Education Committee Highlights WGC-2021 | part 1.3

The Hunt for New Modifiable Risk Factors for Glaucoma

Currently, the only modifiable risk factor for glaucoma is Intraocular pressure. Research is ongoing to explore how some of the day-to day factors such as diet, air pollution, physical activity, systemic medication, and sleep affect an individual’s risk of glaucoma. Drs. Yvonne Buys and Anne Coleman introduced the speakers who would be talking about non IOP related modifiable risk factors for progression of glaucoma.

You are what you eat: Diet and Glaucoma
Several Randomised controlled trials have shown the impact of dietary interventions on health outcomes. In his talk, Dr. Louis Pasquale highlighted the need to consider genetics when considering relationship between diet and complex diseases. In a recent study, Dr. Pasquale and colleagues found that among participants with the strongest genetic predisposition to elevated IOP, greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence. Additionally, strong pre-clinical data has shown that Niacinamide (Vitamin B3) may improve mitochondrial function and thus act as a neuroprotective agent for glaucoma. In his concluding remarks, he advocated dietary supplements as an adjunctive therapy to achieve desired results.

It’s what you breath: Pollution and Glaucoma
Dr. Paul Foster has been studying the relationship between glaucoma and air pollution. He elaborated on how air pollution contributed to respiratory, cardiovascular and even neurodegenerative disease by causing inflammation and oxidative stress. Individuals who were exposed to high levels of black carbon, were likely to have high intraocular pressure, if they were genetically predisposed to oxidative stress. He cited a prospective study using the UK Biobank data that showed a significant association existed between higher particulate matter exposure and both a higher risk of self-reported glaucoma and thinner macular ganglion cell-inner plexiform layer, independent of intraocular pressure. Dr. Foster’s concluding remarks were that fine particulate matter had a detrimental effect on glaucoma by a neurotoxic or vascular mechanism.

It’s how (much) you move: Physical Activity and Glaucoma
Prof. Pradeep Ramulu, presented his research examining the relationship between glaucoma and physical activity. He talked about a longitudinal, observational study in which the participants wore accelerometers for a week to define average footsteps per day, minutes of moderate-to-vigorous and non-sedentary activity. Visual field measurements before and after physical activity assessment were retrospectively analysed to measure rates of visual field loss. Increased walking, greater time spent doing moderate-to-vigorous physical activity and in non-sedentary activity were associated with slower rates of visual field loss in patients with glaucoma on treatment.

Prof. Ramulu also cited a study by Williams et al that examined the relationship between glaucoma and physical activity in 29,854 male runners, who were followed prospectively for 7.7 years. The risk of glaucoma decreased 5% per kilometre per day run, suggesting that vigorous physical activity may reduce glaucoma risk. Prof. Jonathan Crowston’s research group has shown that exercise has a protective effect mediated through the action of brain-derived neurotrophic factor (BDNF) in mice. Human studies have also shown that BDNF is released with exercise and that patients with glaucoma release lower levels of BDNF compared to controls. Prof. Ramulu suggested that ophthalmologists and optometrists should recommend exercise to their patients with glaucoma but that this should be offered in conjunction to IOP-lowering therapy.

It’s what you put in your Body: Systemetic Medications and Glaucoma
Dr. Anthony Khawaja summarized the findings of a recent review he co-authored on systemic medications that may modulate the risk of glaucoma. He mentioned that several classes of systemic medications are known to, or suspected to, modulate glaucoma risk, either through their direct effects on intraocular pressure (IOP) or via mechanisms independent of IOP. Steroids have been found to be the most notorious to increase the risk of open angle glaucoma, while systemic beta blockers on the other hand decreased the risk of glaucoma by virtue of their effect on the blood pressure. Anticholinergics result in a pupil block and sulfa derivative drugs like Topiramate cause ciliochoroidal edema, thus increase the risk of angle closure glaucoma.

He emphasized the need for taking thorough drug history from time-to-time and if the patients were starting any systemic medications that could result in angle closure, to advise patients to seek consultation as regards a prophylactic laser iridotomy. He cited the EPIC Norfolk study which showed that statin users were more likely to have lower IOP than non-statin users because they were more likely to be using systemic beta blockers.

Dr. Khawaja also cited another study that identified associations between systemic medications and primary open-angle glaucoma (POAG) using United States insurance claims data. In this study, Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG and the most significant drug in this class was citalopram. On the other hand, Calcium channel blockers were strongly associated with an increased risk of POAG; the most significant drug in this class was amlodipine. He concluded that the Drug-glaucoma association was influenced by not only the drug effect but also the underlying disease, prescribing patterns, ethnicity and other confounding factors.

It’s how you sleep: Apnea, Sleep Position and Glaucoma
The evidence for OSA and open angle glaucoma has been conflicting. Prof. David Mackey talked about the physiological changes associated with obstructive sleep apnea (OSA). To measure OSA, an overnight polysomnography in a sleep laboratory is the ideal test. Prof. Mackey cited the Raine study, which showed that OSA could be associated with preclinical retinal nerve fibre layer thinning in young adults, although it was not as remarkable in middle aged adults. Data from the Busselton Health Study, the United Kingdom Biobank and the Canadian Longitudinal Study on Aging has shown an association of OSA with glaucoma. He said further research is required to see the effect of Continuous Positive airway Pressure (CPAP) on the optic nerve.

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