Duration of corneal anaesthesia following multiple doses and two concentrations of tetracaine hydrochloride eyedrops on the normal equine cornea

Reasons for performing study: There is a clinical impression that tetracaine hydrochloride (THCl) eyedrops is a suitable topical anaesthetic in horses. Objective: To determine the duration of corneal anaesthesia following instillation of multiple doses and 2 concentrations of THCl in 10 healthy horses. Methods: The corneal touch threshold (CTT) was determined, in both eyes, before (basal CTT) and after application of one drop of 0.5%THCl, 2 drops at a 1 min interval of 0.5%THCl or one drop of 1%THCl. CTT was measured in mm every 5 min until complete recovery of the basal CTT. Treatments were separated by an interval of at least one week. Results: Corneal sensitivity was significantly reduced from baseline values for 30, 60 and 50 min after application of one drop of 0.5%THCl, 2 drops of 0.5%THCl and one drop of 1%THCl, respectively. Mean maximal anaesthetic effects, corresponding to a CTT of 0 mm, lasted 5.5, 16 and 15.25 min and maximal anaesthetic effect was present in 55, 90 and 80% of eyes, 5 min after application of one drop of 0.5%THCl, 2 drops of 0.5%THCl and one drop of 1%THCl, respectively. Conclusions: The application of a second drop or the use of more concentrated eyedrops significantly increases duration of both anaesthesia and maximal anaesthetic effect. Potential relevance: Duration of corneal anaesthesia following tetracaine instillation was established enabling a better use when performing diagnostic and therapeutic procedures. Comparison of tetracaine with other ocular anaesthetics needs to be published in the future.     

Increased drug concentration and repeated eye drop administration as strategies to optimize topical drug delivery: A fluorophotometric study in healthy dogs

Objectives

Determine tear film kinetics with different fluorescein concentrations and repeated eye drop administration at various time intervals.

Animals Studied

Six healthy Beagles.

Procedures

Six experiments were conducted on separate days: single eye drop administration (control) or two separate eye drops administered at 30 s, 1, 2, 5, and 10 min intervals. For each experiment, one eye received 0.3% fluorescein solution while the other eye received 1% fluorescein solution, and tear fluid was collected with capillary tubes at 0, 1, 5, 10, 20, 30, 40, 50, 60, 90, 120, and 180 min. Fluorescein concentrations were measured using automated fluorophotometry.

Results

Compared with 0.3% solution, eyes receiving 1% fluorescein solution had significantly higher tear film concentrations (p ≤ .046) and the area-under-the-fluorescein-time curve was twofold greater (p = .005). Compared with control: (i) Tear film concentrations were significantly higher for up to 20 min when repeating administration 30 s to 5 min after the first drop (p ≤ .006); (ii) The highest increase in area-under-the-curve was obtained with 2 and 5 min intervals for 0.3% (+109%–130%) and 1% solutions (+153%–157%); (iii) The highest increase in median precorneal retention time (defined as tear film concentration < 5% from baseline values) was obtained with 5 min intervals for 0.3% (55 min vs. 15 min in control) and 2–5 min intervals for 1% solutions (50 min vs. 25 min in control).

Conclusions

Drug delivery to the ocular surface can be enhanced by using more concentrated formulations and/or by repeating eye drop administration 2–5 min after the first dose.     

Effect of topical 1% tropicamide on Schirmer tear test results in clinically normal horses

Objective  To observe the effect of topical 1% tropicamide on equine tear production as measured by Schirmer I tear test.
Materials and methods  Fourteen adult horses received one drop of 1% tropicamide ophthalmic solution in one eye and the opposite eye served as the control. The tear production in both eyes was tested at 1, 2, 4, 6, and 24 h after 1% tropicamide administration.
Results  Measurements made 1 h after treatment revealed a significant reduction in Schirmer tear test values in tropicamide treated eyes ( P  = 0.002). The observed decrease in tear production was maintained up to 4 h after treatment ( P  = 0.002). Although tropicamide-induced decrease in STT values was observed in the treated eyes, the contralateral eyes did not show significant changes in Schirmer tear test results.
Conclusion  Single dose of topical 1% tropicamide resulted in statistically significant reduction in Schirmer tear test values in clinically normal horses.     

