Dr. Dubielzig is a founder, former managing member, and currently provides consulting on ocular pathology.
Dr. Dubielzig is a Board Certified Veterinary Pathologist, and Professor of Pathology, School of Veterinary Medicine, University of Wisconsin-Madison. He is primarily interested in comparative ocular pathology, but has written and lectured widely on diverse topics concerning veterinary ophthalmic pathology, laboratory animal ocular pathology and comparative ocular morphology.
Dr. Dubielzig has authored more than 200 publications, and is recognized for his ground-breaking observations of the spontaneous ocular diseases of animals. He runs an active mail-in ocular pathology service that processes more than 3000 specimens annually. He also provides consulting to industries on the development of ocular lesions.
A Transient Developmental Background Finding in the Retina Observed in Neonatal Dogs in Juvenile Toxicology Studies.
Toxicol Pathol. 2019 May 07;:192623319844470
Authors: Petruska JM, Remick AK, Lejeune T, Vezina M, Robinson K, Bussières M, Gilger BC, Dubielzig RR
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 [PubMed - as supplied by publisher]
Is There an Increased Prevalence of Asteroid Hyalosis in Eyes with Uveal Melanoma? A Histopathologic Study.
Ocul Oncol Pathol. 2017 Nov;3(4):259-261
Authors: Burris CKH, Azari AA, Kanavi MR, Dubielzig RR, Lee V, Gottlieb JL, Potter HD, Kim K, Raven ML, Rodriguez ME, Reddy DN, Albert DM
During the planning meeting for the Collaborative Ocular Melanoma Study (COMS) prior to the start of patient recruitment in 1986, there was an interest expressed in determining whether a relationship existed between the presence of uveal melanoma (UM) and asteroid hyalosis (AH). To answer this question, the ophthalmic examination form (unlike the pathology form for enucleated eyes) for each COMS patient asked whether AH was present or not. Though an increased prevalence was not found, this result was never published. A recent unpublished study at the University of Wisconsin School of Veterinary Medicine indicated a higher prevalence of AH in canine eyes with UM when compared to control eyes (without tumor) enucleated for goniodysgenesis. This further increased our interest in revisiting the published literature, clinical records, and histopathology slides of the enucleated eyes from the COMS study, as well as the histopathology slides on file in the University of Wisconsin Eye Pathology Laboratory. While cases with both AH and UM were occasionally encountered in the literature, clinically, we could not find a previous study focusing on these two processes. This study was conducted to explore whether such an association exists.
PMID: 29344477 [PubMed]
Iridociliary cysts masquerading as neoplasia in cats: a morphologic review of 14 cases.
Vet Ophthalmol. 2017 Jul 06;:
Authors: Fragola JA, Dubielzig RR, Bentley E, Teixeira LBC
OBJECTIVE: To report 14 neoplasia-free feline eyes enucleated for suspected intraocular neoplasia containing only iridociliary cysts. To analyze clinical findings that may have led veterinarians to suspect neoplasia in these globes.
PROCEDURES: The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were searched to identify neoplasia-free feline globes enucleated for suspected neoplasia. Clinical data were obtained from medical records, veterinarian surveys, and COPLOW submission forms. All samples were examined grossly and histologically.
RESULTS: All eyes were free of neoplasia and contained one or more iridociliary cysts. Nine of 14 globes were enucleated by or based on the recommendation of a board-certified veterinary ophthalmologist. In eight of 14 cases, the submitting clinician listed melanoma as the only suspected diagnosis; in six of 14 cases, 'tumor' or 'mass' was listed. Clinical examination revealed a darkly pigmented intraocular mass in 11 of 14 cases. The mass was clinically perceived to be within the iris in seven of 14 cases. When examined histologically, 11 of 14 eyes contained multiple cysts, 13 of 14 contained multiloculated cysts, eight of 14 had a hyperplastic iris pigmented epithelium or cysts with thick black walls, and five of 14 had cysts prolapsed into the anterior chamber.
CONCLUSIONS: Although most iridociliary cysts in cats are easily diagnosed on clinical examination, a subset may be mistaken for neoplasia. In cases of suspected iris melanoma, iridociliary cysts should be considered as a differential diagnosis, especially if a mass appears to emanate from behind the iris, dyscoria is present, or if similar changes are noted in the contralateral eye.
PMID: 28685998 [PubMed - as supplied by publisher]
Mandibular odontoameloblastoma in a rat and a horse.
J Vet Diagn Invest. 2017 May 01;:1040638717711996
Authors: Murphy B, Bell C, Koehne A, Dubielzig RR
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 [PubMed - as supplied by publisher]
Do you see what I see? Optical morphology and visual capability of 'disco' clams (Ctenoides ales).
Biol Open. 2017 May 15;6(5):648-653
Authors: Dougherty LF, Dubielzig RR, Schobert CS, Teixeira LB, Li J
The 'disco' clam Ctenoides ales (Finlay, 1927) is a marine bivalve that has a unique, vivid flashing display that is a result of light scattering by silica nanospheres and rapid mantle movement. The eyes of C. ales were examined to determine their visual capabilities and whether the clams can see the flashing of conspecifics. Similar to the congener C. scaber, C. ales exhibits an off-response (shadow reflex) and an on-response (light reflex). In field observations, a shadow caused a significant increase in flash rate from a mean of 3.9 Hz to 4.7 Hz (P=0.0016). In laboratory trials, a looming stimulus, which increased light intensity, caused a significant increase in flash rate from a median of 1.8 Hz to 2.2 Hz (P=0.0001). Morphological analysis of the eyes of C. ales revealed coarsely-packed photoreceptors lacking sophisticated structure, resulting in visual resolution that is likely too low to detect the flashing of conspecifics. As the eyes of C. ales are incapable of perceiving conspecific flashing, it is likely that their vision is instead used to detect predators.
PMID: 28396488 [PubMed]
Orbital rhabdomyosarcoma and traumatic neuroma following enucleation for a uveal schwannoma in a dog: a case report.
Clin Case Rep. 2017 Mar;5(3):300-307
Authors: McDonald JE, Knollinger AM, Teixeira LB, Dubielzig RR
A 4-year-old, female spayed Siberian husky with history of a uveal schwannoma presented for orbital swelling 9 months after enucleation. A second, malignant tumor developed in the same orbit. Therefore, uveal schwannomas may warrant early surgical intervention in the dog.
PMID: 28265395 [PubMed - in process]
Diversity of Photoreceptor Arrangements in Nocturnal, Cathemeral and Diurnal Malagasy Lemurs.
J Comp Neurol. 2017 Jan 05;:
Authors: Peichl L, Kaiser A, Rakotondraparany F, Dubielzig RR, Goodman SM, Kappeler AP
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. This article is protected by copyright. All rights reserved.
PMID: 28054342 [PubMed - as supplied by publisher]
Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin.
Invest Ophthalmol Vis Sci. 2016 Sep 01;57(11):4859-4868
Authors: Teixeira LB, Hoeve JN, Mayer JA, Dubielzig RR, Smith CM, Radcliff AB, Duncan ID
Purpose: We determined whether the chronic lack of optic nerve myelination and subsequent axon loss is associated with optical coherence tomography (OCT) changes in the retinal nerve fiber layer (RNFL), and whether this models what occurs in multiple sclerosis (MS) and confers its use as a surrogate marker for axon degeneration.
Methods: Using an animal model of Pelizaeus-Merzbacher disease (shp) bilateral longitudinal measurements of the peripapillary RNFL (spectral-domain OCT), electroretinograms (ERG), and visual evoked potentials (VEP) were performed in affected and control animals from 5 months to 2 years and in individual animals at single time points. Light and electron microscopy of the optic nerve and retina and histomorphometric measurements of the RNFL were compared to OCT data.
Results: Of the shp animals, 17% had an average reduction of OCT RNFL thickness on the superior retinal quadrant compared to controls (P < 0.05). Electroretinograms showed normal photopic A- and B-waves but flash VEPs were disorganized in shp animals. Morphologically, the shp retinas and optic nerves revealed significant RNFL thinning (P < 0.001) without retinal ganglion cell (RGC) loss, decrease total and relative retinal axonal area, and loss of optic nerve axons. There was strong positive correlation between OCT and morphometric RNFL thickness measurements (r = 0.878, P = 0.004).
Conclusion: The loss of optic nerve axons demonstrated in the shp model resulted in moderate thinning of the RNFL confirmed by OCT and histology. These results indicate that OCT-derived RNFL measurement can be a useful surrogate biomarker of optic nerve axon loss and potentially disease progression in demyelinating diseases.
PMID: 27654412 [PubMed - as supplied by publisher]
Late prostatic metastasis of an uveal melanoma in a miniature Schnauzer dog.
