Ocular distribution and toxicity of intravitreal injection of triamcinolone acetonide in normal equine eyes

Objective  To determine ocular distribution and toxicity of a single injection of intravitreal triamcinolone acetonide (TA) in normal horses.
Animals studied  Six adult horses, donated to North Carolina State University.
Procedures  Six horses were injected intravitreally with either 10, 20, or 40 mg ( n  = 2 each) of TA. The opposite eye of each horse was injected with balanced salt solution (BSS). Ocular toxicity was assessed by biomicroscopy, tonometry, indirect ophthalmoscopy, and electroretinogram. Aqueous humor (AH), vitreous humor (VH), and plasma samples were collected. Horses were euthanized 7 or 21 days after injection and eyes enucleated for histopathology. TA concentrations in AH, VH, and plasma were measured by HPLC.
Results  Three control eyes and one TA eye developed inflammation after injection or collection of AH. Positive bacterial cultures ( Corynebacterium spp., Staphylococcus spp., and Streptococcus spp.) were obtained from three of these eyes. Other than transient corneal edema in TA injected eyes, which resolved by 7 days after injection, no other changes were observed. TA crystals were visible within the vitreous body. No evidence of TA toxic effect was noted on histopathology. TA was detected in all AH and VH samples from treated eyes following injection. Drug was not detected in the plasma.
Conclusions  There was no evidence of overt toxicity from intravitreal TA in normal horses and a single intravitreal injection resulted in TA ocular levels for 21 days. However, the risk for bacterial infections with intravitreal injection or anterior chamber aspirations in horses is high. Use of topical and systemic antibiotics after injection is recommended.     

Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses

OBJECTIVE: To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses. ANIMALS: 11 healthy adult horses. PROCEDURE: Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured. RESULTS: Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.     

The effect of topical administration of atropine sulfate on the normal equine pupil: influence of age, breed and gender

Objectives The purpose of this study was to determine the influence of age, breed and gender on vertical pupil diameter (VPD) following a single dose of 1% atropine sulfate ophthalmic solution in the normal equine eye. Animals studied Thirty‐two horses of various ages, breeds and genders were included. The horses had no history or clinical signs of ophthalmic disease. All horses studied had darkly pigmented irides. Procedures Two milligrams of 1% atropine sulfate ophthalmic solution was topically administered as a single dose in the right eye of each horse on Day 0. The VPD (mm) was measured in both eyes using digital calipers prior to treatment and every 24 h after administration for 2 weeks (Days 1–14). Duration of effect on VPD was then calculated for treated and untreated eyes. Data were also analyzed for effect of age, breed and gender on mean VPD, maximum VPD and time to maximum VPD. Results The VPD in the treated eye was significantly elevated compared to baseline measurements and compared to the untreated eye at all time points. Arabians had a greater mean VPD at Day 0 and on several days following treatment. Females had greater mean VPD compared to males on 5 out of 15 days. Conclusions Duration of mydriasis after administration of 1% atropine sulfate ophthalmic solution in the normal equine eye is greater than 14 days. Horses of the Arabian breed and female horses may be more sensitive to effects of cholinergic blockade in the eye.     

The use of mitomycin C as an adjunctive treatment for equine ocular squamous cell carcinoma

OBJECTIVE: To assess the effectiveness of topical mitomycin C application as an alternative adjunctive therapy to CO2 laser ablation in the treatment of equine ocular squamous cell carcinoma. DESIGN: A retrospective clinical study of eight client owned horses in which 10 affected eyes were treated for ocular squamous cell carcinoma over a 17 month period. (March 2003 to August 2004). PROCEDURE: Each horse was given a general anaesthetic to allow CO2 laser ablation of the lesion(s). Mitomycin C at a concentration of 0.4 mg/mL was then applied intraoperatively to the affected areas for 1 or 5 minutes. Postoperatively a triple antibiotic eye ointment was applied to the eye twice daily and each horse was treated with systemic non-steroidal anti-inflammatory drugs for 7 days. RESULTS: Recurrence following treatment was noted in three eyes. Two of these were retreated and no further signs developed. The remaining eye was enucleated at the request of the owner. Overall 90% of treated eyes appeared free of tumour a minimum of 11 months post treatment. CONCLUSION: In this case series mitomycin C appeared to offer a valid alternative to other adjunctive therapies currently employed in the treatment of equine ocular squamous cell carcinoma.     

