Review of Ophthalmology Online



Vol. 22, #6  •   Monday, February 8, 2021


In this Issue:



Prediction of VF Progression from OCT Structural Measures

Researchers tested the hypothesis that visual field progression can be predicted from baseline and longitudinal optical coherence tomography structural measures, as part of a prospective cohort study.

A total of 104 eyes (104 patients) with ≥3 years of follow-up and ≥5 VF exams were enrolled. Researchers defined VF progression based on pointwise linear regression on 24-2 VF (≥3 locations with slope ≤-1.0 dB/year and p<0.01). They used elastic net logistic regression (ENR) and machine learning (ML) to predict VF progression with:
• demographics;
• baseline circumpapillary retinal nerve fiber layer and macular ganglion cell/inner plexiform layer (GCIPL) thickness;
• RNFL and GCIPL change rates at central 24 superpixels; and
• three “eccentricities” at 3.4, 5.5 and 6.8 degrees from the fovea and hemimaculas. Areas under the ROC curve were used to compare models.

Here were some of the findings:
• Average follow-up and period of VF exams were 4.5 ±0.9 and 8.7 ±1.6 years, respectively.
• VF progression was detected in 23 eyes (22 percent).
• ENR was used to detect rates of change of the superotemporal RNFL sector and GCIPL in five central superpixels, and at 3.4 degrees and 5.6 degrees eccentricity to determine best predictor subsets (AUC=0.79 ±0.12).
• Best ML predictors consisted of baseline superior hemimacular GCIPL thickness and GCIPL change rates at 3.4 degrees eccentricity and three central superpixels (AUC=0.81 ±0.10).
• Models using GCIPL-only structural variables performed better than RNFL-only models.

Researchers wrote that VF progression can be predicted with clinically relevant accuracy from baseline and longitudinal structural data. They added that further refinement of proposed models would assist clinicians with timely prediction of functional glaucoma progression and clinical decision-making.

SOURCE: Nouri-Mahdavi K, Mohammadzadeh V, Rabiolo A, et al. Prediction of visual field progression from OCT structural measures in moderate to advanced glaucoma. Am J Ophthalmol 2021; Jan 29. [Epub ahead of print].



Fundus Autofluorescence in nAMD & Clinicopathologic Correlation to MA

Investigators wrote that macular atrophy of retinal pigment epithelium and photoreceptors leads to vision loss in neovascular age-related macular degeneration despite successful treatment with anti-angiogenic agents. To better understand macular atrophy, confirm the cellular basis of fundus autofluorescence (FAF) imaging and inform management of nAMD, they performed a histological analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD.

The case study and clinicopathologic correlation involved a White woman in whom AMD findings of inactive subretinal fibrosis (right eye) were followed for nine years, using FAF and optical coherence tomography. The woman had no detectable subretinal fluid or other recurrent exudation, and no intravitreal injections before her death at age 90 years. The right eye was preserved 6.25 hours after death, post-fixed in osmium tannic acid paraphenylenediamine and prepared for submicrometer epoxy resin sections (n=115), with 19 matched to clinical OCT B-scans.

Main outcome measures included light microscopic morphology of a hyperautofluorescent (hyperFAF) area attributed to prior exudation (“floodplain” hyperFAF), hypoautofluorescent (hypoFAF) spots of MA and areas of unremarkable FAF.

Here were some of the findings:
• Floodplain hyperFAF was visible throughout the nine-year follow-up, with several hypoFAF atrophic spots expanding within it over time.
• The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic, yet continuous, RPE in histology. The hypoFAF spots inside the floodplain corresponded with complete retinal pigment epithelium and outer retinal atrophy (cRORA) on OCT, and loss of both photoreceptors and RPE in histology.
• In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer.

Investigators wrote that FAF imaging involved optical signal modulation by photoreceptors as well as emission signal sources in RPE. They found that HyperFAF attributed to an exudative floodplain signaled loss of photoreceptors over continuous RPE, and in MA signaled loss of both cell layers. Investigators suggested that FAF imaging should be interpreted with the multilayer perspective provided by OCT for maximal value. Finally, they added, prevention of exudation in nAMD may preserve photoreceptors.

