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.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).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).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.