Assessment of Early Glaucomatous Optic Neuropathy in the Dog by Spectral Domain Optical Coherence Tomography (SD-OCT).

BACKGROUND: Inherited primary open-angle glaucoma (POAG) in Beagle dogs is a well-established large animal model of glaucoma and is caused by a G661R missense mutation in the ADAMTS10 gene. Using this model, the study describes early clinical disease markers for canine glaucoma. METHODS: Spectral-domain optical coherence tomography (SD-OCT) was used to assess nine adult, ADAMTS10-mutant (median age 45.6 months, range 28.8-52.8 months; mean diurnal intraocular pressure (IOP): 29.9 +/- SEM 0.44 mmHg) and three related age-matched control Beagles (mean diurnal IOP: 18.0 +/- SEM 0.53 mmHg). RESULTS: Of all the optic nerve head (ONH) parameters evaluated, the loss of myelin peak height in the horizontal plane was most significant (from 154 +/- SEM 38.4 µm to 9.3 +/- SEM 22.1 µm; p < 0.01). There was a strong significant negative correlation between myelin peak height and IOP (Spearman correlation: -0.78; p < 0.003). There were no significant differences in the thickness of any retinal layers evaluated. CONCLUSIONS: SD-OCT is a useful tool to detect early glaucomatous damage to the ONH in dogs before vision loss. Loss in myelin peak height without inner retinal thinning was identified as an early clinical disease marker. This suggests that initial degenerative changes are mostly due to the loss of myelin.

The future of canine glaucoma therapy.

Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO-VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP-lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.

Survey of cytokines in normal canine tears by multiplex analysis: A pilot study.

OBJECTIVES: The purpose of this pilot study was to use a multiplexed assay to measure cytokines in normal stimulated canine tears. METHODS: 25 healthy dogs were included in the study. Stimulated tears were collected in capillary tubes from the right (OD) and left (OS) eyes and stored at -80 °C until batch sample analysis was performed. The samples were analyzed utilizing Luminex® canine-validated multiplex beads on a Bio-Rad multiplex analyzer for IL-2, IL-6, IL-7, IL-8, IL-10, TNF-α, and IFN-γ. Based upon previous human studies, tears were initially evaluated at a 1:10 dilution. Eight random samples were later re-analyzed without dilution. RESULTS: Diluting the samples 1:10 rendered all analytes undetectable except IL-8. A repeat analysis of eight randomly selected undiluted samples still demonstrated very low cytokine levels except for IL-8 (16/16 eyes; 2254 ±â€¯1677 pg/ml OD, 1095 ±â€¯786.8 pg/ml OS); and IFN-γ (15/16 eyes; 13.37 ±â€¯13.08 pg/ml OD,16.08 ±â€¯19.4 pg/ml OS). CONCLUSION: This pilot study is the first to analyze cytokines in canine tears. This study demonstrated that IL-8 is consistently detected in both diluted and undiluted samples, but undiluted samples may be superior to 1:10 diluted samples for evaluation of other cytokines in canine tears.

Comparative evaluation of aqueous humor viscosity.

OBJECTIVE: To evaluate aqueous humor viscosity in the raptor, dog, cat, and horse, with a primary focus on the barred owl (Strix varia). ANIMALS STUDIED: Twenty-six raptors, ten dogs, three cats, and one horse. PROCEDURE: Animals were euthanized for reasons unrelated to this study. Immediately, after horizontal and vertical corneal dimensions were measured, and anterior chamber paracentesis was performed to quantify anterior chamber volume and obtain aqueous humor samples for viscosity analysis. Dynamic aqueous humor viscosity was measured using a dynamic shear rheometer (AR 1000 TA Instruments, New Castle, DE, USA) at 20 °C. Statistical analysis included descriptive statistics, unpaired t-tests, and Tukey's test to evaluate the mean ± standard deviation for corneal diameter, anterior chamber volume, and aqueous humor viscosity amongst groups and calculation of Spearman's coefficient for correlation analyses. RESULTS: The mean aqueous humor viscosity in the barred owl was 14.1 centipoise (cP) ± 9, cat 4.4 cP ± 0.2, and dog 2.9 cP ± 1.3. The aqueous humor viscosity for the horse was 1 cP. CONCLUSIONS: Of the animals evaluated in this study, the raptor aqueous humor was the most viscous. The aqueous humor of the barred owl is significantly more viscous than the dog (P < 0.0001). The aqueous humor viscosity of the raptor, dog, cat, and horse can be successfully determined using a dynamic shear rheometer.

