Volume 16, Number 8June 2020THE LATEST PUBLISHED RESEARCH WELCOME to Review of Ophthalmology's Retina Online newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease. INSIDE THIS ISSUE:
Intravitreal Anti-VEGF Cost Savings with Increased Bevacizumab Reimbursement & Utilization Scientists modeled Medicare Part B and patient savings associated with increased bevacizumab payment and utilization for intravitreal anti-vascular endothelial growth factor therapy, as part of a cost analysis. “Trinity” Regimen with Aflibercept for Treatment-naïve nAMD: 2-Year OutcomesResearchers evaluated the advantages of the so-called trinity regimen for treatment-naïve neovascular age-related macular degeneration, which involves using three treatment methods— pro re nata, treat-and-extend (TAE) and fixed regimen—that are changed depending on recurrence frequency. Thirty-one treatment–naïve nAMD eyes were treated using the novel regimen with an intravitreal aflibercept injection and evaluated after 24 months. After the initial treatment, PRN or TAE (for four or eight weeks) were selected per the recurrence interval. When the recurrence interval became constant, the treatment regimen was transitioned from a TAE to a fixed regimen. When the recurrence frequency became irregular, it was changed to TAE. Here were some of the findings:
Researchers concluded that the trinity regimen delivered the benefits of the PRN, TAE and fixed regimens while minimizing injections during the early treatment phase without visual loss. SOURCE: Wakuta M, Nomi M, Ogata T, et al. A Trinity regimen with aflibercept for treatment-naïve neovascular age-related macular degeneration: 2-year outcomes. Graefes Arch Clin Exp Ophthalmol 2020; May 21. [Epub ahead of print]. U.K. Researchers Test Automated ScreeningResearchers in London compared the performance of an Automated retinal image analysis software, EyeArt (Eyenuk, Woodland Hills, Calif.) to human grading. The researchers performed imaging with mydriasis (two-field protocol) with the EIDON platform (CenterVue, Padua, Italy) and standard National Health Service Diabetic Eye Screening Programme fundus cameras. Human grading was carried out according to NDESP protocol. Images were processed by the EyeArt V.2.1.0 system. The reference standard for analysis was the human grade of standard NDESP images. Association of CRP Levels with ARMS2 and CFH Variants in AMDResearchers assessed whether plasma high-sensitivity C-reactive protein (hs-CRP) levels were associated with exudative age-related macular degeneration as well as variants of ARMS2 A69S and CFH I62V in patients with exudative AMD. They conducted a case-control study comparing CRP with exudative AMD including individuals with polypoidal choroidal vasculopathy, typical AMD, retinal angiomatous proliferation and CRP. Researchers measured plasma CRP from peripheral blood using latex nepherometry for all participants. They performed genotyping of ARMS2 A69S and CFH I62V for all patients with exudative AMD using TaqMan technology. Here are some of the findings:
Researchers found that plasma hs-CRP was elevated independent of variants of ARMS2 A69S and CFH I62V in patients with exudative AMD. Source: Shijo T, Sakurada Y, Fukuda Y, et al. Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration. Ophthalmology Retina 2020; June 7. [Epub ahead of print]. Long-term Intravitreal Anti-VEGF Injections for Wet AMDResearchers determined the long-term visual outcomes and intravitreal injection burden of individuals with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections, as part of a retrospective, cohort study. Participants included individuals with exudative AMD treated with intravitreal anti-VEGF injections with annual office visits for at least seven years. Researchers measured Snellen visual acuity at baseline and then annually until the last year of follow-up. The number of injections was recorded on an annual basis during each year of follow-up. Main outcome measure included the change in the frequency of injections over time along with the change in visual acuity each year from the baseline visit up through seven years. During this time, a total of 533 eyes of 429 patients were treated for wet AMD. Of these eyes, 391 eyes (73 percent) met the inclusion criteria of annual office visits. Here are some of the findings: In a real-world setting, researchers found that eyes that maintained consistent, long-term follow-up received a significant number of intravitreal injections per year—significantly more than eyes with inconsistent follow up. They also reported that eyes with 20/40 or better vision at the study’s conclusion received more injections per year than eyes with