Evaluation of a commercial NGS service for detection of bacterial and fungal pathogens in infectious ulcerative keratitis.

OBJECTIVES: To compare results from a commercial next-generation sequencing (NGS) service to corneal cytology and culture for identification of causative organisms in veterinary patients presenting for infectious ulcerative keratitis (IUK). PROCEDURE: Swabs for corneal aerobic and fungal cultures and DNA swabs for NGS were submitted for canine and equine normal controls (n = 11 and n = 4, respectively) and IUK patients (n = 22 and n = 8, respectively) for which microbrush cytology specimens confirmed the presence of infectious organisms. The sensitivity of the NGS results was compared with bacterial and fungal culture results. Concordance between the NGS and culture results was determined. RESULTS: The NGS results were positive for bacterial and fungal organisms in 5 and 1 normal and 18 and 1 IUK cases, respectively. Bacterial and fungal cultures were positive for 7 and 2 normal and 20 and 5 IUK cases, respectively. Sensitivity of NGS was 82.14% (95% confidence interval (CI), 63.11% to 93.94%) and specificity was 76.47% (95% CI, 50.10% to 93.19%). Concordance (complete and partial) between identified bacterial and fungal organisms was found in 79% and 100% of cases, respectively. NGS identified organisms in 3 culture-negative IUK samples. CONCLUSION: A commercial NGS service may be useful in the identification of causative agents in IUK cases with a sensitivity greater than the sensitivity previously reported for aerobic culture. Further testing is needed to determine the clinical significance of additional organisms isolated by NGS from infected cases, as well as organisms isolated from normal corneas.

Cataracts and phacoemulsification in the Siberian Husky: A retrospective and multicentric study (2008-2018).

PURPOSE: To compare cataract characteristics and complications related to cataracts and phacoemulsification in the Siberian Husky (Huskies) versus other canine breeds (non-Huskies). ANIMALS: A total of 50 Huskies (92 eyes) and 96 non-Huskies (182 eyes) were evaluated. METHODS: Medical records of Huskies (at four university veterinary hospitals, 2008-2018) and non-Huskies (Colorado State University, 2017-2018) diagnosed with cataracts were reviewed. Age of dog, cataract stage at presentation, and pre- and post-operative complications were recorded and analyzed. RESULTS: Mean (±standard deviation) age at presentation was significantly lower in Huskies (3.5 ± 3.3 years) compared to non-Huskies (9.5 ± 2.9 years) (p < .0001). Huskies more commonly presented with hereditary cataracts than non-Huskies (84% versus 52%) and a significantly higher percentage of non-Huskies presented with diabetic cataracts than Huskies (48% versus 16%; p = .0001). Cataract stage at presentation did not differ between Huskies and non-Huskies. Phacoemulsification was performed in 40% (20 out of 50 dogs, 39 out of 92 eyes) of Huskies and 42% (40 out of 96 dogs, 74 out of 182 eyes) of non-Huskies. Pre-operative and post-operative retinal detachment were more common in Huskies than non-Huskies (13% versus 2% and 10% versus 1%, respectively) but the difference was not significant. Other post-operative complications occurred with similar frequency in both groups (p ≥ .17). CONCLUSIONS: Huskies evaluated for cataracts were younger and less likely to present with diabetic cataracts than other canine breeds and, although not statistically significant, had a clinically important increased risk of retinal detachment pre- and post-phacoemulsification.

Determination of trypan blue efficacy in the mitigation of ex vivo canine PCO formation.

