OCR Text |
Show Journal of Clinical Neuro-ophthalmology 7(2): 84-86, 1987. Editorial Comment Should Ethambutol Be Barred? © 1987 Raven Press, New York In this issue of the Journal, Doctors Devita, Miao, and Sadun document two patients treated for renal tuberculosis with ethambutol who suffered profound and permanent loss of vision down to legal blindness in both eyes. The first patient took 1,200 mg/day (13.6 mg/kg), and 6 months later had 20/20 acuity in both eyes. He identified 19 of 20 Ishihara color plates, showed normal tangent screen visual fields, and had normal optic discs. Because of this minimal deficit in color vision the ethambutol was discontinued. However, 2 weeks later the vision was 20/60 and 20/25; -2 days after that, it was 20/100 and 20/50; and 3 months after stopping ethambutol, vision was 20/200 and 20/300. One year after stopping the drug, vision was 20/200 in the right eye and 20/400 in the left eye, and he had bilateral cecocentral field defects. The "bottom line" here was that the patient took a dosage of the medication within proper advised limits, was followed regularly, had the drug discontinued immediately when he missed only one color plate in both eyes, and yet continued to have a progressive loss of vision due to an inexorable optic neuropathy that left him permanently blind. The second case was a 41-year-old man who had a history of pulmonary tuberculosis at age 8, which was previously treated with isoniazid. After careful evaluation a diagnosis of renal tuberculosis was made. He was started on isoniazid, rifampin, and pyridoxine. He had 20/25 vision in both eyes, normal color vision, and mild temporal pallor of the discs. Ethambutol was started at a dose of 2,000 mg/day (20.95 mg/kg) and after 60 days this was decreased to 1,200 mg/day (12.5 mg/kg). Thirty days after starting ethambutol, vision was 20/30 in both eyes. However, 3 months after starting ethambutol, he noted a loss of vision down to 20/60 in both eyes and color vision was definitely impaired. Although ethambutol was discontinued, the acuity continued to deteriorate. Two months after stopping the drug, his vision was 20/300 and fi"':''1geI counting. In summary, this patient devel- 84 oped a bilateral optic neuropathy 30 days after starting ethambutol, and visual acuity progressively deteriorated after 5 months to 20/400 in both eyes, and showed no improvement despite prompt discontinuance of ethambutol. One might think that these cases are exceptions, that the physician need only be overly concerned when a patient has abnormal renal function, and that the dose employed was on the high side of the advised regimen in the second case. My clinical experience has confirmed exactly the warnings given by the authors. Before citing personal cases, the statements given in the 1987 Physician's Desk Reference are of interest. On pages 1107-1108 of the 1987 Physician's Desk Reference under Myambutol (Lederle's ethambutol hydrochloride), the following statements are made, which are pertinent to the paper under consideration and are quoted directly. "Patients with decreased renal function need the dosage reduced as determined by serum levels of Myambutol, since the main path of excretion of this drug is by the kidneys." The Physician's Desk Reference further states, "Because this drug may have adverse effects on vision, physical examination should include ophthalmoscopy, finger perimetry and testing of color discrimination./I Under Adverse Reactions, the statements are as follows: Myambutol may produce decrease in visual acuity which appears to be due to optic neuritis and to be related to dose and duration of treatment. The effects are generally reversible when administration of the drug is discontinued promptly. [italics added] In rare cases recovery may be delayed for up to one year or more and the effect may possibly be irreversible in these cases. Patients should be advised to report promptly to their physician any change of visual acuity. The change in visual acuity may be unilateral or bilateral and hence each eye must be tested separately and both eyes tested together. Testing of visual acuity should be performed before beginning Myambutol therapy and periodically during drug administration, except that it should be done monthly when a patient is on a dosage of more than 15 mgm per kg per day. Recovery of visual acuity generally occurs over a EDITORIAL: SHOULD ETHAMBUTOL BE BARRED? 