Effect of once daily topical 0.3% naltrexone on tear parameters and corneal sensitivity in dogs with uncontrolled keratoconjunctivitis sicca: a double-masked randomized placebo-controlled clinical trial.

OBJECTIVE: To determine the effect of once daily topical 0.3% naltrexone (NTX) on tear production, tear film breakup time (TFBUT), and corneal sensitivity in dogs with uncontrolled keratoconjunctivitis sicca (KCS). ANIMALS STUDIED: Sixteen dogs with uncontrolled KCS. PROCEDURES: A randomized placebo-controlled trial was performed in 16 dogs with topical 0.3% NTX once daily or topical saline solution drops once daily. A baseline was obtained at week 0 for tear production (Schirmer tear test 1 and 2-STT1, STT2), TFBUT, and corneal sensitivity. STT1, STT2, and TFBUT were then subsequently measured at weeks 1, 2, and 4 while on NTX or saline drops. Corneal sensitivity measures were repeated at week 4. The drops were subsequently discontinued and all parameters rechecked at week 5. RESULTS: There was no statistically significant difference in tear parameters or corneal sensitivity between the NTX-treated and the saline-treated groups. CONCLUSION: Topical 0.3% NTX given as a once daily dose over 4 weeks did not alter tear production, tear film stability, or corneal sensitivity in dogs with uncontrolled KCS.

Effect of topical naltrexone 0.3% on corneal sensitivity and tear parameters in normal brachycephalic dogs.

OBJECTIVE: To determine the effect of topical naltrexone 0.3% on tear production, corneal sensitivity, and tear film stability in normal brachycephalic dogs. ANIMALS STUDIED: Twenty-two normal brachycephalic dogs. PROCEDURES: Measurements of tear production (Schirmer tear test I and II), intraocular pressure (IOP), central corneal sensitivity (CS), and tear film breakup time (TFBUT) were collected at time 0, 1, and 24 h after administration of either naltrexone (NTX) 0.3% or placebo (SV). Naltrexone or SV was then administered once daily for 1 week, and the above measurements were repeated at 7 days, then again 7 days after discontinuing medication. Owners scored the degree of comfort, redness, rubbing, squinting, and tearing. Serum was collected at time 0, 1, 24 h, and 7 days to determine systemic concentrations. RESULTS: Owners reported no significant change in the degree of comfort, redness, rubbing, squinting, or tearing. Naltrexone was detected in serum of all treated dogs 1-h postadministration (average: 908 pg/mL, range: 319-1570 pg/mL) and in two dogs at the 1-week time point. Naltrexone was not detected at the 24-h time point. There was no significant effect of NTX on STT1, STT2, IOP, CS, or TFBUT. CONCLUSIONS: Naltrexone 0.3% is well tolerated and safe when applied topically to the eye once daily. Naltrexone 0.3% did not show any significant effects on corneal parameters as measured in this study. At once, daily dosing NTX is systemically absorbed; however, the degree of systemic absorption is not likely to be clinically significant.

Histologic evaluation of the immediate effects of diamond burr debridement in experimental superficial corneal wounds in dogs.

PURPOSE: To evaluate the corneal changes immediately after diamond burr debridement of superficial corneal wounds in dogs. Spontaneous chronic corneal epithelial defects (SCCEDs) are the most common form of canine recurrent corneal ulcers. The diamond burr has been used in the management of corneal lesions in humans since 1983. Recently, it has been successfully used in the treatment of SCCEDs in dogs; however, little has been documented as to its mechanism of action. METHODS: Five adult female research dogs euthanized for reasons unrelated to the study were included, providing 10 normal eyes. An excimer laser spatula was used for epithelial removal after delineation with an 8 mm punch biopsy trephine. Diamond burr debridement was performed for 30 and 45 s in five eyes each (groups 1 and 2 respectively). The procedure was performed on the ventral half of the experimental defect as well as ventral normal cornea, immediately after euthanasia, and prior to enucleation. Samples were processed routinely for histologic evaluation and stained with periodic acid-Schiff. RESULTS: No stromal defects could be identified under light microscopy. In experimental corneal wounds, multi-focal areas remained covered by the epithelial basement membrane (BM) after diamond burr treatment in both groups (group 1 = 48% ± 16SD, group 2 = 26% ± 12SD). Removal of BM on group 2 was significantly higher than group 1 (P < 0.05). CONCLUSIONS : The diamond burr allows a safe method of debridement and does not create defects beyond the epithelial BM in corneal wounds in normal dogs. Evaluation of the diamond burr debridement in cases of SCCEDs is warranted.

