What Have We Learned From the Idiopathic Intracranial Hypertension Treatment Trial the William F. Hoyt Lecture.

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.