PIE POST (APVRS 2021 Edition) - DAY 1

The 14th APVRS Congress Opened Beyond All Limits

by Joanna Lee

On December 11, 2021, the Asia-Pacific Vitreo-retina Society kicked off its firstever virtual congress (its 14th!) – the APVRS 2021 Virtual. This marks the first online event since the Society’s inaugural congress was held in Hong Kong in 2006. This year’s theme Beyond All Limits, serves to show the industry’s spirit to overcome the current setbacks and challenges posed by the ongoing COVID-19 pandemic.

Day 1 of APVRS 2021 Virtual welcomed more than 1,500 registered participants with a virtual walk down memory lane, tracing the footsteps of past APVRS congresses throughout countries in the Asia-Pacific region, including Australia, China, India, Japan, Malaysia, South Korea and Thailand.

During the opening ceremony, Dr. Andrew Chang, organizing committee chair and APVRS secretary general, expressed his gratitude to everyone involved with this year’s Congress. He gave a special shout-out to APVRS Scientific Program Chair Prof. Paisan Ruamviboonsuk and the APVRS Organizing Committee, who together, assembled a stellar

line-up of programs and speakers covering the diverse subspecialties and topics in the field of vitreoretina.

Prof. Dennis Lam, honorary congress president of APVRS 2021 Virtual and the APVRS immediate past president, conveyed a special thanks to all sponsors for their support, as well as gratitude to congress participants. “Your participation has made all the hard work worthwhile,” he said.

For those unable to join the Congress virtually this weekend, scientific sessions will be available on-demand until March 2022 on the APVRS 2021 Virtual platform.

The APVRS 2021 Virtual Tano Lecture

The APVRS Tano Lecture was established in 2009 in memory of Prof. Yasuo Tano, one of the Society’s founding presidents. Each year, APVRS honors an individual with the Tano

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Lecture for their exemplary leadership and significant contributions to advancing the understanding, diagnosis and treatment of vitreoretinal diseases.

Prof. Chi-Chun Lai is the recipient of the 14th APVRS Congress Tano Lecture.He is the superintendent of the Chang Gung Memorial Hospital (Keelung) in Taipei, as well as an ophthalmology professor at the Chang Gung Memorial Hospital and Chang Gung University. He is the current president and one of the founding members of the APVRS.

His presentation, titled Management of Macular Hole Retinal Detachment , traced the evolution of surgical techniques — ultimately, leading to his team’s exciting novel technique that uses a sub-perfluoro-n-octane (sub-PFO) injection of ocular viscoelastic device (OVD) to stabilize inverted ILM flap onto the macular hole (MH).

The evolution of MHRD treatment

Macular hole retinal detachment (MHRD) is a vision-threatening complication in highly myopic eyes. The ideal treatment remains under development and long-term functional results are still unfavorable.

The evolution of treatment has been gradual. Beginning prior to the 1990s, with macular buckle surgery; then vitrectomy in the 1990s; the introduction of Tano’s brush ILM peeling and OCT for diagnosis in 2000; and ILM (internal limiting membrane) flaps in 2010. Today, macular plug, ILM insertion and autologous retinal graft (ARG) are emerging, and more novel techniques are expected in the future.

Prof. Lai then shared some of the history and outcomes of these surgical techniques.

The late Prof. Tano, for whom the award lecture is named, invented the diamonddusted silicone cannula (or Tano’s brush). The instrument has been shown to be effective in removing epiretinal membrane (ERM) while increasing the reattachment rate in MHRD. In fact, Tano’s brush was 100% effective in both these areas, while the previous conventional method for macular hole

surgery yielded only a 45.5% success rate.

In 2000, vitrectomy followed by laser photocoagulation on macular hole performed under perfluorocarbon liquid with silicone oil tamponade, was suggested as the best method. Three years later, Prof. Yasushi Ikuno and Prof. Tano pioneered another method. They used OCT to evaluate the macular hole’s closure status; thereafter, they performed vitrectomy and removed the premacular vitreous via Tano’s brush, and stained and peeled the ILM with silicone gas.

