Although mitochondrial mutation abundance has been recognized to increase in an age-dependent manner, the impact of mutation has been more difficult to establish. Using quantitative polymerase chain reaction, we measured the intracellular abundance of mutant and wild-type mitochondrial genomes along the length of individual laser-captured microdissected muscle fibers from aged rat quadriceps. Aged muscle fibers possessed segmental, clonal intracellular expansions of unique somatically derived mitochondrial DNA (mtDNA) deletion mutations. When the mutation abundance surpassed 90% of the total mitochondrial genomes, the fiber lost cytochrome c oxidase activity and exhibited an increase in succinate dehydrogenase activity. In addition to the mitochondrial enzymatic abnormalities, some fibers displayed abnormal morphology such as fiber splitting, atrophy, and breakage. Deletion mutation accumulation was linked to these aberrant morphologies with more severe cellular pathologies resulting from higher deletion mutation abundance. In summary, our measurements indicate that age-induced mtDNA deletion mutations expand within individual muscle fibers, eliciting fiber dysfunction and breakage.

Purpose To describe the prevalence and interrelationships of epiretinal membranes, vitreomacular traction, macular cysts, paravascular cysts, lamellar macular holes, full-thickness macular holes, and visual impairment in a population-based study of older adults. Design Cross-sectional study. Participants There were 1913 participants aged 63–102 years at the 20-year Beaver Dam Eye Study follow-up examination in 2008–2010, of whom 1540 (2980 eyes) had gradable spectral-domain optical coherence tomography (SD-OCT) scans of the macula in at least one eye. Methods The presence of epiretinal membranes and other retinal lesions was determined by standardized grading of macular SD-OCT scans and photographs of three standard fields. Main Outcome Measures Epiretinal membranes, vitreomacular traction, macular cysts, paravascular cysts, lamellar macular holes, full-thickness macular holes, and visual impairment. Results Using SD-OCT the prevalences of epiretinal membranes (34.1%), vitreomacular traction (1.6%), macular cysts (5.7%), paravascular cysts (20.0%), lamellar macular holes (3.6%), and full-thickness macular holes (0.4%) were estimated. The prevalences of macular cysts (P<0.001), epiretinal membranes (P<0.001), and vitreomacular traction (P=0.005) increased with age, the prevalence of paravascular cysts (P=0.05) decreased with age, and the prevalence of lamellar macular holes was not associated with age (P=0.70). The prevalences of macular cysts, lamellar macular holes, and epiretinal membranes were higher in eyes with a history of cataract surgery. Macular cysts and epiretinal membranes were more common in eyes with retinal diseases such as proliferative diabetic retinopathy, retinal vein occlusion, and retinal detachment than in eyes without these conditions. Macular cysts, epiretinal membranes, and full-thickness macular holes were associated with visual impairment. While adjusting for age and sex, macular cysts (odds ratio [OR] 3.96; P<0.0001), paravascular cysts (OR 1.45, P=0.007), lamellar macular holes (OR 10.62; P<0.001), vitreomacular traction (OR 2.72, P=0.01) and visual impairment (OR 3.23; p<0.001) were more frequent in eyes with epiretinal membranes compared to eyes without. Conclusions Epiretinal membranes are associated with macular cysts, paravascular cysts, lamellar macular holes, vitreomacular traction, and visual impairment. Further follow-up will allow better understanding of the natural history of epiretinal membranes and vitreomacular traction and their relationships to the development of macular cysts and lamellar macular holes in the aging population.

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IMPORTANCE Artifacts can affect optical coherence tomographic angiography (OCTA) images and may be associated with misinterpretation of OCT scans in both clinical trials and clinical settings.OBJECTIVES To identify the prevalence and type of artifacts in OCTA images associated with quantitative output and to analyze the role of proprietary quality indices in establishing image reliability.

