Diagnosis of multiple sclerosis using optical coherence tomography supported by explainable artificial intelligence.

BACKGROUND/OBJECTIVES: Study of retinal structure based on optical coherence tomography (OCT) data can facilitate early diagnosis of relapsing-remitting multiple sclerosis (RRMS). Although artificial intelligence can provide highly reliable diagnoses, the results obtained must be explainable. SUBJECTS/METHODS: The study included 79 recently diagnosed RRMS patients and 69 age matched healthy control subjects. Thickness (Avg) and inter-eye difference (Diff) features are obtained in 4 retinal layers using the posterior pole protocol. Each layer is divided into six analysis zones. The Support Vector Machine plus Recursive Feature Elimination with Leave-One-Out Cross Validation (SVM-RFE-LOOCV) approach is used to find the subset of features that reduces dimensionality and optimises the performance of the classifier. RESULTS: SVM-RFE-LOOCV was used to identify OCT features with greatest capacity for early diagnosis, determining the area of the papillomacular bundle to be the most influential. A correlation was observed between loss of layer thickness and increase in functional disability. There was also greater functional deterioration in patients with greater asymmetry between left and right eyes. The classifier based on the top-ranked features obtained sensitivity = 0.86 and specificity = 0.90. CONCLUSIONS: There was consistency between the features identified as relevant by the SVM-RFE-LOOCV approach and the retinotopic distribution of the retinal nerve fibres and the optic nerve head. This simple method contributes to implementation of an assisted diagnosis system and its accuracy exceeds that achieved with magnetic resonance imaging of the central nervous system, the current gold standard. This paper provides novel insights into RRMS affectation of the neuroretina.

Retinal neurodegeneration in patients with type 2 diabetes mellitus without diabetic retinopathy.

In diabetes mellitus (DM) patients retinal complications were typically considered part of a vascular process. Recent research suggests that retinal degeneration in DM might also be caused by a neuropathy that could precede microvascular alterations. The present work reviews the currently available bibliography about neurodegeneration in patients with type 2 DM (DM2) without diabetic retinopathy (DR). In patients with non-severe, early DM2 without DR and good metabolic control visual function parameters show early abnormalities that precede clinical DR (in which we diagnose with a conventional ophthalmological examination). Using optical coherence tomography (OCT) technology, a reduction in macular and peripapillary thickness has been observed in different studies. Recent researches suggest that systemic complications (especially ischaemia) and a possible microvascular alteration eventually contributes to retinal neurodegeneration, which opens the door to new studies that include new techniques for evaluating the microvascularization of the retinal layers.

Neurodegeneración retiniana en pacientes diabéticos tipo 2 sin retinopatía diabética / Retinal neurodegeneration in patients with type 2 diabetes mellitus without diabetic retinopathy

La retinopatía diabética (RD) tradicionalmente se ha considerado parte de un proceso vascular. Investigaciones recientes sugieren que la degeneración de la retina en la diabetes mellitus (DM) podría ser causada también por una neuropatía y que la neurodegeneración retiniana precedería a las alteraciones microvasculares. El presente artículo revisa la bibliografía existente sobre neurodegeneración en pacientes con DM tipo 2 (DM2) sin RD. En los pacientes con DM2 no severa, temprana, con buen control metabólico y sin RD, las pruebas de función visual muestran anormalidades precoces que anteceden a la aparición de la RD clínica (la que diagnosticamos con una exploración oftalmológica convencional). Utilizando la tomografía de coherencia óptica (OCT) se observa que en estos pacientes existe una disminución en el espesor de distintas capas de la retina, tanto en el área macular como peripapilar. Recientes estudios sugieren que las complicaciones sistémicas (especialmente la isquemia) y una posible alteración microvascular contribuyen a la neurodegeneración retiniana, lo que abre la puerta a nuevos estudios que incluyan nuevas técnicas de evaluación de la microvascularización de las capas internas de la retina como la angio-OCT (AU)

