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.
C5 Inhibitor Avacincaptad Pegol for GA Due to AMD
Researchers wrote that avacincaptad pegol, a complement C5 inhibitor, met its prespecified primary efficacy endpoint in reducing the mean GA growth rate in participants with AMD and was well-tolerated in a randomized Phase II/III pivotal trial. They added that the complement pathway may play a key role in the pathogenesis of age-related macular degeneration.
They assessed the safety and efficacy of avacincaptad pegol (Zimura), a C5 inhibitor, in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study). The international, prospective, randomized, double-masked, sham-controlled Phase II/II clinical trial included 286 participants with GA secondary to AMD.
The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence at three time points: baseline; month six; and month 12.
Here were some of the findings:
- The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4 percent (p=0.0072) for the avacincaptad pegol 2 mg cohort and 27.8 percent (p=0.005) for the avacincaptad pegol 4 mg cohort as compared to their corresponding sham cohorts.
- The results for both dose groups were statistically significant.
- Avacincaptad pegol was generally well-tolerated after monthly administration over 12 months.
- No avacincaptad pegol-related adverse events or inflammation were reported.
- No ocular serious adverse events and no cases of endophthalmitis were found.
- The most frequent ocular adverse events were related to the injection procedure.
Researchers concluded that intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12-month period. They wrote that, as C5 inhibition theoretically preserves C3 activity, it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).
SOURCE: Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: A randomized pivotal phase II/III trial. Ophthalmology 2020; Aug 31. [Epub ahead of print].
Progression of Photoreceptor Degeneration in GA Secondary to AMD
Researchers wrote that sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy secondary to age-related macular degeneration. Toward that end, they quantified photoreceptor degeneration outside regions of GA in eyes with nonexudative AMD, evaluated its association with future GA progression and characterized its spatio-temporal progression.
In the monocenter cohort study ("Directional Spread in Geographic Atrophy") and analysis of data from a normative data study at a tertiary referral center, 158 eyes of 89 individuals (51 women and 38 men) with a mean age of 77.7 ±7.1 years (median area of GA of 8.87 mm2 [IQR, 4.09 to 15.60]; median follow-up of 1.1 years [IQR, 0.52 to 1.7 years]) were included, as well as 93 normal eyes from 93 participants.
Researchers segmented longitudinal spectral-domain optical coherence tomography volume scans (121 B-scans across 30 degrees x 25 degrees) with a deep learning pipeline and standardized them in a pointwise manner with age-adjusted normal data (z scores). They quantified the outer nuclear layer (ONL), photoreceptor inner segment (IS) and outer segment (OS) thickness along evenly spaced contour lines surrounding GA lesions. In addition, they applied linear mixed models to assess the association between photoreceptor-related imaging features and GA progression rates, and characterized the pattern of photoreceptor degeneration over time.
The main outcome measure was association of ONL thinning with follow-up time (after adjusting for age, retinal topography [z score] and distance to the GA boundary).
Here are some of the findings:
- The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; CI, 0.80 to 0.85; compared with manual markings) and revealed a marked interpatient variability in photoreceptor degeneration.
- The ellipsoid zone loss-to-GA boundary distance and OS thickness were prognostic for future progression rates.
- Outer nuclear layer and IS thinning over time was significant even when adjusting for age (estimate of -0.16 µm/y; CI, -0.30 to -0.02) and proximity to the GA boundary (estimate of -0.17 µm/y; CI, -0.26 to -0.09).
Researchers found that distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable. The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Researchers concluded that macula-wide photoreceptor laminae thinning represents a potential candidate endpoint for monitoring treatment effects, beyond GA lesion size progression.
SOURCE: Pfau M, von der Emde L, de Sisternes L, et al. Progression of photoreceptor degeneration in geographic atrophy secondary to age-related macular degeneration. JAMA Ophthalmol. 2020; Aug. 13. [Epub ahead of print].
Progression to Late AMD in AREDS 1 and 2
Researchers analyzed associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration and its subtypes. They also analyzed progression to large drusen and interactions with AMD genotype.
In the post hoc analysis of two controlled clinical trial cohorts—Age-Related Eye Disease Study (AREDS; recruitment 1992 to 1998) and AREDS2 (recruitment 2006 to 2008)—researchers assessed eyes with no late AMD at baseline in AREDS participants (n=4,504) and AREDS2 participants (n=3,738): a total of 14,135 eyes. The mean age was 71 ±6.7 years, and 56.5 percent were female.
