Advanced Imaging Spurs New AMD Nomenclature
International experts create new set of terms.
■ Most of the standard definitions and classifications relating to neovascular AMD date back to the era when fundus photography and fluorescein angiography were the gold standards of retinal imaging. With much more advanced imaging techniques now available, such as OCT and OCTA, retina specialists and researchers believed it was time to conduct a comprehensive review all of the old definitions relating to wet AMD and come up with a set of new ones more in keeping with the state of retinal imaging as it exists today. To build a consensus, a number of group meetings of experts were held under the auspices of the Macula Society. The participants formed an international panel of retinal specialists, imaging experts, and ocular pathologists. The project was named Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group (CONAN).
In an article recently appearing in the journal Ophthalmology, the expert panel notes that “using OCT and OCT angiography does not replace fluorescein angiography or color photography; rather, these additional forms of imaging augment those forms of imaging and provide additional data to improve classification possibilities.” The panel decided that familiar old terms such as “occult CNV,” “classic CNV,” and “minimally classic CNV” should be replaced by more precise definitions. For example, the new definition of occult CNV is this: “Type 1 macular neovascularization represents areas of neovascular complexes arising from the choroid and imaged with OCT as an elevation of the RPE by material with heterogeneous reflectivity; vascular elements may be seen. OCT angiography shows vessels below the level of the RPE.”
There are scores of such changes in the new nomenclature listed in the Ophthalmology article. The authors conclude that “advances in diagnostic imaging and learnings from therapeutic outcomes have substantially changed the understanding of neovascular AMD as a morphologic disease entity. The substitution of largely angiographic definitions by OCT-based feature identification, the insight into the origins of neovascular development, including both the retina and choroid, and the differentiation of neovascular and atrophic pathways including their concomitant occurrence are prominent examples of evolution of disease conceptualization and the need for adjustment in AMD terminology.”
Home-Based OCT Uses AI to Track Wet AMD Activity
System identifies the source, location, and volume of fluids.
■ Two independent data trials have confirmed that the investigational Notal OCT Analyzer (NOA) has the ability to accurately track neovascular AMD disease activity across large longitudinal data sets. The pipeline artificial intelligence-based image analysis algorithm is designed to provide automated detection, localization, and quantification of fluid on OCT images in neovascular AMD. NOA uses a machine-learning algorithm and image recognition computational technique to distinguish between normal morphologic structures and those associated with disease-related changes that occur as a result of fluid that is present under and within the retina.
The first trial evaluated the performance of NOA in sequential OCT exams on an in-office Spectralis OCT and Notal Vision’s home OCT product. Using 173 eyes from 89 patients, NOA and masked human readers identified the presence or absence of intraretinal and subretinal fluid and its volume. The data showed a strong correlation of retinal fluid quantification between NOA and human graders with a correlation coefficient of 0.96.
The second trial studied the association between fluctuations in macular fluid volume and visual acuity following treatment with anti-VEGF therapy in neovascular AMD. An analysis of 5,281 in-office OCT images acquired from 403 patients over a 10-year period was performed using NOA. The results showed that greater fluctuations in retinal thickness resulted in worse visual outcomes in anti-VEGF-treated exudative AMD eyes.
Notal Vision’s home-based, NOA-enabled, OCT pipeline technology received FDA breakthrough device designation at the end of 2018, and the company is in the process of obtaining FDA clearance for the technology.
Ophthalmologists Weigh in on Prior Authorization Issues
One writer suggests a more even-handed approach.
■ The majority of the 406 ophthalmologists who responded to an AAO survey said that prior authorization, a cost-management tool required by health insurance companies, is delaying or disrupting the sight-saving care they give their patients. Insurance companies use prior authorization to control costs by reducing medically unnecessary tests and procedures. Instead of accomplishing this goal, the survey found that many health plans, including Medicare Advantage plans, have used prior authorization indiscriminately, creating treatment delays that may endanger patient health.
This new study indicates these delays are needless. Half of the ophthalmologists responding to the study said their authorization requests are approved from 75% to more that 90% of the time. However, an opinion piece published recently on the JAMA Network suggests 3 solutions to “right-size” prior authorizations and prevent inappropriate prescription delays and denials by health insurers. According to the article by Jack Resneck, MD, of the University of California, San Francisco, the following steps could improve the process:
- Health plans should eliminate prior authorization requirements for medications that have very low final denial rates, lack evidence of unwarranted variation in utilization, or for which lower cost or safer but effective alternatives do not exist.
- For patients who are stable with chronic treatment, insurers should offer protections to minimize disruptions and inefficiencies that occur when patients change health plans or when plans add new prior authorization/step therapy requirements to existing formularies.
- Insurers should enable easy access to formulary status, prior authorization requirements, and cost sharing for medications and alternatives for physicians during face-to-face interactions with a patient at the point of care.
“Rather than an unrealistic call to abolish prior authorization, these are balanced proposals intended to refocus medication utilization review tools on the appropriate use of high-cost new drugs for which the benefits, risks, and value are still being evaluated,” concluded Dr. Resneck.
