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.
Real-world Outcomes Following 12 Months of Intravitreal Aflibercept Monotherapy in DME: APOLLON Study
Researchers reported the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema in French clinical practice, as part of APOLLON, a prospective, observational cohort study of individuals with DME.
Effectiveness was evaluated by change from baseline in best-corrected visual acuity at 12 months in treatment-naïve patients (i.e., hadn’t received any anti-vascular endothelial growth factor agent, laser or steroid at IVT-AFL treatment start) and previously-treated patients (i.e., previously treated with anti-VEGF agents other than IVT-AFL, laser or steroids at IVT-AFL treatment start). Secondary endpoints included change in central retinal thickness over 12 months, frequency of injections and proportion of patients with safety events. Here were some of the findings:
• Of the 147 individuals followed for at least 12 months and included in the effectiveness analysis, 52.4 percent (n=77) were treatment-naïve and 47.6 percent (n=70) were previously treated.
• Mean (standard deviation) BCVA score at baseline was 62.7 (14.3) Early Treatment Diabetic Retinopathy Study letters in treatment-naïve individuals and 60 (13.7) ETDRS letters in previously-treated patients.
• At month 12, mean change in BCVA was + 7.8 ±12.3 letters in treatment-naïve individuals and +5 ±11.3 letters in previously-treated patients.
• Mean CRT decreased in both cohorts.
• The mean number of IVT-AFL injections at month 12 was 7.6 ±2.5 for treatment-naïve individuals and 7.6 ±2.3 for previously-treated individuals. Of 388 people included in the safety analysis, ocular treatment-emergent adverse events occurred in 54.1 percent (n=210) of individuals.
Researchers determined that IVT-AFL treatment was associated with improvements in functional and anatomic outcomes in treatment-naïve and previously-treated patients with DME in France.
Source: Korobelnik JF, Daien V, Faure C, et al. Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: Results from the APOLLON study. Ophthalmology 202; Jan 2. [Epub ahead of print].
Effects of Intravitreal Triamcinolone Acetonide in DME Refractory to Anti-VEGF Treatment
Investigators assessed the efficacy and safety of primary intravitreal triamcinolone acetonide (IVTA) in eyes affected by diabetic macular edema refractory to anti-vascular endothelial growth factor therapy, as part of a retrospective, observational study.
The medical records of individuals attending a clinic from March 2013 to September 2018, with refractory macular edema were reviewed. Participants included patients who were injected at least once with IVTA and completed six months of observation. Best-corrected Snellen visual acuity, central macular thickness, intraocular pressure and adverse events were examined at baseline, and at one, two, three and six months.
Sixty-four eyes of 54 subjects were included. Here were some of the findings:
• The mean VA improved significantly at all time points compared to pre-treatment (p<0.0001), with the greatest mean improvement at one month (0.3 logMAR).
• The reduction in mean CMT was also significant at all follow-up exams compared with baseline (p<0.0001), with the greatest decrease at one month (113.68 ±53.78 μm).
• A poorer VA before injection was a factor that influenced visual gain one month post-treatment (0.247 logMAR units/unit increase in baseline VA, p=0.006).
• The most common AE associated with IVTA treatment was elevated IOP (11 eyes), observed significantly more often after IVTA injections containing a preservative (25.8 percent) than after those that were preservative-free (9.1 percent) (p=0.033).
Investigators wrote that IVTA injection could be an alternative steroid treatment for DME refractory to anti-VEGF therapy.
Source: Hong IH, Choi W, Han JR. The effects of intravitreal triamcinolone acetonide in diabetic macular edema refractory to anti-VEGF treatment. Jpn J Ophthalmol 2020; Jan 3. [Epub ahead of print].
Aflibercept Plus Micropulse Laser vs. Aflibercept Monotherapy for DME: 1-Year Results
Scientists evaluated the role of adjuvant micropulse laser with aflibercept injections in the management of treatment-naïve, center-involving DME, looking at decreased treatment burden and increased efficacy after one year.
