Nutritional and Toxic Optic Neuropathies

  • Jane W. Chan


The symptoms and signs of nutritional and toxic optic neuropathies are similar in that they usually present simultaneously and bilaterally. Symptoms are progressive with bilateral symmetric visual loss without pain. Some patients may initially only observe dyschromatopsia, such that certain colors, such as red, are not as bright. Usually only one eye may be involved in the early stages before the other becomes symptomatic. If one eye is severely affected while the other eye has completely normal findings, however, then the diagnosis of nutritional or toxic optic neuropathy is questionable. A gradual progressive blurriness, then cloudiness, often forms at the point of fixation.1


Optic Nerve Visual Loss Optic Neuritis Optic Neuropathy Optic Disc Edema 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Miller NR, Newman NJ, editors. Walsh and Hoyt’s clinical neuro-ophthalmology, 5th ed., vol. l. Baltimore: Williams & Wilkins; 1998.Google Scholar
  2. 2.
    Knox DL, Chen MF, Guilarte TR, Dang CV, Burnette J. Nutritional amblyopia. Folic acid, vitamin B-12, and other vitamins. Retina 1982; 2(4):288–293.PubMedGoogle Scholar
  3. 3.
    Biousse V, Newman NJ. Neuro-ophthalmology of mitochondrial diseases. Curr Opin Neurol 2003;16(1):35–43.PubMedGoogle Scholar
  4. 4.
    Johnson RT, Griffin JW, McArthur JC, editors. Current therapy in neurologic disease, 6th ed. St. Louis: Mosby; 2002, p. 363–365.Google Scholar
  5. 5.
    Miller NR, Newman NJ, editors. Walsh and Hoyt’s clinical neuro-ophthalmology: the essentials, 5th ed. Baltimore: Williams & Wilkins; 1998.Google Scholar
  6. 6.
    Carelli V, Ross-Cisneros FN, Sadun AA. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int 2002;40(6):573–584.PubMedGoogle Scholar
  7. 7.
    Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltim) 1991;70(4): 229–245.Google Scholar
  8. 8.
    Agamanolis DP, Chester EM, Victor M, Kark JA, Hines JD, Harris JW. Neuropathology of experimental vitamin B12 deficiency in monkeys. Neurology 1976;26(10):905–914.PubMedGoogle Scholar
  9. 9.
    Dang CV. Tobacco-alcohol amblyopia: a proposed biochemical basis for pathogenesis. Med Hypotheses 1981;7(11):1317–1328.PubMedGoogle Scholar
  10. 10.
    Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988; 1(8):623–634.PubMedGoogle Scholar
  11. 11.
    Hampton CK, Garcia C, Redburn DA. Localization of kainic acid-sensitive cells in mammalian retina. J Neurosci Res 1981;6(1):99–111.PubMedGoogle Scholar
  12. 12.
    Ingvar M. Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage. Ann NY Acad Sci 1986;462: 194–206.PubMedGoogle Scholar
  13. 13.
    Raley-Susman KM, Miller KR, Owicki JC, Sapolsky RM. Effects of excitotoxin exposure on metabolic rate of primary hippocampal cultures: application of silicon microphysiometry to neurobiology. J Neurosci 1992;12(3):773–780.PubMedGoogle Scholar
  14. 14.
    Schiller PH, Logothetis NK, Charles ER. Functions of the colour-opponent and broad-band channels of the visual system. Nature (Lond) 1990;343(6253):68–70.Google Scholar
  15. 15.
    Cleland BG, Levick WR, Sanderson KJ. Properties of sustained and transient ganglion cells in the cat retina. J Physiol 1973;228(3):649–680.PubMedGoogle Scholar
  16. 16.
    Sadun AA, Martone JF, Muci-Mendoza R, et al. Epidemic optic neuropathy in Cuba. Eye findings. Arch Ophthalmol 1994;112(5):691–699.PubMedGoogle Scholar
  17. 17.
    Roman GC. An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy. J Neurol Sci 1994;127(1):11–28.PubMedGoogle Scholar
  18. 18.
    Macias-Matos C, Rodriguez-Ojea A, Chi N, Jimenez S, Zulueta D, Bates CJ. Biochemical evidence of thiamine depletion during the Cuban neuropathy epidemic, 1992–1993. Am J Clin Nutr 1996;64(3):347–353.PubMedGoogle Scholar
  19. 19.
    Thomas PK, Plant GT, Baxter P, Bates C, Santiago Luis R. An epidemic of optic neuropathy and painful sensory neuropathy in Cuba: clinical aspects. J Neurol 1995;242(10):629–638.PubMedGoogle Scholar
  20. 20.