Moh's micrographic surgery for the management of a periocular mast cell tumor in a dog.

A 3-year-old neutered male boxer dog presented with a 6-month history of a waxing and waning mass of the left dorsotemporal eyelid margin. Cytology and biopsy confirmed a diagnosis of mast cell neoplasia. Systemic staging of the dog failed to reveal any evidence of metastatic neoplasia. Owing to the location of the tumor within the eyelid margin and the wide surgical margins recommended for excision of mast cell tumors, Mohs micrographic surgery (MMS) was chosen for its potential to conserve tissues while providing intraoperative confirmation the tumor was completely excised. Utilizing MMS horizontal sectioning technique, 100% of the surgical margins were assessed prior to closure of the surgical wound. This represents the first time a comprehensive MMS protocol was used in a veterinary patient under general anesthesia.

Use of phenol red thread tests to evaluate tear production in clinically normal Amazon parrots and comparison with Schirmer tear test findings.

OBJECTIVE: To determine phenol red thread test (PRTT) values in eyes of clinically normal Hispaniolan Amazon parrots before and after topical application of an ophthalmic anesthetic agent and compare findings with Schirmer tear test (STT) values. DESIGN: Evaluation study. ANIMALS: 24 Amazona ventralis parrots from a research colony. PROCEDURES: On 4 occasions (1-week intervals), all birds underwent a thorough ophthalmic examination of both eyes, which included (in sequence) performance of a PRTT and an STT; topical ocular application of proparacaine hydrochloride; and performance of another PRTT and another STT. Correlations between PRTT and STT values recorded with and without topical anesthesia were assessed. RESULTS: Without topical anesthesia, mean +/- SD PRTT value was 12.5 +/- 5.0 mm/15 s (range, 1 to 25 mm/15 s). With topical anesthesia, the PRTT value was 12.6 +/- 5.4 mm/15 s (range, 2 to 24 mm/15 s). Without topical anesthesia, mean STT value was 7.9 +/- 2.6 mm/min (range, 0 to 13 mm/min). With topical anesthesia, the STT value was 5.1 +/- 3.3 mm/min (range, 0 to 18 mm/min). The correlation of PRTT and STT values recorded with or without topical anesthesia was weak (r = 0.51 and r = 0.32, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the PRTT and STT were both viable methods for measurement of tear production in Hispaniolan Amazon parrots. Topical application of an ophthalmic anesthetic agent did not have a significant effect on the PRTT values but significantly decreased the STT values.

Bilateral intraocular glandular choristomas in a Thoroughbred foal.

Intraocular choristomas are rare anomalies in domestic animals and are often associated with multiple ocular malformations. A Thoroughbred foal presented for ocular abnormalities and was diagnosed with microphthalmia, corneal dermoids, severe anterior segment dysgenesis (including glandular choristomas), aphakia, retinal dysplasia, and optic nerve hypoplasia. Morphological, histochemical, and immunohistochemical comparisons were made between ocular choristomatous tissues from this foal and lacrimal gland, third eyelid gland, nasopharynx, trachea, and lacrimal sac/nasolacrimal duct from normal horses. Morphologically the choristomatous tissues (glands and epithelium lining the anterior segment) were most similar to the lacrimal sac. Histochemistry of glandular components found the glands associated with the lacrimal sac/nasolacrimal duct to be serous, as was the glandular intraocular choristomas. Our findings suggest that the origin of intraocular glandular choristomas in this case is from the lacrimal sac.

Multifocal chorioretinal lesions in Borzoi dogs.

