From the editors of Review of Ophthalmology and Retina Specialist
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.
Systemic Corticosteroid Use After CSC Diagnosis
Researchers analyzed the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy diagnosis, as part of a retrospective, claims-based analysis.
Participants included a nationally representative sample of commercial insurance beneficiaries who received care between 2007 and 2015. Researchers limited the study population to beneficiaries with incident CSC diagnosed by an eye-care provider, excluding those with other major ophthalmologic comorbidities.
They developed a non-CSC comparison cohort matched to CSC patients on age, sex, general health (Charlson Comorbidity Index) and geographic region. They compared systemic corticosteroid prescriptions before and after CSC diagnosis, and by provider type (optometrist vs. ophthalmologist). Researchers also evaluated the likelihood of receiving steroids among CSC patients vs. matched controls, using logistic and Cox proportional hazard regression models.
Main outcome measures included: frequency of systemic corticosteroid prescriptions among CSC patients within 12 months pre-diagnosis, and at six, 12 and 24 months post-diagnosis; median time to steroid initiation and discontinuation; and odds of receiving post-diagnosis steroids among CSC patients and controls.
Researchers identified 3,418 CSC patients. Here were some of the findings:
- Nearly 39 percent (n=1,326) were prescribed systemic steroids at some point during the analysis period, compared with 23 percent of matched controls (4,033 of 17,178 patients).
- More than 12 percent of CSC patients (n=430) received steroids within a year pre-diagnosis, and nearly 12 percent (n=404) received steroids within one year post-diagnosis.
- Most patients who received post-diagnosis steroids were steroid- naïve (n=231).
- The most common steroid prescribed was oral prednisone (an approximately one-month supply).
- Among those receiving steroids, CSC patients had longer median time to first post-diagnosis steroid prescription (1.82 years vs. 0.50 year for controls) and longer time to last steroid prescription (1.62 years vs. 0.35 year for non-CSC patients).
- Although CSC patients were significantly less likely to receive steroids at six months post-diagnosis compared with matched non-CSC patients (OR=0.72; CI, 0.59 to 0.89), they were significantly more likely to receive steroids by two years post-diagnosis.
- Prescribing patterns were similar for patients diagnosed by an ophthalmologist vs. optometrist.
Scientists found that, despite evidence showing steroids contribute to CSC development, many patients continue to be prescribed systemic corticosteroids after CSC diagnosis. They added that their results suggest a need for greater communication and collaboration among providers to ensure clinical practice reflects evidence-based recommendations.
Source: Azad AD, Zhou M, Afshar AR, et al. Systemic corticosteroid use after central serous chorioretinopathy diagnosis. Ophthalmology 2020; June 30. [Epub ahead of print].
Nonexudative Macular Neovascularization - A Systematic Review of Prevalence, Natural History and Recent Insights from OCTA
Researchers wrote that nonexudative MNV is now known to be more prevalent in individuals with age-related macular degeneration than initially thought and is bringing new insights into both the natural history and management of this disease. The researchers reviewed the available literature on the prevalence, incidence, natural history and exudative conversion rates of subclinical (treatment-naïve) nonexudative macular neovascularization in individuals with AMD.
They conducted a literature search on PubMed, Scopus and Web of Science, along with a manual search, from January 2014 to June 2019. They included studies that used optical coherence tomography angiography as a primary diagnostic tool to evaluate subclinical (treatment-naïve), nonexudative, neovascular AMD.
Of the 258 screened articles, 12 were included. Here were some of the findings:
- The prevalence of subclinical nonexudative neovascular AMD in the fellow eyes of patients with unilateral exudative AMD ranged from 6.25 to 27 percent.
- Although the lesions weren’t associated with a significant decrease in visual acuity, the presence of nonexudative MNV appeared to be an important predictor of exudative disease.
- Incidence of exudation in the reviewed studies ranged from 20 to 80 percent (follow-up six months to two years).
- Some evidence revealed that nonexudative MNV may slow down the growth of adjacent geographic atrophy.