    Gay J, Porrata C, Hernandez M, et al. Dietary factors in epidemic neuropathy on the Isle of Youth, Cuba. Bull Pan Am Health Org 1995; 29(1):25–36.Google Scholar
  21. 21.
    Johns DR, Neufeld MJ, Hedges TR III. Mitochondrial DNA mutations in Cuban optic and peripheral neuropathy. J Neuro-Ophthalmol 1994;14(3):135–140.Google Scholar
  22. 22.
    Mojon DS, Kaufmann P, Odel JG, et al. Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy. Neurology 1997; 48(1):19–22.PubMedGoogle Scholar
  23. 23.
    Lincoff NS, Odel JG, Hirano M. “Outbreak” of optic and peripheral neuropathy in Cuba? JAMA 1993;270(4):511–518.PubMedGoogle Scholar
  24. 24.
    Tucker K, Hedges TR. Food shortages and an epidemic of optic and peripheral neuropathy in Cuba. Nutr Rev 1993;51(12):349–357.PubMedGoogle Scholar
  25. 25.
    Solberg Y, Rosner M, Belkin M. The association between cigarette smoking and ocular diseases. Surv Ophthalmol 1998;42(6):535–547.PubMedGoogle Scholar
  26. 26.
    Dunphy EB. Alcohol and tobacco amblyopia: a historical survey. XXXI DeSchweinitz lecture. Am J Ophthalmol 1969;68(4):569–578.PubMedGoogle Scholar
  27. 27.
    Pearce JM. Neurological aspects of alcoholism. Br J Hosp Med 1977;18(2):132, 134, 136-7.PubMedGoogle Scholar
  28. 28.
    Samples JR, Younge BR. Tobacco-alcohol amblyopia. J Clin Neuro-Ophthalmol 1981;1: 213–218.Google Scholar
  29. 29.
    Smiddy WE, Green WR. Nutritional amblyopia. A histopathologic study with retrospective clinical correlation. Graefes Arch Clin Exp Ophthalmol 1987;225(5):321–324.PubMedGoogle Scholar
  30. 30.
    Rizzo JF III, Lessell S. Tobacco amblyopia. Am J Ophthalmol 1993;116(1):84–87.PubMedGoogle Scholar
  31. 31.
    Pryor WA. Biological effects of cigarette smoke, wood smoke, and the smoke from plastics: the use of electron spin resonance. Free Radic Biol Med 1992;13(6):659–676.PubMedGoogle Scholar
  32. 32.
    Ballinger SW, Bouder TG, Davis GS, Judice SA, Nicklas JA, Albertini RJ. Mitochondrial genome damage associated with cigarette smoking. Cancer Res 1996;56(24):5692–5697.PubMedGoogle Scholar
  33. 33.
    Kennedy JR, Elliot AM. Cigarette smoke: the effect of residue on mitochondrial structure. Science 1970;168:1097–1098.PubMedGoogle Scholar
  34. 34.
    Newman NJ, Torroni A, Brown MD, Lott MT, Fernandez MM, Wallace DC. Epidemic neuropathy in Cuba not associated with mitochondrial DNA mutations found in Leber’s hereditary optic neuropathy patients. Cuba Neuropathy Field Investigation Team. Am J Ophthalmol 1994;118(2):158–168.PubMedGoogle Scholar
  35. 35.
    Gill GV, Bell DR. Persisting nutritional neuropathy amongst former war prisoners. J Neurol Neurosurg Psychiatry 1982;45(10):861–865.PubMedGoogle Scholar
  36. 36.
    Carroll FD. Nutritional amblyopia. Arch Ophthalmol 1966;76(3):406–411.PubMedGoogle Scholar
  37. 37.
    King JH Jr, Passmore JW. Nutritional amblyopia: a study of American prisoners of war in Korea. Am J Ophthalmol 1955;39(4 pt 2): 173–186.PubMedGoogle Scholar
  38. 38.
    Montgomery RD, Cruickshank EK, Robertson WB, McNemeney WH. Clinical and pathological observations on Jamaican neuropathy: a report on 206 cases. Brain 1964;87:425–462.PubMedGoogle Scholar
  39. 39.
    Osuntokun BO, Osuntokun O. Tropical amblyopia in Nigerians. Am J Ophthalmol 1971;72(4): 708–716.PubMedGoogle Scholar
  40. 40.
    McMartin KE, Ambre JJ, Tephly TR. Methanol poisoning in human subjects. Role for formic acid accumulation in the metabolic acidosis. Am J Med 1980;68(3):414–418.PubMedGoogle Scholar
  41. 41.
