Diabetic retinopathy in sub-Saharan Africa: meeting the challenges of an emerging epidemic

BACKGROUND: Sub-Saharan Africa faces an epidemic of diabetes. Diabetes causes significant morbidity including visual loss from diabetic retinopathy, which is largely preventable. In this resource-poor setting, health systems are poorly organized to deliver chronic care with multiple system involvement. The specific skills and resources needed to manage diabetic retinopathy are scarce. The costs of inaction for individuals, communities and countries are likely to be high. DISCUSSION: Screening for and treatment of diabetic retinopathy have been shown to be effective, and cost-effective, in resource-rich settings. In sub-Saharan Africa, clinical services for diabetes need to be expanded with the provision of effective, integrated care, including case-finding and management of diabetic retinopathy. This should be underpinned by a high quality evidence base accounting for differences in diabetes types, resources, patients and society in Africa. Research must address the epidemiology of diabetic retinopathy in Africa, strategies for disease detection and management with laser treatment, and include health economic analyses. Models of care tailored to the local geographic and social context are most likely to be cost effective, and should draw on experience and expertise from other continents. Research into diabetic retinopathy in Africa can drive the political agenda for service development and enable informed prioritization of available health funding at a national level. Effective interventions need to be implemented in the near future to avert a large burden of visual loss from diabetic retinopathy in the continent. SUMMARY: An increase in visual loss from diabetic retinopathy is inevitable as the diabetes epidemic emerges in sub-Saharan Africa. This could be minimized by the provision of case-finding and laser treatment, but how to do this most effectively in the regional context is not known. Research into the epidemiology, case-finding and laser treatment of diabetic retinopathy in sub-Saharan Africa will highlight a poorly met need, as well as guide the development of services for that need as it expands

Posterior segment eye disease in sub-Saharan Africa: review of recent population-based studies.

OBJECTIVE: To assess the burden of posterior segment eye diseases (PSEDs) in sub-Saharan Africa (SSA). METHODS: We reviewed published population-based data from SSA and other relevant populations on the leading PSED, specifically glaucoma, diabetic retinopathy and age-related macular degeneration, as causes of blindness and visual impairment in adults. Data were extracted from population-based studies conducted in SSA and elsewhere where relevant. RESULTS: PSEDs, when grouped or as individual diseases, are a major contributor to blindness and visual impairment in SSA. PSED, grouped together, was usually the second leading cause of blindness after cataract, ranging as a proportion of blindness from 13 to 37%. CONCLUSIONS: PSEDs are likely to grow in importance as causes of visual impairment and blindness in SSA in the coming years as populations grow, age and become more urban in lifestyle. African-based cohort studies are required to help estimate present and future needs and plan services to prevent avoidable blindness

First Prospective Cohort Study of Diabetic Retinopathy from Sub-Saharan Africa High Incidence and Progression of Retinopathy and Relationship to Human Immunodeficiency Virus Infection

PurposeTo describe the prevalence, incidence, and progression of retinopathy and to report associations with demographic, clinical, and biochemical variables in people with diabetes in Southern Malawi.DesignProspective cohort study.ParticipantsSubjects were systematically sampled from 2 primary care diabetes clinics.MethodsWe performed the first prospective cohort study of diabetic retinopathy from Sub-Saharan Africa over 24 months. Visual acuity, glycemic control, blood pressure, human immunodeficiency virus (HIV) status, urine albumin-to-creatinine ratio, hemoglobin, and lipids were assessed. Retinopathy was graded at an accredited reading center using modified Wisconsin grading of 4-field mydriatic photographs.Main Outcome MeasuresIncidence of sight-threatening retinopathy and progression of retinopathy by 2 steps on the Liverpool Diabetic Eye Study Scale.ResultsA total of 357 subjects were recruited to the 24-month cohort study. At baseline, 13.4% of subjects were HIV positive and 15.1% were anemic. The 2-year incidence of sight-threatening diabetic retinopathy (STDR) for subjects with level 10 (no retinopathy), level 20 (background), and level 30 (preproliferative) retinopathy at baseline was 2.7% (95% confidence interval [CI], 0.1–5.3), 27.3% (95% CI, 16.4–38.2), and 25.0% (95% CI, 0–67.4), respectively. In a multivariate logistic analysis, 2-step progression of diabetic retinopathy was associated with glycosylated hemoglobin (odds ratio [OR], 1.27; 95% CI, 1.12–1.45), baseline grade of retinopathy (OR, 1.39; 95% CI, 1.02–1.91), and HIV infection (OR, 0.16; 95% CI, 0.03–0.78). At 2 years, 17 subjects (5.8%) lost ≥15 letters.ConclusionsIncidence of STDR was approximately 3 times that reported in recent European studies. The negative association of HIV infection with retinopathy progression is a new finding

Incremental cost-effectiveness of screening and laser treatment for diabetic retinopathy and macular edema in Malawi