- As long as exudation didn’t occur, it appeared that subclinical nonexudative MNV wasn’t responsible for the deterioration of visual function.
Resarchers wrote that nonexudative MNV is an asymptomatic condition. Although nonexudative MNV appeared to be a precursor to the formation of exudative neovascular AMD, there was evidence suggesting a protective effect in slowing the progression of GA, they added. Researchers wrote further that early detection of nonexudative MNV before exudation develops should result in better monitoring of patients who are at high risk of conversion to exudative AMD. Though no controlled clinical trial has been performed to provide definitive recommendations, the authors of the studies included in this review agreed that nonexudative lesions shouldn’t be treated until symptomatic exudation develops. Moreover, researchers wrote, the existence of a nonexudative form of neovascular AMD would suggest that the term "neovascular AMD" should be preceded by either "exudative" or "nonexudative" when describing this neovascular stage of AMD.
SOURCE: Laiginhas R, Yang J, Rosenfeld PJ, et al. Nonexudative macular neovascularization - A systematic review of prevalence, natural history, and recent insights from OCT angiography. Ophthalmol Retina 2020;4:7:651-61.
Outcomes by Baseline Choroidal Neovascularization Features in AMD: Post Hoc Analysis of the VIEW Studies
Investigators assessed the influence of baseline choroidal neovascularization features on visual change and fluid resolution following anti-vascular endothelial growth factor treatment of eyes with neovascular age-related macular degeneration, as part of a post hoc analysis of 52-week data from the Phase III VIEW 1 and VIEW 2 clinical trials.
Participants included 1,804 patients with nAMD. Investigators analyzed integrated data from VIEW 1 and 2 of 1,804 eyes receiving intravitreal aflibercept injections (IAI) 2 mg every four weeks, IAI 2 mg every eight weeks after three initial monthly doses; and ranibizumab every four weeks with documented baseline CNV type, total area and leakage area. They evaluated time to an event and cumulative incidence by Kaplan-Meier analysis, and estimated relative risks using proportional hazards analysis.
Main outcomes measures included cumulative incidence of time to first sustained vision gain of ≥15 Early Treatment Diabetic Retinopathy Study letters, vision loss of >5 ETDRS letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by optical coherence tomography with respect to CNV type, total CNV and leakage area.
Here were some of the findings:
- Eyes with predominantly classic CNV (mean best-corrected visual acuity: 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of ≥15 letters than eyes with occult CNV (mean BCVA: 57.9 letters at baseline, p<0.01).
- Eyes with occult CNV at baseline showed higher incidence rates of first sustained absence of retinal fluid and of intraretinal fluid than eyes with predominantly classic CNV (both p<0.01).
- With increasing baseline CNV total area and leakage area, the incidence rate of first sustained gain of ≥15 letters decreased.
- Although baseline CNV total area didn’t have an effect, increasing baseline CNV leakage area (per 10 mm2) was associated with a decreased incidence rate of sustained absence of retinal fluid and of intraretinal fluid (both p<0.05).
Investigators wrote that the post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD following anti-VEGF treatment.
SOURCE: Steinle NC, Du W, Gibson A, et al. Outcomes by baseline choroidal neovascularization features in age-related macular degeneration: A post hoc analysis of the VIEW Studies. Ophthalmol Retina 2020; July 8. [Epub ahead of print].
MA Incidence & Progression in nAMD Eyes Treated with VEGF Inhibitors Using a T&E or PRN Regimen: MANEX Study
Researchers compared the incidence and progression of macular atrophy in eyes with neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor agents using a treat-and-extend or pro re nata regimen over four years in a real-life setting, as part of a multicenter, retrospective, comparative study.
Participants included 264 individuals with treatment-naïve nAMD. Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n=163) or PRN (n=101) regimen. Eyes were included if they had received anti-VEGF injections for at least four years, and had annual fundus autofluorescence (FAF) and optical coherence tomography imaging using the Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios.
