Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and a major cause of preventable visual impairment and blindness worldwide. With the global rise in diabetes prevalence and population aging, the number of adults and older people at risk of vision‑threatening DR is projected to increase substantially in the coming decades. The clinical and economic burden of DR is particularly pronounced in low‑ and middle‑income countries, where access to eye care and screening services remains limited¹.

Hyperglycemia is necessary but not sufficient for the development of DR. Many individuals live with diabetes for decades without developing sight‑threatening changes, whereas others progress rapidly despite apparently similar glycemic exposure. This heterogeneity highlights the contribution of multiple determinants beyond blood glucose levels, including socio-demographic characteristics, comorbidities, biochemical markers, lifestyle behaviors, and health‑system factors^1,2,3.

Several large observational studies and screening program analyses have evaluated predictors of incident DR, progression to proliferative DR or diabetic macular edema (DME), and occurrence of sight‑threatening DR (STDR). However, much of the literature combines younger and older adults, and focuses either on type 1 or type 2 diabetes without specific consideration of elderly populations, in whom multimorbidity, frailty, and social factors may play a greater role^2,4,5.

This narrative review aims to synthesize current evidence on determinants of DR in adults and elderly individuals with diabetes, with an emphasis on factors that are potentially modifiable in clinical practice and public health programs. The inclusion of summary tables is intended to facilitate rapid understanding and application of the evidence by clinicians, researchers, and policymakers^2,6,7.

Design A narrative review approach was adopted to provide an integrated overview of determinants of DR among adults and elderly individuals with diabetes. The goal was to summarize and organize key risk factors, rather than to estimate pooled effect sizes. Eligibility criteria • Population: Adults (≥18 years) with type 1 or type 2 diabetes, with particular attention to older adults (commonly defined as ≥60 or ≥65 years). • Outcomes: Any form of DR (non proliferative or proliferative), DME, or STDR. • Study designs: Cross sectional and case–control studies, prospective or retrospective cohorts, large screening program analyses, and systematic reviews or meta analyses. • Determinants: Socio-demographic variables (age, sex, socioeconomic status), diabetes related clinical characteristics (duration, HbA1c, age at onset), comorbidities and biochemical parameters (hypertension, dyslipidemia, nephropathy, albuminuria, renal function, anemia, serum electrolytes), lifestyle/behavioral factors (smoking, alcohol, physical activity, obesity), and health system or self care–related factors (access to screening, education, home glucose monitoring). Search strategy Relevant literature was identified from electronic databases such as PubMed and Google Scholar using combinations of the following keywords: “diabetic retinopathy”, “risk factors”, “determinants”, “elderly”, “older adults”, “type 2 diabetes”, “duration of diabetes”, “hypertension”, “anemia”, and “nephropathy”. Reference lists of key articles and reviews were screened to identify additional relevant studies. Because this was a narrative rather than a systematic review, formal quality assessment and meta analysis were not performed. Instead, emphasis was placed on consistency of associations across studies, biological plausibility, and clinical relevance in adult and elderly populations. Data abstraction and synthesis Findings from included studies were extracted and grouped under pre specified domains. Tables were constructed to summarize determinants, typical directions of association (risk vs protective), and brief commentary on mechanisms or practical implications.

Overview of determinant domains

Table 1 shows the main categories of determinants of DR among adults and elderly individuals with diabetes. Subsequent sections elaborate each domain.

Table 1. Major domains of determinants of diabetic retinopathy in adults and elderly individuals with diabetes

* “Typical direction” refers to findings reported in the majority of studies; exceptions and heterogeneity are noted in the text.
** Insulin use often reflects advanced disease rather than being a causal determinant.

Socio-demographic determinants

Age

Most population‑based studies report increasing prevalence of DR with advancing age, particularly beyond 60 years, largely reflecting cumulative exposure to hyperglycemia, hypertension, and other metabolic disturbances. In multivariable models that adjust for duration of diabetes, the association between chronological age and DR sometimes attenuates, suggesting that duration and age at onset may be more important than age alone.

Sex

Many community‑based surveys find higher crude DR prevalence among men than women, potentially due to higher prevalence of smoking, occupational stress, and other cardiovascular risk factors, or gendered differences in health‑seeking behavior. However, after adjustment for clinical and behavioral variables, the independent effect of sex is often weak or inconsistent.

Socioeconomic status

Low socioeconomic status (SES)—captured through low household income, lower education, or residence in deprived areas—is associated with higher risk of DR and STDR in several studies. Mechanisms include reduced access to diabetes care and ophthalmic services, reduced capacity to purchase medications or healthy foods, and lower health literacy.

