PSP and PD are distinct clinicopathological entities. PSP is a tauopathy involving neurofibrillary tangles and severe central atrophy, while PD is a α-synucleinopathy, with substantial, often asymmetrical Lewy Body deposition and subsequent nigral neuronal loss. In clinical practice, the distinction is determined through clinical observations, such as sustained dopaminergic response in PD, and vertical gaze palsy in PSP. The distinction can be challenging when clinical symptoms are subtle and L-dopa response equivocal. Recent evidence of paravascular glymphatic transport in the retina and optic nerve and impaired glymphatic function in tauopathies suggest the neural retina and optic nerve may be prone to neuropathic accumulation of abnormal tau in degenerative tauopathies, resulting in a greater degree of expected retinal nerve fiber layer (RNFL) thinning in PSP than PD, suggesting its putative role as a diagnostic biomarker to distinguish the two.