worse than 20/40 vision. Source: Kung FF, Starr MR, Bui YT, et al. Long term follow-up of patients with exudative age-related macular degeneration treated with intravitreal anti-vascular endothelial growth factor injections. Ophthalmology Retina 2020; May 18. [Epub ahead of print]. Changes in Choroidal Thickness from CNVScientists evaluated topographic changes in choroidal thickness during development of choroidal neovascularization in treatment-naive age-related macular degeneration and tested the value of such changes as a predictive tool of CNV development. This retrospective cohort included 86 eyes that developed CNV from intermediate AMD, 43 eyes with intermediate AMD and 36 eyes without AMD. Patients with intermediate AMD underwent spectral-domain optical coherence tomography using enhanced depth imaging mode every six months until CNV was detected. Choroidal neovascularization was localized to one of the subfields of the Early Treatment of Diabetic Retinopathy Study grids on fluorescein angiography. The average choroidal thickness of each subfield was calculated. Here were some of the findings:
Scientists found that choroidal neovascularization development accompanied choroidal thickening of the corresponding subfield. They added that regular measurement of choroidal thickness may assist in prediction of CNV. SOURCE: Park JY, Kang M-J, Kim BGi, et al. Topographic changes in choroidal thickness in age-related macular degeneration during the development of active choroidal neovascularization. Ophthalmology Retina 2020; May 18. [Epub ahead of print]. Deep Learning Automated Detection of Reticular Pseudodrusen from Fundus Autofluorescence Images or Color Fundus Photographs in AREDS2Investigators developed and evaluated deep learning models for detecting reticular pseudodrusen (RPD) using fundus autofluorescence (FAF) images or color fundus photographs (CFP), in the context of age-related macular degeneration. They applied deep learning models to the Age-Related Eye Disease Study 2 (AREDS2) dataset, and included 11,535 FAF and 11,535 CFP images from longitudinal follow-up of 2,450 participants in the AREDS2 dataset. They derived Gold standard labels from reading center grading of the FAF images and transferred them to the corresponding CFP images. They also trained a deep learning model to detect RPD in eyes with intermediate to late AMD, using FAF images (FAF model). Using labels transferred from FAF to corresponding CFP images, they trained a second deep learning model to detect RPD from CFP (CFP model). Investigators compared model performance with that of four ophthalmologists using a random subset from the full test set. Main outcome measures included area under the curve; kappa; accuracy; and F1-score. Here were some of the findings:
Investigators found that deep learning-enabled automated detection of RPD presence from FAF images achieved a high level of accuracy—equal or superior to that of ophthalmologists. They also reported that automated RPD detection using CFP achieved a lower accuracy that still surpassed that of ophthalmologists. As such, the investigators determined that deep learning models can assist, and even augment, the detection of this AMD-associated lesion. SOURCE: Keenan TD, Chen Q, Peng Y, et al. Deep learning automated detection of reticular pseudodrusen from fundus autofluorescence images or color fundus photographs in AREDS2. Ophthalmology 2020; May 20. [Epub ahead of print]. Haller’s Vessels Patterns in Non-nAMDResearchers assessed the optical coherence tomography en face reconstruction of the choroid in different phenotypes of non-neovascular age-related macular degeneration to identify the relative distribution of the vascular patterns of the Haller’s layer in each AMD category.
Qualitative analysis of the en face images provided by Cirrus HD-OCT 5000 (Carl Zeiss Meditech) was performed, identifying five arrangements of Haller’s vessels: temporal herringbone, branched from below, laterally diagonal, double arcuate and reticular. Choroidal thickness was measured from structural OCT. Healthy age-matched subjects were included as a control group.
Researchers wrote that different phenotypes of non-neovascular AMD present a specific distribution of vascular arrangement on en face OCT. They reported that the temporal herringbone and the reticular pattern (the ones more associated in a physiological setting) disclosed a thicker choroid compared with the arrangements more represented in non-neovascular AMD-correlated phenotypes. SOURCE: Sacconi R, Cicinelli MV, Borrelli E, et al. Haller’s vessels patterns in non-neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2020; June 13. [Epub ahead of print].
