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posterior segment • innovation • enlightenment

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PIE M A G A ZINE ’ S D A ILY CONGR E S S NE W S ON T HE P O S T E RIOR S E GME N T

HIGHLIGHTS out how to handle 04 Find challenging cases amid challenging times AI to gene therapy 08 From — Get a lowdown on exciting innovations in ophthalmological research the Pandemic! 11 Beat Check out some clinical practices for effective remote monitoring of retinal diseases

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Choriocapillaris A robust new biomarker in AMD diagnosis

by Olawale Salami

O

ptical coherence tomography angiography (OCTA) visualization and quantification of choriocapillaris blood flow dynamics provide a robust new biomarker for assessing AMD. While choriocapillaris flow deficits increase with age, especially centrally, flow deficits continue to progress during agerelated macular degeneration (AMD) evolution Choriocapillaris flow deficits may predict the appearance of drusen, progression to nascent geographic atrophy, and the development and enlargement of atrophy in eyes with neovascularization. The choriocapillaris is a highly vascularized layer located posterior to Bruch’s membrane and the retinal pigment epithelium that has historically been challenging to visualize with conventional imaging.

Studying changes in blood flow dynamics in AMD Dr. Srinivas Sadda and colleagues at the Doheny Eye Institute have utilized OCTA to study the changes in blood flow dynamics associated with AMD. “AMD is a complex disease in which multiple factors, such as inflammation, aging, genetics, and oxidative damage play different roles in driving the observed changes in the choriocapillaris,” explained Dr. Sadda during the EURETINA 2021 Virtual Congress. “We and others have sought to understand how age affects the choriocapillaris.” Their studies have shown that choriocapillaris flow deficit appears to worsen with age, compared to younger individuals. “These changes are more significant around the center of the fovea. When drusen develop in patients with AMD, they tend to appear more centrally,” said Dr. Sadda. Therefore, his team investigated possible associations between choriocapillaris flow limitations and the localization of drusen in AMD.


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OZURDEX® acts fast1,2 and lasts3–5 with less treatment visits compared with anti-VEGFs,5 making it the enduring partner you need. Effective DME treatment doesn’t have to be a burden.6

The most commonly reported adverse events reported following treatment with OZURDEX® are those frequently observed with ophthalmic steroid treatment or intravitreal injections (elevated IOP, cataract formation and conjunctival or vitreal haemorrhage respectively). Less frequently reported, but more serious, adverse reactions include endophthalmitis, necrotizing retinitis, retinal detachment and retinal tear. Licences may vary by country, please refer to your local country SmPC. DME, diabetic macular edema; IOP, intraocular pressure; VEGF, vascular endothelial growth factor. 1. Lo Giudice G et al. Eur J Ophthalmol 2018;28(1):74–79. 2. Veritti D et al. Ophthalmologica 2017;238(1–2):100–105. 3. Escobar-Barranco JJ et al. Ophthalmologica 2015;233(3–4):176–185. 4. Allergan. OZURDEX® Summary of Product Characteristics. 5. Kodjikian L et al. Biomed Res Int 2018:8289253. 6. Boyer DS et al. Ophthalmology 2014;121:(10):1904–1914.

INDICATIONS & USAGE: OZURDEX® contains a corticosteroid indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), for the treatment of non-infectious uveitis affecting the posterior segment of the eye, and for the treatment of patients with visual impairment due to diabetic macular edema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy. DOSAGE & ADMINISTRATION: For ophthalmic intravitreal injection only. The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. DOSAGE FORMS & STRENGTHS: Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR™ solid polymer drug delivery system. CONTRAINDICATIONS: Ocular or periocular infections. Advanced glaucoma. Aphakic eyes with ruptured posterior lens capsule. Eyes with ACIOL, iris or transscleral fixated IOLs and rupture of the

posterior lens capsule. Hypersensitivity. WARNINGS AND PRECAUTIONS: Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, retinal detachments, and implant migration into the anterior chamber. Patients should be monitored following the injection. Patients who has a tear in the posterior lens capsule (e.g., due to cataract surgery), or who had an iris opening to the vitreous cavity (e.g., due to iridectomy) are at risk of implant migration into the anterior chamber. Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance establishment of secondary ocular infections due to bacteria, fungi, or virus. Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex. ADVERSE REACTIONS: In controlled studies, the most common adverse reactions reported by 20–70% of patients were cataract, increased intraocular pressure and conjunctival haemorrhage.