Fundus photographs were collected at annual study visits and graded centrally for late AMD. The dietary intake of multiple nutrients was calculated for each participant from food-frequency questionnaires.
Main outcome measures included progression to late AMD, geographic atrophy, neovascular AMD and (separate analyses) large drusen.
Here were some of the findings:
• Over a median follow-up of 10.2 years, of the 14,135 eyes, 32.7 percent progressed to late AMD.
• For nine nutrients (vitamins A, B6 and C; folate, β-carotene, lutein/zeaxanthin, magnesium, copper and alcohol), high intake levels were significantly (p≤0.0005) associated with decreased risk of late AMD.
• For three nutrients (saturated fatty acid, monounsaturated fatty acid and oleic acid) high intake levels were significantly associated with increased risk.
• Similar results were observed for GA.
• Regarding neovascular AMD, nine nutrients were nominally associated with decreased risk (vitamins A and B6; β-carotene, lutein/zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid and alcohol) and three with increased risk (saturated fatty acid, monounsaturated fatty acid and oleic acid).
• In separate analyses (n=5,399 eyes of 3,164 AREDS participants), 12 nutrients were nominally associated with decreased risk of large drusen.
Researchers concluded that a higher dietary intake of multiple nutrients—including minerals, vitamins and carotenoids—was associated with decreased risk of progression to late AMD. These associations were stronger for GA than for neovascular AMD. The researchers also noted that the same nutrients tended to have protective associations against large drusen development. Furthermore, strong genetic interactions existed for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. Researchers suggested that the data may justify further research into underlying mechanisms and randomized trials of supplementation.
SOURCE: Agrón E, Mares J, Clemons TE, et al. Dietary nutrient intake and progression to late age-related macular degeneration in the Age-Related Eye Disease Studies 1 and 2. Ophthalmology 2020; Aug. 25. [Epub ahead of print].
Using Machine Learning to Predict AMD Progression
Researchers wrote that existing prediction models for advanced age-related macular degeneration are based on a restrictive set of risk factors. They aimed to develop a comprehensive prediction model, applying a machine learning algorithm allowing selection of the most predictive risk factors automatically.
Two population-based cohort studies were utilized. The Rotterdam Study I (RS-I, training set) included 3,838 participants ages 55 years or older, with a median follow-up period of 10.8 years and with 108 incident cases of advanced AMD. The ALIENOR study (test set) included 362 participants ages 73 years or older, with a median follow-up period of 6.5 years and with 33 incident cases of advanced AMD.
The prediction model used the bootstrap lasso for survival analysis to select the best predictors of incident advanced AMD in the training set. Predictive performance of the model was assessed using the area under the receiver operating characteristic curve. Main outcome measures included incident advanced AMD (atrophic and/or neovascular), based on standardized interpretation of retinal photographs.
The prediction model retained:
• a combination of phenotypic predictors (based on the presence of intermediate drusen; hyper-pigmentation in one or both eyes; and Age-Related Eye Disease Study simplified score);
• a summary genetic risk score based on 49 single nucleotide polymorphisms;
• diet quality;
• education; and
• pulse pressure.
Here were some of the findings:
• The cross-validated AUC estimation in RS-I was:
o 0.92 (0.88 to 0.97) at five years;
o 0.92 (0.90 to 0.95) at 10 years; and
o 0.91 (0.88 to 0.94) at 15 years.
• In ALIENOR, the AUC reached 0.92 at five years (0.87 to 0.98).
• In terms of calibration, the model tended to underestimate the cumulative incidence of advanced AMD for the high-risk groups, especially in ALIENOR.
Researchers reported that the prediction model reached high discrimination abilities, paving the way toward making precision medicine for AMD patients a reality in the not-too-distant future.
SOURCE: Ajana S, Cougnard-Grégoire A, Colijn JM, et al. Predicting progression to advanced age-related macular degeneration from clinical, genetic and lifestyle factors using machine learning. Ophthalmology 2020;Sep 2. [Epub ahead of print].
Risk of Systemic Adverse Events Following Intravitreal Bevacizumab, Ranibizumab and Aflibercept in Routine Clinical Practice
Researchers wrote that intravitreal anti-VEGF pharmacotherapy plays a central role in the management of neovascular age-related macular degeneration, diabetic retinal disease and retinal venous occlusive disease. They added that, within clinical trials, rates of systemic serious adverse events following anti-VEGF treatment have been low; however, the comparative systemic safety profile of common anti-VEGF agents remains incompletely understood. The goal of this study was to compare the systemic safety of intravitreal bevacizumab, ranibizumab and aflibercept in real-world practice.
