Richard Dubielzig

Vet Pathol. 2023 Mar;60(2):185-189. doi: 10.1177/03009858221143400. Epub 2022 Dec 21.

ABSTRACT

Sebaceous carcinomas of the human ocular adnexa commonly exhibit pagetoid spread, mutations in tumor-suppressor genes, and protooncogene copy number gain. Sebaceous carcinomas are rarely reported in other species, and while the Meibomian gland (MG) represents the most common ocular adnexal structure of the canine eyelid to develop neoplasia, most are clinically and histologically benign. The objective of this study was to compare molecular features of canine MG carcinomas and adenomas. Two retrospectively identified MG carcinomas were subject to immunohistochemistry and qPCR. When compared with normal glands, MYC was upregulated in benign and malignant MG neoplasms. Aberrant p53 expression was restricted to the nuclei of intraepithelial neoplastic cells in MG carcinomas. Adipophilin expression was diminished in MG neoplasms compared with the normal MG. Our findings, if confirmed in a larger cohort of cases, could suggest that MG oncogenesis in a dog may exhibit similar molecular features as their human counterparts.

PMID:36541627 | DOI:10.1177/03009858221143400

Vet Ophthalmol. 2021 May;24(3):218-228. doi: 10.1111/vop.12872. Epub 2021 Feb 17.

ABSTRACT

PURPOSE: Review octopus ocular anatomy and describe the histopathologic findings in three octopuses diagnosed with phakitis and retinitis.

ANIMALS: Two common octopuses (Octopus vulgaris) and one giant Pacific octopus (Enteroctopus dofleini) with a history of ophthalmic disease.

METHODS: A literature search was performed for the ocular anatomy section. Both eyes from all three octopuses, and two control eyes, were submitted for histopathologic evaluation. Hematoxylin and eosin stain was used for standard histopathologic evaluation; GMS stain was used to screen for fungi, gram stain for bacteria; and Fite's acid fast stain for acid fast bacteria.

RESULTS: Anatomically, the anterior chamber of the octopus has direct contact with ambient water due to an opening in the dorsal aspect of a pseudocornea. The octopus lens is divided into anterior and posterior segments. The anterior half is exposed to the environment through the opening into the anterior chamber. Neither part of the lens has a lens capsule. The retina is everted, unlike the inverted vertebrate retina, and consists of just two layers. Histopathology revealed inflammatory phakitis and retinitis of varying severity in all six eyes of the study animals. No intraocular infectious organisms were recognized but one common octopus eye had clusters of coccidian parasites, identified as Aggregata sp., in extraocular tissues and blood vessels.

CONCLUSION: We describe inflammatory phakitis and retinitis in two species of octopuses. The underlying cause for the severe intraocular response may be direct intraocular infection, water quality, an ocular manifestation of a systemic disease, or natural senescence.

PMID:33596337 | DOI:10.1111/vop.12872

Vet Ophthalmol. 2020 May;23(3):472-479. doi: 10.1111/vop.12742. Epub 2020 Feb 3.

ABSTRACT

PURPOSE: To investigate the relationship between phylogeny and amount of shade in a species' habitat regarding the presence or absence of an iridal granula iridica (GI) in a large sample of Artiodactyl and Perissodactyl clades and using online resources.

METHODS: The Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) archives were searched for glass slide material from Artiodactyl (even-toed) and Perissodactyl (odd-toed) ungulates. The slides were examined, and the presence or absence of the GI was noted. The phylogenetic tree of the ungulate species was inferred using TimeTree (http://www.timetree.org), and the habitat data are derived from Animal Diversity Web (https://animaldiversity.org/). We assessed the probability of the presence of GI occurring given the amount of shade in a species' environment using phylogenetic logistic regression.

RESULTS: Forty-eight artiodactyl species were able to be evaluated and tabulated. Nine perissodactyl species were able to be evaluated. The phylogenetic logistic regression showed that the probability of GI presence was lower in artiodactyl species that inhabited shaded environments (β_shaded = -1.774). Arctiodacyl species inhabiting a nonshaded environment were slightly more probable to have the GI present (β_nonshaded = 0.023), with species inhabitating ambiguously shaded environments having a high probability of GI presence (β_ambiguous = 2.214).

CONCLUSIONS: Our results suggest that the GI may be a common morphological feature to shade the pupil in nonshaded environments, and, in its absence, increase the amount of light reaching the retina to improve vision in shaded environments for hooved mammals. Further research on the functional optics of the GI and studies that include additional ungulate species would further elucidate phylogenetic and ecological factors influencing the occurrence of GI in hooved mammals.

PMID:32012413 | DOI:10.1111/vop.12742

Toxicol Pathol. 2019 Jun;47(4):528-541. doi: 10.1177/0192623319844470. Epub 2019 May 7.

ABSTRACT

In a juvenile toxicology program, an unexpected finding of vacuolation of inner nuclear, ganglion cell, and nerve fiber layers of the retina was observed microscopically in routine Davidson's fixed and hematoxylin and eosin-stained tissue sections of eyes in beagle dogs at approximately 5 weeks of age. There was no necrosis or degeneration of the affected cells and no associated inflammation. Fluorescein angiography revealed no vascular leakage. Optical coherence tomography (OCT) indicated swollen cells in the same layers of the retina as observed at light microscopic examination. Transmission electron microscopy revealed that the retinal vacuolation likely was consistent with intracellular swelling of amacrine, horizontal, and/or bipolar cells of the inner nuclear layer as affected cells had an expanded cytoplasm but contained normal nucleus and organelles. As assessed by animal behavior and full-field electroretinography, the retinal vacuolation appeared to have no impact on visual function. Retinal vacuolation was seen in approximately 40% of dogs at 5 weeks of age using OCT and/or light microscopic examination. Because the change was transient and age related, did not result in degenerative retinal changes, and was not present in dogs older than 5 weeks of age, it was considered a background developmental observation in beagle dogs.

