Optical Coherence Tomography Reflectivity as a Diagnostic Tool and Neurological Biomarker in Sialidosis Type I

Sialidosis type I (ST-1) is a rare lysosomal storage disease (LSD) caused by NEU1 gene mutations, leading to progressive neurological and visual dysfunction. The classical macular cherry-red spot (CRS) is considered a hallmark ocular sign, but its diagnostic value, particularly in older patients, remains unclear. This study aimed to characterize ocular manifestations and evaluate optical coherence tomography (OCT) reflectivity as a potential structural biomarker of neurological function. In this 2-year prospective cohort study, 15 genetically confirmed ST-1 patients underwent neurological evaluations every 6 months and annual ophthalmic assessments including best-corrected visual acuity (BCVA), fundus photography, OCT, and visual evoked potential (VEP). OCT reflectivity of the inner retina (R_in) and ellipsoid zone at the foveola (R_ez) was quantified using greyscale analysis. Fifteen age-matched healthy controls were included for comparison. CRS was present in 46.7% of patients, predominantly in younger individuals. OCT revealed significantly elevated R_in and R_ez in ST-1 patients compared to controls (p < 0.0001), including in those without clinically visible CRS. OCT reflectivity was strongly associated with neurological severity but not with BCVA. Conversely, BCVA correlated with parafoveal and ganglion cell complex thinning and with delayed VEP latency. Age-related declines in reflectivity, retinal thickness, and BCVA were observed in ST-1 but not in controls. These findings highlight OCT reflectivity is a more sensitive biomarker than the CRS for diagnosing ST-1 and reflects neurological severity even in patients without visible CRS. Importantly, the structure-function relationship between OCT parameters and neurological outcomes suggests broader applicability in LSD and other neurodegenerative conditions.