Assessment of functional and morphometric endpoints in patients with non-arteritic anterior ischemic optic neuropathy (NAION)

  • Christoph Kernstock
  • Flemming Beisse
  • Sarah Wiethoff
  • Andrea Mast
  • Elke Krapp
  • Regine Grund
  • Janko Dietzsch
  • Wolf Lagrèze
  • Dominik Fischer
  • Ulrich Schiefer



The primary objective of this bi-center explorative pilot study was the quantitative assessment of visual field defects and retinal nerve fiber layer thickness (RNFT) over 6 months in patients with acute non-arteritic anterior ischemic optic neuropathy (NAION), in order to elucidate the natural course of NAION and provide a reference dataset for future treatment studies.


16 patients (age 41–80 years, nine males, seven females) suffering from acute NAION and presenting within 7 days after onset of symptoms were included in this study. The following examinations were carried out at the initial visit (month 0) and at months 2, 4 and 6: entire (90°) visual field examination with automated static white-on-white perimetry, quantified by mean defect (MD); peripapillary retinal nerve fiber layer thickness (RNFT) measurement with spectral domain optical coherence tomography (SD-OCT); assessment of distant best correct visual acuity (D-BCVA) and a quantification of the relative afferent pupillary defect (RAPD) using the swinging flashlight test with neutral density filters. Perimetric Mean Defect (MD) and RNFT values were each compared between the consecutive visits using the non-parametric Friedman test.


The initial MD was 6.2 dB (IQR 5.0–7.4) without significant changes further on. RNFT was 183 μm (IQR 148–252) initially, decreased significantly at month 2 (78 μm (IQR 71–93) and further at month 4 (64 μm (IQR 58–74) and 6 (61 μm (IQR 52–81), Friedman test, p < 0.001). Initially, RNFT was above normal limits (due to swelling) in 15/16 patients; at month 2 it was below normal limits in 13/16 patients, at month 4 in 12/13 patients and at month 6 in 9/10 patients. 7/16 patients exhibited segmental swelling of the optic disc, whereas the entire circumference of the optic disc showed RNFL thickening in 9/16 patients.


Functional deficits were present directly after onset of NAION and did not change relevantly further on. Morphological changes comprise severe swelling after onset of NAION, which rapidly turns into atrophy. Already after 2 months more than 80 % of the patients showed a RNFT below normal limits. Progressive RNFL thinning between month 2 and month 4 suggests ongoing atrophy, whereas a stable morphologic end point is reached after month 4.


NAION Natural course Optical coherence tomography Perimetry Visual field 


Conflict of interest


Disclosure statements

Ulrich Schiefer was supported by Allergan Inc. Irvine, USA, Alcon Inc. Freiburg, DE, Pfizer Inc. Karlsruhe, DE, MSD Inc, Munich, DE; Servier Inc. Suresnes, FRANCE, and is consultant of Haag Streit Inc., Köniz. Switzerland.

Christoph Kernstock was supported by Kerstan Foundation; Retina Implant AG, Reutlingen, DE


