Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis

Background: Contemporary data on causes of vision impairment and blindness form an important basis for recommendations in public health policies. Refreshment of the Global Vision Database with recently published data sources permitted modeling of cause of vision loss data from 1990 to 2015, further disaggregation by cause, and forecasts to 2020. Methods: Published and unpublished population-based data on the causes of vision impairment and blindness from 1980 to 2015 were systematically analysed. A series of regression models were fit to estimate the proportion of moderate and severe vision impairment (MSVI; defined as presenting visual acuity <6/18 but ≥3/60 in the better eye) and blindness (presenting visual acuity <3/60 in the better eye) by cause by age, region, and year. Findings: Among the projected global population with MSVI (216.6 million; 80% uncertainty intervals [UI] 98.5-359.1), in 2015 the leading causes thereof are uncorrected refractive error (116.3 million; UI 49.4-202.1), cataract (52.6 million; UI 18.2-109.6), age-related macular degeneration (AMD; 8.4 million; UI 0.9-29.5), glaucoma (4.0 million; UI 0.6-13.3) and diabetic retinopathy (2.6 million; UI 0.2-9.9). In 2015, the leading global causes of blindness were cataract (12.6 million; UI 3.4-28.7) followed by uncorrected refractive error (7.4 million; UI 2.4-14.8) and glaucoma (2.9 million; UI 0.4-9.9), while by 2020, these numbers affected are anticipated to rise to 13.4 million, 8.0 million and 3.2 million, respectively. Cataract and uncorrected refractive error combined contributed to 55% of blindness and 77% of MSVI in adults aged 50 years and older in 2015. World regions varied markedly in the causes of blindness, with a relatively low prevalence of cataract and a relatively high prevalence of AMD as causes for vision loss in the High-income subregions. Blindness due to cataract and diabetic retinopathy was more common among women, while blindness due to glaucoma and corneal opacity was more common among men, with no gender difference related to AMD. Conclusions: The numbers of people affected by the common causes of vision loss have increased substantially as the population increases and ages. Preventable vision loss due to cataract and refractive error (reversible with surgery and spectacle correction respectively), continue to cause the majority of blindness and MSVI in adults aged 50+ years. A massive scale up of eye care provision to cope with the increasing numbers is needed if one is to address avoidable vision loss

Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis

Background: Global and regional prevalence estimates for blindness and vision impairment are important for the development of public health policies. We aimed to provide global estimates, trends, and projections of global blindness and vision impairment. Methods: We did a systematic review and meta-analysis of population-based datasets relevant to global vision impairment and blindness that were published between 1980 and 2015. We fitted hierarchical models to estimate the prevalence (by age, country, and sex), in 2015, of mild visual impairment (presenting visual acuity worse than 6/12 to 6/18 inclusive), moderate to severe visual impairment (presenting visual acuity worse than 6/18 to 3/60 inclusive), blindness (presenting visual acuity worse than 3/60), and functional presbyopia (defined as presenting near vision worse than N6 or N8 at 40 cm when best-corrected distance visual acuity was better than 6/12). Findings: Globally, of the 7·33 billion people alive in 2015, an estimated 36·0 million (80% uncertainty interval [UI] 12·9–65·4) were blind (crude prevalence 0·48%; 80% UI 0·17–0·87; 56% female), 216·6 million (80% UI 98·5–359·1) people had moderate to severe visual impairment (2·95%, 80% UI 1·34–4·89; 55% female), and 188·5 million (80% UI 64·5–350·2) had mild visual impairment (2·57%, 80% UI 0·88–4·77; 54% female). Functional presbyopia affected an estimated 1094·7 million (80% UI 581·1–1686·5) people aged 35 years and older, with 666·7 million (80% UI 364·9–997·6) being aged 50 years or older. The estimated number of blind people increased by 17·6%, from 30·6 million (80% UI 9·9–57·3) in 1990 to 36·0 million (80% UI 12·9–65·4) in 2015. This change was attributable to three factors, namely an increase because of population growth (38·4%), population ageing after accounting for population growth (34·6%), and reduction in age-specific prevalence (–36·7%). The number of people with moderate and severe visual impairment also increased, from 159·9 million (80% UI 68·3–270·0) in 1990 to 216·6 million (80% UI 98·5–359·1) in 2015. Interpretation: There is an ongoing reduction in the age-standardised prevalence of blindness and visual impairment, yet the growth and ageing of the world’s population is causing a substantial increase in number of people affected. These observations, plus a very large contribution from uncorrected presbyopia, highlight the need to scale up vision impairment alleviation efforts at all levels

Skeletal Muscle Cells Express ICAM-1 after Muscle Overload and ICAM-1 Contributes to the Ensuing Hypertrophic Response

<div><p>We previously reported that leukocyte specific β2 integrins contribute to hypertrophy after muscle overload in mice. Because intercellular adhesion molecule-1 (ICAM-1) is an important ligand for β2 integrins, we examined ICAM-1 expression by murine skeletal muscle cells after muscle overload and its contribution to the ensuing hypertrophic response. Myofibers in control muscles of wild type mice and cultures of skeletal muscle cells (primary and C2C12) did not express ICAM-1. Overload of wild type plantaris muscles caused myofibers and satellite cells/myoblasts to express ICAM-1. Increased expression of ICAM-1 after muscle overload occurred via a β2 integrin independent mechanism as indicated by similar gene and protein expression of ICAM-1 between wild type and β2 integrin deficient (CD18-/-) mice. ICAM-1 contributed to muscle hypertrophy as demonstrated by greater (p<0.05) overload-induced elevations in muscle protein synthesis, mass, total protein, and myofiber size in wild type compared to ICAM-1-/- mice. Furthermore, expression of ICAM-1 altered (p<0.05) the temporal pattern of Pax7 expression, a marker of satellite cells/myoblasts, and regenerating myofiber formation in overloaded muscles. In conclusion, ICAM-1 expression by myofibers and satellite cells/myoblasts after muscle overload could serve as a mechanism by which ICAM-1 promotes hypertrophy by providing a means for cell-to-cell communication with β2 integrin expressing myeloid cells.</p> </div

ICAM-1 localization in control muscle of wild type mice.

