Retinal Ganglion Cell and Microvascular Density Loss in Hereditary Spastic Paraplegia

Overview

Journal Restor Neurol Neurosci

Publisher Sage Publications

Specialty Neurology

Date 2024 Jan 13

PMID 38217556

Authors

Gabrielle N Turski

Christopher A Turski

Marcus Grobe-Einsler

Xenia Kobeleva

Jennifer S Turski

Frank G Holz

Robert P Finger

Thomas Klockgether

Affiliations

Soon will be listed here.

Abstract

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.

References

Linsenmeier R, Zhang H . Retinal oxygen: from animals to humans. Prog Retin Eye Res. 2017; 58:115-151. PMC: 5441959. DOI: 10.1016/j.preteyeres.2017.01.003. View

Shribman S, Reid E, Crosby A, Houlden H, Warner T . Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches. Lancet Neurol. 2019; 18(12):1136-1146. DOI: 10.1016/S1474-4422(19)30235-2. View

Schule R, Holland-Letz T, Klimpe S, Kassubek J, Klopstock T, Mall V . The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity. Neurology. 2006; 67(3):430-4. DOI: 10.1212/01.wnl.0000228242.53336.90. View

Campbell J, Zhang M, Hwang T, Bailey S, Wilson D, Jia Y . Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography. Sci Rep. 2017; 7:42201. PMC: 5301488. DOI: 10.1038/srep42201. View

Schule R, Wiethoff S, Martus P, Karle K, Otto S, Klebe S . Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients. Ann Neurol. 2016; 79(4):646-58. DOI: 10.1002/ana.24611. View

Lallemant-Dudek P, Durr A . Clinical and genetic update of hereditary spastic paraparesis. Rev Neurol (Paris). 2020; 177(5):550-556. DOI: 10.1016/j.neurol.2020.07.001. View

Fink J . Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms. Acta Neuropathol. 2013; 126(3):307-28. PMC: 4045499. DOI: 10.1007/s00401-013-1115-8. View

Vavla M, Paparella G, Papayannis A, Pascuzzo R, Girardi G, Pellegrini F . Optical Coherence Tomography in a Cohort of Genetically Defined Hereditary Spastic Paraplegia: A Brief Research Report. Front Neurol. 2019; 10:1193. PMC: 6884025. DOI: 10.3389/fneur.2019.01193. View

Lauermann J, Woetzel A, Treder M, Alnawaiseh M, Clemens C, Eter N . Prevalences of segmentation errors and motion artifacts in OCT-angiography differ among retinal diseases. Graefes Arch Clin Exp Ophthalmol. 2018; 256(10):1807-1816. DOI: 10.1007/s00417-018-4053-2. View

10.

Schmitz-Hubsch T, Tezenas Du Montcel S, Baliko L, Berciano J, Boesch S, Depondt C . Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006; 66(11):1717-20. DOI: 10.1212/01.wnl.0000219042.60538.92. View

11.

Tesson C, Koht J, Stevanin G . Delving into the complexity of hereditary spastic paraplegias: how unexpected phenotypes and inheritance modes are revolutionizing their nosology. Hum Genet. 2015; 134(6):511-38. PMC: 4424374. DOI: 10.1007/s00439-015-1536-7. View

12.

Wiethoff S, Zhour A, Schols L, Fischer M . Retinal nerve fibre layer loss in hereditary spastic paraplegias is restricted to complex phenotypes. BMC Neurol. 2012; 12:143. PMC: 3564819. DOI: 10.1186/1471-2377-12-143. View

13.

Salinas S, Proukakis C, Crosby A, Warner T . Hereditary spastic paraplegia: clinical features and pathogenetic mechanisms. Lancet Neurol. 2008; 7(12):1127-38. DOI: 10.1016/S1474-4422(08)70258-8. View

14.

Souza P, Pinto W, Batistella G, Bortholin T, Oliveira A . Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks. Cerebellum. 2016; 16(2):525-551. DOI: 10.1007/s12311-016-0803-z. View

15.

Blackstone C, OKane C, Reid E . Hereditary spastic paraplegias: membrane traffic and the motor pathway. Nat Rev Neurosci. 2010; 12(1):31-42. PMC: 5584382. DOI: 10.1038/nrn2946. View

16.

Lauermann J, Treder M, Heiduschka P, Clemens C, Eter N, Alten F . Impact of eye-tracking technology on OCT-angiography imaging quality in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2017; 255(8):1535-1542. DOI: 10.1007/s00417-017-3684-z. View

17.

Marcotulli C, Leonardi L, Tessa A, De Negris A, Cornia R, Pierallini A . Early-onset optic neuropathy as initial clinical presentation in SPG7. J Neurol. 2014; 261(9):1820-1. DOI: 10.1007/s00415-014-7432-6. View

18.

Aly L, Noll C, Wicklein R, Wolf E, Romahn E, Wauschkuhn J . Dynamics of Retinal Vessel Loss After Acute Optic Neuritis in Patients With Relapsing Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2022; 9(3). PMC: 8931743. DOI: 10.1212/NXI.0000000000001159. View

19.

Fouquet S, Vacca O, Sennlaub F, Paques M . The 3D Retinal Capillary Circulation in Pigs Reveals a Predominant Serial Organization. Invest Ophthalmol Vis Sci. 2017; 58(13):5754-5763. DOI: 10.1167/iovs.17-22097. View

20.

Harding A . Classification of the hereditary ataxias and paraplegias. Lancet. 1983; 1(8334):1151-5. DOI: 10.1016/s0140-6736(83)92879-9. View