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Toxic Optic Nerve Disease

Toxic optic nerve damage and blindness can be caused by a large number of poisionous substances, drugs, nutritional deficiencies, metabolic disorders and radiation.

Smoking, alcohol, barbiturates, DDT, lead, and aniline dyes; some antibiotics and other prescribed drugs such as digitalis, ergotamine, inderal, ethambutol and suramin sodium used to treat heart disease, migraine, hypertension, tuberculosis and HIV respectively are just a few examples known or suspected to cause optic nerve damage in some situations. Many of these agents lead to permanent blindness but visual loss can be stopped in some if diagnosed early.

Benzalkonium chloride, a quaternary ammonium compound surfactant preservative very commonly used in eye drops for glaucoma, has been found to potently induce mitochondrial dysfunction and preferentially affect LHON mutant cells in pharmaceutical concentrations.

Visual loss from nutritional deficiency occurs less frequently in developed countries and occasionally in strict vegan vegetarians with vitamin B12 and B1 deficiencies.

Metabolic problems such as sugar diabetes, kidney failure and thyroid disease can cause optic neuropathy likely through build up of toxic substances within the body.

Ultra violet radiation in sunlight can cause a chain reaction of damaging free radical release in the eye which is thought to contribute to premature aging processes in the eye and vision loss.

Toxic optic nerve disease requires much more study but it is known to be similar to LHON, which suggests common pathophysiological mechanisms. It is also known that people can inherit tendencies to be susceptible to toxic substances. Such is the case with LHON and smoking and interestingly, in a parallel mitochondrial disease, aminoglycoside (antibiotic)-induced nerve deafness.

It is highly recommended that those with a family history of optic nerve or retinal disease enquire themselves and with their health professional about possible eye toxicity before being exposed to any drug or substance.

Examples of known or suspected eye toxins and recommended references are found below.

Medications with demonstrated adverse effects on mitochondria in LHON [* strong evidence]:
Antimicrobials: Erythromycin*, Ethambutol*, Linezolid*, Chloramphenicol*, Aminoglycosides, Tetracyclines. Hyperbaric oxygen; Quaternary ammonium compounds; Ringer’s lactate.

Classes of drugs with potential for adverse mitochondrial effects in LHON:
Antidepressants; Antipsychotics; Barbiturates; Anxiety medications; Anticonvulsants; Cholesterol medications; Inflammatory/analgesic medications; Anti-arrhythmic medications; Beta blockers; Antiviral medications; Chemotherapeutics; Diabetes medications.

Eye Neurotoxins - A sample list.
SubstanceDescription
Tobacco smoke Known to be associated with colour vision defects. LHON gene carriers are more likely to lose vision.
Alcohol (Ethanol) Tobacco-alcohol amblyopia syndrome. LHON gene carriers are more likely to lose vision.
Ultra violet radiation Excessive amounts implicated in adult onset macular degeneration
Methyl Alcohol Acutely toxic
Carbon monoxide Seen in accidental or suicide attempt exposure. Possibly part of the mechanism of tobacco smoke neurotoxicity. Binds to heme groups in blood hemoglobin, metabolic regulatory proteins and the mitochondial electron transport chain.
Toluene Excessive amounts implicated in adult onset macular degeneration
Thallium  
Erythromycin Antibiotic. Can cause mitochondrial dysfunction in LHON carriers.
Ethambutol Anti tuberculosis antibiotic. Can cause mitochondrial dysfunction in LHON carriers.
Chloramphenicol Antibiotic. Can cause mitochondrial dysfunction in LHON carriers.
Linezolid Antibiotic. Can cause mitochondrial dysfunction in LHON carriers.
Isoniazid Anti tuberculosis antibiotic.
Chloroquine Anti malarial and anti rheumatic.
Tetracycline antibiotics Possibly can precipitate Mitochondrial Dysfunction in LHON carriers.
Aminoglycoside antibiotics Possibly can precipitate Mitochondrial Dysfunction in LHON carriers.
Suramin sodium Anti HIV drug. Causes optic neuropathy.
Ziduvodine Anti HIV drug. Causes retinopathy.
Vigabatrin Anti epilepsy drug associated with visual field defects. GABA transaminase inhibitor.
Chlorpropamide Anti diabetes tablet.
Metformin Anti diabetes tablet. Theoretical issue with LHON.
Digitalis Heart antiarhythmic acting as a Na+,K+-ATPase (sodium pump) inhibitor.
Amiodarone Heart antiarhythmic.
Propranolol Heart antiarhythmic/ Beta-blocker/anti high blood pressure drug. Lowers intraocular pressure and may predispose to anterior ischemic optic neuropathy.
Prazosin (Minipress) and Terazosin (Hytrin) Alpha blocker/anti High Blood Pressure/counter prostatism drugs. Low night time blood pressure and may predispose to anterior ischemic optic neuropathy.
Quinineanti malarial
Sildenafil (Viagra) Anti impotence drug. One report of associated anterior ischemic neuropathy.
5-FU Anti cancer drug.
Taxane Anti cancer drug. Can induce glaucomatous optic nerve disease.
Vioform Antibiotic topical and antidiarrheal.
Benzalkonium Chloride Common eye drop preservative and household disinfectant. Potently induces mitochondrial dysfunction and preferentially affects LHON mutant cells.
Hyperbaric oxygen Can precipitate mitochondrial dysfunction in LHON carriers.
Ringer's lactate or Hartmanns solution Can precipitate Mitochondrial Dysfunction in LHON carriers.

References:

Kailenn Tsao, Phil A Aitken, Donald R Johns. Smoking as an aetiological factor in a pedigree with Leber's hereditary optic neuropathy [full text] Br J Ophthalmol 1999;83:577-581 ( May )

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells. Sandipan Datta; Christophe Baudouin; Francoise Brignole-Baudouin; Alexandre Denoyer; Gino A. Cortopassi. Investigative Ophthalmology & Visual Science April 2017, Vol.58, 2406-2412. doi:10.1167/iovs.16-20903

Toxic medications in Leber's hereditary optic neuropathy. Kogachi K, Ter-Zakarian A, Asanad S, Sadun A, Karanjia R. Mitochondrion. 2019 May;46:270-277. doi: 10.1016/j.mito.2018.07.007. Epub 2018 Aug 4. PMID: 30081212 full text paywall: https://doi.org/10.1016/j.mito.2018.07.007

toxic+optic+neuropathy PubMed search

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