Effect of Topical 1% Tetracaine Hydrochloride on Intraocular Pressure in Ophthalmologically Normal Horses; a Pilot Study

The aim of this study was to evaluate the effect of topical 1% tetracaine hydrochloride on the intraocular pressure (IOP) in ophthalmologically normal horses. Thirty eyes of 15 clinically normal horses were used for this study. The animals were randomly assigned to two groups (treatment and control). Prior to the instillation of 1% tetracaine or placebo, the baseline IOPs (T0) of each animal were recorded in both groups. Then one drop of tetracaine was instilled randomly into one eye of each horse in the treatment group (8 horses). In the control group (7 horses), one drop of artificial tear was instilled in one randomly selected eye. The measurements were repeated at 2 minutes (T2), 5 minutes (T5), 15 minutes (T15), and 30 minutes (T30) post instillation via a rebound tonometer. There was no significant difference in the treatment group (P = .3). The peak IOP measured at T2 returned to the baseline value at T30. No significant difference was found in the mean IOP values between the treatment and the control groups, or between the males and females on any of the occasions (P > .05). The Results of this study revealed a nonsignificant increase of the IOP 2 minutes post instillation of 1% tetracaine in horses.     

Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis

OBJECTIVE: To examine in vitro effects of various antiproteolytic compounds on activity of matrix metalloproteinase (MMP)-2 and -9 in the tear film of horses with active corneal ulcers. SAMPLE POPULATION: Samples of tear film obtained from the eyes of 34 horses with active ulcerative keratitis. PROCEDURE: Horses were sedated, and tear samples were collected from the lower fornix of 34 ulcerated eyes by use of capillary tubes. The protease inhibitors 0.2% EDTA, 0.1% doxycycline, 10% N-acetylcysteine (NAC), 0.1% solution of a modified dipeptide that contains hydroxamic acid (ie, ilomostat), 0.1% alpha1-proteinase inhibitor (PI), 0.5% alpha1-PI, and 100% fresh equine serum (ES) were used to treat pooled samples. Amount of latent and active MMP-2 and -9 was measured by optical density scanning of gelatin zymograms of treated and untreated tear samples. RESULTS: Pooled tear samples obtained from ulcerated eyes contained the latent and active forms of MMP-2 and -9. Compared with MMP activity in untreated samples, total MMP activity (sum of all bands detected) observed on the gelatin zymogram gels was reduced by 99.4% by EDTA, 96.3% by doxycycline, 98.8% by NAC, 98.9% by ilomostat, 52.4% by 0.1% alpha1-PI, 93.6% by 0.5% alpha1-PI, and 90.0% by ES. CONCLUSIONS AND CLINICAL RELEVANCE: We documented that EDTA, doxycycline, NAC, ilomostat, alpha1PI, and ES inhibited MMP activity in vitro. Because these compounds use different mechanisms to inhibit various families of proteases in the tear film of horses, a combination of these protease inhibitors may be beneficial for treatment of corneal ulcers in horses.     

Evaluation of tear film proteinases in horses with ulcerative keratitis

Ulcerative keratitis is a common and potentially blinding ocular disease of horses, capable of progressing to corneal perforation in as little as 24 h. This rapid stromal degeneration is mediated in part by exogenous and endogenous proteinases. We measured and compared the concentrations of two matrix metalloproteinases (MMP-2 and MMP-9) and a serine proteinase (neutrophil elastase) present in the precorneal tear film of normal horses and horses with rapidly progressing ulcerative keratitis. Precorneal tear film samples were collected from 23 ulcerated and 21 unaffected eyes of 23 horses with unilateral ulcerative keratitis, and from 33 normal eyes of 17 control horses. MMP-2, MMP-9, and neutrophil elastase were identified by casein and gelatin zymography and quantified by computerized image analysis. Median MMP-9 levels were significantly higher in the precorneal tear film of young control horses vs. older control horses ( P  = 0.005). Median MMP-2, MMP-9, and neutrophil elastase levels were significantly higher in the precorneal tear film of ulcerated eyes when compared to age-matched normal controls ( P  = 0.004, P  = 0.001, and P  = 0.012, respectively). Median MMP-2 levels were also significantly higher in the precorneal tear film of contralateral eyes of affected horses when compared to age-matched normal controls ( P  = 0.004). No significant differences in median proteinase levels were detected between 'sterile' ulcers and those from which bacteria or mixed infections (bacteria and fungi) were isolated. However, median MMP-2 and neutrophil elastase levels were significantly higher in the precorneal tear film of eyes with 'sterile' ulcers when compared with ulcerated eyes from which fungi were isolated ( P < 0.05). The results of this study support the use of topical antiproteinase therapy which targets both MMPs and serine proteinases in progressive equine ulcerative keratitis.     