The prospective, single-center, randomized trial included 40 eyes (40 individuals) with previously untreated center-involved DME. Individuals were randomly assigned to receive either aflibercept plus micropulse laser (group A) or aflibercept monotherapy (group B).
Overall, 40 individuals were included in the study; they were randomized into either group A (aflibercept + micropulse; 20 patients) or group B (aflibercept monotherapy; 20 patients). The mean number of injections after the loading dose was 4.5 ±1.4 in group A and was 5.4 ±1.7 in group B, and the difference between both groups was statistically significant (p=0.029).
Scientists determined that adding 577-nm micropulse laser to aflibercept was effective for treatment-naïve DME and was associated with decreased number of injections.
SOURCE: Abouhussein MA, Gomaa AR. Aflibercept plus micropulse laser versus aflibercept monotherapy for diabetic macular edema: 1-year results of a randomized clinical trial. Int Ophthalmol 2020; Jan 9. [Epub ahead of print].
Structural En Face OCT Imaging to Identify Leaky Microaneurysms in DME
Scientists studied the correspondence between fluorescein angiography and structural en face optical coherence tomography in the identification of leaky microaneurysms in diabetic macular edema.
Fourteen eyes of eight individuals with DME (six males and two females, mean age 67.3 ±8.5) were included. For all eyes, scientists obtained a 6 × 6 mm structural en face image of the middle retina and superimposed it on a FA image. They evaluated the reflectivity, capsulation and association with intraretinal cystic fluid (IRCF) of microaneurysms on en face, depending on their leaky status on FA. Here were some of the findings on the 320 leaky microaneurysms evaluated:
• A total of 280 (89 ±8.2 percent) coincided with those on en face OCT images.
• Twenty-nine leaky microaneurysms (10.6 ±6.9 percent) were hyperreflective, and 20 (6.5 ±7.8 percent) demonstrated capsular appearance.
• A majority (97.9 ±3.2 percent) were associated with IRCF.
• From 146 found only on en face images, 130 (88.2 ±15.7 percent) were hyperreflective, 33 (23.9 ±15.6 percent) demonstrated capsular structure and 13 (9.2 ±15 percent) demonstrated no associated IRCF.
• After exclusion of microaneurysms of the inner retina, 95.4 ±5.4 percent were identified on en face images.
• En face imaging demonstrated 83.5-percent sensitivity and 89.4-percent specificity (area under the ROC curve, 0.87) in the identification of leaky microaneurysms.
Scientists reported that structural en face imaging was comparable to FA in identifying leaky microaneurysms in DME. They added that moderate reflectivity, the absence of capsular structure and neighboring intraretinal cystic fluid indicated leaky microaneurysms.
SOURCE: Maltsev DS, Kulikov AN, Burnasheva MA, et al. Structural en face optical coherence tomography imaging for identification of leaky microaneurysms in diabetic macular edema. Int Ophthalmol 2019; Dec 3. [Epub ahead of print].
Retinal Leakage Index Dynamics on Ultra-Widefield FA in Eyes Treated with Intravitreal Aflibercept for PDR: RECOVERY Study
Researchers aimed to characterize leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. The prospective study enrolled subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every four weeks (2q4) or every 12 weeks (2q12).
Researchers analyzed ultra-widefield fluorescein angiography images obtained at baseline, 24 and 48 weeks using a semiautomated leakage segmentation platform. They calculated panretinal and zonal leakage indices.
Forty eyes of 40 subjects were included, and mean age was 48 ±12.1 years. Mean number of injections was 11 ±1.7 in the 2q4 arm and 4 ±0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 group was 5.1 percent, and median baseline leakage index in the 2q12 arm was 4.3 percent (p=0.28). Here were some of the findings:
• At 24 and 48 weeks, the 2q4 group significantly improved to 1.1 percent (-79 percent, p<0.0001).
