VEGF and Anti-VEGF Therapies — Side Effects: What Studies Report

What the term covers in the published literature

Vascular endothelial growth factor (VEGF) is a family of secreted signalling proteins that act on endothelial receptors to regulate blood vessel formation, vascular permeability and tissue perfusion. A 2025 review in Signal Transduction and Targeted Therapy summarised VEGF signalling from molecular mechanisms through to therapeutic targeting in health and disease, describing the pathway as central to both normal vascular maintenance and to disorders driven by abnormal vessel growth (PMID 40383803).

That distinction matters for any safety question. In the peer-reviewed record, adverse events discussed under the heading "VEGF" overwhelmingly belong to agents that inhibit VEGF signalling — monoclonal antibodies, antibody fragments, fusion proteins and small-molecule kinase inhibitors used in ophthalmology and oncology. Reports describing the administration of VEGF protein itself to humans as a treatment do not appear in the verified literature summarised on this page, and that absence is stated here plainly rather than filled in with inference.

This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about a medicine, a symptom or a treatment decision. Nothing below is a protocol, a comparison of products, or a suggestion that any compound be used.

Ocular anti-VEGF therapy: What Studies Report

The densest body of safety reporting concerns drugs injected into the eye to suppress VEGF-driven leakage and neovascularisation in neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). Across these agents, the adverse events researchers described most often were inflammatory or vascular events inside the eye rather than systemic complaints.

Brolucizumab: What Studies Report

A 2021 review in the Journal of Ophthalmic & Vision Research catalogued the side effects reported with brolucizumab, with intraocular inflammation and associated retinal vascular events forming the core of the safety discussion (PMID 34840689). The authors framed these as events that emerged in post-approval reporting and prompted closer scrutiny of inflammatory signals after intravitreal injection.

A 2022 guidance paper in Archivos de la Sociedad Española de Oftalmología set out management recommendations for brolucizumab, describing how clinicians were advised to recognise, grade and respond to inflammatory events after injection (PMID 35882576). The existence of a dedicated management document is itself informative: researchers treated the inflammatory signal as clinically consequential enough to warrant standardised surveillance rather than routine observation alone.

High-dose aflibercept: What Studies Report

A 2024 case series in BMC Ophthalmology described intraocular inflammation (IOI) related to 8 mg aflibercept, documenting inflammatory presentations following the higher-dose formulation (PMID 39623439). Because a case series counts events without a comparator arm, the authors could describe what occurred and in what pattern, but the design did not establish how often IOI occurred relative to lower-dose regimens or to other agents.

Faricimab: What Studies Report

Faricimab is a bispecific molecule that blocks both VEGF-A and angiopoietin-2, and it has been examined in several pooled analyses. A 2024 meta-analysis in Ophthalmologica evaluated the efficacy and safety of intravitreal faricimab across nAMD, DME and RVO, reporting ocular adverse event data alongside visual and anatomical outcomes and describing the overall tolerability profile as consistent with established anti-VEGF therapy (PMID 39362194).

A 2024 systematic review and network meta-analysis in BMJ Open Ophthalmology assessed faricimab in nAMD against comparator anti-VEGF agents and reported both efficacy and safety endpoints within the same indirect-comparison framework (PMID 39043575). Separately, a 2024 review in the International Journal of Retina and Vitreous summarised real-world evidence for dual VEGF-A and ANG-2 inhibition with faricimab in nAMD and DME, drawing on clinical practice cohorts rather than randomised trials (PMID 38233896). Real-world series capture events in broader, less selected populations, but they also lack randomisation and standardised event adjudication, which the authors of such reviews generally treat as a limitation on interpretation.

Systemic VEGF blockade: What Studies Report

Bevacizumab and bleeding-related findings

Bevacizumab is a humanised monoclonal antibody against VEGF-A used systemically in oncology. A 2024 report in Dermatology Online Journal described bevacizumab-induced subungual haemorrhage — bleeding beneath the nail plate — as a cutaneous adverse event attributed to the drug (PMID 39680968). This was a single-patient report. Case reports establish that an event can occur and generate hypotheses about mechanism; they do not estimate incidence, and researchers routinely note that a single observation cannot be generalised to a population.

Kinase inhibitors and kidney findings

Small-molecule kinase inhibitors used in oncology intersect multiple signalling pathways, and renal adverse events have been documented in individual patients. A 2021 case report in Cureus described dasatinib-induced nephrotic syndrome, with proteinuria developing during treatment (PMID 34912656). As with the bevacizumab report, the design was a single case: the authors documented the temporal association and clinical course rather than a causal rate.

