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Acetazolamide improved vision in patients with high intracranial pressure

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Reserve use for patients with severe papilledema

Acetazolamide has been used for decades in patients with high intracranial pressure (or pseudotumor cerebri), but this is the first randomized clinical trial to show the drug’s efficacy, wrote Dr. Jonathan C. Horton.

"The study design posed a dilemma," Dr. Horton wrote. "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."

Therefore, "it was impressive that the NORDIC investigators still managed to uncover evidence for a statistically significant benefit from acetazolamide treatment," Dr. Horton wrote. He noted the treatment effect of 2.27 dB in patients with grades 3-5 papilledema, versus –0.67 dB in patients with grades 1-2 disease. Thus, "the clinical importance of the NORDIC trial will be greatest for patients with severe papilledema, who stand to gain the most from the drug," he said. "Patients with pseudotumor cerebri who have only a few decibels of visual field loss should not necessarily be treated with acetazolamide. The adverse effects of the drug may outweigh the slight improvement in visual function."

Dr. Horton is a neuro-ophthalmologist and professor at the University of California, San Francisco. He reported that he has no conflicts of interest. These remarks were taken from his editorial accompanying Dr. Wall’s report (JAMA 2014;311:1618-9).


 

FROM JAMA

In patients with idiopathic intracranial hypertension and mild vision loss, adding oral acetazolamide to a low-sodium weight loss diet improved visual field function more than diet alone, researchers reported. The study was published online April 22 in JAMA.

Perimetric mean deviation (PMD) – the primary outcome measure – differed by less than 1 dB between the two groups, reported Dr. Michael Wall of the University of Iowa Hospitals and Clinics in Iowa City and his associates with the Neuro-Ophthalmology Research Disease Investigator Consortium (NORDIC). The clinical relevance of the difference "remains to be determined," the investigators said.

The researchers randomized 165 patients with idiopathic intracranial hypertension and mild vision loss (PMD, –2 to –7 dB) to oral acetazolamide or placebo. Patients received up to 4 g acetazolamide twice daily. Initial doses were increased until papilledema grade fell below 1 on the Frisén scale and PMD improved to at least –1 dB in both eyes. Both groups also followed a diet and lifestyle modification program, according to the investigators (JAMA 2014;311:1641-51[doi:10.1001/jama.2014.3312]).

Baseline PMD was –3.53 dB in both groups. At 6 months, PMD averaged –2.10 dB in the acetazolamide group and –2.82 dB in the placebo group (treatment difference, 0.71 dB; 95% CI, 0- 1.43 dB; P = .050).

The acetazolamide group also had greater mean improvements in papilledema grade (treatment effect, –0.70; 95% CI, –0.99 to –0.41; P less than .001) and vision-related quality of life on the VFQ-25 (Visual Functioning Questionnaire–25) survey tool (treatment effect, 6.35; 95% CI, 2.22-10.47; P = .003). And the treatment group lost 4.05 kg more weight than the exercise-only group (95% CI, –6.27 to –1.83 kg; P less than .001), the researchers said. A statistical mediation analysis showed that most of the effect of acetazolamide on PMD was not due to weight loss, they reported.

However, the functional importance of specific decibel improvements in PMD are poorly understood, Dr. Wall and his associates noted. "Our chosen minimal clinically important difference for PMD was 1.3 dB and was based on a small pilot study designed to estimate the level of decibels at which a clinician makes a decision to change therapy," they said. "Our estimated treatment effect was only approximately half of this value."

The acetazolamide group was significantly more likely to develop paresthesia, dysgeusia, fatigue, decreased carbon dioxide level, nausea, vomiting, diarrhea, and tinnitus than the exercise-only group, the investigators reported. "No participant, to our knowledge, experienced permanent morbidity from receiving acetazolamide," they added.

The National Eye Institute funded the study. Two coauthors reported receiving personal fees from Teva Pharmaceutical Industries, which produces generic acetazolamide.

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