CAKE POST (WGC 2021 Edition) - ISSUE 1

Let’s

WGC 2021 Beyond Borders Kicks Off Virtual Meeting

by Hazlin Hassan

The 9th meeting of the World Glaucoma Association World Glaucoma e-Congress (WGC 2021) opened yesterday, with some 2,800 delegates from over 100 countries taking part virtually. opened yesterday, with some 2,800 delegates from over 100 countries taking part virtually.

“The World Glaucoma Association is an independent organization that unites all national and regional glaucoma associations, reaching over 12,000 eyecare providers in the world,” said WGA President Fabian Lerner in a welcome message on the congress website. WGC 2021 will offer educational exchanges, scientific news, and best practice updates.

Covering topics from basic science and genetics of glaucoma, to the latest developments in the medical and surgical management of glaucoma, this is a not-to-be-missed event for glaucoma specialists, or any ophthalmologist with an interest in the disease.

Delegates can access the latest updates in glaucoma care and discuss current, innovation-

Featuring messages of Zen and new ideas in managing NTG from the Presidential Symposium

driven patient outcomes through interactive sessions over four days of live presentations, with 70 scientific sessions and more, from June 30 to July 3, 2021.

Messages from Japan

The congress, which takes place every two years, is being hosted virtually by the Japan Glaucoma Society (JGS) this year. As such, participants can discover the wonders of Japan through the social and cultural activities available during the virtual meeting.

Daiko Matsuyama, deputy head priest of the Taizo-in temple in Kyoto, Japan, shared a thought-provoking message during the opening ceremony of the congress. “Because of the COVID-19 pandemic, many people are suffering from anxiety and seeking spiritual well-being,” said Matsuyama, adding that he has noticed that many visitors who visited the temple to undergo training enjoyed their meals more after having led a monastic life.

“We lead very busy and complicated lives, and we have no time to concentrate on things. In Zen teachings, we teach meditation. When we eat, when we walk, when we sleep, we can be mindful,” shared the head priest.

Highlights from the Presidential Symposium

Day 1 of WGC 2021 also featured the Presidential Symposium on Normal Tension Glaucoma (NTG), which touched on this form of glaucoma in which damage occurs to the optic nerve without intraocular pressure (IOP) exceeding the normal range.

There are clear morphological differences between glaucomatous optic neuropathy and any vascular optic neuropathy, said Dr. Jost Jonas, from the Department of Ophthalmology and Medical Faculty Mannheim at the Ruprecht-KarlsUniversity in Heidelberg, Germany.

Dr. Jonas noted several of these differences. For example, rim loss is found only in glaucoma (except giant cell arteritis) but not in vascular optic neuropathies.

Meanwhile, beta zone is found in all glaucoma types, but not in vascular optic neuropathies. He concluded that in cases of glaucomatous optic neuropathy, either IOP is elevated or orbital CSF (cerebrospinal fluid) pressure is low. Further, in patients with arterial hypotension, reduction in CSF pressure is greater than simultaneous reduction of IOP which leads to an increased translamina cribrosa pressure difference.

“The morphologic differences between glaucomatous and vascularassociated optic neuropathy contradict a primary role of a vasculopathy in the pathogenesis of glaucomatous optic nerve damage,” said Dr. Jonas.

Systemic and ocular risk factors

Professor Ki Ho Park, from the Seoul National University College of Medicine in South Korea, spoke about systemic and ocular risk factors for NTG.

“The average immunity is closely

associated with inflammatory cytokines in the nervous system,” he said, adding that Helicobacter pylori (H. pylori) infection is known to be associated with glaucoma, in which autoimmune response and inflammatory cytokines are one of the important mechanics of optic nerve damage.

“Our group has investigated the association between H. pylori infection and normal tension glaucoma in Korea,” he said. The study suggests that H. pylori infection may be associated with an increased risk for NTG and that H. pylori may play a role in the development or progression of NTG as a secondary aggravating factor because of the coexistence of other main causes, or it may be the primary cause.

In summary, aberrant immunity along with inflammatory cytokines is associated with glaucoma, said Dr. Park. “The breakdown of blood brain barrier (BBB) is essential in aberrant immunity in glaucoma. Disc hemorrhage and parapapillary atrophy indicate the locations of the breakdown of blood brain barrier,” he said, adding that silent cerebral infarct, or small vessel disease, is also associated with NTG.

Ocular hypertensive therapy

Tetsuya Yamamoto, professor emeritus of Gifu University and head professor at Kazuo Iwata Memorial Kaijin Glaucoma Center, Japan, talked about the Efficacy of Ocular Hypotensive Therapy for Normal Tension Glaucoma.

He said that ocular hypotensive therapy is effective to stabilize the visual field in NTG. The visual field is almost stabilized in the majority of cases when the IOP is maintained to be 10 mmHg or less for over 10 years, shared Prof. Yamamoto.

“This piece of evidence demonstrates that NTG is an IOP-dependent disease,” he said, adding that the favorable effect is more apparent in surgically-treated cases.

Trabeculectomy is also effective, even in cases with preoperative IOP of 12 mmHg or less. He continued that the visual field is almost stabilized in the majority of the cases when the IOP is maintained to be 10 mmHg or less.

“IOP lowering is effective in stabilizing the visual field of NTG. The target IOP is

10 mmHg or less,” he concluded.

Progression despite IOP reduction

Dr. Louis Pasquale, site chair of the Department of Ophthalmology at Mount Sinai Hospital, New York, USA, spoke about Progression despite IOP reduction: Non-IOP lowering treatments for normal tension glaucoma

“Progressive normal tension glaucoma is a public health problem. Unilateral blindness rates from normal tension glaucoma have been estimated at 10% at 20 years, bilateral blindness rates from normal tension glaucoma is about 1.4% at 20 years,” he said. “In most instances, we do not identify the real reason why patients are progressing, and there are no proven ways to halt progression in normal tension glaucoma, either by IOP lowering, or by non-IOP lowering approaches.”