Licenses may vary by country, please consult your local Summary of Product Characteristics. Adverse events should be reported to your Ministry of Health and local Allergan office. JOB CODE: INT-OZU-2050218 DATE OF PREPARATION: NOVEMBER 2020

OZURDEX® is not licensed for use in DME in China.


PIE magazine’s Daily Congress News on the Posterior Segment

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Loss of retinal sensitivity Additional experimental data point towards an increasingly important role of the choriocapillaris in defining the transitional stages of AMD. “There has been a lot of interest in studying retinal changes that signify aging to AMD transition using retinal structural imaging and retinal sensitivity. And recent data suggests loss of scotopic sensitivity early on in AMD,” shared Dr. Sadda. Could scotopic function be a good marker of transition between aging and early AMD? Dr. Sadda and his team addressed this question by evaluating scotopic microperimetry and OCT angiography data in patients with early AMD. “We found that patients with worse choriocapillaris flow density also had worse retinal sensitivity,” noted Dr. Sadda.

Tracking underlying blood flow to predict drusen lesions In the transition from early AMD to intermediate AMD, Dr. Sadda said they see progressively more significant drusen. “The flow deficit is worse in the area directly below the drusen, compared to areas beyond the drusen,” he shared. “This suggests that the location of the drusen may be related to the severity of the flow limitation in the choriocapillaris. This raises the question of whether the choriocapillaris can predict where drusen will appear in patients with AMD.” Using structural OCT, the team at Doheny eye institute tracked the choriocapillaris blood flow deficit prospectively from baseline in patients with AMD. “By identifying areas with the worst blood flow, we could predict areas where drusen would appear,” noted Dr. Sadda.

Choriocapillaris assessment: New predictor of geographic atrophy A new tool for AMD classification Dr. Sadda and his team recognized that Dr. Sadda followed up patients with intermediate AMD over 12 months using OCTA and found that many patients who were deemed to have clinically stable intermediate AMD had worsening choriocapillaris flow deficits. “Interestingly, we could break down this broad category of intermediate AMD further because we now have OCT risk factors for progression to advanced AMD, namely hyperreflective cores within drusen and intraretinal hyperreflective foci.” In advanced AMD with neovascularization, halos around neovascular lesions may be related to exudation and choriocapillaris impairment. “Working with several collaborators, we explored halos in neovascular lesions’ proximity and found that choriocapillaris flow deficits were more remarkable in these regions,” explained Dr. Sadda.

Neovascularization: A response to choriocapillaris insufficiency? By examining the choriocapillaris flow in the peripheral parts of the macula in patients, Dr. Sadda and colleagues found a correlation between flow deficits and neovascularization. “Eyes with type 3 neovascularization demonstrate diffuse flow deficits similar to those encountered in patients with geographic atrophy. This observation led to the formulation of our working hypothesis that neovascularization may develop in response to choriocapillaris insufficiency,” said Dr. Sadda.

atrophy could occur even when patients develop neovascularization, despite theories suggesting the potential benefits of type 1 neovascularization. Additional research highlighted gaps in the current understanding of the nature of these benefits. Could anti-VEGF therapy, by eliminating neovascularization, promote the development of atrophy? What factors are responsible for the preservation of the retina and prevention of atrophy in some eyes? Could type 1 lesion represent a surrogate for the choriocapillaris? Using histopathologic correlation studies, Dr. Sadda and colleagues demonstrated that type 1 neovascular lesions could develop capillary-like neo-vessels with fenestrations that resemble the native choriocapillaris, which is visible by OCTA. However, this visualization requires the use of thin OCT slabs. “We observed that eyes that progressed to atrophy had reduced percentages of neo-choriocapillaris coverage, which did not increase over time. Conversely, eyes with a broader range of neochoriocapillaris did not progress atrophy,” explained Dr. Sadda. OCTA visualization and quantification of choriocapillaris blood flow dynamics provide a robust new biomarker for assessing AMD. While choriocapillaris flow deficits increase with age, flow deficits continue to progress during the evolution of AMD. Importantly, choriocapillaris flow deficits may predict the appearance of drusen, progression to nascent geographic atrophy, and the development and enlargement of atrophy in eyes with neovascularization.

