Distinctive histopathologic features of canine optic nerve hypoplasia and aplasia: a retrospective review of 13 cases

Canine optic nerve hypoplasia (ONH) and aplasia (ONA) are significant neuro-ophthalmologic disorders that have been reported in several species. The purpose of this study was to describe the distinctive histopathologic features of ONH and ONA in canine patients identified from a collection of 20 000 ocular submissions at the comparative ocular pathology laboratory of Wisconsin from 1989 to 2006. The following information about ONH and ONA cases was collected: signalment, and clinical and gross findings, including unilateral vs. bilateral involvement. Microscopic evaluation was performed, with attention to optic nerve malformation, retinal ganglion cell (RGC) and nerve fiber layer (NFL) loss, and retinal disorganization. The distribution of retinal vasculature was recorded and a search for unusual findings of ONH and ONA was performed. Information and histologic documentation was available for 13 cases. Eight cases of ONH and five cases of ONA were identified. The average group age was 20.2 months and 16.1 months, respectively. The most common breed was the Shih Tzu (3/13). ONH usually presented bilaterally (7/8); all ONA cases presented as a unilateral disease (5/5). The morphologic findings in the optic nerve (ON) in ONH included variable degrees of ON hypoplasia and gliosis, as well as ectopic vestigial ON remnants within orbital nerves and connective tissues. The NFL was detected in the majority of the ONH cases; however, RGCs were rare or absent. Mild retinal disorganization was seen occasionally. Most cases of ONH were associated with regional peripheral retinal blood vessel extension into the vitreous, leaving the peripheral retina avascular. In ONA cases the retinal blood vessels, NFL and RGCs were totally absent and retinal disorganization was severe. Distinctive microscopic features encountered in ONA included anterior segment dysgenesis in some cases. The retina in these cases was stretched across the posterior lens capsule, never making contact with the posterior pole of the globe. The current study reviews the human and veterinary literature pertaining to ONH and ONA, compares ONH and ONA in dogs, and presents related ophthalmic histopathologic findings that have not been reported previously.     

Bilateral traumatic optic nerve avulsion in a Thoroughbred gelding

This report describes an unusual case of acute blindness following traumatic head injury in a mature horse. The horse fell over backwards and subsequently presented with bilateral blindness and epistaxis. Vision did not return following medical supportive therapy and euthanasia was elected. Post mortem findings revealed a basisphenoid fracture and bilateral optic nerve avulsion rostral to the optic chiasm, an uncommon presentation of traumatic blindness not previously reported in the horse.     

Primary bilateral corneal nerve sheath neoplasm in a dog

A 15‐year‐old, neutered male, Shih Tzu cross developed progressive corneal stromal thickening and vascularization of the right eye, and 5 months later, of the left eye. Both eyes became blind due to extensive corneal opacification and were enucleated. Light microscopic examination revealed a diffuse corneal infiltrate of neoplastic mesenchymal cells, and immunohistochemistry revealed diffuse cytoplasmic vimentin immunoreactivity and variable cytoplasmic and nuclear immunoreactivity for S100 in the neoplastic cells. Transmission electron microscopy revealed desmosomes between contiguous cells, thread‐like cytoplasmic processes coated with basement membrane, extracellular bundles of collagen, and axonal degeneration consistent with features of a nerve sheath neoplasm. This is the first report of primary, bilateral corneal nerve sheath sarcoma in a canine.     

A case of primary choroidal malignant melanoma in a cat

This report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15‐year‐old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement.     

CASE REPORT: Bilateral vision loss in a captive cheetah (Acinonyx jubatus)

The following case report describes a 1‐year‐old female cheetah (Acinonyx jubatus) with bilateral blindness and unresponsive pupils. For comparison, a second healthy 2.5‐year‐old male cheetah without visual deficits was also examined. Clinical examination of both animals included biomicroscopy, indirect ophthalmoscopy, tonometry, and electroretinography. The young female cheetah showed no menace response, no direct or indirect pupillary light reflex, and no dazzle reflex in either eye. Fundus lesions, as detected by indirect ophthalmoscopy, are described for the female animal. In both eyes, the fundus color was green/turquoise/yellow with multiple hyperpigmented linear lesions in the tapetal area around the optic nerve. The optic nerve head was dark gray and about half the normal size suggesting bilateral optic nerve hypoplasia and retinal dysplasia or differentially optic nerve atrophy and chorioretinal scarring. The ERG had low amplitudes in the right eye but appeared normal in the left eye compared with the male cheetah. Blood levels did not suggest current taurine deficiency. This is addressed to some degree in the discussion. Bilateral optic nerve hypoplasia or optic nerve atrophy is a rare anomaly in cats and has not yet been described in a cheetah.     

