Prognosis and impact of equine recurrent uveitis.

REASONS FOR PERFORMING STUDY: Equine recurrent uveitis (ERU) is a leading cause of vision loss in horses. OBJECTIVES: To assess the prognosis and impact of ERU on affected horses and their owners by evaluating the signalment, treatment and outcome (including the loss of use, vision assessment and economic loss). STUDY DESIGN: Retrospective impact study. METHODS: Medical records of horses presenting to the North Carolina State University Veterinary Health Complex (NCSU-VHC) with ERU between 1999 and 2014 were reviewed. Signalment, clinical signs, ophthalmic examination findings, treatments and outcomes were evaluated. Owner questionnaires were completed regarding vision, job/role, monetary value, diagnostic and treatment costs, concurrent illness and outcomes. RESULTS: Records of 224 horses (338 eyes) with ERU were reviewed. There was an overrepresentation of Appaloosas (54; 24.1%), Hanoverians (11; 4.9%) and other Warmbloods (13; 5.8%). Ninety-six eyes (28.4%) were diagnosed as blind and 38 eyes (11.2%) with glaucoma on initial evaluation. Leptospirosis titres of serum and/or aqueous humour were obtained in 88 horses and were positive in 40 horses (45.5%), with L. pomona being the most frequently isolated serovar. Globe loss at the NCSU-VHC occurred in 41 ERU eyes (12.1% of total). Owner questionnaires were evaluated in 194 horses (86.6%) and 91 horses (46.9%) were reported blind in the affected eye(s). Fifty-seven horses (29.4%) did not return to their previous role, while 61 (31.4%) performed at a reduced level. Equine recurrent uveitis decreased the monetary value of 164 horses. Twenty-nine horses (14.9%) were euthanised and 37 (19.1%) underwent change in ownership as a direct result of ERU. CONCLUSIONS: The impact of ERU is attributed to the high frequency of blindness, globe loss and loss of function. Euthanasia and change of ownership are common sequelae to the progressive nature of ERU. These factors, along with financial costs of the disease, have a significant impact on affected horses and their owners.

Equine recurrent uveitis: the viewpoint from the USA.

Equine recurrent uveitis (ERU) is a common disease in horses in the USA. There have been many advances in the treatment of ERU; however, frequent misdiagnosis of ERU occurs in cases of primary corneal or uveal disease. It is critical to remember that primary uveitis (i.e. one bout of inflammation) is a different disease to ERU, which is an immune mediated recurrent uveitis. Standard symptomatic anti-inflammatory therapy is effective to control most cases of ERU; however, some horses require advanced therapy, such as placement of drug delivery devices or removal of the vitreous, when they fail to respond to the standard therapy.

International Equine Ophthalmology Consortium (IEOC) Symposium.

This first IEOC symposium met its goals of gathering a group of leading equine ophthalmology clinicians and researchers to identify the challenges of the field. To facilitate collaboration, notes from round-table discussions, including the ideas and plans that were discussed are being complied and will be distributed to the attendees. Development of an IEOC membership organisation and website was discussed and supported by the group in an effort further to advance the science of equine ophthalmology. To present results from the collaborations made at this first IEOC meeting, an IEOC mini-symposium will be held at the American College of Veterinary Ophthalmologists Annual Meeting in Chicago Illinois, on 6th November 2009. The second annual IEOC symposium will be held in Vienna, Austria on 4th and 5th June 2010.

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.

Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses.

In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post-injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post-injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.

Proteinases of the cornea and preocular tear film.

