CAKE POST (WGC 2021 Edition) - ISSUE 4

Brooke Herron Editor

Ruchi Mahajan Ranga

Brandon Winkeler

Andrew Sweeney

Chris Higginson

Hazlin Hassan

Joanna Lee

Sam McCommon

Tan Sher Lynn

Maricel Salvador

WGC Day 4 Cherry Blossoms,

Conference Finale and the Fourth of July

by Andrew Sweeney

Japanese culture is well known for its appreciation of the cherry blossom … when the eponymous tree lets loose its flowery petals — and indeed the season is one of the busiest periods in Japan. Thousands travel to the country to witness the blossoming and many more locals travel domestically to view the staggered blooms. You can find this phenomenon in dozens of examples of indigenous art, as well as in prose and poetry.

Indeed, the cherry blossom was traditionally associated with the ancient Samurai class: fearless warriors who made up a small percentage of feudal Japanese society, but nonetheless continue to exercise remarkable

cultural pull to this day. The beautiful but brief experience of the cherry blossom was held up as a metaphor for the life of the warrior, glorious yet brief, falling away from life as petals fall from the tree. A poignant reminder that nothing in life, no matter how great or wonderful, lasts forever.

And so like the cherry blossom tree, we come to the last day of the World Glaucoma e-Congress (WGC 2021) — and while the flowery analogy might be a little gushy, the Media MICE team has thoroughly enjoyed this conference and we’re sad to see it go. Despite the huge difference in time zones managed by organizers, the high production values and detailed content of the various symposiums are to be commended. We will, of course, be happy to return to sleep at more reasonable hours (and not miss the remaining Euro 2020 games or celebrate the 4th of July) but what are sleep,

football and fireworks to the world of ophthalmology?

You call that glaucoma? This is glaucoma...

Now only a truly international conference like WGC 2021 would be describable using the Japanese cherry blossom metaphor, and then start its last day with a decidedly Antipodean flavor. Australian and New-Zealand Glaucoma Society — Change What You Do! Change How You Think! was one of the first symposiums of the day and provided some fantastically crikey(!) insights into glaucoma from the land Down Under and further abroad.

The first speaker of the symposium was Dr. Graham E. Lee, a professor of ophthalmology, at the University of Queensland (Brisbane, Australia). Dr. Lee spoke about some of the most common surgical techniques employed by his society’s members with a particular focus on trabeculectomy. He reported that a slim majority favor no pre-treatment, around two-thirds prefer day surgery, and that a vast majority (of around 95%) prefer to use monitored local anesthesia.

The other key speaker from the symposium was Prof. Robert Casson, the head of the Discipline of Ophthalmology and Visual Science at Adelaide University (Australia). Prof. Casson presented his view on how glaucoma will progress in the coming years and identified it as a key public health issue for a number of factors. These include:

the aging global population; the fact that 50% of individuals suffering from glaucoma are undiagnosed; and that there are serious shortcomings in funding for treatment in low-income countries.

Diabetes and glaucoma

Glaucoma is finally getting the recognition for the public health threat it is. But what happens when the disease is present in a patient with another condition that’s more widely associated with a large public health impact? This was the topic of a presentation by a group of researchers from the All India Institute of Medical Science (AIIMS, New Delhi, India), led by Dr. Swechya Neupane. Their research, the Prevalence of Glaucoma in Patients Having Diabetic Retinopathy (DR), examined how glaucoma impacts diabetics.

The Indian researchers wanted to identify both the prevalence of glaucoma, as well as the various types of glaucoma that may be encountered. The study ran for two years and examined subjects who were 40-years-old or over, and included screening procedures such as fundus exams and gonioscopy. The study found that 28.7% of DR patients surveyed had glaucoma, and of these, the plurality at 44.2% were primary angle-closure suspects, followed by 27.9% with primary angle-closure glaucoma.

We would be remiss if we didn’t feature a presentation focused on IOP, given its (very) close association with glaucoma. And we found a particularly interesting take on the subject: Intraocular Pressure (IOP) In Children With Acute

Lymphoblastic Leukemia (ALL). Given by Dr. Noa Geffen, an ophthalmologist at the Rabin Medical Center (Petah Tikvah, Israel), the presentation revealed how elevated IOP and steroid-induced glaucoma are side effects of ALL treatment. Dr. Geffen collected data on pediatric patient demographics, as well as white blood cell counts, triglyceride levels and blast percentages in the bone marrow.

