Clinical background

TON patients usually present with a history of exposure to a foreign substance. Except in a few cases of acute toxicities, e.g., methanol or cyanide toxicity, onset occurs only after several months of exposure. The acute toxicities usually cause irreversible damage to the visual system, while damage in subacute cases of TON is usually reversible, especially if exposure to the toxin is stopped. Both eyes are involved; however, in some cases it may be a number of weeks before the damage is clinically evident in the second eye. There are no pathognomonic features in the diagnosis of TON. The disease is painless, so if the patient experiences eye pain, clinicians should consider another diagnosis. The observant patient may note dyschromatopsia as an early complaint. This may present as certain colors not appearing as vivid or bright as usual, or as generalized suppression of overall color vision. Blurred vision followed by a generalized decrease, primarily of central vision, is an early symptom ( Box 46.4 ).

Historical background

One of the first case studies of a suspected TON was of tobacco–alcohol amblyopia. This was described by Beer in 1817 with extensive follow-up studies by others in the late 1800s. However, the first to put the TON in perspective was George Edmund de Schweinitz in 1897. de Schweinitz wrote the initial classic paper on “toxic amblyopia,” helping ophthalmologists understand the importance of these adverse effects on the optic nerve and also expanding our knowledge of optic nerve pathology. He used the term “toxic amblyopia” as a general designation for diseases of visual loss secondary to exposure to external poisons.

Epidemic nutritional optic neuropathy (ENON) was best documented by physicians treating Allied prisoners during World War II and in studies of Cuban epidemic optic neuropathy (CEON). In both groups, signs and symptoms occurred in the undernourished only after roughly 4 months (or more) of poor diet. These studies, especially those of CEON, gave birth to the classic paper proposing nongenetic MON.

Epidemiology

TON are rare except in epidemics, where the cause was initially unknown, such as in Cuba with CEON or in the far East with the amebicides diiodohydroxyquin or iodochlorhydroxyquin. However, once the causative factor or factors are suspected, the incidence of TON is small. Socioeconomics often play a role, especially in TON, which may be multifactorial since in these diseases syndrome malnutrition is often prominent. Also, as in CEON, home-brewed alcohol may be a factor, and home brew was more commonly consumed in the lower-income communities. Age is important, as shown with cocaine optic neuropathy. This is only seen in newborns whose mothers were users of cocaine during pregnancy. TON associated with home-brewed alcohol or tobacco use is seen more commonly in males. In some cases, TON are caused by occupational exposure to toxins, as with arsenic or cyanide.

To date, TON may not have clearcut subsets in which disease severity or protection from the disease is genetically driven. There are, however, case reports of “idiosyncratic” dramatic loss of vision (within days) whereas the usual history is of many months of toxin exposure. Dotti et al described a case of ethambutol-induced optic neuropathy possibly aggravated by a genetic predisposition to optic nerve pathology. There are many ways that genetics can be involved, from how the toxin is absorbed to how it is metabolized or interacts with other factors. In time, we will probably find that there will be subsets of this disease in which genetics will play a role.

Diagnostic workup

The level of workup depends on the clinical findings and what tests are available in the medical community. At a minimum, the examination should include:

• 1.
  

  A suspicion that a toxin is involved and a careful history with inquiries about possible exposure, as well as consideration of the probability of others who were exposed having a similar disease pattern.

  
  
• 2.
  

  An ophthalmic examination with dilation of the pupils, manifest refraction, Amsler grid, color vision testing, and detailed optic nerve evaluation.

  
  
• 3.
  

  Visual fields testing, e.g., Humphrey 24-2.

Depending on the suspected cause of disease and the availability of the tests, the examination may also include photographs of the optic disc, visual evoked potential testing, and contrast sensitivity tests using either Arden or Pelli–Robson contrast sensitivity plates.

Differential diagnosis

If there is bilateral uncorrected visual loss with otherwise normal findings, one should consider:

• 1.
  

  Toxic and nutritional optic neuropathies

  
  
• 2.
  

  Ruling out maculopathy. This may require fluorescein angiography or focal electroretinograms for diagnosis

  
  
• 3.
  

  Conversion disorder or malingering

  
  
• 4.
  

  MON

  
  
• 5.
  

  Kjer’s optic neuropathy

  
  
• 6.
  

  Compressive or infiltrative optic chiasm lesion

  
  
• 7.
  

  Demyelinating, inflammatory, or infectious optic neuritis, which rarely affects both eyes

  
  
• 8.
  

  Nonarteritic ischemic optic neuropathy.