Abstract
Hereditary and acquired metabolic optic neuropathies are both characterized by similar clinical manifestations with preferential involvement of the papillomacular bundle (PMB). PMB fibers are most susceptible to injury as they are small, unmyelinated, and have high energy demands. These optic neuropathies share a presumed common pathophysiology of mitochondrial dysfunction.
Acquired mitochondrial optic neuropathies (MONs) can be categorized into four classes based on etiology: (1) nutritional, (2) drug induced, (3) toxic, and (4) combined metabolic optic neuropathies. Nutritional optic neuropathies, rare in the United States, usually occur with general malnutrition, malabsorption, or alcoholism. The most common nutritional optic neuropathies are due to deficiencies in vitamin B12, folic acid, thiamine, vitamin E, and zinc. A variety of medications cause optic neuropathy by interfering with mitochondrial function. Ethambutol, chloramphenicol, linezolid, erythromycin, streptomycin, and antiretroviral drugs can cause a drug-related MOP especially in genetically predisposed individuals. In many cases, drug toxicity is dose and duration dependent and discontinuation of the drug in a timely manner can lead to significant visual recovery. The most common causes of toxic optic neuropathies are methanol, ethylene glycol, and toluene. Combined nutritional and toxic optic neuropathies have been reported in Cuba, known as the Cuban epidemic of optic neuropathy, tobacco–alcohol amblyopia, prisoners of war, and Strachan’s syndrome.
A number of drugs are associated with optic neuropathy without involving mitochondrial mechanisms such as amiodarone, disulfiram, inferferon-α, infliximab, clomiphene, tamoxifen, and sildenafil. Radiation is also known to induce ischemic optic neuropathy, typically about 18 months after treatment.
MONs are increasingly recognized as a spectrum of conditions that reach a similar end point by compromising a common mitochondrial pathway. Clinicians should be aware of nutritional deficiencies, drugs, and toxins that can cause MON. Prompt recognition of this association is critical in preventing irreversible and profound visual loss.
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References
Sadun AA, Win PH, Ross-Cisneros FN, Walker SO, Carelli V. Leber’s hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans Am Ophthalmol Soc. 2000;98:223–35.
Carelli V, Ross-Cisneros F, Sadun AA. Mitochondrial dysfunction as a cause of optic neuropathies. Prog Retin Eye Res. 2004;23:53–89.
Miller NR, Newman NJ. editors. Walsh and Hoyt’s clinical neuro-ophthalmology, 5th edition, vol. l. Baltimore: Williams and Wilkins; 1998.
Biousse V, Newman NJ. Neuro-ophthalmology of mitochondrial diseases. Curr Opin Neurol. 2003;16:35–43.
Johnnson RT, Griffin JW, McArthur JC, editors. Current therapy in neurologic disease. 6th ed. St. Louis, MO: Mosby; 2002. p. 363–5.
Carelli V, Ross-Cisneros FN, Sadun AA. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int. 2002;40:573–84.
Cohen H. Optic atrophy as the presenting sign in pernicious anaemia. Lancet. 1936;2:1202.
Hamilton EA, Ellis PP, Sheets F. Visual impairment due to optic neuropathy in pernicious anemia: report of a case and review of the literature. Blood. 1959;14:378–85.
Foulds SW, Chisholm AI, Stewart BJ, Wilson MT. The optic neuropathy of pernicious anemia. Arch Ophthalmol. 1969;82:427–32.
Chavala SH, Kosmorsky GS, Lee MK, Lee MS. Optic neuropathy in vitamin B12 deficiency. Eur J Intern Med. 2005;16:447–8.
Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore). 1991;70:229–45.
Andrès E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171:251–9.
Chavala SH, Kosmorsky GS, Lee MK, Lee MS. Optic neuropathy in vitamin B12 deficiency. Eur J Intern Med. 2005;16:447–8.
Larner AJ. Visual failure caused by vitamin B12 deficiency optic neuropathy. Int J Clin Pract. 2004;58:977–8.
Stambolian D, Behrens M. Optic neuropathy with vitamin B12 deficiency. Am J Ophthalmol. 1977;83:465–8.
Areekul S, Roongpisuthipong C, Churdchu K, Thanomsak W. Optic neuropathy in a patient with vitamin B12 deficiency: a case report. J Med Assoc Thai. 1992;75:715–8.
Moschos M, Droutsas D. A man who lost weight and his sight. Lancet. 1998;351:1174.
Björkenheim B. Optic neuropathy caused by vitamin-B12 deficiency in carriers of the fish tapeworm, Diphyllobothriumlatum. Lancet. 1966;1:688–90.
Agamanolis DP, Chester EM, Victor M, Kark JA, Hines JD, Harris JW. Neuropathology of experimental vitamin B12 deficiency in monkeys. Neurology. 1976;26:905–14.
Dang CV. Tobacco-alcohol amblyopia: a proposed biochemical basis for pathogenesis. Med Hypotheses. 1981;7:1317–28.
Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988;1:623–34.
Hampton CK, Garcia C, Redburn DA. Localization of kainic acid-sensitive cells in mammalian retina. J Neurosci Res. 1981;6:99–111.
Ingvar M. Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage. Ann N Y Acad Sci. 1986;462:194–206.
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;12:773–80.
Schiller PH, Logothetis NK, Charles ER. Functions of the colour-opponent and broad-band channels of the visual system. Nature. 1990;343:68–70.
Sadun AA, Martone JF, Muci-Mendoza R, Reyes L, DuBois L, Silva JC, Roman G, Caballero B. Epidemic optic neuropathy in Cuba. Eye findings. Arch Ophthalmol. 1994;112:691–9.
Pan BX, Ross-Cisneros FN, Carelli V, Rue KS, Salomao SR, Moraes-Filho MN, et al. Mathematically modeling the involvement of axons in Leber’s hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2012;53:7608–17.
McMartin KE, Ambre JJ, Tephly TR. Methanol poisoning in human subjects. Role for formic acid accumulation in metabolic acidosis. Am J Med. 1980;8:414–8.
Golnik KC, Schaible ER. Folate-responsive optic neuropathy. J Neuroophthalmol. 1994;14:163–9.
Hsu CT, Miller NR, Wray ML. Optic neuropathy from folic acid deficiency without alcohol abuse. Ophthalmologica. 2002;216:65–7.
de Silva P, Jayamanne G, Bolton R. Folic acid deficiency optic neuropathy: a case report. J Med Case Rep. 2008;2:299.
Knox DL, Chen MF, Guilarte TR, Dang CV, Burnette J. Nutritional amblyopia. Folic acid, vitamin B-12, and other vitamins. Retina. 1982;2:288–93.
Tousignant B, Brian G, Venn BJ, Gould C, McKay R, Williams S. Optic neuropathy among a prison population in Papua New Guinea. Ophthalmic Epidemiol. 2013;20:4–12.
Lessell S. Nutritional disorders: ophthalmological aspects. Bull Soc Belge Ophtalmol. 1983;208 Pt 1:469–72.
