Non-Proliferative Diabetic Retinopathy

Nonproliferative Diabetic Retinopathy (NPDR): Detection, Stages, and Management

Nonproliferative diabetic retinopathy (NPDR) is the early stage of diabetic retinopathy, characterized by vascular damage to the retina without neovascularization. Although it is not immediately vision-threatening, its progression can lead to serious complications if left uncontrolled.

What happens in NPDR?

Chronic hyperglycemia damages retinal capillaries, causing:

Weakening of vascular walls → Microaneurysms (small dilated red dots).

Increased vascular permeability → Lipid exudates (yellow deposits of proteins/lipids).

Retinal edema (thickening of the retina).

Small vessel obstruction → Intraretinal hemorrhages (dark red spots).

Retinal ischemia (areas without oxygen, called "areas of non-perfusion").

NPDR Classification (ETDRS)

NPDR is divided into three stages according to its severity:

Mild NPDR

Isolated microaneurysms.

Moderate NPDR

Microaneurysms + intraretinal hemorrhages ± hard exudates.

Severe NPDR 4-2-1 sign:

- Hemorrhages in 4 quadrants.

- "String of pearls" veins in 2+ quadrants. (High probability of evolving to proliferative).

- Intraretinal microvascular abnormalities (IRMA) in 1+ quadrants.

Symptoms: How to suspect nonproliferative diabetic retinopathy (NPDR)?

In mild/moderate stages:

Asymptomatic (which is why annual fundus examination is crucial).

In severe NPDR or with associated macular edema:

Blurred vision (if the macula is involved).

Difficulty reading or seeing fine details.

Colors are less vibrant.

Diagnosis

Fundoscopy with pupillary dilation:

Evaluates for microaneurysms, hemorrhages, and exudates.

Optical Coherence Tomography (OCT):

Detects diabetic macular edema (retinal thickening >300 μm).

Fluorescein angiography:

Identifies ischemic areas and vascular leaks.

Important:

Diabetic macular edema (DME) can occur at any stage of NPDR and is the leading cause of vision loss at this stage.

Management and Treatment

1. Tight Metabolic Control

HbA1c goal: <7% (or <8% in older adults).

Blood pressure control: <130/80 mmHg.

Lipids: LDL <100 mg/dL (in diabetics).

2. Ophthalmologic Follow-up

Stage of Nonproliferative Diabetic Retinopathy (NPDR): Frequency of Check-ups

Mild: Every 12 months.

Moderate: Every 6-12 months.

Severe: Every 3-6 months.

3. Specific Treatments

✔ Diabetic macular edema (DME):

Intravitreal injections of anti-VEGF (Aflibercept, Ranibizumab).

Steroid implants (Ozurdex®) in refractory cases.

Focal laser (if leaks are localized).

✔ Severe NPDR (close to proliferative):

Urgent referral to a retinal specialist to prevent neovascularization.

What Happens if Not Treated?

Progression to proliferative retinopathy (50-75% of cases of severe Nonproliferative Diabetic Retinopathy (NPDR).

Chronic macular edema: Irreversible loss of visual acuity.

Macular ischemia: Distorted central vision or scotomas.

Factors that Accelerate Progression

❌ HbA1c >9%.

❌ Uncontrolled hypertension.

❌ Pregnancy (hormonal changes worsen DR).

❌ Diabetic kidney disease.

Key Message for Patients

"NPDR doesn't show symptoms until it's too late": Annual fundus examination is your best protection.

"Diabetes control slows retinal damage": Each point decrease in HbA1c reduces the risk of progression by 35%.