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.
Outcomes of Eyes with Intraocular Inflammation after Brolucizumab: Post Hoc Analysis of HAWK and HARRIER
This analysis of the Phase III HAWK and HARRIER trials sought to provide insights on the timing of presentation, management and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials.
The post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER included 49 eyes of 1,088 brolucizumab-treated eyes (3 mg or 6 mg) that experienced at least one IOI-related AE.
Researchers analyzed reports of IOI-related AEs and provided statistics for outcome measures. The main outcome measures included incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes and brolucizumab treatment after the first IOI-related AE.
Here are some of the findings:
• A total of 70 IOI-related AEs were reported in 49 eyes.
• Prior to the onset of first IOI-related AE, eyes received a mean of 3.9 ±2.2 brolucizumab injections.
• Median (25th to 75th percentile) time to first IOI-related AE from the last administered brolucizumab injection was 18 (four to 29) days.
• Of the 70 AEs, 61 (87.1 percent) were treated, the majority with topical corticosteroids; systemic and intraocular corticosteroids were used for three AEs each.
• Overall, inflammation resolved completely in 39 eyes (79.6 percent), resolved with sequelae in five eyes (10.2 percent), and it didn’t resolve in five eyes (10.2 percent) by the end of the study.
• Overall, mean best-corrected visual acuity change was:
o from baseline to the end of the study: -0.84 ±20.6 ETDRS letters;
o before AE to the lowest BCVA in three months after AE: -16.31 ±17.6 letters; and
o from before AE to the end of the study was -0.22 ±18.9 letters.
• Of the 36 eyes (73.5 percent) that continued on brolucizumab after the first IOI-related AE, 24 completed the trials and 12 discontinued them; the mean BCVA change in the eyes was 2.6 ±17.6, 7.8 ±13.2 and -7.7 ±21.3 letters, respectively, from baseline to the end of the study.
• The remaining 13 eyes (26.5 percent) weren’t treated with brolucizumab after the first IOI-related AE and had a mean BCVA change of -10.4 ±25.5 letters from baseline to the end of the study.
Researchers wrote that their findings highlighted the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.
SOURCE: Singer M, Albini TA, Seres A, et al. Clinical characteristics and outcomes of eyes with intraocular inflammation after brolucizumab: Post hoc analysis of HAWK and HARRIER. Ophthalmol Retina 2021; May 7. [Epub ahead of print].
Efficacy & Safety of Biosimilar FYB201 Compared with Ranibizumab in nAMD
Investigators assessed the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in individuals with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration.
This prospective, multicenter, evaluation-masked, parallel-group, 48-week, Phase III randomized study included 477 patients randomly assigned to receive FYB201 (n=238) or reference ranibizumab (n=239).
Patients received FYB201 or ranibizumab 0.5 mg by intravitreal injection in the study eye every four weeks.
The primary endpoint was change from baseline in best-corrected visual acuity by Early Treatment Diabetic Retinopathy Study letters at eight weeks prior to the third monthly intravitreal injection. Biosimilarity of FYB201 to its originator was assessed via a two-sided equivalence test, with an equivalence margin in BCVA of three ETDRS letters.
Here are some of the findings:
• BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week eight.
• The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was -0.4 ETDRS letters; CI, -1.6 to 0.9.
• The primary endpoint was met, as the CI was within the predefined equivalence margin.
• Adverse events were comparable between treatment groups.
Investigators found that the FYB201 biosimilar referenced ranibizumab in terms of clinical efficacy, and ocular and systemic safety in the treatment of patients with nAMD.
SOURCE: Holz FG, Oleksy P, Ricci F, et al.; COLUMBUS-AMD Study Group. Efficacy and safety of biosimilar FYB201 compared with ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2021; May 3. [Epub ahead of print].
Anti-VEGF-resistant Subretinal Fluid Associated with Better Vision and Reduced Risk of Macular Atrophy
Scientists evaluated relationships between subretinal fluid (SRF), macular atrophy (MA) and visual outcomes in ranibizumab-treated neovascular age-related macular degeneration.