SOURCE: Chen L, Messinger JD, Ferrara D, et al. Fundus autofluorescence in neovascular age-related macular degeneration, a clinicopathologic correlation relevant to macular atrophy. Ophthalmol Retina 2021; Feb 1. [Epub ahead of print].



Vertical Scrolling Axis of Corneal Endothelial Grafts for DMEK

Scientists wrote that heterogeneity in scrolling behavior of Descemet’s membrane endothelial keratoplasty grafts complicates DMEK surgery. This prospective, observational study assessed scrolling axes of DMEK grafts relative to the donor's eye.

The eye bank randomly marked the rim of corneoscleral donor buttons during trephination and recorded the position relative to the donor's axis. Surgeons, masked to the absolute position of the eye bank marking, recorded the scrolling axis relative to the eye bank marking and DMEK upside-down orientation. The scrolling axis was categorized as vertical (0 to 30 degrees, and 150 to 180 degrees), oblique (>30 to 60 degrees, and 120 to <150 degrees) and horizontal (>60 to <120 degrees). Scrolling patterns of corneas from the same donor were assessed.

Scrolling patterns of 202 donor corneas from 149 donors were determined. Here were some of the findings:
• The donor graft scrolled predominantly vertically to the donor's cornea (75 percent; CI, 68 to 80 percent).
• Horizontal axes (11 percent) and oblique axes (14 percent) were less common.
• The median deviation in scrolling axes after unfolding the grafts was zero degrees from the original scrolling axis (interquartile range, 0 to 15), indicating that scrolling axes were stable.
• Fellow eyes of 46 donors had 3.55 times higher odds of a nonvertical scrolling pattern if the first eye had a nonvertical scrolling pattern (CI, 1.37 to 9.20), suggesting that donor factors influencing both eyes could contribute to scrolling patterns.

Scientists reported that DMEK grafts have a natural and stable scrolling tendency at the vertical axis of donor cornea. They added that anticipating scrolling axes might help improve preparation techniques for DMEK grafts and outcomes.

SOURCE: Wacker K, Fritz M, Grewing V, et al. Vertical scrolling axis of corneal endothelial grafts for Descemet membrane endothelial keratoplasty. Cornea 2020; Dec 8. [Epub ahead of print].


Extended Dosing Under Anti-VEGF Treatment of Exudative AMD

Researchers assessed disease stability (absence of intraretinal and/or subretinal fluid) and the percentage of eyes able to extend treatment intervals to ≥12 weeks in exudative age-related macular degeneration.

The authors performed a systematic literature search to identify clinical studies reporting treatment outcomes for ranibizumab, aflibercept and brolucizumab in exudative AMD under a treat-and-extend protocol with a follow-up of ≥12 months. Weighted mean differences and subgroup comparisons were used to integrate the different studies.

This meta-analysis of 29 published series included 27 independent samples and 5,629 patients. Here were some of the findings:
• In the pooled group, disease stability was reported in 62.9 percent and 56 percent, after 12 and 24 months of treatment, respectively.
• In the pooled group, treatment intervals were extended to ≥12 weeks in 37.7 percent and 42.6 percent, after 12 and 24 months of treatment, respectively.
• Ranibizumab, aflibercept and brolucizumab differed regarding their potential to achieve disease stability over 12 and 24 months, respectively:
   o (after 12 months) 56.3 percent, 64.5 percent and 71.5 percent; and
   o (after 24 months) 50 percent, 52.7 percent and 75.7 percent; (p=<0.001)
• Ranibizumab, aflibercept and brolucizumab differed regarding their potential to achieve disease stability after an interval extension to ≥12 weeks over 12 and 24 months, respectively:
   o (after 12 months) 28.6 percent, 34.2 percent and 53.3 percent; and
   o (after 24 months) 34.2 percent, 47.7 percent, and 41.7 percent; (p=< 0.001).

Researchers concluded that the percentage of eyes achieving disease stability regressed with two of three treatments in the second year, while the percentage of eyes receiving a ≥12-week interval increased disease stability in two of three treatments. They added that the discrepancy may reflect challenges in balancing treatment burden and under-treatment.

