Comparison of the TONOVET Plus®, TonoVet®, and Tono-Pen Vet™ tonometers in normal cats and cats with glaucoma.

OBJECTIVES: To determine the accuracy, precision, and clinical applicability of the ICare® TONOVET Plus (TVP) in cats. ANIMALS AND PROCEDURES: IOP readings obtained with the TVP were compared to values obtained concurrently with the original TONOVET (TV01) and Tono-Pen Vet™ (TP) in 12 normal cats (24 eyes) and 8 glaucomatous LTBP2-mutant cats (13 eyes) in vivo. Reproducibility of TVP readings was also assessed for three observers in the above cats. The anterior chambers of five different normal cat eyes were cannulated ex vivo. IOP was measured with the TVP, TV01, and TP at manometric IOPs ranging from 5 to 70 mmHg. Data were analyzed by linear regression, ANOVA and Bland-Altman plots. ANOVA was used to assess reproducibility of TVP readings obtained by different observers and an ANCOVA model controlled for variation of individual cats. p < .05 was considered significant. RESULTS: TVP values strongly correlated with TV01 values (y = 1.045x + 1.443, R2 = .9667). The TP significantly underestimated IOP relative to the TVP and TV01, particularly at high IOP. IOP values obtained by 1 observer were significantly higher (~1 mmHg average) compared to the other 2 observers via ANCOVA analysis (p = .0006479 and p = .0203). Relative to manometry, the TVP and TV01 were significantly more accurate (p < .0001) and precise (p < .0070) than the TP in ex vivo eyes. CONCLUSIONS: IOP readings obtained with the TVP and TV01 are broadly interchangeable between models and between observers, but subtle differences may be important in a research context. TP readings vastly underestimate high IOP in feline glaucoma.

Evoked potentials as a biomarker of remyelination.

Multiple sclerosis (MS) is a common cause of neurologic disease in young adults that is primarily treated with disease-modifying therapies which target the immune and inflammatory responses. Promotion of remyelination has opened a new therapeutic avenue, but how best to determine efficacy of remyelinating drugs remains unresolved. Although prolongation and then shortening of visual evoked potential (VEP) latencies in optic neuritis in MS may identify demyelination and remyelination, this has not been directly confirmed. We recorded VEPs in a model in which there is complete demyelination of the optic nerve, with subsequent remyelination. We examined the optic nerves microscopically during active disease and recovery, and quantitated both demyelination and remyelination along the length of the nerves. Latencies of the main positive component of the control VEP demonstrated around 2-fold prolongation during active disease. VEP waveforms were nonrecordable in a few subjects or exhibited a broadened profile which precluded peak identification. As animals recovered neurologically, the VEP latencies decreased in association with complete remyelination of the optic nerve but remained prolonged relative to controls. Thus, it has been directly confirmed that VEP latencies reflect the myelin status of the optic nerve and will provide a surrogate marker in future remyelination clinical trials.

Outer retinal thickness and visibility of the choriocapillaris in four distinct retinal regions imaged with spectral domain optical coherence tomography in dogs and cats.

PURPOSE: To evaluate the outer retinal band thickness and choriocapillaris (CC) visibility in four distinct retinal regions in dogs and cats imaged with spectral domain optical coherence tomography (SD-OCT). To attempt delineation of a fovea-like region in canine and feline SD-OCT scans, aided by the identification of outer retinal thickness differences between retinal regions. METHODS: Spectralis® HRA + OCT SD-OCT scans from healthy, anesthetized dogs (n = 10) and cats (n = 12) were analyzed. Scanlines on which the CC was identifiable were counted and CC visibility was scored. Outer nuclear layer (ONL) thickness and the distances from external limiting membrane (ELM) to retinal pigment epithelium/Bruch's membrane complex (RPE/BM) and ELM to CC were measured in the area centralis (AC), a visually identified fovea-like region, and in regions superior and inferior to the optic nerve head (ONH). Measurements were analyzed using a multilevel regression. RESULTS: The CC was visible in over 90% of scanlines from dogs and cats. The ONL was consistently thinnest in the fovea-like region. The outer retina (ELM-RPE and ELM-CC) was thickest within the AC compared with superior and inferior to the ONH in dogs and cats (p < .001 for all comparisons). CONCLUSIONS: The CC appears a valid, albeit less than ideal outer retinal boundary marker in tapetal species. The AC can be objectively differentiated from the surrounding retina on SD-OCT images of dogs and cats; a fovea-like region was identified in dogs and its presence was suggested in cats. These findings allow targeted imaging and image evaluation of these regions of retinal specialization.

