What is the recommended treatment for wet macular degeneration?

Treatment for Wet Macular Degeneration

Anti-VEGF therapy is the primary recommended treatment for wet (neovascular) age-related macular degeneration, with intravitreal injections of aflibercept, ranibizumab, brolucizumab, or bevacizumab being the standard of care. 1, 2

First-Line Treatment Options

• Aflibercept (Eylea) - FDA-approved for wet AMD, administered as 2 mg intravitreal injections every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks 3
• Ranibizumab (Lucentis) - Typically administered monthly or as needed (PRN) 1, 2
• Brolucizumab (Beovu) - FDA-approved in October 2019, demonstrated superior reductions in central subfield thickness compared to aflibercept 1, 2
• Bevacizumab (Avastin) - Used off-label and shown to be effective but may be slightly less effective than other monthly anti-VEGF regimens 1, 2

Administration Protocols

• Initial treatment typically begins with three monthly loading doses (every 4 weeks) 3, 2
• After the loading phase, several maintenance regimens are available:
  • Fixed monthly injections - Most effective but highest treatment burden 1, 2
  • Every 8 weeks dosing - For aflibercept after 3 monthly loading doses, shown to be clinically equivalent to monthly ranibizumab 3, 4
  • PRN (as needed) - Treatment based on disease activity, but may not maintain initial visual gains with longer follow-up 1, 5
  • Treat-and-extend - Gradually increasing intervals between injections once disease stabilization is achieved, frequently used in clinical practice 1, 2

Efficacy Considerations

• All anti-VEGF agents have demonstrated efficacy in maintaining vision (defined as losing <15 letters on ETDRS chart) 3, 4
• Monthly regimens are slightly more effective than PRN regimens, with approximately 1.7 letters better visual acuity 2, 6
• Aflibercept dosed every 8 weeks after 3 monthly loading doses showed similar efficacy to monthly ranibizumab in the VIEW 1 and VIEW 2 studies 3, 4
• Long-term outcomes show that 50% of patients maintained visual acuity of 20/40 at 5-year follow-up 1, 2

Special Considerations

Small Subretinal Hemorrhages

• Anti-VEGF therapy is the recommended management approach 1

Larger Submacular Hemorrhages

• Options include pneumatic displacement procedures, tissue plasminogen activator (tPA), and/or pars plana vitrectomy, though evidence is limited 1, 2

Retinal Pigment Epithelium Tears/Rips

• May occur with or without treatment but are not a contraindication to continued anti-VEGF therapy 1

Potential Complications of Anti-VEGF Treatment

• Endophthalmitis (cumulative ≤1.0% over 1 year in VIEW studies) 1, 2
• Non-infectious inflammation, retinal tear, or detachment 1
• Theoretical risks for systemic arterial thromboembolic events, though clinical trial results remain inconclusive 1, 2
• Increased intraocular pressure 3

Monitoring and Follow-up

• Regular examinations using biomicroscopy of the fundus, optical coherence tomography (OCT), and fluorescein angiography as needed 2
• Patients should be instructed to report symptoms of endophthalmitis, retinal detachment, or decreased vision promptly 1, 3
• Fellow eye monitoring is crucial as it remains at high risk for developing advanced AMD 2

Treatment Selection Algorithm

1. First choice: Aflibercept 2 mg every 8 weeks after 3 monthly loading doses - offers similar efficacy to monthly regimens with reduced injection burden 3, 4
2. Alternative options:
   • Ranibizumab monthly if more frequent monitoring is possible 1, 2
   • Brolucizumab if there is persistent fluid despite other anti-VEGF agents 1
   • Bevacizumab if cost is a significant concern (off-label) 1, 2

Practical Considerations

• Informed consent should include discussion of potential complications and the off-label status of bevacizumab 1, 2
• The risks, benefits, and alternatives should be thoroughly discussed with the patient 1
• Anti-VEGF therapy does not cure wet AMD but aims to stabilize and potentially improve vision 2, 7