Penetration of topically administered dexamethasone disodium phosphate and prednisolone acetate into the normal equine ocular fluids.

BACKGROUND: Topical dexamethasone and prednisolone are currently the mainstay treatment for equine ophthalmic inflammatory diseases, such as equine recurrent uveitis. Comparative pharmacokinetic studies in horses are lacking and current guidelines are mainly based on empirical data and extrapolation from other species. OBJECTIVES: To investigate the penetration and local concentrations of topically applied dexamethasone and prednisolone in normal equine ocular fluids and serum. STUDY DESIGN: Prospective randomised experimental pharmacokinetic study. METHODS: Twenty-one Shetland ponies without ophthalmic disease were treated bilaterally topically every 2 hours during 24 hours to obtain steady state drug concentrations. One eye was treated with 0.15 mg of dexamethasone disodium phosphate (0.1%), and the other eye was simultaneously treated with 1.5 mg of prednisolone acetate (1%). Serum samples were taken prior to the induction of general anaesthesia. Aqueous and vitreous humour samples were taken during euthanasia at time points after administration of the last dose (t = 5 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min). Each pony was randomly assigned to one time point, and three ponies were sampled per time point. Dexamethasone and prednisolone concentrations were measured by liquid chromatography-mass spectrometry. RESULTS: The mean dexamethasone concentration in aqueous humour was 32.4 ng/mL (standard deviation [SD] 10.9) and the mean prednisolone concentration was 321.6 ng/mL (SD 96.0). In the vitreous and in serum samples concentrations of both corticosteroids were below the limit of detection (LOD 2.5 ng/mL). MAIN LIMITATIONS: The study group was limited to subjects without evidence of current ophthalmic disease. A limited number of time points were measured. CONCLUSIONS: Potentially effective dexamethasone and prednisolone concentrations were measured in the anterior chamber, but vitreal concentrations were negligible. Systemic uptake was low. Therefore, treatment with only topically administered corticosteroids is deemed insufficient in horses in cases of posterior uveitis. Further studies evaluating other routes of administration are warranted.

Clinical, ultrasonographic, and histopathologic findings in seven horses with Descemet's membrane detachment: A case series.

OBJECTIVE: To describe ultrasonography as a diagnostic method of in vivo Descemet's membrane detachment (DMD) in horses. ANIMALS STUDIED: Seven horses (three Icelandic horses, two Dutch Warmblood horses, one Appaloosa, and one Welsh Pony), presenting with moderate-to-severe focal or diffuse corneal edema, in whom DMD was suspected on ultrasonographic examination and confirmed with histopathology, were studied. PROCEDURE: A retrospective analysis of case records of horses with suspected DMD was performed. RESULTS: Median age at presentation was 14 years (range 11-24). Clinical signs in eyes with DMD were unilateral in all horses and included blepharospasm and epiphora (6/7), buphthalmos (5/7), moderate-to-severe focal or diffuse corneal edema (7/7), corneal epithelial bullae (4/7), corneal neovascularization (4/7), Haab's striae (2/7), corneal endothelial precipitates (1/7), fibrin in the anterior chamber (1/7), focal cataract (2/7), and pigment deposits on the anterior lens capsule (1/7). During transpalpebral ultrasonography, a distinct linear echogenic structure was noted in the anterior chamber, initially diverging from, and later running parallel to, the posterior lining of the cornea in all eyes studied. In all cases, the cornea was severely thickened and echogenic, consistent with edema, and DMD was suspected. In all horses, the clinical signs progressed and the affected eye was eventually enucleated. Histopathology revealed DMD (7/7), spindle cell proliferation (4/7), Descemet's membrane reformation (3/7), and inflammation of the anterior uvea (5/7). Overall incidence was 1.04%. CONCLUSIONS: Ultrasonography is an adequate tool in diagnosing DMD in horses. Descemet's membrane detachment should be included in the differential diagnosis in horses with dense focal or diffuse corneal edema.

The effects of topical dorzolamide 2% and brinzolamide 1%, either alone or combined with timolol 0.5%, on intraocular pressure, pupil diameter, and heart rate in healthy cats.

