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Report

The future of glaucoma on show in Melbourne

02/07/2019By Lewis Williams PhD
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The 2019 edition of the World Glaucoma Congress was held in Melbourne from 27-30 March at the Melbourne Convention and Exhibition Centre. In part one of his report, LEWIS WILLIAMS relays all the latest developments that have been made across the broad field of glaucoma research.

The World Glaucoma Congress (WGC) is an initiative of the World Glaucoma Association (WGA), an organisation that bills itself as an independent, impartial, ethical, and global group dedicated to glaucoma science and care. Its primary aim is to eliminate glaucoma-related disability worldwide. The WGC is held every second year, with this year’s event held in Melbourne from 27-30 March.

The local organising committee read as a who’s who of Australian glaucoma science and practice. The WGA boasts additional Australian connections, starting with current president and recently appointed managing director of Melbourne’s CERA, Professor Keith Martin. Sydney-based ophthalmologist Clinical Associate Professor Paul Healey is the WGA Treasurer.

The academic program was supported by industry-sponsored symposia, a glaucoma film festival, scheduled poster sessions, wet labs covering relevant techniques, and a trade display. After the official opening ceremony, the program proper was launched with the Presidential Symposium, titled Game Changers in Glaucoma.

Game changers in glaucoma

Professor Robert Weinreb, chairman and distinguished professor of ophthalmology and director of the Shiley Eye Institute at the Department of Ophthalmology, UC San Diego, was one of the many leading glaucoma figures from around the world that presented at the WGC. His first presentation was titled: Making Sense of IOP in Glaucoma Management.

His opening statement was that single measures of intraocular pressure (IOP) were “an absurd way of managing glaucoma”, especially in view of the diurnal variation known to exist. He reported that circadian rhythm was also not relevant, because IOP “varies all the time, varies at a single time, as well as over time”. In fact, he described repeated values taken at a particular time as a “lottery”, since IOP varied day-to-day, at the same time of day, and over 24 hours. He stated that the worst time of day was in the early morning. Other factors affecting IOP include cortisol levels, heart rate, and blood pressure.

Patients with primary open angle glaucoma (POAG) have higher frequencies and more severe episodes of silent myocardial ischemia, and stroke sufferers are more likely to report increased arthritic joint pain and joint awareness. In afternoons and evenings, sufferers are more likely to experience asthma, elevated blood pressure, and heartburn.

Overnight there is an increase in blood sugar levels, blood pressure, and body temperature, as well as a lowered heart rate. However, IOP increases overnight. In about 66% of people, the IOP is highest and the aqueous outflow the lowest when supine during sleep. However, the episcleral venous pressure exhibits little or no change. Importantly, ocular perfusion pressures are lowest at night, the time when beta-blockers are ineffective.

Ocular perfusion pressures (systolic and diastolic) are equal to systolic and diastolic blood pressures minus the IOP. To provide a diurnal increase in perfusion pressures, prostaglandin analogues (PGAs) that work night and day are preferred. Carbonic anhydrase inhibitors (CAIs), such as acetazolamide, also offer diurnal efficacy. Regardless, Weinreb supported laser trabeculectomy as a suitable glaucoma treatment because it too works night and day.

Harking back to the absurdity of single IOP measures, even in a consulting room setting, he raised the desirability of an implantable IOP sensor that could be inserted during cataract surgery, so that IOP can be measured continuously if needed. He noted that the actual human diurnal IOP range has yet to be determined, and continuous measures of IOP will give better insight into both it and the glaucomas. His parting advice was to prescribe PGAs as first-line therapy and CAIs as second-line treatment.

Professor Tony Realini, director: glaucoma fellowship, and clinical research at West Virginia University followed with a lecture complementing Weinreb’s titled: The Role of SLT (selective laser trabeculectomy). In the context of the POAG options of medication, laser treatment, or surgery, he examined safety and efficacy, prioritising safety.

He described the glaucoma medications as being “mostly safe, less effective, and subject to poor compliance”, and surgery as being “less safe but having greater efficacy”. He also believes that the risks of surgery are overstated. Quoting the CIGTS (Collaborative Initial Glaucoma Treatment Study, 1999) and the TVT (Tube vs Trabeculectomy Study, 2005) he accepted that surgery has complications but stated that most adverse outcomes were self-limiting, with no or few threats tovision experienced.

The downsides of medications include the ongoing issue of compliance, tolerability of the pharmaceuticals used, the cost of treatment, and the frequent need to prescribe multiple drugs to achieve a satisfactory outcome. His approach is laser treatment first because it has no compliance issues and in the US, SLT is covered by medical insurance, whereas medications are often not.

As far back as the 1980s, SLT was shown to offer better results that medication. He admitted that in SLT it is more difficult to accurately target tissue, but progressive changes in the visual field (VF) and optic nerve head (ONH) were better with laser treatment. He rated the earlier argon laser trabeculoplasty (ALT) as inferior to SLT. Importantly, he reported that there are no complications from repeated SLTs.

In light of several clinical trials that showed the superiority of SLT versus alternative therapies, including the effects on quality of life, Realini posed the question: Why hasn’t SLT become the first line of glaucoma therapy? He also believes it is time to discuss if SLT is a barrier to the implantation of minimally invasive glaucoma surgery (MIGS).

His experience suggests that SLT needs to be repeated somewhere between every one and three years, albeit with the expectation that the IOP change achieved from the initial SLT is unlikely to be equalled with subsequent treatments. Because it is so difficult for patients to make informed decisions about their glaucoma treatment, he suggested ophthalmologists should add their personal preferences to discussions. However, he admitted there can be ethical overtones to encouraging specific treatment options.

Side effects of SLT can include inflammatory cells in the anterior chamber (AC) for one to seven days, although rarely is there flare in the AC. AC cells and possibly flare are more likely in people of colour. No anti-inflammatory treatment is required after SLT, and attempts to use it have made no difference. There are no ramifications for the crystalline lens as a result of SLT, so secondary cataracts are not an issue.

Worldwide, there have been 11 reports of transient corneal oedema, but questions have been raised about the possibility that the corneas affected had corneal pigment deposits that resulted in very localised heating due to laser energy absorption by the pigment. Realini advises 360 ° trabeculectomies bilaterally, but if the patient’s angle is heavily pigmented or suffers from pigment dispersion syndrome, he recommended treating 180 ° in the first session and completing the task a week later.

KEYNOTE SPEAKERS

Annie Gibbons

Christopher Grikscheit

Ivan Goldberg

Grant Wilson

Michael Skalicky

Paul Healey

Robert Weinreb

Tony Realini

 

Glaucoma Australia's Patient Symposium

Led by Glaucoma Australia’s CEO Ms Annie Gibbins, the symposium attracted a large number of glaucoma patients, many of whom were already well informed judging by the conversations and questions that ensued. One of the main attractions was the address by Professor Ivan Goldberg whose involvement with GA & glaucoma patients spans many years. His communications skills are well known and a significant drawcard. He has appointments at Sydney Eye Hospital and is a past head of various glaucoma societies both locally and overseas.

He confirmed to the audience that glaucoma was still the most common cause of preventable blindness, is a progressive disease that gave no warning of its presence until moderately advanced, treatments are usually effective, requires life-long management, and compliance remains the biggest problem.

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Detailing the effects of the disease, he targeted retinal ganglion cells (RGCs), noting that by the age of 50, some 250,000 of the normal population of around 1.2 million RGC were “gone” in non-glaucomatous people. When glaucoma is diagnosed, one aim of treatment is to slow the rate of glaucoma-accelerated RGC loss so that it approximates the normal loss rate.

He described glaucoma as a condition that “erodes” nerves and increases the depth of the cupping of the ONH. He confirmed that the disliked visual field testing is still the main test of retinal function. In his view, there is a need for an alliance between the patient and the practitioner, and a patient-centric approach was one of the best ways of achieving it.

