# Sphingolipidoses and Retinal Involvement: A Comprehensive Review
## 4 Subtypes of Sphingolipidoses
### Fabry Disease
#### 4.7.2 Retinal Manifestations  
Symptoms of FD are often nonspecific or subtle, resulting in frequent diagnostic delay [137]. Among ocular signs, cornea verticillata is the most commonly noted manifestation [11]. Other findings include anterior capsular or posterior subcapsular cataracts. A hallmark feature of FD is vessel tortuosity and venous vascular aneurysmal dilation in conjunctival and retinal vessels [131]. Posterior segment involvement includes optic neuropathies and retinal vasculopathies, such as retinal vein and retinal artery occlusion [10], which can result in retinal ischemia and are considered medical emergencies [138; 139]. Vascular occlusions occur due to the deposition of accumulated material within smooth muscle and vascular endothelial cells, leading \begin{table}
\begin{tabular}{p{42.7 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt} p{56.9 pt}} \hline \hline
**Disease** (**Incidence**) & **Defective Enzyme (**Mutated Gene**) & **Primary Storage Compound** & **System Symptoms and Manifestation** & **Oular Manifestation (Non-Retinal and Retinal Manifestations)** \\ \hline \hline \multirow{8}{*}{**F Fabry Disease** (1-40,000-1:117,000) [130] & Alpha-galactosidase A (xq22.1 cGLA) & Globotriao-Sylceramide (GL3) & Angidexatomas [132], acorpassthesias [132], neuropathic pain [132], gastrointestinal symptoms [132], renal dysfunction [134], left ventricular hypertrophy, cardiac arrhythmias, cardiac valves abnormalities, myocardial ischemic attacks, cerebrovascular occlusions, early strokes [129] & **Non retinal manifestations**: retinal vein occlusion, retinal artery occlusion [131], choroidal neovascularization, retinal vessels aneurysmal dilation [10], retinal vessels tortuosity [136] \\ \hline \hline \end{tabular}
\end{table} 
Table 8: Summary of the characteristics of Fabry disease. to vascular luminal narrowing. Moreover, an increase in pro-aggregatory factors and a reduction in fibrinolytic activity contribute to an elevated risk of vascular occlusion [139]. In FD, retinal vascular occlusion may represent an early clinical manifestation, even in the absence of other systemic or ophthalmologic findings. Consequently, some authors recommend screening for FD in patients presenting with such occlusive events [139]. A comprehensive understanding of these pathophysiological mechanisms is crucial for early diagnosis and timely intervention, aiming to prevent severe retinal complications that may lead to irreversible visual impairment. Additionally, macular choroidal neovascularization has been reported [11; 135]. OCT-A is useful in analyzing retinal vascular changes, allowing quantification of the retinal vascular plexuses density and peripapillary capillaries. Retinal vessel density (VD) values were found to be significantly reduced in both the macular superficial capillary plexus and deep capillary plexus when compared to those of a healthy control group. Furthermore, the foveal avascular zone (FAZ) was notably larger in affected individuals. The authors speculated that a reduced macular blood supply due to structural retinal vessel alterations could lead to increased thrombotic risk in FD [10]. Another study found larger FAZ areas and lower superficial capillary plexus and deep capillary plexus VD values in FD patients compared to controls [137]. However, no significant discrepancies in FAZ size between FD patients and controls were found in one study, where the authors observed a higher foveal VD in patients with FD. The authors proposed a correlation between the presence of cornea verticillata, plasma lyso-Gb3 levels (a biomarker of FD), and foveal VD, suggesting that this association could potentially serve as a biomarker for FD [140]. A schematic representation of the FAZ enlargement in a patient with FD is shown in Figure 3.  
Through SD-OCT it was shown that hyperreflective foci (HRF) in the inner retinal layers are prevalent among FD patients [141]. HRFs are defined as isolated point-like artifacts (10-30 \(\upmu\)m) with high-intermediate reflectivity and no shadowing cone [142].