Volume 18, Number 4
THE 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:
Aflibercept for Retinal Nonperfusion in PDR
Investigators in Regeneron’s RECOVERY study note that retinal nonperfusion (RNP) is an important biomarker for diabetic retinopathy. Data suggests that consistent anti-VEGF pharmacotherapy can slow RNP development, the researchers add. RECOVERY evaluated the impact of aflibercept (Eylea, Regeneron) on RNP among eyes with proliferative DR.
This prospective randomized clinical trial with treatment crossover in the second year looked at eyes with PDR and RNP.
At baseline, subjects were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2-mg aflibercept. At the beginning of year two, the treatment arms were crossed over so monthly dosed subjects subsequently received quarterly dosing while quarterly dosed subjects subsequently received monthly dosing.
Main outcome measures included change in total RNP area through year two. Secondary outcomes included DR severity scale (DRSS) scores, best-corrected visual acuity, central subfield thickness, additional measures of RNP including ischemic index (ISI) and adverse events incidence. Means and 95 percent confidence intervals were calculated.
Here are some of the findings:
Investigators wrote that through year two of RECOVERY, both treatment arms experienced significant increases in retinal nonperfusion. Despite expansion of RNP area in nearly all subjects, 82 percent demonstrated an improvement in DRSS levels from baseline with no subject experiencing worsening in DRSS.
SOURCE: Wykoff CC, Nittala MG, Boone CV, et al; RECOVERY Study Group. Final outcomes from the randomized RECOVERY trial of alfibercept for retinal nonperfusion in proliferative diabetic retinopathy. Ophthalmol Retina 2022; Mar 4. [Epub ahead of print].
Vitrectomy for Diabetic Complications: A Pooled Analysis
Investigators reported updated clinical outcomes in subjects undergoing pars plana vitrectomy using modern techniques and equipment for the treatment of proliferative diabetic retinopathy-related complications.
The pooled analysis included five randomized clinical trials conducted at the same institution, and study and control subjects from the trials.
A total of 943 subjects prospectively underwent small-gauge PPV with anti-vascular endothelial growth factor pretreatment for PDR-related complications and completed six-month follow up.
Here are some of the findings:
Investigators wrote that clinical outcomes in patients undergoing PPV for PDR-related complications compared favorably to those reported prior to small-gauge PPV and anti-VEGF pretreatment.
SOURCE: Rush RB, Rush SW, Reinauer RM, et al. Vitrectomy for diabetic complications: A pooled analysis of randomized controlled trials utilizing modern techniques and equipment. Retina 2022; Mar 8. [Epub ahead of print].
Prevalence & Treatment of DME and Vision-threatening DR Among Medicare Part B Beneficiaries
Researchers wrote that, while diabetes prevalence among U.S. adults has increased in recent decades, few studies document trends in diabetes-related eye disease.
They examined 10-year trends (2009 to 2018) in annual prevalence of Medicare beneficiaries with diabetes with a diagnosis of diabetic macular edema or vision-threatening diabetic retinopathy (VTDR), and looked at trends in treatment.
In this cross-sectional study using Centers for Medicare & Medicaid Services research identifiable files, data for patients 65 years and older were analyzed from claims. Beneficiaries were continuously enrolled in Medicare Part B fee-for-service insurance for the calendar year and had a diagnosis of diabetes on one or more inpatient claims, or two or more outpatient claims during the calendar year or one-year period.
Using diagnosis and procedure codes, annual prevalence was determined for beneficiaries with one or more claims for:
Racial and ethnic disparities in diagnoses and treatment were presented for 2018.
In 2018, 6,960,823 beneficiaries (27.4 percent) had diabetes. Half were ages 65 to 74 years (49.7 percent), half (52.7 percent) were women and 75.7 percent were non-Hispanic White. Here are some of the findings:
Researchers reported that, from 2009 to 2018, prevalence of DME or VTDR increased among Medicare Part B FFS beneficiaries in tandem with an increase in anti-VEGF treatment, and decline in laser photocoagulation and vitrectomy.
SOURCE: Lundeen EA, Andes LJ, Rein DB, et al. Trends in prevalence and treatment of diabetic macular edema and vision-threatening diabetic retinopathy among Medicare Part B fee-for-service beneficiaries. JAMA Ophthalmol 2022; Mar 3. [Epub ahead of print].
OCT Reveals Rod Photoreceptor Degeneration in Early DR
This study evaluated the feasibility of optical coherence tomography detection of photoreceptor abnormality and verified whether the photoreceptor abnormality was predominantly in rods in early diabetic retinopathy.
