Novel Missense Mutations in <i>BEST1</i> Are Associated with Bestrophinopathies in Lebanese Patients

To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A&gt;G, p.(Asp70Gly) in exon 3, M2, c.1403C&gt;T; p.(Pro468Leu) in exon 10 and M3, c.830C&gt;T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion

Self‐reported dual sensory impairment, dementia, and functional limitations in Medicare beneficiaries

BackgroundVision and hearing impairments often co‐exist with dementia, and all are independently associated with limitations in daily activities. Our aim was to examine the association of dual sensory impairment with functional limitations, and further examine the combined estimated association of sensory impairment and dementia with these functional limitations.MethodsCross‐sectional analysis of the National Health and Aging Trends Study (NHATS), a population‐based cohort of Medicare beneficiaries, was performed. Participants were selected from the 2015 round. Survey weighted Poisson regression models adjusted for dementia, demographics, and health status variables examined the association of self‐reported dual sensory impairment (no sensory impairment, single sensory impairment, dual sensory impairment) with scores of limitations in mobility, self‐care, and household activities. Models were repeated to take into account the combined effects of dual sensory impairment and dementia.ResultsOverall, 7124 participants representative of Medicare beneficiaries 65 years or older were included. Of them, 43.9% were 75 years or older and 55.3% were female. Older adults with dual sensory impairment had greater limitations with mobility (prevalence rate ratio [PRR] = 1.45, 95% CI = 1.28–1.63), self‐care (PRR = 1.41, 95% CI = 1.25–1.59), and household activities (PRR = 1.54, 95% CI = 1.37–1.72) compared with those without sensory impairment. They also had greater limitations than those with a single sensory impairment across the different activity categories. In models taking into account the combined estimated effect of both sensory impairment and dementia, those with dual sensory impairment and dementia had greater limitations than those without sensory impairment or dementia in each category (mobility: PRR = 1.85, 95% CI = 1.59–2.14, self‐care: PRR = 1.86, 95% CI = 1.59–2.18, household: PRR = 2.41, 95% CI = 2.09–2.77).ConclusionsOlder adults with dual sensory impairment had greater functional limitations compared with those without sensory impairment and those with a single sensory impairment. Strategies to improve visual and/or hearing function (e.g., sensory aids, rehabilitation) could potentially help prevent or minimize disability, even among those with dementia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171253/1/jgs17448.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171253/2/jgs17448-sup-0001-Tables.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171253/3/jgs17448_am.pd

A Global Assessment of Eye Health and Quality of Life A Systematic Review of Systematic Reviews

IMPORTANCE: More than 1 billion people worldwide have vision impairment or blindness from potentially preventable or correctable causes. Quality of life, an important measure of physical, emotional, and social well-being, appears to be negatively associated with vision impairment, and increasingly, ophthalmic interventions are being assessed for their association with quality of life. OBJECTIVE: To examine the association between vision impairment or eye disease and quality of life, and the outcome of ophthalmic interventions on quality of life globally and across the life span, through an umbrella review or systematic review of systematic reviews. EVIDENCE REVIEW: The electronic databases MEDLINE, Ovid, Embase, Cochrane Database of Systematic Reviews, Proquest Dissertations, and Theses Global were searched from inception through June 29, 2020, using a comprehensive search strategy. Systematic reviews addressing vision impairment, eye disease, or ophthalmic interventions and quantitatively or qualitatively assessing health-related, vision-related, or disease-specific quality of life were included. Article screening, quality appraisal, and data extraction were performed by 4 reviewers working independently and in duplicate. The Joanna Briggs Institute critical appraisal and data extraction forms for umbrella reviews were used. FINDINGS: Nine systematic reviews evaluated the association between quality of life and vision impairment, age-related macular degeneration, glaucoma, diabetic retinopathy, or mendelian eye conditions (including retinitis pigmentosa). Of these, 5 were reviews of quantitative observational studies, 3 were reviews of qualitative studies, and 1 was a review of qualitative and quantitative studies. All found an association between vision impairment and lower quality of life. Sixty systematic reviews addressed at least 1 ophthalmic intervention in association with quality of life. Overall, 33 unique interventions were investigated, of which 25 were found to improve quality of life compared with baseline measurements or a group receiving no intervention. These interventions included timely cataract surgery, anti-vascular endothelial growth factor therapy for age-related macular degeneration, and macular edema. CONCLUSIONS AND RELEVANCE: There is a consistent association between vision impairment, eye diseases, and reduced quality of life. These findings support pursuing ophthalmic interventions, such as timely cataract surgery and anti-vascular endothelial growth factor therapy, for common retinal diseases, where indicated, to improve quality of life for millions of people globally each year