Microvascular Breakdown Due to Retinal Neurodegeneration in Ataxias

Abstract

A BS TRACT: Background: Neurodegenerative ataxias are devastating disorders of the cerebellum and spinal cord, accompanied by death of retinal ganglion cells, leading to relentlessly progressive decline of motor coordination and permanent disability. Retinal microvascular affection has not yet been determined. Objectives: The aim of this study is to assess whether retinal microvascular alterations occur and, if so, whether they are concurrent with or follow cell death in the retina in neurodegenerative diseases. Methods: This study involves the cross-sectional observational study of 43 patients with ataxia and 43 controls enrolled from August 1, 2018, to September 30, 2020. The extent of ataxia was determined by the Scale for the Assessment and Rating of Ataxia. Changes in retinal vasculature were examined by optical coherence tomography angiography (OCT-A) and retinal cell and fiber density by OCT in ataxias concurrently. Results: When comparing the ataxia cohort with healthy subjects, ataxia patients exhibited reduced vessel density in the radial peripapillary capillary (RPC) network (P = 0.005), capillary density inside the optic nerve head (cdONH) (P < 0.001), nasal superficial vascular plexus (P = 0.03) as well as reduced ganglion cell layer (GCL) volume (P = 0.04), and temporal peripapillary retinal nerve fiber layer thickness (P = 0.04). Mixed effect analysis modeling laterality confirmed these findings. Conclusions: These findings demonstrate a distinct pattern of concurrent changes in vessel density of the retinal superficial vascular complex, encompassing the superficial vascular plexus, RPC network and cdONH, and retinal GCL volume, providing new insights into the ongoing degeneration in ataxias. Our findings may have relevance for design of novel therapeutic approaches for ataxias and possibly other neurodegenerative diseases.

Reply to: “Microvascular Breakdown Due to Retinal Neurodegeneration in Ataxias”

“…We thank Dr. Tensini and colleagues 1 for their interest in and appreciation of our study describing concurrent retinal microvascular and structural changes in degenerative ataxias shown by optical coherence tomography (OCT) angiography (OCT-A) and OCT. 2 In the previous study, Tensini et al 3 compared diseasespecific effects on retinal morphology in spinocerebellar ataxia types 3 and 10 using OCT. In our study, we used OCT in parallel with OCT-A to assess alterations of retinal microvasculature and morphology simultaneously.…”

“…Christopher A. Turski, MD, 1,2 * Gabrielle N. Turski, MD, 2,3 Jennifer Faber, MD, 2,4 Stefan J. Teipel, MD, 5,6 Frank G. Holz, MD, 7 Thomas Klockgether, MD, 2,4 and Robert P. Finger, MD 7…”

“…We thank Dr. Tensini and colleagues 1 for their interest in and appreciation of our study describing concurrent retinal microvascular and structural changes in degenerative ataxias shown by optical coherence tomography (OCT) angiography (OCT‐A) and OCT. 2 …”

“…Our study showed changes in retinal vessel density in the superficial vascular complex primarily involving the radial peripapillary capillary network, the capillary density inside the optic nerve head, and the nasal region of the macular superficial vascular plexus in most patients with ataxia across all studied diseases. 2 The limited size of each disease group did not allow for the detailed assessment of disease‐specific alterations. Nevertheless, we fully agree with Dr. Tensini and coworkers 1 that disease‐specific changes might be expected for retinal microvasculature, because they have been found for retinal morphology.…”

Retinal ganglion cell and microvascular density loss in hereditary spastic paraplegia

“…We recently discovered a reduction of retinal microvascular density in patients with degenerative ataxias, including autosomal dominantly inherited spinocerebellar ataxias (SCAs) ( Turski et al, 2022 ). This is intriguing due to the fact that a concept of clinical overlap between HSP and hereditary ataxias has recently been postulated, suggesting a shared vulnerability of cerebellar and corticospinal neurons to common pathophysiological processes ( Synofzik & Schüle, 2017 ).…”