Central corneal dermoid in a Labrador retriever puppy.

An eight-week-old, male Labrador retriever puppy was presented with an abnormal appearance of the left cornea, observed after the eyelids opened in the second week of life. Ocular examination showed a large central dermoid of the left cornea. The dermoid was excised by superficial keratectomy, and healing was uneventful. The dermoid was classified as a Mann's second type. To the authors' knowledge, a Mann's second type corneal dermoid has not previously been reported in a dog.

Diabetes mellitus and bilateral cataracts in a kitten.

An 18-week-old male domestic long-hair kitten was presented with a history of polyuria and polydipsia for several weeks. The general condition was unremarkable, but the kitten was considerably smaller than expected for the age and showed cataracts in both eyes. Serum glucose concentrations were persistently elevated and based on clinical findings and an elevated serum fructosamine concentration, a diagnosis of diabetes mellitus was established. Diabetes mellitus is not commonly diagnosed in young kittens, nor are cataracts recognised as a frequent feature of this disease in cats. The cataracts progressed in spite of the insulin therapy and the kitten was euthanised 10 weeks after referral. Histopathological examination of the pancreas revealed few and small islets of Langerhans compared to the examination of pancreas from a healthy kitten of the same age. Histopathological changes in the eyes included cataracts affecting both cortex and nucleus.

Pathology of canine cataract surgery complications.

AIM: To compare pathological complications arising from 2 methods of canine cataract surgery, manual extracapsular cataract extraction (MECCE) and the more automated phacoemulsification and aspiration (PA). METHODS: Case material presented to the Comparative Ophthalmic Pathology Laboratory, University of North Carolina over the previous 20 years (1979-1999) was searched for cases with a history of prior cataract surgery. Data were obtained from the pathology accession forms, and submitting veterinarians were contacted to verify and complete missing data where possible. The slides were re-examined, histological features of surgical complications were noted and secondary changes recorded. RESULTS: Fourteen canine post-cataract-surgery cases were reviewed, the average age of the group being 7.7 years. Of the 14 eyes, 7 had surgery performed using MECCE, and 7 using PA. Of the 7 eyes that underwent MECCE surgery, 5 were enucleated and diagnosed on both clinical and pathological grounds with glaucoma. Of the 7 eyes that underwent PA, 4 were diagnosed with infectious endophthalmitis. CONCLUSIONS: Complications observed were related to the surgical technique performed. Failures of manual extracapsular surgical procedures were more commonly associated with postoperative synechia and glaucoma, compared with failures of phacoemulsification, which were more commonly associated with infection and rhegmatogenous retinal detachments. CLINICAL RELEVANCE: To minimise post surgical complications, MECCE should be accompanied by rigorous efforts to reduce surgically induced inflammation, while PA should be performed using excellent aseptic technique. It is important with both techniques to totally remove cortical material while maintaining the integrity of the posterior capsule.

Morphologic alterations in the anterior lens capsule of canine eyes with cataracts.

OBJECTIVE: To examine the morphologic changes in the anterior lens capsule and lens epithelium of canine eyes with cataracts. SAMPLE POPULATION: Anterior lens capsules from the eyes of 25 dogs with cataracts and from an additional 10 canine globes with lenses subjectively assessed to be normal. PROCEDURE: Thickness of each anterior lens capsule was measured by use of a digital microscopic camera and imaging software. All 25 capsules from eyes with cataracts were submitted for light microscopy; 4 were also submitted for electron microscopy. RESULTS: Thickness of the anterior lens capsule increased with age for the normal lenses and the lenses with cataracts; the change with age was similar for both groups. Light microscopy revealed fibrous metaplasia of lens epithelial cells in 7 of 25 anterior lens capsules with focal thickenings of the posterior aspect of the capsule. Electron microscopy revealed deposition of collagen and basement membrane-like material by fibroblast-like cells. CONCLUSIONS: Results indicate that thickness of the anterior lens capsule in dogs increases with age and that this increase in thickness is not significantly different between normal lenses and lenses with cataracts. In addition, epithelial cells from lenses with cataracts may undergo metaplasia to form plaques composed of fibrous tissue and ectopic basement membrane produced by epithelial cells.

