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Department of Pharmacology, Jamia Hamdard, New Delhi, India
Diabetes mellitus is a major microvascular complication of diabetes and a common cause of preventable vision impairment in working-age adults, diabetic retinopathy (DR). This review aims to update the reader on the epidemiology, pathophysiology, prevention, diagnosis and treatment of DR based on the results of landmark clinical trials and recent advances as of 2024. Around a third of people with diabetes will get DR and almost 10% will develop sight-threatening DR. Prevention is based on tight glycemic, blood pressure and lipid control, and frequent retinal assessments, which prevent diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR), due to oxidative stress, inflammatory response, formation of advanced glycation end-products and vascular endothelial growth factor (VEGF)-mediated angiogenesis. There has been recent progress in diagnosis, such as optical coherence tomography (OCT), OCT angiography, widefield retinal imaging, screening, and teleophthalmology that has improved early detection and disease monitoring. Center involving diabetic macular edema (DME) is usually treated first with intravitreal anti-VEGF agents and in selected patients with corticosteroid implants, panretinal photocoagulation, and vitrectomy. While there is considerable therapeutic advances, DR is a chronic, recurrent disease and should be managed on an individual, long-term basis. Future studies should be aimed at optimizing personalized treatment strategies, assessing the effectiveness in real world and increase equitable access to screening programs.
Diabetic retinopathy (DR) is a microvascular complication of both type 1 and type 2 diabetes mellitus (DM), which is one of the most common causes of vision impairment and blindness in working age adults worldwide. If left untreated, early disease may be without symptoms, but advanced disease proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME)) can cause significant and permanent loss of sight. The review brings together the latest insights into prevention, diagnosis, and treatment strategies for DR, highlighting evidence-based interventions and technologies. Prevention focuses on tight control of glycemia, blood pressure, and lipids, as well as specific screening programmes, and landmark trials like the DCCT and UKPDS have proved intensive glycemic control decreases the occurrence and advancement of DR [1,2]. Modern diagnostic methods have developed from clinical ophthalmoscopy to widefield fundus imaging, optical coherence tomography (OCT) and OCT-angiography (OCTA) that enhance the sensitivity of diagnosis and allow quantitative monitoring of retinal structure and perfusion [3-5]. Prospective studies, such as randomized trials and registries, are still ongoing to further refine long-term outcomes and real-world effectiveness of treatment paradigms, which have changed significantly with the use of intravitreal anti-VEGF agents for DME and PDR, along with laser photocoagulation and vitrectomy for selected indications [6–9]. Challenges with access to care, adherence and implementation of screening are also discussed, as well as future directions, including sustained release drug delivery, gene based therapies, teleophthalmology and screening. This review aims to synthesize, in a concise and up-to-date format, the evidence from clinical trials and pragmatic considerations to inform prevention strategies, advances in diagnosis, and therapeutic options for DR that will improve patient outcomes, for clinicians, researchers, and policymakers.
Epidemiology and Risk Factors
The estimated prevalence of any DR in people with diabetes is about 34% and of sight-threatening DR about 10% [1]. Common risk factors include: diabetes duration, inadequate control (glycated haemoglobin >6.5%), hypertension, dyslipidaemia, pregnancy and renal disease. New evidence also indicates that social determinants of health, lack of access to health care and some ethnic groups are associated with increased risk for delayed diagnosis and poorer outcomes [2,3].
Pathophysiology – From microvascular damage to vision loss.
DR begins with biochemical and hemodynamic changes in the retina caused by chronic hyperglycemia and leads to damage of the microvasculature. The mechanisms involved include: increase in polyol pathway flux, advanced glycation end product formation, oxidative stress, inflammation, and up-regulation of vascular endothelial growth factor (VEGF). Blood–retinal barrier breakdown, capillary dropout, retinal ischemia, and neovascularization typical of proliferative DR are associated with these processes [4,5] and are a major cause of vision loss, as they cause leakage of fluid into the retina and result in diabetic macular edema (DME).
Prevention and Risk Reduction
Primary prevention involves risk factor optimization and enhancing access to screening. Evidence-based measures include:
Intensive glycemic control: Intensive glycemic control decreases the occurrence and development of DR in both type 1 and type 2 diabetes (from long-term follow-up data from the DCCT and UKPDS) [6,7].
Control of blood pressure – tight BP control lowers the risk of progression of DR and DME [8].
Lipid management: Fenofibrate has been found to have a beneficial effect on the slowing up of DR in some trials, beyond its cardiovascular effects [9].
Smoking cessation and general cardiovascular risk reduction – minimise microvascular and macrovascular complications.
Accessible screening programmes: Population level retinal screening with prompt referral is essential for prevention of vision loss, and teleophthalmology has improved the reach in underserved areas [10].
|
Risk Factor |
Effect on DR |
Clinical Significance |
Risk Factor |
|
Long duration of diabetes |
Increases cumulative retinal damage |
Strongest predictor of DR progression |
Long duration of diabetes |
|
Poor glycemic control (High HbA1c) |
Accelerates microvascular injury |
Increases incidence and severity |
Poor glycemic control (High HbA1c) |
|
Hypertension |
Worsens retinal vascular damage |
Promotes DR progression and DME |
Hypertension |
|
Dyslipidemia |
Contributes to retinal exudates |
Associated with diabetic macular edema |
Dyslipidemia |
|
Pregnancy |
May accelerate DR progression |
Requires closer retinal monitoring |
Pregnancy |
|
Renal disease |
Indicates systemic microvascular damage |
Associated with advanced DR |
Renal disease |
Table 1. Major Risk Factors for Diabetic Retinopathy
Screening and Diagnostic Strategies.
In-person dilated fundus examination, digital fundus photography with centralized grading, and point of care retinal imaging in primary care are current approaches to early detection through screening which is the most effective public-health intervention to prevent vision loss caused by DR. Screening intervals are risk-stratified: annual screening is typical; longer intervals are safe in low-risk people who have good control [11].
Improved sensitivity using advances in diagnostic imaging and earlier detection of pathology:
Optical coherence tomography (OCT): Gold standard test for the detection and quantification of macular edema; cross-sectional retinal anatomy for the treatment plan and monitoring [12].
OCT angiography (OCTA): Noninvasive imaging of microvasculature of the retina and choroid; has been used for the detection of early nonperfusion and neovascularisation, but suffers from artefacts and field of view limitations [13].
Wide-field fundus photography and fluorescein angiography: These can be used to assess peripheral ischemia and neovascularization; fluorescein angiography is still useful for some decisions about treatment [14,15].
Principles and options for treatment.
The treatment for DR will depend on the stage and the presence or absence of DME and/or presence of proliferative disease. Systemic risk control, intravitreal pharmacotherapy, laser treatment and vitreoretinal surgery are used when necessary to integrate with management. It is necessary to have shared decision making and individual care.
Diabetic Macular Edema (DME)
Anti-VEGF drugs are the first choice in the treatment of center involving DME. In randomized trials, agents like ranibizumab, aflibercept and bevacizumab have been shown to be effective at improving vision and central retinal thickness. Comparative trials indicate that aflibercept may be more effective at producing visual gains in eyes with poorer baseline vision, but cost and access will determine the choice of agent.
Insufficient response to anti-VEGF, pseudophakic eyes, or problems with adherence to frequent injections are indications for intravitreal corticosteroid implants (e.g., dexamethasone, fluocinolone), and may lead to cataract progression and elevation of intraocular pressure [19].
When DR is more advanced, it is called Proliferative Diabetic Retinopathy (PDR).
Historically, panretinal photocoagulation (PRP) has been effective in preventing severe vision loss due to PDR, and is commonly recommended for high-risk PDR. Anti-VEGF therapy has proven to cause regression of the retinal neovascularization, permitting medical management in many cases; however, PRP may still be a preferred treatment for those who have poor follow-up or a need for rapid and long-lasting regression [20,21].