Development and validation of methods to visualize conventional aqueous outflow pathways in canine primary angle closure glaucoma.

PURPOSE: Angle closure glaucoma (PACG) is highly prevalent in dogs and is often refractory to medical therapy. We hypothesized that pathology affecting the post-trabecular conventional aqueous outflow pathway contributes to persistent intraocular pressure (IOP) elevation in dogs with PACG. The goal of this study was to determine the potential for aqueous angiography (AA) and optical coherence tomography (OCT) to identify abnormalities in post-trabecular aqueous outflow pathways in canine PACG. METHODS: AA and anterior segment OCT (Spectralis HRA + OCT) were performed ex vivo in 19 enucleated canine eyes (10 normal eyes and 9 irreversibly blind eyes from canine patients enucleated for management of refractory PACG). Eyes were cannulated and maintained at physiologic IOP (10-20 mmHg) prior to intracameral infusion of fluorescent tracer. OCT scleral line scans were acquired in regions of high and low perilimbal AA signal. Eyes were then perfusion fixed and cryosections prepared from 10/10 normal and 7/9 PACG eyes and immunolabeled for a vascular endothelial marker. RESULTS: Normal canine eyes showed segmental, circumferential limbal AA signal, whereas PACG eyes showed minimal or no AA signal. AA signal correlated with scleral lumens on OCT in normal dogs, but lumens were generally absent or flattened in PACG eyes. Collapsed vascular profiles were identified in tissue sections from PACG eyes, including those in which no lumens were identified on AA and OCT. CONCLUSIONS: In canine eyes with PACG, distal aqueous outflow channels are not identifiable by AA, despite normalization of their IOP, and intra-scleral vascular profiles are collapsed on OCT and histopathology.

Mapping retinal ganglion cell somas in a large-eyed glaucoma model.

Purpose: The purpose of this study was to identify a robust, representative region of interest (ROI) for studies of retinal ganglion cell (RGC) soma loss in feline congenital glaucoma (FCG), a spontaneous, large-eyed glaucoma model. Methods: Seven FCG and three wild-type (wt) eyes were collected from 10 adult cats of both sexes. Eyes enucleated postmortem were immediately fixed overnight in 4% paraformaldehyde and then stored in 0.1 M PBS at 4 °C. The retinas were wholemounted, Nissl stained with cresyl violet, and imaged using light microscopy. Somas of RGCs were manually identified according to long-established morphological criteria and quantified using a semiautomated method; their coordinates were used to create density maps and plots of the retinal topography. The RGC axon counts for the corresponding eyes were obtained from glutaraldehyde-fixed, resin-embedded optic nerve cross-sections stained with 0.1% p-phenylenediamine (PPD) using a semiautomated counting method. Correlations between total optic nerve axons and RGC soma counts were assessed by linear regression. A k-means cluster algorithm was used to identify a retinal ROI, with further definition using a probability density algorithm. Results: Interindividual variability in RGC total soma counts was more pronounced in FCG cats (mean = 83,244, range: 0-155,074) than in wt cats (mean = 117,045, range: 97,373-132,972). In general, RGC soma counts were lower in FCG cats than they were in wt cats. RGC axon counts in the optic nerve cross-sections were lower than, but strongly correlated to, the total RGC soma count across all cats (in wt and FCG retinas; R2 = 0.88) and solely FCG eyes (R2 = 0.92). The k-means cluster algorithm indicated a region of the greatest mean difference between the normal wt retinas and FCG-affected retinas within the temporal retina, incorporating the region of the area centralis. Conclusions: As in other species, RGC soma count and topography are heterogeneous between individual cats, but we identified an ROI in the temporal retina for future studies of RGC soma loss or preservation in a large-eyed model of congenital glaucoma. Many of the methods refined and established to facilitate studies in this FCG model will be broadly applicable to studies in other large-eyed models.

