Inner Retinal Layer Changes Reflect Changes in Ambulation Score in Patients with Primary Progressive Multiple Sclerosis
Abstract
:1. Introduction
2. Results
2.1. Study Cohorts
2.2. Cross-Sectional Retinal Layer Analysis
2.3. Longitudinal Retinal Layer Analysis
2.4. Deterioration in Ambulatory Function Associates with Macular Layer Degeneration
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Optical Coherence Tomography (OCT)
4.3. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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HC | PPMS | RRMS | p-Value HC vs. PPMS | p-Value HC vs. RRMS | p-Value PPMS vs. RRMS | |
---|---|---|---|---|---|---|
General Demographic Data | ||||||
Total subjects (n) | 61 | 57 | 62 | |||
Total eyes (n) Eyes scanned at Cirrus (n) Eyes scanned at Spectralis (n) | 121 0 121 | 108 44 64 | 114 39 75 | |||
Female, n (% of subjects) | 38 (62%) | 25 (44%) | 40 (65%) | 0.045 1 | 0.798 1 | 0.024 1 |
Age at OCTbas, mean ± SD (years) | 36.64 ± 12.82 | 54.12 ± 10.68 | 37.19 ± 10.75 | <0.001 2 | 0.796 2 | <0.001 2 |
Number of OCT scans, median (range: minimum to maximum) | 2 (2–5) | 3 (2–7) | 3 (2–7) | <0.001 3 | <0.001 3 | 0.377 3 |
Follow-up time, median (IQR) (months) | 7 (6–21) | 40 (22–76.2) | 28 (18.75–64.5) | <0.001 3 | <0.001 3 | 0.060 3 |
Multiple-Sclerosis-Specific Data | ||||||
Age at initial onset, mean ± SD (years) | 45.09 ± 10.10 | 30.52 ± 10.53 | <0.001 2 | |||
Disease duration, median (IQR) (years) | 7 (4–10.5) | 2 (0–10) | 0.002 3 | |||
Immunotherapy during observation period, n (treated subjects)/N (information available) (% of N) | 34/44 (77%) | 53/59 (90%) | 0.082 1 | |||
EDSS at OCTbas, median (IQR) | 4.25 (3.00–6.00) | 2.0 (1.75–3.50) | <0.001 2 | |||
Deterioration in ambulatory functional score (AS), n (deteriorated subjects)/N (information available) (% of N) | 16/37 (43%) | 9/50 (18%) | 0.010 1 |
HC vs. PwMS | PPMS vs. RRMS | |||||||
---|---|---|---|---|---|---|---|---|
HC | PwMS | ß (SE) | p-Value 1 | PPMS | RRMS | ß (SE) | p-Value 2 | |
Peripapillary Scan (MSK and LMU) | ||||||||
pRNFL, mean in µm (95% CI) N (eyes) | 100.24 (97.36–103.12) 121 | 94.47 (92.43–96.52) 222 | −5.765 (1.82) | 0.002 | 96.54 (92.99–100.10) 108 | 91.45 (87.99–94.91) 114 | 5.091 (2.81) | 0.072 |
Macula Scan (LMU) | ||||||||
TMV, mean in mm3 (95% CI) N (eyes) | 8.85 (8.76–8.94) 118 | 8.62 (8.54–8.71) 138 | −0.221 (0.06) | <0.001 | 8.66 (8.54–8.79) 63 | 8.55 (8.43–8.66) 75 | 0.115 (0.10) | 0.232 |
GCIP, mean in mm3 (95% CI) N (eyes) | 1.14 (1.11–1.16) 118 | 1.05 (1.02–1.07) 138 | −0.093 (0.01) | <0.001 | 1.05 (1.02–1.09) 63 | 1.02 (0.99–1.06) 75 | 0.033 (0.03) | 0.266 |
INL, mean in mm3 (95% CI) N (eyes) | 0.97 (0.95–0.98) 118 | 0.98 (0.96–0.99) 138 | 0.008 (0.01) | 0.434 | 0.97 (0.95–1.00) 63 | 0.97 (0.95–0.99) 75 | 0.003 (0.02) | 0.850 |
ONPL, mean in mm3 (95% CI) N (eyes) | 2.593 (2.529–2.657) 120 | 2.614 (2.555–2.674) 130 | 0.022 (0.05) | 0.630 | 2.632 (2.563–2.700) 63 | 2.571 (2.505–2.638) 67 | 0.060 (0.05) | 0.269 |
HC vs. PwMS | PPMS vs. RRMS | |||||||
---|---|---|---|---|---|---|---|---|
HC | PwMS | ß (SE) | p-Value 1 | PPMS | RRMS | ß (SE) | p-Value 2 | |
Peripapillary Scan, relative annual change (MSK and LMU) | ||||||||
pRNFL mean in % (95% CI) N (eyes) | −0.131 (−0.436–0.174) 102 | −0.730 (−0.942–−0.519) 208 | −0.600 (0.191) | 0.002 | −0.597 (−0.877–−0.317) 100 | −0.833 (−1.103–−0.562) 108 | 0.235 (0.218) | 0.282 |
Macula Scan, relative annual change (LMU) | ||||||||
TMV mean in % (95% CI) N (eyes) | −0.076 (−0.234–0.083) 110 | −0.188 (−0.332–−0.044) 133 | −0.112 (0.110) | 0.309 | −0.226 (−0.417–−0.036) 61 | −0.200 (−0.371–−0.028) 72 | −0.027 (0.145) | 0.854 |
