# Sphingolipidoses and Retinal Involvement: A Comprehensive Review
## 4 Subtypes of Sphingolipidoses
### Niemann-Pick Disease
#### 4.1.2 Retinal Manifestations
These findings have been confirmed by SD-OCT, which reveals focal thickening with high reflectivity in the GCL of the fovea [3]. Further confirmation was provided by light microscopy and electron microscopy of the retina, where lipid-rich material organized into lamellar inclusions were observed at the level of the retinal ganglion cells [67]. According to other authors, lipid deposits are localized not only in the GCL but also within the inner plexiform layer and inner nuclear layer. The fact that their terminal sections are present in the foveal slope may explain why hyperreflectivity extends across this region [68]. This theory is supported by histological evidence indicating that membranous cytoplasmic bodies were observed not only in retinal ganglion cells, but also in amacrine cells, Muller cells, glial cells, and photoreceptors. However, the observation that these bodies assumed a more regular configuration specifically within the retinal ganglion cells, in contrast to a more irregular and vacuolated appearance in the other retinal layers, may provide an explanation for the stronger reflectance signal generated in the GCL that could lead to a misleading impression of exclusive GCL involvement [67]. Vertical hyperreflectivity was detected at the fovea extending from the internal limiting membrane (ILM) to the external limiting membrane (ELM) in case reports where the authors suggested that the deposits may be localized within the foveal Muller glia [39; 67]. The pronounced metabolic activity of Muller glial cells could account for their predisposition to sphingomyelin accumulation in this region [67]. Additionally, lipid deposits with a distinct irregular morphology were observed on the retinal surface, projecting into the vitreous [37]. The clinical observation of perimacular gray discoloration during fundus examination has been further investigated through histological analysis in murine knockout models of the NPD Type C, revealing an elevated production of interleukin-1\(\beta\) in astrocytes and heightened activation of microglial cells. These findings support the hypothesis of a significant proinflammatory role of lipid deposits in retinal pathology [3]. Similar histopathological changes were identified in regions corresponding to areas of optic nerve pallor [3]. OCTA in NPD type B showed that the perimacular vessels exhibited increased tortuosity, and areas of non-flowing capillaries in the superficial retinal plexus [37]. These OCTA findings may indicate a more aggressive progression of disease [37]. Ophthalmic pathological findings generally do not lead to visual impairment [69]. However, the performance of functional tests is critical, as they may reveal alterations. mfERG provides a predictive functional assessment in NPD type B patients with ocular involvement. In areas corresponding to lipid deposition, the mfERG results appear depressed with prolonged latency [16]. Another recommended test is microperimetry, a diagnostic technique employed to assess visual sensitivity mediated by the central retina [70]. Microperimetry shows a mild reduction in retinal sensitivity in areas of retinal accumulation [63].