Microstructure and resident cell-types of the feline optic nerve head resemble that of humans.

The lamina cribrosa (LC) region of the optic nerve head (ONH) is considered a primary site for glaucomatous damage. In humans, biology of this region reflects complex interactions between retinal ganglion cell (RGC) axons and other resident ONH cell-types including astrocytes, lamina cribrosa cells, microglia and oligodendrocytes, as well as ONH microvasculature and collagenous LC beams. However, species differences in the microanatomy of this region could profoundly impact efforts to model glaucoma pathobiology in a research setting. In this study, we characterized resident cell-types, ECM composition and ultrastructure in relation to microanatomy of the ONH in adult domestic cats (Felis catus). Longitudinal and transverse cryosections of ONH tissues were immunolabeled with astrocyte, microglia/macrophage, oligodendrocyte, LC cell and vascular endothelial cell markers. Collagen fiber structure of the LC was visualized by second harmonic generation (SHG) with multiphoton microscopy. Fibrous astrocytes form glial fibrillary acidic protein (GFAP)-positive glial columns in the pre-laminar region, and cover the collagenous plates of the LC region in lamellae oriented perpendicular to the axons. GFAP-negative and alpha-smooth muscle actin-positive LC cells were identified in the feline ONH. IBA-1 positive immune cells and von Willebrand factor-positive blood vessel endothelial cells are also identifiable throughout the feline ONH. As in humans, myelination commences with a population of oligodendrocytes in the retro-laminar region of the feline ONH. Transmission electron microscopy confirmed the presence of capillaries and LC cells that extend thin processes in the core of the collagenous LC beams. In conclusion, the feline ONH closely recapitulates the complexity of the ONH of humans and non-human primates, with diverse ONH cell-types and a robust collagenous LC, within the beams of which, LC cells and capillaries reside. Thus, studies in a feline inherited glaucoma model have the potential to play a key role in enhancing our understanding of ONH cellular and molecular processes in glaucomatous optic neuropathy.

Validation and comparison of four handheld tonometers in normal ex vivo canine eyes.

OBJECTIVES: To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer and the Tono-Pen AVIA Vet™ applanation tonometer for intraocular pressure (IOP) measurement in normal ex vivo canine eyes and comparison to earlier models of these tonometers. ANIMALS & PROCEDURES: The anterior chambers of six normal dog eyes were cannulated ex vivo. IOP was measured with the TONOVET (TV01), TONOVET Plus, Tono-Pen Vet™, and Tono-Pen AVIA Vet™ at manometric IOPs ranging from 5 to 70 mm Hg. Data were analyzed by linear regression, ANOVA and Bland-Altman plots. A P value ≤ .05 was considered significant. RESULTS: Intraocular pressure values obtained using the TONOVET Plus and TV01 were significantly more accurate than with the Tono-Pen VET and Tono-Pen AVIA Vet, particularly at higher IOPs (30-70 mm Hg). Accuracy was not significantly different between any of the devices in the low to normal physiologic IOP range (5-25 mm Hg). Level of precision was high for all devices, though the TONOVET Plus was more precise than the Tono-Pen Vet in the 5-25 mmHg range and the TV01 was more precise than the Tono-Pen AVIA Vet over the whole IOP range. CONCLUSIONS: All devices underestimated IOP, particularly at higher pressures. Rebound tonometers were more accurate over the full range of IOP tested and in the high IOP range; however, there were no significant differences in accuracy among devices in the physiologic IOP range. All tonometers can provide clinically useful IOP readings in dogs, but rebound and applanation tonometers should not be used interchangeably.

