Overview
Age-Related Macular Degeneration (AMD)
1. Clinical Overview
Summary
Age-Related Macular Degeneration (AMD) is the leading cause of irreversible blindness in the developed world in people over 50 years. It affects the macula – the central part of the retina responsible for detailed central vision (Reading, Driving, Recognising faces). AMD exists in two forms: Dry AMD (Geographic Atrophy) – the more common, slowly progressive form characterised by drusen and retinal pigment epithelium (RPE) atrophy; and Wet AMD (Neovascular AMD) – the more severe form caused by choroidal neovascularisation (CNV) leading to rapid, potentially severe vision loss. Wet AMD is a medical emergency requiring urgent anti-VEGF intravitreal injections (Ranibizumab, Aflibercept, Faricimab) within 2 weeks of symptom onset to preserve vision. Risk factors include age, smoking, family history, and race (White > Black). [1,2,3]
Clinical Pearls
Dry = Drusen = Slow: Yellow deposits under the retina. Progressive but slow (Years to decades).
Wet = New Vessels = Fast = Emergency: Choroidal neovascularisation (CNV). Can cause severe vision loss in weeks. Urgent anti-VEGF.
Amsler Grid: Home monitoring tool. Patient stares at central dot – Distorted/Wavy lines = Wet AMD developing.
2-Week Rule: Anti-VEGF injection should be given within 14 days of symptom onset for wet AMD (Urgent referral).
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Age | Risk increases exponentially after 50. Affects 30% of over 75s. |
| Sex | Female > Male (Slight predominance). |
| Race | White > Asian > Black (Difference in wet AMD). |
Risk Factors
| Risk Factor | Notes |
|---|---|
| Age | Strongest risk factor. |
| Smoking | 2-3x increased risk. MOST MODIFIABLE FACTOR. |
| Family History | First-degree relative = 50% higher risk. |
| Genetics | CFH gene variants (Complement Factor H). |
| Cardiovascular Disease | Hypertension, Atherosclerosis. |
| Obesity | Increases risk. |
| Sunlight Exposure | Possibly (UV/Blue light). |
Protective Factors
- Dietary antioxidants (Lutein, Zeaxanthin – Found in green leafy vegetables).
- Omega-3 fatty acids.
- Smoking cessation.
3. Pathophysiology
Anatomy
- Macula: Central 5mm of retina. Contains fovea (Highest cone density). Responsible for detailed central vision.
- Retinal Pigment Epithelium (RPE): Supports photoreceptors. Phagocytoses outer segments.
- Bruch's Membrane: Barrier between RPE and choroidal circulation.
- Choroid: Blood supply to outer retina.
Dry AMD (Geographic Atrophy)
- Drusen Formation: Yellow deposits of lipid, protein, and inflammatory material accumulate between RPE and Bruch's membrane.
- Hard Drusen: Small, discrete. Common in normal ageing.
- Soft Drusen: Larger, confluent. Associated with AMD progression.
- RPE Dysfunction: Drusen impair RPE function.
- RPE Atrophy: Geographic areas of RPE loss → Photoreceptor degeneration.
- Vision Loss: Gradual central vision loss over years.
Wet AMD (Neovascular AMD)
- Angiogenic Stimulus: Hypoxia and inflammation upregulate VEGF (Vascular Endothelial Growth Factor).
- Choroidal Neovascularisation (CNV): New, fragile vessels grow from choroid through Bruch's membrane under (or into) the retina.
- Leakage and Haemorrhage: CNV vessels are leaky → Subretinal fluid, Haemorrhage, Lipid exudates.
- Scarring: Chronic CNV → Disciform scar → Permanent central vision loss.