PMID:31064296 | DOI:10.1177/0192623319844470

J Vet Dent. 2014 Dec;31(4):245-248. doi: 10.1177/089875641403100404.

ABSTRACT

A variety of procedures involving the caudal oral cavity risk iatrogenic introduction of an instrument into the globe. The clinical and histologic features of 10 cases of ocular disease after dental procedures are reviewed. Eight dogs and 2 cats presented with clinical panophthalmitis 3-days to 6-weeks following dental procedures for which each animal underwent palliative and diagnostic enucleation. Histologic findings were consistent with contaminated, traumatic perforation and panophthalmitis. Traumatic panophthalmitis and its sequelae are painful conditions with poor prognoses. Suspected or confirmed cases of ocular injury at the time of dental procedures warrant immediate evaluation and aggressive intervention. This series emphasizes how profound damage can occur to the eye when instruments are not carefully and safely handled in the oral cavity.

PMID:30870962 | DOI:10.1177/089875641403100404

Vet Pathol. 2019 Mar;56(2):259-268. doi: 10.1177/0300985818798087. Epub 2018 Sep 16.

ABSTRACT

Feline neovascular vitreoretinopathy (FNV) is a newly recognized rare condition affecting kittens and young domestic cats. This study investigated the clinical and pathologic findings in 22 cats with FNV. In affected cats, ophthalmoscopy of the fundus (when visible) revealed avascular peripheral retinae and epiretinal vascular membranes. Frequent nonspecific clinical findings were buphthalmos ( n = 21), medically uncontrollable glaucoma ( n = 22), and lenticular abnormalities ( n = 13). Anterior segment dysgenesis (ASD) was detected clinically in affected cats ( n = 6). The fellow eye was affected in 11 of 18 cats to a variable degree or appeared clinically normal in 7 of 18 cats. The globes were examined histologically and using immunohistochemistry for vimentin, glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, laminin, factor VIII-related antigen (FVIII-RA), and smooth muscle actin (SMA). Histologically, diagnostic features included laminin-positive epiretinal vascular membranes affecting the central retina, with an avascular peripheral retina and gliosis. Enucleated globes exhibited multiple additional abnormalities, including corneal disease ( n = 15), anterior segment dysgenesis ( n = 21), lymphoplasmacytic anterior uveitis ( n = 19), peripheral anterior synechiae ( n = 20), retinal degeneration ( n = 22), and retinal detachment ( n = 19). Gliotic retinae labeled strongly for GFAP and vimentin with reduced expression of synaptophysin and neurofilament, consistent with degeneration or lack of differentiation. While an avascular peripheral retina and epiretinal fibrovascular membranes are also salient features of retinopathy of prematurity, there is no evidence to support hyperoxic damage in cats with FNV. The cause remains unknown.

PMID:30222091 | DOI:10.1177/0300985818798087

Vet Ophthalmol. 2019 Jan;22(1):76-87. doi: 10.1111/vop.12571. Epub 2018 Apr 24.

ABSTRACT

Corneal vascular neoplasms (hemangioma and hemangiosarcoma) are rare in all species. Reported cases are single case reports in a single species. Archived cases of corneal hemangioma and hemangiosarcoma from dogs, cats, and horses were obtained from the Comparative Ocular Pathology Lab of Wisconsin (COPLOW, Madison, WI), tabulated, and examined. This retrospective study describes the breeds, ages, tumor types, and characteristics of vascular neoplasms that appeared to be primarily corneal in location, in feline, canine, and equine patients, with gross and histologic images. There is a discussion of predisposing factors and speculated association with chronic ocular surface disease.

PMID:29689619 | DOI:10.1111/vop.12571

J Vet Diagn Invest. 2017 Jul;29(4):536-540. doi: 10.1177/1040638717711996. Epub 2017 May 26.

ABSTRACT

Odontoameloblastoma (OA) is a mixed odontogenic tumor that is an ameloblastoma with concurrent histologic evidence of odontoma differentiation. As a mixed tumor, OA is a tripartite lesion comprised of neoplastic odontogenic epithelium, induced dental ectomesenchyme (dental pulp), and mineralized dental matrix. Although rare, OA represents a diagnostic conundrum, as it is histologically closely related to 2 other mixed odontogenic tumors: odontoma (complex and compound) and ameloblastic fibro-odontoma. Herein we describe an OA arising from the mandible of a 4-mo-old Fischer 344 rat that had been exposed in utero to the mutagen ENU (N-ethyl-N-nitrosourea), and a naturally occurring lesion in a 2-y-old Appaloosa horse. In order to satisfy the diagnostic criteria for this lesion, mineralized dental matrix in relationship to neoplastic odontogenic epithelium must be identifiable within the OA lesion. This group of odontogenic tumors is differentiated by the degree to which the dental matrix is organized and the relative proportions of pulp ectomesenchyme, odontogenic matrix, and odontogenic epithelium.

PMID:28545325 | DOI:10.1177/1040638717711996

J Comp Neurol. 2019 Jan 1;527(1):13-37. doi: 10.1002/cne.24167. Epub 2017 Mar 10.