The post hoc HARBOR trial (NCT00891735) analysis included ranibizumab-treated (0.5 or 2.0 mg monthly or as needed, all treatment arms pooled) eyes with nAMD and baseline (screening, baseline and week 1) SRF. SRF presence, SRF thickness (0, >0 to 50, >50 to 100 and >100 µm) and subretinal fluid volume (SRFV) were determined by spectral domain optical coherence tomography. Best-corrected visual acuity was assessed. MA was identified using fluorescein angiograms and color fundus photographs, as well as SD-OCT.
Seven hundred eighty-five of 1,097 eyes met analysis criteria. Here are some of the findings:
- In eyes without baseline MA, residual vs. no SRF at month (M) 3 was associated with lower MA rates at M12 (5.1 vs. 22.1 percent) and M24 (13.3 vs. 31.2 percent) (both p<0.0001); MA percentages at M12/M24 were similar among patients with residual SRF at M6.
- Higher baseline SRFV was associated with a lower MA rate.
- Greater mean BCVA was observed with residual SRF of any thickness (>0-50 µm, 71.2 letters; >50-100 µm, 71.3 letters; >100 µm, 69.2 letters) vs. no SRF (63.6 letters), but the change in BCVA from baseline to M12 or M24 was the same for eyes with or without treatment-resistant subretinal fluid (TR-SRF) at M3 or M6.
Scientists wrote that TR-SRF wasn’t detrimental to vision outcomes over two years, regardless of thickness. They added that MA rates were significantly higher without TR-SRF.
SOURCE: Zarbin MA, Hill L, Maunz A, et al. Anti-VEGF-resistant subretinal fluid is associated with better vision and reduced risk of macular atrophy. Br J Ophthalmol 2021; May 26. [Epub ahead of print.]
Early Predictive Factors of Visual Loss in nAMD Under Anti-VEGF: The GEFAL Study
Investigators evaluated early predictive factors of visual loss in individuals treated with anti-vascular endothelial growth factor injections under an as-needed regimen for neovascular age-related macular degeneration.
The post-hoc analysis of the randomized controlled trial GEFAL comparing ranibizumab and bevacizumab for neovascular AMD in 393 patients age 50 and older with neovascular AMD was based on one-year data from individuals included in the study.
Patients were put into one of three categories according to the BCVA change at three months (M3) and one year:
1) patients with no vision loss ≥5 letters at M3 and at one year (absence of loss ≥5-letters);
2) patients with no vision loss ≥5-letters at M3 but loss ≥5 letters at one year (secondary loss ≥5 letters); and
3) patients with vision loss ≥5 letters at M3 and one year (initial loss ≥5 letters). The threshold of at least five letters lost indicated clinical significance.
The following factors were evaluated at baseline and at M3: age; sex; BCVA; presence of fluid; central macular thickness; angiographic choroidal neovascularization subtype; CNV area measured in disk area on fluorescein angiography; and the number of intravitreal injections.
Here are some of the findings:
• 225 patients (57.3 percent) didn’t lose ≥5 letters; a secondary loss of ≥5 letters after M3 was found in 109 patients (27.7 percent); and an initial loss of ≥5 letters of BCVA was found in 59 patients (15 percent).
• Baseline characteristics were comparable between the three groups except for the total CNV area, which was larger in the initial and the secondary loss groups (p=0.0412).
• At M3 a significant association was found between presence of subretinal fluid (p=0.0318) and vision loss of ≥5 letters, with an even stronger significant association between the presence of intraretinal fluid (p=0.0066) and vision loss of ≥5 letters.
Investigators found that a large CNV area at baseline was significantly associated with initial or secondary loss of visual acuity ≥5 letters despite anti-VEGF injections. They added that the presence of fluid, both subretinal and intraretinal at M3, was found in patients with poorer trajectories.
SOURCE: Kodjikian L, Rezkallah A, Decullier E, et al; GEFAL Study Group. Early predictive factors of visual loss at 1-year in neovascular age-related macular degeneration under anti-VEGF in the GEFAL study. Ophthalmol Retina 2021; May 12. [Epub ahead of print].