In this study, only 44% of patients’ macular holes closed, but they had better visual acuity (VA) than those whose MH didn’t close. “This indicates that macular hole closure is very important in the treatment of MHRD,” said Prof. Lai. Undeterred, in 2006, Prof. Lai and his team investigated a range of surgical methods to treat MHRD; however, their results varied.

Then, the inverted ILM membrane flap technique was invented for large macular holes.

A 2012 review comparing surgical methods revealed more anatomical success for the vitrectomy and macular buckle over pneumatic (gas) methods. However, the study numbers for macular buckle surgery were smaller. Vitrectomy has now become the preferred way to treat MHRD.

Notably, another advance was recorded in Dr. Shoji Kuriyama’s study, which uses the inverted ILM technique for treating macular hole in high myopes. “Despite only having three hole closures out of hole eyes, this was considered a success in the 10 years prior,” Prof. Lai remarked.

Thus far, there has been a low success rate of retinal reattachment and macular hole closure. Other factors include the long duration in a prone position and poor postoperative VA.

Improving MHRD treatment

Seeing many gaps to improve the treatment for MHRD, Prof. Lai and his team conducted a study using inverted ILM repositioning on 27 patients,

employing a blood clot to seal the hole. Their method resulted in retinal reattachment and MH closure in 96% of eyes in a single surgery; meanwhile, vision improved in 67% of the eyes. “We had a great improvement using this ‘very brutal’ method,” he said.

Subsequently, many modified ILM flap techniques have been used for treating MHRD. One of the latest studies demonstrated that the ILM insertion method to be more effective than ILM removal, with better BCVA achieved in the former. “These days, we propose inverted ILM flaps along with ILM insertion to mitigate MHRD,” said Prof. Lai.

This current technique uses Tano’s brush and multiple ILM inverted flaps to cover the macular hole. “Under sub-PFO, it is easier for us to invert the ILM flap. Then, we remove more ILM to release the traction in the MH,” he explained, during a demonstration of his surgery.

“In what we call our ‘spot’ technique, we inject viscoelastics under PFO and stabilize the flap,” continued Prof. Lai. “Our preliminary result showed 100% of the cases (8 of 8) using this method achieved retinal reattachment and MH closure, as well as visual improvement in most cases.

For long-term results, he shared that his team of younger researchers are looking into a three-year study of MH treatment using macular plugs. They found that in 35 cases, two had a MH reopening and one had persistent subretinal fluid for over one year. However, the study also highlighted the progression of myopic maculopathy after vitrectomy in some of the cases, which worsens visual acuity.

“In summary, MHRD treated via vitrectomy and ILM flaps showed very good anatomical outcomes, but only fairly good VA recovery, so we need more studies on this,” said Prof. Lai. “If patients have a progression of myopic maculopathy and glaucoma, they may risk worsened vision during the recovery period.

“Sustainable and long-term visual recovery is still a challenging issue in MHRD. In the future, I hope we can have better ways to improve VA in MHRD cases,” he concluded.

Treating the Untreatable with Gene Therapy

by Nick Eustice

Advances in mapping the human genome have opened doors to understanding the body’s most fundamental blueprints. And with that understanding we have begun to see treatment options emerge for ailments which were always believed to be beyond the scope of medicine. Retinal diseases are one major area where treatment options have always been quite limited, but where gene therapy can bring us new hope.

During the first plenary session of the 14th Congress of the Asia-Pacific Vitreoretina Society (APVRS 2021 Virtual), Dr. Andreas Lauer, Casey Eye Institute (Portland, Oregon), presented a lecture entitled CRISPR: The Future of Treatment of Untreatable Retinal Diseases. In this presentation, he discussed the early results of the currently ongoing BRILLIANCE clinical trial, wherein gene editing procedures are being used to treat genetic mutations that lead to Leber congenital amaurosis type 10, a rare form of genetic blindness.