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COVID-19 and Ocular Comorbidities Handling challenging cases amid challenging times by Nick Eustice

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he first day of the EURETINA 2021 Virtual opened with interesting sessions — one of them dealt with particularly challenging diagnostic and treatment solutions in retinopathy. Each of the speakers addressed out-ofthe-ordinary situations, sharing unique sets of circumstances that led them to explore treatment options that are quite uncommon.

COVID-19 and progressive diabetic retinopathy One of the session’s presenters that stood out was Dr. Nigel Davies from St. Thomas Hospital in London, who presented a very interesting case involving the most commonly talked-about disease of the past two years: COVID-19. His patient, a 45-year-old man who suffers from type II diabetes, had sought treatment for visual impairment brought on as a result of progressive diabetic retinopathy (PDR). Just as treatment options were being planned, the patient contracted a severe case of COVID-19 and had to be immediately admitted to the intensive care unit. There he had to be ventilated for three months before making a recovery. While the patient was lucky to have survived his ordeal, it left him traumatized and wheelchair-bound. He was reluctant to even return to his ophthalmologist for new diagnostic procedures. Not surprisingly, his untreated condition had worsened, and he had difficulty seeing

out of his right eye. Upon evaluation, he was informed that he would need additional procedures to treat his diminishing eyesight in both his right and left eyes.

Treatment options and family support The patient was devastated. After his intense and life-threatening three-month experience of being treated for COVID, he was terrified at the prospect of further medical care. He was especially frightened of receiving general anesthetic, and the prognosis led him to tears. He at first refused treatment, particularly for his left eye, where he had not detected any diminished visual ability. The patient’s emotional stress was at first paralyzing. Fortunately, he received a lot of support and encouragement from his doctors and his family. A counselor and psychologist provided further clinical support and as a result, he was persuaded to receive necessary treatment. The patient received an intravitreal dosage of bevacizumab, as well as a vitrectomy and endolaser surgery on his right eye. Due to the nature of the procedure and the patient’s concerns, this was only accomplished using sedation and local anesthetic. One week later, the patient had the same procedure on his left eye. While the procedures were largely successful in inhibiting further degeneration of the patient’s condition, he did experience a cavity hemorrhage as a side effect of the treatment in

his left eye. At the time of Dr. Davies’ presentation, the patient had left the country to visit family and had not pursued treatment.

The need for quick action This presentation draws our attention to a number of issues, all of which affected this unfortunate patient at once. To begin with, it highlights the essential role which psychological care can have in treatment, particularly when a patient is resistant to being treated at all. This is, of course, especially true when a patient has been through considerable trauma recently. However, it serves as a reminder that even under ordinary circumstances emotional support can be essential to delivering effective treatment. Further, this case illustrates the need for quick action in treating PDR. In just a few short months, this patient’s condition had worsened quite rapidly. While his life-threatening condition made treatment impossible during this time, the delay had made his prognosis significantly worse. Finally, this account also brings to light the added dangers which COVID-19 presents in the ophthalmological field. For while this disease is, of course, first and foremost a respiratory infection, it also carries with it the danger of hypoxia, coagulopathy, and proning. As our world adapts to the many challenges that COVID-19 presents on a global scale, it is vital to be mindful of the impact that it can have upon one’s practice as well.


PIE magazine’s Daily Congress News on the Posterior Segment

Up for the

Challenge How to manage special and difficult vitreoretinal cases by Tan Sher Lynn

D

ealing with special and difficult cases of vitreoretinal diseases has always been a challenge among ophthalmologists. So, during the first day of the EURETINA 2021 Virtual Congress, retinal experts shared their knowledge, techniques, and experiences on ways to best manage them, providing new and old insights alike.