Pharmacokinetics of topically applied ciprofloxacin in equine tears

OBJECTIVE: To evaluate the pharmacokinetics of topically applied ciprofloxacin 0.3% ophthalmic solution in tears of healthy horses. ANIMAL STUDIED: Twenty healthy, adult, mixed-breed horses. PROCEDURES: Twenty study horses were confirmed free of ophthalmic disease by complete ophthalmic examination. Seventy microliters of 0.3% ciprofloxacin (Ciloxan) was placed in the ventral cul-de-sac of each eye using a microliter syringe and 19-g cannula. Population kinetics were carried out by sampling the tear film from the lower cul-de-sac of each eye with tear test strips at 5, 10, 15 and 30 min and 1, 2, 4 and 6 h post administration for a total of five samples at each time-point. Sample collection time was 15 s. Concentrations of ciprofloxacin were determined using high performance liquid chromatography. RESULTS: Mean (+/-SD) of the Schirmer tear test results from all eyes was 23.4 +/- 4.8 mm wetting in 1 min. Mean concentration of ciprofloxacin in the tears at 5 min post administration was 498.4 +/- 266.8 microg/g. Mean concentration rapidly declined and began to plateau at 30 min. The mean tear concentrations of ciprofloxacin at 30 min and at 1, 2, 4 and 6 h were 66.6 +/- 56.0, 60.25 +/- 55.7, 42.25 +/- 30.9, 36.25 +/- 32.0, and 45.5 +/- 46.5 microg/g, respectively. CONCLUSIONS: The pharmacokinetics of ciprofloxacin in normal horses are similar to those in rabbits and humans. Topical application of ciprofloxacin resulted in a mean tear concentration of ciprofloxacin that remained above the MIC(90) levels for most pathogenic bacteria for 6 h post administration.     

Profiles of matrix metalloproteinase activity in equine tear fluid during corneal healing in 10 horses with ulcerative keratitis

OBJECTIVE: Levels of tear film matrix metalloproteinases (MMPs) activity are significantly elevated in horses with ulcerative keratitis and contribute to the excessive breakdown of stromal collagen. Changes in the amount of proteolytic activity in horse tear film during corneal healing and stromal remodeling have not yet been reported, but we hypothesize they should decrease. In the present study we analyzed serial tear fluid from horses with ulcerative keratitis to identify any changes in MMP activity during corneal healing and stromal remodeling. PROCEDURES: Samples of tear fluid were obtained from both eyes of 10 horses with ulcerative keratitis on the day of admission (day 1) at the hospital and then at various time points until complete healing of the cornea. Tear film MMP2 and MMP9 activity was determined by quantitative gelatin zymography. In all cases medical treatment included topical applications of equine serum, antibiotics, atropine and systemic administration of anti-inflammatory drugs. Surgical procedures were performed in several cases on day 2 in addition to the medical treatment. RESULTS: The mean total MMP activity (+/- SD) measured in relative standard units (RSU) in the tear fluid of the ulcerated eye (2.44 +/- 1.44) of the 10 horses was significantly higher than the mean in the contralateral eye (0.81 +/- 0.68) (P = 0.006), on the day of admission at the VMTH. The mean MMP activity in these ulcerated eyes significantly decreased (-82.4%) between the first day of admission and the day when the ulcer had completely healed (P = 0.0002). The activity level in the healed eye (0.43 +/- 0.17) was not significantly different to the one in the contralateral eye (0.36 +/- 0.18) on the day of complete corneal healing (P = 0.374). The level of MMP activity in the contralateral eye also decreased from 0.81 +/- 0.68-0.36 +/- 0.18 but this decrease (56%) was not significant (P = 0.069). CONCLUSIONS: Ulcerative keratitis in horses is associated with initially high levels of tear film proteolytic activity that decrease as the ulcers heal. The success of medical and surgical treatment of the corneal ulcers is reflected by the enzyme activity in tears. In horses successful treatment does lead to a rapid reduction in tear film proteolytic activity that corresponded with the improvement in the clinical signs of corneal ulceration. Measurement of MMP activity in the tear film might represent a way to monitor the progression of corneal healing in horses with ulcerative keratitis.     