Evaluation of the ocular penetration of topical alpha-luminol (Galavit®/GVT®).

PURPOSE: Oxidative stress plays a major role in the pathogenesis of many neurodegenerative diseases. It has also been implicated as part of the pathogenic mechanisms in the development of glaucoma. Alpha-luminol has shown profound anti-inflammatory and antioxidant effects in both experimental animal and human clinical studies. The purpose of this pilot study was to investigate for the first time the ocular penetration of topical alpha-luminol. METHODS: Nine animals were divided into three treated groups (three animals each; one drop OU/n = 18), each group receiving a different concentration of the eyedrop (0.5%, 1.5%, 2.5%). Aqueous humor and peripheral blood samples were obtained from each rabbit at three different timepoints (20 min, 4 h and 12 h). Samples were analyzed by means of high performance liquid chromatography and mass spectrometry; median values were compared. RESULTS: Alpha-luminol was found in the aqueous humor in all treated groups at all timepoints. At the 2nd and 3rd timepoints (4 h and 12 h), aqueous humor levels decreased significantly (P < 0.05) for two of the three dosages tested and it was not detectable in some eyes. The highest aqueous humor concentration of the drug was 272 ng/mL after 20 min (0.0217% of one drop, 2.5% group). Alpha-luminol was found in the vitreous in two animals, one in the 1.5% and another in the 2.5% group (16.4 and 21.5 ng/mL, respectively), at 12 h. CONCLUSIONS: Topically administered alpha-luminol readily penetrates into the anterior chamber and can penetrate into the vitreous chamber. Further investigation is warranted to better understand the intraocular pharmacokinetics of alpha-luminol.

Iridociliary melanoma with secondary lens luxation: distinctive findings in a long-horned cowfish (Lactoria cornuta).

This report describes a long-horned cowfish, which was diagnosed with buphthalmia and lens sub-luxation in the right eye, conditions that progressed to complete anterior lens luxation and secondary keratoconus. Three months after the initial evaluation, a pigmented mass was observed protruding from the vitreous. An enucleation was performed under general anesthesia. Ocular histopathology revealed an iridociliary melanoma. Reports of intraocular melanomas are extremely rare in fish. To the authors' knowledge, this is the first report of an iridociliary melanoma that led to buphthalmia, lens luxation, and keratoconus in a fish. Histological findings of lens luxation are also demonstrated. Due to the presence of a complex suspensory apparatus involving the teleost lens, this report speculates that lens luxation is a more devastating disease process in teleosts than in mammals.

Prevalence of serum antibodies against Bartonella species in the serum of cats with or without uveitis.

Bartonella henselae has been implicated as a causative agent of chronic uveitis in people and in some cats. The objective of this study was to determine whether Bartonella species seroprevalence or titer magnitude varies among cats with uveitis, cats without ocular diseases recorded and healthy cats, while controlling for age and risk of flea exposure based on state of residence. There was no difference in seroprevalence rates or titer magnitude between cats with uveitis and cats with non-ocular diseases. Healthy cats were more likely to be seropositive for Bartonella species than cats with uveitis. The median Bartonella species titer was 1:64 for all groups, although healthy cats were more likely to have higher titers than cats with uveitis and cats with non-ocular disease. The results suggest that serum antibody tests alone cannot be used to document clinical uveitis associated with Bartonella species infection.

Effect of topical ophthalmic application of cidofovir on experimentally induced primary ocular feline herpesvirus-1 infection in cats.

