Macular degeneration - age-related
Exam Tips
- In OSCEs, unilateral symptoms may be missed by patients; always test each eye separately and ask specifically about distortion using an Amsler grid.
- Rapid-onset central distortion or scotoma in an older adult is wet AMD until proven otherwise and requires urgent same-day ophthalmology referral.
- Dry AMD progresses more slowly and is not treated with anti-VEGF; anti-VEGF is for neovascular activity demonstrated clinically/OCT.
- Distinguish central vision loss of AMD from glaucoma (typically peripheral first) and cataract (global blur/glare without metamorphopsia).
- Use image-based revision: fundus photos of drusen/pigment change and OCT examples of subretinal fluid versus geographic atrophy are high-yield for UK written and clinical exams.
Definition
Age-related macular degeneration (AMD) is a chronic degenerative disorder of the macula in people usually older than 50 years, causing progressive loss of central vision while peripheral vision is typically preserved. It is characterised by drusen and retinal pigment epithelium (RPE) change, and may progress to either atrophic (geographic atrophy) disease or neovascular (wet) disease with choroidal neovascularisation and rapid visual decline.
Pathophysiology
AMD develops through age-related dysfunction at the photoreceptor-RPE-Bruch membrane-choriocapillaris interface. Lipid-rich deposits (drusen) accumulate in and beneath Bruch membrane, with oxidative stress, complement-mediated inflammation, mitochondrial injury, and impaired RPE phagocytosis of photoreceptor outer segments driving progression. In dry AMD, progressive RPE and photoreceptor loss leads to sharply demarcated geographic atrophy; in wet AMD, VEGF-driven choroidal neovascular vessels breach Bruch membrane, leak fluid or blood into subretinal/intraretinal spaces, and eventually cause fibrovascular scarring and permanent central vision loss.
Risk Factors
- Increasing age (strongest risk factor)
- Smoking (major modifiable risk; dose-response with pack-years)
- Family history/genetic susceptibility (high heritability)
- Female sex
- Northern European ancestry
- AMD in the fellow eye
- Hypertension and cardiovascular disease
- Obesity (BMI >= 30 kg/m^2)
- Diet low in antioxidants/carotenoids and high in saturated fat/high glycaemic load
- Physical inactivity
Clinical Features
Symptoms
- Painless central visual blurring (often initially unilateral)
- Metamorphopsia (straight lines appear wavy on reading/window frames)
- Central scotoma (grey or black patch in central vision)
- Reduced reading ability and difficulty recognising faces
- Glare sensitivity and reduced contrast sensitivity
- Delayed dark adaptation
- Photopsia or flashing lights (especially if concurrent vitreoretinal pathology)
- Visual hallucinations in severe sight loss (Charles Bonnet syndrome)
Signs
- Reduced best-corrected visual acuity
- Drusen at the macula (yellow subretinal deposits)
- Macular pigmentary change (hyperpigmentation/hypopigmentation)
- Geographic atrophy with well-demarcated RPE loss in dry AMD
- Subretinal/intraretinal fluid, haemorrhage, or exudation in wet AMD
- Fibrotic macular scar in inactive late wet AMD
Investigations
Management
Lifestyle Modifications
- Urgent ophthalmology referral if wet AMD suspected (new distortion or rapid central vision loss should be treated as same-day/next-day eye emergency pathway)
- Smoking cessation support (most effective modifiable intervention for progression risk)
- Optimise cardiovascular risk factors (blood pressure, weight, physical activity)
- Dietary advice: leafy greens, oily fish, low saturated fat/high-fibre lower glycaemic pattern
- Low-vision support, falls-risk reduction, driving advice, and registration for visual impairment when appropriate
Pharmacological Treatment
Intravitreal anti-VEGF therapy for neovascular (wet) AMD
- Aflibercept 2 mg intravitreal injection (typically every 4 weeks for first 3 doses, then usually every 8 weeks; treat-and-extend regimens used in practice)
- Ranibizumab 0.5 mg intravitreal injection monthly until disease control, then interval adjusted
- Faricimab 6 mg intravitreal injection (4-week loading doses followed by interval extension up to 16 weeks in suitable responders)
- Brolucizumab 6 mg intravitreal injection (loading then 8-12 weekly maintenance in selected patients)
Given by specialist ophthalmology services with OCT-guided monitoring. Contraindications include active/suspected ocular or periocular infection and active severe intraocular inflammation. Safety warnings: endophthalmitis, retinal detachment, traumatic lens injury, raised intraocular pressure, and potential arterial thromboembolic events; use caution in recent MI/stroke. Brolucizumab has important warning for intraocular inflammation/retinal vasculitis and retinal vascular occlusion.
Adjunctive therapy (selected cases)
- Verteporfin photodynamic therapy 6 mg/m^2 IV with laser activation (mainly selected polypoidal choroidal vasculopathy or specific lesion profiles)
Post-treatment photosensitivity risk: avoid direct sunlight/bright indoor light for about 48 hours; monitor for infusion-site and visual adverse effects.
Surgical / Interventional
- No routine curative surgery for AMD; intravitreal injection procedures are the key interventional treatment for wet AMD
- Selected specialist procedures for complications (for example, surgery for retinal detachment or non-clearing vitreous haemorrhage when present)
Complications
- Progressive central visual impairment and legal blindness registration
- Fibrotic macular scarring (late wet AMD)
- Bilateral disease over time (fellow-eye conversion risk)
- Depression, loss of independence, reduced quality of life
- Falls, fractures, and reduced mobility
- Charles Bonnet syndrome (complex visual hallucinations with preserved cognition)
- Treatment-related harms: endophthalmitis, retinal detachment, lens trauma, photosensitivity (PDT)
Prognosis
Peripheral vision is usually retained, but central vision may decline substantially, especially in untreated neovascular AMD where deterioration can occur over weeks to months. Early AMD has relatively low short-term progression risk, intermediate AMD has a meaningful 5-year conversion risk, and advanced disease in one eye confers significant risk to the other eye. Prognosis in wet AMD has improved markedly with prompt anti-VEGF treatment, with many patients stabilising vision, although some still lose >= 3 Snellen lines over long-term follow-up.
Sources & References
🏥BMJ Best Practice(1)
💊BNF Drug References(5)
- Aflibercept [Specialist drug][management.pharmacological]
- Bevacizumab [Specialist drug][management.pharmacological]
- Brolucizumab [Specialist drug][management.pharmacological]
- Faricimab [Specialist drug][management.pharmacological]
- Verteporfin [Specialist drug][management.pharmacological]
✅NICE Guidelines(1)
- Macular degeneration - age-related[overview]
📖Textbook References(20)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1090, 1091)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1824)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1092)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1764, 1765)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1831)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1101, 1102)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1101)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1836)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1100, 1101)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1100, 1101)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1763, 1764)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 509)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 671, 672)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 509, 510)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 515)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 514, 515)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 671, 672)[context]
- Oxford Handbook of Clinical Diagnosis (Huw Llewelyn, Hock Aun Ang, Keir Lewis etc.) (Z-Library).pdf(pp. 509, 510)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 648, 649)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 648, 649)[context]