Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions.
OBJECTIVE
To investigate the potential links between thinning of retinal ganglion cell axons in eyes of patients with multiple sclerosis (MS) without past optic neuritis (ON) and MS-related inflammatory damage of the posterior visual pathway.


METHODS
Temporal retinal nerve fiber layer (tRNFL) thickness was analyzed in eyes with no history of ON (NON) from 53 patients with relapsing-remitting MS. Fifty normal age- and sex-matched controls were examined with optical coherence tomography. Low-contrast visual acuity charts were used for functional assessment of vision. The optic tract (OT) and optic radiation (OR) were identified using probabilistic tractography, and volume of T2 fluid-attenuated inversion recovery lesions and diffusion tensor imaging (DTI) indices were measured within both structures. Cross-sectional diameter of the OT was also calculated.


RESULTS
tRNFL thickness was significantly reduced in NON eyes and was associated with reduced low-contrast visual acuity. Lesions within the OR were detected in the majority of patients. There was a significant correlation between thinning of the tRNFL and OR lesion volume (adjusted for non-OR lesion volume, age, sex, and disease duration). tRNFL thickness also correlated with OR DTI indices. No OT lesions were identified in any of the patients and no relationship between retinal nerve fiber layer loss and potential markers of OT lesions was found.


CONCLUSIONS
The results demonstrate a strong tract-specific association between loss of tRNFL fibers and MS-related inflammation within OR.
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia. sasha@eye.usyd.edu.au.
Alexander
A
Klistorner
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Prima
P
Sriram
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Nikitha
N
Vootakuru
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Chenyu
C
Wang
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Michael H
MH
Barnett
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Raymond
R
Garrick
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
John
J
Parratt
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Netta
N
Levin
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Noa
N
Raz
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Anneke
A
Van der Walt
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Lynette
L
Masters
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Stuart L
SL
Graham
From the Department of Ophthalmology (A.K., N.V.) and the Brain and Mind Institute (C.W., M.H.B., L.M.), University of Sydney; the Australian School of Advanced Medicine (A.K., P.S., S.L.G.), Macquarie University; St. Vincent Hospital (R.G.); North Shore Hospital (J.P.), Sydney, Australia; Hadassah Hebrew University Medical Center (N.L., N.R.), Jerusalem, Israel; the Department of Neurology (A.V.d.W.), Royal Melbourne Hospital; and Concord Hospital (C.Y.), Sydney, Australia.
Con
C
Yiannikas
D000328:Adult; D001369:Axons / Q000473:pathology*; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications*; D009412:Nerve Fibers / Q000473:pathology; D009900:Optic Nerve / Q000473:pathology*; D009902:Optic Neuritis / Q000209:etiology* / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence