From the editors of Review of Ophthalmology:
In this issue: (click heading to view article)
Association of Intravitreal Aflibercept with OCTA Vessel Density in PDR
Researchers wrote that previous studies have evaluated the association between anti-vascular endothelial growth factor therapy and macular vessel density, but they have been confounded by the presence of macular edema, which may be associated with artifacts and segmentation errors in optical coherence tomography angiography. So the researchers evaluated the association of intravitreal aflibercept with changes in macular vascular density using OCTA in individuals with proliferative diabetic retinopathy without diabetic macular edema.
This post hoc analysis of a randomized clinical trial used data on 40 eyes of 40 patients with PDR without DME enrolled in the Intravitreal Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy (RECOVERY) clinical trial from August 1, 2016, to June 31, 2017. (Aflibercept's maker Regeneron was a collaborator on the trial.) Three patients were lost to follow-up at month 12, and five patients were excluded from analysis because of poor OCTA image quality, leaving 16 patients in each cohort in the final analysis. Data analysis was performed from March 1, 2018, to January 15, 2019. In the RECOVERY trial, patients were randomized into cohorts receiving 2 mg of aflibercept injections monthly (n=20) or quarterly (n=20), and treated for 12 months.
The percentage of vascular density (in total scan, and foveal and parafoveal regions) was compared before and after 12 months of therapy. The sample for this OCTA analysis included 32 eyes from 32 patients (mean [SD] age, 48.37 [12.30] years; 17 [53.1 percent] male). Here were some of the findings:
- The mean (SD) total scan vascular density for the superficial vascular complex was 42.28 percent (4.03 percent; CI, 40.63 to 43.93 percent) at baseline and 39.64 percent (4.01 percent; CI, 37.91 to 41.37 percent) at month 12 (p=0.69).
- For the deep vascular complex, the mean (SD) vascular density was 48.42 (4.99 percent; CI, 46.36 to 50.47 percent) at baseline and 45.69 percent (4.63 percent; CI, 43.69 to 47.70 percent) at month 12 (p=0.40).
- For the choriocapillaris, the mean (SD) vascular density was 64.42 percent (3.36 percent; CI, 63.04 to 65.81 percent) at baseline and 62.55 percent (4.79 percent; CI, 60.48 to 64.62 percent) at month 12 (p=0.16).
- No difference was found in vascular density parameters between monthly and quarterly injection arms at month 12.
Researchers found that macular vascular density didn’t change after 12 months of intravitreal aflibercept therapy. They wrote that this finding may represent a beneficial association between anti-VEGF therapy and macular vascular density given that nonperfusion is expected to progress in diabetic retinopathy.
SOURCE: Alagorie AR, Nittala MG, Velaga S, et al. Association of intravitreal aflibercept with optical coherence tomography angiography vessel density in patients with proliferative diabetic retinopathy: A secondary analysis of a randomized clinical trial. JAMA Ophthalmol 2020; June 25. [Epub ahead of print].
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Evaluation of RNFL & GGC Thickness in Adult Offspring of POAG Patients
The aim of this study was to investigate retinal nerve fiber layer and ganglion cell complex thickness in adult offspring of primary open-angle glaucoma patients and to compare the results with those of individuals without a family history of glaucoma disease.
This cross-sectional observational study included 40 eyes of 40 individuals with a self-reported family history for POAG, and 40 eyes of 40 healthy individuals without a family history of glaucoma. Retinal nerve fiber layer and macular ganglion cell complex thickness were measured by spectral-domain optical coherence tomography, and the results were compared between the two groups.
- In adult offspring of POAG patients, RNFL and GCC thickness were thinner in all quadrants.
- The average RNFL (p=0.039) and GCC (p=0.015) were decreased significantly).
- In the inferior quadrant, thinning in RNFL (p=0.024) and GCC (p=0.039) thickness was especially significant.
- No significant differences were found between the groups in terms of values for MD (p=0.064) and PSD (p=0.091).
Investigators reported that, in adult offspring of POAG patients, especially in the inferior quadrant, RNFL and GGC thicknesses were significantly lower than those in subjects without a family history. They added that prospective, controlled clinical trials with longer follow-up would be needed to better understand whether these changes are an early indicator of glaucoma and the progression of glaucoma disease.
SOURCE: Bilgin S. The evaluation of retinal nerve fiber layer and ganglion cell complex thickness in adult offspring of primary open-angle glaucoma patients. J Glaucoma 2020; Jun 16. [Epub ahead of print].