Distribution of kanamycin in ocular tissues of calves

The ocular distribution of kanamycin following intramuscular, bulbar subconjunctival injection, or after constant rate intravenous infusion to calves was studied. Steady-state plasma concentrations of kanamycin were achieved in either normal calves, or in those experimentally infected with Moraxella bovis, and the concentrations of kanamycin in the serum, aqueous humor, vitreous body, tears, and the ocular tissues were measured. Kanamycin was not detected in the retina, lens, vitreous body, or the aqueous humor of any eyes, but the concentration of drug in the tears, conjunctiva, cornea and the orbital lacrimal gland of these calves ranged between 18 and 21% of that in serum. At steady-state plasma levels, the kanamycin concentrations in tears from eyes with keratoconjunctivitis and from normal eyes were similar. A study using lyophilized, powdered, ocular tissues in vitro showed that kanamycin was highly bound to the bovine retina and iris, and could be eluted using 0.2 N NaOH. The binding of kanamycin to other ocular tissues, including cornea, conjunctiva and lens, was significantly less. The concentration of kanamycin in the serum and the tears of calves was also measured after intramuscular or bulbar subconjunctival injection. After intramuscular administration of kanamycin (10 mg/kg of body-weight), the mean serum concentration was maximal at 1 h (32 micrograms/ml) and remained greater than or equal to 1.0 microgram/ml for 8 h. The mean tear concentration was maximal (3.1 micrograms/ml) at 30 min, and remained greater than or equal to 1.5 micrograms/ml for only 2.5 h. Following bulbar subjunctival administration of kanamycin (100 mg, single subconjunctival dose), the mean tear concentration was 1127 micrograms/ml at 30 min, less than or equal to 4.1 micrograms/ml at 4 h, and thereafter was less than or equal to 1.0 microgram/ml. It was concluded that kanamycin has limited distribution to the ocular tissues following parenteral administration. Binding of the drug to the ocular pigments may be responsible for its limited intraocular penetration.     

Effects of topical administration of 0.005% latanoprost solution on eyes of clinically normal horses.

OBJECTIVE: To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration. ANIMALS: 20 adult clinically normal horses. PROCEDURE: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora, blepharospasm, blepharedema, and aqueous flare were recorded prior to IOP measurement. RESULTS: IOP was reduced from baseline by a mean value of 1.03 mm Hg (5%) in males and 3.01 mm Hg (17%) in females during the treatment period. Miosis developed in all treated eyes and was moderate to marked in 77% of horses, with the peak effect observed 4 to 8 hours after drug administration. Conjunctival hyperemia, epiphora, blepharospasm, and blepharedema were present in 100, 57, 42, and 12% of treated eyes, respectively, 2 to 24 hours following drug administration. Aqueous flare was not observed at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Although IOP was reduced with every 24-hour dosing of latanoprost, the frequency of prostaglandin-induced adverse events was high. Because recurrent uveitis appears to be a risk factor for glaucoma in horses, topical administration of latanoprost may potentiate prostaglandin-mediated inflammatory disease in affected horses.     

