Journal of Neurology

, Volume 259, Issue 7, pp 1390–1398 | Cite as

Detection of clinical and subclinical retinal abnormalities in neurosarcoidosis with optical coherence tomography

  • Christopher Eckstein
  • Shiv Saidha
  • Elias S. Sotirchos
  • Gita Byraiah
  • Michaela Seigo
  • Aleksandra Stankiewicz
  • Stephanie B. Syc
  • E’Tona  Ford
  • Srilakshmi Sharma
  • Peter A. Calabresi
  • Carlos A. Pardo
Original Communication


The aim of this work was to determine if neurosarcoidosis (NS) patients exhibit quantitative and/or qualitative in vivo evidence of retinal abnormalities on optical coherence tomography (OCT). Retinal imaging was performed using spectral-domain Cirrus HD-OCT in 20 NS patients (40 eyes) and 24 age-matched healthy controls (48 eyes). Study participants also underwent magnetic resonance imaging of the brain and spine, cerebrospinal fluid (CSF) analysis, and detailed neurological and ophthalmological evaluation. Quantitative OCT abnormalities of average macular thickness (AMT), peri-papillary retinal nerve fiber layer (RNFL) thickness, or both, were detectable in 60% of NS patients. Of NS patients with ocular symptomatology, 75% demonstrated quantitative OCT abnormalities, while only 25% had detectable abnormalities on detailed ophthalmological assessment. Furthermore, 33% of NS patients without ocular symptoms had quantitative OCT changes, while only 8% had abnormal ophthalmologic examination. RNFL and macular thinning and swelling were significant in the NS cohort compared to healthy controls (variance ratio testing; RNFL: p = 0.02, AMT: p = 0.006). AMT also correlated inversely with disease duration (rs = −0.65, p = 0.002). Patient proportions with OCT abnormalities did not differ according to NS subtype (myelopathic, meningeal, or encephalitic NS), CSF findings, or immunotherapy exposure. No qualitative OCT abnormalities were detected. Retinal abnormalities occur in all NS subtypes, and may be clinical or subclinical. Our findings suggest OCT may enable greater detection of retinal abnormalities in NS than ophthalmological assessment alone, and have implications for the assessment of ocular involvement in NS, and sarcoidosis in general. Longitudinal NS studies utilizing OCT are warranted.