Watch for high IOP in leukemia patients

Of the 90 subjects (one of whom regrettably died during the course of the study), 71% had IOP of >21 mmHg, and 39% had IOP of >25 mmHg. Out of this group, 9% required hypotensive medical treatment to stop their IOP from rising even further. According to Dr. Geffen, increased IOP may be associated with elevated blood viscosity. The study concluded that the severity of a patient’s ALL is correlated with a higher risk of high IOP, and that patients with the highest degree of ALL severity should have their IOP closely monitored.

From starting the day with a report on Antipodean ophthalmology and glaucoma treatment to the final sessions covering tube surgery, artificial intelligence and controversies in glaucoma surgery, we’re sad to see WGC 2021 go. (But those celebrating the 4th of July are ending the conference with full fireworks, literally!). This is especially so, as the final session of the day was in fact a karaoke event which — while filling your Scottish correspondent with absolute and abject horror — was certainly popular among other members of the Media MICE team. Who knows, perhaps this is an idea we can carry forward until more real-world conferences make a full comeback in the post-COVID-19 era.

There are still loads of symposiums, papers, abstracts and films to check out on the WGC’s virtual platform, so make sure you swing on by — there’s some seriously cool stuff out there that we know you’ll love. In the meantime, think not on the quick blossoming of the petal and its fall into oblivion, for all good things must come to an end. The tree that gives life to the flower continues to grow, and that means there’ll be more ophthalmology conferences coming up to look forward to, so we will see you at the next one.

As most in the western hemisphere celebrate 4th of July, the World Glaucoma Association (WGA) took glaucoma on the brightest world stage, beyond borders, at WGC 2021.

Unmet Needs and Opportunities in Glaucoma Treatment

by Brooke Herron

On the final day of the World Glaucoma e-Congress (WGC 2021), an expert panel reinforced and discussed current clinical challenges faced by glaucoma specialists in an Allergan (an AbbVie company) sponsored symposium titled Clinical Challenges in Glaucoma and Role of Earlier Intervention. Let’s dig in...

Eight unmet needs and challenges

While there are many unmet needs and challenges in glaucoma, Prof. Keith Martin, from the Centre for Eye Research Australia in Melbourne, presented a small subset including eight key areas:

1. Better classification of glaucoma: For primary open-angle glaucoma (POAG), different mechanisms are often lumped together because they have a final common pathway that looks pretty similar … but lumping together glaucoma subgroups has been unhelpful. “With genetic profiling, we finally have the chance to start to unpack that and I think that will help us target our therapies.”

2. New strategies to improve adherence: It doesn’t matter how good the drugs are, if patients aren’t adherent, they’re not going to get the beneficial effect. “I think that’s part of the justification for the development of slow-release treatments and other new ways of dosing with glaucoma medications.”

3. Better understanding of glaucoma pathogenesis: “Glaucoma doesn’t just involve loss of retinal ganglion cells (RCGs).”

4. Better IOP measures: “What we really need are new ways to measure IOP more dynamically under longer periods of time … and I think the most exciting technology [being developed] are IOP sensors.”

5. Enhanced risk prediction: “We can determine a large proportion of the risk for glaucoma from a single genetic profile from a patient.”

6. Neuroprotection and neuroenhancement: “We need to make neuroprotection trials feasible … I have a big interest in neuroprotective gene therapies for glaucoma, and this is a technology that’s really hit its day.”

7. Optic nerve repair: “We’ve discovered several ways we can use CRISPR technology to reprogram Müller cells in the retina into photoreceptors.”

8. Personalized glaucoma care: “We can think more about individualizing surgical treatment based on aqueous outflow.”

Limitations and opportunities in treatment

Dr. Anthony Khawaja, from Moorfields Hospital (London, UK), began by describing the major glaucoma medication classes and their side effects: “In fact, many of our glaucoma patients’ only symptoms are from treatment side effects … and something all drops can contribute to is ocular surface disease (OSD),” he said, adding this is common in 31-60% of glaucoma patients.

The higher the number of drops, the higher the prevalence for OSD, continued Dr. Khawaja.

Regarding future directions for medical therapy, he said: “[We can] improve adherence with modern technology … and there are emerging new drug delivery methods which may increase adherence and reduce OSD. There’s also growing evidence that genomics will enable us to predict which patients will respond well, or otherwise, to individual treatments.”

Next, Prof. Herbert Reitsamer, from Paracelsus Medical University Salzburg (Austria), discussed minimally invasive glaucoma surgery (MIGS) and the different outflow pathways they target. “Different MIGS procedures have different risk profiles and efficacy in terms of how well they lower IOP,” he explained.