4. Differential Diagnosis
| Condition | Key Features |
|---|---|
| Age-Related Macular Degeneration | Elderly, Central vision loss, Drusen/CNV on OCT. |
| Diabetic Macular Oedema | Diabetic, Microaneurysms, Exudates, Thickened macula on OCT. |
| Macular Hole | Central scotoma, "Hole" on OCT, Usually post-vitreous detachment. |
| Epiretinal Membrane | Distortion, "Cellophane" membrane on macula, Macula pucker. |
| Central Serous Chorioretinopathy (CSCR) | Younger patients (30-50), Stress-related, Subretinal fluid, Usually resolves. |
| Myopic Maculopathy | High myopia, CNV, Lacquer cracks, Posterior staphyloma. |
| Best Disease | Inherited, Vitelliform lesion ("Egg yolk"), EOG abnormal. |
5. Clinical Presentation
Symptoms
| Symptom | Notes |
|---|---|
| Gradual Central Vision Loss | Difficulty reading, Seeing faces. |
| Metamorphopsia | Distortion – Straight lines appear wavy. Key symptom of Wet AMD. |
| Central Scotoma | Dark or blank spot in central vision. |
| Reduced Contrast Sensitivity | Dull colours. |
| Charles Bonnet Syndrome | Visual hallucinations (Complex, non-threatening) due to visual cortex deafferentation. |
Dry vs Wet AMD Presentation
| Feature | Dry AMD | Wet AMD |
|---|---|---|
| Onset | Gradual (Years) | Sudden (Days-Weeks) |
| Distortion | Minimal | Prominent (Metamorphopsia) |
| Severity | Mild-Moderate vision loss | Severe vision loss |
| Urgency | Routine | URGENT (2-week referral) |
Examination Findings
| Finding | Dry AMD | Wet AMD |
|---|---|---|
| Drusen | Present | May be present |
| RPE Changes | Pigment clumping, Atrophy | Variable |
| Subretinal Fluid | Absent | Present |
| Haemorrhage | Absent | Subretinal/Subepithelial blood |
| Grey-Green Membrane | Absent | CNV membrane may be visible |
Amsler Grid
Patient fixates on central dot.
Common presentation.
Normal
Grid lines appear straight.
Abnormal
Wavy lines, Missing areas = Macular pathology.
6. Investigations
Imaging
| Modality | Role |
|---|---|
| Fundoscopy / Slit Lamp Biomicroscopy | Direct visualisation of drusen, haemorrhage, RPE changes. |
| Optical Coherence Tomography (OCT) | Gold Standard. Shows retinal layers in cross-section. Detects subretinal fluid, CNV, Drusen, Atrophy. |
| OCT Angiography (OCT-A) | Non-invasive visualisation of CNV blood flow. |
| Fluorescein Angiography (FFA) | Invasive (IV dye). Classic CNV leak pattern. Used when OCT equivocal or for treatment planning. |
| Indocyanine Green Angiography (ICG) | Choroidal imaging. Polypoidal choroidal vasculopathy (PCV). |
| Fundus Autofluorescence (FAF) | Maps RPE health. Identifies geographic atrophy. |
OCT Findings
| Finding | Interpretation |
|---|---|
| Drusen | Dome-shaped RPE elevations. |
| Subretinal Fluid | Dark (Hyporeflective) space under retina = Active Wet AMD. |
| Intraretinal Fluid | Cysts within retina = Active disease. |
| Pigment Epithelial Detachment (PED) | RPE lifted off Bruch's membrane. |
| RPE Atrophy | Thin/Absent RPE = Geographic atrophy. |
| Subretinal Hyperreflective Material (SHRM) | Mixed tissue (Fibrin, Blood, CNV). |
7. Management
Management Algorithm
SUSPECTED AMD
(Central vision loss, Elderly patient)
↓
CLINICAL ASSESSMENT
- Visual acuity (Snellen/LogMAR)
- Amsler grid
- Dilated fundoscopy
- Optical Coherence Tomography (OCT)
↓
CLASSIFY AMD TYPE
┌────────────────┴────────────────┐
DRY AMD (Geographic Atrophy) WET AMD (Neovascular)
↓ ↓
ROUTINE MANAGEMENT **URGENT REFERRAL**
(Target: Treatment within 2 weeks)
Dry AMD Management
| Intervention | Notes |
|---|---|
| Lifestyle Modification | Stop smoking. Healthy diet (Green leafy vegetables). |
| AREDS2 Supplements | Antioxidant vitamins (Vitamin C, E, Lutein, Zeaxanthin, Zinc). Slows progression in intermediate AMD. |
| Monitoring | Amsler grid at home. Annual review. |
| Low Vision Aids | Magnifiers, Large print, Screen readers. |
| No Curative Treatment | Geographic atrophy has no proven treatment (Trials ongoing – Pegcetacoplan). |
Wet AMD Management
| Intervention | Notes |
|---|---|
| Anti-VEGF Intravitreal Injections | First-line treatment. Blocks VEGF → Reduces leakage and CNV growth. |
| Agents | Ranibizumab (Lucentis), Aflibercept (Eylea), Faricimab (Vabysmo), Bevacizumab (Off-label, Cost-effective). |
| Regimen | Loading: 3 monthly injections. Maintenance: Treat-and-Extend or PRN based on OCT response. |
| Frequency | May require ongoing injections for years (Typically 6-8/year). |
| Response | Vision stabilises in ~90%. Vision improves in ~30-40%. |
| Photodynamic Therapy (PDT) | Rarely used now. For polypoidal choroidal vasculopathy (PCV). |
Anti-VEGF Injection Procedure
- Performed in clinic (Clean room/Theatre).