    Golnik KC, Schaible ER. Folate-responsive optic neuropathy. J Neuro-Ophthalmol 1994; 14(3):163–169.Google Scholar
  42. 42.
    Hsu CT, Miller NR, Wray ML. Optic neuropathy from folic acid deficiency without alcohol abuse. Ophthalmologica 2002;216(1):65–67.PubMedGoogle Scholar
  43. 43.
    Lessell S. Nutritional disorders: ophthalmological aspects. Bull Soc Belge Ophtalmol 1983;208(pt 1):469–472.PubMedGoogle Scholar
  44. 44.
    van Noort BA, Bos PJ, Klopping C, Wilmink JM. Optic neuropathy from thiamine deficiency in a patient with ulcerative colitis. Doc Ophthalmol 1987;67(1–2):45–51.PubMedGoogle Scholar
  45. 45.
    Larsen PD, Mock DM, O’Connor PS. Vitamin E deficiency associated with vision loss and bulbar weakness. Ann Neurol 1985;18(6): 725–727.PubMedGoogle Scholar
  46. 46.
    Solomons NW, Russell RM. The interaction of vitamin A and zinc: implications for human nutrition. Am J Clin Nutr 1980;33(9):2031–2040.PubMedGoogle Scholar
  47. 47.
    Russell RM, Cox ME, Solomons N. Zinc and the special senses. Ann Intern Med 1983;99(2): 227–239.PubMedGoogle Scholar
  48. 48.
    Karcioglu ZA. Zinc in the eye. Surv Ophthalmol 1982;27(2):114–122.PubMedGoogle Scholar
  49. 49.
    De Palma P, Franco F, Bragliani G, et al. The incidence of optic neuropathy in 84 patients treated with ethambutol. Metab Pediatr Syst Ophthalmol 1989;12(1–3):80–82.PubMedGoogle Scholar
  50. 50.
    Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Two years of clinical experience with biliopancreatic bypass for obesity. Am J Clin Nutr 1980;33(2 suppl):506–514.PubMedGoogle Scholar
  51. 51.
    Eells JT, Henry MM, Lewandowski MF, Seme MT, Murray TG. Development and characterization of a rodent model of methanol-induced retinal and optic nerve toxicity. Neurotoxicology 2000;21(3):321–330.PubMedGoogle Scholar
  52. 52.
    Hsu HH, Chen CY, Chen FH, Lee CC, Chou TY, Zimmerman RA. Optic atrophy and cerebral infarcts caused by methanol intoxication: MRI. Neuroradiology 1997;39(3): 192–194.PubMedGoogle Scholar
  53. 53.
    Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol 1986;1(5):309–334.PubMedGoogle Scholar
  54. 54.
    Tephly TR, Makar AB, McMartin KE. Methanol: its metabolism and toxicity. In: Majchrowicz E, Noble EP, editors. Biochemistry and pharmacology of ethanol, vol. 1. New York: Plenum; 1979. p. 145–162.Google Scholar
  55. 55.
    Nicholls P. Formate as an inhibitor of cytochrome c oxidase. Biochem Biophys Res Commun 1975;67(2):610–616.PubMedGoogle Scholar
  56. 56.
    Guyton AC. Textbook of medical physiology. Philadelphia: Saunders; 1981.Google Scholar
  57. 57.
    Sharpe JA, Hostovsky M, Bilbao JM, Rewcastle NB. Methanol optic neuropathy: a histopathological study. Neurology 1982;32(10): 1093–1100.PubMedGoogle Scholar
  58. 58.
    Wyndham RA. Experimental demyelination of the central nervous system. II: Respiratory enzyme systems of the brain in poisoning with cyanide and with azide. Aust J Exp Biol Med Sci 1941;19:243–248.Google Scholar
  59. 59.
    Kiyokawa M, Mizota A, Takasoh M, AdachiUsami E. Pattern visual evoked cortical potentials in patients with toxic optic neuropathy caused by toluene abuse. Jpn J Ophthalmol 1999;43(5):438–442.PubMedGoogle Scholar
  60. 60.
    Hormes JT, Filley CM, Rosenberg NL. Neurologic sequelae of chronic solvent vapor abuse. Neurology 1986;36(5):698–702.PubMedGoogle Scholar
  61. 61.
    Verslegers W, De Deyn PP. Visual impairment due to optic neuropathy in 2 patients on amiodarone, and ethambutol and isoniazide therapy, respectively. Ned Tijdschr Geneeskd 2001; 145(38):1872.PubMedGoogle Scholar
  62. 62.
