Relationships Between Retinal Axonal and Neuronal Measures and Global Central Nervous System Pathology in Multiple Sclerosis

Abstract

To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS).

Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis

“…23,24 Considering region-specific pathologic differences, prior studies have found limited correlations between measures of SC and brain atrophy (SC-CSA and BPF), suggesting that pathogenic mechanisms in MS evolve independently to an extent in the brain and SC, particularly in progressive phases of disease, supporting the idea that MS disease mechanisms may differentially affect specific regions of the CNS. 14,25,26 Our observations of moderate correlations between SC and retinal measures, but absent correlations between measures of SC and brain atrophy support the notion that MS disease pathology is nonuniform in distinct CNS compartments, 27,28 and suggest there are clinically relevant pathologic processes occurring in the SC and retina that are distinct from those in the brain. Moreover, our observations of stronger SC and retinal correlations in progressive patients support the view that immunopathologic and tissue injury mechanisms of MS differ by disease subtype, and may be indicative of more uniform pathologic changes occurring in PPMS and SPMS, although these progressive MS subtypes may not be equivalent pathologically.…”

“…Our findings expand on prior studies that demonstrated that retinal layers (pRNFL and GCL 1 IPL) reflect global clinical and radiologic CNS processes in MS, and that specific retinal layers may reflect differential pathologic processes, including neurodegeneration and inflammation. 27,29 Our findings suggest that not only do retinal and SC-MRI measures reflect global pathologic processes in MS that are not adequately captured by brain atrophy alone, but that the regional and global pathologic processes that SC-MRI reflect are distinct from those that are captured by retinal measures, and that these processes independently contribute to mediating clinical disability in various functional systems. These findings highlight the importance of including an assessment of multiple compartments of the CNS affected by MS to better understand both global and regional disease processes, their interplay, and how they contribute to clinical disability in various functional systems.…”

Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis

“…23,24 Considering region-specific pathologic differences, prior studies have found limited correlations between measures of SC and brain atrophy (SC-CSA and BPF), suggesting that pathogenic mechanisms in MS evolve independently to an extent in the brain and SC, particularly in progressive phases of disease, supporting the idea that MS disease mechanisms may differentially affect specific regions of the CNS. 14,25,26 Our observations of moderate correlations between SC and retinal measures, but absent correlations between measures of SC and brain atrophy support the notion that MS disease pathology is nonuniform in distinct CNS compartments, 27,28 and suggest there are clinically relevant pathologic processes occurring in the SC and retina that are distinct from those in the brain. Moreover, our observations of stronger SC and retinal correlations in progressive patients support the view that immunopathologic and tissue injury mechanisms of MS differ by disease subtype, and may be indicative of more uniform pathologic changes occurring in PPMS and SPMS, although these progressive MS subtypes may not be equivalent pathologically.…”

“…Our findings expand on prior studies that demonstrated that retinal layers (pRNFL and GCL 1 IPL) reflect global clinical and radiologic CNS processes in MS, and that specific retinal layers may reflect differential pathologic processes, including neurodegeneration and inflammation. 27,29 Our findings suggest that not only do retinal and SC-MRI measures reflect global pathologic processes in MS that are not adequately captured by brain atrophy alone, but that the regional and global pathologic processes that SC-MRI reflect are distinct from those that are captured by retinal measures, and that these processes independently contribute to mediating clinical disability in various functional systems. These findings highlight the importance of including an assessment of multiple compartments of the CNS affected by MS to better understand both global and regional disease processes, their interplay, and how they contribute to clinical disability in various functional systems.…”

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

“…It is suggested that INL and ONL thinning in MS may also reflect global CNS processes. 31 Given that retinal layer thinning reflects brain atrophy and that neurodegeneration is considered the primary basis for disability in MS, our study findings provide further support that NAT may be a highly effective therapy in RRMS.…”

OCT measurements of optic nerve head changes in idiopathic intracranial hypertension

“…Reduced RNFL and GCL thicknesses are established abnormalities in multiple sclerosis (MS) [17]. But GCL thickness appears to correlate better than RNFL thickness with visual function [18] and is, at least in part, superior over RNFL thickness measurements regarding reproducibility in MS [18,19].…”

Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis

“…23,24 Considering region-specific pathologic differences, prior studies have found limited correlations between measures of SC and brain atrophy (SC-CSA and BPF), suggesting that pathogenic mechanisms in MS evolve independently to an extent in the brain and SC, particularly in progressive phases of disease, supporting the idea that MS disease mechanisms may differentially affect specific regions of the CNS. 14,25,26 Our observations of moderate correlations between SC and retinal measures, but absent correlations between measures of SC and brain atrophy support the notion that MS disease pathology is nonuniform in distinct CNS compartments, 27,28 and suggest there are clinically relevant pathologic processes occurring in the SC and retina that are distinct from those in the brain. Moreover, our observations of stronger SC and retinal correlations in progressive patients support the view that immunopathologic and tissue injury mechanisms of MS differ by disease subtype, and may be indicative of more uniform pathologic changes occurring in PPMS and SPMS, although these progressive MS subtypes may not be equivalent pathologically.…”

“…Our findings expand on prior studies that demonstrated that retinal layers (pRNFL and GCL 1 IPL) reflect global clinical and radiologic CNS processes in MS, and that specific retinal layers may reflect differential pathologic processes, including neurodegeneration and inflammation. 27,29 Our findings suggest that not only do retinal and SC-MRI measures reflect global pathologic processes in MS that are not adequately captured by brain atrophy alone, but that the regional and global pathologic processes that SC-MRI reflect are distinct from those that are captured by retinal measures, and that these processes independently contribute to mediating clinical disability in various functional systems. These findings highlight the importance of including an assessment of multiple compartments of the CNS affected by MS to better understand both global and regional disease processes, their interplay, and how they contribute to clinical disability in various functional systems.…”

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

“…It is suggested that INL and ONL thinning in MS may also reflect global CNS processes. 31 Given that retinal layer thinning reflects brain atrophy and that neurodegeneration is considered the primary basis for disability in MS, our study findings provide further support that NAT may be a highly effective therapy in RRMS.…”

OCT measurements of optic nerve head changes in idiopathic intracranial hypertension

“…Reduced RNFL and GCL thicknesses are established abnormalities in multiple sclerosis (MS) [17]. But GCL thickness appears to correlate better than RNFL thickness with visual function [18] and is, at least in part, superior over RNFL thickness measurements regarding reproducibility in MS [18,19].…”

Relationships between quantitative spinal cord MRI and retinal layers in multiple sclerosis

“…23,24 Considering region-specific pathologic differences, prior studies have found limited correlations between measures of SC and brain atrophy (SC-CSA and BPF), suggesting that pathogenic mechanisms in MS evolve independently to an extent in the brain and SC, particularly in progressive phases of disease, supporting the idea that MS disease mechanisms may differentially affect specific regions of the CNS. 14,25,26 Our observations of moderate correlations between SC and retinal measures, but absent correlations between measures of SC and brain atrophy support the notion that MS disease pathology is nonuniform in distinct CNS compartments, 27,28 and suggest there are clinically relevant pathologic processes occurring in the SC and retina that are distinct from those in the brain. Moreover, our observations of stronger SC and retinal correlations in progressive patients support the view that immunopathologic and tissue injury mechanisms of MS differ by disease subtype, and may be indicative of more uniform pathologic changes occurring in PPMS and SPMS, although these progressive MS subtypes may not be equivalent pathologically.…”

“…Our findings expand on prior studies that demonstrated that retinal layers (pRNFL and GCL 1 IPL) reflect global clinical and radiologic CNS processes in MS, and that specific retinal layers may reflect differential pathologic processes, including neurodegeneration and inflammation. 27,29 Our findings suggest that not only do retinal and SC-MRI measures reflect global pathologic processes in MS that are not adequately captured by brain atrophy alone, but that the regional and global pathologic processes that SC-MRI reflect are distinct from those that are captured by retinal measures, and that these processes independently contribute to mediating clinical disability in various functional systems. These findings highlight the importance of including an assessment of multiple compartments of the CNS affected by MS to better understand both global and regional disease processes, their interplay, and how they contribute to clinical disability in various functional systems.…”

Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

“…It is suggested that INL and ONL thinning in MS may also reflect global CNS processes. 31 Given that retinal layer thinning reflects brain atrophy and that neurodegeneration is considered the primary basis for disability in MS, our study findings provide further support that NAT may be a highly effective therapy in RRMS.…”

OCT measurements of optic nerve head changes in idiopathic intracranial hypertension

“…Reduced RNFL and GCL thicknesses are established abnormalities in multiple sclerosis (MS) [17]. But GCL thickness appears to correlate better than RNFL thickness with visual function [18] and is, at least in part, superior over RNFL thickness measurements regarding reproducibility in MS [18,19].…”