September 2014


September  has  been a busy month in the world of research. You may notice that my blog has a slight genetics slant, this is due to my background in genetics research and my belief  that it underpins the future of tailor made therapies. The genetics studies described lead us one step closer to a cure/prevention for glaucoma. Before reading the dry eye article I was unaware just how prevalent it is! Very interesting that it is associated  to long term pain syndromes also. I think we are all relieved to see that Cochrane has released a review regarding the Avastin and Lucentis debate – the amount the NHS could save by using  Avastin is astronomical. Lastly the association of exfoliation syndrome and being outdoors raises many questions about the role UV light plays in the pathogenesis of this disease. I hope you enjoy reading about these studies as much as I did and remember, if you want to contact me I’d love to hear from you!


This email address is being protected from spambots. You need JavaScript enabled to view it.">This email address is being protected from spambots. You need JavaScript enabled to view it. 

ABCA1 variants linked to glaucoma risk

The identification of ABCA1 variants associated with risk of developing glaucoma is reported in three independent studies published online this September in Nature Genetics. These findings may lead to better diagnostic tools or therapies for glaucoma.

Glaucoma is a group of eye disorders that cause progressive damage to the optic nerve and can lead to permanent blindness. Though high intraocular pressure is a common risk factor for developing glaucoma, people with normal eye pressure can also develop the disease.

One study found variants near the two genes ABCA1 and PMM2, which are associated with glaucoma risk, with or without high intraocular pressure, in individuals from China and Singapore1. Both genes have been previously implicated in other eye disorders, but not glaucoma. In a second study, variants near three genes, including ABCA1, were found to be associated with glaucoma risk in Australians and Americans of European descent2. The third study combines genetic data from 18 populations, including people of Asian and European descent, and also identifies ABCA1 as a risk gene for both high intraocular pressure and glaucoma3.

ABCA1 is a major regulator of cellular cholesterol and lipid levels. Previous studies have found that this gene is expressed at higher than normal levels in the blood of glaucoma patients, and therefore this may represent a promising drug target.



 1.Yuhong Chen et al. Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma. Nature Genetics doi:10.1038/ng.3078


2.Pirro G Hysi et al. Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nature Genetics doi:10.1038/ng.3087


3.Puya Gharahkhani et al. Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. Nature Genetics doi:10.1038/ng.3079



Around 1 in 10 UK women has dry eye disease, requiring artificial tears


Around one in 10 women in the UK has dry eye disease, requiring artificial tears or gel to lubricate the eyes and protect them from damage, reveals a study published online in the British Journal of Ophthalmology.

Altered pain perception and psychological factors may be involved in the condition, the researchers report.

The symptoms of dry eye disease include the sensation of grit in the eye, frequently accompanied by itching, burning and visual disturbance. The causes are poorly understood.

The participants consisted of almost 4000 women aged 20 to 87 (average age 57) from the TwinsUK cohort, drawn from the registry held at St Thomas' Hospital in London. This cohort is widely regarded as representative of the UK general population, and has been used to look at a wide range of diseases and genetic traits over the years.

The prevalence of dry eye disease, and the frequency and severity of symptoms, were assessed through questionnaires mailed out to the women. At the same time 681 randomly selected twins from the cohort, who were taking part in a subsidiary study on pain, supplied additional information on dry eye symptoms and rated their own health on a five point scale.

Around one in 10 of the women (9.6%) had been diagnosed with dry eye disease, which was being treated with artificial tear eye drops or gel. One in five (just under 21%) had experienced symptoms in the past three months.

The analysis showed that the prevalence of a diagnosis of dry eye disease rose with age, from 2.7% among women in their 30s to one in five of those in their 90s.

Cataract surgery, age related macular degeneration, and glaucoma were all significantly associated with dry eye disease, as was the use of contact lenses. Autoimmune diseases, such as thyroid problems, rheumatoid arthritis, and allergies asthma and eczema were also linked to a heightened risk. Furthermore, fertility problems were strongly associated with dry eye disease, as was osteoarthritis.

The strongest associations were found with long-term pain syndromes (known as chronic pain syndromes), such as irritable bowel syndrome, pelvic pain, and chronic widespread pain syndrome (also known as fibromyalgia). People with these conditions also tended to have depression and migraine - risk factors for dry eye disease in their own right.

The responses to the health questionnaire showed that people with dry eye symptoms rated their health, on average, worse than those without symptoms. They highlighted difficulties watching TV, driving, working online, and experienced discomfort in places that were air conditioned or where the air was dry.

The authors conclude that dry eye disease is very common among women and that it has a significant impact on perceived quality of life. They add that their findings suggest that altered pain perception as well as psychological factors may influence the development of the condition and symptom severity, and that some patients might be helped by treating the pain rather than just lubricating the eyes.




Jelle Vehof, Diana Kozareva, Pirro G Hysi, Christopher J Hammond. Prevalence and risk factors of dry eye disease in a British female cohort. British Journal of Ophthalmology, doi:10.1136/bjophthalmol-2014-305201, published 3 September 2014.



