Toxin-Induced Vision Loss

By Lewis Nelson, MD

A 34-year-old man was brought to the emergency department by emergency medical services after he ingested a bottle of unidentified pills and ethanol in an apparent suicide attempt. The patient was comatose on arrival. His pulse was 110, but all other vital signs were normal.

Physical examination revealed mydriasis, nonfocal neurologic findings, and no toxicologic syndromes. Oxygen saturation as measured by pulse oximetry was 99%, and a fingerstick test revealed a glucose level of 110 mg/dL. Serum chemistry, arterial blood gas analysis, and other laboratory test results were within reference range, except for the ethanol level, which was 120 mg/dL. An electrocardiogram showed sinus tachycardia with a QRS duration of 110 milliseconds.

Three hours after admission, the patient fully awakened and stated that he could not see, although he seemed only minimally concerned about that. He had no light perception and his pupils were 6 to 7 mm in diameter and minimally reactive to light. The globes, retinas, and extraocular movements were normal. Opticokinetic nystagmus was absent.

 
CAUSES OF BLINDNESS

Although many drugs and toxins are known to cause blindness, such an event is rare. Vasodilators, for example, can lower blood pressure to such an extent that ischemia of the occipital cortex occurs. Hypotension-induced infarction is far more likely in an elderly patient than in a patient as young and presumably healthy as the one discussed here. Carbon monoxide and hydrogen sulfide poisoning can also cause cortical blindness. Because the pupillary light reflex does not require cortical input, however, it should remain normal despite total vision loss.

Methanol is perhaps the most common cause of toxin-induced vision loss. The optical effects of methanol occur through its metabolic conversion to formic acid, a direct retinal toxin. However, this conversion, which is mediated by alcohol dehydrogenase, is competitively blocked by ethanol, so the ethanol level seen in this patient effectively rules out consequential methanol poisoning--unless, that is, the patient ingested ethanol after methanol-induced blindness occurred.

Even in the absence of ethanol, certain key features of methanol toxicity were lacking in this case. For one thing, methanol produces a metabolic acidosis, so a patient with methanol poisoning would be hyperventilating to compensate. Moreover, the acidosis should be apparent on arterial blood gas or serum chemistry analyses. Finally, in patients with blindness caused by methanol poisoning, the funduscopic examination usually reveals an "angry" fundus.

Cocaine, ergot alkaloids, and other agents that provoke diffuse vasospasm can cause retinal ischemia and blindness. Retinal pallor, arterial vasoconstriction, or other visible retinal changes would then be expected, however. Phencyclidine has been indirectly linked to vision loss through "sun-gazer's retinopathy," ultraviolet damage to the retina caused by prolonged staring at the sun. Incidentally, the syndrome of toxic effects associated with anticholinergic agents in which patients are said to be "blind as a bat" refers not to actual vision loss but to loss of accommodation or near focus.

On extensive questioning, the patient admitted to having ingested 30 tablets of quinine, 300 mg each, in a suicide attempt three or four hours before his arrival in the emergency department.

 
CLOSER LOOK AT QUININE

Quinine is derived from the bark of the cinchona tree, as are aspirin and quinidine. It has long been used in herbal and homeopathic remedies and has only recently been removed from the market as a nonprescription treatment for leg cramps. Quinine is a popular heroin adulterant, because its bitter taste resembles that of heroin. Tonic water contains approximately 2 mg of quinine per ounce. Worldwide, quinine is widely used as an antimalarial agent, especially in regions where chloroquine resistance is endemic. This patient had apparently accumulated quinine pills while on a peacekeeping effort in Africa when he was in the Marine Corps.

Quinine shares many properties with the other drugs derived from the cinchona tree. Like salicylates, it can induce cinchonism, a toxic syndrome of nausea, vomiting, tinnitus, dizziness, and headache. Like quinidine, its optical isomer, it produces cardiotoxic effects similar to those of the type Ia antiarrhythmic agents, including impaired inotropy and such myocardial electrical abnormalities as QRS and QT prolongation.

However, among the cinchona derivatives, quinine is unique in its ability to cause blindness. In a retrospective study of 165 consecutive patients with acute quinine poisoning, Boland and coworkers noted the presence of visual symptoms in 42%, tinnitus in 38%, and altered mental status in 14%, including deep coma in 4% (The Lancet, vol. 1, p. 384, 1985). Of the patients with visual symptoms, a little more than half had total blindness; 19 patients were left with permanent visual deficits. Initially, the visual changes induced by quinine were attributed to retinal vasospasm and ischemia. Some experts now think, however, that quinine or one of its metabolites is a direct retinal toxin.

In the Lancet study, the risk of blindness seemed to correlate roughly with quinine levels: patients whose plasma quinine concentrations were greater than 10 µg/mL 10 hours after exposure were most likely to suffer vision loss. Measurements of plasma quinine levels are of limited value in actual clinical practice, however, because turnaround time is long and therapeutic interventions are limited.

 
TREATMENT OPTIONS

Although several case reports have touted stellate ganglion blocks as a means of stopping vasospasm and curing blindness, subsequent studies have failed to confirm any benefit. Earlier reports of efficacy may have resulted from a reporting bias. Fortunately, visual changes caused by quinine poisoning generally resolve with supportive care.

Oral administration of activated charcoal has been shown to reduce the half-life of quinine in human volunteers who received nontoxic ingestions. When Sabato and coworkers compared methods of enhancing the elimination of the drug after absorption, they found that forced diuresis was better than hemodialysis, plasma exchange, and peritoneal dialysis for increasing quinine clearance (Clinical Nephrology, vol. 16, p. 264, 1981). However, neither they nor others have ever shown that increasing clearance speeds recovery. Moreover, forced diuresis is a potentially dangerous procedure and is almost never indicated. Although the clinical value of charcoal hemoperfusion has not been adequately studied, it may surpass those other methods of enhancing elimination.

In this case, the patient was given several oral doses of activated charcoal. He also received intravenous saline at three times the infusion rate needed to maintain fluid requirements, and his urinary pH remained below 7.5. No other method of enhancing elimination was attempted, and he was not given stellate ganglion block therapy. His vision improved during the next two days and his electrocardiogram return to normal in 12 hours without specific therapy. He was discharged to the psychiatric service.