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Tear Inflammatory Molecules & Clinical Correlations in EDE Caused by MGD
Scientists compared the levels of inflammatory molecules in tear samples between patients with meibomian gland dysfunction-related evaporative dry eye (EDE) and healthy subjects, and analyzed the correlations between the levels of tear inflammatory molecules and ocular surface parameters.
A total of 30 MGD-related EDE patients (48 eyes) and 10 healthy volunteers (15 eyes) were enrolled. Dry eye-related examinations and questionnaires were obtained from all participants. The levels of nine inflammatory molecules were determined through multiplex bead analysis. Here were some of the findings:
- Inflammatory molecules including ICAM-1, IFN-γ, CXCL8/IL-8, IL-6, TNF-α and IL-12p70 were detected in 100 percent of patients; while IL-1α was detected in 56.25 percent; IL-1β was detected in 13.60 percent; and IL-10 was detected in 45.83 percent of patients.
- ICAM-1, IL-8, IL-6, TNF-α, IL-12p70 and IFN-γ were detected in 86.67 to 100 percent of healthy subjects, and detection rates of IL-10, IL-1α and IL-1β were below 50 percent.
- Levels of IL-8, IL-6, IFN-γ and ICAM-1 were significantly higher in the patient group compared with the control group.
- IL-8 and IL-6 were negatively correlated with the Schirmer I test.
- IFN-γ was negatively correlated with tear-film breakup time.
- ICAM-1 and IL-6 were positively correlated with meibography scores.
Scientists determined that individuals with MGD-related EDE had higher levels of inflammatory molecules in their tears, and some molecules were correlated with ocular surface parameters. They wrote the findings suggested that inflammation played an important role in MGD-related EDE, and that several inflammatory molecules could be used in the diagnosis and treatment of MGD-related EDE.
SOURCE: Wu X, Chen X, Ma Y, et al. Analysis of tear inflammatory molecules and clinical correlations in evaporative dry eye disease caused by meibomian gland dysfunction. Int Ophthalmol 2020; June 29. [Epub ahead of print].
Retinal Specialist vs. AI Detection of Retinal Fluid Using OCT
Researchers evaluated the performance of retinal specialists in detecting retinal fluid presence in spectral-domain optical coherence tomography macular volume scans from eyes with age-related macular degeneration, and compared their performance with the artificial intelligence-based Notal OCT Analyzer (NOA). The work was funded by Notal Vision, and two of the authors are employees of the company.
The prospective comparison included retinal fluid grades from human retinal specialists and the NOA on SD-OCT scans from two commonly used devices (Cirrus and Spectralis).
Participants included 1,127 eyes of 651 Age-Related Eye Disease Study 2 10-year (AREDS2-10Y) participants with SD-OCT scans graded for fluid presence/absence by reading center (RC) graders.
The AREDS2-10Y investigators graded each SD-OCT scan for the presence/absence of intraretinal and subretinal fluid. Separately, the same scans were graded (with masking to the investigator results) by the NOA and RC graders, and used as the ground truth. Main outcome measures included accuracy (primary), in addition to sensitivity, specificity, precision and F1-score. The mean participant age was 80 ±7.6 years. Here were some of the findings:
- Of the 1,127 eyes, retinal fluid was present in 32.8 percent.
- For detecting retinal fluid (intraretinal or subretinal), the researchers (retinal specialists) had the following grades:
- accuracy, 0.805 (CI, 0.780 to 0.828);
- sensitivity, 0.468 (CI, 0.416 to 0.520);
- specificity, 0.970 (CI, 0.955 to 0.981);
- precision, 0.883 (CI, 0.829 to 0.924); and
- F1-score, 0.611.
- The NOA had the following grades:
- accuracy, 0.851 (CI, 0.829 to 0.871);
- sensitivity, 0.822 (CI, 0.779 to 0.859);
- specificity, 0.865 (CI, 0.839 to 0.889);
- precision, 0.749 (CI, 0.704 to 0.790); and
- F1-score, 0.784.
- For detecting intraretinal fluid, the researchers (retinal specialists) had the following grades:
- accuracy, 0.815 (CI, 0.792 to 0.837);
- sensitivity, 0.403 (CI, 0.349 to 0.459); and
- specificity, 0.978 (CI, 0.966 to 0.987).
- For detecting intraretinal fluid, the NOA metrics were:
- accuracy, 0.877 (CI, 0.857 to 0.896);
- sensitivity, 0.763 (CI, 0.713 to 0.808); and
- specificity, 0.922 (CI, 0.902 to 0.940).
