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Eye fluid protein levels may predict need for macular degeneration therapy
Researchers have found that levels of a specific protein help accurately predict whether people with the wet form of age-related macular degeneration will need lifelong, frequent eye injections to preserve vision.
They say the protein could also be targeted by new therapies to halt vision loss among patients with the disorder, caused by abnormal growth of blood vessels that leak fluid or bleed into the portion of the retina needed for central vision
The Johns Hopkins Medicine findings were published on June 2 in the Journal of Clinical Investigation Insight.
Vision loss
Overall, age-related macular degeneration is the most common cause of vision loss among people age 50 and older, affecting an estimated 7.3 million individuals in the United States.
Standard treatment of wet age-related macular degeneration requires monthly or twice-monthly eye injections of so-called anti-VEGF drugs that slow or stop the growth of leaky blood vessels and, in most cases, stave off further vision loss.
Because the injections are inconvenient, costly, uncomfortable, and carry risk of infection, retinal detachment and other side effects, the research team has long been studying ways to identify subgroups of patients who can safely reduce – or even cease – eye injection therapies without further vision loss.
“The proteins in the eye may help us identify patients who can safely be weaned off these therapies or transition to other, new ways of delivering these drugs to the retina,” said Akrit Sodhi, associate professor of ophthalmology and the Branna and Irving Sisenwein Professor in Ophthalmology at the Wilmer Eye Institute at the Johns Hopkins University School of Medicine.
Biomarkers
For the current study, Sodhi’s team investigated whether measurable levels of certain proteins in the eye could be used as predictors, known as biomarkers, of disease stabilisation or progression despite treatment.
First, the team collected samples of eye fluid from 38 patients at the beginning of their treatment for macular degeneration at the Wilmer Eye Institute between 2013 and 2020 in two Maryland locations.
These patients were then grouped based on the frequency with which they required treatment at the end of one year.
The researchers then screened the samples of each of these groups for proteins linked to the development of abnormal blood vessels.
Among the proteins present, the researchers found that one, named angiopoietin-like 4, was present at higher levels in patients who required monthly treatment when compared with patients who were eventually able to reduce the frequency of injections or even stop treatment without further vision loss.
Accurate prediction
Using statistical models, Sodhi’s team found that relatively higher levels of angiopoietin-like 4 (higher than 4.22 ng/mL) accurately predicted actual clinical outcomes in the patient population, identifying with 91 per cent sensitivity those patients who would continue to require monthly eye injections to preserve their vision.
However, they found that measuring only angiopoietin-like 4 led to many false-positives, with one third of the patients flagged by the test not requiring monthly therapy.
In a bid to improve the accuracy of the prediction model, they paired measurements of angiopoietin-like 4 with VEGF, the protein specifically targeted by current wet macular degeneration treatments.
With both of these proteins, the researchers were able to correctly identify with 76 per cent sensitivity and 85 per cent specificity patients who likely need monthly eye injections; this group of wet macular degeneration patients could benefit from newer longer acting anti-VEGF therapies.
Potential therapeutic
In animal experiments, the researchers next examined whether blocking angiopoietin-like 4 in the eye could be a potential therapeutic approach for wet age-related macular degeneration.
The researchers used nanoparticles developed in collaboration with Jordan Green, Professor of Biomedical Engineering at the Johns Hopkins University School of Medicine, to deliver RNA interference (RNAi) designed to target the expression of either angiopoietin-like 4 or VEGF in the retina in mice with eye lesions similar those in patients with wet age-related macular degeneration.
Mice that received either the angiopoietin-like 4-blocking RNAi treatment or the VEGF-blocking RNAi treatment, both had lower levels of abnormal blood vessel growth than mice which received control treatment.
However, in mice that received RNAi targeting both VEGF and angiopoietin-like 4, the treatment showed an additive effect, with even lower abnormal blood vessel growth than RNAi targeting either protein alone.
Similar results
As an alternative to using RNAi as a therapy, the researchers tested a naturally-found protein called soluble neuropilin, which the researchers have previously shown have a quenching effect on VEGF and angiopoietin-like 4 in studies in diabetes.
The researchers tested soluble neuropilin by injecting the protein into the eyes of mice.
The test yielded similar results as the RNAi, effectively treating the growth of the abnormal blood vessels, revealing that targeting both angiopoietin-like 4 and VEGF together leads to effective relief of wet age-related macular degeneration lesions.