Assessment of ascorbate ocular disposition in the conscious rabbit: an approach using the microdialysis technique.

PURPOSE: This study was performed to evaluate the transport kinetics of ascorbate in aqueous humor of conscious rabbits. METHODS: Following the development of a spectrophotometric assay for ascorbate in serum, aqueous humor and microdialysate, and preliminary studies of ascorbate systemic disposition in the rabbit, microdialysis probes were placed into the anterior chamber of one eye, and the posterior chamber of the contralateral eye, of four New Zealand white rabbits. After a one-month recovery period, conscious rabbits were placed in restraining devices, and marginal ear veins were cannulated for repeat blood sampling and ascorbate administration. A tracer i.v. bolus of (14)C-ascorbate, followed by stepwise increasing i.v. infusions of unlabelled ascorbate, was administered. Estimates of basal ascorbate transport into aqueous were determined by analysis of tracer ( 14)C-ascorbate in microdialysis probe effluent and serum. Kinetic modeling was employed to assess ascorbate disposition during infusion. RESULTS: Systemic disposition of exogenously administered ascorbate was well characterized by a two-compartment model. Kinetic modeling returned physiologically realistic volumes for the posterior chamber, and reliable estimates governing ascorbate flux into, between, and from the posterior and anterior chambers. CONCLUSIONS: In vivo assessment of ascorbate kinetics in aqueous humor and blood of the rabbit was facilitated by the microdialysis technique. Contrary to reports in the literature, ascorbate saturable uptake from blood to aqueous was not observed at physiologic blood concentrations ( approximately 11 to 30 mg/L).

Implantation of a foldable intraocular lens in dogs.

A 1-piece, tripod-shaped, acrylic intraocular lens was implanted in the posterior chamber after phacoemulsification to remove cataracts in 20 eyes of 16 dogs. Biomicroscopy and intraocular pressure measurements were performed at 1, 8, 30, and 90 days after surgery; retinoscopy was performed at day 30. Complications were not encountered during implantation of the lens. All dogs had mild ocular inflammation characterized predominantly by aqueous flare and mild corneal edema at day 1, which resolved completely by day 8; 3 eyes had mild hyphema at day 1, which resolved by day 8. Three eyes developed fibrin in the anterior chamber, which resolved by day 30. Two eyes developed distorted pupils caused by adherence of vitreous humor or fibrin to the incision site. Postoperative intraocular pressure ranged from 7 to 21 mm Hg. Implantation resulted in 9 emmotropic eyes, 5 myopic eyes, and 6 hyperopic eyes. Maintenance of central lens position was excellent in 19 eyes; in 1 eyes, a disclocated superior haptic at day 2 was easily repositioned.

Topical exposure of the eyes to the organophosphorus insecticide malathion: lack of visual effects.

Concern for toxicity following exposure to organophosphorus insecticides led us to investigate whether topical application of either malathion or malathion mixed in a protein bait as used for aerial spray applications could be toxic to the ocular/visual system. Adult male Long-Evans rats were either untreated or treated with malathion alone (two drops per day in each eye), bait alone (six drops per day in each eye) or malathion and bait (six drops per day in each eye). The dose levels of malathion alone and malathion and bait were chosen based on pilot work and provided approximately equivalent amounts of active ingredient. The rats were treated 5 days a week for 4 weeks. During the final week of treatment, the rats were implanted surgically with cranial recording electrodes overlying the visual projection area of the cerebral cortex. Visual pattern-evoked potentials (PEPs) were elicited with vertical sinusoidal gratings at three levels of stimulus spatial frequency (0. 08, 0.16 and 0.32 cycles per degree) and three levels of visual contrast (0.15, 0.30 and 0.60). After spectral analysis of the PEP waveforms, the amplitude and phase at the stimulus rate (F1) and the first harmonic (F2) were determined. Although F1 and F2 parameters were influenced significantly by manipulation of the stimulus parameters, no significant differences were observed that could be attributed to treatment with the test substances. In addition, an ophthalmological examination of the eyes and a light microscopic evaluation of ocular tissues, including retina and optic nerve, revealed no treatment-related lesions. The dose levels used in this study were high-approximately 84000 times the exposure per unit surface area expected from aerial spraying-and yet the visual function of the treated subjects was apparently normal. This study identified no significant toxicological concerns regarding direct ocular contact exposure to malathion.

