TY - JOUR
T1 - Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy
AU - International Multiple Sclerosis Visual System (IMSVISUAL) Consortium
AU - Sotirchos, Elias S.
AU - Gonzalez Caldito, Natalia
AU - Filippatou, Angeliki
AU - Fitzgerald, Kathryn C.
AU - Murphy, Olwen C.
AU - Lambe, Jeffrey
AU - Nguyen, James
AU - Button, Julia
AU - Ogbuokiri, Esther
AU - Crainiceanu, Ciprian M.
AU - Prince, Jerry L.
AU - Calabresi, Peter A.
AU - Saidha, Shiv
N1 - Funding Information:
This study was funded by the NIH National Institute of Neurological Disorders and Stroke (R01NS082347 to P.A.C.), National MS Society (FP‐1607‐24999 to E.S.S., RG‐1606‐08768 to S.S., TR 3760‐A‐3 to P.A.C., RG 4212‐A‐4 to L.J.B. subcontracted to P.A.C.), Race to Erase MS (to S.S.), and ACTRIMS (to IMSVISUAL).
Publisher Copyright:
© 2020 American Neurological Association
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Objective: Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)-derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing–remitting multiple sclerosis (RRMS). Methods: 178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow-up of 3.7 years. Results: The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. However, independent of age, PMS was associated with faster pRNFL (−0.34 ± 0.09%/yr, p < 0.001) and GCIPL (−0.27 ± 0.07%/yr, p < 0.001) thinning, as compared to RRMS. In both MS and controls, higher baseline age was associated with faster inner nuclear layer (INL) and outer nuclear layer (ONL) thinning. INL and ONL thinning were independently faster in PMS, as compared to controls (INL:−0.09 ± 0.04%/yr, p = 0.03; ONL:−0.12 ± 0.06%/yr, p = 0.04), and RRMS (INL:−0.10 ± 0.04%/yr, p = 0.01; ONL:−0.13 ± 0.05%/yr, p = 0.01), whereas they were similar in RRMS and controls. Unlike RRMS, disease-modifying therapies (DMTs) did not impact rates of retinal layer atrophy in PMS. Interpretation: PMS is associated with faster retinal atrophy independent of age. INL and ONL measures may be novel biomarkers of neurodegeneration in PMS that appear to be unaffected by conventional DMTs. The effects of aging on rates of retinal layer atrophy should be considered in clinical trials incorporating OCT outcomes. ANN NEUROL 2020;87:885–896.
AB - Objective: Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)-derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing–remitting multiple sclerosis (RRMS). Methods: 178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow-up of 3.7 years. Results: The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. However, independent of age, PMS was associated with faster pRNFL (−0.34 ± 0.09%/yr, p < 0.001) and GCIPL (−0.27 ± 0.07%/yr, p < 0.001) thinning, as compared to RRMS. In both MS and controls, higher baseline age was associated with faster inner nuclear layer (INL) and outer nuclear layer (ONL) thinning. INL and ONL thinning were independently faster in PMS, as compared to controls (INL:−0.09 ± 0.04%/yr, p = 0.03; ONL:−0.12 ± 0.06%/yr, p = 0.04), and RRMS (INL:−0.10 ± 0.04%/yr, p = 0.01; ONL:−0.13 ± 0.05%/yr, p = 0.01), whereas they were similar in RRMS and controls. Unlike RRMS, disease-modifying therapies (DMTs) did not impact rates of retinal layer atrophy in PMS. Interpretation: PMS is associated with faster retinal atrophy independent of age. INL and ONL measures may be novel biomarkers of neurodegeneration in PMS that appear to be unaffected by conventional DMTs. The effects of aging on rates of retinal layer atrophy should be considered in clinical trials incorporating OCT outcomes. ANN NEUROL 2020;87:885–896.
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U2 - 10.1002/ana.25738
DO - 10.1002/ana.25738
M3 - Article
C2 - 32285484
AN - SCOPUS:85084240696
SN - 0364-5134
VL - 87
SP - 885
EP - 896
JO - Annals of neurology
JF - Annals of neurology
IS - 6
ER -