Iris abscesses with and without intralenticular fungal invasion in the horse.

OBJECTIVE: To describe clinical and histologic findings in horses with iris abscesses. Design Retrospective medical records study. ANIMALS STUDIED: Medical records of horses that had iris abscesses at the University of Florida Veterinary Medical Center, Peterson & Smith Equine Hospital, and Veterinary Eye Specialists of London, Ontario, from 2005 to 2008 were reviewed. PROCEDURE: Data collected from the medical records included signalment, clinical and histologic descriptions of ocular lesions, therapy, complications, and visual outcomes. RESULTS: The medical records of two Quarterhorses, one pony, one warmblood, one Westphalian, and one Arab horse with unilateral iris abscesses were identified. Mild-to-severe clinical signs of iridocyclitis were present in all six eyes with iris abscesses. The eyes of two horses with iris abscesses were also associated with deep stromal abscesses and responded to medical therapy alone in one case, and medical therapy and corneal transplantation in the other. Iris abscesses in two horses were also associated with intralenticular invasion due to a Cladosporium and a Fusarium-type fungus respectively, and resulted in enucleations. Two horses with iris abscesses and no apparent lens involvement resolved with medical therapy in one case and surgical removal of the iris abscess and medical therapy in the other. CONCLUSIONS: This is the first clinical report of iris abscesses in the horse, and the first histologic report of fungal invasion of the horse lens.

Use of a biosynthetic material to repair the surgical defect following excision of an epibulbar melanoma in a cat.

A limbal melanoma was surgically excised from the OS of a 4-year-old castrated male Domestic Short-haired cat (DSH). The resultant scleral defect was repaired by placement of A-cell bio-scaffold material. The patient responded well in the postoperative period with no apparent discomfort, nor any observable complications. No signs of recurrence have been evident nearly 2.5 years following surgical removal. A-cell appears to be a safe and reasonable option to lend support to corneoscleral defects following removal of neoplastic lesions. It carries with it the advantages of availability, minimal host rejection, and reduced potential for iatrogenic spread of infections agents.

Angiopoietin-like 7 secretion is induced by glaucoma stimuli and its concentration is elevated in glaucomatous aqueous humor.

PURPOSE: To investigate the possibility that Angiopoietin-like 7 (ANGPTL7) protein is involved in the pathogenesis of glaucoma. METHODS: Primary human trabecular meshwork (TM) cells and corneoscleral explants were stimulated with either dexamethasone (DEX) or transforming growth factor beta (TGFbeta), and ANGPTL7 protein secreted into culture medium was determined by Western blot analysis. The effect of stable overexpression of ANGPTL7 in transfected immortalized TM cell lines on collagen expression was investigated by immunocytochemistry. Localization of ANGPTL7 protein in human eyes was determined by immunohistochemistry. The concentration of ANGPTL7 protein in aqueous humor (AH) from patients with glaucoma and control patients was compared by Western blot analysis. The beagle model of primary open-angle glaucoma (POAG) was used to correlate ANGPTL7 protein levels in canine AH with disease progression. RESULTS: TGFbeta and DEX stimulated secretion of ANGPTL7 protein by TM cells and corneoscleral explants. Overexpression of ANGPTL7 by immortalized TM cell lines increased expression of type I collagen. Expression of ANGPTL7 protein was located in the corneal stroma, near the limbus, and throughout the sclera, with lower expression in the TM. In the lamina cribrosa, ANGPTL7 expression was associated with the cribriform plates. The concentration of ANGPTL7 protein was elevated in AH from patients with glaucoma and increased as disease progressed in POAG beagle dogs. CONCLUSIONS: Induction of ANGPTL7 secretion by glaucoma stimuli and increased concentration of ANGPTL7 in glaucomatous AH suggest that ANGPTL7 is overexpressed in glaucoma. Since overexpression of ANGPTL7 increases collagen expression, a potential disease mechanism, ANGPTL7 could have a pathogenic role in glaucoma, and may serve as a potential therapeutic target.

Blood flow velocity response of the ophthalmic artery and anterior optic nerve head capillaries to carbogen gas in the rhesus monkey model of optic nerve head ischemia.

