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posterior segment • innovation • enlightenment

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HIGHLIGHTS Ophthalmic treatments 04 can be costly...but there are ways to save. ROP patients 07 Will finally benefit from tech advancements in treatment? Experts are hopeful... respond to tough 10 Experts questions in surgical

The Hidden Risks of Diabetic Retinopathy by Hazlin Hassan


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iabetic retinopathy (DR) is the most common microvascular complication of diabetes and remains one of the leading causes of blindness worldwide among adults aged 20-74 years. New insights into the management of DR may be able to pave the way for better treatments than ever before. An outstanding line-up of experts presented their findings on a wide variety of issues related to the disease during sessions on the second day of the American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020).

Two for the price of one While almost everyone likes a good bargain, sometimes getting two for the price of one is not everyone’s idea of a sweet deal. Almost half of patients with diabetic macular edema (DME) in one eye developed DME in the fellow eyes over 2 years of follow-up, according to studies on the incidence of new DME in fellow eyes of patients (VISTA and VIVID studies). “The time to development of DME in the fellow eye was approximately 6 months,” said Dr. Sumit Sharma of the Cleveland Clinic Cole Eye Institute (Ohio, USA). A shorter duration of diabetes and thicker baseline CST in the study eye were identified as key risk factors for DME development in the fellow eye. In addition, the rate of DME development

in the fellow eye increased with the increasing numbers of risk factors. “These findings suggest that patients with DME in one eye should be closely Cont. on Page 3 >>


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26 July 2020 | Issue #3

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PIE magazine’s Daily Congress News on the Posterior Segment

>> Cont. from Page 1

monitored for DME development in the fellow eye,” said Dr. Sharma.

DR linked to cerebral vascular accidents Diabetic retinopathy is significantly associated with the future risk of cerebral vascular accidents (CVAs), myocardial infarctions (MI) and death even after adjusting for traditional cardiovascular and diabetic risk factors with higher degrees of retinopathy appearing to be associated with higher risk, reported Dr. Bobeck Modjtahedi, from Southern California Permanente Medical Group (SCPMG, USA). A retrospective study of 68, 206 patients with type 2 diabetes mellitus revealed that 2.5% suffered a MI, 3.3% suffered a CVA, and 5% died within five years of retinal evaluation. “These findings highlight the importance of retinal exam findings as retinopathy severity may help identify patients at heightened risk for morbidity and mortality,” said Dr. Modjtahedi.

Proliferative DR in NPDR eyes “When left untreated, nearly half of eyes with severe nonproliferative diabetic retinopathy (NPDR) progressed to proliferative diabetic retinopathy (PDR) within 4 years in routine clinical practice in the US,” said Dr. Ehsan Rahimy of Palo Alto Medical Foundation (California, USA).

severe NPDR and 11% had unspecified NPDR. The 4-year risk of progression to PDR was 14.9% in the overall patient population. This risk increased with higher NPDR severity (mild 7.7%, moderate 21.4% and severe 48.1%).

Dual-targeted treatment of persistent DME shows promise Dual-targeted inhibition of VEGF-C/-D and VEGF-A may hold promise in the management of DME, reported Dr. David Boyer, of Retina-Vitreous Associates Medical Group (USA), citing a study evaluating the safety, visual function and anatomic outcomes of switching patients with persistent DME from anti-VEGF-A monotherapy to combination therapy of OPT-302 with aflibercept.

“These findings highlight the importance of retinal exam findings as retinopathy severity may help identify patients at heightened risk for morbidity and mortality,” - Dr. Bobeck Modjtahedi

“Switching to combination OPT-302 with aflibercept from prior anti-VEGF-A monotherapy in eyes with persistent DME was well tolerated with improved visual and anatomic outcomes in patients

with persistent DME despite prior antiVEGF-A monotherapy,” said Dr. Boyer.

