Glaucoma: An overview of its pathophysiology and current management

by Chiara Parisotti

Could a new healthcare app optimise the remote management of glaucoma?

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Glaucoma is one of the leading causes of irreversible vision loss, affecting around 70 million people worldwide [1]. My interest stems from both my grandfather and father having the condition, meaning that I’m also at risk.

I’m studying for a biochemistry degree at Imperial College London. As part of the course, I’m currently undertaking an attachment with Stgilesmedical, a health writing, research, and education organisation based in London and Berlin. The company is presently supporting an energetic digital health start-up that is developing a simple app to help with the remote management of glaucoma.

Glaucoma is caused by the build-up of fluid within the eye, leading to an increase in pressure in the back of the eye and damage to the optic nerve. It tends to develop later in life, with 2% of people over 40 and 10% of people over 75 reportedly developing the disease [1]. Left untreated, it can lead to irreversible vision loss.

The features of glaucoma generally develop slowly and insidiously. Typically, these include blurred vision and the appearance of rainbow-coloured rings around bright lights. As the condition worsens, peripheral vision is lost.

Unfortunately, by the time symptoms develop, irreversible eye damage has already occurred. This is one of the reasons why routine eye testing is important. Detection outside the hospital generally involves measuring intraocular pressure using a “puff test.” Alternatively, the optic nerve can be examined by means of optical coherence tomography.

There is also a rare, rapidly progressive form of the disease that is variably associated with intense eye pain, nausea and vomiting, severe headaches, red eyes, and sudden loss of vision. This requires urgent treatment.

Aqueous humour is continually produced to fill the eye. Primary glaucoma, the most common form of the disease, occurs when the aqueous humour is unable to drain through the trabecular meshwork at the same rate as it is produced. The trabecular meshwork is an area of specialist tissue around the eye. Blockage results in an increase in intraocular pressure, which in turn damages the optic nerve and leads to visual loss.

There are two types of primary glaucoma: open-angle (over 80% of cases [1]) or angle-closure. These terms refer to the angle the iris makes with the cornea. In angle-closure glaucoma, this angle becomes too narrow as the iris is forced against the cornea, blocking the flow of the aqueous humour. In open-angle glaucoma, the iris is in the correct position, but there is resistance to flow through the trabecular meshwork.

Another common form of the disease is secondary glaucoma, which is due to an underlying eye condition such as inflammation secondary to trauma. More rarely, those affected may have a congenital form of glaucoma. This is present from birth and usually due to malformation of the eye drainage structures during foetal development.

As always in medicine, there are many subcategories; my family has a variant of open-angle glaucoma called pigmentary glaucoma. The blockage in the trabecular meshwork is due to pigment shedding into the aqueous humour when the iris rubs against the fibres holding it in place. This pigment is then deposited in the trabecular meshwork, with glaucoma eventually forming in 30% of cases [2]. A feature of pigmentary glaucoma is that it typically presents earlier, between 20 and 40 years of age [3].

It’s not always clear why primary glaucoma develops: several genetic abnormalities have been identified, but they account for fewer than 10% of cases [4]. Predisposing factors including increasing age and being of African, Caribbean, or Asian descent. Also, being near- or farsighted, or having low blood pressure, inflammation, or diabetes, all put you at greater risk.

To reduce the risk of vision loss, it’s important to schedule routine eye tests at least every two years following a diagnosis of increased intraocular pressure. Any deficit cannot be regained, even with aggressive treatment.

Medical treatments to reduce intraocular pressure operate by promoting outflow of aqueous humour. A 20–50% improvement may be expected [1]. Treatments usually involve the instillation of eye drops, typically prostaglandin analogues such as latanoprost. Regular application is important. Unfortunately, these agents tend to lose effectiveness over time. Second-line drug treatments include carbonic anhydrase inhibitors, β-blockers, or α-agonists.

A minority of sufferers require surgery, the most common option being argon laser trabeculoplasty (ALT). This procedure involves lasering the trabecular network to remove tissue and thus improve drainage. Following treatment, intraocular pressure generally falls by 20–30%. The operation is successful in about 75% of people with open-angle glaucoma, but due to the trauma it causes to the trabecular meshwork, it can’t usually be repeated. The newer procedure of selective laser trabeculoplasty (SLT), a more subtle approach, targets specific cells within the trabecular meshwork. It is similarly effective to ALT but can be repeated. The benefits of each operation can be expected to last a maximum of five years.

Another surgical option is trabeculectomy, which lowers interocular pressure by removing a piece of the trabecular meshwork. Benefits can last for several decades, though 20% of subjects experience failure within the first year, with an additional 2% losing benefit in each subsequent year [5]. One complication is that trabeculectomy can result in intraocular pressure becoming too low, leading to temporary blockages of vision known as choroidal detachments.

It’s a disappointing fact that even if treatment for glaucoma successfully lowers intraocular pressure, this may not prevent progressive damage to the optic nerve. Also, the disease develops even in people with low intraocular pressure. Nearly 30% of patients given pressure-lowering treatment eventually lose sight in one eye and nearly 10% become legally blind [6]. Those who have been diagnosed with the condition therefore have to carefully consider which treatments would best suit them, and in what order.

Because of the limitations associated with current treatments, many researchers are focusing on neuroprotection: the protection or regeneration of nerve cells involved in vision. A possible avenue might be the manipulation of neurotrophic factors, small molecules that support the survival and development of nerve cells. Another could be tozasertib, a kinase inhibitor that induces cell cycle arrest — studies of rats with induced glaucoma suggest tozasertib treatment may protect the optic nerve.

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Appamedix is developing a simple app to help with the remote management of glaucoma.

The value of mobile phone apps is now being realised, with apps being developed for many conditions. Stgilesmedical GmbH in Berlin is currently supporting an energetic start-up, Appamedix, with its Glaucare app. This digital assistant addresses two problems: poor drop compliance and limited availability of ophthalmologists.

Many patients are required to self-manage complex drop schedules. Most start off well but compliance generally drops by 50% at the end of the first year, and by 33% after two years. Each year in Germany, around 2,000 people become blind because of glaucoma. Also, specialist care is limited, with waiting times to see an ophthalmologist typically between 3 and 24 months across Europe.

The Glaucare app provides a reminder to glaucoma sufferers to take their drops, a compliance register, a management diary, and a means of storing additional data such as changes in symptoms and self-recorded intraocular pressure. In the future, it will provide a channel for two-way communication with the appropriate healthcare professionals, a feature likely to be of great value in remote areas and developing countries.

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