PURPOSE: To determine the effect on blood flow velocity of the ophthalmic artery and anterior superficial optic nerve head (ONH) capillaries by changing inhaled gas from 100% oxygen to carbogen (95% oxygen, 5% CO(2)) in rhesus monkeys receiving chronic unilateral orbital endothelin-1 administration. METHODS: The right eye of six young male rhesus monkeys (Macaca mulatta) received endothelin-1 (ET-1) by osmotic minipumps to the perineural optic nerve (0.3 microg/day) for 8 months. Three additional monkeys (control group) received the ET-1 vehicle (Sham) solution to the right optic nerve for the same period of time. The left eye served as a nontreated control in both groups. The blood flow velocities of the anterior ONH capillaries and ophthalmic artery were assessed in both eyes using confocal laser scanning flowmetry (CSLF) and color Doppler imaging (CDI), respectively. RESULTS: A slight increase in the CDI blood flow velocities and a small decrease in the resistive index of the ophthalmic artery, and increased flow of the ONH capillaries in rhesus monkeys were detected when inhaled gas was changed from 100% oxygen to carbogen. The difference in CSLF blood flow in the nasal ONH between the endothelin-1 (ET-1) treated right eye and the normal left eye of the same individual monkeys was significantly greater than the difference in blood flow between the Sham-treated right eye and the normal left eye in control animals under the conditions of carbogen and oxygen inhalation. CONCLUSION: Carbogen inhalation slightly influences the microcirculation of the globe and ONH in rhesus monkeys. These data suggest that low dose ET-1 administration has a subtle vasorelaxing effect in the ONH microcirculation in this animal model of ONH ischemia.

Endothelin-1, nitric oxide, and glutamate in the normal and glaucomatous dog eye.

PURPOSE: To document differences in the levels of the endothelin-1 peptide, nitric oxide, and glutamate in aqueous humor and vitreous in the dog eye with spontaneous glaucoma compared to the normal dog eye. METHODS: Samples of aqueous humor and vitreous from enucleated normal eyes (n = 21) of 14 dogs and glaucomatous eyes (n = 8) of eight dogs were collected. Levels of endothelin-1, nitric oxide, and glutamate were measured by enzyme immunoassay. RESULTS: Endothelin-1 aqueous humor levels (mean +/- SD) increased significantly from 3.05 (+/- 1.66) pg/mL for the normal eyes to 6.22 (+/- 2.83) pg/mL for the glaucomatous eyes (P = 0.0054). The increase in vitreous from 1.83 (+/- 1.66) pg/mL for the normal eyes to 2.86 (+/- 1.31) pg/mL for the glaucomatous eyes was not significant (P = 0.0840). Nitric oxide levels (mean +/- SD) increased significantly in aqueous humor from 4.12 (+/- 2.64) microM for the normal eyes to 12.95 (+/- 14.42) microM for the glaucomatous eyes (P = 0.0141). The vitreous levels increased from 4.86 (+/- 3.92) microM for the normal eyes to 15.33 (+/- 16.22) microM for the glaucomatous eyes (P = 0.0179). Glutamate levels (mean +/- SD) decreased nonsignificantly in aqueous humor from 2.35 (+/- 3.84) microM for the normal eyes to 1.61 (+/- 0.74) microM for the glaucomatous eyes (P = 0.9377) and in vitreous from 1.37 (+/- 1.89) microM for the normal eyes to 1.02 (+/- 1.11) microM for the glaucomatous eyes (P = 0.3303). CONCLUSION: Endothelin-1 and nitric oxide increased in aqueous humor and vitreous of dogs with spontaneous glaucoma while the changes in glutamate varied.

Suspected ivermectin toxicosis in a miniature mule foal causing blindness.

A 9-week-old miniature mule foal presented to the Veterinary Medical Teaching Hospital for acute blindness, ataxia, and depression following an overdose of an over-the-counter ivermectin-based de-worming medication. Ophthalmic examination and electrodiagnostic evaluation eliminated outer retinal abnormalities as the primary cause of the bilateral blindness, implicating instead a central neurologic effect of the drug. With symptomatic and supportive care, the foal recovered fully and regained its vision.

Equine amniotic membrane transplantation for corneal ulceration and keratomalacia in three horses.

PURPOSE: Amniotic membrane has antifibrotic, anti-angiogenic and antiprotease properties. This retrospective study was designed to investigate the use of equine amniotic membrane transplants (AMT) at preserving vision, maintaining the structural integrity of the globe and maximizing cosmesis in equine eyes with corneal ulceration and severe keratomalacia. METHODS: Equine amnion had previously been aseptically harvested from a 12-year-old Thoroughbred mare during an elective Cesarean section. Sections of amnion were stored at -80 degrees C and thawed as needed. Records of equine cases at the University of Florida with keratomalacia that received an AMT without adjunctive conjunctival grafting were examined. Clinical description, details of medical and surgical treatment, globe survival and visual outcome were documented. Etiologies were determined by cytology, culture or histology. RESULTS: Three horses with corneal ulceration and severe keratomalacia received an AMT without conjunctival graft between December 2002 and April 2003. Pseudomonas spp. were cultured from all three eyes, with evidence of a concurrent fungal infection in two eyes. The three ulcers were 50, 72, and 76% of corneal diameter, and each one worsened in the face of aggressive medical therapy. In all three cases, the AMT sloughed over a 4 to 6-week period. At last follow-up, all three eyes receiving AMT were comfortable and receiving no medication, with light perception and an inconsistent location-dependent menace response. All three horses returned to their prior work. CONCLUSIONS: Results of a small number of equine AMT suggest that amnion can be used successfully to preserve both globe structure and limited vision, as well as optimize cosmesis, in horse eyes with corneal ulceration and severe keratomalacia.

