PURPOSE:To determine the frequency, patterns, associations, and biomechanical implications of retinal and choroidal folds in papilledema due to idiopathic intracranial hypertension (IIH). METHODS:Retinal and choroidal folds were studied in patients enrolled in the IIH Treatment Trial using fundus photography (n = 165 study eyes) and spectral-domain optical coherence tomography (SD-OCT; n = 125). We examined the association between folds and peripapillary shape, retinal nerve fiber layer (RNFL) thickness, disc volume, Frisén grade, acuity, perimetric mean deviation, intraocular pressure, intracranial pressure, and refractive error. RESULTS:We identified three types of folds in IIH patients with papilledema: peripapillary wrinkles (PPW), retinal folds (RF), and choroidal folds (CF). Frequency, with photos, was 26%, 19%, and 1%, respectively; SD-OCT frequency was 46%, 47%, and 10%. At least one type of fold was present in 41% of patients with photos and 73% with SD-OCT. Spectral-domain OCT was more sensitive. Structural parameters related to the severity of papilledema were associated with PPW and RF, whereas anterior deformation of the peripapillary RPE/basement membrane layer was associated with CF and RF. Folds were not associated with vision loss at baseline. CONCLUSIONS:Folds in papilledema are biomechanical signs of stress/strain on the optic nerve head and load-bearing structures induced by intracranial hypertension. Folds are best imaged with SD-OCT. The patterns of retinal and choroidal folds are the products of a complex interplay between the degree of papilledema and anterior deformation of the load-bearing structures (sclera and possibly the lamina cribrosa), both modulated by structural geometry and material properties of the optic nerve head. (ClinicalTrials.gov number, NCT01003639.).

Purpose

Optical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting.

Methods

At entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods.

Results

The average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm-derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation-derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods.

Conclusions

Spectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.).

Purpose

The accepted method to evaluate and monitor papilledema, Frisén grading, uses an ordinal approach based on descriptive features. Part I showed that spectral-domain optical coherence tomography (SD-OCT) in a clinical trial setting provides reliable measurement of the effects of papilledema on the optic nerve head (ONH) and peripapillary retina, particularly if a 3-D segmentation method is used for analysis.(1) We evaluated how OCT parameters are interrelated and how they correlate with vision and other clinical features in idiopathic intracranial hypertension (IIH) patients.

Methods

A total of 126 subjects in the IIH Treatment Trial (IIHTT) OCT substudy had Cirrus SD-OCT optic disc and macula scans analyzed by using a 3-D segmentation algorithm to derive retinal nerve fiber layer (RNFL) thickness, total retinal thickness (TRT), retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) thickness, and ONH volume. The SD-OCT parameter values were correlated with high- and low-contrast acuity, perimetric mean deviation, Frisén grading, and IIH features.

Results

At study entry, the average RNFL thickness, TRT, and ONH volume showed significant strong correlations (r ≥ 0.90) with each other. The same OCT parameters showed a strong (r > 0.76) correlation with Frisén grade and a mild (r > 0.24), but significant, correlation with lumbar puncture opening pressure. For all eyes at baseline, neither visual acuity (high or low contrast) nor mean deviation correlated with any OCT measure of swelling or GCL+IPL thickness.

Conclusions

In newly diagnosed IIH, OCT demonstrated alterations of the peripapillary retina and ONH correlate with Frisén grading of papilledema. At presentation, OCT measures of papilledema, in patients with newly diagnosed IIH and mild vision loss, do not correlate with clinical features or visual dysfunction. (ClinicalTrials.gov number, NCT01003639.).

Purpose

To assess treatment efficacy using spectral-domain (SD) optical coherence tomography (OCT) measurements of papilledema in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT), which evaluated the effects of acetazolamide and weight management and of placebo and weight management in eyes with mild visual loss.

Design

Randomized double-masked control clinical trial of acetazolamide plus weight management compared with placebo plus weight management in subjects with mild visual field loss and previously untreated idiopathic intracranial hypertension (IIH).

Participants

Eighty-nine (43 acetazolamide treated, 46 placebo treated) of 165 subjects meeting IIHTT entry criteria.

Methods

Subjects underwent perimetry, papilledema grading (Frisén method), high- and low-contrast visual acuity, and SD OCT imaging at study entry and 3 and 6 months. Study eye results (worse perimetric mean deviation [PMD]) were used for most analyses.

Main outcome measures

Retinal nerve fiber layer (RNFL) thickness, total retinal thickness (TRT), optic nerve (ONH) volume, and retinal ganglion cell layer (RGCL) measurements derived using 3-dimensional segmentation.

Results

Study entry OCT values were similar in both treatment groups. At 6 months, the acetazolamide group had greater reduction than the placebo group for RNFL thickness (175 μm vs. 89 μm; P = 0.001), TRT (220 μm vs. 113 μm; P = 0.001), and ONH volume (4.9 mm(3) vs. 2.1 mm(3); P = 0.001). The RNFL thickness (P = 0.01), TRT (P = 0.003), and ONH volume (P = 0.002) measurements also showed smaller increases in subjects who lost 6% or more of study entry weight. The acetazolamide (3.6 μm) and placebo (2.1 μm) groups showed minor RGCL thinning (P = 0.06). The RNFL thickness, TRT, and ONH volume measurements showed moderate correlations (r = 0.48-0.59; P ≤ 0.0001) with Frisén grade. The 14 eyes with RGCL thickness less than the fifth percentile of controls had worse PMD (P = 0.001) than study eyes with RGCL in the fifth percentile or more.

Conclusions

In IIH, acetazolamide and weight loss effectively improve RNFL thickness, TRT, and ONH volume swelling measurements resulting from papilledema. In contrast to the strong correlation at baseline, OCT measures at 6 months show only moderate correlations with papilledema grade.