PURPOSE: To determine whether trypan blue (TB) reduces canine lens epithelial cell (LEC) or corneal endothelial cell (CEC) viability in vitro; if cell death is noted, to subsequently evaluate the molecular mechanism. METHODS: Cellular viability was determined using a lactate dehydrogenase (LDH) assay. In TB-treated LECs, caspase 3/7 activity was assessed to evaluate apoptosis; autophagy was evaluated using immunoblotting against LC3 and p62. To evaluate the effects of TB on ex vivo posterior capsule opacification (PCO), following mock cataract surgery, lens capsules were treated with TB and subsequently maintained in culture to determine LEC migration and proliferation. RESULTS: Following acute exposure, TB did not significantly reduce LEC or CEC viability at any of the concentrations tested. Increased caspase 3/7 activity was found in LEC cultures treated with TB for an extended period of time; no change in LC3 or p62 expression was noted. Ex vivo PCO formation was not significantly altered by TB treatment. CONCLUSIONS: Acute exposure to TB did not reduce LEC or CEC viability, and only longer exposure to TB was able to initiate apoptosis. Treatment with intraocular TB at the time of cataract surgery is likely safe to the CECs but will not prevent PCO formation.

An association between systemic cyclosporine administration and development of acute bullous keratopathy in cats.

OBJECTIVE: To determine whether any association exists between the onset of feline acute bullous keratopathy (ABK) and administration of systemic corticosteroid or immunosuppressive therapy. ANIMALS STUDIED: Medical records of cats diagnosed with ABK between the years of 2000 and 2008 were retrospectively reviewed. Breed, age at diagnosis, weight, systemic disease status, eye affected, ophthalmic examination findings, systemic and topical therapy instituted, dosage and duration of therapy, visual outcome and histopathological analyses were recorded in cases meeting the inclusion criteria. RESULTS: A total of 12 cats of a surveyed population of 70 167 met the inclusion criteria with 17/24 eyes affected by ABK. Medical and/or surgical therapy was utilized for management of ABK with 13/17 eyes remaining sighted at the time of last follow-up. In a subset of cases corneal cytology, aerobic bacterial culture, FHV-1 PCR, virus isolation and/or histopathology were performed; no infectious organisms were identified. A rupture in Descemet's membrane of the cornea was identified histologically in two globes. A total of 10 of 12 cats had been previously diagnosed with ongoing systemic disease. A total of 10 of 12 cats were receiving systemic therapy, and a significant association (P < 0.001) was noted between systemic administration of corticosteroids and/or cyclosporine A and the development of ABK. A total of 8 of 10 cats were administered oral prednisolone at doses between 1-2 mg/kg every 12-24 h. A total of 5 of 8 cats receiving oral prednisolone were concurrently administered oral cyclosporine at doses of 1.5-7 mg/kg every 12-24 h. Systemic cyclosporine therapy was found to be a significant risk factor (P < 0.001) for ABK development, while systemic prednisolone was not significant (P = 0.10). CONCLUSIONS: Systemic cyclosporine administration appears to be a risk factor for development of ABK in the population of cats studied.

Cyclosporine A prevents ex vivo PCO formation through induction of autophagy-mediated cell death.

The purpose of this study was to determine the Cyclosporine A (CsA) dose and minimum drug delivery time needed to prevent posterior capsule opacification (PCO) in an ex vivo canine model and evaluate the mechanism of CsA-induced cell death. Canine lens epithelial cells (LEC) were treated with CsA and changes in cell migration, proliferation, and density were monitored over time. CsA-treated LEC underwent transmission electron microscopy (TEM), immunofluorescence, and immunoblotting in the presence or absence of autophagy inhibitors to evaluate the mechanism of cell death. Lens capsules were harvested from canine cadaver eyes for an ex vivo model of PCO. Lens capsules were treated with CsA for 1, 2, 3, 4, 5, 6, or 7 days, and subsequently maintained in culture for a total of 28 days in the absence of drug. CsA reduced LEC viability in a dose dependent manner. Morphologically, CsA-treated LEC were swollen, had intact nuclei, lacked peripheral chromatin condensation, and demonstrated prominent vacuolization; TEM revealed autophagosomes. LC3-II protein expression and acridine orange fluorescence increased in CsA-treated cells. A small non-significant induction of cleaved caspase-3 was observed in CsA-treated LEC. Lens capsules treated with 5, 6, or 7 days of 10 µg/mL CsA showed a significant decrease in ex vivo PCO formation; 6 days of drug delivery prevented PCO. This study finds that morphologic changes, formation of acidic vesicles, and increased expression of LC3-II supports the hypothesis that CsA mediates LEC death via autophagy; this is a novel finding in the lens. Induction of CsA-induced apoptosis was minimal. Six days of intracapsular CsA drug delivery prevented ex vivo PCO formation.

Effects of pulsed fluid lens capsule washing following phacoemulsification on lens epithelial cells and posterior capsule opacification formation ex vivo.

BACKGROUND: The aim of the study was to evaluate ex vivo the effects of using a custom tip to direct a pulsed stream of fluid to remove residual lens epithelial cells (LECs) and reduce posterior capsule opacification (PCO) formation following phacoemulsification. METHODS: Twenty-four canine cadaver eyes were assigned to one of three treatment groups. Six eyes (Control Group) had standard phacoemulsification only, nine eyes (Group 1) had standard phacoemulsification followed by capsular washing using intermediate settings (power = 40%, pulses per second [PPS] = 50, 30 s washing per capsule hemisphere), and nine eyes (Group 2) had standard phacoemulsification followed by aggressive capsular washing (power = 60%, PPS = 50, 60 s washing per capsule hemisphere). RESULTS: Control lens capsules had diffuse LECs remaining following standard phacoemulsification and complete ex vivo PCO formation (confluent LECs on the posterior capsule) within 4 ± 2 days (range 2-8 days). Group 1 lens capsules had focal, equatorial LEC clusters remaining following treatment, and complete PCO formation within 9 ± 2 days (range 5-11 days). Group 2 lens capsules had little to no LECs observed following treatment; 5 of 9 capsules had complete PCO formation within 13 ± 2 days (range 9-14 days), and 4 of 9 capsules had no PCO formation by 24 days post-treatment. CONCLUSIONS: Pulsed fluid lens capsule washing is capable of removing LECs and delaying PCO formation in canine eyes following phacoemulsification ex vivo. Use of more aggressive capsular washing settings resulted in more effective LEC removal and subsequent delay of ex vivo PCO.

Retrospective study of the prevalence of keratoconjunctivitis sicca in diabetic and nondiabetic dogs after phacoemulsification.

OBJECTIVE: To evaluate the prevalence of keratoconjunctivitis sicca (KCS) in diabetic and nondiabetic dogs following phacoemulsification. PROCEDURES: Medical records were reviewed for signalment, body weight, diabetes status, and STT at the preoperative and all postoperative examinations. A clinical diagnosis of KCS was defined as a STT <15 mm/min with compatible clinical signs. Schirmer tear test values and the prevalence of KCS based on STT <15 mm/min were evaluated at 2-4, 5-8, 9-14, 15-20, and 41-52 weeks postoperatively. Size of dog (large, >10 kg; small, ≤10 kg) and STT ranges (<15 mm/min, 15-22 mm/min and >22 mm/min) were categorized for analysis of effect of body weight and STT on prevalence of KCS. RESULTS: One hundred and seventeen nondiabetic (198 eyes) and 118 diabetic dogs (228 eyes) were evaluated. KCS was diagnosed in nearly twice as many diabetics as nondiabetics (27.4% vs. 15.4%) within 2 weeks postoperatively (P = 0.0088). Percentage of eyes with KCS among all dogs decreased over time and did not differ significantly after the first postoperative visit. Diabetic small dogs were 1.7 times more likely to have KCS than nondiabetic small dogs (P = 0.0052). Preoperative STT was significantly associated with likelihood of postoperative KCS among large (P < 0.0001), but not small dogs (P = 0.0781). Among large dogs, eyes with STTs between 15 and 22 mm/min were approximately 3 times more likely to be diagnosed with KCS after surgery than those with STT >22 mm/min. CONCLUSION: The greatest risk for KCS for all dogs is during the first 2 weeks postoperatively. Populations at greatest risk for postoperative KCS are small dogs, small diabetic dogs, and large dogs with preoperative STT ≤22.

Trans-corneal reduction of anterior lens luxation in dogs with lens instability: a retrospective study of 19 dogs (2010-2013).

