Restoration of function following traumatic superior eyelid avulsion in a horse treated with advancement flap blepharoplasty (H-plasty) and subdermal hyaluronic acid filler.

OBJECTIVE: To describe the successful restoration of superior eyelid function in a horse following traumatic avulsion using an advancement flap blepharoplasty and subdermal hyaluronic acid filler. ANIMAL STUDIED: A 21-year-old American Paint Horse stallion who was attacked by a fellow stallion resulting in numerous traumatic injuries including avulsion of approximately 75% of the left superior eyelid. PROCEDURES: With standing sedation and locoregional anesthesia, the superior eyelid wound was debrided and an advancement flap blepharoplasty (H-plasty) and temporary tarsorrhaphy were performed. Routine healing of the surgical site occurred over the subsequent weeks, though lagophthalmos persisted. At 2 and 4 weeks post-operatively, 2.4% cross-linked hyaluronic acid was injected subdermally into the superior eyelid to attempt to improve corneal coverage. At 8 weeks post-operatively, a complete blink was restored and the cosmetic outcome was good. CONCLUSIONS: Injection of subdermal hyaluronic acid filler following eyelid injuries or blepharoplastic procedures that result in lagophthalmos can improve corneal coverage by the eyelids and allow for maintenance of a comfortable and visual eye.

Breed predispositions to congenital and juvenile cataracts in horses at two academic institutions.

BACKGROUND: Determination of horse breeds predisposed to congenital and juvenile cataracts will enable investigations into potential genetic mechanisms for cataracts in horses. OBJECTIVE: To investigate horse breed predispositions to congenital and juvenile cataracts in two academic referral populations. STUDY DESIGN: Retrospective case series. METHODS: Medical record identification of horses diagnosed with congenital or juvenile cataracts at the Cornell University Equine Hospital (2000-2022) and the University of California-Davis (UCD) Large Animal Clinic (1990-2021). Signalment, examination findings and treatments were recorded. Descriptive statistics were performed, and breed over-representations were determined using Chi-squared or Fisher's exact tests. RESULTS: Thirty-one (Cornell) and 70 (UCD) horses with congenital or juvenile cataracts were identified, for a total of 101 affected horses. Seventy-eight horses were affected bilaterally and 23 were affected unilaterally, for a total of 179 affected eyes. Standardbreds were significantly over-represented at both institutions, comprising 32.5% of congenital/juvenile cataract cases and 10% of the equine hospital population at Cornell (p < 0.001) and 4.3% of cataract cases and 1.3% of the equine hospital population at UCD (p = 0.03). Thoroughbreds were under-represented for congenital and juvenile cataracts at both institutions (p = 0.03 Cornell, p = 0.01 UCD). MAIN LIMITATIONS: Retrospective study, potential for selection bias. CONCLUSIONS: The over-representation of the Standardbred breed for congenital and juvenile cataracts at two institutions suggests an underlying genetic basis in the breed. Future genetic and genomic studies are warranted to investigate heritable cataracts in Standardbred horses.

Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds.

Congenital stationary night blindness (CSNB) is an ocular disorder characterized by nyctalopia. An autosomal recessive missense mutation in glutamate metabotropic receptor 6 (GRM6 c.533C>T, p.(Thr178Met)), called CSNB2, was previously identified in one Tennessee Walking Horse and predicted to reduce binding affinity of the neurotransmitter glutamate, impacting the retinal rod ON-bipolar cell signaling pathway. Thus, the first aim was to identify the allele frequency (AF) of CSNB2 in breeds with reported cases of CSNB and breeds closely related to the Tennessee Walking Horse. The second aim was to perform ocular examinations in multiple breeds to confirm the link between genotype and CSNB phenotype. In evaluating 3518 horses from 14 breeds, the CSNB2 allele was identified in nine previously unreported breeds. The estimated AF was highest in pacing Standardbreds (0.17) and lowest in American Quarter Horses (0.0010). Complete ophthalmic examinations and electroretinograms (ERG) were performed on 19 horses from three breeds, including one CSNB2 homozygote from each breed. All three CSNB2/CSNB2 horses had an electronegative ERG waveform under scotopic light conditions consistent with CSNB. The remaining 16 horses (seven CSNB2/N and nine N/N) had normal scotopic ERG results. All horses had normal photopic ERGs. This study provides additional evidence that GRM6 c.533C>T homozygosity is likely causal to CSNB in Tennessee Walking Horses, Standardbreds, and Missouri Fox Trotting Horses. Genetic testing is recommended for breeds with the CSNB2 allele to limit the production of affected horses. This study represents the largest across-breed identification of CSNB in the horse and suggests that this disorder is likely underdiagnosed.

