A mathematical model to predict the evolution of retinal nerve fiber layer thinning in multiple sclerosis patients

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Many studies of MS patients have described axonal loss in the optic nerve of the retina, and specifically progressive thinning of the retinal nerve fiber layer (RNFL). We hypothesize that RNFL thinning involv...

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Bibliographic Details
Published in:Computers in biology and medicine 2019-08, Vol.111, p.103357-103357, Article 103357
Main Authors: Montolío, Alberto, Cegoñino, José, Orduna, Elvira, Sebastian, Berta, Garcia-Martin, Elena, Pérez del Palomar, Amaya
Format: Article
Language:English
Subjects:
Biomarkers
Central nervous system
Correlation analysis
Degeneration
Differential equations
Evolution
Evolutionary algorithms
Genetic algorithm
Genetic algorithms
Inflammation
Longitudinal studies
Longitudinal study
Mathematical models
Multiple sclerosis
Nervous system
Neurodegeneration
Neurodegenerative diseases
Neurological diseases
Optic nerve
Optical Coherence Tomography
Optics
Patients
Retina
Retinal nerve fiber layer
Thickness measurement
Thinning
Tomography
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Summary:Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Many studies of MS patients have described axonal loss in the optic nerve of the retina, and specifically progressive thinning of the retinal nerve fiber layer (RNFL). We hypothesize that RNFL thinning involves the participation of 2 processes that cause CNS damage: autoimmune inflammation and axonal degeneration. To test this hypothesis, we developed a mathematical model based on ordinary differential equations to relate the evolution of RNFL thickness (measured by optical coherence tomography [OCT]) with that of the Expanded Disability Status Scale (EDSS) score in MS patients. Data were obtained from a longitudinal study of 114 MS patients who were followed-up for 10 years. After adjusting the parameters using a genetic algorithm, the model's prediction of the evolution of RNFL thickness accurately reflected the progression revealed by the 10-year clinical data. Our findings suggest that differences in the relative contributions of autoimmune inflammation and axonal degeneration can account for the complex dynamics of MS, which vary from one patient to the next. Moreover, our results show that CNS damage occurs cumulatively from the onset of MS and that most RNFL thinning occurs before the appearance of significant disability. RNFL thickness could therefore serve as a reliable biomarker of MS disease course. Our proposed methodology would enable the use of OCT data from new MS patients to predict the evolution of RNFL thinning and hence the progression of MS in individual patients, and to facilitate the selection of patient-specific therapies. •Retinal nerve fiber layer (RNFL) thickness could serve as a reliable biomarker of multiple sclerosis disease (MS) course.•Autoimmune inflammation and axonal degeneration can account for the complex dynamics of MS.•Most RNFL thinning occurs before the appearance of significant disability in MS patients.•The use of Optical Coherence Tomography data can be used to predict the progression of MS patients.
ISSN:0010-4825
1879-0534
DOI:10.1016/j.compbiomed.2019.103357