Free labial mucocutaneous graft for eyelid reconstruction in four dogs.

PURPOSE: To describe a technique for eyelid margin reconstruction following large mass resection utilizing a free labial mucocutaneous graft. METHODS: Four dogs (4 eyes) underwent en bloc eyelid mass excision under general anesthesia. Measurements were made of the mass followed by free labial mucocutaneous graft retrieval, resection of the mass, and then transplantation of retrieved region of labial mucocutaneous tissue into the resulting defect. RESULTS: Three patients underwent eyelid margin reconstruction with a free labial mucocutaneous graft. One patient received a pedicle advancement graft combined with a free labial mucocutaneous graft. In all cases, a length of 120%-150% of the eyelid defect was retrieved from the oral labia. Postoperative follow-up ranged from 6 weeks to 4 months. All cases had superficial graft necrosis and depigmentation of the donor tissue with total healing time taking up to 8 weeks. All cases had an esthetic and functional reconstruction. CONCLUSIONS: This technique allows reconstruction of the majority of the eyelid margin, greater than that which can be closed primarily. Due to tissue sloughing, the healing time can be extended but cosmetic outcomes are good. Eyelid reconstruction utilizing a free labial graft restored a mucocutaneous margin and recreated a functional eyelid, thus avoiding trichiasis or secondary keratitis.

An investigation into the development of qualitative tear film disorders in dogs following cryoepilation for distichiasis.

OBJECTIVE: The aim of this prospective study was to compare tear film quality between dogs who have previously undergone cryoepilation for distichiasis to a reference population. ANIMALS STUDIED: Nine dogs (17 eyes) were recruited after surgery and were compared to a reference population of 21 dogs (42 eyes). PROCEDURES: Canine patients who had previously undergone cryoepilation for distichiasis for a minimum of 1 month prior to examination were recruited. A complete ophthalmic examination was performed by an ABVO resident (BDR), with additional tear tests, including tear film interferometry, infra-red meibography, and a tear film break-up time (TFBUT) performed. The tear test results were compared to a reference population obtained from client-owned dogs with no history of ophthalmic complaints, a normal ophthalmic examination performed by an ABVO resident (BDR) and a Schirmer Tear Test-1 > 15 mm/min. Statistical analysis was performed of the results obtained. RESULTS: The treated group was significantly more affected with meibomian gland dropout (MG-dropout) in 11/17 (64.7%) cases, compared to the reference population of 2/21 (9.5%) (p < .01). The treated group had an odds ratio of 23.8 to develop MG-dropout compared to the reference population (p < .01). Tear film breakup time (TFBUT) was significantly shorter in the treatment group (5.8 ± 2.6 s) compared to the reference population (10.1 ± 1.1 s) (p < .001). In the treatment group, 12/17 (70.5%) of treated eyes had a TFBUT < 5 s compared to 2/21 (9.5%) of the reference population. CONCLUSION: Cryoepilation for distichaiasis appears to be a risk factor for developing MG-dropout and qualitative tear film disorders post-operatively in canines.

A Comprehensive Study of the Retinal Phenotype of Rpe65-Deficient Dogs.

The Rpe65-deficient dog has been important for development of translational therapies of Leber congenital amaurosis type 2 (LCA2). The purpose of this study was to provide a comprehensive report of the natural history of retinal changes in this dog model. Rpe65-deficient dogs from 2 months to 10 years of age were assessed by fundus imaging, electroretinography (ERG) and vision testing (VT). Changes in retinal layer thickness were assessed by optical coherence tomography and on plastic retinal sections. ERG showed marked loss of retinal sensitivity, with amplitudes declining with age. Retinal thinning initially developed in the area centralis, with a slower thinning of the outer retina in other areas starting with the inferior retina. VT showed that dogs of all ages performed well in bright light, while at lower light levels they were blind. Retinal pigment epithelial (RPE) inclusions developed and in younger dogs and increased in size with age. The loss of photoreceptors was mirrored by a decline in ERG amplitudes. The slow degeneration meant that sufficient photoreceptors, albeit very desensitized, remained to allow for residual bright light vision in older dogs. This study shows the natural history of the Rpe65-deficient dog model of LCA2.

