CAKE POST (WGC 2021 Edition) - ISSUE 2

On the Hunt for New, Modifiable Risk Factors in Glaucoma

Ah, the age-old question: What came first, the chicken or the egg? While that answer is still under debate, glaucoma specialists have their own version of this query: Are there modifiable risk factors for glaucoma — like diet, exercise, air pollution, sleep and systemic medications? And can an increase in one (or more) of these factors lower the odds of developing glaucoma?

Thus, on Day 2 of World Glaucoma e-Congress (WGC 2021), an expert panel shared their research on this interesting topic.

“Currently, the only modifiable risk factor for glaucoma is intraocular pressure (IOP) and we’re really good at lowering this — however, some patients continue to progress despite low IOP,” said Dr. Yvonne Buys (Canada), who co-moderated the session, along with Dr. Anne Coleman (USA). “Today, we will explore other possible risk factors.”

It’s what you eat

While the origin of the phrase “you are what you eat” can be attributed to France in the 1820s, the question is: Should we also account for genetics when assessing the relationship between diet and complex disease? This question was posed by Prof. Louis Pasquale, professor of ophthalmology at the Icahn School of Medicine at Mount Sinai, (New York, USA). He said that the answer appears to be “yes.”

“We published a study showing dietary nitrates from leafy green vegetables were associated with a reduced risk of primary open-angle glaucoma (POAG),” shared Prof. Pasquale,

by Brooke Herron

adding that the biologic effects of diet need to be considered relevant to the glaucomatous disease process.

“I would hypothesize that mitochondrial function is an excellent target to look at in this regard,” he continued. Further, nicotinamide (or vitamin B3) may improve mitochondrial function in glaucoma. “There is strong preclinical data that high dose vitamin B3 is neuroprotective in glaucoma models.”

Prof. Pasquale concluded: “Certainly, a dietary interventional study with positive results would represent a major advance in the field of glaucoma.” Food for thought, indeed.

It’s what you breathe

Prof. Paul Foster, professor of glaucoma studies at Moorfields Eye Hospital, (London, United Kingdom) has been studying the relationship between air pollution and glaucoma rates. He explained that although air pollution consists of gaseous, organic compounds (i.e., metals) and

particulate matter (PM), it’s the last one — PM — that has the greatest link to human disease.

He then pointed to a research paper (the Chennai Glaucoma Study) that has long interested him: “It raised questions about possible environmental factors affecting the rate of glaucoma … and the key finding here is that the rate of openangle glaucoma in urban participants was double that in rural populations.”

More recently, there’s been a study looking at the relationship between black carbon exposure, subdivided according to the genetic predisposition to oxidative stress and IOP. “What was found, was that the people who were exposed to higher levels of black carbon were more likely to have a higher IOP if they were predisposed to oxidative stress, compared to those who weren’t,” he explained.

Prof. Foster then detailed a study performed in the U.K. that studied PM2.5 in 2010. “The headline result was that PM2.5 levels were associated with a 6% increase in the odds of self-reported glaucoma,” he shared. “However, the most striking finding was that a much thinner ganglion cell-inner plexiform layer (GC-IPL) with increasing levels of PM2.5 exposure and this appeared to be independent of IOP.

It’s how much you move

“The idea that exercise might protect against glaucoma is not at all a new one,” began Dr. Pradeep Ramulu, a glaucoma specialist at John Hopkins Wilmer Eye Institute (Maryland, USA).

He also came across this concept when looking into dose-response between visual field (VF) loss severity and objectively measured physical activity (PA) in glaucoma patients: “We found that indeed, people who are more affected by visual field loss did less physical activity.”

In his study, interestingly, PA was not affected by mobility problems or fear of falling — which was specific to glaucoma. Dr. Ramulu then pointed to a male runner’s longitudinal study, which showed that PA could protect

against glaucoma: “Men who ran faster at baseline were less likely to get glaucoma (37% less incidence), and in fact, those who ran the fastest — none of them got glaucoma. There was also a lower incidence in those that ran more, suggesting that it might not only be fitness but also the amount of activity that people do.”

However, he said that to really believe there is an association, there has to be a mechanism behind it — and exercise has been proven to show numerous benefits. “In mice, for example, the positive effect of exercise has been shown to be mediated through BDNF (brain-derived neurotrophic factor) and its receptor TrkB,” said Dr. Ramulu. “There’s also strong evidence that in humans BDNF is released with exercise and that it’s also less available in patients with glaucoma.”

He continued: “We’ve also found that there could be benefits of physical activity on treated glaucoma patients as well … we found that more active patients have slower progression.”

So, does he tell his patients to exercise? “Absolutely, I do,” concluded Dr. Ramulu, adding that although definitive evidence is lacking, advocating for exercise is good medicine.

It’s what you put in your body

Many glaucoma patients use a number of systemic medications, said Dr. Anthony Khawaja, a glaucoma specialist at Moorfields Eye Hospital. Along with colleagues, he has recently published a review on systemic medication that may modulate the risk of glaucoma. He then covered various medications that can have an effect.

“Medications that are known to increase openangle glaucoma (OAG) risk — and this isn’t controversial — we all know what steroids do.

Bang,bang:Change

And it occurs with all types of steroids, particularly those that end up close to the trabecular meshwork (TM), so more commonly with intraocular compared to topical or oral,” explained Dr. Khawaja.

Alternately, there are medications that are known to decrease OAG risk. This includes systemic beta blockers, which profoundly lower IOP. He then covered medications that are known to increase acute angle-closure, like anticholinergics, as well as those that are implicated (which is a long list).