Table 2. Selected socio-demographic determinants of diabetic retinopathy

Diabetes-related clinical determinants

Duration of diabetes

Duration of diabetes is among the strongest and most consistent determinants of DR in adults and elderly populations. Prevalence and severity of DR increase markedly after 10–15 years of diagnosed diabetes, especially when glycemic and blood pressure control are suboptimal. Longer duration also interacts with other factors (e.g., anemia, nephropathy), amplifying risk.

Glycemic control (HbA1c, fasting glucose)

Elevated HbA1c and fasting plasma glucose are key modifiable determinants. Higher HbA1c is consistently associated with incident DR, faster progression from non‑proliferative to proliferative stages, and development of DME. Intensive glycemic control in large randomized trials has been shown to reduce onset and progression of DR, though the degree of benefit must be balanced against risks such as hypoglycemia in frail older adults.

Type of diabetes and age at onset

Individuals with type 1 diabetes and those with early‑onset type 2 diabetes typically accumulate longer exposure to hyperglycemia and therefore face greater lifetime risk of DR. Among adults with type 2 diabetes, earlier age at diagnosis has been associated with higher DR risk at a given chronological age and duration.

Treatment modality

Insulin therapy is often associated with higher DR prevalence in observational studies; however, this likely reflects greater disease severity and longer duration rather than a direct effect of insulin. Failure of oral agents and delayed intensification of treatment may also contribute to cumulative microvascular damage.

Comorbidities and biochemical determinants

Hypertension, dyslipidemia, nephropathy, and hematologic abnormalities contribute to microvascular injury and are important determinants of DR.

Hypertension

Systemic hypertension, particularly uncontrolled elevated systolic blood pressure, is independently associated with both DR prevalence and progression. Blood pressure lowering—especially using agents that block the renin–angiotensin system—has been shown to reduce DR progression in some trials, supporting causality.

Dyslipidemia

Abnormal lipid profiles, including elevated total cholesterol, LDL‑cholesterol, and triglycerides, have been associated with presence and severity of DR and DME. Hard exudates and macular changes are especially linked to hyperlipidemia. While trial evidence on the specific effect of statins on DR is mixed, lipid control is recommended for overall vascular risk reduction.

Renal involvement (albuminuria and reduced eGFR)

Albuminuria and impaired renal function are strong markers of systemic microvascular injury and are consistently associated with DR, STDR, and DME. Coexistence of diabetic nephropathy and retinopathy indicates advanced microvascular disease and identifies a subgroup at particularly high risk.

Neuropathy and diabetic foot disease

Peripheral neuropathy and diabetic foot ulcers correlate with DR, reflecting shared risk factors (long duration, poor metabolic control) and global microvascular compromise. Patients with foot disease often have limited mobility and may struggle to attend retinal screening appointments.

Anemia and hematologic factors

Anemia has been identified as an independent determinant of DR in some cohorts, particularly among individuals with long‑standing diabetes. Reduced hemoglobin concentration may exacerbate retinal hypoxia and ischemia, promoting progression to more severe stages of DR. Elevated hematocrit or increased blood viscosity may also contribute to microvascular occlusion.

Electrolyte disturbances and other markers

Recent studies have implicated higher serum sodium and potassium, as well as abnormalities in inflammatory markers, as potential determinants of DR and DME. These associations may reflect underlying renal dysfunction, medication use, or broader metabolic derangement, and warrant further investigation.

Table 3. Clinical and biochemical determinants of diabetic retinopathy

Lifestyle and behavioral determinants

Obesity and body mass index (BMI)

The relationship between BMI and DR is complex and sometimes nonlinear. Some studies report higher DR prevalence among individuals with obesity, while others suggest an inverse or U‑shaped association, possibly due to weight loss in advanced disease. Overall, obesity is linked to type 2 diabetes onset and cardiometabolic risk, but its independent role in DR remains uncertain after adjusting for glycemia and blood pressure.

Smoking and alcohol use

Cigarette smoking has been associated with higher DR risk in some studies, but not consistently across all populations. Confounding by other cardiovascular risk factors and survival bias complicate interpretation. Alcohol use shows heterogeneous associations: some data suggest that heavy consumption increases vascular risk, whereas light‑to‑moderate intake may show neutral or even protective associations, potentially reflecting healthier lifestyles overall.

Physical activity and adherence to treatment

Limited evidence indicates that regular physical activity and good adherence to antidiabetic medications and dietary recommendations are associated with lower DR risk, likely mediated through improved glycemic and blood pressure control. Conversely, non‑adherence, irregular medication intake, and high‑calorie diets contribute to uncontrolled diabetes and thus higher DR risk.