When there is non-clearing vitreous hemorrhage or tractional retinal detachment with or threatening to involve the macula, or when there is combined pathology, surgical intervention (pars plana vitrectomy) is indicated. The outcomes and recovery of small gauge vitrectomy has improved with advances [22].
Treatment Algorithms and Practical Considerations
Clinically relevant considerations:
Promptly start anti-VEGF treatment for center-involving DME and re-evaluate often using OCT to adjust treatment frequency.
Steroids are an option for long-term treatment of DME following anti-VEGF or if injections are not used consistently; monitor for increase in intraocular pressure.
With PDR, consider the combination of anti-VEGF with PRP depending on the severity of the disease, the ability of the patient to adhere to the follow-up, and availability of the therapy.
Optimize glycemia, blood pressure and lipids as part of systemic disease management, in concert with primary care and endocrinology.
Ensure access to treatment: patient education, teleophthalmology when possible, and focus on high-risk patients for face-to-face evaluation.
New therapies and research areas.
DR research is ongoing on several fronts: longer acting anti-VEGF agents and systems which will decrease the burden of injection, multi-targeted agents targeting inflammation and Ang/ Tie pathways, gene and cell therapy and enhanced biomarkers based on OCT/OCTA and systemic proteomics. Port-delivery systems, sustained-release implants and new biologics have been tried to make the treatment more durable without compromising efficacy and safety [23–25].
Health Systems and Population-Level Approaches.
At scale, there is a need for DR screening to be integrated into primary care, for task shifting to trained graders and usage of AI for drug-rationing, for financing DR care and surgical interventions and for patient-centred education and adherence promotion. Low and middle-income countries have specific problems; scalable training and telemedicine programs have been successful if tailored to the local context [26].
The prognosis is favorable and long-term follow-up is possible.
Many patients can have reading vision and function in the everyday activities they perform after timely detection and treatment. DR is, however, chronic and recurrent – it can continue to advance even when the system is under control, and requires regular monitoring. Periodic imaging should be performed (with OCT for surveillance of DME) and retinal examination frequency should be modified according to baseline severity and previous response to treatment [27].
There are some restrictions on the current evidence. Current evidence is limited. While randomized trials have supported the current therapies, there are still gaps in evidence regarding optimal individualized retreatment regimens, long-term comparative effectiveness in different real-world populations, cost-effectiveness of various screening modalities in different populations and contexts, and best practices for integrating AI into clinical workflows. Trials that are more inclusive, with inclusion of under-respresented populations are necessary to assure generalizability.
SUMMARY AND RECOMMENDATIONS
1) Focus on prevention (intensive glycemic, blood pressure management and organized screening). 2) Conduct OCT-based evaluation and direct treatment of DME; anti-VEGF is first line treatment for DME involving change of centre.
3) In PDR, anti-VEGF medication can be an effective alternative to PRP for many patients, but PRP is still valuable when follow up is not assured.
4) Optimize system-level solutions, such as teleophthalmology, Interprofessional care, to increase reach.
5) Promote registry and pragmatic trials to fill gaps in evidence and to assess long-term effects.
Acknowledgments: This review draws on peer-reviewed literature and key randomized controlled trials (RCTs), meta-analyses, and guideline statements that are as up to date as 2024.
REFERENCES
GH Khan, M Aqil, KK Pillai, MA Ahmad, P Kapur, MR Ain, SS Al-Ghamdi, ...
Asian Pacific Journal of Tropical Disease 4, S347-S352
GH Khan, M Aqil, KK Pillai, MA Ahmad, P Kapur, MR Ain, SS Al-Ghamdi, ...
Asian Pacific Journal of Tropical Disease 4, S347-S352
Md. Afroz Ahmad*, Diabetic Retinopathy: Current Perspectives On Prevention, Diagnosis, And Treatment, Int. J. Sci. R. Tech., 2026, 3 (8), 338-343. https://doi.org/10.5281/zenodo.21872655
10.5281/zenodo.21872655