Carroll FD. The Etiology and Treatment of Tobacco-Alcohol Amblyopia. Trans Am Ophthalmol Soc. 1943;41:385–431.
van Noort BA, Bos PJ, Klopping C, Wilmink JM. Optic neuropathy from thiamine deficiency in a patient with ulcerative colitis. Doc Ophthalmol. 1987;67:45–51.
Yeh WY, Lian LM, Chang A, Cheng CK. Thiamine-deficient optic neuropathy associated with Wernicke's encephalopathy in patients with chronic diarrhea. J Formos Med Assoc. 2013;112:165–70.
Larsen PD, Mock DM, O'Connor PS. Vitamin E deficiency associated with vision loss and bulbar weakness. Ann Neurol. 1985;18:725–7.
Solomons NW, Russell RM. The interaction of vitamin A and zinc: implications for human nutrition. Am J Clin Nutr. 1980;33:2031–40.
Russell RM, Cox ME, Solomons N. Zinc and the special senses. Ann Intern Med. 1983;99:227–39.
Karcioglu ZA. Zinc in the eye. Surv Ophthalmol. 1982;27:114–22.
De Palma P, Franco F, Bragliani G, Michetti L, Marescotti A, Pirazzoli G, et al. The incidence of optic neuropathy in 84 patients treated with Ethambutol. Metab Pediatr Syst Ophthalmol. 1989;2:80–2.
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;33:506–14.
Becker DA, Balcer LJ, Galetta SL. The Neurological Complications of Nutritional Deficiency following Bariatric Surgery. J Obes. 2012;2012:608534.
Juhasz-Pocsine K, Rudnicki SA, Archer RL, Harik SI. Neurologic complications of gastric bypass surgery for morbid obesity. Neurology. 2007;68:1843–50.
Spinazzi M, Angelini C, Patrini C. Subacute sensory ataxia and optic neuropathy with thiamine deficiency. Nat Rev Neurol. 2010;6:288–93.
Ramos-Leví AM, Sánchez-Pernaute A, Rubio Herrera MA. Dermatitis and optic neuropathy due to zinc deficiency after malabsortive bariatric surgery. Nutr Hosp. 2013;28:1345–7.
Mroczkowski MM, Redgrave GW, Miller NR, McCoy AN, Guarda AS. Reversible vision loss secondary to malnutrition in a woman with severe anorexia nervosa, purging type, and alcohol abuse. Int J Eat Disord. 2011;44:281–3.
Nightingale LM, Paviour DC. Nutritional optic and peripheral neuropathy: a case report. Cases J. 2009;2:7762.
Milea D, Cassoux N, LeHoang P. Blindness in a strict vegan. N Engl J Med. 2000;342:897–8.
Pineles SL, Avery RA, Liu GT. Vitamin B12 optic neuropathy in autism. Pediatrics. 2010;126:e967–70.
Sobel RS, Yanuzzi LA. Optic nerve toxicity. A classification. In: Singerman I, Jampol LM, editors. Retinal and choroidal manifestations of disease. Baltimore: Williams & Wilkins; 1991. p. 226–50.
Kozak SF, Inderlied CB, Hsu HY, Heller KB, Sadun AA. The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy. Diagn Microbiol Infect Dis. 1998;30:83–7.
Chan JW, Castellanos A. Infliximab and anterior optic neuropathy: case report and review of the literature. Graefes Arch Clin Exp Ophthalmol. 2010; 248:283–7.
World Health Organization. Global tuberculosis control: surveillance, planning, financing: WHO report 2008. WHO/HTM/TB/2008.393. Geneva: World Health Organization; 2008.
Sadun AA, Wang MY. Ethambutol optic neuropathy: how we can prevent 100,000 new cases of blindness each year. J Neuroophthalmol. 2008;28:265–8.
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;162:107–14.
Pineles SL, Wilson CA, Balcer LJ, Slater R, Galetta SL. Combined optic neuropathy and myelopathy secondary to copper deficiency. Surv Ophthalmol. 2010;55:386–92.
Leopold IH. Zinc deficiency and visual impairment. Am J Ophthalmol. 1978;85:871–5.
Delacoux E, Moreau Y, Godefroy A, Evstigneef T. Prevention of ocular toxicity of ethambutol: Study of zincaemia and chromatic analysis. J Fr Ophtalmol. 1978;1:191–6.
Chung H, Yoon YH, Hwang JJ, Cho KS, Koh JY, Kim JG. Ethambutol-induced toxicity is mediated by zinc and lysosomal membrane permeabilization in cultured retinal cells. Toxicol Appl Pharmacol. 2009;235:163–70.
Carr RE, Henkind P. Ocular manifestations of ethambutol, Toxic amblyopia after administration of an experimental antituberculous drug. Arch Ophthalmol. 1962;67:566–71.
Citron K. Ethambutol. A review with special reference to ocular toxicity. Tubercle. 1969;50(Suppl):32–6.
Leibold JE. Drugs having a toxic effect on the optic nerve. Int Ophthalmol Clin. 1971;11:137–57.
Bronte Stewart J, Pettigrew AR, Foulds WS. Toxic optic neuropathy and its experimental production. Trans Ophthalmol Soc U K. 1976;96:355–8.
Yoshikawa T, Nagami P. Adverse drug interactions in TB therapy: Risks and recommendations. Geriatrics. 1982;37:61–8.
Fledelius HC, Petrera JE, Skjødt K, Trojaborg W. Ocular ethambutol toxicity. Acta Ophthalmol. 1987;65:251–5.
Kahana LM. Toxic ocular effects of ethambutol. Can Med Assoc J. 1987;137:212–6.
Smith JL. Should ethambutol be barred? J Clin Neuroophthalmol. 1987;7:84–6.
Kahana LM. Ethambutol and the eye. Lancet. 1988;2:627.
Rahman M, Nizam R. Ethambutol toxic neuroretinopathy in Bangladesh. Pak J Ophthalmol. 1989;5: 37–40.
Kumar A, Sandramouli S, Verma L, Tewari HK, Khosla PK. Ocular ethambutol toxicity: Is it reversible? J Clin Neuroophthalmol. 1993;13:15–7.
Choi SY, Hwang JM. Optic neuropathy associated with Ethambutol in Koreans. Korean J Ophthalmol. 1997;11:106–10.
Murray FJ. U.S. Public Health Service experience with ethambutol. International Congress of Chemother, Vienna 1967;6:33–382.
Alvarez KL, Krop LC. Ethambutol-induced ocular toxicity revisited. Ann Pharmacother. 1993;27:102–3.
Thomas RJ. Neurotoxicity of antibacterial therapy. South Med J. 1994;87:869–74.
Chuenkongkaew W, Samsen P, Thanasombatsakul N. Ethambutol and optic neuropathy. J Med Assoc Thai. 2003;86:622–5.
Chan RY, Kwok AK. Ocular toxicity of ethambutol. Hong Kong Med J. 2006;12:56–60.