Table 4. Lifestyle and behavioral determinants of diabetic retinopathy

Health‑system and self‑care determinants

Access to screening and ophthalmic services

Regular retinal screening is essential for early detection and treatment of DR. Barriers such as travel distance, cost, lack of integrated screening programs, limited ophthalmologist availability, and low awareness often lead to delayed diagnosis, with patients presenting only when vision is already compromised.

Self-monitoring and health education

Availability and regular use of a home glucometer, participation in diabetes education programs, and good understanding of complications are associated with better metabolic control and lower risk or slower progression of DR in some studies. Conversely, low awareness of DR and its treatability is common among older adults, leading to underutilization of screening services.

Continuity of care and healthcare utilization

Frequent missed appointments, fragmentation of care, and lack of coordination between diabetes and eye care services contribute to suboptimal risk factor control and delayed treatment. Integrated care pathways and recall systems can improve screening coverage and follow‑up.

Table 5. Health‑system and self‑care determinants of diabetic retinopathy

This narrative review highlights the multifactorial and interdependent nature of determinants of DR among adults and elderly individuals with diabetes. The most consistently reported determinants across studies—longer duration of diabetes, poor glycemic control, and hypertension—underscore the central role of chronic metabolic and vascular exposure in driving retinal microvascular damage8. Clinical and biochemical comorbidities, particularly nephropathy, albuminuria, dyslipidemia, and anemia, further refine risk profiles and often co occur in patients with advanced disease. These determinants are clinically useful because they are usually monitored in routine diabetes care, enabling clinicians to identify high risk individuals who warrant closer ophthalmic surveillance5,8,9. Socio-demographic and socioeconomic factors shape exposure to these clinical determinants through differences in lifestyle, health literacy, and access to care. Low income, low educational attainment, and rural residence are associated with higher risk of undiagnosed or advanced DR, especially in elderly populations who may face mobility limitations and financial constraints10,11. Behavioral and health system determinants are particularly amenable to intervention. Evidence suggests that structured education, improved treatment adherence, self monitoring, and integration of DR screening into primary care and community programs can mitigate risk even in the presence of non modifiable factors such as age and duration of diabetes. Teleophthalmology and mobile screening units may be especially beneficial for older adults living in remote or underserved areas12. Implications for practice 1. Risk stratification: Clinicians should consider a combination of determinants—duration of diabetes, HbA1c, blood pressure, renal function, anemia, and SES—when stratifying patients for screening frequency and intensity of risk factor management. 2. Integrated care models: Co management by diabetologists, ophthalmologists, nephrologists, and primary care providers is essential for individuals with coexisting nephropathy or other microvascular complications. 3. Elderly focused interventions: For older adults, interventions must account for polypharmacy, frailty, cognitive impairment, and social support, to avoid overtreatment while still preventing progression of DR. 4. Policy and programmatic responses: Health systems should prioritize DR screening and treatment within national diabetes programs, ensuring financial protection and equitable access, particularly for low income and rural elderly populations. Research gaps • Longitudinal studies specifically focused on elderly individuals with diabetes are needed to clarify temporal relationships and interactions among determinants. • The roles of anemia, electrolyte disturbances, and inflammatory markers require further investigation, including interventional studies evaluating whether their correction alters DR risk. • More evidence is needed on the effectiveness and cost effectiveness of integrated screening models and teleophthalmology in real world older populations.

Overview of determinant domains

Table 1 shows the main categories of determinants of DR among adults and elderly individuals with diabetes. Subsequent sections elaborate each domain.

Table 1. Major domains of determinants of diabetic retinopathy in adults and elderly individuals with diabetes

* “Typical direction” refers to findings reported in the majority of studies; exceptions and heterogeneity are noted in the text.
** Insulin use often reflects advanced disease rather than being a causal determinant.

Socio-demographic determinants

Age

Most population‑based studies report increasing prevalence of DR with advancing age, particularly beyond 60 years, largely reflecting cumulative exposure to hyperglycemia, hypertension, and other metabolic disturbances. In multivariable models that adjust for duration of diabetes, the association between chronological age and DR sometimes attenuates, suggesting that duration and age at onset may be more important than age alone.

Sex

Many community‑based surveys find higher crude DR prevalence among men than women, potentially due to higher prevalence of smoking, occupational stress, and other cardiovascular risk factors, or gendered differences in health‑seeking behavior. However, after adjustment for clinical and behavioral variables, the independent effect of sex is often weak or inconsistent.