Clin Case Rep. 2016 Jul;4(7):647-52
Authors: Delgado E, Silva JX, Pissarra H, Peleteiro MC, Dubielzig RR
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 [PubMed]
Feline Epitheliotropic Mastocytic Conjunctivitis in 15 Cats.
Vet Pathol. 2016 Jul 01;:
Authors: Beckwith-Cohen B, Dubielzig RR, Maggs DJ, Teixeira LB
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 [PubMed - as supplied by publisher]
Glaucoma with Descemet's membrane detachment in five horses.
Vet Ophthalmol. 2016 May 18;:
Authors: Henriksen ML, La Croix N, Wilkie DA, Lassaline-Utter M, Brantman KR, Beamer GL, Teixeira LB, Dubielzig RR
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 [PubMed - as supplied by publisher]
Third eyelid gland neoplasms of dogs and cats: a retrospective histopathologic study of 145 cases.
Vet Ophthalmol. 2015 Apr 1;
Authors: Dees DD, Schobert CS, Dubielzig RR, Stein TJ
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 [PubMed - as supplied by publisher]
Suspected malignant transformation of B lymphocytes in the equine cornea from immune-mediated keratitis.
Vet Ophthalmol. 2015 Apr 28;
Authors: Vallone LV, Neaderland MH, Ledbetter EC, Dubielzig RR
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 [PubMed - as supplied by publisher]
Ultrastructural abnormalities of the trabecular meshwork extracellular matrix in Cyp1b1-deficient mice.
Vet Pathol. 2015 Mar;52(2):397-403
Authors: Teixeira LB, Zhao Y, Dubielzig RR, Sorenson CM, Sheibani N
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 [PubMed - in process]
Conjunctival habronemiasis in a square-lipped rhinoceros (Ceratotherium simum).
Vet Ophthalmol. 2015 Mar 28;
Authors: Horowitz IH, Dubielzig RR, Botero-Anug AM, Lucio-Forster A, Bowman DD, Rosenzweig AB, Frenkel S, Ofri R
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 [PubMed - as supplied by publisher]
Short posterior ciliary artery anatomy in normal and acutely glaucomatous dogs.
Vet Ophthalmol. 2015 Feb 10;
Authors: Fick CM, Dubielzig RR
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 [PubMed - as supplied by publisher]
Malignant uveal schwannoma with peripheral nerve extension in a 12-week-old color-dilute Labrador Retriever.
Vet Pathol. 2015 Jan;52(1):181-5
Authors: Duke FD, Teixeira LB, Galle LE, Green N, Dubielzig RR
The formalin-fixed, amber-colored right globe from a 12-week-old female silver Labrador Retriever dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for light microscopic evaluation. The clinical history described a collapsed anterior chamber and multifocal nodular lesions in the peripheral iris. Histologically, immunohistochemically, and ultrastructurally, the uveal mass was consistent with a malignant schwannoma; there was extension along peripheral nerves within the sclera. The signalment and behavior of the neoplasm distinguish it from the uveal schwannoma of blue-eyed dogs and bear some resemblance to the ocular lesions in human neurofibromatosis. The dilute color mutation may contribute to the cause. Six weeks later, the dog did not develop any additional masses.
PMID: 24513800 [PubMed - in process]
Subconjunctival hibernoma in a dog.
Vet Ophthalmol. 2015 Jan;18(1):78-82
Authors: Stuckey JA, Rankin AJ, Romkes G, Slack J, Kiupel M, Dubielzig RR
A 10-year-old, castrated male, German Shepherd mixed-breed dog was presented to Kansas State University Veterinary Health Center for evaluation of a subconjunctival swelling in the ventral fornix of the left orbit. The owner elected to pursue excision of the mass 2 years after initial consultation following a sudden change in the size and color of the lesion. An excisional biopsy was performed, and the mass along with its associated capsule were submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for histopathologic evaluation, which confirmed the diagnosis of a hibernoma. Fourteen months following excision, the patient showed no evidence of tumor regrowth.
PMID: 24238154 [PubMed - in process]
Squamous Papillomas of the Conjunctiva in Dogs: A Condition Not Associated With Papillomavirus Infection.
Vet Pathol. 2014 Oct 28;
Authors: Beckwith-Cohen B, Teixeira LB, Ramos-Vara JA, Dubielzig RR
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 [PubMed - as supplied by publisher]
Histopathological study of the causes for failure of intrascleral prostheses in dogs and cats.
Vet Ophthalmol. 2014 Sep;17(5):343-50
Authors: Naranjo C, Dubielzig RR
OBJECTIVE: To characterize the histopathological causes for failure of intrascleral prosthesis placement in dogs and cats.
PROCEDURES: The Comparative Ocular Pathology Laboratory of Wisconsin database was searched to find canine and feline evisceration samples that were diagnosed with neoplasia. A second population included canine and feline scleral shells that were removed after an evisceration surgery had been performed. The causes for removal were divided into: neoplasia, corneal abnormalities, and other causes.
RESULTS: In dogs, 163 of 1985 evisceration samples (8.21%) contained a neoplasm, whereas 17 of 88 (19.31%) evisceration samples in cats contained a neoplasm. In dogs, severe corneal disease was diagnosed in 38 of 80 scleral shells (46.25%) and neoplasia was diagnosed in 31 of 80 scleral shells (38.75%). Malignant melanoma was the most frequently diagnosed tumor, in 14 of 31 scleral shells. In cats, eight of 12 scleral shells contained a tumor (66.7%), with feline diffuse iris melanoma being diagnosed most commonly (six of eight shells). Two of 12 feline scleral shells had severe corneal disease (16.7%). Epithelial downgrowth, lining the inner aspect of the fibrous tunic, was seen in 14 of 38 canine scleral shells and in two of two feline scleral shells with severe corneal disease.
CONCLUSIONS: Severe corneal disease and neoplasia are the most common causes for intrascleral prosthesis failure in dogs, whereas neoplasia is the single most common cause for intrascleral prosthesis failure in cats.
PMID: 23905626 [PubMed - indexed for MEDLINE]
Clinical and histological characteristics of canine ocular gliovascular syndrome.
Vet Ophthalmol. 2014 Sep 1;
Authors: Treadwell A, Naranjo C, Blocker T, Zarfoss M, Dubielzig RR
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 [PubMed - as supplied by publisher]
Presumed primary intraocular chondrosarcoma in cats.
J Vet Diagn Invest. 2014 Sep;26(5):664-8
Authors: Beckwith-Cohen B, Teixeira LB, Dubielzig RR
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 [PubMed - in process]
Periocular extracranial cutaneous meningiomas in two dogs.
J Vet Diagn Invest. 2014 May 6;26(4):575-579
Authors: Teixeira LB, Pinkerton ME, Dubielzig RR
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 [PubMed - as supplied by publisher]
Clinical, morphologic, and immunohistochemical features of canine orbital hibernomas.
Vet Pathol. 2014 May;51(3):563-8
Authors: Ravi M, Schobert CS, Kiupel M, Dubielzig RR
Hibernomas are uncommon benign tumors of brown fat that occur in humans and various animal species. They have not been observed in the orbit of dogs, humans, or other animals. Here we report clinical, light and electron microscopic, and immunohistochemical features of a series of 7 hibernomas arising in the orbital region of dogs. These neoplasms occurred in adult dogs with no breed predilection. The mean age of the affected dogs was 10.4 years (range, 8-13 years). All neoplasms presented as soft lobular masses composed of predominantly round or polygonal neoplastic cells with granular eosinophilic and vacuolated cytoplasm resembling adipocytes. The cytoplasm contained large numbers of pleomorphic mitochondria with dense matrices and indistinct cristae. Immunohistochemical evaluation confirmed positive labeling of neoplastic cells from all cases with uncoupling protein 1 (UCP-1) consistent with brown fat differentiation. Interestingly, rare neoplastic cells also expressed myogenin and myoD, possibly suggesting a common progenitor cell for neoplastic brown adipose and skeletal muscle cells.
PMID: 23794150 [PubMed - indexed for MEDLINE]
Presumed solitary intraocular or conjunctival lymphoma in dogs and cats: 9 cases (1985-2013).
J Am Vet Med Assoc. 2014 Feb 15;244(4):460-70
Authors: Wiggans KT, Skorupski KA, Reilly CM, Frazier SA, Dubielzig RR, Maggs DJ
OBJECTIVE: To determine prevalence, reason for evaluation, treatment, and outcome for dogs and cats with presumed solitary ocular lymphoma (PSOL).
DESIGN: Retrospective case series.
ANIMALS: 7 dogs and 2 cats with PSOL.
PROCEDURES: Medical records were reviewed. Progression-free survival time (PFST) and overall survival time (OST) were determined.
