Papilledema Outcome Evaluation in the OCT Substudy of the Idiopathic Intracranial Hypertension Treatment Trial

Abstract

Purpose: To demonstrate the effect of therapy on quantitative imaging of papilledema in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT). The IIHTT showed that acetazolamide (ACZ) was efficacious in improving mild visual field loss in patients with IIH. We showed that spectral domain optical coherence tomography (SD-OCT) combined with custom 3-segmentation analysis provides reliable continuous measurements of structural changes in the optic nerve head and retina due to papilledema (OCT Sub-Study Committee, IOVS in press).

Methods: Eighty-nine (43 ACZ, 46 placebo treated) IIHTT subjects were evaluated at study entry and at 3 and 6 months with standard automated perimetry, Frisén grading of photos, high and low contrast visual acuity, and OCT imaging using the Cirrus SD-OCT. OCT data were analyzed using custom 3-D segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve volume (ONHV), and retinal ganglion cell layer (GCL) measurements. Results for ‘study eyes’ (with worse perimetric mean deviation, PMD, at baseline) were used for most analyses.

Results: At study entry, distributions of OCT measures were similar in both treatment groups. At 6 months, ACZ group eyes showed greater mean reductions in RNFL (175 µm vs. 89 µm, p=0.001), TRT (220 µm vs. 113 µm, p=0.001), and ONHV (4.9 mm³ vs. 2.1 mm³, p=0.001) than placebo group eyes. For both treatment groups, subjects with weight loss > 6% had greater mean reductions in RNFL (156 µm vs. 103 µm, p=0.01), TRT (201 µm vs 127 µm, p=0.003), and ONHV (4.3 mm³ vs. 2.6 mm³, p=0.002) than those with less weight loss. GCL thinning was minor in the ACZ (3.6 µm) and placebo (2.1 µm) groups. Interocular correlations were > 0.8 for all 3-D segmentation derived measurements. At 6 months, RNFL, TRT, and ONHV correlated with Frisén grade (r=0.48-0.59, p<0.0001). At 6 months, the 21 eyes with GCL thickness <5^th percentile of controls had worse PMD (p=0.01) and both high (p=0.05) and low (p=0.01) contrast acuity than for eyes with GCL > 5^th percentile.

Conclusions: OCT measures of swelling due to papilledema in IIH are effectively improved with ACZ and weight loss. In contrast to the strong correlation at baseline (IOVS in press), 6 month RNFL, TRT, and ONHV show only moderate correlations with papilledema grade.