So, what do these drug-glaucoma associations mean? “They might mean that the drug affects the biology of the glaucoma, or it might be the underlying disease you’re treating that affects glaucoma … maybe it’s just the prescribing patterns or other confounding factors. Or could it even be something like ethnicity?” he shared in conclusion.

It’s how you sleep

The final presenter was Prof. David Mackey, professor of ophthalmology at the University of Western Australia, who discussed if obstructive sleep apnea (OSA) is linked to glaucoma. OSA results in physiological changes during sleep and has been strongly associated with hypertension, myocardial infarction, stroke and increased mortality.

“Eye disease is linked to OSA, including glaucoma — both normal tension and open-angle,” said Prof. Mackey. “The evidence for association of OSA and glaucoma has been conflicting, with many papers showing an association … but there are some well-designed large studies that did not detect an increase in glaucoma in OSA.”

From three large studies (Raine, Busselton, and UKBB and CLSA), he concluded that: “We do find an association, but these are not large associations and further research is required.

This session certainly gave us a lot to digest — and if these modifiable activities can help prevent or slow the progression of glaucoma, we’re here for it.

yourdietanddon’t getglaucoma…?

A Cat By Any Other Name

And the numerous ways in which to treat glaucoma

by Hazlin Hassan

Just as there is more than one way to skin a cat (so they say) … there is more than one approach to glaucoma treatment.

In a highly enlightening session by the Asia-Pacific Glaucoma Society at World Glaucoma e-Congress (WGC 2021) called Dilemmas in Glaucoma Management: The Asia-Pacific Perspective, glaucoma surgeons took opposing sides on how to manage the different types of glaucoma.

On managing APAC: Surgery or medication?

The best initial management of acute primary angle closure (APAC) is to do an immediate argon laser peripheral iridoplasty (ALPI) and early lens extraction, said Professor Clement Tham, chairman of the Department of Ophthalmology and Visual Sciences at the Chinese University of Hong Kong.

He argued that long-term clinical outcomes of immediate ALPI showed no systemic adverse effects and no serious local adverse effects compared to systemic medications, which had potentially serious systemic adverse effects.

He acknowledged, however, that there may be limitations to laser peripheral iridoplasty (LPI): “The laser machine may not be readily available around the clock everywhere, it requires expertise and experience, and it still takes time to reduce IOP.”

Prof. Dr. Mimiwati Zahari from University Malaya Medical Centre (Malaysia)

disagreed and said that ALPI has disadvantages including “that it could be costly for patients to undergo the procedure, and it required a surgeon with sufficient skills.” The procedure is

also not effective in eyes with significant peripheral anterior synechiae (PAS).

Further, there are many potential complications of ALPI including iris atrophy, corneal endothelial burns and IOP spikes, among others. It could also cause injury to the cornea and infection, as well as added pain. In addition, it will not eliminate pupillary blocks.

In summary, medical therapy versus ALPI/AC paracentesis may give a slower rate of IOP lowering, but there is no evidence that the short delay causes more damage to the optic nerve or anterior segment structures.

“Medical therapy is safe, without the surgical and laser-related potential complications, which can be made worse by the technical difficulties faced in an acute setting,” she said.

“There are no long-term benefits in choosing ALPI/AC paracentesis over the traditional and well accepted method of medical treatment. Given its relative safety and efficacy, the initial treatment for acute angle closure should be medication.”

On managing JOAG: Trabeculectomy or MIGS?

Dr. Visanee Tantisevi, associate professor at the Faculty of Medicine, Chulalongkorn University (Thailand), argued for the use of MIGS to treat uncontrolled IOP in juvenile open-angle glaucoma (JOAG) — a rare subset of glaucoma diagnosed in individuals aged between 3 and 40-years-old. More often than not, these patients have an active lifestyle and may be busy taking care of their families — or they enjoy working and need to resume their daily life as soon as possible.

She said that the drawbacks of trabeculectomy are that it can be unpredictable and it requires suturing. On the other hand, MIGS requires less operation time, causes less traumatized tissue, and allows for a more controllable aqueous flow guard.

Meanwhile, Dr. Vijaya Lingam, senior consultant at Medical Research Foundation, Sankara Nethralaya (India) argued for the use of trabeculectomy for uncontrolled IOP in JOAG.

“JOAG patients are diagnosed at a young age, so they will have a longer life expectancy. The resulting visual impairment and blindness [from glaucoma] can significantly impair the patient’s quality of life and limit daily living activities. So, it is important to control the IOP,” she said.

Most of the time, doctors start with medical management, but in many cases surgery becomes essential at some point. “The challenge we have with the surgery is to preserve the vision by controlling the IOP,” continued Dr. Lingam.

However, challenges arise from various factors: young age, a high IOP with progressive damage, the disease’s genetic nature with angle dysgenesis, and because it is a rare disease.

“The best shot we have is to do a procedure that gives good control of IOP. In a rare disease with a poor prognosis, the first shot is the best. Choose a surgery that gives good outcomes,” concluded Dr. Lingam.

Top Surgeons Share Their Pearls for Filtering Surgeries

by Hazlin Hassan

When blebs get complicated

For complications involving blebs, Dr. Tarek Shaarawy, head, Glaucoma Sector, Geneva University Hospitals, Switzerland, provided a way to fix these pesky things.

All things bright and beautiful — or in this case — all things to do with filtering surgeries. In this session on Day 2 of World Glaucoma e-Congress (WGC 2021), renowned glaucoma surgeons from around the world share their Advanced Tips for Filtering Surgeries.

Tips on stents and shunts

Allergan’s XEN Gel Microstent and Santen’s PreserFlo MicroShunt are just some of the tools developed for subconjunctival MIGS, created with the aim of improving both predictability and the safety profile of bleb-forming procedures. During this session, two surgeons shared their experience on how best to utilize these cutting-edge instruments.