Male pseudohermaphroditism in a Labrador Retriever,and a review of mammalian sexual differentiation

CASE HISTORY: An 8-month-old Labrador Retriever was referred with a history of ambiguous external genitalia.

CLINICAL FINDINGS AND TREATMENT: Clitoromegaly within apparent vulval folds, and an adjacent subcutaneous mass were noticed on external examination. An intra-abdominal testicle, with epididymis and suspected vas deferens ducts, was found during exploratory celiotomy. Incision over the subcutaneous mass revealed the accompanying testicle. Clitoridectomy was performed and an os clitoris removed. Normal juvenile testes were diagnosed on histology of the gonads. Chromosomal studies revealed a normal 78, XY male chromosomal constitution. Due to the combination of a male karyotype (78, XY), the presence of testicular tissue in the gonads, and the appearance of the external genitalia, a diagnosis of male pseudohermaphroditism (MPH) was made.

CLINICAL RELEVANCE: This case presents the first report of MPH in a Labrador Retriever, and highlights the diagnostic steps recommended when confronted with a dog with ambiguous external genitalia.     

Genetic analysis of optic nerve head coloboma in the Nova Scotia Duck Tolling Retriever identifies discordance with the NHEJ1 intronic deletion (collie eye anomaly mutation)

Collie eye anomaly (CEA) encompasses a spectrum of different ophthalmic phenotypes from clinically inconsequential choroidal hypoplasia to blindness from coloboma of the optic nerve head (ONH). A previous study found a 7.8‐kb deletion in intron 4 of the NHEJ1 gene to be associated with CEA. A genetic test based on this association is recommended for many breeds, including the Nova Scotia Duck Tolling Retriever (NSDTR). Collection of ONH coloboma‐affected NSDTR showed lack of concordance of the NHEJ1 intronic deletion with ONH coloboma. Using genomewide single nucleotide polymorphism (SNP) genotyping in 7 ONH coloboma‐affected NSDTR cases and 47 unaffected NSDTR controls with no ophthalmic signs, one SNP, located on chromosome 7, demonstrated genomewide significance. However, high genomic inflation may have confounded the results. Therefore, the genomewide association study was repeated using EMMAX to control for population structure in the cohort of 7 cases and 47 controls. However, no regions of the genome were significantly associated with ONH coloboma. These results failed to document significant association with the CEA locus. Due to the complex genetic etiology of ONH coloboma, the NHEJ1 intronic deletion test results should be carefully considered when making breeding decisions. If the goal is to select for visually competent dogs, our data suggest that eye examinations of puppies would be more effective as a guide in selection of breeding pairs than relying solely on currently available genetic tests.     

Porencephaly with an optic organ abnormality in a beagle dog

A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral hemisphere and an adhesion area between the cerebral cortex and the skull, which was partially thickened. Additionally, the right optic nerve showed a slight decrease in diameter. Histopathological examination revealed increased glial fibers and collagen fibers, hemosiderin deposition, and an increased number of microglia in the adhesion area, along with a marked reduction of the cerebral parenchyma. In the right eyeball, the retina and optic nerve showed focal atrophy in the nerve fiber layer and inner granular layer to full retinal atrophy and hypoplasia of the myelinated nerve fibers, respectively. Electron microscopic examination revealed hypoplasia of the myelin sheath of nerve fibers in the right optic nerve. This is an extremely rare case of porencephaly and congenital optic nerve hypoplasia, along with independent retinal thinning.     

Rapid diagnosis of retina and optic nerve abnormalities in canine patients with and without cataracts using chromatic pupil light reflex testing

Objective To develop fast and reliable testing routines for diagnosing retina and optic nerve diseases in canine cataract patients based on chromatic properties of the pupillary light reflex response. Procedures Seventy‐seven canine patients with a history of cataract and decreased vision (43 patients with cataracts and no evidence of retina or optic nerve disease, 21 patients with cataracts and retinal degeneration [RD], 13 patients with cataracts and retinal detachment [RDT]), 11 canine patients with optic neuritis (ON) and 23 healthy dogs were examined using chromatic pupillary light reflex (cPLR) analysis with red and blue light and electroretinography. Results Electroretinography analysis showed statistically significant deficits in a‐ and b‐wave amplitudes in dogs with cataracts and RD, or cataracts and RDT, when compared to dogs with cataracts without evidence of retinal abnormalities. Evaluation of b‐wave amplitudes showed that presence of 78.5‐μV (or lower) amplitudes had high sensitivity of 100% (95% CI: 87.2–100%) and high specificity of 96.7% (95% CI: 88.4–100%) in RD and RDT. Evaluation of cPLR responses using red light showed that presence of the pupil end constriction diameter of 5.5 mm (or higher) had moderately high sensitivity of 76.5% (95% CI: 50.1–93.2%) and high specificity of 100% (95% CI: 91.2–100%) in detecting RD and RDT. Optic neuritis patients had absent cPLR responses, regardless of the visual status. Conclusions and Clinical Relevance Chromatic evaluation of the pupillary light reflex is a rapid and accurate test for diagnosing retina and optic nerve diseases in canine patients.     

