Blindness, optic atrophy and sinusitis in the horse.

OBJECTIVE: The case histories described each presented with a visual deficit, varying from permanent total blindness with ophthalmoscopic evidence of optic atrophy to variable and transient visual disturbances, including occasional blindness, but with absence of ophthalmoscopic or any other ocular abnormality. ANIMALS STUDIED: Three horses of widely different age and type, but all with an original history of upper respiratory tract infection. PROCEDURE: All three cases were examined by a specialist veterinary ophthalmologist. In addition, magnetic resonance imaging (MRI) and, where possible, postmortem and histopathological examinations were performed. RESULTS: The common factor to all three cases proved to be infection of the spheno-palatine sinuses with subsequent distension and compression of adjacent optic nerve(s) and optic chiasm. CONCLUSIONS: Specialist veterinary ophthalmological examination proved of extremely limited value. The importance of MRI (and CT) scans for accurate diagnosis, and therefore possible successful treatment, is emphasized. Our cases were compared with similar cases in man, where visual disturbances due to spheno-palatine sinus involvement are recognized, but rare, in similar situation.

Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the cavalier King Charles spaniel.

OBJECTIVES: To record a previously unreported congenital and hereditary condition affecting the eyes and skin in the cavalier King Charles spaniel. METHODS: Nineteen cases (13 litters) were investigated, with particular reference to eye and skin clinical signs. In addition, five generation pedigrees were obtained and studied from all cases with the exception of one. RESULTS: The eye signs were due to keratoconjunctivitis sicca, a common ocular disease in the dog, but rarely of congenital origin. The skin signs were of an ichthyosiform dermatosis; ichthyosis being a rare skin disease in the dog. In human beings, ichthyosis is a similar disease, mainly inherited and with a neonatal onset, and sometimes accompanied by other developmental defects. In the cavalier King Charles spaniel, the coat abnormality was noted at birth by the breeders as a 'curly coat', with deterioration of the skin signs as the animal became adult. CLINICAL SIGNIFICANCE: These two conditions occurring together in this breed is well recognised by some breeders but rarely by the veterinary profession. Successful treatment is not possible, although some improvement, particularly of the keratoconjunctivitis sicca, can be obtained. The probable hereditary nature of the condition is an important factor for control.

Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis.

Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of canine chromosome CFA15 that is syntenic with a region of human chromosome 14 (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene. Mutations in RPGRIP1 have been shown to cause Leber congenital amaurosis, a group of retinal dystrophies that represent the most common genetic causes of congenital visual impairment in infants and children. Using the newly available canine genome sequence we sequenced RPGRIP1 in affected and carrier MLHDs and identified a 44-nucleotide insertion in exon 2 that alters the reading frame and introduces a premature stop codon. All affected and carrier dogs within an extended inbred pedigree were homozygous and heterozygous, respectively, for the mutation. We conclude the mutation is responsible for cord1 and demonstrate that this canine disease is a valuable model for exploring disease mechanisms and potential therapies for human Leber congenital amaurosis.

Keratomycosis in six horses in the United Kingdom.

Six horses with keratomycosis were examined and three different clinical expressions of the disease were recognised. The diagnostic work-up and response to treatment is described.

Multiple ocular colobomas in the snow leopard (Uncia uncia).

Two singleton female snow leopard cubs are reported with bilateral central upper lid colobomas. In addition, one cub had a coloboma of the fundus in one eye extending from the lower optic disc region. Surgical treatment by wedge resection was successful in both cases. Details of ocular colobomas in other snow leopards reported in the literature are described and it is suggested that the exact etiology of the condition in this species may be discovered by further study of similar colobomas in the domestic cat.

Relationship of the degree of goniodysgenesis and other ocular measurements to glaucoma in Great Danes.

OBJECTIVES: To assess the association between goniodysgenesis, ocular measurements, and glaucoma in Great Danes. ANIMALS: 180 Great Danes. PROCEDURE: Eye examination and measurements were obtained from 180 Great Danes; for 30 of these dogs, depth of the anterior chamber, vitreal body length, and total depth of the globe were also measured. These data were merged with electronic pedigree information on 43,371 kennel club registered Great Danes. Relationships among goniodysgenesis, ocular measurements, and glaucoma and the heritability of goniodysgenesis were estimated. RESULTS: The degree of goniodysgenesis was significantly and positively associated with the likelihood of glaucoma. There was a significant association between the degree of goniodysgenesis in offspring and parents. The estimated heritability of the degree of goniodysgenesis was 0.52. The depth of the anterior chamber of the eye was also a good predictor of goniodysgenesis (ie, the dog was almost certain to have glaucoma if the depth was < 3.7 mm). If both parents had goniodysgenesis < 70%, then with 95% confidence, the occurrence of glaucoma in the ensuing offspring would be < 4/1000. This strategy translates to ensuring that the depth of the anterior chamber of the eye is > 3.7 mm for both parents. CONCLUSIONS AND CLINICAL RELEVANCE: The strong and significant correlation among goniodysgenesis, other eye measurements, and glaucoma and the significant heritability of goniodysgenesis suggests that glaucoma may be heritable in Great Danes. If so, glaucoma can be controlled by breeding only from sires and dams with a minimum degree of goniodysgenesis.

Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration.

PURPOSE: To determine whether ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) treatment leads to long-term photoreceptor survival in hereditary retinal degeneration. METHODS: An autosomal dominant feline model of rod-cone dystrophy was used throughout the study with two normal animals. In the first experiment, intravitreal injections of a human CNTF analogue (Axokine; Regeneron Pharmaceuticals, Tarrytown, NY) were administered to one eye of each animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. Clinical and histopathologic examinations were performed at 5.5, 9.5, and 13.5 weeks. In the second experiment, animals (n = 17) were randomly assigned to receive intravitreal injections of either Axokine (at half the initial dose), human BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same therapy was repeated every 4 weeks in each group. Clinical and histopathologic examinations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor survival was assessed by cell counting. Apoptotic cells were identified by morphology and a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique. In the third experiment, two normal animals were treated with Axokine as in the first experiment. Glial fibrillary acidic protein ((GFAP) immunohistochemistry was performed to assess glial cell reaction. RESULTS: In the first two experiments, Axokine significantly prolonged photoreceptor survival (P < 0.01) and reduced the presence of apoptotic cells (P < 0.05) and TUNEL-positive cells (P < 0.05). In the second experiment, results in the the BDNF- and sham-injected eyes were not significantly different from those in the untreated eyes. Minimal posterior subcapsular cataract and mild retinal folds were found in all Axokine-treated eyes in both dystrophic and normal animals. These complications were milder in the second experiment when injections were started later and at a reduced dose. GFAP immunolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS: Axokine, but not BDNF, delays photoreceptor loss in this hereditary retinal degeneration. Repeated injections maintain the protective effect.

An immunohistochemical study of an autosomal dominant feline rod/cone dysplasia (Rdy cats).

An autosomal dominant, early onset feline model of rod/cone dysplasia has been described. The clinical features, light and electron microscopy, and the electrophysiology were documented. We have now examined in more detail the histopathological and immunohistochemical changes during the early phase of the disease using antibodies against opsin, synaptophysin, glial fibrillary acidic protein (GFAP) and an epithelial marker (MNF118). We have also demonstrated programmed cell death by a modified TUNEL (Terminal deoxynucleotidyl transferase, Uridine triphosphate, Nick End Labelling) technique. In the Rdy cats, there was significant photoreceptor degeneration between 5 and 17 weeks of age. The TUNEL-labeled cell and pyknotic cell counts in the outer nuclear layer peaked at around 9 weeks of age. Accumulation of opsin in the entire outer nuclear layer of the retina was noted with opsin-immunolabeled rod neurite sprouting. There was a reduction in synaptophysin immunoreactivity in the outer plexiform layer. The Muller cells were activated and expressed GFAP. No significant change of immunolabeling of MNF118 was found. These findings closely parallel those seen in human RP.

Lacrimal pseudotumour in a young bull terrier.

An inflammatory mass arising from the lower lacrimal canaliculus of unknown cause is reported in a dog. A 10-month-old Staffordshire bull terrier was presented with a history of epiphora and a red mass protruding from the left lower lacrimal punctum. The tissue was removed and histopathological examination of the lesion revealed a mass of highly vascularised granulation tissue with areas of epithelial ulceration and multiple stromal haemorrhages. Fibrosis and collagen deposition were evident as was a cellular infiltrate composed primarily of neutrophils and plasma cells. Regrowth necessitated further attempts at complete excision before a permanent cure was achieved.

Canine conjunctival papilloma: a review of five cases.

Five cases of unilateral bulbar conjunctival papillomata are reported in five different breeds of dog. The dogs ranged from six to nine years of age, four were female and one was male. In all but one case the mass was an incidental finding. The morphology and histopathology are described. The authors have been unable to find any details or descriptions of this type of papilloma in the veterinary literature.

Treatment of keratoconjunctivitis sicca in dogs with cyclosporine ophthalmic ointment: a European clinical field trial.