Ultrasound biomicroscopy of the equine iridocorneal angle.

BACKGROUND: The iridocorneal angle (ICA) is the major pathway of aqueous humour outflow from the anterior chamber of the eye. Ultrasound biomicroscopy (UBM) has been utilised to characterise the morphology of this drainage pathway in numerous species. UBM may allow for early recognition of aqueous humour outflow obstructions in horses, allowing for earlier recognition of risk for glaucoma, a vision-threatening and painful disease. UBM morphology of the normal equine ICA has yet to be described. OBJECTIVES: To determine the ultrasonographic morphology of the equine ICA by UBM in standing sedated horses. STUDY DESIGN: In vivo experimental study. METHODS: Thirty healthy adult horses underwent UBM of the ICA at four locations (superior, temporal, inferior, nasal) of each eye utilising standing sedation, topical anaesthesia and auriculopalpebral perineural anaesthesia. Anatomic structures were defined on ultrasound images through comparison to published histologic photomicrographs of the equine ICA. RESULTS: Ultrasound imaging of the ICA at all four locations was easily performed in standing, sedated horses. High-resolution images of the ICA allowed for identification of the pectinate ligament, corneoscleral trabecular meshwork (TM), uveal TM and supraciliary TM. MAIN LIMITATIONS: Pupil size was midrange in all eyes, but was not strictly controlled. Lighting conditions not controlled. Various breeds included. CONCLUSION: In vivo UBM of the equine ICA is feasible and provides high-resolution images of the structures of the aqueous humour outflow pathway.

Shope fibroma of the eyelid margin in a domestic rabbit.

OBJECTIVE: To describe the clinical and histopathologic features as well as response to treatment of a solitary Shope fibroma affecting the eyelid margin of a domestic rabbit. ANIMAL STUDIED: A seven-year-old female intact domestic rabbit with a progressively enlarging firm, pedunculated, and encrusted inferior eyelid mass of the left eye of 1-month duration. PROCEDURES: Under general anesthesia, the crust was removed revealing an ulcerated mass that was excised via a house-shaped resection and submitted for histopathology. Purulent discharge associated with the mass was swabbed for aerobic and anaerobic bacterial culture and sensitivity testing. Histopathology revealed intraepithelial, cytoplasmic leporipoxviral inclusion bodies consistent with Shope fibroma virus. There was no growth on aerobic or anaerobic bacterial culture. The lesion was completely excised, and no recurrence was noted during a 3-month follow-up period. CONCLUSIONS: The solitary nature and clinical appearance of this eyelid margin Shope fibroma are unique. Shope fibroma should be considered a differential diagnosis for eyelid masses in rabbits even in the absence of other cutaneous masses. Thorough systemic evaluation to attempt to distinguish Shope fibroma from malignant myxomatosis should be performed.

Corneal thickness and anterior chamber depth of the normal adult horse as measured by ultrasound biomicroscopy.