• At week 24, the 2q12 group demonstrated non-significant improvement (3.4 percent; -21 percent, p=0.47); by week 48, improvement was significant (1.4 percent; -68 percent, p=0.02).
• The 2q4 group resulted in lower leakage index (1.1 percent) compared with the 2q12 group at 24 weeks (3.4 percent)(p=0.008), but by 48 weeks, leakage index was similar between both groups (1.1 percent [2q4 group] vs. 1.4 percent [2q12 group]; p=0.34).
Researchers found that proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at one year. Monthly dosing provided more rapid reductions in leakage index compared with quarterly dosing.
Source: Babiuch AS, Wykoff CC, Srivastava SK, et al. Retinal leakage index dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the RECOVERY study. Retina 2020; Jan 8. [Epub ahead of print].
Study Finds Association Between Poor Diet & AMD
Age-related macular degeneration is the leading cause of irreversible vision loss among the elderly, investigators wrote. They analyzed the association between dietary patterns and food groups (used to make them) with the 18-year incidence of AMD.
ARIC (Atherosclerosis Risk in Communities) participants who showed changes in AMD lesions between retinal photographs taken at visit three and visit five were graded side by side to determine incident AMD (any=144; early=117; late=27).
Investigators used a 66-line-item-food-frequency questionnaire administered at visit one and visit three to identify 29 food groups. They used principal component analysis to derive dietary patterns from average food group servings, and logistic regression to estimate ORs and 95% CIs for incident AMD (any, early and late) by tertiles of dietary pattern scores, adjusted for age, race, education, total calories and smoking status. Further, p-trend was estimated using continuous scores. Here were some of the findings:
•"Western” (unhealthy) and “prudent” (healthy) dietary patterns were identified.
• No significant associations were observed between dietary pattern and “incident any” or “incident early” AMD. However, a three-fold higher incidence of late AMD was observed among participants with a Western pattern score above, compared with below, the median score (OR=3.44; CI, 1.33 to 8.87, p=0.014).
• The risk of developing late AMD was decreased, but not statistically significantly, among participants with a prudent pattern score above, compared with below, the median (OR=0.51; CI, 0.22 to 1.18, p=0.054).
Investigators found that diet patterns weren’t significantly associated with “incident any” or “incident early” AMD. However, they reported that a consumption of a Western pattern diet could be a risk factor for development of late AMD.
Source: Dighe S, Zhao J, Steffen L, et al. Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study. Br J Ophthalmol 2019; Dec 6. [Epub ahead of print].
Investigation of Genetic Base in AMD Treatment
Scientists aimed to determine whether gene polymorphisms associated with age-related macular degeneration influence treatment response, specifically the antioxidant supplementation in dry-AMD patients, as well as the anti-vascular endothelial growth factor therapy in neovascular-AMD patients.
A total of 170 patients with dry AMD and 52 neovascular AMD patients were genotyped for the following single nucleotide polymorphisms (SNPs):
• rs1061170/Y402H in the CFH gene
• rs10490924/A69S in the ARMS2 gene
• rs9332739/E318D and rs547154/IVS10 in the C2 gene
• rs4151667/L9H and rs2072633/IVS17 in the CFB gene
Treatment response was evaluated by comparing visual acuity and optical coherence tomography between baseline and end of the treatment. Here were some of the findings:
• Τhe CFH/Y402H variant was associated with the response to antioxidants in dry AMD patients.
• Carriers of one or two CFH risk alleles displayed a lower chance of responding compared with those with no risk allele.
• No association of antioxidants’ response and ARMS2/A69S genotype was identified.
• The analysis of the C2 and CFB genetic variants (protective SNPs) revealed that antioxidant supplementation was much more effective in protective SNP carriers.
• In neovascular AMD patients, the analysis indicated that Y402H homozygous patients were less likely to respond to anti-VEGF therapy compared with heterozygous.
