Changes

October 2025 — reviewed. A literature search was conducted in September 2025 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to the recommendations have been made.

Update

Goals

To support primary care professionals to:

• Recognise the key features of age-related macular degeneration (AMD)
• Facilitate prompt diagnosis and treatment of neovascular AMD
• Ensure that people with AMD receive appropriate advice, information, and support

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

Serious eye disorders

• Adults with late age‑related macular degeneration (wet active) start treatment within 14 days of referral to the macular service.
• Adults with late age‑related macular degeneration (wet active) have monitoring for both eyes.
• Adults with serious eye disorders are given a certificate of vision impairment as soon as they are eligible.

[NICE, 2019]

What is it?

• Age-related macular degeneration (AMD) is a potentially progressive disorder of the macula that typically affects people aged over 50 years — it is the commonest cause of severe irreversible visual impairment in older adults in the developed world.
• AMD is characterized by the presence of one or more of the following:
  
  • Drusen — at least intermediate drusen (63 micrometres or more in diameter). These may be visible on ophthalmoscopy as pale yellow spots on the retina. 
    • Drusen are collections of lipid material that accumulate beneath the retinal pigment epithelium (RPE) and within Bruch’s membrane. 
  • RPE abnormalities — areas of hypopigmentation or hyperpigmentation.
  • Geographic atrophy — breakdown of light-sensitive cells in the macula causes one or more sharply demarcated areas of partial or complete depigmentation (atrophy) of the RPE. The areas of atrophy can enlarge over time. Atrophy may or may not involve the fovea (the central part of the macula). 
  • Choroidal neovascularization (CNV, also called exudative, or wet disease) — the development of new blood vessels in the choroid. CNV breaches the normal anatomical barrier of Bruch’s membrane and invades the subpigment epithelial and or subretinal spaces. 
    • The new vessels are unlike normal retinal vessels and easily bleed or leak blood constituents, resulting in distortion and scarring of the retina.
  • Polypoidal choroidal vasculopathy (PCV) — characterized by multiple and recurrent serosanguineous RPE detachments. 
  • Reticular pseudodrusen (also referred to as subretinal drusenoid deposits). 
  • Retinal angiomatous proliferation — characterized by proliferation of retinal capillaries in the paramacular area that may present as intraretinal, subretinal, or CNV.

[NICE, 2018; Guymer, 2023; AAO, 2024; Fleckenstein, 2024; RCO, 2024] 

How is it classified?

NICE classifies age-related macular degeneration (AMD) as follows:

• No AMD — no signs of AMD, or small (hard) drusen less than 63 micrometres in diameter. 
  • Small drusen are sometimes called drupelets and are commonly found in older people.
• Early AMD 
  • Low risk of progression — medium drusen (63–124 micrometres in diameter), or pigmentary abnormalities. 
  • Medium risk of progression — large drusen (125 micrometres or more in diameter), or reticular drusen, or medium drusen with pigmentary abnormalities.
  • High risk of progression — large drusen with pigmentary abnormalities, or reticular drusen with pigmentary abnormalities, or vitelliform lesion without significant visual loss (best-corrected acuity better than 6/18), or atrophy smaller than 175 micrometres and not involving the fovea.
• Late AMD 
  • Intermediate — retinal pigment epithelial (RPE) degeneration and dysfunction (presence of degenerative AMD changes with subretinal or intraretinal fluid in the absence of neovascularization), serous pigment epithelial detachment (PED) without neovascularization.
  • Wet active — classic choroidal neovascularization (CNV), occult (fibrovascular PED and serous PED with neovascularization), mixed (predominantly or minimally classic CNV with occult CNV), retinal angiomatous proliferation (RAP), polypoidal choroidal vasculopathy (PCV).
  • Dry — geographic atrophy (in the absence of neovascular AMD), significant visual loss (6/18 or worse) associated with: 
    • Dense or confluent drusen or
    • Advanced pigmentary changes and/or atrophy or 
    • Vitelliform lesion.
  • Wet inactive — fibrous scar, sub-foveal atrophy or fibrosis secondary to an RPE tear, atrophy (absence or thinning of RPE and/or retina), cystic degeneration (persistent intraretinal fluid or tubulations unresponsive to treatment). 
    • Note: eyes may still develop or have a recurrence of late AMD (wet active).

[NICE, 2018; RCO, 2024] 

How common is it?

• Advanced age-related macular degeneration (AMD) is the commonest cause of severe visual impairment in older adults in the developed world and the cause of around half of registrations of visual impairment or blindness in the UK.
  • Worldwide, it is estimated that 196 million people have AMD, and this is projected to rise to 288 million people by 2040.
  • In the UK, it was estimated that in 2020, 645,000 people had late AMD, 340,000 people were affected by geographic atrophy, and 339,000 people had neovascular AMD.
    • By 2050, it is expected that UK rates will be 1.3 million people with late AMD, 720,000 people with geographic atrophy, and 683,000 people with neovascular AMD.
• It is estimated that about 80% of people with AMD have non-neovascular or atrophic AMD, although vascular AMD is responsible for 90% of the severe visual acuity loss.
  • In 2013, approximately 450,000 people in the UK had severe visual impairment or blindness due to advanced AMD, and this is projected to increase to over 1.2 million people by 2050.