OBJECTIVES: To identify the prevalence of Borzoi chorioretinopathy in western Canada, characterize lesions with fluorescein angiography, determine if lesions were progressive, clarify the association of progressive retinal atrophy and investigate the etiology. MATERIALS AND METHODS: Serial ophthalmic examination, fundus photography, electroretinography, and fluorescein angiography were used to evaluate Borzoi dogs with lesions of Borzoi chorioretinopathy. Pedigree analysis and test breeding of two affected dogs were completed to determine the heritability of Borzoi chorioretinopathy. RESULTS: One hundred three Borzoi dogs were examined between 1998 and 2003. Focal, peripheral, tapetal, hyper-reflective and pigmented areas consistent with focal retinal degeneration and RPE pigmentation were identified in 12 dogs between 7 months and 7 years of age. Seven males and five female dogs were affected. Ophthalmoscopy and fundus photography over 5 years revealed individual lesions that did not progress or coalesce in 12 affected dogs. Electroretinography of affected and normal Borzoi dogs confirmed that retinal function was similar in normal and affected dogs up to 7 years of age. Fluorescein angiography was performed in three affected dogs and confirmed intact blood-ocular barriers, focal retinal pigment epithelium hypertrophy, and focal absence of choroiocapillaris corresponding to chronic, focal lesions. Pedigree analysis precluded simple dominant, X-linked dominant, or X-linked recessive inheritance. One male dog from the test-bred litter developed bilateral lesions at 14 months of age. Simple recessive, polygenetic, and acquired etiologies of these lesions cannot be ruled out at this time. CONCLUSIONS: Borzoi chorioretinopathy is an acquired condition that initially manifests as focal retinal edema and loss of choriocapillaris and tapetum. With time the retina degenerates becoming hyper-reflective and with RPE hyper-pigmentation and clumping within the borders of the tapetal lesions. Choriocapillaris remains hypofluorescent on fluorescein angiography. Progressive retinal atrophy was excluded as an etiology of multifocal chorioretinopathy in Borzois dogs. This condition is not inherited by simple autosomal dominant or sex-linked modes of inheritance.

Qualitative tear film and conjunctival goblet cell assessment of cats with corneal sequestra.

OBJECTIVES: To evaluate the tear film qualitatively and conjunctival goblet cell numbers in cats with and without corneal sequestra. ANIMALS STUDIED AND PROCEDURES: This was a prospective evaluation of 11 cats with corneal sequestra and 14 control eyes that were either the contralateral normal eye when the sequestrum was unilateral or from control cats of similar age with no ocular disease. All cats in this study were examined by a veterinary ophthalmologist. The ophthalmic examinations included a neuro-ophthalmic evaluation, Schirmer tear tests, fluorescein staining, tear film break-up times, applanation tonometry, biomicroscopy, and indirect ophthalmoscopy. The palpebral conjunctiva at the dorsal nasal, ventral nasal, dorsal temporal and ventral temporal fornices were biopsied after topical anesthetic was applied to the cornea and conjunctiva. The conjunctival biopsies were fixed in formalin and sectioned routinely and stained with hematoxylin and eosin, and periodic acid-Schiff. These slides were examined by light microscopy by a blinded examiner. Goblet cell numbers were compared to conjunctival basal epithelial cell numbers by region. The goblet cell numbers by region from the eyes with sequestra was statistically compared to those from eyes without sequestra, with a student's paired t-test. Conjunctival swabs were collected from the cats with corneal sequestra and submitted for polymerase chain reaction for Herpes felis, Chlamydia psiitticia, and Mycoplasma felis. The corneal sequestra were removed by surgical keratectomy and fixed and stained routinely, and examined by light microscopy. RESULTS: No neurologic abnormalities were detected in any of the cats. The Schirmer tear tests (eyes with sequestra 14+/-5.1 mm/min; normal eyes 15+/-6.8 mm/min) and intraocular pressures (eyes with sequestra 21+/-6.6; normal eyes 22+/-5.8) were within normal reference ranges for cats. Biomicroscopic examinations revealed varied sizes and depths of brown- and amber-colored corneal sequestra. No abnormalities were noted on indirect ophthalmoscopic examinations. The tear film break-up time was 21 s (+/-12) for the normal eyes (n=14) and 14 s (+/-13) in eyes with corneal sequestra (n=11). The average goblet/epithelial cell ratios by region for the normal eyes and the eyes with sequestra respectively were 0.66, 0.56 for the dorsal nasal fornix, 0.68, 0.57 for the ventral nasal fornix, 0.63, 0.48 for the temporal dorsal fornix, and 0.55, 0.49 for the temporal ventral fornix. There were no significant differences in tear film break-up times and goblet cell numbers in eyes with corneal sequestra and those without sequestra. Three conjunctival swabs from two of 11 cats with sequestra were positive with PCR for Herpes felis virus. These included one cat with bilateral sequestra and one cat with unilateral corneal sequestrum. CONCLUSIONS: The pathogenesis of feline corneal sequestra does not appear to be linked primarily to abnormal goblet cell numbers, qualitative tear film abnormalities, and accelerated tear film break-up time.