Telescreening, a boon for high-risk populations In high risk populations, the rates of retinal pathology are significantly higher. “Diabetic telescreening is an effective strategy to identify patients that need intervention and reduces the barriers associated with noncompliance,” said Dr. Matthew Ohr from Ohio State University Wexner Medical Center (USA). That observation was based on a study of medical records of diabetic patients who underwent telescreening retinal imaging between May 2019 and August 2019. Imaging of 200 eyes from 100 patients was performed on an ultra-widefield camera (UWF Primary) (Optos, Fife, UK) by medical assistants in the primary care office and read by a retinal specialist. A total of 68 patients had identifiable pathology, 88 eyes had mild nonproliferative DR (NPDR),11 eyes were noted to have moderate NPDR, while 6 eyes had severe NPDR. One patient was found to have undiagnosed high risk PDR. Eight eyes were noted to have clinically significant DME. “With minimal training, non-ophthalmic medical assistants can be trained to capture high quality non-mydriatic ultrawidefield fundus photos for diabetic screening,” said Dr. Ohr.

Baseline NPDR severity was a strong predictor of progression to PDR, according to a retrospective analysis of electronic medical records (Vestrum Health Retina Research Dataset; Naperville, IL, USA) during January 2013 through June 2019 from adult eyes diagnosed with NPDR without DME and prior intravitreal anti-VEGF treatment. Eyes were excluded if they converted to PDR or DME within 1 week of index NPDR diagnosis or showed evidence of AMD or retinal vein occlusion during the study period. Results of 135,324 eyes included in the study showed that 52% had mild NPDR, 29% had moderate NPDR, 8% had

It’s not as easy as taking a selfie, but non-ophthalmic assistants, using a suitable device, can be trained to take fundus photos of the eye.



26 July 2020 | Issue #3

macular edema (DME). According to data presented by Dr. Sun, over ten years, aflibercept represented a national cost of $28.8 billion versus $14.42 billion for laser treatment and $15.7 billion for observation. After two years, there was no difference in visual acuity (VA) between the three treatments, though aflibercept was given if VA decreased from the baseline in either of the other treatment groups.

Insights from the Socioenomic and Practice Management Panel by Sam McCommon


he symposium on socioeconomics and practice management took a whimsical turn to begin. Taking the idea of a round table to its logical conclusion, the ophthalmologists in the first segment attending said table donned fanciful names like those from Arthurian legend. The second segment was more sober, though equally enlightening and equally focused on the broad picture.

• Treat-and-extend, the most popular treatment protocol • Pro re nata (PRN), in which patients were screened once a month to determine if injections were necessary • Injection series, a varion on automatic therapy that includes examination and a series of injections

Dr. Alex Leder shared a study that compared the costs of four treatment options for neovascular age-related macular degeneration (nAMD). These options were:

According to Dr. Leder’s study, while automatic therapy had the lowest annual cost for exams and optical coherence tomography (OCT) testing, it was the most expensive in terms of drug and injection cost. Conversely, PRN cost the most for exams and OCT testing but was the least expensive option for drug and injection cost. An important note was that drug and injection cost far outweighed exam and testing cost. Dr. Leder also noted an additional bonus of using a PRN strategy: The more exams a person undergoes, the earlier nAMD can be detected.

• Automatic therapy, in which patients got injected every month with exams once a year

Dr. Jennifer Sun shared interesting data on nationwide costs comparing treatments for central-involved diabetic

Saving money Saving patients money when possible is generally a good idea and can help keep patients happy. To wit, two of the presentations focused on ways to reduce treatment costs.

Dr. Sun’s conclusion? Doctors and patients might choose an observation strategy for DME, withholding anti-VEGF treatments unless vision worsens.

Opioids in ophthalmology The opioid epidemic is a serious public health crisis, but it may not always be at the forefront of ophthalmologists minds. As Dr. Jonathan Prenner puts it, “Sometimes we can feel isolated from it given the closed ecosystem we live in.” To address that, Dr. Yoshihiro Yanekawa conducted a study on the rate of opioid prescriptions by ASRS members. On average, members wrote 11 opioid prescriptions per year — a rate higher than the national average. Dr. Yanekawa pointed out that the numbers of prescriptions — 15,000 in total — were being driven by a minority of ASRS members. His study showed 24% of members wrote more than 10 prescriptions and 6% wrote more than 50. Additionally, there was a higher rate in the South than the rest of the country (USA). He also noted that, since this data came from a medicare database, it’s quite possible that the numbers are significantly higher since younger patients weren’t being accounted for. In general, opioid prescription numbers have been going down in the last few years, said Dr. Yanekawa, though he feared the opioid crisis was getting worse in tandem with COVID-19. In treating his patients, Dr. Yanekawa only recommends over-the-counter medication.

