Acetazolamide modestly improved vision in patients with idiopathic intracranial hypertension (IIH) and mild vision loss in a new study.
"This is the first strong evidence that the drug works in this condition," Michael Wall, MD, from the University of Iowa, Iowa City, told Medscape Medical News. He added: "Acetazolamide has been shown effective before at reducing spinal pressure but not for improving vision. This is by far the most complete study in this field. We showed it reduced intracranial pressure, improved quality of life, reduced papilledema grade, and improved vision."
The Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC) IIH Study is published online April 22 in JAMA.
In an accompanying editorial, Jonathan C. Horton, MD, Beckman Vision Center, University of California, San Francisco, says the trial provides the "solid evidence" that has been lacking for acetazolamide as a treatment for patients with high intracranial pressure, also known as pseudotumor cerebri.
"The NORDIC trial has demonstrated that acetazolamide, along with a weight reduction diet, results in modest improvement in visual field function for patients with mild pseudotumor cerebri." Dr. Horton writes. "Additional studies are needed to refine the management of patients with pseudotumor cerebri to ensure preservation of visual function."
In the article, Dr. Wall and colleagues explain that IIH is a disorder primarily of overweight women of childbearing age, characterized by increased intracranial pressure with its associated signs and symptoms, including debilitating headaches and vision loss. Acetazolamide is commonly used to treat this condition, but strong evidence to support its use is lacking.
For the NORDIC study, 165 patients with IIH and mild visual loss were randomly assigned to receive acetazolamide or placebo for 6 months. All participants were also asked to follow a low-sodium weight-reduction diet.
The primary outcome — the average improvement in perimetric mean deviation (PMD, a measure of global visual field loss) — was greater with acetazolamide than with placebo (1.43 dB versus 0.71 dB). In addition, there were improvements in papilledema (optic disc swelling) and quality of life, as well as greater weight loss, in patients in the acetazolamide group.
But because the improvement of PMD was less than that previously deemed to be clinically significant, the researchers conclude that the clinical importance of this improvement remains to be determined.
Expanding on this to Medscape Medical News, Dr. Wall explained that a prior pilot study suggested that an improvement in PMD of 1.3 dB was needed for clinical significance. But he pointed out that patients with higher-grade papilledema had a greater improvement in vision: 2.27 dB.
"That is far in excess of what we were expecting," he said. "So there is certainly a clinically significant improvement in these patients with a large degree of optic nerve swelling."
He continued: "It is clear that the drug works and helps people. But the fact that we enrolled quite mild patients in general meant that there was not that much room for improvement. More severe patients would probably have shown more benefit. I certainly use the drug in more severe patients in practice."
But Dr. Wall noted that it is difficult to enroll more severe patients in a placebo-controlled trial because many choose to have surgery. "The next study we need to do is acetazolamide versus surgery in these more severe patients."
Weight Loss Also Important
Given that weight loss is also important for improving vision in these patients, the researchers performed a statistical analysis to separate the effect of acetazolamide from that of the weight loss.
"This concluded that the effect of acetazolamide was independent of weight loss," Dr. Wall commented. "It appears that both factors combined to show a benefit. The acetazolamide effect mostly occurred in the first month, whereas the weight loss only started to have an effect in the second to third month of the study."
The researchers gave acetazolamide up to the maximum tolerated dose, and the average dose given was 2.5 g/day. Dr. Wall said, "Patients decided themselves how much they could tolerate. I wouldn't say side effects were an issue — if they were, then the dose was reduced. But patients still reported higher quality-of-life scores on the drug than on placebo, which would suggest side effects were not a big problem."
The study was supported by the National Eye Institute. Author disclosures are available with the original article.
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Cite this: Drug Improves Vision in Idiopathic Intracranial Hypertension - Medscape - Apr 24, 2014.