OBJECTIVE: To investigate the effects of topical dorzolamide 2% q8h and brinzolamide 1% q8h, administered either alone (A and B, respectively) or in combination with topical timolol 0.5% q12h (C and D, respectively), on the circadian pattern of intraocular pressure (IOP), the pupil size, and heart rate in healthy cats. METHODS: In this prospective, randomized, double-blinded study, 10 healthy, adult cats were randomly assigned to one of four groups and the eye to be medicated was randomly assigned. IOP, pupil diameter, and heart rate were measured at 3-hour intervals. A 5 days' adjustment period was followed by a 5 days' placebo (baseline) period. Then, all groups of cats received all four treatments (A-D) according to a Latin square-based rotating schedule. Five days' medication periods were alternated with 3 days' washout periods. RESULTS: Mean baseline IOP was 13.6 ± 2.7 mm Hg. All treatments resulted in a statistically significant decrease in mean IOP in the treated eye: A: -2.33 mm Hg (95% CI: -2.71, -1.94), B: -1.91 mm Hg (95% CI: -2.30, -1.53), C: -2.36 mm Hg (95% CI: -2.74, -1.97), and D: -2.37 mm Hg (95% CI: -2.76, -1.98) and the nontreated eye: A: -0.19 mm Hg (95% CI: -0.28, -0.11), B: -0.18 mm Hg (95% CI: -0.27, -0.10), C -0.31 mm Hg (95% CI: -0.40, -0.23), and D: -0.24 mm Hg (95% CI: -0.32, -0.15). Timolol resulted in an additional, significant decrease in IOP of 4% and 5%, respectively, compared to A and B, and in mild bradycardia and miosis. CONCLUSIONS: Topical administration of dorzolamide 2% and brinzolamide 1% q8h significantly decreased IOP in healthy cats. Supplemental timolol 0.5% eye drops q12h resulted in an additional, statistically significant reduction of IOP.

Intraocular lens power calculation for the equine eye.

BACKGROUND: Phacoemulsification and intraocular lens (IOL) implantation during cataract surgery in horses occur with increasing frequency. To reduce the postoperative refractive error it is necessary to determine the proper IOL power. In the present study retinoscopy, keratometry and ultrasonographic biometry were performed on 98 healthy equine eyes from 49 horses. The refractive state, corneal curvature (keratometry) and the axial location of all optical interfaces (biometry) were measured. The influences of breed, height at the withers, gender and age on values obtained and the comparison between the left and right eye were evaluated statistically. Corresponding IOL power were calculated by use of Binkhorst and Retzlaff theoretical formulas. RESULTS: Mean ± SD refractive state of the horses was + 0.32 ± 0.66 D. Averaged corneal curvature for Haflinger, Friesian, Pony, Shetland pony and Warmblood were 21.30 ± 0.56 D, 20.02 ± 0.60 D, 22.61 ± 1.76 D, 23.77 ± 0.94 D and 20.76 ± 0.88 D, respectively. The estimated postoperative anterior chamber depth (C) was calculated by the formula C = anterior chamber depth (ACD)/0.73. This formula was determined by a different research group. C and axial length of the globe averaged for Haflinger 9.30 ± 0.54 mm and 39.43 ± 1.26 mm, for Friesian 10.12 ± 0.33 mm and 42.23 ± 1.00 mm, for Pony 8.68 ± 0.78 mm and 38.85 ± 3.13 mm, for Shetland pony 8.71 ± 0.81 mm and 37.21 ± 1.50 mm and for Warmblood 9.39 ± 0.51 mm and 40.65 ± 1.30 mm. IOL power was calculated with the Binkhorst and Retzlaff theoretical formulas. Calculated IOL power for the several breeds ranged from 18.03 D to 19.55 D. The mean value across all horses was 18.73 D determined with Binkhorst formula and 18.54 D determined with Retzlaff formula. CONCLUSIONS: Mean result of this study is: an 18.5 D IOL seemed to be the most appropriate to achieve emmetropia after IOL implantation in horses. Cataract surgery without IOL implantation results in hyperopic and visual compromised horses. Retinoscopy, keratometry and ultrasonographic biometry should be performed on every affected horse and postoperative visual outcome should be determined.

Evaluation of ultrasound velocity in enucleated equine aqueous humor, lens and vitreous body.

BACKGROUND: Sonographic ophthalmic examinations have become increasingly important in veterinary medicine. If the velocity of ultrasound in ocular tissues is known, the A-mode ultrasound method may be used to determine the axial intraocular distances, such as anterior chamber depth, lens thickness, axial length of the vitreous and axial globe length, which are required for intraocular lens (IOL) power calculations. To the authors' knowledge, the velocity of ultrasound in the ocular tissues of the horse was not previously determined. In the present study, 33 lenses, 29 samples of aqueous and 31 of vitreous from 35 healthy equine eyes have been examined. The corresponding ultrasound velocities are reported in dependence of age, temperature, gender and elapsed time after enucleation. RESULTS: The velocity of ultrasound at 36°C in equine aqueous, lens and vitreous are 1529 ±10 m/s, 1654± 29 m/s and 1527 ±16 m/s respectively, and the corresponding conversion factors are 0.998± 0.007, 1.008 ±0.018 and 0.997 ±0.010. A linear increase of the speed of ultrasound with increasing temperature has been determined for aqueous and vitreous. No temperature dependence was found for the speed of ultrasound in the lens. The ultrasound velocity did not significantly differ (95%) on the basis of gender, age or time after enucleation during the first 72 hours after death. CONCLUSIONS: Compared to human eyes, the ultrasound velocity in equine lental tissue deviates by one percent. Therefore, axial length measurements obtained with ultrasound velocities for the human eye must be corrected using conversion factors. For the aqueous and vitreous, deviations are below one percent and can be neglected in clinical settings.