“The ideal placement of the XEN Gel Stent is as easy as 1,2,3,” said Associate Professor Shamira Perera, a senior consultant ophthalmologist, Glaucoma Service at Singapore National Eye Centre, adding that the injector can be held in different hand positions.

He noted that it’s important to check that you have the stent placed in the needle, and to be careful not to turn it upside down because it can slip out. “It’s also important to have your Healon and air syringe at hand for injection into the supra-Tenon’s space,” shared Prof. Perera.

“The different hand position for entry depends on your approach: You can either go for the superior approach and a backhanded insertion, or we can go for a temporal sitting approach.

It’s important to avoid the trabecular meshwork because it can bleed,” he added.

The PreserFlo MicroShunt is an aqueous shunt — a small, tube-like drainage device used to control IOP by creating an escape tunnel to safely drain any excess fluid inside the eye into a small blister, or filtering bleb, behind the eyelid. From there, the fluid is slowly absorbed into the bloodstream.

“I’ve had the PreserFlo for three years now and I think genuinely it has been a bit of a game-changer,” said Dr. Leon Au, consultant ophthalmologist, Manchester Royal Eye Hospital, United Kingdom.

Some of the tips he shared: “You definitely want to stay away from the superior rectus. Apply high-dose mitomycin-C (MMC) with sponges, not by injection. Ensure meticulous closure of the tenon over the device which can sometimes take 45 minutes.”

“Some people will say that there are good blebs and bad blebs. I would argue that all blebs are bad because all blebs are not natural,” said Dr. Shaarawy. “We look at those blebs that we create surgically, and we think that we have gifted the patients with an incredible gift of beautiful reservoirs of aqueous, but it’s not really the case.”

He shared a case that was referred to him: a male patient with postop hypotony or low IOP, and a bleb that did not look very healthy. A thorough gonioscopy was carried out, but nothing was found; however, after pressure was placed, the bleb was found to be leaking.

While playing a video of the bleb revision surgery, he advised surgeons to be meticulous when fixing the bleb, which he likens to a house.

“Why remove the whole bleb? Let’s do some very meticulous dissection. Just remove the roof of the bleb. The part that is leaking, we dissect it very, very gently. I don’t want to damage anything under it. Remember that this is a bleb that is probably working very well. If I can just replace this area, then we can possibly live happily ever after. So, we remove this area. And now the question is, would it close by itself or do I have to do sort of an autologous graft? It seems to me that it is not too complicated to reconstruct the roof, so the roof has been demolished. Now we need to build a new one, and we think it is not too complicated,” explained Dr. Shaarawy.

Following the operation, the patient’s pressure rose to 11, and vision returned to 100%.

Singapore’s Glaucoma Doctors Deploy Telemedicine Amid Pandemic

by Hazlin Hassan

in the clinic, is being used to reduce in-person consultations. In addition to virtual consultations, it also helps to shorten waiting times in the clinic and pharmacy by delivering medications to patients’ homes.

“Between June 2020 to April 2021, we have seen 90 patients, the majority of whom were elderly and over the age of 65. Some 20% of these patients were escalated to the face-to-face clinic because of new complaints or elevated eye pressure,” said Dr. Yip.

Telemedicine is not a new concept but thanks to the coronavirus, the use of it has surged as doctors seek to keep the spread of COVID-19 at bay and maintain social distancing — all while continuing to provide healthcare services to patients. Such was the collective sentiment of the panel from the Glaucoma Association of Singapore who presented on Day 2 at the World Glaucoma e-Congress (WGC 2021).

A virtual glaucoma clinic, also known as the Glaucoma Observation Clinic (GLOC), at the Singapore National Eye Centre (SNEC), sees patients with eyes at low risk of developing significant visual loss, said Dr. Annabel Chew, a consultant at the Centre’s Glaucoma Department.

Those who test negative for glaucoma or who have stable glaucoma can get test results at home, instead of seeing a doctor to get the results. “The overall rate of glaucoma progression in our patients was 1.8%,” she noted.

The average time taken for the doctor to complete a GLOC review was 5.8 minutes, compared to 19.5 minutes in the glaucoma clinic. Doctors will be able to review a larger volume of patients in the same amount of time, she said.

“In conclusion, our SNEC virtual glaucoma clinics are efficient in managing stable glaucoma patients,

have been well received by patients, and increase the capacity of our conventional glaucoma clinic to treat patients with more complex needs.”

Numbers fall due to COVID-19 fears

During Singapore’s lockdown period, known as a circuit breaker in the citystate, Tan Tock Seng Hospital’s eye clinic saw a drop in the number of patients from more than 600 per day to 200. This fell to 137 per day on average during a COVID-19 outbreak at the hospital in May this year, said Dr. Vivien Yip, deputy head of service (glaucoma) at Tan Tock Seng Hospital.

“Patients fear contracting COVID-19, because of the long waiting times and the increased exposure to the virus in the clinic. Some glaucoma patients miss their appointments, they run out of their eye drops. And they may even have undetected progression of their disease,” she added.

Health care providers on the other hand, are struggling to deal with a backlog of postponed cases and surgeries, and trying to triage patients safely and efficiently. As a result, the Virtual Ophthalmology Service (TVOS), first conceptualized in 2018 to combat high patient loads and long waiting times

Serving international patients via telemedicine

Many people from around the region flock to Singapore to seek medical care. But since the pandemic, overseas patients can no longer enter Singapore for their regular doctors’ visits due to border closures. This prompted Dr. Daniel Su, from Eye & Retina Surgeons, Singapore, to offer patients telemedicine service.

