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Remodeling of the fovea in Parkinson disease

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

To quantify the thickness of the inner retinal layers in the foveal pit where the nerve fiber layer (NFL) is absent, and quantify changes in the ganglion cells and inner plexiform layer. Pixel-by-pixel volumetric measurements were obtained via Spectral-Domain optical coherence tomography (SD-OCT) from 50 eyes of Parkinson disease (PD) (n = 30) and 50 eyes of healthy control subjects (n = 27). Receiver operating characteristics (ROC) were used to classify individual subjects with respect to sensitivity and specificity calculations at each perifoveolar distance. Three-dimensional topographic maps of the healthy and PD foveal pit were created. The foveal pit is thinner and broader in PD. The difference becomes evident in an annular zone between 0.5 and 2 mm from the foveola and the optimal (ROC-defined) zone is from 0.75 to 1.5 mm. This zone is nearly devoid of NFL and partially overlaps the foveal avascular zone. About 78 % of PD eyes can be discriminated from HC eyes based on this zone. ROC applied to OCT pixel-by-pixel analysis helps to discriminate PD from HC retinae. Remodeling of the foveal architecture is significant because it may provide a visible and quantifiable signature of PD. The specific location of remodeling in the fovea raises a novel concept for exploring the mechanism of oxidative stress on retinal neurons in PD. OCT is a promising quantitative tool in PD research. However, larger scale studies are needed before the method can be applied to clinical follow-ups.

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References

  • Aaker GD, Myung JS, Ehrlich JR et al (2008) Detection of retinal changes in Parkinson’s disease with spectral-domain optical coherence tomography. Clin Ophthalmol 4:1427–1432

    Google Scholar 

  • Altintas O, Iseri P, Ozkan B, Caglar Y (2008) Correlation between retinal morphological and functional findings and clinical severity in Parkinson’s disease. Documenta Ophthal 1116:137–146

    Article  Google Scholar 

  • Archibald NK, Clarke MP, Mosimann UP, Burn DJ (2009) The retina in Parkinson’s disease. Brain 132(Pt 5):1128–1145

    Google Scholar 

  • Archibald NK, Clarke MP, Mosimann UP, Burn DJ (2011) Retinal thickness in Parkinson’s disease. Parkinsonism Relat Disord. 17(6):431–436 (Epub 2011 Mar 31)

    Google Scholar 

  • Bagci AM, Shahidi M, Ansari R et al (2008) Thickness profiles of retinal layers by optical coherence tomography image segmentation. Am J Ophthalmol 146:679–687

    Article  PubMed  Google Scholar 

  • Biehlmaier O, Alam M, Schmidt WJ (2007) A rat model of Parkinsonism shows depletion of dopamine in the retina. NeurochemInt 50:189–195

    Article  CAS  Google Scholar 

  • Bodis-Wollner I (1990) Visual deficit related to dopamine deficiency in experimental animals and Parkinson’s disease. Trends Neurosci 13:296–301

    Article  PubMed  CAS  Google Scholar 

  • Bodis-Wollner I (2009) Retinopathy in Parkinson disease. J Neural Transm 116:1493–1501

    Article  PubMed  Google Scholar 

  • Bodis-Wollner I (2012) Foveal vision is impaired in Parkinson’s disease. A review. Parkinsonism Relat Disord pii: S1353–8020(12):295–297. doi:10.1016/j.parkreldis.2012.07.012 [Epub ahead of print]

  • Bodis-Wollner I, Harnois C, Bobak P, Mylin LH (1983) On the possible role oftemporal delays of afferent processing in Parkinson’s disease. J Neural Trans Suppl 19:243–252

    Google Scholar 

  • Braak H, Del Tredici K, Bratzke H, Hamm-Clement J, Sandmann-Keil D, Rüb U (2002) Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson’s disease (preclinical and clinical stages). J Neurol 249:1–5

