Glaucoma management in adults: an update

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As a GP [general practitioner], glaucoma is one of the conditions that's on my try-not-to-miss list. It's a tricky one because it's typically asymptomatic until irreversible vision loss has occurred. So of course, early detection is key to make sure we can get treatment started and prevent permanent visual loss. I'm Laura Beaton, your host for today's podcast, and my guest is Dr Alp Atik, consultant ophthalmologist, and head of the glaucoma unit at the Royal Victorian Eye and Ear Hospital here in Melbourne, who will update us on glaucoma management in adults. Alp, thanks so much to you and to your co-authors for this article and taking the time today to talk with me.

Thanks, Laura, and thank you for your interest in our specialty.

I'm a generalist, but it is always wonderful to talk with subspecialists about the nitty-gritty of a condition, but also really helpfully, what are the things that we need to know about your subspecialty, particularly, when do we need to get you involved urgently? Can we start off today with a reminder of what glaucoma is and the various different types?

Glaucoma is a group of progressive optic neuropathies that is characterised by end-stage damage to the optic nerve, which is the nerve that connects the eye to the brain. There are multiple different ways of classifying it, but the 2 broad classifications is open-angle glaucoma and angle-closure glaucoma. And these 2 classifications are based on whether the anterior chamber angle, which is where the aqueous humour drains out of our eye, is open or closed. There are then subcategories within each category such as primary and secondary, but generally, the broad classification is according to the state of the anterior chamber angle.

So whether or not that fluid is able to flow out or whether it's blocked off?

That's absolutely right. So whether there is an anatomical barrier that has closed off that drainage angle, which is angle-closure glaucoma, or whether that drainage angle is visible and open but still not functioning properly, which is open-angle glaucoma.

And you did mention the fact that this is chronic progressive, but, of course, there is a very acute emergency in glaucoma, which is when that drainage blocks off quite quickly.

Correct. We call that an episode of acute angle closure. The anterior chamber angle is 360 degrees circumferentially around the eye. And when that completely shuts off, you continue to produce aqueous humour, but that aqueous humour has nowhere to go as a result of that leading to an acute rise in intraocular pressure, which can cause significant optic nerve damage in a very quick way.

And I guess in many ways, fortunately, this is actually the glaucoma that is presenting with symptoms. So these are your red flag eye symptoms that you're going to be sending someone to an ophthalmologist today, or if there is no ophthalmologist around, a local emergency department. Can we just run through those red flag symptoms?

Absolutely. The red flags can also be broken down into 2. There's the actual acute angle-closure episode, which causes a fairly sudden onset eye pain, a mid-dilated fixed pupil, eye redness, and a fog or a mistiness over the cornea, which is the front window of the eye. That is associated with an episode of acute angle closure where the eye pressure has gone up significantly, usually above 40, 50, or 60 millimetres of mercury [mmHg].

The interesting thing about this situation is that sometimes you do get warning signals, and it is important when you've got a patient suspicious of glaucoma or if they have been identified as having very narrow anterior chamber angles, either by their optometrist or ophthalmologist, to ask about some early signs of intermittent angle closure where the angle may be closing off but not completely.

Things to ask for would be headaches, especially unilateral headaches, episodes of transient vision loss, episodes of nausea and vomiting, and a very specific symptom, which is seeing halos, especially against lights. Patients who have these episodes should be seen by an optometrist or ophthalmologist for formal assessment of their anterior chamber angles.

That's helpful to have those warning bell signs as well as the more obvious red flag presentation of acute angle closure. Glaucoma mostly is progressive, asymptomatic, chronic, painless, and that's the primary open-angle glaucoma, which was always high intraocular pressure. But I was interested to read that for some people, even though there is pathology progressing, the pressure might actually be in a normal range.

Absolutely. The whole concept of normal intraocular pressure being 21 mmHg or under is actually based on an epidemiological study from the 1950s where they found that in an Anglo-Saxon cohort, the vast majority of the population, so within 2 standard deviations of the mean, had an intraocular pressure of 21 mmHg, but there's no clear physiologic or anatomical bound to that limit. And really, the nuance of glaucoma is whether any pressure is causing optic nerve damage.

