Introduction
Aflibercept (Eylea®) is a recombinant fusion protein specifically designed as a vascular endothelial growth factor (VEGF) inhibitor for ophthalmic use. Developed by Regeneron Pharmaceuticals, it is approved for the treatment of various retinal diseases characterized by abnormal angiogenesis and vascular permeability. Eylea represents a significant advancement in the management of sight-threatening retinal conditions, offering patients improved visual outcomes with a less frequent dosing regimen compared to some alternatives.
Mechanism of Action
Aflibercept functions as a VEGF trap by binding to placental growth factor (PIGF) and all isoforms of VEGF-A and VEGF-B with high affinity. It acts as a soluble decoy receptor that prevents these ligands from binding to their native receptors (VEGFR-1 and VEGFR-2) on endothelial cells. By inhibiting VEGF-mediated signaling pathways, aflibercept:
- Reduces pathological angiogenesis
- Decreases vascular permeability
- Minimizes retinal edema
- Suppresses neovascularization
This mechanism helps stabilize vision and can lead to visual improvement in patients with retinal vascular diseases.
Indications
Eylea is FDA-approved for the following ophthalmic indications:
- Neovascular (Wet) Age-Related Macular Degeneration (AMD)
- Macular Edema Following Retinal Vein Occlusion (RVO)
- Diabetic Macular Edema (DME)
- Diabetic Retinopathy in patients with DME
- Retinopathy of Prematurity (ROP) in preterm infants
Dosage and Administration
Standard dosing: 2 mg (0.05 mL) by intravitreal injection Dosing regimens:- AMD, RVO, DME: Monthly injections for first 3 months, then every 2 months
- Diabetic Retinopathy: Individualize based on disease activity
- ROP: 0.4 mg (0.01 mL) injection in each eye
- Must be administered by qualified ophthalmologists
- Strict aseptic technique required
- Pre- and post-injection monitoring essential
- Topical anesthesia and broad-spectrum microbicide required
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations
- Elderly: No dosage adjustment required
- Pediatrics: Safety established for ROP treatment
Pharmacokinetics
Absorption: Local ocular administration with minimal systemic exposure Distribution: Primarily confined to vitreous humor and retina Metabolism: Presumed to be metabolized via proteolytic pathways Elimination: Systemic elimination half-life approximately 5-6 days Systemic exposure: Minimal systemic absorption following intravitreal administrationContraindications
- Ocular or periocular infections
- Active intraocular inflammation
- Hypersensitivity to aflibercept or any component of the formulation
- Patients with known hypersensitivity to Chinese Hamster Ovary (CHO) cell products
Warnings and Precautions
Boxed Warning: None Important precautions:- Endophthalmitis and retinal detachments: May occur following intravitreal injections
- Increased intraocular pressure: Monitor and manage appropriately
- Thromboembolic events: Potential risk of arterial thromboembolic events
- Fetal toxicity: Based on animal studies, may cause fetal harm
- Non-ocular VEGF inhibition: Theoretical systemic effects
Drug Interactions
Formal drug interaction studies have not been conducted. However:
- Other VEGF inhibitors: Potential additive systemic effects
- Anticoagulants/antiplatelets: May increase risk of bleeding complications
- Other intravitreal medications: Should be separated by appropriate intervals
Adverse Effects
Most common adverse reactions (≥5%):- Conjunctival hemorrhage (25%)
- Eye pain (9%)
- Cataract (7%)
- Vitreous detachment (6%)
- Vitreous floaters (6%)
- Increased intraocular pressure (5%)
- Endophthalmitis (<0.1%)
- Retinal detachment (0.6%)
- Retinal tear (0.6%)
- Traumatic cataract (0.6%)
- Arterial thromboembolic events (1.8%)
Monitoring Parameters
Ocular monitoring:- Visual acuity at each visit
- Intraocular pressure within 30 minutes post-injection
- Retinal examination for disease activity
- Signs of infection or inflammation
- Blood pressure (baseline and periodic)
- Neurological symptoms (for CVA/TIA)
- Cardiovascular symptoms
- Optical coherence tomography (OCT)
- Fluorescein angiography when indicated
- Visual field testing as needed
Patient Education
Key points for patients:- Report any eye pain, redness, sensitivity to light, or vision changes immediately
- Understand the importance of regular follow-up visits
- Be aware of potential temporary visual disturbances after injection
- Inform all healthcare providers about Eylea treatment
- Use caution when driving or operating machinery after injection
- Report any systemic symptoms such as headache, confusion, or limb weakness
- Discuss pregnancy plans with healthcare provider
- Procedure takes approximately 15-30 minutes
- Mild discomfort during injection is normal
- May experience floaters or blurred vision temporarily
- Need to arrange transportation after procedure
References
1. Eylea® (aflibercept) Prescribing Information. Regeneron Pharmaceuticals, 2023. 2. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. 3. Brown DM, Schmidt-Erfurth U, Do DV, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122(10):2044-2052. 4. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1):193-201. 5. American Academy of Ophthalmology Retina/Vitreous Preferred Practice Pattern Guidelines. 2022. 6. ClinicalTrials.gov: Various phase III studies (VIEW, VIVID, VISTA, COPERNICUS, GALILEO).