Constant rate infusion for topical ocular delivery in horses: a pilot study

OBJECTIVE: To assess the efficacy and kinetics of a continuous infusion modality for topical ophthalmic drug delivery via subpalpebral lavage in horses. ANIMALS STUDIED: Five ophthalmically normal horses PROCEDURES: A constant-rate continuous delivery pump was used to apply 0.01% fluorescein solution to the eyes of five ophthalmically normal horses via subpalpebral lavage. Fluorescein was applied at a rate of 0.14 mL/h for 72 h. Tear samples were collected from the ventral conjunctival fornix at regular intervals via capillary tube and tear fluorescein concentrations were determined via spectral assay. Laboratory studies to evaluate the procedures used in the study also were performed. RESULTS: Overall mean tear film fluorescein concentration was approximately 20% of the applied concentration of fluorescein. However, tear film fluorescein concentrations varied considerably between horses and over time. Dilution varied from 0.62% to 60% of the applied concentration. Air pockets sporadically appeared in subpalpebral lavage tubing lines, resulting in discontinuous topical application of fluorescein. CONCLUSIONS: Constant-rate delivery of ophthalmic medications using a continuous infusion pump may provide a valuable method of topical drug delivery if tear film dilution of drugs is taken into account.     

Determination of reference values for intraocular pressure and Schirmer tear test in clinically normal ostriches (Struthio camelus)

The purpose of this study was to establish normal physiologic reference values for intraocular pressure (IOP) and Schirmer tear test (STT) results in clinically normal ostriches (Struthio camelus). Twenty ostriches of both sexes, 10 juveniles (1.5-2 yr of age) and 10 adults, were included in this study. Complete ophthalmic examination was performed prior to this investigation. STT was performed by inserting a standard sterile STT strip over the ventral lid margin into the ventral conjunctival sac for 60 sec. Following the STT, IOP was measured using applanation tonometry with the Tono-Pen Vet tonometer after topical instillation of one drop of 0.5% proparacaine ophthalmic solution. The mean +/- SD and range of Tono-Pen readings of IOP for all birds was 18.8 +/- 3.5, with a range of 12-24. Mean IOP in juvenile ostriches was 19.7 +/- 3.6. Mean IOP in adult ostriches was 16.9 +/- 2.9. There was no statistically significant difference between young and adult birds (P = 0.07). The mean STT values in the present study were 16.3 +/- 2.5 mm/1 min when measurements from both eyes were averaged. Mean STT in juvenile and adult ostriches was 15.4 +/- 1.8 and 17.2 +/- 2.9 mm/1 min, respectively. There was no statistically significant difference between young and adult birds (P = 0.11). No statistically significant differences between genders were found for any of the results (P > or = 0.41). In conclusion, this study provides normal reference range values for STT and IOP in clinically healthy ostriches.     

Anaesthetic and cardiorespiratory effects of propofol at 10% for induction and 1% for maintenance of anaesthesia in horses

Reasons for performing study: Studies have demonstrated the clinical usefulness of propofol for anaesthesia in horses but the use of a concentrated solution requires further investigation. Objectives: To determine the anaesthetic and cardiorespiratory responses to a bolus injection of 10% propofol solution in mature horses. Methods: Three randomised crossover experimental trials were completed. Trial 1: 6 horses were selected randomly to receive 10% propofol (2, 4 or 8 mg/kg bwt i.v.). Trial 2: 6 horses received 1.1 mg/kg bwt i.v. xylazine before being assigned at random to receive one of 5 different doses (1–5 mg/kg bwt) of 10% propofol. Trial 3: 6 horses were sedated with xylazine (0.5 mg/kg bwt, i.v.) and assigned randomly to receive 10% propofol (3, 4 or 5 mg/kg bwt, i.v.); anaesthesia was maintained for 60 min using an infusion of 1% propofol (0.2‐0.4 mg/kg bwt/min). Cardiorespiratory data, the quality of anaesthesia, and times for induction, maintenance and recovery from anaesthesia and the number of attempts to stand were recorded. Results: Trial 1 was terminated after 2 horses had received each dose of 10% propofol. The quality of induction, anaesthesia and recovery from anaesthesia was judged to be unsatisfactory. Trial 2: 3 horses administered 1 mg/kg bwt and one administered 2 mg/kg bwt were not considered to be anaesthetised. Horses administered 3–5 mg/kg bwt i.v. propofol were anaesthetised for periods ranging from approximately 10–25 min. The PaO₂ was significantly decreased in horses administered 3–5 mg/kg bwt i.v. propofol. Trial 3: The quality of induction and recovery from anaesthesia were judged to be acceptable in all horses. Heart rate and rhythm, and arterial blood pressure were unchanged or decreased slightly during propofol infusion period. Conclusions: Anaesthesia can be induced with a 10% propofol solution and maintained with a 1% propofol solution in horses administered xylazine as preanaesthetic medication. Hypoventilation and hypoxaemia may occur following administration to mature horses. Potential relevance: Adequate preanaesthetic sedation and oxygen supplementation are required in horses anaesthetised with propofol.     