And in many cases, including cases where patients may not have raised intraocular pressure, it is easy to fall into the trap of missing optic nerve damage just because you feel that the intraocular pressure is normal. Now, the intraocular pressure is an independent risk factor for glaucoma damage, but not everyone with high intraocular pressure gets glaucoma. And as we talked about, not everyone with normal intraocular pressure is safe. So the IOP, or the intraocular pressure, is a lever that we change, but not the disease itself.

So as a helpful reminder where our normal, quote unquote, reference ranges come from and the fact that that may or may not be, quote unquote, normal or non-harmful. One of the things that's really helpful in your article is around we don't have formal screening, so how do we identify these people who are at higher risk? As you said, they need their intraocular pressure checked, but they also need their optic nerve looked at. Who are the people who we really should be recommending earlier and more frequent eye checks?

That's an excellent question. Generally speaking, glaucoma is a disease that gets progressively riskier with age. The reason for that is as we get older, our eye wall stiffens and isn't able to absorb some of the changes in our aqueous fluid inflow and outflow that a younger, more plastic eye is able to absorb. So risk factors for glaucoma would be people who are over 50 years of age. We also ask about patients who have a family history of glaucoma, especially first-degree relatives.

I would advise anyone who has a family history of glaucoma to have yearly or twice a year eye checks from the age of 40. There is also some association with being particularly long-sighted or short-sighted. Patients who have African or East Asian ancestry are at higher risk of developing glaucoma and the glaucoma in those patients is more difficult to treat. And also, if there are any risk factors in a patient's history such as previous eye trauma, previous surgery, or prolonged corticosteroid use, these are all independent risk factors for glaucoma that should be looked at.

So it sounds like it's both earlier and more frequent eye reviews.

Correct. The difficulty with glaucoma is because it is asymptomatic until it's too late, we sort of colloquially know it as the silent thief of sight and we're only able to detect progression at a stage where the glaucoma is not likely to have an impact on quality of life through formal testing. So a formal visit to an optometrist or ophthalmologist is essential for early detection and treatment.

In your article, you do mention that 2-yearly might be appropriate, but for some people who are higher risk, you are recommending yearly or twice a year. Does someone need to see an ophthalmologist if they do have high risk factors for glaucoma or is it based on how their eyes progress over time?

It's a little bit of both. I think anyone who has risk factors for developing glaucoma, especially family history, should get reviewed by an eye specialist. Subsequent monitoring can be done with an optometrist or an ophthalmologist depending on risk or stage of disease. If patients are deemed to be unstable or progressing, they really should be managed by an ophthalmologist. But regular screening, especially those at low risk or mild disease which has been stable, can absolutely be managed by our optometry colleagues.

And I guess without a formal screening programme, we're doing case finding for people who are at higher risk and we might just all remind ourselves of those warning signs of a potential impending angle closure and potentially those people need to be seen, maybe not today, but within a couple of weeks. What's the timeframe for people who you think might need to be seen for concerns about angle closure, but maybe it hasn't actually happened, might be intermittent?

Yeah, the timing of that would really be dependent on the severity and frequency of the symptoms. If it's something that is happening on a regular basis for a patient, then the eye should be reviewed by an ophthalmologist within a matter of days or up to weeks. If the symptoms are just very intermittent, once or twice a year, then that initial review can be done in weeks or a month or 2. But the important aspect of this entity of acute angle closure is that irreversible vision loss or optic nerve damage can be prevented with early treatment. So the earlier the eye is reviewed in the presence of some of those acute angle-closure symptoms, the less risk of developing acute angle closure.

Glaucoma does need specialist diagnosis, as you said. And while this article isn't about the diagnosis of glaucoma, when we advise that someone does need a comprehensive eye assessment, what kind of tests can we let our patients know to expect when they go to see either you or an optometrist?

Glaucoma is often co-managed between optometry and ophthalmology. Initial screening can be done by both, and that would involve taking a patient's history, especially asking about the risk factors that we've talked about, followed by an examination of the optic nerve, looking at various risk factors or signs of glaucoma.

The assessment would then involve an anatomical examination of the optic nerve through what we call an OCT [optical coherence tomography] of the retinal nerve fibre layer or the ganglion cell layer, which are essentially layers of the retina that thin out with progressive glaucoma, and then the performance of a visual field test, which looks at the function of the optic nerve.