OBJECTIVE: To determine corneal thickness (CT) and axial anterior chamber depth (ACD) using ultrasound biomicroscopy (UBM) in normal adult horses. To compare corneal thickness measurements between UBM and ultrasonic pachymetry. ANIMALS STUDIED: Sixty eyes of 30 healthy adult horses aged 8-24 years. PROCEDURES: Ultrasonic pachymetry (velocity of 1640 m/s) was utilized to obtain measurements of the central, superior, temporal, inferior, and nasal cornea. Triplicate images of the same corneal locations were acquired using UBM (50 MHz). Images of the axial anterior chamber were used to measure ACD. Intraocular pressure (IOP) was estimated using rebound tonometry, and axial globe length was measured using ultrasonographic biometry. RESULTS: CT (mean ± SD µm) measured by UBM was 854 ± 61 (central), 994 ± 58 (superior), 930 ± 57 (temporal), 979 ± 55 (inferior), and 898 ± 48 (nasal). CT measured by UBM was greater than that measured by ultrasonic pachymetry at all locations and was statistically significant at all locations except inferior (p = 0.0006-0.048). No sex nor age effect was detected for CT at any location. The repeatability of ultrasonic pachymetry was superior to that of UBM. Mean ± SD ACD was 5.74 ± 0.41 mm. A weak positive correlation was identified between central CT and IOP and between central CT and axial globe length. CONCLUSIONS: Normal data for CT and ACD of the adult horse obtained using UBM are provided. CT determined by UBM was greater relative to pachymetry at all corneal locations.

Generation of a Biobank From Two Adult Thoroughbred Stallions for the Functional Annotation of Animal Genomes Initiative.

Following the successful creation of a biobank from two adult Thoroughbred mares, this study aimed to recapitulate sample collection in two adult Thoroughbred stallions as part of the Functional Annotation of the Animal Genome (FAANG) initiative. Both stallions underwent thorough physical, lameness, neurologic, and ophthalmic (including electroretinography) examinations prior to humane euthanasia. Epididymal sperm was recovered from both stallions immediately postmortem and cryopreserved. Aseptically collected full thickness skin biopsies were used to isolate, culture and cryopreserve dermal fibroblasts. Serum, plasma, cerebrospinal fluid, urine, and gastrointestinal content from various locations were collected and cryopreserved. Under guidance of a board-certified veterinary anatomic pathologist, 102 representative tissue samples were collected from both horses. Whole tissue samples were flash-frozen and prioritized tissues had nuclei isolated and cryopreserved. Spatially contemporaneous samples of each tissue were submitted for histologic examination. Antemortem and gross pathologic examination revealed mild abnormalities in both stallions. One stallion (ECA_UCD_AH3) had unilateral thoracic limb lameness and bilateral chorioretinal scars. The second stallion (ECA_UCD_AH4) had subtle symmetrical pelvic limb ataxia, symmetrical prostatomegally, and moderate gastrointestinal nematodiasis. DNA from each was whole-genome sequenced and genotyped using the GGP Equine 70K SNP array. The genomic resources and banked biological samples from these animals augments the existing resource available to the equine genomics community. Importantly we may now improve the resolution of tissue-specific gene regulation as affected by sex, as well as add sex-specific tissues and gametes.

Choroidal neuroendocrine neoplasia in a dog.

OBJECTIVE: To report onset and progression of clinical signs of a neuroendocrine neoplasm (NEN) presumed metastatic to the choroid in a dog. ANIMALS STUDIED: A 7.5-year-old female spayed German shepherd dog mix referred for advanced imaging and evaluation of a subretinal mass in the right eye. PROCEDURES: Procedures performed included general physical and ophthalmic examinations; ocular, orbital, and abdominal ultrasonography; thoracic radiographs; cranial magnetic resonance imaging; serologic testing for infectious agents; analysis of hematologic as well as serum and urine biochemical parameters; echocardiography; electrocardiography; cytologic assessment of lymph nodes; and histopathology and immunohistochemistry of the enucleated globe. RESULTS: Examination and imaging identified a pigmented mass within and expanding the superior choroid. Following enucleation, a choroidal NEN with tumor emboli in scleral blood vessels was diagnosed by histopathologic assessment and confirmed by immunohistochemical labelling. Despite extensive and repeated diagnostic testing over many months, a putative primary site was not identified until 19 months after the initial ocular signs were noted. At that time, a heart-base mass and congestive heart failure were highly suggestive of a chemodectoma. CONCLUSION: This comprehensive report of a NEN presumed metastatic to the choroid in a dog suggests that ocular disease can be a very early and solitary sign of NEN in the dog.

Subcutaneous administration of triamcinolone as part of the management of feline eosinophilic keratoconjunctivitis.

