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Abstract
OBJECTIVE
To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs.
ANIMALS
12 purpose-bred Beagles.
PROCEDURES
Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration.
RESULTS
Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone.
CLINICAL RELEVANCE
Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.
Abstract
OBJECTIVE
To compare single and triplicate applanation tonometry values across previous intraocular pressure (IOP) studies in dogs.
ANIMALS
116 ophthalmologically normal dogs.
PROCEDURES
Triplicate IOP readings (n = 1432) from studies evaluating effect of anesthetic protocols were analyzed to estimate a range of probable differences between averaged triplicate and first, averaged and lowest, and first and lowest IOPs. The decrease in variability with triplicate measurements and the magnitude of effects on statistical power were quantified.
RESULTS
The 2.5th to 97.5th interpercentile range for differences of averaged triplicate values minus first IOP readings was –3 to 2.7 mm Hg; for averaged minus lowest: 0 to 3.7 mm Hg; for first minus lowest: 0 to 5 mm Hg. The 95% prediction interval for differences in study group means (n = 160 groups, n = 5 to 11 eyes per group) based on averaged minus first measurements was –1.0 to 0.9 mm Hg with associated SDs reduced by 4% on average. Analysis of previous studies using averaged instead of first IOP values resulted in minimal decreases in SEs of 3–9% (0.03 to 0.09 mm Hg). Of 11 comparisons found significant with averaged data, 2 (18%) were found nonsignificant with first measurements. Of 96 comparisons found nonsignificant with averaged data, 3 (3%) were found significant with first measurements.
CLINICAL RELEVANCE
With applanation tonometry in ophthalmologically normal dogs, no clinically meaningful difference was found between the first, lowest, or averaged triplicate IOP measurements, but the first reading has a larger variance and hence will result in lower statistical power.
Abstract
OBJECTIVE
To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG).
SAMPLE
Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs.
PROCEDURES
A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared.
RESULTS
Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes.
CLINICAL RELEVANCE
MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.
Abstract
OBJECTIVE
To calculate the necessary pseudophakic intraocular lens (IOL) power to approximate emmetropia in adult tigers.
ANIMALS
17 clinically normal adult tigers.
PROCEDURES
33 eyes of 17 clinically normal adult tigers underwent routine ophthalmic examination and B-scan ultrasonography while anesthetized for unrelated procedures. Specific ultrasound data (globe measurements and corneal curvature) and estimated postoperative IOL positions were utilized to calculate predicted IOL power by use of Retzlaff and Binkhorst theoretical formulas. Applanation tonometry and refraction were also performed.
RESULTS
Mean ± SD axial globe length was 29.36 ± 0.82 mm, preoperative anterior chamber depth was 7.00 ± 0.74 mm, and crystalline lens thickness was 8.72 ± 0.56 mm. Mean net refractive error (n = 33 eyes) was +0.27 ± 0.30 diopters (D). By use of the Retzlaff formula, mean predicted IOL power for the postoperative anterior chamber depth (PACD), PACD – 2 mm, and PACD + 2 mm was 43.72 ± 4.84 D, 37.62 ± 4.19 D, and 51.57 ± 5.72 D, respectively. By use of the Binkhorst equation, these values were 45.11 ± 4.91 D, 38.84 ± 4.25 D, and 53.18 ± 5.81 D, respectively. Mean intraocular pressure for all eyes was 14.7 ± 2.69 mm Hg.
CLINICAL RELEVANCE
The calculated tiger IOL was lower than reported values for adult domestic felids. Further studies evaluating actual PACD and pseudophakic refraction would help determine the appropriate IOL power to achieve emmetropia in this species.
Abstract
OBJECTIVE
To determine intra- and interobserver reliability of a fluorescein stain–based tear film breakup time (TFBUT) test as performed in a clinical environment with and without administration of a topical anesthetic.
ANIMALS
21 privately owned dogs.
PROCEDURES
A randomized study design was used. Two independent observers that commonly perform the TFBUT test in clinical practice read the same description of TFBUT. Observers performed TFBUT testing for each dog before and after topical administration of 0.5% proparacaine solution in 4 testing periods with a 1-hour interval between periods. Intraclass correlation coefficient (ICC) analysis was used to assess inter- and intraobserver test reliability. Linear mixed models were used to assess the main effects of testing period, observer, eye, and presence of ophthalmic disorders and their interactions on TFBUT.
