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Report

The ever-increasing cost of glaucoma

04/10/2018By Richard Chiu • Staff Journalist
Glaucoma is one of Australia’s most infamous sight threatening conditions, yet despite a mountain of work from researchers and public health advocates, we’re still struggling to contain its inexorable rise. RICHARD CHIU investigates what is being done to fight this silent vision thief and why this work is so important.

The statistics behind glaucoma are well documented, yet collated together they still paint a scary picture of the task faced by those fighting it, both now and into the future.

The disease is the second leading cause of global blindness and third leading cause of visual impairment, with the number of people affected expected to reach 80 million by 2020 – 11 million of whom will suffer from bilateral blindness. In Australia, the disease affects approximately 300,000 people, and estimates suggest our ageing population will see that increase to around 380,000 by 2025.

About 50% of those with glaucoma are either unaware of the condition or refuse to believe they have it. For every 50 Australians, one will develop the condition in their lifetime, and those of us fortunate enough to live to 80 will have a one in eight chance of being affected.

Work is constantly being done by some of our finest ophthalmic researchers to improve both the diagnosis and the treatment of glaucoma, while a greater emphasis on general awareness should hopefully see more people diagnosed earlier and treated more effectively. However, even with progress being made, the disease is still likely to have a significant impact on the economy for the foreseeable future.


The economic cost

Current data on glaucoma’s economic impact on Australia is scarce, but a 2011 study by the Centre for Eye Research Australia (CERA) estimated that health system costs related to primary open-angle glaucoma could reach $784 million by 2025. When indirect costs and costs of loss of wellbeing are taken into account, that figure explodes to $4.3 billion.

Should these estimates prove accurate, they would represent a $429 million and $2.4 billion increase, respectively, from primary open-angle glaucoma costs recorded in 2005.

Meanwhile, a UK study published earlier this year, conducted by Deloitte Access Economics, the Royal National Institute of Blind People, and the University of Leeds, indicates the high economic cost of glaucoma is not restricted to Australia.

According to the study, glaucoma represents 7% of all healthcare costs attributed to the five major forms of blindness or vision loss (excluding residential care and community care services, expenditure associated with injurious falls, and capital and administration expenditure), which in 2013 equated to approximately £209.5 million (AU$376.2 m).

The study also estimated the overall impact of glaucoma-related disability and premature death on patient wellbeing, which the authors described as the “burden of disease” and measured in DALYs (disability-adjusted life years, aka ‘years of healthy life lost’). Developed by the World Health Organisation (WHO), DALYs have two components – the years of healthy life lost due to disability (YLD) and the years of life lost due to premature death (YLL).

According to the report, in 2013 there were nearly 10,000 DALYs attributed to glaucoma in the UK – 15% of the total 205,372 attributed to vision loss and blindness. The researchers then used a mechanism derived from a 2008 study led by Professor of Health Economics Helen Mason, to apply a monetary value for each DALY, which was estimated as £88,825 (AU$159,754).

Using this methodology, the economic cost associated with the loss of wellbeing and “burden of disease” for glaucoma in the UK in 2013 was £888.25 million (AU$1.59 b). Furthermore, while the report didn’t differentiate between glaucoma and other conditions when calculating the overall indirect economic of blindness and vision loss (£28.1 billion [AU$50.54 b]), it did estimate that the overall cost had increased by 27.8% over the previous five years.

“While unavoidable, age-related conditions contribute greatly towards the growing economic costs and burden of sight loss and blindness,” study states.

“The increase is driven by higher prevalence as well as an estimated 39% increase in health system expenditures … and over a 50% increase in non-admitted expenditures.”

However, despite the sharp increase in costs, the report also offered some hope.

“A substantial proportion of this is still preventable. For example, it has been estimated that the majority of visual impairment worldwide, including blindness, may be preventable using cost-effective treatment methods that are already available,” it stated.

“Further, WHO Member States [Australia included] have committed to reducing the prevalence of avoidable visual impairment by 25% by 2019 compared to the baseline established by the WHO in 2010.”

The human and economic costs of glaucoma are such that it now forms a research priority for countries globally, with Australia at the forefront of some of the most cutting-edge solutions.



Genetics

One of the research areas that holds the most promise for improving both the diagnosis and treatment of glaucoma is genetics. As recently as last year, the Federal Government awarded nearly $9.5 million to genetics research aimed at preventing glaucoma blindness through personalised treatments.

“The potential to personalise treatment through genetics is exciting,” Minister for Aged Care and Indigenous Health Mr Ken Wyatt said at the announcement.

“Research based on knowledge of the genes that lead to glaucoma blindness will have important real-world impacts in reducing the worldwide suffering caused by this common condition.”