ABSTRACT

The lemurs of Madagascar (Primates: Lemuriformes) are a monophyletic group that has lived in isolation from other primates for about 50 million years. Lemurs have diversified into species with diverse daily activity patterns and correspondingly different visual adaptations. We assessed the arrangements of retinal cone and rod photoreceptors in six nocturnal, three cathemeral and two diurnal lemur species and quantified different parameters in six of the species. The analysis revealed lower cone densities and higher rod densities in the nocturnal than in the cathemeral and diurnal species. The photoreceptor densities in the diurnal Propithecus verreauxi indicate a less "diurnal" retina than found in other diurnal primates. Immunolabeling for cone opsins showed the presence of both middle-to-longwave sensitive (M/L) and shortwave sensitive (S) cones in most species, indicating at least dichromatic color vision. S cones were absent in Allocebus trichotis and Cheirogaleus medius, indicating cone monochromacy. In the Microcebus species, the S cones had an inverse topography with very low densities in the central retina and highest densities in the peripheral retina. The S cones in the other species and the M/L cones in all species had a conventional topography with peak densities in the central area. With the exception of the cathemeral Eulemur species, the eyes of all studied taxa, including the diurnal Propithecus, possessed a tapetum lucidum, a feature only found among nocturnal and crepuscular mammals.

PMID:28054342 | DOI:10.1002/cne.24167

Clin Case Rep. 2016 May 28;4(7):647-52. doi: 10.1002/ccr3.536. eCollection 2016 Jul.

ABSTRACT

This manuscript describes a previously unreported clinical case of canine uveal melanoma in a miniature Schnauzer dog with an unusual location of metastasis (prostate) and delayed occurrence (3 years after primary tumor diagnosis and enucleation). Immunohistochemical labeling of both tumors with Melan A, Ki-67, and c-kit added some valuable information.

PMID:27386120 | PMC:PMC4929797 | DOI:10.1002/ccr3.536

Vet Pathol. 2017 Jan;54(1):141-146. doi: 10.1177/0300985816653793. Epub 2016 Jul 11.

ABSTRACT

Mast cell infiltration occurs in malignant, inflammatory (eg, allergic, infectious), and idiopathic disease processes in humans and animals. Here, we describe the clinical and histological features of a unique proliferative conjunctivitis occurring in 15 cats. Ocular specimens were examined histologically, and polymerase chain reaction (PCR) for feline herpesvirus 1 (FHV-1) was performed on ocular tissues obtained from 10 cats. Cats had a median age of 8 years (range: 7 months-17.5 years). The known median duration of ocular lesions prior to biopsy was 4 months (range: 1 week-3 years). Ocular disease was unilateral in 12 cats, and 9 cats had coexisting corneal disease. Clinically and histologically, proliferative or nodular conjunctival lesions were noted in 13 cats. The nictitating membrane was affected in 10 cats. Histologically, lesions were characterized by mixed inflammatory infiltrates with an abundance of Giemsa-positive and toluidine blue-positive intraepithelial and subepithelial mast cells, marked edema, and papillary epithelial hyperplasia. Feline herpesvirus 1 was demonstrated by PCR in 1 of 10 cats tested. Follow-up information was available for 14 cats: 8 had no recurrence during a median follow-up period of 17.5 months (range: 4.5-30 months), 2 underwent orbital exenteration, 3 had recurrence that was medically managed, and 1 cat had diffuse conjunctivitis at the time of biopsy and recurrence was deemed irrelevant. Various ocular medications were administered before and after surgical biopsy. This condition was designated as feline epitheliotropic mastocytic conjunctivitis, with intraepithelial mast cells being an essential feature and papillary epithelial proliferation being characteristic but not diagnostic alone. The condition appears to be uncommon and benign. Although the cause is unknown, an allergic component is possible.

PMID:27371540 | DOI:10.1177/0300985816653793

Vet Ophthalmol. 2017 May;20(3):273-279. doi: 10.1111/vop.12388. Epub 2016 May 18.

ABSTRACT

PURPOSE: To describe the clinical and histopathologic features of glaucoma associated with Descemet's membrane (DM) detachment in five horses without prior history of intraocular surgery.

ANIMALS STUDIED: Three Appaloosa horses and two Thoroughbreds were included in this study. The affected horses ranged in age from 16 to 27 years and presented with severe diffuse corneal edema.

PROCEDURE: Five eyes were enucleated due to intraocular hypertension and/or chronic corneal ulceration. The enucleated globes were evaluated by the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Each globe was routinely processed for histopathology and analyzed by light microscopy. A histologic diagnosis of glaucoma was reached by demonstrating a loss of optic nerve axonal tissue by measuring neurofilament-immunopositive axons with automated image analysis software.

RESULTS: All five horses presented with unilateral severe diffuse corneal edema that had developed between 2 and 16 weeks prior to enucleation. Intraocular pressures for the affected eyes were between 9 and 87 mmHg prior to enucleation. Descemet's membrane detachment was identified histopathologically in all five globes (5/5, 100%). All five eyes had an avascular spindle cell proliferation filling the space between the displaced peripheral DM and the corneal stroma. Neurofilament immunostaining revealed axonal loss consistent with glaucoma.

CONCLUSION: Equine glaucoma may be associated with Descemet's membrane detachment. This detachment and glaucoma is a possible differential diagnosis for severe equine corneal edema. In this case series, an eye with a DM detachment had a poor prognosis for retention.

PMID:27191927 | DOI:10.1111/vop.12388

Vet Ophthalmol. 2017 Jan;20(1):73-78. doi: 10.1111/vop.12356. Epub 2016 Feb 12.

ABSTRACT

This retrospective study identified 12 cases (6 canine and 6 feline) of ocular lymphoma with extensive retinal involvement and relative sparing of other ocular tissues. Our objectives were to describe the morphologic and immunohistochemical features of retinal lymphoma, assess the degree of correlation to the human counterpart, assign subtypes based on the veterinary-adapted WHO classification system, and promote accurate reporting of retinal involvement in cases of intraocular lymphoma. Our findings suggest that a distinct retinal tropism is quite rare, representing approximately 1% of all cases of canine and feline ocular lymphoma. No breed or sex predispositions were identified. The mean age of the affected animal was 7 years (range 4-10) and 11 years (range 6-19) for dogs and cats, respectively. Nine cases (5 canine and 4 feline) were classified as diffuse large B-cell lymphoma (DLBCL) subtype. The remaining cases were classified as peripheral T-cell lymphoma (PTCL).

