Age-related Macular Degeneration

Pathology

Advanced AMD is classified as

  • Neovascular AMD

  • Atrophic AMD

Neovascular AMD is characterised by neovascular proliferation underneath the neuroretina. This is also called choroidal neovascularisation.

Atrophic AMD is characterised by atrophy of the RPE and overlying neurosensory retina. This is also called geographic atrophy

Choroidal neovascularisation and geographic atrophy may develop in the same eye, because they are on the same continuum of disease activity

In addition to choroidal neovascularisation, there are two other forms of AMD-associated neovascularisation - polypoidal choroidal vasculopathy - retinal angiomatous proliferation

Neovascular amd is responsible for the majority of severe vision loss

The fluid in macular degeneration can be due to leaky blood vessels or haemorrhage

Reference: Ape RS 2021 in NEJM

Diagnosis

Epidemiology (the patient)

  • Non-modifiable risk factors

    • Age

    • Genetics (strong predisposition)

    • Appears to affect men and women similarly

  • Modifiable risk factors

    • Uncontrolled hypertension

    • Smoking

    • Being overweight

The presentation

  • Painless vision loss

  • Progressive, particularly of central vision

  • Can be acute in the context of neovascular AMD (e.g. blood or fluid accumulation)

Establishing the diagnosis

  • Historically, angiography with fluorescein or indocyanine was used to assess the choroidal or retinal vasculature

  • Indocyanine was particularly useful for identifying the choroidal vasculature for polypoidal choroidal vasculopathy or retinal angiomatous proliferation

  • This has now largely been replaced by optical coherence tomography

  • Fundus autofluorescence is useful to assess the health of the retinal pigment epithelium

  • Identifying polypoidal choroidal vasculopathy is important because when present, treatment with photodynamic therapy may be beneficial

Reference: Ape RS 2021 in NEJM

Management

Address modifiable risk factors:

  • Uncontrolled hypertension

  • Smoking

  • Being overweight

For intermediate severity, that is, before geographic atrophy of choroidal neovascularisation, there is some evidence that oral supplementation may slow disease progression.

Age related eye disease studies (AREDS)

AERDS I supplementation protocol included:

  • Vitamin C 500 mg

  • Zinc 80 mg with Copper 2 mg (added to avoid zinc-related copper deficiency)

  • Vitamin E 400 IU

  • Beta carotene 15 mg

Beta carotene has been associated with an increased risk of lung cancer amongst current or past smokers

In the age related eye disease study 2 (AREDS II), beta carotene was replaced with

  • Lutein 10 mg

  • Zeaxanthin 2 mg

So the the AREDS II formula is:

  • Vitamin C 500 mg

  • Zinc 80 mg with Copper 2 mg (added to avoid zinc-related copper deficiency)

  • Vitamin E 400 IU

  • Lutein 10 mg

  • Zeaxanthin 2 mg

Reference: Ape RS 2021 in NEJM

Polypoidal choroidal vasculopathy

  • Photodynamic therapy is a treatment modality for polypoidal choroidal vasculopathy

  • Photodynamic therapy involves an intravenous injection of verteporfin, a compound which can be photoactivated and selectively binds to abnormal blood vessels. Verteporfin is then activated with a lower power laser to induce vascular regression

  • a combination of photodynamic therapy and anti-VEG thearpy results in greater gain in visual acuity in polypoidal choroidal vasculopathy. This benefit has been observed when photodynamic therapy is used in conjunction to ranibizumab but not with aflibercept

Reference: Ape RS 2021 in NEJM

Patient Information

What do I have?

  • Age related macular degeneration

  • The macula is the central part of your vision

  • With age, you get a build up of debris in the layer just under the special sensory cells of your eye

  • This debris is then associated with death of the supporting and special sensory cells in the area, causing loss of vision

  • You can also have abnormal blood vessels grow, which then cause bleeding and swelling that clouds your vision

Ref: Fleckenstein 2024 JAMA review

Why me?

  • It is unclear exactly what causes age related macular degeneration

  • Research shows that some things are associated with an increased risk of developing macular degeneration. Some of these are modifiable, and others are not

  • Non-modifiable risk factors include

    • Getting older (age)

    • Genetic predisposition (strong)

  • Modifiable risk factors include

    • Having high (uncontrolled) blood pressure

    • Smoking

    • Being overweight

Reference: Ape RS 2021 in NEJM