The investment, which supported the work of Flinders University Professor Jamie Craig along with three other key researchers – Professor David Mackey (University of Western Australia), Associate Professor Stuart MacGregor (The Council of the Queensland Institute of Medical Research) and Associate Professor Alex Hewitt (University of Tasmania) – will help develop existing research that has already begun to deliver results.

Earlier this year it was announced a collaborative genome-wide study of more than 134,000 people undertaken by the group found 101 genetic markers that influence intraocular pressure, 40 of which also increased a person’s risk of glaucoma.

According to the study, individuals with a large number of these genetic markers had an almost six-fold increased risk of developing glaucoma compared to someone who had fewer genetic variants.

“We have used DNA from thousands of patients with glaucoma to understand how these new genetic discoveries about eye pressure influence the risk of an individual developing severe vision loss from glaucoma,” Craig explained.

“We are getting much better at predicting these outcomes in patients and this will help us find people at risk and get them on sight-saving treatment early in the course of the disease.”

Meanwhile registries, such as The Australian and New Zealand Registry of Advanced Glaucoma, and the Save Sight Institute’s Fight Glaucoma Blindness registry, are collecting clinical information and DNA to help ascertain new genetic risk profiles.

Elsewhere around the world, genetics and gene editing have also been identified as potentially productive research areas that could lead to important treatment breakthroughs. One of the more unique projects involves a team of scientists from the University of Iowa (UI), who are investigating whether disrupting a mutated gene responsible for some forms of glaucoma could help save millions from blindness.

Mutations in the myocilin gene are implicated in juvenile and adult-onset primary open-angle glaucoma. By using CRISPR-Cas9 to remove the mutated myocilin protein from the gene in a mouse model of human glaucoma and cultured human cells, the researchers found they were able to lower intraocular pressure and therefore prevent glaucomatous damage.

“As scientists, we don’t want to just discover a diseased gene, we want to understand what the gene does and, in this case, have a better understanding of glaucoma so that it can be more effectively treated,” chair of Molecular Genetics at UI and study senior author Dr Val Sheffield said.

“No one knows what this gene does, except that its mutant form causes glaucoma.”

Myocilin is present in the trabecular network responsible for regulating intraocular pressure and a mutated gene of the protein can cause pressure to build up. However, disrupting the mutated gene stopped the production of the mutant protein in the mouse model and eventually prevented the human form of glaucoma from occurring.

The same gene editing technology stopped myocilin expression in perfusion cultured human eyes, which the researchers suggest, could translate into new and unique therapies in treating myocilin glaucoma.

Crucially, progress is also being made in relation to gene delivery that should assist future attempts at treating the disease with gene therapy.

Researchers from the University of Wisconsin-Madison have been developing a technique that uses a vector based on feline immunodeficiency virus (FIV) to deliver genes to specific sites in the body. Until late last year, their efforts had been frustrated by the eye’s innate ability to interfere with gene delivery – after entering the eye, defensive molecules would drag the virus particle into the proteasome, where it was degraded.

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However, a new technique helped overcome the issue and could pave the way for a variety of new novel therapies.

“We wanted to know if temporarily blocking the proteasome could prevent the destruction of the gene delivery vector and enhance delivery,” explained study co-investigator Professor Curtis Brandt.

“We have shown that this strategy does work in eye organ culture. Once we do further work on efficiency and identify which gene to deliver, then we are probably ready to move toward clinical trials.”

Brandt and his colleague, Professor Paul Kaufman, were able to track their experiment by placing identifying markers on the FIV virus, which was then sent to cells of the trabecular meshwork, both with and without a chemical that blocked proteasomes.

They found disrupting the proteasome roughly doubled the transfer of genes entering the target cells, while simultaneously spreading them more uniformly across the meshwork tissue. Theoretically, delivering more copies of the gene should give a greater therapeutic effect, opening the meshwork drain and reducing pressure inside the eye.


Alternative research

Genetics and gene therapy show great promise for improving the diagnosis and treatment of glaucoma, but they represent just a portion of the wider gamut of investigations currently underway dedicated to improving outcomes related to the disease.

Other glaucoma-related Australian research highlights over the past 12 months include; CERA’s establishment of a world-first human trial to test whether high dosage vitamin B3 can be used to support existing therapies for glaucoma; results from the first 18 months of the Centre for Eye Health’s collaborative eyecare clinic, which led to better care and relieved pressure on the Prince of Wales Hospital Ophthalmology Department; and a Macquarie University (MU) discovery that a naturally occurring protein in the body, neuroserpin, is critical to maintaining a healthy retina and protecting against glaucoma.

According to the MU researchers, neuroserpin regulates enzymes that help maintain a natural protective environment in the eye. Neuroserpins are particularly sensitive to oxidation through environmental factors, such as smoking.

“Over a long period of time, increased enzyme activity gradually digests the eye tissue and promotes cell death causing the adverse effects associated with glaucoma,” lead author Dr Vivek Gupta from the Faculty of Medicine and Health Sciences said.