PMID:26868476 | DOI:10.1111/vop.12356

J Am Vet Med Assoc. 2015 Dec 15;247(12):1419-26. doi: 10.2460/javma.247.12.1419.

ABSTRACT

CASE DESCRIPTION: 6 dogs (10 eyes) with keratitis following long-term topical treatment with a carbonic anhydrase inhibitor (CAI) were evaluated. In 4 dogs (6 eyes), CAI treatment was discontinued. Three dogs (4 eyes) underwent enucleation because of end-stage corneal disease. One dog was treated differently in each eye and thus was represented in both aforementioned groups.

CLINICAL FINDINGS: Following initiation of treatment with a CAI (ie, brinzolamide or dorzolamide), the median time to development of severe ocular signs was 266 days (range, 133 to 679 days). Clinically severe ocular signs included ulcerative and nonulcerative perilimbal keratitis or severe diffuse keratitis with marked vascularization. The keratitis was refractory to treatment with anti-inflammatory medications. Histologic and immunohistochemical examination of enucleated globes was performed in 3 affected dogs and in 1 dog with keratitis that recovered. Corneal lesions included 2 distinct inflammatory infiltrates with plasma cells predominating in the anterior stroma and both T cells and neutrophils in the epithelium. Stromal plasma cells and overlying epithelium exhibited strong positive immunoreactivity for IgG.

TREATMENT AND OUTCOME: Topical CAI treatment was discontinued in 4 dogs after a median of 209 days (range, 44 to 433 days), and in these dogs, clinical improvement was evident within 2 to 4 days of CAI treatment cessation. Signs of keratitis resolved in 12 to 25 days in these 4 dogs, and median follow-up time after CAI discontinuation was 25.5 months (range, 6 to 42 months), during which time signs of corneal disease did not recur.

CLINICAL RELEVANCE: On the basis of this small series, presumed topical CAI-associated keratitis in dogs appeared to be an uncommon immune-mediated disease that was not responsive to corticosteroid treatment. Affected patients improved rapidly, but only after discontinuation of CAI treatment. In dogs with glaucoma, clinicians should consider the development of punctate keratopathy and severe diffuse keratitis as potential adverse effects related to topical administration of CAIs, even after previously uneventful long-term use.

PMID:26642138 | DOI:10.2460/javma.247.12.1419

Vet Ophthalmol. 2016 Nov;19(6):510-517. doi: 10.1111/vop.12320. Epub 2015 Oct 6.

ABSTRACT

An adult silver arowana (Osteoglossum bicirrhosum) presented with a 2-month history of acute onset ventral strabismus of the right eye associated with a cystic structure overlying the dorsal aspect of the globe. Aspiration of the cyst, removal of redundant conjunctival tissue, and apposition of the surgical edges of the conjunctiva did not correct the strabismus. Magnetic resonance imaging of the head and histopathology of the eye did not reveal significant differences between affected and unaffected eyes except for a more posterior dorsal rectus muscle insertion site in the affected eye. This case report documents and describes a syndrome well known among arowana hobbyists as 'drop eye'.

PMID:26439990 | DOI:10.1111/vop.12320

Vet Ophthalmol. 2016 May;19(3):206-13. doi: 10.1111/vop.12285. Epub 2015 Jun 3.

ABSTRACT

OBJECTIVE: To describe five cases of protozoal keratitis or conjunctivitis in dogs with chronic preexisting ocular surface disease treated with long-term immunosuppression.

ANIMALS STUDIED: Five dogs that developed corneal or conjunctival mass lesions.

PROCEDURES: The database of the Comparative Ocular Pathology Laboratory of Wisconsin was searched for canine cases diagnosed with corneal or conjunctival protozoal infection. Five cases were identified, and tissues were examined using routine and special histochemical stains: immunohistochemical labels for Neospora caninum, Toxoplasma gondii, and Leishmania spp., and tissue sample PCR for Leishmania spp., Trypanosoma cruzi, tissue coccidia (i.e., T. gondii/Sarcocystis/Neospora), piroplasms, trichomonads, and Acanthamoeba. Electron microscopy was performed for two cases, and serology for N. caninum and T. gondii was available for three cases.

RESULTS: Preexisting ocular diseases included keratoconjunctivitis sicca and pigmentary keratitis (n = 4) and pyogranulomatous meibomian adenitis (n = 1). All dogs were treated with tacrolimus or cyclosporine for at least 1.2 years. Dogs were presented with fleshy corneal or conjunctival masses that were clinically suspected to be neoplastic (n = 4) or immune mediated (n = 1). Histologic examination revealed granulomatous inflammation with intralesional protozoal organisms. Amoeba (n = 2), T. gondii (n = 2), or Leishmania mexicana (n = 1) were identified using molecular techniques. Serological tests were negative.

CONCLUSIONS: Protozoal keratitis and conjunctivitis without systemic involvement appears rare and may be associated with chronic preexisting ocular surface disease treated with long-term immunosuppression. Based upon clinical appearance, lesions could be confused with neoplasia. This is the first report of amoebic keratoconjunctivitis in dogs and of L. mexicana in dogs in the United States.

PMID:26037023 | DOI:10.1111/vop.12285

Vet Ophthalmol. 2016 Mar;19(2):172-9. doi: 10.1111/vop.12275. Epub 2015 Apr 28.