RESULTS: Animals with intraocular (4 dogs and 1 cat) or conjunctival (3 dogs and 1 cat) lymphoma represented 0.1% and 0.08% of patients with lymphoma evaluated at the hospital during the study period, respectively. Animals with intraocular lymphoma represented 0.19% of all patients with uveitis; animals with conjunctival lymphoma represented 0.16% of all patients with conjunctivitis. Tumors included B-cell (2 intraocular and 1 conjunctival), non-B-cell, non-T-cell (1 intraocular), and T-cell (3 conjunctival) neoplasms; immunophenotype of 2 uveal lymphomas was not determined. Treatments included enucleation (4 intraocular) and chemotherapy (3 intraocular and 2 conjunctival). All dogs with intraocular lymphoma developed neurologic signs. Lymph node metastasis was detected in 2 patients with conjunctival lymphoma. Median PFST and OST were 178 days for all animals with PSOL, dogs with PSOL, and animals with intraocular lymphoma. Median PFST and OST for animals with conjunctival lymphoma were 221 and 549 days, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated PSOL was uncommon, but should be considered a differential diagnosis for animals with uveitis or conjunctivitis. Performance of MRI and cytologic analysis of CSF and regional lymph node aspirate samples may be beneficial for such patients. Prognosis seemed to be better for animals with conjunctival lymphoma than it was for those with intraocular lymphoma.
PMID: 24479461 [PubMed - indexed for MEDLINE]
A partial gene deletion of SLC45A2 causes oculocutaneous albinism in Doberman pinscher dogs.
PLoS One. 2014;9(3):e92127
Authors: Winkler PA, Gornik KR, Ramsey DT, Dubielzig RR, Venta PJ, Petersen-Jones SM, Bartoe JT
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 [PubMed - in process]
Investigation of prognostic indicators for human uveal melanoma as biomarkers of canine uveal melanoma metastasis.
J Small Anim Pract. 2013 Nov;54(11):584-93
Authors: Malho P, Dunn K, Donaldson D, Dubielzig RR, Birand Z, Starkey M
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 [PubMed - indexed for MEDLINE]
Comparative ocular anatomy in a blind African cichlid fish, Lamprologus lethops.
Vet Ophthalmol. 2013 Sep;16(5):359-64
Authors: Schobert CS, Stiassny ML, Schwab IR, Zeiss C, Schelly RC, Dubielzig RR
OBJECTIVE: Troglomorphic fishes provide excellent comparative models for studying eye evolution. We describe the gross and microscopic anatomy of ocular structures of the depigmented, blind cichlid, Lamprologus lethops, and its putative sister species, Lamprologus tigripictilis collected from the lower Congo River in the Democratic Republic of Congo.
PROCEDURES: Both species were fixed, paraffin-sectioned and stained. Immunohistochemical staining for rhodopsin markers was also performed.
RESULTS: The globe in L. lethops is smaller than its sighted congener and recessed beneath bone and skin. The scleral profile maintains a wrinkled spherical shape, and the choroid is occupied by adipose tissue containing no rete mirabilis. The globe in L. lethops is foreshortened in the anterior-posterior dimension and deviated dorsally toward the midline with no extraocular muscles. At the posterior pole of the globe, there is an open periocular space containing no cell bodies. In L. tigripictilis, no choroidal adipose tissue is seen and a rete mirabilis is present. The retina of L. lethops is thinner compared with L. tigripictilis. Both species have scleral cartilage and fully developed lenses. Rhodopsin is present in the inner and outer segments of both species.
CONCLUSIONS: Ocular adaptations evolve over time as a response to a life in darkness. Combining ocular anatomy, developmental data, and genetics will lead to insights about evolution in these fishes and contribute to understanding how ocular evolution works in other vertebrates.
PMID: 23186233 [PubMed - indexed for MEDLINE]
Primary primitive neuroectodermal tumors of the retina and ciliary body in dogs.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:87-93
Authors: Regan DP, Dubielzig RR, Zeiss CJ, Charles B, Hoy SS, Ehrhart EJ
We describe the clinical, histological, and immunohistochemical features of primary intraocular primitive neuroectodermal tumors in eight dogs. Four of eight tumors exhibited histological features similar to human retinoblastomas characterized by Flexner-Wintersteiner rosettes, and fleurettes, and demonstrated variable immunoreactivity for retinal markers opsin, S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). All dogs with tumors displaying histological and immunohistochemical features of retinal differentiation were ≤2 years of age. All tumors diagnosed as medulloepitheliomas (n = 4) did not display histological and immunohistochemical features of retinal differentiation and were present in dogs 7 years or older. Age of onset, in conjunction with immunohistochemistry for opsin, S-Ag, and IRBP, is an important aid in the differentiation of primary, primitive neuroectodermal tumors arising within the canine ciliary body, retina, and optic papilla.
PMID: 23675855 [PubMed - indexed for MEDLINE]
Tapetal dysplasia in a Swedish Vallhund dog.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:145-50
Authors: Scott EM, Teixeira LB, Dubielzig RR, Komáromy AM
OBJECTIVE: To describe the gross, histopathological, and ultrastructural findings in a dog with bilateral tapetal dysplasia.
PROCEDURES: The globes of a 15-year-old neutered male Swedish Vallhund dog with a ventrally displaced tapetum in both eyes were fixed in 10% formalin and submitted to the Comparative Ocular Pathology Laboratory of Wisconsin for histological evaluation. Sections were stained with hematoxylin and eosin, Masson's trichrome, and Melan-A immunohistochemistry (IHC), and tissues were subsequently processed for transmission electron microscopy.
RESULTS: Bilateral fundic and gross examination revealed a tapetal fundus inferior to the optic nerve head (ONH) and a nontapetal fundus with mild scattering of tapetal tissue superior to the ONH. Histologically, there was decreased pigmentation of the retinal pigment epithelium with only a few melanin granules in the peripheral retina. The affected tapetum was relatively acellular and fibrous with occasional tapetal cells scattered throughout the inner choroid or displaced into the vascular outer choroid. Special stains revealed that the tapetum was mostly composed of collagen (Masson's trichrome) and failed to express Melan-A (IHC) unlike a normal canine control tapetum. Ultrastructurally, the tapetum was markedly dysplastic both superior and inferior to the ONH with no uniformly arranged tapetal cells. The few cells identified within the tapetum contained irregularly arranged and disorganized electron-dense structures within their cytoplasm, which were interpreted as dysplastic tapetal rodlets.
CONCLUSIONS: Based on microscopic and ultrastructural findings, this is the first report of tapetal dysplasia in a dog.
PMID: 23406395 [PubMed - indexed for MEDLINE]
Metastatic uveal schwannoma of blue-eyed dogs.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:141-4
Authors: Duke FD, Brudenall DK, Scott EM, Teixeira LB, Dubielzig RR
A formalin-fixed left, blue eye, from a 9-year-old, spayed female beagle dog was submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) for light microscopic evaluation. The history included glaucoma and an abnormal appearance for 6 months and then the development of a uveal mass. The histologic diagnosis was a spindle cell tumor of blue-eyed dogs (SCTBED). In June of 2012, the dog was euthanized due to ailing health, and there was radiographic and postmortem examination evidence of neoplastic metastasis. This is the first reported case of this primary ocular neoplasm metastasizing, and we propose to rename SCTBED as a uveal schwannoma of blue-eyed dogs.
PMID: 23281783 [PubMed - indexed for MEDLINE]
An unusual case of ocular melanosis and limbal melanocytoma with benign intraorbital extension in a dog.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:117-22
Authors: Dees DD, Maclaren NE, Teixeira L, Dubielzig RR
This case report describes concurrent ocular melanosis and limbal melanocytoma in a 6-year-old Golden Retriever dog. Three years prior, the pet was examined for progressive corneal pigmentation and started on topical Tacrolimus but was subsequently lost to followup. Current ophthalmic examination revealed a large pigmented limbal mass and severe corneal pigmentation of the left eye as well as a small focal raised pigmented mass of the right third eyelid. Due to extent and rapidity of tumor growth, the left eye was removed via transconjunctival enucleation and submitted for histopathologic examination. At the time of surgery, numerous orbital structures including intraorbital fat, extraocular muscles, and portions of the proximal nasolacrimal drainage apparatus contained multifocal areas of black pigmentation. These tissues were subsequently removed and submitted for microscopic analysis. The pigmented mass of the right third eyelid was also excised. Histopathology of the left eye and orbital contents revealed a limbal melanocytoma extending to the bulbar conjunctiva and orbital space forming a large, markedly necrotic mass. Diffuse, severe ocular melanosis, abnormal stromal pigmentation of the sclera and orbital tissues, and corneal stromal pigmentation were noted. The mass of the right third eyelid was confirmed to be a conjunctival melanocytoma. To the authors' knowledge, this is the first report of concurrent ocular melanosis and limbal melanocytoma with orbital infiltration. The peculiar multifocal distribution of melanocytes throughout ocular connective tissues may explain the development of multiple melanocytic lesions in this patient.