Conditions involving VEGF elevation: What Studies Report

Some diseases are characterised by excess VEGF signalling rather than by its blockade, and the 2025 mechanistic review described how dysregulated VEGF activity contributes to pathological vascular permeability and abnormal vessel formation across disease states (PMID 40383803). POEMS syndrome is one such context studied in trials of immunomodulatory drugs. A 2020 prospective single-arm clinical trial in Internal Medicine evaluated lenalidomide in patients with thalidomide-refractory POEMS syndrome, reporting treatment outcomes and tolerability in that cohort (PMID 32009091). A single-arm design means observed events cannot be separated from the underlying disease course without a control group.

Preclinical and early-stage findings: What Studies Report

Two entries in the verified set describe laboratory rather than clinical work, and neither carried human safety data.

A 2024 study in Circulation Research examined the contribution of VEGF-B-induced endocardial endothelial cell lineage in physiological versus pathological cardiac hypertrophy, distinguishing between adaptive and maladaptive patterns of heart growth in the experimental model (PMID 38655691). The study addressed mechanism in a controlled biological system; researchers did not report clinical adverse events, and findings at that level do not transfer directly to human outcomes.

A 2025 report in iScience described the design of an Fc-engineered tetravalent bispecific antibody targeting PD-1 and VEGF, with the authors reporting cooperative biological effects of the dual-target construct in preclinical characterisation (PMID 40034861). This was molecular engineering and preclinical evaluation; no human tolerability profile was established in that work.

What the reported events look like side by side

Where human safety data are absent

Several questions that people bring to the phrase "VEGF side effects" are not answered by the literature verified for this page, and the honest answer is that the data are missing rather than reassuring:

• VEGF administered as a therapy in humans. No trial in this verified set reported the tolerability of exogenous VEGF protein given to people, so no adverse-event profile for that use can be described here.
• Research-use-only peptide preparations. No study in this set evaluated the purity, identity or human safety of unapproved VEGF-related preparations; materials labelled for research use are not evaluated for human administration by regulators.
• Long-term outcomes of dual-pathway blockade. The faricimab real-world review summarised clinical-practice experience in nAMD and DME (PMID 38233896), but extended-horizon comparative safety across many years was not the scope of that work.
• Human data for the PD-1/VEGF bispecific construct. The design paper reported preclinical cooperative effects only (PMID 40034861).

How to read this evidence base

Three structural features shape what these reports can and cannot show. First, study design sets the ceiling on the claim: a case report of subungual haemorrhage documents that the event occurred in one patient receiving bevacizumab (PMID 39680968), while a meta-analysis of faricimab pooled randomised data across three retinal indications (PMID 39362194). Those are different grades of evidence about different questions.

Second, route matters. Intravitreal injection concentrates drug in the eye, and the events researchers described most often in that setting were ocular — inflammation and vascular occlusion (PMID 34840689). Systemic administration in oncology generated a different pattern of reports, including bleeding and renal findings (PMID 34912656).

Third, blocking a pathway is not the same as supplying it. The mechanistic review described VEGF signalling as pleiotropic across tissues, which is why interference with it produces effects in organs beyond the intended target (PMID 40383803). Findings about inhibitors cannot be inverted to predict what the ligand would do.

Readers evaluating any of this material should treat it as a summary of published reports, not as a basis for personal decisions. Questions about symptoms, medications or eligibility for a therapy belong with a licensed clinician who can assess an individual case.

References

• Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives (Signal Transduction and Targeted Therapy, 2025)
• Side Effects of Brolucizumab (Journal of Ophthalmic & Vision Research, 2021)
• Guidance on brolucizumab management recommendations (Archivos de la Sociedad Espanola de Oftalmologia, 2022)
• Aflibercept high-dose (8mg) related intraocular inflammation (IOI) - a case series (BMC Ophthalmology, 2024)
• Efficacy and Safety of Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration, Diabetic Macular Edema, and Retinal Vein Occlusion: A Meta-Analysis (Ophthalmologica, 2024)
• Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis (BMJ Open Ophthalmology, 2024)
• Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME (International Journal of Retina and Vitreous, 2024)
• Bevacizumab-induced subungual hemorrhage (Dermatology Online Journal, 2024)
• Dasatinib-Induced Nephrotic Syndrome: A Case Report (Cureus, 2021)
• Lenalidomide Treatment for Thalidomide-refractory POEMS Syndrome: A Prospective Single-arm Clinical Trial (Internal Medicine, 2020)
• Contribution of VEGF-B-Induced Endocardial Endothelial Cell Lineage in Physiological Versus Pathological Cardiac Hypertrophy (Circulation Research, 2024)
• Design of a fragment crystallizable-engineered tetravalent bispecific antibody targeting programmed cell death-1 and vascular endothelial growth factor with cooperative biological effects (iScience, 2025)