From the editors of Review of Ophthalmology:
AUGUST IS CHILDREN’S EYE HEALTH AND SAFETY MONTH
In this issue: (click heading to view article)
Quantification of Fluid Resolution and VA Gain in Patients with DME Using Deep Learning
Researchers wrote that optical coherence tomography can acquire large amounts of data on diabetic macular edema, but many morphologic features have yet to be identified and quantified. In their study, they aimed to examine the volumetric change of intraretinal and subretinal fluid in DME during anti-vascular endothelial growth factor treatment using deep learning algorithms. One of the authors received fees from Novartis and Roche/Genentech, and has a patent to analyze optical coherence tomographic images pending. Another author received grants from Regeneron and Genentech during the conduct of the study
The post hoc analysis of a randomized clinical trial, the Diabetic Retinopathy Clinical Research Network (protocol T), assessed 6,945 spectral-domain OCT volume scans of 570 eyes from 570 study participants with DME. The original trial was performed from August 21, 2012, to October 18, 2018. The current analysis was performed from December 7, 2017, to January 15, 2020.
Participants were treated according to a predefined, standardized protocol with aflibercept, ranibizumab or bevacizumab, with or without deferred laser.
Main outcomes and measures included the association of treatment with IRF and SRF volumes, and best-corrected visual acuity during 12 months using deep learning algorithms.
Of 570 study participants (302 [53 percent] male; 369 [65 percent] white; mean age, 43.4 ±12.6 years), here were some of the findings:
- The mean fluid volumes in the central 3 mm were:
- 448.6 nL (CI, 412.3 to 485.0 nL) of IRF and 36.9 nL (CI, 27 to 46.7 nL) of SRF at baseline; and
- 161.2 nL (CI, 135.1 to 187.4 nL) of IRF and 4.4 nL (CI, 1.7 to 7.1 nL) of SRF at 12 months.
- The presence of SRF at baseline was associated with a worse baseline BCVA Early Treatment Diabetic Retinopathy Study score of 63.2 (CI, 60.2 to 66.1) (approximate Snellen equivalent of 20/63 [CI, 20/50 to 20/63]) vs. 66.9 (CI, 65.7 to 68.1) (approximate Snellen equivalent, 20/50 [CI, 20/40 to 20/50]) in eyes without SRF (p<.001).
- The presence of SRF at baseline was associated with a greater gain in ETDRS score (0.5; CI, 0.3 to 0.8) every four weeks during follow-up vs. 0.4 (CI, 0.3 to 0.5) in eyes without SRF at baseline (p=0.02) when adjusted for baseline BCVA.
- Aflibercept was associated with greater reduction of IRF volume compared with bevacizumab after the first injection (difference, 79.8 nL; CI, 5.3 to 162.5 nL; p<0.001) and every four weeks thereafter (difference, 10.4 nL; CI, 0.7 to 20.0 nL; p=.004).
- Ranibizumab was associated with a greater reduction of IRF after the first injection compared with bevacizumab (difference, 75.2 nL; CI, 1.4 to 154.7 nL; p<.001).
Researchers found that automated segmentation of fluid in DME revealed that the presence of SRF was associated with a lower baseline BCVA but with good response to anti-vascular endothelial growth factor therapy. They added that such automated spectral-domain OCT analyses may be used clinically to assess anatomical change during therapy.
SOURCE: Roberts PK, Vogl W, Gerendas BS, et al. Quantification of fluid resolution and visual acuity gain in patients with diabetic macular edema using deep learning: A post hoc analysis of a randomized clinical trial. JAMA Ophthalmol 2020; July 23. [Epub ahead of print.]
Complimentary CME Education Videos
Predicting Adherence with the Glaucoma Treatment Compliance Assessment Tool
Investigators used a questionnaire called The Glaucoma Treatment Compliance Assessment Tool (GTCAT), developed by physicians at the Devers Eye Institute in Portland, Oregon, to identify multiple patient-specific factors associated with adherence that could help inform personalized interventions to optimize glaucoma adherence. They studied health behavior factors related to glaucoma adherence in individuals with self-reported poor adherence.
A research coordinator used the Chang Adherence Measure and the Morisky Medication Adherence Scale to identify subjects with poor self-reported glaucoma medication adherence, and enrolled them in a three-month study to electronically monitor medication adherence. At enrollment, the coordinator administered the GTCAT. Investigators calculated the percentage of prescribed doses taken over a three-month period using an electronic dose monitor (AdhereTech). They used Rasch analysis, and univariate and multivariable regression to determine the GTCAT statements that predicted electronically monitored adherence.