[NICE, 2018; AAO, 2024; Fleckenstein, 2024; RCO, 2024] 

What are the risk factors?

• The main risk factors for the development of advanced age-related macular degeneration (AMD) include:
  • Increasing age.
    • A large meta-analysis of data from Australia, the US and Europe found that the prevalence of late-stage AMD in white populations was 0.3 per 1000 in people aged 55 to 59 years, 5.7 per 1000 in people aged 75 to 79 years, and 36.7 per 1000 in people aged 90 years or older.
    • Female sex — AMD is slightly more common in women than in men.
    • Family history of AMD — estimated heritability of late-stage AMD is approximately 71%.
    • Northern European ancestry.
  • Smoking is the main modifiable risk factor — it significantly increases the risk of developing AMD and is a risk factor both for new-onset AMD and for progression of existing AMD to advanced disease.
    • There is a dose-response relationship — the risk increases with the number of pack-years of smoking.
    • Current smokers have a two- to three-fold increased risk of developing AMD, and those with a genetic susceptibility are also more likely to develop AMD if they smoke.
    • The risk of developing new-onset AMD in people who have stopped smoking for 20 years or more is the same risk as non-smokers.
    • Stopping smoking reduces the risk of AMD progression in people with existing disease.
  • Other risk factors include:
    • Hypertension.
    • History of cardiovascular disease.
    • Presence of AMD in the other eye.
    • Obesity — BMI of 30 kg/m² or higher. 
    • Diet:
      • Low in omega-3 and 6, vitamins (A, C, and E), carotenoids (for example, lutein), and minerals (for example, zinc).
      • High in saturated fat and cholesterol.
      • With a high glycaemic index.
    • Inactivity.

  [NICE, 2018; Heesterbeek, 2020; Thomas, 2021; AAO, 2024; Fleckenstein, 2024; RCO, 2024] 

What is the prognosis?

• Central visual loss is common, but total visual loss is extremely rare in people with age-related macular degeneration (AMD).
• Generally, early and intermediate AMD is not associated with disturbances of central visual function — vision loss is usually due to the development of advanced AMD.
• For people with early AMD, there is a low risk of progression (1.3%) to advanced AMD after 5 years in either eye. 
  • In a 10-year follow-up study of people with small drusen or no drusen at baseline, approximately 15% developed large drusen at 10 years.
• For people with intermediate AMD, the risk of progression to advanced AMD after 5 years is approximately 18%. 
  • For people with large drusen in one eye, the rate of development to advanced AMD is 6.3% at 5 years and 26% for people with multiple bilateral large drusen. 
  • In a 10-year follow-up study of people with medium drusen present in one eye at baseline, 37% developed large drusen compared with 71% for people with medium drusen in both eyes.
  • When medium drusen are present at baseline, progression to advanced AMD is 14% at 10 years.
• For people with advanced AMD, the risk of developing advanced AMD in the other eye ranges from 22–50% at 5 years. 
  • Geographic atrophy usually results in less severe visual impairment than neovascular AMD, and it occurs more slowly.
    • Doubling of the visual angle (loss of three or more lines on a visual acuity chart) has been reported to occur in up to 50% of people with geographic atrophy over a 2-year period. 
    • A longitudinal study of geographic atrophy found that three lines of visual acuity are lost in about 31% of people within 2 years of diagnosis, and in about 53% of people within 4 years. 
  • Neovascular AMD, left untreated, progresses to moderate or severe visual loss that can be rapid, within weeks or months. 
    
    • A meta-analysis of interventional studies found that in people with untreated neovascular AMD, the mean visual acuity change progressed from one line lost at 3 months to around three lines after 12 months and four lines lost after 24 months.
    • The risk of neovascular AMD developing in the second eye is 12% at 1 year and 27% at 4 years.
• For people who receive timely treatment for neovascular AMD, the prognosis has greatly improved in recent years. 
  
  • Seven year follow up of people treated for neovascular AMD found that 43% maintained or improved their visual acuity, while 34% lost three or more lines on a visual acuity chart. 
    
    • Factors that affect the effectiveness of anti-angiogenic therapy include visual acuity and lesion size at diagnosis, and the number of injections received.

[Wong, 2008; Bloch, 2012; Schmidt-Erfurth, 2014; NICE, 2018; AAO, 2024; RCO, 2024] 

What are the possible complications?

• Complications of age-related macular degeneration (AMD) include: 
  • Visual impairment and blindness. 
  • Complications of visual impairment.
    • Depression — this occurs in up to 44% of people with advanced AMD and at twice the rate compared with the general population of similar age without advanced AMD. 
    • Visual hallucinations (Charles Bonnet syndrome) — this may occur in people with severe visual impairment and range from simple patterns of straight lines to detailed pictures of people or buildings. Hallucinations related to AMD are not a symptom of mental illness; they typically improve by 18 months, but can last many years.
    • Falls and fractures. 
    • Limitations in mobility, activities of daily living, and physical performance. 
    • Reduced quality of life. 
• Complications of treatments include: 
  • Photosensitivity reaction after photodynamic therapy.
  • Endophthalmitis, traumatic lens injury, and retinal detachment after intravitreal injection with vascular endothelial growth factor (VEGF) treatment.