- Topical anaesthesia.
- Povidone-iodine antisepsis.
- Injection into vitreous cavity.
- Risks: Endophthalmitis (Rare, ~1:2000), Retinal detachment, Subconjunctival haemorrhage.
8. Complications
| Complication | Notes |
|---|---|
| Legal Blindness | Central vision loss progresses. Peripheral vision preserved. |
| Disciform Scar | End-stage wet AMD. CNV fibrosis. Irreversible central vision loss. |
| Falls and Fractures | Visual impairment increases fall risk. |
| Depression | Significant psychosocial impact. |
| Charles Bonnet Syndrome | Visual hallucinations. Benign but distressing. |
9. Prognosis and Outcomes
| AMD Type | Prognosis |
|---|---|
| Dry AMD | Slowly progressive. May take 10-20 years to advanced stage. 10-15% convert to Wet AMD. |
| Wet AMD (Treated) | Vision stabilises in 90%. Improves in 30-40%. Requires ongoing treatment. |
| Wet AMD (Untreated) | Rapid severe vision loss. Disciform scar. Legal blindness. |
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| AMD Management | NICE NG82 (2018) | Anti-VEGF for wet AMD within 14 days. AREDS2 for intermediate dry AMD. |
| Royal College of Ophthalmologists | RCOphth | Treatment pathways, Injection protocols. |
Landmark Trials
| Trial | Findings |
|---|---|
| MARINA / ANCHOR | Ranibizumab superior to sham/PDT. Established anti-VEGF. |
| VIEW 1/2 | Aflibercept non-inferior to Ranibizumab. |
| AREDS / AREDS2 | Antioxidant supplements slow progression in intermediate AMD. Lutein/Zeaxanthin replaces beta-carotene. |
| CATT | Bevacizumab non-inferior to Ranibizumab (Cost-effective option). |
11. Patient and Layperson Explanation
What is Macular Degeneration?
The macula is the central part of the back of your eye (Retina). It is responsible for detailed vision – reading, driving, recognising faces. In AMD, this part wears out or develops abnormal blood vessels.
What is the difference between Dry and Wet AMD?
- Dry AMD: Slow wear and tear. Yellow deposits (Drusen) build up. Vision gradually fades over years.
- Wet AMD: New, leaky blood vessels grow under the retina. Vision can drop suddenly in days to weeks. This is an EMERGENCY.
How do I know if I have Wet AMD?
Look at straight lines (Door frame, Amsler grid). If they appear wavy or distorted, contact your eye clinic urgently. Do NOT wait.
What is the treatment?
- Dry AMD: No cure yet, but vitamins (AREDS2) may slow progression. Stop smoking!
- Wet AMD: Injections into the eye (Anti-VEGF) every few weeks. This can stabilise or improve vision if started quickly.
Will I go completely blind?
AMD affects central vision (Reading, Faces). Peripheral vision (Getting around) is usually preserved. Most people do NOT go completely blind, but driving and reading may become difficult.
12. References
Primary Sources
- National Institute for Health and Care Excellence. Age-related macular degeneration (NG82). 2018. nice.org.uk/guidance/ng82
- Flaxel CJ, et al. Age-Related Macular Degeneration Preferred Practice Pattern. Ophthalmology. 2020;127(1):P1-P65. PMID: 31757503.
- Age-Related Eye Disease Study 2 Research Group. Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration (AREDS2). JAMA. 2013;309(19):2005-2015. PMID: 23644932.
13. Examination Focus
Common Exam Questions
- Difference between Dry and Wet AMD: "What is the key pathological difference?"
- Answer: Dry = Drusen, RPE atrophy. Wet = Choroidal Neovascularisation (CNV).
- Treatment for Wet AMD: "What is first-line treatment?"
- Answer: Anti-VEGF Intravitreal Injections (Ranibizumab, Aflibercept).
- OCT Finding: "What OCT finding indicates active Wet AMD?"
- Answer: Subretinal Fluid (Or Intraretinal fluid/Cysts).
- Risk Factor: "What is the strongest modifiable risk factor?"
- Answer: Smoking.
Viva Points
- 2-Week Target: NICE mandates treatment initiation within 14 days for wet AMD. Delays = Worse outcomes.
- AREDS2: Replaced beta-carotene with Lutein/Zeaxanthin (Due to lung cancer risk in smokers with beta-carotene).
- Charles Bonnet Syndrome: Visual hallucinations in low vision. Patients often don't report (Fear of being labelled "crazy"). Ask directly.
- Bevacizumab (Avastin): Off-label, Much cheaper. Used extensively worldwide. Efficacy similar to Ranibizumab.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.