application of 0.005% latanoprost solution in dogs with glaucoma warrants investigation.