Development of tear production and intraocular pressure in healthy canine neonates.

OBJECTIVE: The aim of this study was to investigate the development of aqueous tear production and intraocular pressure in healthy canine neonates between 2 and 12 weeks of age. ANIMALS: One litter, consisting of 8 healthy Beagle dogs--four males and four females-was used. PROCEDURES: Between the age of 2 and 12 weeks, tear production and intraocular pressure were measured weekly in both eyes. Tear production was measured by Schirmer tear test, before (STT1) and after (STT2) topical anesthesia and drying of the conjunctival sac. Intraocular pressure (IOP) was measured using a rebound tonometer. As no significant differences existed between left and right eye measurements (STT1, STT2, and IOP) at all time points, only right eye measurements were further analyzed. RESULTS: STT1, STT2, and IOP values increased significantly until the age of 9 weeks for STT1, until the age of 10 weeks for STT2, and until the age of 6 weeks and again between 10 and 11 weeks of age for IOP. IOP decreased significantly between 11 and 12 weeks of age. There were no significant differences in STT1, STT2, and IOP between males and females, except for IOP at 10 and 12 weeks of age. No significant correlation was demonstrated between body weight and STT1 or STT2. CONCLUSIONS: STT1, STT2, and IOP values increased significantly in the first weeks after birth. The results of this study indicate that separate reference values for tear production and intraocular pressure need to be established for neonatal dogs.

Distichiasis in a ferret (Mustela putorius furo).

A 4-year-old intact male ferret was presented to the Ophthalmology Service of the Department of Clinical Sciences of Companion Animals of Utrecht University with chronic blepharospasm, epiphora, and conjunctivitis of the right eye. Examination of the eye revealed mild conjunctivitis and three hairs protruding from the openings of meibomian glands in the upper eyelid, providing the clinical diagnosis of distichiasis. The distichia were removed by transconjunctival unipolar electrocautery. Recovery was uneventful, but the original signs recurred 10 weeks after surgery. Ophthalmic examination revealed another distichia at a different location in the same eyelid and it was removed by full-thickness wedge excision. Histopathological examination failed to reveal the exact origin of the distichia. To our knowledge, this is the first reported case of distichiasis in a ferret.

Eosinophilic keratoconjunctivitis in two rabbits.

The purpose of this case report is to describe the clinical course and cytologic findings, treatment, and outcome of eosinophilic keratoconjunctivitis in two rabbits. Ophthalmic examination revealed ocular discharge, dacryocystitis, blepharitis, conjunctivitis, white conjunctival and corneal plaques, corneal vascularization, and stromal infiltration with different degrees of severity in each case. In case 2 there was also ulcerative disease of the cornea. Computerized tomography scan of the head, corneal biopsy for histopathologic examination with additional Luna and Giemsa stain were performed in case 2 and conjunctival as well as corneal specimens were obtained for bacteriologic culture and cytologic examination in case 1. Based on test results, a diagnosis of eosinophilic keratoconjunctivitis was made in case 2 and a tentative diagnosis of eosinophilic keratoconjunctivitis was made in case 1. Response to treatment with a topical steroid and topical cyclosporin was supportive of the diagnosis in both cases and shared many similarities with the response to treatment previously described in cats. Eosinophilic keratitis should be considered as part of a differential diagnosis list in rabbits with a history of keratitis.

Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene.

Canine generalized progressive retinal atrophy (gPRA) is characterized by continuous degeneration of photoreceptor cells leading to night blindness and progressive vision loss. Until now, mutations in 11 genes have been described that account for gPRA in dogs, mostly following an autosomal recessive inheritance mode. Here, we describe a gPRA locus comprising the newly identified gene coiled-coil domain containing 66 (CCDC66) on canine chromosome 20, as identified via linkage analysis in the Schapendoes breed. Mutation screening of the CCDC66 gene revealed a 1-bp insertion in exon 6 leading to a stop codon as the underlying cause of disease. The insertion is present in all affected dogs in the homozygous state as well as in all obligatory mutation carriers in the heterozygous state. The CCDC66 gene is evolutionarily conserved in different vertebrate species and exhibits a complex pattern of differential RNA splicing resulting in various isoforms in the retina. Immunohistochemically, CCDC66 protein is detected mainly in the inner segments of photoreceptors in mouse, dog, and man. The affected Schapendoes retina lacks CCDC66 protein. Thus this natural canine model for gPRA yields superior potential to understand functional implications of this newly identified protein including its physiology, and it opens new perspectives for analyzing different aspects of the general pathophysiology of gPRA.