ABSTRACT

OBJECTIVE: To describe clinical, in vivo confocal microscopic, histopathologic, polymerase chain reaction assay for antigen receptor rearrangement (PARR) and immunohistochemical features of a horse with suspected malignant transformation of corneal B lymphocytes in immune-mediated keratitis (IMMK) and to also report surgical management and adjunctive treatment including topical and radiation therapies.

CASE DESCRIPTION: A 15-year-old Oldenburg gelding was examined for presumptive progressive stromal IMMK of the right eye which became refractory to medical management. Corneal in vivo confocal microscopy revealed a marked infiltration of neovascularization, leukocytes, and dendritic cells. Superficial keratectomy was performed. Histopathologic and immunohistopathologic abnormalities of the cornea were restricted to the anterior and mid-stroma and included sheets of medium-size atypical lymphocytes which stained positively for CD79a and CD20 and also demonstrated clonal rearrangements of immunoglobulin heavy chain 2 (IGH2) and 3 (IGH3) confirming B-cell lymphoma. Complete physical examination, complete blood count, serum chemistry, thoracic radiographs, and thoracic ultrasound were performed. No evidence of systemic metastasis was found. Adjunctive local therapy included topical dexamethasone, mitomycin C, and radiation therapy using electronic surface brachytherapy. Follow-up at 16 months revealed a lack of corneal infiltrate and progressive clearing of corneal fibrosis and superficial pigment.

CONCLUSIONS: This case represents a unique presentation of primary corneal lymphoma in the horse. Tumor development was associated with chronic IMMK and chronic topical anti-inflammatory therapy. Surgical excision with adjunctive therapy using mitomycin C and electronic surface brachytherapy was well tolerated and considered curative. Future immunohistochemistry and PARR will be important in characterizing the IMMK syndrome and its variations.

PMID:25919039 | DOI:10.1111/vop.12275

Vet Ophthalmol. 2016 Mar;19(2):130-7. doi: 10.1111/vop.12270. Epub 2015 Apr 1.

ABSTRACT

PURPOSE: To describe clinical and pathological features of canine orbital rhabdomyosarcoma (COR).

METHODS: Retrospective review of patients with COR from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin and the University of Wisconsin Veterinary Medical Teaching Hospital (1983-2014).

RESULTS: Eighteen cases of COR were identified, all diagnosed in an 8-year period (2006-2014). Affected dogs were typically young (range 1-8; median 2 years), and both sexes were equally represented. Common clinical signs included exophthalmos (16/18) with dorsolateral deviation of the globe (10/18) and elevation of the nictitans (12/18). Ultrasonography, performed in nine cases, revealed an orbital mass with mixed echogenicity and posterior globe indentation. Advanced imaging, performed in nine cases, demonstrated a soft tissue mass with variable contrast enhancement and lysis of the orbital bones (5/9). Histologically, all tumors were subclassified as embryonal rhabdomyosarcoma. All neoplasms demonstrated positive immunohistochemical labeling for desmin, and 14/18 were positive for skeletal muscle actin. Follow-up information was available for 15/18 cases. Older dogs, aged 6-8 years, had no clinical signs of recurrence or metastasis 8-13 months postdiagnosis (4/4). Most younger dogs (9/11), aged 1-4 years, were euthanized within 6 months (median 2.5 months) of diagnosis due to recurrence at the surgical site (5/9) and/or metastasis (5/9).

CONCLUSIONS: Canine orbital rhabdomyosarcoma is a highly malignant neoplasm in juvenile dogs, but may be amenable to surgical resection in older dogs. This duality in biologic behavior may reflect differences in tissue of origin between juvenile onset tumors and adult onset tumors.

PMID:25846977 | DOI:10.1111/vop.12270

Vet Ophthalmol. 2016 Mar;19(2):138-43. doi: 10.1111/vop.12273. Epub 2015 Apr 1.

ABSTRACT

PURPOSE: To describe the various types of primary neoplasms affecting the third eyelid (TEL) gland of dogs and cats.

METHODS: A retrospective search of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database was performed. Veterinary ophthalmologists, primary care veterinarians, and, when appropriate, owners were contacted for patient follow-up information. Patient data points collected included species, age, sex, breed, laterality, tumor type, surgical margins, recurrence, metastasis, and length of follow-up.

RESULTS: A total of 127 canine and 18 feline cases met the inclusion criteria. The most common canine TEL gland tumor was adenocarcinoma (n = 108; 85.0%) followed by adenoma (n = 18; 14.2%) and squamous cell carcinoma (SCC) (n = 1; 0.8%). For canine cases with follow-up information available (n = 62), 8.1% had confirmed or suspected metastasis and 11.3% had confirmed or suspected local recurrence of disease. The most common feline TEL gland tumor was adenocarcinoma (n = 15; 83.3%) followed by SCC (n = 3; 16.7%). For feline cases with follow-up information available (n = 9), 40.0% had confirmed or suspected metastasis and 30.0% had confirmed or suspected local recurrence of disease.

CONCLUSIONS: This study determined that adenocarcinoma was the most common third eyelid gland tumor in both dogs and cats. The overall survival times were less, and metastatic occurrence and recurrence rates appeared to be higher for feline tumors as compared to those diagnosed in dogs. This is the first report of SCC originating from glandular ductular epithelium.

PMID:25827973 | DOI:10.1111/vop.12273

Vet Ophthalmol. 2016 Mar;19(2):161-6. doi: 10.1111/vop.12269. Epub 2015 Mar 28.