    Feiner LA, Younge BR, Kazmier FJ, Stricker BH, Fraunfelder FT. Optic neuropathy and amiodarone therapy. Mayo Clin Proc 1987;62(8): 702–717.PubMedGoogle Scholar
  63. 63.
    Gittinger JW Jr, Asdourian GK. Papillopathy caused by amiodarone. Arch Ophthalmol 1987; 105(3):349–351.PubMedGoogle Scholar
  64. 64.
    Mindel JS. Amiodarone toxic optic neuropathy: reasons for doubting its existence [lecture]. North AmericanNeuro-Ophthalmology Society Annual Meeting, Feb 25-Mar 2, 2006, Tucson, AZ.Google Scholar
  65. 65.
    Savino PJ. Amiodarone Associated Optic Neuropathy. Paper presented at: North American Neuro-ophthalmological Society Annual Meeting; February 25-March 2, 2006; Tucson, AZ.Google Scholar
  66. 66.
    Chen D, Hedges TR. Amiodarone optic neuropathy: review. Semin Ophthalmol 2003;18(4): 169–173.PubMedGoogle Scholar
  67. 67.
    Johnson LN, Krohel GB, Thomas ER. The clinical spectrum of amiodarone-associated optic neuropathy. J Natl Med Assoc 2004;96(11): 1477–1491.PubMedGoogle Scholar
  68. 68.
    Pollak PT, Bouillon T, Shafer SL. Population pharmacokinetics of long-term oral amiodarone therapy. Clin Pharmacol Ther 2000;67(6):642–652.PubMedGoogle Scholar
  69. 69.
    Singh BN. Amiodarone: the expanding antiarrhythmic role and how to follow a patient on chronic therapy. Clin Cardiol 1997;20(7):608–618.PubMedGoogle Scholar
  70. 70.
    Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the Ischemic Optic Neuropathy Decompression Trial. Arch Ophthalmol 1996;114(11): 1366–1374.Google Scholar
  71. 71.
    Somani P. Basic and clinical pharmacology of amiodarone: relationship of antiarrhythmic effects, dose and drug concentrations to intracellular inclusion bodies. J Clin Pharmacol. 1989;29(5):405–412.PubMedGoogle Scholar
  72. 72.
    Garrett SN, Kearney JJ, Schiffman JS. Amiodarone optic neuropathy. J Clin NeuroOphthalmol 1988;8:105–111.Google Scholar
  73. 73.
    Mansour AM, Puklin JE, O’Grady R. Optic nerve ultrastructure following amiodarone therapy. Clin Neuro-Ophthalmol 1988;8(4): 231–237.Google Scholar
  74. 74.
    Yoon YH, Jung KH, Sadun AA, Shin HC, Koh JY. Ethambutol-induced vacuolar changes and neuronal loss in rat retinal cell culture: mediation by endogenous zinc. Toxicol Appl Pharmacol 2000;162(2):107–114.PubMedGoogle Scholar
  75. 75.
    Shiraki H. Neuropathy due to intoxication with anti-tuberculous drugs from neuropathological viewpoint. Adv Neurol Sci 1973;17:120.Google Scholar
  76. 76.
    Melamud A, Kosmorsky GS, Lee MS. Ocular ethambutol toxicity. Mayo Clin Proc 2003;78(11): 1409–1411.PubMedGoogle Scholar
  77. 77.
    Fang JT, Chen YC, Chang MY. Ethambutolinduced optic neuritis in patients with end stage renal disease on hemodialysis: two case reports and literature review. Renal Fail 2004;26(2): 189–193.Google Scholar
  78. 78.
    Harley RD, Huang NN, Macri CH, Green WR. Optic neuritis and optic atrophy following chloramphenicol in cystic fibrosis patients. Trans Am Acad Ophthalmol Otolaryngol 1970;74(5): 1011–1031.PubMedGoogle Scholar
  79. 79.
    Linezolid. In: Physicians’ desk reference, 61st ed. Montvale: Thomson PDR; 2007. p. 2652.Google Scholar
  80. 80.
    Lee E, Burger S, Shah J, et al. Linezolid-associated toxic optic neuropathy: a report of 2 cases. Clin Infect Dis 2003;37(10):1389–1391.PubMedGoogle Scholar
  81. 81.
    Corallo CE, Paull AE. Linezolid-induced neuropathy. Med J Aust 2002;177(6):332.PubMedGoogle Scholar
  82. 82.