“As the months progressed, it was clear that international travel restrictions were going to be in place for a lot longer,” he said. Therefore, Dr. Su advised patients to find a local ophthalmologist to perform an examination and then he would schedule video calls with them.

“After the examination is completed, we would all gather around the webcam and discuss the patient’s condition and answer any questions,” he explained, adding that this gave patients reassurance during this challenging time.

“They want us to be aware of their progress, their eye pressure and the medications they’re using. They find comfort in hearing our voice and seeing us. Despite not being able to perform the physical examination ourselves, we are able to suggest changes to the management plan if needed,” concluded Dr. Su.

To MIGS or Not to MIGS

That is the Question

When it comes to glaucoma management, one of the most popular terms of late is MIGS, or minimally invasive glaucoma surgery. These procedures are less invasive than traditional glaucoma surgery and provide efficacy in lowering IOP — but are they for everyone? Experts weighed in on the subject matter on Day 2 of the World Glaucoma e-Congress (WGC 2021)...

Filtering versus MIGS

A debate for the ages: Which is better, filtering or MIGS? On the pro-filtering side was Dr. Antonio Fea from the Ophthalmic Hospital of Turin (Italy). Dr. Fea said there are several problems with MIGS. This includes a higher requirement of mitomycin-C (MMC), as well as the fact that posterior filtration determines less fibrotic reaction, among others.

But he said that the main issue is that MIGS is “an unknown and unproven pathway, whereas in filtration we have a procedure that is endorsed by years of clinical experience.” In addition, MIGS is an expensive procedure that the majority of people cannot afford.

Next, on the pro-MIGS side was Dr. Mitchell Lawlor from the University of Sydney (Australia). He said: “Although there are patients who are not best served by MIGS, there are many — such as those trying to reduce their use of topical medication and those who need only slight IOP reductions — who MIGS would work very well for.

Trabecular bypass with KDB versus Trabectome

Dr. Ricardo Guedes from the Paletta Guedes Eye Institute (Brazil) began by reminding the audience that the Kahook Dual Blade (KDB, New World

by Chris Higginson

Medical, California, USA) is a single-use ophthalmological knife that removes the trabecular meshwork (TM), whereas the Trabectome (NeoMedix, California, USA) uses plasma to cauterize and ablate the nasal arc TM.

While there are only a few studies that compare the two techniques, existing data suggest that they offer very similar results for IOP lowering. There is possibly a slightly better removal of the TM with Trabectome, where the KDB can provide a slight reduction in medication. He concluded that, “most research, especially randomized control trials, needs to be done to compare the two techniques in the future.”

GATT versus Viscodilation

Next, Dr. Paul Harasymowycz from the University of Montreal (Canada) compared gonioscopy-assisted transluminal trabeculotomy (GATT) with viscodilation.

He said that GATT can be used to remove 180 or 360 degrees of the TM and is usually reserved for young patients — especially those who are myopic or phakic. It generally achieves good results with a significant reduction in IOP, although it can result in hyphema.

“On the other hand, viscodilation, using stents similar to the Hydrus (Ivantis, California, USA), has been shown, at 12 and 24 months, to lower IOP, with most patients having IOP of ≤18 mmHg,” shared Dr. Harasymowycz, adding that it also offers freedom from secondary surgery and less medication.

iStent versus Hydrus

Clinical trials show that Hydrus is a little more efficacious and offers almost five times the lumen outflow compared to

the original iStent (Glaukos, California, USA), which itself provides more than twice the flow of the iStent Inject (Glaukos), said Dr. Leon Au from the Manchester Royal Eye Hospital (United Kingdom).

He said the iStent Inject is significantly simpler and easier to use, although it needs to be done carefully as it can be over-implanted due to the firing mechanism. The newly released iStent Inject W (Glaukos), however, has a wider flange, which helps avoid the problem of over-implantation.

XEN versus Preserflo

Dr. Kaweh Mansouri from the University of Colorado (USA) described the XEN Gel Stent (Allergan, an AbbVie company, Dublin, Ireland) as a 6 mm cross-linked gel stent and the PreserFlo (Santen, Tokyo, Japan) as an 8.5 mm microshunt, with a slightly larger luminal flow.

He discussed the literature analyzing both techniques and concluded that they had comparable results in POAG eyes in terms of IOP lowering and surgical success, with a similar safety profile. Dr. Mansouri concluded that a head-to-head comparison is necessary.

The economics and ethics of MIGS

Although researchers are good at announcing their conflicts of interests, it is well known that there are often further conflicts. “We may be crossing the line into papers becoming product promotions rather than scientific studies,” cautioned Dr. Yvonne Buys from the University of Toronto (Canada).

MIGS uptake has been slow in some places due to the uncertainty of evidence. In some cases, it has been found to not be cost-effective in comparison to filtration surgery or laser therapy. Therefore, people must ask themselves: What is the point of having devices or medicines that are not affordable to the majority of the public?

Indeed, there were many more highlights and sound arguments in this session than we could ever cover here … but these insights are always appreciated as the rise of MIGS continues.

Achieve consistent, long-term IOP control for end-stage glaucoma.

The Molteno3 ® features a smooth polypropylene plate that is designed to reduce bleb brosis

SMALL IN SIZE, BIG ON EFFICACY

The Molteno3® SS-185 offers the same clinical ef cacy as larger plates.

Molteno3® is the slimmest plate on the market at 0.4mm and slides easily between the EOM.

