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Toxic/Nutritional Optic Neuropathy

  • Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
 
Updated: May 09, 2016
 

Background

The anterior visual pathway is susceptible to damage from toxins or nutritional deficiency. These disorders tend to be classified under the heading toxic/nutritional optic neuropathy, a syndrome characterized by papillomacular bundle damage within the optic nerves, central or cecocentral scotoma, and reduction of color vision. Both toxicity and malnutrition, acting either independently or together, have been implicated in the pathogenesis of these disorders. Although these problems have been classified as optic neuropathies, in most of these entities, the primary lesion has not actually been localized to the optic nerve and may possibly originate in the retinal ganglion cells or nerve fiber layers, chiasm, or even the optic tracts.

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Pathophysiology

The exact mechanism by which nutritional deficits damage the optic nerve has not been elucidated. Although the etiology is likely multifactorial, most clinicians agree that in patients who abuse ethanol and tobacco, malnourishment is often present and undernutrition, rather than direct toxicity, is the principal cause of the visual loss. Specific deficiencies of vitamin B-12 (cyanocobalamin), thiamine (vitamin B-1), other B-complex vitamins (riboflavin, niacin, and pyridoxine), and folic acid, as well as reduced systemic levels of other proteins with sulfur-containing amino acids, may play a role.

Whether tobacco or ethanol has a direct toxic effect on the optic nerve remains unclear. Why certain other agents are toxic to the optic nerve, particularly the portion that comprises the papillomacular bundle, also remains largely unestablished. Whether an unusual configuration of the vascular supply of the optic nerve head in certain individuals predisposes them to the accumulation of toxic agents has been questioned.

Ethyl alcohol, like tobacco, produces its toxic effects through metabolic means. Extended high-dosage exposure may lead to folate or vitamin B-12 deficiency, resulting in accumulation of formic acid, inhibiting the electron transport chain and mitochondrial function, ultimately resulting in impairment of adenosine triphosphate (ATP)–mediated axonal transport within nerves, including the optic nerve.

The toxin methyl alcohol (methanol) causes focal delamination of the optic nerve in animal experiments and in humans.

All of these deficiencies or toxicities affect mitochondrial oxidative phosphorylation. In essence, the toxic and nutritional optic neuropathies are actually acquired mitochondrial optic neuropathies, similar in clinical picture to congenital mitochondrial optic neuropathies.

It has been hypothesized that the chelating properties of ethambutol are what contribute to its neurotoxicity, but this has yet to be proven. The mechanism of the neurotoxicity that occurs from the cardiac antiarrhythmic amiodarone also remains unclear, with researchers believing that it may relate to lipid accumulation in optic nerve axons, with subsequent impedance of axoplasmic flow.

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Epidemiology

Frequency

United States

Toxic and nutritional optic neuropathies are not common in the United States. In the general population, nutritional amblyopia is more common among tobacco and alcohol abusers and those who are undernourished. Toxic optic neuropathies usually are associated with exposure of employees in a workplace, ingestion of materials/foods containing toxic substances, or systemic medications.

International

Nutritional optic neuropathy is definitely more prevalent in regions of famine, such as in Africa, where it may take on epidemic proportions.

Mortality/Morbidity

Morbidity of these disorders depends on risk factors, the underlying etiology, and the duration of symptoms before the institution of treatment. A patient with advanced optic atrophy is less likely to recover visual function than a patient who does not have such pathologic changes.

Race

These disorders have no racial predilection. All races are susceptible.

Sex

These disorders are found equally in both males and females.

Age

Any age may be affected by toxic optic neuropathies, but nutritional optic neuropathies are very rare in children, perhaps since drinking and smoking are much less frequent in this age group. Historically, toxic optic neuropathy was formerly seen in children with chronic pulmonary conditions, such as cystic fibrosis, when treated with chloramphenicol.

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Contributor Information and Disclosures
Author

Andrew A Dahl, MD, FACS Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Andrew A Dahl, MD, FACS is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Intraocular Lens Society, American Medical Association, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Medical Society of the State of New York, New York State Ophthalmological Society, Outpatient Ophthalmic Surgery Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Andrew W Lawton, MD Neuro-Ophthalmology, Ochsner Health Services

Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, Southern Medical Association

Disclosure: Nothing to disclose.

Acknowledgements

Robert C Sergott, MD Professor of Ophthalmology, Department of Ophthalmology, Thomas Jefferson University; Consulting Surgeon, Wills Eye Hospital, Children's Hospital of Philadelphia

Disclosure: Nothing to disclose.

Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Aftab Zafar, MD Consulting Staff, Department of Ophthalmology, St Mary's General Hospital

Aftab Zafar, MD is a member of the following medical societies: Canadian Medical Association, Canadian Ophthalmological Society, College of Physicians and Surgeons of Ontario, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References
  1. Lim SA. Ethambutol-associated optic neuropathy. Ann Acad Med Singapore. 2006 Apr. 35(4):274-8. [Medline].