Reactivation of retinopathy of prematurity Prof. Anat Loewenstein from Tel Aviv, Israel, talked about a case involving a 64-year-old man who had reactivation of retinopathy of prematurity (ROP). The man had decreased vision in the right eye (visual acuity of 6/10) one day before admission and was found to have vitreous hemorrhage (VH) in the eye. He had recurrent VH episodes and peripheral pigmentary changes without holes or tears. One year later, the patient came in again with VH at the right eye. Further talk with the patient revealed that he was a preterm infant with a birth weight of 1500 g. “So we suspected he had a vitreoretinal tear,” shared Prof. Loewenstein. “He underwent pars plana vitrectomy (PPV). The tear was found, vitreous hemorrhage was removed, and extensive laser therapy was performed on the temporal retina.” According to Prof. Loewenstein, ROP is a disease with self-limited fibrovascular proliferation and exudation in most cases. “Most cases of ROP never require treatment,” she added. “For severe cases that require treatment, the majority respond well to treatment with peripheral ablation.” Reactivation of ROP occurs in 3.6% of patients after previous regression and

can cause exudation and retinal tears. “VH may occur, in rare instances, secondary to undiagnosed ROP. The mean age of ROP reactivation is 25-34, but it can occur in the seventh decade of life, as in this patient, especially if they were preterm and had a low birth weight. Ultra-widefield fluorescein angiography in late reactivation of ROP is useful, and may show arteriovenous (AV) loops, microaneurysms, leakage, and neovascularization,” shared Prof. Loewenstein.

Dissociation between OCT and angiography Meanwhile, Prof. David E. Pelayes from the Maimonides University Argentina presented a case involving a 57-yearold female patient with a history of breast cancer (advanced IIIB T4a N2) who underwent chemotherapy. Her ophthalmological examination revealed her vision as 20/50 (right eye) and 20/60 (left eye) and intraocular pressure (IOP) as normal. Cystoid macular edema (CME) was observed at the posterior segment. Optical coherence tomography (OCT) showed macular edema in both eyes, while no leakage was detected with fluorescein angiography (FA), and autofluorescence is negative.

“The accumulation of fluid in the intracellular space may lead to CME without evidence of leakage on FA,” shared Prof. Pelayes. “This condition can be seen in other diseases like niacin maculopathy, Goldmann-Favre syndrome, and congenital X-linked retinoschisis (CXLRS), which were ruled out on the basis of history and clinical examination. CME without fluorescein leakage is secondary to paclitaxel use,” he added. Prof. Pelayes explained that paclitaxel is an antimicrotubule agent that inhibits normal reorganization of the microtubule network within cells. “Adverse effects include myelosuppression, dermatitis, asthenia, alopecia, and mucositis. In the eye, we can see mild conjunctival chemosis, corneal epitheliopathy, corneal edema, keratitis, and retinopathy.” He added that in most cases, the cessation of paclitaxel can lead to improvement of VA and resolution of CME. “This is one of the few conditions where we can see the dissociation between the OCT and FA. At the moment, only 12 cases of CME secondary to paclitaxel have been reported. In general, VA improved when the drug is discontinued, but in a small number of cases, complications occur,” shared Prof. Pelayes.

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methods put together by the Classification of Atrophy Meetings (CAM) program. This methodology involves the categorization of data obtained by optical coherence tomography (OCT) into a recognizable framework that can be used to identify early signs of AMD.

What’s New with AMD treatment? Breakthroughs in managing this common yet enigmatic disease

by Nick Eustice

A

ge-related macular degeneration (AMD) is a condition common throughout the eye-care profession, yet one that remains fairly unknown to the general public. Indeed, within the field of ophthalmology, AMD is more accurately described as an area of exploration rather than well-trodden terrain, as innovations and treatments are in constant development. This broad topic was the subject of the EURETINA 2021 Virtual’s second panel discussion yesterday, whose focus was largely on breakthrough innovations.