NIH Study Affirms AREDS2 Results
Researchers from the National Eye Institute performed a 10-year follow-on study of the Age-Related Eye Disease Study 2, and found that the results confirm those of the original, five-year study. They shared their results at the recent meeting of the Association for Research in Vision and Ophthalmology.
The AREDS2 clinical trial randomly assigned participants with bilateral intermediate AMD or late AMD in one eye to lutein/zeaxanthin and/or omega-3 fatty acids or placebo. Secondary randomization also evaluated varying doses of beta-carotene (0 vs. 15 mg) and zinc (25 vs. 80 mg). At the end of the clinical trial, a follow-up study was conducted with telephone calls every six months to the surviving AREDS2 participants from the central coordinating center to collect outcome data and adverse events for safety monitoring for an additional five years.
In the study, 6,360 eyes (3,887 patients) were analyzed and 3,047 (48 percent) progressed to late AMD. The main effects of lutein/zeaxanthin vs. no lutein-zeaxanthin and of omega-3 fatty acids vs. no omega-3 fatty acids resulted in hazard ratios of 0.91 (95% CI: 0.89-0.99) (p=0.03) and 1.00 (0.92-1.09) (p=0.91), respectively. When the lutein/zeaxanthin main effect analysis was restricted to those randomized secondarily to beta-carotene, the HR was 0.80 (0.69-92) (p=0.003).
On direct analysis of lutein/zeaxanthin vs. beta-carotene, the HR was 0.85 (0.74-0.98) (p=0.026). For the comparisons of low vs. high zinc and no beta-carotene vs. beta-carotene, the HRs were 1.04 (p=0.48) and 1.04 (p=0.50), respectively. For those randomized to beta-carotene, the odds ratio (OR) of developing lung cancer was 1.92 (1.11-3.31)(p=0.02) while the OR for those randomized to lutein/zeaxanthin was 1.19 (0.82-1.73) (p=0.35).
The researchers say that, again, they showed that lutein/zeaxanthin was safer than using beta-carotene, as the latter was found to double the chance of lung cancer. They say the use of lutein/zeaxanthin showed a more favorable response when compared with beta-carotene.
SOURCE: Chew EY, Clemons TE, Keenan TD, et al. The results of the 10 year follow-on study of the age-related eye disease study 2 (AREDS2). Presented at the 2021 ARVO Annual Meeting.
Prevalence of Visual Acuity Loss or Blindness in the US: A Bayesian Meta-analysis
Investigators wrote that globally, more than 250 million people live with visual acuity loss or blindness, and people in the United States fear losing vision more than memory, hearing or speech. But they added, it appeared there were no recent empirical estimates of visual acuity loss or blindness for the United States.
As such, the investigators produced estimates of visual acuity loss and blindness by age, sex, race/ethnicity and U.S. state. They obtained data from the American Community Survey (2017), National Health and Nutrition Examination Survey (1999 to 2008), and National Survey of Children's Health (2017), as well as population-based studies (2000 to 2013).
All relevant data from the US Centers for Disease Control and Prevention's Vision and Eye Health Surveillance System were included. The prevalence of visual acuity loss or blindness was estimated, stratified when possible by factors including U.S. state, age group, sex, race/ethnicity and community-dwelling or group-quarters status. Data analysis occurred from March 2018 to March 2020.
Main outcomes or measures included the prevalence of visual acuity loss (defined as a best-corrected visual acuity greater than or equal to 0.3 logMAR) and blindness (defined as a logMAR of 1.0 or greater) in the better-seeing eye.
For 2017, this meta-analysis generated an estimated U.S. prevalence of 7.08 (95% uncertainty interval, 6.32 to 7.89) million people living with visual acuity loss, of whom 1.08 (95% uncertainty interval, 0.82 to 1.30) million people were living with blindness. Of this, 1.62 (95% uncertainty interval, 1.32 to 1.92) million persons with visual acuity loss were younger than 40 years, and 141,000 (95% uncertainty interval, 95,000 to 187,000) persons with blindness were younger than 40 years.
Investigators reported that this analysis of all available data with modern methods produced estimates substantially higher than those previously published.