Investigators acquired OCT images from normal eyes, diabetic eyes with no diabetic retinopathy (NoDR) and those with mild NPDR. Investigators determined quantitative features, including thickness measurements quantifying band distances and reflectance intensity features among the external limiting membrane (ELM), inner segment ellipsoid (ISe), interdigitation zone (IZ) and retinal pigment epithelium. Comparative OCT analysis of the central fovea, parafovea and perifovea were implemented to verify the photoreceptor abnormality was predominately in rods in early DR.
Thickness abnormalities between the ISe and IZ showed a decreasing trend among cohorts. Investigators observed reflectance abnormalities of the ELM, IZ and ISe between healthy, NoDR, and mild NPDR eyes. The normalized ISe/RPE intensity ratio revealed a significant decreasing trend in the perifovea, but no detectable difference in the central fovea.
Quantitative OCT analysis consistently revealed outer retina, i.e., photoreceptor, changes in diabetic patients with NoDR and mild NPDR. Investigators wrote that comparative analysis of the central fovea, parafovea and perifovea confirmed that the photoreceptor abnormality was predominantly in rods in early DR.
SOURCE: Le D, Son T, Lim JI, Yao X. Quantitative optical coherence tomography reveals rod photoreceptor degeneration in early diabetic retinopathy. Retina 2022; Mar 11. [Epub ahead of print].
MNV Lesion Type and Vision Outcomes in AMD: Post Hoc Analysis of HARBOR
Researchers characterized the relationships between Consensus on Neovascular Age-Related Macular Degeneration Nomenclature (CONAN) Study Group classifications of macular neovascularization and visual responses to ranibizumab in patients with neovascular age-related macular degeneration.
This post hoc analysis of the Phase III HARBOR trial of ranibizumab in nAMD included analyses of:
Here are some of the findings:
Researchers found that differences in BCVA outcomes between CONAN lesion type subgroups supported the use of an anatomic classification system to characterize MNV and prognosticate visual responses to anti-vascular endothelial growth factor therapy for nAMD.
SOURCE: Freund KB, Staurenghi G, Jung JJ, et al. Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: Post hoc analysis of HARBOR. Graefes Arch Clin Exp Ophthalmol 2022; Mar 3. [Epub ahead of print].
Brolucizumab for Pre-treated Patients with CNV & Signs of Tachyphylaxis to Aflibercept and Bevacizumab
Researchers wrote that treatment of choroidal neovascularization due to age-related macular degeneration is challenging since an increasing number of patients show reduced morphological response to conventional treatment with intravitreal injections. This study tested the hypothesis that the newly introduced anti-VEGF antibody brolucizumab shows promising results in pre-treated patients, as well as in cases of tachyphylaxis to aflibercept or bevacizumab.
Thirty-six eyes of 34 patients with a history of at least 10 anti-VEGF injections as well as persistent retinal fluid following the past five monthly injections with aflibercept and bevacizumab, prior to first treatment with brolucizumab, were included. Morphological and functional treatment responses were compared before and after switching to brolucizumab.
Here are some of the findings:
Researchers reported that brolucizumab was effective not only in treatment-naïve patients, as shown in the HAWK and Harrier trials, but also in pre-treated patients. They added that the data also suggested that brolucizumab was effective in patients with signs of tachyphylaxis to other anti-VEGF agents.
SOURCE: Boltz A, Radunsky K, Weingessel B, et al. Brolucizumab for pre-treated patients with choroidal neovascularization and signs of tachyphylaxis to aflibercept and bevacizumab. Graefes Arch Clin Exp Ophthalmol 2022; Mar 29. [Epub ahead of print].
Fundus Autofluorescence and En Face OCT Measurements of GA
Investigators evaluated the correlation between fundus autofluorescence and en face spectral-domain optical coherence tomography measurements of geographic atrophy associated with age-related macular degeneration, as part of a retrospective, cross-sectional study.
A total of 270 eyes from 172 subjects with GA associated with AMD were included. Subjects with atrophic AMD with both FAF (Heidelberg HRA + Spectralis) and dense volume (128 B-scans over 6 x 6 mm) SD-OCT (Cirrus OCT) imaging were included in this retrospective analysis.
The borders of all areas of definite decreased autofluorescence (DDAF) corresponding to GA were manually outlined on FAF images by certified graders at the Doheny Image Reading Center (DIRC) using validated planimetric grading tools. In addition, GA was delineated automatically from en face OCT (at the level of the choroid) using instrument software (Cirrus v.6.2), and segmentation errors were manually corrected prior to computation of the GA area. FAF- and SD-OCT-derived measurements were correlated. Main outcome measures included correlation between SD-OCT and FAF measurements of GA area.
Here are some of the findings:
Investigators reported that SD-OCT-derived measurements of GA correlated well with areas of definite decreased autofluorescence obtained from fundus autofluorescence images. As such, they wrote that manual correction of SD-OCT segmentation errors can further improve this correlation.