Time for Consistent, Long-term IOP Control in End-Stage and Complex Glaucoma

by Brooke Herron

In some instances, it’s best not to mess with a good thing. A good example of this is the Molteno3® Glaucoma Drainage Device (GDD; Nova Eye Medical, Fremont, California), which was first introduced back in 1966. This device is the culmination of 50 years of R&D, and it not only illustrates the history and research into bleb formation and function, it is also considered to be the gold standard of GDD technology. The Molteno3 has been implanted in thousands of patients worldwide and delivers consistent, long-term reduction in intraocular pressure (IOP) in patients with severe or complex glaucoma.

Benefits of the Molteno3

So, what’s so great about the Molteno3? Well, at just 0.4 mm it’s the slimmest plate on the market, and its patented Primary Drainage Area technology enables it to achieve the same clinical outcomes as larger plate alternatives. What’s more? Because it slides easily between tissue planes and adjacent extraocular muscles, it allows for a shorter, more simplified surgical procedure with less patient discomfort. Plus, if needed, repositioning is relatively easy to achieve the desired outflow.

If you ask, most glaucoma specialists will have an opinion on blebs … and the good news here is that the device has a smooth, contoured polypropylene plate designed to reduce fibroblast cell adhesion, leading to a reduced risk of bleb fibrosis. Indeed, the Molteno3 has one of the lowest reported rates of bleb encapsulation.

Need for speed (in the OR)

Neither patients nor surgeons want long surgeries. Good news then: A 2020 study* published in Glaucoma Ophthalmology reported the surgical time of the Molteno3 SS-185 to be 15.7 minutes faster than the Baerveldt® BG-101-350 (Johnson & Johnson).

This data was from a retrospective, nonrandomized, noninferiority, multicenter study that compared the two devices — and ultimately reinforced the surgical utility of Molteno3 compared to Baerveldt. The Molteno3 was in target IOP range and also had a slight advantage in IOP reduction at 24 months compared to Baerveldt at 16.6 mmHg versus 17.0mmHg, respectively. This disproves the perception that a larger plate is needed in order to achieve long-term IOP reduction.

Moving on to failure rates: These were 27.5% for Molteno3 and 45.5% for Baerveldt. Impressively, the authors shared that 100% of the Molteno3 GDDs were implanted by residents or fellows — and this is testament to the simplified surgical technique required.

More data from WGC 2021

An abstract from the World Glaucoma e-Congress (WGC 2021) by Drs. Maxwell Dixon, and Arsham Sheybani, titled Differences Between Large Plate

Size Non-Valved Glaucoma Drainage Devices, identified differences in clinical parameters following placement of one of two non-valved GDDs in their largest commercially available size.

The authors performed a subanalysis on 99 patients who underwent placement of the 350 mm2 plate size Baerveldt (n= 63) or 245 mm2 Molteno3 (n=36), with or without concurrent cataract extraction and implantation of intraocular lens (IOL).

The authors found that average IOP following surgery was 14.3 mmHg with Baerveldt and 13.8 mmHg with the Molteno3 (p = 0.61) and IOP decreased an average of 9.1 and 10.2 mmHg with the Baerveldt and Molteno3, respectively (p = 0.55).

“Although both the Baerveldt and Molteno3 GDDs were similarly successful in lowering IOPs, most patients still needed to use pressurelowering medications following implantation,” said the authors in conclusion. “Overall, the use of either the Baerveldt or Molteno3 GDD is justifiable to lower IOP or reduce medication burden when more conservative management has failed.”

* Dixon AM, Moulin TA, Margolis MS, et al. Comparative Outcomes of the Molteno3 and Baerveldt Glaucoma Implants. Ophthalmol Glaucoma. 2020;3(1):40-50.

The LiGHT Study Brings SLT into the Light for Glaucoma Treatment

by Sam McCommon

SLT safety and efficacy: Firstline treatment status

Day 2 of the World Glaucoma e-Congress (WGC 2021) featured a clinical trial summary session, which led to some meaty information. If you want to stay abreast of the most up-to-date glaucoma studies, well, this is the presentation for you.

We’ll take a look at some of the highlights of the presentations — most notably the Laser in Ocular Glaucoma and Hypertension (LiGHT) study,¹ which presented some valuable takeaways. Let’s dive into the LiGHT study, because there’s some fun stuff in here.

Selective laser trabeculoplasty for the win

IOP controlling eye drops have long been one of the first lines of defense against glaucoma, but the LiGHT study suggests that a change may potentially be in order. To keep you from having to skim too far, the conclusion is this: Selective laser trabeculoplasty (SLT) should be offered as a first-line treatment for openangle glaucoma and hypertension. SLT offers some significant advantages over eye drops.

The study was first referenced by Dr. Kuldev Singh, with Stanford University (California, USA). As Dr. Singh noted, the primary outcome studied was health-related quality of life (HRQoL) at 3 years; secondary outcomes included disease-specific HRQoL, clinical effectiveness and safety. The study compared a medication-first approach with a laser-first approach.

SLT and medications performed equally well regarding the primary outcome,

though SLT performed slightly better in terms of IOP goals.

One significant benefit of SLT, as opposed to medication, that Dr. Singh raised was that it was more cost-effective than medication, especially over the long-term.

But the cost of medications isn’t the only problem. Dr. Gus Gazzard, author of the study and ophthalmologist at University College London (United Kingdom), noted several other issues with medication. One of the most notable barriers is patient compliance, persistence and adherence: Dr. Gazzard pointed out that roughly one-third of patients discontinue or change their medication within the first year of prescription.

Dr. Singh did have a valid point regarding medicine and noncompliance, however — not all noncompliance is a bad thing since, in some cases, glaucoma is overtreated. Indeed, glaucoma medications can also lead to reduced surgical success rates and multiple side effects — both local and systemic.