Maintenance and repair of corneal stromal extracellular matrix (ECM) requires a tightly coordinated balance of ECM synthesis, degradation and remodeling in which proteolytic enzymes (proteinases) perform important functions. There are natural proteinase inhibitors present in preocular tear film (PTF) and cornea simultaneously with proteinases that prevent excessive degradation of normal healthy tissue. Disorders occur when there is an imbalance between proteinases and proteinase inhibitors in favor of the proteinases, causing pathologic degradation of stromal collagen and proteoglycans in the cornea. Two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are of major importance in terms of remodeling and degradation of the corneal stromal collagen. Immunohistochemical studies have shown different origins of MMP-2 and -9. MMP-2 is synthesized by corneal keratocytes and performs a surveillance function in the normal cornea, becoming locally activated to degrade collagen molecules that occasionally become damaged. Alternatively, MMP-9 may be produced by epithelial cells and polymorphonuclear neutrophils following corneal wounding. Because the cornea is in close contact with the preocular tear film (PTF), proteinases have been evaluated in the PTF. In damaged corneas, total proteolytic activity in the tear fluid was found to be significantly increased compared to normal eyes and contralateral eyes. Studies analyzing the proteolytic activity in serial PTF samples during corneal healing led to the following conclusions: ulcerative keratitis in animals is associated with initially high levels of tear film proteolytic activity, which decrease as ulcers heal; proteinase levels in melting ulcers remain elevated leading to rapid progression of the ulcers. The success of medical and surgical treatment of the corneal ulcers is reflected by the proteolytic activity in tears. In animals, successful treatment leads to a rapid reduction in tear film proteolytic activity that corresponds with the improvement in the clinical signs of corneal ulceration. The in vitro effects of various compounds on proteolytic activity in the tear fluid of animals with ulcerative keratitis have been evaluated and their important inhibitory effects have been confirmed. Because these various compounds utilize different mechanisms to inhibit various families of proteinases, a combination of these proteinase inhibitors may be beneficial.

Superficial, nonhealing corneal ulcers in horses: 23 cases (1989-2003).

OBJECTIVE: To characterize superficial, nonhealing corneal ulcers in the horse and to assess the affect of age, breed, sex, inciting cause of the ulcer, and treatment on healing time of these ulcers. DESIGN: Retrospective study. ANIMALS: Twenty-three horses with superficial, nonhealing corneal ulcerations. PROCEDURE: Medical records from 1989 to 2003 of horses diagnosed with superficial, nonhealing corneal ulcers were reviewed. Signalment, duration of clinical signs, ophthalmic abnormalities, treatment and response to treatment were recorded. Horses were treated, in addition to medical therapy, using debridement, debridement and grid keratotomy, superficial keratectomy, and superficial keratectomy with conjunctival graft placement. RESULTS: Mean age +/- SD of horses was 13.7 +/- 5.8 years. The mean time of presence of the corneal ulceration was 38.9 +/- 21.3 days. Mean time to complete re-epithelialization of the corneal ulcers after treatment was 20 +/- 14.7 days. Horses treated with debridement alone, grid keratotomy and superficial keratectomy healed in a mean time of 15.3 +/- 14.6 days, 16 +/- 12.6 days, and 22.8 +/- 6.7 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Horses treated with a single debridement at initial evaluation healed in a significantly shorter time period than horses treated with grid keratotomy or superficial keratectomy. The latter two procedures may be beneficial in the treatment of nonhealing ulceration in horses, but the results of this study suggest that these procedures should only be performed following failure of the ulcer to heal after epithelial debridement.

Bartonella vinsonii subspecies berkhoffi as a possible cause of anterior uveitis and choroiditis in a dog.