PMID: 23134502 [PubMed - indexed for MEDLINE]
Metaherpetic corneal disease in a dog associated with partial limbal stem cell deficiency and neurotrophic keratitis.
Vet Ophthalmol. 2013 Jul;16(4):282-8
Authors: Ledbetter EC, Marfurt CF, Dubielzig RR
OBJECTIVE: To describe clinical, in vivo confocal microscopic, histopathologic, and immunohistochemical features of a dog with metaherpetic corneal disease that developed subsequent to a protracted episode of canine herpesvirus-1 (CHV-1) dendritic ulcerative keratitis.
CASE DESCRIPTION: A 7-year-old, spayed-female, Miniature Schnauzer was treated for bilateral CHV-1 dendritic ulcerative keratitis. Following resolution of ulcerative keratitis, sectoral peripheral superficial corneal gray opacification, vascularization, and pigmentation slowly migrated centripetally to the axial cornea of both eyes. Corneal sensitivity measured with a Cochet-Bonnet esthesiometer was dramatically and persistently reduced. In vivo corneal confocal microscopic examination revealed regions of epithelium with a conjunctival phenotype. In these areas, the surface epithelium was thin, disorganized, and composed of hyper-reflective epithelial cells. Goblet cells and Langerhans cells were frequent, and the subbasal nerve plexus was completely absent or markedly diminished. Histopathologic abnormalities in the globes were restricted to the superficial cornea and included sectoral corneal conjunctivalization, increased anterior stromal spindle cells, and vascularization. Immunohistochemical evaluation of the corneas with anti-neurotublin antibody demonstrated attenuation of the epithelial and subbasal nerve plexuses with marked stromal hyperinnervation and increased numbers of morphologically abnormal neurites.
CONCLUSIONS: Similar to herpes simplex virus keratitis in humans, CHV-1 ulcerative keratitis may be associated with the development of chronic degenerative corneal disease in dogs. In the described dog, this chronic corneal disease included progressive corneal opacification because of partial limbal stem cell deficiency and neurotrophic keratitis. Long-term monitoring of dogs following resolution of active CHV-1 keratitis may be indicated, particularly when ulcerations persist for an extended period.
PMID: 22958361 [PubMed - indexed for MEDLINE]
Early histopathologic changes in the retina and optic nerve in canine primary angle-closure glaucoma.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:79-86
Authors: Scott EM, Boursiquot N, Beltran WA, Dubielzig RR
OBJECTIVE: To characterize the morphology of canine globes enucleated 1-5 days after the onset of overt clinical disease recognized by the owner.
PROCEDURES: Paraffin-embedded globes from 47 dogs with acute primary angle-closure glaucoma (PACG) and 10 control dogs free of ocular disease were sectioned in the vertical plane sampling the optic nerve. Hematoxylin and eosin (H&E)-stained sections were used to count ganglion cell numbers. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify cell death, and MHCII immunohistochemistry was used to evaluate for antigen-presenting phagocytes in a smaller subset of cases.
RESULTS: MHCII-labeled phagocytes were present in the optic nerve and retina within the first 24 h of documented glaucoma suggesting an early up-regulation. Globes removed within 1 day of overt clinical disease had a mild neutrophilic infiltrate in the retina and optic nerve as well as marked ganglion cell necrosis. By 5 days after clinical signs appear, there is a rapid decline in the number of ganglion cells and cell death detected by TUNEL labeling in the outer and inner nuclear layers of the retina, but not the ganglion cell layer. The neuropil of the optic nerve progresses from edema and neutrophilia to malacia.
CONCLUSIONS: These findings suggest that retinal and optic nerve degeneration in dogs with PACG progresses rapidly to irreversible tissue loss within days of recognizable clinical disease.
PMID: 23826772 [PubMed - indexed for MEDLINE]
Restrictive orbital myofibroblastic sarcoma in a cat--cross-sectional imaging (MRI & CT) appearance, treatment, and outcome.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:123-9
Authors: Thomasy SM, Cissell DD, Arzi B, Vilches-Moure JG, Lo WY, Wisner ER, Dubielzig RR, Maggs DJ
A 16-year-old spayed female cat was evaluated for lagophthalmos and chronic exposure keratitis in both eyes. Ophthalmic examination revealed upper and lower eyelid entropion of the left eye (OS) and markedly decreased retropulsion, restricted eye movement, marked episcleral congestion, and severe keratitis of both eyes (OU). Magnetic resonance imaging of both orbits revealed extensive, irregular, contrast-enhancing tissue without evidence of osteolysis considered compatible with diffuse inflammatory tissue. Feline herpesvirus DNA was not detected in conjunctival samples. Partial temporary tarsorrhaphies were placed OU, and the cat was treated with topically administered erythromycin ointment OU, orally administered famciclovir and prednisolone, and sublingually administered buprenorphine. Little improvement was noted after 2 weeks. Six weeks after initial presentation, a left exenteration was performed and histopathology was consistent with idiopathic sclerosing orbital pseudotumor (ISOP). Ten weeks after initial presentation, the patient represented for weight loss and jaw pain. Computed tomography demonstrated disease progression in the right orbit and the patient was euthanized. Histopathology of the decalcified skull revealed an aggressive and highly infiltrative mass involving the right orbit with extension to the maxilla, hard palate, nasal cavity and gingiva most consistent with feline restrictive orbital myofibroblastic sarcoma (FROMS). Clinical data from this patient support the reclassification of ISOP as FROMS. MRI and CT may provide supportive evidence for FROMS, but histopathology is necessary for definitive diagnosis. Aggressive and early surgical treatment, including bilateral exenteration, with adjunctive radiotherapy and/or chemotherapy should be considered for patients with FROMS.
PMID: 23281709 [PubMed - indexed for MEDLINE]
Characterization of ocular gland morphology and tear composition of pinnipeds.
Vet Ophthalmol. 2013 Jul;16(4):269-75
Authors: Kelleher Davis R, Doane MG, Knop E, Knop N, Dubielzig RR, Colitz CM, Argüeso P, Sullivan DA
OBJECTIVE: The importance of tear film integrity to ocular health in terrestrial mammals is well established, however, in marine mammals, the role of the tear film in protection of the ocular surface is not known. In an effort to better understand the function of tears in maintaining health of the marine mammal eye surface, we examined ocular glands of the California sea lion and began to characterize the biochemical nature of the tear film of pinnipeds.
PROCEDURES: Glands dissected from California sea lion eyelids and adnexa were examined for gross morphology, sectioned for microscopic analysis, and stained with hematoxylin and eosin. The tear film was examined using interferometry. Tears were collected from humans and pinnipeds for the analysis of protein and carbohydrate content.
RESULTS: The sea lion has sebaceous glands in the lid, but these glands are different in size and orientation compared with typical meibomian glands of terrestrial mammals. Two other accessory ocular glands located dorsotemporally and medially appeared to be identical in morphology, with tubulo-acinar morphology. An outer lipid layer on the ocular surface of the sea lion was not detected using interferometry, consistent with the absence of typical meibomian glands. Similar to human tears, the tears of pinnipeds contain several proteins but the ratio of carbohydrate to protein was greater than that in human tears.
CONCLUSIONS: Our findings indicate that the ocular gland architecture and biochemical nature of the tear film of pinnipeds have evolved to adapt to the challenges of an aquatic environment.
PMID: 23067374 [PubMed - indexed for MEDLINE]
Ocular comparative anatomy of the family Rodentia.
Vet Ophthalmol. 2013 Jul;16 Suppl 1:94-9
Authors: Rodriguez-Ramos Fernandez J, Dubielzig RR
There is little information regarding ocular anatomy and histology in many of the rodent species. Histological analyses for morphologic features were performed in 31 globes from 18 rodent species submitted to and archived at the Comparative Ocular Pathology Laboratory of Wisconsin. The following measurements were taken: thickness of the cornea, corneal epithelium, corneal stroma, Descemet's membrane, and retina. H&E sections were evaluated for the following anatomical features: presence of pigmented epithelial cells in the peripheral cornea, presence and location of Schlemm's canal, presence of iridal sphincter and dilator and ciliary body muscles, presence of pars plicata and plana, presence of retinal vessels, presence of lamina cribrosa, and presence of tapetum lucidum. The springhaas was the only rodent in our collection that presented a well-developed tapetum lucidum fibrosum. The presence of retinal vessels was variable: vessels were observed in all of the members of the mouse-related clade, except the springhaas and the beaver, in all of the squirrel-related clade members, and in none of the Ctenohystrica. In the flying squirrels, blood vessels extended to the outer limiting membrane in the photoreceptor layer. Beavers, chinchillas, capybara, and guinea pigs lacked vessels within the retina; however, they had vessels within the optic nerve head. Ground squirrels have an optic nerve head, which is linear in the horizontal plane and an asymmetric retina. The tree-dwelling squirrels have a rounded but still elongated optic nerve, and the flying squirrel has a round optic nerve head like all the other rodents.