PIE magazine’s Daily Congress News on the Posterior Segment

Practice Valuation Know your Worth by Brooke Herron


t’s safe to say that ophthalmologists generally don’t get into the practice of eye surgery to file insurance reimbursements. However, practical aspects of medicine (such as this) confront doctors daily, even when planning patient treatment. Therefore, on the second day of the American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020), important updates on insurance coding and reimbursement were covered by experts, as well as tips for practice benchmarking.

Let’s talk value “The currency of our work in not in dollars, it’s in RVUs,” began Christina Weng, MD, MBA, during the session on Coding and Reimbursement. “RVU pegs a specific CPT code to a value relative to others and that is what indirectly correlates to the payment rate,” she added. Physicians can have an impact on the work relative value unit (wRVU) calculations through RUC (Relative Value Scale Update Committee) surveys, which are sent out through specialty and subspecialty societies, like ASRS. There are several factors that comprise a wRVU, including time, technical skill and effort, mental effort and complexity in decision-making, and psychological stress. She notes that objective valuation of RVUs can be challenging — however, a process or procedure map can help with this. She recommends that surgeons involve an independent, experienced specialist who is dedicated to this task and include a careful timestamp for each step in the workflow. “Then you want to be able to generalize this information, over a variation of different patients, different satellite centers, even different days of the week, as we know that efficiency can vary amongst all these elements,” added Dr. Weng.

What’s all the RUCkus about? “The AMA RUC Committee is the Supreme Court of reimbursement for Medicare,” said John Thompson, MD. “They actually put a tremendous amount of effort to assign a fair value to virtually all medical procedures and evaluations.” Most retina procedure codes have experienced large reductions in work values from 2008 to 2018, and that’s primarily because surgeons are faster, continued Dr. Thompson. Therefore, he emphasized the importance of ophthalmologists taking the time to fill out of the emailed RUC survey: “Answer the survey honestly, knowing that your average intraservice time is the most important survey question. So, please be realistic about how long it takes (not your best, but not your worst) . . . take the time to complete it carefully, because in this particular situation, time is money,” he concluded.

Ch-ch-ch-changes Nothing lasts forever, including RVU codes. Thankfully, Ankoor Shah, MD, provided a brief rundown of changes coming in 2020 and 2021.

Extended ophthalmoscopy is probably the biggest change in 2020; meanwhile changes to E/M (evaluation and management) will take the reins in 2021, he explained. “In extended ophthalmoscopy, there was significant rationale for change and that was based on increased utilization,” said Dr. Shah. “As a consequence, the 25 [92225] and 26 [92226] codes were eliminated and new codes were created, the 01 [92201] and 02 [92202].” Therefore, the procedure still exists, but the codes have significantly changed, he continued. “For E/M visits, these will change substantially and will likely increase reimbursements.”

Speaking of value RetinaPractiCare 2.0 is a project to benchmark retinal practice financial and productivity management. Through this initiative, the project collects data on practice demographics, revenue, expenses and practice metrics to allow practices to compare themselves to aggregate data from other practices anonymously, said Dr. Thompson. He continued that practices need this because “we’re under great financial pressure from CMS and other payers, and this will determine where you’re doing well and where you need improvement,” he explained.