<p>Representative images from confocal microscopy. A) ICAM-1 (green), B) WGA (membrane marker; red) and ICAM-1 (green), C) CD31 (endothelial cell marker; purple), and D) Merged image of ICAM-1 (panel A), and CD31 (panel C). Co-localization analysis revealed that the majority (90–95%) of the ICAM-1 labeling in control muscles was expressed by CD31+ endothelial cells. ICAM-1 was not found on the membrane of myofibers in control muscles.</p

ICAM-1 expression by cultured skeletal muscle cells.

<p>A) Representative flow cytometric quadrant plots of control and TNF-α treated (10 ng/ml for 24 h) cultures of myoblasts. ICAM-1 was detected using a phycoerythrin (PE) conjugated antibody; whereas, myoblasts were identified using an AlexaFlour® 649 (AF649) α7 antibody. ICAM-1 was not expressed by C2C12 and primary myoblasts in control cultures; whereas, TNF-α treatment caused ICAM-1 to be expressed by 30% and 15% of C2C12 and primary myoblasts, respectively. B) Representative western blots for ICAM-1 expression in C212 and primary cells treated with differentiation medium for up to 6 d (20 ug of protein/lane). A cell lysate of a myeloid cell line (RAW 264.7 cells; 5 ug of protein) was used a positive control (+CT). Membranes were probed for α-tubulin (50 kDa) to serve as a control for sample loading. ICAM-1 was not detected in differentiating or differentiated cultures. C) Representative western blot for ICAM-1 after treating proliferating myoblasts or differentiated myotubes (4 d in differentiation medium) with TNF-α (10 ng/ml for 24 h) (20 ug of protein/lane). TNF-α treatment resulted in a ICAM-1 band that was of the same molecule weight (110 kDa) as those found in plantaris muscles from control (CT) and 7 d overloaded (7 d) wild type mice (15 ug of protein/lane).</p

Protein synthesis, measured using the nonradioactive SUnSET technique, in plantaris muscles.

<p>A) Representative western blot (50 ug of protein/lane) of puromycin in control (CT) and 7 d overloaded muscles of wild type (WT) and ICAM-1-/- (IC) mice. B) Coomassie blue stained 10% SDS PAGE gel containing the same samples shown in panel A. C) Quantitative analysis of the relative abundance of puromycin incorporation into proteins (n = 7-8/group). #, significant interaction at 7 d of overload. *, significantly elevated at 7 d of overload compared to controls for wild type mice.</p

ICAM-1 localization in 7 and 14 d overloaded muscles of wild type mice.

<p>Representative images from confocal microscopy. A) ICAM-1 (green) was found to be co-localized to CD31+ endothelial cells (cyan) and to be associated with the membrane of myofibers (WGA+; red). Cells (DAPI+; blue) in the interstitium were also found to express ICAM-1 (arrow). Column labeled as “MERGED” represents an overlay of the ICAM-1, CD31, WGA and DAPI images. B) Higher magnification clearly revealed the colocalization of ICAM-1 (green) with the membrane marker WGA (red) in overloaded muscles. Column labeled as “MERGED” include images of ICAM-1, WGA, and DAPI.</p

Measures of skeletal muscle hypertrophy.

<p>A) Wet plantaris mass in control and overloaded mice (n = 16-20/group). B) Total protein in muscle homogenates of control (n = 6/group) and overloaded mice (n = 8/group). C) Mean cross-sectional area of normal myofibers in control (n = 1813 and 1697 myofibers for wild type and ICAM-1-/- mice, respectively)/strain) and 14 d overloaded (n = 2617 and 1096 myofibers for wild type and ICAM-1-/- mice, respectively) muscles. D) Frequency distribution of the size of normal myofibers at 14 d of overload #, significant interaction at 14 and 21 d of overload. *, significantly higher at 14 and/or 21 d of overload relative to respective controls.</p

ICAM-1 and CD11b localization in 7 d overloaded muscle of wild type mice.

<p>Representative images from confocal microscopy. ICAM-1 (green) and CD11b (red) co-localized on the membrane of myofibers (arrow) and CD11b+ cells were closely associated with ICAM-1+ myofibers (arrowhead). Numerous CD11b+ cells residing in overloaded muscles expressed ICAM-1.</p

Gene and protein expression of ICAM-1.

<p>A) Fold change in ICAM-1 gene expression (n = 8/group). Gene transcripts tended (p = 0.054) to be lower at 14 d relative to 3 d of overload for both strains of mice. B) Representative western blot of ICAM-1 (110 kDa) in control and overloaded (3, 7, and 14 d) muscles of wild type and CD18-/- mice (15 ug of protein/lane). C) Quantitative analysis of ICAM-1 protein (n = 7/group). *, significantly elevated at each overload time point compared to control levels for both strains of mice.</p