Comparison of Photographic Screening Methods for Diabetic Retinopathy - A Meta-analysis.

INTRODUCTION: Diabetic Retinopathy (DR) is a leading cause of irreversible visual impairment and blindness in both developed and developing countries. Although the merits of DR screening are well recognized, significant variations in screening practices including imaging modality still exists. PURPOSE: To evaluate and compare the sensitivity and specificity of mydriatic and non-mydriatic photographic screening methods using 7-Field fundus photography or dilated fundus examination (DFE) by an ophthalmologist as reference standard. METHODS: A systematic review using PRISMA Guidelines was conducted by online search of MEDLINE, Web of Science, and other repositories of all available studies from 1990 until 2019. A total of 62 studies were included in the meta-analysis from a total of 406 suitable abstracts screened and 95 articles reviewed in full. Data were collected using a standardized extraction form independently, with all authors masked to others' search results. RESULTS: For the detection of any DR (ADR), sensitivity ranged from 81% with single field to a maximum of 99% for 4-7 fields and wide-angle images. For detection of referable DR (RDR) sensitivity ranged from 76% for single field to 93% for wide-angle photography. Specificity was lowest at 91% for wide-angle images and greatest at 99% for three field photography. Study heterogeneity was noted to be significant, which was partly attributed to the range of DR classification between studies. CONCLUSIONS: The sensitivity and specificity of DR screening are positively associated with number of photographic fields. Pooled estimates suggest non-mydriatic two-field photography may be sufficient for screening detection of ADR and RDR.

δ-Tocotrienol is the Most Potent Vitamin E Form in Inhibiting Prostate Cancer Cell Growth and Inhibits Prostate Carcinogenesis in Ptenp-/- Mice.

Vitamin E compounds, consisting of α, ß, γ, and δ forms of tocopherols and tocotrienols, display different cancer preventive activities in experimental models. Tocotrienols may have higher potential for clinical use due to their lower effective doses in laboratory studies. However, most studies on tocotrienols have been carried out using cancer cell lines. Strong data from animal studies may encourage the use of tocotrienols for human cancer prevention research. To examine the cancer inhibitory activity of different vitamin E forms, we first investigated their inhibitory activities of different vitamin E forms in prostate cancer cell lines. We found that δ-tocotrienol (δT3) was the most effective form in inhibiting cell growth at equivalent doses. Because of this in vitro potency, δT3 was further studied using prostate-specific Pten-/- (Ptenp-/-) mice. We found that 0.05% δT3 in diet reduced prostate adenocarcinoma multiplicity by 32.7%, featuring increased apoptosis and reduced cell proliferation. The inhibitory effect of 0.05% δT3 in diet was similar to that of 0.2% δ-tocopherol (δT) in diet reported previously. Our further study on the δT3-induced transcriptome changes indicated that δT3 inhibited genes in blood vessel development in the prostate of Ptenp-/- mice, which was confirmed by IHC. Together, our results demonstrate that δT3 effectively inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, which involves inhibition of proliferation and angiogenesis and promotion of apoptosis. PREVENTION RELEVANCE: We demonstrated that δ-tocotrienol is the most active vitamin E form in inhibiting the growth of several prostate cancer cell lines. In transgenic Ptenp-/- mice, δ-tocotrienol inhibited the formation of prostate cancer. This result would encourage and help design clinical studies for the application of δ-tocotrienol for prostate cancer prevention.

High-fat diet-induced hyperinsulinemia promotes the development of prostate adenocarcinoma in prostate-specific Pten-/- mice.

Metabolic syndrome (MetS) and its four clinical entities, central obesity, insulin resistance, hypertension and dyslipidemia, are implicated in increasing the risk and mortality of cancer in several organs. However, it is unclear how they are associated with increased risk of prostate cancer. To elucidate the mechanistic link between MetS and prostate carcinogenesis, we characterized the development of MetS and prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice fed a high-fat (HF) diet. We found that male Ptenp-/- mice on an HF diet gained excess body weight and elevated blood glucose, insulin and insulin-like growth factor 1 (IGF1) levels at 20 weeks of age and were obese at 40 weeks. Prostate adenocarcinoma multiplicity at 40 weeks was significantly higher in the mice on an HF diet, suggesting that the HF diet promotes the development of prostate adenocarcinoma. Increased cell proliferation and enhanced AKT activation were found in the prostates of mice on an HF diet. Further transcriptome study revealed that receptor tyrosine kinase regulation, which mediates insulin/IGF1 signaling, was one of the top enriched pathways by HF diet-induced transcriptome changes. Together, our results suggest that HF diet-induced hyperinsulinemia leads to increased activation of insulin/IGF1/AKT signaling in lesioned prostates, promoting the development of adenocarcinoma.

Female Gender Remains a Significant Barrier to Access Cataract Surgery in South Asia: A Systematic Review and Meta-Analysis.

PURPOSE: To determine whether the female gender is a barrier for the access to cataract surgery services in South Asia in the last two decades. METHODS: Eligible cross-sectional studies were identified via computer searches and reviewing the reference lists of the obtained articles. The cataract surgical coverage (CSC) by sex based on person and eyes at visual acuity <3/60 and 6/18 is extracted. Pooled odds ratios (ORs) for males receiving cataract surgery in comparison with females were calculated by a random effect model. RESULTS: Sixteen studies with 135972 subjects were included in the final analysis. The pooled ORs of CSC by sex on a person basis at visual acuity <3/60 and at visual acuity <6/18 were 1.46 (95% CI: 1.23-1.75) and 1.14 (95% CI: 1.05-1.24), respectively. For CSC on a per-eye basis at visual acuity <3/60, the associations were statistically significant, with a pooled OR of 1.40 (95% CI: 1.16-1.70). The values of population attributable risk percentage at a per-person and per-eye basis at visual acuity <3/60 were 6.28% and 7.48%, respectively. Subgroup analyses by design and location types attained similar results as the primary analyses. There was no evidence of publication bias. CONCLUSIONS: The female gender remains a significant barrier for the access to cataract surgery in South Asia. Visual impairment, including blindness, from unoperated cataract, could be reduced by approximately 6.28% with the elimination of gender disparities to access. More efforts are needed to increase eye care service utilization by female population.

Longitudinal changes in global cataract surgery rate inequality and associations with socioeconomic indices.

IMPORTANCE: Cataract is the leading cause of blindness and the second leading cause of vision impairment. The majority of people with vision impairment reside in low-resource settings with limited access to cataract surgery and services. BACKGROUND: Cataract surgery rate (CSR) is a proxy measure for eye care service delivery and estimating the burden of cataract disease. This research aims to evaluate the longitudinal changes of CSR inequality globally and by income groups. DESIGN: Systematic review. PARTICIPANTS: Studies published from January 2000 to December 2015 were considered for inclusion into the review. METHODS: CSR data were retrieved from a systematic review of published literature (OVID Medline, Embase, PubMed, ISI, Web of Science), unpublished reports and data repositories. MAIN OUTCOME MEASURES: Inequality of CSR was measured on a global scale and between countries grouped by income levels using the Gini coefficient and concentration index, with respect to the human development index (HDI). RESULTS: Overall, correlations between HDI and gross domestic product (GDP) per capita vs CSRs were observed with R2 values of 49.2% (ß = 5.01, P < 0.001) and 38.9% (ß = 0.56, P < 0.001), respectively. Analysis of longitudinal CSR data using generalized estimation equation models revealed strong associations between CSR and HDI (P < 0.001), GDP (P < 0.001) and the proportion of people aged ≥50 (P = 0.001). Overall, the trend of inequality in worldwide CSR remained relatively stable. CONCLUSIONS AND RELEVANCE: Inequalities in cataract service provision were found between countries grouped by income and associated with socioeconomic indicators.

Longitudinal changes in intraocular pressure and association with systemic factors and refractive error: Lingtou Eye Cohort Study.

OBJECTIVES: To investigate the longitudinal changes in intraocular pressure (IOP) and its associations with refractive error and systemic determinants in a Chinese geriatric population. DESIGN: Prospective cohort study. SETTING: Guangzhou Government Servant Physical Check-up Center, Guangzhou, China. PARTICIPANTS: 4413 government employees aged no less than 40 years (41.9% female) attending annual physical and eye examinations were included in this study. The inclusion criterion was having attended the 2010 follow-up examination. The exclusion criteria include glaucoma or intraocular surgery history, IOP >21 mm Hg at any visit or without available IOP data at all visits from 2010 to 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome measure was IOP at each follow-up visit from 2010 to 2014. Mixed-effect model was used to assess the relationship between longitudinal changes in IOP and potential risk factors. RESULTS: For the 2653 participants who had available IOP data at both the 2010 and 2014 follow-up visits, the average change in IOP was an increase of 0.43 (95% CI 0.36 to 0.50) mm Hg. For the whole study population and in the optimised mixed model, there was a non-linear increase of IOP with age (P<0.001), with greater changes in younger subjects and in women (P<0.001 and P=0.002, respectively). Elevations in systolic blood pressure, diastolic blood pressure, body mass index (BMI) and fasting plasma glucose (FPG), as well as a myopic shift (all with P<0.001), during the follow-up were associated with an increasing trend of IOP, while serum lipids were found to be not significantly associated. CONCLUSIONS: In this cohort of elderly Chinese adults, IOP increases non-linearly with ageing. People with increasing blood pressure, BMI, FPG and myopic progression are more likely to have IOP elevation over time.

A Global View on Output and Outcomes of Cataract Surgery With National Indices of Socioeconomic Development.

Purpose: Cataract blindness accounts for a substantial proportion of blindness worldwide. Understanding the correlations between national levels of socioeconomic development with the quantity and quality of cataract surgery may provide insight for the prioritization and resource allocation for blindness prevention programs. Methods: The relationships between human development index (HDI), gross domestic product (GDP) per capita, and cataract surgical coverage (CSC) and visual outcome of cataract surgery were examined in a multinational study utilizing secondary data from the repository for Rapid Assessment of Avoidable Blindness (RAAB), World Health Organization, Global Burden of Disease, United Nations, and the World Bank. Results: A total of 266 RAAB studies across 73 countries/territories were retrieved. Linear regression model results revealed strong associations of HDI with prevalence of cataract blindness (ß = -7.056, P < 0.001), CSC (ß = 60.808, P = 0.004), proportion of intraocular lens (IOL) implantation (ß = 87.040, P = 0.001), and proportion of cases with good vision outcomes among operated eyes (ß = 73.351, P < 0.001) in studies performed between 1995 and 2009. Similar associations were observed for studies performed between 2010 and 2015. In addition, countries with lower GDP per capita showed a higher rate of cataract blindness (ß = -0.527, P = 0.001), lower CSC (ß = 9.800, P < 0.001), lower percentage of IOL implantation (ß = 6.871, P = 0.001), and fewer patients with good vision outcomes after surgery (ß = 7.959, P < 0.001). After controlling survey year, country, and other factors, GDP per capita and HDI were also found to be significantly associated with CSC and visual outcomes after cataract surgery (all P < 0.05). Conclusions: We documented the strong associations of socioeconomic indices with quantity and quality of cataract surgery. These socioeconomic indicators should be considered as important factors for developing strategies aimed to improve worldwide cataract surgery service delivery.