Recent Posts
Connect with:
Monday / May 20.
HomemistoryIt’s All In the Genes MD: Understanding the Generational Link

It’s All In the Genes MD: Understanding the Generational Link

A breakthrough treatment for wet AMD could improve the quality of life for patients and reduce their ongoing costs. Meanwhile, new preventative advice – which simply comes down to diet – could help delay the onset or slow the progression of this cruel degenerative disease that affects approximately one in seven Australians over the age of 50 – and in 70 per cent of cases is caused by genetics.[/vc_column_text][/vc_column]

This year during Macular Degeneration Awareness Week (Sunday 27 May – Saturday 2 June), the Macular Degeneration Foundation is calling all Australians to make their family’s macular health a priority by having their eyes tested and macula checked. That’s important because the individuals most at risk are people over 50 with a family history of the disease.

The degenerative disease can be triggered by genetic mutations, oxidative damage or as a response to injury or tissue damage and is generally classified into early (typically non visually impairing) and late (visually impairing) stages. Late AMD can be further divided into ‘wet’ (neovascular) and dry (atrophic) forms. Studies have shown that two thirds of late cases are neovascular compared to one third of cases, which are atrophic. The progression from early to late stage AMD can occur rapidly in some patients and more slowly in others.

According to a recent Deloitte Access Economics Report (October 2011) commissioned by the Macular Degeneration Foundation and co-authored by Paul Mitchell, Professor of Ophthalmology at the University of Sydney and Director of Ophthalmology for the Sydney West Area, without effective prevention and treatment programs, the number of people with some evidence of MD would increase by 70 per cent to 1.7 million by 2030.

Up to 70 per cent of cases of MD have a genetic link

Managing the Risks

The Australian National Preventative Health Agency recognises that some risk factors for chronic disease are out of our control, such as age, sex and genetics. Other factors – both lifestyle and biomedical – can be modified. Importantly, early detection provides the chance to slow the disease and apply treatment, which these days, can save sight.

Julie Heraghty, CEO of the Macular Degeneration Foundation, told mivision that the eye care profession is successfully educating patients on the risks and symptoms of Macular Degeneration and encouraging preventative behaviour.

“In a recent survey we conducted, almost all optometrists who responded to the survey (99 per cent) said they collected information on the family history of their older patients, which is a sizeable increase since we first conducted the survey.

“This is so important, because there’s a 50 per cent chance of developing Macular Degeneration when a direct family member, like a parent or sibling, has the disease,1 and it is known that up to 70 per cent of cases of MD have a genetic link.”2

She said optometrists must also encourage conversations between patients and their families. “These conversations can save sight,” said Ms. Heraghty.

Common Misconceptions
A recent Galaxy survey conducted by the Macular Foundation found almost three quarters of the population (71 per cent) underestimate the genetic risk associated with MD, and only one in five (16 per cent) correctly identify the chance of developing MD as 50 per cent if you have a direct family history.3

Additionally, one in three Australians incorrectly believes vision loss caused by MD is a normal part of ageing.

The survey showed that most of those interviewed incorrectly identified iron (55 per cent) and calcium (38 per cent) as nutrients important for eye health.

“There is more to be done in educating people of all ages about Macular Degeneration and how they can reduce their risk through something as simple as making changes in their diet,” said Ms. Heraghty.

Breakthrough Diet News

Those changes include switching from carbohydrates with a high glycemic index (high GI) to low GI carbs, which Prof. Paul Mitchell has now confirmed, can lower the risk of developing Macular Degeneration.

That means people at risk of MD should replace foods such as processed white bread and white potatoes with high GI foods including grains, pasta and legumes.

This advice comes on top of what we have known for some time: that diets rich in lutein, zeaxanthin, zinc and omega-3s found in fish are crucial for macular health.

However, experts say the levels of minerals and vitamins required for macular health would be difficult to obtain from diet alone and therefore supplements are important.

In 2001 a clinical trial of the AREDS Formula which combined 500 milligrams of vitamin C; 400 international units of vitamin E; 15 milligrams of beta-carotene; 80 milligrams of zinc as zinc oxide; and two milligrams of copper as cupric oxide was found to reduce the rate progression from intermediate AMD to advanced by about 25 per cent. (Copper was added to the AREDS formulations containing zinc to prevent copper deficiency, which may be associated with high levels of zinc supplementation. Note also that high doses of beta-carotene supplementation have been shown to increase the risk of lung cancer in smokers and ex-smokers which is why it has been removed from many products). The MD Foundation’s Medical Committee supports this recommendation.

Although not a cure for AMD, the researchers found that the AREDS formulation may “play a key role in helping people at high risk of developing advanced AMD keep their remaining vision”.

