Explain diabetic retinopathy, its screening guidelines, prevention, and management.

Diabetic Retinopathy: Pathophysiology, Screening, Prevention, and Management

What is Diabetic Retinopathy?

Diabetic retinopathy is a microvascular complication of both type 1 and type 2 diabetes that damages the retinal blood vessels and represents the leading cause of preventable blindness in working-age adults. 1 The disease progresses through stages from nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR), with diabetic macular edema (DME) potentially occurring at any stage. 1, 2

Disease Progression and Classification

The International Clinical Diabetic Retinopathy Disease Severity Scale divides the disease into five stages: no apparent retinopathy, mild NPDR, moderate NPDR, severe NPDR, and PDR, with macular edema assessed independently. 2

Key Pathophysiologic Features:

• Nonproliferative changes include microaneurysms, intraretinal hemorrhages, venous beading, hard exudates (lipid deposits), and intraretinal microvascular abnormalities. 1
• Proliferative disease represents an angiogenic response to extensive retinal ischemia, characterized by neovascularization on the optic disc or along vascular arcades. 1
• Diabetic macular edema involves retinal thickening that can occur at any stage and threatens central vision when it involves the foveal center. 1

Risk Factors

The primary risk factors that increase retinopathy development and progression include:

• Chronic hyperglycemia (most significant modifiable risk factor) 1
• Duration of diabetes (strongest predictor overall) 1
• Hypertension (established risk factor for macular edema and PDR) 1, 3
• Dyslipidemia 1, 3
• Nephropathy (strongly associated with retinopathy presence) 1
• Pregnancy (can aggravate existing retinopathy, especially with poor glycemic control) 1, 3

Prevention Strategies

Intensive diabetes management targeting near-normoglycemia (HbA1c <7%), combined with blood pressure control to <130/80 mmHg and lipid optimization, reduces the risk of developing diabetic retinopathy by approximately 67% and slows progression by 33%. 3

Glycemic Control:

• Target HbA1c <7% through intensive diabetes management. 3
• Large prospective randomized studies (DCCT, UKPDS) demonstrated that intensive glycemic control prevents and delays both onset and progression of diabetic retinopathy. 1, 3

Blood Pressure Management:

• Maintain blood pressure <130/80 mmHg. 3
• ACE inhibitors or ARBs are preferred first-line agents for patients with diabetes and hypertension, especially when retinopathy is present. 3
• The UKPDS demonstrated that lowering blood pressure decreases retinopathy progression. 1, 3

Lipid Control:

• Optimize serum lipid levels to reduce retinopathy risk and slow progression. 1, 3

Important Caveat:

Aspirin therapy for cardioprotection should NOT be discontinued due to retinopathy concerns, as aspirin does not increase the risk of retinal hemorrhage. 1, 3

Screening Guidelines

Type 1 Diabetes:

Perform initial dilated comprehensive eye examination within 5 years after diabetes onset, then annually if any retinopathy is present. 1, 4, 3

Type 2 Diabetes:

Perform initial dilated comprehensive eye examination at the time of diagnosis, then annually if any retinopathy is present. 1, 3

Modified Screening Intervals:

• If no retinopathy is found for one or more annual exams AND glycemia is well controlled, screening every 1-2 years is acceptable. 1, 3, 2
• More frequent examinations (every 3 months or more) are required if retinopathy is progressing or sight-threatening. 1, 2

Special Populations:

Pregnancy:

• Women with preexisting type 1 or type 2 diabetes planning pregnancy or who become pregnant require eye examination before pregnancy or in first trimester. 3
• Monitor every trimester and for 1 year postpartum, as pregnancy may aggravate retinopathy (pooled progression rate of 15% for new retinopathy development, 31% for worsening NPDR, and 6.3% progression from NPDR to PDR per 100 pregnancies). 1, 3
• Laser photocoagulation can minimize vision loss risk during pregnancy for high-risk PDR or center-involved DME. 1
• Anti-VEGF medications are contraindicated in pregnancy due to theoretical risks to fetal vasculature. 1

Youth with Diabetes:

• Screen by dilated fundoscopy at or soon after diagnosis and annually thereafter for youth with type 2 diabetes. 3

Referral Criteria

Promptly refer patients with any of the following to an ophthalmologist experienced in diabetic retinopathy management: 1, 2

• Any level of diabetic macular edema
• Moderate or worse NPDR (precursor to PDR)
• Severe NPDR
• Any proliferative diabetic retinopathy

Treatment Options

Panretinal Laser Photocoagulation (PRP):

PRP remains the traditional standard treatment to reduce the risk of vision loss in patients with high-risk PDR and, in some cases, severe NPDR. 1, 4

• The Diabetic Retinopathy Study (1978) showed PRP reduced severe vision loss from 15.9% in untreated eyes to 6.4% in treated eyes. 1
• Greatest benefit occurs in eyes with high-risk characteristics (disc neovascularization or vitreous hemorrhage with any retinal neovascularization). 1
• The Early Treatment Diabetic Retinopathy Study verified benefits for high-risk PDR and severe NPDR. 1

Anti-VEGF Therapy:

Intravitreal anti-VEGF injections (ranibizumab, aflibercept) are non-inferior to PRP for proliferative diabetic retinopathy and are FDA-approved for this indication. 1, 4

Advantages of anti-VEGF over PRP: 1

• Less peripheral visual field loss
• Fewer vitrectomy surgeries for secondary complications
• Lower risk of developing diabetic macular edema

Disadvantages of anti-VEGF: 1

• Requires greater number of visits and treatments than PRP
• May not be optimal for patients with poor follow-up compliance

Center-Involved Diabetic Macular Edema:

Intravitreal anti-VEGF injections are indicated as first-line treatment for center-involved DME that threatens reading vision. 1

• Focal/grid laser photocoagulation is now considered second-line treatment for DME. 1
• The ETDRS showed focal laser reduced visual angle doubling from 20% in untreated eyes to 8% in treated eyes with clinically significant macular edema. 1

Vitrectomy:

Vitrectomy is beneficial for severe proliferative retinopathy with vitreous hemorrhage that severely reduces visual acuity. 5

Common Pitfalls to Avoid

• Do not delay screening in type 2 diabetes—examination must occur at diagnosis, not years later, as many patients already have retinopathy at diagnosis. 3
• Do not assume asymptomatic patients are safe—advanced stages of diabetic retinopathy and macular edema can be present without visual symptoms. 1, 2
• Do not withhold aspirin therapy—retinopathy is not a contraindication to aspirin for cardioprotection. 1, 3
• Avoid rapid glycemic improvement in patients with existing retinopathy—rapid implementation of intensive glycemic management is associated with early worsening of retinopathy. 1
• Do not use anti-VEGF therapy in pregnant patients—laser photocoagulation is the treatment of choice during pregnancy. 1

Monitoring and Follow-up

The preventive effects of therapy and the fact that patients with PDR or macular edema may be asymptomatic provide strong support for systematic screening rather than symptom-based evaluation. 1 Treatment for diabetic retinopathy may be 90% effective in preventing severe vision loss using current therapeutic strategies. 1