OBJECTIVE: To evaluate the success rate and outcome of trans-corneal reduction of anterior lens luxation (TR-ALL) in dogs with lens instability. ANIMALS STUDIED: Nineteen dogs with anterior lens luxation. PROCEDURES: Medical records of dogs with anterior lens luxation (ALL) were reviewed: dogs were included if TR-ALL was performed followed by medical therapy in the form of topical 0.005% latanoprost ophthalmic solution. The duration of ALL, vision status, ophthalmic examination abnormalities, reason for performing TR-ALL and details of TR-ALL were recorded. Success rate for TR-ALL as well as postprocedure complications were also assessed. RESULTS: Twenty eyes from 19 dogs met the inclusion criteria. Median age was 6.5 years (0.3-15 years) and 47% were terriers (9/19). Successful TR-ALL was achieved in 85% of eyes (17/20); failure was attributed to posterior synechia or vitreous expansion. Short-term complications included corneal ulceration (2/20) and anterior uveitis (3/20); recurrence of anterior luxation occurred in only one dog. Median follow-up for visual eyes (11) following successful TR-ALL was 353 days (range of 1 to 1182 days). Vision was retained in 54.5% (6/11) of eyes with a median time to vision loss of 12 months as a result of glaucoma or presumed retinal detachment. CONCLUSIONS: Trans-corneal reduction of ALL provides a non-surgical alternative to intracapsular lens extraction (visual eyes) or enucleation (nonvisual eyes) in dogs. Long-term visual outcome of TR-ALL is comparable to intracapsular lens extraction for ALL.

Equine glaucoma: a histopathologic retrospective study (1999-2012).

PURPOSE: To characterize and describe the histopathologic findings in equine globes enucleated due to glaucoma. METHODS: Medical records at The Ohio State University from 1999 to 2012 were reviewed retrospectively. Signalment, history, and treatment data were collected, and histologic slides of enucleated globes were examined and lesions recorded. Twenty-three eyes from 23 horses were eligible for inclusion in this study. RESULTS: The majority of affected horses were > 15 years of age (65%). The ages ranged from 5 to 35 years (mean = 17.4 years). The left eye was affected in 10 cases (43%) and the right eye in 13 cases (57%). There were 13 mares (56%) and 10 geldings (44%). Quarter Horses (30%), Appaloosas (26%), and Thoroughbreds (22%) were the most common breeds in the study population. The most common histopathologic changes included hypercellularity of the optic nerve (93%), retinal atrophy (89%), corneal vascularization (83%), descemetization of pectinate ligaments (83%), hypercellularity of the anterior corneal stroma (75%), posterior bowing of the iris base (74%), ciliary body atrophy (74%), corneal striae (70%), pars plana elongation (60%), cataract (53%), and collapsed ciliary cleft/trabecular meshwork (52%). Evidence of uveitis (cataract, lymphoplasmacytic infiltration of the uvea, and/or anterior or posterior synechiae) was present in 20/23 eyes (87%). CONCLUSIONS: Equine glaucoma most commonly occurs secondary to uveitis with Appaloosas and older horses predisposed. Histologic changes are comparable to prior reports of chronic glaucoma; notable findings not previously described in the horse were posterior bowing of the iris base and relative sparing of the superior retina from atrophy associated with elevated IOP.

The location of sites and effect of semiconductor diode trans-scleral cyclophotocoagulation on the buphthalmic equine globe.