Early results look promising

Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR, are the sequences of genetic code that form the basis of many cutting-edge treatments

for mutations in human DNA. Until now, retinal treatments using CRISPR have only been conducted ex vivo — utilizing cells taken from the patient in a procedure conducted in a lab. This new treatment allows on-site delivery of the CRISPR plasmid package directly into the patient’s body, and is the first of any such application ever conducted.

The editing complex being applied in this trial, EDIT-101, is an AAV5 viral vector that specifically targets the part of the retina where viable photoreceptors are found. It is administered by a direct subretinal injection into the parafoveal region. When applied, EDIT-101 targets the mutated CEP290 gene within the 12th chromosome that causes Leber congenital amaurosis type 10. It causes a deletion within the genome that corrects the mutation and results in a healthy and consistent protein.

The BRILLIANCE study has treated seven patients thus far, and Dr. Lauer presented some encouraging results from the first and second phases of this trial. To begin with, no dose-limiting toxicity or severe adverse effects have been observed in any of the patients. The only reported side effects were eye pain and mild inflammation, both of which were a result of the surgical procedure.

Six months after the administration of EDIT-101, the patients were tested using best corrected visual acuity (BCVA), full field light sensitivity threshold tests (FST) and visual navigation courses (VNC). The results of these tests have been mixed, but overall quite positive. While not all patients experienced improvement in their vision, several experienced significant improvements in one or more areas of assessment. Several patients were significantly more capable of navigating a course while avoiding obstacles in varying degrees of light, and some reported a regained ability to perceive color.

While these are very early results, Dr. Lauer says that there are sufficient positive results to suggest positive biological activity, and potential clinical benefits. The lack of serious side effects has also led to a pediatric cohort in this study, which is currently enrolling.

While this is just the first such study being conducted, it is extremely exciting to see the possibilities presented by CRISPR for patients with serious genetic conditions. We are only at the beginning of a very exciting time, which could bring hope for curing patients who were once believed to be incurable.

Diabetic Retinopathy

New Methods and New Definitions

by Sam McCommon

The limits of the current DR severity scale

Dr. Jennifer Sun, Harvard University (Cambridge, Massachusetts, USA) shared her thoughts on the current five-stage DR severity scale. To put it bluntly, she has judged them and found them wanting.

Her well thought out laundry list of issues with the severity scales include the following:

• They don’t visualize the peripheral retina or evaluate the neural retina

• They don’t include a number of changes that occur before the development of clinically evident retinopathy

• They don’t incorporate measures of systemic health

• They’re not directly tied to visual outcomes other than those based on BCVA

• They’re not quantitative and they’re difficult to use in practice

• They don’t address worsening or improvement in eyes with PDR

What would a vitreoretinal conference be without a discussion on diabetic retinopathy (DR) and retinal vascular diseases? Well, it wouldn’t be right, we know that. Fortunately, the 14th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2021 Virtual) did their due diligence and held a discussion on development in DR post haste.

Of course, there were some valuable takeaways to be had. We’ll look at two in particular: New tools in the diagnosis of early DR, and the limitations of the current DR severity scale.

New methods in the diagnosis of early DR

Catching DR as early as possible can help reduce the effects of the condition, so the better tools we have to detect it, the more vision will be saved. Dr. Seung Young Yu, Kyung Hee University Medical Center (Seoul, Korea), led us through some of the latest innovations.

Some of these developments are the result of improved imaging tools.

Choosing which parameters to use also makes a difference — vessel density (VD) or nonperfusion area (NPA), or even how large of a field of view. As Dr. Yu explained, mid-peripheral microvascular nonperfusion taken from a 10x10mm² showed the highest sensitivity for determining DR severity based on the five-grade-scale, compared to images from 3x3 or 6x6 mm² fields. Defining NPA on a texture-based method can be performed by isolating sliding square kernels of 17x17 pixels. A nonperfusion area can be determined by a region where the average of a square kernel is below a threshold of 0.2.