Dilated Choroidal Veins & Myopic Macular Neovascularization Recurrence
Researchers looked at a possible correlation between the presence of macular dilated choroidal vein (DCV) and the recurrence of myopic macular neovascularization (MNV) after anti-vascular endothelial growth factor treatment.
The medical records of 168 eyes of 163 patients with myopic MNV were reviewed for the presence of macular DCV and episodes of recurrences. A macular DCV was defined as a choroidal vein whose diameter was two times larger than the adjacent veins coursing in the macular area of 5.5 mm diameter.
• Macular DCV existed in 47 eyes (28 percent) with myopic MNV.
• Seventy eyes (41.7 percent) had recurrence during a mean follow-up period of 52.5 ±23 months.
• Recurrence was found in 28 of 47 eyes (59.6 percent) with DCV, which was significantly more frequent than in the 42 of the 121 eyes (34.7 percent) without DCV (p=0.003).
• Cox model analysis showed that macular DCV was an independent risk factor (HR, 2; CI, 1.1 to 3.5) for recurrence.
• The recurrence rate was significantly higher in eyes with DCV within the first two years after the onset than in eyes without DCV.
Researchers concluded that macular DCVs may be indicators of a more aggressive phenotype of eyes with myopic MNV. They suggested that these eyes need careful monitoring after anti-VEGF therapies.
SOURCE: Xie S, Du R, Fang Y, et al. Dilated choroidal veins and their role in recurrences of myopic macular neovascularisations. Br J Ophthalmol 2021; Apr 28. [Epub ahead of print].
Intravitreal Conbercept for DME
Researchers evaluated the efficacy and safety of intravitreal injections of conbercept vs. laser photocoagulation in the treatment of diabetic macular edema.
A 12-month multicenter, randomized, double-masked, double-sham, parallel controlled, Phase III trial (Sailing Study) was followed by a 12-month open-label extension study. Patients with center-involved DME were randomly assigned to receive either laser photocoagulation followed by pro re nata sham intravitreal injections (laser/sham) or sham laser photocoagulation followed by PRN 0.5 mg conbercept intravitreal injections (sham/conbercept). Individuals who entered the extension study received PRN conbercept treatment. The primary endpoint was the change in best-corrected visual acuity from baseline.
A total of 248 eyes were included in the full analysis set, and 157 eyes continued in the extension study. Here are some of the findings:
• Significant improvement in mean change in BCVA from baseline to month 12 was observed in the sham/conbercept group (8.2 ±9.5 letters), whereas no improvement was observed in the laser/sham group (0.3 ±12 letters).
• Individuals in the laser/sham group showed a marked improvement in BCVA after the switch to conbercept in the extension study, and there was no difference in BCVA between the two groups at the end of the extension study.
Researchers reported that the use of a conbercept PRN intravitreal injection regimen improved the BCVA of DME patients, and its efficacy was better than that of laser photocoagulation, which was also observed when eyes treated with laser alone were switched to conbercept.
SOURCE: Liu K, Wang H, He W, et al. Intravitreal conbercept for diabetic macular oedema: 2-year results from a randomised controlled trial and open-label extension study. Br J Ophthalmol 2021 ; May 17. [Epub ahead of print].
OCTA-measured Area of Retinal Neovascularization Predictive of Treatment Response and PDR Progression
The purpose of this study was to evaluate the area of retinal neovascularization in patients with treatment-naïve proliferative diabetic retinopathy, as measured by optical coherence tomography angiography as a marker of subsequent treatment response after panretinal photocoagulation, and to determine if this area correlated with area of retinal neovascularization as measured by fluorescein angiography.
En face OCTA scans (4.5 × 4.5 mm) of neovascularizations were obtained at baseline before PRP and at month three and six (M3 and M6) after treatment. Progression of PDR was defined as lesion growth (assessed by ophthalmoscopy and widefield fundus photo) or increasing leakage by Optos ultra-widefield FA. Patients were divided into two groups: progression or non-progression. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze differences between groups and between time points. Areas of retinal neovascularizations (OCTA and FA) were calculated by algorithms developed in Python (version 3.6.8, the Python Software Foundation).
Here are some of the findings:
- Of 21 eyes included, 14 had disease progression.
