Machine learning in diagnosis and disability prediction of multiple sclerosis using optical coherence tomography.

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system, especially the brain, spinal cord, and optic nerve. Diagnosis of this disease is a very complex process and generally requires a lot of time. In addition, treatments are applied without any information on the disability course in each MS patient. For these two reasons, the objective of this study was to improve the MS diagnosis and predict the long-term course of disability in MS patients based on clinical data and retinal nerve fiber layer (RNFL) thickness, measured by optical coherence tomography (OCT). MATERIAL AND METHODS: A total of 104 healthy controls and 108 MS patients, 82 of whom had a 10-year follow-up, were enrolled. Classification algorithms such as multiple linear regression (MLR), support vector machines (SVM), decision tree (DT), k-nearest neighbours (k-NN), Naïve Bayes (NB), ensemble classifier (EC) and long short-term memory (LSTM) recurrent neural network were tested to develop two predictive models: MS diagnosis model and MS disability course prediction model. RESULTS: For MS diagnosis, the best result was obtained using EC (accuracy: 87.7%; sensitivity: 87.0%; specificity: 88.5%; precision: 88.7%; AUC: 0.8775). In line with this good performance, the accuracy was 85.4% using k-NN and 84.4% using SVM. And, for long-term prediction of MS disability course, LSTM recurrent neural network was the most appropriate classifier (accuracy: 81.7%; sensitivity: 81.1%; specificity: 82.2%; precision: 78.9%; AUC: 0.8165). The use of MLR, SVM and k-NN also showed a good performance (AUC ≥ 0.8). CONCLUSIONS: This study demonstrated that machine learning techniques, using clinical and OCT data, can help establish an early diagnosis and predict the course of MS. This advance could help clinicians select more specific treatments for each MS patient. Therefore, our findings underscore the potential of RNFL thickness as a reliable MS biomarker.

Monitoring New Long-Lasting Intravitreal Formulation for Glaucoma with Vitreous Images Using Optical Coherence Tomography.

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine-Laponite (BRI/LAP) can be monitored non-invasively using vitreoretinal interface imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterisation was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

The Innate Immune Cell Profile of the Cornea Predicts the Onset of Ocular Surface Inflammatory Disorders.

Ocular surface inflammatory disorder (OSID) is a spectrum of disorders that have features of several etiologies whilst displaying similar phenotypic signs of ocular inflammation. They are complicated disorders with underlying mechanisms related to several autoimmune disorders, such as rheumatoid arthritis (RA), Sjögren's syndrome, and systemic lupus erythematosus (SLE). Current literature shows the involvement of both innate and adaptive arms of the immune system in ocular surface inflammation. The ocular surface contains distinct components of the immune system in the conjunctiva and the cornea. The normal conjunctiva epithelium and sub-epithelial stroma contains resident immune cells, such as T cells, B cells (adaptive), dendritic cells, and macrophages (innate). The relative sterile environment of the cornea is achieved by the tolerogenic properties of dendritic cells in the conjunctiva, the presence of regulatory lymphocytes, and the existence of soluble immunosuppressive factors, such as the transforming growth factor (TGF)-ß and macrophage migration inhibitory factors. With the presence of both innate and adaptive immune system components, it is intriguing to investigate the most important leukocyte population in the ocular surface, which is involved in immune surveillance. Our meta-analysis investigates into this with a focus on both infectious (contact lens wear, corneal graft rejection, Cytomegalovirus, keratitis, scleritis, ocular surgery) and non-infectious (dry eye disease, glaucoma, graft-vs-host disease, Sjögren's syndrome) situations. We have found the predominance of dendritic cells in ocular surface diseases, along with the Th-related cytokines. Our goal is to improve the knowledge of immune cells in OSID and to open new dimensions in the field. The purpose of this study is not to limit ourselves in the ocular system, but to investigate the importance of dendritic cells in the disorders of other mucosal organs (e.g., lungs, gut, uterus). Holistically, we want to investigate if this is a common trend in the initiation of any disease related to the mucosal organs and find a unified therapeutic approach. In addition, we want to show the power of computational approaches to foster a collaboration between computational and biological science.

Intervertebral disc degeneration: an experimental and numerical study using a rabbit model.

Animal models have been extensively used for the study of degenerative diseases and evaluation of new therapies to stop or even reverse the disease progression. The aim of this study is to reproduce lumbar intervertebral disc degeneration in a rabbit model by performing a percutaneous annular puncture at L4L5 level. The effect of this damage on the spine behaviour was analysed combining three different techniques: imaging processing, mechanical testing and computational modelling. Twenty New Zealand white rabbits were divided into control and experimental groups and followed up during 6 months. Intervertebral disc height, as well as nucleus area and signal intensity, decreased with degeneration while storage and loss moduli increased. Both changes may be related to the loss of water and tissue fibrosis. Similar but slighter changes were reported for adjacent discs. A finite element model was built based on MRI and mechanical testing findings to add new biomechanical information that cannot be obtained experimentally. Four stages were computationally simulated representing the different experimental phases. The numerical simulations showed that compressive stresses in the damaged and adjacent discs were modified with the progression of degeneration. Although extrapolation to humans should be carefully made, the use of numerical animal models combined with an experimental one could give a new insight of the overall mechanical behaviour of the spine.