Santaella RM, Fraunfelder FW. Ocular adverse effects associated with systemic medications : recognition and management. Drugs. 2007;67:75–93.
Asayama T. Two cases of bitemporalhemianopsia due to ethambutol. Jpn J Clin Ophthalmol. 1969;23: 1209–12.
Kho RC, Al-Obailan M, Arnold AC. Bitemporal visual field defects in ethambutol-induced optic neuropathy. J Neuroophthalmol. 2011;31:121–6.
Lim SA. Ethambutol-associated optic neuropathy. Ann Acad Med Singapore. 2006;35:274–8.
Chen HY, Lai SW, Muo CH, Chen PC, Wang IJ. Ethambutol-induced optic neuropathy: a nationwide population-based study from Taiwan. Br J Ophthalmol. 2012;96:1368–71.
World Health Organization. Treatment of tuberculosis: guidelines for national programmes. 3rd ed. Geneva: World Health Organization; 2003. WHO/CDS/TB/2003.313.
Griffith DE, Brown-Elliott BA, Shepherd S, McLarty J, Griffith L, Wallace Jr RJ. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2005;172:250–3.
Barron GJ, Tepper L, Iovine G. Ocular toxicity from Ethambutol. Am J Ophthalmol. 1974;77:256–60.
Citron KM, Thomas GO. Ocular toxicity from Ethambutol. Thorax. 1986;41:737–9.
Blumberg HM, Burman WJ, Chaisson RE, Daley CL, Etkind SC, Friedman LN, American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167:603–62.
World Health Organization. Ethambutol efficacy and toxicity. Literature review and recommendation for daily and intermittent dosage in children. Geneva, Switzerland: WHO; 2006.
Donald PR, Maher D, Maritz JS, Qazi S. Ethambutol dosage for the treatment of children: literature review and recommendations. Int J Tuberc Lung Dis. 2006;10:1318–30.
Kim U, Hwang JM. Early stage ethambutol optic neuropathy: retinal nerve fiber layer and optical coherence tomography. Eur J Ophthalmol. 2009;19:466–9.
Talbert Estlin KA, Sadun AA. Risk factors for ethambutol optic toxicity. Int Ophthalmol. 2010;30:63–72.
Tsai RK, Lee YH. Reversibility of Ethambutol optic neuropathy. J Ocul Pharmacol Ther. 1997;13:473–7.
Woung LC, Jou JR, Liaw SL. Visual function in recovered Ethambutol optic neuropathy. J Ocul Pharmacol Ther. 1995;11:411–9.
De Vita EG, Miao M, Sadun AA. Optic neuropathy in ethambutol treated renal tuberculosis. J Clin Neuroophthalmol. 1987;7:77–83.
Wang MY, Sadun AA. Drug-related mitochondrial optic neuropathies. J Neuroophthalmol. 2013;33:172–8.
Cornblath WT, Clavert PC. Best catch from NANOSNET. II. Monitoring for Ethambutol optic nerve toxicity. J Neuroophthal. 2002;22:124–5.
Fraunfelder FW, Sadun AA, Wood T. Update on ethambutol optic neuropathy. Expert Opin Drug Saf. 2006;5:615–8.
Kandel H, Adhikari P, Shrestha GS, Ruokonen EL, Shah DN. Visual function in patients on ethambutol therapy for tuberculosis. J Ocul Pharmacol Ther. 2012;28:174–8.
Menon V, Jain D, Saxena R, Sood R. Prospective evaluation of visual function for early detection of ethambutol toxicity. Br J Ophthalmol. 2009;93:1251–4.
Chai SJ, Foroozan R. Decreased retinal nerve fibre layer thickness detected by optical coherence tomography in patients with ethambutol-induced optic neuropathy. Br J Ophthalmol. 2007;91:895–7.
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;74:1011–31.
Gilman AG, Goodman LS, Rail TW, Murad F, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 7th ed. New York, NY: Macmillan; 1985. p. 1179–83.
Smith U, Smith DS, Yunis AA. Chloramphenicol-related changes in mitochondrial ultrastructure. J Cell Sci. 1970;7:501–21.
Godel V, Nemet P, Lazar M. Chloramphenicol optic neuropathy. Arch Ophthalmol. 1980;98:1417–21.
Birmingham MC, Rayner CR, Meagher AK, Flavin SM, Batts DH, Schentag JJ. Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program. Clin Infect Dis. 2003;36:159–68.
Fiscella RG, Lai WW, Buerk B, Khan M, Rodvold KA, Pulido JS, Labib S, Shapiro MJ, Blair NP. Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration. Ophthalmology. 2004;111:1191–5.
Rucker JC, Hamilton SR, Bardenstein D, Isada CM, Lee MS. Linezolid-associated toxic optic neuropathy. Neurology. 2006;66:595–8.
McKinley SH, Foroozan R. Optic neuropathy associated with linezolid treatment. J Neuroophthalmol. 2005;25:18–21.
Saijo T, Hayashi K, Yamada H, Wakakura M. Linezolid-induced optic neuropathy. Am J Ophthalmol. 2005;139:1114–6.
Javaheri M, Khurana RN, O'hearn TM, Lai MM, Sadun AA. Linezolid-induced optic neuropathy: a mitochondrial disorder? Br J Ophthalmol. 2007;91:111–5.
De Vriese AS, Coster RV, Smet J, Seneca S, Lovering A, Van Haute LL, et al. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin Infect Dis. 2006;42:1111–7.
Physicians’ Desk Reference, 5th ed. Montvale: Thomson PDR, Linezolid; 2004. p. 2808–15.
Lee E, Burger S, Shah J, Melton C, Mullen M, Warren F, Press R. Linezolid-associated toxic optic neuropathy: a report of 2 cases. Clin Infect Dis. 2003;37:1389–91.
Corallo CE, Paull AE. Linezolid-induced neuropathy. Med J Aust. 2002;177:332.
Rho JP, Sia IG, Crum BA, Dekutoski MB, Trousdale RT. Linezolid-associated peripheral neuropathy. Mayo Clin Proc. 2004;79:927–30.
Spellberg B, Yoo T, Bayer AS. Reversal of linezolid-associated cytopenias, but not peripheral neuropathy, by administration of vitamin B6. J Antimicrob Chemother. 2004;54:832–5.
Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. Prog Retin Eye Res. 2011;30:81–114.
Walker GF. Blindness during streptomycin and chloramphenicol therapy. Br J Ophthalmol. 1961;45:555–9.
Lewis W, Dalakas MC. Mitochondrial toxicity of antiviral drugs. Nat Med. 1995;1:417–22.
Samuels DC. Mitochondrial AZT, metabolism. IUBMB Life. 2006;58:403–8.
Scruggs ER, Dirks Naylor AJ. Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy. Pharmacology. 2008;82:83–8.
Shaikh S, Ta C, Basham AA, Mansour S. Leber hereditary optic neuropathy associated with antiretroviral therapy for human immunodeficiency virus infection. Am J Ophthalmol. 2001;131:143–5.