A 2-year old, neutered, female spaniel mixed breed was referred to the North Carolina State University Veterinary Teaching Hospital for evaluation of bilateral anterior uveitis. The dog was febrile and, in addition to anterior uveitis, multifocal hyporeflective lesions were present in the tapetal fundus of both eyes. The antibody titer for Bartonella vinsonii subspecies berkhoffi was positive (1 : 512). Aqueous paracentesis was performed for PCR in an attempt to detect B. vinsonii in the eye but was unsuccessful. The ocular manifestations of Bartonella infection in humans are currently expanding as more sensitive serologic and PCR techniques are being developed to identify Bartonella spp. In addition to optic neuritis and neuroretinitis, retinochoroidal lesions are one of the most common manifestations of B. henselae infection, and are frequently accompanied by vitreous or anterior segment inflammation. Diagnosis of a Bartonella infection in humans can be made on serology alone, in conjunction with ocular examination findings. The ultimate proof of B. vinsonii (berkhoffi) as a direct cause of ocular disease would be detection of the infectious agent in the eye. However, it is unknown at this time whether Bartonella causes ocular disease primarily, secondarily via an autoimmune reaction, or both. Due to the difficulties associated with culture of Bartonella spp. and the limitations of PCR, serology is currently the most useful tool for screening dogs for possible Bartonella spp. infection. In the case presented here, even though the PCR was negative, the clinical signs of anterior uveitis and choroiditis might reasonably be associated with B. vinsonii (berkhoffi) seroreactivity, which was repeatable on three separate occasions. Clinical improvement was also accompanied by a post-treatment decrease in B. vinsonii (berkhoffi) seroreactivity, potentially supporting resolution of Bartonella infection in this dog. This is the first reported case of a possible association between uveitis, choroiditis and Bartonella infection in the dog, without clinical manifestations of other organ or tissue involvement. Future studies based on PCR analysis of intraocular fluids may clarify the involvement of B. vinsonii (berkhoffi) in dogs with intraocular inflammatory disease. Furthermore, performing fluorescein angiography in dogs with elevated Bartonella titers may also prove useful in the identification and characterization of lesions.

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.

Transpupillary diode laser retinopexy in dogs: ophthalmoscopic, fluorescein angiographic and histopathologic study.

OBJECTIVE: To evaluate the ophthalmoscopic, fluorescein angiographic and light microscopic effects of diode laser retinopexy application in the tapetal and nontapetal fundus in the dog, and to ascertain appropriate laser power settings for production of photocoagulative lesions in these two regions. ANIMALS STUDIED: Three adult female Beagle dogs. PROCEDURES: Laser burns were applied to selected areas in the fundus with an indirect headset delivery system using settings varying from 100 to 200 milliWatts (mW) and from 100 to 600 milliSeconds (mS) with total delivered energy ranging between 15 and 100 milliJoules (mJ). The dogs were then monitored by ophthalmoscopic examination and fluorescein angiography at regular intervals for 7-28 days. Histopathologic studies were performed at 7, 14 and 28 days after laser application. RESULTS: The diode laser produced ophthalmoscopically visible lesions in the nontapetal fundus with all laser settings used, and the appearance of these lesions corresponded to the energy levels used, and degree of pigment in the lased region. Gray-white colored lesions with minimal subsensory retinal edema were seen with settings as low as 100 mWatts/150 mSeconds. In the tapetal fundus, laser burns were more difficult to produce, less repeatable, and required higher energy levels. Laser burns appeared as bronze, dark green or black discolorations of the tapetum with varying degrees of subsensory retinal edema. Lesions were more reproducible and were achieved with lower settings in the tapetal area of the tapetal/nontapetal junction. Ophthalmoscopically, depigmentation and repigmentation of the RPE (nontapetal fundus) and degenerative changes in the overlying retina (tapetal fundus) developed in the laser burns over the 28-day study period. Fluorescein angiographic studies showed disruption of the blood-retinal barrier at the level of the RPE and fluorescein leakage into the subsensory retinal space was seen in most lesions at 24 h, was minimal at 3 days, and had resolved by 7 days. Histologically, grayish-white lesions in the nontapetal fundus, and bronze to small black lesions in the tapetal fundus were typically characterized by outer retinal necrosis and RPE migration. Gliosis was considered minimal, was confined to the retina, and no inflammatory cells were seen. Peripheral intense white lesions (nontapetum) and lesions with a black center (tapetal fundus) were characterized by more extensive panretinal and choroidal necrosis. Most of the nontapetal lesions and a few in the tapetal fundus showed the formation of a central retinal detachment. CONCLUSIONS: The diode laser effectively produces lesions suitable for retinopexy in both the nontapetal, pigmented fundus and the tapetal fundus, although variably so in the latter region. Initial laser settings of 100-150 mW/200 mS for the pigmented fundus, and 150 mW/200-300 mS for the peripheral tapetal fundus are recommended, and the clinician should gradually increase time interval settings to achieve a grayish-white lesion in the nontapetum, and a bronze to slightly black lesion in the tapetal fundus. If possible, retinopexy should be applied to the peripheral tapetal area or tapetal/nontapetal junction.

