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.).

Objective

To evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing-remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS).

Methods

Individuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6-monthly thereafter).

Results

OCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS-associated optic neuritis--group differences (95% CI) over 3 years: pRNFL: -1.86 (-2.54, -1.17) µm; mGCIPL: -2.03 (-2.78, -1.28) µm (both p < 0.0001; effect sizes 0.39 and 0.34). Greater inner retinal layer atrophy was observed in individuals diagnosed with RRMS <3 years versus >5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy (p < 0.0001). There was no correlation of OCT data with disability progression.

Interpretation

OCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.

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.

Artificial intelligence (AI)-based diagnostic algorithms have achieved ambitious aims through automated image pattern recognition. For neurological disorders, this includes neurodegeneration and inflammation. Scalable imaging technology for big data in neurology is optical coherence tomography (OCT). We highlight that OCT changes observed in the retina, as a window to the brain, are small, requiring rigorous quality control pipelines. There are existing tools for this purpose. Firstly, there are human-led validated consensus quality control criteria (OSCAR-IB) for OCT. Secondly, these criteria are embedded into OCT reporting guidelines (APOSTEL). The use of the described annotation of failed OCT scans advances machine learning. This is illustrated through the present review of the advantages and disadvantages of AI-based applications to OCT data. The neurological conditions reviewed here for the use of big data include Alzheimer disease, stroke, multiple sclerosis (MS), Parkinson disease, and epilepsy. It is noted that while big data is relevant for AI, ownership is complex. For this reason, we also reached out to involve representatives from patient organizations and the public domain in addition to clinical and research centers. The evidence reviewed can be grouped in a five-point expansion of the OSCAR-IB criteria to embrace AI (OSCAR-AI). The review concludes by specific recommendations on how this can be achieved practically and in compliance with existing guidelines.