Main outcome measures included MA incidence and progression over four years, association between treatment strategy and number of injections. Here were some of the findings:
- At baseline, MA was present in 24 percent of T&E group and 20 percent of the PRN group (p=0.32).
- At year four, in the T&E group, 27 percent of eyes (34/124) without baseline MA had detectable MA; and in the PRN group, 25 percent of eyes (20/81) without baseline MA had detectable MA.
- In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (p=0.23)
- Multivariate analysis for baseline predictors of MA growth including older age, poorer baseline VA and presence of RAP revealed a higher risk of greater MA progression (p=0.03).
- Regression analysis demonstrated no association between T&E and PRN treatment strategies relative to the risk of developing new MA during four years of follow-up, or risk of progression of pre-existing MA at year four (p=0.692).
Researchers reported that, over four years, neither incidence nor progression of macular atrophy in nAMD eyes treated with anti-VEGF injections were influenced by the treatment regimen or injection frequency. They added that eyes treated with a T&E regimen received more injections and had better visual outcomes compared with those treated with a PRN approach.
Source: Spooner KL, Fraser-Bell S, Cozzi M, et al. Macular atrophy incidence and progression in eyes with neovascular age-related macular degeneration treated with VEGF inhibitors using a treat-and-extend or a pro-re-nata regimen. Four year results of the MANEX study. Ophthalmology Retina 2020; June 13. [Epub ahead of print].
Predicting Progression of AMD Using OCT and Fundus Photography
Scientists compared the performance of automatically quantified optical coherence tomography imaging biomarkers and conventional risk factors manually graded on color fundus photographs to predict progression to late age-related macular degeneration.
As part of a longitudinal observational study, 280 eyes from 140 individuals with bilateral large drusen were included. All underwent OCT and CFP imaging at baseline and were then reviewed at six-month intervals to determine the progression to late AMD. CFPs were manually graded, and OCT scans underwent automated image analyses to quantify risk factors and imaging biomarkers, respectively, based on drusen and AMD pigmentary abnormalities. Four predictive models for progression to late AMD or atrophic AMD-only were developed (each including age), based on:
- CFP only (two parameters);
- OCT biomarkers, minimal (three parameters);
- OCT biomarkers, extended (seven parameters); and
- CFP and OCT combined (eight parameters).
Main outcome measures included performance of predicting progression to late AMD, based on the area under the receiver operating characteristic curve for correctly predicting progression. Here were some of the findings:
- The AUC for predicting late AMD development was similar for the models based on CFP alone (model one: 0.80), OCT alone (models two and three: 0.82 for both) and when using both modalities together (model four: 0.85).
- These models performed similarly for predicting the endpoint of atrophic AMD only (AUC=0.83 (model one), 0.84 (model two), 0.85 (model three) and 0.88 (model four).
Scientists wrote that OCT imaging biomarkers could provide an automatic method of risk stratification for eyes at risk of progression to vision-threatening late AMD as well as manual grading of CFP.
SOURCE: Wu Z, Bogunovic H, Asgari R, Schmidt-Erfurth U, et al. Predicting progression of age-related macular degeneration using optical coherence tomography and fundus photography. Ophthalmol Retina 2020; Jun 26. [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, the authors say that 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].
Validation of a Compensation Strategy Used to Detect Choriocapillaris Flow Deficits Under Drusen With Swept-Source OCT Angiography
A compensation strategy developed to measure the choriocapillaris (CC) flow deficits (FDs) under drusen was tested in eyes with large drusen from age-related macular degeneration before and after the drusen spontaneously resolved without evidence of disease progression.
As part of a prospective, observational consecutive case series, individuals with AMD were enrolled in a prospective SS-OCT imaging study (PLEX Elite 9000, Carl Zeiss Meditec). Researchers followed consecutive eyes with large drusen, and retrospectively identified eyes that underwent spontaneous collapse of drusen without evidence of disease progression. Drusen-resolved regions were manually outlined. CC FDs were measured using a previously published compensation strategy that adjusted for the decreased signal intensity underlying drusen. Both the percentage of FDs and the mean FD sizes (MFDSs) were measured before and after drusen resolution. Here were some of the findings:
- Resolution of drusen was identified in eight eyes from eight patients.
