Webinar Reminds Ophthalmology about Retina Awesomeness

Webinar Reminds Retina: It’s totally far out Dude

Ophthalmology about The retina is indeed awesome — not just in the California ‘90s, Retina Awesomeness skater boy sense — but it is truly something that inspires awe in those by Andrew Sweeney who see and study it. Thus, the name “Retinawesome” is There are moments in history when countries, people, cultures and the like experience a collective fascinating developments in retina as of late. far more prescient as a title for an ophthalmology webinar than one may initially suspect. The 8th meeting of this online symposium, which took place on moment of inspiration. This is when This is fitting as the retina is a great February 20, was another development remarkable developments in science and symbol of ophthalmology — it is in retina’s apparent “Renaissanceart can be achieved — for example, one the means by which we create two esque” moment. such moment in European history was dimensional images of the visual the Renaissance, a period of rebirth and world and it acts as an image sensor At nearly 5 hours long, there was rediscovery in art, science and culture. for the brain. A simple explanation of certainly plenty of material for the retina function from a lay website like webinar’s viewers to digest. It drew Is ophthalmology experiencing a Wikipedia which says “light striking the ophthalmologists from over a dozen similar “zeitgeisty” moment in regard retina initiates a cascade of chemical countries in four continents, all to retina? Perhaps so. And while all and electrical events” has a real effect presenting their own retina-related case of ophthalmology excites the Media of profundity. studies. Issues ranged from diabetic MICE team, we have witnessed some vitrectomy, to managing severely

traumatized eyes and retinal surgery techniques.

A reasonable place to start with the Retinawesome 08 webinar is A Very Reasonable Approach for Treating the Refractory Macular Hole. This presentation was given by Dr. Yusuke Oshima from the Oshima Eye Clinic in Osaka, Japan. Dr. Oshima’s report focused on a new surgical technique involving the application of sub-retinal fluid to close refractory full thickness macular holes.

Dr. Oshima described one surgical case study that involved a patient with macular hole retinal detachment caused by vitreoretinal traction and a history of proliferative diabetic retinopathy. He used what he described as standard (non-inverted) surgical techniques in an attempt to close the patient’s macular hole. However, he was unable to do so. He responded by using the subretinal fluid technique successfully; this resulted in no retinal penetration and a postoperative visual acuity improvement from 20/200 to 20/100.

Of course, macular holes are traumatic for all patients, but there are different forms of macular hole trauma. For a deep dive into the vagaries of macular holes, watch Chronic Traumatic Macular Hole by Dr. Wai-Ching Lam from the University of Hong Kong. Dr. Lam reported that trauma is the second most common cause of macular hole.

Dr. Lam also stated that macular hole incidence is 1.4%. This is followed closely by globe trauma, which occurs at a rate of 0.15%, and open globe injuries, which are frequently caused by antero-posterior vitreoretinal and tangential retinal traction. While spontaneous closure occurs in 50% of pediatric patients, this drops to 28.6% among adults, and to zero after 67.3 weeks. Dr. Lam recommended the use of surgical techniques including pars plana vitrectomy and epiretinal membrane peeling, which has a 73% success rate in treating macular holes.

Peeling and zipping

The keynote speaker of Retinawesome 08 was Dr. Barbara Parolini, an Italian ophthalmologist who operates her own clinic in San Martino Buon Albergo, Veneto. She presented Intraoperative OCT: The Beauty of Confirmation, an examination of optical coherence tomography (OCT) and the guidance it offers when peeling membranes. Dr. Parolini stated that peeling requires OCT guidance as both the retina and membranes are transparent (as opposed to the choroid which is colored) and thus require a distinguishing method.

Dr. Parolini reported that staining is offered as a solution, but in her words “it does not solve all the problems.” As examples, she cited an inability to see contrast, difficulty in verifying the position of an internal limiting membrane (ILM) flap under air, and in verifying the reaction of the retina during peeling at the risk of iatrogenic lesions. Emphasizing the efficacy of OCT, she said it is particularly useful when there is no contrast for the presence of choroidal atrophy, when light reflexes work under air tamponade, and finally, when the surgeon has concerns about inducing iatrogenic lesions.