Genomic analysis for virulence determinants in feline herpesvirus type-1 isolates.

Feline herpesvirus type 1 (FHV-1) is a widespread cause of respiratory and ocular disease in domestic cats. A spectrum of disease severity is observed in host animals, but there has been limited prior investigation into viral genome factors which could be responsible. Stocks of FHV-1 were established from oropharyngeal swabs obtained from twenty-five cats with signs of infection housed in eight animal shelters around the USA. A standardized numerical host clinical disease severity scoring scheme was used for each cat from which an isolate was obtained. Illumina MiSeq was used to sequence the genome of each isolate. Genomic homogeneity among isolates was relatively high. A general linear model for fixed effects determined that only two synonymous single nucleotide polymorphisms across two genes (UL37/39) in the same isolate (from one host animal with a low disease severity score) were significantly associated (p ≤ 0.05) with assigned host respiratory and total disease severity score. No variants in any isolate were found to be significantly associated with assigned host ocular disease severity score. A concurrent analysis of missense mutations among the viral isolates identified three genes as being primarily involved in the observed genomic variation, but none were significantly associated with host disease severity scores. An ancestral state likelihood reconstruction was performed and determined that there was no evidence of a connection between host disease severity score and viral evolutionary state. We conclude from our results that the spectrum of host disease severity observed with FHV-1 is unlikely to be primarily related to viral genomic variations, and is instead due to host response and/or other factors.

Comparison of outcomes in cataractous eyes of dogs undergoing phacoemulsification versus eyes not undergoing surgery.

OBJECTIVE: To compare outcomes of surgical intervention and nonsurgical management of canine cataracts. METHODS: Records of patients examined for cataracts from January 2007 to February 2018 were divided into two groups: nonsurgical and surgical. The nonsurgical group was further subdivided based on whether the decision not to pursue surgery was elected by owners, or based on ophthalmologist's advice. Inclusion criteria included 6 months of follow-up. Success in the nonsurgical group was defined as a comfortable eye with no potentially painful complications, and success in the surgical group additionally required vision. Time-to-failure (complications) was assessed with Cox proportional hazards models. RESULTS: A total of 72 eyes (41 dogs) were included in the nonsurgical group, and 126 eyes (67 dogs) were surgically treated. There was no difference in gender or age; however, the surgical group had significantly more diabetic eyes (56.3% vs 15.3%; P < .001) and patient eyes with longer follow-up times (median 37.6 months vs 22.1 months; P < .001) than the nonsurgical group. There was no statistically significant difference in complication rates between the nonsurgical group (15/72 [20.8%]) and the surgical group (23/126 [18.3%]; HR: 2.22 [0.97, 5.0]; P = .060). However, the complication rate in the ophthalmologist-led nonsurgical group was significantly greater than in the owner-led nonsurgical group (P = .019) and the surgical group (P = .002). CONCLUSIONS: When using relevant outcomes, whether or not a cataractous eye has surgery does not affect long-term complications; additionally, nonsurgical eyes that are poor surgical candidates have a higher complication rate than eyes deemed suitable for phacoemulsification for which owners elected not to pursue cataract surgery.

Validation of the Icare® TONOVET plus rebound tonometer in normal rabbit eyes.

To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer for measuring intraocular pressure (IOP) in normal rabbit eyes, as well as compare it to three other commercially available tonometers: the Icare® TONOVET (TV01), Tono-Pen Vet™, and Tono-Pen AVIA Vet™. The anterior chambers of both eyes of three New Zealand White rabbits were cannulated, post-mortem. IOP was measured using each of the above four tonometers at manometric pressures ranging between 5 mmHg and 70 mmHg. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. A p-value of ≤0.05 was considered significant for all statistical tests. IOP values obtained with the TONOVET Plus (in 'lapine' mode) were significantly closer to manometric IOP than those obtained with the other tonometers tested. The TV01 (in 'd' dog setting) and Tono-Pen AVIA Vet™ were significantly more accurate compared to the Tono-Pen Vet™. All tonometers had high levels of precision, though the TONOVET Plus and TV01 were significantly more precise compared to the Tono-Pen AVIA Vet™. All tonometers tended to underestimate IOP, particularly at high pressures, however the TONOVET Plus was highly correlated with manometric IOP in the clinically relevant range of 5-50 mmHg. The TONOVET Plus is an appropriate choice of instrument for measuring IOP in rabbit eyes in both research and clinical settings.