Socioeconomic status

Low socioeconomic status (SES)—captured through low household income, lower education, or residence in deprived areas—is associated with higher risk of DR and STDR in several studies. Mechanisms include reduced access to diabetes care and ophthalmic services, reduced capacity to purchase medications or healthy foods, and lower health literacy.

Table 2. Selected socio-demographic determinants of diabetic retinopathy

Diabetes-related clinical determinants

Duration of diabetes

Duration of diabetes is among the strongest and most consistent determinants of DR in adults and elderly populations. Prevalence and severity of DR increase markedly after 10–15 years of diagnosed diabetes, especially when glycemic and blood pressure control are suboptimal. Longer duration also interacts with other factors (e.g., anemia, nephropathy), amplifying risk.

Glycemic control (HbA1c, fasting glucose)

Elevated HbA1c and fasting plasma glucose are key modifiable determinants. Higher HbA1c is consistently associated with incident DR, faster progression from non‑proliferative to proliferative stages, and development of DME. Intensive glycemic control in large randomized trials has been shown to reduce onset and progression of DR, though the degree of benefit must be balanced against risks such as hypoglycemia in frail older adults.

Type of diabetes and age at onset

Individuals with type 1 diabetes and those with early‑onset type 2 diabetes typically accumulate longer exposure to hyperglycemia and therefore face greater lifetime risk of DR. Among adults with type 2 diabetes, earlier age at diagnosis has been associated with higher DR risk at a given chronological age and duration.

Treatment modality

Insulin therapy is often associated with higher DR prevalence in observational studies; however, this likely reflects greater disease severity and longer duration rather than a direct effect of insulin. Failure of oral agents and delayed intensification of treatment may also contribute to cumulative microvascular damage.

Comorbidities and biochemical determinants

Hypertension, dyslipidemia, nephropathy, and hematologic abnormalities contribute to microvascular injury and are important determinants of DR.

Hypertension

Systemic hypertension, particularly uncontrolled elevated systolic blood pressure, is independently associated with both DR prevalence and progression. Blood pressure lowering—especially using agents that block the renin–angiotensin system—has been shown to reduce DR progression in some trials, supporting causality.

Dyslipidemia

Abnormal lipid profiles, including elevated total cholesterol, LDL‑cholesterol, and triglycerides, have been associated with presence and severity of DR and DME. Hard exudates and macular changes are especially linked to hyperlipidemia. While trial evidence on the specific effect of statins on DR is mixed, lipid control is recommended for overall vascular risk reduction.

Renal involvement (albuminuria and reduced eGFR)

Albuminuria and impaired renal function are strong markers of systemic microvascular injury and are consistently associated with DR, STDR, and DME. Coexistence of diabetic nephropathy and retinopathy indicates advanced microvascular disease and identifies a subgroup at particularly high risk.

Neuropathy and diabetic foot disease

Peripheral neuropathy and diabetic foot ulcers correlate with DR, reflecting shared risk factors (long duration, poor metabolic control) and global microvascular compromise. Patients with foot disease often have limited mobility and may struggle to attend retinal screening appointments.

Anemia and hematologic factors

Anemia has been identified as an independent determinant of DR in some cohorts, particularly among individuals with long‑standing diabetes. Reduced hemoglobin concentration may exacerbate retinal hypoxia and ischemia, promoting progression to more severe stages of DR. Elevated hematocrit or increased blood viscosity may also contribute to microvascular occlusion.

Electrolyte disturbances and other markers

Recent studies have implicated higher serum sodium and potassium, as well as abnormalities in inflammatory markers, as potential determinants of DR and DME. These associations may reflect underlying renal dysfunction, medication use, or broader metabolic derangement, and warrant further investigation.

Table 3. Clinical and biochemical determinants of diabetic retinopathy

Lifestyle and behavioral determinants

Obesity and body mass index (BMI)

The relationship between BMI and DR is complex and sometimes nonlinear. Some studies report higher DR prevalence among individuals with obesity, while others suggest an inverse or U‑shaped association, possibly due to weight loss in advanced disease. Overall, obesity is linked to type 2 diabetes onset and cardiometabolic risk, but its independent role in DR remains uncertain after adjusting for glycemia and blood pressure.

Smoking and alcohol use

Cigarette smoking has been associated with higher DR risk in some studies, but not consistently across all populations. Confounding by other cardiovascular risk factors and survival bias complicate interpretation. Alcohol use shows heterogeneous associations: some data suggest that heavy consumption increases vascular risk, whereas light‑to‑moderate intake may show neutral or even protective associations, potentially reflecting healthier lifestyles overall.