Clinical Associate Professor Paul Healey, who holds positions at USyd and in private practice, followed Goldberg. His presentation was titled Lab Based Research. He gave genetics as possibly the most common cause of glaucoma and nominated it as being one of the most inherited diseases, making lifestyle largely irrelevant. He floated questions about whether it is possible to identify those susceptible, whether genes be manipulated beneficially, and even if those things were possible, can we afford to do it as a society.

In some cases, genes with small variations can be associated with glaucoma. However, in a 1997 paper that had Professor David Mackey (CERA, later Lions Eye Institute, Perth) as a co-author, a gene that causes POAG was identified but could only explain about 3.9% of cases. To date, some 12 genes have been implicated in glaucoma’s aetiology, but almost 57% of people with those genes do not have glaucoma, suggesting the situation is more complicated than first thought. One suggestion is a combination of genes is required to result in disease.

Can genes be manipulated? Healey noted that gene therapy, a 1977 idea, was a way of altering a disease pathway beneficially, often using a viral ‘Trojan horse’ to get the genes required into the eye. He gave the gene therapy strategies as: the introduction of a missing gene (haplosufficiency), preventing the ongoing activity of an undesired gene (gene silencing), and improving the local gene environment (gene modulation).

According to Healey, some genes increase neuron susceptibility, while in other cases there are more genes present than needed. He saw potential for geno-pharmaceuticals made in the patient’s eye, expecting that lower dosages would be required alongside fewer side-effects. All stages of a disease pathway can be affected: gene creation, their effects, and the gene regulators. Those proposed treatment possibilities amount to personalised medicine.

Another approach that is the subject of much research is that of neuroprotection – how functioning RGCs and neurons can be protected from deleterious processes in disease. In glaucoma, BDNF transport is impeded and, in animal studies at least, about 90% of the damage can be reduced by treatment. Already, a Japanese pharmaceutical company has acquired the IP rights to the research.

Are such treatments likely to be affordable? Healey believes so, based on the expectation that mass production will lead to cheaper and quicker techniques being developed. Importantly, he pointed out that there were no ongoing treatment costs incurred. In his view, we cannot afford not to do it. He described gene therapy as 21st century pharma. He did not hold out much hope for routine genetic testing because of the ‘who’ and ‘when’ factors which, when added to the rare ability to correct any diseases identified, makes the whole idea less attractive.

Dr Simon Skalicky from the Royal Victorian Eye and Ear Hospital and a federal GA councillor, gave an overview of clinical advances in glaucoma. To the lay audience, he described glaucoma as a progressive, irreversible disease of the optic nerve. Clinically, glaucoma management involves measurement of the IOP, assessment of the visual fields looking for losses, and viewing of the optic nerve head. Treatment was a lowering of IOP if it is elevated via medication, laser, or surgery. He told the audience that monitoring, including with OCT, was just as important as treatment.

He mentioned iStent implantation (bypasses the trabecular meshwork, the stent’s head is located in Schlemm’s canal) at the time of cataract surgery and the XEN Gel Implant (non-biodegradable, gelatin, in the sub-conjunctival space) as examples of a MIGS approach to treatment. Where medications are used, the use of preservative-free options was advised.

He equated early detection with sight saved, and described SLT as both a means of increasing the drainage pathway and a way of stimulating the cells of the trabecular meshwork. He described the implantation of two iStents as being the functional equivalent of one type of glaucoma eyedrop. Implanted iStents will at least reduce the need for eyedrops, even if they do not eliminate it completely. The XEN Implant is used in unstable glaucoma cases. Sometimes it is necessary to use a combination of therapies.

The floor was then handed over to a glaucoma patient to relay their personal experiences and give their perspective. Mr Christopher Grikscheit has had his glaucoma diagnosed for 12 years, and reported slower visual perception, decreased-contrast vision, problems with computer screens, and bumping into things. He has magnifying glasses distributed throughout his home. He experiences good days and bad days visually, and appreciates the wealth of glaucoma information available online. In his view, glaucoma management is the patient’s responsibility and good communications between the relevant optometrist and ophthalmologist is essential.