He called for an international consortium devoted to solving the problem of progressive normal tension glaucoma. “We need to know why a normal tension glaucoma patient is progressing and it’s important to start out by saying that not all progression is glaucomatous.”

One non-glaucomatous red flag includes very rapid progression, greater than one decibel per year. “We need to know how fast a normal tension glaucoma patient is progressing,” said Dr. Pasquale. Typical progression for this disease is about 0.2 to 0.5 decibels per year, but some patients can experience rapid progressive rates between 1 and 2 decibels.

A strong family history of normal tension glaucoma starting in young adult adulthood should prompt a search for Mendalian variants, he said.

One interesting finding he shared was that meditation decreased IOP in primary open-angle glaucoma (POAG), and that diurnal fluctuation of IOP also decreases with meditation.

To summarize, the successful management of NTG starts with ruling out non-glaucomatous optic nerve disease, knowing the age of onset and rate of glaucoma progression, considering what is causing the progression, and setting a proper target IOP.

Throwing a Phaco Party in Primary Angle Closure Disease

Day one of the World Glaucoma e-Congress (WGC 2021) featured a deep dive into the world of primary angle closure disease. This session produced some fantastic takeaways and knowledge you can really sink your teeth into, or feast your eyes on, or whatever other figure of speech you like.

We’d love to cover all of the topics in this piece, but there was one particular bit of information that stood out — and that was the use of phacoemulsification as a glaucoma treatment.

Phaco for glaucoma

Dr. Mingguang He, of the Centre for Eye Research Australia at the University of Melbourne, led us to an interesting conclusion — that phacoemulsification of a clear lens can lead to a significant improvement in IOP in glaucoma, as well as better visual quality in general. This repurposing of a common treatment gives surgeons a valuable additional tool in the fight against both primary angle closure (PAC) and acute primary-angle closure (APAC).

Laser peripheral iridotomy (LPI) is usually considered the primary treatment for PAC, so why not just use that?

Well, as a study published by Dr. He in Ophthalmology in 2007 showed, 20% of patients still had closed angles immediately after LPI, with a pupillary block rate of 80% and a non-pupillary block or mixed of 20%.¹

Dr. He also pointed out that while LPI is certainly valuable, its success depends on many things, including the stage of the disease. As he noted, satisfactory IOP control can be achieved in 42 to 72% of cases with LPI alone for symptomatic ACG before glaucomatous optic neuropathy (GON) has developed. After GON has developed, however, LPI is insufficient, and nearly 100% of patients will require further treatment to control IOP.

In 2012, a study noted that IOP

by Sam McCommon

dropped significantly and remained lower after cataract surgery.² So, Dr. He now argues that phacoemulsification of a clear lens can lead to even better long-term results than LPI. For example, additional glaucoma surgery following phaco was essentially nonexistent — 1 in 208 patients in one study, as opposed to 24 out of 211 following LPI. Notably, of those 24 LPI patients that needed additional surgery, 16 needed lens extraction.

Overall, Dr. He recommends that clear lens extraction should be considered for PACG or PAC with elevated IOP, somewhere north of 30 mmHg. In addition to better IOP control, it leads to better visual acuity and contrast sensitivity, better visual function and quality of life, and fewer complications than LPI.

Combining phaco and trabeculectomy

The suggestion was echoed by Dr. Clement C. Tham, from the WGA’s board of governors and chairman and professor of ophthalmology at the Chinese University of Hong Kong. Dr. Tham introduced us to his philosophy regarding phaco and trabeculectomy — which can be combined.

Trabeculectomy alone is generally of limited role for phakic PACG patients for a few reasons. It can lead to an even shallower anterior chamber and malignant glaucoma, a 33% chance of cataract progression within two years and subsequent cataract surgery, and thus, presents more complications and risks.

While trabeculectomy led to a lower immediate drop in IOP over a 24-month period, patients with medically uncontrolled PACG who had undergone phaco surgery had effectively the same sustained IOP reduction as the trabeculectomy patients. And while

trabeculectomy patients required fewer medications to control PACG as opposed to phaco patients, there was still a significant reduction in the number of drugs needed for the phaco group.

So, phaco can be valuable for PACG in its own right. But sometimes it’s not enough. As Dr. Tham pointed out, lens extraction alone may not be sufficient if very advanced GON requires a very low target IOP, or grossly controlled IOP leads to excessively high IOP and a strong dependence on medications.

In such a case, phaco plus trabeculectomy may be the best bet. Patients who had undergone phacotrabeculectomy surgery required even fewer medications than trabeculectomy patients, indicating the surgeries had complementary properties.

Dr. Tham shared that, in his practice, he has slotted a combination of phaco and endoscopic cyclophotocoagulation (ECP) between phaco and phacotrabeculectomy as another option, using the treatments as a sliding scale in terms of invasiveness and IOP reduction. Less serious cases can be treated with just phaco; more serious ones need phacotrabeculectomy.

References:

1. He M, Friedman DS, Ge J, et al. Laser peripheral iridotomy in primary angle-closure suspects: biometric and gonioscopic outcomes: the Liwan Eye Study. Ophthalmology. 2007;114(3):494-500.

2. Mansberger SL, Gordon MO, Jampel H, et al. Ocular Hypertension Treatment Study Group. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study. Ophthalmology. 2012;119(9):1826-31.

Ain’t no party like a phacoemulsification party...

Management Changes in

With the introduction of new devices and therapies, especially in minimally invasive glaucoma surgery (MIGS), the management and treatment of glaucoma is shifting — and providing more options than ever before for patients and doctors to consider.

Thus, experts convened during a plenary industry symposium, sponsored by Allergan, an AbbVie company (Dublin, Ireland), to discuss Challenges of current glaucoma management and future perspectives.

“We want to highlight a couple of important areas where we think management changes are happening … and how technology and research is guiding how we manage glaucoma patients,” began moderator and panelist, Dr. Ike Ahmed from the University of Toronto, Canada.