Physical activity and adherence to treatment

Limited evidence indicates that regular physical activity and good adherence to antidiabetic medications and dietary recommendations are associated with lower DR risk, likely mediated through improved glycemic and blood pressure control. Conversely, non‑adherence, irregular medication intake, and high‑calorie diets contribute to uncontrolled diabetes and thus higher DR risk.

Table 4. Lifestyle and behavioral determinants of diabetic retinopathy

Health‑system and self‑care determinants

Access to screening and ophthalmic services

Regular retinal screening is essential for early detection and treatment of DR. Barriers such as travel distance, cost, lack of integrated screening programs, limited ophthalmologist availability, and low awareness often lead to delayed diagnosis, with patients presenting only when vision is already compromised.

Self-monitoring and health education

Availability and regular use of a home glucometer, participation in diabetes education programs, and good understanding of complications are associated with better metabolic control and lower risk or slower progression of DR in some studies. Conversely, low awareness of DR and its treatability is common among older adults, leading to underutilization of screening services.

Continuity of care and healthcare utilization

Frequent missed appointments, fragmentation of care, and lack of coordination between diabetes and eye care services contribute to suboptimal risk factor control and delayed treatment. Integrated care pathways and recall systems can improve screening coverage and follow‑up.

Table 5. Health‑system and self‑care determinants of diabetic retinopathy

This narrative review highlights the multifactorial and interdependent nature of determinants of DR among adults and elderly individuals with diabetes. The most consistently reported determinants across studies—longer duration of diabetes, poor glycemic control, and hypertension—underscore the central role of chronic metabolic and vascular exposure in driving retinal microvascular damage8. Clinical and biochemical comorbidities, particularly nephropathy, albuminuria, dyslipidemia, and anemia, further refine risk profiles and often co occur in patients with advanced disease. These determinants are clinically useful because they are usually monitored in routine diabetes care, enabling clinicians to identify high risk individuals who warrant closer ophthalmic surveillance5,8,9. Socio-demographic and socioeconomic factors shape exposure to these clinical determinants through differences in lifestyle, health literacy, and access to care. Low income, low educational attainment, and rural residence are associated with higher risk of undiagnosed or advanced DR, especially in elderly populations who may face mobility limitations and financial constraints10,11. Behavioral and health system determinants are particularly amenable to intervention. Evidence suggests that structured education, improved treatment adherence, self monitoring, and integration of DR screening into primary care and community programs can mitigate risk even in the presence of non modifiable factors such as age and duration of diabetes. Teleophthalmology and mobile screening units may be especially beneficial for older adults living in remote or underserved areas12. Implications for practice 1. Risk stratification: Clinicians should consider a combination of determinants—duration of diabetes, HbA1c, blood pressure, renal function, anemia, and SES—when stratifying patients for screening frequency and intensity of risk factor management. 2. Integrated care models: Co management by diabetologists, ophthalmologists, nephrologists, and primary care providers is essential for individuals with coexisting nephropathy or other microvascular complications. 3. Elderly focused interventions: For older adults, interventions must account for polypharmacy, frailty, cognitive impairment, and social support, to avoid overtreatment while still preventing progression of DR. 4. Policy and programmatic responses: Health systems should prioritize DR screening and treatment within national diabetes programs, ensuring financial protection and equitable access, particularly for low income and rural elderly populations. Research gaps • Longitudinal studies specifically focused on elderly individuals with diabetes are needed to clarify temporal relationships and interactions among determinants. • The roles of anemia, electrolyte disturbances, and inflammatory markers require further investigation, including interventional studies evaluating whether their correction alters DR risk. • More evidence is needed on the effectiveness and cost effectiveness of integrated screening models and teleophthalmology in real world older populations.

Determinants of DR among adults and elderly individuals with diabetes span socio-demographic, clinical, biochemical, behavioral, and health system domains. While age and duration of diabetes cannot be modified, many other determinants—including glycemic and blood pressure control, management of dyslipidemia and nephropathy, correction of anemia, and improvements in access to screening and education—are amenable to intervention.

Targeted, multidisciplinary strategies that address these determinants holistically are essential to reduce the growing burden of visual impairment due to DR in aging diabetic populations.

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12. Wondmeneh TG, Mohammed JA. Prevalence of diabetic retinopathy and its associated risk factors among adults in Ethiopia: a systematic review and meta‑analysis. Sci Rep. 2024;[published online 16 Nov 2024]. doi:10.1038/s41598‑024‑78596‑9.