# Sphingolipidoses and Retinal Involvement: A Comprehensive Review
## 1 Introduction
Spectral-domain optical coherence tomography (SD-OCT) is a non-invasive rapid imaging technique used in routine ophthalmologic examination that renders an in vivo simil-histological cross-sectional view of the retina layers [7]. It serves as a critical diagnostic modality for the retinal evaluation of sphingolipidoses, as it can facilitate diagnosis and the monitoring of ocular manifestations [8]. A frequently observed finding in various lipid storage disorders is hyperreflectivity of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) [6]. Although in cases of suspected lipid storage disorders SD-OCT serves as a fundamental diagnostic tool for detecting retinal involvement, a definitive diagnosis requires the assessment of enzymatic deficiencies and multisystem involvement [6]. OCT angiography (OCTA) is a dye-free technique used to assess the ocular microvasculature, including the macula, choroid, and optic nerve capillaries [9]. This imaging method has been suggested as an additional technique to observe the microvasculature for the diagnostic workup of sphingolipidoses, such as FD, and facilitates the monitoring of disease progression [10]. A characteristic finding is retinal vessel tortuosity, which is observed in FD, as well as in several other sphingolipidoses [11]. The evaluation via OCTA imaging proves to be a rapid, non-invasive, and reproducible diagnostic biomarker [12]. The application of electrophysiological assessments, including the electroretinography (ERG) and visually evoked potentials (VEPs), has been shown to be essential for the diagnosis of sphingolipidoses and serves as a valuable tool in differentiating between these disorders [13]. ERG, which records the electrical response of the retina to light stimuli, enables the identification of functional retinal alterations associated with a wide range of pathologies [14]. In the context of sphingolipidoses, ERG is particularly effective in detecting subclinical functional changes, even in cases where patients remain asymptomatic from a visual standpoint [15]. For instance, in NPD and GD, regions of the retina corresponding to lipid deposition exhibit a significant depression in multifocal ERG (mfERG) responses [16; 17]. VEPs are electrophysiological assessments used to evaluate the functional integrity of the optic nerves, visual pathways, and occipital cortex [17]. In demyelinating leukodystrophies, such as KD and MDL, lipid accumulation within the nervous system leads to demyelination, resulting in alterations in VEPs responses [18]. Furthermore, VEPs have been observed to be reduced or pathological in murine models of TSD and SD [19]. This review aims to increase the awareness and knowledge of retinal sphingolipidoses, particularly given their rarity. Given the paucity of the comprehensive literature systematically examining the retinal manifestations of all sphingolipidosis subtypes, we aim to address this gap by offering guidance on the most appropriate ophthalmological multimodal imaging techniques and detailing the expected findings. Furthermore, we highlight the promising role of these techniques in multidisciplinary clinical management, including diagnosis, assessment of disease progression, and evaluation of responses to systemic therapies.