ABSTRACT

A captive female square-lipped rhinoceros born in 1993 had been showing intermittent signs of bilateral conjunctivitis and conjunctival proliferation since 1998. Periodic improvement was noted, especially in winter, but overall the condition had deteriorated over the years. Treatment with various topical, intralesional, and systemic antibiotics and glucocorticosteroids was largely ineffective, as were repeated dewormings. No primary cause for these lesions was found in biopsies taken in 2000 and 2006, although a severe infiltrate of numerous eosinophils was observed in the latter. As the condition worsened, secondary corneal changes were noted, and eventually vision was lost due to proliferative conjunctival tissue. Aggressive resection of the proliferating tissue in 2013 restored vision and submitted biopsies yielded a diagnosis of severe allergic conjunctivitis, eosinophilic granuloma, and habronematid (Habronema or Draschia) larval infection. As no other rhinoceros in the herd was affected, including two calves born to the patient who were in close contact with their mother, it was concluded the presentation was most likely due to a hypersensitivity reaction to the dead or dying larvae. Fly repellent is now regularly applied around the eye of this rhinoceros, and a protective face mask has been fitted. Ongoing periodic relapses are treated with oral ivermectin, topical antibiotics, and steroids.

PMID:25818990 | DOI:10.1111/vop.12269

Vet Ophthalmol. 2016 Jan;19(1):43-9. doi: 10.1111/vop.12254. Epub 2015 Feb 10.

ABSTRACT

OBJECTIVE: To quantify the total number and luminal areas of the short posterior ciliary arteries (SPCA) surrounding the canine optic nerve at the level of the sclera/lamina cribrosa in normal dogs and compare this data to dogs with a history of acute (≤7 days) glaucoma.

PROCEDURES: Twelve normal globes were obtained through Harlan Laboratories, the UW-Madison School of Veterinary Medicine necropsy service and via enucleation submissions to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Ten globes with a history of acute glaucoma were obtained from submissions to the COPLOW. Optic nerves were cross-sectioned in 20 micron steps, and five distinct levels were identified: the retinal nerve fiber layer; the retinal pigmented epithelium and neural canal opening; the choroid/pre-lamina; the sclera/lamina cribrosa; and the retro-lamina. At the level of the sclera/lamina cribrosa, SPCA profiles were counted and the luminal area was measured using Cell Sens software. Normal and glaucomatous globes were compared using ANOVA.

RESULTS: Statistically significant smaller luminal areas and fewer numbers of arteries were recorded between normal and glaucomatous globes.

CONCLUSIONS: The glaucomatous eyes in this study have SPCA with decreased lumina, suggestive of a vascular pathology present at the early stages of clinical glaucoma. Smaller lumina may be a contributing factor to the ischemia, necrosis, and the eventual full-thickness retinal atrophy often seen in glaucomatous dogs.

PMID:25675855 | DOI:10.1111/vop.12254

Vet Rec. 2015 Feb 7;176(6):147. doi: 10.1136/vr.102638. Epub 2014 Oct 15.

ABSTRACT

To evaluate the outcome of eyes with a confirmed iridociliary epithelial tumour (ICET) following biopsy. Forty-two specimens were selected from the Comparative Ocular Pathology Laboratory of Wisconsin database, including 11 globes enucleated following ICET biopsy and 31 iridociliary biopsies with a confirmed ICET. Histopathology was performed for all specimens. When identified, the corneal surgical wound was examined in enucleated globes. Tumour type and margins were determined for biopsy specimens and follow-up was obtained when possible. Biopsies were performed for diagnosis, debulking or excision. 30/31 biopsies had dirty margins, and iridociliary adenomas were indistinguishable from adenocarcinomas by biopsy. Upon biopsy submission 5/23 biopsies were reported as incisional and 18/23 as excisional. Follow-up information was obtained for 14/18 of those reported as excisional. 8/14 had documented recurrence within 5.0±5.6 months and 6/14 had no recurrence at 21.5±13.6 months postoperatively. Three enucleated globes were diagnosed with iridociliary adenocarcinomas and eight with iridociliary adenomas. The corneal surgical wound was sampled in 8/11 globes. There was a synechia to the surgical wound in 3/8 globes, and in 3/8 globes there were neoplastic cells within or adjacent to the surgical wound. The postoperative success of ICET excision is highly variable; complete excision is rarely achieved and recurrence is common. Biopsy effects on ocular tissues may result in synechia and other surgical complications. ICET can be diagnosed by biopsy, but adenomas are indistinguishable from adenocarcinomas.

PMID:25319595 | DOI:10.1136/vr.102638

Vet Pathol. 2015 Jul;52(4):676-80. doi: 10.1177/0300985814556185. Epub 2014 Oct 28.

ABSTRACT

Papillomas of the conjunctival surface in people can be of viral or nonviral origin and are found in high association with human papillomavirus. Canine conjunctival papillomas are seldom described, and published accounts have mostly been associated with canine oral papillomavirus infection. Here, we describe conjunctival squamous papillomas that do not express papillomavirus proteins and compare them with papillomavirus-associated conjunctival papillomas. Conjunctival squamous papillomas presented a distinct histopathologic profile and lacked the cytopathic effects seen in viral papillomas. They appeared as exophytic, papilliferous, pedunculated lesions with delicate fronds and angular terminal margins. Squamous papillomas presented with a delicate fibrovascular core and were associated both clinically and grossly with a feeder vessel. Pigmentation was variable within the epithelium and stroma of these lesions, and inflammatory infiltrates were characteristically minimal. Conjunctival squamous papillomas resembled squamous papillomas of the skin; however, they lacked significant hyperkeratosis. Compared with conjunctival viral papillomas, these masses occurred in older dogs and were smaller and solitary. Furthermore, polymerase chain reaction and immunohistochemistry failed to demonstrate papillomavirus genetic material and antigens in conjunctival squamous papillomas. Both viral and nonviral conjunctival papillomas were considered benign.