26 July 2020 | Issue #3

When Scientific Precision Meets Robotic Automation


by Joanna Lee

he race to discover new therapies has always been challenging, if not more in recent times. Nevertheless, the power of automation through robotics has been one of the most responsive solutions, aiding large pharmaceutical companies in their need for precision, repeatability and to capture data when it comes to pharmaceutical processes of discovery. Here’s where HighRes Biosolutions (Massachusetts, USA) enters the labs: building complex robotics systems for bio-pharmaceutical research. It stands in the intersection where biological science meets with robotics automation, serving all, from global leaders to small startups, searching for new therapies in the treatment of diseases. Their solutions are a combination of standard elements configured and customized specifically for each end

HighRes Biosolutions combines robotics to facilitate discoveries through a variety of life science devices created to realize certain scientific experiments in order to generate data related to the discovery of new therapies. The philosophy behind their architecture is simple – come up with systems where scientists can best apply their scientific knowledge skills and let the automation perform what humans cannot do. It is best that robotics respond with flexibility corresponding to the science as required. This is because of the constant immense challenge reflected in the reality – the dynamism of developing new technologies in biological science is extremely high. As each scientific development takes place, corresponding mapping systems would be needed in the applications linked with the robotics. To capture precisely the design, one would need to understand the customer’s science itself.

Hereditary Retinal Diseases and Genetics by Hazlin Hassan


hile many inherited ocular diseases are considered untreatable, the world’s renowned experts are actively seeking treatments for ophthalmic genetic diseases such as retinitis pigmentosa (RP) and retinoschisis. The latest studies on gene-based therapies were among some of the exciting topics being discussed during the second day of the virtual American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020).

hRPCs trial to progress to phase 3 There are currently no FDA approved therapies for retinitis pPigmentosa (RP). Allogeneic human retinal progenitor cells (hRPCs) secrete neurotrophic factors that promote retinal photoreceptor cell survival and function. This paracrine mechanism has shown promise as a therapeutic strategy for RP, a hereditary

customer based on the science they’re seeking to accomplish.

blinding disease.

“Results from a Phase 2b trial assessing the efficacy and safety of intravitreal injections of hRPCs for the treatment of RP demonstrate favorable biological activity and an excellent safety profile,” said Dr. Anthony Joseph of the Ophthalmic Consultants of Boston (USA).This warrants progression to phase 3 trials.

Gene therapy for X-Linked RP X-Linked is the most severe form of RP, with early onset and rapid progression, with severe visual impairment by the third to fourth decade. AAV5-RPGR, delivered by subretinal injection, was developed to deliver stable gene sequence to rod and cone photoreceptors, driving expression of functional RPGR protein, resulting in rescue of photoreceptor function and consequently improving vision. “Six-month results from a phase 1/2 clinical trial, showed that there was statistically significant improvement in central retinal sensitivity observed

For HighRes Biosolutions, understanding customers’ requirements has been perfected almost to a science, so to speak, in order to stay ahead and in sync with customers’ rapid progress and ambitions while treading the frontiers of biological research. Being one of the leaders in the field, HighRes Biosolutions counts many global pharmaceuticals leaders as its partners in advancing towards the cutting edge, with names like Regeneron among many recognized giants in the field using its technology. In fact, PIE magazine spotted a HighRes Biosolutions robot in Regeneron’s booth video at the American Society of Retina Specialists (ASRS) Annual Meeting — a clear indicator of the importance of robotic automation to Regeneron. The constant challenge in matching scientific solutions with robotic automation to deliver better pharmaceuticals as an outcome remains as fuel for its ongoing solutions.

in treated eyes,” said Dr. Michel Michaelides from Moorfields Eye Hospital (United Kingdom). Low and intermediate dose cohorts achieved improvements in retinal sensitivity across multiple metrics and modalities. These doses are being further explored in the ongoing randomized, controlled doseexpansion phase of the study.

SD-OCT reveals retinal splitting changes in XLRS patients A study undertaken to explore any correlation between visual function and macular morphological characteristics evaluated by spectral domain OCT (SDOCT) in X-Linked retinoschisis (XLRS), revealed various retinal splitting changes in patients with XLRS, said Dr. Honghua Yu, from Guangzhou Liuhuaqiao Hospital (China). The SD-OCTA images of 72 eyes of 46 patients from 16 families, showed that macular schisis cavities were present in all 72 eyes and peripheral retinoschisis were present in 34 eyes. The defects might be indicators for evaluating the macular and the visual function.

