Intravitreal anti-VEGF therapy and risk of limb complications in individuals with diabetic eye disease
Main finding · Lower extremity amputation (LEA)Result — go to the resultHazard ratio 1.54 95 % CI 1.38–1.72Authors' conclusion
Anti-VEGF therapy in DED was linked to increased DFU and LEA risk, especially in high-risk subgroups. Prospective studies are needed for confirmation.
Study context
- Population
- Adults with diabetic eye disease receiving intravitreal anti-VEGF injections, U.S. electronic health records network34,070 per group after matching
- Participants
- 448,100 adults
- Exposure
- ≥3 intravitreal anti-VEGF injections vs ≤2
- IVIn = 34,070
- Controlsn = 34,070reference
- Outcome
- Lower extremity amputation (LEA)
Methodological detailspropensity-score matched (1:1), U.S. electronic health records network
- Propensity-score matched (1:1)
- U.S. electronic health records network
Main finding
As reported in the abstract
Hazard ratio
1.54
95 % CI 1.38–1.72
IVIvs Controls
HR 1.54 (95 % CI 1.38–1.72)
Observational data: associations, not effects.
Further findings
| Outcome | HR (CI) | |
|---|---|---|
| Above-ankle LEA | 1.31 (1.08–1.59) | |
| DFU | 1.36 (1.30–1.42) | |
| 0.512Hazard ratio (log scale) |
Lower extremity amputation (LEA) in subgroups with proliferative diabetic retinopathy (PDR), peripheral artery disease (PAD), end-stage renal disease (ESRD) or prior diabetic foot ulcer (DFUs)
- LEA risk greater with IVI vs controls in subgroups with PDR, PAD, ESRD or DFUs
Comparison among ranibizumab, aflibercept and bevacizumab
- Risks were similar across agents
Original publication
Intravitreal anti-VEGF therapy and risk of limb complications in individuals with diabetic eye disease. Diabetes Res Clin Pract. Published 5 September 2025. doi:10.
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