SOURCE: Velaga SB, Nittala MG, Hariri A, et al. Correlation between fundus autofluorescence and en face optical coherence tomography measurements of geographic atrophy. Ophthalmol Retina 2022; Mar 22. [Epub ahead of print].
Laser & Anti-VEGF Treatment for Drusenoid PED in AMD
Researchers investigated the 24-month primary endpoint outcomes of drusenoid pigment epithelial detachment after laser and intravitreal anti-VEGF treatment following a 12-month interim safety analysis.
Twenty-one patients with treatment-naïve bilateral intermediate AMD with dPED and visual acuity ≤83 letters (Snellen 20/23) were enrolled. The subject eye received low-energy Pascal laser (532 nm) treatment, and the fellow eye was used as the control. Intravitreal injections were administered at three-month intervals from baseline to 12 months. Treatment outcomes, safety and development of advanced AMD lesions were analyzed.
Here are some of the findings:
Researchers wrote that laser and anti-VEGF treatment may be a potential treatment option for intermediate AMD with dPED. However, they added, the relatively high rate of secondary iRORA and cRORA development suggested that long-term follow-up is necessary to clarify the safety and efficacy of the treatment.
SOURCE: Kim MS, Ryoo NK, Park KH. Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration: 24-month outcomes. Graefes Arch Clin Exp Ophthalmol 2022; Mar 21. [Epub ahead of print].
Plasma Omega-3 Fatty Acids & Early AMD
Researchers examined the association between omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and age-related macular degeneration in the Multi-ethnic Study of Atherosclerosis (MESA) cohort.
MESA was a multicenter, prospective cohort study studying risk factors for cardiovascular disease in four ethnic groups. A total of 6,814 participants of White, African-American, Hispanic/Latino and Chinese descent, ages 45 to 84 years, were recruited. Those found to have cardiovascular disease were excluded.
The study population included all MESA participants with baseline PUFA measurements and retinal photography at exam five (n=3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log-link) determined associations between PUFA levels and AMD.
Researchers found a significant association between increasing DHA levels and increasing DHA + EPA levels with reduced risk for early AMD (n=214 participants with early AMD; n=99 [46.3 percent] were non-White). EPA levels alone weren’t significantly associated with AMD.
Researchers found that increasing levels of DHA were associated with reduced risk for early AMD in a multi-ethnic cohort. They wrote that the study represented the first racially diverse study demonstrating an association between omega-3 PUFAs and AMD risk.
SOURCE: Karger AB, Guan W, Nomura SO, et al. Association of plasma ω-3 fatty acids with early age-related macular degeneration in the Multi-Ethnic Study of Atherosclerosis (MESA). Retina 2022; Mar 9. [Epub ahead of print].
Association of Choroidal Thickness with RRD Repair
Investigators compared the choroidal thickness before and after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment repair, as part of a retrospective case series of RRD patients presenting between January 2015 and September 2020.
Subfoveal choroidal thickness (SFCT) and anatomical success were measured in post-PPV and fellow eyes at presentation, and at three and six months after PPV for RRD repair.
A total of 93 patients (59 percent male) with a mean age of 61.8 ±15.2 years were included. Here are some of the findings:
Investigators reported that eyes with rhegmatogenous retinal detachments demonstrated thinning in the subfoveal choroidal thickness after vitrectomy surgery. Given that eyes with recurrent retinal detachment presented with thicker choroids at baseline, researchers suggest that thicker SFCT at presentation may play a role in retinal re-detachment.
SOURCE: Trivizki O, Eremenko R, Au A, et al. The association of choroidal thickness with rhegmatogenous retinal detachment repair. Retina 2022; Feb 25. [Epub ahead of print].
B+L and Clearside Launch Xipere
Bausch + Lomb and Clearside Biomedical announced the U.S. commercial launch of Xipere (triamcinolone acetonide injectable suspension), the first and only therapy approved by the FDA for suprachoroidal use for the treatment of macular edema associated with uveitis. Read more.
Apellis Reports 18-month Pegcetacoplan Findings
Apellis Pharmaceuticals announced longer-term data from the Phase III DERBY and OAKS studies. The company says the data shows that intravitreal pegcetacoplan, an investigational, targeted C3 therapy, continued to reduce geographic atrophy lesion growth and demonstrate a “favorable” safety profile at month 18 for the treatment of GA secondary to age-related macular degeneration. The data will be included in the New Drug Application that the company plans to submit to the FDA in the second quarter of 2022, Apellis says. Read more.