SOURCE: Garweg JG, Gerhardt C. Disease stability and extended dosing under anti-VEGF treatment of exudative age-related macular degeneration (AMD) — a meta-analysis. Graefes Arch Clin Exp Ophthalmol 2021; Feb 2. [Epub ahead of print].




Industry News

J&J Vision Gets FDA Nod for Tecnis Eyhance & Tecnis Eyhance Toric II IOLs

Johnson & Johnson Vision announced the FDA approved the Tecnis Eyhance and Tecnis Eyhance Toric II intraocular lenses. J&J says the lenses’ “breakthrough” refractive surface is designed to slightly increase depth of focus and provide good contrast sensitivity in low light. Read more.



WebMD Announces New Effort to Combat Vaccine Misinformation

WebMD says that misinformation is continuing to undermine public confidence in the Covid-19 vaccines, so it’s launched the WebMD Covid-19 Vaccine Misinformation Center to help combat inaccuracies with facts. According to WebMD, “The center provides reliable vaccine resources and online tools to help consumers make informed decisions, driven by science, and features articles and videos on topics including vaccine myths and how they take root, public health challenges and the role of social media in misinformation.” Medscape, a division of WebMD Health Corp., will feature content and resources at its Covid-19 Resource Center, including vaccine overviews, late-stage vaccine development updates and news on vaccine research. WebMD and Medscape have also joined with corporate, nonprofit and media leaders in a global public service campaign, VaxFacts, to identify and counter misleading vaccine information. Led by HealthGuard, WebMD says the campaign features a browser extension that flags health hoaxes, provides credibility ratings for hundreds of websites and guides users to sources that offer trusted information. So far, HealthGuard has flagged nearly 400 websites for publishing misinformation and myths about COVID-19 vaccines. Read more.



Gemini Initiates of GEM103 Phase IIa Study

Gemini Therapeutics announced the start of a Phase IIa trial advancing GEM103 as a potential add-on therapy for patients with wet age-related macular degeneration who have, or may be at risk for, macular atrophy but require ongoing anti-vascular endothelial growth factor treatment. Topline data related to safety, tolerability, effect on intraocular CFH levels and biomarkers is expected in the second half of 2021. Read more.

Adverum Announces Publication of Preclinical Safety Data on ADVM-022

Adverum Biotechnologies announced the publication of preclinical data on ADVM-022 intravitreal gene therapy in Translational Vision Science & Technology. One finding included that a single IVT injection of ADVM-022 (2 x 10^12 vg/eye in this study) appeared to be safe and well-tolerated, and resulted in sustained expression of aflibercept with no detectable adverse effects on normal retinal structure or function measured out to 30 months. ADVM-022 is in clinical trials for wet age-related macular degeneration and diabetic macular edema. Read more.



Complimentary CME Education Videos




Inflammasome Publishes Dry AMD Data

Inflammasome Therapeutics reported that data published in Proceedings of the National Academy of Sciences “confirms the company’s proprietary compounds hold promise in preventing and treating age-related macular degeneration.” The paper reveals that patients taking certain nucleoside reverse transcriptase inhibitors (NRTIs) to prevent HIV infection have a 40 percent lower risk of developing dry AMD compared to matched controls. Researchers at Inflammasome Therapeutics are developing these drugs as treatments for dry AMD. Read more.



Nanoscope Receives Retinal Organoid Challenge Award From NIH

Nanoscope Therapeutics researchers, in collaboration with the University of Colorado and Miami University, were awarded the top prize from the 3D-ROC challenge from the National Institute of Health, for generating a physiologically relevant three-dimensional retinal organoid. The organoids provide a unique opportunity for evaluating novel gene therapies, including multi-characteristic opsin (MCO) gene therapy for vision restoration. Nanoscope is evaluating the effectiveness of MCO optogenetic therapy, which has shown promise in restoring sight in blind subjects. Read more.



FastBack Launches FastCheck Thermal Imaging & Facial Recognition System

FastBack announced the launch of FastCheck, a thermal imaging and facial recognition system to “keep businesses healthy, secure and organized” in the era of COVID-19. Designed to instantly read body temperature within two feet, the smart technology visually and/or audibly sends alerts via a green (go) or red (stop—elevated temperature alert) signal, reminds individual to wear a mask if not detected and keeps records for contact tracing, among other features. Learn more.











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