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

ACUTE

early stage (AREDS 1 and 2)

1st line – observation ± specialist referral

Back
ACUTE
|
early stage (AREDS 1 and 2)
1st line – 

observation ± specialist referral

The Age-Related Eye Disease Study Group (AREDS) classifies AMD as category 1 in patients with no or a few small (<63 micrometres in diameter) drusen; and category 2 in patients with many small drusen or a few intermediate-sized (63-124 micrometres in diameter) drusen, or mild abnormalities of the retinal pigment epithelium.[34]

There is no known effective treatment for these categories, and management is based on observation and risk factor modification.

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, particularly for patients: who experience subjective visual changes or abnormality on Amsler examination; or in whom the diagnosis is uncertain and/or atypical features are present.

Plus – risk factor modification

Back
ACUTE
|
early stage (AREDS 1 and 2)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[9][23]​​[24][25]​​​​[26]​​[27]​​

Supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

intermediate-stage (AREDS 3)

1st line – antioxidant and mineral supplementation

Back
ACUTE
|
intermediate-stage (AREDS 3)
1st line – 

antioxidant and mineral supplementation

The Age-Related Eye Disease Study Group (AREDS) classifies 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.[34]

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

Plus – risk factor modification

Back
ACUTE
|
intermediate-stage (AREDS 3)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
intermediate-stage (AREDS 3)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

advanced-stage atrophic (dry) (AREDS 4)

1st line – observation

Back
ACUTE
|
advanced-stage atrophic (dry) (AREDS 4)
1st line – 

observation

The Age-Related Eye Disease Study Group (AREDS) classifies AMD as category 4 atrophic (dry) in patients with geographic atrophy involving the foveal centre.[34]

No current treatment has been shown to be effective.

Repeat eye examination after 6 to 24 months may be considered for patients who remain asymptomatic, and these patients should be seen as soon as possible if they develop symptoms suggestive of choroidal neovascularisation.[23]

Plus – risk factor modification

Back
ACUTE
|
advanced-stage atrophic (dry) (AREDS 4)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
advanced-stage atrophic (dry) (AREDS 4)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

Consider – antioxidant and mineral supplementation

Back
ACUTE
|
advanced-stage atrophic (dry) (AREDS 4)
Consider – 

antioxidant and mineral supplementation

Additional treatment recommended for SOME patients in selected patient group

Patients who have progressed to intermediate or advanced AMD in at least one eye can consider taking micronutrient supplements, which may decrease the risk of progression to advanced or late AMD in the less-involved eye.[23]

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

advanced-stage exudative (wet) (AREDS 4)

1st line – intravitreal vascular endothelial growth factor inhibitor

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
1st line – 

intravitreal vascular endothelial growth factor inhibitor

The Age-Related Eye Disease Study Group classifies AMD as category 4 exudative (wet) in patients with neovascular maculopathy, including CNV, serous and/or haemorrhagic detachment of the retina or retinal pigment epithelium (RPE), retinal hard exudates, subretinal and sub-RPE fibrovascular proliferation, or disciform scar (subretinal fibrosis).[34]

Intravitreal injection with vascular endothelial growth factor inhibitors represents the first-line treatment for CNV.[23][47]​ Ranibizumab, aflibercept, brolucizumab, and faricimab are approved for this condition.[48][49]​​[50]​[51]​​​[52][53]​ Bevacizumab is not licensed for intravitreal injection, but head-to-head studies indicate that its efficacy is similar to that of ranibizumab.[54][55][56]​ Bevacizumab that has been repackaged for intravitreal injection with inadequate aseptic technique has, however, been associated with endophthalmitis.[57] One systematic review of randomised controlled trials comparing bevacizumab and ranibizumab did not detect a difference in systemic safety between the two drugs.[58] [ Cochrane Clinical Answers logo ]

Treatment is given as soon as possible after identification of CNV activity, to prevent irreversible retinal damage.

Treatment typically involves a series of injections, and frequency is determined by clinical response to therapy.[74][75] Various regimens are being used.

