Journal of Neuro-Ophthalmology, June 1988, Volume 8, Issue 2

Amiodarone Optic Neuropathy

Bilateral optic nerve swelling occurred in a patient who had other findings typical of amiodarone toxicity. These included verticillate keratopathy, tremor, gait ataxia, and pulmonary fibrosis. Cessation of amiodarone therapy was followed by slow resolution of optic nerve swelling over 6 months; however, generalized constriction of the visual fields persisted. Several proposed mechanisms of optic nerve swelling secondary to amiodarone toxicity are discussed. Corroborative evidence in the literature suggests the possibility of a unique type of toxic optic neuropathy in this patient.

Tournai of Cliniall Neuro-ophthalmo[ogy 8(2): 105-110, 1988. Amiodarone Optic Neuropathy Samuel N. Garrett, M.D., John J. Kearney, M.D., and Jade S. Schiffman, M.D. (9 1988 Raven Press, Ltd., New York Bilateral optic nerve swelling occurred in a patient who had other findings typical of amiodarone toxicity. These included verticillate keratopathy, tremor, gait ataxia, and pulmonary fibrosis. Cessation of amiodarone therapy was followed by slow resolution of optic nerve swelling over 6 months; however, generalized constric­tion of the visual fields persisted. Several proposed mechanisms of optic nerve swelling secondary to amio­darone toxicity are discussed. Corroborative evidence in the literature suggests the possibility of a unique type of toxic optic neuropathy in this patient. Key Words: Amiodarone-Optic neuropathy-Border tissue of Elschnig- Verticillate keratopathy. From the Ophthalmology Service, Department of Surgery, Letterman Army Medical Center, Presidio of San Francisco, California. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Depart­ment of the Army, Department of Defense, or the U.S. Govern­ment. This work was presented at the Pacific Coast Oto-Ophthal­mological Society Meeting in Seattle, Washington, on July 1, 1987. Address correspondence to Captain S. N. Garrett, MC, at Box 1585, Letterman Army Medical Center, Presidio of San Francisco, CA 94129-6700, U.S.A. Address reprint requests to Technical Publications Editor HSHH-CSD-TP, Letterman Army Medical Center, Presidio of San Francisco, CA 94129-6700, U.S.A. 105 Amiodarone hydrochloride is an iodinated ben­zofurane derivative recently approved for the con­trol of refractory ventricular dysrhythmias (1). The amphiphilic nature of the drug causes it to accu­mulate within lysosomes and alter their function, producing abnormal inclusions in the cell cyto­plasm and rendering the cell less functionally competent (2). Most patients taking this drug de­velop a verticillate keratopathy, which only infre­quently produces symptoms of glare, halos, andl or decreased vision (3-5). Other reported ocular side effects are lens opacity and irritation of eyelid skin (5,6). Systemic side effects are many and in­clude tremor, gait ataxia, peripheral neuropathy, pulmonary toxicity, thyroid dysfunction, photo­sensitivity, gastrointestinal disturbance, and drug interactions (7 -12). Recently, three cases of disc swelling have been reported that involved patients taking amio­darone. The swelling in one of these patients was reportedly caused by pseudotumor cerebri, and in the others the cause of the swelling was unclear. We know of several other unreported cases of disc swelling in patients taking amiodarone, some of which were thought to represent a form of ante­rior ischemic optic neuropathy. In this report, we describe bilateral optic disc swelling in a patient who had typical ocular and systemic amiodarone toxicity, and we suggest a new theory of toxic optic neuropathy based on corroborative evidence in the literature. CASE REPORT A 51-year-old white man underwent eye exami­nation in July, 1985 before starting amiodarone therapy for refractory ventricular tachycardia. His visual acuity was 20/20 in each eye. His visual fields, pupils, and ocular motility were normal. Ophthalmoscopy showed normal optic nerves, a few scattered macular drusen in the retina of each 106 S. N. GARRETT ET AL. FIG. 1. Fundoscopic appearance of optic discs in December, 1985 in (A) right eye and (B) left eye. eye, and a small choroidal nevus in the left eye. The patient was placed on a regimen of 1200 mg amiodarone daily, which was lowered to 800 mg daily 8 weeks later with good control of his dys­rhythmia. Concurrent medications were isosor­bide dinitrate, ibuprofen, diltiazem, and sucral­fate. In September, 1985, the patient developed tremor, gait ataxia, and gradual onset