- The average interval between the two visits was 7.8 months.
- The average drusen volumes measured between visits were 0.23 mm3 and 0.04 mm3, respectively.
- After the drusen resolved, the average follow-up time without evidence of disease progression was 10.1 months.
- When the two visits were compared, there were no statistically significant differences in any of the CC parameters within the drusen resolved regions once the compensation strategy was applied (all p-values >0.22).
Researchers wrote that, in their naturally occurring experiment in which drusen collapsed without evidence of disease progression, the CC parameters were similar once the compensation strategy was applied before and after the drusen resolved.
Source: Shi Y, Chu Z, Wang L, et al. Validation of a compensation strategy used to detect choriocapillaris flow deficits under drusen with swept source OCT angiography. Am J Ophthalmol. July 1. [Epub ahead of print].
Short-term Effect of a Single Lapse in Anti-VEGF Treatment for DME Within Routine Clinical Practice
Anti-vascular endothelial growth factor therapy has been shown to be effective for DME, though the injections are costly and require frequent visits, which increases the risk for unintended treatment lapses. Because of this risk, investigators aimed to characterize the effects of an unintended treatment lapse in patients with DME undergoing anti-VEGF therapy.
This retrospective chart review compared patients seen in a multicenter institutional practice with DME exhibiting an unintended minimum three-month lapse in anti-VEGF treatment, with a control group of DME patients receiving regular anti-VEGF treatment without lapses. The primary outcome was the difference in central subfield thickness between the control group and the treatment lapse group at six months following treatment lapse. Here were the findings:
- A total of 164 patients were evaluated: 82 patients in the treatment lapse group and 82 patients in the control group.
- The average age was 65 years, and the average lapse in treatment was 6.2 ±3.5 months (range: three to 24 months).
- Comparison of data revealed no significant differences in CST between the lapse group (359.9 ±108.3 μm) and control group (335.4 ±94.6 μm; p=0.066) or in visual acuity between the lapse group (66.5 ±14.3) and control group (68.9 ±14.5; p=0.136).
- Study limitations included a relatively small sample size, its retrospective nature and that only a single lapse was evaluated.
Investigators wrote that an unintended, single, relatively short-term lapse in anti-VEGF treatment in patients with DME didn’t appear to result in significant anatomic or visual compromise upon resumption of regular follow-up and treatment.
SOURCE: Yalamanchili SP, Maatouk CM, Enwere DU, et al. The short-term effect of a single lapse in anti-vascular endothelial growth factor treatment for diabetic macular edemawithin routine clinical practice. Am J Ophthalmol 2020 ; July 5. [Epub ahead of print].
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 age: 48.37 ±12.30 years; 17 ±53.1 percent male). Here were some of the findings:
- The mean total scan vascular density for the superficial vascular complex was 42.28 ±4.03 percent; (CI, 40.63 to 43.93 percent) at baseline and 39.64 ±4.01 percent; (CI, 37.91 to 41.37 percent) at month 12 (p=0.69).
- For the deep vascular complex, the mean vascular density was 48.42 ±4.99 percent; (CI, 46.36 to 50.47 percent) at baseline and 45.69 ±4.63 percent; (CI, 43.69 to 47.70 percent) at month 12 (p=0.40).
- For the choriocapillaris, the mean vascular density was 64.42 ±3.36 percent; (CI, 63.04 to 65.81 percent) at baseline and 62.55 ±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].
Vascular Complexity Analysis in OCTA of DR
Researchers aimed to verify the feasibility of using vascular complexity features for objective differentiation of controls and nonproliferative diabetic retinopathy and proliferative DR patients.