RESULTS
Mean TFBUT measurements performed by observer 1 and observer 2 were 5.9 seconds and 8.6 seconds, respectively, when adjusted for other effects in the model. Intraobserver ICC was poor for one observer and moderate for the other. Interobserver ICC was poor without use of topical anesthetic and slightly lower when anesthetic was used. Observer and testing period were each significantly associated with TFBUT; the measurements decreased and were more variable after multiple applications of fluorescein stain and proparacaine.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested tear film stability is negatively affected by topical administration of 0.5% proparacaine solution and repeated applications of fluorescein stain. The TFBUT test as performed in this study had poor to moderate reliability.
Abstract
OBJECTIVE
To identify and characterize abnormalities of iris vasculature in dogs with diabetes mellitus, compared to clinically normal, age-matched control dogs, by means of anterior segment angiography.
ANIMALS
10 dogs with naturally occurring diabetes mellitus and 10 age-matched control dogs with no ocular or systemic disease.
PROCEDURES
The day before iris vasculature abnormality (IVA) assessment, all dogs underwent complete physical and ophthalmic examinations and baseline clinicopathologic analyses. For diabetic dogs, serum fructosamine concentration and a 12-hour blood glucose concentration curve were generated. The next day, all dogs were sedated and anterior segment angiography (following IV injection of indocyanine green [1 mg/kg] and subsequently sodium fluorescein [20 mg/kg]) was performed with a full-spectrum camera and camera adapter system. Group findings were compared, and multiple linear regression analysis was performed to identify potential factor associations with IVAs.
RESULTS
During anterior segment angiography, the arterial, capillary, and venous phases were identified in all dogs. Times to onset of all phases in diabetic dogs were significantly less than those in control dogs. Vascular disruptions within the peripupillary region (evident following sodium fluorescein administration) were common in diabetic dogs. Severity of dye leakage into the iris stroma and aqueous humor was significantly greater in diabetic dogs than in control dogs. Duration of disease, mean blood glucose concentration, and serum fructosamine concentration were significantly associated with IVAs.
CONCLUSIONS AND CLINICAL RELEVANCE
In diabetic dogs, anterior segment angiography revealed IVAs that were not evident in control dogs. The severity of those changes appeared to be associated with disease duration and blood glucose regulation.
Abstract
OBJECTIVE
To assess the feasibility of ocular ultrasonography for measurement of the ratio of optic nerve sheath diameter (ONSD) to eyeball transverse diameter (ETD) in dogs with various morphologies and to evaluate the interob-server reliability of the ONSD/ETD ratio and its correlation with various morphological variables.
ANIMALS
45 healthy dogs of various breeds.
PROCEDURES
Height, head circumference, body weight, body condition score, intraocular pressure, and blood pressure were recorded for each dog. Unsedated dogs underwent bilateral ocular ultrasonography once. A veterinarian and board-certified ophthalmologist who were unaware of subject signalment independently reviewed the ultrasonographic videos and selected 1 image for each eye on which the ETD and ONSD were measured. The ONSD/ ETD ratio was calculated and compared between the 2 observers. Correlations between the ONSD/ETD ratio and various physiologic and morphological variables were assessed.
RESULTS
172 ONSD/ETD ratios were recorded. The ONSD/ETD ratio was calculated for at least 1 eye for 44 of the 45 (98%) dogs. Mean ± SD time required to complete the ultrasonographic examination was 90 ± 30 seconds (range, 15 seconds to 3 minutes). The mean ± SD ONSD/ETD ratio was 0.17 ± 0.01 (range, 0.15 to 0.20). The ONSD/ETD ratio did not differ significantly between the left and right eyes or the 2 observers and was not correlated with any of the variables assessed.
CONCLUSIONS AND CLINICAL RELEVANCE
Ocular ultrasonography was a rapid, noninvasive, and reliable method for measurement of the ONSD/ETD ratio. The ONSD/ETD ratio did not appear to be influenced by dog morphology.
Abstract
OBJECTIVE
To investigate the effects of orally administered trazodone on intraocular pressure (IOP), pupil diameter measured in the vertical plane (ie, vertical pupil diameter [VPD]), selected physical examination variables, and sedation level in healthy equids.
ANIMALS
7 horses and 1 pony.