    Article  Google Scholar 

  • Chui TY, Zhong Z, Song H, Burns SA (2012) Foveal avascular zone and its relationship to foveal pit shape. Optom Vis Sci 89(5):602–610

    Article  PubMed  Google Scholar 

  • Cubo E, Tedejo RP, Rodriguez Mendez V et al (2010) Retinal thickness in Parkinson’s disease and essential tremor. Mov Disord 25:2461–2462

    Article  PubMed  Google Scholar 

  • DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845

    Article  PubMed  CAS  Google Scholar 

  • Djamgoz MB, Hankins MW, Hirano J, Archer SN (1997) Neurobiology of retinal dopamine in relation to degenerative states of the tissue. Vis Res 37:3509–3529

    Article  PubMed  CAS  Google Scholar 

  • Dowling JE, Ehinger B (1978) Synaptic organization of the dopaminergic neurons in the rabbit retina. J Comp Neurol 180:203–220

    Article  PubMed  CAS  Google Scholar 

  • Dubis AM, Hansen BR, Cooper RF et al (2012) The relationship between the foveal avascular zone and foveal pit morphology. Invest Ophthalmol Vis Sci 53(3):1628

    Article  PubMed  Google Scholar 

  • Engle RF (1983) Wald, likelihood ratio, and lagrange multiplier tests in econometrics. In: Intriligator MD, Griliches Z (eds) Handbook of econometrics II, pp 796–801. Elsevier. ISBN978-0-444-86185-6

  • Esteve-Rudd J, Campello L, Herrero MT et al (2010) Expression in the mammalian retina of parkin and UCH-L1, two components of the ubiquitin-proteasome system. Brain Res 1352:70–82

    Article  PubMed  CAS  Google Scholar 

  • Frederick JM, Rayborn ME, Laties AM et al (1982) Dopaminergic neurons in the human retina. J Comp Neurol 210:65–79

    Article  PubMed  CAS  Google Scholar 

  • Ghilardi MF, Chung E, Bodis-Wollner I et al (1988) Systemic 1-methyl, 4-phenyl 1–2-3-6 tetrahydropyridine (MPTP) administration decreases retinal dopamine concentration in primates. Life Sci 4(3):255–6263

    Article  Google Scholar 

  • Ghilardi MF, Marx MS, Bodis-Wollner I, Camras CB, Glover AA (1989) The effect of intraocular 6-hydroxydopamine on retinal processing of primates. Ann Neurol 25:357–364

    Article  PubMed  CAS  Google Scholar 

  • Gottlob I, Weghaupt H, Vass C, Auff E (1989) Effect of levodopa on the human pattern electroretinogram and pattern visual evoked potentials. Graefes Arch Clin Exp Ophthalmol 227:421–427

    Article  PubMed  CAS  Google Scholar 

  • Hajee M, March W, Wolintz A et al (2009) Inner retinal layer thinning in Parkinson disease. Arch Ophthalmol 127:737–741

    Article  PubMed  Google Scholar 

  • Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143:29–36

    PubMed  CAS  Google Scholar 

  • Harnois C, DiPaolo T (1990) Decreased dopamine in the retinas of patients with Parkinson disease. Invest Ophthalmol Vis Sci 31:2473–2475

    PubMed  CAS  Google Scholar 

  • Hendley ED, Snyder SH (1972) Stereoselectivity of catecholamine uptake in noradrenergic and dopaminergic peripheral organs. Eur J Pharmacol 19:56–66

    Article  PubMed  CAS  Google Scholar 

  • Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442

    Article  PubMed  CAS  Google Scholar 

  • Hokoc JN, Mariani AP (1987) Tyrosine hydroxylase immunoreactivity in the rhesus monkey retina reveals synapses from bipolar cells to dopaminergic amacrine cells. J Neurosci 7(9):2785–2793

    PubMed  CAS  Google Scholar 

  • Huang D, Swanson EA, Lin CP et al (1991) Optical coherence tomography. Science 254:1178–1181