Findings from The EYE-RISK ConsortiumAs part of a case-control association analysis, researchers aimed to identify metabolites associated with age-related macular degeneration. In addition, they looked at the effect of AMD-associated genetic variants on metabolite levels, and investigated associations between identified metabolites and activity of the complement system—one of the main AMD-associated disease pathways.
Researchers found that lipoprotein levels were associated with AMD-associated genetic variants, with strong associations between most of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. They suggested this finding may indicate biological interactions between the main AMD disease pathways and that multiple pathways may need to be targeted simultaneously for successful treatment of AMD. Angiographic Evidence that Intraretinal Microvascular Abnormalities Can Evolve into NeovascularizationScientists wrote that the hallmark of proliferative diabetic retinopathy is retinal neovascularization. Tortuous intraretinal vascular segments known as intraretinal microvascular abnormalities (IRMAs) are a known risk factor for NV, but whether IRMA represents a biomarker or a vascular precursor lesion to NV hasn’t been demonstrated. The purpose of this study was to document that IRMA may directly evolve into NV. In a retrospective analysis of a prospective, observational case series, participants included individuals with treatment-naïve PDR. Patients were imaged longitudinally with fluorescein angiography (FA) and swept-source OCT angiography (SS-OCTA) before and after panretinal photocoagulation (PRP). Main outcome measures included presence and co-localization of IRMA and NV on serial FA and SS-OCTA. Here were some of the findngs:
Scientists reported that diabetic retinal NV can develop from IRMA. They added that early identification of IRMAs may be an accurate means of predicting progression to PDR, and frequent monitoring of IRMAs with SS-OCTA may facilitate early diagnosis of PDR. SOURCE: Russell JF, Shi Y, Scott NL, et al. Longitudinal angiographic evidence that intraretinal microvascular abnormalities can evolve into neovascularization. Ophthalmol Retina 2020; June 13. [Epub ahead of print]. Fluctuations in Macular Thickness in RVO Treated with Anti-VEGF AgentsScientists evaluated macular thickness fluctuations in individuals with retinal vein occlusions treated with anti-vascular endothelial growth factor agents, and assessed whether patients with larger fluctuations had poorer visual outcomes, as part of a retrospective cohort study. Participants included treatment-naïve patients with RVO followed over 12 months of treatment. From optical coherence tomography technology, scientists collected central subfield thickness (CST), cube volume (CV) and cube average thickness (CAT) at baseline, three, six, nine and 12 months. They calculated standard deviations across 12 months. And they performed mixed effects regression to examine the relationship between macular thickness SD and 12-month visual acuity. In addition, they performed standard multiple regression to identify predictors of macular thickness SD. Main outcome measures included SD across 12 months for CST, CV and CAT; and VA at 12 months. Scientists evaluated 134 eyes, including 71 branch RVO and 63 central RVO. Here were some of the findings:
Scientists reported that larger macular thickness fluctuations were associated with poorer visual outcomes in patients with RVO treated with anti-VEGF agents. They added that macular thickness fluctuations in addition to absolute macular thickness may be important prognostic biomarkers in these patients. SOURCE: Chen AX, Greenlee TE, Conti TF, et al. Fluctuations in macular thickness in patients with retinal vein occlusion treated with anti-vascular endothelial growth factor agents. Ophthalmology Retina 2020; May 28. [Epub ahead of print]. FDA APPROVES UPDATED NOVARTIS BEOVU LABEL Novartis announced the FDA approved a label update for Beovu (brolucizumab) to include additional safety information regarding retinal vasculitis and retinal vascular occlusion. This approval follows Novartis’ announcement that it would pursue worldwide label updates after a review and further characterization of rare post-marketing Beovu safety events. The company says this is one of many efforts it’s taking to help physicians to make informed decisions on the use of Beovu, including the establishment of an internal team collaborating with global experts to examine root causes, risk factors, mitigation and potential treatment protocols for the adverse events in question. Read more.
