Retinal ganglion cell and microvascular density loss in hereditary spastic paraplegia

Background: Hereditary spastic paraplegia (HSP) is characterized by progressive degeneration of distal axons in the long corticospinal tracts. Loss of retinal cells and microvascular networks has neither been suspected nor investigated. We concurrently examined the retinal microvasculature and retinal layer morphology in patients with HSP to assess whether retinal features may portray disease and its progression. Methods: Fifteen patients with HSP and 30 healthy controls were included in this cross-sectional case-control study. Disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Severity of ataxia was determined by the Scale for the Assessment and Rating of Ataxia (SARA). Retinal microvasculature was measured by means of optical coherence tomography angiography (OCT-A) and morphology of retinal layers using structural OCT. Mixed-effects models were applied for data analysis. Results: HSP patients showed significantly reduced vessel density of the superficial vascular plexus (SVP), reduced ganglion cell layer (GCL) volume, reduced inner plexiform layer (IPL) volume and reduced temporal-inferior peripapillary retinal nerve fiber layer (pRNFL) thickness versus healthy controls. GCL volume reduction correlated significantly with the worsening of visual acuity and higher SARA scores. Conclusions: These findings demonstrate that, in HSP both cells and vascular networks of the retina are compromised. Assessment of the retinal GCL, IPL and SVP may aid in diagnosis and monitoring of disease progression as well as provide novel structural outcome measures for clinical trials.