“The AREDS formula is the first demonstrated treatment for people at high risk for developing advanced AMD,” said Dr. Frederick Ferris, director of clinical research at the US National Eye Institute and chairman of the AREDS. “Slowing the progression of AMD to its advanced stage will save the vision of many who would otherwise have had serious vision impairment.”

Blackmores markets Macu-Vision, a formula based on the AREDS study and Lutein-Vision to help prevent macular degeneration. According to the company, the carotenoids lutein and zeaxanthin form the macular pigment in the human eye, which filters harmful blue light and reduces oxidative damage to the retina and lens. Population studies suggest high dietary intake of lutein and zeaxanthin may protect against MD and its progression. Lutein-Vision also contains selenium, which helps preserve the clarity of the lens and healthy eye function.

According to the Macular Degeneration Foundation’s survey, there has been an increase in the number of optometrists discussing diet, yet still only 17 per cent are having these conversations. This, says Ms. Heraghty, highlights a real opportunity for optometrists to advise, guide and influence their patients to help address this chronic disease through prevention. She added that the MD Foundation is available to support that aim.

Lucentis Halts Progression

In recent years the greatest advance in the treatment of blindness has been the development of the anti-VEGF agent, ranibizumab. Trademarked by Novartis as Lucentis, ranibizumab has been found to halt the progression of wet AMD and may also provide some improvement.

According to the Macular Degeneration Foundation of Australia, studies have demonstrated that around 95 per cent of the eyes treated with ranibizumab (0.5mg) at monthly intervals, maintained stable vision within 15 letters. Almost 40 per cent of the treated eyes improved by more than 15 letters.

Patients who do not qualify for PBS reimbursed Lucentis are often prescribed the closely related yet less expensive bevacizumab, trademarked Avastin by Roche. Although Avastin has shown to provide similar results to Lucentis, small differences in retinal thickness, favouring Lucentis, have been identified. Nine studies are currently underway around the world comparing the safety and efficacy of Avastin and Lucentis.

Sadly, for those patients with atrophic – or dry – AMD there is currently no treatment available. However it is clear that controlling modifiable risk factors (diet, stopping smoking etc) can prevent the delay and onset of the more advanced stages of this disease.

Eylea: Less Injections, Same Result

Now a new generation drug is promising to achieve the same results for wet AMD with less intravitreal injections and therefore less impact on the lives of patients. Eylea (aflibercept), developed by Bayer, has been approved by the Therapeutics Goods Administration but is not yet listed on the Pharmaceutical Benefits Scheme (PBS). The company hopes to release the product to the Australian market within months.

Bayer describes Eylea as the first fully recombinant human, soluble Vascular Endothelial Growth Factor (VEGF) receptor fusion protein approved in Australia for the treatment of wet AMD.

It works by blocking VEGF-A that triggers the growth of blood vessels in the retina. Additionally, it blocks placental growth factor (PIGF), which is also implicated in the development of wet AMD.

Prof. Mitchell said, “the main advantage of Eylea is that treatment is initiated with one injection per month for three consecutive months, and then is given on a two monthly basis, while it is recommended that Lucentis is given at monthly intervals.”

He said while most clinicians tend to increase the period between Lucentis injections to decrease the burden on patients, many were now returning to more regular monthly injections after experiencing episodes of activity.

Clinical trials revealed that patients treated with Eylea every eight weeks, following three initial monthly doses, maintained similar visual acuity to those treated with the Lucentis, which required monthly injections.

“Fewer injections could substantially improve the quality of life of patients with wet AMD and help overcome some of the barriers to treatment, including cost, injection fatigue and waiting time,” said Prof. Mitchell.

The Costs

With the incidence of MD expected to increase due to our ageing population, the future could see the enormous burden of care falling onto the Australian community – at huge cost both psychologically and financially.

Almost 50 per cent of MD patients surveyed recently by the Macular Degeneration Foundation said they would expect to rely on their partner if they were to lose their sight to the disease. In older age groups, the figures were slightly lower, and 14 per cent expected to turn to a child for support. These figures increase with age.

As well as the cost of care, there is the significant cost of treatment, which includes regular appointments with specialists and OCTs. This is something that the Macular Degeneration Foundation has been fighting to reduce. “Our primary goal is to make treatment affordable and accessible,” said Ms. Heraghty. “OCTs are now considered standard treatment and, at anywhere upward from $80 per OCT, this is proving to be a barrier for treatment for many patients. “We’re pushing the Federal Government for some consideration of reimbursement for OCTs but progress is slow,” she said.

At a national level, Deloitte Access Economics calculations reports the cost of vision loss associated with AMD in 2010 totalled AUD $48,028 per patient or a national total of about AUD $5b. This calculation includes an allowance for health system costs including productivity losses, carer opportunity costs and other indirect costs as well as direct financial costs. 78 per cent of the cost is associated with the loss of quality of life – otherwise known as the ‘burden of disease’.