This was a cross-sectional study conducted in a tertiary, subspecialty academic practice. The cohort included 20 control subjects, and 60 NPDR and 56 PDR patients. Three vascular complexity features-including vessel complexity index, fractal dimension and blood vessel tortuosity-were derived from each optical coherence tomography angiography image. A shifting-window measurement was further implemented to identify local feature distortions due to localized neovascularization and mesh structures in PDR.
Here were some of the findings:
- With mean value analysis of the whole image, only the vessel complexity index and blood vessel tortuosity were able to classify NPDR vs. PDR patients.
- Comparative shifting-window measurements revealed increased sensitivity of complexity feature analysis, particularly for NPDR vs. PDR classification.
- A multivariate regression model indicated that the combining all three vascular complexity features with shifting-window measurements provided the best classification accuracy for controls versus NPDR vs. PDR.
Researchers concluded that vessel complexity index and blood vessel tortuosity were the most sensitive in differentiating NPDR and PDR patients. They added that a shifting-window measurement increased the sensitivity significantly for objective optical coherence tomography angiography classification of diabetic retinopathy.
SOURCE: Alam M, Le D, Lim JI, et al. Vascular complexity analysis in optical coherence tomography angiography of diabetic retinopathy. Retina 2020; June 18. [Epub ahead of print].
Rates of Eye Care and Diabetic Eye Disease Among Insured Patients with Newly Diagnosed Type 2 Diabetes
Researchers determined rates of eye examinations and diabetic eye disease in the first five years after diagnosis of type 2 diabetes (DM2) among continuously insured adults, as part of a retrospective, longitudinal cohort study.
Insured patients ages 40 or older with newly diagnosed DM2 (n=42,684), and control patients without diabetes matched on age, sex and race were identified from a nationwide commercial claims database containing data from 2007 to 2015.
All patients were tracked for six years: one year prior to, and five years after, the index diabetes diagnosis. Receipt of eye care for individual patients was identified using International Classification of Diseases 9th edition (ICD-9) procedure codes or Current Procedural Terminology codes indicating an eye exam, as well as encounters indicating the patient was seen by an ophthalmologist. A diagnosis of diabetic eye disease was determined by using ICD-9 codes.
Main Outcome Measures included annual receipt of eye care as well as development of diabetic eye disease, namely diabetic retinopathy. Associations between these outcomes and demographic factors were tested with multivariable logistic regression.
Here were some of the findings:
- Diabetic patients received more eye exams than controls in each year, but no more than 40.4 percent of diabetics received an eye exam in any given year.
- Patients with Medicare Advantage received fewer eye exams at five years (OR 0.79, p<0.01) than those with private insurance, but were less likely to develop DR (OR 0.71, p<0.01).
- Hispanic patients had higher rates of DR (OR 1.60, p<0.01) and received fewer eye exams (OR 0.75, p<0.01) at five years, compared to white patients.
- Men received fewer eye exams (OR 0.84, p<0.01) and were more likely to develop DR at five years (OR 1.17, p<0.01) than women.
- Patients with higher education were more likely to receive an eye exam and less likely to develop DR.
Researchers determined that the majority of diabetic patients didn’t receive adequate eye care within the five years after initial diabetes diagnosis, despite having insurance. They suggested that efforts should be made to improve adherence to screening guidelines, especially for patients in vulnerable populations.
SOURCE: Gange WS, Xu BY, Lung K, et al. Rates of eye care and diabetic eye disease among insured patients with newly-diagnosed type 2 diabetes. Ophthalmology Retina 2020; July 9. [Epub ahead of print].
Novel Method for Averaging OCTA Images
Investigators developed a method of averaging optical coherence tomography angiography images to improve visualization of choriocapillaris structure.
They placed a stack of OCT angiographic data from vascular layers into the red-green-blue channels of a conventional digital color image. And they placed the superficial plexus in the blue channel, choriocapillaris in the green and deep vascular plexus in the red channel. The investigators registered the red-green-blue images derived from nine separate OCTA scans using an automatic registration sequence, and averaged the images. The averaged red-green-blue image was then split into the three averaged component layers. The flexible technique can use any vascular layer, such as macular neovascularization.