PROCEDURES
Food was withheld for 12 hours prior to drug administration. After baseline (time 0) sedation scoring, physical examination, and measurement of IOP and VPD, equids received 1 dose (approx 6 mg/kg) of trazodone orally. Examination and measurement procedures were repeated 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Blood samples were collected at each time point for analysis of plasma trazodone concentrations. Repeated-measures analysis was used to compare examination results between downstream time points and baseline.
RESULTS
7 of 8 equids had mild sedation from 0.5 to 8 hours after treatment; compared with baseline values, mean IOP was significantly lower from 0.5 hours to 8 hours, mean VPD was significantly smaller at 0.5 hours, and mean rectal temperature was significantly lower from 1 to 8 hours after drug administration. Adverse effects (signs of excitement in 1 equid and sweating in 4) were self-limiting and considered minor. Mean maximum plasma concentration of trazodone was 1,493 ng/mL 0.75 hours after administration, and terminal half-life of the drug was 9.96 hours.
CONCLUSIONS AND CLINICAL RELEVANCE
The described oral dose of trazadone elicited sedation with a few self-limiting adverse effects in the study sample. Drug effects on IOP and VPD may alter ocular examination findings. Further investigation is warranted prior to use of trazodone for sedation in equids, particularly those with ophthalmic conditions.
Abstract
OBJECTIVE
To investigate the effects of short-term and prolonged topical instillation of 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, and 0.03% flurbiprofen sodium on corneal sensitivity (CS) in ophthalmologically normal cats.
ANIMALS
12 healthy adult domestic shorthair cats.
PROCEDURES
In the first of 2 study phases, each cat received 0.1% diclofenac sodium, 0.5% ketorolac tromethamine, 0.03% flurbiprofen sodium, and saline (0.9% NaCl; control) solutions (1 drop [0.05 mL]/eye, q 5 min for 5 treatments) in a randomized order with a 2-day washout period between treatments. For each cat, an esthesiometer was used to measure CS before treatment initiation (baseline) and at 15, 30, 45, and 60 minutes after the last dose. There was a 2-day washout period between phases. The second phase was similar to the first, except each treatment was administered at a dosage of 1 drop/eye, twice daily for 5 days and CS was measured before treatment initiation and at 15 minutes and 24 and 48 hours after the last dose. The Friedman test was used to evaluate change in CS over time.
RESULTS
None of the 4 treatments had a significant effect on CS over time in either study phase.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that neither short-term nor prolonged topical instillation of 3 NSAID ophthalmic solutions had any effect on the CS of healthy cats. Given potential differences in cyclooxygenase expression between healthy and diseased eyes, further investigation of the effects of topical NSAID instillation in the eyes of cats with ocular surface inflammation is warranted.
Abstract
OBJECTIVE
To determine the effects of gabapentin, tramadol, and meloxicam on tear production, intraocular pressure (IOP), pupillary diameter, tear break-up time, and corneal touch threshold in healthy dogs when given orally for 3 days.
ANIMALS
9 healthy research Beagles.
PROCEDURES
A randomized, blinded, case-crossover study with a 6-sequence, 3-treatment, and 3-period design was performed. A 7-day acclimation period was followed by 3 treatment phases, each with a 3-day treatment period followed by a 7-day washout period for 3 different drugs. Block randomization was used to group dogs for treatments with drug A (gabapentin), B (tramadol), or C (meloxicam). Measurements of tear production, IOP, pupillary diameter, tear break-up time, and corneal touch threshold were performed on a schedule. A generalized mixed-effects linear regression model was created for each ocular variable, accounting for repeated measures within individuals.
RESULTS
Intraocular pressure was the only variable to have differed substantially between the first 5 and last 2 days of the acclimation period. When treatment phase, day, time of day, dog identification, baseline value, and eye were accounted for, the mean IOP was lower for dogs during treatment phases with gabapentin or tramadol, compared with meloxicam, but this difference was not considered clinically meaningful.
CONCLUSIONS AND CLINICAL RELEVANCE
Results indicated that a minimum 5-day acclimation period is necessary for IOP measurements to return to baseline in dogs. The statistically identified effect of gabapentin and tramadol on IOP in dogs of the present study warrants further investigation. It is possible that at higher dosages, or in dogs with glaucoma, this effect may become clinically significant.