High-res retinal imaging to identify early signs of AMD “There is no effective treatment for atrophic AMD,” noted presenter Dr. Steffen Schmitz-Valckenberg of the University of Utah. Dr. SchmitzValckenberg spoke about new approaches being taken to combat this condition. All previous trials, he said, have aimed to slow down atrophy of vision which is already taking place. However, recent studies have been taking a more preemptive approach: to try and intervene early, before degeneration of

the macula has begun to cause loss of vision. This new aim presents researchers with a new challenge: to “identify and establish biomarkers for early atrophy development and progression”. While the appearance of drusen, or spots on the macula, are the best known and most common signs of atrophy, Dr. Schmitz-Valckenberg pointed out that atrophy does not always produce large enough drusen that they can be identified. Further, these only appear once atrophy has begun and do not provide an early enough indicator to attempt treatments that may preempt AMD in the first place. Instead, Dr. Schmitz-Valckenberg advocates the diagnostic imaging

With AMD affecting such a wide swath of the population, it is no surprise that its treatment and potential prevention are major topics at this year’s conference.

This high-resolution system for retinal imaging allows for early identification of lesions and patterns, which can be used in the future for early interventional clinical trials. As this technology remains very cutting-edge, Dr. Schmitz-Valckenberg said: “We are close to detection methods that would be acceptable to regulatory authorities, but we do not have them yet”.

Use of the port delivery system in AMD treatment As the panel moved from the topic of early detection methods to that of current trends in treatment, the subject turned to antivascular endothelial growth factor therapy (anti-VEGF). In particular, bevacizumab was cited by panelist Dr. Ramin Tadayoni. Bevacizumab is the most commonly prescribed treatment for AMD, and its administration has shown good results in slowing the loss of vision in patients. Bevacizumab is not without certain drawbacks, however, as Dr. Tadayoni pointed out. Key among these is the regularity of treatments required for the administration of the drug, which is administered by intravitreal injection. “Timing and regimen are as important as the treatment itself,” shared Dr. Tadayoni. “And the correlation between regularity of treatment and results are demonstrable.” As many patients are discouraged by the prospect of receiving intravitreal injections on a regular basis, Dr. Tadayoni mentioned the port delivery system as a viable alternative. This device, which is implanted in the surface of the eye itself, requires substantially less frequent injections and has shown the possibility of being a more effective solution. With AMD affecting such a wide swath of the population, it is no surprise that its treatment and potential prevention are major topics at this year’s conference. As the research continues to grow, we are sure to see more and more exciting developments in the effort to preserve the eyesight of elderly patients.


PIE magazine’s Daily Congress News on the Posterior Segment

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The Role of Anti-VEGF Therapy in Diabetic Retinopathy Experts share new studies and management strategies by Tan Sher Lynn

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e know too well that dealing with vision loss is difficult for patients, particularly those who have diabetic macular edema (DME) and non-proliferative diabetic retinopathy (NPDR). The topic is among the highlights during the first day of the EURETINA 2021 Virtual, with experts sharing their thoughts on new studies and treatment strategies that work for them.

Managing patients with DME and good visual acuity Patients with DME and vision loss need anti-vascular endothelial growth factor (anti-VEGF) therapy and can benefit greatly from it. “However, it is less clear on what should we do in DME patients without visual acuity (VA) loss. Should we give them anti-VEGF or laser treatment, or should we just observe them?” asked Prof. Reinier Schlingemann from Amsterdam UMC, The Netherlands. According to Prof. Schlingemann, this question was accurately addressed by the DRCR.net Protocol V study where patients with central involved DME (CI-DME) and VA of 0.8 are treated with either aflibercept, laser, or observation. Results show that 5-letter loss at 2 years was the same across the three groups. In fact, in the observation group, only onethird (34%) needed aflibercept at some time. Hence, the authors concluded that observation without treatment, unless VA worsens, might be a reasonable strategy in treating such patients. “Meanwhile, the Early Treatment Diabetic Retinopathy Study (ETDRS) showed that patients with clinically significant macular edema (CSME), whether outside the center or center involving, did better with laser than observation. This is not related to VA. In fact, two-third (63%) of the patients in this study have a VA of 0.8

or better,” he said.

