Objective—To determine the effect of acute (clinical history of glaucoma for ≤ 2 days) and chronic (clinical history of glaucoma for 7 days) goniodysgenesis-related glaucoma on various stress-inducible proteins in canine retinas.
Sample Population—15 canine retinas (5 from control eyes, 5 from eyes with acute glaucoma, and 5 from eyes with chronic glaucoma).
Procedures—Globes were obtained from the Comparative Ocular Pathology Laboratory of Wisconsin. Eyes were characterized on the basis of clinical history. The distribution of glial fibrillary acidic protein (GFAP), heat shock protein (HSP) 60, and hypoxia-inducible factor (HIF)-1α was determined by use of immunohistochemical analysis.
Results—Intensity of GFAP staining increased with temporal progression of glaucoma. In specimens from eyes with acute glaucoma, staining for HSP 60 was more variable among eyes, compared with that of the control eyes, whereas specimens from eyes with chronic glaucoma typically had less HSP 60 staining than was evident in the control eyes. Neither the control eyes nor specimens from the eyes with acute glaucoma had nuclear staining for HIF-1α in the retinas. Four of 5 specimens from eyes with chronic glaucoma had nuclear staining for HIF-1α in cells of the outer nuclear layer. Staining for HIF-1α was distributed segmentally in regions of more severe atrophy and disorganization.
Conclusions and Clinical Relevance—Results of the study reported here supported a clinically evident, rapidly progressive disease with a shift in cell regulation between acute and chronic glaucoma and also supported ischemia as a mechanism of retinal injury in this disease.
Objective—To investigate cellular death in the neurosensory
portion of the retina during the first 7 days
after onset of clinical signs of overt primary angle-closure
glaucoma (PACG) in dogs.
Sample Population—14 globes from dogs with
PACG and 2 normotensive globes from dogs with
PACG in the opposite eye.
Procedures—Retinas were examined via light
microscopy and terminal deoxynucleotidyl transferase-
mediated biotin-dUTP nick end-labeling.
Results—Necrosis of ganglion cells and segmental
degeneration of the nerve fiber layer rapidly progressed
to scattered full-thickness retinal attenuation
and disorganization. Apoptosis was detectable within
1 day after onset of PACG and was prominent by 3
days. Necrosis of ganglion cells was significantly
greater in retinas affected for ≤ 1 day, compared with
retinas affected for > 1 day. In contrast, apoptosis in
the ganglion cell layer was significantly greater in retinas
affected for > 1 day, compared with retinas affected
for ≤ 1 day. End-stage retinal atrophy was seen by
Conclusions and Clinical Relevance—The presence
of necrotic ganglion cells within 1 day after onset of
clinical signs suggests a narrow window of opportunity
to initiate effective therapy in overt PACG.
Photoreceptor death is an important and striking
aspect of neurosensory retinal degeneration after
acute onset of PACG. (Am J Vet Res 2002;63:257–261)
Objective—To determine whether cyclooxygenase-2 (COX-2) is expressed in benign or malignant canine uveal melanocytic neoplasms and whether expression correlates with malignancy.
Sample Population—Tissue sections from 71 globes; 57 with benign (n = 15), malignant (34), or mixed (8) uveal melanocytic neoplasms; 10 with nonneoplastic disease; and 4 with no abnormalities.
Procedures—Bleached sections from all globes and canine kidney were incubated with mouse monoclonal antibody directed against rat COX-2 protein or mouse antibody isotype control. Location, intensity, and percentage of immunolabeled cells were scored.
Results—Expression of COX-2 was detected in all but 5 globes, all of which contained neoplasms. Expression of COX-2 was detected in regions infiltrated by neoplasia in 21 globes; however, definitive labeling of tumor cells was detected in only 2 of those. In the remaining 19 globes, COX-2 expression was detected in areas also labeled in globes without disease and globes with nonneoplastic disease, especially the aqueous outflow tract and ciliary body. However, only globes with uveal malignant melanomas had detectable COX-2 expression in the iris. Expression of COX-2 was detected in the ciliary body of more globes with uveal malignant melanoma (20/34) than in those without disease (1/4), with nonneoplastic disease (4/10), or with melanocytoma (3/15) or mixed neoplasms (3/8).