Evidence is emerging that proactive treatment regimens with either fixed dosing or 'treat-and-extend' dosing may be the best way to achieve and maintain the best vision over a prolonged period of time.[90][91][92][93][94][95]

The 'treat-and-extend' dosing approach has become increasingly popular; it aims to proactively continue treatment by sequentially increasing treatment interval or reducing it as necessary, typically at 2-4 week intervals, up to a maximum of 12-16 weeks, depending on the drug used. The aim is to treat at an individualised interval that maintains disease stability.[61][62][63][64]

Ranibizumab, aflibercept, brolucizumab, and faricimab have been approved for 'treat-and-extend' or ‘personalised’ dosing regimens, thereby reducing the number of patient visits and injections and lowering direct annual medical costs, compared with monthly injections.[60]​ A higher dose of aflibercept, given up to every 16 weeks, has been approved in the US for neovascular AMD based on the outcomes of the PULSAR trial.[65][66]​ This has the potential to enable more patients to be treated at longer intervals. However, maximum dose intervals should follow local guidance.

Fixed dosing at extended intervals has been reported in the HAWK and HARRIER studies of brolucizumab versus aflibercept.[67] Adverse events of intraocular inflammation, vasculitis, and retinal occlusive vasculitis have been reported in relation to brolucizumab at slightly higher rates than with other VEGF inhibitors.[67][68][69]​ 

Following the early termination of the MERLIN trial, which trialled the off-label use of brolucizumab with a 4-week dosing interval, the drug company confirmed that clinicians should not treat patients with brolucizumab at intervals of less than 8 weeks, following the first three doses; this includes individualised dosing under specialist guidance.[70] The UK Medicines and Healthcare products Regulatory Agency (MHRA) recommends that after the three loading injections, doses of brolucizumab should be given at least 8 weeks apart to reduce adverse events.[71]

Faricimab is a bispecific antibody that can simultaneously bind and neutralise VEGF-A and angiopoietin-2. The phase 2 STAIRWAY study assessed the extended durability of faricimab dosed up to every 16 weeks. A proportion of patients receiving 12-weekly and 16-weekly doses showed outcomes comparable to monthly ranibizumab. Faricimab is approved in the US and Europe for the treatment of wet AMD based on the results of four phase 3 studies (TENAYA, LUCERNE, YOSEMITE and RHINE) that found faricimab was well tolerated and non-inferior for visual gains over a year when given at intervals of up to 4 months and compared with aflibercept given every 2 months.[48][72]

Treatment response is monitored closely with optical coherence tomography (OCT).

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 a small risk of endophthalmitis, damage to the lens, and retinal detachment; in particular, the risk of endophthalmitis can be reduced by using appropriate aseptic techniques.[73][74][75][76][77][78]​ 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 obscured visual field). If endophthalmitis develops, prompt treatment with intravitreal antibiotics is recommended.

Where available, biosimilars can be used according to local guidelines.

Primary options

ranibizumab intravitreal: 0.5 mg intravitreally into affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance

OR

aflibercept intravitreal: standard-dose regimen: 2 mg intravitreally into affected eye(s) every 4 weeks for 3 doses, followed by 2 mg every 8 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; treatment interval may be individualised according to disease activity under specialist guidance

OR

brolucizumab intravitreal: 6 mg intravitreally into 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

More

OR

faricimab intravitreal: 6 mg intravitreally into 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 affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance

Plus – risk factor modification

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

Consider – antioxidant and mineral supplementation

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
Consider – 

antioxidant and mineral supplementation

Additional treatment recommended for SOME patients in selected patient group

For reducing risk of second eye involvement, if second eye not affected yet.

Patients who have progressed to intermediate or advanced AMD in at least one eye can consider taking micronutrient supplements, which may decrease the risk of progression to advanced or late AMD in the less-involved eye.[23]

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

2nd line – thermal laser photocoagulation

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
2nd line – 

thermal laser photocoagulation

The Age-Related Eye Disease Study Group (AREDS) classifies AMD as category 4 exudative (wet) in patients with neovascular maculopathy, including CNV, serous and/or haemorrhagic detachment of the retina or retinal pigment epithelium (RPE), retinal hard exudates, subretinal and sub-RPE fibrovascular proliferation, or disciform scar (subretinal fibrosis).[34]

Thermal laser photocoagulation is a rarely used method of ablating CNV.

Treatment is given as soon as possible after identification of CNV activity, to prevent irreversible retinal damage. This treatment may only be considered for small, well demarcated extrafoveal CNV; it is no longer a treatment for subfoveal CNV given its destructive nature.[83][84] A retinal specialist’s opinion is required to assess the risk of the laser causing the side effect of a scotoma in the visual field.

Treatment response is monitored closely with fluorescein angiography and optical coherence tomography.

Recurrence may occur and re-treatments may be necessary.[83][84][85]

Although thermal laser photocoagulation can be considered for small extrafoveal CNV, the first-choice treatment for extrafoveal CNV is intravitreal injection with vascular endothelial growth factor inhibitors.

