There are four major sight threatening conditions in our community – cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD). Of these, up until now AMD has had the most dismal prognosis. The purpose of this paper is to bring you up to date on what AMD is and how it affects vision, and to explain how new and exciting forms of treatment are completely changing our management of this condition.

What is macular degeneration?

Macular degeneration is the term given to a group of conditions causing progressive loss of central vision, leading to inability to read, recognise faces and drive. This has a significant effect on patients’ independence and quality of life. The most common type is age related macular degeneration (AMD). As the name implies, age is the major risk factor. AMD is the most common cause of irreversible visual loss in the elderly in the developed world.

Between the ages 65 and 75 about 10 percent of people have some impairment of vision due to AMD, and over 75 years about 30 percent are affected. Even in late stages people usually maintain peripheral vision and can see to walk around (often with difficulty), but it is the loss of central vision that has the most devastating effect on lifestyle.

Macular Structure and Function

The macula is the central posterior portion of the retina. It contains the highest concentration of photoreceptors, specifically retinal cones, and is one of the most metabolically active areas of the body. The macula is responsible for central high resolution visual acuity such as for reading and any fine detail. The other retinal photoreceptors are the rods, which are more in the peripheral retina and are responsible for night vision and peripheral visual fields.

The central part of the macula (fovea) contains no blood vessels but derives its oxygen and nutrient supply from the adjacent vascular layer – the choroid. Separating these two layers of the eye is a membrane called the retinal pigment epithelium (RPE) which is very important, controlling movement of nutrients and oxygen between the macula and the choroid


AMD is an exaggeration of the normal ageing process and the early signs are usually discrete yellow spots at the macula (drusen – Fig.3), together with hyperpigmentation or depigmentation of the RPE. This can then progress to either of two forms:

  1. Dry (atrophic) AMD, which is characterised by geographic atrophy of the RPE – in other words the RPE gradually wears out with age.
  2. Wet (neovascular) AMD, the feature of which is the growth of abnormal blood vessels (choroidal neovascular membranes – CNVM) through the RPE and then these are at risk of bleeding causing a more dramatic and sudden visual loss than the gradually progressive geographic atrophy of dry AMD. The end stage of wet AMD is a formation of a sub-retinal fibroglial scar.

The 2 types have different characteristics : atrophic AMD is the more common, and the deterioration in vision tends to be slow and gradual. Neovascular AMD has a more sudden onset, and is more rapidly progressive and destructive.

Risk Factors

There are “uncorrectable” risk factors – advancing age, family history, genetic (more common in Caucasians, as increased melanin in the choroid is protective), and also several clear “correctable” factors – smoking (3x higher risk, dose-duration related), vascular markers (hypertension, obesity), nutritional ( high dietary intake of vegetable fat, low intake of antioxidants and zinc). The effect of cataract surgery on the progression of AMD remains uncertain – while some studies point to an acceleration of AMD after cataract surgery, others show no effect.


Diagnosis of AMD is following a thorough retinal examination, together with retinal photography, fluorescein angiography and an optical coherence tomography scan.

FA involves an intravenous injection of fluorescein dye and then high speed photography to examine the circulation in the retina, looking for abnormal CNVM. Fluorescein dye outlines the normal retinal vessels, and will leak out of the abnormal vessel walls in CNVMs, with specific patterns of pooling.

OCT is new technology – an infra-red retinal scan, giving a cross sectional view of the layers of the retina, specifically looking for intraretinal fluid or fibrosis. This is a non-invasive investigation, with no injections required. The newest high definition spectral OCTs give wonderful views of each layer of the retina, allowing detailed analysis.

It is vital to differentiate the wet and dry forms of AMD, as the treatment and prognosis is different in each.

Treatment of dry AMD

Dry AMD is the atrophic form, with a slowly progressive loss of RPE and photoreceptors in the fovea, leading to gradually progressive loss of central vision. It is essentially considered to be untreatable, but there are ways to slow down the progression.

  1. AREDS

    The Age-Related Eye Disease Study (AREDS) involved 3640 patients with AMD.

    AREDS found that the following combination of antioxidants and zinc may help protect against advanced AMD : vitamin C 500mg, vitamin E 400 international units, beta carotene 15mg, zinc 80mg, copper 2mg ( added because high levels of zinc may cause copper deficiency). Over a 5 year period those on the AREDS formulation had a 25% reduction in the progression from intermediate to advanced AMD. There are a number of preparations available in Australia based on the AREDS formulation – “Macuvision”, “Luteinvision” –and most ophthalmologists advise patients with AMD to take these daily. It may not be appropriate for all patients – one study found that beta carotene causes a 17% increase in the relative risk of lung cancer in smokers.