OBJECTIVE: To evaluate the efficacy of twice-daily ophthalmic application of 0.5% cidofovir solution in cats with experimentally induced primary ocular feline herpesvirus-1 (FHV-1) infection. ANIMALS: Twelve 6-month-old sexually intact male cats. PROCEDURES: Cats were randomly assigned to either a treatment or control group. Ocular infection with FHV-1 was induced (day 0) in all cats via inoculation of both eyes with 10(4) plaque-forming units of a plaque-purified FHV-1 field strain. Twice daily for 10 days beginning on day 4 after virus inoculation, the treatment group received 1 drop of 0.5% cidofovir in 1% carboxymethylcellulose in both eyes, and the control group received 1 drop of 1% carboxymethylcellulose in both eyes. A standardized scoring method was used to evaluate clinical signs of FHV-1 infection in each cat once daily for 24 days. The amount of ocular viral shedding was assessed by use of a quantitative real-time PCR procedure every 3 days during the study period. Clinical scores and viral quantification were averaged over the pretreatment (days 0 to 3), treatment (days 4 to 14), and posttreatment (days 15 to 24) periods for each cat. RESULTS: During the treatment period, clinical scores and amount of viral ocular shedding were significantly lower in the treatment group, compared with findings in the control group. CONCLUSIONS AND CLINICAL RELEVANCE: Twice-daily application of 0.5% cidofovir solution in both eyes significantly decreased the amount of viral shedding and the severity of clinical disease in cats with experimentally induced ocular FHV-1 infection.

Prevalence of feline herpesvirus 1, Chlamydophila felis, and Mycoplasma spp DNA in conjunctival cells collected from cats with and without conjunctivitis.

OBJECTIVE: To use PCR assays to determine the prevalence of feline herpesvirus 1 (FHV-1), Chlamydophila felis, and Mycoplasma spp DNA in conjunctival cells collected from cats with and without conjunctivitis; to compare results of conventional and real-time fluorogenic PCR assays for amplification of FHV-1 DNA; and to determine whether copy numbers of FHV-1 DNA are correlated with conjunctivitis. ANIMALS: 55 cats with active conjunctivitis, 39 healthy cats that never had conjunctivitis, and 32 cats with a history of conjunctivitis that had been resolved for at least 3 months. PROCEDURES: Samples were obtained by rolling cotton-tipped applicators on the ventral conjunctiva of awake cats treated topically with proparacaine. The DNA was extracted from the swab specimens and assessed in PCR assays to detect DNA of FHV-1 (fluorogenic PCR assay and conventional PCR assay), Mycoplasma spp (conventional PCR assay), and C felis (conventional PCR assay). RESULTS: Overall prevalence rates of FHV-1, C felis, and Mycoplasma spp as assessed by the conventional PCR assays were 6.7%, 3.2%, and 9.6%, respectively. Percentage concordance between conventional PCR and fluorogenic PCR assays for FHV-1 was 92.5%. There were no significant differences among the 3 groups of cats for the mean copy number of FHV-1 divided by the copy number of glyceraldehyde-3-phosphate dehydrogenase. CONCLUSIONS AND CLINICAL RELEVANCE: Mycoplasma spp were the most prevalent organism detected and was associated with conjunctivitis. This study could not confirm that there are increased copy numbers of FHV-1 DNA in cats with conjunctivitis, compared with the copy numbers for cats without conjunctivitis.

Evaluation of retinal images for identifying individual dogs.

OBJECTIVE: To F whether vessels in the ocular fundus changed over the lifetime of Beagles and whether any changes were substantial enough to likely preclude positive identification of individual dogs by use of their retinal vascular patterns. ANIMALS: 18 Beagles. PROCEDURES: Fundic photographs of both eyes of 18 Beagles taken at 1 or 3, 5, and 7 or 9 years of age were digitalized. Photographs were analyzed by use of 2 software programs. One was used to determine vessel numbers and widths and the other to determine the locations of the 3 largest vessels. Measurements were compared over time periods in the life of each dog. Only observations made at baseline (1 or 3 years of age) and again at 5 and 9 years of age were included in the statistical analysis, as these points were common to all dogs. RESULTS: No significant changes in numbers or locations of the blood vessels were detected over time. Widths of the vessels decreased significantly as the dogs aged. CONCLUSIONS AND CLINICAL RELEVANCE: The ocular fundus of Beagles changed over each dog's lifetime in that the retinal blood vessels became smaller but did not change in number or location. Results suggest that digitalized retinal images can likely be used to identify dogs over their lifetimes.

Depletion of taurine and glutamate from damaged photoreceptors in the retinas of dogs with primary glaucoma.