PURPOSE: To determine appropriate location and energy settings for trans-scleral cyclophotocoagulation (TSCPC) for buphthalmic equine globes. ANIMALS: Eleven horses with a buphthalmic eye blinded by glaucoma presented for enucleation. METHODS: Globe and corneal dimensions were measured via ultrasonography and calipers, and TSCPC was performed under general anesthesia immediately prior to enucleation. Part 1: In nine globes, sixty sites were lasered 4 mm posterior to the limbus in the dorsotemporal and ventrotemporal quadrants at settings of 1500 milliwatts and 1500 ms. Globes were processed and sectioned sagitally over the temporal aspect in two blocks, each with five histologic sections examined by light microscopy. A digital imaging system was used to determine the location and length of the pars plicata on one slide from each block. Part 2: Based on results in Part 1, two globes were measured and lasered using the same time and energy settings at the following distances posterior to the limbus: 8 mm dorsally, 6 mm dorsotemporally, 5 mm ventrotemporally, and 5 mm ventrally. RESULTS: Globe and corneal dimensions exceeded normal values in all globes. Part 1: In all nine globes, photocoagulation affected the anterior ciliary processes and iris base and in 8/9 coagulation of the pectinate ligaments was noted. Part 2: In both globes, coagulation was confined to the pars plicata. CONCLUSIONS: The previously recommended TSCPC sites are located too far anteriorly for a buphthalmic globe. Buphthalmic equine globes should have TSCPC performed at the following distances posterior to the limbus: 6-8 mm dorsally, 5-6 mm dorsotemporally, 4-5 mm ventrotemporally, and 4-5 mm ventrally.

Corneal dystrophy in Friesian horses may represent a variant of pellucid marginal degeneration.

OBJECTIVE: To describe the clinical presentation, treatment, and outcome of a corneal dystrophy in Friesian horses and to analyze affected horses' pedigrees to investigate its heritability. ANIMALS: Nine Friesians with bilateral disease were identified. PROCEDURE: Retrospective medical record review was used to identify Friesian horses exhibiting bilateral symmetric corneal lesions. Variables identified from medical records included patient sex and age at diagnosis; location, depth and size of corneal lesions; medical and surgical therapy instituted; and visual outcome. A four-generation pedigree for each included horse was used to construct a combined pedigree. RESULTS: The nine included horses had an average age at diagnosis of the first eye of 10.7 years, with males (8/9) significantly more frequently affected than females (1/9), P = 0.012. Lesions were inferior and averaged 5 mm in diameter. Depth ranged from superficial facets to perforations, which developed in nine of 18 eyes. Eight of nine perforations were surgically repaired, with seven of eight repaired eyes visual at last follow-up. All nine eyes that had not perforated remained visual. All affected horses shared a common ancestor within six generations. CONCLUSIONS: This form of corneal dystrophy in Friesian horses, characterized by bilateral symmetric stromal loss, appears to be progressive but responds well to surgical repair, occurs more frequently in males, may have a genetic component in Friesian horses, and may be a variant of pellucid marginal degeneration.

The long-term effects of semiconductor diode laser transscleral cyclophotocoagulation on the normal equine eye and intraocular pressure(a).

OBJECTIVE: To describe the long-term histologic and intraocular pressure (IOP) lowering effects of diode laser transscleral cyclophotocoagulation (TSCP) on the normal equine eye. ANIMALS: Eight normal adult horses. PROCEDURES: TSCP was performed in one randomly assigned eye. Sixty spots were treated at settings of 1500 ms and 1500 mW. Two horses were randomly selected for euthanasia at 2, 4, 12, or 24 weeks post-TSCP. Both eyes were enucleated and histologically evaluated. Intraocular pressure was measured by applanation tonometry prior to TSCP, immediately post-TSCP, twice daily for 7 days post-TSCP and then monthly until study conclusion. A longitudinal model estimated the average IOP values for the treated and untreated eyes at 1 week, 1, 3, and 6 months post-TSCP. RESULTS: All treated eyes at all time periods exhibited four characteristic histologic lesions: scleral collagen hyalinization, ciliary body pigment dispersion and clumping, focal disruption of the ciliary body epithelium, and focal ciliary process atrophy. After TSCP, there were no significant changes in IOP from baseline for the control eyes, while the IOP in treated eyes was significantly decreased from baseline (P < 0.05) at all time periods. The estimated decrease in IOP in the treated eyes compared to baseline IOP at 6 months was -3.76 mmHg for an average decrease in IOP of 20% from baseline. CONCLUSION: Diode laser TSCP produces histologic lesions in the equine ciliary body that result in a significant and sustained decrease in IOP. TSCP may be an effective management for equine glaucoma.

