title: CROP - The Clinico-Radiologico-Ophthalmological Paradox in Multiple Sclerosis: Are Patterns of Retinal and MRI Changes Heterogeneous and Thus Not Predictable?
abstract: BACKGROUND
  To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration.
  
  
  METHODS
  28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study.
  
  
  RESULTS
  There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability.
  
  
  CONCLUSIONS
  Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.
authors.affiliation: Department of Neurology, SMZ-Ost Donauspital, A-1220 Langobardenstrasse 122, Vienna, Austria.|Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, A-1220 Langobardenstrasse 122, Vienna, Austria.
authors.forename: Fahmy
authors.initials: F
authors.lastname: Aboulenein-Djamshidian
authors.affiliation: High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, A-1090 Währingergürtel 18-20, Vienna, Austria.|Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Krššák
authors.affiliation: Department of Ophthalmology, Medical University of Vienna, A-1090 Währingergürtel 18-20, Vienna, Austria.|Department of Ophthalmology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Nermin
authors.initials: N
authors.lastname: Serbecic
authors.affiliation: Department of Neurology, SMZ-Ost Donauspital, A-1220 Langobardenstrasse 122, Vienna, Austria.|Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, A-1220 Langobardenstrasse 122, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Rauschka
authors.affiliation: Department of Ophthalmology, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Beutelspacher
authors.affiliation: High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, A-1090 Währingergürtel 18-20, Vienna, Austria.
authors.forename: Ivica Just
authors.initials: IJ
authors.lastname: Kukurová
authors.affiliation: High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, A-1090 Währingergürtel 18-20, Vienna, Austria.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Valkovič
authors.affiliation: Nuffield Department of Surgical Sciences, Division of Medical Sciences, University of Oxford, Oxford, United Kingdom.
authors.forename: Adnan
authors.initials: A
authors.lastname: Khan
authors.affiliation: Division of Neuroradiology and Musculo-Skeletal Radiology, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, A-1090 Währinger Gürtel 18-20, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Prayer
authors.affiliation: Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, A-1220 Langobardenstrasse 122, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kristoferitsch
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D020528:Multiple Sclerosis, Chronic Progressive / Q000473:pathology; D012160:Retina / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014795:Visual Pathways / Q000473:pathology*; D055815:Young Adult