Purpose To examine relationships of age, sex, and systemic and ocular conditions with retinal thickness measured by spectral-domain ocular coherence tomography (SD-OCT) in participants without retinal disease. Design Longitudinal study. Methods Setting Population-based cohort. Study Population Persons aged 43-86 years living in Beaver Dam, Wisconsin in 1988-1990. Observation Procedures Retinal thickness was measured via SD-OCT at the Beaver Dam Eye Study examination in 2008-2010. Retinal disease was determined by ophthalmoscopy, fundus photography, or SD-OCT. Main Outcome Measures Retinal thickness from the inner limiting membrane to Bruch's membrane. Results The retina was thickest in the inner circle (mean 334.5 μm) and thinnest in the center subfield (285.4 μm). Mean retinal thickness decreased with age in the inner circle (P<0.0001) and outer circle (P<0.0001). Adjusting for age, eyes in men had thicker retinas than eyes in women in the center subfield (P<0.001) and inner circle (P<0.001). Sex, axial length/corneal curvature ratio, and peak expiratory flow rate were associated with center subfield thickness. Sex and peak expiratory flow rate were associated with retinal thickness in the inner circle. Alcohol consumption, age, axial length/corneal curvature ratio, cataract surgery, ocular perfusion pressure, and peak expiratory flow rate were associated with retinal thickness in the outer circle. Conclusions This study provides data for retinal thickness measures in eyes of individuals aged 63 years and older without retinal disease. This information may be useful for clinical trials involving the effects of interventions on retinal thickness and for comparisons with specific retinal diseases affecting the macula.

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SummaryMitochondrial DNA (mtDNA) deletion mutations colocalize with electron transport system (ETS) abnormalities in rhesus monkey skeletal muscle fibers. Using laser capture microdissection in conjunction with PCR and DNA sequence analysis, mitochondrial genomes from single sections of ETS abnormal fibers were characterized. All ETS abnormal fibers contained mtDNA deletion mutations. Deletions were large, removing 20-78% of the genome, with some to nearly all of the functional genes lost. In one-third of the deleted genomes, the light strand origin was deleted, whereas the heavy strand origin of replication was conserved in all fibers. A majority (27/39) of the deletion mutations had direct repeat sequences at their breakpoints and most (36/39) had one breakpoint within or in close proximity to the cytochrome b gene. Several pieces of evidence support the clonality of the mtDNA deletion mutation within an ETS abnormal region of a fiber: (a) only single, smaller than wild-type, PCR products were obtained from each ETS abnormal region; (b) the amplification of mtDNA from two regions of the same ETS abnormal fiber identified identical deletion mutations, and (c) a polymorphism was observed at nucleotide position 16103 (A and G) in the wild-type mtDNA of one animal (sequence analysis of an ETS abnormal region revealed that mtDNA deletion mutations contained only A or G at this position). Species-specific differences in the regions of the genomes lost as well as the presence of direct repeat sequences at the breakpoints suggest mechanistic differences in deletion mutation formation between rodents and primates.

Purpose: To evaluate the prevalence of intermediate-stage age-related macular degeneration (AMD) in patients with the acquired immunodeficiency syndrome (AIDS). Design: Cross sectional study of patients with AIDS enrolled in the Longitudinal Study of the Ocular Complications of AIDS Methods: Intermediate-stage AMD was determined from enrollment retinal photographs by graders at a centralized Reading Center, using the Age-Related Eye Disease Study grading system. Graders were masked as to clinical data. Results: Of 1825 participants with AIDS and no ocular opportunistic infections, 9.9% had intermediate-stage AMD. Risk factors included age, with an odds ratio (OR) of 1.9 (95% confidence interval [CI] 1.6, 2.3, P<0.001) for every decade of age; the prevalence of AMD ranged from 4.0% for participants 30–39 years old to 24.3% for participants ≥60 years old. Other risk factors included the HIV risk groups of injection drug use (OR= 2.4, 95% CI 1.5, 3.9, P<0.001) or heterosexual contact (OR=1.9, 95% CI 1.3, 2.8, P=0.001). Compared with the HIV-uninfected population in the Beaver Dam Offspring Study, there was an approximate 4-fold increased age-adjusted prevalence of intermediate-stage AMD. Conclusions: Patients with AIDS have an increased age-adjusted prevalence of intermediate-stage AMD compared with that found in a non-Human Immunodeficiency Virus (HIV)-infected cohort evaluated with similar methods. This increased prevalence is consistent with the increased prevalence of other age-related diseases in antiretroviral-treated, immune-restored, HIV-infected persons when compared to non-HIV-infected persons.