Age Related Macular Degeneration

Age related macular degeneration is a progressive degenerative condition of the macula, the central region of the retina responsible for fine, detailed central vision. It is the leading cause of irreversible central visual loss in older adults in high income settings.

It is classified into dry (non-exudative, atrophic) and wet (exudative, neovascular) forms. The dry form accounts for the substantial majority of cases overall. It generally produces more gradual, slowly progressive visual decline.

The wet form is less common but accounts for the majority of severe, rapid vision loss. This reflects pathological choroidal neovascularisation, the mechanism of this subtype.

Accurate distinction between the two forms carries direct, critical treatment implications, given the availability of effective, disease modifying treatment specifically for wet disease.

Pathophysiology and classification

• Dry disease reflects progressive accumulation of drusen (extracellular deposits beneath the retinal pigment epithelium) together with progressive retinal pigment epithelium atrophy. In more advanced disease, photoreceptor atrophy occurs (geographic atrophy, the most advanced stage of dry disease).
• Dry disease produces gradual, progressive central visual decline over years, without the acute, rapid deterioration of wet disease.
• Wet disease reflects pathological growth of new, abnormal blood vessels from the underlying choroid through Bruch membrane into the subretinal or sub-retinal pigment epithelial space (choroidal neovascularisation).
• These fragile new vessels are prone to leakage of fluid and blood, producing macular oedema and haemorrhage and, over time, fibrous scarring. This accounts for the more acute, rapid pattern of central visual decline in this subtype.
• Risk factors include advancing age (the single strongest overall risk factor) and family history, reflecting significant genetic susceptibility.
• Smoking is the single most important modifiable risk factor, with a substantial, well established, dose-dependent association with both disease development and progression.
• Cardiovascular risk factors including hypertension contribute to a lesser extent.

• The characteristic presentation across both forms is progressive, painless central visual loss, characteristically sparing peripheral vision.
• Sparing of peripheral vision distinguishes the condition from many other causes of significant visual impairment. Affected individuals generally retain the ability to navigate their environment using peripheral vision. Tasks requiring fine, detailed central vision, including reading and facial recognition, become progressively, substantially impaired.
• Metamorphopsia (distortion of straight lines, appearing wavy or bent) is a characteristic, particularly useful symptom of macular pathology.
• Metamorphopsia that develops acutely or progressively worsens raises concern for wet disease, given its association with the macular oedema and distortion of active choroidal neovascularisation.
• Dry disease typically produces gradual, slowly progressive central visual blurring and difficulty with tasks requiring fine detail (reading, recognising faces), developing over months to years.
• Wet disease characteristically produces a more acute or rapidly progressive onset of central visual distortion or loss, developing over days to weeks. This warrants urgent ophthalmological assessment, given the time-sensitive nature of effective treatment for this subtype.
• A central or paracentral scotoma (area of absent or significantly reduced vision within the central visual field) develops with disease progression across both forms. Its pattern and severity reflect the extent and location of the macular pathology.

• Dilated fundoscopic examination is the essential initial clinical assessment. It shows drusen and retinal pigment epithelial changes in dry disease, or macular oedema, haemorrhage, or exudate suggestive of active choroidal neovascularisation in wet disease.
• Optical coherence tomography is the essential, standard imaging investigation for diagnosis and, critically, ongoing monitoring of treatment response in wet disease.
• It gives detailed, cross-sectional visualisation of the retinal layers. It allows direct identification and quantification of macular oedema, subretinal or sub-retinal pigment epithelial fluid, and haemorrhage characteristic of active choroidal neovascularisation.
• Fluorescein angiography supports confirmation and characterisation of choroidal neovascularisation where wet disease is suspected, and directly informs treatment planning. Optical coherence tomography angiography is increasingly used as a non-invasive alternative that avoids intravenous dye injection.
• The Amsler grid is a simple, valuable, patient-administered home monitoring tool for individuals with confirmed dry age related macular degeneration or at high risk of progression.
• It allows early self-detection of new or worsening metamorphopsia, which may indicate progression to wet disease. This supports prompt presentation for urgent ophthalmological reassessment, given the time-sensitive nature of effective treatment.

• Dry age related macular degeneration management centres on risk factor modification, particularly smoking cessation given its substantial, well established relevance to disease progression.
• Nutritional supplementation reduces the risk of progression to advanced disease in patients with intermediate stage dry disease. Use the formulation demonstrated effective in clinical trials: a defined combination of antioxidant vitamins, zinc and, in more recent formulations, lutein and zeaxanthin.
• Complement inhibitor therapy (pegcetacoplan or avacincaptad pegol, given as regular intravitreal injection) is an emerging treatment option for geographic atrophy, the advanced form of dry disease. It modestly reduces the rate of geographic atrophy progression.
• This is a relatively recent development for a previously entirely untreatable stage. Treatment benefit is generally modest, so discuss individually the balance of potential benefit against the burden of regular, ongoing intravitreal injection.
• Wet age related macular degeneration is treated with regular intravitreal injection of an anti-vascular endothelial growth factor agent (including ranibizumab, aflibercept, bevacizumab, and, more recently, faricimab).
• These agents directly target and suppress pathological choroidal neovascularisation. Treatment is highly effective and has fundamentally transformed the prognosis of this condition.
• Treatment is typically an initial loading course of regular monthly injections, followed by an individualised, ongoing maintenance regimen guided by optical coherence tomography monitoring of treatment response.
• Prompt referral for urgent ophthalmological assessment and treatment initiation is essential for any suspected new or progressing wet disease. Treatment delay reduces the likelihood of an optimal, durable visual outcome with anti-vascular endothelial growth factor treatment.
• Low vision rehabilitation services provide magnification aids and other assistive devices, practical support and advice on adaptation to visual impairment, and, where relevant, registration as visually impaired to support access to additional services.
• These services are valuable for patients with significant, established visual impairment from either form. They are particularly relevant for advanced dry disease, where disease modifying treatment is more limited than the highly effective options for wet disease.
• Regular, structured, ongoing ophthalmological follow up underpins longitudinal management of this common, significant condition. It includes continued optical coherence tomography monitoring for wet disease patients receiving anti-vascular endothelial growth factor treatment, and monitoring for dry disease progression and potential development of wet disease in either eye.