• Regarding the ARMS2/A69S genotype, carriers of the risk variant experienced significantly worse treatment outcomes compared with wild-type patients.
Scientists found that, in AMD patients, the efficacy of the antioxidant supplementation and the anti-VEGF therapy appeared to differ by genotype. They added that the detection of genetic variants, associated with treatment responsiveness, could lead to improved visual outcomes through genotype-directed therapy.
Source: Gourgouli K, Gourgouli I, Tsaousis G, et al. Investigation of genetic base in the treatment of age-related macular degeneration. Ophthalmology 2020; Jan 8. [Epub ahead of print].
Natural History of GA Secondary to AMD from the Proxima A and B Clinical Trials
Researchers aimed to better characterize visual function decline and geographic atrophy progression secondary to age-related macular degeneration, as part of the Proxima A and B global, prospective, non-interventional, observational clinical trials that were originally intended to support the approval of the now defunct lampalizumab program for dry AMD.
Eligible participants were ≥50 years of age. Those in Proxima A had bilateral GA without choroidal neovascularization in either eye (n=295). Those in Proxima B had GA with no CNV in the study eye and CNV ±GA in the fellow eye (fellow eye CNV cohort, n=168); or GA with no CNV in the study eye without CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n=32).
Researchers evaluated changes in visual function and imaging/anatomic parameters over time using a mixed model for repeated measurement accounting for key baseline characteristics.
Main outcome measures included pre-specified endpoints such as change in GA area from baseline, best-corrected visual acuity score assessed by ETDRS and BCVA under low-luminance conditions (LLVA). Here were some of the findings:
• At 24 months, the adjusted mean (standard error [SE]) change in GA lesion area from baseline was:
o 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A);
o 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B); and
o 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B).
• GA progression was greater in individuals with baseline non-subfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all subjects).
• Fellow-eye conversion to GA occurred in 30 percent, and to CNV in 6.7 percent of participants in the Proxima B intermediate AMD cohort at month 12.
• Adjusted mean changes in spherical-equivalent BCVA and LLVA (ETDRS letters)
in the study eye from baseline to 24 months were, respectively:
o -13.88 (1.40) and -7.64 (1.20) in the Proxima A group;
o -9.49 (1.29) and -7.57 (1.26) in the Proxima B fellow eye CNV cohort; and
o -11.48 (3.39) and -8.37 (3.02) in the Proxima B fellow eye intermediate AMD cohort.
Researchers wrote that the prospective Proxima A and B studies highlighted the severe functional impact of GA and the rapid rate of GA lesion progression over a two-year period, including in individuals with unilateral GA at baseline.
Source: Holekamp N, Wykoff CC, Schmitz-Valckenberg SS, et al. Natural history of geographic atrophy secondary to age-related macular degeneration: Results from the prospective Proxima A and B clinical trials. Ophthalmology 2019; Dec 14. [Epub ahead of print].
Lifecycles of Subretinal Drusenoid Deposits & Outer Retinal Atrophy in AMD
Researchers described the progression and regression of individual subretinal drusenoid deposits (SDDs) and surrounding photoreceptors in individuals with age-related macular degeneration over a 3.5-year period, using multimodal imaging including adaptive optics scanning laser ophthalmoscopy, as part of a longitudinal, observational study.
Four individuals with intermediate AMD were included. Researchers imaged six eyes of four individuals with intermediate AMD four times over 3.5 years. Five eyes of three individuals had only SDDs and no drusen. Researchers assessed SDD presence and progression by multimodal imaging and a three-stage grading system based on spectral-domain coherence tomography. They examined the morphology and fine structures of individual SDD lesions identified at baseline by AOSLO at follow-up visits. And they evaluated reflectivity of photoreceptors surrounding SDDs in AOSLO and SD-OCT.