As part of the retrospective cohort study, researchers used a large U.S. administrative claims database of commercially insured and Medicare Advantage enrollees to identify adult cohorts receiving initial anti-VEGF injections for nAMD, DRD and RVO between January 1, 2007 and June 30, 2018. They included individuals with one year of insurance coverage prior to initial treatment.
Researchers compared predefined systemic outcomes between anti-VEGF agents occurring within 180 days of treatment initiation using propensity score-weighted Cox proportional hazards models.
Primary outcomes were acute myocardial infarction (MI), acute cerebrovascular disease (CVD), major bleeding and all-cause hospitalization. Here were some of the findings:
- A total of 87,844 individuals received initial anti-VEGF injections for nAMD, DRD and RVO (69,007, bevacizumab; 10,895, ranibizumab; and 7,942, aflibercept).
- Post-injection, 180-day event rates per 100 patients for MI, CVD, major bleeding and all-cause hospitalization were similar, respectively, for:
- bevacizumab (0.64, 0.59, 0.34 and 10.41);
- ranibizumab (0.62, 0.53, 0.40 and 9.44); and
- aflibercept (0.63, 0.60, 0.20 and 9.88).
- No differences were identified in the risk of MI, CVD, major bleeding or all-cause hospitalization when comparing the risk-adjusted effect of treatment initiation, with:
- bevacizumab vs. ranibizumab (all p>0.05):
- MI: HR: CI, 0.96 (0.74,1.25);
- CVD: 1.04 (0.78,1.38);
- Major bleeding: 0.85 (0.61,1.19); and
- All-cause hospitalization: 1.03 (0.96,1.10); or
- bevacizumab vs. aflibercept (all p>0.05):
- MI: HR: CI, 0.95 (0.68,1.33);
- CVD: 0.99 (0.71, 1.38);
- Major bleeding: 1.02 (0.60,1.74); and
- All-cause hospitalization: 1.01 (0.93,1.10); or
- aflibercept vs. ranibizumab (all p>0.05):
- MI: HR: CI, 0.91 (0.62,1.35);
- CVD: 1.12 (0.74,1.69);
- Major bleeding: 0.96 (0.53,1.73).
- All-cause hospitalization: 1.02 (0.92,1.13).
Researchers observed no differences in the risk of acute myocardial infarction, cerebrovascular disease, major bleeding or all-cause hospitalization following treatment initiation with intravitreal bevacizumab, ranibizumab or aflibercept during routine clinical practice.
SOURCE: Maloney MH, Payne SR, Herrin J, et al. Risk of systemic adverse events following intravitreal bevacizumab, ranibizumab, and aflibercept in routine clinical practice. Ophthalmology 2020; Aug. 8. [Epub ahead of print.]
Anti-VEGF Agents’ Efficacy in Wet AMD
When initiating anti-vascular endothelial growth factor treatment for individuals with neovascular age-related macular degeneration, knowledge of prognostic factors is important for advising patients and guiding treatment. Scientists hypothesized that eyes with greater fluctuation in retinal thickness over time would have worse outcomes than eyes with less variation. They investigated whether visual and anatomic outcomes in nAMD eyes initiating anti-VEGF treatment were associated with fluctuations in retinal thickness.
In the study using data from the Comparison of Age-Related Macular Degeneration Treatments Trials and the Inhibition of VEGF in Age-Related Choroidal Neovascularization randomized clinical trial, individuals with previously untreated nAMD were included. Data were collected from February 2008 to November 2012, and analyzed from April 2017 to April 2020.
Foveal center point thicknesses (FCPTs) were extracted from 1,165 study eyes from CATT and 566 study eyes from the IVAN trial, excluding those with three measurements or less. The researchers calculated the standard deviation of FCPT for each eye and grouped them by FCPT SD quartile. They quantified the associations of FCPT SD quartile with outcomes at month 24 or the last available visit by linear or logistic regression, adjusting for baseline best-corrected visual acuity, randomized allocations to drug and treatment regimen, BCVA, development of fibrosis and development of macular atrophy.