Optical coherence tomography Neurosarcoidosis Optic neuropathy Uveitis Retina 


  1. 1.
    Newman LS, Rose CS, Maier LA (1997) Sarcoidosis. N Engl J Med 336(17):1224–1234PubMedCrossRefGoogle Scholar
  2. 2.
    Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H Jr, Bresnitz EA, DePalo L, Hunninghake G, Iannuzzi MC, Johns CJ, McLennan G, Moller DR, Newman LS, Rabin DL, Rose C, Rybicki B, Weinberger SE, Terrin ML, Knatterud GL, Cherniak R (2001) Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 164:1885–1889 10 Pt 1PubMedGoogle Scholar
  3. 3.
    Iwai K, Tachibana T, Takemura T, Matsui Y, Kitaichi M, Kawabata Y (1993) Pathological studies on sarcoidosis autopsy. I. Epidemiological features of 320 cases in Japan. Acta Pathol Jpn 43(7-8):372–376PubMedGoogle Scholar
  4. 4.
    Patel AV, Stickler DE, Tyor WR (2007) Neurosarcoidosis. Curr Treat Options Neurol 9(3):161–168PubMedCrossRefGoogle Scholar
  5. 5.
    Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK (1978) Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 86(5):648–655PubMedGoogle Scholar
  6. 6.
    Jabs DA, Johns CJ (1986) Ocular involvement in chronic sarcoidosis. Am J Ophthalmol 102(3):297–301PubMedGoogle Scholar
  7. 7.
    James DG (1964) The diagnosis and treatment of ocular sarcoidosis. Acta Med Scand Suppl 425:203–208PubMedGoogle Scholar
  8. 8.
    Bonfioli AA, Orefice F (2005) Sarcoidosis. Semin Ophthalmol 20(3):177–182PubMedCrossRefGoogle Scholar
  9. 9.
    Hunter DG, Foster CS (1994) Ocular manifestations of sarcoidosis. In: Albert D, Jakobiec FA (eds) Principles and Practice of Ophthalmology. WB Saunders, Philadelphia, pp 443–450Google Scholar
  10. 10.
    Frohman LP, Guirgis M, Turbin RE, Bielory L (2003) Sarcoidosis of the anterior visual pathway: 24 new cases. J Neuroophthalmol 23(3):190–197PubMedCrossRefGoogle Scholar
  11. 11.
    Balcer LJ (2006) Clinical practice. Optic neuritis. N Engl J Med. 354 (12):1273–1280. doi:10.1056/NEJMcp053247 Google Scholar
  12. 12.
    Burton EV, Greenberg BM, Frohman EM (2011) Optic neuritis: A mechanistic view. Pathophysiology 18(1):81–92. doi:10.1016/j.pathophys.2010.04.009 PubMedCrossRefGoogle Scholar
  13. 13.
    Saidha S, Eckstein C, Ratchford J (2010) Optical coherence tomography as a marker of axonal damage in multiple sclerosis. CML-Mult Scler 2:33–43Google Scholar
  14. 14.
    Stavrou P, Linton S, Young DW, Murray PI (1997) Clinical diagnosis of ocular sarcoidosis. Eye (Lond) 11(Pt 3):365–370CrossRefGoogle Scholar
  15. 15.
    Rothova A, Lardenoye C (1998) Arterial macroaneurysms in peripheral multifocal chorioretinitis associated with sarcoidosis. Ophthalmology 105(8):1393–1397PubMedCrossRefGoogle Scholar
  16. 16.
    Rothova A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A (1996) Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol 80(4):332–336PubMedCrossRefGoogle Scholar
  17. 17.
    Staurenghi G, Invernizzi A, de Polo L, Pellegrini M (2010) Diagnosis and detection. Eur J Ophthalmol 21(S6):27–36PubMedGoogle Scholar
  18. 18.
    Ouyang Y, Keane PA, Sadda SR, Walsh AC (2010) Detection of cystoid macular edema with three-dimensional optical coherence tomography versus fluorescein angiography. Invest Ophthalmol Vis Sci 51(10):5213–5218. doi:10.1167/iovs.09-4635 PubMedCrossRefGoogle Scholar
  19. 19.
    Genead MA, Fishman GA (2011) Cystic macular oedema on spectral-domain optical coherence tomography in choroideremia patients without cystic changes on fundus examination. Eye (Lond) 25(1):84–90. doi:10.1038/eye.2010.157 CrossRefGoogle Scholar
  20. 20.
    Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA et al (1991) Optical coherence tomography. Science 254(5035):1178–1181PubMedCrossRefGoogle Scholar
  21. 21.
    Hrynchak P, Simpson T (2000) Optical coherence tomography: an introduction to the technique and its use. Optom Vis Sci 77(7):347–356PubMedCrossRefGoogle Scholar
  22. 22.
    Frohman EM, Fujimoto JG, Frohman TC, Calabresi PA, Cutter G, Balcer LJ (2008) Optical coherence tomography: a window into the mechanisms of multiple sclerosis. Nat Clin Pract Neurol 4(12):664–675. doi:10.1038/ncpneuro0950 PubMedCrossRefGoogle Scholar
  23. 23.
    Burkholder BM, Osborne B, Loguidice MJ, Bisker E, Frohman TC, Conger A, Ratchford JN, Warner C, Markowitz CE, Jacobs DA, Galetta SL, Cutter GR, Maguire MG, Calabresi PA, Balcer LJ, Frohman EM (2009) Macular volume determined by optical coherence tomography as a measure of neuronal loss in multiple sclerosis. Arch Neurol 66(11):1366–1372. doi:10.1001/archneurol.2009.230 PubMedCrossRefGoogle Scholar
  24. 24.
    Zajicek JP, Scolding NJ, Foster O, Rovaris M, Evanson J, Moseley IF, Scadding JW, Thompson EJ, Chamoun V, Miller DH, McDonald WI, Mitchell D (1999) Central nervous system sarcoidosis—diagnosis and management. Qjm 92(2):103–117PubMedCrossRefGoogle Scholar