Pharmacokinetics and metabolism of dantrolene in horses

Dantrolene is a skeletal muscle relaxant used commonly in performance horses to prevent exertional rhabdomyolysis. The goal of the study reported here was to begin to characterize cytochrome P450-mediated metabolism of dantrolene in the horse and describe the pharmacokinetics of the compound, formulated as a capsule or a compounded paste formulation, following oral administration. Dantrolene is rapidly metabolized to 5-hydroxydantrolene both in vivo and in vitro. Preliminary work with equine liver microsomes suggest that two enzymes are responsible for the metabolism of dantrolene, as evidenced by two distinct K(m) values, one at high and one at low substrate concentrations. For the pharmacokinetic portion of the study, a randomized, balanced 2-way crossover design was employed wherein eight healthy horses received a single oral dose of either capsules or paste followed by a 4 week washout period prior to administration of the second formulation to the same horse. Blood samples were collected at time 0 (prior to drug administration) and at various times up to 96 h postdrug administration. Plasma samples were analyzed using liquid chromatography-mass spectrometry and data analyzed using both noncompartmental and compartmental analysis. Peak plasma concentrations were 28.9 ± 21.6 and 37.8 ± 12.8 ng/mL for capsules and paste, respectively and occurred at 3.8 h for both formulations. Dantrolene and its major metabolite were both below the limit of detection in both plasma and urine by 168 h postadministration.     

Ocular parameters related to drug delivery in the canine and equine eye: aqueous and vitreous humor volume and scleral surface area and thickness

OBJECTIVE: To measure the ocular surface area, scleral thickness, and the aqueous and vitreous humor volumes in the canine and equine eye. Animals studied Fourteen canine and 16 equine cadaver eyes. PROCEDURE: Eyes were measured either fresh or following fixation in formalin. Ocular surface area was calculated using the fluid displacement method. Globes were hemisected and aqueous and vitreous humor were collected and quantitated. Scleral thickness was measured by digital caliper, by image projection, and by ultrasonic biomicroscopy (UBM). RESULTS: Mean +/- standard deviation (SD) scleral surface areas in canine and equine eyes were 12.87 +/- 2.24 and 57.23 +/- 5.63 cm2, respectively. Mean +/- SD aqueous humor volume was 0.77 +/- 0.24 in the dog and 3.04 +/- 1.27 mL in the horse. Mean vitreous humor volume was 1.7 +/- 0.86 mL for the canine eye and 26.15 +/- 4.87 mL for the equine eye. In canine and equine eyes, the sclera was thinnest at the ocular equator: 0.34 +/- 0.13 mm (canine) and 0.53 +/- 0.1 (equine). There were no significant differences between the direct caliper and projected thickness measurements or differences between measurements in the superior, inferior, nasal, and temporal quadrants of the eye. Scleral thickness in fresh tissue was greater than in fixed tissue at most sites. CONCLUSIONS: The UBM measurement method appeared to be most consistent and reproducible when compared to direct measurement techniques. Formalin fixation of the eyes was associated with significantly thinner scleral tissue than with fresh ocular tissue.     

Kinetics of uptake and effects of topical indomethacin application on protein concentration in the aqueous humor of dogs

The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Visual outcome in a group of dogs with ocular blastomycosis treated with systemic antifungals and systemic corticosteroids

OBJECTIVE: To evaluate the success of the use of systemic corticosteroids and antifungal medications in the treatment of dogs with ocular lesions associated with systemic blastomycosis. DESIGN: Retrospective study. ANIMALS STUDIED: Medical records of 25 dogs diagnosed with blastomycosis, via either cytology or histopathology, at the Purdue University Veterinary Teaching Hospital between 1 January 2000 and 1 January 2005, were reviewed. PROCEDURE: Data collected from the medical records included signalment, presence and progression of ocular lesions, antifungal drugs administered, oral and topical corticosteroid administration, length of follow-up, response to treatment, and visual outcome. RESULTS: Of the 25 cases reviewed, 12 dogs (19 eyes) with follow-up information were found to have lesions consistent with ocular blastomycosis. Length of follow-up in the 12 cases ranged from 1 month to 31 months with a mean of 9 months. Antifungal therapy for all cases consisted of oral itraconazole (5 mg/kg every 24 h) initially. In seven cases, the antifungal drug administered was changed from itraconazole to oral fluconazole. Two of these also received intravenous amphotericin B, and two received additional treatment with itraconazole. All 12 dogs also received oral prednisone. The dose of oral prednisone utilized ranged from 0.2 mg/kg/day to 1.4 mg/kg/day with a mean of 0.7 mg/kg/day; the duration of oral prednisone administration ranged from 2 weeks to 8.5 months with a mean of 3 months. Topical prednisolone was a component of the treatment of 16 of the 19 eyes. Duration of topical prednisolone treatment ranged from 1 month to 30 months with a mean of 5 months. Lesions not located in the eyes exhibited a positive response to treatment in 11 (92%) of the 12 dogs. Overall, 14/19 (74%) affected eyes were visual at the time of their final recheck. All eyes with mild or moderate lesions and 5/10 (50%) severely affected eyes were visual at their last recorded recheck examination. CONCLUSIONS: The administration of systemic corticosteroids did not appear to adversely affect the survival rate and might have played a role in preservation of vision in a majority of dogs in this group with ocular blastomycosis.     