Of the 1,731 participants, 1,058 (61.1 percent) were female, and the mean age was 78.6 years. The median (interquartile range) FCPT SD was 40.2 (27.1 to 61.2) in the IVAN cohort and 59 (38.3 to 89.4) in the CATT cohort.
Here were some of the findings:
• After adjusting for baseline BCVA and trial allocations, BCVA worsened significantly across the quartiles of FCPT SD; the difference between the first and fourth quartiles was -6.27 Early Treatment Diabetic Retinopathy Study letters (CI, -8.45 to -4.09).
• The risk of developing fibrosis and macular atrophy also increased across FCPT SD quartiles.
• Odds ratios ranged from:
o 1.40 (CI, 1.03 to 1.91) for quartile two, to 1.95 (CI, 1.42 to 2.68) for quartile four for fibrosis; and
o from 1.32 (CI, 0.90 to 1.92) for quartile two, to 2.10 (CI, 1.45 to 3.05) for quartile four for macular atrophy.
Scientists determined that greater variation in retinal thickness in eyes with nAMD during treatment with anti-VEGF was associated with worse BCVA, and development of fibrosis and macular atrophy in the post hoc analyses, despite protocol-directed treatment frequency. They advised that practitioners may want to consider variation in retinal thickness when advising patients about their prognosis.
Source: Evans RN, Reeves BC, Maguire MG, et al. Associations of variation in retinal thickness with visual acuity and anatomic outcomes in eyes with neovascular age-related macular degeneration lesions treated with anti-vascular endothelial growth factor agents. JAMA Ophthalmol 2020; Aug 20. [Epub ahead of print].
Effect of Aflibercept on DR Severity & Visual Function
Researchers evaluated the effect of intravitreal aflibercept on diabetic retinopathy severity and visual function in subjects with proliferative diabetic retinopathy without diabetic macular edema, as part of a multicenter clinical trial, the RECOVERY study.
Forty eyes of 40 subjects with PDR and no DME were enrolled in this study. Subjects were randomized into monthly and quarterly 2 mg aflibercept injection cohorts and treated over a period of 12 months. All subjects underwent ultra-widefield fundus imaging, including pseudocolor and fluorescein angiography using an Optos 200Tx device.
Main outcome measures included severity of retinopathy at baseline, month six, and month 12, evaluated by certified reading center graders using the diabetic retinopathy severity scale. DRSS scores were correlated with the 25-item and 39-item Visual Function Questionnaire scores at baseline and month 12.
Mean age of the subjects was 48.2 years (range: 25 to 75); mean duration of diabetes mellitus was 16.1 years (range: two to 36 years); and median HbA1c was 8.8 percent (IQR: 7.4 to 10). Here were some of the findings:
• Both monthly and quarterly groups demonstrated a statistically significant regression in DRSS from baseline to month 12 (p<0.001).
• The monthly group demonstrated a statistically significant greater regression of DRSS score at the month six visit compared to the quarterly group (p=0.019). However, the difference between the groups became statistically insignificant at the month 12 visit (p=0.309).
• At month 12, no difference was found in mean VFQ-25 and VFQ-39 composite scores between the monthly group (p=0.947) and quarterly group (p=0.921).
• At month 12, the improvement in mean composite scores below was significantly correlated with improvement in DRSS:
o for VFQ-25: r=0.384, p=0.039; and
o for VFQ-39: r=0.361, p=0.046.
Researchers wrote that, in this study of eyes with PDR without DME, monthly and quarterly aflibercept injection groups showed significant improvement in diabetic retinopathy severity at month 12 compared to baseline. They added that the improvement in DRSS was associated with an improvement in VFQ composite score.
SOURCE: Alagorie AR, Velaga S, Nittala MG, et al. Effect of aflibercept on diabetic retinopathy severity and visual function in the RECOVERY study for proliferative diabetic retinopathy. Ophthalmol Retina 2020; Aug 31. [Epub ahead of print].
Aflibercept With or Without Suprachoroidally Injected Triamcinolone Acetonide Formulation (CLS-TA) for DME
This study evaluated the potential safety, efficacy and durability advantages of CLS-TA administered suprachoroidally in conjunction with intravitreal aflibercept compared to aflibercept monotherapy for the treatment of diabetic macular edema.
TYBEE was a prospective, randomized, controlled, double-masked study. Subjects were randomized 1:1 to CLS-TA in conjunction with aflibercept (active) or aflibercept monotherapy (control) and tracked over 24 weeks.
