Workup for Optic Atrophy

  • Bart Chwalisz
  • Dean M. CestariEmail author
  • François-Xavier Borruat


Optic nerve atrophy is a common neuro-ophthalmic problem. It represents the end result of either ascending degeneration after destruction of ganglion cells in the retina, or descending atrophy following destruction of nerve fibers in the optic nerve, chiasm, optic tract and sometimes the retrogeniculate visual pathways. It usually presents with optic nerve pallor that is typically (but not invariably) associated with decreased visual function. The key task in the evaluation is to determine whether there is an on-going process causing destruction of ganglion cells, as determining the cause may allow halting progression of vision loss, and sometimes even visual recovery. This chapter discusses how a careful neuro-ophthalmic history and exam can often establish an etiology or at least substantially narrow the differential diagnosis and guide further workup. OCT analysis can often clarify the clinical picture, and in addition may allow quantitative analysis over time. Of all diagnostic studies, neuroimaging (typically MRI with contrast) has by far the highest yield. Further testing should be performed in a directed fashion.


Optic atrophy Optic neuropathy Vision loss Optic disc pallor OCT 


  1. 1.
    Walsh FB. Papilledema; optic neuritis; optic atrophy. In: Walsh FB, editor. Clinical neuro-ophthalmology. Baltimore: Williams & Wilkins Co; 1947. p. 388–401.Google Scholar
  2. 2.
    Sadun AA, Agarwal MR. Topical diagnosis of acquired optic nerve disorders. In: Miller NR, Newman NJ, Biousse V, Kerrison JB, editors. Walsh and Hoyt’s clinical neuro-ophthalmology. 6th ed. LWW: Baltimore; 2005. p. 197–236.Google Scholar
  3. 3.
    Mitchell JR, Olveira C, Tsiouris AJ, Dinkin MJ. Corresponding ganglion cell atrophy in patients with postgeniculate homonymous visual field loss. J Neuroophthalmol. 2015;35:353–9.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Anderson DR. Ascending and descending optic atrophy produced experimentally in squirrel monkeys. Am J Ophthalmol. 1973;76:693–711.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Quigley HA, Anderson DR. The histologic basis of optic disk pallor in experimental optic atrophy. Am J Ophthalmol. 1977;83:709–17.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Lee AG, Chau FY, Golnik KC, et al. The diagnostic yield of the evaluation for isolated unexplained optic atrophy. Ophthalmology. 2005;112:757–9.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Wright JE, McNab AA, McDonald WI. Primary optic nerve sheath meningioma. Br J Ophthalmol. 1989;73:960–6.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Santiesteban-Freixas R, Mendoza-Santiesteban CE, Columbie-Garbey Y, et al. Cuban epidemic optic neuropathy and its relationship to toxic and hereditary optic neuropathy. Semin Ophthalmol. 2010;25:112–22.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Wall M. Optic atrophy. Surv Ophthalmol. 1991;36:51–8.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Dutton JJ. Gliomas of the anterior visual pathway. Surv Ophthalmol. 1994;38:427–52.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Krobel GB, Charles H, Smith RS. Granulomatous optic neuropathy. Arch Ophthalmol. 1981;99:1053–5.CrossRefGoogle Scholar
  12. 12.
    Duke-Elder GI, Stewart S. System of ophthalmology. In: Neuro-ophthalmology, vol. XII. London: Kimpton; 1971.Google Scholar
  13. 13.
    Repka MX, Savino PJ, Schatz NJ, Sergott RC. Clinical profile and long-term implications of anterior ischemic optic neuropathy. Am J Ophthalmol. 1983;96:478–83.CrossRefGoogle Scholar
  14. 14.