Collectively, these experiments provide the foundation for studies examining therapies targeting both VEGF and ANGPTL4, and help explain why elevated levels of these two proteins in the eyes of patients predicts how patients respond to current therapies targeting only VEGF.
“Angiopoietin-like 4 and VEGF act synergistically to create more severe choroidal neovascular lesions in the eye. They could, potentially, be used as both a biomarker as well as a treatment target,” said Sodhi.
Gut-friendly foods such as kimchi and kombucha may carry hidden risks for heart health when eaten in excess, the British Heart Foundation (BHF) has warned.
The charity said foods marketed as prebiotic, probiotic or otherwise good for the gut can support the microbiome, but some may also be high in salt or sugar, which can raise the risk of cardiovascular disease.
Products highlighted by the British Heart Foundation included kimchi, kombucha, fruit yoghurts, smoothies and sauerkraut. It said there is no harm in including them as part of a healthy diet, but advised people to check labels for added salt and sugar and eat them in moderation.
Tracy Parker, the charity’s nutrition lead, said: “We encourage everyone to choose foods that can keep their gut microbiome healthy. The benefits are clear, and we are continuing to improve our understanding of how a gut-friendly diet may help our hearts.
“A lot of these products can contain high levels of salt or sugar though, so it is important to be aware of the potential drawbacks.
“By ensuring you check package labels for added salt and sugars, and eat each in moderation, you can make sure the risks do not outweigh the benefits for your heart health.”
Fermented foods such as kimchi and sauerkraut are rich in probiotics, the healthy bacteria produced during fermentation that can help support a diverse and healthy gut microbiome.
However, both are traditionally made using a lot of salt, which can raise blood pressure if eaten frequently or in large quantities. High blood pressure is known to increase the risk of heart attack and stroke.
Kombucha, a fermented tea, also contains probiotics and can be a healthier alternative to fizzy drinks, but many commercial and shop-bought versions contain added sugar.
Eating too much sugar can lead to weight gain, which can increase the risk of heart attack, stroke and other cardiovascular disease.
Fruit yoghurts can contain probiotic live bacteria cultures, but may also be high in sugar and have fewer live cultures than plain versions.
The charity said plain yoghurt with live and active cultures on the label can be a lower-sugar option, with whole fruit added at home for sweetness.
Smoothies made with whole fruits provide prebiotic fibre, which feeds beneficial gut bacteria and supports digestive health.
They can also provide vitamins and antioxidants, especially when made with a variety of plant-based ingredients.
But blending breaks down the structure of fruit, releasing free sugars that behave like added sugars in the body and can cause faster rises in blood sugar levels.
Regularly consuming too much sugar can lead to weight gain, which can increase the risk of developing type 2 diabetes, heart disease and kidney disease.
The charity said only one 150ml serving of any smoothie counts towards five-a-day, and suggested adding nuts or seeds for extra protein and fibre to help keep blood sugar levels more stable.
The BHF also noted that some shop-bought sauerkraut is pasteurised, which removes most of the live bacteria.
It advised checking the label, eating small portions and choosing unpasteurised products for those seeking the probiotic benefits.
The charity said beneficial gut bacteria produce short-chain fatty acids during digestion, which are linked to reduced inflammation, better metabolism and better heart and circulatory health.
These good bacteria also help digest polyphenols, natural plant chemicals thought to have antioxidant properties and which may help lower blood pressure.
By contrast, harmful gut bacteria, which thrive on diets high in fat and red meat, produce chemicals that can cause problems in the heart and blood vessels by increasing inflammation and altering how cholesterol is processed in the body.
Beneficial bacteria thrive on varied diets high in prebiotics, non-digestible fibres found in foods such as wholegrains, oats, beans, lentils, bananas and onions.
People with diabetes may have undiagnosed heart failure that could be detected by a simple screening blood test, research suggests.
The TARTAN-HF trial found that one in four patients with diabetes who had at least one other risk factor for heart failure had undiagnosed heart failure detected through screening with a blood test and ultrasound scanning of the heart.
Experts said the findings show the extent of unrecognised heart failure in people with diabetes, and how the condition can be detected using a widely available blood test called NT-proBNP, which measures how much strain the heart is under.
They suggest a heart failure screening programme for diabetics could improve diagnosis rates, lead to earlier treatment and potentially reduce the risk of hospitalisation and death.
The study, involving 700 patients, was led by the University of Glasgow in collaboration with AstraZeneca, Roche Diagnostics, Us2.ai, NHS Greater Glasgow and Clyde and NHS Lanarkshire.