Functional and structural analysis of the visual system in the rhesus monkey model of optic nerve head ischemia.

PURPOSE: A redistribution of neurochemicals has been identified in the visual cortex of monkeys with laser-induced glaucoma. Examined were functional, structural, and neurochemical changes to the retina, optic nerve, and central visual system in a nonhuman primate model of optic nerve head (ONH) ischemia caused by sustained unilateral administration of endothelin (ET)-1 to the optic nerve. METHOD: ET-1 or sham control solution was delivered by osmotic minipump to the retrolaminar region of one optic nerve of rhesus monkeys (Macaca mulatta) for 1.5 years. ONH topography and blood flow velocity were serially studied with scanning laser tomography and laser Doppler flowmetry, respectively. Retinal and cortical electrophysiologic measurements from pattern-derived stimuli were obtained quarterly. Immunohistochemistry was used to identify the distribution of calbindin (CB) and c-Fos labeled neurons in the visual cortex areas V1 and V2, and lateral geniculate nucleus (LGN). Retinal ganglion cell counts and optic nerve axon density were determined by light microscopy. RESULTS: No significant changes in retinal and ONH morphology, ONH blood flow velocity, and retinal and cortical pattern-derived functional activity were detected. Measurement of CB-positive cell density in V1 and V2 showed a significant decrease in CB labeling to the contralateral side of the ET-1-treated eye (P < 0.04). CB-positive cells were present in the magnocellular layers of the LGN with no differences noticed between the ET-1- and sham-treated eyes. c-Fos-labeled neurons were found in striate area V1 and extrastriateV2 of both groups. No c-Fos labeling was observed in the LGN. CONCLUSIONS: Administering ET-1 to the orbital optic nerve alters neuronal metabolic activity in the visual cortex in rhesus monkeys. Metabolic activity reductions in the visual cortex precede the ability to detect functional and structural alterations in the retina, ONH, and visual cortex in this animal model.

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.

Long-term effect of retinal ganglion cell axotomy on the histomorphometry of other cells in the porcine retina.

PURPOSE: To determine the effect of retinal ganglion cell axotomy on the thickness of inner plexiform, inner nuclear, and outer plexiform layers, as well as the densities of short- and middle-to-long-wavelength cones, in the porcine retina. METHODS: Unilateral retinal ganglion cell axotomy was performed in seven domestic pigs by either surgical optic nerve section or peripapillary argon laser photocoagulation. Damage to the retinal vasculature was ruled out with fluorescein angiography. Histologic examination of the retinal tissue was performed nine months later. Cone densities were determined immunohistochemically with the anti-visual pigment antibodies COS-1 and OS-2. Image analysis of semithin retinal cross sections was used to measure the thickness of the retinal layers. The effect of axotomy was quantified by optic nerve axon counts and estimations of retinal ganglion cell counts. The data were compared between the eyes with axotomy and the contralateral normal eye using the nonparametric Wilcoxon rank sum test. RESULTS: Treatment of the peripapillary retina with the argon laser resulted in a median decrease in axon counts and retinal ganglion cell density estimates of 31%. No optic nerve axons and cells resembling retinal ganglion cells were found in the eyes with transected optic nerves. There was no significant difference in either the thickness of any retinal layers or cone densities between axotomized and normal control eyes. CONCLUSION: No signs of retrograde transsynaptic degeneration were observed in porcine retinas nine months after retinal ganglion cell axotomy.

The effect of an L-type calcium channel blocker on the hemodynamics of orbital arteries in dogs.

PURPOSE: (1) To determine the effect of the l-type calcium channel blocker amlodipine on color Doppler ultrasound-determined vascular resistance and blood flow velocities in the distal retrobulbar arteries of dogs; (2) to determine any effect of blood pressure and PCO2 rate on such color Doppler-determined circulatory measurements. METHODS: Color Doppler imaging measurements of the short posterior ciliary artery, long posterior ciliary artery, and ophthalmic artery of normal eyes of 10 dogs were obtained under isofluorane anesthesia before and 1 week after oral amlodipine administration. Mean systemic arterial blood pressure and PCO2 were monitored. RESULTS: The mean resistive index decreased significantly in the short posterior ciliary artery (P = 0.0347), in the long posterior ciliary artery (P = 0.0092), and ophthalmic artery (P = 0.0004) following systemic amlodipine administration. The end diastolic velocity increased significantly in the long posterior ciliary artery (P = 0.0368) and ophthalmic artery (P < 0.0001). The peak systolic velocity increased significantly in the ophthalmic artery (P = 0.0256). Mean systemic arterial blood pressure was significantly negatively associated with resistive index (P < 0.0001) and significantly associated with the log of the end diastolic velocity (P < 0.0001). CONCLUSIONS: Systemically administered amlodipine increases color Doppler imaging-determined blood flow velocity and decreases vascular resistive index in the ophthalmic artery, short posterior ciliary artery and long posterior ciliary artery of normal dogs. Changes in systemic arterial blood pressure can significantly affect the measurement of color Doppler imaging parameters.

