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

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

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt