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Identifying Peripapillary Radial Capillary Plexus Alterations in Parkinson’s Disease Using OCT Angiography

Published:March 10, 2021DOI:https://doi.org/10.1016/j.oret.2021.03.006

      Purpose

      To compare radial peripapillary capillary (RPC) plexus vascular parameters and retinal nerve fiber layer (RNFL) thickness between those with Parkinson’s disease (PD) and controls.

      Design

      Prospective, cross-sectional study.

      Participants

      A total of 151 eyes of 81 PD participants and 514 eyes of 266 controls.

      Methods

      Participants underwent OCT angiography (OCTA) imaging using the Zeiss Cirrus HD-5000 AngioPlex (Carl Zeiss AG). Capillary perfusion density (CPD) and capillary flux index (CFI) were assessed using a 4.5 × 4.5-mm peripapillary scan, and RNFL thickness was assessed using a 200 × 200-μm optic nerve cube OCT scan. Hoehn and Yahr clinical staging for PD was determined by an experienced movement disorders specialist. Generalized estimating equations adjusted for age and sex were used for analysis.

      Main Outcome Measures

      Differences in RNFL thickness, CPD, and CFI as assessed using multivariable generalized estimating equations between individuals with PD and controls.

      Results

      After adjustment for age and sex, average CPD (0.446% ± 0.018% vs. 0.439% ± 0.017%, P < 0.001) and CFI (0.434 ± 0.031 vs. 0.426 ± 0.036, P = 0.008) were significantly higher in PD eyes. Average RNFL thickness was similar between groups (PD 89.71 ± 10.45 μm vs. control 88.20 ± 10.33 μm, P = 0.19). Significant correlations between Hoehn and Yahr stage and OCTA parameters were not observed. The OCTA parameters were not significantly different between eyes of the same patient.

      Conclusions

      Increased peripapillary microvascular density and flux were detected in a large cohort of individuals with PD compared with controls after adjusting for age and sex; however, RNFL thickness was similar between groups. Peripapillary OCTA parameters may not correlate with the severity of PD. OCTA may serve as a noninvasive method to identify novel biomarkers for the early diagnosis of PD; as such, this methodology deserves further investigation.

      Keywords

      Abbreviations and Acronyms:

      CFI (capillary flux index), CI (confidence interval), CPD (capillary perfusion density), OCTA (OCT angiography), PD (Parkinson’s disease), RNFL (retinal nerve fiber layer), RPC (radial peripapillary capillary)
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      References