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SAMSUNG BIOEPIS ANNOUNCES INTERIM RESULTS FROM PHASE III PROPOSED RANIBIZUMAB BIOSIMILAR TRIAL Samsung Bioepis announced the primary endpoints were met in its randomized, double-masked Phase III trial comparing the efficacy, safety and immunogenicity of SB11, a ranibizumab biosimilar candidate in patients with neovascular age-related macular degeneration. The company says the study achieved its primary endpoints—change from baseline in best-corrected visual activity at week eight and central subfield thickness at week four. Read more. IVERIC ANNOUNCES ZIMURA 18-MONTH DATA Iveric Bio announced 18-month results from the company's first Phase III clinical trial (OPH2003) for Zimura (avacincaptad pegol), a novel complement C5 inhibitor, for the treatment of geographic atrophy secondary to age-related macular degeneration. The company says that the 18-month data supports the previously announced 12-month data from this trial, at which timepoint Zimura met the pre-specified primary efficacy endpoint with statistical significance. Read more. LINEAGE ANNOUNCES RESTORATION OF RETINAL TISSUE IN OPREGEN PHASE I/IIA STUDY Lineage Cell Therapeutics announced that restoration of retinal tissue was observed in a patient enrolled in a Phase I/IIa study of its lead product candidate, OpRegen, a retinal pigment epithelium cell transplant therapy in development for the treatment of dry age-related macular degeneration. Lineage plans to host a live call on June 8 to discuss the findings. Read more. FDA GRANTS 510(K) CLEARANCE FOR VASOPTIC'S RETINAL IMAGING DEVICE Vasoptic Medical received 510(k) clearance from the FDA to market its XyCAM RI—a noninvasive retinal imager designed to capture and provide dynamic blood flow information for clinical use. The company says the XyCAM RI enables ophthalmologists to rapidly assess the vascular status of the retina. Read more.SOURCE: Vasoptic Medical, June 2020 Scientists Rescue Mini Retinas from Eye Disease Via New Gene Therapy Approach Scientists have known for some time that mutations in the gene RP2 are associated with retinitis pigmentosa. However, no therapies exist to treat people living with a number of RP diseases. Researchers from Trinity College Dublin and University College London teamed up with the goal of treating RP. Their results are published in Stem Cell Reports. The team used a modified common virus to deliver a normal, functioning copy of the RP2 gene into “mini retinas,” which had been engineered from stem cells and which contained the defective version of the gene. The “mini retinas,” developed in University College London, simulated the RP2 disease in patients successfully took up the functioning RP2 gene following the viral delivery and produced the essential protein associated with it. The treated mini retinas showed significant improvement, the researchers say. Read more.SOURCE: Trinity College Dublin, June 2020 GRAYBUG APPOINTS DR. ZAMIRI AS CHIEF MEDICAL OFFICER Graybug Vision appointed Parisa Zamiri, MD, PhD, as the company’s chief medical officer, effective June 1, 2020. Graybug says Dr. Zamiri is a physician-scientist with “deep expertise” in pharmaceuticals. Dr. Zamiri joins Graybug Vision from Novartis, where she most recently held the position of vice president, global head of clinical development and therapeutic area head for ophthalmology. Read more.SOURCE: Graybug Vision, May 2020 FDA REVOKES EMERGENCY USE AUTHORIZATION FOR EMERGENCY USE OF ORAL FORMULATIONS CQ & HCQ FOR COVID-19 The FDA revoked Emergency Use Authorization (EUA) for emergency use of oral formulations of chloroquine phosphate and hydroxychloroquine sulfate for certain patients with COVID-19 based on new information and clinical results concluding that this drug may not be effective to treat COVID-19 and that the drug’s potential benefits for such use do not outweigh its known and potential risks. In a letter dated June 15, 2020, to Gary L. Disbrow, PhD, deputy assistant secretary, at the Biomedical Advanced Research and Development Authority at the U.S. Department of Health and Human Services, Denise M. Hinton, chief scientist of the FDA, said the FDA had determined that the criteria under section 564(c) of the Act for issuance of the EUA were no longer met. Read more.SOURCE: FDA, June 2020 Review of Ophthalmology's® Retina Online is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 11 Campus Boulevard, Newtown Square, PA 19073. |