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Objective: Optical coherence tomography (OCT) investigations have revealed that the thickness of inner retinal layers becomes decreased in multiple sclerosis (MS) patients, compared to healthy control (HC) individuals. To date, a number of studies have applied machine learning to OCT thickness measurements, aiming to enable accurate and automated diagnosis of the disease. However, there have much less emphasis on other less common retinal imaging modalities, like infrared scanning laser ophthalmoscopy (IR-SLO), for classifying MS. IR-SLO uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position., Methods: We incorporated two independent datasets of IR-SLO images from the Isfahan and Johns Hopkins centers, consisting of 164 MS and 150 HC images. A subject-wise data splitting approach was employed to ensure that there was no leakage between training and test datasets. Several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, and a CNN with a custom architecture were employed. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features subsequently given as inputs to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP)., Results: The custom CNN (85 % accuracy, 85 % sensitivity, 87 % specificity, 93 % area under the receiver operating characteristics [AUROC], and 94 % area under the precision-recall curve [AUPRC]) outperformed state-of-the-art models (84 % accuracy, 83 % sensitivity, 87 % specificity, 92 % AUROC, and 94 % AUPRC); however, utilizing a combination of the CAE and MLP yields even superior results (88 % accuracy, 86 % sensitivity, 91 % specificity, 94 % AUROC, and 95 % AUPRC)., Conclusions: We utilized IR-SLO images to differentiate between MS and HC eyes, with promising results achieved using a combination of CAE and MLP. Future multi-center studies involving more heterogenous data are necessary to assess the feasibility of integrating IR-SLO images into routine clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Within the domain of multiple sclerosis (MS), the precise discrimination between active and inactive lesions bears immense significance. Active lesions are enhanced on T1-weighted MRI images after administration of gadolinium-based contrast agents, which brings about associated complexities. This study investigates the potential of deep learning to differentiate between active and inactive lesions in MS using non-contrast FLAIR-type MRI data, presenting a non-invasive alternative to conventional gadolinium-based MRI methods., Methods: The dataset encompasses 9097 lesion images collected from 130 MS patients across four distinct imaging centers, with post-contrast T1-weighted images as the benchmark reference. We initially identified and labeled the lesions and carefully selected corresponding regions of interest (ROIs). These ROIs were employed as inputs for a convolutional neural network (CNN) to predict lesion status. Also, transfer learning was utilized, incorporating 12 pre-trained CNN models. Subsequently, an ensemble technique was applied to 3 of best models, followed by a systematic comparison of the results., Results: Through a 5-fold cross-validation, our custom designed network exhibited an average accuracy of 85 %, a sensitivity of 95 %, a specificity of 75 %, and an AUC value of 0.90. Among the pre-trained models, ResNet50 emerged as the most effective, achieving a specificity of 58 %, an accuracy of 75 %, a sensitivity of 91 %, and an AUC value of 0.81. Our comprehensive evaluations encompassed the receiver operating characteristic curve, precision-recall curve, and confusion matrix analyses., Conclusion: The findings underscore the efficacy of the proposed CNN, trained on FLAIR MRI data ROIs, in accurately discerning active and inactive lesions without reliance on contrast agents. Our multicenter study of 130 patients with diverse imaging devices outperforms the other single-center studies, achieving superior sensitivity and specificity. Unlike studies using multiple modalities, our exclusive use of FLAIR images streamlines the process, and our streamlined approach, excluding conventional pre-processing, demonstrates efficiency. The external validation conducted on diverse datasets, coupled with the analysis of dilated masks, underscores the adaptability and efficacy of our custom CNN model in discerning between active and inactive lesions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Several machine learning studies have used optical coherence tomography (OCT) for multiple sclerosis (MS) classification with promising outcomes. Infrared reflectance scanning laser ophthalmoscopy (IR-SLO) captures high-resolution fundus images, commonly combined with OCT for fixed B-scan positions. However, no machine