OBJECTIVES: The aim of this retrospective case-control study was to report the efficacy of subcutaneous triamcinolone as part of a regimen for feline eosinophilic keratoconjunctivitis (FEK). METHODS: Records and clinical photographs were reviewed and lesions semiquantitatively graded for cats with cytologically confirmed FEK. Clinical data were compared between a study population of nine cats (11 eyes) treated with, and a reference population of seven cats (eight eyes) treated without, a median of 0.11 mg/kg (range 0.10-0.20 mg/kg) of triamcinolone acetonide subcutaneously. RESULTS: Breed, sex, age and prevalence of corneal ulceration at presentation; corneal disease severity before and at the initiation of immunomodulation; and duration of antiviral treatment before immunomodulation did not differ significantly between populations (P ⩾0.059). Corneal plaques resolved in five cats each from the study and reference populations (P = 0.366). Median (range) time from immunomodulation to corneal plaque resolution did not significantly differ (P = 0.246) between the study (median 14 days; range 8-38 days) and reference (median 28 days, range 14-46 days) populations. No adverse reactions were attributed to triamcinolone administration, and all corneal ulcers in the study population re-epithelialized within 14 days (range 8-38 days) following triamcinolone injection. Time to corneal ulcer re-epithelialization following triamcinolone injection varied minimally in those receiving antivirals prior to (8 or 30 days until re-epithelialization), simultaneously with (38 days) or after (14 or 24 days) triamcinolone. CONCLUSIONS AND RELEVANCE: In otherwise healthy cats with FEK, subcutaneous administration of triamcinolone appears to be well tolerated and as efficacious as conventional topical immunomodulatory therapies. It may be especially useful in ulcerated eyes where topical immunomodulation is contraindicated.

DDB2 Genetic Risk Factor for Ocular Squamous Cell Carcinoma Identified in Three Additional Horse Breeds.

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye. A missense variant within the gene damage-specific DNA binding protein 2 (DDB2 c.1013C>T, p.Thr338Met) was previously identified as a causal recessive genetic risk factor for the development of ocular SCC within Haflingers, Belgian Draft horses, and Rocky Mountain Horses, but not in the Appaloosa or Arabian breeds. This study aimed to evaluate three cases of ocular SCC in additional breeds and determine if DNA testing for the DDB2 variant in warmblood horses and Connemara ponies is warranted. Histopathology confirmed ocular SCC in all three cases and DNA testing confirmed each horse was homozygous for the DDB2 risk factor. The DDB2 risk allele frequency was estimated to be 0.0043 for Holsteiners (N = 115), 0.014 for Belgian Warmbloods (N = 71), and 0.22 for Connemara Ponies (N = 86). Taken together these data support using DNA testing for DDB2 in Connemara Ponies to assist in mate selection and clinical management. Given the low observed allele frequencies in both the Holsteiner and Belgian Warmblood breeds and that the case under investigation was a warmblood cross-bred, evaluating additional SCC affected warmbloods is warranted to fully determine the importance of DDB2 genotyping as a risk factor in warmblood breeds.

Ocular disease in horses with confirmed ocular or central nervous system Borrelia infection: Case series and review of literature.

OBJECTIVE: To describe the clinical presentation, treatment, and clinical outcome of horses with ocular disease and evidence of systemic or ocular Lyme disease. ANIMALS STUDIED: Five horses met the inclusion criteria of ocular disease with evidence of B burgdorferi present in ocular or CNS tissues. PROCEDURE: The goal of this study was to describe the clinical presentation and progression of ocular disease when associated with ocular or CNS B burgdorferi infection in horses. A retrospective review of medical records was performed on horses admitted for ocular disease with evidence of B burgdorferi infection between 1998 and 2015. The diagnosis of B burgdorferi-associated uveitis was based on histopathologic lesions of lymphohistiocytic and suppurative uveitis/endophthalmitis and intralesional argyrophilic spirochetes in either ocular or CNS tissue consistent with Borrelia. Leptospiral uveitis was ruled out by PCR. RESULTS: All five horses in the current study had intraocular inflammation at the time of presentation. Medical management with anti-inflammatories was successful in controlling uveitis in the two horses in which treatment of uveitis was attempted. Systemic treatment with oral tetracyclines was unsuccessful in a single case in which treatment of Borrelia was attempted. Four horses were euthanized due to progression of neurologic disease. The surviving horse had an enucleation performed and did not show systemic signs. CONCLUSIONS: Infection with Borrelia burgdorferi should be considered in endemic areas as a differential for horses with ocular disease, in particular, uveitis. The prognosis for uveitis and neurologic disease associated with Lyme disease was poor in the current study.

Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis.

Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS-441524 (5-10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]-PCR) and serial ocular imaging using Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS-441524 shows clinical efficacy and may result in clearance and long-term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

Additional Evidence for DDB2 T338M as a Genetic Risk Factor for Ocular Squamous Cell Carcinoma in Horses.

Squamous cell carcinoma (SCC) is the most common periocular cancer in horses and the second most common tumor of the horse overall. A missense mutation in damage-specific DNA-binding protein 2 (DDB2, c.1012 C>T, p.Thr338Met) was previously found to be strongly associated with ocular SCC in Haflinger and Belgian horses, explaining 76% of cases across both breeds. To determine if this same variant in DDB2 contributes to risk for ocular SCC in the Arabian, Appaloosa, and Percheron breeds and to determine if the variant contributes to risk for oral or urogenital SCC, histologically confirmed SCC cases were genotyped for the DDB2 variant and associations were investigated. Horses with urogenital SCC that were heterozygous for the DDB2 risk allele were identified in the Appaloosa breed, but a significant association between the DDB2 variant and SCC occurring at any location in this breed was not detected. The risk allele was not identified in Arabians, and no Percherons were homozygous for the risk allele. High-throughput sequencing data from six Haflingers were analyzed to ascertain if any other variant from the previously associated 483 kb locus on ECA12 was more concordant with the SCC phenotype than the DDB2 variant. Sixty polymorphisms were prioritized for evaluation, and no other variant from this locus explained the genetic risk better than the DDB2 allele (P = 3.39 × 10-17, n = 118). These data provide further support of the DDB2 variant contributing to risk for ocular SCC, specifically in the Haflinger and Belgian breeds.

Equine eosinophilic keratoconjunctivitis in California: retrospective study of 47 eyes from 29 cases (1993-2017).

OBJECTIVE: (a) To evaluate the epidemiology of equine eosinophilic keratoconjunctivitis (EK) in the western United States, (b) to ascertain the efficacy of keratectomy and diamond burr debridement vs medical management alone, (c) to determine the efficacy of various medical therapies, and (d) to further characterize the histopathologic findings of the disease in horses. ANIMALS STUDIED: Twenty-nine horses (47 eyes) diagnosed with EK from 1993 to 2017. PROCEDURE: Retrospective medical record review; owner questionnaire. RESULTS: Average age of presentation was 11 ± 4 years. Warmbloods were significantly overrepresented (P = 0.024). Twenty horses were treated with medical therapy alone, five were treated with superficial lamellar keratectomy, and four were treated with diamond burr debridement. Follow-up data were available for 38 eyes of 23 horses. Median time to resolution for horses treated with either superficial keratectomy or diamond burr debridement (62 days) was not statistically significantly different from those that underwent medical therapy alone (46 days; P = 0.33). Eyes treated with topical steroids had a statistically significant longer median time to resolution (61 days) compared to those that did not receive topical steroid (44 days; P = 0.023). Common histopathologic findings in keratectomy samples included the presence of eosinophils, vascularization, and an eosinophilic membrane spanning areas of ulceration. CONCLUSION: In this population, time to EK resolution was similar for horses treated with medical and surgical management. The use of topical steroids was associated with a prolonged time to resolution. Keratectomy samples from horses with EK had similar findings to those reported in other species.

Traumatic phacocele in an American Miniature Horse.

An 18-year-old American Miniature Horse mare was presented with a complaint of a scleral swelling affecting the right eye and a history of suspected trauma 6 weeks prior to evaluation. Clinical findings included severe blepharospasm, a bulbous swelling of the dorsotemporal bulbar conjunctiva, and phthisis bulbi. Ocular ultrasound was recommended but declined. Enucleation was elected for the blind, painful eye and was performed standing. Gross and histopathologic examinations of the globe were consistent with extrusion of the lens to the episcleral space, which is classified as a traumatic phacocele when associated with naturally occurring trauma. The location of lens entrapment suggested globe rupture occurred at the limbus, which is described as one of the weakest points of the equine globe. Subconjunctival dislocation of the lens and development of a traumatic phacocele should be considered as a differential diagnosis for horses presenting with subconjunctival masses, apparent aphakia, and historical trauma.