Measurement of phenol red thread tear test in Arabian and throughbred horses

Objective To determine physiologic levels of tear production in Arabian (AH) and throughbred horses (TH) by using phenol red thread test (PRT). Animals studied The study was performed on 16 AH and 14 TH, ranging from 2.5 to 24 years of age, housed in a stable situated in the Sanliurfa of Turkey. Procedures For the measurement of PRT, the strip was placed under the lower eyelid approximately one‐third the distance from the temporal to nasal canthus and left for 15 s. The length of the wet area was measured in mm and compared among breed, sex, and age groups and between eyes of both sides. Results The mean length of the wet area was in AH and TH were 30.22 ± 0.99 mm ranging from 16 to 41 and 31.00 ± 1.4 mm ranging from 14 to 47, respectively. There were no significant differences in tear production among breed, sex, or age groups. The values measured for left eyes were significantly higher than those for right eyes (P < 0.05). Conclusions Phenol red thread test measurement is easily used, with no pain, and a comfortable method. PRT can be used in equine ophthalmology on a routine basis to the measurement of tear production. These normal PRT values help diagnosis keratoconjunctivitis sicca in horses.     

Qualitative tear film and conjunctival goblet cell assessment of cats with corneal sequestra

OBJECTIVES: To evaluate the tear film qualitatively and conjunctival goblet cell numbers in cats with and without corneal sequestra. ANIMALS STUDIED AND PROCEDURES: This was a prospective evaluation of 11 cats with corneal sequestra and 14 control eyes that were either the contralateral normal eye when the sequestrum was unilateral or from control cats of similar age with no ocular disease. All cats in this study were examined by a veterinary ophthalmologist. The ophthalmic examinations included a neuro-ophthalmic evaluation, Schirmer tear tests, fluorescein staining, tear film break-up times, applanation tonometry, biomicroscopy, and indirect ophthalmoscopy. The palpebral conjunctiva at the dorsal nasal, ventral nasal, dorsal temporal and ventral temporal fornices were biopsied after topical anesthetic was applied to the cornea and conjunctiva. The conjunctival biopsies were fixed in formalin and sectioned routinely and stained with hematoxylin and eosin, and periodic acid-Schiff. These slides were examined by light microscopy by a blinded examiner. Goblet cell numbers were compared to conjunctival basal epithelial cell numbers by region. The goblet cell numbers by region from the eyes with sequestra was statistically compared to those from eyes without sequestra, with a student's paired t-test. Conjunctival swabs were collected from the cats with corneal sequestra and submitted for polymerase chain reaction for Herpes felis, Chlamydia psiitticia, and Mycoplasma felis. The corneal sequestra were removed by surgical keratectomy and fixed and stained routinely, and examined by light microscopy. RESULTS: No neurologic abnormalities were detected in any of the cats. The Schirmer tear tests (eyes with sequestra 14+/-5.1 mm/min; normal eyes 15+/-6.8 mm/min) and intraocular pressures (eyes with sequestra 21+/-6.6; normal eyes 22+/-5.8) were within normal reference ranges for cats. Biomicroscopic examinations revealed varied sizes and depths of brown- and amber-colored corneal sequestra. No abnormalities were noted on indirect ophthalmoscopic examinations. The tear film break-up time was 21 s (+/-12) for the normal eyes (n=14) and 14 s (+/-13) in eyes with corneal sequestra (n=11). The average goblet/epithelial cell ratios by region for the normal eyes and the eyes with sequestra respectively were 0.66, 0.56 for the dorsal nasal fornix, 0.68, 0.57 for the ventral nasal fornix, 0.63, 0.48 for the temporal dorsal fornix, and 0.55, 0.49 for the temporal ventral fornix. There were no significant differences in tear film break-up times and goblet cell numbers in eyes with corneal sequestra and those without sequestra. Three conjunctival swabs from two of 11 cats with sequestra were positive with PCR for Herpes felis virus. These included one cat with bilateral sequestra and one cat with unilateral corneal sequestrum. CONCLUSIONS: The pathogenesis of feline corneal sequestra does not appear to be linked primarily to abnormal goblet cell numbers, qualitative tear film abnormalities, and accelerated tear film break-up time.     