Feline Neovascular Vitreoretinopathy and Anterior Segment Dysgenesis With Concurrent Glaucoma in Domestic Cats.

Feline neovascular vitreoretinopathy (FNV) is a newly recognized rare condition affecting kittens and young domestic cats. This study investigated the clinical and pathologic findings in 22 cats with FNV. In affected cats, ophthalmoscopy of the fundus (when visible) revealed avascular peripheral retinae and epiretinal vascular membranes. Frequent nonspecific clinical findings were buphthalmos ( n = 21), medically uncontrollable glaucoma ( n = 22), and lenticular abnormalities ( n = 13). Anterior segment dysgenesis (ASD) was detected clinically in affected cats ( n = 6). The fellow eye was affected in 11 of 18 cats to a variable degree or appeared clinically normal in 7 of 18 cats. The globes were examined histologically and using immunohistochemistry for vimentin, glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, laminin, factor VIII-related antigen (FVIII-RA), and smooth muscle actin (SMA). Histologically, diagnostic features included laminin-positive epiretinal vascular membranes affecting the central retina, with an avascular peripheral retina and gliosis. Enucleated globes exhibited multiple additional abnormalities, including corneal disease ( n = 15), anterior segment dysgenesis ( n = 21), lymphoplasmacytic anterior uveitis ( n = 19), peripheral anterior synechiae ( n = 20), retinal degeneration ( n = 22), and retinal detachment ( n = 19). Gliotic retinae labeled strongly for GFAP and vimentin with reduced expression of synaptophysin and neurofilament, consistent with degeneration or lack of differentiation. While an avascular peripheral retina and epiretinal fibrovascular membranes are also salient features of retinopathy of prematurity, there is no evidence to support hyperoxic damage in cats with FNV. The cause remains unknown.

Relationship between corneal sensitivity, corneal thickness, corneal diameter, and intraocular pressure in normal cats and cats with congenital glaucoma.

OBJECTIVE: To determine the effect of feline congenital glaucoma (FCG) on corneal sensitivity, and relationships between corneal sensitivity, central corneal thickness (CT), and corneal diameter (CD). ANIMALS AND PROCEDURES: Corneal sensitivity (estimated by corneal touch threshold [CTT] using Cochet-Bonnet esthesiometry); CT using ultrasonic pachymetry; intraocular pressure (IOP) using rebound tonometry; and maximal horizontal CD were measured in 16 normal and 14 FCG cats, both males and females, aged 7 months-3.5 years. All procedures complied with an Institutional Animal Care and Use Committee-approved protocol. Data were analyzed by linear regression: paired Student's t tests for between-eye comparisons, and unpaired Student's t tests for comparisons between groups. Relationships between parameters were evaluated by Pearson correlation coefficients and linear mixed effects modeling. For statistical tests, with the exception of values that were Benjamini-Hochberg adjusted for multiple comparisons, P-values < 0.05 were considered significant. RESULTS: Mean CTT and CT values were lower in FCG eyes relative to normal eyes, but differences were not statistically significant. Mean CD was significantly larger in FCG eyes relative to normal eyes, and there was a significant negative correlation between CD and CTT in FCG (r = -0.8564, corrected P = 0.005). These associations were confirmed in linear mixed effects models. CONCLUSIONS: Eyes with FCG have significantly larger CDs when compared with normal eyes, and larger CDs correlated with decreased corneal sensitivity in this group. Further studies are warranted to explore the effect of buphthalmos and corneal enlargement on corneal sensitivity and innervation in feline subjects with chronic glaucoma.