    Smith JL, Hoyt WF, Susac JO. Ocular fundus in acute Leber hereditary optic neuropathy. Arch Ophthalmol. 1973;90:349–54.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF. Inherited mitochondrial optic neuropathies. J Med Genet. 2009;46:145–58.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Nikoskelainen E. The clinical findings in Leber’s hereditary optic neuroretinopathy. Leber’s disease. Trans Ophthalmol Soc UK. 1985;104:845–52.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Fraser JA, Biousse V, Newman NJ. The neuro-ophthalmology of mitochondrial disease. Surv Ophthalmol. 2010;55:299–334.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Lessell S, Gise RL, Krobel GB. Bilateral optic neuropathy with remission in young men. Variation on a theme by Leber? Arch Neurol. 1983;40:2–6.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Wingerchuk DM, Lennon VA, Lucchinetti CF, et al. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6:805–15.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Nikoskelainen E, Sogg RL, Rosental AR, et al. The early phase in Leber hereditary optic atrophy. Arch Ophthalmol. 1977;95:969–78.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Frisen L. Fundus changes in acute malnutritional optic neuropathy. Arch Ophthalmol. 1983;101:577–9.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Stambolian D, Behrens M. Optic neuropathy associated with vitamin B12 deficiency. Am J Ophthalmol. 1977;83:465–8.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Cullom ME, Heher KL, Miller NR, et al. Leber’s hereditary optic neuropathy masquerading as tobacco-alcohol amblyopia. Arch Ophthalmol. 1993;111:1482–5.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Avery RA, Fisher MJ, Liu GT. Optic pathway gliomas. J Neuro-ophthalmol. 2011;31:269–78.CrossRefGoogle Scholar
  25. 25.
    Greenfield DS, Siatkowski RM, Glaser JS, et al. The cupped disc. Who needs neuroimaging? Ophthalmology. 1998;105:1866–74.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    DeWitt CA, Johnson LN, Schoenleber DB, et al. Visual function in patients with optic nerve pallor (optic atrophy). J Natl Med Assoc. 2003;95:394–7.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Boghen DR, Glaser JS. Ischemic optic neuropathy. Brain. 1975;98:689–708.CrossRefGoogle Scholar
  28. 28.
    Drance SM. The visual field of low tension glaucoma and shock-induced optic neuropathy. Arch Ophthalmol. 1977;95:159–1361.Google Scholar
  29. 29.
    Fineberg E, Thompson HS. Quantitation of the afferent pupillary defect. In: Smith JL, editor. Neuro-ophthalmology focus. New York: Masson; 1979. p. 25–9.Google Scholar
  30. 30.
    Fraser CL, White AJR, Plant GT, Martin KR. Optic nerve cupping and the neuro-ophthalmologist. J Neuro-ophthalmol. 2013;33:377–89.CrossRefGoogle Scholar
  31. 31.
    Sadun AA, Lessell S. Brightness-sense and optic nerve disease. Arch Ophthalmol. 1985;103:39–43.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Trobe JD, Glaser JS, Cassady JC. Optic atrophy: differential diagnosis by fundus observation alone. Arch Ophthalmol. 1980;98:1040–5.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Fournier AV, Damji KF, Epstein DL, Pollock SC. Disc excavation in dominant optic atrophy. Differentiation from normal tension glaucoma. Ophthalmology. 2001;108:1595–602.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Danesh-Meyer HV, Savino PJ, Sergott RC. The prevalence of cupping in end-stage arteritic and non-arteritic anterior ischemic optic neuropathy. Ophthalmology. 2001;108:593–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Kanamori A, Nakamura M, Matsui N, et al. Optical coherence tomography detects characteristic retinal nerve fiber layer thickness corresponding to band atrophy of the optic discs. Ophthalmology. 2004;111:2278–83.PubMedCrossRefGoogle Scholar
  36. 36.
    Jonas JB, Fernandez MC, Naumann GOH. Glaucomatous optic nerve atrophy in small discs with low cup-to-disc ratios. Ophthalmology. 1990;97:1211–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Quigley HA. Open-angle glaucoma. NEJM. 1993;328:1097–106.PubMedCrossRefGoogle Scholar
  38. 38.
    Remo S Jr, Vessani RM. New findings in the evaluation of the optic disc in glaucoma diagnosis. Curr Opin Ophthalmol. 2007;18:122–8.CrossRefGoogle Scholar
  39. 39.
    Bynke H, Holmdahl G. Megalopapilla: a differential diagnosis in suspected optic atrophy. Neuro-ophthalmology. 1981;2:53–7.CrossRefGoogle Scholar
  40. 40.