Editor’s Note:

“As such, we can conclude that, in patients without CI-DME and vision loss, ETDRS laser or focal FA/ICG guided laser, preferably >10001500 micron from fixation can be considered,” added Prof. Schlingemann. He explained that in patients with CI-DME without visual loss, based on the Protocol V study, we can consider observation. “However, in the presence of symptoms and/or risk factors for VA loss, such as higher central subfield thickness (>300-400), moderately server NPDR or worse, being treated with anti-VEGF in the other eye, having an older age, metamorphopsia, and documented loss of >1 line of VA, one should consider antiVEGF or laser treatment.” Prof. Schlingemann continued: “When anti-VEGF is necessary because of VA loss in patients who are observed, bevacuzimab may be an acceptable choice if VA is higher than 0.4, based on DRCR.net Protocol S study.”

Understanding the role of anti-VEGF in NPDR Should physicians treat patients with non-proliferative diabetic retinopathy (NPDR) with anti-VEGF agents? According to Dr. Jennifer Sun from the USA, this question was addressed by two studies this year — the Protocol W and PANORAMA randomized clinical trials. Protocol W showed that early aflibercept treatment reduces the risk of developing DME or proliferative diabetic retinopathy (PDR) over two years by proximately three folds. Eyes treated with aflibercept

in the PANORAMA study also showed a reduction in the likelihood of getting vision-threatening complications. “Nevertheless, results from Protocol W showed that the mean VA letter score change from baseline was not different at two years between the aflibercepttreated and sham group. The PANORAMA study also did not show differences in VA outcomes at week 100 between eyes that are treated with aflibercept versus sham,” noted Dr. Sun. Dr. Sun shared that it is unclear whether the benefit of anti-VEGF treatment will translate into long-term improvements in visual outcomes for patients. “Anti-VEGF therapy likely does not reverse underlying diseases,” she said. “It is also unknown whether early treatment will reduce overall long-term treatment burden. Given these caveats, routine anti-VEGF treatment of eyes with NPDR and without DME does not seem warranted at this time. Longer-term data from the ongoing Protocol W study may help to address some of these issues,” she suggested.


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indicated that the PDT showed no additional benefit to the application of aflibercept on its own. These results demonstrate that this drug, already used in age-related macular degeneration (AMD), macular edema, and diabetic retinopathy, may have farther-reaching applications than previously believed.

Use of Luxturna in the treatment of retinal dystrophy

Eye Care

Revolution A lowdown on exciting innovations in ophthalmological research by Nick Eustice

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hat’s the role of artificial intelligence (AI) in research methods in ophthalmology? This and other exciting innovations in ophthalmological research were showcased by the European Vision Institute Clinical Research Network (EVICR.net) at the EURETINA 2021 Virtual’s afternoon session yesterday. EVICR.net is a network of 96 research sites throughout 16 countries in Europe, organized by, but not limited to, the European Union. They aim to establish cooperation and standardization in ophthalmological research throughout the continent and beyond, and their projects are both robust and diverse.

The exciting role of AI in ophthalmology Dr. Scholl Hendrik, chair of the Department of Ophthalmology at the University of Basel and chairman of EVICR.net’s Steering Committee, presented a number of recent developments which EVICR.net has been

able to achieve. One of the most radical changes, spanning numerous studies, is the involvement of AI in research methods. “Techniques such as convolution neural networks and random forest regression have recently allowed numerous groups to drastically increase the accuracy of structural function correlation in the context of macular diseases, including geographic atrophy,” said Dr. Hendrik. In other words, computers have been able to aid in the analysis of graphical elements and values within large sets of data in ways that they have never been used before. This could have the long-term benefit of recognizing patterns, which neither machines nor human researchers have been able to do in the past. One such study which Dr. Scholl presented was The Atlantic Study. This project has been the first large-scale study comparing aflibercept monotherapy in the treatment of patients with polypoidal choroidal vasculopathy (PCV) supported by adjunctive photodynamic therapy (PDT). These results have

Another substantial development that Dr. Hendrik shed light on was a recent study of Luxturna for the treatment of RP65 retinal dystrophy. In 2018, Luxturna was the first approved retinal gene therapy in Europe. Since that time, EVICR.net has conducted a large-scale survey of its use in treating retinal dystrophy generally, and in treating RP65 derived retinopathy specifically. While positive results were reported at Euretina in 2019, more mature results released within the last 2 months have yielded far more detailed sets of data. While these are still being analyzed, the potential for gene therapy is both vast and exciting.