  1. 1.
    Hayreh SS (1981) Anterior ischemic optic neuropathy. Arch Neurol 38:675–678PubMedCrossRefGoogle Scholar
  2. 2.
    Hayreh SS (2011) Management of ischemic optic neuropathies. Indian J Ophthalmol 59:123–136PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Kerr NM, Chew SSSL, Danesh-Meyer HV (2009) Non-arteritic anterior ischaemic optic neuropathy: a review and update. J Clin Neurosci 16:994–1000PubMedCrossRefGoogle Scholar
  4. 4.
    Hayreh SS, Zahoruk RM (1981) Anterior ischemic optic neuropathy. VI. In juvenile diabetics. Ophthalmologica 182:13–28PubMedCrossRefGoogle Scholar
  5. 5.
    Hayreh SS, Zimmerman MB (2008) Nonarteritic anterior ischemic optic neuropathy: refractive error and its relationship to cup/disc ratio. Ophthalmology 115:2275–2281PubMedCrossRefGoogle Scholar
  6. 6.
    Beck RW, Hayreh SS (2000) Role of aspirin in reducing the frequency of second eye involvement in patients with non-arteritic anterior ischaemic optic neuropathy. Eye (Lond) 14(Pt 1):118CrossRefGoogle Scholar
  7. 7.
    Beck RW, Hayreh SS, Podhajsky PA et al (1997) Aspirin therapy in nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 212–217Google Scholar
  8. 8.
    Sergott RC, Cohen MS, Bosley TM, Savino PJ (1989) Optic nerve decompression may improve the progressive form of nonarteritic ischemic optic neuropathy. Arch Ophthalmol 107:1743–1754PubMedCrossRefGoogle Scholar
  9. 9.
    IONDT Group (1995) Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA 273:6225–6632Google Scholar
  10. 10.
    Hayreh SS, Zimmerman MB (2008) Non-arteritic anterior ischemic optic neuropathy: role of systemic corticosteroid therapy. Graefes Arch Clin Exp Ophthalmol 246:1029–1046PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Rebolleda G, Pérez-López M, Casas-LLera P, Contreras I, Muñoz-Negrete FJ (2013) Visual and anatomical outcomes of non-arteritic anterior ischemic optic neuropathy with high-dose systemic corticosteroids. Graefes Arch Clin Exp Ophthalmol 251:255–260. doi: 10.1007/s00417-012-1995-7 PubMedCrossRefGoogle Scholar
  12. 12.
    Modarres M, Falavarjani KG, Nazari H, Sanjari MS, Aghamohammadi F, Homaii M, Samiy N (2011) Intravitreal erythropoietin injection for the treatment of non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol 95:992–995PubMedCrossRefGoogle Scholar
  13. 13.
    Hayreh SS (2011) Treatment of non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol 95:1617–1618PubMedCrossRefGoogle Scholar
  14. 14.
    Schiefer U, Pascual JP, Edmunds B, Feudner E, Hoffmann EM, Johnson CA, Lagrèze WA, Pfeiffer N, Sample PA, Staubach F, Weleber RG, Vonthein R, Krapp E, Paetzold J (2009) Comparison of the new perimetric GATE strategy with conventional full-threshold and SITA Standard strategies. Investig Ophthalmol Vis Sci 50:488–494CrossRefGoogle Scholar
  15. 15.
    Kernstock C, Dietzsch J, Januschowski K, Schiefer U, Fischer MD (2012) Optical coherence tomography shows progressive local nerve fiber loss after disc hemorrhages in glaucoma patients. Graefes Arch Clin Exp Ophthalmol 250:583–587PubMedCrossRefGoogle Scholar
  16. 16.
    Ferris FL, Kassoff A, Bresnick GH, Bailey I (1982) New visual acuity charts for clinical research. Am J Ophthalmol 94:91–96PubMedGoogle Scholar
  17. 17.
    Bach M (2007) The freiburg visual acuity test-variability unchanged by post-hoc re-analysis. Graefes Arch Clin Exp Ophthalmol 245:965–971PubMedCrossRefGoogle Scholar
  18. 18.
    Bendschneider D, Tornow RP, Horn FK, Laemmer R, Roessler CW, Juenemann AG, Kruse FE, Mardin CY (2010) Retinal nerve fiber layer thickness in normals measured by spectral domain OCT. J Glaucoma 19:475–482PubMedCrossRefGoogle Scholar
  19. 19.
    Hayreh SS (2011) Acute retinal arterial occlusive disorders. Prog Retin Eye Res 30:359–394PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Hayreh SS, Zimmerman B (2005) Visual field abnormalities in nonarteritic anterior ischemic optic neuropathy: their pattern and prevalence at initial examination. Arch Ophthalmol 123:1554–1562PubMedCrossRefGoogle Scholar
  21. 21.