    Article  PubMed  CAS  Google Scholar 

  • Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184

    Article  PubMed  CAS  Google Scholar 

  • Ikeda H, Head GM, Ellis CJ (1994) Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson’s disease and a follow up study. Vis Res 34:2629–2638

    Article  PubMed  CAS  Google Scholar 

  • Inzelberg R, Ramirez JA, Nisipeanu P, Ophir A (2004) Retinal nerve fiber layer thinning in Parkinson disease. Vis Res 44:2793–2797

    Article  PubMed  Google Scholar 

  • La Morgia C, Carbonelli M, Barboni P (2011) Age-related temporal loss of retinal nerve fibers in Parkinson disease: a mitochondrial pattern? Invest Ophthalmol Vis Sci 52. E-Abstract 2984. Eur J Neurol. doi: 10.1111/j.1468-1331.2012.03701.x (Epub ahead of print)

  • Loduca AL, Zhana CHI, Zelkha R, Shahidi M (2010) Thickness mapping of retinal layers with spectral-domain optical coherence tomography. Am J Ophthalmol 150:849–855

    Article  PubMed  Google Scholar 

  • Mariani AP, Hokoc JN (1988) Two types of tyrosine hydroxylase-immunoreactive amacrine cell in the rhesus monkey retina. J Comp Neurol 276(1):81–91

    Article  PubMed  CAS  Google Scholar 

  • Martínez-Navarrete GC, Martín-Nieto J, Esteve-Rudd J et al (2007) Alpha synuclein gene expression profile in the retina of vertebrates. Mol Vis 13(949–61):32

    Google Scholar 

  • Moschos MM et al (2011) Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss. Eur J Ophthalmol 21:24–29

    Article  PubMed  Google Scholar 

  • Nguyen-Legros J (1998) Functional neuroarchitecture of the retina: hypothesis on the dysfunction of retinal dopaminergic circuitry in Parkinson’s disease. Surg Radiol Anat 10:137–144

    Article  Google Scholar 

  • Peppe A, Stanzione P, Pierantozzi M et al (1998) Does pattern electroretinogram spatial tuning alteration in Parkinson’s disease depends on motor disturbances or retinal dopaminergic loss? Electroencephalogr Clin Neurophysiol 106:374–382

    Article  PubMed  CAS  Google Scholar 

  • Provis JM, Hendrickson AE (2008) The foveal avascular region of developing human retina. Arch Ophthalmol 126:507–511

    Article  PubMed  CAS  Google Scholar 

  • Sartucci F, Orlandi G, Bonuccelli U, Borghetti D, Murri L, Orsini C et al (2006) Chromaticpattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophycompared with Parkinson's disease. Neurol Sci 26(6):395–401

    Google Scholar 

  • Stanzione P, Fattapposta F, Tagliati M, D’Alessio C, Marciani MG, Foti A et al (1990) Dopaminergic pharmacological manipulations in normal humans confirm the specificity of the visual (PERG-VEP) and cognitive (P300) electrophysiological alterations in Parkinson’s disease. Electroencephalogr Clin Neurophysiol Suppl 41:216–220

    Google Scholar 

  • Tagliati M, Bodis-Wollner I, Kovanecz I, and Stanzione P (1994) Spatial frequency tuning of the monkey pattern ERG depends on D2 receptor-linked action of dopamine. Vision Res 34:2051–2057

    Google Scholar 

  • Tagliati M, Bodis-Wollner I, Yahr M (1995) The pattern electroretinogram in Parkinson’s disease reveals lack of retinal spatial tuning. Electoenceph Clin Neurophysiol 100:1–11

    Article  Google Scholar 

  • Tan JM, Wong ES, Lim KL (2009) Protein misfolding and aggregation in Parkinson’s disease. Antioxid Redox Signal 11:2119–2134