All about the MACUSTAR Project The MACUSTAR project is yet another highly ambitious study being undertaken by EVICR.net. Focusing on AMD, the study seeks to chart the progression of this untreatable condition from its earliest onset using random forest regression models of AI. This study, conducted upon a sample group of 767 screened patients at various stages of AMD, seeks to develop verifiable tests for changes within the patients’ macula, with the eventual goal of developing treatments that can slow the growth of the disease’s symptoms within its most aggressively affected sufferers. The project is ongoing, and it is anticipated that results will be forthcoming in next year’s EURETINA, and likely the following one as well. With greater advances in machine learning, communication technology, and cooperation within the EU’s structure, EVICR.net is engaging in research projects that were entirely impossible a few short years ago. It is encouraging to see such great leaps forward being taken, and one can only imagine what breakthroughs may be achieved in the not-too-distant future.


PIE magazine’s Daily Congress News on the Posterior Segment

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10 September 2021 | Issue #1

clinics for indications, such as psoriasis and rheumatoid arthritis.

Time to Step on the Brakes Putting a stop to recurrent inflammation in uveitis and endophthalmitis by Olawale Salami

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umulative damage from repeated inflammatory episodes affecting the posterior segment has been associated with significant visual morbidity. “The fluocinolone acetonide intravitreal implant (ILUVIEN, Alimera Sciences, Inc., Georgia, USA) was developed to prevent this kind of recurrent inflammation and protect the posterior segment of the eye,” shared Dr. Carlos Pavesio of the Moorfields Eye Hospital NHS Trust, London, UK, during his presentation at the EURETINA 2021 Virtual yesterday. “The approval was based on the outcome of the PSV-FSA-001 study, which was designed as a phase 3, prospective, double-blind, multicenter study,” Dr. Pavesio explained. “Subjects with non-

“The fluocinolone acetonide intravitreal implant (ILUVIEN, Alimera Sciences, Inc., Georgia, USA) was developed to prevent recurrent inflammation and protect the posterior segment of the eye.” - Dr. Carlos Pavesio, London, UK

Dr. Nguyen added: “In an upcoming phase 2 trial, we aim to evaluate the efficacy and safety of Izokibep, an IL-17 inhibitor, in the treatment and prevention of relapse and recurrence of noninfectious, intermediate, posterior, or panuveitis, including an initial pilot phase. This study is currently being launched in Europe and the US.”

Blocking OXPAP-C and CXCL-1 holds promise in infectious endophthalmitis When considering therapeutic strategies for endophthalmitis, we think of antibiotics that kill organisms and steroids that target inflammatory cascades and neutrophils.

infectious uveitis of the posterior segment were randomly assigned to receive either the implant or a sham injection. The primary outcome measure was the proportion of patients with recurrence of uveitis at six-month follow-up, with additional assessments up to 36 months.”

According to Dr. Michelle Callegan of the Dean McGee Eye Institute at the University of Oklahoma in the United States: “There are two critical areas of concern that impact treatment effectiveness: antibiotic resistance and the role of virulent organisms in unleashing toxins and hyperinflammation”.

On the latest follow-up results, Dr.Pavesio shared: “Our results showed that at 36 months, there was no recurrence in 34.5% of patients treated with ILUVIEN, compared to 2.4 %in the sham-treated group. Therefore, the implant resulted in a significant reduction in recurrences during this period. Recurrence in the fellow eye was also significantly reduced over the 36 months.”

“In our work on anti-inflammatory molecules, our overarching hypothesis is that organisms trigger inflammatory cascades in the cells lining the inner limiting membrane, either by direct contact or by interaction with the products they secrete,” explained Dr. Callegan.