    Rho JP, Sia IG, Crum BA, Dekutoski MB, Trousdale RT. Linezolid-associated peripheral neuropathy. Mayo Clin Proc 2004;79(7): 927–930.PubMedGoogle Scholar
  83. 83.
    Spellberg B, Yoo T, Bayer AS. Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6. J Antimicrob Chemother 2004;54(4): 832–835.PubMedGoogle Scholar
  84. 84.
    Frippiat F, Bergiers C, Michel C, Dujardin JP, Derue G. Severe bilateral optic neuritis associated with prolonged linezolid therapy. J Antimicrob Chemother 2004;53(6):1114–1115.PubMedGoogle Scholar
  85. 85.
    Zyrox (linezolid) [package insert]. Rydaimere, New South Wales: Pharmacia Australia; 2002.Google Scholar
  86. 86.
    McKinley SH, Foroozan R. Optic neuropathy associated with linezolid treatment. J NeuroOphthalmol 2005;25(1):18–21.PubMedGoogle Scholar
  87. 87.
    Baron S, Tyring SK, Fleischmann WR Jr, et al. The interferons. Mechanisms of action and clinical applications. JAMA 1991;266(10): 1375–1383.PubMedGoogle Scholar
  88. 88.
    Lohmann CP, Kroher G, Bogenrieder T, Spiegel D, Preuner J. Severe loss of vision during adjuvant interferon alfa-2b treatment for malignant melanoma. Lancet 1999;353(9161):1326.PubMedGoogle Scholar
  89. 89.
    Purvin VA. Anterior ischemic optic neuropathy secondary to interferon alfa. Arch Ophthalmol 1995;113(8):1041–1044.PubMedGoogle Scholar
  90. 90.
    Taylor JL, Grossberg SE. The effects of interferon-alpha on the production and action of other cytokines. Semin Oncol 1998;25(1 suppl 1):23–29.PubMedGoogle Scholar
  91. 91.
    Foroozan R. Unilateral pallid optic disc swelling and anemia associated with interferon alpha treatment. J Neuro-Ophthalmol 2004;24(1): 98–99.Google Scholar
  92. 92.
    Gabler B, Kroher G, Bogenrieder T, Spiegel D, Preuner J, Lohmann CP. Severe, bilateral vision loss in malignant melanoma of the skin. Anterior ischemic optic neuropathy with irreversible vision and visual field loss in adjuvant interferon alfa-2b therapy. Ophthalmologe 2001; 98(7):672–673.PubMedGoogle Scholar
  93. 93.
    Vardizer Y, Linhart Y, Loewenstein A, Garzozi H, Mazawi N, Kesler A. Interferon-alphaassociated bilateral simultaneous ischemic optic neuropathy. J Neuro-Ophthalmol 2003;23(4): 256–259.Google Scholar
  94. 94.
    Gupta R, Singh S, Tang R, Blackwell TA, Schiffman JS. Anterior ischemic optic neuropathy caused by interferon alpha therapy. Am J Med 2002;112(8):683–684.PubMedGoogle Scholar
  95. 95.
    Norcia F, Di Maria A, Prandini F, Redaelli C. Natural interferon therapy: optic nerve ischemic damage? Ophthalmologica 1999;213(5): 339–340.PubMedGoogle Scholar
  96. Infliximab. In: Physician’s desk reference, 61st ed. Montvale: Thomson PDR; 2007. p. 971.Google Scholar
  97. 97.
    Foroozan R, Buono LM, Sergott RC, Savino PJ. Retrobulbar optic neuritis associated with infliximab. Arch Ophthalmol 2002;120(7):985–987.PubMedGoogle Scholar
  98. 98.
    Mejico LJ. Infliximab-associated retrobulbar optic neuritis. Arch Ophthalmol 2004;122(5): 793–794.PubMedGoogle Scholar
  99. 99.
    ten Tusscher MP, Jacobs PJ, Busch MJ, de Graaf L, Diemont WL. Bilateral anterior toxic optic neuropathy and the use of infliximab. BMJ 2003;326(7389):579.PubMedGoogle Scholar
  100. 100.
    Roch LM II, Gordon DL, Barr AB, Paulsen CA. Visual changes associated with clomiphene citrate therapy. Arch Ophthalmol 1967;77(1): 14–17.PubMedGoogle Scholar
  101. 101.
    Padron Rivas VF, Sanchez Sanchez A, Lerida Arias MT, Carvajal Garcia-Pardo A. Optic neuritis appearing during treatment with clomiphene. Aten Primaria 1994;14(7):912–913.PubMedGoogle Scholar
  102. 102.
