Although smoking and alcohol are known to increase incidence of Leber's Hereditary Optic Neuropathy (LHON) only smoking increases severity of LHON.

Abstract

Purpose: To characterize clinical outcome in a previously described pedigree with Leber's Hereditary Optic Neuropathy (LHON) in relation to environmental toxin exposure.

Methods: Clinical data was collected as previously described (Sadun, F. et al., Am J Ophthalmol. 2004 Feb;137(2):271-7). Patients were characterized by disease status: affected (n=34), carriers (n=150) and controls (n=298). We used an OLS regression to look between and within groups for differences in optical characteristics, namely visual acuity (Va) and color vision (CVa), controlling for age and gender. We then used the regression to look for differences in clinical outcomes within these groups for environmental exposures including smoking, alcohol and occupational exposure to toxic chemicals. As all analyses were based on the same dataset, we adjusted for “multiple looks” using the Bonferroni Correction.

Results: As expected, the affected group had a statistically worse Va compared to the control group. There was no significant difference between the control and carrier groups. Increasing age was found to be correlated with reduced Va in both control and carrier groups. In controls, occupational exposure to toxins did not impact Va. There was no significant difference in Va within the control group between those who smoked regularly or consumed alcohol and those who did not smoke or consume alcohol regularly. However, within both the carrier and affected LHON groups, having smoked regularly was associated with a significantly poorer Va. Notably, using alcohol was associated with a significantly better Va relative to those who did not. This is contrary to our expectations given the published data showing that alcohol consumption increases incidence of LHON in carriers (Sadun, F. et al., 2004 and Kirkman, MA et al., Brain. 2009 Sep;132(Pt 9):2317-26). The explanation might be related to alcohol producing contrary effects at different dosing. Unfortunately, the present data set did not provide accurate quantification of alcohol consumption. CVa was significantly worse in carriers and affected patients when compared to controls.

Conclusions: This is the first study to quantify visual acuity changes relative to toxic exposures in a large pedigree of LHON patients. Increasing age and smoking were associated with decreased visual acuity in both the affected and carrier groups.

Keywords: 600 mitochondria • 531 ganglion cells • 613 neuro-ophthalmology: optic nerve