Diabetic retinopathy

Last updated: February 10, 2023

Summary

Diabetic retinopathy is a vascular disease of the retina that is usually asymptomatic in the early stages but can lead to visual impairment and blindness as the disease progresses. The majority of cases of diabetic retinopathy are detected during screening examinations. Further tests (optical coherence tomography, fluorescein angiography) may be performed to determine severity or identify complications. Management for all patients includes optimization of treatment for diabetes, managing risk factors for atherosclerotic cardiovascular disease (ASCVD), and referral to an ophthalmologist for further management and monitoring. Further treatment depends on the subtype (nonproliferative diabetic retinopathy or proliferative diabetic retinopathy), presence of macular edema, and severity of diabetic retinopathy and includes panretinal photocoagulation (PRP), intravitreal anti-vascular endothelial growth factor (VEGF) and vitrectomy.

Overview of diabetic retinopathy

Diabetic retinopathy is usually detected on routine screening, and then classified and treated based on the presence of neovascularization, retinal thickening, and disease severity. ^[1]

Overview of diabetic retinopathies ^[1]^[2]
	Nonproliferative retinopathy (NPDR)	Proliferative retinopathy (PDR)	Diabetic macular edema (DME)
Mechanism	Retinal vessel microangiopathy → blood leaks → retinal hemorrhages	Retinal vessel microangiopathy → chronic retinal hypoxia → abnormal proliferation of blood vessels → traction on retina → retinal detachment	Retinal vessel microangiopathy → blood leaks → retinal hemorrhages → retinal infiltration with lipids and fluid → macular edema
Examination findings (dilated comprehensive eye exam or retinal photography)	Microaneurysms Caliber changes in veins Intraretinal hemorrhage Hard exudates Retinal edema Cotton-wool spots Intraretinal microvascular abnormalities (IRMA)	Findings of nonproliferative retinopathy are usually present. Neovascularization is the hallmark of PDR Fibrovascular proliferation → vitreous hemorrhage, traction retinal detachment Rubeosis iridis → secondary glaucoma ^[3]	Clinically significant retinal thickening and edema involving the macula, associated hard exudates May occur in all stages of NPDR and PDR
Vision loss	May result from macular edema	May result from vitreous hemorrhage, retinal detachment, or neovascular glaucoma	May lead to vision loss
Treatment ^[1]	Treatment of diabetes and underlying ASCVD risk factors Mild-to-moderate: observation only; reassess every 6–12 months Severe: Consider PRP or anti-VEGF therapy.	Treatment of diabetes and underlying ASCVD risk factors PRP (usually first-line) and/or anti-VEGF therapy	Treatment of diabetes and underlying ASCVD risk factors PRP, focal and/or grid laser, and anti-VEGF therapy may be considered depending on severity.

Vitrectomy may be required for patients with complications, e.g., tractional retinal detachment, vitreous hemorrhage ^[1]

Proliferative diabetic retinopathy Tractional retinal detachment in proliferative diabetic retinopathy Nonproliferative diabetic retinopathy Neovascularization in proliferative diabetic retinopathy . Neovascularization of the iris (rubeosis iridis)

Epidemiology

After 15 years, approx. 80% of patients with type 1 diabetes will develop retinopathy. ^[1]
Among patients > 30 years old with type 2 diabetes: ^[1]
- Patients not requiring insulin
  - Approx. 25% will develop retinopathy within 5 years of diagnosis.
  - Approx. 50% will develop retinopathy within 19 years.
- Patients requiring insulin
  - Approx. 40% will develop retinopathy within 5 years of diagnosis.
  - Approx. 85% will develop retinopathy within 19 years.
Diabetic retinopathy is the most common cause of visual impairment and blindness in patients aged 20–74 years. ^[4]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Development and progression of diabetic retinopathy is associated with: ^[2]^[4]

Diabetes-related factors
- Poor glycemic control
- Increased duration of diabetes
- Presence of diabetic nephropathy
Other cardiovascular risk factors
- Hypertension
- Dyslipidemia
Puberty
Pregnancy
History of cataract surgery

Clinical features

Early stages: usually asymptomatic ^[2]
Patients may experience symptoms of associated complications, e.g., macular edema, vitreous hemorrhage, and retinal detachment. ^[5]
- Blurred vision
- Floaters
- Photopsia
- Scotoma
- Sudden, painless vision loss
Later stages: significant visual impairment progressing to blindness

Screening

Modalities ^[1]^[4]
- Dilated comprehensive eye examination performed by an ophthalmologist/optometrist
- Retinal photography
Onset
- Type 1 DM: within 5 years of the onset of disease ^[1]^[6]
- Type 2 DM: at the time of diagnosis ^[1]
Interval: every year ^[1]

Less frequent retinopathy screening (e.g., every 2 years) may be considered in consultation with an ophthalmologist or optometrist for patients with diabetes who have a normal initial eye exam and good glycemic control. ^[4]^[6]

Diagnostics

General principles ^[1]^[4]

Usually detected on screening
Symptomatic patients should undergo a comprehensive eye examination (including slit lamp examination and fundoscopy) with the pupil dilated.
Ancillary testing, e.g., optical coherence tomography (OCT), fluorescein angiography, may be performed to:
- Assess disease severity.
- Determine treatment approach and assess response.
- Exclude differential diagnoses of sudden vision loss.

