Introduction

Age-related macular degeneration is the most common cause of blindness in the UK. Degeneration of the central retina (macula) is the key feature with changes usually bilateral. ARMD is characterised by degeneration of retinal photoreceptors that results in the formation of drusen which can be seen on fundoscopy and retinal photography.

Classification

Traditionally two forms of macular degeneration are seen:
  • dry (90% of cases, geographic atrophy) macular degeneration: characterised by drusen - yellow round spots in Bruch's membrane
  • wet (10% of cases, exudative, neovascular) macular degeneration: characterised by choroidal neovascularisation. Leakage of serous fluid and blood can subsequently result in a rapid loss of vision. Carries worst prognosis

Recently there has been a move to a more updated classification:
  • early age-related macular degeneration (non-exudative, age-related maculopathy): drusen and alterations to the retinal pigment epithelium (RPE)
  • late age-related macular degeneration (neovascularisation, exudative)

Epidemiology

  • Incidence: 110.00 cases per 100,000 person-years
  • Peak incidence: 70+ years
  • Sex ratio: 1:1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Risk factors
  • Advancing age itself is the greatest risk factor for ARMD. The risk of ARMD increases 3 fold for patients aged older than 75 years, versus those aged 65-74.
  • Smoking is another key risk factor in the development of ARMD, current smokers are twice as likely as non-smokers to have ARMD related visual loss, and ex-smokers have a slightly increased risk of developing the condition, (OR 1.13).
  • Family history is also a strong risk factor for developing ARMD. First degree relatives of a sufferer of ARMD are thought to be four times more likely to inherit the condition.
  • Other risk factors for developing the condition include those associated with increased risk of ischaemic cardiovascular disease, such as hypertension, dyslipidaemia and diabetes mellitus.

Clinical features

Patients typically present with a subacute onset of visual loss with:
  • a reduction in visual acuity, particularly for near field objects
  • difficulties in dark adaptation with an overall deterioration in vision at night
  • fluctuations in visual disturbance which may vary significantly from day to day
  • they may also suffer from photopsia, (a perception of flickering or flashing lights), and glare around objects

Signs:
  • distortion of line perception may be noted on Amsler grid testing
  • fundoscopy reveals the presence of drusen, yellow areas of pigment deposition in the macular area, which may become confluent in late disease to form a macular scar.
  • in wet ARMD well demarcated red patches may be seen which represent intra-retinal or sub-retinal fluid leakage or haemorrhage.

Fundoscopy showing dry macular degeneration


Investigations

Investigations:
  • slit-lamp microscopy is the initial investigation of choice, to identify any pigmentary, exudative or haemorrhagic changes affecting the retina which may identify the presence of ARMD. This is usually accompanied by colour fundus photography to provide a baseline against which changes can be identified over time.
  • fluorescein angiography is utilised if neovascular ARMD is suspected, as this can guide intervention with anti-VEGF therapy. This may be complemented with indocyanine green angiography to visualise any changes in the choroidal circulation.
  • ocular coherence tomography is used to visualise the retina in three dimensions, because it can reveal areas of disease which aren't visible using microscopy alone.

Management

Treatment:
  • the AREDS trial examined the treatment of dry ARMD in 3640 subjects. It showed that a combination of zinc with anti-oxidant vitamins A,C and E reduced progression of the disease by around one third. Patients with more extensive drusen seemed to benefit most from the intervention. Treatment is therefore recommended in patients with at least moderate category dry ARMD.
  • Vascular endothelial growth factor, (VEGF) is a potent mitogen and drives increased vascular permeability in patients with wet ARMD. A number of trials have shown that use of anti-VEGF agents can limit progression of wet ARMD and stabilise or reverse visual loss. Evidence suggests that they should be instituted within the first two months of diagnosis of wet ARMD if possible. Examples of anti-VEGF agents include ranibizumab, bevacizumab and pegaptanib,. The agents are usually administered by 4 weekly injection.
  • Laser photocoagulation does slow progression of ARMD where there is new vessel formation, although there is a risk of acute visual loss after treatment, which may be increased in patients with sub-foveal ARMD. For this reason anti-VEGF therapies are usually preferred.