- Median OCTA area didn’t differ between the two groups (progression vs. non-progression) at baseline (76.40 ±162.03 vs. 72.62 ±94.15, p=0.43) but were statistically significantly larger in the progression group at M6 (276.69 ±168.78 vs. 61.30 ±70.90, p=0.025).
- Median FA area didn’t differ in the progression vs. the non-progression group at BL (111.42 ±143.08 vs. 60.80 ±54.83, p=0.05) or at M6 (200.12 ±91.81 vs. 123.86 ±162.16, p=0.62).
- Intraclass correlation between area by OCTA and FA was -5.99 (CI, -35.28 to 0.993), p=0.71.
In this study of patients with treatment-naïve PDR, researchers showed that increasing area of retinal neovascularization measured by OCTA at M6 indicated progression of disease after PRP. The results suggest that area by OCTA reflects disease activity and that it can be used as an indicator to monitor the progression of PDR over time, and to evaluate treatment response six months after PRP.
SOURCE: Vergmann AS, Sørensen KT, Torp TL, et al. Optical coherence tomography angiography measured area of retinal neovascularization is predictive of treatment response and progression of disease in patients with proliferative diabetic retinopathy. Int J Retina Vitreous 2020; Nov 4;6(1):49.
Using OCTA to Compare Central Macular Fluid Volume & Central Subfield Thickness in DME
Scientists wrote that diabetic macular edema is the predominant cause of visual impairment in patients with type 1 or 2 diabetes. Automated fluid volume measurements using optical coherence tomography may improve the diagnostic accuracy of DME screening. As such, they assessed the diagnostic accuracy of an automated central macular fluid volume quantification using OCT for DME.
A cross-sectional observational study was conducted at a tertiary academic center among 215 patients with diabetes (one eye each) enrolled from January 26, 2015, to December 23, 2019. All participants underwent comprehensive examinations, 6 × 6-mm macular structural OCT horizontal raster scans, and 6 × 6-mm macular OCT angiography volumetric scans. From January 1 to March 30, 2020, two retinal specialists reviewed the structural OCT scans independently and diagnosed DME if intraretinal or subretinal fluid was present. Diabetic macular edema was considered center involved if fluid was present within the central fovea (central 1-mm circle). A third retinal specialist arbitrated any discrepancy. The mean central subfield thickness within the central fovea was measured on structural OCT horizontal raster scans. A deep learning algorithm automatically quantified fluid volumes on 6 × 6-mm OCT angiography volumetric scans and within the central foveas (CMFV).
Main outcomes and measures included the area under the receiver operating characteristic curve (AUROC), and the sensitivity and specificity of CST and CMFV for DME diagnosis.
Investigators enrolled one eye each of 215 patients with diabetes (117 women [54.4 percent]; mean age, 59.6 ±12.4 years. Here were some of the findings:
- Diabetic macular edema was present in 136 eyes; 93 cases of DME were center involved.
- The AUROC of CMFV for diagnosis of center-involved DME (0.907 [CI, 0.861 to 0.954]) was greater than the AUROC of CST (0.832 [CI, 0.775 to 0.889]; p=0.02).
- With the specificity set at 95 percent, the sensitivity of CMFV for detection of center-involved DME (78.5 percent [CI, 68.8 to 86.3 percent]) was higher than that of CST (53.8 percent [CI, 43.1 to 64.2 percent]; p=0.002).
- Center-involved DME cases not detected by CST but detected by CMFV were associated with:
- a thinner CST (290.8 μm [CI, 282.3 to 299.3 μm] vs. 369.4 μm [CI, 347.1 to 391.7 μm]; p<0.001);
- higher proportion of previous macular laser treatment (11 of 28 [39.3 percent; CI, 21.5 to 59.4 percent] vs. 12 of 65 [18.5 percent; CI, 9.9 to 30]; p=0.03); and
- female sex (20 of 28 [71.4; CI, 51.3 to 86.8 percent] vs. 31 of 65 [47.7 percent; CI, 35.1 to 60.5 percent]; p=0.04).