PMID:25352202 | DOI:10.1177/0300985814556185

Vet Ophthalmol. 2015 Sep;18(5):371-80. doi: 10.1111/vop.12209. Epub 2014 Sep 1.

ABSTRACT

OBJECTIVE: To characterize the clinical, diagnostic, and histopathologic findings in dogs with canine ocular gliovascular syndrome (COGS).

PROCEDURES: The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were used to identify eyes with COGS. Histopathological inclusion criteria included: a neovascular membrane extending from the optic nerve head or retina, clusters of spindle cells lacking vascularization within the vitreous, and histological signs of glaucoma. Special and immunohistochemical (IHC) staining techniques were performed. Clinical data, treatments, and outcomes were obtained from case records and information provided by submitting veterinarians.

RESULTS: Thirty-seven eyes of 36 dogs were identified with COGS. The average age at diagnosis was 8.8 years (±2.2). The relative risk for a Labrador retriever affected by COGS was significantly greater (9.3 times) (P < 0.0001) when compared to all other dog breeds within the COPLOW database. Most dogs presented with hyphema and secondary glaucoma; average intraocular pressure was 39 mmHg (±19). Average time to enucleation or evisceration was 27 days. Vitreal cells stained positive with IHC for glial fibrillary acidic protein in 14 of 17 globes, and vascular endothelial growth factor was expressed in the vitreal cells in five of five globes.

CONCLUSIONS: We have defined a syndrome associated with vitreal glial cell aggregates and neovascular proliferation from the optic nerve or retina, which leads to neovascular glaucoma. The inflammation and secondary glaucoma resulting from this syndrome appear poorly responsive to conventional medical therapies. The exact etiology of COGS remains undetermined, but a systemic etiology is unlikely.

PMID:25174277 | DOI:10.1111/vop.12209

J Vet Diagn Invest. 2014 Sep;26(5):664-8. doi: 10.1177/1040638714542961. Epub 2014 Jul 23.

ABSTRACT

Following unilateral enucleation, 4 Domestic Shorthair cats with an average age of 12.5 years (range: 9-16 years) were histologically diagnosed with a presumed primary intraocular chondrosarcoma at the Comparative Ocular Pathology Laboratory of Wisconsin (Madison, Wisconsin). Medical records and follow-up were available for 3 of the 4 cats. Clinically, only 1 eye was affected in each cat; a mass lesion was noted in 2 cats, and a neoplasm was suspected in the other 2 cats. Grossly, 3 tumors presented as coalescing, poorly demarcated, white, friable masses filling the vitreous and intraocular chambers; 1 tumor presented as a solitary, well-demarcated, tan mass involving the iris and ciliary body. Histologically, all 4 neoplasms were composed of haphazardly arranged plump neoplastic spindle cells surrounded by irregular islands and thick trabeculae of abundant, variably basophilic, and Alcian blue-positive chondromatous matrix. None of the cats presented histologically or clinically with signs suggestive of feline posttraumatic ocular sarcoma. Two cats are still alive and healthy 6 months and 3 years following enucleation. One cat died 6 months following enucleation; however, this cat suffered from poorly controlled diabetes mellitus, and the cause of death is undetermined. No other tumors or skeletal lesions were identified that could suggest a metastatic tumor to the eye. The origin of primary intraocular chondrosarcoma is unclear, but is presumed to be ocular multipotent mesenchymal stem cells. Four cases of intraocular chondrosarcoma in cats not associated with the posttraumatic sarcoma complex of intraocular tumors are described.

PMID:25057162 | DOI:10.1177/1040638714542961

Vet Pathol. 2015 Mar;52(2):397-403. doi: 10.1177/0300985814535613. Epub 2014 May 30.

ABSTRACT

Cytochrome P450 1B1 (CYP1B1) is highly expressed in human and murine ocular tissues during development. Mutations in this gene are implicated in the development of primary congenital glaucoma (PCG) in humans. Mice deficient in Cyp1b1 (Cyp1b1(-/-) ) present developmental abnormalities similar to human primary congenital glaucoma. The present work describes the ultrastructural morphology of the iridocorneal angle of 21 eyes from 1-week-old to 8-month-old Cyp1b1(-/-) mice. Morphometric and semiquantitative analysis of the data revealed that 3-week-old Cyp1b1(-/-) mice present a significantly (P < .005) decreased amount of trabecular meshwork (TM) collagen and higher TM endothelial cell and collagen lesion scores (P < .005) than age-matched controls. Collagen loss and lesion scores were progressively increased in older animals, with 8-month-old animals presenting severe atrophy of the TM. Our findings advance the understanding of the effects of CYP1B1 mutations in TM development and primary congenital glaucoma, as well as suggest a link between TM morphologic alterations and increased intraocular pressure.

PMID:24879660 | PMC:PMC4285769 | DOI:10.1177/0300985814535613

J Vet Diagn Invest. 2014 Jul;26(4):575-579. doi: 10.1177/1040638714533116.

ABSTRACT

Cutaneous meningiomas are rare tumors in human beings and animals. Two canine cases of cutaneous meningiomas affecting the eyelid are described in the current study: the first from a 5-week-old female Springer Spaniel dog with an 8 cm in diameter congenital mass expanding the left upper eyelid and medial canthus; the second from a 10-year-old female spayed Maltese-Poodle mix dog with 3 firm subcutaneous nodules affecting the right upper eyelid. All masses were removed surgically. Histologically, tumors were composed of spindle-to-epithelioid cells arranged in small lobules forming solid concentric whorls. Neoplastic cells were positive for vimentin and S100 and negative for pancytokeratin, glial fibrillar acid protein, and neurofilament. Transmission electron microscopy revealed meningothelial cells with convoluted interdigitating processes, desmosomes, and hemidesmosomes, and moderate numbers of cytoplasmic microfilaments. None of the cases presented a primary neuroaxial meningioma. The first case presents clinicopathological features consistent with human type I (congenital) cutaneous meningioma. The second case is consistent with a type II (acquired ectopic) tumor, and both are hypothesized to arise from ectopic arachnoid cells displaced during development.

