Surgical management of unilateral restrictive strabismus in an 8-month-old dog.

CASE HISTORY: An 8-month-old male, entire, mixed-breed dog was presented with a 1-month history of left exophthalmos and green mucopurulent ocular discharge. Subsequently, exophthalmos resolved but esotropia (medial strabismus) developed in the left eye, prompting referral to an ophthalmologist. CLINICAL FINDINGS: At the initial referral consultation, enophthalmos and esotropia of the left eye were identified. The patient showed mild improvement after a 3-week tapering course of oral prednisolone and doxycycline. MRI was performed and showed left medial rectus muscle atrophy with increased contrast enhancement which was consistent with chronic extraocular muscle myositis (EOM). A forced duction test was performed to confirm the diagnosis of fibrosing esotropia, which is likely a sequela of chronic EOM. DIAGNOSIS: Fibrosing esotropia presumably caused by untreated EOM. TREATMENT AND OUTCOME: One month later, esotropia progressed to a marked ventro-medial strabismus resulting in visual deprivation. Surgical release of the ventral oblique, medial and ventral recti muscles was performed, resulting in immediate resolution of the enophthalmos. Despite a tapering post-operative course of oral prednisolone, mild esotropia was present 4 weeks later. In an effort to stabilise the globe position, the low dose of prednisolone was increased to a higher anti-inflammatory dose before slowly tapering over 2 months. The vision in the left eye was improved after surgery and has been maintained since without further treatment. CLINICAL RELEVANCE: This is the first documented case of fibrosing esotropia in a young dog with prior signs of acute exophthalmos. Fibrosing esotropia has been documented in certain breeds or as a sequela to chronic EOM. In this patient, it was presumably caused by EOM, which was strongly supported by the case history, progression and MRI findings. Most historical reports of EOM described it as a bilateral condition that resolves with systemic corticosteroids at an anti-inflammatory dose. EOM has been shown to also present unilaterally and it can progress to strabismus if not promptly recognised and treated with systemic steroids. Surgical management can restore vision when severe strabismus results in visual deprivation.

Medial strabismus (esotropia) at rest associated with contralateral paramedian thalamic ischemic infarction in 2 dogs.

Pseudoabducens paralysis resulting in resting medial strabismus (esotropia) is a rare consequence of a contralateral paramedian thalamic ischemic infarction in people. To date, esotropia has been reported in dogs in association with ipsilateral abducens neuropathy or extraocular myopathy, but not secondary to thalamic lesions. A 7-year-old male neutered Border Collie and a 12-year-old female neutered cross-breed dog were presented with peracute nonprogressive vestibular ataxia. Neurological examination identified right esotropia, nonambulatory tetraparesis, right head tilt, vestibular ataxia and nystagmus. Lesions in both dogs were localized to the vestibular system with thalamic involvement. Magnetic resonance imaging of the brain identified a left paramedian thalamic lacunar ischemic infarct in both dogs. Interruption of descending inhibitory pathways that decussate in the subthalamic region and innervate the contralateral motor nucleus of the oculomotor nerve leads to hypertonicity of the medial rectus. These cases indicate that esotropia is a rare but highly localizing sign in dogs with contralateral thalamic infarcts.

GWAS Hits for Bilateral Convergent Strabismus with Exophthalmos in Holstein Cattle Using Imputed Sequence Level Genotypes.

Bilateral convergent strabismus with exophthalmos (BCSE) is a malformation of the eyes and is recognized as a mild but progressive disorder that affects cattle in the first two years of life. This most likely inherited disorder is rarely described in cattle resembling autosomal dominantly inherited forms of human progressive external ophthalmoplegia (PEO). In German Braunvieh cattle, two linked genome regions were found that could be responsible for the development and/or progression of BCSE. The goal of this study was to phenotypically characterize BCSE in Holstein cattle from Germany and Switzerland as well as to identify associated genome regions by GWAS. The clinicopathological phenotype of 52 BCSE-affected Holstein cattle was in accordance with the phenotype described in German Braunvieh cattle, but in addition, signs of degeneration and cellular infiltration in the eye muscles were found. By using imputed sequence level genotype data, three genome-wide significant GWAS hits were revealed on different chromosomes that were not detected by initial GWAS based on high density SNP array data highlighting the usefulness of this approach for mapping studies. The associated genome regions include the ABCC4 gene as well as markers adjacent to the NCOR2 and DNAJC3 genes all illustrating possible functional candidate genes. Our results challenge a monogenic mode of inheritance and indicate a more complex inheritance of BCSE in Holstein cattle. Furthermore, in comparison to previous results from German Braunvieh cattle, it illustrates an obvious genetic heterogeneity causing BSCE in cattle. Subsequent whole genome sequencing (WGS)-based analyses might elucidate pathogenic variants in the future.

PLXNC1 and RDH13 associated with bilateral convergent strabismus with exophthalmus in German Brown cattle.