Retinal findings

Findings in diabetic retinopathy ^[1]^[2]
		Features
NPDR	Mild NPDR	≥ 1 capillary microaneurysms
	Moderate NPDR	≥ 1 of the following: Capillary microaneurysms (to a greater extent than in mild NPDR) Intraretinal hemorrhages Hard exudates ^[2] Cotton wool spots Mild intraretinal microvascular abnormalities or signs of ischemia
	Severe NDPR	≥ 1 of the following: In all 4 retinal quadrants: capillary microaneurysms, dot intraretinal hemorrhages In ≥ 2 retinal quadrants: signs of ischemia (e.g., venous beading) In ≥ 1 retinal quadrant: moderate intraretinal microvascular abnormalities
PDR	Nonhigh-risk PDR	Neovascularization Criteria for high-risk PDR not met
PDR	High-risk PDR	Neovascularization On the optic disc or within 1 disc diameter Or elsewhere in the eye, if accompanied by vitreous and/or preretinal hemorrhage
Clinically significant macular edema		Within 500 microns of the center of the macula Retinal thickening Hard exudates (if associated with adjacent retinal thickening) Within 1 disc diameter of the center of the macula: any zone of retinal thickening ≥ 1 disc size in any area If OCT has been performed, can be further categorized into: ^[7] Center-involving DME: ≥ 1 mm diameter retinal thickening in a central subfield Noncenter-involving DME: ≥ 1 mm diameter retinal thickening that does not involve a central subfield

Management

Approach ^[1]^[4]

Refer all patients with diabetic retinopathy to an ophthalmologist.
Optimize glycemic control with: ^[8]
- Antihyperglycemic treatment of diabetes
- Lifestyle recommendations for patients with diabetes mellitus
Manage ASCVD risk factors.
- Treat hypertension if present (see “Approach to management of hypertension”).
- Initiate treatment for lipid disorders as indicated (see “Guidelines for lipid-lowering therapy”).
- Continue aspirin if indicated for another condition. ^[1]
Screen for additional microvascular complications of diabetes because of the high risk of co-occurrence.
Arrange follow-up eye exams at regular intervals. ^[1]
For patients with significant vision impairment, consider:
- Referral for vision rehabilitation
- Assessment for fitness to drive

Early detection and treatment of diabetic retinopathy can prevent 90% of blindness. ^[1]

Treatment by retinopathy subtype ^[1]^[4]

Nonproliferative retinopathy
- Mild NPDR to moderate NPDR: Observation only; repeat dilated comprehensive eye examination every 6–12 months.
- Severe NPDR: Treat as proliferative retinopathy with panretinal laser photocoagulation (PRP) and/or anti-VEGF therapy.
Proliferative retinopathy: PRP and/or anti-VEGF therapy
- Both PRP and anti-VEGF therapy are equally effective.
- PRP is usually preferred as treatment occurs in a single session (reduces risk of loss to follow-up). ^[1]
- Anti-VEGF injections alone can be considered for patients who are highly motivated and have no barriers to follow-up.
- Additional treatments should be utilized if after initial treatment, any of the following are present:
  - New vitreous hemorrhage or neovascularization
  - Failure of existing neovascularization to regress
Macular edema ^[1]
- Center-involving macular edema
  - First line: Intravitreal anti-VEGF therapy
  - Consider PRP or focal and/or grid laser depending on severity of retinopathy.
- Noncenter-involving macular edema: PRP, anti-VEGF, or focal and/or grid laser therapy may be used depending on severity of retinopathy.
Refractory disease or severe complications (e.g., tractional retinal detachment, vitreal hemorrhage): Consider vitrectomy.

Prevention

Optimize management of diabetes to ensure patients meet glycemic targets for DM. ^[1]^[4]
Manage ASCVD risk factors. ^[4]
Educate patients on the importance of screening for complications of diabetes. ^[9]
- Ensure patients are aware that they may not experience symptoms until the disease is advanced.
- Address risk factors for poor adherence (see “Managing chronic conditions”).
Advise patients to seek immediate medical attention if they notice any changes in their vision.

Advise patients to attend regular screenings as microvascular complications are usually asymptomatic until significant damage has occurred. ^[1]

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