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Recently reported results from a multicentre, randomised, double-masked, placebo-controlled study provide the first solid evidence to support oral acetazolamide as treatment for visual loss associated with idiopathic intracranial hypertension (IIH) (JAMA. 2014;311(16):1641-51).

Funded by the National Eye Institute of the National Institutes of Health, the IIH Treatment Trial included 165 adults enrolled at 38 North American study sites. Eligible patients met modified Dandy criteria for IIH, were untreated for IIH, and had mild visual loss [perimetric mean deviation (PMD) between -2dB and -7dB], bilateral papilledema and elevated cerebrospinal fluid (CSF) opening pressure.

All patients were offered a weight loss programme incorporating lifestyle/behavioural modification and a low-sodium weight-reduction diet plan. They were randomised 1:1 to treatment with a maximally tolerated dosage of acetazolamide or matching placebo. Acetazolamide was initiated at 500mg BID and titrated up to a maximum of 4 g/day based on disease signs and symptoms and adverse events.



Mean change in PMD from baseline to six months in the most affected eye was analysed as the primary outcome variable, and improvement occurred in both the acetazolamide (1.43dB) and control groups (0.71dB). However, the treatment effect (difference between groups) was statistically significant and stronger among eyes with higher (grade 3-5) versus lower (grade 1-2) papilledema grades (2.27dB vs −0.67dB).

Compared to placebo, acetazolamide was also associated with a statistically significant benefit for greater reduction in optic disc swelling (mean papilledema grade change, −1.31 vs. −0.61) and greater improvement in vision-related and other quality of life measures. There were also significant differences favouring acetazolamide over placebo in analyses of visual field change and papilledema grade for the fellow eye along with trends for a lower treatment failure rate (1.2 per cent vs 7.6 per cent) and greater CSF pressure lowering (−117.3 vs −72.2mmHg) in the acetazolamide group.

Patients in both groups experienced significant weight loss from baseline, although acetazolamide-treated patients lost significantly more weight than the controls (−7.50 vs −3.45kg), perhaps due to acetazolamide-related side effects. However, a separate analysis established that the treatment effect of acetazolamide on PMD was not mediated by its association with greater weight loss, and the medication was well-tolerated. While adverse events and adverse event-related withdrawals were more common with acetazolamide, there were no unexpected or known permanent untoward side effects associated with its use.

Michael Wall MD, IIHTT director and professor, Departments of Neurology and Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, told EuroTimes, “For the first time, data from a properly controlled clinical trial is available to guide therapy for patients with IIH.

Although the effect size of 0.71dB may not be a clinically significant amount of visual improvement, the fact that visual quality of life measures were also significantly better in the acetazolamide group suggests the effect is clinically meaningful.”

Dr Wall said that based on the study outcomes, the investigators strongly suggest that patients with mild visual loss and moderate to marked papilledema associated with IIH be treated with acetazolamide at the maximally tolerated dosage coupled with a low sodium weight loss programme. Since the combined medical regimen was also found to significantly lower CSF pressure, improve general and visual quality of life scores and reduce papilledema, it is also suggested for all patients with IIH-related visual loss, he said.

“Patients with papilledema grades 1 or 2 and no visual field loss can be managed with diet alone, but should be followed closely and started on acetazolamide if they worsen,” Dr Wall added.

He suggested the combined medical regimen or surgery could be considered for IIH patients with worse visual loss (PMD >-7dB).

“Another clinical trial will be needed to establish an evidence base to make recommendations for management of patients with IIH having more severe visual loss. However, starting with the medical intervention and transitioning to surgery if there is worsening would seem to be a reasonable compromise,” Dr Wall said.


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