“The way I use implants is I define target pressure and then I look at the potential of the various MIGS that are available — and whether or not MIGS makes sense anyway. It depends on whether there is severe, moderate or mild glaucoma and it also depends on the rate of progression, life expectancy, untreated IOP ... and there are many other risk factors that need to be taken into consideration,” shared Prof. Reitsamer.

During the Q&A, the panel discussed subthreshold laser therapy (SLT). “The biggest driver of whether SLT works or not is how high the IOP is,” said Dr. Khawaja. “The future is being able to predict who’s going to be a really good candidate for SLT… and rather than working at 60%, maybe if we can look at genetic markers or just look at clinical factors that can predict response, we can get that up to 80-90%.”

Symposium Covers Glaucoma Challenges in Russia, Belarus and Beyond

by Andrew Sweeney

If any one concept or idea has been emphasized at the World Glaucoma e-Congress (WGC 2021), it’s that glaucoma is a truly global issue. It’s one of the most common eye diseases in the world and we’ve heard from multiple delegates, guests and societies about the severity of the condition in their countries. Information from some countries, particularly those in East Asia, are more familiar to our regular CAKE readers, while others may be less so.

In the English-speaking ophthalmology community, we don’t tend to hear much from the countries of the former Soviet Union, but we’re happy to say that is changing. At our recent CAKE & PIE Expo (C&PE 2021), we were joined by the Russian Ophthalmology Society, which organized their own symposium. During the last day of WGC 2021, we also got to enjoy Commonwealth Independent States Glaucoma Society — Doctor and Patient — Where is the Stop Red Line? Here, the commonwealth refers to the CIS, a group of countries made up mostly of post-Soviet republics.

From Russia, with valuable patient demographic advice

The first speaker was Dr. Anna Movsisyan, an ophthalmologist at the Moscow Healthcare Department Hospital for Veterans No. 2 (Russia), who laid out a high-quality report on the characteristics of glaucoma in her country. In particular, Dr. Movsisyan gave insight into the duration of glaucoma

soreness among Russian patients, which on average lasts for 12 years. The onset of the disease is usually between the ages of 55 and 60, with more severe outcomes occurring after the age of 73.

Dr. Movsisyan also shed light on a study that highlighted the ethnic characteristics of glaucoma regarding soreness. As stated, the onset for Russian patients is 12 years, but according to Dr. Movsisyan, the average duration is 13 years for Latin Americans, 10.5 years for Asians, and 15.4 years for African Americans. Finally, she reported on issues with glaucoma treatment compliance in Russia, stating that up to 25% of patients do not follow their recommended treatment plan.

Coping with COVID-19 in Europe’s last closed state

Now we’re all familiar with the troubles experienced by ophthalmologists and other medical personnel during the COVID-19 pandemic, but imagine going through that strife in a politically closed society with limited resources

for the national healthcare system. That was the predicament faced by doctors working in Belarus, which was the subject of a presentation by Dr. Tatsiana Imshenetskaya of the Belarusian Medical Academy of Postgraduate Education in Minsk. She reported how ophthalmologists in her country were at particularly high risk as the one-meter distance required to examine patients made safe social distancing difficult.

Dr. Imshenetskaya reported that several changes had to be made to glaucoma treatment in Belarus, including a preference for non-penetrating glaucoma surgery, minimizing patient followup and an increasing preference for valved drainage devices. She also stated that the risk of intraoperative and postoperative complications had increased, as had the risk of choroidal detachment. In her concluding remarks, Dr. Imshenetskaya said that clinicians need to rate non-compensated glaucoma as an urgent patient condition in the post-COVID-19 era, and to consider a more individual approach toward patient outcomes.

Top Tips from the Land Down Under (and New Zealand, too)

by Joanna Lee

Besides the risks, detecting glaucoma also remains a challenge. The landmark Australian Blue Mountain Eye Study from 1996 found a 50% rate of undiagnosed glaucoma. Remarkably, the 2019 Australian National Eye Health Survey found the prevalence of undiagnosed glaucoma still remained at 50%.

The Australian and New Zealand Glaucoma Society (ANZGS) showcased a glimpse of the current practices in glaucoma intervention while reflecting on future challenges for managing the disease and patient care. A session at the World Glaucoma e-Congress (WGC 2021) moderated by Professor Alex Hewitt from the Centre for Eye Research Australia and the University of Tasmania, Professor Graham Lee, a professor of ophthalmology in Brisbane and co-founder of the International Ophthalmology Portal, gave an update of trabeculectomy, especially looking at “tips and tricks of ANZ (Australian and New Zealand) glaucoma surgeons.”

