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Do you have restless leg syndrome? I understood from your eyes

Abstract

Purpose

According to many studies in the literature, there is a strong association between restless leg syndrome and dopaminergic dysfunction. Dopamine is also the major catecholamine in the retina and is also a possible transmitter of the amacrine and interplexiform cells. The aim of this study is to investigate the possible association between RLS and retinal thickness.

Methods

In this study, we included 33 patients who were diagnosed with idiopathic RLS according to the “International RLS Study Group” criteria and 31 healthy subjects. All the patients and controls underwent routine ophthalmologic examination and had spectral-domain optical coherence tomography (OCT) performed. We compared the retinal thickness of the patients and control subjects.

Results

In the RLS group, foveal thickness was thinner then controls. Also, only inferior, superior, and temporal quadrant retina nerve fiber layer (RNFL) thickness were significantly thinner in the RLS group. The parafoveal ganglion cell complex (GCC) in the superior temporal, inferior temporal, inferior nasal quadrant, and perifoveal superior nasal thickness was also significantly thinner in the patient group. Pearson correlation analyses showed that there were statistically significant negative correlations between disease duration and macular GCC and RNFL thickness. Negative correlations were also detected between parafoveal superior, temporal, inferior and nasal macular thickness, parafoveal superior nasal, inferior temporal GCC thickness, and perifoveal superior nasal GCC thickness and disease duration.

Conclusion

According to our results; most retinal layers are thinner in RLS patients, so it can be considered that OCT has a predictive value for progression of RLS.

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References

  1. Trotti LM (2017) Restless legs syndrome and sleep-related movement disorders. Continuum (Minneap Minn) 23(4, Sleep Neurology):1005–1016. https://doi.org/10.1212/CON.0000000000000488

    Article  Google Scholar 

  2. Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelman JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB (2014) Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med 15(8):860–873. https://doi.org/10.1016/j.sleep.2014.03.025

    Article  PubMed  Google Scholar 

  3. Marin LF, Carvalho LBC, Prado LBF, Oliveira ASB, Prado GF (2017) Restless legs syndrome is highly prevalent in patients with post-polio syndrome. Sleep Med 37:147–150. https://doi.org/10.1016/j.sleep.2017.06.025

    Article  PubMed  Google Scholar 

  4. Chesson AL Jr, Wise M, Davila D, Johnson S, Littner M, Anderson WM, Hartse K, Rafecas J (1999) Practice parameters for the treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine. Sleep 22(7):961–968

    Article  PubMed  Google Scholar 

  5. Connor JR, Wang XS, Allen RP, Beard JL, Wiesinger JA, Felt BT, Earley CJ (2009) Altered dopaminergic profile in the putamen and substantia nigra in restless leg syndrome. Brain 132(Pt 9):2403–2412. https://doi.org/10.1093/brain/awp125

    Article  PubMed  PubMed Central  Google Scholar 

  6. Thorpy MJ (2012) Classification of sleep disorders. Neurotherapeutics 9(4):687–701. https://doi.org/10.1007/s13311-012-0145-6

    Article  PubMed  PubMed Central  Google Scholar 

  7. Turjanski N, Lees AJ, Brooks DJ (1999) Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 52(5):932–937. https://doi.org/10.1212/WNL.52.5.932

    Article  CAS  PubMed  Google Scholar 

  8. Bogan RK (2014) From bench to bedside: an overview of rotigotine for the treatment of restless legs syndrome. Clin Ther 36(3):436–455. https://doi.org/10.1016/j.clinthera.2014.01.021

    Article  CAS  PubMed  Google Scholar 

  9. Rohrer B, Stell WK (1995) Localization of putative dopamine D2-like receptors in the chick retina, using in situ hybridization and immunocytochemistry. Brain Res 695(2):110–116. https://doi.org/10.1016/0006-8993(95)00700-Z

    Article  CAS  PubMed  Google Scholar 

  10. Tian N, Xu HP, Wang P (2015) Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina. Eur J Neurosci 41(1):17–30. https://doi.org/10.1111/ejn.12783

    Article  PubMed  Google Scholar 

  11. Dearry A, Edelman JL, Miller S, Burnside B (1990) Dopamine induces light-adaptive retinomotor movements in bullfrog cones via D2 receptors and in retinal pigment epithelium via D1 receptors. J Neurochem 54(4):1367–1378. https://doi.org/10.1111/j.1471-4159.1990.tb01971.x

    Article  CAS  PubMed  Google Scholar 

  12. Kafieh R, Rabbani H, Kermani S (2013) A review of algorithms for segmentation of optical coherence tomography from retina. J Med Signals Sens 3(1):45–60

    PubMed  PubMed Central  Google Scholar 

  13. Chorostecki J, Seraji-Bozorgzad N, Shah A, Bao F, Bao G, George E, Gorden V, Caon C, Frohman E, Bhatti MT, Khan O (2015) Characterization of retinal architecture in Parkinson’s disease. J Neurol Sci 355(1–2):44–48. https://doi.org/10.1016/j.jns.2015.05.007

    Article  PubMed  Google Scholar 

  14. Bittersohl D, Stemplewitz B, Keseru M, Buhmann C, Richard G, Hassenstein A (2015) Detection of retinal changes in idiopathic Parkinson’s disease using high-resolution optical coherence tomography and Heidelberg retina tomography. Acta Ophthalmol 93(7):e578–e584. https://doi.org/10.1111/aos.12757