Microdialysis evaluation of the ocular pharmacokinetics of propranolol in the conscious rabbit.

PURPOSE: This study was conducted to assess the effects of anesthesia and aqueous humor protein concentrations on ocular disposition of propranolol. METHODS: Rabbits were anesthetized and a microdialysis probe was inserted into the anterior chamber of one eye; the contralateral eye served as a control. At timed intervals after probe placement, a 100-microl sample of aqueous humor was aspirated from each eye to determine protein concentration. In vitro protein binding parameters were used to simulate the impact of protein concentration on propranolol disposition. To assess the influence of anesthesia, probes were implanted in the anterior chamber of each eye. After >5-day stabilization, conscious and anesthetized rabbits (n = 3/group) received a 200-microg topical dose of [3H]DL-propranolol in each eye; propranolol was assayed in probe effluent. RESULTS: Changes in aqueous humor protein concentrations were observed following probe insertion. Simulations demonstrated that the unbound propranolol AUC (approximately 2.4-fold) in aqueous humor should be reduced due to protein influx. Intraocular propranolol exposure in anesthetized rabbits was approximately 8-fold higher than in conscious rabbits, and approximately 1.9-fold higher than in rabbits without a post-surgical recovery period. CONCLUSIONS: Anesthesia and time-dependent aqueous humor protein concentrations may alter ocular pharmacokinetics, and must be taken into account in the design of microdialysis experiments.

Primary corneal papilloma and squamous cell carcinoma associated with pigmentary keratitis in four dogs.

Squamous cell carcinoma (SCC) and squamous papilloma are rarely reported as primary lesions of the cornea in dogs. One case of corneal papilloma and 3 cases of SCC, each arising as a primary central corneal neoplasm rather than spreading from adjacent limbal conjunctiva, were reviewed. The most common cause of SCC in animals is chronic exposure of lightly pigmented epithelium to UV light; however, all dogs in this study had a history of chronic pigmentary keratitis. Three of the 4 dogs were of brachycephalic breeds with naturally proptotic eyes and oversized palpebral fissures that may have exposed the cornea to greater excessive solar radiation. Alternatively, mechanical factors that caused chronic changes in the cornea may have been causative factors for induction of primary dysplastic or neoplastic changes. Primary corneal neoplasia should be considered in the differential diagnosis of corneal masses.

Ocular infections with dematiaceous fungi in two cats and a dog.

Pigmented fungi were identified in ocular tissues from 2 cats and 1 dog. The first cat was euthanatized because of acute anterior uveitis that was unresponsive to treatment. On histologic examination, intraocular structures had been obliterated and replaced by a gray coagulum of inflammatory infiltrates and fungal elements. The second cat was treated for unilateral glaucoma that was unresponsive to treatment. A large retrobulbar mass, discovered and removed during an enucleation procedure, contained plant-origin foreign material. Keratitis, episcleritis, and orbital cellulitis with fungal elements were found on examination of the enucleated globe. The dog, examined because of a presumed corneal scratch of 2 weeks' duration that was unresponsive to treatment, had a corneal lesion subsequently removed by lamellar keratectomy that contained fungi on histologic examination. Infections caused by dematiaceous fungi are not common in domestic animals, and, to our knowledge, such infections in the eye have not been described.

The organophosphate pesticide chlorpyrifos affects form deprivation myopia.