Main outcome measures included morphology, fine structure and size of SDD lesions by AOSLO; photoreceptor integrity surrounding SDDs via AOSLO and SD-OCT; and retinal layer thicknesses via SD-OCT. Here were some of the findings:
• Individual SDDs followed independent lifecycle trajectories, exhibiting growth, shrinkage, fusion and disappearance.
• Alterations in shape, morphology and internal structure weren’t obviously due to presence of invading phagocytes.
• Of 822 lesions across all stages examined at baseline, 566 (69 percent) grew, 123 (15 percent) shrank, 47 (6 percent) remained of similar size, 86 (11 percent) disappeared and five (0.6 percent) reappeared after regression.
• A return of characteristic photoreceptor reflectivity in AOSLO (punctate) and in SD-OCT (prominent ellipsoid zone) was observed after regression of some SDD in five eyes of four individuals.
• All eyes exhibited thinning of photoreceptor layers, despite intact retinal pigment epithelium, to ∼70 percent of baseline thicknesses, as well as poorly visible or undetectable outer retinal bands.
Researchers wrote that AOSLO and SD-OCT imaging of individual SDDs over 3.5 years revealed independent trajectories of progression and regression, which they believed reflected the activities of local outer retinal cells. They added that restoration of some photoreceptor reflectivity and intact RPE after SDD regression should be seen in the larger context of outer retinal atrophy, previously suggested as a new form of advanced AMD and replicated in the current findings.
Source: Zhang Y, Wang X, Sadda SR, et al. Lifecycles of individual subretinal drusenoid deposits and evolution of outer retinal atrophy in age-related macular degeneration. Ophthalmology Retina 2019; Oct. 30. [Epub ahead of print].
Efficacy of a T&E Regimen with Ranibizumab in nAMD
Scientists wrote that, although the Canadian Treat-and-Extend Analysis Trial With Ranibizumab in Patients With Neovascular Age-Related Macular Disease (CANTREAT) study provided data to show noninferiority of treat-and-extend (T&E) strategies at 12 months, few data exist on 24-month T&E trials compared with monthly dosing.
Scientists compared the efficacy of ranibizumab using a T&E regimen to monthly dosing in treatment-naive patients with neovascular age-related macular degeneration after 24 months. The randomized, open-label, multicenter, noninferiority intent-to-treat trial with a margin of -5 letters in best-corrected visual acuity from baseline to 12 months between groups was conducted at 27 treatment centers in Canada. Participants included 580 individuals with treatment-naive choroidal neovascularization secondary to AMD. The study was conducted from May 8, 2013, to Aug. 28, 2018, and the researchers analyzed data between Aug. 29 and Sep. 12, 2018.
Patients with nAMD were randomized 1:1 to receive intravitreal ranibizumab 0.5 mg in either a T&E or monthly dosing regimen. Main outcomes and measures included mean change in BCVA in Early Treatment of Diabetic Retinopathy Study letters from baseline to month 24.
Of the 580 randomized individuals, 350 were women (60.3 percent) and 547 were white (94.3 percent). Mean age was 78.8 ±7.8 years. By the end of month 24, 466 of the 580 randomized patients (80.3 percent) had completed the study, and participants in the T&E arm received a mean of 17.6 injections compared with 23.5 injections for the monthly arm, for a difference of 5.9 injections and visits over two years (CI, 5.4-6.5; p<0.001). Here were some of the findings:
• The mean BCVA improvement in the T&E arm (6.8 ±14.1) letters, was better than the monthly arm (6 ±12.6) letters (difference: 0.9; CI, -1.6 to 3.3; p=0.21).
• In the T&E group, 25.5 percent of the group had a gain of 15 or more letters vs. 23.1 percent of the monthly treatment group (difference: 2.4 percent; CI, -6.8 to 11.6 percent; p=0.59).
• In the T&E group, 6.5 percent had a loss of 15 or more letters vs. 5.8 percent of the monthly treatment group (difference: -0.7 percent; CI, -9.9 to 8.5 percent; p=0.85).