    Ambati BK, Rizzo JF III. Nonglaucomatous cupping of the optic disc. Int Ophthalmol Clin. 2001;41:139–49.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Bianchi-Marzoli S, Rizzo JF III, Brancato R, Lessell S. Quantitative analysis of optic disc cupping in compressive optic neuropathy. Ophthalmology. 1995;102:436–40.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Hayreh SS, Jonas JB. Optic disc morphology after arteritic anterior ischemic optic neuropathy. Ophthalmology. 2001;108:1586–94.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Danesh-Meyer H, Savino PJ, Spaeth GL, Gamble GD. Comparison of arteritis and nonarteritic anterior ischemic optic neuropathies with the Heidelberg retina tomograph. Ophthalmology. 2005;112:1104–12.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Kline LB, Glaser JS. Dominant optic atrophy. Arch Ophthalmol. 1997;97:1680–6.CrossRefGoogle Scholar
  45. 45.
    Trobe JD, Glaser JS, Cassady JC, et al. Nonglaucomatous excavation of the optic disc. Arch Ophthalmol. 1980;98:1046–50.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    O’Neill EC, Danesh-Meyer HV, Kong GXY, et al. Optic disc evaluation in optic neuropathies. The optic disc assessment project. Ophthalmology. 2011;118:964–70.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Torres Dias D, Ushida M, Battistella R, et al. Neurophthalmological conditions mimicking glaucomatous optic neuropathy: analysis of the most common causes of misdiagnosis. BMC Ophthamol. 2017;17:2.CrossRefGoogle Scholar
  48. 48.
    Kamal D, Hitchings R. Normal tension glaucoma – a practical approach. Br J Ophthalmol. 1998;82:835–40.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Tuulonen A, Airaksinen PJ. Initial glaucomatous optic disk and retinal nerve fiber layer abnormalities and their progression. Am J Ophthalmol. 1991;111:485–90.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Nicolela MT, Drance SM. Various glaucomatous optic nerve appearances. Clinical correlations. Ophthalmology. 1996;103:640–9.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Levin PS, Newman SA, Quigley HA, Miller NR. A clinicopathologic study of optic neuropathies associated with intracranial mass lesions with quantification of remaining axons. Am J Ophthalmol. 1983;95:295–306.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Quigley HA, Sommer A. How to use nerve fiber layer examination in the management of glaucoma. Trans Am Ophthalmol Soc. 1987;85:254–72.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Hoyt WF, Schlicke B, Eckelhoff RJ. Fundoscopic appearance of a nerve fiber bundle defect. Br J Ophthalmol. 1972;56:577–83.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Frisen L, Claesson M. Narrowing of the retinal arterioles in descending optic atrophy. A quantitative clinical study. J Ophthalmology. 1984;91:1342–6.CrossRefGoogle Scholar
  55. 55.
    Duke-Elder S. System of ophthalmology. In: Diseases of the retina, vol. X. London: Kimpton; 1967. p. 577–622.Google Scholar
  56. 56.
    Frisen L, Hoyt WF, Tengroth BM. Optociliary veins, disc pallor and visual loss. A triad of signs indicating spheno-orbital meningioma. Acta Ophthalmol. 1973;51:241–9.CrossRefGoogle Scholar
  57. 57.
    Smith JL. Pseudohemangioma of the optic disc following ischemic optic neuropathy. J Clin Neuro-ophthalmol. 1985;5:81–9.Google Scholar
  58. 58.
    Friedland S, Winterkorn JMS, Burde RM. Luxury perfusion following anterior ischemic optic neuropathy. J Neuro-ophthalmol. 1996;16:163–71.CrossRefGoogle Scholar
  59. 59.
    Burde RM. Optic disc risk factors for non-arteritic ischemic optic neuropathy. Am J Ophthalmol. 1993;116:759–64.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Kennedy F. Retrobulbar neuritis as an exact diagnostic sign of certain tumors and abscesses in the frontal lobe. Am J Med Sci. 1911;142:355–68.CrossRefGoogle Scholar
  61. 61.