Plus – risk factor modification

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

Consider – antioxidant and mineral supplementation

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
extrafoveal choroidal neovascularisation (CNV)
Consider – 

antioxidant and mineral supplementation

Additional treatment recommended for SOME patients in selected patient group

For reducing risk of second eye involvement, if second eye not affected yet.

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]​

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

1st line – intravitreal vascular endothelial growth factor inhibitor

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
juxtafoveal choroidal neovascularisation (CNV)
1st line – 

intravitreal vascular endothelial growth factor inhibitor

The Age-Related Eye Disease Study Group classifies AMD as category 4 exudative (wet) in patients with neovascular maculopathy, including CNV, serous and/or haemorrhagic detachment of the retina or retinal pigment epithelium (RPE), retinal hard exudates, subretinal and sub-RPE fibrovascular proliferation, or disciform scar (subretinal fibrosis).[34]

Intravitreal injection with vascular endothelial growth factor inhibitors represents the first-line treatment for CNV.[23][47]​ Ranibizumab, aflibercept, brolucizumab, and faricimab are approved for this condition.[48][49]​​[50][51]​​[52][53]​ Bevacizumab is not licensed for intravitreal injection, but head-to-head studies indicate that its efficacy is similar to that of ranibizumab.[54][55][56]​ Bevacizumab that has been repackaged for intravitreal injection with inadequate aseptic technique has, however, been associated with endophthalmitis.[57] One systematic review of randomised controlled trials comparing bevacizumab and ranibizumab did not detect a difference in systemic safety between the two drugs.[58] [ Cochrane Clinical Answers logo ]

Treatment is given as soon as possible after identification of CNV activity, to prevent irreversible retinal damage.

Treatment typically involves a series of injections, and frequency is determined by clinical response to therapy.[74][75] Various regimens are being used.

Evidence is emerging that proactive treatment regimens with either fixed dosing or 'treat-and-extend' dosing may be the best way to achieve and maintain the best vision over a prolonged period of time.[90][91][92][93][94][95]

The 'treat-and-extend' dosing approach has become increasingly popular; it aims to proactively continue treatment by sequentially increasing treatment interval or reducing it as necessary, typically at 2-4 week intervals, up to a maximum of 12-16 weeks, depending on the drug used. The aim is to treat at an individualised interval that maintains disease stability.[61][62][63][64]

Ranibizumab, aflibercept, brolucizumab, and faricimab have been approved for 'treat-and-extend' or ‘personalised’ dosing regimens, thereby reducing the number of patient visits and injections and lowering direct annual medical costs, compared with monthly injections.[60]​ Higher doses of aflibercept, given up to every 16 weeks, have been approved in the US for neovascular AMD based on the outcomes of the PULSAR trial.[65][66]​ This has the potential to enable more patients to be treated at longer intervals. However, maximum dose intervals should follow local guidance.

Fixed dosing at extended intervals has been reported in the HAWK and HARRIER studies of brolucizumab versus aflibercept.[67] Adverse events of intraocular inflammation, vasculitis, and retinal occlusive vasculitis have been reported in relation to brolucizumab at slightly higher rates than with other VEGF inhibitors.[67][68][69]​ 

Following the early termination of the MERLIN trial, which trialled the off-label use of brolucizumab with a 4-week dosing interval, the drug company confirmed that clinicians should not treat patients with brolucizumab at intervals of less than 8 weeks, following the first three doses; this includes individualised dosing under specialist guidance.[70] The UK Medicines and Healthcare products Regulatory Agency (MHRA) recommends that after the three loading injections, doses of brolucizumab should be given at least 8 weeks apart to reduce adverse events.[71]

Faricimab is a bispecific antibody that can simultaneously bind and neutralise VEGF-A and angiopoietin-2. The phase 2 STAIRWAY study assessed the extended durability of faricimab dosed up to every 16 weeks. A proportion of patients receiving 12-weekly and 16-weekly doses showed outcomes comparable to monthly ranibizumab. Faricimab is approved in the US and Europe for the treatment of wet AMD based on the results of four phase 3 studies (TENAYA, LUCERNE, YOSEMITE and RHINE) that found faricimab was well tolerated and non-inferior for visual gains over a year when given at intervals of up to 4 months and compared with aflibercept given every 2 months.[48][72]

Treatment response is monitored closely with optical coherence tomography (OCT).