To make that a bit simpler, pixelate an image of vascularization and look for the dark spot, then enhance. That’s the NPA. The extent of the NPA and the VD on optical coherence tomography angiography (OCTA) are highly correlated with DR severity on color fundus photos.

Dr. Yu touched briefly on deep learning methods, which we’ve deeply learned have excellent potential for diagnosing DR. But let’s get to another issue before we get carried away...

• There are several more that we literally don’t have space for in this article

To improve this situation, Dr. Sun proposed the Restoring Vision: A JDRF Moonshot Initiative (an initiative launched by the JDRF and the Mary Tyler Moore & S. Robert Levine, MD Charitable Foundation which has convened global research leaders to design a next-generation strategy for reversing blindness in individuals with type 1 diabetes), which leads to the Diabetic Retinal Disease (DRD) Staging Project. This would essentially result in a revised, multidimensional DRD staging system to better define DRD stage, individual risk for disease worsening, predict and measure responses to therapies, support clinical trials evaluating novel therapies, and have a readily usable interface for both researchers and clinicians.

If that sounds breathless to you, you’re probably right — it’s ambitious, but ambition is the name of the game in DR. With diabetes becoming a worldwide crisis, DR will be something we all will unfortunately hear more about. Kudos to Dr. Sun and her colleagues for their ambition and the scope of their vision.

Innovation and Controversies in Surgical Retina

by Sam McCommon

If you know us at PIE magazine, then you know we’re all about innovation and controversies in the ophthalmic space. And hey, if you didn’t know us, now you do a bit better. So, we were excited to cover exactly that topic on day one of the 14th Congress of the Asia-Pacific Vitreoretina Society (APVRS 2021 Virtual). There’s always room for debate and improvement in medicine, and we’re into surfing the waves of change. Surf’s up, so let’s go.

Role of vitrectomy for endophthalmitis

Dr. Sanyam Bajimaya led us through a fascinating discussion on the role of vitrectomy in the treatment of endophthalmitis. Just for reference, postoperative endophthalmitis rates range from 0.04% all the way to 4%, with post cataract surgery rates at 0.265%. That’s indeed quite a range, but there is an equally wide range of organisms that can be responsible for different types of endophthalmitis. While the vast majority of causative organisms are bacteria, with the most common being coagulasenegative staphylococci, up to 8% are

fungal — something worth keeping in mind.

Rates of postoperative endophthalmitis are higher by nearly an order of magnitude when intracameral (IC) cefuroxime isn’t used—and in the United States, it’s by more than that. That makes a compelling case for IC cefuroxime to be standard, as endophthalmitis rates have dropped significantly everywhere it’s used. In South Asia, Dr. Bajimaya noted, IC moxifloxacin is common and is effective as well.

But what’s this got to do with vitrectomy? Well, quite a bit. Dr. Bajimaya pointed out that the overall clinical picture can be confirmed by a culture of the organisms, with aspirates from the aqueous and vitreous cavity. However, it’s significantly easier to isolate a causative organism with vitreous compared to aqueous. Dr. Bajimaya told us the possibility of isolating an organism from vitreous was 56-70%, compared to 36-40% from aqueous. For reference, the safest method for obtaining a vitreous sample is a vitreous biopsy of 0.2-0.3 ml of vitreous. This should be performed as soon as possible — within an hour of diagnosis,

according to Dr. Bajimaya.

Let’s not forget that this is a section on controversies, which acute post cataract endophthalmitis presents. There are two competing treatment methods. The first, suggested by the Endophthalmitis Vitrectomy Study, comprises a vitreous tap and anterior chamber sampling combined with intravitreal antibiotics and steroids in cases where visual acuity is better than hand movement. The ESCRS method, on the other hand, proposes a primary vitrectomy in addition to intravitreal antibiotics and steroids in all cases.