Zipper syndrome… different and much less fun than ziplining.

mention Dr. Athanasius Nikolopoulos, who presented Zipper Syndrome Treatment in Retina Detachment. Zipper syndrome was described as “multiple tears in one meridian in a retina detachment without proliferative vitreoretinopathy.” Dr. Nikolopoulos recommended that if a clinician discovers zipper syndrome, then they should not rely on a simple primary vitrectomy, and should instead use a 360 laser.

Editor’s Note:

The 8th Retinawesome webinar was streamed on February 20, 2021 and was organized by the Retinawesome group headed by Dr. Hudson Nakamura, a retina and vitreous specialist based in Goiânia, Brazil. Held roughly once a month, the webinars are available to view on the YouTube Channel: Retinawesome Retina & Vitreous International.

Real World Results Highlight Gene Therapy Success

by Andrew Sweeney

If you could go into your DNA to take a look at your genes in detail, and add or replace them to your heart’s content, what would you do? Personally, I wonder if I would be able to cure my allergies to peanuts and almonds, which has always been something of a drag while traveling. Maybe you could have some fun with your eyes, perhaps giving yourself heterochromia … or X-Men-style super powerful laser beam eyes that could shoot objects in space.

Okay, maybe the last point would be a diabolical step too far, and these examples may be dubious, but there are some pretty interesting ophthalmological developments in this field. New treatments are emerging for a wide array of conditions, from age-related macular degeneration (AMD) to X-linked retinitis pigmentosa. Indeed, it is an exciting time to be involved in gene therapy.

The recent Ophthalmology Innovation Summit (OIS) Gene Therapy Showcase served to highlight gene therapy’s remarkable development, including presentations from companies in the field. Covered below is the second part of the webinar — the Gene Therapy Panel Outlook — which was an informative conversation about gene therapy from some of the field’s leading thinkers.

Gene therapy: It’s alive!

Moderator Dr. Thomas Ciulla, clinical professor of ophthalmology at Indiana University School of Medicine (USA), opened the panel by describing gene therapy in retina as “the epicenter of so much innovation.”

Indeed, ophthalmology has the distinction of getting the first FDA approval for gene therapy with voretigene neparvovec-rzyl (Luxturna; Spark Therapeutics, Pennsylvania, USA). Administered as a subretinal injection, Luxturna was approved for patients with confirmed biallelic RPE65 mediated inherited retinal disease. working, it’s a real thing, it’s not a myth anymore. We are seeing patients going one or two years without receiving injections; it’s exciting to be part of this evolution in gene therapy,” said Dr. Arshad Khanani, a clinical associate professor at the University of Nevada (USA).

Dr. Khanani described his work with suprachoroidal delivery, a new potential route for drug administration to the posterior segment of the eye. This involves the delivery of an injection into the suprachoroidal space, or a subretinal delivery via the Orbit Biomedical’s 510k approved microcannula, which has now been acquired by Gyroscope Therapeutics (London, UK). Along with Dr. Jeffrey S. Heier, the director of retina research at Ophthalmic Consultants of Boston (USA), Dr. Khanani was heavily involved in clinical trials examining suprachoroidal delivery.

“The real world data on diseases like neovascular AMD and diabetic macular edema has shown that undertreatment

of patients almost universally prevents us from achieving the outcomes seen in gene therapy phase 3 studies. These results show us the means of achieving long-term durability and maintenance, and doing away with compliance as an issue,” Dr. Heier said.