    Lawton AW. Optic neuropathy associated with clomiphene citrate therapy. Fertil Steril 1994;61(2):390–391.PubMedGoogle Scholar
  103. 103.
    Noureddin BN, Seoud M, Bashshur Z, Salem Z, Shamseddin A, Khalil A. Ocular toxicity in lowdose tamoxifen: aprospective study. Eye 1999;13(pt 6):729–733.PubMedGoogle Scholar
  104. 104.
    Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med 1998;338(20):13971404. Erratum in N Engl J Med 1998;339(1):59.Google Scholar
  105. 105.
    Pomeranz HD, Smith KH, Hart WM Jr, Egan RA. Sildenafil-associated nonarteritic anterior ischemic optic neuropathy. Ophthalmology 2002;109(3):584–587.PubMedGoogle Scholar
  106. 106.
    Pomeranz HD, Bhavsar AR. Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases. J Neuro-Ophthalmol 2005;25(1):9–13.Google Scholar
  107. 107.
    Akash R, Hrishikesh D, Amith P, Sabah S. Case report: association of combined nonarteritic anterior ischemic optic neuropathy (NAION) and obstruction of cilioretinal artery with overdose of Viagra. J Ocul Pharmacol Ther 2005; 21(4):315–317.PubMedGoogle Scholar
  108. 108.
    Beck RW, Servais GE, Hayreh SS. Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology 1987;94(11):1503–1508.PubMedGoogle Scholar
  109. 109.
    Burde RM. Optic disk risk factors for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 1993;116(6):759–764.PubMedGoogle Scholar
  110. 110.
    Doro S, Lessell S. Cup-disc ratio and ischemic opticneuropathy. ArchOphthalmo1985;103(8): 1143–114.Google Scholar
  111. 111.
    Boshier A, Pambakian N, Shakir SA. A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil. Int J Clin Pharmacol Ther 2002;40(9):422–423.PubMedGoogle Scholar
  112. 112.
    Cunningham AV, Smith KH. Anterior ischemic optic neuropathy associated with viagra. J Neuro-Ophthalmol 2001;21(1):22–25.Google Scholar
  113. 113.
    Dheer S, Rekhi GS, Merlyn S. Sildenafil associated anterior ischaemic optic neuropathy. J Assoc Physicians India 2002;50:265.PubMedGoogle Scholar
  114. 114.
    Egan R, Pomeranz H. Sildenafil (Viagra) associated anterior ischemic optic neuropathy. Arch Ophthalmol 2000;118(2):291–292.PubMedGoogle Scholar
  115. 115.
    Neufeld AH, Sawada A, Becker B. Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc Natl Acad Sci U S A 1999;96(17):9944–9948.PubMedGoogle Scholar
  116. 116.
    Sponsel WE, Paris G, Sandoval SS, et al. Sildenafil and ocular perfusion. N Engl J Med 2000;342(22):1680.PubMedGoogle Scholar
  117. 117.
    Grunwald JE, Siu KK, Jacob SS, Dupont J. Effect of sildenafil citrate (Viagra) on the ocular circulation. Am J Ophthalmol 2001;131(6):751–755.PubMedGoogle Scholar
  118. 118.
    Bollinger K, Lee MS. Recurrent visual field defect and ischemic optic neuropathy associated with tadalafil rechallenge. Arch Ophthalmol 2005;123(3):4001.Google Scholar
  119. 119.
    Escaravage GK Jr, Wright JD Jr, Givre SJ. Tadalafil associated with anterior ischemic optic neuropathy. Arch Ophthalmol 2005;123(3): 399–400.PubMedGoogle Scholar
  120. 120.
    Peter NM, Singh MV, Fox PD. Tadalafil-associated anterior ischaemic optic neuropathy. Eye 2005; 19(6):715–717.PubMedGoogle Scholar
  121. 121.
    Jiang GL, Tucker SL, Guttenberger R, et al. Radiation-induced injury to the visual pathway. Radiother Oncol 1994;30(1):17–25.PubMedGoogle Scholar
  122. 122.
    Kline LB, Kim JY, Ceballos R. Radiation optic neuropathy. Ophthalmology 1985;92(8): 1118–1126.PubMedGoogle Scholar
  123. 123.
    Millar JL, Spry NA, Lamb DS, Delahunt J. Blindness in patients after external beam irradiation for pituitary adenomas: two cases occurring after small daily fractional doses. Clin Oncol (R Coll Radiol) 1991;3(5):291–294.Google Scholar
  124. 124.