The evolution of trabeculectomy

Trabeculectomy has evolved ever since its introduction in 1968. The Moorfields Safer Surgery System for Trabeculectomy, developed by Sir Professor Peng Khaw (of Moorfields Eye Hospital, London, United Kingdom) in the recent decades remains a major influence for this surgical technique.

In the study, 49 glaucoma specialists were surveyed via an ANZGS meeting using a 39-question online poll. The goal of the survey was to find out what glaucoma specialists would typically do for routine adult trabeculectomy for primary open-angle glaucoma (POAG). The study showed that although a wide range of trabeculectomy techniques exist among ANZGS surgeons, there are some consistent practices currently in use.

Some of these are: creating a corneal traction suture (94%) using 7-0 vicryl or silk; a fornix-based conjunctival flap (92%); using anti-metabolites like mitomycin-C in 98% among the respondents. They also looked at how these different techniques are applied: pledget (78%), injection (16%), and 80% administer a 0.02-0.03% solution.

Peripheral iridectomy was done 98% for phakic eyes and 72% for pseudophakic eyes. Variations in techniques such as the use of the Ong Speculum and scleral flap formation were discussed (70% of surgeons use the rectangular flap). Prof. Lee also discussed the pre-placed scleral flap suture technique (used by 63% of the surveyed specialists). Finally, the discussion of the survey also covered testing the flow of the scleral flap, conjunctival closure and postoperative care.

10 challenges

Reprising his Gillies Lecture at the ANZGS talk, Professor Robert Casson, professor of ophthalmology at the University of Adelaide presented Glaucoma: Challenges for the 21st Century, where he highlighted 10 challenges for the disease moving forward. Here are some of the points he shared.

The first challenge, and perhaps the greatest, is of the aging population. As people live longer, the challenge is how to maintain healthy eyes. Thus, he says that economic and political reforms are needed to mitigate this in the long run. The second challenge is in determining how prevalent the problem might be. With a growing global population and the prevalence of angle-closure glaucoma among Asians, only about 50 studies have been done over the last 30 years (and only 5 studies from Africa). His proposed solution, besides empowering local teams to conduct epidemiological surveys, was to have support from a dedicated professional glaucoma epidemiological team like his “Vision Loss Expert Group.”

Understanding the risk factors for progression is another issue. Here, he discussed polygenic risk score (PRS) which uses the calculated sum from many small genetic variants. The disadvantages of PRS currently lie with the lack of data on non-European populations and not having the optimal mathematical model for quantitative genetics. However, fostering more PRS analyses in Asia, while rethinking the mathematical model for the latter, could mitigate this hurdle.

He continued that many glaucoma specialists may have overlooked patients’ quality of life (QoL) in the interest of preserving vision. This remains a challenge, he said while explaining the need to develop research and clinical tools to measure glaucoma patients’ QoL.

New treatments are also a challenge but also an area of excitement. Besides the available modalities to reduce IOP and medication, he said “neuroprotection is a tough nut to crack,” citing his interest in the area of bioenergetics while showing his study, which looked at the vitreous reservoir as a potential for energy substrates. Prof. Casson also pointed to interesting research that has looked into vitamin B3 as a potential glaucoma treatment, and cited his current investigation into pyruvate as a bioenergetic neuroprotective agent as another new potential on the frontier of treatment.

Optimizing Outcomes for Glaucoma Surgery

by Tan Sher Lynn

Until today, trabeculectomy remains the most effective method for long-term lowering of intraocular pressure (IOP). However, the procedure poses some early and late onset complications. Dr. Naveed Nilforushan from the Iran University of Medical Sciences shared some considerations that could make trabeculectomy safer and more effective.

According to Dr. Nilforushan, patient selection is the most important predictor of outcome in trabeculectomy. “A person who often travels to remote areas without access to medical care, or one who engages in water-based sports, or uses contact lenses, isn’t a good candidate for this surgery,” he said.

Other risk factors for failure or complication include multiple prior surgeries, uncontrolled uveitis, dry eye, inflamed and thin conjunctiva, angleclosure glaucoma and high hyperopia, uncontrolled diabetes, high blood pressure and clotting disorders. A history of a bad outcome after filtration surgery in the fellow eye should also be taken seriously.

“All lid problems, such as trichiasis, entropion and blepharitis should be treated before the surgery. If there is a

conjunctival injection, the patient should be given a short preoperative course of topical steroids. It is also very important to control the IOP as much as possible before starting the surgery.

“Surgical success is highly related to regular and timely follow-ups. The goals are to monitor for complications and identify factors that may jeopardize long-term bleb function. Most early complications are transient, and serious complications like choroidal hemorrhage are fortunately rare,” said Dr. Nilforushan.