Scientists wrote that a change in vision from baseline wasn’t worse with a T&E compared with a monthly regimen of ranibizumab for nAMD through 24 months, achieving clinically meaningful improvements in BCVA despite fewer injections and visits.
SOURCE: Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a treat-and-extend regimen with ranibizumab in patients with neovascular age-related macular disease: A randomized clinical trial. JAMA Ophthalmol 2020; Jan 9. [Epub ahead of print].
Topographic Analysis of Photoreceptor Loss Correlated with nAMD Disease Morphology
Researchers quantified morphologic photoreceptor integrity during anti-vascular endothelial growth factor therapy of neovascular age-related macular degeneration, and correlated these findings with disease morphology and function.
This post hoc analysis included spectral-domain optical coherence tomography data on 185 patients acquired at baseline, month three and month 12 in a multicenter, prospective trial. Researchers manually quantified loss of the ellipsoid zone (EZ) in all optical coherence tomography volumes. And they automatically segmented intraretinal cystoid fluid, subretinal fluid (SRF) and pigment epithelial detachments in the full volumes using validated deep learning methods. Further, they performed spatiotemporal correlation of fluid markers with EZ integrity as well as bivariate analysis between EZ integrity and best-corrected visual acuity. Here were some of the findings:
• At baseline, EZ integrity was predominantly impaired in the fovea, showing progressive recovery during anti-VEGF therapy.
• Topographic analysis at baseline revealed EZ integrity to be more likely intact in areas with SRF.
• A correlation was observed between EZ integrity and resolution of SRF.
• Foveal EZ integrity correlated with BCVA at all time points.
Researchers determined that improvement of EZ integrity during anti-VEGF therapy for nAMD occurred predominantly in the fovea and that photoreceptor integrity correlated with BCVA. They also reported that EZ integrity was preserved in areas of SRF and showed deterioration upon SRF resolution.
SOURCE: Riedl S, Cooney L, Grechenig C, et al. Topographic analysis of photoreceptor loss correlated with disease morphology in neovascular age-related macular degeneration. Retina 2019; Nov 13. [Epub ahead of print].
Patching Retinal Breaks with Healaflow in 27-Ga. Vitrectomy for RRD
Scientists reported the surgical outcomes of primary rhegmatogenous retinal detachment repaired by 27-gauge pars plana vitrectomy combined with Healaflow patch and air tamponade. According to its maker, Simovision, Healaflow is a slowly resorbable viscoelastic implant indicated for penetrating and non-penetrating glaucoma surgery.
In an initial in vitro experiment, they observed and compared the dissolution and displacement of the dispersion spots of 0.05-mL Healaflow and sodium hyaluronate. They then performed a prospective, interventional cohort study on 38 eyes in 37 consecutive individuals with primary RRD. All eyes underwent PPV combined with Healaflow patch and air tamponade; the postoperative period didn’t involve prone positioning. Scientists evaluated primary and final anatomical attachment rate, best-corrected visual acuity, and intraoperative and postoperative complications. Here were some of the findings:
• In the in vitro experiment, the viscoelastic Healaflow remained adherent, with no change in the size of the area; however, the control dissolved completely in the balanced salt solution.
• The study included 16 women (43.2 percent) and 21 men (56.8 percent) (mean age, 59.5 ±9.5 years; mean follow-up period, 8.9 ±3.8 months).
• A single break was present in 21 (55.3 percent) cases, and two to five breaks were present in 17 cases (44.8 percent).
• The macula was involved in 25 (65.8 percent) cases and attached in 13 cases (34.2 percent) intraoperatively.
• Initial reattachment was achieved in 37 (97.4 percent) cases and final reattachment was achieved in 38 cases (100 percent).
• In one case (2.6 percent), the macula re-detached because of failure of the chorioretinal scar to develop around the treated break.
