Standard blood study results were normal, including erythrocyte sedimentation rate (29), white blood cell count (3300 with relative lymphopenia [16%]), hemoglobin (13.5 mg%), prothrombin time, partial thromboplastin time, protein S, protein C, antithrombin III, antiphospholipid Ab, methyltetrahydrofolate reductase, hyperviscosity indices, antinuclear antibody, venereal disease research laboratory titer, and cryoglobulins. Thyroid-stimulating hormone was on the upper edge of normal values; other thyroid function test results were normal.
Lumbar puncture had an opening pressure of 80 mm water. Cranial and orbital computed tomography findings were normal. Fluorescein angiography demonstrated late optic disc leakage with no retinal pathology. Interferon-α polyethylene glycol was discontinued.
Two days later, the patient noted a black shadow obscuring his right visual field. Visual acuity was 20/60 OD, 20/80 OS. The relative afferent pupil defect had changed from the left to the OD. Fundus examination in the OD showed enlargement of the optic nerve edema. Visual field demonstrated progression of the field defects in the OD (Fig. 6).
The patient was treated with intravenous methylprednisolone 1 g/d for 3 days, with tapering of prednisone over the next 14 days with no apparent improvement. Over the next 2 months, visual acuities improved to 20/30 in both eyes without any change in the visual field defects. Three months later, fundus examination demonstrated optic disc pallor in both eyes.
We describe two patients undergoing treatment with interferon-α who developed bilateral simultaneous optic neuropathy within 3 months of starting this medication. Case 1 had established risk factors for conventional AION, including diabetes, hypertension, ischemic heart disease, and hypercholesterolemia. However, we believe that interferon-α treatment may have been a contributing factor, given that conventional AION very rarely develops simultaneously in both eyes (8). Furthermore, interferon-α has been implicated in vascular retinopathy (5) in patients with diabetes and hypertension. The contribution of the patient's essential thrombocytosis, known to predispose to retinal vascular occlusions, is unknown (9–11).
Case 2 had none of the systemic risk factors for conventional AION. We doubt that the HCV alone precipitated AION. In patients with chronic HCV infection, optic neuritis has been reported in only one patient who was not previously treated with interferon-α (12). This patient had several signs related to systemic vasculitis, including purpura and cryoglobulinemia. The authors attributed these features to HCV infection. Because our patient did not have systemic symptoms of vasculitis, we had ruled out essential mixed cryoglobulinemia, and because corticosteroids did not reverse the optic neuropathy, it is unlikely that the HCV caused the AION.
Alternately, there is evidence that ties AION to interferon-α treatment. Three reported cases of AION (6,7) have occurred within 1 week to 3 months of starting interferon-α treatment in patients who lacked typical risk factors for AION. Purvin (6) suggested involvement of the posterior ciliary arteries rather than the retinal vessels as a possible cause for AION. Lohmann (7) postulated that interferon-α is able to produce autoantibodies and subsequently cause deposition of immune complexes in the small retinal or optic nerve arteries. Interferon-α is also able to stimulate other cytokines that can cause an inflammatory reaction of the blood vessels that might subsequently lead to ischemia (6,7,13).
Although Case 2 suffered continued deterioration of vision after discontinuation of interferon-α therapy, this could have been due to the long half-life of the polyethylene glycol variant. The continued deterioration stands in contrast to other patients described, who stabilized or even improved (14) after discontinuation of interferon-α treatment.
In view of the possible poor visual outcome associated with interferon-α treatment, we suggest that patients who are candidates for this treatment be assessed beforehand for crowded discs and systemic risk factors for conventional AION. It is also important to examine patients during treatment, because some patients who have developed interferon-α–associated retinopathy are asymptomatic, and retinal changes in the reversible phase can be detected. We recommend ophthalmic screening that includes baseline and follow-up examinations every 3 to 4 months (15).
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© 2003 Lippincott Williams & Wilkins, Inc.
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