DIAGNOSTIC OPHTHALMOLOGY

History and clinical signs

A 10-year-old, spayed female, German shepherd-cross was referred to the Atlantic Veterinary College (AVC) ophthalmology service for acute onset of blindness. The dog had shown unusual behavior, characterized by periodic yelping and lethargy 1 mo prior to presentation at the AVC. The dog's behavior appeared to have improved transiently following treatment with cephalexin at 22 mg/kg body weight (BW), PO, for 10 d. On presentation, the dog was star-gazing and had difficulty navigating from the waiting area toward the examination room. Physical examination revealed that abnormalities were limited to the visual pathways; the dog was unable to negotiate an obstacle course under both photopic and scotopic conditions. Menace responses were absent bilaterally. Both pupils were dilated, and direct and consensual pupillary light reflexes (PLRs) were noted to be sluggish, bilaterally. Palpebral and oculocephalic reflexes were normal. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 24 mm/min in each eye. Applanation tonometry (Tonopen XL; Biorad Ophthalmic Division, Santa Clara, California, USA) showed that intraocular pressures were 15 mmHg and 16 mmHg in the right and left eye, respectively. Neither cornea retained fluorescein dye stain (Fluor-I-Strip AT; Ayerst Laboratories, St. Laurent, Quebec). Transilluminator and slit lamp biomicroscopic (Kowa SL-14; Kowa, Tokyo, Japan) examinations revealed mild bilateral scalloping of the pupillary margins, consistent with senile iris atrophy. Also, there were bilateral lenticular sclerosis and incipient anterior cortical cataracts of the right lens. Indirect ophthalmoscopy (Keeler All Pupil Indirect; Keeler Instruments, Broomall, Pennsylvania, USA) revealed similar findings in both eyes (Figure 1).

Figure 1. Fundic photograph from the right eye of a 10-year-old, German shepherd-cross with acute blindness. The left fundus was similar in appearance.

What are your clinical diagnoses, lesion localization, and diagnostic plans?

Our diagnoses were blindness, incipient anterior cortical cataracts, senile iris atrophy, and lenticular sclerosis. The unilateral and focal nature of the cataract excluded it as a cause of the loss of vision. The mild iris atrophy and lenticular sclerosis were incidental ocular changes associated with old age. Abnormalities were not present in either fundus (Figure 1). Given both the lack of ocular disease to account for the blindness and the concurrent mydriasis and sluggish PLRs, the cause of the blindness was localized to areas rostral to, and including, the optic chiasm. Conversely, blindness localized to lesions solely affecting the occipital (visual) cortex (cortical blindness) do not cause pupillary abnormalities. Differential diagnoses for prechiasmal blindness, in the face of normal fundi, include sudden acquired retinal degeneration (SARD), bilateral optic neuritis (retrobulbar or intracranial), and optic chiasmal neoplasm, granuloma, compression, or trauma. To differentiate among these diseases, an electroretinogram (ERG) was advised. A photopic ERG was done and revealed normal retinal function bilaterally, thereby ruling out SARD. A complete blood cell count and total body serum biochemical analysis were carried out; the results were unremarkable. Advanced imaging, in the forms of computed tomography (CT) or magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) collection were further diagnostic tests considered with a view to confirming the anatomic site of the lesion and the cause for the blindness. The owner consented to CT.