The EVS recommendation is for a vitrectomy combined with intravitreal antibiotics and steroids in cases where visual acuity can’t detect hand movement. There are indeed advantages to early therapeutic vitrectomy. They include:

• Clearing of ocular media

• Removal of potential bacterial toxins

• Reduction of bacterial load

• Better dispersion of antibiotics

• Removal of vitreous scaffolding to prevent tractional retinal detachment (TRD)

After the vitrectomy, intravitreal antibiotics can be repeated every 48 hours according to the response. Dr. Bajimaya suggested that vancomycin combined with amikacin or ceftazidime appears to be the best association for postoperative endophthalmitis. If things get worse after 24-48 hours of intravitreal antibiotics, a vitrectomy should be considered. If there’s no worsening, topical fortified drops and cycloplegics should do the trick.

So, why shoot for early surgical intervention? For one thing, as Dr. Bajimaya said, “the volatile mixture of organisms, endotoxins and exotoxins, cell walls, and various harmful enzymes are in direct contact with the retina. Even if intravitreal antibiotics kill the bacteria, continual damage can be inflicted by the inflammatory debris that remains in the eye.”

Early intervention leads to more complete intervention, and can prevent further

retinal damage. For reference, vitrectomy performed within seven days of the initial event for exogenous endophthalmitis can help improve surgical outcomes.

Gene therapies for inherited retinal diseases

Gene therapy has been an exciting field since its inception, especially in ophthalmology and especially since the development of CRISPR. The first gene therapy for an inherited disease, Luxturna® (voretigene neparvovec; Spark Therapeutics, Philadelphia, Pennsylvania, USA), was first approved as recently as 2017. So, to say this is the “Wild West” of medicine isn’t that far off, except there’s definitely a sheriff in town.

Dr. Suber Huang led us through this discussion, first describing inherited retinal diseases and pointing out that retinal degenerations include both single gene and multifactorial conditions. While there’s currently no cure for degenerative retinal diseases, ophthalmologists are leading the charge in gene therapy.

Gene therapy primarily works to compensate for or replace a defective gene. There are multiple vectors here, including replacement/compensation, long-term drug delivery (like with protein, RNA fragment, small molecule), or the insertion of a new gene, à la CRISPR.

So, will gene therapy become mainstream for inherited retinal diseases? In the short term, the answer appears to be no. We’re simply too early in the development of gene therapies for them to be mainstream yet — we don’t know where we are. For example, we still don’t know the function of many of the millions of base pairs.

Understanding the interactions between all these genes will need to happen before we understand the long term consequences of, y’know … messing with them.

Moreover, using an adenovirus to insert a specific gene into a cell is “a very delicate process” as Dr. Huang put it, and it’s one we don’t directly control.

Gene therapy faces many limitations — for example, it’s not the same as gene editing, or tissue replacement, or cell-based therapy. It’s simply inserting a single gene inside the eye. Even the gene therapy payload is limited by the capsid protein shell.

There are valuable strategies to treat inherited retinal diseases, however. For one thing, as Dr. Huang pointed out, single gene defects cause the majority of these retinal dystrophies. Gene augmentation has great promise if delivered early in the disease. However, patients who are too far gone are probably not good candidates for treatment.

Instead, advanced disease may need cell replacement therapy to regain vision. In these cases, pluripotent stem cells and CRISPR-Cas9 gene editing now exist. These models are currently being investigated in animal and in in-vitro studies. Overall, CRISPR is a valuable strategy for treating inherited retinal degenerative diseases, says Dr. Huang.

For now, however, the role of gene therapy will remain limited — but the whole medical community will be watching this space for developments. The future is bright, but the near term is a bit murky and there’s much work to be done.