    Article  PubMed  CAS  Google Scholar 

  • Tick S, Rossant F, Ghorbel I et al (2011) Foveal shape and structure in a normal population. Invest Ophthalmol Vis Sci 52:5105–5110

    Article  PubMed  Google Scholar 

  • Wagner-Schuman M et al (2011) Race- and sex-related differences in retinal thickness and foveal pit morphology. Invest Ophthalmol Vis Sci 52:625–634

    Article  PubMed  Google Scholar 

  • Witkovsky P (2004) Dopamine and retinal function. Doc Ophthalmol 108(1):17–40

    Article  PubMed  Google Scholar 

  • Witkovsky P, Gabriel R, Krizaj D (2008) Anatomical and neurochemical characterization of dopaminergic interplexiform processes in mouse and rat retinas. J Comp Neurol 510:158–174

    Article  PubMed  CAS  Google Scholar 

  • Wojtkowski M, Bajraszewski T, Gorczynska I et al (2004) Ophthalmic imaging by spectral optical coherence tomography. Am J Ophthalmol 138:412–419

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The National Parkinson Foundation and Michael J. Fox Foundation provided Partial indirect Funding/Support. William Brunken, PhD, John Danias, MD, PhD, Douglas Lazzaro, MD, Marilee P. Ogren-Balkema, PhD and John Dowling, PhD provided critical revisions and suggestions on an early and Edward Chay, MD on a later version of the manuscript. Dr. M. Asim Javaid provided much assistance during the study and made comments on earlier versions of this work. Galina Glazman, Hunter College student, and Dr. N. Sohail provided much laboratory assistance. The SUNY Downstate Academic Center for Scientific Computing (Jeremy Weedon, PhD and Matt Avitable, PhD) had advised us on several aspects of the study. We benefited from very substantial discussions with Samantha Slotnick, OD and Jerome Sherman, OD of the SUNY College of Optometry and SUNY Eye Institute.

Conflict of interest

Authors do not have a financial relationship with the National Parkinson Foundation and Michael J. Fox Foundation that sponsored the research. The authors declare that they have no conflict of interest.

Ethical standard

All human studies have been approved by SUNY Downstate Medical Center Institutional Review Board and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. All persons gave their informed consent prior to their inclusion in the study.

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Correspondence to I. Bodis-Wollner.

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702_2012_909_MOESM1_ESM.doc

Supplementary material 1 The standard output of the OCT equipment with the grid centered on the foveola. This illustration represents the recording of a 74-year-old HC. The subject fixates on a central fixation target and the equipment allows the operator to center the measuring grid (see the illustration). Post-recording, some corrections are possible but it is preferable to center the grid close to the central pixel, certainly not more distant than one pixel. Underneath each 0.25 by 0.25 square the volume is measured for thickness at that point. Figure represents the actual output of the OCT equipment, for a 74-year-old healthy Caucasian male. Upper left hand corner: color-coded thickness map of the foveal region, centered on the foveola. Below: a table of full thickness values in each labeled segment of the foveal image. Numbers represent mean thickness values in each perifoveolar ring, as defined by the ETDRS (Early Treatment Diabetic Retinopathy Study) protocol (see text). Top right: color-coded average volumes plotted in each region. Bottom right; the foveolar centered measuring grid with color-coded thickness values. Next to the grid left: an image of the vertical cross section of the fovea through the foveola. Bottom of the grid: the horizontal (temporo-nasal) cross section of the fovea. Many studies calculate macular volumes in the three zones of the EDTRS protocol (top right, above) and measure thickness of the full retina, or measure thickness at selected points of the image, using manual cursors (see text). Our measures reflect volumes in each pixel depicted in the grid. (DOC 465 kb)

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Spund, B., Ding, Y., Liu, T. et al. Remodeling of the fovea in Parkinson disease. J Neural Transm 120, 745–753 (2013). https://doi.org/10.1007/s00702-012-0909-5

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  • DOI: https://doi.org/10.1007/s00702-012-0909-5

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