Results of the retinal segmentation for patients with a history of unilateral ON, patients’ eyes with MME and controls.

<p><b>Abbreviations:</b> MME = microcystic macular edema; ON = optic neuritis; mRNFL = macular retinal nerve fiber layer; GCIPL = ganglion cell and inner plexiform layer; INL = inner nuclear layer; SD = standard deviation; GEE = generalized estimation equation.</p

Segmentation of retinal layers.

<p>(A) Sample ring scan with additional layer segmentation. Layers from top: Nerve fiber layer (NFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PRL) and retinal pigment epithelium (RPE). (B) Comparison of the mean thickness of the additional retinal layers between healthy controls (in blue) and SCA1 patients (in red).</p

Single case reports of SCA1 patients.

<p>Single case reports of SCA1 patients.</p

Disease severity in MS patients.

<p><b>Abbreviations:</b> MME = microcystic macular edema; MS = multiple sclerosis ON = optic neuritis; SD = standard deviation; Min = minimum value; Max = maximum value; EDSS = Expanded Disability Status Scale; MSSS = Multiple Sclerosis Severity Score.</p

Ocular key data of MME and non-MME eyes.

a)<p>The contralateral eyes of unilateral MME eyes were excluded.</p><p><b>Abbreviations:</b> MME = microcystic macular edema; MS = multiple sclerosis; NMO = neuromyelitis optica spectrum diseases; CRION = chronic relapsing inflammatory optic neuropathy; ON = optic neuritis; pRNFL = peripapillary retinal nerve fiber layer; TMV = total macular volume; SD = standard deviation; Min = minimum value; Max = maximum value.</p

Differences of RNFLT between SCA1 and HC.

<p>(A) Average RNFLT (in µm) of the total ring scan (G) and in the different sectors (nasal-superior (NS), nasal (N), nasal-inferior (NI), temporal-inferior (TI), temporal (T) and temporal-superior (TS)). Error bars indicate standard deviation. Significance levels (*** for p<0.001, ** for p<0.01 and * for p<0.05) were calculated by GEE. (B) Mean RNFLT profile of both study groups in µm. (C) Both eyes (OD = right, OS = left) of a sample patient (upper line) with typical RNFLT sectors in comparison with matched healthy control (bottom line). The colors of the sectors are related to the comparison with the Spectralis normative database. Green indicates thickness values within the 95%-percentile of the database, while sectors in yellow were thinner than the 5%-percentile of the normative database and sectors in red were within the lowest 1%.</p

Differences in the outer plexiform layer (OPL) in repeated OCT measurements.

<p>(A) and (B) show two repeated OCT measurements (16 min between both examinations) of the same subject with the same scan settings (Scan V-25-1024 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137316#pone.0137316.g001" target="_blank">Fig 1</a>). On the left, the fundus images are given with an overlay of the OPL thickness maps generated by the Eye Explorer software (Heidelberg Engineering, Germany). The B-scans (with and without OPL segmentation lines) are shown on the right and are located at the position indicated by the green line on the fundus images. (C) The difference map on the left was calculated by subtracting the OPL thickness map in (A) from the map in (B) (custom Matlab program). The values in the grid are the mean OPL thickness differences for each sector. The right graph maps the OPL thickness of the B-scans in (A) (green line) and (B) (blue line), respectively. The red line indicates the difference between the repeated B-scans.</p

Explanation of different thickness estimates used for the simulation of repeatability.

<p>The red areas or points on the fundus images indicate the values that were averaged to generate the layer thickness estimates. The text to the right of each image refers to (top-to-bottom): 1) the used OCT device 2) the applied scan as elucidated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137316#pone.0137316.g001" target="_blank">Fig 1</a>; 3) the (subset of) B-scans used for the thickness estimate; 4) the procedure used to calculate the thickness estimates; 5) the program used for calculating the thickness estimate. The last column indicated the article(s) in which the layer estimated was applied. For a detailed overview of the segmentation methods applied in the retrieved articles, see Table B in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137316#pone.0137316.s002" target="_blank">S1 File</a>. Note: the number and spacing of B-scans on the fundus image for the thickness estimates C and E are not correct due to space limitations.</p

Inter-eye differences in patients with unilateral history of optic neuritis.

<p>A) Differences in inner nuclear layer (INL) thickness between affected and unaffected eyes of patients with a unilateral history of optic neuritis categorized by diagnosis. Eyes belonging to one patient are connected by lines. Lines in blue indicate eyes, which the INL of the optic neuritis eyes was thicker compared to the contralateral unaffected eyes, whereas red lines show the contrary. B) Correlation of inter-eye INL thickness differences with inter-eye macular retinal nerve fiber layer (mRNFL) thickness differences (LR: P<0.001). C) Correlation of inter-eye INL thickness differences with inter-eye ganglion cell and inner plexiform layer (GCIPL) thickness differences (LR: P = 0.011).</p

Coefficient of repeatability (CR) for different thickness estimates and retinal layers in MS/CIS patients and healthy controls.

<p>Coefficient of repeatability (CR) for the distinct cohorts of healthy controls (HC) and patients (MS) ordered for (A) the 12 thickness estimates (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0137316#pone.0137316.g003" target="_blank">Fig 3</a>) and (B) the 7 retinal layers. <b>Abbreviations</b>: <b>mRNFL</b> = macular retinal nerve fiber layer, <b>GCL</b> = ganglion cell layer, <b>IPL</b> = inner plexiform layer, <b>GICP</b> = combined GCL and IPL, <b>INL</b> = inner nuclear layer, <b>OPL</b> = outer plexiform layer, <b>ONL</b> = outer nuclear layer.</p