Stages of Proliferative Diabetic Retinopathy (PDR)
Proliferative diabetic retinopathy (PDR) is characterized by the onset of neovascularization at the inner surface of the retina and into the vitreous, induced by global retinal ischemia, and can be classified into moderate PDR and high-risk PDR based on specific clinical findings. 1
Progression to PDR
Diabetic retinopathy follows a predictable progression from nonproliferative diabetic retinopathy (NPDR) to PDR:
NPDR stages (precursors to PDR):
- Mild NPDR: Microaneurysms, occasional blot hemorrhages or hard exudates
- Moderate NPDR: More extensive microaneurysms, hemorrhages
- Severe NPDR: Characterized by the "4-2-1 rule" (any of these features):
- Extensive intraretinal hemorrhages in 4 quadrants
- Venous beading in 2+ quadrants
- Intraretinal microvascular abnormalities (IRMA) in 1+ quadrant
- Very severe NPDR: Two or more of the severe NPDR features 1
Transition to PDR:
- The risk of progression from severe NPDR to PDR is high (15% within 1 year)
- Very severe NPDR has a 45% risk of progressing to PDR within 1 year 1
PDR Stages
1. Early/Moderate PDR
- Characterized by neovascularization of the retina
- New vessels elsewhere (NVE) in the retina
- New vessels on or near the optic disc (NVD) that occupy less than one-quarter to one-third disc area
- No vitreous or preretinal hemorrhage 1
2. High-Risk PDR
High-risk PDR is defined by the presence of any of the following features:
- Neovascularization at the optic disc (NVD) that occupies ≥1/4 to 1/3 disc area, even without vitreous hemorrhage
- Any neovascularization with vitreous or preretinal hemorrhage
- New vessels elsewhere (NVE) that are at least one-half disc area in size with vitreous or preretinal hemorrhage 1
3. Advanced PDR Complications
- Vitreous hemorrhage
- Fibrovascular proliferation
- Traction retinal detachment
- Neovascular glaucoma (from new vessels growing on the iris and anterior chamber angle)
- Epiretinal membrane formation 1
Risk Factors for PDR Progression
Several factors influence the progression of PDR:
- Baseline PDR severity: Worse baseline levels of PDR are associated with a 3.97 times higher risk of PDR progressing, regardless of treatment 1
- Glycemic control: Higher HbA1c levels increase risk of progression (adjusted OR ranges from 1.11 to 2.10) 2
- Duration of diabetes: Strong predictor for development and progression of retinopathy 1
- Renal disease: Markers of renal disease (nephropathy, elevated creatinine) increase risk of progression 2
- Treatment type: In patients receiving PRP, those receiving pattern scan versus conventional single-spot PRP had a 2.04 times higher risk of worsening PDR 1
Treatment Implications Based on PDR Stage
Moderate PDR
- Close monitoring (every 2-4 months)
- Consider early PRP, especially for patients with very severe NPDR and non-high-risk PDR 1
- Anti-VEGF therapy may be considered as an alternative to PRP in patients with reliable follow-up 1, 3
High-Risk PDR
- Expeditious PRP is strongly recommended
- Anti-VEGF therapy (such as ranibizumab) may be used as an alternative to PRP in selected patients with reliable follow-up 1, 3
- Combined approaches may be necessary in some cases 4
Important Clinical Considerations
- PDR can progress rapidly without appropriate intervention
- Patients with PDR undergoing anti-VEGF injections who are lost to follow-up have worse outcomes than those who received PRP 1
- Additional PRP or anti-VEGF therapy should be considered when:
- Neovascularization fails to regress
- Neovascularization increases
- New vitreous hemorrhage develops
- New areas of neovascularization appear 1
Pitfalls and Caveats
- Visual acuity may be preserved even in advanced PDR, leading to delayed diagnosis and treatment
- Anti-VEGF therapy alone requires consistent follow-up; patients with poor compliance may benefit more from PRP 3
- When patients undergo anti-VEGF treatment and the treatment is stopped after edema is controlled, closer follow-up is necessary as progression of retinopathy may accelerate 1
- Early detection and treatment of PDR is critical, as PRP is 90% effective in preventing severe vision loss when applied at appropriate stages 1