A new therapy for posterior uveitis The cytokine network in uveitis involves signaling along the Th-1, Th-2, and Th-17 pathways, with subsequent production of IL-1, IL-4, IL-17, and IL-22. “We and others have observed elevated IL-17 in the tissues of patients with noninfectious uveitis, and there is a clear rationale for developing an IL17 inhibitor for non-infectious uveitis, including the unmet medical need for targeted therapy which may yield better efficacy and safety,” shared Dr. Quan Nguyen of the Byers Eye Institute, Stanford University, during his presentation. In addition, there are existing anti Th-17 therapies in the

“TLR signaling is vital to these inflammatory cascades in endophthalmitis. Our work shows that the inhibition of CXCL-1, a major chemoattractant, can significantly reduce inflammation of bacillus and staph aureus models of endophthalmitis in mice,” Dr. Callegan said about the most critical signaling pathways. “We also show that blocking OXPAP -C, a naturally occurring oxidized phospholipid, led to reduced inflammation in mice with endophthalmitis.” On clinical implications, Dr. Callegan concluded: “Therefore, we propose that blocking the CXCL-1 and OXPAP-C pathways could significantly abrogate inflammation arising from infectious endophthalmitis”.


PIE magazine’s Daily Congress News on the Posterior Segment

Beating the

Pandemic mic Clinical practices for effective remote monitoring of retinal diseases by Elisa DeMartino

Symposium Session: Remote Monitoring of Retinal Diseases and the Implications of Durable, Long-Acting Therapeutics in Clinical Practice, Especially in Times of Covid-19

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eesh, that title is a mouthful — or rather, an eyeful. And, apparently, lately, we’re all getting an eyeful. Of our mouthfuls. Not following? All right, let’s break down the topic here. Since the start of corona lockdowns a year and a half ago, healthcare practitioners have faced new challenges in providing effective care for patients, with in-person visits at best inconvenient and at worst impossible. While remote monitoring of eye disease is not brand new, some technologies were called to action rather suddenly, giving at-home care options big shoes to fill. Specialists gathered on one of the final sessions of the first day of the EURETINA 2021 Congress to discuss these challenges.

At-home eye tests: Triaging patients before they go to hospitals Dr. Dawn Sim, consultant ophthalmologist at Moorfield Eye Hospital in the UK, discussed some of the at-home eye test options in her experience. “A key strategy we have utilized in the UK is the power of triaging patients prior to attendance to a hospital,” she explained, introducing her remote take on industry-recognized forward triaging. She presented promising results, such as a low-tech eye test which can be done at home using a printout on

Technological illiteracy can be a barrier to at-home vision tests.

standard A4 paper. A low-tech eye test is major given that technological proficiency can be a challenge for so many elderly patients. Such a barrier was felt by a woman in a case study presented by Dr. Sim. The woman’s appointment time for bilateral edema injections fell in March 2020 around the time of the first, most severe lockdowns. The hospital prescribed the use of the Alleye vision test, which detects AMD and DME and alerts the eye-care provider when vision scores are too low. The program, however, requires a touch-screen device — something the patient didn’t have. Fortunately, she was lent an iPod Touch and was able to wait until June 2020 before having to visit the hospital in person.

Remote monitoring for slowrelease drug devices Dr. SriniVas Sadda from the Doheny Eye Institute in Los Angeles spoke on the importance of remote monitoring for slow-release drug devices in particular. “There’s no question that we are entering this era of long-acting delivery approaches,” he asserted, citing examples of slow-release ranibizumab and axitinib. Many more long-acting agents are in development, being designed to provide 6+ months on average of disease activity control without the need for treatment. “The idea is to get

many months with a single treatment.” He warned, however, that remote monitoring will still be essential.

More challenges with retinal treatment amid the mask era Tuning in from the Japanese Retina Vitreous Society, Dr. Taiji Sakamoto introduced a possible new problem with retinal treatment during the COVID19 pandemic. He cited a surge in ocular infection during this “mask era” potentially due to masks causing airflow to move from a person’s mouth directly to their own eyes. Oral pathogens including streptococcus and enterococcus were found in patients’ eyes post-IVI and particularly post-vitrectomy surgeries. Dr. Sakamoto noted, though, that this might be a culturally specific finding due to Japanese peoples’ tendency to wear masks more often, even inside. “My wife loves to wear a mask because she doesn’t like to wear makeup,” he explained. “Maybe she doesn’t want to kiss you,” one of the other speakers comically suggested. If only that were the sole reason to wear a mask nowadays! I think we can all agree with Dr. Sakamoto when he said: “What I’m longing for is life with no mask!”.

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10 September 2021 | Issue #1

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