PIE magazine’s Daily Congress News on the Posterior Segment

Tackling Retinopathy of Prematurity by Sam McCommon

When you stare into the abyss, the abyss stares back and laughs when you make a funny face.


ffecting prematurely born infants, the underdevelopment of eyes can lead to retinopathy of prematurity (ROP). Treatments are advancing, according to experts who convened at the virtual American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020). Below are some of the highlights of studies presented…

Machine learning in ROP Technological advances allow for some pretty neat progress in the medical sciences. Using machine learning for diagnoses, especially when combined with telemedicine, is one of those techniques that sound like it’s from the future — but it’s here now. Dr. Omar Punjabi has been working on just that. As his overview noted, “automated image processing and deep machine learning approaches have the potential to accurately detect zone, different stages of ROP and the presence of plus disease.” Images were uploaded to the software which would then produce a diagnosis. The system looks promising indeed: It had a global accuracy of 98.3% correct diagnoses among 1400 wide-field retinal

images of 111 prematurely-born infants. In a cool turn of events, the software for this program was developed by a highschool student Dr. Punjabi described as a rockstar. When asked how long it would take for this process to be used routinely, Dr. Punjabi demurred and noted that the dataset would have to be tested across different institutions — as well as with different cameras. For example, Dr. Punjabi and his team developed a 3D printer adapter that connects to a cell phone, and then used tomography to stitch together the images and get good results.

Aflibercept for oxygeninduced ROP Dr. Andres Gonzales and his team conducted a study on mice to test the effects of two doses of aflibercept on regrowth of retinal vasculature following oxygen-induced injury of physiologic vascularization. Their conclusion? A dose of 100 nanograms (ng) was more effective than 1000 ng in allowing more regrowth. Additionally, the avascular retina within the hyperoxia-induced injured retina persisted at day 25 — 11 days after injection.

Maintaining visual field in children with severe ROP Visual development is crucial to normal brain development. As Dr. Alay Banker pointed out, two thirds of brain function is related to vision. Furthermore, 75% of normal brain development in the early years of life is because of vision. So, maintaining a healthy visual field is ultimately central to normal brain development. His study compared children at age 10 who had received laser or anti-VEGF treatment as a primary monotherapy for treating severe ROP. The children in the anti-VEGF group had better preservation of their central visual field and a less affected peripheral visual field than in the laser group. However, issues like poor visual acuity, amblyopia, and strabismus presented as potential issues. This is the first such study of visual field on ROP children, so more studies will likely follow.

Long-term complications of lasers on ROP Dr. Audina Berrocal shared a retrospective from 2005-2015 examining anterior segment abnormalities following laser ROP treatment. After panretinal photocoagulation (PRP) treatment, 79% of infants treated had developed pachyphakia, microcornea and angle closure (PMAC) at a median of five years later. Dr. Berrocal said: “We postulated that the cause had to do with anterior segment ischemia at the time of laser surgery. This leads to a smaller cornea and cellular laxity that makes the lens become pachyphakic. A lot of these kids have lenses that are five millimeters in width or bigger. So, by having this lens that’s so big and a smaller cornea, it pushes forward and you have PMAC.” She noted that she hasn’t seen this PMAC in the anti-VEGF age — the cases only occurred when the infant had extensive laser treatments. For those who were treated with lasers, she recommends following up on the patient by measuring the corneal diameter, checking the size of the lens and tracking intraocular pressure.





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The perfect petal Srinivas Joshi, MD, began the symposium by discussing Multi-Layered Inverted Internal Limiting Membrane (ILM) Flap: A Unique Technique for Closure of Large Macular Holes. This study comprised 103 eyes of 99 patients. During the procedure, the internal limiting membrane (ILM) was stained with Brilliant Blue G (BBG) and multiple flaps were created in a petaloid fashion around the macular hole, then positioned over the hole under perfluorocarbon liquids (PFCL) (a.k.a. heavy liquids). “The advantages of this technique are that even if one petal goes off, the rest of the petal still remains,” shared Dr. Joshi.

Pucker up Another paper looked at Relation of Anatomy with Function Following the Surgical Treatment of Idiopathic Epiretinal Membrane: A MultiCenter Retrospective Study, presented by Sengul Ozdek, MD. This study included 634 eyes with idiopathic macular pucker treated via vitrectomy with or without phacoemulsification.


itrectomy is often the first line surgical treatment for macular conditions, including for macular holes which cause blurred and/or distorted vision. To further examine the components of surgery for macular conditions, experts convened to share best practices during the Macular Surgery Symposium (1-2) on the second day of the American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020).

