Global Prevalence of Presbyopia and Vision Impairment from Uncorrected Presbyopia: Systematic Review, Meta-analysis, and Modelling

Topic: Presbyopia prevalence and spectacle-correction coverage were estimated by systematic review and meta-analysis of epidemiologic evidence, then modeled to expand to country, region, and global estimates. Clinical Relevance: Understanding presbyopia epidemiologic factors and correction coverage is critical to overcoming the burden of vision impairment (VI) from uncorrected presbyopia. Methods: We performed systematic reviews of presbyopia prevalence and spectacle-correction coverage. Accepted presbyopia prevalence data were gathered into 5-year age groups from 0 to 90 years or older and meta-analyzed within World Health Organization global burden of disease regions. We developed a model based on amplitude of accommodation adjusted for myopia rates to match the regionally meta-analyzed presbyopia prevalence. Presbyopia spectacle-correction coverage was analyzed against country-level variables from the year of data collection; variation in correction coverage was described best by a model based on the Human Development Index, Gini coefficient, and health expenditure, with adjustments for age and urbanization. We used the models to estimate presbyopia prevalence and spectacle-correction coverage in each age group in urban and rural areas of every country in the world, and combined with population data to estimate the number of people with near VI. Results: We estimate there were 1.8 billion people (prevalence, 25%; 95% confidence interval [CI], 1.7–2.0 billion [23%–27%]) globally with presbyopia in 2015, 826 million (95% CI, 686–960 million) of whom had near VI because they had no, or inadequate, vision correction. Global unmet need for presbyopia correction in 2015 is estimated to be 45% (95% CI, 41%–49%). People with presbyopia are more likely to have adequate optical correction if they live in an urban area of a more developed country with higher health expenditure and lower inequality. Conclusions: There is a significant burden of VI from uncorrected presbyopia, with the greatest burden in rural areas of low-resource countries

Global Vision Impairment Due to Uncorrected Presbyopia

Objectives: To evaluate the personal and community burdens of uncorrected presbyopia. Methods: We used multiple population-based surveys to estimate the global presbyopia prevalence, the spectacle coverage rate for presbyopia, and the community perception of vision impairment caused by uncorrected presbyopia. For planning purposes, the data were extrapolated for the future using population projections extracted from the International Data Base of the US Census Bureau. Results: It is estimated that there were 1.04 billion people globally with presbyopia in 2005, 517 million of whom had no spectacles or inadequate spectacles. Of these, 410 million were prevented from performing near tasks in the way they required. Vision impairment from uncorrected presbyopia predominantly exists (94%) in the developing world. Conclusions: Uncorrected presbyopia causes widespread, avoidable vision impairment throughout the world. Alleviation of this problem requires a substantial increase in the number of personnel trained to deliver appropriate eye care together with the establishment of sustainable, affordable spectacle delivery systems in developing countries. In addition, given that people with presbyopia are at higher risk for permanently sight-threatening conditions such as glaucoma and diabetic eye disease, primary eye care should include refraction services as well as detection and appropriate referral for these and other such conditions

Mathematical predictions of oxygen availability in micro- and macro-encapsulated human and porcine pancreatic islets

Optimal function of immunoisolated islets requires adequate supply of oxygen to metabolically active insulin producing beta-cells. Using mathematical modeling, we investigated the influence of the pO2 on islet insulin secretory capacity and evaluated conditions that could lead to the development of tissue anoxia, modeled for a 300 μm islet in a 500 μm microcapsule or a 500 μm planar, slab-shaped macrocapsule. The pO2 was used to assess the part of islets that contributed to insulin secretion. Assuming a 500 μm macrocapsule with a 300 μm islet, with oxygen consumption rate (OCR) of 100-300 nmol min-1 mg-1 DNA, islets did not develop any necrotic core. The nonfunctional zone (with no insulin secretion if pO2  < 0.1 mmHg) was 0.3% for human islets (OCR ~100 nmol/min/mg DNA) and 35% for porcine islets (OCR ~300 nmol/min/mg DNA). The OCR of the islet preparation is profoundly affected by islet size, with optimal size of <250 μm in diameter (human) or <150 μm (porcine). Our data suggest that microcapsules afford superior oxygen delivery to encapsulated islets than macrocapsules, and optimal islet function can be achieved by encapsulating multiple, small (<150 μm) islets with OCR of ~100 nmol min-1 mg-1 DNA (human islets) or ~200 nmol min-1 mg-1 DNA (porcine islets)

Postnatal β2 adrenergic treatment improves insulin sensitivity in lambs with IUGR but not persistent defects in pancreatic islets or skeletal muscle

Placental insufficiency causes intrauterine growth restriction (IUGR) and disturbances in glucose homeostasis with associated β adrenergic receptor (ADRβ) desensitization. Our objectives were to measure insulin-sensitive glucose metabolism in neonatal lambs with IUGR and to determine whether daily treatment with ADRβ2 agonist and ADRβ1/β3 antagonists for 1 month normalizes their glucose metabolism. Growth, glucose-stimulated insulin secretion (GSIS) and glucose utilization rates (GURs) were measured in control lambs, IUGR lambs and IUGR lambs treated with adrenergic receptor modifiers: clenbuterol atenolol and SR59230A (IUGR-AR). In IUGR lambs, islet insulin content and GSIS were less than in controls; however, insulin sensitivity and whole-bodyGUR were not different from controls.Of importance, ADRβ2 stimulation with β1/β3 inhibition increases both insulin sensitivity and whole-body glucose utilization in IUGR lambs. In IUGR and IUGR-AR lambs, hindlimb GURs were greater but fractional glucose oxidation rates and ex vivo skeletal muscle glucose oxidation rates were lower than controls. Glucose transporter 4 (GLUT4) was lower in IUGR and IUGR-AR skeletal muscle than in controls but GLUT1 was greater in IUGR-AR. ADRβ2, insulin receptor, glycogen content and citrate synthase activity were similar among groups. In IUGR and IUGR-AR lambs heart rates were greater, which was independent of cardiac ADRβ1 activation. We conclude that targeted ADRβ2 stimulation improved whole-body insulin sensitivity but minimally affected defects in GSIS and skeletal muscle glucose oxidation. We show that risk factors for developing diabetes are independent of postnatal catch-up growth in IUGR lambs as early as 1 month of age and are inherent to the islets and myocytes

