Intravitreal Anti VEGF Drugs

Intravitreal anti vascular endothelial growth factor (anti VEGF) drugs block the growth factor that drives abnormal new vessel growth and leakage in the retina and choroid. They are first-line treatment for neovascular age-related macular degeneration, diabetic macular oedema, macular oedema from retinal vein occlusion, myopic choroidal neovascularisation and retinopathy of prematurity, and are used in proliferative diabetic retinopathy and neovascular glaucoma.

Mechanism. Bevacizumab (a full antibody), ranibizumab (an antibody fragment) and brolucizumab bind VEGF-A; aflibercept (a fusion protein) binds VEGF-A, VEGF-B and placental growth factor; faricimab binds VEGF-A and angiopoietin-2. Reduced signalling shrinks neovascular vessels and decreases leakage and macular thickness.

Pharmacokinetics. Injected into the vitreous, giving high retinal concentrations with low systemic exposure. Intravitreal half-life is about 4 to 9 days; clinical effect lasts 4 to 12 weeks. Small amounts reach the systemic circulation and lower plasma VEGF, most with aflibercept and bevacizumab.

• Bevacizumab 1.25 mg in 0.05 mL (off-label): cheapest and widely used where cost matters; drawn into syringes by a compounding pharmacy; effect comparable to ranibizumab in macular degeneration and diabetic macular oedema.
• Ranibizumab 0.5 mg (0.3 mg in diabetic macular oedema): licensed; biosimilars lower cost.
• Aflibercept 2 mg: licensed; longer interval between doses.
• Faricimab 6 mg and brolucizumab 6 mg: longer intervals (up to 16 weeks); brolucizumab has a higher risk of intraocular inflammation and vasculitis.

Regimens.

• Neovascular age-related macular degeneration: loading with 3 monthly injections, then monthly dosing, or as-needed, or a treat-and-extend schedule lengthening the interval by 2 weeks if the macula is dry. Aflibercept 2 mg: every 4 weeks for 3 doses, then every 8 weeks.
• Diabetic macular oedema: 5 monthly doses of aflibercept (or ranibizumab monthly until stable), then as-needed or treat-and-extend; laser or steroid implants are used when response is poor.
• Retinal vein occlusion: monthly until vision stable, then as-needed.
• Retinopathy of prematurity: bevacizumab or ranibizumab in a lower dose (for example ranibizumab 0.1 mg), by a specialist, with long follow-up.
• Proliferative diabetic retinopathy and vitreous haemorrhage: injection 3 to 7 days before vitrectomy to reduce bleeding; or as an alternative to panretinal laser.

Procedure. Aseptic technique in a clean room: povidone-iodine 5 percent on the conjunctiva, topical anaesthesia, lid speculum, injection 3.5 mm (pseudophakic or aphakic) to 4 mm (phakic) from the limbus, and check of optic nerve perfusion after injection. Topical antibiotics after injection are not needed.

Selection. Choose by cost and availability: bevacizumab first where resources are limited, switch to a licensed agent if response is poor after 3 to 6 doses. Treat diabetes, blood pressure and lipids alongside.

Contraindications. Active ocular or periocular infection; active intraocular inflammation; hypersensitivity.

Serious effects. Endophthalmitis (about 1 in 2,000 to 3,000 injections), retinal tear and detachment, traumatic cataract, intraocular inflammation (more with brolucizumab, with retinal vasculitis), sustained rise of intraocular pressure and transient pressure spike after injection, vitreous haemorrhage. Systemic arterial thromboembolic events are a theoretical risk, so caution after recent stroke or myocardial infarction.

Common effects. Subconjunctival haemorrhage, floaters, eye pain, conjunctival hyperaemia, foreign body sensation.

Interactions. None clinically relevant; combine with panretinal laser for proliferative disease.

Monitoring. Visual acuity, pressure and optical coherence tomography at each visit; instruct patients to return the same day for increasing pain, redness, reduced vision or light sensitivity in the days after injection; check perfusion of the optic disc and pressure immediately after injection.

Special groups. Pregnancy: avoid unless benefit clearly outweighs risk; effective contraception during and for 3 months after treatment. Breastfeeding: avoid or use with caution. Children: retinopathy of prematurity under specialist care. Region: diabetic retinopathy and macular oedema are increasing in East Africa, and monthly injections are limited by cost, distance and follow-up; bevacizumab is the practical first choice, so repackaging must be under sterile conditions with a clear recall system.