“I believe it’s more a natural healing process due to the loss of retinal tissue,” he said, adding that the presence of this epiretinal membrane reflects on the loss of retinal tissue rather than the progression to full thickness macular hole.

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26 July 2020 | Issue #3

Results showed that the peeled ILM contained numerous Müller cell fragments that may induce gliosis, creating a stronger centripetal pull and resulting in hole closure. Additionally, when the peeled ILM is left attached around a macular hole, it could stimulate gliosis in the retina or on the surface of the macula.

Oh, epiretinal perforation . . . Next, Ismael Chehaibou, MD, discussed results and tips from a study titled, Spontaneous Conversion of Lamellar Macular Holes to Full Thickness Macular Holes: Clinical Features and Surgical Outcomes. On the role of epiretinal perforation in progression to full thickness macular holes, Dr. Chehaibou explained, “There is a high rate of epiretinal perforation in these cases with lamellar macular holes . . . I do not think that this perforation has any tractional effect in contributing to full thickness or inflammation.

The main conclusions were that the best corrected visual acuity (BCVA) improved by 2 lines in 71%; and 37% had final BCVA of 20/25. It was found that BCVA and central macular thickness (CMT) were strongly correlated at all times, and that neither ILM peeling nor the use of tamponade added to BCVA improvement. Overall, the main prognostic factors were better preoperative BCVA and an intact ellipsoid zone. “The results were interesting because I was peeling the ILM in all the epiretinal membranes (ERM) but I have seen that the ILM peeling did not add anything to the visual gain or to the anatomic behavior of the fovea after surgery. So, it may even cause some negative results to the anatomy of the fovea,” explained Dr. Ozdek. She continued: “That’s why we should not insist on peeling the ILM . . . but also we know that most of the ILM is peeled spontaneously together with the ERM, so if that occurs it’s okay, but you don’t have to insist on it.” Furthermore, when they checked the foveal thickness increase after the surgery, which may indicate indirect cystoid macular edema (CME), it was more prevalent in the combined group [vitrectomy + phaco], concluded Dr. Ozdek.

PIE magazine’s Daily Congress News on the Posterior Segment

Intravitreal and Suprachoroidal Therapies Promising Effective Options against NIU-PS by Joanna Lee

Future intravitreal-based therapies look set to be an effective option along with suprachoroidal therapies in controlling the recurrence of non-infectious uveitis affecting the posterior segment (NIU-PS).


ontinuing the investigations into fluocinolone acetonide intravitreal (FAi) treatment ever since its introduction in 2018, Dr. Dilraj Grewal and his fellow researcher Dr. Dario Paggiarino (who is also chief medical officer at EyePoint Pharmaceuticals) found that over 55% of the recurrences in the FAi group were because of patients using systemic antiinflammatory medications (oral corticosteroids or systemic

immunosuppressants) over the 3-year trial. In their study, Evaluating the True 3-Year Recurrence Rate in Non-infectious Posterior Segment Uveitis following an Injectable Fluocinolone Acetonide Insert (FAi), the subjects were deemed as failures even if they have used the medication for non-ocular or other eye conditions. The research concluded that the true 3-year recurrence rate in eyes treated with FAi might even be below 56%. FAi has been available under the brand name Yutiq™ (EyePoint Pharmaceuticals, Massachusetts, USA).

Researchers are looking into new treatments for non-infectious uveitis affecting the posterior segment.