learning research has utilized IR-SLO images for automated MS diagnosis., Methods: This study utilized a dataset comprised of IR-SLO images and OCT data from Isfahan, Iran, encompassing 32 MS and 70 healthy individuals. A number of convolutional neural networks (CNNs)-namely, VGG-16, VGG-19, ResNet-50, ResNet-101, and a custom architecture-were trained with both IR-SLO images and OCT thickness maps as two separate input datasets. The highest performing models for each modality were then integrated to create a bimodal model that receives the combination of OCT thickness maps and IR-SLO images. Subject-wise data splitting was employed to prevent data leakage among training, validation, and testing sets., Results: Overall, images of the 102 patients from the internal dataset were divided into test, validation, and training subsets. Subsequently, we employed a bootstrapping approach on the training data through iterative sampling with replacement. The performance of the proposed bimodal model was evaluated on the internal test dataset, demonstrating an accuracy of 92.40% ± 4.1% (95% confidence interval [CI], 83.61-98.08), sensitivity of 95.43% ± 5.75% (95% CI, 83.71-100.0), specificity of 92.82% ± 3.72% (95% CI, 81.15-96.77), area under the receiver operating characteristic (AUROC) curve of 96.99% ± 2.99% (95% CI, 86.11-99.78), and area under the precision-recall curve (AUPRC) of 97.27% ± 2.94% (95% CI, 86.83-99.83). Furthermore, to assess the model generalization ability, we examined its performance on an external test dataset following the same bootstrap methodology, achieving promising results, with accuracy of 85.43% ± 0.08% (95% CI, 71.43-100.0), sensitivity of 97.33% ± 0.06% (95% CI, 83.33-100.0), specificity of 84.6% ± 0.10% (95% CI, 71.43-100.0), AUROC curve of 99.67% ± 0.02% (95% CI, 95.63-100.0), and AUPRC of 99.65% ± 0.02% (95% CI, 94.90-100.0)., Conclusions: Incorporating both modalities improves the performance of automated diagnosis of MS, showcasing the potential of utilizing IR-SLO as a complementary tool alongside OCT., Translational Relevance: Should the results of our proposed bimodal model be validated in future work with larger and more diverse datasets, diagnosis of MS based on both OCT and IR-SLO can be reliably integrated into routine clinical practice.

Background: The aim of this study was to identify and compare the characteristics of retinal nerve layers using spectral domain-optical coherence tomography (SD-OCT) in neuromyelitis optica spectrum disorder (NMOSD), relapsing-remitting multiple sclerosis (RRMS) and healthy controls (HCs)., Methods: It is a cross-sectional population-based study in Isfahan, Iran. We enrolled 98 participants including 45 NMOSD patients (90 eyes), 35 RRMS patients (70 eyes) and 18 HCs (36 eyes). Evaluation criteria were thickness of different sectors in peripapillary retinal nerve fiber layer (pRNFL) and intra-retinal layers around the macula. History of previous optic neuritis (ON) was obtained through chart review and medical record., Results: Without considering ON, total macular, ganglion cell layer (GCL) and pRNFL were significantly thinner in both groups of patients compared to HCs. On macular examination, GCL and total macular thickness were significantly thinner than HCs in all NMOSD and RRMS eyes with and without history of ON. While there was no significant difference between MS-ON and MS without a history of ON in the macular measures, the reduction in total macular and GCL thickness was significantly greater in NMOSD-ON compared to NMOSD without a history of ON. Also in NMOSD-ON eyes, the RNFL, GCL, IPL and GCIPL layers were significantly thinner than that of MS-ON. On the other hand, the pRNFL study showed significant thinning of all quadrants in the RRMS and NMOSD groups relative to HCs. While the decrease of pRNFL thickness in the eyes of NMOSD-ON and MS with and without a previous history of ON was significantly greater than that of HCs, no difference was observed between NMOSD without ON and HCs. In addition, in NMOSD patients, pRNFL was significantly thinner in eyes with history of ON compared to non ON-eyes. Furthermore, in patients with a history of ON, reduction in all sectors of pRNFl (except in T) was significantly greater in NMOSD compared to MS patients., Conclusion: Our findings showed that although macular and retinal damage occurred in both NMOSD and RRMS patients without significant differences, the severity of injury in eyes with history of ON was significantly higher in NMOSD compared to MS patients, that could be considered as a marker to distinguish them. In addition, our results confirmed the absence of subclinical optic nerve involvement in NMOSD unlike MS patients., (Copyright © 2020 Elsevier B.V. All rights reserved.)