Evaluation of the ocular penetration of topical alpha-luminol (Galavit®/GVT®)

Purpose Oxidative stress plays a major role in the pathogenesis of many neurodegenerative diseases. It has also been implicated as part of the pathogenic mechanisms in the development of glaucoma. Alpha‐luminol has shown profound anti‐inflammatory and antioxidant effects in both experimental animal and human clinical studies. The purpose of this pilot study was to investigate for the first time the ocular penetration of topical alpha‐luminol. Methods Nine animals were divided into three treated groups (three animals each; one drop OU/n = 18), each group receiving a different concentration of the eyedrop (0.5%, 1.5%, 2.5%). Aqueous humor and peripheral blood samples were obtained from each rabbit at three different timepoints (20 min, 4 h and 12 h). Samples were analyzed by means of high performance liquid chromatography and mass spectrometry; median values were compared. Results Alpha‐luminol was found in the aqueous humor in all treated groups at all timepoints. At the 2nd and 3rd timepoints (4 h and 12 h), aqueous humor levels decreased significantly (P < 0.05) for two of the three dosages tested and it was not detectable in some eyes. The highest aqueous humor concentration of the drug was 272 ng/mL after 20 min (0.0217% of one drop, 2.5% group). Alpha‐luminol was found in the vitreous in two animals, one in the 1.5% and another in the 2.5% group (16.4 and 21.5 ng/mL, respectively), at 12 h. Conclusions Topically administered alpha‐luminol readily penetrates into the anterior chamber and can penetrate into the vitreous chamber. Further investigation is warranted to better understand the intraocular pharmacokinetics of alpha‐luminol.     

Equine keratomycoses in California from 1987 to 2010 (47 cases)

Reasons for performing study: Equine keratomycosis in the western USA has received little study, probably owing to its low prevalence. Objectives: To determine clinical features, predominant fungal isolates, treatment modalities and outcomes of horses with keratomycosis in California and compare these with results from different geographic regions. Methods: Records of horses presented to the University of California‐Davis Veterinary Medical Teaching Hospital (UCD‐VMTH) with confirmed keratomycosis between 1987 and 2010 were reviewed for this retrospective study. Information retrieved from the record included background, ophthalmic examination findings, treatment prior to and following presentation, visual outcome, and ocular survival. Results: A total of 48 eyes in 47 horses met the inclusion criteria and comprised 2% of cases presented to the UCD‐VMTH ophthalmology service. Prior to presentation, 20 horses (43%) received at least one topically administered anti‐inflammatory medication. Keratomycosis was confirmed by fungal culture in 38 horses (81%), by histopathology in 2 horses (4%) and by cytology in 7 horses (15%). Forty‐four isolates were identified in the 38 horses cultured; Aspergillus was the most common isolate (64%) and a novel isolate, Papulospora, was identified in 2 horses. Treatment consisted of medication only (73%), medical and surgical treatment (25%), or immediate enucleation (2%). Globe retention was 77% and vision retention was 53%. Corneal perforation was significantly associated with loss of vision (P<0.001). Conclusions: Keratomycosis is relatively uncommon in horses presented for ophthalmic conditions at UCD‐VMTH. Corneal perforation was a negative prognostic indicator for vision in this population of northern Californian horses.     

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.     