In diabetes mellitus (DM) patients retinal complications were typically considered part of a vascular process. Recent research suggests that retinal degeneration in DM might also be caused by a neuropathy that could precede microvascular alterations. The present work reviews the currently available bibliography about neurodegeneration in patients with type 2 DM (DM2) without diabetic retinopathy (DR). In patients with non-severe, early DM2 without DR and good metabolic control visual function parameters show early abnormalities that precede clinical DR (in which we diagnose with a conventional ophthalmological examination). Using optical coherence tomography (OCT) technology, a reduction in macular and peripapillary thickness has been observed in different studies. Recent researches suggest that systemic complications (especially ischaemia) and a possible microvascular alteration eventually contributes to retinal neurodegeneration, which opens the door to new studies that include new techniques for evaluating the microvascularization of the retinal layers (AU)

Analysis of Retinal Layers in Fibromyalgia Patients with Premium Protocol in Optical Tomography Coherence and Quality of Life.

PURPOSE: To evaluate the inner retinal layers in fibromyalgia (FM) patients compared to control subjects using posterior pole protocol (PPole) analysis in optical coherence tomography (OCT) and to correlate structural retinal changes with subjective quality of life. METHODS: Seventy-four eyes of healthy subjects and 55 eyes of those with FM were analyzed. All subjects underwent retinal evaluation using the PPole protocol for Spectralis OCT (Heidelberg Engineering) to obtain measurements of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) in the macular area. The EuroQol (EQ-5D) questionnaire and Fibromyalgia Impact Questionnaire (FIQ) were performed to analyze health-related quality of life. Additionally, the FM group was divided into three groups depending on the disease phenotype (atypical, depressive, and biological). RESULTS: Patients with FM presented with a reduction of the RNFL thickness compared to controls in 17/64 cells of the PPole area, and a reduction of the GCL thickness in 47/64 cells. Depressive FM phenotype showed the greatest number of cells with significant reduction compared with the control group in both RNFL and GCL layers. A correlation between temporal-inferior cells of the GCL and the EuroQol 5D questionnaire results was observed. CONCLUSIONS: Patients with FM present with a reduction of the inner retinal layers in the macular area. This degeneration correlates with disease severity/reduced quality of life in these patients. The PPole protocol for OCT is a non-invasive and fast tool that might help clinicians diagnose and monitor neurodegeneration in FM patients.

The use of optical coherence tomography in the evaluation of patients with bipolar disorder. / Utilidad de la tomografía de coherencia óptica en la evaluación de los pacientes con trastorno bipolar.

Bipolar disorder (BD) is a mental disorder characterised by episodes of extremal mood changes. In recent years, some researchers found neurodegeneration in patients with BD using Magnetic Resonance Imaging. Evaluation of the optic nerve and the retinal layers using optical coherence tomography (OCT) has proved to be a useful, non-invasive tool for diagnosis and monitoring of neurodegenerative diseases. Accordingly, a decrease in the retinal nerve fibre layer and the ganglion cell complex measured by OCT was found in patients with BD in different studies, suggesting that BD is a neurodegenerative process in addition to a psychiatric disorder. Therefore, the neuro-ophthalmological evaluation of these patients could be used as a marker for diagnosis of this disease. This work analyses literature on retinal degeneration in bipolar disorder patients, and evaluates the ability of OCT devices in the detection of neuronal degeneration affecting the different retinal layers in these patients, and its possible role in the diagnosis and monitoring of the disease.

Early diagnosis of multiple sclerosis by OCT analysis using Cohen's d method and a neural network as classifier.

BACKGROUND: The consequences of inflammation, demyelination, axonal degeneration and neuronal loss in the central nervous system, typical of the development of multiple sclerosis (MS), are manifested in thinning of the retina and optic nerve. The purpose of this work is to diagnose early-stage MS patients based on analysis of retinal layer thickness obtained by swept-source optical coherence tomography (SS-OCT). METHOD: OCT (Triton® SS-OCT device -Topcon, Tokyo, Japan-) recordings were obtained from 48 control subjects and 48 recently diagnosed MS patients. The following thicknesses were measured on a 45 × 60 grid: retinal nerve fibre layer (RNFL), ganglion cell layer (GCL+), GCL++, retinal thickness and choroid. Using Cohen's d effect size, it was determined the regions and layers with greatest capacity to discriminate between control subjects and patients. Points exceeding the threshold set were used as inputs for an automatic classifier: support vector machine and feed-forward neural network. RESULTS: In MS at clinical onset the layer with greatest discriminant capacity is GCL++ [AUC = 0.83] which exhibits a horseshoe-like macular topographic distribution. It is followed by retina, GCL+ and RNFL; choroidal thicknesses do not provide discriminatory capacity. Using a neural network as a classifier between controls and MS patients, obtains sensitivity of 0.98 and specificity of 0.98. CONCLUSIONS: This work suggest that OCT may serve as an important complementary role to other clinical tests, particularly regarding neurodegeneration. It is possible to characterise structural alterations in retina and diagnose early-stage MS with high degree of accuracy using OCT and artificial neural networks.