PMID: 23734597 [PubMed - indexed for MEDLINE]
Septic implantation syndrome in dogs and cats: a distinct pattern of endophthalmitis with lenticular abscess.
Vet Ophthalmol. 2013 May;16(3):180-5
Authors: Bell CM, Pot SA, Dubielzig RR
OBJECTIVE: To summarize the clinical and pathologic findings in a group of dogs and cats with progressive clinical ocular disease, which were diagnosed with suppurative endophthalmitis and lens capsule rupture.
ANIMALS STUDIED: Twenty cats and forty-six dogs that underwent unilateral enucleation or evisceration for intractable uveitis and/or glaucoma.
PROCEDURE: Biopsy submission requests and microscopic case material were evaluated for clinical and histological features, including history of ocular trauma, duration of ocular disease, pattern of inflammation, and the presence of intralenticular microorganisms.
RESULTS: The median duration for cats and dogs was 6 and 5 weeks, respectively. A history of trauma was reported for four (20%) cats and 18 (39%) dogs. All confirmed cases of trauma-three in cats and 14 in dogs-were caused by a cat scratch. Microscopically, all cases had suppurative endophthalmitis centered on the lens, lens capsule rupture, cataract, and lenticular abscess. Infectious organisms were identified by Gram stain within the lens of 14 (70%) cats and 30 (65%) dogs. Gram-positive cocci were seen most commonly. Male cats were overrepresented as compared to females. There were no apparent gender, age or breed predilections in dogs.
CONCLUSIONS: A unique pattern of slowly progressive or delayed-onset endophthalmitis with lens capsule rupture, lenticular abscess, and frequently intralenticular microorganisms is associated with traumatic penetration of the globe and lens capsule. The term Septic Implantation Syndrome (SIS) is favored in lieu of 'phacoclastic uveitis' to avoid confusion with phacolytic uveitis and to clearly implicate the role of intralenticular microorganisms in the pathogenesis.
PMID: 22812929 [PubMed - indexed for MEDLINE]
Canine ocular onchocercosis in the United States is associated with Onchocerca lupi.
Vet Parasitol. 2013 Mar 31;193(1-3):297-301
Authors: Labelle AL, Maddox CW, Daniels JB, Lanka S, Eggett TE, Dubielzig RR, Labelle P
Canine ocular onchocerciasis has a worldwide distribution and has been associated in Europe with Onchocerca lupi based on morphologic and molecular analysis. In the United States, canine ocular onchocerciasis is reportedly associated with Onchocerca lienalis. This association is based solely on histopathologic examination of ocular tissues. The purpose of this study was to use molecular analysis of formalin-fixed, paraffin-embedded canine ocular tissue to determine the genetic identity of Onchocerca associated with canine ocular onchocerciasis in the United States. PCR and DNA sequencing of the mitochondrial cytochrome oxidase I (cox1) and NADH hydrogenase 5 (nd5) genes demonstrated >99% similarity between the sequences obtained from canine ocular tissues previously diagnosed with onchocerciasis. The obtained sequences were most similar to O. lupi (>99% similarity). This report confirms for the first time that O. lupi is associated with canine ocular onchocerciasis in the United States, contrary to previously published reports.
PMID: 23276598 [PubMed - indexed for MEDLINE]
Systemic distribution of viral antigen in alpacas persistently infected with bovine pestivirus.
Vet Pathol. 2013 Mar;50(2):308-17
Authors: Henningson JN, Steffen DJ, Topliff CL, Kurth KL, Dubielzig RR, Brodersen BW, Bedenice D, Eskridge KM, Callan RJ, Reggiardo C, Rupp GP, Kelling CL
Recently, confirmed occurrences of persistent bovine viral diarrhea virus (BVDV) infection in North American alpacas have raised concerns about the role of persistently infected (PI) alpacas in transmission of virus among herds, yet only limited pathological descriptions of persistent infections in alpacas have been reported. The objective of this study was to characterize BVDV antigen distribution in 10 PI alpacas of varying age and to compare viral antigen distribution and localization in tissues of PI alpacas with 5 PI calves of varying age. Ocular dysplasia was evident in 1 PI alpaca, constituting the first reported congenital ocular lesion in PI alpacas. Viral antigen was widely distributed in alpaca tissues and was prominent in neurons, endothelial cells, and vascular tunica media myocytes but had limited distribution in lymphoid tissues and moderate distribution in epithelium of several organ systems of alpacas. Macrophages in the alpaca gastrointestinal system submucosa and lymph node medullary sinuses often had prominent labeling. In addition, only 1 alpaca had antigen labeling in the bone marrow in contrast to PI cattle. Labeled cells in calf tissues were more widely distributed, occurring prominently in lymphoid and epithelial tissues. Common features of the 2 host species were widespread antigen labeling and absence of lymphoid depletion.
PMID: 22688584 [PubMed - indexed for MEDLINE]
Histopathological and immunohistochemical features of vitreoretinopathy in Shih Tzu dogs.
J Comp Pathol. 2013 Feb;148(2-3):230-5
Authors: Papaioannou NG, Dubielzig RR
Fifty cases of Shih Tzu ocular vitreoretinopathy were selected from the database of the Comparative Ocular Pathology Laboratory of Wisconsin. Cases with severe coexisting conditions (e.g. corneal disease, uveitis or endophthalmitis) were excluded. Microscopical changes were evaluated and immunohistochemistry was used to define spindle cells, gliosis and the presence of basement membranes in the vitreous. Expression of glial fibrillary acidic protein, vimentin and smooth muscle actin was also performed. The mean age of the 50 cases was 10.1 years (range 2.5-15 years). The most characteristic microscopical abnormalities (50/50 cases) were retinal detachment and extensive retinal tear. Additionally, extracellular, eosinophilic matrix material admixed with few spindle cells, and pre-iridal fibrovascular membrane, goniodysgenesis, secondary glaucoma, hypermature and subcapsular cataract were detected. The spindle cells within the collagen matrix were strongly labelled for expression of vimentin, with weaker expression of smooth muscle actin.
PMID: 22819016 [PubMed - indexed for MEDLINE]
Bilateral buphthalmia in a 4-month-old Texas longhorn steer.
Vet Pathol. 2013 Jan;50(1):212-4
Authors: Jones ML, Beck AP, Dubielzig RR
Congenital ocular disease occurs uncommonly in cattle, with multiple abnormalities reported only sporadically in the literature. This report describes a case of anterior segment dysgenesis resulting in glaucoma in a 4-month-old Texas Longhorn steer. On clinical exam, bilateral buphthalmia was present and intraocular pressures exceeded 47 mm Hg in both eyes. On histopathologic examination, the iridocorneal angle and filtration apparatus were distorted due to collapse of the ciliary cleft and anterior displacement of the anterior portion of the ciliary body. No evidence of inflammation or other causes of glaucoma were recognized.
PMID: 22688589 [PubMed - indexed for MEDLINE]
Ocular lesions following suspected lightning injury in a horse.
Vet Ophthalmol. 2012 Jul;15(4):276-9
Authors: Evans PM, Armour MD, Dubielzig RR
PURPOSE: To describe the gross and histopathological ocular findings in a horse following suspected lightning injury.
METHODS: The eyes of a 2-year-old thoroughbred gelding were clinically and histopathologically evaluated following a severe lightning storm following euthanasia because of visual impairment.
RESULTS: Severe corneal edema and hydrops were noted clinically oculus dexter. Indirect ophthalmoscopy revealed bilateral symmetrical raised hyporeflective peripapillary geographic lesions. Histopathologic evaluation revealed corneal edema in the right eye with normal corneal endothelium. Posterior segment evaluation revealed localized, pericentral choroidal lesions characterized by the presence of hemorrhage, early fibrosis, and minimal lymphoplasmacytic, neutrophilic, and histiocytic inflammation with spindle cell proliferation. The retinas overlying the choroidal lesions were necrotic and mostly absent. Peripheral to the focal lesion, the retina abruptly returned to normal architecture peripheral to a zone of apoptotic photoreceptors. Centrally, swollen axons extended into the optic disc.
CONCLUSIONS: There have been few descriptions of ocular lesions in animals following suspected lightning injury. We believe these findings to be unique because of the type of thermal injury that may be characteristic of lightening injury. We do not know whether these lesions would have progressed over time.
PMID: 22212169 [PubMed - indexed for MEDLINE]
Osteosarcoma of the maxilla with concurrent osteoma in a southern sea otter (Enhydra lutris nereis).