Medical management of deep ulcerative keratitis in cats: 13 cases.

CASE SERIES SUMMARY: Described are 13 cats diagnosed with deep ulcerative keratitis and successfully managed medically without grafting procedures. Typical treatment involved frequent topical application of serum and antibiotics (usually a fluoroquinolone and a cephalosporin). Seven cats also received systemic antibiotics. Analgesia was achieved using various combinations of topical atropine and systemic buprenorphine, robenacoxib or corticosteroids. Six cats were hospitalized for a median (range) period of 2.5 (1-8) days, typically because of frequent medication administration. Median (range) follow-up time was 41.5 (9-103) days. Median (range) number of recheck examinations was 4 (2-6). Median (range) time to corneal re-epithelialization was 21 (9-103) days. Median (range) topical antibiotic course was 29.5 (16-103) days. Median (range) duration of Elizabethan collar use was 28 (13-73) days. At the time of writing, no further recheck examinations were recommended for 10 cats; median (range) time between initial to final examinations in these cats was 35 (20-103) days. All cats retained the affected globes and were apparently comfortable and visual at the latest recheck examination. RELEVANCE AND NOVEL INFORMATION: These cases reveal that aggressive medical management is highly successful in select cats with deep ulcerative keratitis, and can result in a cosmetically acceptable, apparently comfortable and visual globe. However, therapy is intensive with frequent administration of multiple topical and sometimes systemic medications, and requires multiple veterinary visits over many weeks. Referral to a veterinary ophthalmologist for consideration of surgical stabilization is recommended, as not all cases may be amenable to the medical therapy described here.

Limbal squamous cell carcinoma in a Rocky Mountain Horse: Case report and investigation of genetic contribution.

OBJECTIVE: To document a case of limbal squamous cell carcinoma (SCC) in a Rocky Mountain Horse stallion determined to be homozygous for the genetic risk factor (DDB2 c.1013C>T) strongly associated with the disease in Haflinger and Belgian horses, and to determine the frequency of this allele in a larger population of Rocky Mountain Horses. ANIMALS STUDIED: One privately owned Rocky Mountain Horse and 84 Rocky Mountain Horses screened for allelic frequency. PROCEDURES: A complete ophthalmic examination was performed on a Rocky Mountain Horse stallion for assessment of a mass affecting the right eye. A clinical diagnosis of suspected limbal SCC was made, and routine keratoconjunctivectomy and adjunctive strontium irradiation were performed. Genotyping for the DDB2 c.1013C > T (rs1139682898) risk variant was performed utilizing an allele-specific PCR assay on DNA isolated from whole blood and hair follicles. RESULTS: Histopathology confirmed the limbal mass to be consistent with SCC. The horse was genotyped as homozygous for the DDB2 c.1013C >T risk variant. The frequency of the variant allele among a population of 84 Rocky Mountain Horses was found to be 0.20. CONCLUSION: The Rocky Mountain Horse breed possesses the DDB2 variant allele determined to be a significant risk factor for ocular SCC in the Haflinger and Belgian breeds. Genotyping additional Rocky Mountain Horses diagnosed with ocular SCC as well as confirmed healthy controls for this variant should be undertaken to determine whether a significant association exists between ocular SCC and the variant in the Rocky Mountain Horse breed.

Multiple ocular developmental defects in four closely related alpacas.