Effects of gabapentin and trazodone on electroretinographic responses in clinically normal dogs.

OBJECTIVE: To compare electroretinographic (ERG) responses obtained in dogs before and after oral administration of gabapentin, trazodone, and a combination of both medications. ANIMALS: 12 clinically normal dogs. PROCEDURES: A short-protocol ERG with 20 minutes of dark adaption was recorded for all dogs to establish baseline ERG responses. Dogs then received gabapentin (approx 30 mg/kg), trazadone (approx 20 mg/kg or approx 5 mg/kg), or a combination of gabapentin (approx 20 mg/kg) and trazodone (approx 5 mg/kg) orally, and the same ERG protocol was repeated 2 hours later. Dogs were given a washout period of at least 1 week between treatments. RESULTS: a-Wave amplitudes were significantly (P = 0.018) decreased after administration of the combination of gabapentin and trazodone. b-Wave amplitudes were significantly decreased after administration of the 20-mg/kg dose of trazodone (P = 0.006) and after administration of the combination of gabapentin and trazodone (P = 0.002). Heavier dogs that received higher total doses of trazodone had decreases in a-wave amplitude after administration of the 20-mg/kg dose of trazodone and in b-wave amplitude after administration of the 5-mg/kg dose of trazodone. CLINICAL RELEVANCE: High doses of trazodone and the combination of gabapentin and trazodone significantly decreased a-wave and b-wave amplitudes in clinically normal dogs. However, the effects on retinal responses had little clinical importance. Therefore, these medications can be used safely in a clinical setting; however, further studies are needed in dogs with retinal disease.

Semiconductor diode laser transscleral cyclophotocoagulation for the treatment of glaucoma in horses: a retrospective study of 42 eyes.

OBJECTIVE: To evaluate the outcome of diode laser transscleral cyclophotocoagulation (TSCP) for the treatment of glaucoma in horses. PROCEDURE: Medical records at The Ohio State University were reviewed. All horses that underwent diode laser TSCP between the years of 1995 and 2007 were included. Preoperative, procedural and clinical follow-up data were collected, and telephone follow-up was performed. RESULTS: Forty-two eyes of 36 horses were included. Twenty-four hours prior to surgery mean intraocular pressure (IOP) was 37.17 + or - 13.48 mmHg (42 eyes). Forty-one of 42 eyes (98%) were sighted and 39 of 39 (100%) of eyes were receiving topical glaucoma medication. At 3-5 weeks postoperatively the average IOP was 19.36 + or - 12.04 mmHg (22 eyes). IOP remained significantly lower than pretreatment values at all periods of clinical follow-up (P < 0.05). There was no significant difference in vision outcome, or the requirement for topical glaucoma medication relative to pretreatment values at any follow-up period. Hyphema in 5 of 42 eyes was the only complication noted. Of the 27 eyes seen for clinical follow-up, 2 were enucleated because of refractory elevation of IOP. Mean telephone follow-up was 49 months. Twenty-one of 22 owners contacted (95%) reported that the treatment had been of value, 14 of 22 eyes (64%) were receiving topical glaucoma medication, and 13 of 22 eyes (59%) were considered sighted. CONCLUSIONS: Diode laser TSCP aided in the control of IOP and maintenance of vision but did not eliminate the need for topical glaucoma medication during the period of clinical follow-up.

In vivo effects of adjunctive tetracycline treatment on refractory corneal ulcers in dogs.