GCIP mean in % (95% CI) N (eyes) | −0.462 (−0.714–−0.209) 112 | −0.372 (−0.602–−0.141) 133 | 0.090 (0.175) | 0.608 | −0.160 (−0.486–0.166) 62 | −0.601 (−0.892–−0.309) 71 | 0.440 (0.247) | 0.077 |
INL mean in % (95% CI) N (eyes) | 1.210 (0.750–1.670) 103 | 0.326 (−0.077–0.730) 133 | −0.884 (0.312) | 0.005 | 0.158 (−0.252–0.569) 61 | 0.248 (−0.122–0.618) 72 | −0.090 (0.313) | 0.775 |
ONPL mean in % (95% CI) N (eyes) | −0.078 (−0.359–0.203) 112 | −0.317 (−0.578–−0.056) 130 | −0.239 (1.973) | 0.226 | −0.312 (−0.640–0.016) 61 | −0.308 (−0.613–−0.003) 69 | −0.004 (0.253) | 0.986 |
RRMS vs. PPMS Stable AS | PPMS Stable vs. Deterioration in AS | ||||||||
---|---|---|---|---|---|---|---|---|---|
RRMS Stable AS (t-Test) | PPMS Stable AS (t-Test) | PPMS Deterioration AS (t-Test) | p-Value (t-Test) | p-Value (ANCOVA) | r | p-Value (t-Test) | p-Value (ANCOVA) | r | |
Peripapillary Scan (MSK and LMU) | |||||||||
Relative annual change in pRNFL mean in %, (SD) | −0.766 (2.256) | −1.102 (1.797) | −0.656 (1.019) | 0.365 | 0.956 | 0.048 | 0.192 | 0.362 | 0.101 |
Macula Scan (LMU) | |||||||||
Relative annual change in TMV mean in %, (SD) | −0.186 (0.648) | 0.001 (0.856) | −0.544 (0.688) | 0.239 | 0.987 | 0.002 | 0.025 | 0.032 | 0.310 |
Relative annual change in GCIP mean in %, (SD) | −0.325 (0.912) | 0.278 (1.640) | −1.012 (1.103) | 0.060 | 0.004 | 0.295 | 0.005 | 0.006 | 0.390 |
Relative annual change in INL mean in % (SD) | 0.451 (1.450) | 0.724 (2.643) | −0.154 (0.878) | 0.516 | 0.681 | 0.043 | 0.179 | 0.203 | 0.187 |
Relative annual change in ONPL mean in %, (SD) | −0.291 (1.631) | 0.150 (1.672) | −0.979 (1.163) | 0.223 | 0.856 | 0.019 | 0.015 | 0.020 | 0.336 |
Ambulation Functional Score | EDSS | |||||
---|---|---|---|---|---|---|
All PwMS | PPMS | PPMS | ||||
HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |
Relative annual atrophy rate of pRNFL (in ‰) | 1.009 (0.979–1.040) | 0.550 | 1.024 (0.992–1.057) | 0.143 | 1.021 (1.002–1.040) | 0.030 |
Relative annual atrophy rate of TMV (in ‰) | 1.265 (1.132–1.414) | <0.001 | 1.309 (1.155–1.483) | <0.001 | 1.172 (1.081–1.270) | <0.001 |
Relative annual atrophy rate of GCIP (in ‰) | 1.093 (1.041–1.148) | <0.001 | 1.112 (1.053–1.174) | <0.001 | 1.059 (1.016–1.104) | 0.007 |
Relative annual atrophy rate of INL (in ‰) | 1.017 (0.973–1.062) | 0.456 | 1.026 (0.972–1.084) | 0.352 | 1.004 (0.974–1.035) | 0.779 |
Relative annual atrophy rate of ONPL (in ‰) | 1.013 (1.001–1.025) | 0.036 | 1.161 (1.086–1.241) | <0.001 | 1.026 (0.977–1.078) | 0.301 |
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Gernert, J.A.; Böhm, L.; Starck, M.; Buchka, S.; Kümpfel, T.; Kleiter, I.; Havla, J. Inner Retinal Layer Changes Reflect Changes in Ambulation Score in Patients with Primary Progressive Multiple Sclerosis. Int. J. Mol. Sci. 2023, 24, 12872. https://doi.org/10.3390/ijms241612872
Gernert JA, Böhm L, Starck M, Buchka S, Kümpfel T, Kleiter I, Havla J. Inner Retinal Layer Changes Reflect Changes in Ambulation Score in Patients with Primary Progressive Multiple Sclerosis. International Journal of Molecular Sciences. 2023; 24(16):12872. https://doi.org/10.3390/ijms241612872
Chicago/Turabian StyleGernert, Jonathan A., Luise Böhm, Michaela Starck, Stefan Buchka, Tania Kümpfel, Ingo Kleiter, and Joachim Havla. 2023. "Inner Retinal Layer Changes Reflect Changes in Ambulation Score in Patients with Primary Progressive Multiple Sclerosis" International Journal of Molecular Sciences 24, no. 16: 12872. https://doi.org/10.3390/ijms241612872