Sarrvesa Singh ( left ) Clinical research co-ordinator , Strathfield Retina Clinic , Sydney , NSW .

Carina Truong ( centre ) Clinical research co-ordinator , Strathfield Retina Clinic , Sydney , NSW .

Nauman Ahmed ( right ) Medical student , University of Sydney , Sydney , NSW .

Dr James Wong ( left ) Medical director , Strathfield Retina Clinic , Sydney , NSW .

Dr Hemal Mehta ( right ) Co-director of clinical trials research , Strathfield Retina Clinic , Sydney , NSW .

First published online on 10 February 2023

INTRODUCTION

AGE-related macular degeneration

is the leading cause of irreversible blindness in developed countries . 1

Patients are required to be aged over 50 to meet the definition of age-related macular degeneration ( AMD ), and the condition becomes more common with each passing decade . The disease affects central vision , causing distortion of straight lines and central scotomas . Functionally , this can lead to reduced reading speed , loss of sufficient vision for safe driving , increased risk of falls , loss of independence and depression .

AMD is initially characterised by the development of drusen and retinal pigment epithelium ( RPE ) pigmentary changes ( either increased or decreased ) at the central retina ( macula , see figure 1 ). There are two late-stage manifestations of this disease : neovascular and atrophic AMD . Without treatment , wet ( neovascular ) AMD leads to a rapid reduction in central vision . However , with the advent of intravitreal vascular endothelial growth factor inhibitors ( anti-VEGF drugs ), timely and sustained therapy can lead to good visual outcomes . Newer treatments with

extended duration of action are being developed to reduce the treatment burden for patients with wet AMD .

Dry ( atrophic ) AMD is the more common late manifestation of AMD , accounting for more than 90 % of cases . 2 This progresses much more gradually .

Beyond smoking cessation and vitamin supplementation , to date , there has been little to slow the disease progression of dry AMD to eventual geographic atrophy with foveal involvement . However , this is likely to change , with promising late-phase clinical trials for dry AMD — in particular , those targeting the complement pathway .

This How to Treat covers diagnosis and management of neovascular ( wet ) and atrophic ( dry ) AMD and aims to inform GPs of the latest diagnostic tools , referral pathways and treatment options .

RISK FACTORS

IN addition to ageing , risk factors for

late-stage AMD include genetic variations and lifestyle factors , such as direct sun exposure , diet and smoking . 3

Family aggregation studies have

identified that first-degree relatives of patients with AMD are 2.4 times more likely to develop the condition than relatives of patients without a family history . 4

The two genes that have shown the strongest association with AMD risk are complement factor H ( CFH ) and age-related maculopathy susceptibility 2 ( ARMS2 ). 4

Direct sun exposure can contribute to oxidative stress in retinal tissue , with the formation of reactive oxygen species and mitochondrial damage . 5

The association between diet and AMD is often explained through obesity , with cohort studies identifying an increased risk of late AMD in obese individuals . 6

However , independent of obesity , animal studies have also identified that diets high in fat and glucose impact the gut microbiome and , in turn , influence the progression of AMD . 7

Smoking is a key reversible risk factor . Smokers have an increased rate of early AMD ( approximately 1.5 times that of non-smokers ) and late AMD ( approximately 3.5 times that of non-smokers ). 8

EPIDEMIOLOGY

AMD is the leading cause of irreversible blindness in developed countries and accounts for 8.7 % of all worldwide blindness . 9

The projected number of people globally with AMD in 2020 was 196 million ( 95 % confidence interval : 140- 261 million ), increasing to 288 million by 2040 ( 95 % confidence interval : 205-399 million ). This health issue is increasingly common with an ageing population .

The prevalence of late AMD in large population-based studies is 0.2 % in the age range of 55-64 before a sharp increase to 13.1 % in those older than 85 . 10 A European analysis stratified by age further illustrates this point , reporting the prevalence of early / intermediate AMD rising from 9.3 % in those aged 55-64 to 26.9 % in those over 75 .

There is a higher prevalence of AMD in European than Asian populations ( early : 11.2 % vs 6.8 %; any : 12.3 % vs 7.4 %). People of European descent have a higher prevalence of geographic atrophy subtype ( 1.11 %; 95 %; confidence interval : 0.53-2.08 ) than those with African ( 0.14 %; 0.04- 0.45 ), Asian ( 0.21 %; 0.04-0.87 ) and