Ethambutol Optic Neuropathy

Paul D. Chamberlain; Ama Sadaka; Shauna Berry; Andrew G. Lee


Curr Opin Ophthalmol. 2017;28(6):545-551. 

In This Article


There is currently no effective treatment for EON. However, if detected early and with prompt discontinuation of ethambutol, between 30 and 64% of patients show some improvement in their visual disturbances over a period of several months.[4,5,31,58,59] In patients who show improvement, however, few will have full recovery, with an average improvement of two lines on the Snellen chart.[4,7,31] One small case series of 10 patients with EON found that in patients over 60 years old the recovery rate was only 20%, whereas it was 80% for patients less than 60 years old, suggesting that increased age may prognosticate poorer recovery.[58] Ophthalmologists who suspect EON should contact the ethambutol-prescribing provider immediately to discuss discontinuation or reduction of prescription dosing.

Understanding the pathogenesis of EON is critical to finding an effective treatment. Ocular tissue has high levels of zinc,[60] and several studies have shown that ethambutol causes chelation of zinc[3,61] as well as copper.[62] In addition, other studies have suggested other nutrients that may predict EON development. One study of 50 patients found that decreased levels of vitamin E and vitamin B were associated with EON development,[63] and a small case series reported patients who had visual recovery following cobalamin administration.[64] It is thought that EON may be in part due to a deficiency in these nutrients, particularly zinc and copper, as zinc deficiency has been found to be related to destruction of myelin and glial cell proliferation in rat optic nerves.[65] In addition, patients with low plasma zinc levels have been found to have a higher likelihood of developing EON.[66] Supplementation with zinc and copper for patients taking ethambutol has thus been proposed as a method of reducing the likelihood of EON. Importantly, such supplementation in vitro has not decreased the efficacy of ethambutol in fighting mycobacterium,[1] and did not change the rate of pulmonary TB clearance in a randomized control trial of patients taking micronutrients with ethambutol.[67] However, more research is needed to know if such supplementation is effective in reducing EON risk. Although we do not recommend routinely testing serum zinc or copper levels in patients taking ethambutol, it may provide some benefit for relatively little risk, and supplementation in patients may be undertaken at the provider's discretion.