What are the clinical features of diabetic retinopathy?

Clinical Features of Diabetic Retinopathy

Diabetic retinopathy progresses through distinct stages characterized by specific retinal vascular abnormalities, with nonproliferative disease showing microaneurysms, hemorrhages, and exudates, while proliferative disease demonstrates neovascularization that threatens vision through bleeding and retinal detachment. 1

Nonproliferative Diabetic Retinopathy (NPDR)

The nonproliferative stages are characterized by retinal vascular abnormalities without neovascularization 1:

Early Clinical Features

• Microaneurysms: The first clinically visible manifestation, appearing as small red dots, most commonly in the macular region 2
• Intraretinal hemorrhages: Dot-blot or flame-shaped hemorrhages from leaking vessels 1
• Venous dilation: Early vascular changes indicating disease progression 1
• Cotton wool spots: Nerve fiber layer infarcts appearing as white fluffy patches 1

Progressive Features Indicating Ischemia

As retinal vessel closure progresses, signs of increasing ischemia emerge 1:

• Venous abnormalities: Including dilation, beading (alternating areas of constriction and dilation), and loops 1
• Intraretinal microvascular abnormalities (IRMA): Tortuous intraretinal vascular segments that may be difficult to distinguish from neovascularization 1
• Hard exudates: Yellow-white lipid deposits composed of lipoproteins and proteinaceous material from vascular leakage 1, 3

Severity Classification of NPDR

The American Academy of Ophthalmology classifies NPDR severity using the "4-2-1 rule" for severe NPDR 1:

1. Mild NPDR: At least one microaneurysm present 1
2. Moderate NPDR: Hemorrhages/microaneurysms greater than standard photograph 2A, with soft exudates, venous beading, or IRMA present 1
3. Severe NPDR: At least one of the following:
   • Severe intraretinal hemorrhages and microaneurysms in 4 quadrants
   • Venous beading in 2 or more quadrants
   • Moderate IRMA in 1 or more quadrants 1

Eyes with IRMA have a 1.77-fold increased risk of progressing to proliferative disease, while those with 4-quadrant dot-blot hemorrhages have a 3.84-fold increased risk of vitreous hemorrhage. 1

Proliferative Diabetic Retinopathy (PDR)

PDR represents the advanced stage characterized by neovascularization in response to global retinal ischemia 1:

Neovascularization Patterns

• New vessels on the disc (NVD): Neovascularization on or within 1 disc diameter of the optic disc 1
• New vessels elsewhere (NVE): Neovascularization greater than 1 disc diameter from the optic disc margin, typically along vascular arcades 1

High-Risk PDR Characteristics

High-risk PDR requires prompt panretinal photocoagulation and consideration of anti-VEGF therapy 1:

• NVD equaling or exceeding one-quarter to one-third disc area (standard photograph 10A), with or without hemorrhage 1
• Vitreous or preretinal hemorrhage with any NVD or NVE equaling or exceeding one-quarter disc area 1

Complications of PDR

• Vitreous hemorrhage: From bleeding of fragile new vessels 1
• Fibrous proliferation: New vessels undergo fibrosis and contraction 1
• Epiretinal membrane formation: Causing visual distortion 1
• Tractional retinal detachment: From vitreoretinal traction and retinal tears 1
• Neovascular glaucoma: From new vessels growing on iris and anterior chamber angle structures 1

Worse baseline levels of PDR are associated with a 3.97-fold increased risk of progression regardless of treatment modality. 1

Diabetic Macular Edema (DME)

DME can occur at any stage of diabetic retinopathy and represents a separate vision-threatening manifestation 1:

Clinical Features

• Retinal thickening (edema): From increased vascular permeability 1
• Hard exudates: Lipid deposits adjacent to or involving the macula 1, 3

Clinically Significant Macular Edema (CSME)

CSME requires prompt treatment consideration, particularly when center-involved 1, 3:

• Retinal thickening and/or adjacent hard exudates that involve the center of the macula or threaten to involve it 1
• Hard exudates at or within 500 μm of the center of the macula with adjacent retinal thickening 3

Classification

• Center-involved DME: Retinal thickening with hard exudates involving the central 1mm subfield, requiring prompt ophthalmologic referral 3
• Non-center-involved DME: Retinal thickening with hard exudates not involving the central 1mm 3

Important Clinical Pitfalls

Neurodegeneration occurs early in diabetic retinopathy, potentially before clinically visible microvascular changes, though microaneurysms remain the first detectable clinical feature with standard examination techniques. 1, 4, 2 This emphasizes the importance of regular screening even in patients without visible retinopathy.

Hard exudates may persist even after successful treatment of retinal thickening and do not necessarily indicate active disease. 3 Their presence and location, however, remain important for determining follow-up intervals and treatment decisions.