  25. 25.
    Saidha S, Syc SB, Ibrahim MA, Eckstein C, Warner CV, Farrell SK, Oakley JD, Durbin MK, Meyer SA, Balcer LJ, Frohman EM, Rosenzweig JM, Newsome SD, Ratchford JN, Nguyen QD, Calabresi PA (2011) Primary retinal pathology in multiple sclerosis as detected by optical coherence tomography. Brain 134(Pt 2):518–533. doi:10.1093/brain/awq346 PubMedCrossRefGoogle Scholar
  26. 26.
    Syc SB, Warner CV, Hiremath GS, Farrell SK, Ratchford JN, Conger A, Frohman T, Cutter G, Balcer LJ, Frohman EM, Calabresi PA (2010) Reproducibility of high-resolution optical coherence tomography in multiple sclerosis. Mult Scler 16(7):829–839. doi:10.1177/1352458510371640 PubMedCrossRefGoogle Scholar
  27. 27.
    Cettomai D, Hiremath G, Ratchford J, Venkatesan A, Greenberg BM, McGready J, Pardo CA, Kerr DA, Frohman E, Balcer LJ, McArthur JC, Calabresi PA (2010) Associations between retinal nerve fiber layer abnormalities and optic nerve examination. Neurology 75(15):1318–1325. doi:10.1212/WNL.0b013e3181f735bd PubMedCrossRefGoogle Scholar
  28. 28.
    Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI, Freedman MS, Zackon DH, Kardon RH (2006) Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 59(6):963–969. doi:10.1002/ana.20851 PubMedCrossRefGoogle Scholar
  29. 29.
    Scott CJ, Kardon RH, Lee AG, Frisen L, Wall M (2010) Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch Ophthalmol 128(6):705–711. doi:10.1001/archophthalmol.2010.94 PubMedCrossRefGoogle Scholar
  30. 30.
    Hoye VJ 3rd, Berrocal AM, Hedges TR 3rd, Amaro-Quireza ML (2001) Optical coherence tomography demonstrates subretinal macular edema from papilledema. Arch Ophthalmol 119(9):1287–1290PubMedCrossRefGoogle Scholar
  31. 31.
    Markomichelakis NN, Halkiadakis I, Pantelia E, Peponis V, Patelis A, Theodossiadis P, Theodossiadis G (2004) Patterns of macular edema in patients with uveitis: qualitative and quantitative assessment using optical coherence tomography. Ophthalmology 111(5):946–953. doi:10.1016/j.ophtha.2003.08.037 PubMedCrossRefGoogle Scholar
  32. 32.
    Gupta V, Gupta P, Singh R, Dogra MR, Gupta A (2008) Spectral-domain Cirrus high-definition optical coherence tomography is better than time-domain Stratus optical coherence tomography for evaluation of macular pathologic features in uveitis. Am J Ophthalmol 145(6):1018–1022. doi:10.1016/j.ajo.2008.01.021 PubMedCrossRefGoogle Scholar
  33. 33.
    Hee MR, Puliafito CA, Wong C, Duker JS, Reichel E, Rutledge B, Schuman JS, Swanson EA, Fujimoto JG (1995) Quantitative assessment of macular edema with optical coherence tomography. Arch Ophthalmol 113(8):1019–1029PubMedCrossRefGoogle Scholar
  34. 34.
    Hickman RA, Denniston AK, Yee CS, Toescu V, Murray PI, Gordon C (2010) Bilateral retinal vasculitis in a patient with systemic lupus erythematosus and its remission with rituximab therapy. Lupus 19(3):327–329. doi:10.1177/0961203309347332 PubMedCrossRefGoogle Scholar
  35. 35.
    Frank KW, Weiss H (1983) Unusual clinical and histopathological findings in ocular sarcoidosis. Br J Ophthalmol 67(1):8–16PubMedCrossRefGoogle Scholar
  36. 36.
    Frohman L, Grigorian R, Slamovits T (2001) Evolution of sarcoid granulomas of the retina. Am J Ophthalmol 131(5):661–662PubMedCrossRefGoogle Scholar
  37. 37.
    Wong M, Janowicz M, Tessler HH, Goldstein DA (2009) High-resolution optical coherence tomography of presumed sarcoid retinal granulomas. Retina 29(10):1545–1546PubMedCrossRefGoogle Scholar
  38. 38.
    Gallagher MJ, Yilmaz T, Cervantes-Castaneda RA, Foster CS (2007) The characteristic features of optical coherence tomography in posterior uveitis. Br J Ophthalmol 91(12):1680–1685. doi:10.1136/bjo.2007.124099 PubMedCrossRefGoogle Scholar
  39. 39.
    Kannan B, Govindarajan K, Kummararaj S, Balaji V, Natarajapillai V (2010) Retinal vasculitis in a patient with abdominal tuberculosis. Oman J Ophthalmol 3(2):81–85. doi:10.4103/0974-620X.64232 PubMedCrossRefGoogle Scholar
  40. 40.
    Dale EA, Hood DC, Greenstein VC, Odel JG (2010) A comparison of multifocal ERG and frequency domain OCT changes in patients with abnormalities of the retina. Doc Ophthalmol 120(2):175–186. doi:10.1007/s10633-009-9210-9 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Christopher Eckstein
    • 1
  • Shiv Saidha
    • 1
  • Elias S. Sotirchos
    • 1
  • Gita Byraiah
    • 1
  • Michaela Seigo
    • 1
  • Aleksandra Stankiewicz
    • 1
  • Stephanie B. Syc
    • 1
  • E’Tona  Ford
    • 1
  • Srilakshmi Sharma
    • 2
  • Peter A. Calabresi
    • 1
  • Carlos A. Pardo
    • 1
  1. 1.Department of NeurologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of NeurophthalmologyWilmer Eye Institute, Johns Hopkins HospitalBaltimoreUSA

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