    Miller NR. Optic gliomas: past, present, and future. J Neuro-ophthalmol. 2016;36:460–73.CrossRefGoogle Scholar
  62. 62.
    Moura FC, Medeiros FA, Monteiro MLR. Evaluation of macular thickness measurements for detection of band atrophy of the optic nerve using optical coherence tomography. Ophthalmology. 2007;114:175–81.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Chen JJ, Kardon RH. Avoiding clinical misinterpretation and artifacts of the optical coherence tomography analysis of the optic nerve, retinal nerve fiber layer, and ganglion cell layer. J Neuro-ophthalmol. 2016;36:417–38.CrossRefGoogle Scholar
  64. 64.
    Monteiro MLR, Moura FC, Medeiros FA. Diagnostic ability of optical coherence tomography with a normative database to detect band atrophy of the optic nerve. Am J Ophthalmol. 2007;143:896–9.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Costello F, Coupland S, Hodge W, et al. Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol. 2006;59:963–9.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Contreras I, Noval S, Rebolleda G, Munoz-Negrete FJ. Follow-up of nonarteritic ischemic optic neuropathy with optical coherence tomography. Ophthalmology. 2007;114:2338–44.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Kim TW, Hwang JM. Stratus OCT in dominant optic atrophy; features differentiating it from glaucoma. J Glauocoma. 2007;16:655–8.CrossRefGoogle Scholar
  68. 68.
    Gupta PK, Asrani S, Freedman SF, et al. Differentiating glaucomatous from non-glaucomatous optic nerve cupping by optical coherence tomography. Open Neurol J. 2011;5:1–7.PubMedPubMedCentralGoogle Scholar
  69. 69.
    Gass A, Moseley IF. The contribution of magnetic resonance imaging in the differential diagnosis of optic nerve damage. J Neurol Sci. 2000;172:S17–22.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69:292–302.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364:2106–12.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Waters PJ, McKeon A, Leite MI, et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology. 2012;78:665–71.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Wingerchuk DM, Lennon VA, Pittock SJ, et al. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006;66:1485–9.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Ramanathan S, Dale RC, Brilot F. Anti-MOG antibody: the history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination. Autoimmun Rev. 2016;15:307–24.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Akaishi T, Sato DK, Nakashima I, et al. MRI and retinal abnormalities in isolated optic neuritis with myelin oligodendrocyte glycoprotein and aquaporin-4 antibodies: a comparative study. J Neurol Neurosurg Psychiatry. 2016;87(4):446–8.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Libois A, DeWit S, Poll B, et al. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis. 2007;34:141–4.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoantibody. Ann Neurol. 2001;49:146–54.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Stangel M, Fredrikson S, Meinl E, et al. The utility of cerebrospinal fluid analysis in patients with multiple sclerosis. Nat Rev Neurol. 2013;9:267–76.PubMedCrossRefGoogle Scholar
  79. 79.
    Gaier ED, Boudreault K, Nakata I, et al. Diagnostic genetic testing for patients with bilateral optic neuropathy and comparison of clinical features according to OPA1 mutation status. Mol Vis. 2017;23:548–60.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Lenaers G, Hamel C, Delettre C, et al. Dominant optic atrophy. Orphanet J Rare Dis. 2012;7:46.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Delettre-Cribaillet C, Hamel CP, Lenaers G. Optic atrophy type 1. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, LJH B, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle: University of Washington, Seattle; 1993-2018.2007 Jul 13 [updated 2015 Nov 12].Google Scholar
  82. 82.
    Allen KF, Gaier ED, Wiggs JL. Genetics of primary inherited disorders of the optic nerve: clinical applications. Cold Spring Harb Perspect Med. 2015;5:a017277.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bart Chwalisz
    • 1
  • Dean M. Cestari
    • 1
    • 2
    Email author
  • François-Xavier Borruat
    • 3
  1. 1.Department of OphthalmologyMassachusetts Eye and EarBostonUSA
  2. 2.Center for Thyroid Eye Disease and Orbital SurgeryMassachusetts Eye and EarBostonUSA
  3. 3.Unité de Neuro-ophtalmologieHôpital Ophtalmique Jules-Gonin, Université de LausanneLausanneSwitzerland

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