Low-hemorrhage-risk surgical approach to expose the optic nerve in rabbits without bony removal and rectus resection

Objective  A low-hemorrhage-risk surgical approach to expose the optic nerve (ON) in rabbits through the orbital process of the frontal bone without removal of the bony orbit and resection of the rectus muscle was explored and assessed in this study. This approach will be used to investigate a new visual prosthesis that requires intraorbital ON stimulation with penetrating electrodes.
Animals  Chinese Albino rabbits ( n  = 10).
Methods  Rabbits were classified into a surgery and a control group (five in each). In the surgery group, the ON exposure was explored by the newly proposed surgical approach. Surgical time, blood loss, visually evoked potentials (VEP) at four different scheduled time points, and H&E-stained histology of the ON at one month after surgery were recorded and analyzed to assess the ease and safety of the approach.
Results  The average surgical time for the ON exposure was 16.40 ± 1.14 min with average blood loss of 0.52 ± 0.08 mL. Within the one-month follow-up, the ON exhibited a naturally reversible conduction change in terms of VEP amplitude. Histological examination of the ON was unremarkable. A postoperative mild ptosis of the surgical eye resolved within one month after surgery.
Conclusion  The ease and safety of this new surgical approach allowed it to be easily used by non-expert operators and widely applied in rabbit experiments for various research purposes requiring exposure of the ON.     

Reactive histiocytosis of the orbit and posterior segment in a dog

We present a case of reactive histiocytic disease involving the orbit, optic nerve, retina, and choroid in a Border Collie dog initially presenting for vision loss. Long-term partial return of vision has been achieved with systemic immunosuppression. Anterior segment and ocular surface manifestations of reactive histiocytic disease in dogs are relatively common. Posterior segment and orbital involvement, however, are minimally documented in the existing literature. To the authors' knowledge, this is the first report of disease confined to the orbit and posterior segment as well as the first report of vision loss as a presenting complaint for reactive histiocytic disease. Clinical, magnetic resonance imaging, cytologic, and histopathologic findings are reviewed.     

Chronic lameness caused by vascular compression of the iliac artery and vein by a malignant melanoma in the pelvis of a grey Spanish gelding

An 11-year-old grey Spanish gelding was presented with chronic lameness of the right hindlimb, with abduction of the limb during the swing phase. Based on a comprehensive lameness examination, the problem was localised to the pelvic region. Rectal and ultrasonographic examinations revealed a mass in the pelvic region in close association with the iliac artery and vein, and ultrasonographic indications of vascular compression. Considering the clinical presentation of a grey middle-aged horse with multifocal melanoma-like nodules at the level of the perineum, tail base, preputium and penis, a malignant melanoma with secondary vascular or neurological compression was suspected. Post-mortem and histological examination confirmed the diagnosis of malignant melanoma with vascular compression of the iliac artery and vein and infiltrative growth in the iliac vein.     

Unilateral malignant melanoma of the adrenal gland with metastatic spread to the thorax in a horse

A 7-year-old grey horse that had a history of inappetence, weight loss, weakness, dyspnoea, coughing and intermittent colic was examined post-mortem. A melanoma, confirmed histologically, was found in the right adrenal gland and had eroded into the posterior vena cava. Thoracic metastases were also identified. The skin, including the legs, trunk and perineum was normal with no evidence of melanomas. This was considered to be a primary, malignant melanoma, a novel finding in the adrenal gland of the horse.     

Expression of glial cells molecules in the optic nerve of adult dromedary camel (Camelus dromedarius): A histological and immunohistochemical analysis

