Retinal Inner Nuclear Layer Reflects Disease Severity and Grey Matter Atrophy in Secondary Progressive Multiple Sclerosis

OBJECTIVE: To evaluate retinal layer composition in secondary chronic progressive multiple sclerosis (SPMS) patients in comparison to healthy controls. To elucidate the connection between retinal alterations and MRI, magnetic resonance spectroscopy (MRS) and clinical status in SPMS. BACKGROUND: Neuroinflammatory and neurodegenerative processes are associated with retinal structure changes in MS patients. So far, MRI-based measures are the gold-standard to describe CNS neurodegeneration. Recently, changes in the retinal layer composition and its correlation with disease activity and clinical status were reported, again suggesting the ganglion cell layer (GCL) and the inner nuclear layer (INL) as sites of specific retinal alterations. So far, the association between different retinal layer thicknesses and MRI markers for brain atrophy, MRS and clinical properties were not investigated in a cohort of SPMS patients. DESIGN/METHODS: 28 SPMS patients were prospectively recruited from on-going clinical trials at baseline visit. Retinal layer thicknesses were determined by spectral-domain Optical Coherence Tomography and semi-automated segmentation. MRI-based measures of brain atrophy and MRS parameters were derived from MRI scans at 1.5T. Patients9 history of MS, visual acuity, MSFC and EDSS were assessed. RESULTS: Macular retinal layer thicknesses differed significantly between SPMS patients and healthy controls. The macular retinal nerve fibre layer and the GCL showed the expected thinning in SPMS. The GCL thinning was associated with visual function loss and grey matter atrophy, but not with white matter damage. Importantly, the thickness of the INL, while being reduced on average in SPMS patients, showed a negative association with grey matter atrophy as well as with clinical impairment. CONCLUSIONS: Our data highlight the INL as a site of disease pathology in MS. The associations of INL changes with both clinical disease severity and grey matter atrophy suggest the INL for further investigating disease pathology and use as a potential surrogate marker for disease progression in MS. Supported by: German Research Foundation (DFG Exc 257) to CP, FP and JD. Disclosure: Dr. Pfueller has nothing to disclose. Dr. Klumbies has nothing to disclose. Dr. Freing has nothing to disclose. Dr. Oberwahrenbrock has nothing to disclose. Dr. Zimmermann has nothing to disclose. Dr. Papazoglou has nothing to disclose. Dr. Rinnenthal has nothing to disclose. Dr. Wuerfel has received personal compensation for activities with Novartis. Dr. Paul has received personal compensation for activities with Teva, Sanofi Aventis, Merck Serono, Biogen Idec, Bayer, Novartis, and the Guthy Jackson Charitable Foundation. Dr. Paul has received research support from Bayer-Schering, Merck-Serono, Teva Pharma and Novartis Pharma. Dr. Dorr has nothing to disclose. Dr. Brandt has received personal compensation for activities with Meedical as co-founder and director, from Heidelberg Engineering for speaker honoraria and from Bayer, Novartis Pharma and Biogen Idec for research and travel grants. Dr. Brandt holds stock and/or stock options in Meedical, which sponsored research in which Dr.Brandt was involved as an investigator. Dr. Brandt holds stock and/or stock options in Meedical.