Cheaper alternative to licensed drug for treating age related macular degernaeration has similar side-effects says new Cochrane Review


Health policies which favour using ranibizumab for treating eye disease in older people over safety concerns for a cheaper alternative should take account of a new Cochrane Review. The researchers looked at the results of studies which compared the safety of two drugs used for treating age-related macular degeneration, ranibizumab and bevacizumab. Contrary to what was argued by some experts the review has found that the cheaper drug, bevacizumab, does not appear to increase deaths or serious side-effects compared with ranibizumab in people with neovascular age-related macular degeneration.

Neovascular macular degeneration is a progressive and chronic disease of the eye, and a leading cause of blindness in older people. About one in 10 people with macular degeneration suffers legal blindness. Bevacizumab is a drug that has been developed to treat cancer, while ranibizumab is marketed specifically for age-related macular degeneration. The two drugs are better known by their brand names Avastin (bevacizumab) and Lucentis (ranibizumab). The authors conclude that health policies that favour the much more costly ranibizumab instead of bevacizumab for macular degeneration, for reasons of safety, are not supported by current randomised controlled trial evidence. A larger Cochrane Review, which will assess additional sources of evidence, is now planned to help reduce the remaining uncertainties around the relative benefits and safety of these drugs.

Bevacizumab and ranibizumab are related biological drugs that work to prevent the abnormal growth and swelling of blood vessels that are characteristic signs of macular degeneration. Although the beneficial effects of the two drugs are believed to be similar, only ranibizumab has been licensed as a treatment for macular degeneration; bevacizumab is currently approved only as a cancer therapy. Despite this, an unlicensed preparation of bevacizumab is often used off-label as treatment for macular degeneration, because it is cheaper than ranibizumab. It has been suggested that the two drugs have different safety profiles, such that bevacizumab might cause more systemic harms, and the review investigated this concern.

The review included nine randomised controlled trials (RCTs), three of which had not been published. None of the trails were supported by manufacturers of either treatment, and a total of 3665 participants were used. The drugs were given for up to two years. The review found the systemic safety of bevacizumab for macular degeneration appeared to be similar to that of ranibizumab, except for gastrointestinal disorders. Although no statistically significant differences between the treatments were found, the review does not exclude the possibility that either treatment is less harmful than the other. The researchers estimated that if 1000 people were treated with ranibizumab for one to two years, 34 would die; if treated instead with bevacizumab, between 27 and 53 would die. If 1000 people were treated with ranibizumab, 222 would experience one or more serious systemic adverse events. If 1000 people were treated instead with bevacizumab, between 200 and 291 would experience such an event.

They rated the overall quality of the evidence as low to moderate because of the uncertainty of the findings, and due to other study limitations. Additionally, the review authors indicated that they could not fully assess the quality of three of the studies as they had not yet been published.




Moja L, Lucenteforte E, Kwag KH, Bertele V, Campomori A, Chakravarthy U, D'Amico R, Dickersin K, Kodjikian L, Lindsley K, Loke Y, Maguire M, Martin DF, Mugelli A, Mühlbauer B, Püntmann I, Reeves B, Rogers C, Schmucker C, Subramanian ML, Virgili G., Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration, Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD011230. DOI: 10.1002/14651858.CD011230.pub2, published 15 September 2014.


Outdoor activities may be linked to exfoliation syndrome in eyes


Outdoor activities may increase the odds of developing exfoliation syndrome (XFS) in the eyes, a condition which has been linked to cataracts and glaucoma.

XFS is a harmful aging of the eye associated cataracts, elevated intraocular pressure and retinal vein blockage. There is evidence that climate factors contribute to XFS. For example, aboriginal Australians who spend lots of time outdoors have a higher prevalence of the disorder. The relationship between ultraviolet (UV) radiation (UVR) and XFS however requires further study because reports of a link have not been consistent.

The authors examined the relationship between UVR and XFS in a study with clinic participants in the United States (118 cases, 106 control patients) and Israel (67 cases, 72 control participants). The authors analyzed the latitude where people lived and the average number of hours per week that they spend outside.

Where people live appears linked to XFS, with each degree of weighted lifetime average residential latitude away from the equator associated with an 11 percent increased odds of XFS. Every hour per week spent outside during the summer, averaged over a lifetime, also was associated with a 4 percent increased odds of XFS. The odds of XFS decreased by 2 percent in the United States, but not in Israel, for every 1 percent of average lifetime summer time during the day that sunglasses are worn. In the United States, a history of working over water or snow also was associated with increased odds of XFS. There appeared to be no association between brimmed hat wear and XFS.

This study provides evidence for a role of reflected UV rays in contributing to XFS. It by no means excludes other genetic and environmental mechanisms in XFS pathogenesis. If confirmed in other studies, there could be reason to consider more widespread use of UV-blocking eyewear in the prevention of XFS.




JAMA Ophthalmol. Published online September 4th 2014. doi:10.1001/.jamaopthalmol.2014.3326. accessed September 20th 2014