Demographics of a Large International Population of Patients Affected by Leber's Hereditary Optic Neuropathy.

PURPOSE: To study the demographics of Leber's hereditary optic neuropathy (LHON) using a large international database of people affected by LHON. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand five hundred seventeen people affected by LHON with a known pathogenic genetic mutation. METHODS: Self-reported genetic and demographic data were collected. The data were de-identified and then analyzed. MAIN OUTCOME MEASURES: Leber's hereditary optic neuropathy mutation, gender, age at vision loss onset, and geographical region. RESULTS: The data showed that both females and males can experience symptom onset at any age. We found a 3:1 male-to-female ratio. Interestingly, at younger than 5 years and older than 45 years, the male-to-female ratio of those becoming affected was approximately 1:1. A dramatic peak in age at onset of vision loss was found among males between 14 and 26 years of age. Disease onset in females occurred across all age groups, without any comparable dramatic peak of onset age. This study found that 10% of individuals become affected with LHON after 50 years of age. According to the literature, we found that the m.11778, m.14484, and m.3460 mutations were the most common LHON point mutations in both males and females, with a similar age at onset distribution. CONCLUSIONS: This was the largest study of LHON demographics to date. It showed that women carrying an LHON mutation are at higher risk of losing vision than is generally expected. Unlike the traditional 5:1 male-to-female ratio commonly reported in the literature, we found a 3:1 male-to-female ratio. Earlier studies may have harbored an ascertainment bias of overemphasizing the confirmation of this being a disease of young men. However, our data suggest that LHON is a disease that affects both females and males of all ages. This should prompt physicians to conduct genetic testing for LHON in all patients who meet the clinical criteria, regardless of whether they fit the demographics traditionally associated with the disease. Counseling about LHON should be offered to all maternal bloodline relatives, females and males of all ages, because they are at risk of sudden-onset legal blindness.

An International Study of Emotional Response to Bilateral Vision Loss Using a Novel Graphical Online Assessment Tool.

BACKGROUND: Leber׳s hereditary optic neuropathy usually causes rapid bilateral blindness in young adults, and thus represents a unique and severe psychologic stressor. OBJECTIVE: We aimed to describe adjustment to this major life event, using a new tool to enhance recall of past affective states by using life event-related context. This is the largest (n = 116 with Leber׳s hereditary optic neuropathy), and first study reporting on the emotional aspects of this nontrauma cause of blindness. METHODS: We developed a new online survey tool that allowed study subjects to report their mood over a long period of time, corresponding with dates of relevant life events. RESULTS: The new method provided data of great richness for qualitative and quantitative analysis. Three groups were identified: a group in which majority of them had severe sadness at the point of vision loss followed by a period of recovery, a group whose sadness had not recovered, and a group for whom vision loss was not a major cause of sadness compared with other life events. We identified numerous factors that were important in psychologic recovery, and premorbid psychologic symptoms were more frequent in those who had not yet recovered. CONCLUSIONS: These data may assist behavioral health providers in identifying patients with vision loss to be at risk of mental health problems and in developing support and treatment interventions. We believe this new method has great potential for studying psychologic adjustment retrospectively.

Profound vision loss impairs psychological well-being in young and middle-aged individuals.

PURPOSE: The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. METHODS: A questionnaire was issued to individuals aged 13-65 years with profound vision loss resulting from Leber's hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from -10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. RESULTS: A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = -5) and career goals (median IR = -6) were observed; both ratings were worse (P<0.001) for depressed versus nondepressed subjects. Older age at diagnosis corresponded to higher depression prevalence and increased incidence of negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids (P=0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. CONCLUSION: Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by age and use of electronic vision aids. Ophthalmologists, in addition to managing vision loss, may serve an important role in the emotional adaptation of these patients.