Characterization and prevalence of cataracts in Labrador Retrievers in The Netherlands.

OBJECTIVE: To assess the prevalence and distribution of types of cataract, investigate the effects of selective breeding on cataract development, and identify the relationship between posterior polar cataract and other types of cortical cataracts in Labrador Retrievers in The Netherlands. ANIMALS: 9,017 Labrador Retrievers. PROCEDURES: Records of 18,283 ophthalmic examinations performed by veterinary ophthalmologists from 1977 through 2005 were reviewed. There were 522 dogs affected by hereditary cataracts in 1 or both eyes without progressive retinal atrophy (PRA) and 166 PRA-affected dogs with cataracts. These cataracts were divided into 3 groups: posterior polar (triangular) cataract, extensive immature and mature cataract, and a miscellaneous group. Dogs with PRA were analyzed separately. RESULTS: From 1980 through 2000, the prevalence of hereditary cataracts was stable at 8%. The prevalence of cataracts in offspring of cataract-affected dogs was significantly increased, compared with the prevalence in offspring of nonaffected dogs. The distribution of types of cataract was significantly different between dogs with primary cataracts and PRA-affected dogs. Dogs with posterior polar (triangular) cataracts produced affected offspring with the same distribution of types of cataracts as the entire population of primary cataract-affected dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Cataract development in the Labrador Retriever population in The Netherlands appears to be a predominantly genetic disorder. Posterior polar (triangular) cataracts appear to be related to other types of hereditary cataract. Although there is no conclusive evidence, it seems valid to continue exclusion of all Labrador Retrievers affected by any type of primary cataract from breeding.

Comparison of the use of new handheld tonometers and established applanation tonometers in dogs.

OBJECTIVE: To examine the practical aspects, accuracy, and reproducibility of 2 new automatic handheld tonometers in dogs and compare them with results for 2 established applanation tonometers. ANIMALS: 15 freshly enucleated canine eyes for manometric evaluation and 20 conscious research dogs, 20 client-owned dogs, and 12 dogs with acute glaucoma for clinical tonometry. PROCEDURE: Calibration curves were determined for all 4 tonometers on 15 enucleated canine eyes. Intraocular pressure (IOP) was measured with each tonometer consecutively in conscious dogs, with the MacKay-Marg applanation tonometer as the reference device. Measurements were repeated in 20 sedated dogs. An induction-impact tonometer was evaluated clinically on dogs with acute glaucoma. Additionally, measurements obtained by an experienced and an inexperienced examiner and with or without use of topical anesthesia were compared. RESULTS: The portable pneumatonometer was cumbersome and time-consuming. Compared with results for the reference applanation tonometer, and confirmed by manometry, the portable pneumatonometer increasingly underestimated actual IOP values with increasing IOP. The induction-impact tonometer provided accurate and reproducible measurement values. There was a significant strong correlation between the IOP values obtained by the 2 examiners (r2, 0.82) and also with or without topical anesthesia (r2, 0.86). In dogs with glaucoma, the fitted line comparing values for the reference applanation tonometer and induction-impact tonometer closely resembled an ideal 1:1 relationship. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the portable pneumatonometer in dogs appears to have disadvantages. The induction-impact tonometer appears to provide a promising alternative to the use of applanation tonometers in dogs.

Abnormal ocular pigment deposition and glaucoma in the dog.

The combined occurrence of ocular pigment deposition and glaucoma has been described in Cairn Terriers. Recently, this condition was also observed in two other breeds: the Boxer (two cases) and the Labrador Retriever (one case). Six dogs were referred to the Ophthalmology section of the Department of Clinical Sciences of Companion Animals and to a private referral clinic because of glaucoma or blindness in one or both eyes. In five cases ophthalmic examination showed pigment depositions in the sclera around the entire circumference of the perilimbal zone. Eight enucleated eyes (four eyes of two Cairn Terriers, three eyes of two Boxers and one eye of a Labrador Retriever) were examined microscopically. All eyes showed the same findings: an extensive infiltration of large melanin-containing cells with an eccentric nucleus, located in the iris, ciliary body, retina, choroids and sclera. Transmission electron microscopy of two of the examined eyes revealed that the morphology of most of these cells was consistent with melanophages. While reports in the veterinary literature concerning this condition are limited the cells concerned have been described to be melanocytes. Further research is needed to conclusively identify the cell type. As described in the present report, the histologic and transmission electron microscopic findings suggest a different etiology of the ocular pigment deposition and glaucoma compared with the pigment dispersal syndrome in humans.