Below, we share some of these key insights from this session at Day 1 of the World Glaucoma Congress (WGC 2021).

Toward precision glaucoma

Numerous studies have shown that many glaucoma patients continue to progress despite treatment, shared Dr. Andrew Tatham from the University of Edinburgh, Scotland.

To improve outcomes and reduce percentages of progression, he suggests using precision medicine to classify patients into subgroups based on: susceptibility to disease, biology of disease and response to specific treatment. “The advantage of this is that these subgroups could then be monitored or treated differently to optimize

outcomes in individual patients,” said Dr. Tatham.

For precision glaucoma, we need new treatments that can be targeted to these specific subgroups of patients, he continued. “It’s perhaps not surprising that in a survey, 45% of patients were accepting of more invasive approaches to decrease or avoid use of topical glaucoma medications.”

Advanced clinical programs

Next, Dr. Miriam Kolko from the University of Copenhagen, Denmark, discussed some of the latest innovations in drug delivery. These devices are in various trial phases and include the travoprost punctal plug (OTXTP), travoprost implant (ENV515), travoprost refillable titanium implant and bimatoprost implant.

She then shared current results from the different trials, which show clear clinical benefits. “The adverse events are similar, or even lower, after implantation compared with topical bimatoprost eye drops after two days … so the majority of side effects are due to the procedure,” said Dr. Kolko.

Sustained release implants do represent a new category of treatment and an innovation in glaucoma management, in particular in patients with severe ocular side effects such as dry eye, she said, adding that phase 3 studies are needed to further evaluate the safety and efficacy of these products.

“I would never say that they [implants] are for everybody, but when we talk about precision medicine … we need to personalize the medication and have a

by Brooke Herron

holistic approach,” concluded Dr. Kolka, adding that patients with compliance issues could also be a match for these implants. Another benefit? The implants can always be removed, if needed.

Outflow at the structural level

We know that our current therapeutics in glaucoma have the ability to target different pathways, began Dr. Ahmed. These include conventional (trabecular) and unconventional (uveoscleral), and there are various parameters that affect intraocular pressure (IOP) and its balance of inflow and outflow.

Extracellular matrix (ECM) plays an important role in outflow resistance and ongoing ECM turnover is required to maintain the appropriate outflow resistance, he continued.

“In glaucoma, one of the purported mechanisms of elevated pressure is increased resistance at the ECM level. This is due to the potential imbalance of MMP (activated matrix metalloproteinases) and their tissue inhibitor [of metalloproteinases] (TIMP),” explained Dr. Ahmed. In POAG (primary open angle glaucoma), data suggest that there is an imbalance (with TIMPs dominant).

“When we think about ‘how do these new drugs work?’ and how we deliver them in the eye, they’ve shown some certain phenomena that we can’t quite explain simply by thinking about drugs in the eye. We see the impact of this concentration and we think it’s related to MMP upregulation and its impact on ECM turnover, and the balance between MMPs and TIMPs, as well,” he concluded.

Picture This

The Use of Imaging in Glaucoma Disease

Anterior segment imaging allows for an objective method of visualizing the anterior segment angle. One of the most commonly used devices for anterior segment imaging is anterior segment optical coherence tomography (AS-OCT).

On Day 1 of WGC 2021, during a session on Imaging, experts discussed when to complete anterior segment imaging and various other imaging-related topics.

Transitioning to a new gold standard

Gonioscopy became established in the management of glaucoma in 1938 as the “gold standard for angle evaluation,” said Dr. Chelvin Sng, consultant, National University Hospital, Singapore.

But it has its disadvantages: It’s subjective, requires good technique, it’s affected by room lighting conditions, it requires contact with the eye, which can lead to inadvertent corneal indentation, and it’s also time-consuming.

“Hence, anterior segment imaging has become an important adjunct to gonioscopy,” she said.

“In our study, using pre-iridectomy ASOCT scans, we developed an algorithm, which was able to predict the success of iridotomy with 80% accuracy. And this algorithm was superior to the predictive accuracy of ophthalmologists, so we are now able to offer iridotomy only to those patients who respond well,” continued Dr. Sng. This is now the era of personalized medicine — rather than offering the same treatment to all patients with the same disease, we now offer patients the treatments that they are most likely to respond well to, she added.

This imaging also allows ophthalmologists to identify the mechanism of angle closure, so they

by Hazlin Hassan

can now offer personalized treatment for angle closure glaucoma. In addition, Dr. Sng said that anterior segment imaging also has a role in guiding and monitoring surgery for eyes with very narrow angles.

In summary, anterior segment imaging allows for objective and reproducible assessments of the anterior chamber structures. Further, anterior segment imaging can be used for monitoring and prognosticating trabeculectomy blebs, and may have a role in the context of newer minimally invasive glaucoma surgeries.

Using imaging for monitoring progression

Glaucoma surgeon and NHS Scotland Research Clinician Dr. Andrew Tatham answered the burning question of how to use imaging to monitor glaucoma progression, by cautioning: “It’s very important to emphasize that imaging cannot replace visual field analysis.

“Having said that, of course imaging has some clear advantages: it’s objective, it’s quantitative, it’s preferred by patients (compared to perimetry), and also, changes are often detectable on imaging before they are on visual fields, and the changes on imaging are predictive of future visual field loss,” he noted.

He said first, check quality alignment and segmentation in all scans. He advised to not just rely on the trend analysis report because it provides no information about image quality — and there may be artifacts that give the false impression of progression. Second, it’s very important to look at the whole scan.

“The third thing that I do, is to try and concentrate on changes in the glaucoma hotspots,” continued Dr. Tatham. “Number four is to consider if any change is statistically or clinically significant, and there’s quite a big

difference in those two things, so it’s worth looking at this in some detail.”

Accurate detection of progression requires several elements. “We need good image registration, good reproducibility, a useful dynamic range, an agreed definition of progression, and we need to be able to differentiate glaucomatous and non-glaucomatous change,” he said.