Visual field tests are generally not particularly enjoyed by patients because there is a psychometric component to them, but they are an excellent method by which glaucoma can be diagnosed and monitored, especially in the advanced stage of disease. So an average visit for a glaucoma screen would involve history, examination, and formal investigations looking at the structure and the function of the optic nerve.

Well, now we've talked a lot about glaucoma and we spoke about how mostly this is due to raised intraocular pressure. So it does make sense that the mainstay of treatment has historically, and for a lot of the time still is, eye drops to reduce pressure. There are lots of different classes of medications, and of course, this is outlined very helpfully in the Australian Prescriber article. Table 1 has all the different medications listed by drug class.

There are 4 main classes of eye drops that patients can use for glaucoma. The first are prostaglandin analogues, the second are beta blockers, the third are alpha2-agonists, and the fourth are carbonic anhydrase inhibitors. These 4 drugs work in slightly different ways. Prostaglandin analogues are considered first-line treatment because they are highly effective and just require once-daily dosing, usually at night.

Beta blockers would generally be considered a second-line treatment and they're generally used once or twice a day and can be combined with prostaglandin analogues in patients who don't respond to prostaglandin analogue treatment. The alpha-agonists and the carbonic anhydrase inhibitors are generally seen as third or fourth-line treatment options, but there are various clinical scenarios where we would potentially use them as first-line treatment as well. It really depends on the individual, clinical scenario, as well as patient tolerance and preferences.

And of course, because this is a chronic condition, these are lifelong treatments, so it's really important that people are tolerating the drops okay and are applying them correctly. Can you tell me a little bit about up-titration of these drops, adherence, and how we troubleshoot with people who are maybe having issues with their drops and some side effects?

These questions are really important to ask at every visit to ensure that patients are using their eye drops and tolerating them. There is a vast array of literature on this topic of drop compliance, which shows that compliance may be as high as 90% or as low as 15%, and we don't really know the answer. It is important to make patients comfortable with the fact that an occasional missed drop is actually normal. A lot of people fear divulging incomplete compliance for the risk of being sort of admonished by their clinician. Symptoms initially to look for would be things like red eye, discomfort, symptoms of dry eye. That can happen with all of the classes of medications.

And then there are other more specific symptoms based on the subclass of drops that patients are on. For example, prostaglandin analogues can cause pigmentary change around the eye. So the actual iris colour can change, eyelash growth can enhance and be slightly darker than previous. And after chronic use, it can cause a condition called prostaglandin-associated periorbitopathy where the fat pads or adipose tissue around the eye in the orbit can erode and cause the eye to look like it is sunken in. There are other side effects associated with other subclasses. Beta blockers, for example, are contraindicated in patients with a background of asthma or bradycardia because of the systemic side effects associated with them. So it is important to ask specific questions based on both the patient in front of you, but also the specific medication that they've been prescribed.

And I guess all that troubleshooting, up-titrating, changing medications, is happening in your field, but for the rest of us who are not ophthalmologists, we certainly can be asking about adherence and, of course, normalising how often would you miss your drop? Would it be every day, every other day, couple of times a week, once a month? And then asking about side effects, and if these things are popping up, getting them in to see their specialist a little bit earlier rather than later is probably a good idea.

Absolutely. We would classify drop non-compliance as a type of unstable glaucoma because the patient is not getting required treatment on the eye, and this would absolutely require referral to an ophthalmologist for further assessment.

So now that we've covered the medicines, let's move to the non-medicine treatments for glaucoma because there are anatomical pathologies that are at play here and procedures are available for glaucoma. Let's talk through those and when we use them, when we use them first line, and when we use them if the drops are not able to get the pressure down enough.

Yeah, glaucoma is undergoing a bit of a revolution at the moment in terms of offering patients non-drop treatments, the most popular of which is probably a laser procedure called selective laser trabeculoplasty (SLT). This is done for patients with open-angle glaucoma, so where the anterior chamber angle is sufficiently open for us to be able to see the drainage channel of the eye, which is marked as the trabecular meshwork. What the laser does is essentially create a mild inflammatory response in that trabecular meshwork for the structure to allow increased outflow of the aqueous humour and thus reduction in the intraocular pressure.