The results are reported of a six-week clinical trial of the efficacy of 0.2 per cent cyclosporine ophthalmic ointment for the treatment of chronic idiopathic keratoconjunctivitis sicca in dogs in the United Kingdom, Germany and France. The 87 dogs were referral cases with a history of chronic unresponsive keratoconjunctivitis sicca of which the aetiology was unknown, and they had to meet stringent criteria before being included in the trial. The clinical response to the therapy was monitored after seven, 21 and 42 days and the results for the right and left eyes were analysed separately. There was a statistically significant increase in lacrimal secretion throughout the study, with most of the increase occurring during the first week of treatment. The percentage of eyes with improved lacrimal secretion was higher in the dogs with initial Schirmer tear test values > or = 2 mm/min than in those with initial values of 0 or 1 mm/min. The observed steady improvement in conjunctival health was not always correlated with an improvement in lacrimal secretion. The incidence of blepharospasm, other signs of discomfort and corneal oedema decreased significantly during the study. No improvement in corneal vascularisation or pigmentation was observed during the six-week trial. Overall, 76 per cent of the left eyes and 87 per cent of the right eyes were considered to have improved at the end of the treatment period. No serious adverse reactions were observed and only mild irritation was noticed by the owners immediately after the application of the ointment. This irritation resulted in the recording of an adverse reaction at the scheduled observations in only three cases.

Investigation of the role of opsin gene polymorphism in generalized progressive retinal atrophies in dogs.

The generalized progressive retinal atrophies (gPRAs) form a group of retinal degenerations of pedigree dogs and cats, which have a variety of genetic origins (mostly unknown). We have examined the opsin gene for polymorphisms in several breeds of pedigree dog suffering from distinct forms of gPRA, by methods including single-strand conformation polymorphism analysis, microsatellite analysis and direct sequencing. The breeds examined included the Tibetan terrier, the miniature schnauzer, the Irish setter, the miniature poodle, the Labrador retriever and the English cocker spaniel, as well as individuals from breeds in which PRA has not been described and of mixed breed. Individuals from each of the named breeds suffering from PRA were compared with clinically normal dogs. Two polymorphisms were found. One, segregating within the Tibetan terrier population, but not seen in other breeds, was a synonymous transition at nucleotide position 780 in exon 3. Inheritance of this polymorphism suggests that opsin is unlikely to contain mutations causative of gPRA in this breed. The other polymorphism occurred between all miniature schnauzers examined and dogs of other breeds. It consisted of a single base insertion in intron 2. No polymorphisms in the opsin sequence were detected in any other breed. DNA sequencing allowed rigorous exclusion of mutations in opsin as a cause of gPRA in miniature poodles, English cocker spaniels or Labrador retrievers.

Incidence of the gene mutation causal for rod-cone dysplasia type 1 in Irish setters in the UK.

A survey to establish the UK prevalence of the gene mutation causing the rod-cone dysplasia type one (rcd1) form of generalised progressive retinal atrophy (gPRA) in Irish setters was carried out. The dogs were selected by members of two Irish setter breed societies to provide examples from most of the main breeding lines in the UK. A total of 210 Irish setters were tested and one bitch was found to be a carrier of the rcd1 mutation. These results show that although a confirmed case of rcd1 has not been reported in Irish setters in the UK for over a decade the gene is still present in the gene pool.

Progressive retinal atrophy in miniature longhaired dachshund dogs.

A form of generalized progressive retinal atrophy unlike other previously recorded canine retinal dystrophies has been investigated in Miniature Longhaired Dachshund dogs. Segregation patterns in litters from matings involving affected individuals were consistent with simple autosomal recessive inheritance. The earliest ophthalmoscopic signs, appearing at approximately 6 months of age and coinciding in some cases with the onset of nyctalopia, included changes in the granular appearance of the tapetal fundus followed by generalized tapetal hyper-reflectivity and retinal vascular attenuation; later there was irregular loss of pigment in the non-tapetal fundus and optic atrophy. However, there was marked variation in the age of onset and progression of the disease, even within a single litter. The electroretinogram was normal in waveform and latency in four affected littermates at 10 weeks of age but by 9 months was markedly reduced in amplitude in two pups and virtually extinguished in the others. Significant histological changes at 10.5 weeks of age included thinning of the outer nuclear layer, irregularity and attenuation of the rod photoreceptor outer segments and early disorganization of the rod outer segment disc lamellae. By 25 weeks the photoreceptors were grossly degenerate with short rounded inner segments and only residual amounts of outer segment material remaining. This condition in the Miniature Longhaired Dachshund is later in onset than rod-cone dysplasia in Irish Setters but significantly earlier than progressive retinal atrophy in Tibetan Terriers and progressive rod-cone degeneration in, for example, Miniature Poodles. The condition could therefore serve as a potentially useful model for retinitis pigmentosa in man.

Bilateral optic disc colobomas and microphthalmos in a thoroughbred horse.

A thoroughbred colt had bilateral but unequal microphthalmos together with microcornea, abnormalities of the iris and lens and posterior segment colobomas. The case is compared with other reports of microphthalmos and coloboma in horses.