Identification of clusters in multifocal electrophysiology recordings to maximize discriminant capacity (patients vs. control subjects).

PURPOSE: To propose a new method of identifying clusters in multifocal electrophysiology (multifocal electroretinogram: mfERG; multifocal visual-evoked potential: mfVEP) that conserve the maximum capacity to discriminate between patients and control subjects. METHODS: The theoretical framework proposed creates arbitrary N-size clusters of sectors. The capacity to discriminate between patients and control subjects is assessed by analysing the area under the receiver operator characteristic curve (AUC). As proof of concept, the method is validated using mfERG recordings taken from both eyes of control subjects (n = 6) and from patients with multiple sclerosis (n = 15). RESULTS: Considering the amplitude of wave P1 as the analysis parameter, the maximum value of AUC = 0.7042 is obtained with N = 9 sectors. Taking into account the AUC of the amplitudes and latencies of waves N1 and P1, the maximum value of the AUC = 0.6917 with N = 8 clustered sectors. The greatest discriminant capacity is obtained by analysing the latency of wave P1: AUC = 0.8854 with a cluster of N = 12 sectors. CONCLUSION: This paper demonstrates the effectiveness of a method able to determine the arbitrary clustering of multifocal responses that possesses the greatest capacity to discriminate between control subjects and patients when applied to the visual field of mfERG or mfVEP recordings. The method may prove helpful in diagnosing any disease that is identifiable in patients' mfERG or mfVEP recordings and is extensible to other clinical tests, such as optical coherence tomography.

Diagnostic ability of multifocal electroretinogram in early multiple sclerosis using a new signal analysis method.

PURPOSE: To determine if a novel analysis method will increase the diagnostic value of the multifocal electroretinogram (mfERG) in diagnosing early-stage multiple sclerosis (MS). METHODS: We studied the mfERG signals of OD (Oculus Dexter) eyes of fifteen patients diagnosed with early-stage MS (in all cases < 12 months) and without a history of optic neuritis (ON) (F:M = 11:4), and those of six controls (F:M = 3:3). We obtained values of amplitude and latency of N1 and P1 waves, and a method to assess normalized root-mean-square error (FNRMSE) between model signals and mfERG recordings was used. Responses of each eye were analysed at a global level, and by rings, quadrants and hemispheres. AUC (area under the ROC curve) is used as discriminant factor. RESULTS: The standard method of analysis obtains further discrimination between controls and MS in ring R3 (AUC = 0.82), analysing N1 waves amplitudes. In all of the retina analysis regions, FNRMSE value shows a greater discriminating power than the standard method. The highest AUC value (AUC = 0.91) was in the superior temporal quadrant. CONCLUSION: By analysing mfERG recordings and contrasting them with those of healthy controls it is possible to detect early-stage MS in patients without a previous history of ON.

Effects of aerobic and anaerobic physical conditioning on fibrinolysis.

The effects of aerobic and anaerobic physical conditioning on fibrinolysis were studied before and immediately after physical exercise. Moderately active controls (group A) were compared with aerobically- (group B) or anaerobically-conditioned (group C) subjects. Comparison of the resting parameters revealed that FgDP were significantly higher in group B as a compared to groups A and C. FbDP did not significantly differ between groups B and C and were significantly lower in group A. t-PA antigen and PAI antigen did not significantly differ between the three groups, but t-PA activity was elevated and PAI activity and t-PA/PAI complexes were reduced in group B. Following a maximal exercise test on the treadmill both FbDP and FgDP were significantly increased in all groups, although values for FbDP in group B and values for FgDP in group C reached a higher level than in group A. t-PA antigen and t-PA activity were also increased in the three groups. PAI activity was significantly reduced in groups A and C. t-PA/PAI complexes were significantly enhanced in all cases, but increased to a lower degree in group B. These results indicate that both aerobic and anaerobic physical conditioning induce activation of the fibrinolytic system.