Gazing into Pathologic Myopia

by Joanna Lee

Continued research into pathologic myopia (PM) is vital in the ongoing management of this irreversibly blinding condition. At the 14th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2021 Virtual), experts presented updates in the current pathogenesis and classification of pathological changes in PM, as well as advances in the cuttingedge surgical approach for diseases, such as myopic traction maculopathy.

Punctate inner choroidopathy in PM

Renowned for her work related to myopia, Prof. Kyoko Ohno-Matsui, Tokyo Medical Dental University (Japan), presented her latest investigation: How to determine the incidence and characteristics of punctate inner choroidopathy (PIC) in eyes with pathologic myopia where patchy choroidal atrophy was observed.

Importantly, she shared that “because of the co-existing lesions of myopic maculopathy, PIC can be overlooked in eyes with pathologic myopia.”

After observing retrospective data of fundus records, it’s suggested that eyes with PM should be thoroughly evaluated for PICs. Further, anti-inflammatory therapies may be effective in preventing their progression to patchy atrophy as

well as the development of macular neovascularization (MNV).

Clinical histology of myopia

Dr. Jost Jonas, Ruprecht Karls University (Heidelberg, Germany), revealed that there may be more than meets the eye in regard to the role of Bruch’s membrane, as he shared detailed histological observations of pathologic myopia. He hypothesized that the axial elongation by production and elongation of Bruch’s membrane in the equatorial region may mean that Bruch’s membrane could be biomechanically important in the process of emmetropization (myopization).

Surgical approach for myopic macular diseases

“When dealing with myopic foveoschisis (MF), vitrectomy should be considered before macular hole formation where foveal detachment is the biggest indication,” Prof. Yasushi Ikuno, Ikuno Eye Center (Osaka, Japan) said during the introduction of his fovea-sparing ILM peeling (FSIP) surgical technique study.

Showing two types of myopic macular holes, he said: “The schisis type is likely to progress to retinal detachment in highly myopic eyes.” Prof. Ikuno

concluded that “the inverted ILM (internal limiting membrane) flap is a promising method to close the macular hole.”

More on macula

“In myopic eyes, the geometry of the eyes in shapes and curvatures could be associated with altered physiology and abnormalities,” Prof. Ramin Tadayoni, University of Paris (France), said while explaining more recent enquiries into the dome-shaped macula (DSM).

The dome-shaped macula (DSM) was first observed in 2008, when researchers noticed subretinal fluid was associated with a specific dome shape in the eye. It is not known why there’s an area of relatively lesser eye elongation in the center of the DSM, as it could just be an association of multiple staphylomas surrounding the macula.

The role of choroidal vessels remains unclear and it is uncertain why they are related to subretinal detachment. However, knowing about DSM could help avoid any confusion with subfoveal serous retinal detachment and choroidal neovascularization.

In another exciting development, Dr. Barbara Parolini presented on Customized Treatment of Myopic Traction Maculopathy Based on the MTM Staging System. The MTM Staging System (MSS) shows the evolution of myopic traction maculopathy from stages 1 to 4 and serves as a base for definitions, prognosis and guidelines for treatment.

For example, if there is centrifugal force detaching the sclera from the retina, the sclera should be pushed to the retina with the macular buckle. But if there is a macular hole, it should be treated with vitrectomy, ILM peeling and flap. For combined forces (centrifugal, perpendicular and tangential), combine the treatment, she said.

Other session highlights included the Classification and Grading System on Myopia Macular Disease by Dr. Lin Lu, Zhongshan Ophthalmic Center (China) and The Chicken Soup of Center-Non Peeling ILM Surgery in Pathologic Myopia by Dr. Tzyy-chang Ho, who chaired the session.

Newimaging

capillaries and larger blood vessels.