Dr. Seenu Hariprasad found that using a single sustained-release 0.18 mg FAi for non-infectious NIU-PS saw a decrease in macular edema among patients with non-infectious uveitis affecting the posterior segment (NIUPS), In his presentation titled, Course of Macular Edema Through 36 Months With Fluocinolone Acetonide Intravitreal Insert for Non-infectious Uveitis Affecting the Posterior Segment, sham-treated eyes have also seen a decrease in macular edema most likely through their adjunctive local and systemic anti-inflammatory/immunomodulatory medications which the patients have received. In ASRS 2019, several 36-month studies using the Yutiq insert for noninfectious posterior uveitis and the results also showed low-recurrence rates and VA gains of 3 lines compared with sham. Another therapy that looked promising is the suprachoroidal triamcinolone acetonide suspension (CLS-TA). The investigators evaluated intraocular pressure (IOP) in patients with macular edema secondary to noninfectious uveitis (NIU) after suprachoroidal injections of CLS-TA (triamcinolone acetonide suspension). Comparing this against the IOP of patients in the PEACHTREE trial who were rescued, they found that the ME patients’ IOP did not increase significantly after suprachoroidal injections of CLS-TA. About 10% of the general population in the United States has an allergy to penicillin. Thus when it comes to treating infectious endophthalmitis with intravitreal vancomycin and ceftazidime, doctors may alter their treatment strategies. In his presentation titled Outcomes of Infectious Endophthalmitis in Patients With Systemic Antibiotic Allergies or Cross Reactions to Intravitreal Vancomycin or Ceftazidime, Dr. Prethy Rao reported her team’s single-center, retrospective longitudinal study of endophthalmitis patients with a documented beta-lactam or cephalosporin allergy receiving intravitreal antibiotics between 2005 – 2019. The study showed no documented allergic reactions in these patients after they have received standard intravitreal vancomycin or ceftazidime.



26 July 2020 | Issue #3

Experts Answer the Tough Questions on Surgical Techniques by Brooke Herron


n vitreoretina, surgical techniques are in continuous evolution. From new devices and instruments, to clever surgical maneuvers and more, these advances benefit both patient and surgeon. On the second day of the American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020), recent papers were covered by esteemed surgeons, followed by a Q&A during the Surgical Techniques and Maneuvers (3-5) Symposium. Below, we highlight tips from some of the studies reported on the topic…

Watch the injection pressure “As of June 2020, we’ve treated 126 patients with gene therapy — 118 of

these were subretinal injections, of which 72 used the pneumatic-assisted subretinal delivery with foot pedal control,” began Andreas Lauer, MD, on his presentation titled Creating Blebs for Subretinal Gene Delivery. According to Dr. Lauer, in these 72 patients, there was a greater spread of intraoperative injection pressure and higher pressures, in general, to create the separation of the retina from the retinal pigment epithelium (RPE). For bleb propagation, there is more clustering and lower pressure is needed. When asked why he records injection pressure when creating subretinal blebs, Dr. Lauer explained, “One of my colleagues did some work with subretinal

injection pressure and ascertained that at different pressures there is trauma that occurs to the RPE. Since patients with inherited retinal disease will have a fairly fragile retina, for this procedure to be successful, we want to try to be as precise and gentle as possible when delivering a therapeutic.”

Scleral tunnels key to mitigate tilt Next, Ramon Lee, MD, discussed Refractive Outcomes after Intrascleral Fixation of Intraocular Lens with Pars Plana Vitrectomy from a study of 84 patients. He noted two main points that resulted from this paper: First, refractive outcomes remained stable at the last

PIE magazine’s Daily Congress News on the Posterior Segment

postoperative follow-up, indicating that there are stable scleral tunnel architecture and secure IOL haptics. On measuring the tilt for the lens, Dr. Lee said: “Tilt is tough. Symmetry of your scleral tunnels plays a huge role. The degree and the angle that you put in the scleral tunnels factors in… whether you’re completely 180-degrees apart — that is important.”

Heads up for 3D visualization Katherine Talcott, MD, then answered questions regarding the Comparative Assessment of Conventional MicroscopeIntegrated to Digitally Enabled Intraoperative OCT in Vitreoretinal Surgery in the DISCOVER Study. Of note, the study found that surgical field-based intraoperative optical coherence tomography (iOCT) visualization was very low for the conventional iOCT group (3.3%) compared to the 3D group (67.7%). On the reason for that large disparity, Dr. Talcott explained that in the conventional group, those images tend to be pretty small and transparent, so it can be hard to see individual details of the iOCT images. “The other thing that makes a difference is that they’re only accessible to the surgeon . . . so that’s why in this group it’s more common to look at the accessory screen,” she explained. She says that’s different for the digitally enabled iOCT group: “They’re able to see these images projected onto a larger screen . . . and you can make out much better detail.”