Early-Onset Progressive Degeneration of the Area Centralis in RPE65-Deficient Dogs.

Purpose: Retinal epithelium-specific protein 65 kDa (RPE65)-deficient dogs are a valuable large animal model species that have been used to refine gene augmentation therapy for Leber congenital amaurosis type-2 (LCA2). Previous studies have suggested that retinal degeneration in the dog model is slower than that observed in humans. However, the area centralis of the dog retina is a cone and rod photoreceptor rich region comparable to the human macula, and the effect of RPE65 deficiency specifically on this retinal region, important for high acuity vision, has not previously been reported. Methods: Spectral-domain optical coherence tomography, fundus photography, and immunohistochemistry of retinal wholemounts and sagittal frozen sections were used to define the time-course and cell-types affected in degeneration of the area centralis in affected dogs. Results: Area centralis photoreceptor degeneration was evident from 6 weeks of age, and progressed to involve the inner retina. Immunohistochemistry showed that RPE65-deficient dogs developed early loss of S-cone outer segments, with slower loss of L/M-cone outer segments and rods. Conclusions: Early-onset severe photoreceptor degeneration in the area centralis of dogs with RPE65-deficiency offers a model of the early foveal/perifoveal degeneration in some patients with LCA2. This model could be used to refine interventions aiming to improve function and halt the progression of foveal/perifoveal photoreceptor degeneration.

Successful gene therapy in older Rpe65-deficient dogs following subretinal injection of an adeno-associated vector expressing RPE65.

Young Rpe65-deficient dogs have been used as a model for human RPE65 Leber congenital amaurosis (RPE65-LCA) in proof-of-concept trials of recombinant adeno-associated virus (rAAV) gene therapy. However, there are relatively few reports of the outcome of rAAV gene therapy in Rpe65-deficient dogs older than 2 years of age. The purpose of this study was to investigate the success of this therapy in older Rpe65-deficient dogs. Thirteen eyes were treated in dogs between 2 and 6 years old. An rAAV2 vector expressing the human RPE65 cDNA driven by the human RPE65 promoter was delivered by subretinal injection. Twelve of the 13 eyes had improved retinal function as assessed by electroretinography, and all showed improvement in vision at low lighting intensities. Histologic examination of five of the eyes was performed but found no correlation between electroretinogram (ERG) rescue and numbers of remaining photoreceptors. We conclude that functional rescue is still possible in older dogs and that the use of older Rpe65-deficient dogs, rather than young Rpe65-deficient dogs that have very little loss of photoreceptors, more accurately models the situation when treating human RPE65-LCA patients.

Reproducibility of an objective four-choice canine vision testing technique that assesses vision at differing light intensities.

OBJECTIVE: The increasing importance of canine retinal dystrophy models means accurate vision testing is needed. This study was performed to evaluate a four-choice vision testing technique for any difference in outcome measures with repeated evaluations of the same dogs. ANIMALS STUDIED: Four 11-month-old RPE65-deficient dogs. PROCEDURES: Vision was evaluated using a previously described four-choice vision testing device. Four evaluations were performed at 2-week intervals. Vision was assessed at six different white light intensities (bright through dim), and each eye was evaluated separately. The ability to select the one of the four exit tunnels that was open at the far end was assessed ('choice of exit') and recorded as correct or incorrect first tunnel choice. 'Time to exit' the device was also recorded. Both outcomes were analyzed for significance using anova. We hypothesized that performance would improve with repeated testing (more correct choices and more rapid time to exit). RESULTS: 'Choice of exit' did not vary significantly between each evaluation (P = 0.12), in contrast 'time to exit' increased significantly (P = 0.012), and showed greater variability in dim light conditions. CONCLUSIONS: We found no evidence to support the hypothesis that either measure of outcome worsened with repeated testing; in fact, the 'time to exit' outcome worsened rather than improved. The 'choice of exit' gave consistent results between trials. These outcome data indicate the importance of including a choice-based assessment of vision in addition to measurement of device transit time.

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.

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.