Diabetic retinopathy
Diabetic retinopathy is a complication of diabetes mellitus that damages the blood vessels in the retina—the light-sensitive tissue at the back of the eye responsible for vision—and can lead to severe vision impairment or blindness if untreated.[1] It affects both type 1 and type 2 diabetes, as well as gestational diabetes, and is the leading cause of new cases of blindness in working-age adults in the United States.[2][3] Globally, as of 2024, the prevalence is approximately 25% among people with diabetes.[4] Over time, more than half of people with diabetes will develop some form of diabetic retinopathy.[2] The condition arises primarily from prolonged exposure to high blood sugar levels, which weaken and damage the retinal blood vessels, causing them to leak fluid, swell, or close off, thereby depriving the retina of oxygen and nutrients.[5] In advanced stages, the retina may respond by growing abnormal new blood vessels (neovascularization), which are fragile and prone to bleeding.[1] Key risk factors include the duration of diabetes, poor blood sugar control (e.g., elevated HbA1c levels), high blood pressure, elevated cholesterol, kidney disease, pregnancy, and tobacco use; certain ethnic groups, such as African Americans, Hispanics, and Native Americans, face higher risks.[2][5] About 1 in 15 people with diabetes will develop diabetic macular edema, a common complication where fluid accumulates in the macula (the central part of the retina), leading to central vision loss.[2] Diabetic retinopathy progresses through two main stages: nonproliferative diabetic retinopathy (NPDR), the early phase characterized by microaneurysms, hemorrhages, and cotton-wool spots without new vessel growth; and proliferative diabetic retinopathy (PDR), the advanced phase involving neovascularization that can cause vitreous hemorrhage, retinal detachment, or neovascular glaucoma.[5][3] In the early stages, symptoms are often absent or subtle, but as the disease advances, patients may experience blurred or fluctuating vision, dark or empty areas in the visual field, floaters, difficulty seeing colors, or sudden vision loss.[1] Diagnosis typically involves a comprehensive dilated eye examination, optical coherence tomography (OCT) to detect swelling, and fluorescein angiography to visualize blood vessel abnormalities.[5][2] Treatment strategies aim to slow progression and preserve vision, starting with rigorous management of blood sugar, blood pressure, and cholesterol through lifestyle changes, medications, and insulin therapy.[1] For moderate to severe cases, options include intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as ranibizumab or aflibercept to reduce vessel leakage and growth; focal or panretinal laser photocoagulation to seal leaks or shrink abnormal vessels; or vitrectomy surgery to remove blood or scar tissue in advanced PDR.[5][2] Prevention is critical and involves annual dilated eye exams for all people with diabetes, maintaining HbA1c below 7%, controlling hypertension and dyslipidemia, quitting smoking, and adopting a healthy diet and exercise routine.[3] Early detection and intervention can reduce the risk of severe vision loss by more than 90% in high-risk cases.[6]Definition and Classification
Definition
Diabetic retinopathy is a neurovascular complication of diabetes mellitus that primarily affects the retina, the light-sensitive tissue at the back of the eye, and can lead to progressive vision impairment or blindness if untreated.[7] It occurs in both type 1 and type 2 diabetes due to chronic exposure to high blood sugar levels, which damage the retinal blood vessels over time.[2] As the leading cause of preventable blindness in working-age adults in developed countries, it represents a significant microvascular disorder tied to the duration and severity of hyperglycemia.[8] The condition is broadly distinguished into two main forms: non-proliferative diabetic retinopathy (NPDR), the milder early stage involving damage to existing retinal vessels without new vessel formation, and proliferative diabetic retinopathy (PDR), the more severe advanced stage characterized by abnormal neovascularization driven by retinal ischemia.[5] Hyperglycemia contributes etiologically by inducing metabolic changes, such as activation of the polyol pathway and formation of advanced glycation end products, which increase vascular permeability and promote capillary occlusion.