The utility of the imaging method was demonstrated by the imaging of two different diseases:
- One patient had a history of familial amyloidosis, hypertension, kidney failure, kidney transplantation and prednisone use, followed by central serous chorioretinopathy, which was treated by photodynamic therapy. She had alterations in retinal pigment epithelial pigmentation and widespread abnormalities of autofluorescence. She showed remarkably decreased vascular density and vessel configuration of the choriocapillaris.
- Another patient with pseudoxanthoma elasticum with subretinal drusenoid deposits at an early age also showed marked decreased choriocapillaris density and vascular configuration. These findings were compared with healthy controls of a similar age with no abnormalities.
Investigators wrote that the detailed method was capable of averaging choriocapillaris OCT angiographic images using a simple automatic method. They added that image averaging offers an opportunity to improve noisy OCTA images so that the vascular structure is visible.
SOURCE: Spaide RF, Ledesma-Gil G. Novel method for image averaging of optical coherence tomography angiography images. Retina 2020; Jun 26. [Epub ahead of print].
ADVERUM COMPLETES DOSING IN PHASE I TRIAL OF GENE THERAPY FOR AMD
Adverum Biotechnologies announced the completion of patient dosing in cohort 4 of OPTIC, a Phase I clinical trial for its gene therapy product, ADVM-022. The multicenter, open-label Phase I, dose-ranging trial is designed to assess the safety and tolerability of a single intravitreal administration of ADVM-022 in patients with wet AMD who are responsive to anti-vascular endothelial growth factor treatment. ADVM-022 uses a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Read more.
SOURCE: Adverum Biotechnologies, July 2020
Outlook Completes Patient Enrollment for NORSE 2 Study
Outlook Therapeutics announced the completion of patient enrollment in its NORSE 2 clinical trial for ONS-5010/Lytenava (bevacizumab-vikg), an investigational ophthalmic formulation of bevacizumab for use in retinal indications. The NORSE 2 clinical trial commenced patient enrollment in July 2019, and Outlook says it’s now enrolled 227 patients at 39 clinical trial sites in the United States. Patients in the trial are being treated for 12 months. The primary endpoint for NORSE 2 is the difference in proportion of patients who gain at least 15 letters in best-corrected visual acuity at 11 months for ONS-5010 dosed on a monthly basis, compared to Lucentis, which is being dosed quarterly per the PIER regimen. If approved, ONS-5010 will be the first on-label ophthalmic formulation of bevacizumab for treating retinal diseases, the company says. Read more.
SOURCE: Outlook Therapeutics, July 2020
MEIRAGTX SHARES DATA ON RP TREATMENT
MeiraGTx Holdings, a clinical-stage gene therapy company, recently announced six-month data from the ongoing Phase I/II clinical trial (Trial number: NCT03252847) of AAV-RPGR, an investigational gene therapy in development for the treatment of patients with X-linked retinitis pigmentosa with genetically confirmed variants in the RPGR gene. The company says significant improvement in vision was demonstrated in the dose-escalation phase of the trial, and that AAV-RPGR was found to be “generally well tolerated.” MeiraGTx and Janssen Pharmaceuticals, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, are jointly developing AAV-RPGR as part of a broader collaboration to develop and commercialize gene therapies for the treatment of inherited retinal diseases. Read more.
SOURCE: MeiraGTx, July 2020
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.
