Table 1.
Clinical data.
Table 2.
Metabolites in NAWM and lesion load in the visual pathways in MS patients.
Table 3.
Brain atrophy indices in MS patients.
Table 4.
RNFL and TMV in MS patients, global.
Table 5.
RNFL in MS patients.
Fig 1.
white squares, RRMS without ON; black squares, RRMS with ON; white triangles, SPMS without ON; black triangles, SPMS with ON; black line, linear regression curve. Abbreviations: OD, oculus dexter (right eye); OS, oculus sinister (left eye); RNFL, retinal nerve fiber layer; NAA, N-acetyl-aspartate; Cho, choline; Cr, creatine; NAWM, normal appearing white matter; MIF, the maximum width of the anterior interhemispheric fissure; MSF, the maximum width of the Sylvian fissure; MFSS, the maximum frontal subarachnoid space; EDSS, expanded disability severity scale. a1-g8, linear regression curves for: a1, RNFL vs. NAA (right eye); a2, RNFL vs. NAA (left eye); a3, RNFL vs. Cho (right eye); a4, RNFL vs. Cho (left eye); a5, RNFL vs. Cr (right eye); a6, RNFL vs. Cr (left eye); a7, disease duration vs. NAA in the NAWM; a8, disease duration vs. Cho; b1, RNFL vs. lesion load (right eye); b2, RNFL vs. lesion load (left eye); b3, RNFL vs. lesion load per brain volume (right eye); b4, RNFL vs. lesion load per brain volume (left eye); b5, RNFL vs. lesion load along anterior right visual pathway (right eye); b6, RNFL vs. lesion load anterior right visual pathway (left eye); b7, RNFL vs. lesion load along anterior left visual pathway (right eye); b8, RNFL vs. lesion load anterior left visual pathway (left eye); c1, RNFL vs. lesion load along posterior right visual (right eye); c2, RNFL vs. lesion load along posterior left visual pathway (left eye); c3, RNFL vs. lesion load along posterior left visual (right eye); c4, RNFL vs. lesion load along posterior left visual pathway (left eye); c5, RNFL vs. Evan’s Index (right eye); c6, RNFL vs. Evan’s Index (left eye); c7, RNFL vs. Caudate Head Index (right eye); c8, RNFL vs. Caudate Head Index Index (left eye); d1, RNFL vs. Cella Media Index (right eye); d2, RNFL vs. Cella Media Index (left eye); d3, RNFL vs. Basal Cistern Index (right eye); d4, RNFL vs. Basal Cistern Index Index (left eye); d5, RNFL vs. the maximum width of the 3rd ventricle (right eye); d6, RNFL vs. the maximum width of the 3rd ventricle (left eye); d7, RNFL vs. the maximum of the 4th width ventricle (right eye); d8, RNFL vs. the maximum of the 4th width ventricle (left eye); e1, RNFL vs. MFSS (right eye); e2, RNFL vs. MFSS (left eye); e3, RNFL vs. MIF (right eye); e4, RNFL vs. MIF (left eye); e5, RNFL vs. MSF (right eye); e6, RNFL vs. MSF (left eye); e7, disease duration vs. Evan’s Index; e8, disease duration vs. Caudate Head Index; f1, disease duration vs. Cella Media Index; f2, disease duration vs. the maximum width of the 3rd ventricle; f3, disease duration vs. the maximum width of the 4th ventricle; f4, disease duration vs. MFSS; f5, disease duration vs. MIF; f6, disease duration vs. MSF; f7, disease duration vs. lesion load along both visual pathways; f8, disease duration vs. lesion load along the anterior right visual pathway; g1, disease duration vs. lesion load along the anterior left visual pathway; g2, disease duration vs. lesion load along the posterior right visual pathway; g3, disease duration vs. lesion load along the posterior left visual pathway; g4, disease duration vs. EDSS; g5, disease duration vs. RNFL (right eye); g6, disease duration vs. RNFL (left eye); g7, RNFL (right eye) vs. EDSS; g8, RNFL (right eye) vs. EDSS. Regression analyses demonstrated only weak correlations between the examined parameters a1-g8 of all 28 MS patients included in this study and associated subgroups (RRMS without ON, RRMS with ON, SPMS without ON, SPMS with ON). Of note, the plotted linear regression curves in a1 –g8 are calculated for the analysis of all included MS patient.
Table 6.
Simple regression–linear model: Independent variable, RNFL; dependent variables, NAA, N-acetyl-aspartate; Cho, choline; Cr, creatine; LL per BV, lesionload per Brain Volume, LL AR, lesion load along anterior right visual pathway; LL AL, lesion load along anterior left visual pathway; LL PR, load along posterior right visual pathway; LL PL, load along posterior left visual pathway; Evan’s Index; CHI; CMI; BCI; the maximum width of the 3rd ventricle; the maximum width of the 4th ventricle; MIF, the maximum width of the anterior interhemispheric fissure; MFSS, the maximum frontal subarachnoid space; MSF, the maximum width of the Sylvian fissure; DD, disease duration; EDSS, expanded disability severity scale. 1st row: all right eyes (n = 28; with and without ON) of all included MS patient. 2nd row: all left eyes (n = 28; with and without ON) of all included MS patient. 3rd row: all right eyes of MS patients who never experienced an ON (neither on their right nor on their left eye; RRMS, n = 17, SPMS, n = 2; Table 1). 4th row: all left eyes of MS patients who never experienced an ON (neither on their left nor on their right eye; RRMS, n = 17, SPMS, n = 2; Table 1). Patients are the same as in the 3rd row. 5th row: right eyes of 6 MS patients who experienced an ON on their right eyes (note, 4 out of 6 experienced ON on both eyes, 2 only on their right eyes; Table 1). 6th row: left eyes of 6 MS patients who experienced an ON on their left eyes (note, 4 out of 7 experienced ON on both eyes, 3 only on their left eyes Table 1). For each analysis the correlation coefficient (corr. coeff.), R-squared (percent), the standard error of estimate (STE of Est.) and the p-value (analysis of variance, ANOVA) is given. Since the p-value in the ANOVA table is less than 0.01, there is a statistically significant relationship between the maximum width of the 4th ventricle and the RNFL (for all patients’ right eyes, n = 28, 1st row and for all patient’s left eyes, who never experienced ON, n = 17, 4th row) at 99% confidence level. However, the low correlation coefficient indicates that there is only a weak relationship between the variables. R-squared statistic indicates that the simple/linear regression explains only 24.92% (1st row) or 28.68% (4th row) of the variability of the independent variable. In all other analyses presented here (and performed for the six OCT-Sectors, see material and methods or Table 5) no statistically significant correlation could be found (data not shown).
Fig 2.
CROP, Clinico-Radiologico-Ophthalmological Paradox in MS.
MRI, 3 Tesla, serial sections: 1st row, sagittal, 2nd row, axial and 3rd row, coronar images from a RRMS patient with rather long disease course and highly active disease. Although very high lesion load in the whole brain and visual pathway and obvious brain atrophy the patient had normal RNFL and TMV values. (patient 1, Table 1).