According to him, late complications like thin avascular blebs, leakage, blebitis and hypotonia are more commonly due to prolonged inhibition of fibroblasts by mitomycin-C (MMC). In high-risk patients, alternatives which can be used include collagen matrix (Ologen; Aeon Astron Europe B.V., the Netherlands) and Avastin (Genentech, California, USA).

“To achieve IOP in the low teens, it’s important to make a thinner and smaller scleral flap, and a larger ostium, and use higher dosages and/or longer duration of MMC application, as well as removing the flap suture earlier. Blebs that show signs of encapsulation or failure can be treated more aggressively with additional

treatments of 5-fluorouracil, MMC or early needling,” added Dr. Nilforushan.

Tips for NPGS

Meanwhile, Dr. Ramin Daneshvar from the Mashhad University of Medical Sciences, Iran, shared some important points regarding non-penetrating glaucoma surgery (NPGS).

According to Dr. Daneshvar, when putting in a traction suture, which is the first step of NPGS, more exposure is needed in comparison to trabeculectomy. “Corneal traction sutures are more appropriate than the superior rectus (SR) bridle suture as they can be used to hold the superficial scleral flap,” he said.

“Next is to make the conjunctival peritomy, which should be more extensive than in trabeculectomy. Leakage is not a major issue and good exposure of sclera is essential,” explained Dr. Daneshvar.

“The superficial scleral flap should be made large enough in order to have a sufficiently sized scleral lake. It should not be too thin to avoid staphyloma formation, and not too thick in order to permit sufficient depth. Standard size is 5x5 mm and about 30-50% thick,” he added.

“The deep scleral flap should extend to the level of the uvea. The standard size is 4x4 mm with 95% of thickness. When cutting a deep flap, cut as near the hinge as possible to provide a sufficiently sized trabeculo-Descemet’s membrane (TDM). One should be careful not to traumatize the TDM when cutting the flap,” said Dr. Daneshvar.

A fiber optic device is used for the cannulation of the Schlemm’s canal. Dr. Daneshvar noted that as the illuminated fiber optic passes through the canal, one should be careful as it could be entrapped in the collector channel ostium, misdirected, or it could reach an obstruction in the canal.

“When suturing the superficial flap, usually 5 sutures are required. It can be sutured tightly because there isn’t a need for a subconjunctival bleb. Finally, the closure of the conjunctiva can be done with 2-wing sutures because leakage is not a big issue in NPGS,” he concluded.

Members of the Iranian Glaucoma Society shared tips on preventing trabeculectomy complications, as well as on performing a non-penetrating glaucoma surgery during a symposium at the World Glaucoma e-Congress (WGC 2021).

It’s Not Child’s Play The Genetics of Childhood Glaucoma

by Brooke Herron

All good things must come to an end … and the final day of the World Glaucoma e-Congress (WGC 2021) continued to offer vital information on new technologies and techniques to ophthalmologists beyond borders One such symposium from the Childhood Glaucoma Research Network was The Power and Precision of Genetics in Childhood Glaucoma: No Longer a Shot in the Dark. And we can agree that preserving sight in everyone — and perhaps, particularly in children — is the ultimate goal.

Co-chaired by Miami, Florida, USAbased Dr. Alana Grajewski and Assoc. Prof. Ta-Chen Chang, this symposium reviewed the genetics of childhood glaucoma, as well as potential treatment options.

The genes behind childhood glaucoma

Primary congenital glaucoma (PCG) is the most prevalent form of childhood glaucoma and its impact on a child’s

visual development and overall life can be devastating, began Rachida Bouhenni, PhD, from Akron Children’s Hospital (Ohio, USA). PCG manifests during infancy before the age of 3.

“The exact mechanisms for development of PCG remain unproven; however, developmental arrest in the late embryonic stages leads to defects in the anterior chamber angle (that includes iris insertion and compression of the trabecular beams) has been suggested,” said Dr. Bouhenni.

Three causative genes have been identified: CYP1B1, LTBP2 and TEK. She shared that CYP1B1 is the most common causative gene and most patients with PCG caused by mutations in this gene have a severe disease phenotype. However, the role of CYP1B1 in the eye is not known, explained Dr. Bouhenni.

Further, CYP1B1 accounts for approximately 20% of PCG in Western populations, shared Dr. Terri Young, from the University of Wisconsin (USA),

during her presentation titled Childhood Glaucoma Genetics — A Review of the World’s Literature.

She also discussed juvenile open-angle glaucoma (JOAG), which is usually diagnosed between the age of 4 and 40 years. “These globes may not necessarily show enlargement and these individuals may have what appears to be a normal angle,” said Dr. Young.