Now, luckily, the trabecular meshwork doesn't have any pain receptors, so it's essentially a painless procedure, and some high-level evidence has shown that it generally has an overall success rate of about 75% in patients with high intraocular pressures or open-angle glaucoma. Because of the issues that we've seen with long-term drop use or with drop compliance, a lot of ophthalmologists would offer SLT as a first-line treatment after determining that the angle is open. Another laser treatment that is used is for cases of patients who have narrow angles, and that procedure is called a laser peripheral iridotomy.

This essentially creates a hole in your iris, a very, very small hole that's invisible to the naked eye that equilibriates the pressure both in front and behind the iris and opens up the anterior chamber angle in patients whose angles are closed. Large studies have been conducted on this procedure, which have shown that performing it decreases your risk of an acute angle-closure episode by about 50%. And some people do choose to have this done in cases where their anterior chamber angle may be narrowed.

Interesting. And you did mention that because the trabecular meshwork doesn't have any pain receptors, that's a pretty well-tolerated procedure. Is this just done in rooms?

Yeah, we perform these in little laser rooms in our clinic. We numb the eye surface with some topical anaesthetic drops and place a special lens on the eye that reflects the laser into the trabecular meshwork. The trabecular meshwork is actually invisible when looked on face with the slit lamp. So we apply a small lens on the eye surface, which sometimes patients can find a little bit irritating, especially if it rubs against their eyelashes, but the actual procedure itself is painless and generally very well tolerated.

Is that the same for the iridotomy as well or is that a quite different type of procedure with a different setting?

The iridotomy is slightly painful, especially if it's performed in episodes of acute angle closure. We also know that there are ethnic variations in the thickness of the iris in different patients. So patients who have perhaps a Scandinavian or Anglo-Saxon heritage with green or blue irides are able to have that iridotomy created with very little energy versus patients who may come from East Asia or Africa who have thick brown irides and may require a significant amount of energy to create a patent iridotomy. And because the iris does contain some pain receptors, the patient does feel it a little bit more than a trabeculoplasty, but it is still a fairly well-tolerated procedure that, again, is done in an outpatient setting.

Sounds pretty attractive not to have to use eyedrops every day. It makes sense that people might want to explore these options with their ophthalmologist.

Yeah. The risk of an acute angle-closure episode is generally fairly low. There was a very large study that was performed in China called the ZAP study, which showed that in low-risk patients, so patients who just had narrow anterior chamber angles but no real other risk factor for acute angle closure, the risk of an acute angle-closure episode was about 1% over 5 years, but an iridotomy is still performed because it is a very serious thing for the eye to undergo. I often explain it to patients as almost like a heart attack of the eye. So if we've got a relatively safe procedure that reduces that risk by 50%, I find that the majority of the patients that I'm counselling still prefer to have the procedure done even though the likelihood of having it may not be particularly high.

As we wrap up today, I know we've covered it throughout our conversation, but I will point everyone to Box 2 in the article, which is a really, really handy table of who we need to refer to an ophthalmologist today, who we need to send in a couple of weeks, and who can be seen on a routine basis. Sometimes at the end of an article, we do think about what might be in the research pipeline, what are some emerging therapies overseas or still in development. What are you excited about that might be coming to Australia in the next 5 or 10 years?

There has been some increased research in medications. There are several new medications that are available overseas, which have been shown to reduce intraocular pressure, at least as well as the prostaglandin analogues, but they do have side effects and are not always particularly well tolerated. These include ROCK [Rho-kinase] inhibitors such as medications called netarsudil or ripasudil, which lower intraocular pressure by increasing outflow through the trabecular meshwork. There are also emerging ways in which the selective laser trabeculoplasty can be performed.

There is emerging technology looking at perhaps performing this laser without the use of a lens, so essentially from the outside in rather than using the lens to reflect light from the inside of the eye. There's also more downstream research, especially conducted at the Centre for Eye Research Australia, looking at optic nerve protection and IOP independent treatments to either prevent glaucoma damage or regenerate optic nerve tissue, but those are probably many years away, albeit a very interesting area of research.

Thanks very much, Alp, for talking with us today. I'm sure I'm not alone in finding the eye extremely complex, and it is really helpful to have a clear refresher on these practice points relevant to all health practitioners.

Thank you, Laura. It's been a pleasure to talk to you about glaucoma, and thank you once again for your interest in our subspecialty.

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