SOURCE: Iveric, June 2020
Editorial Endorses Paper Supporting Term "Nonexudative Macular Neovascularization"
In an editorial in the July edition of Ophthalmology Retina, authors wrote that a Laiginhas, et al. review in July Ophthalmology Retina that supports the term nonexudative macular neovascularization (NEMNV) appropriately proposes a unification of the nomenclature to reduce confusion of terminology in the literature. The authors wrote that, this lesion type was identified as a plaque with indocyanine green angiography decades ago, but the advent of OCT angiography has facilitated the identification of this form of neovascularization and refocused interest in this disorder. In the review, the prevalence of NEMNV in the fellow eyes of patients with nAMD and exudation in the first eye was approximately 5 to 25 percent, which the editorial authors noted was significant. They added that this was an even more remarkable finding given that approximately 25 percent of eyes with NEMNV demonstrated exudation within one to two years of baseline detection. Read more.
ALIMERA INITIATES TRIAL TO EVALUATE ILUVIEN AS BASELINE DME THERAPY
Alimera Sciences initiated the company’s NEW DAY clinical trial, a prospective, randomized, controlled, multicenter study of the use of Iluvien (fluocinolone acetonide intravitreal implant) 0.19 mg as a first-line therapy in patients diagnosed with diabetic macular edema. The trial is expected to enroll 320 treatment-naïve, or almost naïve, DME patients in approximately 42 sites around the United states. Read more.
SOURCE: Alimera Sciences, July 2020
NEW EYE DROPS MAY PREVENT A COMMON CAUSE OF BLINDNESS
Researchers at Columbia University’s Irving Medical Center have developed eye drops that could prevent vision loss after retinal vein occlusion. A study in mice suggested that the experimental therapy—which targets a common cause of neurodegeneration and vascular leakage in the eye—could have broader therapeutic effects than existing drugs. Published in Nature Communications
, the study says the new treatment targets an enzyme called caspase-9. Researchers discovered that when blood vessels are injured by retinal vein occlusion, caspase-9 becomes uncontrollably activated, triggering processes that can damage the retina. They found that a topical, highly selective caspase-9 inhibitor improved a variety of clinical measures of retinal function in a mouse model, and that it reduced swelling, improved blood flow and decreased neuronal damage in the retina. Read more.
SOURCE: Columbia University Irving Medical Center, June 2020
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.
SOURCE: Quantel Medical, June 2020
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. Read more.
SOURCE: jCyte, June 2020
ASCLEPIX ANNOUNCES $35 MILLION SERIES A FINANCING
AsclepiX Therapeutics closed a $35 million Series A financing. The company says the proceeds will fund Phase I/IIa clinical trials of AXT107, the AsclepiX’s lead investigational drug, for the treatment of diabetic macular edema, wet age-related macular degeneration and macular edema secondary to retinal vein occlusion. Read more.
SOURCE: AsclepiX Therapeutics, June 2020
OCUTRX VISION SELECTS KARTEN TO FINALIZE OCULENZ AR HEADSET DESIGN
Ocutrx Vision Technologies, a global developer and manufacturer of augmented reality (AR) and extended reality (XR) headsets, says it will soon come out with the finished version of the Oculenz ARwear headset; Karten Design was chosen to enhance design elements for commercial launch next year. The new headset, with a resolution of 60 pixels-per-degree, will be the highest-resolution AR/XR headset in the market, according to the company. In the first quarter of 2021, Ocutrx is planning to release the commercial version of its AR/XR headset that the company says helps improve vision for patients with low vision from conditions such as advanced macular degeneration. Read more.
SOURCE: Ocutrx Vision Technologies, June 2020
U.S. GOVERNMENT SUES REGENERON
The U.S. Attorney’s Office in Masachusetts recently announced that the government has filed a civil False Claims Act complaint
against Regeneron. The complaint alleges that “Regeneron paid tens of millions of dollars in kickbacks for its macular degeneration drug Eylea (aflibercept), using a foundation as a conduit to cover co-pays for Eylea.” For its part, in a statement
Regeneron states, “There is no merit to the civil complaint filed by the U.S. Attorney for the District of Massachusetts. It is unfortunate that a misguided lawsuit is attempting to assign wrongful intent to entirely legal conduct. Regeneron has fully cooperated with the government's investigation and will vigorously defend the company's case.”
SOURCE: Regeneron, June 2020
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