Climbing the family tree

Until 2016, the genetics of PCG looked at trios (parents and child) … and generally, the parents had no history of glaucoma and had an affected child. “But with the advent of deep sequencing technologies, we’ve been able to tease out different genes with a different mode of inheritance and changing the paradigm. One is Schlemm’s canal and understanding its development is a unique hybrid between vascular and lymphatic endothelium,” said Dr. Young.

“Understanding the biology always helps in terms of developing new therapies or revising treatment strategies,” she continued. “It’s apparent — if we’re looking at childhood glaucoma and PCG — that it’s a heterogeneous disorder and the approach for nailing down what the patient and the family needs to be broadened. You want to ascertain more than just the family unit, you want to grab siblings and go up and down the scale in terms of generations (if you can) to get a better understanding of how it’s transmitted in the pedigrees.

“I think that phenotyping is important too, and what we’re finding is that the parents often have signs of early glaucoma but being a silent disease, they may not know it,” said Dr. Young.

GATT for Myocilin JOAG

During her presentation, Dr. Erin Boese from the University of Iowa (USA) shared a successfully treated case study of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) as a Primary Treatment for Myocilin (MYOC) Juvenile Open Angle Glaucoma (JOAG).

The patient was an 11-year-old female who was originally referred for ocular hypertension, presenting with 45 mmHg OD and 38 mmHg OS. “Due to a strong

family history of JOAG, she had been followed every six months for IOP checks and at her last appointment, her IOPs were normal at 12 mmHg in both eyes,” reported Dr. Boese.

This patient had a remarkably strong family history of JOAG, spanning three generations and including 11 people. “Genetic testing identified a myocilin mutation (Asp384Asn) that was coinherited with JOAG in all eight family members who were available for genetic study,” she shared.

“Other than remarkably high IOPs, the rest of her exam was normal,” said Dr. Boese. The patient was placed on dorzolamide, brimonidine and latanoprost. “This regimen got her pressure down to 14 mmHg in both eyes, but unfortunately, brimonidine had to be discontinued due to drop intolerance.”

The remaining drugs stabilized her IOP to the low 20s for a couple of years. “At 15 years of age, her IOP started to climb again and brimonidine was re-added, this time with better tolerance. And when she was 17, her IOP again jumped to 40 mmHg and 45 mmHg in her right and left eyes, respectively,” she continued. At this point oral acetazolamide was added, which brought her IOP back to the mid-20s. Unfortunately, this caused the patient serious fatigue and the decision to pursue surgery was made.

When considering her surgical options, Dr. Boese said they took her myocilin mutation into account, noting that patients with MYOC-associated JOAG tend to have very resilient optic nerves. In this particular patient, four family members had bilateral trabeculectomies.

She continued: “To put it simply, all of these studies that we have to date show that myocilin is as pure a trabecular disease as you can get.”

After noting recent research, Dr. Boese shared that this led to a specific treatment question: Why don’t we bypass the trabecular meshwork (TM) all together with an angle-based procedure?

In 2014, Dr. Grover and his colleagues first described GATT which is a MIGS procedure that fractures through 360-degrees of the TM — the very area affected most by MYOC mutations, said Dr. Boese.

“GATT can be more difficult to perform in these phakic children with minimal angle pigmentation. I’ve started doing what I call the ‘blue donut technique,’” she explained. Trypan blue can be very helpful to better delineate the trabecular meshwork but the long-term effects on clear crystalline lens are unknown.”

To help prevent inadvertent staining of the lens, Dr. Boese deposited dispersive

viscoelastic over the pupil followed by injecting a peripheral donut of trypan blue into the angle via a nasally directed paracentesis wound. She then increased the IOP of the eye to force the trypan blue into the TM, and then rinsed it out.

This patient underwent GATT in her right eye, followed by GATT in her left eye one month later. “Her right eye IOP immediately dropped and then stayed between 10-12 mmHg (off of all glaucoma medications). At her last appointment, 15 months postoperatively, her IOP was 11 mmHg. Her left eye had a small spike to about 25 mmHg at three weeks post-op, which was thought to be due to a residual clot within the goniotomy cleft; this was temporarily treated with dorzolamide and brimonidine and later switched to latanoprost only, before being discontinued altogether. Now, more than one year out, both eyes have an IOP of 11 mmHg.”

This technique, along with all the other research underway, led moderator Dr. Grajewski to conclude that “the advances we’re making in the laboratory will affect our everyday care of these small, important patients.” And indeed, we look forward to hearing more about the important strides that scientists, researchers and ophthalmologists are making to combat this sight-debilitating disease.