Prof. Koh said that OCTA has a number of advantages. These include: OCTA is non-invasive, it has a high resolution (including 3x3 mm scans), it provides flow information without leakage, and facilitates easy measurement of new vessel complexes. He said this imaging device is particularly favorable for the treatment-naive and those patients with subretinal fluid.

Home OCT

Home OCT, combined with telemedicine, has also recently been gaining traction among patients and doctors alike. According to Prof. Anat Loewenstein, Tel Aviv Medical Center (Israel), OCT in the home could have a great impact.

by Andrew Sweeney

Allergan Symposium Highlights OCT Developments

Can you imagine working as an ophthalmologist without imaging technology? Or, your daily life without it? For screening, diagnosis, management and treatment, the modern ophthalmologist uses photography — so any new innovation in this field is all the more welcome. One of the most significant imaging devices is optical coherence tomography (OCT). Now widely utilized, OCT was a major breakthrough when it was developed, and it has helped increase our understanding of ocular pathologies.

Just as OCT was a great moment for ophthalmology, could we be on the cusp of another revolutionary imaging technology? One of the first virtual sessions of the 14th Congress of the Asia-Pacific Vitreo-retina Society (APVRS 2021 Virtual) sponsored by Allergan, an AbbVie company, (Dublin, Ireland), covered new developments in imaging, as well as detail insights into inflammation in diabetic macular edema (DME).

Inflammation: Cause and effect in DME

The session kicked off with Prof. Adrian

Fung, University of Sydney (Australia), who expounded on aspects of macular anatomy with close reference to DME. During his presentation, he provided actionable information on the shape of the inner barrier’s glial cells and reported on the imbalance between fluid entry and fluid exit caused by diabetes. Importantly, Prof. Fung stated that inflammation is both a cause and effect of DME and described its presence “as critical to this disease.”

Advantages of OCTA

Next, Prof. Adrian Koh, Camden Medical Center (Singapore), spoke at great length on the merits of OCT and its latest, related development: optical coherence tomography angiography (OCTA). He began by explaining the differences between the two modalities.

Traditional OCT creates a cross-sectional image of ocular issues by visualizing differences in light scattering properties, said Prof. Koh. Meanwhile, OCTA detects changes in light scattering properties between a series of scans. As a result, the only changing structure in a static eye is red blood cells moving between

“The information generated by teleconnected OCT in our patients’ homes has the potential to support current retinal disease management and any future evolution which may occur in monitoring patterns and drug selection and dosing,” said Prof. Loewenstein.

“The characterization of fluid volume trajectories has the potential to support a management scheme for eyes with wet age-related macular degeneration. This is based on a combination of periodic office visits; monthly remote online review of home OCT data; remote review driven by system notifications of home OCT data, derived from the characteristics of trajectories of fluid volume and location,” she shared.

“Information generated by tele-connected OCT in our patients’ homes has the potential to support current retinal disease management and any future evolution which may occur in monitoring patterns, drug selection and dosing.”

Prof. Anat Loewenstein

Retinal Medicine in the Age of Big Data

by Nick Eustice

Bold moves forward in information technology are often both exciting and a little scary. On the one hand, the integration of bigger and bigger sets of data, combined with technology that can help us discover new correlations within that data, can help tremendously with expanding our knowledge and finding new solutions to problems. On the other hand, however, there are always concerns about privacy, and the fear that this information will become more difficult to control as it moves further away from human interaction.

The study of data sets that are simply too large or complex to be dealt with by traditional means, and the algorithmic processing of that data by computers, is referred to as “big data.” While this science applies across a wide variety of fields and disciplines, it is of particular interest (and potential concern) within the

field of ophthalmology. For, in no other branch of medicine is big data being harnessed to such an extent, and with such groundbreaking results.

