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

Sample scans showing MME in SLO and OCT images.

<p>Sample SLO images (on the left) and sample OCT B-scan images (on the right) from A) MS patient’s eye with a history of ON but without MME, B) an MS patient’s eye with history of ON and MME, C) an NMO patient’s eye with history of ON and MME and D) an eye from a patient with CRION and MME. Whereas the eye from A does not show any signs of MME in either the SLO or OCT B-scan image, all eyes in B-D show similar findings. The SLO images were mirrored where necessary to standardize orientation.</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

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

Demographic overview of the study cohort.

<p><b>Abbreviations:</b> MME = microcystic macular edema; MS = multiple sclerosis; NMO = neuromyelitis optica spectrum diseases; CRION = chronic relapsing inflammatory optic neuropathy; HC = healthy control; RRMS = relapsing-remitting multiple sclerosis; SPMS = secondary-progressive multiple sclerosis; PPMS = primary-progressive multiple sclerosis; CIS = Clinical isolated syndrome; SD = standard deviation; Min = minimum value; Max = maximum value.</p

Sample quantification of SLO MME area.

<p>A) Quantification of the MME-affected area of a sample eye in a SLO image with ImageJ. B) The microcysts in OCT B-scans of the same sample eye mapped onto the SLO image. The yellow lines correspond to the spread of the macular edema in the two example B-scans at the bottom.</p

Retinal morphology in eyes without previous ON.

<p>Results of retinal OCT outcomes of NMOSD and MS patients’ eyes without history of optic neuritis and healthy controls; GEE results showing the differences between NMOSD-NON and MS-NON to healthy controls. Outer retinal layers include outer plexiform layer, outer nuclear layer and inner photoreceptor layer segments.</p><p><b>Abbreviations:</b> NMOSD: neuromyelitis optica spectrum disorder; MS: multiple sclerosis; NON: eyes without history of optic neuritis; HC: healthy controls; OCT: optical coherence tomography; p/mRNFL: peripapillary and macular retinal nerve fiber layer; TMV: total macular volume; GCL: ganglion cell layer; IPL: inner plexiform layer; INL: inner nuclear layer; SD: standard deviation; Min: minimum; Max: maximum; B: coefficient estimate from generalized estimating equation models (GEE), SE: standard error from GEE coefficient estimates.</p

Sample OCT measurement and segmentation.

<p>A) Sample scanning laser ophthalmoscopy image showing the peripapillary ring-scan for retinal nerve fiber layer analysis. Nasal and temporal quadrants were analyzed separately B) Sample scanning laser ophthalmoscopy image showing the B-scans included in the segmentation procedure (green and blue) and the area included into analysis (blue only). C) Sample macular scan showing the segmentation lines and intra-retinal layer layout. Red segmentation lines provided by the software define the macular retinal nerve fiber layer (mRNFL), the ganglion cell layer (GCL), the inner plexiform layer (IPL), the inner nuclear layer (INL), the outer plexiform layer (OPL), the outer nuclear layer (ONL), and inner segments of the photoreceptor layer (IS). OPL, ONL and IS were analyzed combined as outer retinal layers (ORL). D) Sample B-scan of an NMOSD patient with microcystic macular edema (MME).</p

Sample patient data from NMOSD and MS eyes.

<p>A) Peripapillary retinal nerve fiber layer (pRNFL) thickness data (in µm) for average RNFL (G) and sectors (nasal-superior quadrant (NS), temporal-superior (TS), temporal, temporal-inferior (TI), nasal-inferior (NI) and nasal (N)) for a multiple sclerosis (MS) patient’s eye with a previous optic neuritis (ON) (left), a neuromyelitis optica spectrum disorder (NMOSD) patient’s eye with a previous ON without microcystic macular edema (MME) (center), and an NMOSD patient’s eye with previous ON and MME (right). Background colors describe the comparison to a healthy reference group from the device’s database. B) and C) Thickness maps of the retinal ganglion cell layer (GCL, B) and inner nuclear layer (INL, C) respective to the patients’ data from A).</p

Intra-retinal layer thickness in NMOSD-ON eyes with and without microcystic macular edema.

<p>Layer thicknesses for the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL) and the combined outer retinal layers for NMOSD-ON eyes with (MME+, in red) and without (MME-, in blue) microcystic macular edema and healthy controls eyes (HC, in green). Outer retinal layers include outer plexiform layer, outer nuclear layer and inner photoreceptor layer segments.</p