Claudia Hartley

Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed.

The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10–14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (Praw 1.9×10−14; Pgenome = 1.0×10−5) and chromosome 13 (Praw 1.2×10−17; Pgenome = 1.0×10−5), respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in parallel.

Aetiology of Corneal Ulcers Assume FHV-1 Unless Proven Otherwise

Overview Feline ulcerative keratitis is a common presenting complaint and is frequently a sequela of feline herpesvirus 1 (FHV-1) infection; so much so, in fact, that it is fair to assume an FHV-1 aetiology until proven otherwise. Other potential causes of ulceration are trauma or underlying eyelid abnormalities (entropion, ectropion, agenesis, dermoids, neoplasia), lash abnormalities (ectopic cilia, trichiasis), tear film abnormalities or neurological deficiencies (trigeminal nerve paralysis, facial nerve paralysis). Clinical challenges The management of corneal ulceration in cats is frequently challenging, and treatment needs to be tailored carefully to the individual cat, its temperament, and the disease process present. Evidence base The scientific literature on feline ulcerative keratitis is extensive, particularly that related to FHV-1 infection. The aim of this article is to review the aetiology and diagnosis of corneal ulceration in cats with particular reference to the evidence base available. Patient group All age groups and breeds can suffer with ulcerative keratitis. Breed predispositions are present for some forms of corneal ulceration, and these are discussed.

Cutaneous haemangiosarcoma of the lower eyelid in an elderly white cat

A case of cutaneous haemangiosarcoma of the left lower eyelid in a 15-year-old white domestic shorthair cat is reported. A protuberant red mass occupying one-third of the lower eyelid margin length was present. Intermittent haemorrhage occurred from the mass surface. Surgical biopsy had revealed a locally invasive tumour composed of numerous irregular blood-filled spaces lined by a single layer of plump endothelial cells and separated by thin fibrous septa. Mitotic activity was rare and the appearance was consistent with a low-grade haemangiosarcoma. The mass continued to enlarge and referral was sought. Due to financial constraints and the owners wish for a single procedure, enucleation with an axial pattern flap based on the superficial temporal artery was undertaken. Histopathology of the excised tissue confirmed the presence of a well-differentiated haemangiosarcoma. Tumour-free excisional margins were confirmed, the surgical area healed uneventfully, and there has been no recurrence during the subsequent 16 months.

Aetiology of Corneal Ulcers

Overview Feline ulcerative keratitis is a common presenting complaint and is frequently a sequela of feline herpesvirus 1 (FHV-1) infection; so much so, in fact, that it is fair to assume an FHV-1 aetiology until proven otherwise. Other potential causes of ulceration are trauma or underlying eyelid abnormalities (entropion, ectropion, agenesis, dermoids, neoplasia), lash abnormalities (ectopic cilia, trichiasis), tear film abnormalities or neurological deficiencies (trigeminal nerve paralysis, facial nerve paralysis). Clinical challenges The management of corneal ulceration in cats is frequently challenging, and treatment needs to be tailored carefully to the individual cat, its temperament, and the disease process present. Evidence base The scientific literature on feline ulcerative keratitis is extensive, particularly that related to FHV-1 infection. The aim of this article is to review the aetiology and diagnosis of corneal ulceration in cats with particular reference to the evidence base available. Patient group All age groups and breeds can suffer with ulcerative keratitis. Breed predispositions are present for some forms of corneal ulceration, and these are discussed.

Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs – part I: clinical signs, histopathology, and inheritance

The clinical presentation and progression (over 9 months to 13 years) of congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in the Cavalier King Charles spaniel dog are described for six new cases and six previously described cases. Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing. Long-term follow-up of cases (13/25) is described. Immunomodulatory/lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis. Histopathological analysis of samples (skin/footpads/lacrimal glands/salivary glands) for three new cases was consistent with an ichthyosiform dermatosis, with no pathology of the salivary or lacrimal glands identified histologically. Pedigree analysis suggests the syndrome is inherited by an autosomal recessive mode.

Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in Cavalier King Charles spaniel dogs. Part II: candidate gene study.

PURPOSE To identify causative mutation(s) for congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in Cavalier King Charles spaniel (CKCS) dogs using a candidate gene approach. METHODS DNA samples from 21 cases/parents were collected. Canine candidate genes (CCGs) for similar inherited human diseases were chosen. Twenty-eight candidate genes were identified by searching the Pubmed OMIM database (http://www.ncbi.nlm.nih.gov/omim). Canine orthologues of human candidate genes were identified using the Ensembl orthologue prediction facility (http://www.ensembl.org/index.html). Two microsatellites flanking each candidate gene were selected, and primers to amplify each microsatellite were designed using the Whitehead Institute primer design website (http://frodo.wi.mit.edu/primer3/). The microsatellites associated with all 28 CCGs were genotyped on a panel of 21 DNA samples from CKCS dogs (13 affected and eight carriers). Genotyping data was analyzed to identify markers homozygous in affected dogs and heterozygous in carriers (homozygosity mapping). RESULTS None of the microsatellites associated with 25 of the CCGs displayed an association with CKCSID in the 21 DNA samples tested. Three CCGs associated microsatellites were monomorphic across all samples tested. CONCLUSIONS Twenty-five CCGs were excluded as cause of CKCSID. Three CCGs could not be excluded from involvement in the inheritance of CKCSID.

Treatment of Corneal Ulcers: What are the Medical Options?