“This long-term collaborative study has opened up a completely new line of investigation in glaucoma research that will lead to new treatment avenues for the disease.”

Ageing plays a major role in deactivating neuroserpins, along with diseases and other external factors that cause oxidative stress. Once deactivated, it loses its ability to protect the eye, and the retina and optic nerve is compromised, leading to irreversible damage.

Meanwhile, the UNSW’s School of Optometry and Vision Science collaborated with the Centre for Eye Health (CFEH) to develop a method that for the first time allowed observable damage to the optic nerve caused by glaucoma to be accurately and directly linked to vision loss. Previous efforts to link the two had confounded clinicians and researchers alike, as some cases presented no detectable loss of vision despite obvious damage to the optic nerve.

Such a disconnect is contrary to theoretical work that suggests eye structure and eye function should change at the same time. However, the new model, in combination with a new perimetry technique that allows glaucoma to be detected earlier than with Standard Automated Perimetry, can accurately predict changes in ganglion cells that occur with age or with the disease, and correlate them with functional loss.

“By developing better models to describe both functional and structural changes in the ganglion cell layer of the retina, we were able to consolidate our theoretical understanding of retinal changes occurring with age and with disease. This work has shown how they are directly related,” CFEH director Professor Michael Kalloniatis said.

The study, led by Dr Barbara Zangerl, was published in Investigative Ophthalmology and Visual Science in April.

Finally, while much research focuses on what can be done in the future to improve glaucoma treatment, one study published in the January issue of Clinical and Experimental Ophthalmology investigated how better outcomes could be achieved using current medication that is already available.

In an effort to quantify prescribing errors and explore where they occur along the prescribing pathway, Professor Anthony King and Dr Bansri Lakhani analysed data from 109 patients who attended a specialty glaucoma clinic over a five month period.

Of the total 217 individual prescription items involving 266 active ingredients, 71 (33%) had an error. Fifty-three of these errors (75%) were due to possible patient non adherence, while 18 (25%) were process related errors made by healthcare professionals.

“About 8.3% of prescriptions had a healthcare professional related process error,” the researchers wrote.

“These errors are preventable and recognition of these is important to maximise drop adherence and minimise disease progression, requiring increased consultations, and interventions with quality of life and health economic consequences.”

Discrepancies were identified and errors were grouped into one of four categories depending on where in the prescribing pathway they occurred: Incorrect prescribing of the drops by the clinician, incorrect prescribing of the drops by the GP/failure to provide a repeat prescription, incorrect dispensing of the drops by the pharmacist, and possible non-adherence by the patient.


 

Migs update

Despite the August recall of Alcon’s CyPass Micro-Stent, 2018 has been a big year for minimally invasive glaucoma surgery (MIGS) devices in Australia.

Crucially, the Federal Government announced in the 2018-19 Budget that it had agreed to list on the Medicare Benefits Schedule (MBS) the two Medical Services Advisory Committee (MSAC) recommended items for MIGS in combination with cataract surgery from November, where it will replace the interim item number. MSAC is also considering an MBS number for the standalone procedure as well.

Additionally, for the first time in Australia MIGS was performed outside of a major metropolitan city, with four rural patients undergoing the procedure at Broken Hill Base Hospital in March, while the Therapeutic Goods Administration also approved the use of a MIGS device, the Xen Gel Stent, which Australian researchers had developed over the course of two decades.

The almost-transparent microfistula tube is about the size of an eyelash and thinner than a human hair and gets implanted it into the space between the eye’s anterior chamber and conjunctiva, allowing excess fluid to drain from the eye.

However, it’s not the only new MIGS device to become commercially available in 2018. In August, Ivantis announced Australia would be the first global market to have access to its Hydrus Microstent – an eyelash-sized curved, flexible stent made of a super-elastic alloy of nickel and titanium that acts as a scaffold to widen and dilate the natural drainage channel inside the eye.

Yet, despite the increasing options for surgeons and patients alike, it is still unclear as to when, or if, MIGS will receive its own standalone MBS item number. Stakeholders, including Glaucoma Australia (GA), RANZCO, and the Australian Society of Ophthalmologists, have argued the current status quo is untenable as it effectively excludes the many patients who either have already had, or don’t need, cataract surgery – a situation GA’s CEO Mrs Annie Gibbins said was disappointing.

“Tying it to cataract surgery is a prohibitive factor, and the fact that it is still primarily utilised by privately insured patients means it’s not attainable for many people,” Gibbins said.

“There has been quite a strong interest in that from a patient perspective to us, so therefore we’re 100% behind the standalone number.”

The government has said it’s not uncommon for proposals for new services to require more than one submission to MSAC before a recommendation can be made in support of the service. Currently, the Xen Gel Stent is the only device able to be implanted as a standalone procedure.

 

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