“Initially I stated that imaging cannot replace visual field analysis, but perhaps I should have said ‘yet,’ because it is now possible to predict visual field results from OCTA using deep learning, predicting visual fields. This is an exciting possibility, which in the future may improve visual field testing algorithms, or reduce the frequency with which visual field testing is required,” concluded Dr. Tatham.

The role of OCTA

Dr. Harsha Rao, a glaucoma consultant at Narayana Nethralaya, India, talked about OCTA and whether it should be used in clinics.

An OCTA feature in glaucoma is a reduction in the density of superficial vessels. OCTA changes occur before changes take place in the visual field (VF), while a lower baseline vessel density is associated with faster retinal nerve fiber layer thinning.

Progressive reduction in capillaries is also associated with VF progression regardless of glaucoma severity.

“To summarize, OCTA provides unique information about the vascular changes in glaucoma that was not available to clinicians until now. OCTA provides useful information about the risk of glaucoma progression,” said Dr. Rao.

In addition, improved technology has reduced the prevalence of poor quality images and reduced the test-retest reliability of the parameters, as well. Further, OCTA appears to be a better tool than OCT to monitor progression in moderate to advanced glaucoma.

“With all this in mind, I feel that OCTA seems to be ready for the clinics,” he concluded.

It’sin Your Genes Glaucoma Risk

As a customer, have you ever been treated rudely or without consideration by a staff member? It can make you feel like a blank space … treating you as just another member of the public and failing to take your individuality into account. However, when someone provides customer service personalized to you, it makes all the difference — doesn’t it?

A more personalized approach benefits us in all walks of life, whether it be in retail, hospitality or of course, the medical field. Taking an individualized approach to patient care is the gold standard for ophthalmic clinics, so it’s no surprise that the Personalizing the Approach to Your Glaucoma symposium was one of the highlights of Day 1 of the World Glaucoma Congress (WGC 2021). Bringing together doctors from around the world, the symposium had a particular focus on genetics, one of the best routes to truly personalize healthcare.

One of the most noteworthy speakers was Dr. Stuart McGregor, PhD, a professor in statistical genetics at the QIMR Berghofer Medical Research Institute (Herston, Australia). Dr. McGregor’s research was presented during Genetic Risk Profiling and he applied this

science to identifying individuals who are at risk of developing glaucoma. He emphasized that there “are essentially no environmental risks” for glaucoma and that it is one of the most common heritable conditions.

Have you asked your folks about your glaucoma risk?

According to Dr. McGregor, having a first-degree relative who has glaucoma increases one’s risk tenfold. Pointing to information from the U.K. Biobank (a long-term study to examine ethnic predisposition to disease), Dr. McGregor said that Africans have a lower risk, while East Asians have a higher genetic potential. His key takeaway was that better calibration of risk models should be provided.

Glaucoma is, of course, treated with a variety of medications which must be personalized to the patient’s needs — and when required, their genetics. Thus, the presentation on Pharmacogenomics: Customizing Medication Choice examined exactly this issue. Presented by Dr. Pirro Hysi from King’s College London (England), the report focused on balancing efficacy versus toxicity based on individual-level variability.

byAndrew Sweeney

Bearing this in mind, Dr. Hysi spoke at length on the important role absorption plays in individual tolerance. This, he said, is affected by tear film properties (including pH levels) and the cornea’s permeability. As these are determined by genetic factors, he emphasized the importance genetics can play in creating best-quality glaucoma medications.

You

can

use corneas to predict glaucoma

WGC’s Beyond Borders theme may focus on actually crossing borders, but what about crossing time and into the future too? The lecture on Who is Going to Get Worse? Cutting-Edge Methods for Predicting Disease Progression by Dr. Felipe Medeiros, PhD, a professor at Duke University (Durham, North Carolina), presented his research on how risk-modeling for glaucoma can be improved. Pointing out that although research has improved considerably over the past 15 years, he argued that more needs to be done.

Dr. Medeiros pointed to one study that used corneal hysteresis as a risk factor for glaucoma progression. He also highlighted another body of research that examined an ocular coherence tomography (OCT) trained deep learning algorithm to monitor and quantify glaucomatous damage. These, he said, are great examples of new techniques that can provide personalized risk assessment.

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It’s time for a different approach t o t he outflow pathway.

While other MIGS procedures bypass or remove diseased portions of the conventional outflow pathway, iTrack™ ab-interno canaloplasty employs a uniquely different approach that is both stent-free and tissue-sparing.

iTrack™ treats 360º of the conventional outflow pathway, including the collector channels.

iTrack™ preserves the angle and conjunctiva. It also minimizes endothelial cell loss at -4.8% at 12 months.

iTrack™ acts to re-establish natural aqueous flow and avoids the drawbacks of artificial flow.

It’s all Connected Corneal Health, Glaucoma and MIGS

by Brooke Herron

In most things, natural is better than artificial. In glaucoma surgeries, there is also a natural versus artificial aqueous flow — and we’re learning that, especially in patients with corneal disease or previous corneal surgery, one pathway does indeed triumph over the other.

Why outflow matters

In normal eyes, natural aqueous flows through the full 360° of the conventional outflow pathway. Here, aqueous humor passes from the anterior chamber, across the trabecular meshwork and inner wall of Schlemm canal, and into the canal itself. From there, aqueous humor flows into the collector channels and the episcleral venous system. This flow is determined by intraocular pressure (IOP), outflow resistance or facility, the rate of aqueous humor production and episcleral venous pressure.

Simple, so far — right? Well, it depends on the patient. For example, although popular, stent-based MIGS devices bypass the conventional outflow pathway and result in artificial flow. It’s been suggested that these alterations can damage the corneal endothelium and lead to excessive endothelial cell loss (ECL). Not great news, for patients with corneal disease, like Fuchs’ dystrophy and mild-to-moderate primary openangle glaucoma: This artificial or preferential outflow caused by a stent could be damaging.