Practical relevance Corneal ulcers in cats (ulcerative keratitis) are a common presenting complaint, and are a frequent sequela to feline herpesvirus (FHV-1) infection. In fact, it is fair to assume an FHV-1 aetiology until proven otherwise. In practice, therefore, many cases of corneal ulceration can be treated medically, but treatment can frequently be challenging, with the need to tailor therapy carefully to the type of ulcer, the individual cat and its temperament. Patient group All age groups and breeds can suffer with ulcerative keratitis although some breeds are over-represented for some types of corneal ulceration. Evidence base The scientific literature on feline ulcerative keratitis is extensive, particularly that related to FHV-1 infection. This article reviews the medical treatment options for corneal ulceration in cats with reference to the current evidence base.

Ocular alkaline injury in four dogs – presentation, treatment, and follow-up – a case series

PURPOSE To describe presentation, treatment, and follow-up after unilateral alkaline injuries to the eye in four dogs. MATERIAL AND METHOD The case notes of four patients that suffered from alkaline injuries to the eye were included in this series. RESULTS Acute clinical signs included blepharospasm and edema of the eyelids, chemosis and conjunctival hyperemia, conjunctival ischemia, destruction of the corneal epithelium, a whitish haze of the corneal stroma, mild corneal edema, and uveitis. Two patients showed depigmentation of the eyelids. Presumed endothelial cell damage resulted in severe corneal edema in two dogs. Long-term complications included phthisis bulbi, scarring of the eyelids and damage to the meibomian glands, symblepharon formation, conjunctivalization of the cornea, corneal vascularization, pigmentation, and fibrosis. Persisting corneal edema was seen in the dogs with presumed endothelial cell damage. One dog developed a mild bullous keratopathy with superficial corneal ulcerations 4½ years after the injury and had a reduced anterior chamber depth on ultrasound. CONCLUSION The damage to the ocular structures described here mainly affects the ocular surface. One patient presumably suffered an injury to the ciliary body epithelium resulting in a phthisical globe. Chronic corneal edema, conjunctivalization, and scarring can result in permanent visual impairment. Healing of the ocular surface can take weeks and is associated with a dramatic vascular response. However, a severely vascularized cornea has the potential to clear and allow a good visual outcome long term. Ongoing discomfort was only seen in one case with persistent corneal edema and a secondary bullous keratopathy.

CLINICAL AND MAGNETIC RESONANCE IMAGING FEATURES OF IDIOPATHIC OCULOMOTOR NEUROPATHY IN 14 DOGS

Ophthalmoplegia/ophthalmoparesis (internal, external, or both) has been reported in dogs secondary to neoplasia affecting the oculomotor nerve and is usually given a poor prognosis. The purpose of this retrospective study was to describe the clinical findings, magnetic resonance imaging (MRI) findings, management, outcome, and follow-up in a group of canine cases with idiopathic oculomotor neuropathy. Inclusion criteria included cases with ophthalmoplegia/ophthalmoparesis (internal, external or both) as sole neuroophthalmologic signs, complete ophthalmic and neurologic examination, head MRI, and a minimum follow-up period of 1 year. Dogs with progressive neurological signs not related to oculomotor neuropathy were excluded. Fourteen cases met the inclusion criteria. All cases were unilaterally affected. Magnetic resonance imaging showed equivocal enlargement of the oculomotor nerve in three cases, mild enlargement in five, and marked enlargement in six. Contrast enhancement was present in 12 cases, being marked in six. When present, the contrast enhancement was focal in eight cases and diffuse in four. The median follow-up time was 25 months. External ophthalmoparesis improved in seven cases, five cases under no treatment and two under systemic corticosteroid therapy. The clinical signs in the other seven cases remained unchanged. Idiopathic oculomotor neuropathy should be included as a differential diagnosis in dogs presenting with unilateral ophthalmoplegia/ophthalmoparesis (internal, external, or both) with the absence of other neurologic and ophthalmic signs, and with the MRI findings restricted to the oculomotor nerve. Idiopathic oculomotor neuropathy has a good prognosis as the clinical signs do not deteriorate and they can improve without treatment.

Uveal cysts in domestic cats: a retrospective evaluation of thirty-six cases

OBJECTIVE The aim of this retrospective study was to investigate uveal cysts in domestic cats by identifying prevalence, predispositions, location, presumed etiologies, and sequelae. ANIMALS STUDIED The clinical databases of two referral hospitals (The Animal Health Trust in the UK and Animal Eye Care in Australia) were searched to identify cats that had been diagnosed with uveal cysts, either as an incidental finding or as the reason for referral. Thirty-six cases were found. PROCEDURES The signalment of the patients was recorded, along with any relevant previous clinical history, treatment, follow-up, and sequela. The data were compared with the unaffected feline populations examined by ophthalmologists in the two hospitals over the same 10-year time period. RESULTS Thirty-six cats were affected, from a total examined population of 5017 (prevalence 0.72%). Twenty-one of the 36 cats were Burmese. The two centers examined 516 Burmese cats in the same time period, giving an incidence in Burmese cats of 4.1%. The mean age of affected cats at presentation was 10.25 years (SD = 4.12 years), and female cats accounted for 23 of 36 of the cases. Only 2 of 36 cats had concurrent intraocular disease. CONCLUSIONS Uveal cysts in domestic cats are rare ophthalmic findings, and in most cases, they do not cause any clinical problems The Burmese breed is overrepresented in the data, with a relatively high prevalence of uveal cysts.