    Regine WF, Kramer S. Pediatric craniopharyngiomas: long term results of combined treatment with surgery and radiation. Int J Radiat Oncol Biol Phys 1992;24(4):611–617.PubMedGoogle Scholar
  125. 125.
    Roden D, Bosley TM, Fowble B, et al. Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids. Ophthalmology 1990;97(3):346–351.PubMedGoogle Scholar
  126. 126.
    Schoenthaler R, Albright NW, Wara WM, Phillips TL, Wilson CB, Larson DA. Reirradiation of pituitary adenoma. Int J Radiat Oncol Biol Phys 1992;24(2):307–314.PubMedGoogle Scholar
  127. 127.
    Geyer JR, Taylor EM, Milstein JM, et al. Radiation, methotrexate, and white matter necrosis: laboratory evidence for neural radioprotection with preirradiation methotrexate. Int J Radiat Oncol Biol Phys 1988;15(2):373–375.PubMedGoogle Scholar
  128. 128.
    Balsom WR, Bleyer WA, Robison LL, et al. Intellectual function in long-term survivors of childhood acute lymphoblastic leukemia: protective effect of pre-irradiation methotrexate? A Childrens Cancer Study Group study. Med Pediatr Oncol 1991;19(6):486–492.PubMedGoogle Scholar
  129. 129.
    Fishman ML, Bean SC, Cogan DG. Optic atrophy following prophylactic chemotherapy and cranial radiation for acute lymphocytic leukemia. Am J Ophthalmol 1976;82(4):571–576.PubMedGoogle Scholar
  130. 130.
    Marks LB, Spencer DP. The influence of volume on the tolerance of the brain to radiosurgery. J Neurosurg 1991;75(2):177–180.PubMedGoogle Scholar
  131. 131.
    Marks JE, Wong J. The risk of cerebral radionecrosis in relation to dose, time and fractionation. A follow-up study. Prog Exp Tumor Res 1985;29:210–218.PubMedGoogle Scholar
  132. 132.
    Safdari H, Fuentes JM, Dubois JB, Alirezai M, Castan P, Vlahovitch B. Radiation necrosis of the brain: time of onset and incidence related to total dose and fractionation of radiation. Neuroradiology 1985;27(1):44–47.PubMedGoogle Scholar
  133. 133.
    Schultheiss TE, Higgins EM, El-Mahdi AM. The latent period in clinical radiation myelopathy. Int J Radiat Oncol Biol Phys 1984; 10(7):1109–1115.PubMedGoogle Scholar
  134. 134.
    Lampert PW, Davis RL. Delayed effects of radiation on the human central nervous system: “early” and “late” delayed reactions. Neurology 1964;14:912–917.PubMedGoogle Scholar
  135. 135.
    Hopewell JW, van der Kogel AJ. Pathophysiological mechanisms leading to the development of late radiation-induced damage to the central nervous system. Front Radiat Ther Oncol 1999;33:265–275.PubMedGoogle Scholar
  136. 136.
    Myers R, Rogers MA, Hornsey S. A reappraisal of the roles of glial and vascular elements in the development of white matter necrosis in irradiated rat spinal cord. Br J Cancer Suppl 1986; 7:221–223.PubMedGoogle Scholar
  137. 137.
    van der Kogel AJ. Radiation-induced damage in the central nervous system: an interpretation of target cell responses. Br J Cancer Suppl 1986;7:207–217.PubMedGoogle Scholar
  138. 138.
    Omary RA, Berr SS, Kamiryo T, et al. 1995 AUR Memorial Award. Gamma knife irradiation-induced changes in the normal rat brain studied with 1H magnetic resonance spectroscopy and imaging. Acad Radiol 1995;2(12): 1043–1051.PubMedGoogle Scholar
  139. 139.
    Levin LA, Gragoudas ES, Lessell S. Endothelial cell loss in irradiated optic nerves. Ophthalmology 2000;107(2):370–374.PubMedGoogle Scholar
  140. 140.
    Chan YL, Yeung DK, Leung SF, Cao G. Proton magnetic resonance spectroscopy of late delayed radiation-induced injury of the brain. J Magn Reson Imaging 1999;10(2):130–137.PubMedGoogle Scholar
  141. 141.
    Crompton MR, Layton DD. Delayed radionecrosis of the brain following therapeutic xradiation of the pituitary. Brain 1961;84:85–101.PubMedGoogle Scholar
  142. 142.
    Ross HS, Rosenberg S, Friedman AH. Delayed radiation necrosis of the optic nerve. Am J Ophthalmol 1973;76(5):683–686.PubMedGoogle Scholar
  143. 143.