85 period of weeks to months after the drug has been discontinued. Patients have then received Myambutol again without recurrence of loss of visual acuity.... Numbness and tingling of the extremities due to peripheral neuritis have been reported infrequently. IN/TIAL TREATMENT. In patients who have not received previous antituberculous therapy, administer Myambutol15 mgm per kg (7 mg per pound) of body weight as a single oral dose once every 24 hours. RETREATMENT. In patients who have received previous antituberculous therapy, administer Myambutol 25 mgm per kg (11 mgm per pound) of body weight as a single oral dose once every 24 hours. Concurrently administer at least one other antituberculous drug.... After 50 days of myambutol administration, decrease the dose to 15 mgm per kg. During the period when patient is on a daily dose of 25 mgm per kg monthly eye examinations are advised. Because my experience has been similar to Dr. DeVita et al., I looked up my notes on three additional cases of ethambutol optic neuropathy that I have seen and can recall at least one other similar case whose notes are not immediately at hand. These cases can be briefly summarized as follows: Case 1 (MG) A 75-year-old white woman was started on isoniazid, rifampin, and ethambutol in October 1974 for pulmonary tuberculosis. She was taking a total of 900 mg ethambutol/day. Her vision was checked every month. In early July 1975 she began to note decreased vision while driving her car. On July 15, 1975, ethambutol was discontinued but she noted no change in vision thereafter. Dr. Glaser saw her on July 22, 1975 and noted 20/200 vision in both eyes, dense central scotomas, and diagnosed ethambutol optic neuropathy. In June 1975, her vision was normal. However, in July she suddenly couldn't see the chart. The patient's vision stabilized at 20/200 in both eyes, and on her last follow-up on May 9, 1978, her vision was 20/200 in both eyes, she had permanent cecocentral scotomas, and remained permanently legally blind in both eyes 3% years after onset of vision loss. Case 2 (LS) A 66-year-old white man was seen on March 29, 1976. He had pulmonary tuberculosis in 1935, which was treated with bilateral pneumothorax and resulted in apparent remission of the disease for 40 years. In April 1975 he was hospitalized for prostatectomy, and a routine intravenous pyelo-gram revealed a filling defect on the left side. On June 23, 1975, a left nephrectomy was performed, which revealed renal tuberculosis. He was immediately started on rifampin (Rimactane) 300 mg (two capsules daily 1 hour before breakfast), ethambutol 400 mg (three capsules daily each morning for a total of 1,200 mg/day), isoniazid 300 mg/day, and pyridoxine 100 mg/day. He began to note tingling in the toes; he took the medicine between July and October 1975. Isoniazid was discontinued in October because of paresthesias. In November, rifampin was discontinued. He had monthly checks of vision and color vision. Between December 4 and 12, 1975, he noted a rather precipitous drop in vision in both eyes. His ophthalmologist saw him on December 12, 1975, and noted decreased vision, bilateral cecocentral scotomas, and impaired color vision. Ethambutol was promptly discontinued. He weighed 145 pounds and was stable when seen on March 29, 1976. At that time, his vision ~as 20/200 in both eyes and he had bilateral cecocentral scotomas. Subtle papillomacular bundle pallor was noted in the right eye, and the disc in the left eye was considered normal. Fortunately, a follow-up examination in April 1977 by his ophthalmologist revealed that his vision had returned to 20/40 in the right eye and 20/20 in the left eye; color vision was normal in the left eye and slightly defective in the right eye, and no cecocentral scotomas could be plotted. Case 3 (CDeM) A 43-year-old Brazilian woman was seen on December 21, 1979. Her left eye had been amblyopic since birth. In January 1976 she developed a respiratory infection, right lower lobe pleurisy, and a productive cough. Chest x-ray revealed a right lower lobe infiltration and she was said to have "pleurisy with pulmonary tuberculosis." In January 1975 she was started on ethambutol, isoniazide, and rifampin. She took 1,200 mg/day ethambutol for 4 months. By late February 1975 her respiratory