Acute vision loss after general anesthesia in a cat.

A 6-year-old, male castrated, domestic shorthair cat presented with a 2-week history of blindness following general anesthesia. Behavioral changes, lethargy, inappetence and neurological deficits were also noted. Ophthalmic evaluation revealed blindness, normal pupillary light response and dazzle response, but no other abnormalities. Serodiagnostic testing for common infectious agents was negative and a cerebrospinal fluid analysis was normal. History and postmortem examination following euthanasia revealed cerebrocortical necrosis most consistent with anesthesia related hypoxia.

Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.

OBJECTIVE: To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. ANIMALS: 16 horses with recurrent uveitis. PROCEDURES: Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. RESULTS: The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). CONCLUSIONS AND CLINICAL RELEVANCE: This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis.

Effect of an intravitreal cyclosporine implant on experimental uveitis in horses.

The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25 microg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25 microg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFN gamma) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72 h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFN gamma-mRNA were significantly less in eyes with the CsA implant compared to eyes with the polymer only. CsA implants did not completely eliminate the development of a second ('recurrent') experimental inflammatory episode in these horses. However, the duration and severity of inflammation, cellular infiltration, tissue destruction, and pro-inflammatory cytokines RNA transcript levels were significantly less in those eyes implanted with the CsA device.

Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998).

OBJECTIVE: To characterize clinical and clinicopathologic findings, response to treatment, and causes of systemic hypertension in cats with hypertensive retinopathy. DESIGN: Retrospective study. ANIMALS: 69 cats with hypertensive retinopathy. PROCEDURE: Medical records from cats with systemic hypertension and hypertensive retinopathy were reviewed. RESULTS: Most cats (68.1%) were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Cardiac abnormalities were detected in 37 cats, and neurologic signs were detected in 20 cats. Hypertension was diagnosed concurrently with chronic renal failure (n = 22), hyperthyroidism (5), diabetes mellitus (2), and hyperaldosteronism (1). A clearly identifiable cause for hypertension was not detected in 38 cats; 26 of these cats had mild azotemia, and 12 did not have renal abnormalities. Amlodipine decreased blood pressure in 31 of 32 cats and improved ocular signs in 18 of 26 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Primary hypertension in cats may be more common than currently recognized. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years). Amlodipine is an effective antihypertensive agent in cats.

Long-term effect on the equine eye of an intravitreal device used for sustained release of cyclosporine A.