    Lessell S. Friendly fire: neurogenic visual loss from radiation therapy. J Neuro-Ophthalmol 2004;24(3):243–250.Google Scholar
  144. 144.
    Borruat FX, Schatz NJ, Glaser JS. Post-actinic retrobulbar optic neuropathy. Klin Monatsbl Augenheilkd 1996;208(5):381–384.PubMedGoogle Scholar
  145. 145.
    Guy J, Schatz NJ. Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy. Ophthalmology 1986;93(8):1083–1088.PubMedGoogle Scholar
  146. 146.
    Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation optic neuropathy. Ophthalmology 1982;89(12): 1489–1493.PubMedGoogle Scholar
  147. 147.
    Arnold AC. Radiation optic neuropathy. Presented at the 21st annual meeting of the North American Neuro-Ophthalmology Society, Tucson, AZ, February 23, 1995.Google Scholar
  148. 148.
    Borruat FX, Schatz NJ, Glaser JS, Feun LG, Matos L. Visual recovery from radiationinduced optic neuropathy. The role of hyperbaric oxygen therapy. J Clin Neuro-Ophthalmol 1993;13(2):98–101.Google Scholar
  149. 149.
    Kaufman M, Swartz BE, Mandelkern M, Ropchan J, Gee M, Blahd WH. Diagnosis of delayed cerebral radiation necrosis following proton beam therapy. Arch Neurol 1990;47(4):474–476.PubMedGoogle Scholar
  150. 150.
    Spaziante R, de Divitiis E, Stella L, Cappabianca P, Genovese L. The empty sella. Surg Neurol 1981;16(6):418–426.PubMedGoogle Scholar
  151. 151.
    Bernstein M, Laperriere N. Radiation-induced tumors of the nervous system. In: Gutin PH, Leibel SA, Sheline GE, editors. Radiation injury to the central nervous system. New York: Raven Press; 1991.Google Scholar
  152. 152.
    Guy J, Mancuso A, Beck R, et al. Radiationinduced optic neuropathy: a magnetic resonance imaging study. J Neurosurg 1991;74(3): 426–432.PubMedGoogle Scholar
  153. 153.
    Hudgins PA, Newman NJ, Dillon WP, Hoffman JC Jr. Radiation-induced optic neuropathy: characteristic appearances on gadoliniumenhanced MR. AJNR Am J Neuroradiol 1992;13(1):235–238.PubMedGoogle Scholar
  154. 154.
    McClellan RL, el Gammal T, Kline LB. Early bilateral radiation-induced optic neuropathy with follow-up MRI. Neuroradiology 1995;37(2): 131–133.PubMedGoogle Scholar
  155. 155.
    Oppenheimer JH, Levy ML, Sinha U, el-Kadi H, Apuzzo ML, Luxton G, et al. Radionecrosis secondary to interstitial brachytherapy: correlation of magnetic resonance imaging and histopathology. Neurosurgery 1992;31(2):336–343.PubMedGoogle Scholar
  156. 156.
    Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold SC Jr. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology 1994;44(11):2020–2027.PubMedGoogle Scholar
  157. 157.
    Barbosa AP, Carvalho D, Marques L, et al. Inefficiency of the anticoagulant therapy in the regression of the radiation-induced optic neuropathy in Cushing’s disease. J Endocrinol Invest 1999;22(4):301–305.PubMedGoogle Scholar
  158. 158.
    Danesh-Meyer HV, Savino PJ, Sergott RC. Visual loss despite anticoagulation in radiationinduced optic neuropathy. Clin Exp Ophthalmol 2004;32(3):333–335.Google Scholar
  159. 159.
    Landau K, Killer HE. Radiation damage. Neurology 1996;46(3):889.PubMedGoogle Scholar
  160. 160.
    Hammerlund C. The physiological effects of hyperbaric oxygen. In: Kindwall EP, editor. Hyperbaric medicine practice. Flagstaff: Best; 1995.Google Scholar
  161. 161.
    Borruat F-X, Schatz NJ, Glaser JS, et al. Radiation optic neuropathy: report of cases, role of hyperbaric oxygen therapy, and literature review. Neuro-Ophthalmology 1996;16: 255–256.Google Scholar
  162. 162.
    Kellner U, Bornfeld N, Foerster MH. Radiationinduced optic neuropathy following brachytherapy of uveal melanomas. Graefes Arch Clin Exp Ophthalmol 1993;231(5):267–270.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Jane W. Chan
    • 1
  1. 1.Ophthalmology and NeurologyUniversity of Kentucky College of MedicineLexingtonUSA

Personalised recommendations