Effects of oral contraceptives on fibrinolytic response to exercise.

In this study the influence of low-dose oral contraceptives (OC) on the different components of the fibrinolytic system before and immediately after maximal exercise was examined in a group of 18 moderately active women. Nine women using OC and nine control women performed a maximal effort treadmill protocol. Comparison of the resting parameters revealed higher plasma FbDP, plasminogen, alpha 2-antiplasmin and protein C concentrations, and lower PAI activity in the OC group. No differences were observed in plasma concentrations of t-PA antigen, t-PA activity, PAI antigen, antithrombin III, and protein S. Acute maximal exercise resulted in significant increases in t-PA antigen, t-PA activity, t-PA/PAI complexes, and FbDP in both groups of subjects, while PAI activity was reduced. No significant differences were found for the change in those parameters between control and OC users. Exercise induced no variation in any of the groups for PAI antigen, alpha 2-antiplasmin, plasminogen, protein C, or protein S. Our data suggest that changes in the fibrinolytic system induced by physical exercise are not affected by oral contraceptives.

Changes in the fibrinolytic system associated with physical conditioning.

The effects of physical conditioning on plasma fibrinolytic activity were studied in two groups of subjects. Volunteers not engaged in any sport were compared with individuals having been subjected to aerobic conditioning (middle-distance runners, defined as men running more than 80 km per week). Plasma concentrations of the different components of the fibrinolytic system were evaluated before and immediately after a maximal effort treadmill protocol. Comparison of the resting parameters revealed that under basal conditions for plasma concentrations of plasminogen, fibrinogen, alpha 2-antiplasmin, protein C and protein S there were no differences between the two groups. Concentrations of the fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were significantly higher in the runners than in the control group, indicating an increased fibrinolytic potential that seemed to be a consequence of the reduced formation of tissue plasminogen activator-plasminogen activator inhibitor (t-PA-PAI) complexes. Acute maximal exercise resulted in pronounced fibrinolysis, evidenced by the elevation of FbDP and FgDP concentrations, in both groups of subjects. The acceleration of the fibrinolytic activity was larger in conditioned individuals, which could be accounted for by a higher t-PA release and reduced formation of t-PA-PAI complexes when compared to the untrained subjects.

Fibrinogen Logroño. A new case of congenital dysfibrinogenemia.

An abnormal fibrinogen was discovered in a 9-year-old male subject without history of hemorrhagic diathesis. Coagulation time, prothrombin time and Reptilase time were prolonged. The thrombin time was corrected using increasing concentrations of normal plasma and bovine thrombin; there was a partial correction at pH 6.5 and ionic strength 0.05. A study of the family showed that the mother and a brother of the propositus presented the same abnormalities. Analysis of the purified fibrinogen showed normal fibrinopeptide release and normal levels of sialic acid and hexosamines. However, coagulation index, polymerization of fibrin monomers, isoelectric point and sedimentation coefficient were abnormal. In view of the abnormalities described and by comparison with the data reported in the literature, we believe that this should be considered a new variant of the fibrinogen molecule and we have designated it 'fibrinogen Logroño'.

Plasmin inhibitors in different fibrinolytic treatment patterns.

The variations of different antiplasmins were studied in a group of patients suffering from thromboembolic conditions and receiving three different regimens of thrombolytic treatment with streptokinase and urokinase. The evaluation of the antiproteases was carried out by chromogenic substrate and radial immunodiffusion. The different administration patterns of the fibrinolytic agents were followed by a clear drop in fast antiplasmin and alpha 2-macroglobulin, while alpha 1-antitrypsin was increased. Antithrombin-III activity was reduced while its protein rose in the intermittent treatment with streptokinase. In the conventional treatment with streptokinase, both the activity and the protein of antithrombin-III increased. With urokinase both the protein and the activity of antithrombin-III were slightly reduced. Plasminogen and fibrinogen decreased in the different regimens of thrombolytic treatment, being more evident in continuous administration of streptokinase.