    Article  PubMed  Google Scholar 

  15. Guler S, Nesrin Turan F (2015) Turkish version of the Johns Hopkins Restless Legs Syndrome Quality of Life Questionnaire (RLS-QoL): validity and reliability study. Qual Life Res Int J Qual Life Asp Treat Care Rehab 24(11):2789–2794. https://doi.org/10.1007/s11136-015-1003-x

    Article  Google Scholar 

  16. Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4(2):121–132. https://doi.org/10.1016/S1389-9457(02)00258-7

    Article  PubMed  Google Scholar 

  17. Koskderelioglu A, Kusbeci T, Kusbeci OY, Gedizlioglu M (2016) Optic nerve head, retinal nerve fiber layer and macular thickness analysis in restless legs syndrome. Parkinsonism Relat Disord 31:110–115. https://doi.org/10.1016/j.parkreldis.2016.08.003

    Article  PubMed  Google Scholar 

  18. Bara-Jimenez W, Aksu M, Graham B, Sato S, Hallett M (2000) Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. Neurology 54(8):1609–1616

    Article  CAS  PubMed  Google Scholar 

  19. Inzelberg R, Ramirez JA, Nisipeanu P, Ophir A (2004) Retinal nerve fiber layer thinning in Parkinson disease. Vis Res 44(24):2793–2797. https://doi.org/10.1016/j.visres.2004.06.009

    Article  PubMed  Google Scholar 

  20. Moschos MM, Tagaris G, Markopoulos I, Margetis I, Tsapakis S, Kanakis M, Koutsandrea C (2011) Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss. Eur J Ophthalmol 21(1):24–29

    Article  PubMed  Google Scholar 

  21. Yu JG, Feng YF, Xiang Y, Huang JH, Savini G, Parisi V, Yang WJ, Fu XA (2014) Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis. PLoS One 9(1):e85718. https://doi.org/10.1371/journal.pone.0085718

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yavas GF, Yilmaz O, Kusbeci T, Ozturk F (2007) The effect of levodopa and dopamine agonists on optic nerve head in Parkinson disease. Eur J Ophthalmol 17(5):812–816

    Article  CAS  PubMed  Google Scholar 

  23. Carelli V, La Morgia C, Valentino ML, Barboni P, Ross-Cisneros FN, Sadun AA (2009) Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders. Biochim Biophys Acta 1787(5):518–528. https://doi.org/10.1016/j.bbabio.2009.02.024

    Article  CAS  PubMed  Google Scholar 

  24. Mailankody P, Battu R, Khanna A, Lenka A, Yadav R, Pal PK (2015) Optical coherence tomography as a tool to evaluate retinal changes in Parkinson’s disease. Parkinsonism Relat Disord 21(10):1164–1169. https://doi.org/10.1016/j.parkreldis.2015.08.002

    Article  PubMed  Google Scholar 

  25. Frederick JM, Rayborn ME, Laties AM, Lam DM, Hollyfield JG (1982) Dopaminergic neurons in the human retina. J Comp Neurol 210(1):65–79. https://doi.org/10.1002/cne.902100108

    Article  CAS  PubMed  Google Scholar 

  26. Hirasawa H, Puopolo M, Raviola E (2009) Extrasynaptic release of GABA by retinal dopaminergic neurons. J Neurophysiol 102(1):146–158. https://doi.org/10.1152/jn.00130.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Djamgoz MB, Hankins MW, Hirano J, Archer SN (1997) Neurobiology of retinal dopamine in relation to degenerative states of the tissue. Vis Res 37(24):3509–3529. https://doi.org/10.1016/S0042-6989(97)00129-6

    Article  CAS  PubMed  Google Scholar 

  28. Garcia-Martin E, Larrosa JM, Polo V, Satue M, Marques ML, Alarcia R, Seral M, Fuertes I, Otin S, Pablo LE (2014) Distribution of retinal layer atrophy in patients with Parkinson disease and association with disease severity and duration. Am J Ophthalmol 157(2):470–478 e472. https://doi.org/10.1016/j.ajo.2013.09.028

    Article  PubMed  Google Scholar 

  29. Satue M, Obis J, Rodrigo MJ, Otin S, Fuertes MI, Vilades E, Gracia H, Ara JR, Alarcia R, Polo V, Larrosa JM, Pablo LE, Garcia-Martin E (2016) Optical coherence tomography as a biomarker for diagnosis, progression, and prognosis of neurodegenerative diseases. J Ophthalmol 2016:8503859. https://doi.org/10.1155/2016/8503859

    Article  PubMed  PubMed Central  Google Scholar 

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Correspondence to Volkan Solmaz.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria, educational grants, participation in speakers’ bureaus, membership, employment, consultancies, stock ownership, or other equity interest, and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Cite this article

Kose Ozlece, H., Solmaz, V., Özal, S.A. et al. Do you have restless leg syndrome? I understood from your eyes. Sleep Breath 23, 551–557 (2019). https://doi.org/10.1007/s11325-018-1740-5

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  • DOI: https://doi.org/10.1007/s11325-018-1740-5

Keywords

  • Restless leg syndrome
  • OCT
  • Retinal thickness