PMID:24803575 | DOI:10.1177/1040638714533116

Mol Vis. 2014 Mar 28;20:376-85. eCollection 2014.

ABSTRACT

PURPOSE: To describe and validate a semi-automated targeted sampling (SATS) method for quantifying optic nerve axons in a feline glaucoma model.

METHODS: Optic nerve cross sections were obtained from 15 cats, nine with mild to severe glaucoma and six with normal eyes. Optic nerves were dissected, fixed in paraformaldehyde and glutaraldehyde, and processed for light microscopy by resin embedding, sectioning, and staining of axon myelin sheaths with 1% p-phenylenediamine before axon quantification. Commercially available image analysis software was used as a semi-automated axon counting tool (SCT) and was first validated by comparison with a manual axon count (MAC). This counting tool was then used in a SATS method performed by three masked raters and in a semi-automated full count (SAFC) method performed by a single observer. Correlation was assessed between the SCT and MAC using a linear model and analysis of covariance (ANCOVA). Correlation between the SATS and SAFC methods was calculated and the bias, systematic errors, and variance component assessed. The intraclass correlation coefficient (ICC) was determined to establish inter-rater agreement. In addition, the time required to perform the SATS and SAFC methods was evaluated.

RESULTS: Correlation between the axon counts obtained by the SCT and MAC was strong (r = 0.9985). There was evidence of an overcounting of axons by the SCT compared to the MAC with a percentage error rate of 13.0% (95% confidence interval [CI] 11.0%, 15.1%). Both the correlation of SATS count (average per rater) to SAFC (r = 0.9891) and inter-rater agreement (ICC = 0.986) were high. The SATS method presented an overall positive counting error (p<0.001) when compared to the SAFC, consistent with a fixed percentage overestimation of 11.2% (95% CI 8.3%, 14.2%) of the full count. The average time required to quantify axons by the SATS method was 10.9 min, only 27% of that required to conduct the SAFC.

CONCLUSIONS: Our data demonstrate that the SATS method provides a practical, rapid, and reliable means of estimating axon counts in the optic nerves of cats with glaucoma.

PMID:24715755 | PMC:PMC3976691

J Tissue Eng Regen Med. 2016 Dec;10(12):1012-1020. doi: 10.1002/term.1886. Epub 2014 Mar 27.

ABSTRACT

Wound healing is a complex process that requires the intervention of cytoactive factors. The one-time application of soluble factors to a wound bed does not maintain a steady, sufficient concentration. Here we investigated the benefits of anchoring a factor in a wound bed via a tether to endogenous collagen. We used a collagen-mimetic peptide (CMP) as a pylon. The CMP binds to damaged but not intact collagen and thus localizes a pendant cytoactive factor in the regions of a wound bed that require intervention. As a model factor, we chose substance P, a peptide of the tachykinin family that promotes wound healing. Using splinted wounds in db/db mice, we found that the one-time application of a CMP-substance P conjugate enhances wound healing compared to unconjugated substance P and other controls. Specifically, all 16 wounds treated with the conjugate closed more thoroughly and, did so with extensive re-epithelialization and mitigated inflammatory activity. These data validate a simple and general strategy for re-engineering wound beds by the integration of beneficial cytoactive factors. Copyright © 2014 John Wiley & Sons, Ltd.

PMID:24677775 | PMC:PMC4219926 | DOI:10.1002/term.1886

PLoS One. 2014 Mar 19;9(3):e92127. doi: 10.1371/journal.pone.0092127. eCollection 2014.

ABSTRACT

The first white Doberman pinscher (WDP) dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA) and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1) produce a detailed description of the ocular phenotype of WDPs, (2) objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3) determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs); cutaneous tumors were noted in 12/20 WDP (<5 years of age: 4/12; >5 years of age: 8/8) and 1/20 SDPs (p<0.00001). Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968-77,067,051). This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model.

PMID:24647637 | PMC:PMC3960214 | DOI:10.1371/journal.pone.0092127

J Small Anim Pract. 2013 Nov;54(11):584-93. doi: 10.1111/jsap.12141.

ABSTRACT

OBJECTIVE: To evaluate if 14 genes that discriminate metastasising and non-metastasising human uveal melanomas can differentiate metastasising and non-metastasising uveal melanomas in dogs.

METHODS: Nineteen archival biopsies of eyes with a histopathological classification of primary benign (n = 9) and malignant (n = 10) uveal melanoma were selected. Thoracic and/or abdominal metastases confirmed metastatic spread of the primary tumour in seven dogs during the follow-up period. Gene expression was assayed by Reverse Transcription-quantitative Polymerase Chain Reaction. Genes displaying statistically significant differences in expression between the metastasising and non-metastasising tumours were identified.

RESULTS: Four genes (HTR2B, FXR1, LTA4H and CDH1) demonstrated increased expression in the metastasising uveal melanomas.

CLINICAL SIGNIFICANCE: This preliminary study illustrates the potential utility of gene expression markers for predicting canine uveal melanoma metastasis. The genes displaying elevated expression in the metastasising tumours are part of a 12-discriminating gene set used in a routine assay, performed on fine needle aspirate biopsies collected without enucleation, for predicting human uveal melanoma metastasis. Further work is required to validate the results.

PMID:24580015 | DOI:10.1111/jsap.12141