Mackey DA, Fingert JH, Luzhansky JZ, McCluskey PJ, Howell N, Hall AJ, et al. Leber’s hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus. Eye (Lond). 2003;17:312–7.
Ikeda A, Ikeda T, Ikeda N, Kawakami Y, Mimura O. Leber's hereditary optic neuropathy precipitated by ethambutol. Jpn J Ophthalmol. 2006;50:280–3.
Seo JH, Hwang JM, Park SS. Antituberculosis medication as a possible epigenetic factor of Leber’s hereditary optic neuropathy. Clin Experiment Ophthalmol. 2010;38:363–6.
Luca CC, Lam BL, Moraes CT. Erythromycin as a potential precipitating agent in the onset of Leber's hereditary optic neuropathy. Mitochondrion. 2004;4:31–6.
Guillet V, Chevrollier A, Cassereau J, Letournel F, Gueguen N, Richard L, et al. Ethambutol-induced optic neuropathy linked to OPA1 mutation and mitochondrial toxicity. Mitochondrion. 2010;10:115–24.
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. 145–62.
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;21:321–30.
Nicholls P. Formate as an inhibitor of cytochrome c oxidase. Biochem Biophys Res Commun. 1975;67:610–6.
Guyton AC. Textbook of medical physiology. Philadelphia: WB Saunders; 1981.
Sharpe JA, Hostovsky M, Bilbao JM, Rewcastle NB. Methanol optic neuropathy: a histopathological study. Neurology. 1982;32:1093–100.
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;19:243–8.
Hsu HH, Chen CY, Chen FH, Lee CC, Chou TY, Zimmerman RA. Optic atrophy and cerebral infarcts caused by methanol intoxication: MRI. Neuroradiology. 1997;39:192–4.
Sanaei-Zadeh H, Zamani N, Shadnia S. Outcomes of visual disturbances after methanol poisoning. Clin Toxicol (Phila). 2011;49:102–7.
Ingemansson SO. Clinical observations on ten cases of methanol poisoning with particular reference to ocular manifestations. Acta Ophthalmol (Copenh). 1984;62:15–24.
Onder F, Ilker S, Kansu T, Tatar T, Kural G. Acute blindness and putaminal necrosis in methanol intoxication. Int Ophthalmol. 1998–1999;22:81–4.
Stelmach MZ, O'Day J. Partly reversible visual failure with methanol toxicity. Aust N Z J Ophthalmol. 1992;20:57–64.
McKellar MJ, Hidajat RR, Elder MJ. Acute ocular methanol toxicity: clinical and electrophysiological features. Aust N Z J Ophthalmol. 1997;25:225–30.
Paasma R, Hovda KE, Jacobsen D. Methanol poisoning and long term sequelae – a six years follow-up after a large methanol outbreak. BMC Clin Pharmacol. 2009;27:5.
Liu JJ, Daya MR, Carrasquillo O, Kales SN. Prognostic factors in patients with methanol poisoning. J Toxicol Clin Toxicol. 1998;36:175–81.
Dethlefs R, Naraqi S. Ocular manifestations and complications of acute methyl alcohol intoxication. Med J Aust. 1978;2:483–5.
Sharma P, Sharma R. Toxic optic neuropathy. Indian J Ophthalmol. 2011;59:137–41.
Brent J, McMartin K, Phillips S, Aaron C, Kulig K. Fomepizole for the treatment of methanol poisoning. N Engl J Med. 2001;344:424–9.
Sodhi PK, Goyal JL, Mehta DK. Methanol-induced optic neuropathy: treatment with intravenous high dose steroids. Int J Clin Pract. 2001;55:599–602.
Shukla M, Shikoh I, Saleem A. Intravenous methylprednisolone could salvage vision in methyl alcohol poisoning. Indian J Ophthalmol. 2006;54:68–9.
Pakravan M, Sanjari N. Erythropoietin treatment for methanol optic neuropathy. J Neuroophthalmol. 2012;32:325–8.
Jacobsen D, McMartin KE. Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol. 1986;1:309–34.
Gupta SR, Palmer CA, Curé JK, Balos LL, Lincoff NS, Kline LB. Toluene optic neurotoxicity: magnetic resonance imaging and pathologic features. Hum Pathol. 2011;42:295–8.
Kiyokawa M, Mizota A, Takasoh M, Adachi-Usami E. Pattern visual evoked cortical potentials in patients with toxic optic neuropathy caused by toluene abuse. Jpn J Ophthalmol. 1999;43:438–42.
Hormes JT, Filley CM, Rosenberg NL. Neurologic sequelae of chronic solvent vapor abuse. Neurology. 1986;36:698–702.
Sadun AA, Martone JF. Cuba: response of medical science to a crisis of optic and peripheral neuropathy. Int Ophthalmol. 1994–1995;18:373–8.
Sadun AA. Acquired mitochondrial impairment as a cause of optic nerve disease. Trans Am Ophthalmol Soc. 1998;96:881–923.
Román GC. An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy. J Neurol Sci. 1994;127:11–28.
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;64:347–53.
Thomas PK, Plant GT, Baxter P, Bates C, Santiago LR. An epidemic of optic neuropathy and painful sensory neuropathy in Cuba: clinical aspects. J Neurol. 1995;242:629–38.
Gay J, Porrata C, Hernandez M, Clua AM, Arguelles JM, Cabrera A, et al. Dietary factors in epidemic neuropathy on the Isle of Youth, Cuba. Bull Pan Am Health Organ. 1995;29:25–36.
Johns DR, Sadun AA. Cuban epidemic optic neuropathy. Mitochondrial DNA analysis. J Neuroophthalmol. 1994;14:130–4.
Mojon DS, Kaufmann P, Odel JG, Lincoff NS, Marquez-Fernandez M, Santiesteban R, et al. Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy. Neurology. 1997;48:19–22.
Santiesteban-Freixas R, Mendoza-Santiesteban CE, Columbie-Garbey Y, Quevedo AG, Garcia AG, Rodríguez RC. Cuban epidemic optic neuropathy and its relationship to toxic and hereditary optic neuropathy. Semin Ophthalmol. 2010;25:112–22.
Lincoff NS, Odel JG, Hirano M. ‘Outbreak’ of optic and peripheral neuropathy in Cuba? JAMA. 1993;270:511–8.
Tucker K, Hedges TR. Food shortages and an epidemic of optic and peripheral neuropathy in Cuba. Nutr Rev. 1993;51:349–57.
Grzybowski A. Mitochondrial optic neuropathies: additional facts and concepts. Clin Experiment Ophthalmol. 2013 Jun 18. doi: 10.1111/ceo.12148. [Epub ahead of print]
Solberg Y, Rosner M, Belkin M. The association between cigarette smoking and ocular diseases. Surv Ophthalmol. 1998;42:535–47.
Carroll FD. Nutritional amblyopia. Arch Ophthalmol. 1966;76:406–11.
Smiddy WE, Green WR. Nutritional amblyopia. A histopathologic study with retrospective clinical correlation. Graefes Arch Clin Exp Ophthalmol. 1987;225:321–4.