[8] Historically, diabetic retinopathy was first clinically described in 1856 by Austrian ophthalmologist Eduard Jaeger, who used the newly invented direct ophthalmoscope to document macular changes, including yellowish spots and extravasations, in a young patient with advanced diabetes.[9] Although early observations linked these retinal findings to diabetes, the condition was not fully recognized as a specific diabetes-related entity until the 20th century, with advancements in endocrinology and ophthalmology clarifying its pathogenesis.[10] In terms of retinal impact, the disease begins with the formation of microaneurysms—small saccular dilatations of capillaries—and intraretinal hemorrhages from vessel wall weakening, which can leak fluid and cause edema.[8] These early changes may progress to more extensive vascular leakage and, in PDR, to fragile neovascularization on the retina or optic disc, heightening the risk of vitreous hemorrhage and retinal detachment.[11]Stages and types
Diabetic retinopathy is classified using standardized systems to assess disease severity and guide clinical management. The International Clinical Diabetic Retinopathy (ICDR) Disease Severity Scale, developed through international consensus, provides a simplified five-level grading for nonproliferative and proliferative stages, facilitating communication among healthcare providers.[12] This scale emphasizes observable retinal lesions and stratifies risk for progression to vision-threatening complications. In the ICDR scale, nonproliferative diabetic retinopathy (NPDR) progresses from mild to severe forms. Mild NPDR is characterized by the presence of microaneurysms only, representing the earliest detectable vascular changes. Moderate NPDR involves more extensive lesions, such as hemorrhages, microaneurysms, venous beading, and intraretinal microvascular abnormalities (IRMAs), but without meeting criteria for severe disease.[12] Severe NPDR indicates high-risk nonproliferative changes, defined by any of the following: more than 20 intraretinal hemorrhages in each of four quadrants, venous beading in two or more quadrants, or prominent IRMAs in one or more quadrants. Proliferative diabetic retinopathy (PDR) marks the advanced stage, featuring neovascularization on the optic disc (NVD) or elsewhere (NVE), or vitreous/preretinal hemorrhage.[12] High-risk PDR, which carries the greatest threat of severe visual loss, is identified by specific neovascular features: NVD greater than one-fourth to one-third disc area, any NVD with vitreous or preretinal hemorrhage, or NVE greater than one-half disc area with vitreous or preretinal hemorrhage. For research purposes, the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria offer a more granular 13-step severity scale, ranging from no retinopathy to advanced PDR, to ensure consistency in clinical trials and outcome measurements.[13] This scale builds on standardized fundus photography and lesion grading, with steps corresponding to increasing lesion density and extent, such as level 20 for very mild NPDR (microaneurysms only) up to level 80+ for high-risk PDR. Diabetic macular edema (DME), a common concurrent complication that can occur at any retinopathy stage, is classified using optical coherence tomography (OCT) as center-involved DME (involving the foveal center with central subfield thickness ≥300 μm) or non-center-involved DME (edema present but sparing the foveal center).[14] This OCT-based distinction helps predict visual impact and informs treatment decisions, with center-involved DME more likely to cause central vision loss.[15]| ICDR Severity Level | Key Features |
|---|---|
| No apparent retinopathy | No visible lesions |
| Mild NPDR | Microaneurysms only |
| Moderate NPDR | Hemorrhages, microaneurysms, venous beading, cotton-wool spots, but less than severe NPDR criteria |
| Severe NPDR | >20 hemorrhages in each of 4 quadrants, OR venous beading in ≥2 quadrants, OR IRMAs in ≥1 quadrant |
| Proliferative DR | Neovascularization (disc or elsewhere) or vitreous/preretinal hemorrhage |
| ETDRS Scale Steps (Selected) | Description |
|---|---|
| 10 | No retinopathy |
| 20 | Very mild NPDR (microaneurysms only) |
| 35 | Mild NPDR (microaneurysms + hard exudates) |
| 43-53 | Moderate NPDR (increasing hemorrhages, venous changes) |
| 60-70 | Severe NPDR (extensive lesions) |
| 71-80+ | PDR (neovascularization, high-risk characteristics) |