# Sphingolipidoses and Retinal Involvement: A Comprehensive Review
## 6 Conclusions  
Due to the limited studies in the scientific literature and the rarity of the sphingolipidoses, a comprehensive review was conducted to provide an overview of the ophthalmological features and relevant novel retinal diagnostic examinations with multimodal imaging.  
At fundus examination, the most characteristic and frequently observed finding is the cherry-red macula, which is typically seen in GM1 and GM2 gangliosides, NPD (Type A and B), Farber disease and sialidosis. Optic disc pallor or atrophy has been identified in NPD, GM2, MLD, and KD. Other more specific findings include the macular halo in NPD type B, perimacular gray discoloration in NPD type C, and retinal vein occlusion and retinal artery occlusion in FD.  
FAF is a crucial imaging modality to confirm ophthalmoscopic findings. Particularly, the presence of a cherry-red spot in the macula appears as areas of hyperautofluorescence around the fovea, and macular halo are seen as hypoautofluorescent areas.  
SD-OCT is an essential diagnostic tool, particularly useful for detecting early signs of retinal involvement prior to the appearance of funduscopic changes. In NPD, GM1, Farber disease, and MLD, SD-OCT reveals a hallmark feature of hyperreflectivity of the GCL, which is associated with lipid deposits.  
In KD, TSD, SD, and GD, SD-OCT typically shows thinning of the RNFL. This finding reflects the neurodegenerative processes affecting the retina and the central nervous system, making it a potential surrogate marker for tracking disease progression. Atrophy of the RPE and choriorefinal degeneration have been observed in the later stages of these diseases.  
OCTA in FD demonstrates typical vascular changes, including reduced retinal VD and increased vessel tortuosity, which are also observed in NPD type B. Vascular alterations in FD have been further investigated using AO, which identified intracellular lipid deposits in retinal vessels.  
Electrophysiological tests are recommended to detect early functional changes during the preclinical stage and provide evidence of disease progression. The ERG showed depression in NPD Type B, GD and FD, while VEPs were reduced in GM1 and SD, and altered in MLD.  
Despite the promising potential of retinal imaging, the existing literature on this topic is limited, often outdated, and based on histological studies or animal models. For this reason, in addition to SD-OCT, AO may emerge as a promising tool, offering the advantage of visualizing retinal structures in vivo at a cellular level.  
Longitudinal studies are necessary to improve our understanding of the temporal relationship between the progression of sphingolipidoses and retinal changes. By optimizing its use, multimodal retinal imaging could become an indispensable tool for ophthalmologists, enabling them to use retinal findings for early diagnosis and to assess disease progression. In this regard, multimodal retinal imaging could serve as a promising additional tool for assessing response to systemic therapy within a multidisciplinary clinical framework.  
Conceptualization, C.C., D.F. ([PERSON]), D.F. ([PERSON]) and S.A.; methodology, C.C., D.F. ([PERSON]) and D.F. ([PERSON]); formal analysis, C.C., D.F. ([PERSON]), D.F. ([PERSON]) and S.A.; resources C.C., D.F. ([PERSON]), D.F. ([PERSON]), M.D.P., F.D.T. and S.F.; data curation, C.C., D.F. ([PERSON]), D.F., ([PERSON]) M.D.P., F.D.T., S.F. and M.D.P.; writing--original draft preparation, C.C., D.F. ([PERSON]), D.F. ([PERSON]), M.D.P., S.F., F.D.T. and S.A.; writing--review and editing, C.C., D.F. ([PERSON]), D.F. ([PERSON]), S.F., M.D.P. and S.A.; supervision S.A. All authors have read and agreed to the published version of the manuscript. This research received no external funding.  
Not applicable.  
The authors are grateful to [PERSON] and [PERSON] for the illustrations of the figures.  
The authors declare no conflicts of interest.