Dr Kieran Docherty, clinical senior lecturer at the University of Glasgow’s School of Cardiovascular and Metabolic Health, said: “Our results from the landmark TARTAN-HF trial identified heart failure in a large proportion of people living with diabetes, emphasising the need for a heart failure screening strategy in this group of patients.
“We know that many of the symptoms and signs of heart failure are non-specific, and may go unrecognised as potentially being due to heart failure for a long time.
“The strategy used in our trial is simple and easy to implement in clinical practice, and will aid in the early identification of heart failure in people with diabetes, and facilitate the initiation of medications that we know improve outcomes in patients with heart failure.”
The study, which began more than three years ago, involved more than 700 people with diabetes from the two health board areas who had at least one other risk factor for heart failure.
They were randomly assigned either to receive heart failure screening or to continue with their usual care.
Researchers found screening uncovered a large number of previously unrecognised cases of heart failure. Around one in four, or 24.9 per cent, of those screened were found to have the condition within six months, compared with 1 per cent in the group continuing their usual care.
The study, involving patients with type 1 and type 2 diabetes, found almost all of the participants found to have heart failure had preserved ejection fraction, which can be difficult to detect without dedicated testing.
The findings of the TARTAN-HF trial were presented at the American College of Cardiology conference taking place from 28 to 30 March in New Orleans in the US.
Dr Edward Piper, medical director at AstraZeneca UK, said: “Delayed diagnosis and treatment of heart failure in people with type 2 diabetes contributes to poor long-term outcomes. TARTAN-HF demonstrates that targeted, risk-based screening can identify previously undiagnosed heart failure in approximately one in four high-risk patients with diabetes, enabling earlier intervention with guideline-directed therapy.”
Dr Christian Simon, head of global medical affairs at Roche Diagnostics, said: “We are proud to have supported the landmark TARTAN-HF trial. These findings demonstrate the transformative power of early, accessible diagnostics like the NT-proBNP blood test.
“By identifying unrecognised heart failure in people with diabetes, we enable clinicians to initiate appropriate treatments sooner, ultimately improving patient outcomes and lives.”
The UK has launched a £6.3m men’s health fund to back local projects aimed at helping men and boys live longer, healthier lives.
The Men’s Health Community Fund is a partnership between the Department of Health and Social Care, Movember and People’s Health Trust.
The government is contributing £3m, while the two charities are more than doubling that to take the total to £6.3m.
Grants will support community projects reaching underserved men and boys aged 16 and over, particularly in the most disadvantaged areas and at key points in their lives such as becoming a father, losing a job or retiring.
Projects could include support for new fathers, activities for men facing loneliness and social isolation, services to help young men engage with the health system, and support for men in work, out of work and moving into retirement.
The programme will bring together voluntary, community and social enterprise organisations to test new ways of reaching men who are least likely to use traditional health services.
An evaluation funded through the National Institute for Health and Care Research will assess what works and help inform future policy and delivery.
Health and social care secretary Wes Streeting said: “Too many men across the country are living shorter, less healthy lives, particularly those in our most disadvantaged communities.
“This new partnership will help men get the support they need in the places they feel most comfortable, their communities, among people they trust.
“By working with expert charities and local organisations, we can reach the men who are too often missed by traditional services and help them take better care of their mental and physical health.”
“It is a key step in delivering our first ever Men’s Health Strategy and driving forward our ambition to halve the gap in healthy life expectancy between the richest and poorest areas.”
The Men’s Health Strategy sets out plans to tackle the physical and mental health challenges men and boys face.
Men can be less likely to seek help and more likely to suffer in silence, while higher rates of smoking, drinking, gambling and drug use are damaging men’s health and affecting families, workplaces and communities.
The government is also investing £3.6m over the next three years in suicide prevention projects for middle-aged men in local communities across areas of England where men are most at risk, many of which are also among the most deprived. Suicide is one of the biggest killers of men under 50, and three-quarters of all suicides are men.
The projects will aim to break down barriers middle-aged men face in seeking support, including stigma around asking for help and a lack of awareness of what is available and how to access it.
They will be co-designed with experts and men with lived experience of mental health crises and suicidal thoughts.
Gut-friendly foods may damage heart, charity warns
Diabetes patients face increased risk of undiagnosed heart failure
UK government announces £6.3m fund to boost men’s health
Brain health collaboratory launches in Gulf South