of decreased vision in both eyes. He also reported four to five episodes of altered mentation lasting 1 min to 2 h, during which he felt lonesome, lost familiarity with his surroundings, and would not communi­cate. These symptoms increased in severity until his admission to another hospital in November, 1985. At that time, cerebrospinal fluid was ob­tained by lumbar puncture and showed opening pressure of 238 mm, protein elevated at 61 mg/dl, glucose normal at 60 mg/dl, white cell count of 1 lymphocyte per high-power field, and negative bacterial culture. Results of computerized axial to­mography of the head were normal. His visual acuity was 20/30 in each eye. Examination of the cornea showed typical verticillate keratopathy. There was marked swelling of both optic nerve heads. The diagnosis of amiodarone toxicity was made and the drug discontinued. The patient was transferred to our institution in December, 1985, 1 month after amiodarone therapy was discontinued. Tremor and ataxia were prominent but improving at the time of transfer, and he had no evidence of a peripheral neuropathy. His visual symptoms persisted, and visual acuity was 20/25 in both eyes. Intraocular pressure was 18 mm Hg in each eye. Positive findings were the presence of the keratopathy, the marked optic disc swelling with flame hemor­rhages and cotton wool spots in both eyes, and the previously noted macular drusen and cho­roidal nevus. The temporal aspect of the discs showed less edema in both eyes (Fig. 1). Auto­mated perimetry revealed generalized constriction in both eyes (Fig. 2). Electroretinogram, electro- 3V "I I field appearance in December, 1985 in (A) right eye and (B) left eye. I Clin Nl'uro-ophthalmol, Vol. oS, i\'o. ~, 1':ISS' AMIODARONE OPTIC NEUROPATHY Fundoscopfc appearance ot optiC discs in May, 1986 in (A) right eye and (B) left eye. 107 oculogram, and visual evoked potential were normal. Results of Farnsworth D-15 color vision testing were normal. Fluorescein angiography re­vealed diffuse disc leakage of dye at the optic disc. Contrast sensitivity function was depressed at the spatial frequency of 6 cycles/degree. A lumbar puncture was performed. A cerebrospinal fluid ex­amination showed opening pressure of 190 mm, protein elevated at 75 mg/dl, and glucose at 65 mg/dl. There were no cells in the cerebrospinal fluid, and bacteriologic cultures were negative. Repeat computerized axial tomograms showed low normal size of the lateral and third ventricles. A magnetic resonance imaging study of the brain and orbits showed no abnormalities. Results of thyroid function studies were normal. Chest x-ray films revealed a left lower lobe infiltrate, consis­tent with amiodarone pulmonary toxicity. Bron­chioalveolar lavage showed no malignant cells or pathogenic microorganisms. Over the next 2 months, the gait ataxia, tremor, and visual symptoms improved with slow resolu­tion of the disc swelling. In March, 1986, optic disc swelling was still present but was resolving. By May, 1986, the optic nerves were essentially flat with residual hard exudates remaining temporally (Fig. 3). Visual acuity was 20/20 in both eyes. The keratopathy was present but fading. Repeat test of the visual fields revealed a slight progression of the generalized constriction (Fig. 4). A repeat con­trast sensitivity function study showed improve­ment. DISCUSSION We believe this patient had toxic encephalop­athy and toxic optic neuropathy secondary to amiodarone therapy. Two other etiologies were considered. First, pseudotumor cerebri has been reported to occur with oral amiodarone therapy as has transient increased intracranial pressure with intravenous therapy (13,14). We excluded this J Clill Nellro-ophthalmol. Vol. 8, No.2, 1988 AMIODARONE OPTIC NEUROPATHY A B CROSS SECTION OF DETAiL (Fig. A) 109 FIG. 5. (A) Cross-sectional diagram of optic nerve shows anatomy of prelaminar disc. CRA, central retinal artery; PCA, posterior ciliary artery. (B) Detail of box in enlarged portion of (A). Amiodarone-rich choroidal interstitial fluid (arrows) leaks through border tissue of Elschnig into optic nerve. Inset shows inclusions in glial cells. JClin Neuro-ophthalmol. Vol. 8. No.2. 1988 no S. N. GARRETT ET AL. ical amiodarone-related inclusions were found in the choroid plexus of mice in one study. An alter­ation in cellular morphology or function in this tissue may explain the finding of increased level of cerebrospinal fluid protein in patients receiving amiodarone (17). 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