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- Author or Editor: Eric C. Ledbetter x
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Abstract
OBJECTIVE
To determine the effects of orally administered raltegravir in cats with experimentally induced ocular and respiratory feline herpesvirus-1 (FHV-1) infection.
ANIMALS
14 healthy 6-month-old unvaccinated specific pathogen–free cats.
PROCEDURES
On day 0, all cats were experimentally inoculated by topical application of 0.1 mL of a solution containing 106 plaque-forming units of FHV-1 strain FH2CS to the inferior conjunctival fornix of each eye. Cats were randomly assigned to receive either raltegravir (80 mg; n = 7) or lactose (250 mg; vehicle; 7), PO, every 12 hours for 14 days beginning on day 1. Cats were assigned clinical ocular and respiratory disease scores every other day from days 0 to 30. Conjunctival swab specimens were collected for detection of FHV-1 by virus isolation and real-time PCR assay at 3-day intervals from days 0 to 30. Confocal microscopy was performed on days 0 and 10 to assess corneal epithelial leukocyte infiltration. The assessed variables and duration of FHV-1 shedding were compared between the 2 treatment groups.
RESULTS
Cats in both groups developed moderate to severe conjunctivitis and ulcerative keratitis characteristic of FHV-1 infection. Median duration of FHV-1 shedding was shorter and signs of ocular and respiratory disease were less severe for raltegravir-treated cats than for vehicle-treated cats. However, the mean conjunctival FHV-1 titer and corneal epithelial leukocyte count did not differ between the 2 groups.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested orally administered raltegravir might be effective for alleviation of ocular and respiratory signs of FHV-1 infection in cats. (Am J Vet Res 2019;80:490–497)
Abstract
OBJECTIVE To determine the effects of topical ocular application of 1% trifluridine ophthalmic solution in dogs with experimentally induced recurrent ocular canine herpesvirus-1 (CHV-1) infection.
ANIMALS 10 specific pathogen–free Beagles.
PROCEDURES 12 months prior to the beginning of the randomized, masked, placebo-controlled 30-day trial, latent ocular CHV-1 infection was experimentally induced in each dog by topical ocular inoculation of both eyes with a field strain of CHV-1. Recurrent ocular CHV-1 infection was induced by oral administration of prednisolone for 7 days (starting day 1). Starting on the fourth day of prednisolone administration, each dog received 1% trifluridine solution or artificial tears (placebo) topically in both eyes 6 times daily for 2 days and then 4 times daily for 12 days. Ophthalmic examinations were performed every 2 days, and ocular disease scores were calculated. Ocular samples for CHV-1 PCR assays and blood samples for clinicopathologic analyses and assessment of CHV-1 serum neutralization antibody titers were collected at predetermined intervals.
RESULTS Conjunctivitis was clinically detected in all dogs by day 4. Compared with dogs receiving placebo, mean and total clinical ocular disease scores were significantly lower and median CHV-1 shedding duration was significantly shorter for the trifluridine-treated dogs. Both groups had increasing CHV-1 serum neutralization antibody titers over time, but no significant differences between groups were detected. Clinicopathologic findings were unremarkable throughout the study.
CONCLUSIONS AND CLINICAL RELEVANCE Topical ocular application of 1% trifluridine ophthalmic solution was well tolerated and effective at reducing disease scores and viral shedding duration in dogs with experimentally induced ocular CHV-1 infection, but may require frequent administration.
Abstract
OBJECTIVE To determine the in vitro half maximal effective concentration (EC50) of ganciclovir for canine herpesvirus-1 (CHV-1) and to evaluate the efficacy of ganciclovir ophthalmic gel in dogs with experimentally induced ocular CHV-1 infection.
ANIMALS 10 specific pathogen–free adult Beagles.
PROCEDURES Cytotoxicity and EC50 of ganciclovir for CHV-1 were determined during in vitro experiments. During an in vivo experiment, dogs with experimentally induced ocular CHV-1 infections received 1 drop of 0.15% ganciclovir (ganciclovir group; n = 5) or artificial tear (control group; 5) ophthalmic gel in both eyes 5 times daily for 7 days, then 3 times daily for 7 days. For each dog, ophthalmic and confocal microscopic examinations were performed at predetermined times to determine severity of ocular disease and inflammation. Conjunctival swab specimens were collected at predetermined times for PCR assay analysis to determine CHV-1 shedding.