Pryor WA, Arbour NC, Upham B, Church DF. The inhibitory effect of extracts of cigarette tar on electron transport of mitochondria. Free Radic Biol Med. 1992;12:365–72.
Ballinger SW, Bouder TG, Davis GS, Judice SA, Nicklas JA, Albertini RJ. Mitochondrial genome damage associated with cigarette smoking. Cancer Res. 1996;56:5692–7.
Kennedy JR, Elliott AM. Cigarette smoke: the effect of residue on mitochondrial structure. Science. 1970;168:1097–8.
Dunphy EB. Alcohol and tobacco amblyopia: a historical survey. XXXI DeSchweinitz lecture. Am J Ophthalmol. 1969;68:569–78.
Pearce JM. Neurological aspects of alcoholism. Br J Hosp Med. 1977;18:132. 134, 136–7.
Samples JR, Younge BR. Tobacco-alcohol amblyopia. J Clin Neuro Ophthalmol. 1981;1:213–8.
Harrington DO. Amblyopia due to tobacco, alcohol and nutritional deficiency. Differential diagnosis with special reference to the character of the visual field defect. Am J Ophthalmol. 1962;53:967–72.
Grzybowski A, Holder GE. Tobacco optic neuropathy (TON) – the historical and present concept of the disease. Acta Ophthalmol. 2011;89:495–9.
Syed S, Lioutas V. Tobacco-alcohol amblyopia: a diagnostic dilemma. J Neurol Sci. 2013;327:41–5.
Rizzo 3rd JF, Lessell S. Tobacco amblyopia. Am J Ophthalmol. 1993;116:84–7.
Cullom ME, Heher KL, Miller NR, Savino PJ, Johns DR. Leber's hereditary optic neuropathy masquerading as tobacco-alcohol amblyopia. Arch Ophthalmol. 1993;111:1482–5.
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;118:158–68.
Strachan H. On a form of multiple neuritis prevalent in the West Indies. Practitioner. 1897;59:477–84.
Fisher C. Residual neuropathological changes in Canadians held prisoners of war by the Japanese (Strachan’s disease). Can Serv Med J. 1955;11:157–99.
Gill GV, Bell DR. Persisting nutritional neuropathy amongst former war prisoners. J Neurol Neurosurg Psychiatry. 1982;45:861–5.
King Jr JH, Passmore JW. Nutritional amblyopia: a study of American prisoners of war in Korea. Am J Ophthalmol. 1955;39:173–86.
Osuntokun BO. Cassava diet, chronic cyanide intoxication and neuropathy in Nigerian Africans. World Rev Nutr Diet. 1981;36:141–73.
Carton H, Kazadi K, Kabeya O, Billiau A, Maertens K. Epidemic spastic paraparesis in Bandundu (Zaire). J Neurol Neurosurg Psychiatry. 1986;49:620–7.
Ministry of Health, Mozambique. Mantakassa: an epidemic of spastic paraparesis associated with chronic cyanide intoxication in a cassava staple area of Mozambique. Epidemiology and clinical laboratory findings in patients. Bull World Health Organ. 1984; 62:477–484.
Howlett WP, Brubaker GR, Mlingi N, Rosling H. Konzo, an epidemic upper motor neuron disease studied in Tanzania. Brain. 1990;113:223–35.
Montgomery RD, Cruickshank EK, Robertson WB, McNemeney WH. Clinical and pathological observations on Jamaican neuropathy: a report on 206 cases. Brain. 1964;87:425–62.
Osuntokun BO, Osuntokun O. Tropical amblyopia in Nigerians. Am J Ophthalmol. 1971;72:708–16.
Bowman RW, Wedner S, Bowman RF, Masanja H, Bunce C, Wood ML, et al. Optic neuropathy endemic in secondary school children in Dar es Salaam Tanzania. Br J Ophthalmol. 2010;94:146–9.
Plant GT, Mtanda AT, Arden GB, Johnson GJ. An epidemic of optic neuropathy in Tanzania: characterization of the visual disorder and associated peripheral neuropathy. J Neurol Sci. 1997;145:127–40.
Johnson GJ, Mtanda AT, Kinabo NN, Sangawe JLF, Masesa DE, Negral AD. Optic nerve and macular atrophy of unknown origin in Tanzania. Arch Publ Health. 1993;51:561–71.
Hodson KE, Bowman RJ, Mafwiri M, Wood M, Mhoro V, Cox SE. Low folate status and indoor pollution are risk factors for endemic optic neuropathy in Tanzania. Br J Ophthalmol. 2011;95:1361–4.
Dalmar AA, Hodson KE, Plant GT. Epidemic optic neuropathy is evident in the Somalian population. J Neuroophthalmol. 2011;31:127–30.
Chen D, Hedges TR. Amiodarone optic neuropathy – review. Semin Ophthalmol. 2003;18:169–73.
Fraunfelder FT, Fraunfelder FW. Drug-induced ocular side effects. Boston, MA: Butterworth-Heinemann; 2001.
Feiner LA, Younge BR, Kazmier FJ, Stricker BH, Fraunfelder FT. Optic neuropathy and amiodarone therapy. Mayo Clin Proc. 1987;62:702–17.
Macaluso DC, Shults WT, Fraunfelder FT. Features of amiodarone-induced optic neuropathy. Am J Ophthalmol. 1999;127:610–2.
Johnson LN, Krohel GB, Thomas ER. The clinical spectrum of amiodarone-associated optic neuropathy. J Natl Med Assoc. 2004;96:1477–91.
Pollak PT, Bouillon T, Shafer SL. Population pharmacokinetics of long-term oral amiodarone therapy. Clin Pharmacol Ther. 2000;67:642–52.
Singh BN. Amiodarone: the expanding antiarrhythmic role and how to follow a patient on chronic therapy. Clin Cardiol. 1997;20:608–18.
Characteristics of patients with nonarteritic anterior ischemic optic neuropathy eligible for the ischemic optic neuropathy decompression trial. Arch Ophthalmol. 1996;114:1366–74.
Sadun AA. Discussion of claims of the purported clinical spectrum of Amiodarone associated optic neuropathy; 2004 Oct; New Orleans: American Academy of Ophthalmology.
Somani P. Basic and clinical pharmacology of amiodarone: relationship of antiarrhythmic effects, dose and drug concentrations to intracellular inclusion bodies. J Clin Pharmacol. 1989;29:405–12.
Sadun AA, Gurkan S, Patel V. Hereditary, nutritional, and toxic optic atrophies. In: Yanoff M, Duker JS, editors. Ophthalmology. 3rd ed. Edinburgh: Mosby Elsevier; 2008.
Mindel JS. Amiodarone toxic optic neuropathy: reasons for doubting its existence [lecture]. North American Neuro-Ophthalmology Society Annual Meeting; 2006 Feb 25–Mar 2; Tucson, AZ.
Li J, Tripathi RC, Tripathi BJ. Drug-induced ocular disorders. Drug Saf. 2008;31:127–41.