PURPOSE: We performed an association study for bilateral convergent strabismus with exophthalmus (BCSE) in German Brown cattle using single nucleotide polymorphisms (SNPs) located within six positional candidate genes and additional SNPs from bovine SNP databases surrounding these candidate genes. Mutation analyses included synaptotagmin 3 and 5 (SYT3, SYT5), carnitine palmitoyl-transferase 1C (CPT1C) on bovine chromosome 18 (BTA18), and plexin C1 (PLXNC1), intracellular suppressor of cytokine signaling-2 (SOCS2), and kinesin family member 21A (KIF21A) on BTA5. METHODS: For all six candidate genes, we performed cDNA analyses using eye tissues of three BCSE-affected and three unaffected controls and searched the sequences for polymorphisms. Furthermore, we screened a total of 213 SNPs on BTA5 and 136 SNPs on BTA18 from the bovine SNP databases in 29 BCSE-affected German Brown cattle and 23 breed and sex matched controls for association with BCSE. All SNPs detected within the open reading frame (ORF) of the candidate genes and all SNPs from bovine databases putatively associated with BCSE in the detection sample were genotyped in a random sample of 179 BCSE-affected German Brown cows and 161 breed and sex matched controls and tested for association with BCSE. RESULTS: In total, we detected five novel SNPs within the coding sequence of the candidate genes PLXNC1 and KIF21A. The association analyses for single SNPs and haplotypes in 340 German Brown cattle revealed significant associations for five SNPs with BCSE. Four of these five SNPs were located within PLXNC1 and RDH13 and one SNP in the neighborhood of PLXNC1. Each one SNP within PLXNC1 (DN825458:c.168G>T) and RDH13 (AM930553:c.703C>A) were significantly associated with BCSE after correcting for multiple testing whereas all other SNPs failed this significance threshold. The marker-trait associations for haplotypes confirmed the significant associations with BCSE for both genes, PLXNC1 and RDH13. CONCLUSIONS: The association analyses for single SNPs and haplotypes corroborated the results of the linkage study that the centromeric region of BTA5 and the telomeric end of BTA8 harbor genes responsible for BCSE. Intragenic SNPs of the genes PLXNC1 and RDH13 were experiment-wide significantly associated with BCSE and seem to play an important role in the pathogenesis of BCSE.

Linkage of bilateral convergent strabismus with exophthalmus (BCSE) to BTA5 and BTA18 in German Brown cattle.

Bilateral convergent strabismus with exophthalmus (BCSE) is a widespread inherited eye defect in several cattle populations. Its progressive condition often leads to blindness in affected cattle and decreases their usability. Furthermore, the German animal welfare laws prevent breeding with animals whose progeny are expected to be affected by genetic defects. Identifying genes involved in the heredity of BCSE should lead to insights into the molecular pathogenesis of this eye disease and permit the establishment of a genetic test for this disease. A whole-genome scan for 10 families containing a total of 159 genotyped individuals identified two BCSE loci. One BCSE locus mapped to the centromeric region on bovine chromosome (BTA) 5 and the other BCSE locus mapped to the telomeric region of BTA18. Thus, it is possible that two genes are involved in the development of BCSE. Alternatively, one of these loci could be the cause for the development of BCSE and the other locus could affect the progression and severity of the defect.

Horizontal rectus muscle anatomy in naturally and artificially strabismic monkeys.

PURPOSE: Structural abnormalities of extraocular muscles (EOMs) or their pulleys are associated with some forms of human strabismus. This experiment was conducted to investigate whether such abnormalities are associated with artificial or naturally occurring strabismus in monkeys. METHODS: Binocular alignment and grating visual acuities were determined in 10 monkeys representing various species using search coil recording and direct observations. Four animals were orthotropic, two had naturally occurring "A"-pattern esotropia, two had concomitant and one had "V"-pattern esotropia artificially induced by alternating or unilateral occlusion in infancy, and one had "A"-pattern exotropia artificially induced by prism wear. After euthanasia, 16 orbits were examined by high-resolution magnetic resonance imaging (MRI) in the quasi-coronal plane. Paths and sizes of horizontal rectus EOMs were analyzed quantitatively in a standardized coordinate system. Whole orbits were then serially sectioned en bloc in the quasi-coronal plane, stained for connective tissue, and compared with MRI. Nerve and EOM features were analyzed quantitatively. RESULTS: Quantitative analysis of MRI revealed no significant differences in horizontal rectus EOM sizes or paths among orthotropic or naturally or artificially strabismic monkeys. Histologic examination demonstrated no differences in EOM size, structure, or innervation among the three groups, and no differences in connective tissues in the pulley system. The accessory lateral rectus (ALR) EOM was present in all specimens, but was small, inconsistently located, and sparsely innervated. Characteristics of the ALR did not correlate with strabismus. CONCLUSIONS: Major structural abnormalities of horizontal rectus EOMs and associated pulleys are unrelated to natural or artificial horizontal strabismus in the monkeys studied. The ALR is unlikely to contribute to horizontal strabismus in primates. However, these findings do not exclude a possible role of pulley abnormalities in disorders such as cyclovertical strabismus.

Bilateral convergent strabismus with exophthalmus (BCSE) in cattle: an overview of clinical signs and genetic traits.

