Objective—To determine whether repeated exposure to clinically relevant concentrations of tricaine methanesulfonate (MS-222) would alter retinal function or induce histologically detectable retinal lesions in koi carp (Cyprinus carpio).
Procedures—2 fish were euthanized at the start of the study, and eyes were submitted for histologic evaluation as untreated controls. Anesthesia was induced in the remaining fish with 200 mg of MS-222/L and maintained with concentrations of 125 to 150 mg/L for a total exposure time of 20 minutes daily on 1 to 13 consecutive days. On days 1, 7, and 13, electroretinography of both eyes was performed in all fish remaining in the study, and 2 fish were euthanized immediately after each procedure for histologic evaluation of the eyes. Median b-wave amplitudes were compared among study days for right eyes and for left eyes via 1-way repeated-measures ANOVA with a Bonferroni correction for multiple comparisons.
Results—Median b-wave amplitudes on days 1, 7, and 13 were 17.7, 20.9, and 17.6 μV, respectively, for right eyes and 15.1, 16.9, and 14.3 μV, respectively, for left eyes. No significant differences in b-wave amplitudes were detected among study days. No histopathologic abnormalities were identified in the retinas of any fish treated with MS-222 or in control fish.
Conclusions and Clinical Relevance—Short-term exposure of koi carp to clinically relevant concentrations of MS-222 daily for up to 13 days was not associated with changes in retinal structure or function as measured in this study.
Objective—To determine the degree of ocular penetration and systemic absorption of commercially available topical ophthalmic solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin following repeated topical ocular administration in ophthalmologically normal horses.
Animals—7 healthy adult horses with clinically normal eyes as evaluated prior to each treatment.
Procedures—6 horses were used for assessment of each antimicrobial, and 1 eye of each horse was treated with topically administered 0.3% ciprofloxacin or 0.5% moxifloxacin (n = 6 eyes/drug) every 4 hours for 7 doses. Anterior chamber paracentesis was performed 1 hour after the final dose was administered, and blood samples were collected at 24 (immediately after the final dose), 24.25, 24.5, and 25 hours (time of aqueous humor [AH] collection). Plasma and AH concentrations of ciprofloxacin or moxifloxacin were determined by use of high-performance liquid chromatography.
Results—Mean ± SD AH concentrations of ciprofloxacin and moxifloxacin were 0.009 ± 0.008 μg/mL and 0.071 ± 0.029 μg/mL, respectively. The AH moxifloxacin concentrations were significantly greater than those of ciprofloxacin. Mean ± SD plasma concentrations of ciprofloxacin were less than the lower limit of quantification. Moxifloxacin was detected in the plasma of all horses at all sample collection times, with a peak value of 0.015 μg/mL at 24 and 24.25 hours, decreasing to < 0.004 μg/mL at 25 hours.
Conclusions and Clinical Relevance—Moxifloxacin was better able to penetrate healthy equine corneas and reach measurable AH concentrations than was ciprofloxacin, suggesting moxifloxacin might be of greater value in the treatment of deep corneal or intraocular bacterial infections caused by susceptible organisms. Topical administration of moxifloxacin also resulted in detectable plasma concentrations.
Case Description—A 12-year-old castrated male mixed-breed dog was evaluated because of blepharospasm and blindness affecting both eyes.
Clinical Findings—During examination and diagnostic testing of the dog, fine-needle aspirates of splenic nodules were examined microscopically and stage Vb multicentric large-cell lymphosarcoma was identified. Aqueocentesis was performed, and sample analysis revealed intraocular lymphosarcoma; B-cell neoplasia was confirmed by use of a PCR assay for antigen receptor rearrangement (PARR) performed on samples of aqueous humor. Secondary uveitis and glaucoma were detected bilaterally in addition to chronic superficial corneal ulcerations in the left eye.
Treatment and Outcome—Treatment for abdominal and intraocular lymphosarcoma involving administration of vincristine, l-asparaginase, cyclophosphamide, doxorubicin, and prednisone was initiated. Secondary uveitis and glaucoma were controlled with topical treatment; however, the corneal ulceration did not resolve. Seven weeks following diagnosis, the dog died as a result of complications related to systemic neoplasia and chemotherapy.
Clinical Relevance—In the dog of this report, intraocular lymphosarcoma was diagnosed via PARR performed on samples of aqueous humor. Moreover, the immunophenotype of the neoplastic cells was determined by use of that diagnostic technique. Because secondary uveitis is a common finding in dogs and cats with systemic lymphosarcoma, intraocular lymphosarcoma should be considered as a differential diagnosis; furthermore, investigation (eg, PARR performed on aqueous humor samples) to identify the presence of intraocular lymphosarcoma is warranted, thereby allowing targeted interventions to be considered in management of those patients.
Objective—To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses.
Animals—11 healthy adult horses.
Procedure—Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured.
Results—Mean ± SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 ± 0.37 μg/mL, 2.35 ± 0.78 μg/mL, and 2.40 ± 0.29 μg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean ± SD voriconazole concentration in AH after a single orally administered dose was 0.86 ± 0.22 μg/mL.
Conclusions and Clinical Relevance—Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.
Objective—To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses.
Animals—10 client-owned horses with IMMK.
Procedures—Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained). Equine IgG, IgM, and IgA antibodies were used to detect corneal immunoglobulin via direct immunofluorescence (10 eyes). Serum and aqueous humor (AH) samples from 3 horses with IMMK were used to detect circulating and intraocular IgG against corneal antigens via indirect immunofluorescence on unaffected equine cornea.
Results—Percentage scores (scale, 0 to 4) of cells expressing CD3 (median, 2.35 [range, 0.2 to 3.7]; mean ± SD, 2.36 ± 1.08) were significantly greater than scores of cells expressing CD79a (median, 0.55 [range, 0 to 1.5]; mean, 0.69 ± 0.72). All samples stained positively for CD4- and CD8-expressing cells, with no significant difference in scoring. All samples stained positively for IgG, IgM, and IgA. No serum or AH samples collected from horses with IMMK reacted with unaffected equine cornea.
Conclusions and Clinical Relevance—Pathogenesis of superficial stromal IMMK included cell-mediated inflammation governed by both cytotoxic and helper T cells. Local immunoglobulins were present in affected corneas; however, corneal-binding immunoglobulins were not detected in the serum or AH from horses with IMMK.