Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
risk factor modification
Treatment recommended for ALL patients in selected patient group
Patients with age-related macular degeneration (AMD) are encouraged to stop smoking; to eat a balanced diet that has a low glycaemic index and is rich in fruits, vegetables, and fish high in omega-3 fatty acids; and to modify cardiovascular risk factors (including lowering cholesterol and saturated fat intake and controlling hypertension).[4][14][17][33][35]
Supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to late AMD.[55][56]
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antioxidant and mineral supplementation
The Age-Related Eye Disease Study Group (AREDS) classifies age-related macular degeneration (AMD) as category 3 in patients with extensive intermediate drusen or at least one large (≥125 micrometres in diameter) druse, or geographic atrophy not involving the foveal centre.[52]
Evidence from randomised controlled trials and one Cochrane review suggest that antioxidant vitamin and mineral supplementation may reduce the development of late AMD in patients with intermediate AMD.[4][52][56][57]
Replacement is recommended, typically with the AREDS2 formula which contains vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper.[57][63] Although systematic reviews indicate that antioxidant vitamin and mineral supplementation may delay progression to late AMD, they do not show that supplementation prevents or delays the onset of AMD.[57][58]
[ ]
[ ]
A diet of fruits and vegetables rich in antioxidants may also be protective.[59][60][61][62]
risk factor modification
Treatment recommended for ALL patients in selected patient group
Patients with age-related macular degeneration (AMD) are encouraged to stop smoking; to eat a balanced diet that has a low glycaemic index and is rich in fruits, vegetables, and fish high in omega-3 fatty acids; and to modify cardiovascular risk factors (including lowering cholesterol and saturated fat intake and controlling hypertension).[4][14][17][33][35]
Supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to late AMD.[55][56]
[ ]
risk factor modification
Treatment recommended for ALL patients in selected patient group
Patients with age-related macular degeneration (AMD) are encouraged to stop smoking; to eat a balanced diet that has a low glycaemic index and is rich in fruits, vegetables, and fish high in omega-3 fatty acids; and to modify cardiovascular risk factors (including lowering cholesterol and saturated fat intake and controlling hypertension).[4][14][17][33][35]
Supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to late AMD.[55][56]
[ ]
antioxidant and mineral supplementation
Additional treatment recommended for SOME patients in selected patient group
Evidence from randomised controlled trials and one Cochrane review suggest that in patients with late age-related macular degeneration (AMD) in one eye, antioxidant vitamin and mineral supplementation may reduce the development of late AMD in the other eye.[4][52][56][57]
Replacement is recommended, typically with the AREDS2 formula which contains vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper.[57][63] Although systematic reviews indicate that antioxidant vitamin and mineral supplementation may delay progression to late AMD, they do not show that supplementation prevents or delays the onset of AMD.[57][58]
[ ]
[ ]
A diet of fruits and vegetables rich in antioxidants may also be protective.[59][60][61][62]
intravitreal vascular endothelial growth factor (VEGF) inhibitor
Intravitreal injection with a VEGF inhibitor represents the first-line treatment for macular neovascularisation (MNV).[4][43] Treatment is given as soon as possible after identification of MNV activity, to prevent irreversible retinal damage.
Ranibizumab, aflibercept, brolucizumab, and faricimab are approved in the US and Europe for the treatment of MNV.[74][75][76][77][78] Bevacizumab is also widely used around the world, but its use may be off-label in some countries. Dosing regimens include as required dosing, a treat-and-extend dosing approach, and fixed dosing at extended intervals.
Ranibizumab, a recombinant humanised monoclonal antibody fragment that binds to VEGF-A, resulted in significantly reduced vision acuity loss compared with sham injections or verteporfin photodynamic therapy when given monthly for 2 years in clinical trials.[41][70][82]
Aflibercept, a recombinant fusion protein that binds to VEGF-A and VEGF-B, was non-inferior to monthly ranibizumab in maintaining vision when given in clinical trials in monthly or 2-monthly regimens.[41][71][83] In treat-and-extend trials of aflibercept over up to 2 years, treatment improved visual acuity.[84][85] A higher dose of aflibercept, given up to every 16 weeks, has been approved for neovascular age-related macular degeneration (AMD) based on the outcomes of a phase 3, randomised clinical trial in which a higher dose of aflibercept was found to be non-inferior to a lower dose.[86] However, maximum dose intervals should follow local guidance.