J Comp Pathol. 2012 Aug-Oct;147(2-3):391-6
Authors: Rodriguez-Ramos Fernandez J, Thomas NJ, Dubielzig RR, Drees R
Southern sea otters (Enhydra lutris nereis) are threatened marine mammals that belong to the family Mustelidae and are native to the coast of Central California. Neoplasia is reported infrequently in sea otters. An adult female free-ranging southern sea otter was found alive at Pebble Beach, Monterey County, California, on January 1st, 1994 and died soon after capture. The carcass was submitted to the US Geological Survey - National Wildlife Health Center for necropsy examination. Grossly, a mass with rubbery texture was firmly attached to the left maxillary region of the skull and the nasopharynx was occluded by soft neoplastic tissue. Post-mortem skull radiographs showed an oval, smoothly marginated mineralized opaque mass centered on the left maxilla, extending from the canine tooth to caudal to the molar and replacing portions of the zygomatic arch and palatine and temporal bones. The majority of the mass protruded laterally from the maxilla and was characterized by central homogeneous mineral opacity. Microscopically, the mass was characterized by fully differentiated lamellar non-osteonal bone that expanded beyond the margins of the adjacent normal osteonal bone. Sections of the nasopharyngeal mass were comprised of moderately pleomorphic cells with bony stroma. Gross, microscopical and radiological findings were compatible with maxillary osteosarcoma with concurrent osteoma.
PMID: 22520807 [PubMed - indexed for MEDLINE]
Angiofibroma of the nasal cavity in 13 dogs.
Vet Comp Oncol. 2011 Dec;9(4):304-9
Authors: Burgess KE, Green EM, Wood RD, Dubielzig RR
This case series describes a rare entity, nasal angiofibroma, in 13 dogs that were presented to the University of Wisconsin, School of Veterinary Medicine from 1988 to 2000. All dogs in this case series presented with clinical signs and radiographic changes that were strongly suggestive of a locally invasive neoplasm. However, histopathology completed on transnostral core biopsy samples revealed benign appearing vascular proliferation with secondary lymphosuppurative inflammation was established despite cytologic criteria of malignancy present in five dogs. On the basis of the outcomes in this case series, nasal angiofibroma should be considered a differential for dogs presenting with clinical signs consistent with a malignant nasal tumour.
PMID: 22077412 [PubMed - indexed for MEDLINE]
A slowly progressive retinopathy in the Shetland Sheepdog.
Vet Ophthalmol. 2011 Jul;14(4):227-38
Authors: Karlstam L, Hertil E, Zeiss C, Ropstad EO, Bjerkås E, Dubielzig RR, Ekesten B
OBJECTIVE: To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study.
PROCEDURE: Ophthalmic examination including slit-lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course-test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark-adapted b-wave amplitudes. SPR1-dogs had ophthalmoscopic signs of SPR, but normal dark-adapted b-wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark-adapted b-wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination.
RESULTS: The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper-reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b-wave amplitudes throughout dark-adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod-cone degeneration ( prcd )-mutation in three dogs with SPR was negative.
CONCLUSION: Slowly progressive retinopathy is a generalized rod-cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper-reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd-mutation.
PMID: 21733063 [PubMed - indexed for MEDLINE]
Superficial corneal squamous cell carcinoma occurring in dogs with chronic keratitis.
Vet Ophthalmol. 2011 May;14(3):161-8
Authors: Dreyfus J, Schobert CS, Dubielzig RR
OBJECTIVE: Canine corneal squamous cell carcinoma (SCC) is a rare tumor, with only eight cases previously published in the veterinary literature. The Comparative Ocular Pathology Lab of Wisconsin (COPLOW) has diagnosed 26 spontaneously occurring cases, 23 in the past 4 years. This retrospective study describes age and breed prevalence, concurrent therapy, biologic behavior, tumor size and character, and 6-month survival rates after diagnosis.
RESULTS: A search of the COPLOW database identified 26 corneal SCC cases diagnosed from 1978 to 2008. There is a strong breed predilection (77%) in brachycephalic breeds, particularly those prone to keratoconjunctivitis sicca. The mean age was 9.6 years (range 6-14.5 years). Follow-up information >6 months was available for 15 of 26 cases. Recurrence occurred in the same eye in nine cases, seven of which were incompletely excised at the time of first keratectomy. No cases were known to have tumor growth in the contralateral eye and no cases of distant metastases are known. Where drug history is known, 16 of 21 dogs had a history of treatment with topical immunosuppressive therapy (cyclosporine or tacrolimus) at the time of diagnosis.
CONCLUSION: Chronic inflammatory conditions of the cornea and topical immunosuppressive therapy may be risk factors for developing primary corneal SCC in dogs. SCC should be considered in any differential diagnosis of corneal proliferative lesions. Superficial keratectomy with complete excision is recommended, and the metastatic potential appears to be low.
PMID: 21521439 [PubMed - indexed for MEDLINE]
Canine conjunctival mast cell tumors: a retrospective study.
Vet Ophthalmol. 2011 May;14(3):153-60
Authors: Fife M, Blocker T, Fife T, Dubielzig RR, Dunn K
OBJECTIVE: To describe signalment, clinical presentation, treatment, recurrence rate, and outcome of canine conjunctival mast cell tumors (MCTs).
DESIGN: Retrospective study.
PROCEDURES: Canine cases were selected from the Comparative Ocular Pathology Laboratory of Wisconsin, Eye Path Lab of the UK, and California Eye Care for Animals. Thirty-two canine patients were identified as having a MCT presumed to be arising primarily from the conjunctiva. Data were collected from pathology submission request forms; additional information was collected by means of a questionnaire distributed to the veterinary ophthalmologist or veterinarian who performed the surgery. Data collected included age, gender, breed, location of tumor, dimensions of tumor, duration and growth rate, additional diagnostics, surgical descriptions, adjunctive treatment, histologic description, special stains, number of recurrences, and final outcome.
RESULTS: Thirty-two dogs with 33 conjunctival MCTs meeting search criteria were identified. All dogs underwent surgical excision as the primary treatment. Surgical margins were evaluated for 30 tumors and were reported as: incomplete margins in 25 cases, narrow in four cases and complete in one case. Histologic grade was provided for 33 of 33 MCTs and included 10 low (30%), 18 intermediate (55%) and five high-grade (15%) tumors. Follow up information was received for 25 dogs. Four died of unrelated causes, two had local recurrence, 15 were currently disease free (mean 21.4 months postoperatively) and four were reported to be disease free at the reported rechecks but were lost to long term follow up (mean 13 months postoperatively). No dogs in the study were identified that died of MCT related disease.
PMID: 21521438 [PubMed - indexed for MEDLINE]
Diagnostic features of feline restrictive orbital myofibroblastic sarcoma.
Vet Pathol. 2011 May;48(3):742-50
Authors: Bell CM, Schwarz T, Dubielzig RR
A progressive debilitating disease of the orbit and adjacent connective tissues of cats has historically been called feline orbital pseudotumor. The authors reviewed clinical, histopathologic, and diagnostic imaging features of this disease in 12 cases from the Comparative Ocular Pathology Laboratory of Wisconsin. The cats' ages ranged from 7 to 16 years (mean, 10.8 years). All cats had a history of severely restricted mobility of the globe and eyelids with secondary corneal disease. Eleven cats (92%) had concurrent involvement of the contralateral eye and/or the oral cavity. Diffuse scleral or episcleral thickening was seen with computed tomography in all clinically affected eyes. Histologically, an insidious infiltration of neoplastic spindle cells in the orbit, eyelids, and periorbital skin and soft tissues, with collagen deposition and a few perivascular lymphocytes, led to entrapment and restricted mobility of the eyelids and orbital tissues. The tumor failed to form a discrete mass, and it spread along fascial planes to the contralateral orbit and eyelids and/or the lips and oral cavity. In all tested cases (n = 10), neoplastic cells were immunohistochemically positive for vimentin, S100 protein, and smooth muscle actin. The authors adopted the term feline restrictive orbital myofibroblastic sarcoma to reflect the restricted mobility of the eyelids and globe and the imaging and histologic features of an invasive yet low-grade myofibroblastic sarcoma.
PMID: 20516295 [PubMed - indexed for MEDLINE]
Multiple congenital ocular anomalies in Icelandic horses.
BMC Vet Res. 2011;7:21
Authors: Andersson LS, Axelsson J, Dubielzig RR, Lindgren G, Ekesten B
BACKGROUND: Multiple congenital ocular anomalies (MCOA) syndrome is a hereditary congenital eye defect that was first described in Silver colored Rocky Mountain horses. The mutation causing this disease is located within a defined chromosomal interval, which also contains the gene and mutation that is associated with the Silver coat color (PMEL17, exon 11). Horses that are homozygous for the disease-causing allele have multiple defects (MCOA-phenotype), whilst the heterozygous horses predominantly have cysts of the iris, ciliary body or retina (Cyst-phenotype). It has been argued that these ocular defects are caused by a recent mutation that is restricted to horses that are related to the Rocky Mountain Horse breed. For that reason we have examined another horse breed, the Icelandic horse, which is historically quite divergent from Rocky Mountain horses.