Postoperative inflammation can also damage the corneal endothelium and is another cause for concern, specifically in tissue-destructive MIGS procedures like goniotomy. Thus, the optimal procedure for these patients is one that effectively lowers the IOP without causing

unwanted inflammation, corneal damage and decompensation.

Preserving the cornea is crucial

One MIGS device of note — the iTrack™ from Nova Eye Medical (Fremont, California) — improves natural aqueous flow throughout the full circumference of the conventional outflow pathway and thereby limits damage to the cornea. This is in contrast to other MIGS procedures that act to mechanically change or bypass the natural pathway of aqueous outflow. Did we mention that it’s also implant-free and spares tissue — and therefore doesn’t cause that tricky postoperative inflammation and resulting endothelium damage?

Ab interno canaloplasty with iTrack™

Ab interno canaloplasty with iTrack™ combines a process of 360° microcatheterization and viscodilation which targets all aspects of the conventional outflow pathway. This can effectively improve physiologic outflow — instead of opening up one or more isolated drainage points that could create a potentially damaging preferential outflow pathway.

For patients with corneal disease and even previous penetrating keratoplasty, this procedure can be safely performed without damaging the endothelium. Plus,

because it is not a tissue-destructive or an implant-based procedure, other MIGS procedures could be utilized in the future, if needed.

“Show us the science,” you say? Indeed, there’s data presented at the World Glaucoma Congress (WGC 2021) that backs its use.

One presentation is an abstract from Drs. Robert Noecker and David Lubeck, titled One Year Evaluation of Endothelial Cell Density and Loss Following iTrack™ AbInterno Canal Based Surgery.* So, what did they find out?

This prospective, multi-center registry study followed patients for 60 months after iTrack™ ab-interno canal-based surgery combined with cataract surgery.

The authors found that at one year, mean endothelial cell density was -4.8% (SD -6.5%). Compare this with ECL in the control groups of patients undergoing cataract surgery alone in FDA pivotal MIGS trials for iStent and Hydrus, which was -10.0 to -12.3% (SD -11.0 to -12.7%).

By targeting the entire circumference of the conventional outflow pathway, iTrack™ may limit the risk of ECL.This preliminary 12-month data shows that iTrack™ has some of the lowest rates of ECL, which is similar to cataract surgery alone. This is important, particularly for younger patients and those who do not have cataracts.

“Endothelial cell loss occurred primarily in the initial 6 months postoperatively,” shared Drs. Noecker and Lubeck. “iTrack ab-interno canaloplasty causes minimal endothelial cell loss, comparable to cataract surgery alone … and the loss occurring primarily in the initial postoperative period suggests that endothelial cell density will remain stable over longer time periods.”

In the world of MIGS devices, it’s good to have some clear-cut science backing which procedure is best for certain patients — especially those with corneal issues. So, welcome iTrack™ — we look forward to your long-term data.

* Lubeck DM, Noecker RJ. One Year Evaluation of Endothelial Cell Density and Loss Following iTrack AbInterno Canal Based Surgery. 2020. Unpublished data; accepted for presentation at WGC 2021.

What’s new, pussycat?

The Latest in Predicting and Tracking Glaucoma Progression

by Hazlin Hassan

Glaucoma is a major cause of irreversible blindness worldwide, and is predicted to worsen as the world population ages. Vision loss is attributed to the degeneration of retinal ganglion cells (RGC), the retinal neurons involved in the transfer of visual information from the eye to the brain. And unfortunately, conventional clinical tests are unable to detect abnormalities until extensive RGC death and significant vision loss have already taken place.

However, it is known that one of the earliest signs of glaucoma is the process of neuronal apoptosis or RGC cell death — and good news, researchers have come up with a new way to image and track this process of RGC apoptosis in vivo. Known as DARC (detection of apoptosing retinal cells), this is a method where individual nerve cells can be observed dying in the living eye.

The DARC test involves injecting a fluorescent dye into the bloodstream that attaches to retinal cells, and illuminates those that are in the process of apoptosis. This technique may be able to open a new “window” in the cellular mechanisms involved in the development of RGC apoptosis and vision loss in glaucoma.

DARC: Like a crystal ball?

“I’m very excited to share the results that have just come out today, in progress with more research, where we have shown that DARC activity is predictive of expanding geographic atrophy,” said Lead Researcher Professor M. Francesca Cordeiro, from the UCL Institute of Ophthalmology, Imperial College London and Western Eye

Hospital Imperial College Healthcare NHS Trust (United Kingdom).

Among these results? A significantly higher DARC count was seen in the progressing versus stable glaucoma group — as such, this test could have widespread implications for the detection and diagnostics of glaucoma.

The question of risk factors for rapid progression in glaucoma patients was raised by Dr. Monisha Nongpiur, a clinician scientist at Singapore Eye Research Institute.

“While a lot of patients do progress relatively slowly, there are some patients who have fast progression,” said Dr. Nongpiur. Data from major studies have identified a number of ocular and systemic risk factors that are associated with progression.

One of the findings was that the presence of cardiovascular disease was an important, or major, risk factor that was independently associated with rapid progression. Other risk factors associated with rapid progression included those who were in the older age group, with higher peak IOP, and who had undergone glaucoma surgery. Some 6 to 8% of glaucoma patients are at high risk for rapid progression.

“In terms of newer risk factors for glaucoma progression, corneal hysteresis is an important factor to consider in the assessment of progression risk, while polygenic risk scores have the potential for genetic testing in the future to prevent vision loss from glaucoma,” she said.

These can help to identify patients who are at greatest risk for severe disease and allow tailored surveillance and monitoring for those individuals.

Detecting progression in advanced disease

Dr. Jayme Vianna, a glaucoma specialist from Dalhousie University, Canada, talked about the importance of detecting progression in advanced glaucoma.

“One of our goals is to avoid further loss in a patient that is already advanced, so we need to act quickly,” he said.