OBJECTIVE: To determine whether taurine and glutamate contents are reduced in damaged photoreceptors in dogs with primary glaucoma (PG) in a manner consistent with an ischemia-like release of both of these amino acids from damaged cells. SAMPLE POPULATION: Retinas from 6 dogs with PG and 3 control dogs. PROCEDURE: Serial, semithin sections of each canine retina were stained with toluidine blue to identify damaged photoreceptors or via immunogold techniques to quantify taurine and glutamate content in retinal cells. RESULTS: Regions with a thin outer nuclear layer and pathologic nuclear changes in photoreceptors were evident in retinas of dogs with PG. The density of immunostaining for taurine in damaged photoreceptors was significantly reduced to (mean +/- SEM) 37.5 +/- 2.6% of the density in adjacent undamaged photoreceptors. Photoreceptors with decreased taurine immunostaining also had decreased glutamate immunostaining, consistent with ischemia-like release of both of these amino acids from damaged cells. Immunostaining for glutamate, but not taurine, was increased in presumptive radial glial cells (i.e., Miller cells) in damaged regions, consistent with an ischemia-induced redistribution of amino acids in dogs with PG. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal damage in dogs with PG includes ischemia-like losses of taurine and glutamate from photoreceptors and accumulation of glutamate, but not taurine, in nearby Müller cells. These changes are consistent with glutamate release and depletion of intracellular taurine in damaged regions, perhaps contributing to progressive damage in these areas.

Evaluation of glutamate loss from damaged retinal cells of dogs with primary glaucoma.

OBJECTIVE: To determine whether retinal damage in dogs with primary glaucoma (PG) is consistent with ischemia-induced glutamate toxicosis. SAMPLE POPULATION: Retinal tissue sections from 25 dogs with PG and 12 normotensive control dogs. PROCEDURE: Retinal sections from control and glaucomatous dogs were stained for morphometric and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analyses to determine whether retinal damage was consistent with glutamate toxicosis. Immunohistochemical analysis was performed to detect ischemia-like loss of glutamate from neurons in damaged areas. RESULTS: In severely damaged glaucomatous retinas, all neurosensory layers had focal regions that were thin or disrupted. There was less thinning of the outer nuclear layer (ONL) and inner nuclear layer (INL) in moderately damaged retinas than in severely damaged retinas. Acute signs of damage in the INL included cells with dark, condensed chromatin and lightly stained cytoplasm interspersed with a few TUNEL-positive cells, which was consistent with glutamate toxicosis. Glutamate immunoreactivity was reduced in thin areas and in damaged cells of the INL and ONL, which was consistent with glutamate release in damaged areas. Glutamate immunoreactivity was increased in putative Müller cells in damaged areas, which also was consistent with glutamate release. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal damage in dogs with PG differs in intensity in focal areas. Damage in affected regions resembles damage induced by glutamate. Glutamate is lost from damaged neurons and accumulates in Müller cells, which is consistent with increased glutamate release contributing to the damage. Glutamate antagonists may protect INL cells in dogs with glaucoma.

Bartonella species, feline herpesvirus-1, and Toxoplasma gondii PCR assay results from blood and aqueous humor samples from 104 cats with naturally occurring endogenous uveitis.

Toxoplasma gondii, Bartonella henselae and feline herpesvirus-1 (FHV-1) have been implicated as causative agents in feline uveitis. The usefulness of serum and aqueous humor (AH) antibody testing for these agents is limited as antibodies can be detected in both healthy cats and cats with uveitis. Very few studies using polymerase chain reaction (PCR) assays to amplify organism DNA from samples from cats with uveitis have been performed. In this study, assays to detect T gondii antibodies, feline leukemia virus antigen, feline immunodeficiency virus antibody, and Bartonella species antibodies were performed on serum and PCR assays for amplification of T gondii, Bartonella species, and FHV-1 DNA were performed on blood and AH samples from 104 cats with endogenous uveitis and 19 healthy cats. Results suggest the addition of the PCR assay to the diagnostic work-up for cats with uveitis will increase the detection of T gondii and FHV-1; however, the diagnostic usefulness of these additional data is not clear.

Bilateral nasolacrimal duct atresia in a cria.

A 2-month-old, male alpaca had a 1-month history of mucoid ocular discharge from the left eye. Signalment, history and clinical findings were suggestive of a congenital nasolacrimal outflow obstruction. A dacryocystorhinogram confirmed bilateral nasolacrimal duct atresia, which involved the distal half of both nasolacrimal ducts. In order to establish alternative outflow, a conjunctivomaxillosinusotomy and conjunctivorhinostomy were performed on the right and left eye, respectively. The surgical openings remain patent after 11 months, and there have been no clinical signs of nasolacrimal disease.

Retinal pigment epithelial damage, breakdown of the blood-retinal barrier, and retinal inflammation in dogs with primary glaucoma.