Orakzai A, Guerin M, Beatty S. Disulfiram-induced transient optic and peripheral neuropathy: a case report. Ir J Med Sci. 2007;176:319–21.
Baron S, Tyring SK, Fleischmann Jr WR, Coppenhaver DH, Niesel DW, Klimpel GR, Stanton GJ, Hughes TK. The interferons. Mechanisms of action and clinical applications. JAMA. 1991;266:1375–83.
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;353:1326.
Purvin VA. Anterior ischemic optic neuropathy secondary to interferon alfa. Arch Ophthalmol. 1995;113:1041–4.
Taylor JL, Grossberg SE. The effects of interferon-alpha on the production and action of other cytokines. Semin Oncol. 1998;25:23–9.
Rue KS, Hirsch LK, Sadun AA. Impending anterior ischemic optic neuropathy with elements of retinal vein occlusion in a patient on interferon for polycythemia vera. Clin Ophthalmol. 2012;6:1763–5.
Selcukbiricik F, Tural D, Senel TE, Sarıca A, Soyluk O, Serdengecti S. Bilateral ischemic optic neuropathy developed under interferon therapy. Case Rep Ophthalmol Med. 2012;2012:102739.
Seddik H, Tamzaourte M, Rouibaa F, Fadlouallah M, Benkirane A. Irreversible anterior ischemic optic neuropathy complicating interferon alpha and ribaverin therapy. Int J Hepatol. 2011;2011:814242.
Knyazer B, Lifshitz T, Marcus M, Kratz A, Zlotnik A, Levy J. Anterior ischemic optic neuropathy in a patient with hepatitis C treated with interferon-alpha and ribavirin. Isr Med Assoc J. 2011;13:251–3.
Fraunfelder FW, Fraunfelder FT. Interferon alfa-associated anterior ischemic optic neuropathy. Ophthalmology. 2011;118:408–11.e1-2.
Berg KT, Nelson B, Harrison AR, McLoon LK, Lee MS. Pegylated interferon alpha-associated optic neuropathy. J Neuroophthalmol. 2010;30:117–22.
Wei YH, Wang IH, Woung LC, Jou JR. Anterior ischemic optic neuropathy associated with pegylated interferon therapy for chronic hepatitis C. Ocul Immunol Inflamm. 2009;17:191–4.
Kabbaj N, Sentissi S, Mohammadi M, Benaïssa A, Amrani N. Anterior ischemic optic neuropathy complicating interferon alpha and ribavirin therapy in patients with chronic hepatitisC. Gastroenterol Clin Biol. 2009;33:115–7.
Rodney AJ, Gombos DS, Pagliaro LC, Tannir NM. Ischemic optic neuropathy associated with low-dose interferon alfa: report of two cases. Am J Clin Oncol. 2009;32:86–7.
Chan JW. Bilateral non-arteritic ischemic optic neuropathy associated with pegylated interferon for chronic hepatitis C. Eye (Lond). 2007;21:877–8.
Norcia F, Di Maria A, Prandini F, Redaelli C. Natural interferon therapy: optic nerve ischemic damage? Ophthalmologica. 1999;213:339–40.
Vardizer Y, Linhart Y, Loewenstein A, Garzozi H, Mazawi N, Kesler A. Interferon-alpha-associated bilateral simultaneous ischemic optic neuropathy. J Neuroophthalmol. 2003;23:256–9.
Foroozan R. Unilateral pallid optic disc swelling and anemia associated with interferon alpha treatment. J Neuroophthalmol. 2004;24:98–9.
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;98:672–3.
Gupta R, Singh S, Tang R, Blackwell TA, Schiffman JS. Anterior ischemic optic neuropathy caused by interferon alpha therapy. Am J Med. 2002;112:683–4.
Seror R, Richez C, Sordet C, Rist S, Gossec L, Direz G, et al. Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey. Rheumatology (Oxford). 2013;52:868–74.
The Lenercept Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology. 1999;53:457–65.
Van Oosten BW, Barkhof F, Truyen L, et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology. 1996;47:1531–4.
Głabiński A, Mirecka M, Pokoca L. Tumor necrosis factor alpha but not lymphotoxin is overproduced by blood mononuclear cells in multiple sclerosis. Acta Neurol Scand. 1995;91:276–9.
Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1995;92:11294–8.
Foroozan R, Buono LM, Sergott RC, Savino PJ. Retrobulbar optic neuritis associated with infliximab. Arch Ophthalmol. 2002;120:985–7.
Bidaguren A, Müller-Thyssen A, Blanco A, Mendicute J, Ubeda M. [Retrobulbar optic neuritis associated with Infliximab]. Arch Soc Esp Oftalmol. 2007;82:109–12.
Hejazi R, Colombel JF, Peyrin-Biroulet L. Retrobulbar optic neuritis during infliximab treatment for ulcerative colitis. Gastroenterol Clin Biol. 2008;32:162–3.
Mumoli N, Niccoli G, Scazzeri F, Picchietti S, Greco A, Cei M. Infliximab-induced retrobulbar optic neuritis. QJM. 2007;100:531.
Pikkel J. Possible link between infliximab and optic neuritis. Isr Med Assoc J. 2008;10:477–8.
Simsek I, Erdem H, Pay S, Sobaci G, Dinc A. Optic neuritis occurring with anti-tumour necrosis factor alpha therapy. Ann Rheum Dis. 2007;66:1255–8.
Strong BY, Erny BC, Herzenberg H, Razzeca KJ. Retrobulbar optic neuritis associated with infliximab in a patient with Crohn disease. Ann Intern Med. 2004;140:W34.
Tran TH, Milea D, Cassoux N, Bodaghi B, Bourgeois P, LeHoang P. [Optic neuritis associated with infliximab]. J Fr Ophtalmol. 2005;28:201–4.
Mejico LJ. Infliximab-associated retrobulbar optic neuritis. Arch Ophthalmol. 2004;122:793–4.
Winthrop KL, Chen L, Fraunfelder FW, Ku JH, Varley CD, Suhler E, et al. Initiation of anti-TNF therapy and the risk of optic neuritis: from the safety assessment of biologic ThERapy (SABER) study. Am J Ophthalmol. 2013;155:183–9.e1.
ten Tusscher MP, Jacobs PJ, Busch MJ, de Graaf L, Diemont WL. Bilateral anterior toxic optic neuropathy and the use of infliximab. BMJ. 2003;326:579.
Chan JW, Castellanos A. Infliximab and anterior optic neuropathy: case report and review of the literature. Graefes Arch Clin Exp Ophthalmol. 2010;248:283–7.
Roch 2nd LM, Gordon DL, Barr AB, Paulsen CA. Visual changes associated with clomiphene citrate therapy. Arch Ophthalmol. 1967;77:14–7.
Padron Rivas VF, Sanchez Sanchez A, Lerida Arias MT, Carvajal Garcia-Pardo A. [Optic neuritis appearing during treatment with clomiphene]. Aten Primaria. 1994;14:912–3.