RESULTS: We examined 24 Icelandic horses and established that the MCOA syndrome is present in this breed. Four of these horses were categorised as having the MCOA-phenotype and were genotyped as being homozygous for the PMEL17 mutation. The most common clinical signs included megaloglobus, iris stromal hypoplasia, abnormal pectinate ligaments, iridociliary cysts occasionally extending into the peripheral retina and cataracts. The cysts and pectinate ligament abnormalities were observed in the temporal quadrant of the eyes. Fourteen horses were heterozygous for the PMEL17 mutation and were characterized as having the Cyst-phenotype with cysts and occasionally curvilinear streaks in the peripheral retina. Three additional horses were genotyped as PMEL17 heterozygotes, but in these horses we were unable to detect cysts or other forms of anomalies.One eye of a severely vision-impaired 18 month-old stallion, homozygous for the PMEL17 mutation was examined by light microscopy. Redundant duplication of non-pigmented ciliary body epithelium, sometimes forming cysts bulging into the posterior chamber and localized areas of atrophy in the peripheral retina were seen.
CONCLUSIONS: The MCOA syndrome is segregating with the PMEL17 mutation in the Icelandic Horse population. This needs to be taken into consideration in breeding decisions and highlights the fact that MCOA syndrome is present in a breed that are more ancient and not closely related to the Rocky Mountain Horse breed.
PMID: 21615885 [PubMed - indexed for MEDLINE]
Anterior uveal spindle cell tumor in a cat.
Vet Ophthalmol. 2010 Nov;13(6):387-90
Authors: Evans PM, Lynch GL, Dubielzig RR
PURPOSE: To describe a case of anterior uveal spindle cell tumor in a cat with features similar to spindle cell tumor of blue eyed dogs.
METHODS: A 10-year-old female spayed domestic short-haired cat was referred for an iris mass OS. The mass was solitary, nodular, nonpigmented, located medially, and causing dyscoria. A diagnosis of a benign epithelial tumor was suggested by a FNA of the mass. The cat was lost to follow-up for 2 years, after which time she re-presented with glaucoma, blindness and grossly evident iridal mass enlargement OS. Transconjunctival enucleation was performed and the globe submitted for histopathology.
RESULTS: Histopathology of the enucleated globe revealed the superior iris to be infiltrated and effaced by a large population of neoplastic spindle cells. The cells were arranged in streams and bundles and exhibited Antoni-A and Antoni-B tissue patterns, which are characteristic of Schwann cell tumors. Mitotic figures were rare and cellular pleomorphism moderate. Immunohistochemical staining was positive for S-100 protein and glial fibrillary acidic protein (GFAP), and negative for Melan-A. Interestingly, there was no histological evidence of glaucoma.
CONCLUSIONS: Based on its histopathologic characteristics, this iris tumor was diagnosed as a Schwann cell variant of a peripheral nerve sheath tumor (PNST) closely resembling the spindle cell tumor of blue-eyed dogs. Anterior uveal PNST has not been previously reported in cats to the authors' knowledge. The presence of Antoni type A and type B tissue patterns along with immunohistochemical staining may facilitate a diagnosis of PNST and rule out malignant melanoma.
PMID: 21182724 [PubMed - indexed for MEDLINE]
Anatomy of the California sea lion globe.
Vet Ophthalmol. 2010 Sep;13 Suppl:63-71
Authors: Miller SN, Colitz CM, Dubielzig RR
OBJECTIVE: This study analyzed the morphology of the California sea lion globe to determine what features may contribute to their characteristic visual abilities.
PROCEDURE: Globes from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) collection were examined from gross photographs and microscopic sections stained with hematoxylin and eosin, trichrome, smooth muscle actin, and alcian blue periodic acid-Schiff (PAS). Transmission electron microscopy of the cornea and iris was also performed.
CLINICAL RESULTS: There was a round, flattened area ventromedial to the axial cornea. The pupil was tear-drop shaped. Pectinate ligaments were visible without magnification. The retina was holangiotic, containing numerous spoke-like venules and arterioles. The tapetum was green encompassing the entire fundus. The optic nerve was unmyelinated. HISTOLOGICAL RESULTS: The sclera was thinnest equatorially and thickest at the limbus and posterior pole. Bowman's layer was difficult to see by light microscopy but clear with transmission electron microscopy. The cornea had a thick epithelium, thin endothelium and Descemet's membrane, and the stroma thinned axially. The dilator muscle was absent near the pupil, but enlarged and mingled with the sphincter muscle near the iris base. A large, wide ciliary cleft with prominent trabeculae and a single continuous pectinate ligament was present. The corneoscleral trabecular meshwork was discontinuous. A round lens attached to the ciliary body via direct attachment to ciliary processes and delicate zonular ligaments. There was a circumferential muscle at the base of the ciliary processes. A thick tapetum covered the entire fundus except peripherally. The retina was characterized by sparse, large ganglion cells.
PMID: 20840092 [PubMed - indexed for MEDLINE]
A quantitative rabbit model of vaccinia keratitis.
Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4531-40
Authors: Altmann S, Emanuel A, Toomey M, McIntyre K, Covert J, Dubielzig RR, Leatherberry G, Murphy CJ, Kodihalli S, Brandt CR
PURPOSE: The goal of this study was to use multiple quantitative disease measures to evaluate the effect of various viral inocula on the development of vaccinia keratitis in rabbits.
METHODS: Trephined eyes of female rabbits were infected with 10(4), 10(5), 10(6), or 10(7) plaque-forming units (pfu) of the Dryvax strain of the vaccinia virus and scored daily for disease for 14 days according to a modification of the MacDonald-Shadduck scoring system. Ocular viral titers and vaccinia-specific antibody titers were determined by plaque assay and ELISA, respectively.
RESULTS: The amount of virus used for infection affected the severity of disease, with 10(4) pfu eliciting milder keratitis after delayed onset compared with higher amounts of virus. At inocula above 10(5) pfu the course and severity of corneal disease was not significantly different. The time to reach peak titers was delayed in the 10(4) group but peak titers were similar in all groups. Severe conjunctival chemosis interfered with scoring in animals infected with 10(6) or 10(7) pfu. Virus-specific antibody titers were similar in all groups at day 14. Body weights decreased less than 10% in all groups.
CONCLUSIONS: The course of vaccinia keratitis in rabbits paralleled that in humans. A viral inoculum of 10(5) pfu/eye was determined to be optimal for use in further studies of vaccinia keratitis.
PMID: 20375331 [PubMed - indexed for MEDLINE]
Orbital extraskeletal osteosarcoma following enucleation in a cat: a case report.
Vet Ophthalmol. 2010 May;13(3):179-83
Authors: Groskopf BS, Dubielzig RR, Beaumont SL
OBJECTIVE: We present a unique case of a feline orbital extraskeletal osteosarcoma that developed 5 years post-enucleation.
HISTORY: In 2002, an ophthalmologist enucleated the left eye of a 2-year-old neutered male DSH and submitted it to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). COPLOW diagnosed the left eye with feline diffuse iris melanoma. In June 2007, the cat presented to another veterinarian for moderate swelling of the enucleation site. Palpation suggested a firm mass along the lateral orbital rim and an exploratory orbitotomy revealed a cyst with a mass adhered to it and the ventrolateral orbital rim. The cyst and mass were excised by the veterinarian and submitted to COPLOW. COPLOW diagnosed the tissue as an orbital conjunctival inclusion cyst and an acquired orbital osteosarcoma.
CONCLUSIONS: Following the enucleation, retained conjunctival epithelium became embedded in the connective tissue of the orbit and caused a cyst to develop. The cyst wall consisted of a myofibroblastic collagen-rich matrix and acted as a nidus of chronic irritation and tumor growth. This orbital osteosarcoma resembles feline vaccine-associated sarcomas (VAS), feline post-traumatic ocular sarcomas, and microchip-associated sarcomas in terms of it histopathology and its hypothesized pathogenesis related to exposure to antigenic material such as implanted epithelium, lens protein, vaccine components, and microchips as foreign bodies.
PMID: 20500718 [PubMed - indexed for MEDLINE]
Canine mesenchymal hamartoma of the eyelid.
Vet Ophthalmol. 2010 Mar;13(2):94-8
Authors: Kafarnik C, Calvarese S, Dubielzig RR
OBJECTIVE: Characterization of a benign disease syndrome involving the eyelids of dogs, describing the signalment, clinical appearance, anatomic location, and pathologic features.
ANIMAL STUDIED: The records and submitted tissue of 10 dogs with mesenchymal hamartomatous lesions of the periocular connective tissues were retrieved from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database.