- For detecting subretinal fluid, the researchers (retinal specialists) had the following grades:
- accuracy, 0.946 (CI, 0.931 to 0.958);
- sensitivity, 0.583 (CI, 0.471 to 0.690); and
- specificity, 0.973 (0.962-0.982).
- For detecting subretinal fluid, the NOA had the following grades:
- accuracy, 0.863 (CI, 0.842 to 0.882);
- sensitivity, 0.940 (CI, 0.867 to 0.980); and
- specificity, 0.857 (CI, 0.835 to 0.877).
In the large and challenging sample of SD-OCT scans obtained with two commonly used devices, retinal specialists had imperfect accuracy in detecting retinal fluid, with low sensitivity, but their specificity and precision levels were higher than the AI device.
Source: Keenan TD, Clemons TE, Domalpally A, et al. Retinal specialist versus Artificial intelligence detection of retinal fluid from optical coherence tomography: AREDS2 10-year follow-on. Ophthalmology 2020; June 26. [Epub ahead of print].
FDA Accepts Santen’s Premarket Approval Application for DE-128 (MicroShunt)
Santen Pharmaceutical announced that the FDA accepted its Premarket Approval application for DE-128 (MicroShunt) for review. Santen describes the DE-128 as an investigational ab-externo, minimally invasive surgical glaucoma implant designed to reduce intraocular pressure in individuals with primary open-angle glaucoma whose IOP isn’t controlled when using maximum tolerated glaucoma medications. Read more.
CorneaGen Gives Back to Community
CorneaGen, a provider of corneal tissue for transplants, says it’s allocated $100,000 per year to help fund corneal transplant surgeries for Black patients in need of assistance and will offer three paid internships each year for people of color interested in exploring cornea care as a career. Each summer intern will receive a $6,700 stipend for his work in CorneaGen’s Seattle office, which will begin immediately. Read more.
First Patient Dosed in Iveric’s Second Zimura Phase III Clinical Trial
Iveric bio announced the first patient was dosed in GATHER2, also known as ISEE2008, the second Phase III clinical trial for Zimura (avacincaptad pegol), a novel complement C5 inhibitor, in development for the treatment of geographic atrophy secondary to age-related macular degeneration. The company previously announced that Zimura met its pre-specified primary efficacy endpoint and reached statistical significance in GATHER1, also known as OPH2003, the first Phase III clinical trial for Zimura. Read more.
Quantel Medical Completes Ellex Acquisition
Quantel Medical completed its acquisition of Ellex, including the company’s laser and ultrasound technology solutions (with the exception of 2RT and iTrack). The purchase includes the Ellex brand name, its R&D and production site in Adelaide, Australia, and its subsidiaries based in Australia, Japan, the United States, France and Germany. Quantel Medical and Ellex have a shared interest in the development of technologies for the diagnosis and treatment of glaucoma, cataracts, AMD and diabetic retinopathy. Read more.
jCyte Announces Scientific Advisory Board
jCyte announced its scientific advisory board of retinal physicians. The board will provide external scientific review on the company’s research and development programs. Members of the SAB are as follows:
• David S. Boyer, MD, a clinician, surgeon and educator at the Retina-Vitreous Associates Medical Group in Southern California;
• Jeffrey Heier, MD, co-president and medical director, director of the vitreoretinal service and director of retina research at Ophthalmic Consultants of Boston;
• Peter K. Kaiser, MD, the Chaney Family Endowed Chair for Ophthalmology Research and a Professor of Ophthalmology at the Cleveland Clinic Lerner College of Medicine; and
• Baruch D. Kuppermann, MD, PhD, the Roger F. Steinert Professor, Chair of the Department of Ophthalmology and Director of the Gavin Herbert Eye Institute at the University of California, Irvine.
STAAR Surgical Receives CE Mark for Presbyopia-correcting Lens
Staar Surgical announced that EVO Viva, the company’s presbyopia-correcting version of the Implantable Collamer lens, recently received CE Mark approval. Staar says this “next-generation” Implantable Collamer lens is designed to work in harmony with a patient's eye for the correction or reduction of myopia and presbyopia in phakic and pseudophakic eyes. The lens adds near and intermediate vision correction. Read more.
VisionCare Names Ruggia New CEO
VisionCare announced Thomas Ruggia was appointed as chief executive officer, effective July 6. Ruggia will lead the company, with its FDA-approved surgical treatment for macular degeneration, the telescope implant and CentraSight treatment program. Ruggia most recently served as vice president of Customer Experience and Ocular Surface Disease at Johnson & Johnson Vision. At Janssen Pharma, he was was working on an AMD treatment as the commercial strategy leader in ophthalmology. Read more.
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