# Sphingolipidoses and Retinal Involvement: A Comprehensive Review
## 4 Subtypes of Sphingolipidoses
### GM2 Gangliosidosis: Tay Sachs Disease and Sandhoff Disease
#### 4.4.2 Retinal Manifestations  
Bilateral cherry-red spots were described in a report of two pediatric patients with infantile SD [110] and in 18 patients with TSD or SD, 88% had cherry-red spots [111]. The first histopathological evaluation of human retinas in TSD and SD showed an accumulation of deposits at ganglion cell level, which had a more pleomorphic appearance in patients with SD than in those with TSD [115]. More recent studies demonstrated the presence of cytoplasmic inclusions in the retinas of mice with GM2 gangliosidosis, confirming the involvement of ganglion cells and the IPL and INL. However, no deposits were identified at the level of photoreceptor cells [116]. Retinal vessel narrowing, optic disc atrophy, retinitis pigmentosa, and macular atrophy are commonly observed in more advanced stages of the disease. These signs reflect the progressive degeneration of retinal structures as a result of the ganglioside accumulation [117]. TSD and SD result in the accumulation of GM2 gangliosides [27; 112], a type of complex glycosphingolipids that are abundantly expressed within the central nervous system [118]. This accumulation at the brain level leads to early neuronal cell death and progressive neurodegeneration, which is also observed in the retina as ganglion cell loss, likely correlating with the gradual decline in visual function over time [118]. The loss of ganglion \begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Disease** & **Defective Enzyme** & **Primary Storage** & **Systemic Symptoms and Manifestations** & **Ocular Manifestations (Non-Retinal and Retinal Manifestations)** \\ \hline
**Tay-Sachs Disease** & Hexosaminidase A (1:100,000) & (HEXA) & GM2 & dementia (in advanced stages), developmental delay, hyperexcitability, seizure, ataxia, progressive paralysis, vaglés (in later stages) [113] & **Non retinal manifestations:** progressive vision loss (starting around age 2) [55], difficulty in fixation on objects, nystagmus [34], optic atrophy [55], internuclear ophthalmic hypometric saccades [114] \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Summary of the characteristics of [PERSON] disease. \begin{table}
\begin{tabular}{p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Disease** & **Defective Enzyme** & **Primary Storage** & **Systemic Symptoms and Manifestations** & **Ocular Manifestations (Non-Retinal and Retinal Manifestations)** \\ \hline
**Tay-Sachs Disease** & Hexosaminidase A (1:100,000) & (HEXA) & G\(\Omega\) & dementia (in advanced stages), developmental delay, hyperexcitability, seizure, ataxia, progressive paralysis, vaglés (in later stages) [113] & **Non retinal manifestations:** progressive vision loss (starting around age 2) [55], difficulty in fixation on objects, nystagmus [34], optic atrophy [55], internuclear ophthalmic hypometric saccades [114] \\ \hline \hline \end{tabular}
\end{table} 
Table 5: Summary of the characteristics of Tay–Sachs disease. cells can be ophthalmoscopically detected by a reduction over time in the cherry-red spot, which arises from ganglion cell death at sites where gangliosides accumulate. Since the RNFL in SD-OCT is composed of unmyelinated axons of ganglion cells, its thickness is influenced by the number of ganglion cells [119]. As a result, SD-OCT findings in TSD and SD typically demonstrate RNFL thinning, indicative of ganglion cell loss, along with ballooning of the GCL [27]. These changes reflect the neurodegenerative process in the retina and central nervous system [27]. SD-OCT could be particularly useful for detecting early signs of retinal involvement before fundusoscopic changes become apparent. In GM2 case reports, OCT scans showed a thickening of the inner retinal layers with a shadowing effect on the outer layers in presence of the characteristic cherry red macula with a whitish ring area encircling the fovea [117,120].