Yes, they’re all adorable … but could their genetics be taking them down the troublesome road of childhood glaucoma?

Rapid Fire

Bite into These Glaucoma Nuggets

by Tan Sher Lynn

On Day 4 of the World Glaucoma e-Congress (WGC 2021), attendees continued to learn more about glaucoma, including its different (and widely varying) risk factors, MIGS outcomes and more, during a Rapid Fire symposium led by experts from around the world. Below, we cover some of the highlights...

Rubella and newborn glaucoma

Intrauterine infections may affect various structures of the developing fetal eye, leading to glaucoma and cataract in newborns. From a study involving 27 babies with newborn glaucoma, Dr. Sandeep Choudhary, senior resident of the Advanced Eye Centre, PGIMER (Chandigarh, India), found that rubella positive babies have worse corneal clarity (3.8 ± 1.5), smaller axial length (16.58 ± 1.02), smaller corneal diameter (10.9 ± 0.7) and co-existent cataract (30.7%). He also found that the cornea cleared significantly in rubella negative, but not in rubella positive infants despite comparable IOP reduction.

“Newborn glaucoma in rubella positive cases are phenotypically different. The infants are born with smaller eyes and persistent corneal opacity which are not related to raised IOP alone. Cases of unrecognized congenital rubella infection might be mistakenly diagnosed as intractable congenital glaucoma. Hence, any glaucoma with smaller eyes should raise suspicion of glaucoma with rubella,” he said.

Retinitis pigmentosa — a glaucoma risk factor?

Retinitis pigmentosa (RP) is a genetic disorder that involves the breakdown and loss of photoreceptor cells. Patients typically lose night vision and peripheral vision, leading to eventual blindness.

Dr. Yu-Yen Chen from the Taichung Veterans General Hospital (Taiwan), investigated the association between RP and primary angleclosure glaucoma (PACG) through a population-based cohort study spanning more than 13 years using the Taiwan Health Insurance Database.

Results showed that the RP group (n=6223) has a significantly higher prevalence of diabetes (20.4% vs 17.7%), hypertension (38.5% vs 36.3%) and hyperlipidemia (28.6% vs 25.7%) compared to the non-RP group (n=24892). The cumulative incidence of PACG is higher in the non-RP group (1.61%) compared to the RP group (0.81%).

“Previous studies provided some theories on the association between RP and PACG. Patients with RP might have small eyes, cataract or lens subluxation, which predispose them to PACG. My conclusion is, those who suffer from RP will have a significantly higher risk of developing PACG. Understanding this association allows one to understand the need for timely intervention in susceptible eyes,” she said.

Hydrus versus iStent inject

The most commonly used MIGS devices in Australia are Hydrus (Ivantis, California, USA) and iStent Inject (Glaukos, California, USA). Dr. David Holmes (Australia) presented a study that compares these two canal-based MIGS devices in combination with phacoemulsification.

The 24-month outcomes of combined phacoemulsification with either iStent inject or Hydrus showed sustained IOP reduction with a good safety profile. There was no significant difference

in IOP outcomes between the groups. “Our results indicate there may be a small additional reduction in glaucoma medication usage following iStent inject compared to Hydrus. The differences could be further studied with a randomized controlled trial,” he said.

Role of Neuroserpin

Neuroserpin is a serine protease inhibitor common to the retina and other neural tissues. It is important for a healthy retina and has neuroprotective properties. Rashi Rajput, a PhD candidate from Macquarie University (Australia), presented her work which shows that antibody mediated neutralization of neuroserpin exacerbates retinal ganglion cell and optic nerve axonal damage in experimental glaucoma (using mice models).

“Increased structural and functional deterioration of inner retina and optic nerve were observed in glaucoma eyes subjected to neuroserpin neutralization. The loss of neuroserpin also accompanied elevated Beclin1 and LC3II/I expression. Microglia activation as quantified through Iba1 expression increased in the inner retina (inner plexiform layer, IPL) in glaucoma eyes with neuroserpin neutralization. This study demonstrates that neuroserpin plays a role in regulating neurodegenerative processes in the retina in experimental glaucoma conditions. Increasing neuroserpin expression may therefore be beneficial in glaucoma and will be the subject of further studies,” she said.

Beyond Borders

Surgeons to the Rescue

Glaucoma surgeons know that sometimes complications happen, both intra- and postoperatively: blebs can leak or fail, devices can cause issues and other adverse events can occur. On Day 4 of the World Glaucoma e-Congress (WGC 2021), experts from International Society for Glaucoma Surgery (ISGS) shared their tips on these issues and more.