Here were some of the findings:
- The mean adherence was 73.8 ±21.04 percent (range: 13 to 100).
- Rasch analysis showed that the GTCAT had a good overall fit and no differential bias (Anderson Likelihood Ratio [LR] test >0.05).
- Multiple GTCAT statements were associated with adherence, which represented:
- increased knowledge;
- increased cues-to-action;
- decreased barriers;
- less depression; and
- increased self-efficacy (p<0.09 for each).
- The full GTCAT or a subset of statements had a high association with adherence (Rsq range, 0.44 to 0.51; p<0.005 for all).
- The GTCAT identified:
- more than 50 percent of patients who wanted more education about glaucoma;
- more than 68 percent who didn’t use reminders; and
- more than 40 percent who reported having difficulty using the eye drops.
Investigators noted that the GTCAT identified multiple factors associated with adherence. They suggested that clinicians and researchers could use the tool to identify specific barriers to adherence and potentially develop interventions to improve adherence.
SOURCE: Sanchez FG, Mansberger SL, Newman-Casey PA. Predicting adherence with the Glaucoma Treatment Compliance Assessment Tool. J Glaucoma 2020; July 29. [Epub ahead of print].
Complimentary CME Education Videos
Prevalence of Persistent Corneal Epithelial Defects in Chronic Ocular Graft- Versus-Host Disease
Scientists established the prevalence, clinical characteristics and risk factors for persistent corneal epithelial defects (PEDs) in individuals with chronic ocular graft-versus-host disease (oGVHD) and determined visual outcomes after healing, as part of a retrospective cohort study.
They performed a chart review of individuals diagnosed with chronic oGVHD between January 2011 and December 2018, and recorded demographic and clinical characteristics. They analyzed the data to determine prevalence of PEDs, and performed multivariate logistic regression to determine the risk factors associated with them.
Here were some of the findings:
- Scientists identified 405 individuals diagnosed with chronic oGVHD, with a mean age of 60 ±13 years; 58 percent were men.
- The prevalence of PED was 8.1 percent; the median time for PED development after hematopoietic stem cell transplantation was approximately 24 months.
- Median time to PED resolution was 4.5 weeks after starting therapy.
- The mean best-corrected visual acuity declined by two lines post-PED resolution.
- Over eight years, the prevalence rate was: for corneal ulcer, 6.2 percent; for perforation, 4 percent.
- Logistic regression analysis revealed the following were significant risk factors for PED development:
- diabetes (p=0.006);
- limbal stem cell deficiency (LSCD) (p=0.02);
- filamentary keratitis (p=0.02);
- subconjunctival fibrosis (p=0.02); and
- a higher oGVHD NIH score (p=0.01).
Scientists found the prevalence rates of the following in chronic oGVHD to be: PEDs (8.1 percent); corneal ulceration (6.2 percent); and corneal perforation (4 percent). They determined that oGVHD patients with diabetes, LSCD, filamentary keratitis, subconjunctival fibrosis and a high NIH score were at higher risk of developing severe corneal disease.
SOURCE: Sinha S, Singh RB, Dohlman TH, et al. Prevalence of persistent corneal epithelial defects in chronic ocular graft-versus-host disease. Am J Ophthalmol 2020; Jul 24. [Epub ahead of print.]
Timing of Large Submacular Hemorrhage Secondary to AMD Relative to Anti-VEGF Therapy
Researchers characterized the timing of large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration relative to anti-vascular endothelial growth factor therapy, as part of a retrospective, consecutive case series.
A total of 46 eyes of 46 individuals with large SMH due to neovascular AMD selected to undergo pars plana vitrectomy with subretinal tissue plasminogen activator at the Mid Atlantic Retina group of the Wills Eye Hospital were included.
Researchers reviewed patient charts to identify baseline characteristics and anti-VEGF treatment details. They used optical coherence tomography to evaluate pigmented epithelial detachments, SMH and subretinal fluid pre- and post-SMH.
Main outcome measures included the timing of SMH in relation to the last anti-VEGF injection, anti-VEGF treatment status (i.e., naïve, stable or recently extended/shortened were each sub-groups of the main 46-patient group) at the time of SMH and the length of the anti-VEGF treatment interval at the time of bleeding.
Here were some of the findings:
- SMH occurred in 15 individuals (36 percent) who were treatment naïve.