On the other hand, another goal was to also avoid causing harm, as most advanced patients are often already using multiple drugs, and in some cases, surgery may need to be performed, which can lead to quite uncomfortable side effects.

“So, there is a trade off between underdetecting progression, and potentially letting the patient lose even more vision, or over-detecting progression, and possibly doing a procedure that the patient may not need, and then bringing side effects and discomfort to the patient.”

In order to find the best point in this balance, it is essential to have a reliable assessment of progression. “The best way to have a reliable assessment of progression is to collect multiple pieces of information. No single technique is likely to provide a final answer. I recommend using all of them. In addition, we also need to repeat these examinations quite often.

“We don’t want to wait a long time to see that the patient is progressing, because then when you see it, they may have already lost vision. And in advanced cases we commonly have high variability, and then we need to repeat the examinations to reliably detect progression,” said Dr. Vianna.

New Avenues of Research in Glaucoma Treatment

by Chris Higginson

During this session on New Ideas in Glaucoma, six experts covered sizable ground during Day 1 of the World Glaucoma Congress (WGC 2021).

On neovascular coupling

Dr. Adriana Di Polo from the University of Montreal (Canada) spoke about neovascular coupling in glaucoma: New research has found that pericyte neurons can reduce flow in capillaries, where they lower capillary diameter and blood flow as well as causing neovascular degeneration, especially in glaucoma patients.

However, it has been recently discovered that the brain naturally forms IP-TNTs, or nanotubes that link these pericytes and are essential for neurovascular coupling. These IP-TNTs can be easily damaged by excessive calcium uptake therefore, Dr. Di Polo believes that “now we have discovered them and their effect, more research needs to be done to find strategies to protect these nanotubes in order to protect neurovascular health.”

On diagnosing with OCT

Dr. David Huang from the Casey Eye Institute at OHSU (Oregon, USA) spoke about OCT’s ability to diagnose glaucoma versus more traditional methods. By using progression to define glaucoma he compared the sensitivity of disc photographs, OCT, disc clinical (DC) exam and visual field (VF) testing.

He found that disc photographs were the best at predicting early stage glaucoma, but this requires the specialist with years of experience to make the diagnosis. Out of the three clinically available modalities, OCT was better than DC or VF; however, the best sensitivity was found by combining all three. He concluded that “OCT can detect

progression two years before VF in the early stages of glaucoma; however, visual field works better for moderate and late stages.”

On home monitoring

Dr. David Crabb from the University of London (United Kingdom) discussed tracking visual fields from home. For example, the “Eyecatcher” is a portable perimeter test that tracks eye movement, rather than relying on button pressing. It’s designed to be more user-friendly than the standard test and can be taken home for daily testing.

The Eyecatcher, which works on a standard tablet and has been found to work especially well for patients with normal visual fields, helps clinicians better triage patients. Their studies of patients using the Eyecatcher found that there was excellent concordance between the Eyecatcher at the standard Humphrey Field Analyzer test, and that by using frequent tests it is possible to improve the precision of the measurements. This is potentially helpful in clinical trials where patients are less inclined to leave their homes.

On asymmetric responses

Dr. Yvonne Ou from the University of California spoke about asymmetric responses in glaucoma. We know that transient OFF ganglion cells are more easily damaged by IOP than transient ON ganglion cells. Therefore, if we can diagnose loss of the OFF cells, we know there is a potential rise in IOP.

Dr. Ou and her students studied whether a handheld ERG device could detect relative changes to ON/OFF pathways. They found that glaucomatous eyes have a decreased ERG response at higher frequencies, so it is possible to

successfully use the handheld ERG to diagnose loss of OFF ganglion cells. Further, patients prefer the handheld ERG compared to undergoing visual field testing.

On meditation and glaucoma

Dr. Tanuj Dada from the All India Institute of Medical Sciences discussed meditation, noting that a glaucoma diagnosis has been shown to increase anxiety, stress and depression — all of which also increase IOP.

Meditation has been shown to cause a relaxation response, which can bring all mental processes under greater control. Meditation leads to a down-regulation of inflammatory markers and proinflammatory gene expression in older adults.

Dr. Dada said that “just five days meditating for 20 minutes leads to an increase in parasympathetic activity and decrease in sympathetic stress response, and studies in glaucoma patients have found a mean reduction in IOP of 23%.”

On AI in diagnosis

Dr. Chris Leung from the Chinese University of Hong Kong discussed whether it is possible to use artificial intelligence (AI) to diagnose angleclosure glaucoma.

He said that “currently, we rely on anterior segment OCT (AS-OCT) images to detect the presence of iris-trabecular contact. To do this, we have to identify a scleral spur, which is currently done manually; however, recent studies have shown that AI is able to do this as well as a specialist.”

Scientists from around the world collaborated to define the optimal diagnostic criteria to detect gonioscopic angle closure. They concluded that the nature of angle closure defined by the AS-OCT and gonioscopy is different: Iristrabecular contact in AS-OCT is different from invisible posterior trabecular meshwork in gonioscopy. In addition, he added that the difference in clinical consequence in eyes with gonioscopic angle closure, versus those with iristrabecular contact in AS-OCT, needs further research.

Fast and Reliable Perimetry Get

More from your Visual Field Device

by Brooke Herron

If you could wave a magic wand, what would you want from a visual field testing device? More efficiency? More accurate diagnostics? Increased patient comfort? Same day reporting and analysis?

Well, there’s good news: These “wishes” have been granted with the Smartfield (OCULUS Optikgeräte GmbH, Wetzlar, Germany) — a visual field device that can perform standard automated perimetry (SAP) of the central visual field (and beyond) to detect and monitor functional impairment in glaucoma.

Faster testing leads to greater practice efficiency

Although SAP is the gold standard for functional assessment in glaucoma, perimetry is still a subjective exam which can impact reliability (from the device and patient, alike). According to a 2020 study,* there are various factors that underscore the reliability of SAP, such as test–retest variability, fatigue, inattentiveness, advanced functional damage and prolonged test duration.