Lacrimostimulants and lacrimomimetics.

A thorough understanding of tear film physiology and the clinical manifestations of tear film abnormalities enables the veterinarian to diagnose and treat quantitative (decreased aqueous layer) and qualitative (decreased mucin or lipid layers) tear film abnormalities accurately and to monitor the responses to lacrimostimulatory and lacrimomimetic therapy. This article reviews the embryology,anatomy, and physiology of the lacrimal glands; glands of the nictitating membrane; goblet cells; and tarsal glands as well as the pathophysiology of tear film deficiencies. We also review lacrimo-stimulants, including cyclosporine, tacrolimus, sirolimus, pilocar-pine, and lacrimomimetics (tear film replacements).

Inherited retinal dysplasia and persistent hyperplastic primary vitreous in Miniature Schnauzer dogs.

The objectives of this study were to define the clinical syndrome of retinal dysplasia and persistent primary vitreous in Miniature Schnauzer dogs and determine the etiology. We examined 106 Miniature Schnauzers using a biomicroscope and indirect ophthalmoscope. The anterior and posterior segments of affected dogs were photographed. Four enucleated eyes were examined using routine light microscopy and scanning electron microscopy. A pedigree was constructed and related dogs were test-bred to define the mode of inheritance of this syndrome. Congenital retinal dysplasia was confirmed in 24 of 106 related Miniature Schnauzer dogs. Physical and postmortem examinations revealed that congenital abnormalities were limited to the eyes. Biomicroscopic, indirect ophthalmoscopic, and neuro-ophthalmic examinations confirmed that some of these dogs were blind secondary to bilateral retinal dysplasia and detachment (nonattachment) (n = 13), and the remainder had generalized retinal dysplasia (n = 11). Fifteen of these dogs were also diagnosed with unilateral (n = 9) or bilateral (n = 6) persistent hyperplastic primary vitreous. Nutritional, infectious, or toxic etiologies were not evident on physical, postmortem, light microscopic, or transmitting and scanning electron microscopic examination of four affected Miniature Schnauzers. We examined the pedigree and determined that an autosomal recessive mode of inheritance was most likely. Three test-bred litters including those from affected parents, carrier and affected parents, and carrier parents confirmed this mode of inheritance. This study confirms that retinal dysplasia and persistent hyperplastic primary vitreous is a congenital abnormality that is inherited as an autosomal recessive condition in Miniature Schnauzers.

Survival of equine herpesvirus-4, feline herpesvirus-1, and feline calicivirus in multidose ophthalmic solutions.

OBJECTIVE: To determine survival over time of infectious equine herpesvirus-4, feline herpesvirus-1, and feline calicivirus in three commercially available and commonly used ophthalmic solutions (eyewash, fluorescein, and proparacaine HCl). SAMPLE POPULATION: Viruses used in this study were originally isolated from eyes of animals referred to the University of Illinois. Equine herpesvirus-4 was propagated in MDBK cells and feline herpesvirus-1 and feline calicivirus in CRFK cells. PROCEDURE: After separately inoculating a designated solution with a specific titer of an individual virus, solutions were incubated per manufacturer's recommendations, either at 4 degrees C or 25 degrees C. Virus titers within solutions were subsequently measured at 1, 8, and 24 h and 3, 5 and 7 days post inoculation using either plaque or TCID50 assays. RESULTS: Equine herpesvirus-4, feline herpesvirus-1, and feline calicivirus were present in eyewash for 7 days, 5 days, and 7 days, respectively. Eyewash did not decrease survival time of any virus when compared to controls. Equine herpesvirus-4 and feline herpesvirus-1, both enveloped viruses, were not recovered at any time > or = 1 h post inoculation in fluorescein. Feline calicivirus, a nonenveloped virus, was present in fluorescein for 7 days. Equine herpesvirus-4 and feline herpesvirus-1 did not remain infectious in proparacaine at any time > or = 1 h post inoculation, but feline calicivirus was recovered at up to 24 h post inoculation. CONCLUSIONS: Equine herpesvirus-4, feline herpesvirus-1, and feline calicivirus may be readily transmissible via the eyewash solution used in this study. Risk of iatrogenic transmission of the three viruses used in this study was significantly reduced in both fluorescein and proparacaine solutions. Feline calicivirus, the only nonenveloped virus evaluated, remained viable longer in both fluorescein and proparacaine solutions.