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 a small risk of endophthalmitis, damage to the lens, and retinal detachment; in particular, the risk of endophthalmitis can be reduced by using appropriate aseptic techniques.[73][74][75][76][77][78]​​ 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 obscured visual field). If endophthalmitis develops, prompt treatment with intravitreal antibiotics is recommended.

Where available, biosimilars can be used according to local guidelines.

Primary options

ranibizumab intravitreal: 0.5 mg intravitreally into affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance

OR

aflibercept intravitreal: standard-dose regimen: 2 mg intravitreally into affected eye(s) every 4 weeks for 3 doses, followed by 2 mg every 8 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; treatment interval may be individualised according to disease activity under specialist guidance

OR

brolucizumab intravitreal: 6 mg intravitreally into 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

More

OR

faricimab intravitreal: 6 mg intravitreally into 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 affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance

Plus – risk factor modification

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
juxtafoveal choroidal neovascularisation (CNV)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
juxtafoveal choroidal neovascularisation (CNV)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

Consider – antioxidant and mineral supplementation

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
juxtafoveal choroidal neovascularisation (CNV)
Consider – 

antioxidant and mineral supplementation

Additional treatment recommended for SOME patients in selected patient group

For reducing risk of second eye involvement, if second eye not affected yet.

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

1st line – intravitreal vascular endothelial growth factor inhibitor

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
1st line – 

intravitreal vascular endothelial growth factor inhibitor

The Age-Related Eye Disease Study Group classifies AMD as category 4 exudative (wet) in patients with neovascular maculopathy, including CNV, serous and/or haemorrhagic detachment of the retina or retinal pigment epithelium (RPE), retinal hard exudates, subretinal and sub-RPE fibrovascular proliferation, or disciform scar (subretinal fibrosis).[34]

Intravitreal injection with vascular endothelial growth factor inhibitors represents the first-line treatment for CNV.[23][47]​ Ranibizumab, aflibercept, brolucizumab, and faricimab are approved for this condition.[48][49][50][51][52][53]​ Bevacizumab is not licensed for intravitreal injection, but head-to-head studies indicate that its efficacy is similar to that of ranibizumab.[54][55][56]​ Bevacizumab that has been repackaged for intravitreal injection with inadequate aseptic technique has, however, been associated with endophthalmitis.[57] One systematic review of randomised controlled trials comparing bevacizumab and ranibizumab did not detect a difference in systemic safety between the two drugs.[58] [ Cochrane Clinical Answers logo ]

Treatment is given as soon as possible after identification of CNV activity, to prevent irreversible retinal damage.

Treatment typically involves a series of injections, and frequency is determined by clinical response to therapy.[74][75] Various regimens are being used.

Evidence is emerging that proactive treatment regimens with either fixed dosing or 'treat-and-extend' dosing may be the best way to achieve and maintain the best vision over a prolonged period of time.[90][91][92][93][94][95]

The 'treat-and-extend' dosing approach has become increasingly popular; it aims to proactively continue treatment by sequentially increasing treatment interval or reducing it as necessary, typically at 2-4 week intervals, up to a maximum of 12-16 weeks, depending on the drug used. The aim is to treat at an individualised interval that maintains disease stability.[61][62][63][64]

Ranibizumab, aflibercept, brolucizumab, and faricimab have been approved for 'treat-and-extend' or ‘personalised’ dosing regimens, thereby reducing the number of patient visits and injections and lowering direct annual medical costs, compared with monthly injections.[60]​ Higher doses of aflibercept, given up to every 16 weeks, have been approved by the FDA for neovascular AMD based on the outcomes of the PULSAR trial.[65][66]​ This has the potential to enable more patients to be treated at longer intervals. However, maximum dose intervals should follow local guidance.

Fixed dosing at extended intervals has been reported in the HAWK and HARRIER studies of brolucizumab versus aflibercept.[67] Adverse events of intraocular inflammation, vasculitis, and retinal occlusive vasculitis have been reported in relation to brolucizumab at slightly higher rates than with other VEGF inhibitors.[67][68][69]

Following the early termination of the MERLIN trial, which trialled the off-label use of brolucizumab with a 4-week dosing interval, the drug company confirmed that clinicians should not treat patients with brolucizumab at intervals of less than 8 weeks, following the first three doses; this includes individualised dosing under specialist guidance.[70] The UK Medicines and Healthcare products Regulatory Agency (MHRA) recommends that after the three loading injections, doses of brolucizumab should be given at least 8 weeks apart to reduce adverse events.[71]