Glycerol monolaurate inhibits lipase production by clinical ocular isolates without affecting bacterial cell viability

PURPOSE. We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. METHODS. Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 106/mL in varying concentrations of GML up to 25 μg/mL for 24 hours at 378C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS. Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dosedependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P \u3c 0.05) lipase inhibition above concentrations of 15 μg /mL in S. aureus and was not cytotoxic up to 25 μg /mL. For S. epidermidis, GML showed significant (P \u3c 0.05) lipase inhibition above 7.5 μg /mL. CONCLUSIONS. Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability

Regulation of the JNK3 signaling pathway during islet isolation: JNK3 and c-fos as new markers of islet quality for transplantation.

Stress conditions generated throughout pancreatic islet processing initiate the activation of pro-inflammatory pathways and beta-cell destruction. Our goal is to identify relevant and preferably beta-specific markers to assess the activation of beta-cell stress and apoptotic mechanisms, and therefore the general quality of the islet preparation prior to transplantation. Protein expression and activation were analyzed by Western blotting and kinase assays. ATP measurements were performed by a luminescence-based assay. Oxygen consumption rate (OCR) was measured based on standard protocols using fiber optic sensors. Total RNA was used for gene expression analyzes. Our results indicate that pancreas digestion initiates a potent stress response in the islets by activating two stress kinases, c-Jun N-terminal Kinase (JNK) and p38. JNK1 protein levels remained unchanged between different islet preparations and following culture. In contrast, levels of JNK3 increased after islet culture, but varied markedly, with a subset of preparations bearing low JNK3 expression. The observed changes in JNK3 protein content strongly correlated with OCR measurements as determined by the Spearman's rank correlation coefficient rho [Formula: see text] in the matching islet samples, while inversely correlating with c-fos mRNA expression [Formula: see text]. In conclusion, pancreas digestion recruits JNK and p38 kinases that are known to participate to beta-cell apoptosis. Concomitantly, the islet isolation alters JNK3 and c-fos expression, both strongly correlating with OCR. Thus, a comparative analysis of JNK3 and c-fos expression before and after culture may provide for novel markers to assess islet quality prior to transplantation. JNK3 has the advantage over all other proposed markers to be islet-specific, and thus to provide for a marker independent of non-beta cell contamination

A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations

A major goal of modern computational biology is to simulate the collective behaviour of large cell populations starting from the intricate web of molecular interactions occurring at the microscopic level. In this paper we describe a simplified model of cell metabolism, growth and proliferation, suitable for inclusion in a multicell simulator, now under development (Chignola R and Milotti E 2004 Physica A 338 261-6). Nutrients regulate the proliferation dynamics of tumor cells which adapt their behaviour to respond to changes in the biochemical composition of the environment. This modeling of nutrient metabolism and cell cycle at a mesoscopic scale level leads to a continuous flow of information between the two disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with modern computers and tested experimentally.Comment: 58 pages, 7 figures, 3 tables, pdf onl

Postnatal β2 adrenergic treatment improves insulin sensitivity in lambs with IUGR but not persistent defects in pancreatic islets or skeletal muscle

Placental insufficiency causes intrauterine growth restriction (IUGR) and disturbances in glucose homeostasis with associated β adrenergic receptor (ADRβ) desensitization. Our objectives were to measure insulin-sensitive glucose metabolism in neonatal lambs with IUGR and to determine whether daily treatment with ADRβ2 agonist and ADRβ1/β3 antagonists for 1 month normalizes their glucose metabolism. Growth, glucose-stimulated insulin secretion (GSIS) and glucose utilization rates (GURs) were measured in control lambs, IUGR lambs and IUGR lambs treated with adrenergic receptor modifiers: clenbuterol atenolol and SR59230A (IUGR-AR). In IUGR lambs, islet insulin content and GSIS were less than in controls; however, insulin sensitivity and whole-bodyGUR were not different from controls.Of importance, ADRβ2 stimulation with β1/β3 inhibition increases both insulin sensitivity and whole-body glucose utilization in IUGR lambs. In IUGR and IUGR-AR lambs, hindlimb GURs were greater but fractional glucose oxidation rates and ex vivo skeletal muscle glucose oxidation rates were lower than controls. Glucose transporter 4 (GLUT4) was lower in IUGR and IUGR-AR skeletal muscle than in controls but GLUT1 was greater in IUGR-AR. ADRβ2, insulin receptor, glycogen content and citrate synthase activity were similar among groups. In IUGR and IUGR-AR lambs heart rates were greater, which was independent of cardiac ADRβ1 activation. We conclude that targeted ADRβ2 stimulation improved whole-body insulin sensitivity but minimally affected defects in GSIS and skeletal muscle glucose oxidation. We show that risk factors for developing diabetes are independent of postnatal catch-up growth in IUGR lambs as early as 1 month of age and are inherent to the islets and myocytes