RESULTS No in vitro cytotoxic effects were observed for ganciclovir concentrations ≤ 500μM. The EC50 of ganciclovir for CHV-1 was 37.7μM. No adverse effects associated with ganciclovir were observed during the in vivo experiment. Mean ocular disease and inflammation scores for the ganciclovir group were significantly lower than those for the control group. Mean duration of CHV-1 shedding for the ganciclovir group (0.4 days) was significantly shorter than that for the control group (6.2 days).
CONCLUSIONS AND CLINICAL RELEVANCE Topical administration of 0.15% ganciclovir ophthalmic gel was well tolerated and effective in decreasing clinical disease scores, ocular tissue inflammation, and duration of viral shedding in dogs with experimentally induced ocular CHV-1 infection.
Abstract
Objective—To characterize clinical ocular disease, viral shedding, and serologic response associated with primary canine herpesvirus-1 (CHV-1) ocular infection in naïve adult dogs.
Animals—12 specific pathogen-free adult Beagles.
Procedures—Dogs were topically inoculated in the right eye with CHV-1 (infection group; n = 8) or virus-free medium (control group; 4). Dogs were inoculated with or without corneal microtrephination and subconjunctivally administered corticosteroids. Conjunctiva, buffy coat, and serum samples for real-time PCR assay, virus isolation, and serum neutralization (SN) antibody titers were collected until postinfection day (PID) 224, and general physical and ophthalmologic examinations were performed.
Results—Dogs in the infection group developed bilateral, mild to moderate conjunctivitis that reached maximal intensity on PIDs 7 to 10. Ocular viral shedding was detected in all dogs in the infection group between PIDs 3 and 10. Infected dogs developed CHV-1 SN antibody titers, beginning at PID 7 and peaking on PID 21. All buffy coat PCR assay results were negative. Corneal microtrephination and subconjunctival corticosteroid administration did not significantly affect clinical disease or viral shedding. Following recovery from primary infection, dogs remained clinically normal, did not shed virus, and had slowly decreasing SN antibody titers. Dogs in the control group did not develop conjunctivitis, shed virus, or develop CHV-1 SN antibody titers.
Conclusions and Clinical Relevance—Primary ocular infection of adult dogs with CHV-1 was associated with self-limiting conjunctivitis and ocular viral shedding, which was evident in the absence of clinically detectable keratitis or systemic disease. Features of this infection resembled herpes simplex virus primary ocular infection in humans.
Abstract
Objective—To determine the frequency of spontaneous canine herpesvirus-1 (CHV-1) reactivation and ocular viral shedding in latently infected dogs and the effect of topical ocular administration of cyclosporine.
Animals—8 mature Beagles with experimentally induced latent CHV-1 infection.
Procedures—Following induction of primary ocular CHV-1 infection, the presence of reactivatable CHV-1 latency was confirmed by systemically administering prednisolone to the dogs. Dogs were then monitored for 36 weeks via clinical examination and conjunctival sample CHV-1 PCR assay performed at 4-day intervals and CHV-1 virus neutralization antibody assay performed at 2-week intervals. During weeks 16 to 32, dogs were administered 0.2% cyclosporine ointment in both eyes twice daily and blood cyclosporine concentrations were monitored. During weeks 33 to 36, the presence of reactivatable CHV-1 latency was reconfirmed via systemic administration of prednisolone.
Results—Reactivation of latent CHV-1 was not detected via clinical examination or viral shedding during the initial 32 weeks, including before and during topical ocular administration of cyclosporine, and there were no significant differences in CHV-1 virus neutralization titer increases between the study periods. Blood cyclosporine concentrations were less than assay detection limits in all dogs on the sampling days. Systemic administration of corticosteroids repeatedly resulted in ocular disease and viral shedding.
Conclusions and Clinical Relevance—Spontaneous CHV-1 reactivation did not occur frequently in latently infected mature dogs, and this was not altered by topical ocular administration of cyclosporine. This characteristic may be a factor contributing to the lower frequency of recurrent herpetic ocular disease in dogs relative to other host species and their associated alphaherpesviruses.