Faricimab is a bispecific antibody that can simultaneously bind and neutralise VEGF-A and angiopoietin-2. The phase 2 STAIRWAY study assessed the extended durability of faricimab dosed up to every 16 weeks. A proportion of patients receiving 12-weekly and 16-weekly doses showed outcomes comparable to monthly ranibizumab. Faricimab is approved in the US and Europe for the treatment of wet AMD based on the results of four phase 3 studies (TENAYA, LUCERNE, YOSEMITE and RHINE) that found faricimab was well tolerated and non-inferior for visual gains over a year when given at intervals of up to 4 months and compared with aflibercept given every 2 months.[48][72]

Treatment response is monitored closely with optical coherence tomography (OCT).

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 a small risk of endophthalmitis, damage to the lens, and retinal detachment; in particular, the risk of endophthalmitis can be reduced by using appropriate aseptic techniques.[73][74][75][76][77]​​ 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 obscured visual field). If endophthalmitis develops, prompt treatment with intravitreal antibiotics is recommended.

Where available, biosimilars can be used according to local guidelines.

Primary options

ranibizumab intravitreal: 0.5 mg intravitreally into affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance

OR

aflibercept intravitreal: standard-dose regimen: 2 mg intravitreally into affected eye(s) every 4 weeks for 3 doses, followed by 2 mg every 8 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; treatment interval may be individualised according to disease activity under specialist guidance

OR

brolucizumab intravitreal: 6 mg intravitreally into 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

More

OR

faricimab intravitreal: 6 mg intravitreally into 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 affected eye(s) once monthly for the first 3 months; treatment interval may be individualised according to disease activity under specialist guidance

Plus – risk factor modification

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

Consider – antioxidant and mineral supplementation

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
Consider – 

antioxidant and mineral supplementation

Additional treatment recommended for SOME patients in selected patient group

For reducing risk of second eye involvement, if second eye not affected yet.

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]​

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

2nd line – photodynamic therapy using verteporfin

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
2nd line – 

photodynamic therapy using verteporfin

Photodynamic therapy (PDT) using verteporfin for subfoveal CNV lesions (that are predominantly classic on fluorescein angiography) is inferior to VEGF inhibitors, and is no longer recommended as a first-line treatment. Combinations of intravitreal VEGF inhibitors plus PDT have been studied, but there is a lack of evidence that they confer an advantage over intravitreal VEGF inhibitors alone.[23][86][87][88]

Patients receiving photodynamic therapy need to cover all skin surface areas when in sunlight following treatment, to avoid developing a burn-like photosensitivity reaction. Patients with porphyria should not receive photodynamic therapy.

PDT, in combination with VEGF inhibitors, may be considered in the management of idiopathic polypoidal choroidal vasculopathy.[89]

Plus – risk factor modification

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
Plus – 

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with 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).[23][27]​​ However, supplementation with omega-3 long-chain polyunsaturated fatty acids does not influence the risk of progressing to advanced AMD.[37] [ Cochrane Clinical Answers logo ]

Plus – specialist referral

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
Plus – 

specialist referral

Treatment recommended for ALL patients in selected patient group

Evaluation by an ophthalmologist specialising in diseases of the retina is recommended at any point in the disease process, but may be particularly necessary for any patient who reaches Age-Related Eye Disease Study Group (AREDS) category ≥3 in one eye; for patients who experience subjective visual changes or abnormality on Amsler examination; or when diagnosis is uncertain and/or atypical features are present.

Consider – antioxidant and mineral supplementation

Back
ACUTE
|
advanced-stage exudative (wet) (AREDS 4)
|
subfoveal choroidal neovascularisation (CNV)
Consider – 

antioxidant and mineral supplementation

Additional treatment recommended for SOME patients in selected patient group

For reducing risk of second eye involvement, if second eye not affected yet.

Compared with placebo, oral supplementation with antioxidant vitamins plus zinc can significantly reduce the development of advanced AMD in patients with intermediate or advanced AMD in at least one eye.[9][23][34][38][39]

Replacement is recommended with vitamin C, vitamin E, beta‐carotene, and zinc; lutein/zeaxanthin is also a suitable replacement for beta‐carotene among people who smoke.[26][40]​​ 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.[40][41] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] [ Cochrane Clinical Answers logo ] ​ A diet of fruits and vegetables rich in antioxidants may also be protective.[42][43][44][45]​

Supplementation with omega-3 fatty acids does not appear to be beneficial.[26][38][39]​​

Dose depends on formulation used.

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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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