Conclusions and Clinical Relevance—Canine globes with uveal melanocytic neoplasia appeared to express COX-2 in similar sites and with similar intensity as globes without neoplasia. Differentiation of benign from malignant canine uveal melanocytic neoplasms was not possible.
Objective—To determine whether retinal damage in
dogs with primary glaucoma (PG) is consistent with
ischemia-induced glutamate toxicosis.
Sample Population—Retinal tissue sections from 25
dogs with PG and 12 normotensive control dogs.
Procedure—Retinal sections from control and glaucomatous
dogs were stained for morphometric and
terminal deoxynucleotidyl transferase-mediated dUTP
nick-end labeling (TUNEL) analyses to determine
whether retinal damage was consistent with glutamate
toxicosis. Immunohistochemical analysis was
performed to detect ischemia-like loss of glutamate
from neurons in damaged areas.
Results—In severely damaged glaucomatous retinas,
all neurosensory layers had focal regions that were
thin or disrupted. There was less thinning of the outer
nuclear layer (ONL) and inner nuclear layer (INL) in
moderately damaged retinas than in severely damaged
retinas. Acute signs of damage in the INL included
cells with dark, condensed chromatin and lightly
stained cytoplasm interspersed with a few TUNELpositive
cells, which was consistent with glutamate
toxicosis. Glutamate immunoreactivity was reduced
in thin areas and in damaged cells of the INL and
ONL, which was consistent with glutamate release in
damaged areas. Glutamate immunoreactivity was
increased in putative Müller cells in damaged areas,
which also was consistent with glutamate release.
Conclusions and Clinical Relevance—Retinal damage
in dogs with PG differs in intensity in focal areas.
Damage in affected regions resembles damage
induced by glutamate. Glutamate is lost from damaged
neurons and accumulates in Müller cells, which
is consistent with increased glutamate release contributing
to the damage. Glutamate antagonists may
protect INL cells in dogs with glaucoma. (Am J Vet
Objective—To characterize the effects of oral administration of a high dose of enrofloxacin to cats.
Animals—24 (12 male and 12 female) young healthy cats.
Procedures—Cats were allocated on the basis of sex into 2 groups (4 males and 4 females/ group) from which 3 subgroups for 3 durations (3, 5, or 7 days) of enrofloxacin (50 mg/kg, PO, q 24 h) or control solution (1 mL of water, PO, q 24 h) administration that began on day −1 were created. Funduscopic examinations were performed daily. Electroretinography (ERG) was performed before and every 2 to 3 days after the start of oral administration. Four cats/study group were euthanized on days 3, 5, and 7, and eyes were collected for light and electron microscopic evaluations.
Results—Neurologic, funduscopic, and ERG abnormalities were evident only in cats administered enrofloxacin. Funduscopic changes (granular appearance or graying of the area centralis) were noticed on or before day 3 (after only 3 days of enrofloxacin administration), with subsequent similar changes along the visual streak. Vascular attenuation (between days 2 and 4) and generalized tapetal hyperreflectivity (between days 5 and 7) followed. Reduction in b-wave ERG amplitude preceded funduscopic changes. Morphologic changes in the photoreceptor layers correlated with duration of enrofloxacin administration, with generalized degenerative changes evident after 3 doses.
Conclusions and Clinical Relevance—The study indicated that a high dose of enrofloxacin (50 mg/kg/d, PO) induced retinal and systemic changes. Enrofloxacin at 10 times the recommended dosage is acutely toxic to the outer retina of clinically normal cats.
Objective—To compare results of computed tomography (CT) and radiography with histopathologic findings in tracheobronchial lymph nodes (TBLNs) in dogs with primary lung tumors.
Design—Retrospective case series.
Animals—14 client-owned dogs.
Procedures—Criteria for inclusion were diagnosis of primary lung tumor, use of thoracic radiography and CT, and histologic confirmation of TBLN status. Medical records were reviewed for signalment; history; and physical examination, clinicopathologic, radiographic, CT, surgical, and histopathologic findings.
Results—Tracheobronchial lymphadenopathy was not identified via radiography in any dogs. Tracheobronchial lymphadenopathy was diagnosed in 5 dogs via CT. Six dogs had histologic confirmation of metastasis to TBLNs. Radiographic diagnosis yielded 6 false-negative and no false-positive results for tracheobronchial lymphadenopathy. Computed tomography yielded 1 falsenegative and no false-positive results. Sensitivity of CT for correctly assessing TBLN status was 83%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 89%. Dogs with lymphadenopathy via CT, histologic confirmation of TBLN metastasis, or primary tumors with a histologic grade > 1 had significantly shorter survival times than their counterparts.