Participants included treatment-naïve DME subjects with best corrected visual acuity of 20 to 70 letters and central subfield retinal thickness >300 μm.
Subjects in the active group (n=36) received CLS-TA in conjunction with aflibercept at baseline and week 12. Subjects in the control group (n=35) received aflibercept at baseline, weeks four, eight and 12. All subjects were eligible to receive aflibercept as needed at weeks four, eight, 16 and 20 per additional therapy criteria: presence of macular edema CST ≥340 μm; increase in CST of >50 μm associated with a decrease in BCVA (≥6 letters from the previous visit or 10 letters from the best measurement)
The main outcome measure included the mean change in BCVA from baseline; treatment differences were assessed with a two-sided significance level of 0.10.
Here were some of the findings:
- Mean changes from baseline in BCVA at week 24 weren’t statistically different in the active and control groups (+11.4 and +13.8 letters, p=0.288, intention to treat (ITT); +12.3 and +13.5 letters, p=0.664, per protocol (PP) populations, respectively).
- Greater improvement in CST was seen in the active group vs. controls (-212.1 μm and -178.6 μm, p=0.089, ITT; -226.5 μm and -176.1 μm, p=0.035, PP, respectively).
- Eyes in the active group received an average of 2.6 treatments, while eyes in the control group received an average of 4.6 treatments.
- No treatment-related serious AEs were observed.
- Elevated IOP and cataract events trended higher in the active group vs. the control group.
Scientists found that CLS-TA administered suprachoroidally in conjunction with IVT aflibercept in the treatment of DME provided no visual benefit at 24-week follow-up compared with IVT aflibercept monotherapy, although it offered a modest anatomical benefit and the potential to reduce treatment burden. They also reported that ocular adverse events were low for both arms.
SOURCE: Barakat MR, MD, Wykoff CC, Gonzalez V, et al. Aflibercept with or without suprachoroidal CLS-TA for diabetic macular edema: A randomized, double-masked, parallel-design, controlled study. Ophthalmol Retina 2020; Aug. 19. [Epub ahead of print].
Effect of ICD-9 to ICD-10 Transition on Accuracy of Codes for Stage of DR and Related Complications: Results from the CODER Study
When International Classification of Disease version 9 (ICD-9) transitioned to ICD-10, there was a marked increase in the complexity of ICD codes, with potential for improved specificity in clinical database research. This study aimed to characterize the accuracy of coding for stage of diabetic retinopathy and DR-related complications (including vitreous hemorrhage, retinal detachment and neovascular glaucoma) during this transition.
This retrospective chart review of three time periods corresponded to the use of: ICD-9 (2014 to 2015): “early” use of ICD-10 (2015 to 2016); and “late” use of ICD-10 (2018 to 2019).
Subjects were 18 years or older with a DR diagnosis at a multispecialty academic institution
Investigators generated positive predictive value (PPV), negative predictive value (NPV), sensitivity, specificity, and kappa (κ) statistics for each diagnosis. They used generalized estimating equations (GEE) models to assess the significance of the variables.
The main outcome was the proportion of agreement between the ICD code and documented chart standard for stage of DR and DR-related complications.
- A total of 600 individuals were included in the study (average age, 61 years, range, 25 to 93). Overall, there was substantial agreement between the ICD codes for stage of DR and documented standard (κ=0.66).
- The proportion of ICD codes in agreement with the documented standard diagnosis increased with time: 66.5 percent for ICD-9; 78.5 percent for “early” ICD-10; and 83.3 percent for “late” ICD-10.
- The odds of agreement were 2.67 (CI, 1.49 to 4.76, p<0.001) times greater for “early” ICD-10 codes and 3.96 (CI, 2.34 to 6.69, p<0.0001) times greater for “late” ICD-10 codes, compared to ICD-9.
- For specific codes, the overall PPV/NPV/sensitivity/specificity for NPDR and PDR were excellent (>90 percent).
- The odds of agreement were 19.70 (CI, 11.54 to 33.64, p<0.0001) times greater for proliferative DR than non-PDR.
- Compared to the stage of DR, DR-related diagnoses were overall less accurately coded (κ=0.61, 0.48, 0.52 for vitreous hemorrhage, retinal detachment and neovascular glaucoma).
Investigators determined that coding in ICD-10 is more accurate than ICD-9, particularly for PDR compared with non-PDR. They added that the increased accuracy emphasizes the potential for ICD-10 coding to be used effectively in database research.