Missed Visits Mean Decreased Vision in Wet AMD
Adherence is a key to good outcomes.
■ Missing a single ophthalmology appointment over a 2-year period was associated with decreased visual acuity for patients with macular degeneration, according to a new Penn Medicine study. The findings, published recently in JAMA Ophthalmology, suggest that more attention should be paid to ensuring visit adherence for these patients. The authors say the results of the study also have financial implications for clinicians, due to impending changes in Medicare reimbursement. These changes will reportedly shift financial risks to the physician, while also accounting for patient outcomes.
With a research team, Brian VanderBeek, MD, a professor of ophthalmology at the University of Pennsylvania’s Perelman School of Medicine analyzed data from the Comparison of Age-related Macular Degeneration Treatment Trail (CATT) randomized clinical trial. The dataset included 1,178 patients from 44 clinical centers in the United States. During the 2-year clinical trial, patients were required to visit, but not necessarily be treated with injections by, an ophthalmologist once every 4 weeks, totaling 26 visits.
The researchers devised 4 metrics to assess patient adherence, including total number of missed visits, average number of days between visits, longest duration between visits, and visit constancy (the total of 3-month periods with at least 1 visit attended). Those metrics were compared to the patients’ outcomes on their final vision tests.
For all 4 metrics, patients who best adhered to their scheduled visits had better visual outcomes. In fact, each missed visit was associated with an average visual acuity letter score decline of 0.7. Compared to those who attended all of their visits, those who averaged between 36 to 60 days between visits lost 6.1 letters, and those who went more than 60 days between visits lost 12.5 letters.
Research and industry news in retina.
BY JERRY HELZNER, CONTRIBUTING EDITOR
Quidel Gets FDA OK for COVID-19 Diagnostic
■ Quidel Corporation, a provider of diagnostic tests including InflammaDry and QuickVue for ophthalmology, has received Emergency Use Authorization (EUA) from the FDA to market its Lyra SARS-CoV-2 Assay, a real-time test for the qualitative detection of nucleic acid from SARS-CoV-2 in nasopharyngeal or oropharyngeal swab specimens from patients suspected of COVID-19 by their health care provider. The Lyra product line offers polymerase chain reaction (PCR) reagent kits for use by molecular diagnostic laboratories with existing molecular testing infrastructure. These reagents include unique features that provide for simple transport and storage, improved workflow, shorter time to result, and other benefits that favorably affect diagnostic test outcome.
Testing is limited to laboratories certified to perform high-complexity tests. EUAs allow for the early availability of important diagnostic tools when there are no adequate, approved and available alternatives.
“Emergency Use Authorization for our Lyra SARS-CoV-2 Assay allows Quidel to join the global fight against the COVID-19 outbreak by providing health care workers in highly complex laboratories with a fast, accurate tool to diagnose patients infected with the novel coronavirus. The feature benefits of the test system and the Lyra product will contribute substantially to our country’s efforts to fight this pandemic,” said Douglas Bryant, president and CEO of Quidel.
ASRS Voices Concern About Beovu Adverse Events
■ Novartis has begun an external review into the safety of its recently approved wet AMD drug Beovu after the American Society of Retinal Specialists (ASRS) raised concerns. Since the FDA approved Beovu last fall, the ASRS has received reports of 14 cases of vasculitis, of which 11 were designated occlusive retinal vasculitis — a more serious inflammatory eye condition. This is out of approximately 46,000 injections of Beovu following the approval of the anti-VEGF drug. Novartis said it was aware of the reports and stands behind the safety and efficacy of Beovu.
“In addition to our own internal assessment, we have engaged an external safety review committee to further evaluate these post-marketing cases. We will continue to share details as they become available,” the company said in a news release. Novartis said its clinical development and pharmacovigilance teams are working with health care professionals to quickly obtain and evaluate all available information in order to classify the events and identify potential risk factors.
CRISPR Used in Groundbreaking LCA10 Trial
■ Allergan plc and Editas Medicine have begun treatment of the first patient in the BRILLIANCE clinical trial of AGN-151587 (EDIT-101) at Oregon Health & Science University Casey Eye Institute, a world-recognized academic eye center. The trial is a phase 1/2 study for the treatment of patients diagnosed with LCA10 and is the world’s first human study of an in vivo CRISPR genome-editing medicine. The trial, consisting of a single subretinal injection to deliver the gene editing machinery directly to photoreceptor cells, will assess the safety, tolerability, and efficacy of AGN-151587 in approximately 18 patients with LCA10.
“This dosing is a truly historic event — for science, for medicine, and most importantly for people living with this eye disease,” said Cynthia Collins, president and CEO of Editas Medicine in a news release. “The first patient dosed in the BRILLIANCE clinical trial marks a significant milestone toward delivering on the promise and potential of CRISPR medicines to durably treat devastating diseases such as LCA10.”