PURPOSE: The effects of the anti-cholinesterase organophosphate pesticide chlorpyrifos (CPF) on the refractive development of the eye were examined. Form deprivation was used to induce eye growth to address the previously reported relationship between organophosphate pesticide use and the incidence of myopia. METHODS: Chickens, a well-established animal model for experimental myopia and organophosphate neurotoxicity, were dosed with chlorpyrifos (3 mg/kg per day, orally, from day 2 to day 9 after hatching) or corn oil vehicle (VEH) with or without monocular form deprivation (MFD) over the same period. The set of dependent measures included the refractive state of each eye measured using retinoscopy, axial dimensions determined with A-scan ultrasound, and intraocular pressure. RESULTS: Dosing with CPF yielded an inhibition of 35% butyrylcholinesterase in plasma and 45% acetylcholinesterase in brain. MFD resulted in a significant degree of myopia in form-deprived eyes resulting from significant lengthening of the vitreal chamber of the eye. CPF significantly reduced the effect of MFD, resulting in less myopic eyes (mean refraction: VEH-MFD = -16.2 +/- 2.3 diopters; CPF-MFD = -11.1 +/- 1.8 diopters) with significantly shorter vitreal chambers. Nonoccluded eyes were, on average, slightly hyperopic. Treatment with CPF for 1 week in the absence of MFD led to no significant change in ocular dimensions or refraction relative to controls. CONCLUSIONS: The use of form deprivation as a challenge suggests that CPF treatment interferes with the visual regulation of eye growth.

Evaluation of microdialysis sampling of aqueous humor for in vivo models of ocular absorption and disposition.

The dynamics of beta-adrenergic-associated reductions in aqueous humor production for treatment of elevated intraocular pressure are not well understood. In particular, the relationship between ocular pharmacokinetics and pharmacodynamics has yet to be established. This study was undertaken to develop a procedure for examining the ocular absorption and disposition of topically administered ophthalmic beta-adrenergic antagonists in individual animals. Dogs were anesthetized with isoflurane and a microdialysis probe was implanted in the anterior chamber of one eye and perfused with 0.9% saline at a rate of 2 microliters min-1. 3H-propranolol was administered by intracameral injection or topically. Each dog received intracameral and topical propranolol, in alternate eyes on separate days, in a randomized cross-over fashion. Microdialysis probe effluent was collected every 5 min for > or = 2.5 h; concentrations of propranolol were determined by liquid scintillation spectroscopy and were corrected for probe recovery of the substrate as determined by in vivo retrodialysis (approximately 46%) to estimate aqueous humor concentrations. In separate experiments in rabbits, microdialysis probes were implanted in each eye. 3H-propranolol was administered topically to one eye; the contralateral eye received intracameral 3H-propranolol. Model-independent pharmacokinetic parameters for each treatment phase were calculated. The mean +/- S.D. times to peak concentration of propranolol in aqueous humor were 86.6 +/- 47.6 min in the dog and 54.1 +/- 20.4 min in the rabbit. The terminal rate constant was 0.0189 +/- 0.00429 min-1 in the dog vs. 0.00983 +/- 0.00546 min-1 in the rabbit. Intraocular tissue availability of propranolol differed markedly between the dog (n = 3) and rabbit (n = 3) (approximately 0.056 in the dog vs. approximately 0.55 in the rabbit). These results demonstrate the utility of microdialysis sampling for examination of ocular pharmacokinetics.

The use of immunohistochemistry and the polymerase chain reaction for detection of feline leukemia virus and feline sarcoma virus in six cases of feline ocular sarcoma.

Ocular sarcoma was diagnosed by light microscopic examination in enucleated globes (n = 4), orbital tissue biopsy (n = 1) and ocular evisceration contents (n = 1) from six cats. To determine if feline leukemia virus (FeLV) or a replication-defective FeLV, feline sarcoma virus (FeSV), was present in these ocular sarcomas, immunohistochemistry (IHC) and polymerase chain reaction (PCR) for FeLV were utilized. Immunohistochemical staining for FeLV glycoprotein 70 (gp70) was performed on all six formalin-fixed, paraffin-embedded tumors using an avidin-biotin complex technique. DNA was extracted from each specimen and a 166 bp region of the FeLV long-terminal repeat (LTR) was amplified by PCR. All tumors were composed primarily of spindle cells; two neoplasms had PAS-positive basement membrane enveloping areas of spindle cells. All tumors involved the uvea and five of six tumors showed transcleral extension, one of which invaded the optic nerve. Immunohistochemical staining for FeLV gp 70 was negative. PCR to amplify a portion of the FeLV LTR was negative. Based on these findings of these limited number of cases, FeLV/FeSV may not play a role in the tumorigenesis of feline ocular sarcomas. However, additional tumors representing all morphological subtypes should be investigated for the presence of viral antigen and DNA. It is important to determine the etiology and pathogenesis of these malignant ocular sarcomas. If the cell of origin and pathogenesis involve ocular and lenticular injury, and FeLV/FeSV is not present, then the clinical management of cases of feline ocular trauma, uveitis and glaucoma may prevent the development of this tumor.