[NICE, 2018; Thomas, 2021; AAO, 2024; Fleckenstein, 2024; RCO, 2024] 

When should I suspect age-related macular degeneration?

• A person with age-related macular degeneration (AMD) may be asymptomatic, with retinal signs detected incidentally by an optometrist during a routine eye test. 
  • People with early and intermediate AMD may have normal, or near-normal vision. 
• Suspect AMD in people with risk factors for AMD and typical symptoms, including: 
  • Blurring or distortion of vision, typically in people aged over 50 years.  
    
    • With neovascular AMD, visual deterioration can develop quickly — this is often the first symptom. A person may suddenly become unable to read, drive, and see fine detail such as facial expressions and features. 
    • With geographic atrophy, the visual deterioration tends to be gradual — a common presentation is difficulty with reading, initially with the smallest sizes of print and then later with larger print.
    • Sometimes people do not notice visual deterioration when one eye is affected, and the visual loss only becomes apparent when the second eye becomes affected. 
  • Metamorphopsia — distortion of vision, where straight lines (such as window blinds) appear crooked, wavy, or bent. 
  • Scotoma — the person may describe a black or grey patch affecting their central field of vision. 
• Other symptoms that a person with AMD may describe include: 
  • Light glare. 
  • Loss of (or decreased) contrast sensitivity (the ability to discern between different shades). 
  • Size or colour of objects appearing different with each eye. 
  • Abnormal dark adaptation (difficulty adjusting from bright to dim lighting). 
  • Photopsia — a perception of flickering or flashing lights. 
  • Visual hallucinations (Charles Bonnet syndrome) — these can occur with severe visual loss of any cause, including advanced AMD. Visual hallucinations are often not reported unless specifically asked about. 
• On examination:
  • Visual acuity may be reduced. 
  • With fundoscopy by a general practitioner, signs may be difficult to detect, depending on the level of expertise. The following signs may be seen: 
    • Drusen — a frequent feature in the early stages of disease. 
    • Pigmentary, exudative, haemorrhagic, or atrophic changes affecting the macula. 
• Refer urgently to an ophthalmologist for confirmation of the diagnosis if AMD is suspected.

What else might it be?

• If a person presents with symptoms suggestive of age-related macular degeneration (AMD), it is not usually necessary for a primary healthcare professional to consider the differential diagnosis, as urgent specialist assessment is needed. 
• For reference, other conditions that cause painless visual disturbance include: 
  • Refractive error. 
  • Some types of corneal disease (for example, Fuch's endothelial dystrophy). 
  • Cataract. For more information, see the CKS topic on Cataracts.
  • Primary open-angle glaucoma (central visual field loss occurs late in the course of the disease). For more information, see the CKS topic on Glaucoma.
  • Posterior vitreous detachment, vitreous haemorrhage, or retinal detachment (usually present with floaters or flashing lights). For more information, see the CKS topic on Retinal detachment. 
  • Cerebrovascular disease, including amaurosis fugax, stroke, or transient ischaemic attack (TIA). For more information, see the CKS topic on Stroke and transient ischaemic attack. 
  • Retinal arterial occlusion or retinal venous occlusion. 
  • Chemicals or medication — for example, methanol, chloroquine, hydroxychloroquine, isoniazid, thioridazine, isotretinoin, tetracycline, or ethambutol. 
  • Pituitary tumour and papilloedema. 
• Conditions causing similar retinal signs to those observed in AMD include: 
  • Diabetic maculopathy. 
  • High myopia (short-sightedness greater than –6 dioptres) — this can be associated with choroidal neovascularization (CNV), usually occurs at a younger age than AMD, and has a different natural history and response to treatment. 
  • Rare inflammatory syndromes causing CNV (for example, presumed ocular histoplasmosis, punctate inner choroidopathy, multifocal inner choroidopathy). There are usually signs of active or previous uveitis that would not be present in AMD. For more information, see the CKS topic on Uveitis.
  • Central serous retinopathy. 
  • Macular telangiectasia. 
  • Pattern dystrophy — these macular dystrophies may be inherited and are often symmetrical. 
    • Consider the possibility of hereditary macular dystrophies in people aged under 50 years who have clinical features that resemble AMD. 
  • Macular hole. 
  • Traumatic CNV. 
  • Idiopathic CNV.

Scenario: Suspected age-related macular degeneration

From age 50 years onwards.

Scenario: Confirmed age-related macular degeneration

From age 50 years onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of macular degeneration.

Search dates

October 2020 - September 2025

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

• exp Macular Degeneration/
• ("macular degenerationage" or "age related macular degeneration" or "age-related macular degeneration" or AMD or  maculopath$ or "geographic atrophy").ti,ab.

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.