Effect of topical ophthalmic latanoprost on intraocular pressure in normal horses

The ocular effects of latanoprost ophthalmic solution were evaluated in two studies, with eight horses in each study. One eye of each horse was treated with latanoprost ophthalmic solution once daily for 5 days, and the opposite eye received a control solution of sterile eyewash. Intraocular pressure and pupillary diameter were measured daily for 5 days after treatment. Latanoprost had no significant effect on intraocular pressure or pupillary diameter in normal horse eyes compared with control eyes in these studies. Placement of an eyelid nerve block resulted in significantly lower intraocular pressure.     

Doxycycline levels in preocular tear film of horses following oral administration

Objective To determine the concentration of doxycycline in preocular tear film following oral administration in horses as a possible therapeutic modality for infectious and keratomalacic equine keratitis. Procedure Eight broodmares without ocular disease from a Thoroughbred breeding facility were included in this study. Each mare received 20 mg/kg of doxycycline by mouth once daily in the morning for five consecutive days. Tears were collected 1 h after doxycycline administration starting on day one of administration and continuing for 10 consecutive days. Doxycycline levels in the tears were measured using liquid chromatography with tandem mass spectrometric detection (LC-MS/MS). Results Doxycycline was present in the tears of each mare at low µg/mL levels with the highest concentration appearing on the third to fifth days (8.21–9.83 µg/mL). Doxycycline levels had fallen below quantifiable ranges by day 10. No systemic side-effects were noted in any of the horses included in this study. Conclusions Oral doxycycline is present in preocular tear film of normal horses with noninflamed eyes and may be useful as treatment in equine ulcerative keratomalacia. The oral dose listed was tolerated well by the horses in this study. The drug levels attained at 20 mg/kg once daily orally of doxycycline may aid in the treatment of corneal ulceration in horses, but further study is warranted.     

Ocular penetration of intravenously administered enrofloxacin in the horse

REASON FOR PERFORMING STUDY: Information on antibiotic concentrations in the equine eye following systemic therapy is limited. Reports that Leptospira spp. are frequently present in the eyes of horses with recurrent uveitis, emphasises a need for studies on ocular concentrations of specific antibiotics. HYPOTHESES: 1) Enrofloxacin, administered i.v. at 7.5 mg/kg bwt q. 24 h, results in aqueous humour concentrations greater than the reported minimum inhibitory concentration (MIC) for Leptospira pomona. 2) Aqueous humour paracentesis sufficiently disrupts the blood-aqueous humour barrier (BAB) to cause an increase in aqueous humour protein and enrofloxacin concentrations. METHODS: Aqueous humour enrofloxacin and total protein concentrations were determined in 6 healthy, mature horses after i.v. administration of enrofloxacin. Paracentesis was performed on the left eye on Days 3 and 4, 1 h following enrofloxacin administration, to determine enrofloxacin concentrations in healthy eyes and in eyes with mechanical disruption of the BAB. Paracentesis was also performed on the right eye 23 h after enrofloxacin administration. Blood samples were collected from the horses at identical times to determine enrofloxacin aqueous humour:plasma ratios. RESULTS: Mean +/- s.d. enrofloxacin concentration in the aqueous humour 1 h post administration on Day 3 was 0.32 +/- 0.10 mg/l (range 0.18-0.47); and aqueous humour enrofloxacin, total protein and aqueous humour:plasma enrofloxacin ratios were higher on Day 4 than Day 3. CONCLUSIONS AND POTENTIAL RELEVANCE: Following disruption of the BAB, enrofloxacin concentrations were above the reported MIC for Leptospira pomona.     