“The era of big data and machine learning has arrived,” said Dr. Aaron Lee as he began his presentation during the Telemedicine, Artificial Intelligence, and Digital Innovations for Retinal Diseases Symposium on Day 1 of the 14th Congress of the Asia-Pacific Vitreoretina Society (APVRS 2021 Virtual). Dr. Lee’s presentation, entitled Big Data, Challenges of Data Collection and Data Privacy, sought to address some of the delicate issues that can arise from the use of big data in a medical context.

Concerns over privacy

Big data, Dr. Lee said, is typically

analyzed in three different metrics: data velocity, data variety and data volume — and the data within the field of eye care is very big in all three ways. The patient data which is stored in databases happens in near real time, demonstrating its tremendous velocity. It takes a great variety of forms, from OCT scans to surgical videos to medical histories. And when considering volume, we need look no further than the IRIS database, the largest medical database in existence, to see that eye care and big data are very much interwoven.

When considering patient privacy and data analysis, Dr. Lee points out that an inherent tension quite necessarily exists between what is good for society and what can be potentially bad for the individual. For the greater the proliferation of data, the more material there is available for analysis. But for the patient,

one’s personal medical information shouldn’t be shared just anywhere, and with just anyone.

These concerns over patient privacy aren’t just personal ones, either. Both the Health Insurance Portability and Accountability Act (HIPAA) in the United States and the General Data Protection Regulation (GDPR) in the European Union put very strict rules in place for the safekeeping of patient records.

Thus, we arrive at Dr. Lee’s big question: How will we train AI models when the pooling of data creates so many potential pitfalls in the way of patient privacy?

To answer this question, a study was designed by Dr. Lee’s team at the University of Washington, wherein they wrote the preprocessing, packaging and transfer of the deep learning model to be utilized. This data was then uploaded to

INDUSTRY UPDATE

a database, and downloaded for analysis by a team across the country at Tufts University in Massachusetts. The Tufts team then trained their own version of the AI model using their own computer without the transfer of any sensitive data.

How was this achieved? The data scientists used a method known as federated learning. While traditional machine learning models have made use of a single centralized server to which all data sets are uploaded, federated learning makes use of an algorithm trained across multiple, decentralized servers without exchanging any of the actual data being analyzed.

In federated learning, a centralized server chooses a statistical model to be trained. That model is then transmitted to the local servers where the data sets (in our case, patient data) are stored. The AI model is then implemented locally on the

Notal Vision Celebrates AI Analysis of 10 Millionth Test

site, and the results generated are pooled back at the central server. That server is then able to generate one global model, without ever actually accessing any sensitive personal data.

While federated learning as a concept is only in its infancy, Dr. Lee believes it holds considerable promise for developing robust and diverse data sets for machine learning without any potential compromise of protected patient data. These robust data sets are vital to advancements in diagnostic research, without which the discovery of rare manifestations and associations of retinal conditions will not be possible.

As maintaining the delicate balance between better research data and patient privacy is vital in making new discoveries in this age of big data, it is necessary to develop new methods of analysis to ensure that this balance is maintained.

Notal Vision (Manassas, Virginia, USA) recently hit a major milestone: 10 million tests of 20,000 patients have now been analyzed using the company’s ForeseeHome® AMD Monitoring Program. ForseeHome is a comprehensive platform that includes an FDA-cleared device to monitor visual changes in intermediate dry AMD patients at risk of conversion or vision loss from undiagnosed wet AMD. This is important as it monitors patients between office eye exams —

when it’s difficult to manage the acute onset of wet disease that requires timely treatment.

ForseeHome is backed by data: A recent large scale data analysis showed that it provided a significant benefit to patients by helping to detect their wet AMD earlier with better visual acuity. This is a factor previously shown to improve long-term visual outcomes of treatment.

“The real-world data published earlier

this year shows that the performance of the ForeseeHome program resembles the findings from the randomized controlled AREDS2-HOME study, which ultimately led to Medicare coverage of the monitoring service we provide,” said Kester Nahen, PhD, CEO of Notal Vision, in a press release.

Find out more at www.notalvision.com.