Most importantly, it has been observed that the time needed to determine retinal sensitivity during SAP was significantly related to test reliability — and likely the only variable that could be objectively modified — has led researchers to continuously seek out faster test strategies, noted the authors.

Thankfully, the Smartfield device was designed with this efficiency in mind: In fact, testing takes anywhere from 45 seconds to three minutes per eye.

Further, this device can detect glaucoma in its earlier stages, which is critical for preventing progression and saving sight.

Its efficiency and accuracy is a result of multiple features. One, the Smartfield uses a distance target, rather than a near target like most perimeters, with a wide fixation spot. These measurements are then summarized in a standard print-out that can be accessed via any computer in the office network.

Patients are also more comfortable during testing with the device, and can be positioned more easily — this, in turn, also saves time. Eye patches are also not needed, thanks to the Smartfield’s translucent lateral eye shields; in addition, the device’s lenses are more stable with no patient contact. This leads to more accurate results and eliminates the need for retesting, as the patient won’t accidently touch the lens.

The proof is in the pudding

Today, perimetry remains the most valuable tool glaucoma specialists have for a direct and comprehensive measurement of visual function — and to provide a reliable diagnosis. Thus, OCULUS has incorporated additional software solutions into the Smartfield. These include SPARK (which allows for quick and precise measurement of visual fields); GSP (glaucoma staging program, that’s ideal for early detection); PATH (predicting anatomy from thresholds, to estimate retinal nerve fiber layer thickness around the optic nerve); and TNT (threshold noiseless trend, which provides greater sensitivity in

determining early glaucoma progression).

The 2020 study mentioned above compared the Easyfield (EF; another OCULUS SAP device) using SPARK software with the Humphrey Visual Fields Analyzer (HFA; Carl Zeiss Meditec, Jena Germany). The authors said using “a faster VF (visual field) strategy (SPARK) seemed an interesting option, as it resulted in a smaller percentage of eyes with poor reliability indices,” which has notable clinical implications and relevance.

They continued: “In addition, it provided global indices (MD and PSD) values that not only had a relatively good correspondence with conventional functional assessment (over 50% of the observations fell within the predefined clinical agreement limits) but also a significant correlation with structural measurements by OCT.”

When time and reliability matter — and they certainly do when it comes to glaucoma detection — more ophthalmologists are turning toward more efficient devices, like the OCULUS Smartfield. And all around, this is good news: When we detect disease earlier, we can prevent its progression, improve quality of life and save sight.

* Nazareth T, Rocha J, Scoralick ALB, et al. Retinal Sensitivity Thresholds Obtained Through Easyfield and Humphrey Perimeters in Eyes with Glaucoma: A Cross-Sectional Comparative Study. Clin Ophthalmol. 2020;14:4201-4207

The OCULUS Smartfield set-up

A screenshot from the OCULUS Smartfield SPARK

Making your wishes come true: OCULUS Introduces its Shooting Stars

OCULUS perimeters –fast, small, EMR ready

OCULUS perimeters are purposefully optimized for monitoring functional impairment in glaucoma. Marked by shortened examination time, a more intuitive analysis of findings as well as increased patient comfort they each provide a modern all-in-one clinical solution for visual field testing. And all of this despite their small footprint!

Tackling Glaucoma in Sub-Saharan Africa

by Sam McCommon

one per million; in rural areas, it drops to one per seven million. Not all of those ophthalmologists are glaucoma specialists, of course, and in some countries there are no glaucoma specialists at all.

The region most significantly challenged by glaucoma is subSaharan Africa. It’s there you’ll find the highest rates of glaucoma, the highest rates of blindness, the lowest access to medical care, and all sorts of other irksome statistics we’ll get to in greater detail in just a moment.

So, Day 1 of WGC 2021 featured a focused talk on glaucoma in Africa — which, like the continent itself, is much bigger than many outside it seem to understand. But positive change is coming, and the WGC is playing a significant role in it.

The ICO-WGC Fellowship Program

Launched in 2016, the International Council of Ophthalmology (ICO) and the World Glaucoma Congress (WGC) teamed up to offer a three month fellowship to talented candidates from subSaharan Africa to ramp up their skills in glaucoma at a Japanese institution. They then return home and share their expertise in their country, helping in clinics and to raise awareness of the condition.

This year, in addition to other doctors, some ICO-WGC fellows presented their thoughts on the situation in sub-Saharan Africa, what problems they see, and what remedies they have.

Why is glaucoma such a challenge in sub-Saharan Africa?

Glaucoma presents an enormous challenge to sub-Saharan Africa because it’s a multifactorial problem. To oversimplify things, we can break down

the root causes into two categories: genetic and situational.

First, sub-Saharan Africans are more affected by glaucoma than any other group of people, and it appears to be a largely genetic issue. The prevalence differs within countries and between ethnic groups, but overall the facts are striking. In general, glaucoma starts earlier in Africans than other groups — with onethird of patients experiencing glaucoma at younger than 40-year-old. Glaucoma is also more aggressive in Africans, with IOP numbers ranging as high as 50, or even 60 mmHg, in some cases.

Additionally, as Dr. Nkiru Kizor-Akaraiwe, an ophthalmologist at Enugu State University in Nigeria pointed out, subSaharan Africans have a unique optic nerve head, with a smaller neuro-retinal rim and less connective tissue support, leading to an increased susceptibility to damage. This means that greater IOP will be exerted on large discs rather than small optic discs. Additionally, the differences in optic nerve heads mean that early detection of glaucoma is more difficult than in many other regions.

Furthermore, some medicines don’t work as well. Dr. Kizor-Akaraiwe further noted that timolol maleate only lasts six hours in Nigerians, as opposed to the standard 24 hours elsewhere.

This genetic prevalence has been shown by studies of people of sub-Saharan African descent in other parts of the world, and it holds up. So, there are certainly genetic factors at play.