symptoms had completely cleared. Four months after starting ethambutol (May 1975) she called her doctor and reported some decreased vision in her right eye. The ethambutol was stopped instantly. However, vision continued to decrease, so that by October 1975 she was left with stable but low vision. All medication was discontinued by September 1977. In October 1977 her visual acuity was 8/200 in the right eye and 11200 in the left eye, and the impression was bilateral retrobulbar neuritis with optic atrophy associated with J Clin Neuro-ophthalmol, Vol. 7, No.2, 1987 86 J. L. SMITH ethambutol. When seen here on December 12, 1979, her visual acuity was 121200 in the right eye and 6/200 in the left eye. Dense cecocentral scotomas were present in both eyes. Primary optic atrophy was present in the right eye, with an anomalous disc in the left eye. After taking ethambutol 1,200 mglday for 4 months, she was left permanently legally blind with visual acuity of only 121200 in her only good eye, with optic atrophy and cecocentral scotomas. She was seen over 2 years after all antituberculous medication was stopped. Another case comes to mind. A young white man who was a Federal prisoner in Kentucky was treated for tuberculosis with ethambutol. He suffered a rapid drop in vision and was left with less than 20/200 acuity in each eye, bilateral cecocentral scotomas, and optic atropohy. I do not have the notes immediately at hand to document the dosage given to this patient, but as memory serves me, his history was quite typical of the others. Thus, in the three patients who were carefully investigated to exclude other causes of vision loss, two had pulmonary tuberculosis and one had renal tuberculosis. One took 900 mg/day ethambutol and 8 months later noted a rapid drop of vision. Although the medicine was promptly stopped, she was left permanently legally blind. Another, who had renal tuberculosis, took 1,200 mglday ethambutol for 6 months, but experienced a sudden drop of vision; the medicine was immediately stopped, and fortunately vision returned to 20/40 and 20/20 at a follow-up examination 1 year later. The third case took ethambutol 1,200 mg/day for 4 months; his physician discontinued the medicine instantly over the telephone at the first symptom of blurred vision, but the patient was left permanently and legally blind in both eyes at a follow-up 2 years later. The points to be made from these cases are TCIin Neuro-ophthalmol, Vol. i', No. 2, 198~ really quite simple and are tragically evident. Even though patients were given the proper dose of ethambutol, were kept under careful ophthalmological surveillance, and had the drug immediately stopped upon first symptoms or signs of visual dysfunction, only one case, of the five cases documented here (the two by Dr. DeVita et al.) and the three just mentioned, had a return of any visual improvement at all and four were left permanently and legally blind. I believe that ethambutol is too toxic and too capricious in its toxicity on the optic nerve to be used in any patient at all. Obviously, it is a different situation if the patient has a lifethreatening tuberculosis, the organism is resistant to any and all other medications, and the risk is to either let the patient die or take a chance of causing permanent bilateral blindness. However, if I had pulmonary tuberculosis, I'd rather take isoniazid and p-aminosalicyclic acid first, then rifampin if that failed, and only after that didn't work would I consent to being treated with ethambutol. I believe that if a pulmonary specialist comes in the front door with a bottle of ethambutol, you would be well advised to go out the back door. When a patient is cured of pulmonary tuberculosis, they make a full clinical recovery. However, if they are left permanently blind from the treatment, a clinical disaster remains for the rest of the patient's life. It is somewhat analogous to making a diagnosis of pseudotumor cerebri, which will usually resolve on its own and leave the patient normal and healthy for the rest of his or her life, whereas if papilledema management is neglected during the course of the disease, the complication of blindness ensues forever, which is worse than the original disease. I believe ethambutol should be barred. Comments from readers about similar cases or experiences would be welcomed. J. Lawton Smith, M.D. |