WE Must Work Together

It is not just the cost of Macular Degeneration that we will need to be prepared for. With such a high prevalence of MD already in the community and increasing rates of dementia and diabetes, some time soon, we’re likely to be confronted by an elderly generation suffering co-morbidities.

“As Australia’s population ages, families, aged care facilities and the health sector must prepare to care for elderly people with co-morbidities which means we are probably not going to be able to isolate vision loss – we’re going to have to look at the person holistically,” said Ms. Heraghty. “There will be a great need for the health profession to work together to manage the needs of these patients. Optometrists and ophthalmologists will play a key part in this process to ensure they are holistically looked after.”

The Future

In the first application of its kind, RPE cells derived from human embryonic stem cells have been safely used to treat macular degeneration in two patients and there has even been some evidence
in vision improvement.

The pilot study was conducted in two legally blind patients with two different forms of the disease – a woman in her 70s with dry age-related macular degeneration and a woman in her 50s with Stargardt’s macular dystrophy.

According to the report published online in The Lancet, the patient with macular degeneration improved from 21 letters on the Early Treatment Diabetic Retinopathy Study visual acuity chart to 33 letters at week two, and stabilised at 28 though the rest of the study period.

However the improvement was confounded by some improvement on the non-operated eye.

The patient with Stargardt’s disease showed clear improvements in the operated eye only and went from seeing no hand movements at all to being able to see single finger movements. She went from being able to read no letters to five on the diabetic retinopathy acuity chart.

Speaking about the pilot study to Samantha Donovan on ABC radio, Martin Pera, Professor of Stem Cell Sciences at the University of Melbourne, said the very early phase study shows that the approach is feasible and appears to be safe.

A Window of Opportunity

Ms. Heraghty said advances in treatments for MD are truly exciting however accessibility and affordability are the keys.

“Anti-VEGF treatment has changed the landscape of ophthalmology – it’s almost what penicillin was to infection. When I first came to the Foundation in 2004, early detection was critical but with photodynamic therapy, we were limited in what we could achieve. Early detection is now even more critical because with new treatments now we can save sight.”

Low Enzyme

Indicates MD

In early 2011 scientists at the University of Kentucky discovered that levels of an enzyme called DICER1 are low in people with dry MD. This finding could potentially produce an early warning test for people at risk of developing end-stage dry MD (‘geographic atrophy’). To test this theory, they selectively bred mice, which had low DICER1 levels. All of these mice developed degeneration of the macula.

The researchers then found that low DICER1 levels caused a build-up of a toxic RNA molecule in the retina that caused the tissue to degenerate. They went on to develop a drug to block the toxic RNA molecule, which has now been tested in human retina cells grown in a test tube to good effect. Human subjects are yet to be tested and perhaps one day in the future, as a result of this work, an effective drug will be available to prevent macula degeneration.

Understanding the Genetics

Researchers at the UC Santa Barbara, the University of Utah and the University of Iowa have identified 50 genes that can identify people with clinically recognised AMD and distinguish between different stages. Some of these genes can even identify people experiencing changes in the eye before the disease can be diagnosed.

Speaking of the finding, Dr. Marco Zarbin, the chief of ophthalmology at the University of Medicine and Dentistry of New Jersey in Newark said, “This is wonderful research because first of all, it shows a number of pathways involved in the disease process, both in the early and later stages, which creates opportunities to create treatments that might be better than what we have now.”

He said that while some associated genes have been identified in the past, the new study increases the knowledge – or the “genetic fingerprint for at-risk patients”. He added, “If we had perfect treatment for all stages of disease, and perfect treatments that could prevent development of disease before you get it, then genetic screening would make a lot of sense.”

According to the report, one limitation of the findings was that they came from cadaver eyes and that it’s not possible to biopsy human eyes. If the same kinds of genetic information can be found in blood samples, blood tests could eventually determine a person’s genetic disposition to the disease.

Macular Degeneration: The Facts

  • Macular Degeneration is the leading cause of blindness and major vision loss in Australia.1,2
  • There are two classifications of MD: Neovascular – or wet AMD is characterised by a blurring of the central vision and distortion so that straight lines appear crooked. Some patients experience a dark or blank patch of vision and affected colour perceptions. Atrophic – or dry – AMD reduces capacity for near visual tasks as central vision severely deteriorates.
  • 50 per cent of all blindness is due to Macular Degeneration
  • The prevalence of Macular Degeneration increases with age
  • The prevalence of Macular Degeneration is four times that of Dementia and more than half that of Diabetes.1
  • Approximately one in seven Australians over 50 (1 million people) have some evidence of Macular Degeneration.1
  • The number of people with some evidence of Macular Degeneration will increase by 70 per cent to 1.7 million by 2030, in the absence of effective prevention and treatment measures.
  • In 2010, 12 per cent of people over 50 yrs (856,000) had early signs of Macular Degeneration
  • In 2010, 2 per cent of people over 50 (167,000) had late stage Macular Degeneration which included 57,000 with Dry Macular Degeneration and 110,000 people with Wet Macular Degeneration
  • Over 14 per cent of people over 80 (123,000) have vision loss or blindness from Age-related Macular Degeneration1,3

1. ‘Eyes on the future – A clear outlook on age-related macular degeneration’. Report by Deloitte Access Economics & Macular Degeneration Foundation, 2011
2. Taylor H et al, MJA 2005;182:565-568.
3. Mitchell P et al, Ophthalmology 1995;102:1450-1460.