With lasers, however, you know exactly who you’ve treated and how you’ve treated them — and patient compliance is a non-issue.

The safety of laser trabeculoplasty has improved recently, too. The original argon laser trabeculoplasty tended to burn the trabecular meshwork, whereas SLT leaves the meshwork much more intact — as Dr. Gazzard pointed out, even at microscope levels of 1230x, you don’t see signs of physical damage.

One of the most exciting outcomes of the LiGHT study was that 78% of the patients who had undergone the laser-first strategy and were at their target IOP at 36 months required no medications. That’s a huge difference compared to the medicine-first group, only 3% of whom were at zero medications at 36 months.

The IOP bit above is no caveat, either — 74% of laser-first patients were dropfree and at target IOP at 36 months. Furthermore, 77% of those eyes only needed one SLT treatment and there was only one IOP spike that required treatment out of 776 total SLT laser treatments.

In case you’re not tired of good news yet, SLT can also be repeated successfully, if necessary. It can also play a role in many secondary glaucomas as a second line of treatment.

There is one important caveat that Dr. Gazzard noted — SLT is probably less successful for those with their IOP uncontrolled on multiple (3+) medications.

“SLT should be considered for all newly diagnosed POAG/OHT patients as the primary treatment rather than medication. It should also be considered for any patients who are using eye drops and are not currently happy with their medication,” concluded Dr. Gazzard.

1 Gazzard G, Konstantakopoulou E, Garway-Heath D, et al., LiGHT Trial Study Group. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet. 2019;393(10180):1505-1516.

Giving Glaucoma Patients Hope with Regeneration and Restoration

by Brooke Herron

Currently, gene therapy and tissue regeneration are hot topics in medicine — and especially in ophthalmology. And on Day 2 of World Glaucoma e-Congress (WGC 2021), four experts shared the latest research, along with their insights, into this potential new treatment paradigm.

“We’ve learned quite a lot about different strategies and mechanisms to promote tissue engineering, regeneration and functional recovery, from the anterior part of the eye all the way to the brain. Now we have to implement this knowledge to find new therapies and apply it for the benefit of glaucoma patients,” began session chair Prof. Adriana DiPolo from the University of Montreal (Quebec, Canada). Let’s explore these ideas further now...

Growing back the optic nerve

The steps for regenerative medicine based on retinal ganglion cell (RGC) transplantation were covered by Prof. Toru Nakazawa from Tohoku University (Japan). He shared that there are many challenges facing the development of regenerative medicine in glaucoma treatment; however, techniques to generate RGCs from iPSCs (induced pluripotent stem cells) are progressing.

Prof. Nakazawa concluded that regenerative medicine based on RGC transplantation calls for research into the different steps of the research process, including identifying the cell source, transplantation, axonal growth, scarring, enabling synaptogenesis and topography.

Tissue engineering for the anterior segment

“I want to give my patients more than just hope, I want to give them a lower IOP,” began Prof. Nils Loewen from the University of Wurzburg (Germany).

He then provided an overview of how tissue engineering could help achieve this, including restoring outflow with drugs; trabecular cytoablation and repopulation; prostaglandin gene therapy; and chronic distal outflow tract dilation. He then covered each technique and its status in detail.

“We’ve restored outflow with drugs for some time and prostaglandins are particularly good at that,” said Prof. Loewen. “Trabecular cytoablation and repopulation, SLT does this quite well … the others are more or less experimental. Prostaglandin gene therapy has been shown — and it works. Chronic distal outflow dilation, I think we’re pretty close to that.”

Turning stem cells into retinal ganglion cells

“There are shortcomings in traditional models of glaucomatous neurodegeneration,” said Prof. Jason Meyer from the Indiana University School of Medicine (USA).

He shared that although rodent models have a high degree of diversity in RGC subtypes, very little of this actually translates into primates and humans.

“We also know that rodent models lack

a true lamina cribrosa … and this is the primary injury site in glaucoma. Thus, complementary models are needed to bridge this gap toward patient relevance,” Prof. Meyer continued, before discussing his lab’s research into RGCs derived from human pluripotent stem cells (hPSC-RGCs), which can provide insight into human-specific phenotypes.

“These phenotypes can be examined and serve as a platform for therapeutic development,” he concluded.

Gene therapy for optic nerve repair

“There’s been quite amazing progress in the use of gene therapy to treat inherited retinal disease … and gene therapies are also currently in development for the treatment of common eye diseases, and that includes glaucoma,” said Prof. Keith Martin, director at the Centre for Eye Research Australia.

“We’re getting to the point where we can use gene therapy as a tool in many different ways in glaucoma … but I think one of the really exciting things we can do with gene therapy is to stimulate regeneration and facilitate cellular reprogramming,” he continued.

Prof. Martin said that gene therapy is a realistic approach and it’s being done firstly, for neuroprotection to try to slow down the rate of deterioration in people who are resistant to pressure-lowering therapy alone.

“I think gene therapy is also promising in a variety of other ways, and amongst those are for optic nerve regeneration and for cell reprogramming to make more retinal ganglion cells in the retina when they’ve been lost,” he concluded.

Beyond IOP

The Role of Corneal Biomechanics in Glaucoma Progression

by Brooke Herron

HTG. Further, there was “a significant correlation (p<0.05) between mean deviation and pattern SD (MD and PSD) and many dynamic corneal response parameters (DCRs), and POAG patients with softer (or more compliant) corneas were more likely to show visual field defects.”

The authors continued that “the abnormality of corneal biomechanics in NTG (normal tension glaucoma) and the significant correlation with visual field parameters might suggest a new risk factor for the development or progression of NTG.”