• Mean preoperative BCVAs were 1.02 ±0.82 logMAR (median Snellen acuity: 20/125, range: 20/20,000 to 20/20), and mean postoperative BCVAs were 0.23 ±0.17 logMAR (median Snellen acuity: 20/32, range: 20/100 to 20/20)(p<0.001).
• Intraocular pressure was elevated transiently in 28 eyes (73.7 percent).
• No other intraoperative complications or postoperative scleral incision leakage were found.
Scientists wrote that a 27-ga. pars plana vitrectomy combined with Healaflow patch and air tamponade resulted in a high reattachment rate in the treatment of RRD. As such, they added, this strategy potentially may offer patients early visual recovery and less complications.
SOURCE: Ren XJ, Bu SC, Wu D, et al. Patching retinal breaks with Healaflow in 27-gauge vitrectomy for the treatment of rhegmatogenous retinal detachment. Retina 2019; Dec 18. [Epub ahead of print].
GENENTECH/ROCHE COMPLETE PATIENT ENROLLMENT IN TENAYA & LUCERNE PHASE III CLINICAL TRIALS
Genentech and Roche have completed patient enrollment in the TENAYA and LUCERNE Phase III clinical trials investigating faricimab for the treatment of wet age-related macular degeneration. This follows the completion of patient enrollment in the companies’ Phase III YOSEMITE and RHINE diabetic macular edema clinical trials in September 2019. Genentech and Roche are ending 2019 having fully recruited the current faricimab Phase III clinical trial program, including more than 3,000 patients in two diseases, ahead of schedule. The companies say that faricimab is the first bispecific antibody designed specifically for the treatment of retinal diseases. This investigational medicine simultaneously binds to and neutralizes Angiopoietin-2 and vascular endothelial growth factor A. By targeting both Ang2 and VEGF-A, faricimab may lead to improved and sustained efficacy at longer treatment intervals, thereby delivering better vision outcomes for patients, the companies say.
Source: Genentech/Roche, December 2019
LINEAGE REPORTS ADDITIONAL POSITIVE FINDINGS IN OPREGEN STUDY
Lineage Cell Therapeutics says that additional data from its ongoing Phase I/IIa clinical study of OpRegen has been positive. OpRegen is the company’s retinal pigment epithelium transplant therapy for the treatment of dry age-related macular degeneration. The first cohort of four patients treated using a new subretinal delivery system and the company’s new thaw-and-inject formulation has continued to demonstrate notable improvements in vision, Lineage says, with gains of 25 readable letters (or five lines) after six months, as assessed by the Early Treatment Diabetic Retinopathy Scale. Read more.
SOURCE: Lineage Cell Therapeutics, December 2019
NIH TRIAL REPLACES DYING RETINAL CELLS WITH PATIENT-DERIVED STEM CELLS
Researchers at the National Eye Institute are launching a clinical trial to test the safety of a novel, patient-specific stem cell-based therapy to treat geographic atrophy. The therapy takes a patient’s blood cells and converts them into induced pluripotent stem (iPS) cells, which are programmed to become retinal pigment epithelial cells in an effort to ensure the health of remaining photoreceptors by replacing dying RPE with iPSC-derived RPE. Under the Phase I/IIa clinical trial protocol, 12 patients with advanced-stage GA will receive the iPSC-derived RPE implant in one eye and be closely monitored for at least one year to confirm safety. The use of an individual’s autologous blood cells is expected to minimize the risk of implant rejection. Read more.
SOURCE: NIH, December 2019
PROTOKINETIX RETINAL CELL REPLACEMENT THERAPY TESTING COMPLETED
ProtoKinetix completed an in vivo study to assess the effect of AAGP on long-term survival and functional activity of photoreceptor precursor cells in animal ocular models of genetic retinal degeneration. The study aimed to determine the effects of 24-hour pre-treatment with anti-aging glycoprotein (AAGP) PKX-001, 4 mg/mL, at three, 4.5 and six months, and functional activity of PPCs following subretinal transplantation into the eye of immunocompromised rats with genetic retinal degeneration. In vivo tests demonstrated that transplantation of PPCs pre-treated with AAGP resulted in statistically significant improvements in the visual, behavioral and functional analysis responses compared with PPCs without pre-treatment. Read more.