  2. Fenretinide

    Fenretinide is an oral vitamin A protein agonist which reduces the accumulation of vitamin A toxins in the retina – by this means it is believed to slow down the progression of atrophic AMD. Fenretinide is now in Phase II studies in the US Food and Drug Administration (FDA).

  3. What to tell patients with dry AMD

    Patients should be assured that the progress of the disease is slow and that peripheral vision will be maintained even if central vision is lost. Active things that the patient can do include : stopping smoking, keeping blood pressure under control, taking supplementary vitamins – Macuvision, Luteinvision. The question of dietary vegetable oils remains controversial – the most common sense advice is to cut down on canola oils and use olive oil as a margarine and in cooking.


Until recently, the results of therapy for wet AMD have been disappointing. Laser and photodynamic therapy (PDT) are targeted at the individual abnormal neovascular membranes but do not address the underlying stimulus to their formation.


VEG F (vascular endothelial growth factor) –the new paradigm

The advent of anti VEGF therapy for wet AMD has completely altered the way we approach this condition. Previously treatment was aimed at destroying the abnormal blood vessels with laser but this also destroys the surrounding retina, leaving a permanent blind spot (but still better than ongoing haemorrhage). Our aim at best was to halt the progress of the disease to stop vision from getting worse. With anti VEGF therapy, we can now aim to not only stop the progress of the AMD, but in many cases to reverse the process and improve vision. This represents a complete turnaround in our approach to wet AMD – previous therapy was at best “palliative”, but now we are able to offer a “cure.”

VEGF is a platelet derived growth factor involved in angiogenesis. The anti VEGF substances are monoclonal antibodies and their derivatives which act to inhibit the growth of blood vessels. Initially used in the treatment of secondary bowel cancer, they have been found to have a beneficial effect in wet AMD by “turning off” the abnormal blood vessels. Currently, the most effective of the anti VEGF therapies available (and now on the PBS) is Lucentis.

Lucentis inhibits the growth and leakage of the abnormal blood vessels in the retina that are the hallmark of neovascular (“wet”) AMD. The active substance in Lucentis is ranibizumab, which binds selectively to a protein –vascular endothelial growth factor A (VEGF-A) present in the retina.

Lucentis is given as an intravitreal injection into the eye, under local anaesthetic, using a 30 gauge needle. Initially 3 injections are needed at monthly intervals, and after that according to clinical progress. The injections, done in the rooms under sterile conditions, are relatively painless – some people will have eye irritation and intermittent floaters. The most significant potential complication is an infection inside the eye – endophthalmitis – less than 1 in 1000.

Some patients will require injections every 4 to 6 weeks indefinitely. This injection regime, together with the necessary visits for regular check ups, has implications for the ophthalmological workforce – there is a rapidly increasing number of patients needing treatment and ongoing monitoring. The numbers involved threaten to swamp medical retina clinics in the public and private sectors, and part of the new paradigm is how to most efficiently organise clinics to manage the influx of patients.

Refinement of injection schedules is aimed at minimising the number and frequency of injections required, with careful monitoring of each patient’s macular thickness by OCT and visual acuity. Newer anti VEGF agents with longer duration of action are also being evaluated – the ideal would be say a once yearly depot injection.

Future directions

    1. IMT(intraocular macular telescope) and other implantable devices

      When AMD has reached a point where medical therapy is no longer viable ( macular atrophy in dry AMD or fibroglial scar in wet AMD) the patient is dependent on various visual aids – magnifying glass, magnifying projector, talking books etc. Another approach being developed is the surgical implantation of miniature telescopes or mirror combinations to maximise the remaining central vision. These are similar to a standard intra-ocular lens (IOL) used in cataract surgery, but specially modified to provide high magnification.

    2. Stem cell therapy

      Research at Moorfields Eye Hospital in London has shown that embryonic stem cell therapy can prevent blindness in rat and pig eyes. Clinical trials in humans are expected to begin in the next 2 years.

    3. Bionic eye

      As part of the federal government’s response to last year’s 2020 summit, $50 million has been allocated to bionic eye development. There are various prototypes, using a miniature video camera worn on a pair of glasses. This sends an impulse to an array of electrodes implanted in the patient’s retina, which then forms an image stimulating the occipital cortex. Initially people with severe visual loss from hereditary conditions such as retinitis pigmentosa would be trialled, but with increasing experience and refinement this technology may be applicable to AMD.

Related Links: Macular Degeneration Foundation