OBJECTIVE: To evaluate effect of adjunctive treatment with tetracycline analogues on time to complete corneal reepithelialization in dogs with nonhealing (ie, refractory) corneal ulcers. DESIGN: Randomized controlled clinical trial. ANIMALS: 89 dogs with refractory corneal ulcers. PROCEDURES: Corneal ulcers were treated via debridement and grid keratotomy. Dogs were assigned to receive 1 of 3 treatment regimens for up to 6 weeks: doxycycline (5 mg/kg [2.27 mg/lb], PO, q 12 h) with topically applied ophthalmic ointment containing neomycin, polymyxin B, and bacitracin (ie, triple antibiotic ointment; q 8 h); cephalexin (22 mg/kg [10 mg/lb], PO, q 12 h) with topically applied oxytetracycline ophthalmic ointment (q 8 h); or a control treatment of cephalexin (22 mg/kg, PO, q 12 h) with topically applied triple antibiotic ointment (q 8 h). Healing was monitored via measurements of the wound with calipers and evaluation of photographs obtained every 2 weeks. Treatment effectiveness was evaluated by wound healing and decreased signs of pain. RESULTS: The Boxer breed was overrepresented in all groups. At the 2-week time point, wound healing was significantly more common in small-breed dogs, compared with large-breed dogs. Dogs treated with oxytetracycline ophthalmic ointment had a significantly shorter healing time than did dogs receiving the control treatment. Corneal ulcers in dogs that received doxycycline PO healed more rapidly than did ulcers in dogs in the control treatment group; however, this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Topical tetracycline ophthalmic ointment was a safe, inexpensive, and effective adjunctive treatment for refractory corneal ulcers in dogs.

Cause and Treatment of Exophthalmos in Aged Cotton Rats (Sigmodon hispidus).

Aged cotton rats (Sigmodon hispidus) from an established breeding colony displayed signs of spontaneous exophthalmos. Of a total of 118 colony animals that were older than 6 mo of age, 37 (31%) displayed signs of exophthalmos. These rats were clinically healthy and had no other signs of disease. Ophthalmic exams, molecular and microbiologic testing, and histopa- thology were performed to determine the cause of the exophthalmos and to provide appropriate treatment. Environmental monitoring records were also reviewed for vivarium rooms in which the cotton rats were housed. Histopathology findings supported that the exophthalmos in these cotton rats was secondary to retro-orbital thrombosis associated with cardiomyopathy. The exophthalmic eyes were treated by either removal of the affected eye (enucleation) or surgical closure of the eyelids (temporary tarsorraphy). Enucleation of the exophthalmic eye was the best intervention for these aged cotton rats. These findings demonstrate the potential for a high incidence of ocular problems occurring secondary to cardiomyopathy in aged cotton rats. Enucleation as a therapeutic intervention for exophthalmic eyes in aged cotton rats prolongs the morbidity-free time span during which these aged animals can be used experimentally.

MG53 promotes corneal wound healing and mitigates fibrotic remodeling in rodents.

The cornea plays an important role in transmitting light and providing protection to the eye, but is susceptible to injury and infection. Standard treatments for corneal wounds include topical lubricants, antibiotics, bandage contact lens, and surgery. However, these measures are often ineffective. Here we show that MG53, a protein with an essential role in cell membrane repair, contributes to the corneal injury-repair process. Native MG53 is present in the corneal epithelia, tear film, and aqueous humor, suggesting its potential function in corneal homeostasis. Knockout of MG53 in mice causes impaired healing and regenerative capacity following injury. Exogenous recombinant human MG53 (rhMG53) protein protects the corneal epithelia against mechanical injury and enhances healing by promoting migration of corneal fibroblasts. Using in vivo alkaline-induced injury to the rat cornea, we show that rhMG53 promotes re-epithelialization and reduces post-injury fibrosis and vascularization. Finally, we show that rhMG53 modulates TGF-ß-mediated fibrotic remodeling associated with corneal injury. Overall, our data support the bi-functional role of MG53 in facilitating corneal healing and maintaining corneal transparency by reducing fibrosis and vascularization associated with corneal injuries.

Exophthalmus secondary to a sinonasal cyst in a horse.

