Feline herpesvirus type 1 (FHV-1) is a common and important cause of ocular surface disease, dermatitis, respiratory disease, and potentially intraocular disease in cats. Many antiviral drugs developed for the treatment of humans infected with herpesviruses have been used to treat cats infected with FHV-1. Translational use of drugs in this manner ideally requires methodical investigation of their in vitro efficacy against FHV-1 followed by pharmacokinetic and safety trials in normal cats. Subsequently, placebo-controlled efficacy studies in experimentally inoculated animals should be performed followed, finally, by carefully designed and monitored clinical trials in client-owned animals. This review is intended to provide a concise overview of the available literature regarding the efficacy of antiviral drugs and other compounds with proven or putative activity against FHV-1, as well as a discussion of their safety in cats.

Objective

To determine reference values, intertest correlations, and test-retest repeatability of Schirmer tear test 1 (STT-1), phenol red thread test (PRTT), tear film breakup time (TFBUT), tear osmolarity, and meibometry in healthy cats.

Design

Evaluation study.

Animals

135 healthy domestic cats aged 0.5 to 12.8 years.

Procedures

Each test was performed once in 120 cats and repeated in 40. Pearson correlation was used to assess correlation among tests. Intraclass correlation coefficients (ICCs) and 95% limits of agreement (LOA) were used to evaluate test-retest repeatability.

Results

Median (95% central range) values were 18 mm/min (9 to 34 mm/min) for STT-1, 29 mm/15 s (15 to 37 mm/15 s) for PRTT, 12.4 seconds (9.1 to 17.7 seconds) for TFBUT, 322 mOsm/L (297 to 364 mOsm/L) for osmolarity, and 32 meibometry units (MU; 11 to 114 MU) for peak meibometry value. The STT-1 and PRTT values were positively correlated. Age was weakly associated with TFBUT and osmolarity. Meibometry measurements were higher for strips that contacted the tear film (285 MU) than for those that touched the eyelid margin only (32 MU). All ICCs were < 0.75, and 95% LOA were wide.

Conclusions and clinical relevance

Tear deficiency should be suspected in cats with STT-1 < 9 mm/min, PRTT < 15 mm/15 s, or TFBUT < 9 to 10 seconds. Generally poor correlation among tests suggested that thorough tear film analysis requires performance of multiple tests in concert. Relatively poor test-retest repeatability should be considered when repeated tests are used to monitor tear film dysfunction and response to treatment.

Objective

The aim of this study was to evaluate goblet cell density (GCD) and distribution in cats without clinical evidence of ocular surface disease and without histologic evidence of conjunctival disease.

Animals studied

Fourteen Domestic Shorthair cats euthanized for reasons unrelated to this study.

Procedures

Before euthanasia, cats were verified using slit-lamp biomicroscopy and fluorescein staining to be free of eyelid or ocular surface abnormalities. Immediately after euthanasia, bilateral conjunctival specimens including third eyelid (TEL) were collected, routinely processed, and stained with periodic acid-Schiff and hematoxylin and eosin. Thirteen conjunctival regions were identified. For each region, GCD was expressed as the percentage of goblet cells/200 basal epithelial cells.

Results

Mean GCD ranged widely by region: anterior surface of the TEL = 48.8%, fornicial regions = 47.0%, palpebral regions = 38.5%, bulbar regions = 19.6%, and posterior surface of the TEL = 12.6%. The anterior surface of the TEL had significantly higher GCD than did the bulbar and the palpebral regions, but not the fornicial regions. Bulbar conjunctiva had significantly lower GCD than did all other conjunctival regions except the posterior surface of the TEL. No significant difference was noted between GCD of male versus female cats, dorsal versus ventral regions, or lateral versus medial regions.

Conclusions

Although conjunctival GCD ranged widely by region, the anterior surface of the TEL appears to be an excellent location for assessing conjunctival goblet cells in cats because this area has high GCD and is more readily accessible than is the palpebral, fornicial, or bulbar conjunctiva.

Objectives

The aim of this study was to assess the effects of famciclovir administration in cats with spontaneously acquired acute upper respiratory tract disease.