It’s in the YAG The big question asked of Netan Choudhry, MD, during his presentation on Vision Outcomes & OCT Findings after YAG Vitreolysis for Vitreous Opacities (VOYAGE Study) was: Why aren’t we doing YAG more? According to Dr. Choudhry, his study touched upon one of the key answers: “Up to this point, we really haven’t had an objective way to evaluate opacity — for example, what it looks like, where it is, what it’s doing, and the endpoint for treatment.”

“What was unique in our study, is that we used OCT imaging, particular Swept Source, of the vitreous — which was a little bit of a leap forward to actually identify the opacities that the patients were complaining about,” shared Dr. Choudhry. “Then we titrate the treatment to the disappearance of those opacities and we know that we’ve hit the endpoint for the therapy.”


(Don’t) go with the flow Raymond Iezzi, MD, MS, summarized the study on Acute Intraoperative Hypotony During Automate Infusion Control. According to Dr. Iezzi, IOP control systems do not directly measure IOP, rather it’s computed based on infusion flow — and when something restricts the infusion flow, causing acute hypotony, these systems grossly overestimate IOP. “The challenge of course, is if you develop hypotony during vitrectomy under these infusion control systems, the pump will shut off and hitting the pressure to 60 will do nothing because the system thinks the pressure is already 60 because the flow is zero or it’s reduced,” said Dr. Iezzi. “That gives the computer and the system a false impression that pressure in the eye is higher than it actually is. So, you basically have to reposition the infusion line to reduce that partial or complete obstruction, allow that pump to turn back on and go from there,” he explained.


26 July 2020 | Issue #3

Fighting Ocular Cancers through the Years by Hazlin Hassan


hile treating ocular cancer is imperative, some treatments can prove toxic to the patient. The increased use of chemotherapy agents has resulted in longer cancer patient survival but at the same time, inadvertently causes adverse ocular side effects. The Ocular Oncology Symposium at the virtual American Society of Retina Specialists 38th Annual Scientific Meeting (ASRS 2020) discussed an ongoing clinical trial on Au-011 to treat choroidal melanoma and how ocular cancer treatments have evolved over the years.






AU-011 clinical trial for treating choroidal melanoma Dr. Ivana Kim from the Ocular Melanoma Center, Massachusetts Eye and Ear (USA) shared updates from an ongoing Phase 1b/2 Open-Label Clinical Trial Evaluating the Safety and Efficacy of AU-011 for the Treatment of Choroidal Melanoma. Preliminary safety and efficacy of AU-011 has been observed in this ongoing Phase 1b/2 trial, she noted. “The therapy was well tolerated with maintenance of vision and tumor control in the majority of subjects,� said Dr. Kim. Phase 3 studies with sham control are being planned in subjects with documented growth to confirm the safety and efficacy of AU-011 for treating small choroidal melanoma (CM) and high risk indeterminate lesions, she added.

Reducing toxicity while combating cancer Personalized treatment in ocular oncology has incorporated earlier tumor treatment, avoidance of enucleation, and integration of molecular genomics.



“Retinoblastoma treatments have focused on decreased treatment related morbidity, decreasing enucleation while maintaining excellent survival,� said Dr. Timothy Murray of Ocular Oncology and Retina (Florida, USA), who presented on Evolving Treatments in the Absence of Clinical Trials – a three-decade study focused on decreasing treatment related morbidity/mortality. K

This study evaluated the shift in personalized ocular oncology care to deliver earlier treatment, to avoid enucleation, to minimize systemic toxicity, and to use secondary pharmacotherapy to improve outcomes for the most common primary adult and pediatric ocular malignancy. “These advances have come from ocular oncology centers, incorporating advanced therapeutics, without the aid of randomized clinical trials,� added Dr. Murray. “This evolution in care demands outstanding, and ongoing focus by each individual center to evaluate shifting treatments with real-time analysis,� he emphasized.

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