Dealing with the Consequences

Heather Bauer was diagnosed with Wet Macular Degeneration in 1997. She was in her early 70s.

At the time, she’d noticed a slight change in her vision and took herself off to the optometrist to be tested for glasses. When she was told she had Macular Degeneration, she was shocked. “I didn’t know anything about Macular Degeneration so it came as a bit of a shock.”

Mrs. Bauer participated in two trials of Macugen at the Sydney Eye Hospital but experienced no benefits.

Lucentis Benefits

For the past five years, Mrs. Bauer has been treated with Lucentis injections, initially fairly regularly but now at six to eight week intervals.

She first began the treatment, prior to Lucentis being listed on the Pharmaceutical Benefits Scheme (PBS) and so the first three injections cost Mrs. Bauer and her husband Maurice, a total of AUD$6,000. Thanks to the PBS listing, that cost has come down to just under AUD $6 per injection and the best news of all is that for now, Mrs. Bauer’s vision has stabilised. “I have 5 per cent vision in my right eye which is peripheral and 10 per cent in my left. I can see my furniture and what’s in the house, and I’m still cooking and washing. But I can’t go anywhere outside the house on my own – I’m frightened of falling.”

Mrs. Bauer lives at home with her husband who does the heavy cleaning and shopping and takes her to appointments. “He’s a treasure. I’d be lost without him,” she told mivision.

Mr. Bauer said the onset of his wife’s Macular Degeneration was very gradual – over 10 to 12 years – which enabled her to continue landscape painting and gave him the chance to come to terms with the disease. “When Heather was first diagnosed I was really at arms length but when she had radiology treatment on her right eye, it suddenly dawned on me that there was a real problem there.”

In the Family

Mrs. Bauer has two siblings – a younger sister who at 84 has healthy eyes and a younger brother, 82, who also has MD. A heavy smoker, she said his vision deteriorated very quickly but he still has some remaining sight.

As for her children, Mrs. Bauer counsels them regularly on having their eyes checked and maintaining a healthy diet.

“I’ve told them all they must have regular checks and I make sure they follow the dietary recommendations. I’m quite passionate about any treatment that’s available – and I hope that if any of them get the disease, there will be a cure for them by that time.”

Encourage your Patients…

As a healthcare professional, you can help your patients by encouraging them to:
• Speak to their family to find out if they have a family history of Macular Degeneration
• If diagnosed with Macular Degeneration, encourage patients to tell their family, even if it is only in the early stages of MD
• Adopt a healthy lifestyle, control their weight and exercise regularly
• Eat eye health friendly foods, including:
– Fish two to three times a week
– Dark, green leafy vegetables and fresh fruit daily
– Choosing low (or lower) GI carbohydrates whenever possible, e.g. multigrain bread, whole grain cereals, peas, beans, lentils and other fruit and vegetables.
– A handful of nuts each week.
• Quit smoking and talk to their GP for support
and advice
• Discuss the role of a supplement and the individual requirements (in the case of zinc and antioxidant supplements it should be one that conforms to the AREDS formula – further information is available from the MD Foundation)
• Protect their eyes from the sun, especially when young.

Macular Degeneration Awareness Week:

27 May to 2 June

Eye health professionals across Australia will soon receive a Macular Degeneration Awareness Week “Keep your family in the picture” promotional kit.

The kit includes posters, leaflets, “How’s your Macula” stickers, MD Foundation contact cards, and a Foundation resources order form. This includes a free postage offer specifically for Macular Degeneration Awareness Week.

A media release is also available for optometrists to use in their local media leading up to and including MD Awareness Week. Contact the MD Foundation on (AUS) 1800 111 709.

To receive a summary of the latest global research into Macular Degeneration on a weekly basis, call the Foundation on (AUS) 1800 111 709 or email [email protected]


1. Klaver C et al, Arch Ophthalmol 1998;116: 1646-1651.

2. ‘Eyes on the future – A clear outlook on Age-related Macular Degeneration’. Report by Deloitte Access Economics & Macular Degeneration Foundation, 2011

3. Galaxy Research national telephone study February 2012 n=1,100 aged 18 years and over. This is weighted by age and gender in location to Australian population.