Effect of topical tropicamide on tear production as measured by Schirmer's tear test in normal dogs and cats

Objective To evaluate the effect of a single dose of topical 1% tropicamide on tear production as measured by the Schirmer tear test (STT) in the normal dog and cat. Material and methods Twenty‐eight dogs and 32 cats received 50 µl : l of 1% tropicamide in one eye and the opposite eye served as the control. STTs were performed immediately before instillation of tropicamide and then at 1, 4, 8 and 24 h post drug instillation. STT results were compared between the control and treated eyes at the different times. Results Aqueous tear production in dogs, measured by STT, was not significantly reduced. The mean ± SEM STTs for the baseline time for control and tropicamide‐treated eyes were 19.9 ± 0.8 and 20.3 ± 0.8 mm wetting/min, respectively. For the control eyes, the subsequent mean ± SEM STT levels were 20.3 ± 0.9 (1 h), 21.1 ± 0.8 (4 h), 20.1 ± 0.9 (8 h), and 18.7 ± 0.7 (24 h). For the tropicamide‐treated eyes, the subsequent mean ± SEM STT levels were 19.4 ± 0.9 (1 h), 19.3 ± 0.9 (4 h), 20.0 ± 0.9 (8 h), and 18.4 ± 0.8 (24 h). Aqueous tear production of both eyes was significantly reduced in cats at 1 h but returned to baseline by 4 h post tropicamide instillation. The mean ± SEM STT levels for the baseline time in cats for control and tropicamide‐treated eyes were 14.9 ± 0.8 and 14.7 ± 0.8 mm wetting/min, respectively. Subsequent mean ± SEM STT levels for the control eyes were 6.4 ± 1.1 (1 h), 11.9 ± 1.0 (4 h), 13.9 ± 0.8 (8 h), and 16.4 ± 1.0 (24 h). For the tropicamide‐treated eyes, the subsequent mean ± SEM STT levels were 5.3 ± 0.8 (1 h), 10.2 ± 0.8 (4 h), 14.7 ± 1.0 (8 h), and 16.6 ± 1.0 (24 h). Conclusion Single dose 1% tropicamide does not significantly lower tear production rates, as measured by the STT, in normal dogs. However, in normal cats single doses of 1% tropicamide in one eye cause significant reductions in tear production of both eyes at 1 h that recovered to baseline levels by 4 h.     

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.     

Tear-film osmolarity in normal cats and cats with conjunctivitis

Objective To compare the tear‐film osmolarity of normal cats and cats with conjunctivitis. Animal studied The population consisted of shelter, research, and privately owned cats. Procedures Cats were classified as normal or having conjunctivitis. An ophthalmic examination including Schirmer tear test (STT), fluorescein staining, tear‐film break‐up time (TFBUT), intraocular pressure (IOP), and slit‐lamp biomicroscopy of the anterior segment was performed. The severity of conjunctivitis was graded and assigned a numerical score. The Tear Lab^TM Osmolarity System was utilized to determine the tear‐film osmolarity. Unpaired t‐tests were used to compare tear‐film osmolarity, TFBUT, IOP, and STT of the two groups. Results A total of 93 cats (186 eyes) were examined. There were 37 normal cats (74 eyes) and 39 conjunctivitis cats (78 eyes). The mean age was 2.34 years. There was no statistical difference (P = 0.2065) between the median tear‐film osmolarity of normal cats (328.5 ± 17.94 mOsms/L) and conjunctivitis cats (325.0 ± 24.84 mOsms/L). Cats with conjunctivitis had an accelerated TFBUT (P < 0.0001) and lower IOPs (P < 0.0001) as compared to normal cats. No statistical difference was found between STT values (P = 0.1304). Conclusions The median tear‐film osmolarity of normal cats was 328.5 mOsms/L. Despite the accelerated TFBUT, conjunctivitis did not cause a statistically significant change in tear‐film osmolarity. The Tear Lab^TM Osmolarity System was easily used and well tolerated by the cats in the study.     

Pharmacokinetics of carbetocin,a long‐acting oxytocin analogue,following intravenous administration in horses

Reason for performing study: Current therapy protocols to treat persistent post mating endometritis and retained fetal membranes in mares typically include the administration of ecbolic drugs. Evaluation of the pharmacokinetics and tolerability of carbetocin, a long‐acting oxytocin analogue, after i.v. administration is required. Objectives: To determine the pharmacokinetic parameters (principally half‐life) of carbetocin in horses. Methods: Five mature mares and one gelding received 0.175 mg carbetocin i.v. All animals were monitored periodically throughout the study for elevation in rectal temperature, heart rate, respiratory rate and signs of pain or discomfort. Plasma samples were collected for determination of carbetocin concentrations by radioimmunoassay. Results: Administration of carbetocin was well tolerated by all horses and its half‐life was 17.2 min. Conclusions: The half‐life of carbetocin is greater than that previously reported for oxytocin (6.8 min). Potential relevance: Carbetocin is an attractive alternative to oxytocin therapy in broodmare management.