On bleb revision

“Most blebs will need some form of revision. In fact, a third of them, in the first to five years, will need some work,” began Dr. Michael Coote (Australia) during his presentation, Rescuing of Blebs in Glaucoma Surgery. Bleb failure can appear in many places from inadequate outflow, dispersion or absorption, defining “inadequate” as when the total outflow of the eye does not produce target IOP.

To fix the failure, one must diagnose where and why the failure occured. For example, whether it’s due to the internal ostium, the flap (different from ostium), or the bleb itself. After touching on tissue porosity, he walked the audience through a demonstration of a posterior bleb revision.

On shunt complications

Dr. Keith Barton from Moorfields Eye Hospital London, United Kingdom), presented Common Tube Problems and Remedies, discussing the various shunt complications that could occur. He said this includes low IOP, high IOP, corneal endothelial damage, exposure and diplopia.

Low IOP could occur due to an overdraining tube or peri-tubular drainage, which could opt for ligation or stenting; in cases involving high pressure, the tube could be obstructed by iris or vitreous. If tubes aren’t properly placed, corneal endothelial damage could occur. He then shared his study which illustrated how tube insertion is connected to the percentage of loss of

by Joanna Lee

corneal endothelial cell density over time.

When MIGS goes wrong

Next, ISGS President Dr. Tarek Shaarawy presented What Can Go Wrong with MIGS and How to Manage. He said that whether it’s the use of subconjunctival filtration, enhancing Schlemm’s canal, or going into the suprachoroidal space, or even via cyclodestruction — there are advantages and disadvantages with these types of surgeries.

For instance, CyPass MicroStent (Alcon, Geneva Switzerland) was recalled after trials showed a corneal endothelial cell loss of more than 30%. There could also be discomfort or even vision loss after MIGS or even when the devices are taken out, hypotony develops. In this case, he calls for a thorough gonioscopy as low IOP could occur to the clefts found after device removal. He also warned against needling while explaining about hybrid blebs.

On laser treatment

Singapore’s Dr. Paul Chew shared the Do’s and Don’ts for a Complication-free Micropulse Transscleral Laser Therapy

Some of his tips include: awareness of the probe orientation (e.g., which side, toward limbus or lid) and probe positioning (should be 1-2 mm back from limbus), adding to not go too anterior and stay on target.

Dr. Chew said sweep speed is important as well: “Too slow and the heat may build and cause heat damage, while too fast may mean not enough dose is delivered,” he said. If you can’t sweep 180 degrees, covering a quadrant is also advisable, he shared. There should be more than 4-5 sweeps for 50 to 60 seconds of treatment.

Post-op hypotony

How do you deal with postoperative hypotony after trabeculectomy? Dr. Tanuj

Dada from India has the answer, during his presentation titled Complex Problems in Trabeculectomy

Excess filtration of aqueous is the cause for such hypotony, so the scleral flap could be closed without opening the conjunctiva — through what Dr. Dada calls “transconjunctival suturing.” If that doesn’t work, then he suggested an open surgery. After discovering the leakage spot, he showed how he raised the lamellar scleral flap to cover the defective area.

Another case study he presented was of a corneo-scleral trabeculectomy bleb on a patient with a thin, cystic bleb at the corneo-scleral junction at the limbus — which was a challenge to repair. He used optical coherence tomography (OCT) to guide the dissection to excise the entire bleb, which was on the cornea. After removing the bleb, he showed how they dealt with the gap and avoided unnecessary suturing. He also addressed a subsequent defect in the cornea by creating a graft to cover it, as well as an overlay for the conjunctiva.

The burden is global

During his Glaucoma Surgery for the Underprivileged presentation, the ISGS Rights to Vision Chair and President of Sight for Life Foundation, Dr. William Eric Sponsel, discussed the global burden of glaucoma.

He said there are more people with angle-closure glaucoma (which cataract surgery could help). And while cataract surgeries are relatively easier to do, glaucoma surgeries require “sustainable eyecare,” according to Dr. Sponsel. He touched on general principles based on their experience in the field. For instance, in the absence of well-equipped local facilities with skilled follow-up, it may be better for visiting surgeons to perform laser (YAG iridotomy) and cataract surgery. There are many cases of chronic angle closure amenable to YAG iridotomy and argon iridoplasty. He also shared that selective laser trabeculoplasty (SLT) is very effective in POAG. Also, for patients at high risk of visual loss, he suggested to embrace incisional procedures with high IOP-reducing efficacy and lower probability of postoperative complications.