Methods

Twenty-four kittens with clinical signs of acute upper respiratory tract disease were randomly allocated to receive doxycycline (5 mg/kg PO q12h) alone (group D; n = 12) or with famciclovir (90 mg/kg PO q12h; group DF; n = 12) for up to 3 weeks. Clinical disease severity was scored at study entry and daily thereafter. Oculo-oropharyngeal swabs collected at study entry and exit were assessed using quantitative PCR for nucleic acids of feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica and Mycoplasma felis.

Results

The median (range) age of cats was 1.5 (1-6) months in group D vs 1.6 (1-5) months in group DF (P = 0.54). Pathogens detected in oculo-oropharyngeal swabs at study entry included FCV (n = 13/24; 54%), M felis (n = 8/24; 33%), FHV-1 (n = 7/24; 29%), C felis (n = 7/24; 29%) and B bronchiseptica (n = 3/24; 12%). Median (range) duration of clinical signs was 11.5 (3-21) days in group DF and 11 (3-21) days in group D (P = 0.75). Median (range) total disease score at the end of the study did not differ between groups (group D 1 [1-1] vs group DF 1 [1-3]; P = 0.08).

Conclusions and relevance

This study revealed no significant difference in response to therapy between cats treated with doxycycline alone or with famciclovir; cats improved rapidly in both groups. However, identification of FHV-1 DNA was relatively uncommon in this study and clinical trials focused on FHV-1-infected cats are warranted to better evaluate famciclovir efficacy.

Objective

To evaluate diagnostic utility of aqueous humor analysis in animals with anterior uveitis.

Animals

Client-owned dogs (n = 12) and cats (n = 10).

Procedures

Examination findings and diagnostic test results including aqueous humor cytology were compared.

Results

Disease duration prior to aqueocentesis was not significantly different between dogs with idiopathic anterior uveitis and those with an etiologic diagnosis, but was shorter in cats with feline infectious peritonitis (FIP) than those with idiopathic uveitis. Microbial nucleic acids, antigens, or antibodies against them were seldom found in blood/serum; however, serum feline coronavirus titers ≥1:6400 were detected only in cats with FIP. Aqueous humor cytology was diagnostic in no cats and two dogs, both with neoplasia. Although aqueous humor contained predominantly neutrophils in cats with FIP and large reactive lymphocytes and plasma cells appeared more frequent in cats with idiopathic uveitis, neither clinical nor cytologic assessment of anterior chamber contents differed significantly between cats with idiopathic or FIP-associated uveitis. Cytologically assessed plasma cell number was correlated with keratic precipitates and disease duration. Clinically detectable hyphema and cytologic erythrocyte number were correlated. However, cytologic cell grades and clinical grade of flare or cell numbers within the anterior chamber were not correlated.

Conclusions

Aqueous humor cytology permitted diagnosis of neoplasia in dogs with anterior uveitis but was generally not helpful in cats. Poor correlation between clinical and cytologic assessment of cell numbers and type within the anterior chamber dictates that clinical grading should not be the sole criterion for electing to perform aqueocentesis.

Objective

To determine histologic and immunohistochemical predictors of metastasis of feline diffuse iris melanoma (FDIM).

Animals

Globes from 47 client-owned cats enucleated for FDIM between January 1985 and December 2013.

Procedures

Hematoxylin and eosin-stained sections were evaluated for neoplastic invasiveness and cell morphology, necrosis within the neoplasm, inflammation, and glaucoma. Sections were immunolabeled with antibodies against melan-A, PNL2, E-cadherin, or B-Raf, and label intensity, percentage of labeled cells, and label homogeneity were semi-quantitatively graded. Medical records were evaluated, and referring veterinarians and clients were contacted to determine whether cats developed metastasis following enucleation. The log-rank test or Cox proportional hazards model was used to determine associations between histologic or immunohistochemical parameters and metastasis.