Developing a new calculation

To catch NTG in patients before the disease progresses, a new formula was developed: the Dresden biomechanical glaucoma factor (DBGF), which is based on DCR deformation and corneal thickness parameters. A recent study2 tested the ability of DBGF to discriminate between healthy and NTG eyes.

When it comes to glaucoma diagnosis and treatment, managing intraocular pressure (IOP) is often the most commonly discussed factor. However, corneal biomechanics also plays a key role in the disease’s development and progression, as well as accuracy in IOP measurement.

In fact, a recent observational study1 by Dr. Riccardo Vinciguerra and colleagues found that “corneal biomechanics might be a significant confounding factor for IOP measurement that should be considered in clinical decision-making.” (Editor’s note: More on this study below.)

And although this has not gone unnoticed by glaucoma specialists, numerous attempts using different devices to measure IOP and corneal biomechanics haven’t been entirely successful — until now. The CorvisST (Corneal visualization Scheimpflug Technology; OCULUS Optikgeräte GmbH, Wetzlar, Germany), is a noncontact tonometer designed to measure biomechanically corrected IOP (bIOP).

The device records the reaction of the cornea to a defined air pulse using a high-speed Scheimpflug camera that captures more than 4,300 images/ second to allow for highly precise IOP

and corneal thickness measurements. And it has applications beyond glaucoma as well, allowing for detection of ectatic diseases (such as keratoconus) at a very early stage. Below, we take a closer look at what makes this device stand out from the pack...

Corneal biomechanics are a key player

As if managing glaucoma wasn’t difficult enough, simply detecting normal tension glaucoma (NTG) can be a challenge in clinical practice: That’s because measuring IOP doesn’t do much good and the optic nerve head can appear normal.

Thus, Dr. Riccardo Vinciguerra and colleagues decided to take a closer look by comparing bIOP measured via the Corvis ST with Goldmann applanation tonometry (GAT-IOP) in patients with high-tension and normal-tension primary open-angle glaucoma (POAG; HTG and NTG), ocular hypertension (OHT) and controls — and they found significant differences.

Patients with NTG had significantly softer and more deformable corneas compared with controls, OHT and

This multicenter cross-sectional pilot study included both eyes of 70 healthy and 70 NTG patients. The authors calculated the DBGF using five Corvis ST parameters: deformation amplitude ratio progression, highest concavity time, pachymetry slope, bIOP and pachymetry.

They found that “in a threefold crossvalidation, the receiver operating characteristic (ROC) curve confirmed an area under the curve (AUC) of 0.814 with a sensitivity of 76% and a specificity of 77% using a logit cut-off value of a DBGF = 0.5.”

These results show that DBGF is sensitive and specific to discriminate healthy from NTG eyes. Therefore, this formula might help with the differential diagnosis of NTG in daily clinical practice and could be considered as a possible screening method for NTG — and as a result, help prevent undetected NTG disease progression.

References:

1 Vinciguerra R, Rehman S, Vallabh NA, et al. Corneal Biomechanics and Biomechanically-corrected Intraocular Pressure in Primary Open Angle Glaucoma, Ocular Hypertension and Controls. Br J Ophthalmol. 2020; 104(1): 121–126.

2 Pillunat KR, Herber R, Spoerl E, Erb C, Pillunat LE. A new biomechanical glaucoma factor to discriminate normal eyes from normal pressure glaucoma eyes. Acta Ophthalmol. 2019 Nov;97(7):e962-e967.

Deceptive NORMALITY

The internal pressure was completely normal, yet still the balloon burst. Why?

Quick and reliable early detection of normal tension glaucoma

Glaucoma is only young once, making its early detection and treatment all the more important. However, glaucoma is especially often overlooked in eyes with normal IOP. Here’s where the OCULUS Corvis ® ST with its glaucoma screening software comes in useful. It provides quick and reliable measurements based on a unique analysis method, comparing them with normative data to facilitate identification of high-risk patients.

Rapid Fire

Blood Pressure and MIGS

by Sam McCommon

A brief look at MIGS

Three MIGS showed up during this session, each with a bit of a twist, though we’ll only be able to cover two here — one will get its own article at another date. Gurpal Virdi, another medical student (great medical class coming up, right?) presented information on Allergan’s (an AbbVie company, Dublin, Ireland) XEN® stent — but as an ab-externo implant rather than an ab-interno.

As Mr. Virdi’s study showed, the rate of IOP reduction between the two stent locations was remarkably similar, even though patients with the ab-externo version started with higher average IOP. The externo implant also led to fewer glaucoma medications used after three months than the interno. Additionally, ab-externo blebs required less needling and survived nearly twice as long as abinterno blebs.

Pow, pow, pow! Bang, whiz, zoom! That’s how the rapid fire session of the World Glaucoma e-Congress (WGC 2021) went on Day 2, with ammunition in the form of vital ophthalmic goodies whizzing around the room, ricocheting off walls and penetrating brains. In a good way, of course.

Judiciously choosing which bits to put in here was painful, since there were so many information bullets that smacked us in the skull. But for now, let’s start with the biggest “whoa.”

The relationship between blood pressure and IOP

One of the most striking presentations at this particular seminar was presented by none other than a medical student — Eric Lee, a student at Stanford. He doesn’t even have a “Dr.” in front of his name yet, but his suggestions made quite a splash. The link between blood pressure and IOP has long been debated, but here we have real evidence — and it’s not what this writer would have assumed.

First, the structure of the study itself is quite interesting. The study is drawing data from the All of Us Research Program, run by the NIH. In case you’re

curious, its core goals are transparency, diversity and security of participant information. There are currently 200,000 people enrolled in the program, with a goal of 1 million.

