Cathepsin B pH-Dependent Activity Is Involved in Lysosomal Dysregulation in Atrophic Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate in vitro model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients () to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, flow cytometry, and electronic microscopy. The toxicity level of iron after Fe-NTA treatment was evaluated by an MTT test and by the detection of dichloro-dihydro-fluorescein diacetate. Twelve hiPSC-RPE cell lines (6 AMD and 6 controls) were used for the experiment. Under basal conditions, all hiPSC-RPE cells expressed a phenotypic profile of senescent cells with rounded mitochondria at passage 2. However, the treatment with Fe-NTA induced higher reactive oxygen species production and cell death in hiPSC-RPE AMD cells than in hiPSC-RPE Control cells. Interestingly, functional analysis showed differences in lysosomal activity between the two populations. Indeed, Cathepsin B activity was higher in hiPSC-RPE AMD cells compared to hiPSC-RPE Control cells in basal condition and link to a pH more acidic in this cell population. Moreover, oxidative stress exposure leads to an increase of Cathepsin D immature form levels in both populations, but in a higher proportion in hiPSC-RPE AMD cells. These findings could demonstrate that hiPSC-RPE AMD cells have a typical disease phenotype compared to hiPSC-RPE Control cells

The Risks and Benefits of Myopia Control

The prevalence of myopia is increasing around the world, stimulating interest in 3 methods to slow its progression. The primary justification for slowing myopia progression is to 4 reduce the risk of vision loss through sight-threatening ocular pathology in later life. The paper 5 analyzes whether the potential benefits of slowing myopia progression by one diopter justify the 6 potential risks associated with treatments

Prevalence of macular complications related to myopia – Results of a multicenter evaluation of myopic patients in eye clinics in France

Purpose: Uncorrected refractive errors are the first cause of vision impairment worldwide. High myopia is a frequent cause of sight‐threatening chorioretinal complications. The aim of this study was to evaluate the prevalence of macular complications, visual impairment and blindness in patients with myopia. Methods: A cross‐sectional multicenter study carried out in French eye clinics mainly dedicated to refractive errors. Myopia severity was defined as mild (−0.5 to −3 D), moderate (−3 to −6 D), high (−6 to −10 D) and very high (more than −10 D). Macular complications related to myopia included lacquer cracks, myopic choroidal neovascularization, chorioretinal atrophy and retinoschisis. The prevalences of macular complications, blindness and vision impairment were estimated with respect to degree of myopia and age. Eligibility criteria were myopia on the left eye of −0.5 D or more. Exclusion criteria included any missing data related to subjective refractive error, age, gender and any history of cataract or refractive surgery. Results: Data files from 198 641 myopic individuals with a mean age of 34 years (SD: 15 years) were analysed. The prevalence of mild, moderate, high and very high myopia was, respectively, 65.95%, 26.14%, 6.72% and 1.19%. The prevalence of macular complications in the high and very high myopia groups was 0.5% [0.39–0.64] and 4.27% [3.49–5.17]. The prevalence of blindness or vision impairment was observed in 10.10% [8.91–11.39%] of the very high myopic group. At 60 years old or over, the prevalences of blindness or vision impairment were, respectively, 9.75% [7.91–11.85%] and 25.71% [21.00–30.87%] in the high and very high myopia groups. Conclusions: This multicenter cross‐sectional study provides new insights in terms of prevalence of macular complications related to myopia. To our knowledge, this is one of the largest European studies focusing on individuals with myopia, particularly on the macular complications and the functional consequences in relation to myopia

Progression of myopia in teenagers and adults: a nationwide longitudinal study of a prevalent cohort