The dog was premedicated with midazolam (Midazolam Injection; Sabex, Boucherville, Quebec) at 0.2 mg/kg BW and butorphanol (Torbugesic; Ayerst Laboratories, Montreal, Quebec) at 0.1 mg/kg BW, IM. Anesthesia was induced with propofol (Rapinovet; Schering Canada, Pointe-Claire, Quebec) at 6 mg/kg BW, IV, and the dog was intubated. General anesthesia was maintained via a 2 mg/kg BW bolus of propofol, IV. The dog was positioned in sternal recumbency on the imaging table. Computed tomography scans were obtained by using a scanner (CT High Speed CTI; General Electric Medical Systems, Milwaukee, Wisconsin, USA). The tube potential was set at 120 kVp, and exposures were made at 320 mA (noncontrast) and 270 mA (contrast) with a tube angle of zero degrees. Contiguous 3 mm slices were taken in the transverse plane from the rostral limit of the eyes to the foramen magnum. A focal hypodense region was noted in the brain along the base of the calvarium, immediately proximal to the region of the pituitary gland in the noncontrast enhanced CT images. Extending for several slices caudal to the hypodense region, there was lateral ventricular asymmetry and the suggestion of a mass effect. Iodinated contrast material (Omnipaque; Nycomed Imaging AS, Oslo, Norway; 520 mg/kg of iodine) was injected, IV. Contrast enhanced CT images revealed a 15-mm × 14-mm × 13-mm, strongly enhancing mass in the pituitary region (Figure 2). Based on CT findings, a large pituitary mass was diagnosed. Given the appearance of the mass by CT, a pituitary gland macrotumor was the most likely diagnosis. This mass extended dorsorostrad, resulting in optic chiasmal compression and subsequent blindness, and hypothalamic compression. The owner opted not to pursue ancillary diagnostic tests for hyperadrenocorticism and metastatic neoplasia. Prednisone (Novo-Prednisone; Novopharm, Toronto, Ontario), 1 mg/kg BW, PO, was dispensed to help to reduce the inflammation associated with the pituitary mass. The dog was lost to follow-up.

Figure 2. Contrast enhanced transverse computed tomographic image of the head of a blind, 10-year-old German shepherd-cross. Note the large, 15 mm × 14 mm × 13 mm, strongly enhancing mass in the pituitary region (*).

Rostral and middle cranial fossa tumors affecting the optic chiasm and resulting in acute visual deficits in dogs have been reported (1). The primary presenting clinical signs were similar to those in this case and included blindness and dilated nonresponsive pupils (1). Behavioral changes, depression, and lethargy were also described following the onset of blindness (1). In cases of acute optic nerve and chiasmal disease, retinal function is normal, as it was in this dog.

Following elimination of retinal disease, advanced imaging in the forms of CT or MRI are advisable to determine lesion localization, therapeutic options, and prognosis. Computed tomography was used in this case due to its accessibility. Results of the CT scans revealed a pituitary mass > 13 mm in diameter; its appearance and size were suggestive of a pituitary macrotumor. Pituitary lesions, including chromophobe or corticotroph microadenoma, macroadenoma, and carcinoma, have been documented in dogs (2,3,4). Pituitary corticotroph macrotumors have been reported to occur in 10% to 50% of dogs with pituitary-dependent hyperadrenocorticism (4). In one study, the mean age of onset of neurologic signs in dogs affected with functional pituitary macrotumors was 9.5 y (5). No sex predilection was noted; however, most affected dogs were large breeds (5). Neurologic signs, such as stupor, disorientation, inappetance, circling, pacing, or ataxia, may develop in addition to the clinical signs attributable to hypercortisolism (4,5,6). Occasionally, pituitary tumors in dogs result in blindness (1,7,8). A nonfunctional pituitary chromophobe adenoma was diagnosed in a 5-month-old calf with neurological signs and blindness (9). Similar to these reports, the blindness in the dog in this case was due to optic chiasmal compression, secondary to a pituitary mass. The behavioral changes, including periodic yelping and lethargy, were consistent with compression of the hypothalamus. This dog failed to exhibit other signs of systemic illness or alterations in the blood analyses indicative of hyperadrenocorticism; however, further diagnostic tests for an endocrinopathy were not performed (10). Endocrine test results differentiate functional from nonfunctional pituitary tumors; however, they are incapable of distinguishing pituitary macrotumors from microtumors (4). Computed tomography or MRI is needed to confirm the presence of a pituitary macrotumor rather than a microtumor. Megavoltage irradiation has been reported to be an effective therapy for control of functional pituitary macrotumors in dogs with neurologic signs, although success rates with treatment are variable (4,11). Response to this treatment and prognosis may improve if the pituitary tumor is detected at an early stage and if neurologic signs are less severe (4,11).

In cases such as this, in which prechiasmal blindness is suspected, the lack of causative ocular signs (complete bilateral retinal detachments, bilateral generalized retinal degeneration, or bilateral intraocular optic neuritis) should prompt early referral to a specialist for ERGs and advanced imaging. These diagnostic procedures confirm the locale of the lesion, and provide information for therapeutic options and prognosis.