OBJECTIVE: This paper aims to determine if abnormalities of the retinal pigment epithelium (RPE) and retinal inflammation occur in primary glaucoma. PROCEDURE: Twenty-three canine globes with primary glaucoma, goniodysgenesis, and elevated intraocular pressure were evaluated. Sections from 6 control and 23 glaucomatous canine globes were stained with hematoxylin and eosin, Griffonia simplicifolia isolectin B4, or immunohistochemically stained for CD3 or albumin. The retinal sections were evaluated with light microscopy for morphological and immunohistochemical evidence of pigmentary changes and inflammation. RESULTS: Abnormal pigmented cells including displaced RPE cells and macrophages (identified by lectin binding) were found in the neuroretinas and vitreous bodies of glaucomatous eyes. Other abnormalities included hypertrophy of RPE cells and loss of RPE continuity. Regions of neuroretina with more displaced pigment had fewer remaining neurons. Signs of retinal inflammation found in glaucomatous eyes included infiltration with leukocytes, retinal swelling, and albumin leakage from vessels. Accumulation of perivascular CD3-positive T lymphocytes also occurred in glaucomatous retinas. Chronic glaucomatous retinas had increased pigmentary changes, fewer neutrophils, and less swelling than acute glaucomatous retinas. CONCLUSIONS: Disruption of the RPE, increased permeability of the vascular endothelium, accumulation of inflammatory cells, and retinal swelling or thinning occur in canine primary glaucoma. The displacement of pigment and accumulation of inflammatory cells in the neuroretina suggests that inflammation may be an important contributor to retinal damage.

Primary closure of the corneas of two Great Horned owls after resection of nonhealing ulcers.

Two Great Horned owls were presented to the Colorado State University Veterinary Teaching Hospital for evaluation of corneal lesions. Each bird had a corneal ulcer and bullous keratopathy. Following unsuccessful attempts at medical and surgical management, the corneal defects in each bird were treated with penetrating keratoplasties and conjunctival pedicle grafts. In each bird the cornea healed well and regained approximately its normal shape. Both birds fully recovered and have been released into the wild.

Aqueous misdirection and ciliary block (malignant) glaucoma after cataract removal in a llama.

Ciliary block (malignant) glaucoma is caused by the posterior flow of aqueous humor into or behind the vitreous. It is a rare complication of anterior segment surgery in humans. This is a report of ciliary block glaucoma occurring as a postoperative complication of cataract surgery in a llama. Medical management was ineffective in lowering intraocular pressure (IOP). Posterior capsulotomy and anterior hyaloid disruption with a 22-gauge needle, in addition to medical management maintained IOP in the normal range until anterior vitrectomy could be performed. After vitrectomy, glaucoma resolved and medical treatment was no longer necessary.

Treatment of granulomatous meningoencephalomyelitis in a dog.

The clinical work-up, diagnosis and follow-up of an 8-year-old, female-spayed Shih Tzu with diffuse, granulomatous meningoencephalomyelitis (GME)-causing visual deficits is reported. The use of cytosine arabinoside as an alternative treatment for GME is discussed.

Ultrasound biomicroscopy of the feline anterior segment.

Ultrasound biomicroscopy was performed on enucleated feline globes as a model for use in vivo. Quantitative measurements were obtained from the anterior segment using a 50-MHz transducer. Mean values from 26 feline globes were axial corneal thickness, 0.74 mm; anterior chamber depth, 4.20 mm; distance from the first ciliary process to the limbus, 3.17 mm; angle recess, 0.38 mm; angle opening distance, 1.05 mm; iris base width 0.38 mm; iris middle width 0.52 mm; iris tip width 0.13 mm, and iris-lens overlap, 0.69 mm. Distinctive features of the feline anterior segment include a relatively wide iridocorneal angle and deep anterior chamber.

Idiopathic ocular and nasal granulomatous inflammatory disease in a dog.

A young female Akita presented for ocular and nasal lesions. Examination showed bilateral 360 degree limbal masses that extended onto the peripheral cornea. In addition, intranasal granulomatous masses were observed by rhinoscopy. Histopathologic examination with immunohistochemical staining showed that these masses were almost identical and were classified as an idiopathic, T-cell rich, granulomatous inflammation. The dog responded well to anti-inflammatory medication and the disease remains in remission 2 years after the initial presentation.