Acetazolamide Helpful in Idopathic Intracranial HTN with Vision Loss

By Megan Brooks

NEW YORK - In patients with idiopathic intracranial hypertension and mild vision loss, treatment with acetazolamide plus a low-sodium diet led to modest improvement in vision, compared with diet alone, in the NORDIC IIH Treatment Trial.

"This is the first time there has been proof that acetazolamide use in IIH improves visual outcome. Acetazolamide improved vision and symptoms independent of the amount of weight loss. The patients with moderate to severe optic nerve swelling recovered much more vision than those with mild swelling," Dr. Michael Wall of the University of Iowa in Iowa City told Reuters Health by email.

"Acetazolamide, in spite of having side effects, improves patients' quality of life scores," he added.

The study appears in the April 23/30 issue of JAMA, a neurology theme issue.

IIH primarily affects overweight women of childbearing age, resulting in debilitating headaches and vision loss. Acetazolamide is often used to treat IIH, despite a lack of strong evidence to support its use, the authors note.

The NORDIC trialists randomly assigned 165 participants with IIH and mild visual loss to a low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d, 86 patients) or matching placebo for six months (79 patients).

At baseline, perimetric mean deviation (PMD, a measure of global visual field loss) was 3.53 dB in both groups. At six months, PMD was 2.10 dB in the acetazolamide group and 2.82 dB in the placebo group. The difference was less than 1 dB (0.71; p=0.50) and the clinical importance of this improvement "remains to be determined," the authors note.

Although the findings were statistically significant, the improvement was "subtle, less than the 1.3 dB treatment effect predicted by a pilot study," notes Dr. Jonathan Horton of UC San Francisco in an editorial.

"The study design posed a dilemma. Only patients with mild vision loss could be enrolled, because treatment with a placebo could not be justified in individuals with more serious vision loss. However, patients with mild vision loss have little room to improve and therefore any treatment effect will be modest. Having enrolled only patients with mild disease, it was impressive that the NORDIC investigators still managed to uncover evidence for a statistically significant benefit from acetazolamide treatment," Dr. Horton writes.

He adds, "The clinical importance of the NORDIC trial will be greatest for patients with severe papilledema, who stand to gain the most from the drug."

Patients in the acetazolamide group also experienced greater reductions in weight (-7.50 kg vs -3.45 kg with placebo; -4.05 kg treatment effect, p<0.001) and improvements in vision-related quality of life (p=0.003).

"The broad implication is that for the first time, there is evidence from a randomized clinical trial that acetazolamide combined with a low sodium weight reduction program improves vision, reduces optic disc swelling and intracranial pressure and shows improvement in quality of life measures," Dr. Wall said. "The medication was well tolerated with no known permanent untoward side effects."

Dr. Wall said, "Future research should be aimed at finding the cause of idiopathic intracranial hypertension. Secondly, we need another clinical trial to develop protocols for treating more severe visual loss."

Dr. Norton says the NORDIC trial has provided "solid evidence" that patients with IIH can be treated effectively by weight loss and acetazolamide. "Their visual acuity and visual fields should be tested regularly, at a frequency that depends on the severity of their condition. If vision is failing despite medical treatment, rapid surgical intervention is necessary," he writes.

The NORDIC IIH study group reports the baseline clinical and laboratory features of patients enrolled in the trial in a companion paper in JAMA Neurology this week.

They note that IIH is "almost exclusively" a disease of obese young women. The mean age of study patients was 29 years and only four (2.4%) were men.

"Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection," they add.

"We have finally reached a point where this large cohort of patients with IIH is being studied and reported in a detailed fashion," writes Dr. Nicholas Volpe from the Department of Ophthalmology, Feinberg School of Medicine, Northwestern University in Chicago in an editorial.

"This article also raises the distinct possibility that the condition does not occur in men or, at the very least, that men should be thoroughly investigated for secondary causes of intracranial pressure elevation such as sleep apnea or dural arteriovenous malformations," Dr. Volpe says.

"This and subsequent studies from the group will give us the best chance of understanding this vexing condition and its devastating consequences in so many patients. They have established a model for studying this disorder going forward, and NORDIC and the authors are to be congratulated for this critical contribution," he concludes.

SOURCES: https://bit.ly/1f2dFBk and https://bit.ly/1tyEam7

JAMA 2014;311:1618-1619-1641-1651.

JAMA Neurol 2014.

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