Source: Cai CX, Michalak SM, Stinnett SS, et al. Effect of ICD-9 to ICD-10 transition on accuracy of codes for stage of diabetic retinopathy and related complications: Results from the CODER study. Ophthalmol Retina 2020; Aug 15. [Epub ahead of print].
Vitreous Levels of VEGF, Stromal Cell-derived Factor-1α & Angiopoietin-like Protein 2 in Active PDR
Researchers determined the vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1α (SDF-1α) and angiopoietin-like protein 2 (ANGPTL2) in individuals with active proliferative diabetic retinopathy, and assessed their contributions to different clinical presentations of active PDR.
The case-control study included 31 eyes with active PDR and 10 eyes with idiopathic macular hole as controls. Eyes with active PDR were divided into three subgroups: vitreous hemorrhage (VH), tractional retinal detachment (TRD) caused by active fibrovascular membrane (FVM), and coexistence of VH and TRD with FVM. Vitreous samples obtained during vitrectomy were analyzed for concentrations of VEGF, SDF-1α and ANGPTL2.
Here were some of the findings:
- Vitreous level of the following were significantly higher in eyes with active PDR than in controls):
- VEGF (2,021 [168 to 6,550] pg/ml vs. 110.1 [74.5 to 236] pg/ml)(p<0.001);
- SDF-1α (517 [194 to 1,044] pg/ml vs. 388 [320 to 535] pg/ml)(p=0.002); and
- ANGPTL2 (725 [131 to 1,590] ng/ml vs. 196 [75.9 to 437] ng/ml)(p<0.001).
- The concentrations in each active PDR subgroup were also significantly higher than in the control group (p<0.05).
- The vitreous level of ANGPTL2 was significantly higher in eyes with TRD caused by FVM (1,033 ±401 ng/ml) than in eyes with VH (561 ±237 ng/ml)(p=0.008).
Researchers reported that high levels of SDF-1α, ANGPTL2 and particularly VEGF appeared to be associated with PDR. They wrote that, since the vitreous levels of ANGPTL2 tended to be higher in eyes with active fibrovascular tractional detachment, vitreous levels of this chemokine seemed to be affected by the clinical presentation of vascularly active PDR eyes.
SOURCE: Keles A, Sonmez K, Erol YO, et al. Vitreous levels of vascular endothelial growth factor, stromal cell-derived factor-1α, and angiopoietin-like protein 2 in patients with active proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2020; Aug. 19. [Epub ahead of print].
NOVARTIS REPORTS TOPLINE RESULTS FROM PHASE III TRIAL OF BEOVU VS. eylea
Novartis reported the Phase III KITE study assessing the efficacy and safety of Beovu (brolucizumab) 6 mg in diabetic macular edema met its primary and key secondary endpoints, demonstrating non-inferiority vs. Eylea (aflibercept) 2 mg in mean change in best-corrected visual acuity at year one (week 52). Since Beovu has been dealing with issues regarding inflammation in some patients, physicians will be interested to hear that the company says the rate of intraocular inflammation in the study was equivalent between Beovu and Eylea. Read more.
SOURCE: Novartis, September 2020
GENENTECH INITIATES PHASE III TRIAL INVESTIGATING PDS FOR DR
Genentech initiated a Phase III clinical trial investigating the Port Delivery System with ranibizumab for people with diabetic retinopathy. PDS is a permanent refillable eye implant, approximately the size of a grain of rice, which continuously delivers a customized formulation of ranibizumab over a period of months. Pavilion, a Phase III, multicenter, randomized study, will evaluate the efficacy, safety and pharmacokinetics of PDS for the treatment of DR in people without diabetic macular edema. The primary endpoint of Pavilion is the percentage of patients who achieve a two-step or greater improvement in DR severity from baseline at week 52, as measured by the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale. Read more.
SOURCE: Genentech, August 2020
GEMINI ENROLLS FIRST PATIENT IN PHASE IIA STUDY OF GEM103
Gemini Therapeutics initiated enrollment in its Phase IIa ReGAtta study, evaluating GEM103, a recombinant, human complement factor H for the treatment of individuals with geographic atrophy secondary to dry age-related macular degeneration. Read more.