Second, there’s the situational problem. Sub-Saharan Africa is home to only 1.5% of the world’s medical staff, so medical treatment is often sparsely distributed. In urban areas, the ratio of ophthalmologists to population is

Combined, these problems lead to an estimated 97% rate of undiagnosed glaucoma in sub-Saharan Africa. In many cases, as several of the speakers pointed out, patients will only come to the hospital when they are fully blind.

For example, as Dr. Kinkota Makela GuyGuy, an IOC-WGC fellow from the Democratic Republic of Congo shared, patient adherence to medical prescriptions is very low. Many patients will not see differences in their visual acuity when taking medicine to reduce their IOP, and will stop taking it, returning to the hospital only when they’re blind.

Similarly, many in his region associate glaucoma with cataracts, thinking that a visit to the hospital will return their vision to them. Raising awareness and understanding of the disease is of crucial importance, he affirmed.

Best options

Medicine is expensive, patient adherence is low, availability of medicine is scarce, and there are even frequent cases of counterfeit medicine. So, what’s the best solution?

Dr. Dan Kiage, founder and medical director of Kisii Eye Hospital in Kenya, suggested that laser therapy is just about the perfect solution for glaucoma in Africa. It’s cheap, it’s fast, and specialists can be trained in it relatively quickly. While access to therapeutic lasers is limited in much of the continent, he’s hopeful that will improve.

He’s also working on a toolkit for glaucoma to help local practitioners make more informed decisions. This will look like an algorithm, essentially, with a diagnostic checklist, decision flowcharts, practical procedures and levels of care.

Kudos to the fellows for their hard work and to all the ophthalmologists in sub-Saharan Africa who are tackling glaucoma. It’s a big task, but whoever moves mountains has to start with small stones.

Insights from the Latin American Glaucoma Society

by Chris Higginson

During a symposium from the Latin American Glaucoma Society on Day 1 of WGC 2021, seven speakers discussed the most up-to-date glaucoma research happening in the region.

On diagnosis

First up was Dr. Maria Fernanda Delgado, a glaucoma specialist from Colombia, who talked about diagnosing myopia, as well as a split retinal nerve fiber layer (RNFL) bundle.

In mild to moderate myopia, she advises to bear in mind that RNFL and GCIPL (ganglion cell-inner plexiform layer) thickness can be affected. This is because the degree of myopia affects RNFL differently; therefore, when making a diagnosis physicians should always correlate disc size with refractive status. Further, changes in OCT may predict myopia progression.

“When diagnosing a split RNFL bundle, remember reproducibility and stability are key,” said Dr. Delgado, adding that it may be present in healthy eyes and not to mistake it as a wedge defect. She also advised to determine separate normal value ranges.

“Above all, be aware of atypical anatomy of RNFL and follow-up with the patient to analyze the trend,” she concluded.

On combined high myopia and glaucoma

Next was Dr. Roberto Murad Vessani from the Federal University of São Paulo, Brazil, who shared about challenges in diagnosis and follow-up of high myopia and glaucoma, which can be hard to diagnose due to their intersectionality.

When diagnosing glaucoma in myopic patients, he said to “always establish a baseline of structural and functional parameters.” Ophthalmologists should remember that in difficult situations, each patient can be their own

reference in a longitudinal assessment.

“We should evaluate with more criteria, using stereophotography, OCT and IOP — and be careful when establishing the target IOP in all subjects,” said Dr. Vessani.

On peak versus mean fluctuations

Dr. Remo Susanna, Jr. from the University of São Paulo, Brazil, spoke about what matters the most in IOP fluctuation — peak or mean. Multiple published papers have shown that peak IOP is the most important value, with no papers contradicting this.

However, these peaks can be easy to miss due to the natural fluctuations throughout the day. Dr. Susanna suggests that, among all possible methods, the “water drink test” is a cheap, feasible and easy way to compare and estimate peak IOP. Plus, it is easier and more useful than seeking a target mean IOP.

On treating glaucoma and pregnancy

Then, Dr. Wilma Lelis Barboza from the Universidade de Taubaté, São Paulo, Brazil, discussed Glaucoma Drugs in Pregnancy: “With more older women giving birth, we need to consider the effect of glaucoma medication on fetal development.”

Her advice, based on the latest research is that “we should not expose pregnant women to the risk of medication, if it’s not glaucoma and — even then — we should consider the severity.”

Dr. Barboza also advised to avoid using

any drugs until at least the tenth week of pregnancy. Ophthalmologists should also consider laser treatment, and she said it’s better to introduce one treatment at a time, and that in case surgery is advised, it should be performed without mitomycin-C.

On LPI in PACS

The next presentation was by Dr. Fabian Lerner from the University Favaloro School of Medical Sciences, Buenos Aires, Argentina. He talked about primary angle-closure suspect (PACS): Should we perform LPI (laser peripheral iridotomy) or not?

In a study of 889 patients, where half received LPI, investigators found that there was a significant reduction in primary angle closure disease in patients who received the treatment (47% reduction of risk). This was highlighted by Dr. Lerner and he advised that “we should particularly consider LPI for patients in need of frequent dilation or who have difficulty in accessing eye care.”

On phaco versus phaco/ trabeculectomy

Dr. Lisandro Massanori Sakata from Universidade Federal Parana, Brazil, discussed treating PACG (primary angleclosure glaucoma) with phaco versus phaco/trabeculectomy.

In a study of 208 patients, it was found that phaco alone can be a very effective therapy and should be chosen whenever it is safe.“But it should likely consider the glaucoma severity status, as well as the amount and extension of PAS (peripheral anterior synechiae), preop IOP levels, and if the patient is at maximum tolerated therapy or not,” said Dr. Sakata.

The rationale is that, in advanced glaucoma, if phaco fails to lower IOP, the possible result is irreversible blindness. So in such cases, with little room for failure, surgeons should opt for phaco/ trab.