The post-natal development of intraocular pressure in normal domestic cats (Felis catus) and in feline congenital glaucoma.

Intraocular pressure (IOP) is the most consistent risk factor for progressive vision loss in glaucoma. Cats with recessively inherited feline congenital glaucoma (FCG) exhibit elevated IOP with gradual, painless progression of glaucoma similar to humans and are studied as a model of glaucoma in humans and animals. Here, post-natal development of IOP was characterized in normal domestic cats and in cats with FCG caused by a homozygous LTBP2 mutation. Rebound tonometry (TonoVet®, ICare Oy, Finland) was used to measure IOP non-invasively, 2-3 times weekly in 63 FCG and 33 normal kittens, of both sexes, from eyelid opening until 3-6 months of age. IOPs in the left and right eyes of both FCG and normal kittens were compared by paired t-test and linear regression. One-way ANOVA and Tukey-Kramer post-tests were used to compare IOP of cats grouped by age and disease status. A p-value <0.05 was considered significant. In the second week of life, mean IOP was 7.16 mmHg (SD = 1.3) in normal kittens and 8.72 mmHg (SD = 1.4) in kittens with FCG. Mean IOP at age 10 weeks was significantly higher in FCG (19.8 mmHg; 95% CI = 17.7, 21.9  mmHg) than in normal kittens (13.2 mmHg; 95% CI = 11.9, 14.5  mmHg). At 3 months of age, IOP in normal cats reached adult values while IOP in FCG cats continued to increase through at least six months of age. These results provide ranges for normal IOP values in young kittens and confirm that IOP is significantly higher than normal by 10wks of age in this spontaneous feline glaucoma model.

Tonometer validation and intraocular pressure reference values in the normal chinchilla (Chinchilla lanigera).

OBJECTIVES: To determine accuracy and precision of three commonly used tonometers (TonoVet® and TonoLab® (ICare Oy, Finland)-rebound tonometers, and Tono-Pen VET™ (Reichert, NY)-applanation tonometer) in normal chinchillas, and to establish a normal intraocular pressure (IOP) reference range in this species. METHODS: The anterior chambers of three chinchilla eyes were cannulated ex vivo and readings obtained at manometric IOPs from 5 to 80 mmHg, using each of the three tonometers in random order. Data were analyzed by linear regression, ANOVA, and Bland-Altman plots. Tonometry was performed in both eyes of 60 chinchillas (age 8 weeks-16.2 years) using the TonoVet® and relationship between age and IOP analyzed using linear regression. For all statistical tests, P < 0.05 was significant. RESULTS: Intraocular pressure values obtained using the Tono-Pen VET™ and TonoVet® (in dog calibration mode;'d') showed strong linear correlation with manometry within the physiologic and clinically relevant range of IOP (0-50 mmHg). The TonoVet® 'd' setting displayed significantly greater precision over the full range of IOP evaluated than the Tono-Pen VET™, and both TonoVet and Tono-Pen VET™ were significantly more accurate than the TonoLab® tonometer. Mean ± SD IOP (TonoVet® 'd') in chinchillas was 9.7 ± 2.5 mmHg, and the 95% reference interval was 4.7-14.7 mmHg. CONCLUSIONS: Both the Tono-Pen VET™ and TonoVet® provided clinically acceptable estimates of IOP in chinchillas. The TonoVet® provides accurate and precise IOP values, while Tono-Pen VET™ derived measurements showed greater variability. Values obtained either with the TonoLab® or TonoVet® used in the 'unspecified' calibration setting were inaccurate in this species.

Phylogenetic and recombination analysis of the herpesvirus genus varicellovirus.