Lawton AW. Optic neuropathy associated with clomiphene citrate therapy. Fertil Steril. 1994;61:390–1.
Pugesgaard T, Von Eyben FE. Bilateral optic neuritis evolved during tamoxifen treatment. Cancer. 1986;58:383–6.
Colley SM, Elston JS. Tamoxifen optic neuropathy. Clin Experiment Ophthalmol. 2004;32:105–6.
Noureddin BN, Seoud M, Bashshur Z, Salem Z, Shamseddin A, Khalil A. Ocular toxicity in low-dose tamoxifen: a prospective study. Eye (Lond). 1999;13:729–33.
Tarantini A, Faraoni A, Menchini F, Lanzetta P. Bilateral simultaneous nonarteritic anterior ischemic optic neuropathy after ingestion of sildenafil for erectile dysfunction. Case Rep Med. 2012;2012:747658.
O'Malley P. Viagra and vision loss: what is known and unknown. Clin Nurse Spec. 2006;20:227–8.
Calvet C, Martin K, Robert G, Moore N, Eftekhari P, Farghal H, et al. Treatment of erectile dysfunction by phosphodiesterase-5 inhibitors and nonarteritic anterior ischemic optic neuropathy (NAION). Prog Urol. 2007;17:920–7.
Felekis T, Asproudis I, Katsanos K, Tsianos E. A case of nonarteritic anterior ischemic optic neuropathy of a male with family history of the disease after receiving sildenafil. Clin Ophthalmol. 2011;5:1443–5.
Moschos MM, Margetis I. Bilateral simultaneous anterior ischemic optic neuropathy associated with sildenafil. Case Rep Ophthalmol. 2011;2:262–5.
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;338:1397–404.
Lee AG, Newman NJ. Erectile dysfunction drugs and nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 2005;140:707–8.
Pomeranz HD, Smith KH, Hart Jr WM, Egan RA. Sildenafil-associated nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2002;109:584–7.
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;21:315–7.
Beck RW, Servais GE, Hayreh SS. Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology. 1987;94:1503–8.
Burde RM. Optic disk risk factors for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 1993;116:759–64.
Doro S, Lessell S. Cup-disc ratio and ischemic optic neuropathy. Arch Ophthalmol. 1985;103:1143–4.
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;40:422–3.
Cunningham AV, Smith KH. Anterior ischemic optic neuropathy associated with viagra. J Neuroophthalmol. 2001;21:22–5.
Dheer S, Rekhi GS, Merlyn S. Sildenafil associated anterior ischaemic optic neuropathy. J Assoc Physicians India. 2002;50:265.
Egan R, Pomeranz H. Sildenafil (Viagra) associated anterior ischemic optic neuropathy. Arch Ophthalmol. 2000;118:291–2.
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;96:9944–8.
Sponsel WE, Paris G, Sandoval SS, Sanford DK, Harrison JM, Elliott WR, et al. Sildenafil and ocular perfusion. N Engl J Med. 2000;342:1680.
Grunwald JE, Siu KK, Jacob SS, Dupont J. Effect of sildenafil citrate (Viagra) on the ocular circulation. Am J Ophthalmol. 2001;131:751–5.
Bollinger K, Lee MS. Recurrent visual field defect and ischemic optic neuropathy associated with tadalafilrechallenge. Arch Ophthalmol. 2005;123:400–1.
Escaravage Jr GK, Wright Jr JD, Givre SJ. Tadalafil associated with anterior ischemic optic neuropathy. Arch Ophthalmol. 2005;123:399–400.
Peter NM, Singh MV, Fox PD. Tadalafil-associated anterior ischaemic optic neuropathy. Eye. 2005;19:715–7.
Azzouni F, Abu samra K. Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A critical analysis and review of the literature. J Sex Med. 2011;8:2894–903.
Jiang GL, Tucker SL, Guttenberger R, Peters LJ, Morrison WH, Garden AS, et al. Radiation-induced injury to the visual pathway. Radiother Oncol. 1994;30:17–25.
Kline LB, Kim JY, Ceballos R. Radiation optic neuropathy. Ophthalmology. 1985;92:1118–26.
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;3:291–4.
Regine WF, Kramer S. Pediatric craniopharyngiomas: long term results of combined treatment with surgery and radiation. Int J Radiat Oncol Biol Phys. 1992;24:611–7.
Roden D, Bosley TM, Fowble B, Clark J, Savino PJ, Sergott RC, et al. Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids. Ophthalmology. 1990;97:346–51.
Schoenthaler R, Albright NW, Wara WM, Phillips TL, Wilson CB, Larson DA. Re-irradiation of pituitary adenoma. Int J Radiat Oncol Biol Phys. 1992;24:307–14.
Zhao Z, Lan Y, Bai S, Shen J, Xiao S, Lv R, et al. Late-onset radiation-induced optic neuropathy after radiotherapy for nasopharyngeal carcinoma. J Clin Neurosci. 2013;20:702–6.
Mock U, Georg D, Bogner J, Auberger T, Pötter R. Treatment planning comparison of conventional, 3D conformal, and intensity-modulated photon (IMRT) and proton therapy for paranasal sinus carcinoma. Int J Radiat Oncol Biol Phys. 2004;58:147–54.
Claus F, De Gersem W, De Wagter C, Van Severen R, Vanhoutte I, Duthoy W, et al. An implementation strategy for IMRT of ethmoid sinus cancer with bilateral sparing of the optic pathways. Int J Radiat Oncol Biol Phys. 2001;51:318–31.
Bhandare N, Monroe AT, Morris CG, Bhatti MT, Mendenhall WM. Does altered fractionation influence the risk of radiation-induced optic neuropathy? Int J Radiat Oncol Biol Phys. 2005;62:1070–7.
Danesh-Meyer HV. Radiation-induced optic neuropathy. J Clin Neurosci. 2008;15:95–100.
Ove R, Kelman S, Amin PP, Chin LS. Preservation of visual fields after peri-sellar gamma-knife radiosurgery. Int J Cancer. 2000;90:343–50.
Leber KA, Berglöff J, Pendl G. Dose–response tolerance of the visual pathways and cranial nerves of the cavernous sinus to stereotactic radiosurgery. J Neurosurg. 1998;88:43–50.
Abouaf L, Girard N, Lefort T, D’Hombres A, Tilikete C, Vighetto A, et al. Standard-fractionated radiotherapy for optic nerve sheath meningioma: visual outcome is predicted by mean eye dose. Int J Radiat Oncol Biol Phys. 2012;82:1268–77.
Andrews DW, Faroozan R, Yang BP, Hudes RS, Werner-Wasik M, Kim SM, et al. Fractionated stereotactic radiotherapy for the treatment of optic nerve sheath meningiomas: preliminary observations of 33 optic nerves in 30 patients with historical comparison to observation with or without prior surgery. Neurosurgery. 2002;51(4):890–902.
Metellus P, Kapoor S, Kharkar S, Batra S, Jackson JF, Kleinberg L, et al. Fractionated conformal radiotherapy for management of optic nerve sheath meningiomas: long-term outcomes of tumor control and visual function at a single institution. Int J Radiat Oncol Biol Phys. 2011;80(1):185–92.