Preliminary Analysis of LumiThera LIGHTSITE III Study
LumiThera announced findings from its LIGHTSITE III multicenter clinical trial in non-neovascular age-related macular degeneration subjects treated with the Valeda Light Delivery System. Statistically significant improvement was reported in BCVA at 13 months in the photobiomodulation (PBM)-treatment vs. sham-treatment group (p<0.003). A sustained mean increase in ETDRS letter score of 5.5 letters from baseline was seen at 13 months in PBM-treated subjects’ BCVA (p<0.0001). Read more.
Genentech Study Looks at Underrepresented Patient Populations
Genentech launched the Elevatum trial of Vabysmo in specific patient populations with diabetic macular edema. The company says that Black, Hispanic, Latin-American and Indigenous people are disproportionately affected by diabetes, and are at higher risk of developing diabetic macular edema yet are underrepresented in clinical trials, so Genentech designed this Phase IV, multicenter, open-label, single-arm trial to study Vabysmo in these populations. Read more.
Outlook Submits BLA to FDA for ONS-5010
SOURCE: Outlook Therapeutics, March 2022
Lineage’s OpRegen Phase I/IIa Results to Be Reported at ARVO Meeting
Curative Biotechnology & NEI to Study Ocular Metformin in AMD
Curative Biotechnology announced a Cooperative Research and Development Agreement with the National Eye Institute in which the entities will initiate clinical studies to evaluate Curative's proprietary ocular metformin formulation for treatment of intermediate and late-stage age-related macular degeneration disease. Read more.
Akari to Present on AMD and OSD Programs at ARVO Annual Meeting
Akari Therapeutics announced Virginia Calder, professor of ocular inflammation, The Institute of Ophthalmology, UCL and Moorfields Eye Hospital, London, will give an oral and poster presentation at the Association for Research in Vision and Ophthalmology annual meeting, scheduled for May 1 to 4 in Denver, on Akari’s programs using long-acting PAS-nomacopan in age-related macular degeneration and geographic atrophy, and topical nomacopan for ocular surface diseases. Read more.
SOURCE: Akari Therapeutics, March 2022
Ribomic Provides Update on RBM-007 Program in Wet AMD
Ribomic announced results from TEMPURA along with updated data from its TOFU and RAMEN studies with RBM-007, an investigational anti-fibroblast growth factor-2 aptamer, in wet age-related macular degeneration. The company says that the data demonstrated a positive trend in two clinically relevant endpoints, best-corrected visual acuity and central subfield thickness. Read more.
SOURCE: Ribomic, March 2022
Ocuphire Completes Enrollment in ZETA-1
Ocuphire Pharma completed enrollment of 103 diabetic patients with moderately severe to severe, non-proliferative diabetic retinopathy or mild proliferative diabetic retinopathy in ZETA-1, a Phase IIb trial evaluating the efficacy and safety of APX3330 for the treatment of the disease. Read more.
Quest Adds DR Screening in Collaboration with IRIS
Quest Diagnostics announced a collaboration with IRIS (Intelligent Retinal Imaging Systems) to deliver diabetic retinal imaging services through designated Quest patient service centers across the United States. Read more.
First Patient Dosed in Ocugen’s Phase I/II Gene Therapy Trial
Ocugen announced the first patient was dosed in the Phase I/II clinical trial of OCU400, a modifier gene therapy candidate for the treatment of retinitis pigmentosa resulting from mutations in the nuclear receptor subfamily 2 group E member 3 (NR2E3) and Rhodopsin (RHO) genes. Read more.
Cell Fusion Promotes Regenerative Potential of Human Retina
Fusing human retinal cells with adult stem cells could potentially help treat retinal damage and visual impairment, according to findings published in eBioMedicine. A team led by ICREA Research Professor Pia Cosma at the Centre for Genomic Regulation in Barcelona tested whether cell fusion events, which take place in the human retina, could differentiate into cells that turn into neurons, demonstrating the potential for tissue regeneration. The team fused Müller glia with adult stem cells derived from human adipose tissue or bone marrow, and injected the hybrid cells into a growing retinal organoid resembling the human retina. The researchers found the hybrid cells successfully engrafted into the tissue and differentiated into cells that closely resemble ganglion cells. Read more.
Foundation Fighting Blindness Offers Two New Podcasts
Foundation Fighting Blindness released two new Eye on the Cure Podcasts. Episodes 20 features Nancy Holekamp, MD, who discusses new therapies for wet and dry age-related macular degeneration, and emerging treatments for inherited retinal diseases. Episode 21 features jazz singer Katriona Taylor’s journey with Stargardt’s. Listen to the podcasts.
The following companies announced presentations at the at the Association for Research in Vision and Ophthalmology annual meeting being held May 1 to 4 in Denver, and May 11 to 12 virtually.
Review of Ophthalmology's® Retina Online is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 19 Campus Boulevard, Newtown Square, PA 19073.