Objective To investigate the economic impact of introducing targeted screening and laser photocoagulation treatment for sight-threatening diabetic retinopathy and macular edema in a setting with no previous screening or laser treatment for diabetic retinopathy in sub-Saharan Africa. Materials and methods A cohort Markov model was built to compare combined targeted screening and laser treatment for patients with sight-threatening diabetic retinopathy and macular edema against no intervention. Primary outcomes were incremental cost per quality-adjusted life year (QALY) gained and per disability-adjusted life year (DALY) averted. Primary data were collected on 357 participants from the Malawi Diabetic Retinopathy Study, a prospective, observational cohort study. Multiple scenarios were explored and a probabilistic sensitivity analysis was performed. Results In the base case (age: 50 years, service utilization rate: 80%), the cost of the intervention and the years of severe visual impairment averted per patient screened were $209 and 2.2 years respectively. Applying the World Health Organization threshold of cost-effectiveness for Malawi ($679), the base case was cost-effective when QALYs were used ($400 per QALY gained) but not when DALYs were used ($766 per DALY averted). The intervention was more cost-effective when it targeted younger patients (age: 30 years) and less cost-effective when the utilization rate was lowered to 50%. Conclusions Annual photographic screening of diabetic patients attending medical diabetes clinics in Malawi, with the provision of laser treatment for those with sight-threatening diabetic retinopathy and macular edema, appears to be cost-effective in terms of QALYs gained, in our base case scenario. Cost-effectiveness improves if services are utilized more intensively and extended to younger patients

Alterations in cerebral blood flow and cerebrovascular reactivity during 14 days at 5050 m

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Advancing the use of passive sampling in risk assessment and management of contaminated sediments: Results of an international passive sampling inter-laboratory comparison

This work presents the results of an international interlaboratory comparison on ex situ passive sampling in sediments. The main objectives were to map the state of the science in passively sampling sediments, identify sources of variability, provide recommendations and practical guidance for standardized passive sampling, and advance the use of passive sampling in regulatory decision making by increasing confidence in the use of the technique. The study was performed by a consortium of 11 laboratories and included experiments with 14 passive sampling formats on 3 sediments for 25 target chemicals (PAHs and PCBs). The resulting overall interlaboratory variability was large (a factor of ∼10), but standardization of methods halved this variability. The remaining variability was primarily due to factors not related to passive sampling itself, i.e., sediment heterogeneity and analytical chemistry. Excluding the latter source of variability, by performing all analyses in one laboratory, showed that passive sampling results can have a high precision and a very low intermethod variability

Incidence of sight-threatening diabetic retinopathy in an established urban screening programme: An 11-year cohort study

Aims: systematic annual screening to detect sight-threatening diabetic retinopathy (STDR) is established in the United Kingdom. We designed an observational cohort study to provide up-to-date data for policy makers and clinical researchers on incidence of key screening endpoints in people with diabetes attending one screening programme running for over 30 years.Methods: all people with diabetes aged ≥12 years registered with general practices in the Liverpool health district were offered inclusion. Data sources comprised: primary care (demographics, systemic risk factors), Liverpool Diabetes Eye Screening Programme (retinopathy grading), Hospital Eye Services (slit lamp biomicroscopy assessment of screen positives).Results: 133,366 screening episodes occurred in 28,384 people over 11 years. Overall incidences were: screen positive 6.7% (95% CI 6.5–6.8), screen positive for retinopathy 3.1% (3.0–3.1), unassessable images 2.6% (2.5–2.7), other significant eye diseases 1.0% (1.0–1.1). 1.6% (1.6–1.7) had sight-threatening retinopathy confirmed by slit lamp biomicroscopy. The annual incidence of screen positive and screen positive for retinopathy showed consistent declines from 8.8%–10.6% and 4.4%–4.6% in 2007/09 to 4.4%–6.8% and 2.3%–2.9% in 2013/17, respectively. Rates of STDR (true positive) were consistently below 2% after 2008/09. Screen positive rates were higher in first time attenders (9.9% [9.4–10.2] vs. 6.1% [6.0–6.2]) in part due to ungradeable images (4.1% vs. 2.3%) and other eye disease (2.4% vs. 0.8%). 4.5% (3.9–5.2) of previous non-attenders had sight-threatening retinopathy. Compared with people with type 2 diabetes, those with type 1 disease demonstrated higher rates of screen positive (11.9% vs. 6.0%) and STDR (6.4% vs. 1.2%). Overall prevalence of any retinopathy was 27.2% (27.0–27.4).Conclusions: in an established screening programme with a stable population screen, positive rates show a consistent fall over time to a low level. Of those who are screen positive, fewer than 50% are screen positive for diabetic retinopathy. Most are due to sight threatening maculopathy. The annual incidence of STDR is under 2% suggesting future work on redefining screen positive and supporting extended intervals for people at low risk. Higher rates of screen positive and STDR are seen in first time attenders. Those who have never attended for screening should be specifically targeted.</p

Granulocyte-colony stimulating factor for stroke treatment: mechanisms of action and efficacy in preclinical studies

G-CSF is widely employed for the treatment of chemotherapy-induced neutropenia. Recently, neuroprotective effects of G-CSF in animal stroke models were discovered including infarct size reduction and enhancement of functional recovery. The underlying mechanisms of action of G-CSF in ischemia appear to be a direct anti-apoptotic activity in neurons and a neurogenesis inducing capacity. Additional effects may be based on the stimulation of new blood-vessel formation, the stimulation of immunocompetence and -modulation as well as on bone marrow mobilization. In addition to a discussion of these mechanisms, we will review the available preclinical studies and analyze their impact on the overall efficacy of G-CSF in experimental stroke