PROCEDURE: The submitted tissue in each case was stained with hematoxilyn & eosin and Masson's Trichrome stain and examined histopathologically. Clinical information was collected from the submission requests. The clinical history, treatment, and follow-up are described in more detail for one of the 10 dogs.
RESULTS: Seven different breeds, including four Golden Retrievers, were represented. The ages of affected dogs ranged from 6 to 11 years. Eight of 10 lesions were located at the temporal canthus, ranging in diameter from 0.6 to 3 cm. Clinically, the masses were subcutaneous, firm, lobular soft-tissue growths, which were in some cases adherent to the underlying orbital rim, and in others, freely palpable between the skin and conjunctiva of the eyelid. Histologically, all had distinct margins but were not encapsulated and contained normal appearing collagen-rich connective tissue with some adipose tissue. Five also contained fully differentiated skeletal muscle tissue arranged in poorly formed aggregates or as individual muscle fibers.
CONCLUSION: Mesenchymal hamartoma of the eyelid has not been previously described. The mass has a predisposition to occur at the temporal canthus and should be included in the list of differential diagnoses of benign eyelid masses in dogs.
PMID: 20447027 [PubMed - indexed for MEDLINE]
Feline conjunctival melanoma: histopathological characteristics and clinical outcomes.
Vet Ophthalmol. 2010 Jan;13(1):43-6
Authors: Schobert CS, Labelle P, Dubielzig RR
PURPOSE: We report on the histopathology and clinical features of 21 cases of feline conjunctival melanoma.
METHODS: A total of 18 cases are from the COPLOW collection and three cases from Antech Diagnostics. We tabulated the location of the tumor, pigmentation, cell shape, mitotic index and presence of multinucleated tumor cells. Surveys were sent to referring ophthalmologists to obtain further information about each case.
RESULTS: The mean age of the cats was 12.4 years. A total of 11 cases were neutered males, six spayed females, and one each of intact female and male. Thirteen of the 21 cases were located on the bulbar conjunctiva, three on third eyelid only, three on palpebral conjunctiva. Sixteen tumors were pigmented while five were amelanotic. Seventeen of the cases consisted of round cell only while four cases were mixed populations of round and spindle cell. Fourteen of the cases contained multinucleated cells. The mitotic index ranged from 0 to 45 mitotic figures/10 HPF. Of the 13 cases with adequate follow-up information, four showed local recurrence while three reported metastasis. Eight cats had died at the time of the survey. Survival time post-diagnosis ranged from 0.5 to 36 months. Two cases had metastasized to the submandibular lymph nodes and in a third case, an abdominal mass was detected.
CONCLUSIONS: Feline conjunctival melanoma is most frequently found on the bulbar conjunctiva, are mostly round cells and suggest that conjunctival melanoma in cats has a poorer long term prognosis than the same neoplasm in dogs.
PMID: 20149175 [PubMed - indexed for MEDLINE]
Canine pre-iridal fibrovascular membranes: morphologic and immunohistochemical investigations.
Vet Ophthalmol. 2010 Jan;13(1):4-13
Authors: Zarfoss MK, Breaux CB, Whiteley HE, Hamor RE, Flaws JA, Labelle P, Dubielzig RR
OBJECTIVE: Pathologic intraocular neovascularization is a key component of many canine ophthalmic diseases such as uveitis, retinal detachment, intraocular neoplasms, and corneal perforation. The purpose of this study was to evaluate the structure of pre-iridal fibrovascular membranes (PIFMs) associated with several different disease processes and to identify specific factors associated with their development in the canine eye.
PROCEDURE: This study examined 36 enucleated canine eyes with the diagnosis of PIFM and one of the following: lens-induced uveitis, retinal detachment, iridociliary adenoma, corneal perforation, severe hyphema, or vitreal gliovascular membranes (canine ocular gliovascular syndrome, COGS). Three histologic stains and six immunohistochemical stains were performed in all 36 PIFM eyes and four histologically normal eyes, including: hematoxylin and eosin, alcian blue periodic acid schiff (PAS), Masson's trichrome, platelet endothelial cell adhesion molecule-1 (CD31), smooth muscle actin, vimentin, laminin, vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2).
RESULTS: Pre-iridal fibrovascular membrane extracellular matrix staining was consistent with collagen and mucins in all cases and positive for laminin in most cases. All PIFMs contained CD31-positive vessels and predominantly lymphoplasmacytic inflammation. Both PIFM vessels and spindle cells were positive for laminin, vimentin, smooth muscle actin, VEGF, and COX-2. Secondary intraocular pathology and immunohistochemical staining of other intraocular structures are also reported.
CONCLUSIONS: Pre-iridal fibrovascular membrane morphology and immunohistochemical characteristics were similar across six canine disease processes, suggesting analogous pathophysiologic mechanisms. COX-2 and VEGF were identified using immunohistochemistry and may play a role in PIFM development.
PMID: 20149169 [PubMed - indexed for MEDLINE]
Proof of principle of ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy.
Vet Radiol Ultrasound. 2010 Sep-Oct;51(5):561-70
Authors: Lawrence JA, Forrest LJ, Turek MM, Miller PE, Mackie TR, Jaradat HA, Vail DM, Dubielzig RR, Chappell R, Mehta MP
Intensity-modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared with a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT-treated and 2D-treated dogs was 420 and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared with historical controls treated with 2D-RT.
PMID: 20973393 [PubMed - indexed for MEDLINE]
Viral replication rate regulates clinical outcome and CD8 T cell responses during highly pathogenic H5N1 influenza virus infection in mice.
PLoS Pathog. 2010;6(10):e1001139
Authors: Hatta Y, Hershberger K, Shinya K, Proll SC, Dubielzig RR, Hatta M, Katze MG, Kawaoka Y, Suresh M
Since the first recorded infection of humans with H5N1 viruses of avian origin in 1997, sporadic human infections continue to occur with a staggering mortality rate of >60%. Although sustained human-to-human transmission has not occurred yet, there is a growing concern that these H5N1 viruses might acquire this trait and raise the specter of a pandemic. Despite progress in deciphering viral determinants of pathogenicity, we still lack crucial information on virus/immune system interactions pertaining to severe disease and high mortality associated with human H5N1 influenza virus infections. Using two human isolates of H5N1 viruses that differ in their pathogenicity in mice, we have defined mechanistic links among the rate of viral replication, mortality, CD8 T cell responses, and immunopathology. The extreme pathogenicity of H5N1 viruses was directly linked to the ability of the virus to replicate rapidly, and swiftly attain high steady-state titers in the lungs within 48 hours after infection. The remarkably high replication rate of the highly pathogenic H5N1 virus did not prevent the induction of IFN-β or activation of CD8 T cells, but the CD8 T cell response was ineffective in controlling viral replication in the lungs and CD8 T cell deficiency did not affect viral titers or mortality. Additionally, BIM deficiency ameliorated lung pathology and inhibited T cell apoptosis without affecting survival of mice. Therefore, rapidly replicating, highly lethal H5N1 viruses could simply outpace and overwhelm the adaptive immune responses, and kill the host by direct cytopathic effects. However, therapeutic suppression of early viral replication and the associated enhancement of CD8 T cell responses improved the survival of mice following a lethal H5N1 infection. These findings suggest that suppression of early H5N1 virus replication is key to the programming of an effective host response, which has implications in treatment of this infection in humans.
PMID: 20949022 [PubMed - indexed for MEDLINE]
Computed tomography characteristics of canine tracheobronchial lymph node metastasis.
Vet Radiol Ultrasound. 2010 Jul-Aug;51(4):397-403
Authors: Ballegeer EA, Adams WM, Dubielzig RR, Paoloni MC, Klauer JM, Keuler NS
Tracheobronchial lymph node evaluation is critical for accurate staging of canine thoracic neoplasia and is more accurately achieved with computed tomography (CT) than radiography. Thoracic CT scans of 18 canine patients with known tracheobronchial lymph node histopathology and 10 clinically normal dogs were compared to establish if enlargement or contrast enhancement pattern correlated with metastatic status. Absolute lymph node size and three anatomically normalized lymph node ratios were significantly correlated with metastasis or severe granulomatous lymphadenitis (P < 0.0003). Transverse maximum lymph node diameter of 12 mm or lymph node to thoracic body ratio of 1.05 are proposed cutoffs, above which metastatic involvement is very likely; however, only minimal accuracy was gained with normalized ratios. Lymph node contrast enhancement pattern was also significantly correlated to disease. A heterogenous and/or ring pattern was related to metastatic disease (P = 0.03). Recommended protocol for CT examination of the tracheobronchial lymph nodes is 1-1.5 mm slices and intervals, intravenous contrast, and control of respiratory motion.
PMID: 20806871 [PubMed - indexed for MEDLINE]