BACKGROUND: The varicelloviruses comprise a genus within the alphaherpesvirus subfamily, and infect both humans and other mammals. Recently, next-generation sequencing has been used to generate genomic sequences of several members of the Varicellovirus genus. Here, currently available varicellovirus genomic sequences were used for phylogenetic, recombination, and genetic distance analysis. RESULTS: A phylogenetic network including genomic sequences of individual species, was generated and suggested a potential restriction between the ungulate and non-ungulate viruses. Intraspecies genetic distances were higher in the ungulate viruses (pseudorabies virus (SuHV-1) 1.65%, bovine herpes virus type 1 (BHV-1) 0.81%, equine herpes virus type 1 (EHV-1) 0.79%, equine herpes virus type 4 (EHV-4) 0.16%) than non-ungulate viruses (feline herpes virus type 1 (FHV-1) 0.0089%, canine herpes virus type 1 (CHV-1) 0.005%, varicella-zoster virus (VZV) 0.136%). The G + C content of the ungulate viruses was also higher (SuHV-1 73.6%, BHV-1 72.6%, EHV-1 56.6%, EHV-4 50.5%) compared to the non-ungulate viruses (FHV-1 45.8%, CHV-1 31.6%, VZV 45.8%), which suggests a possible link between G + C content and intraspecies genetic diversity. Varicellovirus clade nomenclature is variable across different species, and we propose a standardization based on genomic genetic distance. A recent study reported no recombination between sequenced FHV-1 strains, however in the present study, both splitstree, bootscan, and PHI analysis indicated recombination. We also found that the recently sequenced Brazilian CHV-1 strain BTU-1 may contain a genetic signal in the UL50 gene from an unknown varicellovirus. CONCLUSION: Together, the data contribute to a greater understanding of varicellovirus genomics, and we also suggest a new clade nomenclature scheme based on genetic distances.

Effect of timolol maleate gel-forming solution on intraocular pressure, pupil diameter, and heart rate in normal and glaucomatous cats.

OBJECTIVE: To determine the effects of once-daily topical treatment with timolol maleate gel-forming solution (GFS) on intraocular pressure (IOP), pupil diameter (PD), and heart rate (HR) in normal cats and cats with feline primary congenital glaucoma (FCG). ANIMALS STUDIED AND PROCEDURES: A single drop of timolol maleate 0.5% GFS was administered topically to one randomly assigned eye of 18 adult cats (8 normal, 10 FCG) at 8 am for 8 days; the opposite eye served as the untreated control. IOP was measured in both eyes (OU) every 2 h (PD and HR were measured every 4 h), for 14 h total, 1 day prior to and on days 1 and 8 of treatment. In a second treatment phase, a single drop of timolol was administered at 8 pm for 3 nights and IOP, PD, and HR were measured, as above, beginning at 8 am on day 4. Slit-lamp examinations were conducted prior to and after treatment phases. Comparisons of mean IOP, PD, and HR were made at each time point and between treated and untreated eyes by repeated-measures ANOVA and Tukey-Kramer post hoc test, with P < 0.05 considered significant. RESULTS: Timolol maleate 0.5% GFS had an inconsistent effect on IOP, with maximum IOP-lowering effect (mean = 5.6 mmHg, 17.4%) observed 6 h post-treatment in FCG. The drug caused significant miosis (from 4 to 8 h post-treatment), but had no effect on HR. CONCLUSION: Once-daily application of timolol maleate 0.5% GFS may be of limited clinical benefit in the management of feline congenital glaucoma.

Effects of topical corticosteroid administration on intraocular pressure in normal and glaucomatous cats.