The effects of bimatoprost and unoprostone isopropyl on the intraocular pressure of normal cats

OBJECTIVE: To evaluate the effects on intraocular pressure (IOP), pupillary diameter (PD), blepharospasm score, conjunctival injection score, and aqueous humor flare score when either 0.03% bimatoprost solution is applied once daily or 0.15% unoprostone isopropyl solution is applied twice daily topically to the eyes of normal cats. MATERIALS AND METHODS: The aforementioned parameters were evaluated daily in each of 12 cats throughout the entirety of the study. During an initial 10-day treatment phase a single eye of six of the cats was treated with 0.03% bimatoprost solution while a single eye of the remaining six cats was treated with buffered saline solution (BSS) once daily. During a second 10-day treatment phase a single eye of six of the cats was treated with 0.15% unoprostone isopropyl solution while a single eye of the remaining six cats was treated with BSS twice daily. Contralateral eyes of all cats remained untreated at all time points. RESULTS: Blepharospasm score, conjunctival injection score, and aqueous humor flare score never rose from a value of 0, for any eye of any cat during the study. The mean +/- SD of IOP for eyes treated with 0.03% bimatoprost solution and BSS were 16.55 +/- 3.06 mmHg and 18.02 +/- 3.52 mmHg, respectively. The mean +/- of PD for eyes treated with 0.03% bimatoprost solution and BSS were 5.7 +/- 1.57 mm and 6.39 +/- 1.78 mm, respectively. The mean +/- SD of IOP for eyes treated with 0.15% unoprostone isopropyl solution and BSS were 15.7 +/- 2.91 mmHg and 17.2 +/- 2.9 mmHg, respectively. The mean +/- SD of PD for eyes treated with 0.15% unoprostone isopropyl solution and BSS were 5.8 +/- 1.43 mm and 6.9 +/- 1.37 mm, respectively. There was no significant difference (P > or = 0.05) in IOP or PD between eyes treated with 0.03% bimatoprost solution vs. eyes treated with BSS. Similarly, there was no significant difference (P > or = 0.05) in IOP or PD between eyes treated with 0.15% unoprostone isopropyl solution vs. eyes treated with BSS. CONCLUSION: Neither once daily topical administration of 0.03% bimatoprost solution nor twice daily topical administration of 0.15% unoprostone isopropyl solution significantly affect the IOP of normal cats. Both 0.03% bimatoprost solution and 0.15% unoprostone isopropyl solution induced no significant ocular side effects in normal cats when dosed over a 10-day treatment period.     

Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations

Reasons for performing study: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti‐inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses. Objectives: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria. Methods: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty‐three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined. Results: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half‐life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier‐disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC₅₀ and MIC₉₀ for many gram‐positive equine pathogens. Potential relevance: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC≤0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.     

Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci

Objective To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). Procedure Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow‐up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi‐squared analysis. Age and length of follow‐up time were compared using a student’s t‐test. Results Ninety‐one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty‐eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. Conclusions Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU.     