Parsons JT, Bova FJ, Fitzgerald CR, Mendenhall WM, Million RR. Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors. Int J Radiat Oncol Biol Phys. 1994;30:755–63.
Siddiqui JD, Loeffler JS, Murphy MA. Radiation optic neuropathy after proton beam therapy for optic nerve sheath meningioma. J Neuroophthalmol. 2013;33:165–8.
Mendenhall WM, Riggs CE, Amdur RJ, Hinerman RW, Villaret DB. Altered fractionation and/or adjuvant chemotherapy in definitive irradiation of squamous cell carcinoma of the head and neck. Laryngoscope. 2003;113:546–51.
Sanderson PA, Kuwabara T, Cogan DG. Optic neuropathy presumably caused by vincristine therapy. Am J Ophthalmol. 1976;81:146–50.
Griffin JD, Garnick MB. Eye toxicity of cancer chemotherapy: a review of the literature. Cancer. 1981;48:1539–49.
Geyer JR, Taylor EM, Milstein JM, Shaw CM, Hubbard BA, Geraci JP, et al. Radiation, methotrexate, and white matter necrosis: laboratory evidence for neural radioprotection with preirradiation methotrexate. Int J Radiat Oncol Biol Phys. 1988;15:373–5.
Balsom WR, Bleyer WA, Robison LL, Heyn RM, Meadows AT, Sitarz A, 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;19:486–92.
Fishman ML, Bean SC, Cogan DG. Optic atrophy following prophylactic chemotherapy and cranial radiation for acute lymphocytic leukemia. Am J Ophthalmol. 1976;82:571–6.
Lessell S. Friendly fire: neurogenic visual loss from radiation therapy. J Neuroophthalmol. 2004;24:243–50.
Marks LB, Spencer DP. The influence of volume on the tolerance of the brain to radiosurgery. J Neurosurg. 1991;75:177–80.
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;29:210–8.
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;27:44–7.
Schultheiss TE, Higgins EM, El-Mahdi AM. The latent period in clinical radiation myelopathy. Int J Radiat Oncol Biol Phys. 1984;10:1109–15.
Lampert PW, Davis RL. Delayed effects of radiation on the human central nervous system: “early” and “late” delayed reactions. Neurology. 1964;14:912–7.
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;33:265–75.
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;7:221–3.
van der Kogel AJ. Radiation-induced damage in the central nervous system: an interpretation of target cell responses. Br J Cancer Suppl. 1986;7:207–17.
Omary RA, Berr SS, Kamiryo T, Lanzino G, Kassell NF, Lee KS, 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;2:1043–51.
Levin LA, Gragoudas ES, Lessell S. Endothelial cell loss in irradiated optic nerves. Ophthalmology. 2000;107:370–4.
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;10:130–7.
Crompton MR, Layton DD. Delayed radionecrosis of the brain following therapeutic x-radiation of the pituitary. Brain. 1961;84:85–101.
Ross HS, Rosenberg S, Friedman AH. Delayed radiation necrosis of the optic nerve. Am J Ophthalmol. 1973;76:683–6.
Borruat FX, Schatz NJ, Glaser JS. [Post-actinic retrobulbar optic neuropathy]. Klin Monbl Augenheilkd. 1996;208:381–4.
Guy J, Schatz NJ. Hyperbaric oxygen in the treatment of radiation-induced optic neuropathy. Ophthalmology. 1986;93:1083–8.
Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation optic neuropathy. Ophthalmology. 1982;89:1489–93.
Arnold AC. Radiation optic neuropathy. Presented at the 21st Annual Meeting of the North American Neuro-Ophthalmology Society; 1995 Feb 23; Tucson, AZ.
Schatz NJ, Lichtenstein S, Corbett JJ. Delayed radiation necrosis of the optic nerves and chiasm. In: Glaser JS, Smith JL, editors. Neuro-ophthalmology Symposium of the University of Miami and the Bascom Palmer Eye Institute, vol. 8. St. Louis: CV Mosby; 1978. p. 131–9.
Kim IK, Lane AM, Egan KM, Munzenrider J, Gragoudas ES. Natural history of radiation papillopathy after proton beam irradiation of parapapillary melanoma. Ophthalmology. 2010;117:1617–22.
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;47:474–6.
Spaziante R, de Divitiis E, Stella L, Cappabianca P, Genovese L. The empty sella. Surg Neurol. 1981;16:418–26.
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; 1991.
Guy J, Mancuso A, Beck R, Moster ML, Sedwick LA, Quisling RG, Rhoton Jr AL, Protzko EE, Schiffman J. Radiation-induced optic neuropathy: a magnetic resonance imaging study. J Neurosurg. 1991;74:426–32.
Hudgins PA, Newman NJ, Dillon WP, Hoffman Jr JC. Radiation-induced optic neuropathy: characteristic appearances on gadolinium-enhanced MR. AJNR Am J Neuroradiol. 1992;13:235–8.
McClellan RL, el Gammal T, Kline LB. Early bilateral radiation-induced optic neuropathy with follow-up MRI. Neuroradiology. 1995;37:131–3.
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;31:336–43.
Glantz MJ, Burger PC, Friedman AH, Radtke RA, Massey EW, Schold Jr SC. Treatment of radiation-induced nervous system injury with heparin and warfarin. Neurology. 1994;44:2020–7.
Rizzoli HV, Pagnanelli DM. Treatment of delayed radionecrosis of the brain: a clinical observation. J Neurosurg. 1984;60:589–94.
Danesh-Meyer HV, Savino PJ, Sergott RC. Visual loss despite anticoagulation in radiation-induced optic neuropathy. Clin Experiment Ophthalmol. 2004;32:333–5.
Landau K, Killer HE. Radiation damage. Neurology. 1996;46:889.
Borruat FX, Schatz NJ, Glaser JS, Feun LG, Matos L. Visual recovery from radiation-induced optic neuropathy. The role of hyperbaric oxygen therapy. J Clin Neuroophthalmol. 1993;13:98–101.
Hammerlund C. The physiological effects of hyperbaric oxygen. In: Kindwall EP, editor. Hyperbaric medicine practice. Flagstaff: Best publishing Company; 1995.
Miller NR. Radiation-induced optic neuropathy: still no treatment. Clin Experiment Ophthalmol. 2004; 32:233–5.
Levy RL, Miller NR. Hyperbaric oxygen therapy for radiation-induced optic neuropathy. Ann Acad Med Singapore. 2006;35:151–7.
Kellner U, Bornfeld N, Foerster MH. Radiation-induced optic neuropathy following brachytherapy of uveal melanomas. Graefes Arch Clin Exp Ophthalmol. 1993;231:267–70.
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Wang, M.Y., Sadun, A.A., Chan, J.W. (2014). Nutritional and Toxic Optic Neuropathies. In: Chan, J. (eds) Optic Nerve Disorders. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0691-4_6
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