        • Lotharius J.
        • Brundin P.
        Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein.
        Nat Rev Neurosci. 2002; 3: 932-942
        • Chaudhuri K.R.
        • Healy D.G.
        • Schapira A.H.
        Non-motor symptoms of Parkinson's disease: diagnosis and management.
        Lancet Neurol. 2006; 5: 235-245
        • Archibald N.K.
        • Clarke M.P.
        • Mosimann U.P.
        • Burn D.J.
        The retina in Parkinson's disease.
        Brain. 2009; 132: 1128-1145
        • Armstrong R.A.
        Visual symptoms in Parkinson's disease.
        Parkinsons Dis. 2011; 2011: 908306
        • Borm C.
        • Visser F.
        • Werkmann M.
        • et al.
        Seeing ophthalmologic problems in Parkinson disease: results of a visual impairment questionnaire.
        Neurology. 2020; 94: 1539-1547
        • Garcia-Martin E.
        • Rodriguez-Mena D.
        • Satue M.
        • et al.
        Electrophysiology and optical coherence tomography to evaluate Parkinson disease severity.
        Invest Ophthalmol Vis Sci. 2014; 55: 696-705
        • Kaur M.
        • Saxena R.
        • Singh D.
        • et al.
        Correlation between structural and functional retinal changes in Parkinson disease.
        J Neuroophthalmol. 2015; 35: 254-258
        • Harnois C.
        • Di Paolo T.
        Decreased dopamine in the retinas of patients with Parkinson's disease.
        Invest Ophthalmol Vis Sci. 1990; 31: 2473-2475
        • Ortuño-Lizarán I.
        • Beach T.G.
        • Serrano G.E.
        • et al.
        Phosphorylated α-synuclein in the retina is a biomarker of Parkinson's disease pathology severity.
        Mov Disord. 2018; 33: 1315-1324
        • London A.
        • Benhar I.
        • Schwartz M.
        The retina as a window to the brain-from eye research to CNS disorders.
        Nat Rev Neurol. 2013; 9: 44-53
        • Garcia-Martin E.
        • Larrosa J.M.
        • Polo V.
        • et al.
        Distribution of retinal layer atrophy in patients with Parkinson disease and association with disease severity and duration.
        Am J Ophthalmol. 2014; 157: 470-478
        • Kirbas S.
        • Turkyilmaz K.
        • Tufekci A.
        • Durmus M.
        Retinal nerve fiber layer thickness in Parkinson disease.
        J Neuroophthalmology. 2013; 33: 62-65
        • Lee J.-Y.
        • Kim J.M.
        • Ahn J.
        • et al.
        Retinal nerve fiber layer thickness and visual hallucinations in Parkinson's Disease.
        Mov Disord. 2014; 29: 61-67
        • Moschos M.M.
        • Tagaris G.
        • Markopoulos I.
        • et al.
        Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss.
        Eur J Ophthalmol. 2011; 21: 24-29
        • Pilat A.
        • McLean R.J.
        • Proudlock F.A.
        • et al.
        In vivo morphology of the optic nerve and retina in patients with Parkinson's disease.
        Invest Ophthalmol Vis Sci. 2016; 57: 4420-4427
        • Satue M.
        • Seral M.
        • Otin S.
        • et al.
        Retinal thinning and correlation with functional disability in patients with Parkinson's disease.
        Br J Ophthalmol. 2014; 98: 350-355
        • Yu J.-G.
        • Feng Y.-F.
        • Xiang Y.
        • et al.
        Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis.
        PLoS One. 2014; 9: 85718
        • Hajee M.E.
        • March W.F.
        • Lazzaro D.R.
        • et al.
        Inner retinal layer thinning in Parkinson disease.
        Arch Ophthalmol. 2009; 127: 737-741
        • Garcia-Martin E.
        • Satue M.
        • Fuertes I.
        • et al.
        Ability and reproducibility of Fourier-domain optical coherence tomography to detect retinal nerve fiber layer atrophy in Parkinson's disease.
        Ophthalmology. 2012; 119: 2161-2167
        • Yoon S.P.
        • Grewal D.S.
        • Thompson A.C.
        • et al.
        Retinal microvascular and neurodegenerative changes in Alzheimer's disease and mild cognitive impairment compared with control participants.
        Ophthalmol Retina. 2019; 3: 489-499
        • Jiang H.
        • Delgado S.
        • Liu C.
        • et al.
        In vivo characterization of retinal microvascular network in multiple sclerosis.
        Ophthalmology. 2016; 123: 437-438
        • Kwapong W.R.
        • Ye H.
        • Peng C.
        • et al.
        Retinal microvascular impairment in the early stages of Parkinson's disease.
        Invest Ophthalmol Vis Sci. 2018; 59: 4115-4122
        • Shi C.
        • Chen Y.
        • Kwapong W.R.
        • et al.
        Characterization by fractal dimension analysis of the retinal capillary network in Parkinson disease.
        Retina. 2020; 40: 1483-1491
        • Robbins C.B.
        • Thompson A.C.
        • Bhullar P.K.
        • et al.
        Characterization of retinal microvascular and choroidal structural changes in Parkinson disease.
        JAMA Ophthalmol. 2020; e205730
        • Campbell J.P.
        • Zhang M.
        • Hwang T.S.
        • et al.
        Detailed vascular anatomy of the human retina by projection-resolved optical coherence tomography angiography.
        Sci Rep. 2017; 7: 42201
        • Postuma R.B.
        • Berg D.
        • Stern M.
        • et al.
        MDS clinical diagnostic criteria for Parkinson's disease.
        Mov Disord. 2015; 30: 1591-1601
        • Postuma R.B.
        • Poewe W.
        • Litvan I.
        • et al.
        Validation of the MDS clinical diagnostic criteria for Parkinson's disease.
        Mov Disord. 2018; 33: 1601-1608
        • Rosenfeld P.J.
        • Durbin M.K.
        • Roisman L.
        • et al.
        ZEISS Angioplex spectral domain optical coherence tomography angiography: technical aspects.
        Dev Ophthalmol. 2016; 56: 18-29
        • Hoehn M.M.
        • Yahr M.D.
        Parkinsonism: onset, progression and mortality.
        Neurology. 1967; 17: 427-442
        • Goetz C.G.
        • Poewe W.
        • Rascol O.
        • et al.
        Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.
        Mov Disord. 2004; 19: 1020-1028
      1. Zeiss CIRRUS HD-OCT 5000 User Manual. 2660021169012 Rev. A 2017-12. Carl Zeiss Meditec. Retrieved from https://www.zeiss.co.uk/content/dam/Meditec/gb/Chris/Refractive-Business-Builder/2018Updates/UserGuides/oct_usermanual.pdf. Accessed May 1, 2020.