Abstract
OBJECTIVE
To identify genetic associations with primary glaucoma (PG) in American Cocker Spaniels using a genome-wide association study (GWAS).
ANIMALS
A nationwide ambidirectional case–control cohort study was performed in American Cocker Spaniels that had an ophthalmic examination performed by a veterinarian. Ninety-four dogs with PG (cases) and 111 dogs without glaucoma (controls) met phenotypic criteria and had a blood sample collected after receiving informed owner consent.
PROCEDURES
Genomic DNA was extracted from whole blood samples and genotyped (CanineHD BeadChip, Illumina Inc). A case–control GWAS using a linear mixed model was performed, and 3 significance thresholds were calculated (1) using a Bonferroni correction on all single nucleotide polymorphisms (SNPs) included in the GWAS, (2) using a Bonferroni correction on only the unlinked SNPs from a pruned data set, and (3) using 10,000 random phenotype permutations.
RESULTS
Following genotype data quality control, 89 cases and 93 controls were included in the GWAS. We identified an association on canine chromosome (CFA10); however, it did not reach statistical significance. Potential candidate genes within the surrounding linkage disequilibrium interval include coiled-coil domain containing 85A (CCDC85A) and extracellular growth factor containing fibulin extracellular matrix protein 1 (EFEMP1).
CLINICAL RELEVANCE
Primary glaucoma in the American Cocker Spaniel is a complex heterogeneous disease that may be influenced by a locus on CFA10. The candidate genes CCDC85A and EFEMP1 within the identified linkage disequilibrium interval have been shown to be involved in human open-angle glaucoma.
Abstract
Objective—To determine the in vitro fluoroquinolone susceptibility profiles of Pseudomonas aeruginosa isolates from dogs with ulcerative keratitis.
Animals—27 dogs with P aeruginosa–associated ulcerative keratitis.
Procedures—P aeruginosa isolates from dogs with ulcerative keratitis were collected during a 3-year period. Isolates were tested by use of the disk diffusion method for their susceptibility to 7 fluoroquinolones that are available as commercial ophthalmic preparations. The antimicrobials included second- (ciprofloxacin, ofloxacin, norfloxacin, and lomefloxacin), third- (levofloxacin), and fourth-generation (gatifloxacin and moxifloxacin) fluoroquinolones. Isolates were designated as susceptible, intermediate, or resistant to the various antimicro-bials. The percentage of susceptible isolates was compared among individual fluoroquinolones and among fluoroquinolone generations.
Results—None of the dogs had received topical or systemic fluoroquinolone treatment prior to referral. Twenty-seven P aeruginosa isolates were collected during the study period. In vitro, bacterial resistance to the tested fluoroquinolones was infrequently identified (24/ 27 isolates were susceptible to all fluoroquinolones evaluated); susceptibility percentages ranged from 88.9% to 100% for individual antimicrobials. There were no significant differ-ences among isolate susceptibilities to the individual antimicrobials or among generations of fluoroquinolones.
Conclusions and Clinical Relevance—On the basis of these in vitro data, none of the 7 evaluated fluoroquinolones (individually or collectively by generation) appeared to offer a clinically important advantage in the treatment of P aeruginosa–associated ulcerative keratitis in dogs. Among the P aeruginosa isolates collected from dogs with ulcerative keratitis in this study, the likelihood of susceptibility to the fluoroquinolones evaluated was high.
Abstract
OBJECTIVE
To describe the in vivo confocal microscopy (IVCM) features of the corneal epithelium and stroma in dogs and cats with herpetic dendritic ulcerative keratitis.
ANIMALS
6 client-owned dogs and 10 client-owned cats with herpetic dendritic ulcerative keratitis (affected group) and 10 dogs and 10 cats from specific-pathogen-free laboratory colonies (nonaffected group).
PROCEDURES
After complete ophthalmic examination, IVCM corneal examination was performed on the clinically diseased eyes of animals in the affected group and on both eyes of animals in the nonaffected group. Results by species were compared between groups.
