Review question
We attempted to find all of the published randomised controlled trials (RCT, a type of rigorous study that compares one treatment option against another) that investigated any treatment for idiopathic intracranial hypertension (IIH) in any patient group. We looked at a number of outcomes including reduction in vision, improvement of headache and quality of life.
Background
IIH is a condition in which there is increased pressure inside the head without any detectable cause. IIH occurs most commonly in young women who are obese. Increased pressure inside the head often results in swelling of the optic disc (the point where the optic nerve meets the eye), which is called papilloedema. This swelling in turn causes a potential threat to sight. Different management options or treatments have been suggested for treating people with IIH, such as weight loss, drugs (e.g. diuretics) and surgery (e.g. surgery to the optic nerve, brain surgery to reduce the pressure or weight loss surgery). However, there is no consensus for how IIH should best be treated.
Search date
We searched for all available trials up to 22 July 2015.
Key results
We included two completed RCTs from the UK and US with a total of 211 participants and two ongoing studies. Both completed trials compared acetazolamide to placebo, together with a weight loss intervention in both groups.
In these studies, change in the participant’s central vision was similar in the treatment and control groups as measured by a logMAR chart (a chart with rows of letters). The outcome for this review was reduction in CSF pressure to normal levels which was not reported by the two trials. In one study, people in the acetalozamide group on average experienced a greater reduction in papilloedema as assessed by fundus photographs between baseline and six months in the study eye. Both studies reported headache on visual analogue scales but results were inconclusive. In the study that reported adverse effects, the acetazolamide group was found to have a greater number of adverse effects compared to the placebo controls including diarrhoea, nausea, tinnitus and fatigue. One study reported that quality of life was better for the acetazolamide-treated group. Costs were not reported in either study.
Quality of evidence
Both completed trials had issues such as high loss to follow up and in one trial the participants and trial investigators knew what treatment was being received. The evidence was therefore judged to be of low quality.
More higher-quality RCTs are required in order to adequately assess the effect of acetazolamide therapy in IIH.
Although the two included RCTs showed modest benefits for acetazolamide for some outcomes, there is insufficient evidence to recommend or reject the efficacy of this intervention, or any other treatments currently available, for treating people with IIH. Further high-quality RCTs are required in order to adequately assess the effect of acetazolamide therapy in people with IIH.
Idiopathic intracranial hypertension (IIH) has an estimated incidence of one to three people per 100,000 people per year, and occurs most commonly in obese, young women. IIH is associated with severe morbidity, notably due to a significant threat to sight and severe headache. Several different management options have been proposed. Conservative measures centre on weight loss. Pharmacological therapy includes use of diuretics. Refractory and sight-threatening cases demand surgical intervention, most often in the form of cerebrospinal fluid (CSF) diversion or optic nerve sheath fenestration. Other treatments include venous sinus stenting and bariatric surgery.
To assess the effects of any intervention for IIH in any patient group.
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015 Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2015), EMBASE (January 1980 to July 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 July 2015.
We included only randomised controlled trials (RCTs) in which any intervention was compared to placebo, or to another form of treatment, for people with a clinical diagnosis of IIH.
Two review authors independently assessed the search results for trials to be included in the review. We resolved any discrepancies by third party decision.
We identified two completed RCTs (enrolling a total of 211 participants and conducted in the UK and US) and two ongoing trials that met the inclusion criteria. Both completed trials compared acetazolamide to placebo, in conjunction with a weight loss intervention in both groups. Attrition bias was a problem in both trials with high loss to follow-up, in one study this loss to follow-up occurred particularly in the acetazolamide arm. One trial was unmasked and we judged it to be at risk of performance and detection bias.
In these studies, change in visual acuity was similar in the treatment and control groups as measured by logMAR acuity. In one study people in the acetalomazide group had a similar change in logMAR acuity compared to the placebo group between baseline and 12 months in the right eye (MD 0.04 logMAR, 95% CI -0.08 to 0.16) and left eye (MD 0.03 logMAR, 95% CI -0.09 to 0.15). In the other study people in the acetalomazide group had a similar change in vision over six months compared with people in the placebo group (mean difference in change in letters read was 0.01 (95% CI -1.45 to 1.46). One study reported no cases of visual loss in 21 people treated with acetalomazide compared to 2/20 cases in the placebo group (odds ratio 0.17, 95% CI 0.01, 3.82).
The prespecified outcome for this review was reduction in CSF pressure to normal levels which was not reported by the two trials. One trial reported that, in a subsample of 85 participants who agreed to lumbar puncture at 6 months, people in the acetalomazide group on average had a greater reduction in CSF pressure (MD -59.9 mmH2O, 95% CI -96.4, -23.4).
In one study, people in the acetalozamide group on average experienced a greater reduction in papilloedema as assessed by fundus photographs MD -0.70 (95% CI -1.00 to -0.40) and by clinical grading MD -0.91 (95% CI -1.27 to -0.54) between baseline and six months in the study eye.
Headache was recorded as present/absent in one study at 12 months (OR 0.42, 95% CI 0.12,1.41, 41 participants). Both studies reported headache on visual analogue scales (different ones) but results were inconclusive (MD for change in headache score measured on 10-point visual analogue scale at 12 months was 1.0 (-1.80, 3.70, 41 participants) and MD for change in headache score on a 6 point scale measured at 6 months was -0.45 (-3.5,2.6, number of participants unclear).
In one study, a similar proportion of people in the acetalomazide group were in remission (however, the trial authors did not state their definition of this term) at 12 months compared to the placebo group. However, the 95% CIs were wide and there is considerable uncertainty as to the effect (OR 1.13 (95% CI 0.32 to 3.90, 41 participants).
In one study of 185 participants, people in the acetalomazide group had an increased risk of decreased CO2, diarrhoea, dysgeusia, fatigue, nausea, paresthesia, tinnitus and vomiting compared to people in the placebo group. In general, the estimates of effect were uncertain with wide 95% CIs. Adverse effects were not reported in the other study.
One study reported that quality of life was better in acetazolamide-treated patients based on the visual quality of life (VFQ-25) (MD 6.35, 95% CI 2.22 to 10.47) and the physical (MD 3.02, 95% CI 0.34 to 5.70) and mental (MD 3.45, 95% CI 0.35 to 6.55) components of the 36-Item Short Form Health Survey tool at six months. Costs were not reported in either study.
We judged the evidence to be low certainty (GRADE) downgrading for imprecision and risk of bias.