Bilateral convergent strabismus with exophthalmus (BCSE) is a heritable eye defect prevalent in many cattle breeds and known worldwide. BCSE shows a progressive course often terminating in complete blindness. The onset of the defect can sometimes be slowly progressing (late in life) and, as the first signs of the defect are frequently not noticed prior to first breeding, prevention cannot be achieved only by exclusion of affected animals from the breeding program. This paper provides an overview of the clinical signs, histopathology and genetics of BCSE, its distribution in different cattle breeds and analyses the association between milk production traits and US Brown Swiss. There were different modes of inheritance proposed for BCSE, but although an autosomal dominant major gene is considered most likely in German Brown cattle, an association with milk production traits could not be found. Comparative molecular genetic approaches could help to characterize the responsible genes for this ocular disease in cattle.

Disjunctive optokinetic nystagmus in a naturally esotropic macaque monkey: interaction between nasotemporal asymmetries of versional eye movement and convergence.

OBJECTIVE: To assess the interaction between versional and vergence eye movements in normal and strabismic monkeys. METHODS: Horizontal optokinetic nystagmus (OKN) and vergence were measured using the magnetic scleral search coil technique in a normal adult monkey and a strabismic monkey who had naturally occurring early-onset esotropia. Mean eye velocity and vergence angles were calculated during the slow phases of OKN. RESULTS: The strabismic monkey had a nasotemporal asymmetry of OKN favoring nasally directed motion in each eye. During monocular optokinetic stimulation, mean eye velocities were substantially greater for the adducting as compared to the abducting eye. The velocity of the abducting eye was between 55 and 80% of the velocity of the adducting eye (p < 0.01). As a consequence of the disjunctive movements, the eyes converged an average of 4 +/- 2.8 degrees during OKN. Saccadic analysis documented normal lateral rectus function in each eye. Neither an OKN asymmetry nor disjunctive OKN was observed in the normal monkey. CONCLUSION: Disjunctive OKN in the esotropic monkey suggests that the cerebral maldevelopment responsible for nasally biased OKN also contributes to nasal biases in vergence pathways.

Association analysis between bilateral convergent strabismus with exophthalmus and milk production traits in dairy cattle.

Bilateral convergent strabismus with exophthalmus (BCSE) is characterized in cattle by a symmetrical antero-medial rotation and protrusion of the eyeballs. This eye defect is caused by an inherited, centrally insufficient function of the eye muscles recti laterales and retractores. In German Brown cattle a monogenic, autosomal dominant inheritance proved to be most probable in complex segregation analysis. In our study running between October 1993 and May 1995 a total of 200 affected German Brown cows was studied. The investigation of the association between milk production traits and BCSE was based on 10,960 German Brown cows. The analysis revealed no significant differences between affected and non-affected cows, nor between cow families with and without affected members. There was no indication of an association between milk production traits and occurrence of BCSE within cow families. Linkage or pleiotropy of the BCSE locus with quantitative trait loci for milk production traits may be rather unlikely.

A case of trisomy 22 in a live hereford calf.

A case of the rare genetic trisomy 22 in a live calf is described. The calf had low blood thyroxine level and low growth rate. It had several defects including brachygnathia superior, strabismus convergence, aortal cusp insufficiency and hypertrophy of clitoris. Chromosome analysis was performed on cultured blood lymphocytes and fibroblast cells. In all counted metaphases 61 chromosomes were present. The extra chromosome was identified as a chromosome 22 by R-banding. The defects of the calf have similarities with cases of partial trisomy 3p25-pter in human. This section of the human chromosome 3 corresponds to sections of cattle chromosome 22.

Convergent strabismus in a white Bengal tiger.

A white Bengal tiger was noted to have a convergent strabismus with poor vision since a cub. The tiger and a littermate with normal colouring and apparently normal eyes were anaesthetised for comparative ocular examination. A fundus typical of colour-dilute cats and dogs was noted in the white tiger. Except for strabismus, no abnormalities were observed. Electroretinography showed similar retinal function in both tigers. Possible causes of strabismus considered were an adaptation to genetically determined abnormal visual pathways related to lack of pigment, abnormalities of the abducent nerves and mechanical restricting conditions of the medial rectus muscles.

[Heritability of strabismus convergens with exophthalmos in cattle]. / Zur Erblichkeit von Strabismus convergens mit Exophthalmus beim Rind.

Six pedigrees including 107 animals of the breed German Brown Swiss were available to test for a single gene conditioning for convergent strabismus with exophthalmus. The regressive logit models of the segregation analysis showed that a major gene model with additively acting genes explained the segregation of affected animals in the pedigrees in the best way. Additionally, polygenic and environmental effects might be of importance in the occurrence of convergent strabismus with exophthalmus.

Frequency of naturally occurring strabismus in monkeys.

A colony of Macaca nemestrina monkeys was screened for naturally occurring strabismus. Thirteen cases of naturally occurring strabismus were documented, 12 esotropes and one exotrope. The characteristics of the strabismus in these monkeys were similar to those of human clinical cases. Four of the affected monkeys showed interocular differences in grating acuity. We estimated the incidence of strabismus in the monkey colony to be 4%.