A team led by researchers at Moorfields Eye Hospital and UCL Institute of Ophthalmology (IoO) has today published in The Lancet a review of work going on around the world to treat glaucoma, one of the leading causes of blindness.
Hari Jayaram, lead author, associate professor at UCL Institute of Ophthalmology and director of Moorfields Eye Hospital’s glaucoma service, says: "This seminar brings together much of the evidence for existing treatments for glaucoma, and those in development, together with our thoughts on the most promising areas for future research. We want it to inspire more research in the field and to offer real hope to people with the condition."
Glaucoma is the name given to a group of slowly progressive optic neuropathies that are currently irreversible. It is estimated that 95 million people worldwide have glaucoma, with around 10 million having already lost the sight of at least one eye.
Early detection of this degenerative condition is vital for its treatment, but most people do not experience symptoms as their eyes compensate for their gradual loss of vision. Around 50% of glaucoma is undetected in high-income countries, rising to over 90% in those with lower and middle incomes. Commonly used tests include pressure measurement, tests of a person’s visual field and optical coherence tomography (OCT) scans.
Raised pressure within the eye is associated with glaucoma and lowering this slows its progression. A first-degree family history raises its probability by a factor of eight. Prevalence also rises with age and high or low blood pressure. The authors point out there is no national screening programme, with glaucoma often being discovered during routine eye examinations.
There are two main sub-types. Angle closure accounts for just over 30% of cases, but half of the blindness, the remainder are open angle.
The measurement of eye pressure is not precise, and there can be inconsistencies in measurement for the non-intrusive methods most commonly used, such as puffs of air. This is important, as often the success of treatments is assessed by the lowering of pressure within the eye towards a target level.
Visual field tests suffer from inconsistencies between successive results, but progress is being made on assessing these over longer periods of time, as well as in developing digital tests that can be taken at home.
There is scope for more accuracy in pressure testing, eye scans and visual field tests. Artificial intelligence could be trained to detect early signs of a thinning in nerve fibres at routine eye scans and could help to evaluate the trends for a series of more frequent, self-administered visual field test.
Treatment and research
There has been progress in mainstream treatment of the condition in recent years, which is mainly aimed at lowering the pressure inside the eye. In the UK, NICE, the National Institute for Health and Care Excellence, now recommends the use of laser treatment (selective laser trabeculopathy) ahead of eye drops and surgery for early open angle cases.
New lasers are being tested that can make this easier to administer and less intrusive for patients, paving the way to free up consultant time to treat more complex and advanced cases.
Drops and surgery are aimed at lowering the eye pressure by reducing the amount of aqueous humour in the eye through reducing its production, increasing its outflow from the eye, or both. Patients may not always use drops as frequently as prescribed, as they sting and most patients have no symptoms, so slow-release implants are being investigated, along with injectable drugs.
New classes of drug are best developed, including rho kinase inhibitors (approved as effective in Europe and America, but with known side effects) and latanoprostene bunod.
Surgery may be required for more advanced glaucoma and angle closure, with drainage tube implants and trabulectomy effective in reducing eye pressure, but these procedures require extensive post-operative management and carry substantial risks. MIGS (minimally invasive glaucoma surgery) shows the potential to be safer and simpler, albeit with lower levels of effectiveness, but further evaluation against current surgical techniques and other treatments is required.
While there are 125 genes associated with glaucoma, there is the potential for personalised, cellular and gene therapy treatments, particularly in conjunction with genetic risk profiling.
Stem cells offer the potential to not just lower pressure but to maintain this, and gene therapy has led to some regeneration, but has not yet been tried on humans.
Neuroprotection offers potential, but the failure of the trial of mematine to show an advantage over a placebo has made others reluctant to conduct these high-cost trials; high dose nicotinamide appears promising.
The paper was written by Hari Jayaram, Professor Gus Gazzard from Moorfields Eye Hospital, Professor Miriam Kolko from Copenhagen University Hospital and Professor David S. Friedman from Massachusetts Eye and Ear Hospital.
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