The optic nerve (ON) is an important organ in the visual system of animals, which transfers electrical impulses towards the brain from the retina. High enrichment of glial cells in ON is known to support neuron and regulate retinal homoeostasis. However, research on immunohistochemical of glial cells proteins in the camel is scanty in available literature. Hence, the current work is an attempt to investigate the histomorphology of camel ON with regard to the expression patterns of glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and Iba1 for the three glial subtypes, namely astrocytes, oligodendrocytes and microglia, respectively. Optic nerves from fourteen dromedary camels were dissected and preserved in 10% formalin. Then, the paraffin‐embedding sections were subjected for histochemical and immunohistochemical analysis. Our results demonstrated that ON axons aggregate into fascicles that surrounded by light and densely stained glial cells. Then, we examined the myelin sheath using Heidenhain's and Mallory's phosphotungstic acid staining. Immunoassay results revealed that GFAP is enriched in the ON and distributed evenly, whereas MBP and Iba1 were present at scanty levels. Further analysis of mRNA level of GFAP, MBP and Iba1 in the ON confirmed an elevation of GFAP expression compared to MBP and Iba1. We further found partial co‐localization of different types of glial cells that reflect their coordinated function in the ON. Although our data provide the first evidence for differential expression pattern of glial proteins, further molecular studies still required to reveal the specific function of these molecules in the camel ON.     

Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus

Malignant peripheral nerve sheath tumours (MPNST) of a plexus nerve or nerve root cause significant morbidity and present a treatment challenge. The surgical approach can be complex and information is lacking on outcomes. The objective of this study was to describe surgical complication rates and oncologic outcomes for canine MPNST of the brachial or lumbosacral plexus. Dogs treated for a naïve MPNST with amputation/hemipelvectomy with or without a laminectomy were retrospectively analysed. Oncologic outcomes were disease free interval (DFI), overall survival (OS), and 1- and 2-year survival rates. Thirty dogs were included. The surgery performed was amputation alone in 17 cases (57%), and amputation/hemipelvectomy with laminectomy in 13 cases (43%). Four dogs (13%) had an intraoperative complication, while 11 dogs (37%) had postoperative complications. Histologic margins were reported as R0 in 12 dogs (40%), R1 in 12 dogs (40%), and R2 in five dogs (17%). No association was found between histologic grade and margin nor extent of surgical approach and margin. Thirteen dogs (46%) had recurrence. The median DFI was 511 days (95% CI: 140–882 days). The median disease specific OST was 570 days (95% CI: 467–673 days) with 1- and 2-year survival rates of 82% and 22% respectively. No variables were significantly associated with recurrence, DFI, or disease specific OST. These data show surgical treatment of plexus MPNST was associated with a high intra- and postoperative complication rate but relatively good disease outcomes. This information can guide clinicians in surgical risk management and owner communication regarding realistic outcomes and complications.     

Circulating melanin-containing cells and neutrophils with phagocytized melanin granules in a horse with disseminated melanoma

An 18-year-old, grey, Thoroughbred Cross gelding was referred to the Cummings School of Veterinary Medicine at Tufts University following a 3-week history of low-grade fever of unknown origin, distal limb swelling, and weight loss. Clinical examination identified a few black, round, smooth nodules along the ventral aspect of the proximal tail. Transabdominal ultrasound showed a markedly enlarged heterogenous spleen, hyperechoic liver nodules, and evidence of peritonitis with fibrin deposition. A mature neutrophilia was noted on complete blood count with variable numbers of phagocytized granules within neutrophils. The granules did not stain with Perl's Prussian blue, and were intensely positive when stained with Fontana-Mason, consistent with melanin. On necropsy, the spleen occupied approximately one-third of the abdominal cavity and was diffusely firm with abundant black pigment on cut section. The medullary space of the 18th thoracic vertebra was also diffusely blackened. The splenic, mediastinal, and tracheobronchial lymph nodes were five times the normal size and diffusely pigmented. The final anatomic diagnosis was disseminated malignant melanoma with extensive splenic involvement and hemolymphatic and vascular neoplastic dissemination. To the authors' knowledge, this is the first full report to identify circulating neutrophils containing phagocytized melanin granules, which confirmed an antemortem diagnosis of disseminated melanoma.     

Malignant teratoid medulloepithelioma with brain and kidney involvement in a dog

ANIMAL STUDIED: A tumor of the left eye with involvement of the brain and kidney was diagnosed in a 4-year-old Neapolitan mastiff. PROCEDURE: The dog presented with acute glaucoma of the left eye. Peripheral corneal vascularization and severe corneal edema obscured examination of deeper structures. Because of concurrent progressive neurologic signs the dog was euthanized and a postmortem examination was performed. The eyes, brain and samples from the lung, heart, liver and kidneys were fixed in 4% neutral buffered formalin and embedded in paraffin wax. Sections were examined by light microscopy including histochemical and immunohistochemical staining. RESULTS: The ocular tumor originated from the ciliary body and was composed of small islets and cords of poorly differentiated, oval to polyhedral cells surrounded by abundant ground substance. Areas with chondroid differentiation were observed. Rosettes were not found. Metastases with the same morphology were present in the brain and in one kidney. CONCLUSION: An intraocular malignant teratoid medulloepithelioma with metastases to the brain and kidney is presented.