SOURCE: ProtoKinetix, December 2019
Acucela Announces Positive Preclinical Data Findings for Emixustat Hydrochloride
Acucela announced the publication of positive preclinical data on investigational drug candidate, emixustat hydrochloride (emixustat), in Investigative Ophthalmology & Visual Science. Researchers evaluated the effects of emixustat on retinal metabolism in rat models, specifically oxygen consumption and ion channel activity in the retina under dark conditions. The researchers found that emixustat resulted in decreased oxygen consumption and ion channel activity and noted that the results have implications for the treatment of ischemic retinal diseases, such as diabetic retinopathy, in which hypoxia plays a prominent role. Read more.
SOURCE: Acucela, December 2019
DORC ANNOUNCES FDA APPROVAL OF TISSUEBLUE ORPHAN NDA
The Dutch Ophthalmic Research Center received FDA approval of its New Drug Application for TissueBlue (Brilliant Blue G Ophthalmic Solution) 0.025%. TissueBlue is the first FDA-approved dye for use as an aid in ophthalmic surgery by selectively staining the internal limiting membrane. The stain is injected onto the inner retinal surface for clear staining of the ILM as a way to distinguish it from unstained retina during its removal. Additional highlights include:
• its use with more than 350,000 surgical procedures since launch;
• a unique U.S. formulation featuring pharmaceutical-grade dye material to ensure a higher level of purity than lower-grade (compounded) dyes;
• the inclusion of polyethylene glycol to provide the density required by surgeons to ensure targeted application to the retina; and
• availability in a terminally sterilized, prefilled syringe.
DORC says it expects to start shipping TissueBlue to customers in early April.
SOURCE: Dutch Ophthalmic Research Center, December 2019
2020 ADA STANDARDS OF CARE NOW MENTION ARTIFICIAL INTELLIGENCE
IDx, maker of the IDx-DR artificial-intelligence system for the detection of diabetic retinopathy and macular edema, announced that the American Diabetes Association’s new set of clinical standards mentions the use of autonomous artificial intelligence. The ADA's 2020 Standards of Medical Care in Diabetes states that, "AI systems that detect more than mild diabetic retinopathy and diabetic macular edema authorized for use by the FDA represent an alternative to traditional screening approaches." Read more.
SOURCE: IDx, December 2019
EXONATE & JANSSEN TO DEVELOP RETINAL VASCULAR DISEASE TREATMENTS
Exonate entered into a strategic collaboration agreement with Janssen Pharmaceuticals. Through the collaboration, Exonate will work with Janssen research and development scientists to develop an eye-drop treatment for retinal vascular diseases such as wet AMD and DME using mRNA targeted therapies. Exonate has developed small molecules that inhibit the production of pro-angiogenic vascular endothelial growth factor through the selective inhibition of serine/threonine-protein kinase (SRPK1)-mediated VEGF splicing. The agreement was facilitated by Johnson & Johnson Innovation. Read more.
SOURCE: Exonate, January 2020
CANON REALIGNS STRATEGY TO PREPARE FOR EYE-CARE SYSTEMS GROWTH
The eye-care business operations within Canon U.S.A. has transferred to Canon Medical Systems U.S.A., effective Jan. 1, 2020. The company says Canon’s shift in business operations will enable Canon Medical Systems to offer ophthalmologic solutions to integrated-delivery network customers, while leveraging medical imaging business synergies to address population health challenges associated with chronic conditions such as age-related macular degeneration, diabetic retinopathy and inherited retinal diseases. Canon Medical Systems will add measurement systems, retinal cameras and optical coherence tomography systems to its product line. Read more.
Source: Canon, December 2019
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