SOURCE: Gemini Therapeutics, September 2020
GYROSCOPE GETS FDA NOD FOR ORBIT SUBRETINAL DELIVERY SYSTEM, INITIATES PHASE II PROGRAM EVALUATING GENE THERAPY FOR DRY AMD
Gyroscope Therapeutics announced the FDA granted 510(k) clearance for the Orbit Subretinal Delivery System, indicated for microinjection into the subretinal space at the back of the eye. The associated procedure is designed to avoid damaging the structure of the eye by preventing the need for a vitrectomy, and it eliminates the need to create a retinotomy to access the subretinal space. Read more.
In addition, the company initiated a Phase II clinical trial program evaluating its investigational gene therapy, GT005, for the treatment of geographic atrophy secondary to dry age-related macular degeneration. GT005 is a one-time AAV-based gene therapy delivered under the retina. The trial aims to determine if GT005 can potentially slow the progression of GA. Gyroscope plans to conduct two Phase II trials evaluating GT005. The first, EXPLORE, is a multicenter, randomized trial evaluating the safety and efficacy of GT005 administered as a single subretinal injection. Read more.
SOURCE: Gyroscope Therapeutics Limited, August 2020
4DMT’S FIRST PATIENT DOSED IN PHASE I/II TRIAL OF 4D-125
4D Molecular Therapeutics announced the first patient was dosed in a Phase I/II clinical trial of 4D-125 for x-linked retinitis pigmentosa. 4D-125 is an AAV gene therapy with a proprietary vector designed to deliver a functional copy of the RPGR gene to photoreceptors in the retina. The open-label, dose-exploration and -expansion study is expected to enroll approximately 18 male patients with x-linked retinitis pigmentosa, and assess the preliminary safety, tolerability and biological activity of a single intravitreal injection of 4D-125, in addition to the effect of 4D-125 on visual function and retinal degeneration. Read more.
SOURCE: 4D Molecular Therapeutics, August 2020
LUMITHERA AND DIOPSYS COLLABORATE AND ENROLL FIRST SUBJECT IN ELECTROLIGHT STUDY, LUMITHERA RECEIVES $1.5 MILLION NEI GRANT
LumiThera is collaborating with Diopsys, a provider of visual electrophysiology solutions, to help eye-care professionals accurately and objectively measure retinal and visual pathway function. The collaboration supports a prospective pilot clinical trial in U.S. subjects that will evaluate the ability of the “photobiomodulation” treatment using the Valeda Light Delivery System to improve electroretinogram outcomes in subjects with dry AMD. Read more.
In addition, LumiThera received a small business innovative research Phase II grant from the National Institutes of Health and the National Eye Institute to support a prospective, randomized, multicenter human clinical trial of its light-delivery system in U.S. subjects diagnosed with diabetic retinopathy and diabetic macular edema. Read more.
SOURCE: LumiThera, September 2020
AGTC ANNOUNCES PUBLICATION OF PRECLINICAL DATA THAT SUPPORT CLINICAL DEVELOPMENT OF GENE THERAPY PROGRAM
Applied Genetic Technologies Corporation announced that preclinical data validating the transgene (hRPGRco) being evaluated in the company’s ongoing Phase I/II clinical trial in individuals with x-linked retinitis pigmentosa were published in the July 15, print issue of Human Gene Therapy
. The studies, which evaluated the safety and efficacy of hRPGRco and another XLRP transgene in a canine model of XLRP, demonstrated higher RPGR gene expression than the other transgene at all dose levels evaluated. Following subretinal administration using AGTC’s proprietary AAV2tYF vector, each of the XLRP transgenes corrected rod-cone opsin mislocalization, but the hRPGRco transgene demonstrated a broader therapeutic index. Read more.
SOURCE: Applied Genetic Technologies Corporation, August 2020
QUANTEL LAUNCHES MOSAR IMAGING SYSTEM
Quantel Medical launched Mosar, a new optional imaging system, dedicated to the Easyret yellow retinal laser. Mosar is composed of an HD camera, a screen and a computer. Designed to enhance retinal laser treatment procedures and patient follow-up, Quantel says the new imaging system offers a user-friendly software interface. Read more.
SOURCE: Quantel Medical, September 2020
BVI INTRODUCES PATIENT PACKS
BVI released a line of Patient Packs that it says will help U.S. ophthalmologists bring patients back to the office and surgical suite “with confidence.” BVI Patient Packs provide a ready-to-use package that includes a face mask, bouffant cap, shoe covers and an optional isolation gown along with patient instructions. Read more.
SOURCE: BVI, September 2020
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