Conclusions and Clinical Relevance—Results of CT evaluation of TBLN status were in agreement with histopathologic findings and more accurate than use of thoracic radiography for evaluating TBLNs in dogs with primary lung tumors. Computed tomography imaging should be considered as part of the staging process to more accurately assess the TBLNs in dogs with primary lung tumors.
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.
Case Description—6 dogs (10 eyes) with keratitis following long-term topical treatment with a carbonic anhydrase inhibitor (CAI) were evaluated. In 4 dogs (6 eyes), CAI treatment was discontinued. Three dogs (4 eyes) underwent enucleation because of end-stage corneal disease. One dog was treated differently in each eye and thus was represented in both aforementioned groups.
Clinical Findings—Following initiation of treatment with a CAI (ie, brinzolamide or dorzolamide), the median time to development of severe ocular signs was 266 days (range, 133 to 679 days). Clinically severe ocular signs included ulcerative and nonulcerative perilimbal keratitis or severe diffuse keratitis with marked vascularization. The keratitis was refractory to treatment with anti-inflammatory medications. Histologic and immunohistochemical examination of enucleated globes was performed in 3 affected dogs and in 1 dog with keratitis that recovered. Corneal lesions included 2 distinct inflammatory infiltrates with plasma cells predominating in the anterior stroma and both T cells and neutrophils in the epithelium. Stromal plasma cells and overlying epithelium exhibited strong positive immunoreactivity for IgG.
Treatment and Outcome—Topical CAI treatment was discontinued in 4 dogs after a median of 209 days (range, 44 to 433 days), and in these dogs, clinical improvement was evident within 2 to 4 days of CAI treatment cessation. Signs of keratitis resolved in 12 to 25 days in these 4 dogs, and median follow-up time after CAI discontinuation was 25.5 months (range, 6 to 42 months), during which time signs of corneal disease did not recur.
Clinical Relevance—On the basis of this small series, presumed topical CAI-associated keratitis in dogs appeared to be an uncommon immune-mediated disease that was not responsive to corticosteroid treatment. Affected patients improved rapidly, but only after discontinuation of CAI treatment. In dogs with glaucoma, clinicians should consider the development of punctate keratopathy and severe diffuse keratitis as potential adverse effects related to topical administration of CAIs, even after previously uneventful long-term use.
Objective—To characterize the clinical and morphologic
aspects of aqueous humor misdirection syndrome
(AHMS) in cats and provide a hypothesis
regarding its pathogenesis on the basis of detailed
analysis of affected cats.
Animals—32 cats (40 eyes).
Procedure—Medical records of cats in which AHMS
was diagnosed from July 1997 to August 2003 were
reviewed. In certain cats, results of additional diagnostic
testing were also obtained, including A-scan,
B-scan, and high-resolution ultrasonography; streak
retinoscopy; video keratometry; and infrared neutralizing
videoretinoscopy as well as results of analysis of
flash-frozen sections and histologic examination of
Results—Cats had a uniformly shallow anterior
chamber, intact lens zonules, and a narrowed
approach to an open iridocorneal angle. Mean age of
affected cats was 11.7 years (range, 4 to 16 years),
and female cats were significantly more often affected
than male cats. Clinical signs included mydriasis,
decreased pupillary light reflex, decreased menace
response, and blindness. Glaucomatous changes to
the optic nerve, incipient cataracts, and eventual
blindness were seen. Intraocular pressure was ≥ 20
mm Hg (range, 12 to 58 mm Hg) in 32 of 40 eyes.
Ultrasonography and histologic examination revealed
a thickened anterior vitreal face interposed between
the lens and ciliary body, partial ciliary cleft collapse,
and cavitated vitreal regions. Various treatment
modalities were used.
Conclusions and Clinical Relevance—AHMS affects
older cats, especially females, and may result in glaucoma,
vision loss, and signs of ocular pain. Topical
administration of carbonic anhydrase inhibitors
decreased intraocular pressure. (J Am Vet Med Assoc