RESULTS
In the affected group, all 6 dogs had unilateral ocular lesions (total, 6 eyes examined), whereas 7 cats had unilateral lesions and 3 cats had bilateral lesions (total, 13 eyes examined). For the nonaffected group, 20 cat eyes and 20 dog eyes were examined. Corneal epithelial morphological abnormalities were identified in all examined eyes of animals in the affected group and in no examined eyes of the nonaffected group. Hyperreflective punctate opacities and inflammatory cells were present in all epithelial layers in examined eyes of affected animals but were absent in nonaffected animals. Similarly, Langerhans cells and anterior stromal dendritic cells were identified in corneas of eyes examined for animals in the affected group but not in any eye of animals in the nonaffected group. Stromal changes were less consistent in the affected group, but absent in the nonaffected group.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that herpetic dendritic ulcerative keratitis in dogs and cats is associated with microanatomic corneal abnormalities that can be detected by IVCM.
Abstract
Objective—To isolate and characterize bacteriophages with strong in vitro lytic activity against various pathogenic Pseudomonas aeruginosa strains isolated from dogs with ocular infections.
Sample—26 genetically distinct P aeruginosa isolates.
Procedures—P aeruginosa strains were derived from dogs with naturally acquired ulcerative keratitis. From a large-scale screening for bacteriophages with potential therapeutic benefit against canine ocular infections, 2 bacteriophages (P2S2 and P5U5) were selected; host ranges were determined, and phage nucleic acid type and genetic profile were identified via enzymatic digestion. Electron microscopy was used to characterize bacteriophage ultrastructure. Bacteriophage temperature and pH stabilities were assessed by use of double-layer agar overlay titration. A cocultivation assay was used to evaluate the effect of the bacteriophages on bacterial host growth.
Results—P5U5 was active against all P aeruginosa isolates, whereas P2S2 formed lytic plaques on plates of 21 (80.8%) isolates. For each bacteriophage, the genomic nucleic acid was DNA; each was genetically distinct. Ultrastructurally, P2S2 and P5U5 appeared likely to belong to the Podoviridae and Siphoviridae families, respectively. The bacteriophages were stable within a pH range of 4 to 12; however, titers of both bacteriophages decreased following heating for 10 to 50 minutes at 45° or 60°C. Growth of each P aeruginosa isolate was significantly inhibited in coculture with P2S2 or P5U5; the dose response was related to the plaque-forming unit-to-CFU ratios.
Conclusions and Clinical Relevance—Bacteriophages P2S2 and P5U5 appear to be good candidates for phage treatment of infection caused by pathogenic P aeruginosa in dogs.
Abstract
CASE DESCRIPTION
A 12-year-old neutered male domestic shorthair cat with chronic anterior uveitis and secondary glaucoma of the right eye was examined for persistent blepharospasm 2 weeks after corneal debridement and grid keratotomy for nonhealing superficial ulcerative keratitis.
CLINICAL FINDINGS
Examination of the right eye revealed a central superficial corneal ulcer associated with corneal epithelial and subepithelial infiltrates and mild aqueous flare. Structures consistent with amoeboid cysts and trophozoites were detected in the cornea by in vivo confocal microscopy. Suppurative keratitis was identified cytologically. An Acanthamoeba spp was isolated through culture and identified by a PCR assay of corneal specimens.
TREATMENT AND OUTCOME
Symptomatic and antiamoebic (polyhexamethylene biguanide 0.02% ophthalmic solution) treatments were instituted. Over the following 6 weeks, the cat lost vision in the affected eye and lesions progressed to nonulcerative stromal keratitis associated with a dense paracentral corneal stroma ring infiltrate and anterior lens luxation. The globe was enucleated, and lymphoplasmacytic sclerokeratitis, anterior uveitis, and retinal detachment were noted. Acanthamoeba organisms were detected within the corneal stroma and anterior sclera with histologic and immunohistochemical stains. The amoebae were classified to the Acanthamoeba T4 genotype by DNA sequencing. The cat had no medical problems attributed to Acanthamoeba infection over 36 months after enucleation, until the cat was lost to follow-up.
CLINICAL RELEVANCE
Naturally acquired Acanthamoeba sclerokeratitis is described in a cat for the first time. Acanthamoeba infection should be considered for cats with superficial corneal disease refractory to appropriate treatments and especially occurring after ocular trauma, including keratotomy.