Brolucizumab is a monoclonal antibody fragment that binds to VEGF-A.[41][87] In two phase 3, randomised trials in which brolucizumab was given in a fixed dosing regimen at extended intervals, brolucizumab was non-inferior to aflibercept in its effect on best-corrected visual acuity at 48 and 96 weeks.[67][88] Brolucizumab should not be given at intervals of less than 8 weeks due to the risk of intraocular inflammation, including retinal vasculitis and retinal vein occlusion.[89][90][91] One trial, in which brolucizumab was administered every 4 weeks, was terminated early because there were more intraocular inflammation adverse events in the 4-weekly brolucizumab arm compared with the 4-weekly aflibercept arm.[91] The UK Medicines and Healthcare products Regulatory Agency (MHRA) recommends that after three loading injections, doses of brolucizumab should be given at least 8 weeks apart to reduce adverse events.[92]
Faricimab, a recombinant bispecific monoclonal antibody that can simultaneously bind and neutralise VEGF-A and angiopoietin-2, is approved for the treatment of wet AMD based on the results of two phase 3 studies.[41][74] These trials found that faricimab was non-inferior for change in best-corrected visual acuity over a year when given at intervals of up to 4 months and compared with aflibercept given every 2 months.
Bevacizumab is a recombinant monoclonal antibody that binds to VEGF-A. In the US, the use of bevacizumab is off-label. It is only available as an intravenous formulation (which is approved for other indications), and an intravitreal formulation needs to be compounded from the available intravenous formulation. In Europe, bevacizumab (as bevacizumab gamma) is licensed for the treatment of wet AMD, and a proprietary intravitreal formulation is available. Bevacizumab shows similar efficacy to ranibizumab in head-to-head studies.[41][66][93][94] One systematic review of randomised controlled trials comparing bevacizumab and ranibizumab did not detect a difference in systemic safety between the two drugs.[95]
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In one phase 3, randomised controlled trial, monthly bevacizumab gamma was effective at improving or stabilising visual acuity when compared with ranibizumab dosed monthly for 3 months then quarterly.[96]
Treatment response is monitored closely with optical coherence tomography (OCT).[4][39] Fluorescein +/- indocyanine green angiography is typically taken at baseline and only intermittently thereafter, depending on patient response. OCT angiography has reduced the need for fluorescein angiography.
Significant risks of treatment by intravitreal injection include endophthalmitis, damage to the lens, and retinal detachment.[64][66][67][68][69][70][71] Risk of endophthalmitis can be reduced by using appropriate aseptic techniques.[72] Bevacizumab that has been compounded for intravitreal injection with inadequate aseptic technique has been associated with endophthalmitis.[72] Patients are made aware of signs indicative of endophthalmitis (pain, decreased vision, light sensitivity, and increasing redness) and retinal detachment (flashing lights, new floaters, and partially or completely obscured visual field).[4] If endophthalmitis develops, prompt referral for either vitreous tap followed by intravitreal antibiotics, or pars plana vitrectomy with injection of intravitreal antibiotics should be considered as an emergency.
Where available, biosimilars can be used according to local guidelines.
Primary options
ranibizumab intravitreal: 0.5 mg intravitreally into the affected eye(s) once monthly for 3-4 months initially; treatment interval may be individualised according to disease activity under specialist guidance (every 1-3 months)
OR
aflibercept intravitreal: standard-dose regimen: 2 mg intravitreally into the affected eye(s) every 4 weeks for 3 doses, followed by 2 mg every 8 weeks, treatment interval may be individualised according to disease activity under specialist guidance (every 4-12 weeks); high-dose regimen: 8 mg intravitreally into the affected eye(s) every 4 weeks for 3 doses, followed by 8 mg every 8-16 weeks
OR
brolucizumab intravitreal: 6 mg intravitreally into the affected eye(s) once monthly for 3 months, followed by 6 mg every 8-12 weeks; treatment interval may be individualised according to disease activity under specialist guidance
MoreOR
faricimab intravitreal: 6 mg intravitreally into the affected eye(s) once monthly for 4 months, followed by 6 mg every 8 weeks (at weeks 20, 28, 36, and 44), 12 weeks (at weeks 24, 36, and 48), or 16 weeks (at weeks 28 and 44); treatment interval may be individualised according to disease activity under specialist guidance
Secondary options
bevacizumab: 1.25 mg intravitreally into the affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance
Morerisk factor modification
Treatment recommended for ALL patients in selected patient group
Patients with age-related macular degeneration (AMD) are encouraged to stop smoking; to eat a balanced diet that has a low glycaemic index and is rich in fruits, vegetables, and fish high in omega-3 fatty acids; and to modify cardiovascular risk factors (including lowering cholesterol and saturated fat intake and controlling hypertension).[4][14][17][33][35]
Supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to late AMD.[55][56]
[ ]
antioxidant and mineral supplementation
Additional treatment recommended for SOME patients in selected patient group
Evidence from randomised controlled trials and one Cochrane review suggest that in patients with late age-related macular degeneration (AMD) in one eye, antioxidant vitamin and mineral supplementation may reduce the development of late AMD in the other eye.[4][52][56][57]
Replacement is recommended, typically with the AREDS2 formula which contains vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper.[57][63] Although systematic reviews indicate that antioxidant vitamin and mineral supplementation may delay progression to late AMD, they do not show that supplementation prevents or delays the onset of AMD.[57][58]
[ ]
[ ]
A diet of fruits and vegetables rich in antioxidants may also be protective.[59][60][61][62]
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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