Visual Field Outcomes for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT)

Abstract

Purpose: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) showed that acetazolamide provided a modest, significant improvement in mean deviation (MD). Here, we further analyze visual field changes over the 6-month study period.

Methods: Of 165 subjects with mild visual loss in the IIHTT, 125 had perimetry at baseline and 6 months. We evaluated pointwise linear regression of visual sensitivity versus time to classify test locations in the worst MD (study) eye as improving or not; pointwise changes from baseline to month 6 in decibels; and clinical consensus of change from baseline to 6 months.

Results: The average study eye had 36 of 52 test locations with improving sensitivity over 6 months using pointwise linear regression, but differences between the acetazolamide and placebo groups were not significant. Pointwise results mostly improved in both treatment groups with the magnitude of the mean change within groups greatest and statistically significant around the blind spot and the nasal area, especially in the acetazolamide group. The consensus classification of visual field change from baseline to 6 months in the study eye yielded percentages (acetazolamide, placebo) of 7.2% and 17.5% worse, 35.1% and 31.7% with no change, and 56.1% and 50.8% improved; group differences were not statistically significant.

Conclusions: In the IIHTT, compared to the placebo group, the acetazolamide group had a significant pointwise improvement in visual field function, particularly in the nasal and pericecal areas; the latter is likely due to reduction in blind spot size related to improvement in papilledema. (ClinicalTrials.gov number, NCT01003639.).

Figure 1

Mean threshold change in dB from baseline to 6 months at each test location within each treatment group, with positive values indicating improvement with the treatment failure subjects included. Note that the greatest changes occurred in the periphery and around the blind spot but improvement occurred across the visual field. Green: 2 dB or more improvement. Yellow: 1–2 dB improvement. Red: less than 1 dB improvement.

Figure 2

(A) Magnitude of treatment effect (acetazolamide–placebo) at each test location. (B) Value for statistical significance of the treatment effect at each test location; P < 0.05 shown in darker green.

Figure 3

Mean threshold changes (dB) from baseline to 6 months within each treatment group by zone; the zones are described in Supplementary Figure S1. The acetazolamide treatment group is represented by the dashed line and the placebo group is represented by the solid line. Error bars denote one standard error. Zones of increasing eccentricity are shown on the left and the pericecal zone adjacent to the blind spot is shown on the far right.

Figure 4

Percentages of subjects with a positive slope (estimated using PLR) at each test location by treatment group. Results for acetazolamide are shown on the left and those for placebo on the right. Note that the group differences are minor. Treatment failure subjects did not have enough visual field examinations to be included in these analyses.

Figure 5

Schematic of the visual island of a right eye in IIH modelling damage due to high- and low-grade papilledema. Blue lines represent the profile of the normal visual island through the horizontal meridian. Green dotted line: represents visual loss in the eye with low-grade papilledema. Red dashed line: the visual loss in the eye with high grade papilledema. The x-axis numbers are degrees of visual field eccentricity for a right eye.