Effects of topical administration of 1% brinzolamide on intraocular pressure in clinically normal horses

Reasons for performing study: Only few drugs with limited efficacy are available for topical treatment of equine glaucoma. Objective: To evaluate the effect of topical administration of 1% brinzolamide on intraocular pressure (IOP) in clinically normal horses. Methods: Healthy mature horses (n = 20) with normal ocular findings, were studied. The IOP was measured 5 times daily (07.00, 11.00, 15.00, 19.00 and 23.00 h) over 10 days. On Days 1 and 2, baseline values were established. On Days 3–5 one eye of each horse was treated with one drop of 1% brinzolamide every 24 h immediately following the 07.00 h measurement. On Days 6–8 the same eye was treated with 1% brinzolamide every 12 h (07.00 and 19.00 h). Measurements on Days 9 and 10 documented the return of IOP to baseline values. Statistical analysis of the data was performed. Results: In the treated eye a significant decrease in IOP compared to baseline values was noted during both the 24 and 12 h dosing periods (P<0.001). During the once‐daily treatment protocol an IOP reduction of 3.1 ±1.3 mmHg (14%) from baseline was recorded. During the twice‐daily protocol a total IOP reduction of 5.0 ± 1.5 mmHg (21%) was achieved. Conclusion: Intraocular pressure was significantly decreased by 1% brinzolamide in a once‐daily and a twice‐daily treatment protocol in normotensive eyes. These findings suggest that brinzolamide might also be effective in horses with an elevated IOP. Potential relevance: This drug may be useful for treatment of equine glaucoma.     

The pharmacokinetics of xylazine hydrochloride: an interspecific study

The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half-life ( t _{1/2 β}) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half-life ( t _{1/2 α}) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the plasma is reached after 12–14 min in all the species studied following intramuscular administration. Xylazine bioavailability, as measured by the ratios of the areas under the intravenous and intramuscular plasma concentration versus time curves, ranged from 52% to 90% in dog, 17% to 73% in sheep and 40% to 48% in horse. The low dosage in cattle did not permit calculation. Kinetic data are correlated with clinical data and the origins of interspecific differences are discussed.     

Pharmacokinetics of oral terbinafine in horses and Greyhound dogs

The objective of the study was to assess the pharmacokinetics of terbinafine administered orally to horses and Greyhound dogs. A secondary objective was to assess terbinafine metabolites. Six healthy horses and six healthy Greyhound dogs were included in the pharmacokinetic data. The targeted dose of terbinafine was 20 and 30 mg/kg for horses and dogs, respectively. Blood was collected at predetermined intervals for the quantification of terbinafine concentrations with liquid chromatography and mass spectrometry. The half-life (geometric mean) was 8.1 and 8.6 h for horses and Greyhounds, respectively. The mean maximum plasma concentration was 0.31 and 4.01 μg/mL for horses and Greyhounds, respectively. The area under the curve (to infinity) was 1.793 h·μg/mL for horses and 17.253 h·μg/mL for Greyhounds. Adverse effects observed in one study horse included pawing at the ground, curling lips, head shaking, anxiety and circling, but these resolved spontaneously within 30 min of onset. No adverse effects were noted in the dogs. Ions consistent with carboxyterbinafine, n-desmethylterbinafine, hydroxyterbinafine and desmethylhydroxyterbinafine were identified in horse and Greyhound plasma after terbinafine administration. Further studies are needed assessing the safety and efficacy of terbinafine in horses and dogs.     

Serum hepatitis associated with commercial plasma transfusion in horses

This report describes 4 fatal cases of serum hepatitis associated with the administration of commercial plasma in the horse. Serum hepatitis in the horse is characterized by acute hepatic central lobular necrosis, and it has been associated with the administration of biological products of equine origin. None of these horses had a recent history of equine biologic-origin vaccination; however, they had received 1.5-5 L of commercial plasma, and in I horse, an additional 8 L of fresh blood. Acute, severe colic unresponsive to medical therapy, lethargy, or sudden death developed in these 4 horses 41 to 60 days later. Two of the horses developed encephalopathy, confirmed in 1 horse by the presence of severe diffuse Alzheimer type II astrocytes in the brain. Although the prevalence of serum hepatitis associated with the administration of commercial plasma appears to be low in the horse, it should be considered an uncommon but potentially fatal risk factor.