Passive attenuation of cortical pattern evoked potentials with increasing body weight in young male rhesus macaques.

The purpose of our study was to determine changes in amplitudes and implicit times of retinal and cortical pattern evoked potentials with increasing body weight in young, growing rhesus macaques (Macaca mulatta). Retinal and cortical pattern evoked potentials were recorded from 29 male rhesus macaques between 3 and 7 years of age. Thirteen animals were reexamined after 11 months. Computed tomography (CT) was performed on two animals to measure the distance between the location of the skin electrode and the surface of the striate cortex. Spearman correlation coefficients were calculated to describe the relationship between body weights and either root mean square (rms) amplitudes or implicit times. For 13 animals rms amplitudes and implicit times were compared with the Wilcoxon matched pairs signed rank test for recordings taken 11 months apart. Highly significant correlations between increases in body weights and decreases in cortical rms amplitudes were noted in 29 monkeys (p < 0.0005). No significant changes were found in the cortical rms amplitudes in thirteen monkeys over 11 months. Computed tomography showed a large increase of soft tissue thickness over the skull and striate cortex with increased body weight. The decreased amplitude in cortical evoked potentials with weight gain associated with aging can be explained by the increased distance between skin electrode and striate cortex due to soft tissue thickening (passive attenuation).

Technical issues in electrodiagnostic recording.

Electroretinogram (ERG) and visual-evoked potentials (VEPs) are used in veterinary ophthalmology to assess the functional integrity of the retina and the central visual pathway. The interpretation of altered electrophysiologic potentials in diseases can be of great diagnostic value, although it is important to be aware of technical factors and the limitations of these techniques which may result in over-interpretation and misinterpretation of the recordings, such that they are similar to those found in disease-related electrophysiologic changes. The recorded potentials represent the differences in voltage between the active and reference electrodes. The ground electrode serves as zero. A differential or instrumentation amplifier selectively amplifies signals of interest while rejecting noise. Differences between inputs are amplified, whereas common signals are rejected in a process called common mode rejection (CMR). In order for CMR to be most effective in reducing noise, the electrode impedances should be balanced. Filters are part of the differential amplifier as they remove unwanted noise of a certain frequency. The frequency bandwidth, or passband, is the range of frequencies between low- and high-frequency filter settings that are not filtered out. Major sources of noise that cause interpretation artifacts are power lines, amplifier noise, physiologic activity, electrochemical electrode noise and circular grounds. Noise reduction is achieved with high amplifier input impedance, balanced electrode impedances, CMR, filters and signal averaging. Maintaining electrodes in good condition, achieving proper contact between electrode and animal, and keeping electrode leads short aid in achieving noise reduction.

Endothelin 1 levels in the aqueous humor of dogs with glaucoma.

PURPOSE: Endothelin 1 is a small peptide that is involved in regulation of intraocular pressure and modulation of ocular circulation. To investigate the role of endothelin 1 in canine glaucoma, the authors measured aqueous humor levels of endothelin 1 in healthy dogs and in dogs with hypertensive glaucoma. METHODS: Aqueous humor samples were obtained with general anesthesia from the eyes of healthy dogs (n = 5) and dogs with hypertensive glaucoma (n = 10). Measurements were made by enzyme immunoassay for endothelin 1. RESULTS: The endothelin 1 aqueous humor range was 1.12 - 3.63 pg/mL for healthy dogs and 1.97 - 14.97 pg/mL for glaucomatous dogs. The healthy and glaucomatous canine endothelin 1 aqueous levels (mean +/- SD) were 2.33 +/- 0.90 and 8.11 +/- 5.03 pg/mL, respectively. A two-way analysis of variance indicated that this difference was significant (P = 0.0084). The effect of age on endothelin 1 levels was not significant (P = 0.6283). The large variability found within the glaucomatous group could be explained by the degree of damage of the retina (P = 0.0006). There was no significant correlation between intraocular pressure and endothelin 1 aqueous humor levels within the glaucomatous group (P = 0.29). CONCLUSIONS: The aqueous humor of dogs with hypertensive glaucoma contains significantly higher levels of endothelin 1 than that of healthy dogs.