J Neuroophthalmol. 2026 Jun 1;46(2):271-278. doi: 10.1097/WNO.0000000000002481.
ABSTRACT
BACKGROUND: The Idiopathic Intracranial Hypertension Treatment Trial’s (IIHTT) objective was to evaluate the efficacy and safety of acetazolamide, combined with a low-sodium weight-reduction diet, in improving visual function in patients with idiopathic intracranial hypertension (IIH) and mild visual loss.
METHODS: To accomplish this, a NEI-sponsored multicenter, double-blind, randomized, placebo-controlled clinical trial was performed at 38 North American clinical sites. A total of 165 participants (161 women; mean age 29 years) meeting the modified Dandy criteria with reproducible mild visual loss (perimetric mean deviation [PMD] -2 to -7 dB) were enrolled. Participants were randomized to acetazolamide or placebo, each combined with a structured dietary program. Acetazolamide was initiated at 1 g/day and titrated weekly to a maximum of 4 g/day. The primary outcome was change in PMD at 6 months. Treatment failure was defined by prespecified reproducible PMD worsening criteria. Secondary outcomes included papilledema grade, OCT metrics, cerebrospinal fluid (CSF) pressure, quality of life, weight change, and headache disability.
RESULTS: Acetazolamide produced greater PMD improvement than placebo (1.43 dB vs 0.71 dB; treatment effect 0.71 dB; P = 0.05) and the result was independent of weight loss. Participants with high-grade papilledema had the greatest benefit (2.27 dB). Acetazolamide significantly improved papilledema grade and OCT optic disc volume and reduced CSF pressure by an additional 60-mm H2O compared with placebo (P = 0.002). Quality-of-life scores improved significantly with improvement in vision being the most important factor. Seven participants experienced treatment failure (6 placebo, 1 acetazolamide). Risk factors for treatment failure were high-grade papilledema, more than 30 transient visual obscurations per month, visual acuity loss, and male sex. Compliance of study drug was high (89% vs 93%). Tolerability was excellent when the maximal tolerated dosage was used with no permanent morbidity.
CONCLUSIONS: Acetazolamide plus diet gave statistically significant improvements of visual function, papilledema, CSF pressure, and quality of life in patients with IIH with mild visual loss. A maximally tolerated dose up to 4 g/day is recommended.
PMID:42133960 | DOI:10.1097/WNO.0000000000002481