  2. Orssaud C, Roche O, Dufier JL. Nutritional optic neuropathies. J Neurol Sci. 2007 Nov 15. 262(1-2):158-64. [Medline].

  3. Murphy MA, Murphy JF. Amiodarone and optic neuropathy: the heart of the matter. J Neuroophthalmol. 2005 Sep. 25(3):232-6. [Medline].

  4. Macaluso DC, Shults WT, Fraunfelder FT. Features of amiodarone-induced optic neuropathy. Am J Ophthalmol. 1999 May. 127(5):610-2. [Medline].

  5. Nagra PK, Foroozan R, Savino PJ, et al. Amiodarone induced optic neuropathy. Br J Ophthalmol. 2003 Apr. 87(4):420-2. [Medline].

  6. Nazarian SM, Jay WM. Bilateral optic neuropathy associated with amiodarone therapy. J Clin Neuroophthalmol. 1988 Mar. 8(1):25-8. [Medline].

  7. Grzybowski A, Holder GE. Tobacco optic neuropathy (TON) - the historical and present concept of the disease. Acta Ophthalmol. 2011 Aug. 89(5):495-9. [Medline].

  8. Wilczynski M, Wilczynska O. Severe acute bilateral alcohol-induced toxic optic neuropathy--case report. Klin Oczna. 2012. 114(3):208-12. [Medline].

  9. Wang MY, Sadun AA. Drug-related mitochondrial optic neuropathies. J Neuroophthalmol. 2013 Jun. 33(2):172-8. [Medline].

  10. Becker M, Masterson K, Delavelle J, Viallon M, Vargas MI, Becker CD. Imaging of the optic nerve. Eur J Radiol. 2010 May. 74(2):299-313. [Medline].

  11. Santaella RM, Fraunfelder FW. Ocular adverse effects associated with systemic medications : recognition and management. Drugs. 2007. 67(1):75-93. [Medline].

  12. Zoumalan CI, Agarwal M, Sadun AA. Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2005 May. 243(5):410-6. [Medline].

  13. 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 Jul. 91(7):895-7. [Medline].

  14. Johnson LN, Krohel GB, Thomas ER. The clinical spectrum of amiodarone-associated optic neuropathy. J Natl Med Assoc. 2004 Nov. 96(11):1477-91. [Medline].

  15. Danesh-Meyer H, Kubis KC, Wolf MA. Chiasmopathy?. Surv Ophthalmol. 2000 Jan-Feb. 44(4):329-35. [Medline].

  16. Glaser JS. Nutritional and toxic optic neuropathies. Glaser JS, ed. Neuro-ophthalmology. 3rd ed. Philadelphia: Lippincott; 1999.

  17. Grant WM, Schuman JS. Toxicology of the Eye. 4th ed. Springfield, Ill: Charles C Thomas Publisher; 1993.

  18. Kerrison JB. Optic neuropathies caused by toxins and adverse drug reactions. Ophthalmol Clin North Am. 2004 Sep. 17(3):481-8; viii. [Medline].

  19. Lessell S. Nutritional deficiency and toxic optic neuropathies. Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. 2nd ed. Philadelphia: WB Saunders Co; 2000.

  20. Mantyjarvi M, Tuppurainen K, Ikaheimo K. Ocular side effects of amiodarone. Surv Ophthalmol. 1998 Jan-Feb. 42(4):360-6. [Medline].

  21. Melamud A, Kosmorsky GS, Lee MS. Ocular ethambutol toxicity. Mayo Clin Proc. 2003 Nov. 78(11):1409-11. [Medline].

  22. Miller NR. Anterior toxic optic neuropathies. Walsh and Hoyt's Clinical Neuro-Ophthalmology. 4th ed. Baltimore: Lippincott Williams & Wilkins; 1982. 254-260.

  23. Miller NR. Retrobulbar toxic and deficiency optic neuropathies. Walsh and Hoyt's Clinical Neuro-ophthalmology. 4th ed. Baltimore: Lippincott Williams & Wilkins; 1982. 289-307.

  24. Phillips PH. Toxic and deficiency optic neuropathies. Miller NR, Newman NJ, eds. Walsh and Hoyt's Clinical Neuro-ophthalmology. 6th ed. Baltimore: Lippincott Williams & Wilkins; 2005. 447-463.

  25. Rizzo JF 3rd, Lessell S. Tobacco amblyopia. Am J Ophthalmol. 1993 Jul 15. 116(1):84-7. [Medline].

  26. Sadun AA. Metabolic optic neuropathies. Semin Ophthalmol. 2002 Mar. 17(1):29-32. [Medline].

  27. Woon C, Tang RA, Pardo G. Nutrition and optic nerve disease. Semin Ophthalmol. 1995 Sep. 10(3):195-202. [Medline].

 
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