    Vonthein R, Rauscher S, Paetzold J, Nowomiejska K, Krapp E, Hermann A, Sadowski B, Chaumette C, Wild JM, Schiefer U (2007) The normal age-corrected and reaction time–corrected isopter derived by semiautomated kinetic perimetry reinhard. Am Acad Ophthalmol 114(6):1065–1072Google Scholar
  22. 22.
    Schiefer U, Frick S, Nevalainen J, Grobbel J, Krapp E, Selig B, Vonthein R, Weleber RG, Paetzold J (2009) Age-Corrected Normative Data for the Entire (80°) Visual Field, Assessed With a New Fast Thresholding Estimation (GATE). ARVO, May 2009Google Scholar
  23. 23.
    Cullen JF, Chung SHR (2012) Non-arteritic anterior ischaemic optic neuropathy (NA-AION): outcome for visual acuity and visual field defects, the Singapore scene 2. Singap Med J 53:88–90Google Scholar
  24. 24.
    Beri M, Klugman MR, Kohler JA, Hayreh SS (1987) Anterior ischemic optic neuropathy. VII. Incidence of bilaterality and various influencing factors. Ophthalmology 94:1020–1028PubMedCrossRefGoogle Scholar
  25. 25.
    Newman NJ, Scherer R, Langenberg P, Kelman S, Feldon S, Kaufman D, Dickersin K, Ischemic Optic Neuropathy Decompression Trial Research Group (2002) The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol 134:317–328PubMedCrossRefGoogle Scholar
  26. 26.
    Hayreh SS (2009) Ischemic optic neuropathy. Prog Retin Eye Res 28:34–62PubMedCrossRefGoogle Scholar
  27. 27.
    Ischemic Optic Neuropathy Decompression Trial: twenty-four-month update. Arch Ophthalmol. 2000 Jun;118(6):793–8Google Scholar
  28. 28.
    Scherer RW, Feldon SE, Levin L, Langenberg P, Katz J, Keyl PM, Wilson PD, Kelman SE, Dickersin K, Ischemic Optic Neuropathy Decompression Trial Research Group (2008) Visual fields at follow-up in the ischemic optic neuropathy decompression trial: evaluation of change in pattern defect and severity over time. Ophthalmology 115(10):1809–1817PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Aulhorn E (1975) Die Gesichtsfeldprüfung bei macularen Erkrankungen. Ber Zusammenkunft Dtsch Ophthalmol Ges 73:77–86PubMedGoogle Scholar
  30. 30.
    Frisén L (1982) Swelling of the optic nerve head: a staging Scheme. J Neurol Neurosurg Psychiatry 45:13–18PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Jonas JB, Hayreh SS, Tao Y, Papastathopoulos KI, Rensch F (2012) Optic nerve head change in non-arteritic anterior ischemic optic neuropathy and its influence on visual outcome. PLoS ONE 7:e37499PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Wang J-K, Kardon RH, Kupersmith MJ, Garvin MK (2012) Automated Quantification of Volumetric Optic Disc Swelling in Papilledema Using Spectral-Domain Optical Coherence Tomography. Investigative ophthalmology & visual scienceGoogle Scholar
  33. 33.
    Jansonius NM, Nevalainen J, Selig B, Zangwill LM, Sample PA, Budde WM, Jonas JB, Lagrèze WA, Airaksinen PJ, Vonthein R, Levin LA, Paetzold J, Schiefer U (2009) A mathematical description of nerve fiber bundle trajectories and their variability in the human retina. Vis Res 49:2157–2163PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Jansonius NM, Schiefer J, Nevalainen J, Paetzold J, Schiefer U (2012) A mathematical model for describing the retinal nerve fiber bundle trajectories in the human eye: average course, variability, and influence of refraction, optic disc size and optic disc position. Exp Eye Res 105:70–78PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Christoph Kernstock
    • 1
  • Flemming Beisse
    • 2
    • 3
  • Sarah Wiethoff
    • 4
    • 6
  • Andrea Mast
    • 1
  • Elke Krapp
    • 1
  • Regine Grund
    • 1
  • Janko Dietzsch
    • 1
  • Wolf Lagrèze
    • 2
  • Dominik Fischer
    • 1
  • Ulrich Schiefer
    • 1
    • 5
  1. 1.Center for Ophthalmology, Institute for Ophthalmic ResearchUniversity of TübingenTübingenGermany
  2. 2.University Eye Hospital FreiburgFreiburgGermany
  3. 3.Ophthalmology DepartmentUniversity Hospital HeidelbergHeidelbergGermany
  4. 4.Department of NeurodegenerationHertie-Institute for Clinical Brain Research & German Center of Neurodegenerative DiseasesTuebingenGermany
  5. 5.Competence Center „Vision Research“University of Applied Sciences AalenAalenGermany
  6. 6.UCL Institute of NeurologyQueen SquareLondonUK

Personalised recommendations