GA’s CEO Ms Annie Gibbins then delivered an overview of what support GA was able to provide to patients. Worldwide, glaucoma will affect 79 million people by 2020. In Australia, there are estimated to be 18,000 people who are either blind or severely vision impaired as a result of their glaucoma. There are estimated to be about 300,000 living with glaucoma, some 150,000 of which are unaware or undiagnosed. Surveys suggest that 90% of Australians rate sight as their most valued sense, with some 60% claiming that vision loss is worse than a heart attack or the loss of a limb.

GA offers appropriate referrals, free educational materials, and patient support. Those materials emphasise the risk factors: elevated IOP, being of Asian or African descent, being diabetic, some refractive errors, and being over 50 years of age. She likened GA to being the side-kick to the professionals on the glaucoma referral and treatment pathway.

She itemised the four stages of the glaucoma journey as: suspected diagnosis, confirmed diagnosis, adherence with prescribed treatment (often with the help of family, partners, and carers), and finally, living with glaucoma. Some 23-56% of sufferers have a family history of the disease. As is well documented, only 36-50% of sufferers are fully compliant with prescribed treatment 12 months after a glaucoma diagnosis.

Mr Grant Wilson from Vision Australia provided some insight into the difficulties experienced by glaucoma sufferers. Going back 30 years, he described their job prospects as being piano tuners and switchboard operators. Now with smartphones, apps, GPS devices and soundscape technology it is possible to travel and retrace steps in relative safety. Visual aids targeting factors like glare reduction, suitable lighting, and shading also help.

The ubiquitous personal computer in all its guises has decreased both the need for visual aids and the importance of CCTV-based magnifying devices. Text-to-voice scanning technology such as the OrCam MyEye2, a spectacle-mounted aid, has also played a part. Other aids include QR code scanning, people-recognition systems (from tagged photos), and Aira, a network of trained professional agents to whom the blind or vision impaired can connect with to be informed of what they are ‘looking’ at, what’s in front of them, and details of their immediate environment.

Other possibilities include IrisVision, a wearable device with powerful magnification capabilities, especially at distance, and personal digital assistants such as Google Home, Amazon Alexa, Windows Speech Recognition, and Apple Siri. With all the help available now, it is possible for the blind and vision impaired to undertake or continue full professional careers that were denied to earlier generations.

Perimetry update

Professor Murray Fingeret
Professor Murray Fingeret

Optometrist Professor Murray Fingeret is a founding member and inaugural President of the Optometric Glaucoma Society. He is also a clinical professor at SUNY’s College of Optometry, NYC. He provided an overview of current methods of perimetry including the test offered by the established Humphrey Field Analyser (HFA), the iPad-based Melbourne Rapid Fields, and nascent VR headset-based technology. He predicted that home OCT devices will be available ‘soon’ and for IOP determination, the Icare HOME rebound tonometer is already available.

Fingeret made the observation that disease progression was not going to be determined validly by a once-a-year assessment. He predicted that VR will change perimetry forever and, given that both parties on either side of a perimetric device dislike the task, anything that can improve the patient experience will be welcomed. He expects that eventually, patients will be able to do perimetry themselves.

Currently, a HFA SITA Standard and SITA Fast are widely used. A study by Saunders et al., 2014 confirmed that while SITA Fast was only slightly less precise than SITA Standard, the difference is unlikely to be a problem when monitoring VF deteriorations. For the convenience of all those involved, SITA Fast has become the preferred VF test.

The Australian release of an evolved version, SITA Faster, is imminent following its 2018 US release. Its test-retest data is encouraging and the 24-2C version was mentioned specifically. Fingeret posed the question: Does glaucoma impact the central retinal region more given that 50% of retinal cells are located there? To address concerns, the 24-2C test added 10 additional test points centrally. The alternative 10-2 test cannot adequately monitor changes over time.

Part 2 of this report will appear in the next issue of Insight.

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