- In those treated with anti-VEGF, 19 individuals (45 percent) were on a stable treatment interval, five people (12 percent) had recently extended their interval, and three individuals (7 percent) had shortened their interval.
- The average treatment interval at the time of SMH was 6.8 weeks, with a median seven total injections prior to SMH.
- Seven (26 percent) of treated individuals had a SMH on a four-week dosing interval.
- The average time between last injection and SMH was 29 days.
- Forty-eight percent of anti-VEGF treated patients had a SMH within 30 days of anti-VEGF injection.
- Chi-square analysis found SMH more likely to occur within 30 days of anti-VEGF injection than after 30 days.
Researchers concluded that large SMH in neovascular AMD in a treat-and-extend regimen didn’t appear to be associated with prolonged dosing intervals or recent interval extension. They added that a large proportion of such hemorrhages were likely to be the result of mechanisms other than loss of effective VEGF inhibition.
Source: Matsunaga DR, Su D, Sioufi K, et al. The timing of large submacular hemorrhage secondary to age-related macular degeneration relative to anti-VEGF Therapy. Ophthalmol Retina 2020; Aug. 4. [Epub ahead of print].
RegenxBio Provides Phase I/IIa Trial Update
RegenxBio reported one-year data from individuals in cohorts 4 and 5 of its Phase I/IIa trial of its gene therapy RGX-314 for the treatment of wet age-related macular degeneration. The company says it plans to initiate a program for subretinal delivery of RGX-314 in individuals with wet AMD by the end of 2020. In addition, it announced that a Phase II trial of RGX-314 for the treatment of wet AMD delivered to the suprachoroidal space (AAVIATE) is active and expected to enroll patients in the third quarter of 2020. Read more.
BVI Partners with Haywood to Provide PPE
BVI is partnering with Haywood Vocational Opportunities to provide isolation gowns to U.S. health-care workers on the front lines of the pandemic effort. HVO is a U.S.-based medical product manufacturer that provides vocational training and employment opportunities for adults with disadvantages and disabilities. The partnership formed in late spring in response to the shortage of personal protective equipment caused by the pandemic. Through teamwork between the organizations, an isolation gown was designed, tested, manufactured and released to the market in less than three months. The first recipients of the U.S.-made gowns are health-care workers throughout North Carolina, where HVO is based. Read more.
RETINA-AI Health Raises $5.2M for AI Detection of DR
RETINA-AI Health, which is developing AI technology to enable the diabetic retinal exam to be done in the primary-care setting, raised $5.2 million in a series A financing for artificial intelligence screening of diabetic retinopathy. The capital was raised from private investors, 80 percent of whom are physicians. The company's HUMMINGBIRD DR 100 is a cloud-based AI detector of diabetic retinopathy that interprets the retinal image and returns a PDF report. Read more.
Sight Sciences Announces First Patients Enrolled in ORION
Sight Sciences enrolled the first patients in its ORION multicenter clinical trial, which will build upon clinical evidence for the use of the Omni Surgical System for glaucoma in pseudophakic eyes. The primary effectiveness endpoint is the proportion of eyes with at least a 20-percent decrease in unmedicated mean diurnal intraocular pressure at 12 months. Read more.
Ocugen Receives Fourth FDA Orphan Drug Designation for Gene Therapy
Ocugen announced the FDA granted a fourth Orphan Drug Designation for OCU400 in the treatment of PDE6B gene mutation-associated retinal diseases. Ocugen’s Modifier Gene Therapy Platform addresses multiple diseases, and its novel gene therapy product candidate, OCU400, has the potential to be broadly effective in restoring retinal integrity and function across genetically diverse inherited retinal diseases, the company says. Read more.
Kubota Demonstrates 3-D Imaging Capabilities Using AI on PBOS
Kubota Vision says that it demonstrated 3-D imaging capabilities using artificial intelligence on its Patient Based Ophthalmology Suite (PBOS) in-home optical coherence tomography device. The PBOS is a home-based, self-monitoring miniature OCT device designed to detect disease progression. Read more.
FDA Accepts Investigational New Drug Application for Clearside CLS-AX
Clearside Biomedical announced the FDA accepted its Investigational New Drug application for CLS-AX (axitinib injectable suspension), paving the way for a Phase I/IIa clinical trial of CLS-AX in neovascular age-related macular degeneration by the end of 2020. The trial is expected to be an open-label, dose-escalation study.
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