Jim Mazzo Retires From Zeiss Leadership Post
■ Effective May 1, Jim Mazzo will retire from his position as president of ophthalmic devices and head of the ophthalmic devices strategic business unit for Zeiss. With more than 40 years in the ophthalmic industry, Mazzo led Zeiss Global Ophthalmic Devices to the number 2 industry leader in ophthalmology by creating a strong customer-focused organization within his 3 years with Zeiss, according to the company.
“I look forward to continuing my support for Zeiss as an advisor and my involvement in the ophthalmic community,” said Mazzo.
Dr. Euan Thomson will succeed Mazzo. Dr. Thomson currently holds the position of Head of the Digital Business Unit for Zeiss and will continue to guide digital activities. Andrew Chang, head of sales for ophthalmic devices at Zeiss, will be appointed as president of Carl Zeiss Meditec, Inc. He will continue to lead the global ophthalmic sales organizations including US sales and service.
Fellows Forum Marks 20th Year
■ Seventy second-year vitreoretinal fellows from throughout North America recently attended the 20th annual Retina Fellows Forum in Chicago for a weekend of interactive education and socializing. Barry Kuppermann, MD, PhD, delivered the distinguished guest lecture, “Life and Career as a Journey Rather Than a Destination.”
The fellows enjoyed a weekend of energetic panel discussions covering a broad spectrum of medical and surgical retina issues. New this year was a fellows’ case presentation session moderated by Aleksandra Rachitskaya, MD.
The academic portion of the meeting concluded with the “Real World” panel discussion, during which the faculty and fellows discussed job selection, contract negotiation, practice building strategies, staff management issues, and work–life balance.
The faculty of 9 leading retina specialists was headed by course director Tarek Hassan, MD, and course codirectors Carl Awh, MD, and David Chow, MD. The meeting concluded with the hotly contested Retina Fellows Forum bowling tournament, this year won by Dr. Hassan’s team.
When Sham Is Not Really Sham
■ GenSight Biologics learned a hard lesson when it failed to meet its primary endpoint in 2 phase 3 gene therapy trials for Leber Hereditary Optic Neuropathy (LHON). The trials were based on replacement of the mutated ND4 gene with a replacement ND4 protein (GSO10) and consisted of a treated eye and a sham injection in the fellow eye. LHON is a rare inherited retinal disease characterized by degeneration of retinal ganglion cells. It usually strikes males from age 15 to 35 years, culminating in quick and profound vision loss that results in blindness.
The primary endpoints for GenSight’s 2 phase 3 clinical trials (REVERSE and RESCUE) were vision gains in the treated eye compared to any vision gains in the sham-treated eye. When the treated eyes had vision gains only marginally better than the sham-treated eyes, GenSight was at first surprised but soon discovered that the sham-treated fellow eye was actually gaining a benefit from the gene therapy.
Now, according to Chief Medical Officer Magali Taiel, MD, who joined GenSight after the phase 3 trials were designed, the company has begun the REFLECT trial, in which patients are being treated bilaterally. This trial, if successful, should satisfy the requirements for FDA approval.
“We believe we are on the right track now,” Dr. Taiel told Retinal Physician.
Some in CATT Study Kept Vision Gains Without Treatment
■ Researchers led by Drew Scoles, MD, PhD, of the University of Pennsylvania, set out to determine whether some participants in the 2-year CATT study of patients with wet AMD were able to maintain vision gains despite not being treated for the next 3 years. Their findings were reported in a recent issue of JAMA Ophthalmology.
Among 625 eyes with wet AMD at baseline and a visual acuity measurement at year 5, 40 maintained good vision with no further anti-VEGF treatment. These 40 participants, compared with the much larger group, had a lower mean age of 74.7 years vs 77.7 years and included 26 women (65%). Baseline characteristics were similar between eyes in the better vision group and other groups, except for better visual acuity letter score in the study eye and the fellow eye, as well as the presence of blocked fluorescence seen more often in participants in the better vision group than in the other group (27.5% vs 13.8%). Eyes in the better vision group with as-needed treatment received fewer mean injections in year 1 and year 2 than eyes in the other as-needed group. Mean visual acuity letter score at 5 years was 79.0 (Snellen 20/25) in the better vision group and 57.5 (Snellen 20/80) in the other group. The researchers said their findings suggested that a small proportion of eyes with wet AMD can retain good visual acuity with no treatment for at least 3 years after the initial 2 years of treatment.
Large Study of Anti-VEGF Outcomes Cites Injection Frequency
■ A study of 37,021 eyes that initiated anti-VEGF therapy for wet AMD between October 2009 and November 2016 found a strong correlation between higher numbers of injections and improved BCVA and CRT. In a study led by Szilard Kiss, MD of Weill Cornell Medical Center, mean change from baseline in VA at 12 months tended to increase linearly with the number of anti-VEGF injections administered over the first 12 months: +1.79 vs -0.95 approximate ETDRS letters for eyes receiving ≥7 vs <7 injections. Similarly, the magnitude of the reduction from baseline in CRT at 12 months tended to increase linearly with an increasing number of anti-VEGF injections.
Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, respectively, 19.3%, 15.8%, and 15.5% of eyes showed >10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes showed >10-letter loss. Results of the study appeared in the journal Ophthalmology. RP