Internal sclerostomy with a mechanical trephine versus the neodymium:YAG laser in dogs.

BACKGROUND AND OBJECTIVES: To experimentally compare and contrast the internal sclerostomy produced using a mechanical trephine with that made by an Nd:YAG laser, and to evaluate the healing patterns, efficacy, and technical advantages of each method. MATERIALS AND METHODS: Four healthy dogs with normal eyes were used in this study. The left eye of each dog had an internal sclerostomy performed with an automated mechanical trephine. The right eye of each dog had an internal sclerostomy performed with an Nd:YAG laser. Postoperatively, the intraocular pressure of each eye was measured at regular intervals. The dogs were euthanized successively at 1, 2, 3, and 4 weeks postoperatively, and the morphology of the surgical sites was studied. RESULTS: The Nd:YAG laser was easier to manipulate and technically less demanding than the mechanical trephine. However, the Nd:YAG laser induced more prominent corneal edema and conjunctival hyperemia compared with the automated trephine. Morphology of the tissue response showed tissue necrosis and greater inflammation with the Nd:YAG laser than with the automated trephine. CONCLUSIONS: These two techniques demonstrate differences in technical demands and tissue response. Both are characterized by minimal reactive fibrosis of the episcleral and Tenon's capsule fibroblast.

Feline ocular epithelial response to growth factors in vitro.

OBJECTIVE: To examine the proliferative abilities of growth factors known to participate in wound healing on feline lens, iris pigment, ciliary, and retinal pigment epithelium cultured in vitro. ANIMALS: 8 clinically normal cats. PROCEDURE: Iris pigment, lens, ciliary, and retinal pigment epithelia of normal eyes of cats were isolated and cultured. Morphologic characteristics of primary cell cultures were studied by light and electron microscopy. Subcultures of epithelial cells were exposed to media supplemented with 0.5% fetal bovine serum plus various combinations of insulin and/or growth factors, including transforming growth factor-alpha, epidermal growth factor, acidic fibroblast growth factor, and basic fibroblast growth factor. Growth promoting effects were evaluated by counting with an electronic cell counter. RESULTS: Cells retained many of the morphologic characteristics of in vivo cells. Cell proliferation assays indicated that transforming growth factor-alpha stimulated lens and ciliary epithelial cell growth, and epidermal growth factor enhanced lens and iris pigment epithelial cell growth. Acidic fibroblast growth factor had proliferative effects on lens, iris pigment, and ciliary epithelium. Basic fibroblast growth factor was the most potent stimulator of all mitogens used, and caused substantial proliferation in all cell types. Insulin alone stimulated lens and ciliary epithelial proliferation but, combined with other growth factors, had a synergistic effect with those causing cell proliferation, except acidic fibroblast growth factor with iris pigment epithelium. CONCLUSION: Morphologic studies support the argument that pigment-producing cells are involved in feline ocular sarcoma. Growth factor studies indicated that ciliary epithelium has the most profound proliferative effect of all growth factors used. These data may help guide future studies in determining the cell of origin for feline ocular sarcoma.

The experimental antipsychotic agent 1192U90 targets tapetum lucidum in canine eyes.