Results

Metastasis was suspected or confirmed in 9/47 (19%) cats. Extrascleral extension, necrosis within the neoplasm, a mitotic index of >7 mitoses in 10 high-power (×400) fields, choroidal invasion, and increased E-cadherin and melan-A label intensity were each associated with increased rate of metastasis. PNL2 label homogeneity was associated with decreased rate of metastasis. Decreased PNL2 label intensity and an increasing percentage of neoplastic cells labeled for melan-A each approached significance for increased rate of metastasis.

Conclusions

We report four histologic and three immunohistochemical parameters helpful in determining cats at risk of metastasis of FDIM. Further studies should determine if B-Raf mutations identified in human malignant melanomas are found in cats with FDIM and assess benefits of adjunctive therapy following enucleation of eyes with FDIM bearing poor prognostic indicators.

Objective

To describe the clinical, gross pathologic, and histopathologic findings for a visually impaired 5.8-year-old female alpaca with multiple ocular abnormalities, as well as the clinical findings for three closely related alpacas.

Animals studied

Four alpacas.

Procedures

Ophthalmic examination was performed on a 16-month-old female alpaca following observation of visual impairment while hospitalized for an unrelated illness. Following acute systemic decline and death 4.5 years later, the alpaca's brain, optic nerves, and eyes were examined grossly and histologically. Ophthalmic examination of three closely related alpacas was subsequently performed.

Results

The 16-month-old female alpaca (Alpaca 1) had ophthalmoscopic findings suggestive of a coloboma or hypoplasia of the retinal pigment epithelium (RPE) and choroid, and suspected optic nerve hypoplasia OU. Histopathology performed 4.5 years later revealed moderate to severe choroidal, RPE, and retinal hypoplasia with multifocal retinal detachments OU. However, the optic nerves were normal in size and histologic appearance when compared to an age-matched control. Clinical evaluation of the 2-year-old son of Alpaca 1 revealed iris colobomata OU and choroidal dysplasia/hypoplasia OD in addition to nonpathologic variations in melanin density including heterochromia iridis and a subalbinotic fundus OU. Clinical evaluation of the 13-year-old mother of Alpaca 1 revealed heterochromia iridis, cataracts, and a subalbinotic fundus OU. A 2-year-old half-brother of Alpaca 1 had an RPE and choroidal coloboma OS.

Conclusion

The developmental ocular abnormalities diagnosed in these closely related alpacas are likely hereditary.

Objectives

The aim of this study was to evaluate changes in the conjunctival microbiota of shelter-housed cats with time, upper respiratory disease (URD) and famciclovir administration.

Methods

Cats were assigned to treatment groups on shelter entry. Healthy cats or cats with URD received ~30 mg/kg or ~90 mg/kg of famciclovir or placebo PO q12h for 7 days, or were untreated. Swabs were collected from ventral conjunctival fornices prior to (day 1) and immediately after (day 8) the treatment period. Microbiota analysis was conducted on 124 randomly selected swabs from healthy (56 swabs) or URD-affected (68 swabs) cats. Following DNA extraction and amplification of the V4 region of the 16S rRNA gene, sequences were assembled into operational taxonomic units (OTUs). Over-represented OTUs (as determined by linear discriminate analysis effect size), alpha and beta diversity, and median relative abundance of known feline ocular surface pathogens were assessed for the entire population and in 10 clinically relevant subpopulations of cats.

Results

Bacteria from 33 phyla and 70 genera were identified. Considering all cats, median relative abundance of Mycoplasma increased from day 1 to day 8, while Proteobacteria decreased. Community membership and structure (beta diversity) differed between days 1 and 8 for all famciclovir-treated cats (regardless of health status or dose) and healthy or URD-affected cats (regardless of famciclovir dose). Differences in taxonomic diversity within a sample (alpha diversity) between day 1 and day 8 were not detected in any subpopulations.

Conclusions and relevance

Within 1 week of shelter entry, there were significant changes in community structure and membership of the feline conjunctival microbiota, with a shift towards over-representation of feline ocular surface pathogens. Although famciclovir may impact beta diversity of the feline conjunctival microbiota, absence of change in alpha diversity suggests minimal shift in individual cats.