CASE DESCRIPTION: A 13-year-old female Miniature Horse was evaluated for progressive unilateral exophthalmia of the left globe of 3 weeks' duration. CLINICAL FINDINGS: Results of a physical examination were unremarkable. Ophthalmic examination identified exophthalmus of the left globe with complete resistance to retropulsion and mild blepharoconjunctivitis. Computed tomography revealed a large, space-occupying mass within the left caudal maxillary and left conchofrontal sinuses. The mass extended into the left retrobulbar space and contacted the cribriform plate. Trephination yielded copious amounts of turbid yellow fluid. The diagnosis was a sinonasal cyst. TREATMENT AND OUTCOME: Subtotal surgical excision of the cyst via a frontonasal osteoplastic flap was curative, with complete resolution of the exophthalmus. Histologic examination confirmed diagnosis of a sinonasal cyst. There was no evidence of cyst recurrence by 4 months after surgery. CLINICAL RELEVANCE: Sinonasal cyst should be a differential diagnosis for retrobulbar disease in horses. Exophthalmia may be the only clinical finding in horses with a sinonasal cyst.

Effects of grape seed extract, lutein, and fish oil on responses of canine lens epithelial cells in vitro.

OBJECTIVE To determine the effects of grape seed extract (GSE), lutein, and fish oil containing omega-3 fatty acids on oxidative stress, migration, proliferation, and viability of lens epithelial cells (LECs). SAMPLE Lens capsules or cultured LECs obtained from canine cadavers. PROCEDURES An antioxidant reductive capacity assay was used to determine reducing capability of each substance. The LECs were cultured and incubated with various substances, including N-acetyl cysteine (NAC), when appropriate, and dimethyl sulfoxide (DMSO) as positive and vehicle control substances, respectively. A dichlorofluorescein assay was used to evaluate reactive oxygen species (ROS) production, and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine cell viability. Ex vivo posterior capsule opacification (PCO) was used to evaluate LEC migration and proliferation. RESULTS Antioxidant reductive effects of GSE surpassed those of NAC, lutein, and fish oil containing omega-3 fatty acids. The GSE reduced ROS production in LECs, compared with the DMSO vehicle control, whereas lutein was pro-oxidative. All test substances reduced cell viability. Ex vivo PCO was not altered by GSE, was decreased by lutein, and was increased by fish oil containing omega-3 fatty acids, compared with results for the DMSO vehicle control. CONCLUSIONS AND CLINICAL RELEVANCE Only GSE had significant antioxidant capabilities and reduced ROS production; however, no effect on ex vivo PCO was detected. Fish oil containing omega-3 fatty acids increased ex vivo PCO. No conclusions could be made regarding antioxidant effects of these substances on LECs. These findings suggested that the substances will not decrease PCO.

Objective evaluation of the systemic effects of topical application of 1% atropine sulfate ophthalmic solution in healthy horses.

OBJECTIVE To determine the safety of topical administration of 1% atropine ophthalmic solution in healthy horses by objectively measuring gastrointestinal transit time. DESIGN Randomized, masked, controlled crossover study. ANIMALS 6 adult geldings. PROCEDURES Horses were randomly assigned (3/group) to first receive topical treatment of the left eye with 1% atropine or artificial tears solution; the right eye was left untreated. After 24 hours of treatment every 6 hours, 200 nontoxic beads were administered to each horse via nasogastric intubation and treatment frequency was decreased to every 12 hours for 4 more days. Pupillary light reflexes (PLRs), mydriasis, heart rate, fecal bead passage, abdominal girth measurements, auscultable gut sounds, fecal weight, and clinical signs of abdominal pain were monitored. Following a 4-week washout period, horses received the opposite treatment in the left eye and measurements were repeated. Serum atropine concentration (reflecting systemic absorption) was measured with an ELISA at various points after initial atropine administration. RESULTS No horse had subjective or objective evidence of colic or ileus at any monitoring point. Complete mydriasis of the left eye with absence of the PLR was identified in 5 horses within 6 hours and in all 6 horses within 12 hours after initial atropine administration. One horse had mydriasis with an absent PLR in the untreated eye by day 5 of atropine treatment. At no point was atropine detected in serum samples of any horse. CONCLUSIONS AND CLINICAL RELEVANCE Topical atropine application at clinically appropriate doses induced no evidence of ileus in healthy horses.