To assess the potential adverse effects in people of the antipsychotic agent 1192U90, we dosed mice, rats, beagles, and cynomolgus monkeys for up to 3 mo. In dogs, but not the other species, 1192U90 caused ocular changes detectable ophthalmoscopically as loss of tapetal reflectivity, altered tapetal color, and the appearance of black pigmentation on the tapetal fundus. Eyes from affected dogs had atrophic tapeta lucidum due to cell loss. Rodlets in remaining tapetal cells were separated by electron-lucent spaces or finely granular material, varied in size and shape, and often contained irregularly shaped electron-dense inclusions. Nontapetal ocular structures were unaffected. Because 1192U90 caused no ocular changes in nontapetal species, we hypothesized that it targeted only tapetum lucidum and spared other ocular structures. We tried to test this hypothesis by dosing congenitally atapetal dogs; however, although these dogs were ophthalmoscopically "atapetal," they had scattered tapetal cells visible by electron microscopy, and these tapetal cells had ultrastructural changes indistinguishable from those that occurred in treated normal-eyed dogs. Tapetal degeneration caused by 1192U90 resembled that described in hereditary tapetal degeneration in beagles. That 1192U90 caused no ocular changes in nontapetal species suggests that the ocular changes in dogs do not imply a risk for humans, whose eyes also lack a tapetum lucidum.

Experimental evaluation of a hydroxylapatite reservoir tube shunt in rabbits.

BACKGROUND AND OBJECTIVES: Anterior chamber tube shunts of various design are of increasing importance in the surgical management of refractory glaucoma. However, the reservoirs that are commonly used today are made of a silicone or an acrylic material that may become enveloped by a fibrous capsule, which in turn may impede aqueous resorption. In this study, the authors investigated the properties of hydroxylapatite (HA) as a reservoir in gonioimplants, using three different types of HA reservoir designs. It has been demonstrated that HA orbital implants become vascularized, and the authors hypothesized that this feature of HA might modify the development of the fibrous capsule, enhancing the efficacy and decreasing the size of the implants. MATERIALS AND METHODS: HA reservoirs with Silastic tube shunts were implanted in the right eyes of six Dutch-belted rabbits. Clinical examinations were performed and intraocular pressure was measured periodically for 16 weeks postoperatively. Prior to euthanasia, fluorescein-labeled latex microspheres were injected into the anterior chamber to demonstrate implant patency. Light microscopy was used to study the tissue response to the implants and the pathways of aqueous flow. RESULTS: In general, the authors found a granulomatous inflammatory response to the HA accompanied by neovascularization into the implant and minimal fibrous encapsulation of the reservoir. CONCLUSIONS: The use of HA as a suprascleral reservoir has several advantages, the major one being a theoretical increase in the functional lifetime of the implant.

The ocular effects of intralenticular iron foreign bodies in rabbits.

Optimal treatment of intralenticular metallic foreign-body injuries remains controversial, especially in patients with clear lenses and good vision. Using 20 rabbit eyes, we examined the cataractogenic potential of intralenticular iron and its effects on the retina. Iron wire implanted into the lenses of 12 rabbit eyes caused cataracts in every eye within 4 weeks. However, after 4 1/2 weeks, none of these eyes showed evidence of retinal siderosis. No cataracts developed in five eyes with intralenticular glass, while three with intravitreal iron showed marked retinal toxicity. These results suggest that as long as the lenses remain clear, conservative management of these injuries carries minimal risk of permanent retinal damage.

Lens expression of TGF alpha in transgenic mice produces two distinct eye pathologies in the absence of tumors.

Transgenic mice carrying the rat TGF alpha minigene linked to the alpha A crystallin promoter were generated to investigate the effects of expression of this growth factor in the lens of the eye. All transgenic mice exhibited eye abnormalities in the absence of overt tumors, and two distinct and heritable phenotypes were observed. Five lineages produced 'squinting' transgenic mice characterized by microphthalmic eyes with severe lens and retinal dysplasia, and four lineages produced 'bulged' transgenic mice with eyes that exhibited enlarged globes, lens epithelial hyperplasia, anterior segment dysgenesis, and in some cases retinal dysplasia. The eye perturbations of both phenotypes were evident histologically by 1 week of age, and the eyes of squinting mice were abnormal during embryonic development. The squinting phenotype was dominant over the bulged phenotype in intercrosses, suggesting that position effects from the transgene integration site resulted in differences in TGF alpha expression between the two phenotypes. In situ hybridization showed that TGF alpha transgene expression was confined to the lens or lens rudiment of all transgenic eyes despite the involvement of non-lenticular tissues in the pathology. These results show that inappropriate expression of TGF alpha in the eye can disrupt the communication required to coordinate normal eye development.