OBJECTIVE: To determine the long-term toxicity of an intravitreal device releasing continuous cyclosporinee A (CsA) in normal eyes of horses by evaluating clinical signs, electroretinography, and histopathology. Animals Studied Ten adult horses with normal ophthalmic examinations were used in this study Procedure(s) Four horses had one eye implanted with a CsA device, and six horses had the right eye implanted with a CsA-containing device (10 eyes with CsA in total) and the left eye (six eyes in total) with the device without drug (control). The implants were placed in the vitreous of the eyes through a sclerotomy 1 cm posterior to the limbus in the dorso-temporal quadrant of the eye. Scotopic electroretinograms were performed prior to implantation and at 1 week, and at 1, 3, 6, 9, and 12 months postimplantation. Two of the unilaterally implanted horses were euthanized at 1 weeks postimplantation, and two at 6 weeks postimplantation. Two of the bilaterally implanted horses were euthanized at 6 months, two at 9 months, and two at 12 months postimplantation. At euthanasia, the eyes were removed, aqueous and vitreous humor aspirated, and tissues fixed in 10% buffered formalin and processed for histopathology. CsA concentrations were measured by high pressure liquid chromatography in the aqueous and vitreous humors, and in peripheral blood. RESULTS: The devices were tolerated well in 14 of 16 eyes. There was minimal postoperative inflammation in most eyes, with a normal appearance within 7 days. In two eyes implanted with the CsA device, severe inflammation resulted in phthisis bulbi by 28 days. One of these eyes exhibited suspected bacterial endophthalmitis, and one had a sterile endophthalmitis and cataract presumably from trauma to the lens during implantation. In the other 14 eyes, no change was observed in the scotopic electroretinograms (ERG) from preoperative results, and no significant differences between the right (CsA) and left (control device) eyes were observed. CsA levels in the aqueous and vitreous humor, and peripheral blood were below the detection limit of the HPLC. Histologic findings revealed only a mild lymphoplasmacytic cellular infiltrate in the ciliary body and pars plana near the implantation site. CONCLUSIONS: The CsA devices were well tolerated with no long-term complications from the implants themselves. However, complications may occur from inadvertent implantation trauma or contamination during surgery. The long-term safety of the device may make it useful for delivery of CsA in the control of equine recurrent uveitis.

Effect of single- and multiple-dose 0.5% timolol maleate on intraocular pressure and pupil size in female horses.

OBJECTIVE: To determine the effect of single and multiple-dose 0.5% timolol maleate on intraocular pressure (IOP) and pupil size between 8 AM and 8 PM. Animals Nine female horses with normotensive eyes. Procedure IOP, horizontal and vertical pupil size were measured on a single day, between 8 AM and 8 PM at hours 0, 0.5, 1, 2, 4, 6, 8, 10, and 12. A single dose of 0.5% timolol maleate was applied to both eyes immediately after the first measurement at 8 AM. IOP and pupil size were measured at 8 AM and 4 PM in a 5-day experiment of twice-daily application of 0.5% timolol maleate. RESULTS: A significant decrease in IOP from 24.9 +/- 4.2 mmHg prior to application of timolol maleate to 20.7 +/- 3.1 mmHg (4.2 mmHg = 17%) was observed 8 h after single-dose application. A significant decrease in horizontal pupil size (2.0 mm = 11%) was present 6 h after single-dose application. In the multiple-dose experiment, a significant decrease in IOP was present on days 4 and 5 as compared to IOP measured prior to application of timolol maleate. A significant decrease in horizontal and vertical pupil size was present throughout the 5-day study as compared to the values obtained prior to treatment. CONCLUSIONS: 0.5% timolol maleate significantly decreased IOP and pupil size in normo-tensive eyes of this group of female horses in both single and multiple twice daily applications.

Orbital fibroma in a horse.

An 11-year-old American Quarterhorse gelding presented for moderate periorbital swelling and exophthalmia of the left eye. The menace response, and direct and consensual pupillary light reflexes were absent in the left eye. Conjunctival hyperemia, blepharedema, a mydriatic pupil, resistance to retropulsion, and an increased intraocular pressure were present. A soft-tissue mass could be palpated in the left retrobulbar space by pressing onto the orbit over the supraorbital fossa. Incomplete surgical resection of the mass was performed and histopathologic evaluation was consistent with a fibroma. Normal pupillary light reflexes and vision returned following surgery. The mass has not recurred 14 months after surgery.

Acute renal failure in four cats treated with paromomycin.

Acute renal failure was diagnosed in 4 cats receiving paromomycin orally for treatment of infectious enteritis. All 4 cats responded to fluid therapy and recovered normal or near-normal renal function; however, 3 of the cats subsequently became deaf and developed cataracts. Toxicoses were attributed to a combination of an excessive dosage of paromomycin and absorption of the drug across injured intestinal mucosal epithelium. Pharmacokinetic studies are needed to further define the disposition of paromomycin after oral administration to cats.

Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis.

Equine recurrent uveitis (ERU), a chronic, recurrent inflammation primarily of the anterior uveal tract, is the most common cause of blindness in horses. Recently, T-lymphocytes have been found to be the most numerous cell type to infiltrate the anterior uveal of horses with ERU. In the present study, we characterized the T-lymphocyte population in the anterior uveal tract of eyes of horses with chronic ERU by evaluating the microscopic appearance (histopathologic features), the T-lymphocyte subsets, and the relative levels and amounts of T-lymphocyte cytokine mRNA in the anterior uvea. Seven inflamed eyes (from six horses with chronic ERU) and 5 normal eyes (from five horses with nonocular problems) were studied. After clinical examination, the eyes were removed, ocular fluids were aspirated, and anterior uveal tissues (iris and ciliary body) were processed for histologic and molecular (RNA isolation) analyses. Histologic examination by hematoxylin and eosin (H and E) staining and immunohistochemistry evaluating T-lymphocyte subsets (anti-CD4, CD8, CD5) were performed for each sample. RNA samples were analyzed for levels of messenger (m) RNA specific for interleukin (IL)-2, 4, and interferon-gamma (IFNgamma) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). Eyes with ERU exhibited characteristic clinical signs, including corneal edema, aqueous flare, posterior synechia, corpora nigra degeneration, and cataract formation. Histologically, infiltration of the uveal tract with lymphocytes, plasma cells, and macrophages was most evident in the ciliary body and base of the iris. Loss of tissue structure (destruction) was most evident in the ciliary processes. Infiltrating lymphocytes were predominantly CD4+ T-cells (e.g. 48% CD4+ and 18% CD8+ in the ciliary body stroma), as determined by immunohistochemistry. Few inflammatory cells were observed in the normal eyes. The QRT-PCR results revealed increased transcription of IL-2 and IFNgamma and low IL-4 mRNA expression in eyes with chronic ERU compared to normal eyes, demonstrating a Thelper (Th) 1-like inflammatory response in eyes with ERU.

Low-dose oral administration of interferon-alpha for the treatment of immune-mediated keratoconjunctivitis sicca in dogs.

This preliminary study was designed to evaluate the effectiveness and dosage of oral use of interferon-alpha (IFN-alpha) in the treatment of naturally occurring, immune-mediated, canine keratoconjunctivitis sicca (KCS). Dogs with chronic immune-mediated KCS were selected from the two clinic populations. All medication, except topical artificial tears, was discontinued at least 2 weeks prior to beginning the clinical trial. IFN-alpha was administered orally once daily to the dogs by their owners as the sole therapy for the KCS. Examinations of the dogs were performed every 2 weeks for the duration of the trial (12 weeks). Each dog was given either two or three separate, escalating doses (20, 40, 80 IU of the IFN-alpha. A favorable response was observed in 55% (11/20) of all dogs treated. Clinical findings of those dogs that responded included increased wetting of the eyes, decreased mucus discharge, and fewer signs of discomfort. There was a nearly significant difference (p = 0.08) in pretreatment mean Schirmer's tear test (STT) between the dogs that responded (6.4 +/- SEM 0.62 mm/min) and those that did not respond (4.7 +/- SEM 0.69 mm/min) to the orally administered IFN-alpha. Seven of 11 dogs with favorable outcomes had an increased STT of at least 5 mm/min after treatment with oral IFN-alpha and the group had a post-treatment STT (10.5 +/- SEM 1.4 mm/min) significantly greater than baseline (p = 0.0004). The post-treatment STT of the dogs that did respond was significantly greater (p < 0.01) than the post-treatment mean STT of dogs that did not respond. All dogs that responded did so with the 20 or 40 IU dose of IFN-alpha. No side effects were noted and all dogs tolerated the treatment well.