He and his team conducted an enormous survey of patients, organizing them by billing codes. Their data set is quite solid — in the post-seminar questions, Mr. Lee was asked if they’d excluded patients who had been using beta blockers, for example, and indeed they had.

So, to keep you from holding your breath too long, here is the significant takeaway: Low blood pressure is associated with an increased risk of developing OAG. On the other hand, high blood pressure and medications for it were not associated with a higher risk of OAG.

Now, there are some limitations to the study — certain clinical factors, including IOP, central corneal thickness and refractive error were not available for consideration in the study due to the nature of the data. But the indication that low blood pressure is associated with OAG should be enough to stir the pot and make a case for further investigations into the situation. Congratulations on the good work, Mr. Lee.

Dr. Cathleen McCabe provided some valuable information on the Hydrus® Microstent (Ivantis, Irvine, California, USA) — which, she noted, is the first reported clinical benefit with a MIGS procedure. It’s also the only MIGS study with a 5-year continuous follow-up.

The Hydrus is a flexible, biocompatible 8 mm microstent made out of nitinol, a highly biocompatible material often used in cardiovascular stents. It’s contoured to match canal curvature. Have a look at it, it’s neat. We’re not being paid to say that right now.

The stent spans 90° of the Schlemm’s canal, dilates and scaffolds the canal without obstructing outflow, and bypasses the trabecular meshwork to restore flow of aqueous from the anterior chamber into the canal.

Around two-thirds of the Hydrus patients were medication-free at 60 months, compared to 46% of phaco-only patients. While there was no difference in safety between Hydrus and phaco at 5 years, there was a sustained improvement in IOP reduction and use of medications in the Hydrus group.

To conclude, there was a brief poll of the speakers. The question: Do you combine anti-VEGF with MIGS? The result was a resounding “no” as not a single respondent answered yes. So, there’s that. Keep that in mind. How’s that for a conclusion?

Duck and cover! It’s a barrage of ophthalmic news!

Challenging Surgical Cases from the Brazilian Glaucoma Society

Patients and physicians alike want surgery to be simple and complication free. However, this can’t always be the case, sometimes because issues arise during surgery, and sometimes comorbidities in patients make treatment more difficult. In this session on Day 2 of the World Glaucoma e-Congress (WGC 2021), four experienced surgeons from Brazil shared their experiences and knowledge about what you can do whenever one of those difficult cases walks through the clinic door.

GATT complications

Dr. Bruno Faria from the Instituto de Oftalmologia Marco Rey (Brazil) discussed complications arising during GATT (Gonioscopy-Assisted Transluminal Trabeculotomy) surgery. To begin with, he highlighted to other surgeons that it is possible to perform GATT with a simple polypropylene 5-0 suture, making it significantly cheaper than the standard method. Further, he discussed a particular case where during a gonioscopy, the suture was pushed under the iris. When Dr. Faria realized what had happened, he stopped and carefully removed the suture and performed a trabeculotomy at around 250 degrees, without further complications. Happily, at a follow-up five years later, the patient was medication free and had an IOP of 16 mmHg.

Nanophthalmos

Dr. Fabio Kanadani from the Hospital Universitário Ciências Médicas (Brazil) discussed nanophthalmos, a rare disease characterized by a small eye with a short axial length, severe hyperopia, an elevated lens/eye ratio, and a high incidence of angle-closure glaucoma. In Dr. Kanadani’s patient, many different treatments were already tried by different physicians over many months, until Dr. Kanadani successfully performed phaco and a posterior vitrectomy, followed by a

by Chris Higginson

membranectomy and anterior vitrectomy to remove a thick pupillary membrane which had formed. When advising other physicians he says this disease is always difficult for glaucoma specialists and cataract surgeons as it has a high risk of malignant glaucoma. He suggests other physicians do not wait to act, but move forward with treatment as quickly as possible, perform phaco, as well as posterior vitrectomy as soon as they are able to.

Trabeculectomy in high myopia

Dr. Sergio Henrique Teixeira from Universidade Federal de São Paulo (Brazil) gave advice for performing a trabeculectomy on high myopia patients. Myopia is an increasing issue and the alterations that myopia produces can change the way we both treat and follow glaucoma patients.

Myopia can change every structure of the eye, but especially the vitreo, which is more liquid and the choroid and sclera which can be thinner. He gave some advice about the surgical complications to bear in mind before you go ahead. There is the possibility of hypotony, hypotonic maculopathy, choroidal and retinal detachments, misdirection

glaucoma and the need for other operations all increase.

If the operation is going ahead, before you start make sure you plan carefully and watch out for retinal tears and anatomic alterations. During and after the surgery check the arterial pressure, choose the anesthesia carefully and watch out for the possibility of inflammation. When performing a trabeculectomy, maintain the anterior chamber stability throughout, ensure the flap is thick enough (at least 250 μm) and take care that the flow does not become too much.

Tube implant in eye with staphyloma

Dr. Tiago Prata from the Federal University of São Paulo (Brazil) presented a case of a tube implant in an eye with staphyloma. The patient had many different treatments attempted, none of which were able to relieve the patient’s pain and elevated IOP. However, the multiple CPC procedures, trabeculectomy and MMC used all probably combined to cause a large staphyloma.

To begin with a sclaropatch was carefully applied over the very large staphyloma, which went well. When this was done he moved over to the temporal inferior quadrant to place the Ahmed valve implant, as the staphyloma made it impossible to place it in the superior region, which went well, even though this area is not the first choice for valve placement. Four months post-op the patient had no pain or signs of scleral thinning, and IOP of 14 mmHg with two medications.