Inflammation, such a hot topic right now

Dr. Jose-Alain Sahel, chairman and director of the Department of Ophthalmology at the University of Pittsburgh School of Medicine (USA), talked about his work with optogenetics. Dr. Sahel is working on optogenetic vision restoration, a technique in which “cells in the retina are genetically modified to express light sensitive proteins.” According to Dr. Sahel, this represents a gene independent approach and while it cannot cure disease, optogenetic techniques are showing considerable efficacy in mitigating damage. The exciting developments taking place in gene therapy-focused ophthalmology would be impossible without high-level manufacturing support. For Dr. Peter Francis, PhD, chief scientific officer and therapeutic area head of ophthalmology/ retina at 4D Molecular Therapeutics (California, USA), the complexity of gene therapy had given rise to unusual phenomena like empty capsids during the manufacturing process. Many were produced whole but were unpackaged with the trans-gene, meaning a lot of potentially inflammation causing protein could be delivered.

Dr. Francis said that with modern manufacturing techniques a very high ratio of the capsids now contain the therapeutic trans-gene which helps to reduce inflammatory responses. Inflammation is an important issue in ocular gene therapy, and was a topic of considerable note during the panel. Dr. Glenn Yiu, PhD, an associate professor at the Department of Ophthalmology at the University of California, Davis (USA), spoke about the various forms of inflammation.

“There is a lot of discrepancy in the literature, but if you see inflammation very rapidly within a week, it is unlikely to be a trans-gene expression and is more likely to be a result of the viral particle. If you see inflammation at the one month mark, it is more likely to be the transgene, but it’s a very murky field and studies are ongoing,” Dr. Yiu said.

Editor’s Note:

The Ophthalmology Innovation Summit Gene Therapy Innovation Showcase webinar was held on February 18, 2021. Reporting for this story took place during the event. On March 4, 2021, part 1 of this coverage was published on piemagazine.org.

INDUSTRY UPDATE

Phase 1 Clinical Trial Studying Remote Monitoring with Home OCT in DME and AMD Patients Begins

We all know that regular monitoring is crucial to preserve sight in patients suffering from progressive diseases like wet age-related macular degeneration (nAMD) and diabetic macular edema (DME).

We also know that reducing the frequency of office visits — especially during a global pandemic — is necessary to ensure continued disease management. This is where home monitoring could be a real sight saver, especially since the majority of nAMD and DME suffers are elderly or have preexisting conditions.

Therefore, to learn more about the feasibility and efficacy of home monitoring, Notal Vision, Inc., will provide Home OCT services (through its Notal Vision Diagnostic Clinic) to AsclepiX Therapeutics and its AXT107 phase 1 clinical trial program. In this trial, subjects with DME and nAMD (who also participate in the AsclepiXsponsored CONGO and SHASTA studies) will perform sequential daily self-imaging of their eyes with the self-operated Notal Home OCT device at home. This data will be transmitted from the device’s built-in modem to the secure Notal Health Cloud where the AI-based Notal OCT Analyzer (NOATM) will identify and quantify intra- and subretinal fluid from each daily OCT scan. These images and temporal fluid volume trajectories will be shared with AsclepiX and investigators through the Notal Physician Portal. Further, patient compliance and remote support will be provided via the Notal Vision Diagnostic Clinic, which is the future provider of the Home OCT program.

According to one of the study’s investigators Dr. Arshad M. Khanani, the clinical value and potential benefit of an approach like this is even more crucial during the COVID-19 pandemic.

“Remote OCT monitoring of patients with exudative retinal diseases in a regulatory clinical trial allows AsclepiX Therapeutics to capture critical data points while potentially reducing the burden of frequent office visits,” said Dr. Khanani, who is also the director of clinical research at Sierra Eye Associates in Reno, Nevada (USA). Indeed, the technology could set new standards for data enrichment and patient-centric conduct of clinical trials.

Notal Vision CEO Kester Nahen, PhD, said they are excited to partner with AsclepiX Therapeutics and contribute their remote diagnostic services to the early phase clinical trial as “home OCT monitoring opens new opportunities to enrich clinical trial datasets with inter-visit disease and treatment response knowledge.”