OBJECTIVE: To describe the clinical, gross pathologic, and histopathologic findings for a visually impaired 5.8-year-old female alpaca with multiple ocular abnormalities, as well as the clinical findings for three closely related alpacas. ANIMALS STUDIED: Four alpacas. PROCEDURES: Ophthalmic examination was performed on a 16-month-old female alpaca following observation of visual impairment while hospitalized for an unrelated illness. Following acute systemic decline and death 4.5 years later, the alpaca's brain, optic nerves, and eyes were examined grossly and histologically. Ophthalmic examination of three closely related alpacas was subsequently performed. RESULTS: The 16-month-old female alpaca (Alpaca 1) had ophthalmoscopic findings suggestive of a coloboma or hypoplasia of the retinal pigment epithelium (RPE) and choroid, and suspected optic nerve hypoplasia OU. Histopathology performed 4.5 years later revealed moderate to severe choroidal, RPE, and retinal hypoplasia with multifocal retinal detachments OU. However, the optic nerves were normal in size and histologic appearance when compared to an age-matched control. Clinical evaluation of the 2-year-old son of Alpaca 1 revealed iris colobomata OU and choroidal dysplasia/hypoplasia OD in addition to nonpathologic variations in melanin density including heterochromia iridis and a subalbinotic fundus OU. Clinical evaluation of the 13-year-old mother of Alpaca 1 revealed heterochromia iridis, cataracts, and a subalbinotic fundus OU. A 2-year-old half-brother of Alpaca 1 had an RPE and choroidal coloboma OS. CONCLUSION: The developmental ocular abnormalities diagnosed in these closely related alpacas are likely hereditary.

Corneal sensitivity and tear production in 108 horses with ocular disease.

PURPOSE: To compare corneal sensitivity and tear production in horses with keratitis to horses with other ocular disease. METHOD: Retrospective medical record review was used to identify equine patients presented during a 1-year period for an ocular complaint who had Schirmer Tear Test (STT) or Corneal Touch Threshold (CTT) measured. Variables studied included patient age and sex; affected eye; category of presenting ocular complaint (keratitis vs. other ocular complaint); STT; and CTT. Patients with a complaint of ulcerative keratitis, immune-mediated keratitis, and stromal abscess were categorized in the keratitis group. Patients with a complaint of uveitis, as well as lid, lens, or retinal disease, were categorized in the group having other ocular disease. For patients presenting more than once in 2013, only the first visit at which STT or CTT was measured was included. For patients with bilateral disease, STT and CTT of both eyes were averaged. RESULTS: A total of 108 patients were included, 45 with keratitis and 63 with other ocular disease. Average age was 13.65 years, with more males (77) than females (31). Adjusted for age, STT in affected eyes did not differ significantly between the two groups (keratitis = 29.92 mm/min; other ocular disease = 27.96 mm/min), but CTT was significantly lower in patients with keratitis (33.78 mm) than in patients with other ocular disease (40.10 mm). CONCLUSIONS: Corneal sensitivity may be decreased in patients with keratitis. It is not known whether this is a cause or an effect of corneal disease.

Werner syndrome protein suppresses the formation of large deletions during the replication of human telomeric sequences.

Werner syndrome (WS) is a disorder characterized by features of premature aging and increased cancer that is caused by loss of the RecQ helicase WRN. Telomeres consisting of duplex TTAGGG repeats in humans protect chromosome ends and sustain cellular proliferation. WRN prevents the loss of telomeres replicated from the G-rich strand, which can form secondary G-quadruplex (G4) structures. Here, we dissected WRN roles in the replication of telomeric sequences by examining factors inherent to telomeric repeats, such as G4 DNA, independently from other factors at chromosome ends that can also impede replication. For this we used the supF shuttle vector (SV) mutagenesis assay. We demonstrate that SVs with [TTAGGG]6 sequences are stably replicated in human cells, and that the repeats suppress the frequency of large deletions despite G4 folding potential. WRN depletion increased the supF mutant frequency for both the telomeric and non-telomeric SVs, compared with the control cells, but this increase was much greater (27-fold) for telomeric SVs. The higher SV mutant frequencies in WRN-deficient cells were primarily due to an increase in large sequence deletions and rearrangements. However, WRN depletion caused a more dramatic increase in deletions and rearrangements arising within the telomeric SV (70-fold), compared with non-telomeric SV (8-fold). Our results indicate that WRN prevents large deletions and rearrangements during replication, and that this role is particularly important in templates with telomeric sequence. This provides a possible explanation for increased telomere loss in WS cells.