From the Guidelines
The recommended management for wet macular degeneration primarily involves anti-VEGF (vascular endothelial growth factor) injections into the eye, with a loading phase of monthly injections for three months, followed by individualized maintenance schedules ranging from every 4-12 weeks based on disease activity, as supported by the most recent study from 2022 1.
Key Considerations
- The most effective treatment for wet AMD is intravitreal injections of VEGF inhibitors, which include ranibizumab (Lucentis), aflibercept (Eylea), brolucizumab (Beovu), and bevacizumab (Avastin, off-label) 1.
- Regular monitoring with optical coherence tomography (OCT) is essential to assess treatment response and determine injection frequency, with patients also using an Amsler grid at home to monitor for vision changes between appointments 1.
- Lifestyle modifications are important adjuncts, including smoking cessation, maintaining healthy blood pressure, wearing UV-protective sunglasses, and consuming a diet rich in antioxidants, particularly dark leafy greens 1.
- High-dose antioxidant vitamin supplements (AREDS2 formula) may be recommended alongside anti-VEGF therapy, with early diagnosis and prompt treatment crucial for preserving vision, as anti-VEGF therapy can stabilize vision in most patients and improve vision in approximately one-third of cases 1.
Potential Harms
- Potential harms associated with treatment of AMD with intravitreal injections of VEGF inhibitors include endophthalmitis, ocular hemorrhage, and retinal detachment, although these were found to be similar in VEGF and sham treatment groups 1.
- Serious ocular and cardiovascular adverse events were infrequent and occurred in similar proportions of patients randomized to either aflibercept or ranibizumab, with evidence on the effects of VEGF inhibitors on other harms limited 1.
Treatment Approach
- A continuous, variable dosing regimen that attempts to individualize therapy, commonly referred to as “treat and extend,” is frequently used in clinical practice as an alternative to fixed monthly regimens, with prospective studies showing similar efficacy between monthly and treat-and-extend for bevacizumab and ranibizumab 1.
- For cases resistant to standard anti-VEGF therapy, combination treatments with photodynamic therapy or switching between different anti-VEGF agents may be considered, with the risks, benefits, and complications of the treatment and the alternatives to it discussed with the patient and informed consent obtained 1.
From the FDA Drug Label
The recommended dose for EYLEA is 2 mg (0.05 mL of 40 mg/mL solution) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 3 months, followed by 2 mg (0.05 mL of 40 mg/mL solution) via intravitreal injection once every 8 weeks (2 months). Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every 4 week (monthly) dosing after the first 12 weeks (3 months). Although not as effective as the recommended every 8 week dosing regimen, patients may also be treated with one dose every 12 weeks after one year of effective therapy. Patients should be assessed regularly.
The recommended management for wet macular degeneration is intravitreal injection of aflibercept (EYLEA):
- Initial dose: 2 mg every 4 weeks for the first 3 months
- Maintenance dose: 2 mg every 8 weeks
- Some patients may require monthly dosing after the first 12 weeks
- Alternative dosing regimen: 2 mg every 12 weeks after one year of effective therapy 2
From the Research
Management of Wet Macular Degeneration
The management of wet macular degeneration involves the use of anti-vascular endothelial growth factor (anti-VEGF) agents to prevent further neovascularization. The main goal of treatment is to inhibit choroidal neovascularization (CNV) and improve visual function.
Treatment Options
- Ranibizumab and aflibercept are two available anti-VEGF drugs for the treatment of wet age-related macular degeneration (AMD) 3.
- Bevacizumab is also used off-label for the treatment of neovascular AMD 4.
- Combination therapy with photodynamic therapy and epimacular brachytherapy may be considered, but results have not shown superior visual outcomes to anti-VEGF monotherapy 5.
Treatment Regimens
- Monthly injections of anti-VEGF agents have been shown to be effective in improving visual function and reducing retinal thickness 4, 6.
- Pro re nata (PRN) regimens, where injections are given as needed, may be associated with a reduced risk of endophthalmitis compared to monthly injections 4.
- Treat-and-extend regimens, where injections are resumed if recurrence is detected and then delivered with increasing intervals, may be a preferable option in some cases 3, 4.
- Extended-fixed regimens, where injections are given at fixed intervals, may be similar in efficacy to monthly injections 4.
Efficacy of Treatment
- Intravitreal ranibizumab (IVR) and intravitreal aflibercept have been shown to be effective in improving visual function and reducing retinal thickness 3, 6.
- Bevacizumab has been shown to be effective in reducing retinal thickness and improving visual function, but may be associated with a higher risk of endophthalmitis compared to ranibizumab and aflibercept 4, 7.
- Aflibercept may be a better choice than other anti-VEGF agents for cases of severe increases in pigment epithelial detachment (PED) height 7.