Background- The prevalence of myopia is increasing worldwide. The purpose of this study was to evaluate the progression of myopia in teenagers and adults in France. Methods- This nationwide prospective study followed 630 487 myopic adults and teenagers (mean age 43.4 years±18.2, 59.8% of women) between January 2013 and January 2019. Myopia and high myopia were defined as a spherical equivalent less than or equal to –0.50 and –6.00 diopters (D), respectively. Demographic data were collected at first visit and refractive characteristics were collected at each visit. Analysis of short-term progression (first 12 to 26 months postbaseline) was modelled using analysis of variance (ANOVA). Progression of myopia was stratified according to age, gender and spherical equivalent at first visit. Results- Higher proportions of progressors were observed in the youngest age groups: 14–15 (18.2 %) and 16–17 years old (13.9 %). In multivariate analysis, after adjustment for over age, spherical equivalent and gender, the mean short-term progression decreased from –0.36 D in the 14–15 years age group to –0.13 D in the 28–29 years age group. Young age and higher myopia at baseline together were strongly associated with the risk of developing high myopia, the 5-year cumulative risk being 76% for youngest teenager with higher myopia status at baseline. Conclusion- In this large cohort of myopic teenagers and adults, myopia progression was reported in 18.2% and 13.9% of the 14–15 and 16–17 age groups, respectively. The risk to develop high myopia was higher for younger individuals with higher myopia at baseline examination

Progression of myopia in children and teenagers: a nationwide longitudinal study

Background: Data on myopia prevalence and progression in European children are sparse. The aim of this work was to evaluate the progression of myopia in children and teenagers in a large prospective study. Methods: A prospective study involving a nationwide cohort. Myopia was defined as a spherical equivalent (SE) of ≤ –0.50 diopters (D). Data on refractive error, gender and age were collected in 696 optical centres in France between 2013 and 2019, including 136 333 children (4–17 years old) in the analysis. Progression of myopia was assessed between the first visit and the last visit over up to 6.5 years. Results: Mean age was 11.3±3.8 years (55.0% of female). The proportion of children progressing more than –0.50 D per year was higher in age groups 7–9 years and 10–12 years and in children with SE ≤ –4.00 D at first visit, representing 33.1%, 29.4% and 30.0% of these groups, respectively. In multivariate analysis, progression during the first 11–24 months was higher in the 7–9 and 10–12 age groups (–0.43 D and –0.42 D, respectively), for higher SE at baseline (at least –0.33 D for SE ≤ –1 D) and for girls (–0.35 D). Conclusion: This is the first French epidemiological study to investigate myopia progression in a large-scale cohort of children. Sex, age groups and myopia severity are associated with differing rates of progression

Global estimates on the number of people blind or visually impaired by cataract:a meta-analysis from 2000 to 2020

BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals.METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity &lt;6/18, ≥3/60) and blindness (presenting visual acuity &lt;3/60). Estimates are age-standardized using the GBD standard population.RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%).CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.</p

Global estimates on the number of people blind or visually impaired by cataract:a meta-analysis from 2000 to 2020

BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals.METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity &lt;6/18, ≥3/60) and blindness (presenting visual acuity &lt;3/60). Estimates are age-standardized using the GBD standard population.RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%).CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.</p

IMI-Onset and Progression of Myopia in Young Adults

Myopia typically starts and progresses during childhood, but onset and progression can occur during adulthood. The goals of this review are to summarize published data on myopia onset and progression in young adults, aged 18 to 40 years, to characterize myopia in this age group, to assess what is currently known, and to highlight the gaps in the current understanding. Specifically, the peer-reviewed literature was reviewed to: characterize the timeline and age of stabilization of juvenile-onset myopia; estimate the frequency of adult-onset myopia; evaluate the rate of myopia progression in adults, regardless of age of onset, both during the college years and later; describe the rate of axial elongation in myopic adults; identify risk factors for adult onset and progression; report myopia progression and axial elongation in adults who have undergone refractive surgery; and discuss myopia management and research study design. Adult-onset myopia is common, representing a third or more of all myopia in western populations, but less in East Asia, where onset during childhood is high. Clinically meaningful myopia progression continues in early adulthood and may average 1.00 diopters (D) between 20 and 30 years. Higher levels of myopia are associated with greater absolute risk of myopia-related ocular disease and visual impairment, and thus myopia in this age group requires ongoing management. Modalities established for myopia control in children would be options for adults, but it is difficult to predict their efficacy. The feasibility of studies of myopia control in adults is limited by the long duration required.</p