        • Henkind P.
        Radial peripapillary capillaries of the retina. I. Anatomy: human and comparative.
        Br J Ophthalmol. 1967; 51: 115-123
        • Yu P.K.
        • Cringle S.J.
        • Yu D.-Y.
        Correlation between the radial peripapillary capillaries and the retinal nerve fibre layer in the normal human retina.
        Exp Eye Res. 2014; 129: 83-92
        • Chang R.
        • Chu Z.
        • Burkemper B.
        • et al.
        Effect of scan size on glaucoma diagnostic performance using OCT angiography en face images of the radial peripapillary capillaries.
        J Glaucoma. 2019; 28: 465-472
        • Holmen I.C.
        • Konda M.S.
        • Pak J.W.
        • et al.
        Prevalence and severity of artifacts in optical coherence tomographic angiograms.
        JAMA Ophthalmol. 2019; 138: 119-126
        • La Morgia C.
        • Barboni P.
        • Rizzo G.
        • et al.
        Loss of temporal retinal nerve fibers in Parkinson disease: a mitochondrial pattern?.
        Eur J Neurol. 2012; 20: 198-201
        • Snodderly D.M.
        • Weinhaus R.S.
        • Choi J.C.
        Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis).
        J Neurosci. 1992; 12: 1169-1193
        • Govindpani K.
        • McNamara L.G.
        • Smith N.R.
        • et al.
        Vascular dysfunction in Alzheimer’s disease: a prelude to the pathological process or a consequence of it?.
        J Clin Med. 2019; 8: 651
        • Yang P.
        • Pavlovic D.
        • Waldvogel H.
        • et al.
        String vessel formation is increased in the brain of Parkinson disease.
        J Parkinson Dis. 2015; 5: 821-836
        • Hunter J.M.
        • Kwan J.
        • Malek-Ahmadi M.
        • et al.
        Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer’s disease.
        PLoS One. 2012; 7e36893
        • Ko J.H.
        • Lerner R.P.
        • Eidelberg D.
        Effects of levodopa on regional cerebral metabolism and blood flow.
        Mov Disord. 2015; 30: 54-63
        • Sen A.
        • Tugcu B.
        • Coskun C.
        • et al.
        Effects of levodopa on retina in Parkinson disease.
        Eur J Ophthalmol. 2014; 24: 114-119
        • Figueroa A.G.
        • Boyd B.M.
        • Christensen C.A.
        • et al.
        Levodopa positively affects neovascular age-related macular degeneration.
        Am J Med. 2021; 134 (e3): 122-128
      2. Robbins CB, Grewal DS, Thompson AC, et al. Repeatability of peripapillary optical coherence tomography angiography parameters in older adults. J Vitreoretin Dis. Published online ahead of print. https://doi.org/10.1177/2474126420953968.