OBJECTIVE: The objective of this study was to determine the effect of topical corticosteroid (CCS) therapy on intraocular pressure (IOP) in normal cats and cats with primary feline congenital glaucoma (FCG). ANIMALS STUDIED: Five normal and 11 FCG cats were studied in two cohorts. PROCEDURES: IOP was measured by a single, masked observer, once daily, 3-5 days/week throughout the course of CCS treatment and for up to 11 days after treatment discontinuation. One eye per cat was randomly assigned for treatment twice daily with CCS; balanced salt solution (BSS) applied to the contralateral eye served as a control. Differences between eyes and between weeks of the study period were calculated for each cat. A positive response to CCS was defined as a consistent >15% or >25% higher IOP in the treated relative to control eye in normal and FCG cats, respectively. RESULTS: A total of 8 of 11 FCG cats responded to topical CCS after 1-5 weeks of treatment with an increase in IOP relative to the untreated eye (maximum IOP discrepancy of 56 mmHg). Two of five normal cats responded to topical CCS with an appreciable, but clinically unimportant increase in IOP in the treated eye (maximum IOP discrepancy of 6.4 mmHg). CONCLUSIONS: Our data indicate that the incidence of steroid-induced IOP elevation in cats is lower than that of previously published feline studies. Cats with preexisting compromise in aqueous humor outflow may show a greater, clinically relevant response to topical CCS than normal cats.

Effect of topical latanoprost 0.005% on intraocular pressure and pupil diameter in normal and glaucomatous cats.

OBJECTIVE: To determine the effects of latanoprost on intraocular pressure (IOP) and pupil diameter (PD) in cats with inherited primary congenital glaucoma (PCG) and normal cats. ANIMALS STUDIED AND PROCEDURES: IOP and PD were measured in both eyes (OU) of 12 adult cats (six normal, six PCG), three times per week for 3 weeks prior to, for 3 weeks during, and for 2 weeks following twice-daily treatment with 0.005% latanoprost to the right eye (OD) and vehicle to the left (control) eye (OS). IOP and PD were measured hourly, for 8 h, 1 day prior to, and on the first and last days of treatment. Aqueous humor flow rate (AHF) was determined at baseline and at the end of the treatment phase in six normal cats. RESULTS: Mean IOP was significantly lower in treated vs. control eyes of PCG cats, for up to 8 h following a single latanoprost treatment, and a maximal IOP reduction of 63% occurred in treated eyes at 3 h. Latanoprost acutely lowered IOP in cats with PCG, but this effect appeared to diminish over 3 weeks of treatment. AHF was modestly increased in the treated eyes of normal cats after 3 weeks of latanoprost treatment, although IOP was not significantly affected. Latanoprost caused miosis, with rebound mydriasis at 24 h posttreatment, in the treated eyes of all cats. CONCLUSIONS: Further research is needed to determine the suitability and efficacy of latanoprost treatment for long-term IOP-lowering in cats with PCG or other forms of glaucoma.

Canine orbital rhabdomyosarcoma: a report of 18 cases.

PURPOSE: To describe clinical and pathological features of canine orbital rhabdomyosarcoma (COR). METHODS: Retrospective review of patients with COR from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin and the University of Wisconsin Veterinary Medical Teaching Hospital (1983-2014). RESULTS: Eighteen cases of COR were identified, all diagnosed in an 8-year period (2006-2014). Affected dogs were typically young (range 1-8; median 2 years), and both sexes were equally represented. Common clinical signs included exophthalmos (16/18) with dorsolateral deviation of the globe (10/18) and elevation of the nictitans (12/18). Ultrasonography, performed in nine cases, revealed an orbital mass with mixed echogenicity and posterior globe indentation. Advanced imaging, performed in nine cases, demonstrated a soft tissue mass with variable contrast enhancement and lysis of the orbital bones (5/9). Histologically, all tumors were subclassified as embryonal rhabdomyosarcoma. All neoplasms demonstrated positive immunohistochemical labeling for desmin, and 14/18 were positive for skeletal muscle actin. Follow-up information was available for 15/18 cases. Older dogs, aged 6-8 years, had no clinical signs of recurrence or metastasis 8-13 months postdiagnosis (4/4). Most younger dogs (9/11), aged 1-4 years, were euthanized within 6 months (median 2.5 months) of diagnosis due to recurrence at the surgical site (5/9) and/or metastasis (5/9). CONCLUSIONS: Canine orbital rhabdomyosarcoma is a highly malignant neoplasm in juvenile dogs, but may be amenable to surgical resection in older dogs. This duality in biologic behavior may reflect differences in tissue of origin between juvenile onset tumors and adult onset tumors.