SECOND PRIZE, COS AWARDS FOR EXCELLENCE IN OPHTHALMIC RESEARCH

Author Block: Alexander L. Pearson, Lissa Poincenot, Rustum Karanjia
Author Disclosure Block: A.L. Pearson: None. L. Poincenot: None. R. Karanjia: None.

Abstract Body:

Purpose: Leber’s hereditary optic neuropathy (LHON) is the most common inherited mitochondrial disease. It results in acute/subacute, painless, profound loss of central and color vision. The current literature reports males as 4-5 times more likely than females to be affected by LHON, and that symptom onset occurs during late teen/young adult life. As a result, LHON is usually called a “young man’s disease.” However, this may be a self-fulfilling prophecy, with consequential underdiagnosis of females, older adults and children. The purpose of this study was to analyze the epidemiology of LHON using a large international database of people affected by LHON.

Study Design: Cross-sectional.

Methods: People with a diagnosis of LHON confirmed by genetic testing were contacted through the LHON community and provided self-reported data (age of symptom onset, gender, mutations, and location), which was compiled and analyzed. According to the World Health Organization, young people are individuals between the ages of 10 and 24. As a result, we took “young men” to refer to males between the ages of 10 and 24. Results: 1489 people affected by LHON were included. In contrast to the existing literature, 45% of our data set consisted of “young men”. Unlike the traditional 5:1 male to female ratio, we found a 3:1 M:F ratio. The commonly reported peak in symptom onset (ages 14-26) was found only in males. 10.4% of those affected had LHON onset after age 50, whereas the current literature states only 5%. Below the age of 5 and after 45, the M:F ratio of conversion was approximately 1:1. As per the literature, we found that the m.11778 (69%), m.14484 (17%) and m.3460 (13%) were the most common mutations.

Conclusions: This is the largest epidemiological study of LHON to date. It suggests that females, older adults and children carrying a LHON mutation are at higher risk of losing vision than is generally expected. Contrary to the existing literature, LHON affects females and males of all ages, rather than just young men. This should prompt physicians to conduct genetic testing for LHON in patients who meet the clinical criteria, regardless of whether they fit the traditional demographics.