PurposeThe 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.MethodsA 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.ResultsA 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.ConclusionProfound 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.

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-tofemale 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.

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Summary The best scientific evidence for use of a clinical intervention is based upon data obtained from Phase III clinical trials. The robustness of a clinical trial is dependent on the quality of the metrics collected which in turn is dependent on the design of the study. Clinical trials involving inherited optic neuropathies such as Leber's Hereditary Optic Neuropathy (LHON) encounter some unique challenges which can be divided into two broad groups: patient‐centric factors and test‐centric factors. Patient‐centric factors include the heterogeneous phenotypic presentations in LHON with variable rates of spontaneous recovery and time to nadir and plateau. Test‐centric factors include the subjective nature of most visual metrics; intertest and intratest variability, which is compounded by patient adaptation to visual loss. Collectively these issues must be addressed when designing a clinical trial, especially in rare diseases where patient recruitment can be a challenge

PurposeTo investigate the incidence and characteristics of Charles Bonnet syndrome (CBS) in patients with Leber’s hereditary optic neuropathy (LHON) via an online questionnaire shared with the LHON patient community.MethodsA recently validated French‐Canadian CBS screening questionnaire was adapted to an online bilingual (English‐French) format while being tailored to LHON patients. It was distributed to numerous mailing lists and online communities consisting of LHON patients. The 62‐item questionnaire was organized into 3 parts to cover 9 dimensions: Demographics, Screening questions for CBS, Characteristics of hallucinations, Psychological impact, Psychopathological origin, Coping strategies, Context of appearance of hallucinations, Time‐related matters, Psychosocial support. Quantitative and qualitative response data were used for cross‐sectional analysis.ResultsA total of 63 LHON patients (71% male) completed the questionnaire – with 56% screening positive for CBS. Comparing CBS‐positive and CBS‐negative patients revealed significantly different LHON mutation distributions (p = 0.01137).Among CBS‐positive patients, 74% reported experiencing hallucinations for at least one year. Furthermore, 37% said the images disturb their sleep, while 49% reported they negatively affect their mood. Additionally, only 49% had heard of CBS before and just a single patient (3%) had been diagnosed with CBS by a healthcare professional.ConclusionsThe results show there is a significant prevalence of CBS among LHON patients, but only a minority of these patients are being assessed and managed for the condition. There is also an indication that CBS tends to be long‐lasting and can be associated with various negative health outcomes. Early diagnosis and counseling of patients are important to help alleviate stress and anxiety related to CBS and improve quality of life.