Scientists wrote that the findings suggested that an automated CMFV is a more accurate diagnostic biomarker than CST for DME and may improve screening for DME.
SOURCE: You QS, Tsuboi K, Guo Y, et al. Comparison of central macular fluid volume with central subfield thickness in patients with diabetic macular edema using optical coherence tomography angiography. JAMA Ophthalmol 2021; May 13. [Epub ahead of print].
T&E Regimen with Aflibercept for BRVO: 1-Year Results of PLATON
Investigators evaluated the functional and anatomical outcomes of a treat-and-extend regimen with aflibercept for treatment-naive macular edema secondary to branch retinal vein occlusion.
This prospective, multicenter, noncomparative open-label clinical trial included 48 eyes of 48 patients who received three monthly intravitreal aflibercept injections prior to the T&E regimen. However, if the best-corrected visual acuity was ≥20/20 and the central macular thickness was <250 μm during the loading phase, the patient immediately proceeded to the T&E regimen. The treatment interval was adjusted by four weeks based on changes in CMT. The primary outcome was the mean change in BCVA from baseline to 52 weeks.
Here are some of the findings:
• The mean change in BCVA was 23.6 ±14.2 letters.
• The proportion of patients with a BCVA gain of ≥15 letters was 77.1 percent at 24 weeks and 72.9 percent at 52 weeks.
• The mean reduction in CMT was 326.2 ±235.6 μm at 24 weeks and 324.2 ±238 μm at 52 weeks.
• The mean number of injections was 6.7 ±1.2 (range: 6 to 11; all patients received three monthly intravitreal aflibercept injections) over 52 weeks, and 34 patients (70.8 percent) reached the maximal extension interval of 16 weeks at 52 weeks.
Investigators found that the T&E regimen using aflibercept for ME secondary to BRVO, which has a treatment interval of up to 16 weeks, showed comparable efficacy to the fixed-dosing regimen along with reduced treatment burden.
SOURCE: Park DG, Jeong WJ, Park JM, et al. Prospective trial of treat-and-extend regimen with aflibercept for branch retinal vein occlusion: 1-year results of the PLATON trial. Graefes Arch Clin Exp Ophthalmol 2021; Apr 29. [Epub ahead of print].
FDA Accepts Application for Genentech’s Port Delivery System With Ranibizumab for Treatment of Wet AMD
Genentech announced the FDA accepted its Biologics License Application, under Priority Review, for Port Delivery System with ranibizumab for the treatment of neovascular age-related macular degeneration. If approved, the company’s PDS would be an alternative to frequent injections of anti-vascular endothelial growth factor. The FDA is expected to make a decision on approval by Oct. 23. Read more.
Novartis to Terminate Several Beovu Studies Due to Safety Issues
Novartis reported that it’s terminating its Phase III MERLIN study assessing the efficacy and safety of Beovu (brolucizumab) 6 mg vs. aflibercept 2 mg given every four weeks following the loading phase in patients with wet AMD who have persistent retinal fluid despite anti-VEGF therapy due to higher rates of intraocular inflammation in the Beovu patients.
When given every four weeks in MERLIN, the rate of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, was 9.3 percent with Beovu, versus 4.5 percent for aflibercept. The incidence of RV and RO for Beovu patients was 0.8 percent and 2 percent, respectively, versus no cases of either form of inflammation with aflibercept. The overall rate of vision loss (15 letters or more) due to all causes was 4.8 percent in the Beovu arm vs. 1.7 percent in the aflibercept arm. In terms of efficacy, the company says that Beovu met MERLIN’s primary endpoint of non-inferiority in change in best-corrected visual acuity from baseline and superiority on select anatomical secondary endpoints at year one vs. aflibercept.
As a result of these adverse events, Novartis also stopped all of its other ongoing brolucizumab clinical programs assessing studies with four-week dosing intervals after the loading phase, stating, “Novartis has decided to terminate the MERLIN study and the RAPTOR and RAVEN studies, which were assessing the efficacy and safety of brolucizumab with six initial monthly injections in retinal vein occlusion. All other relevant ongoing trial protocols will be amended to discontinue four week dosing intervals after the loading phase. Clinical trial investigators have been informed and will appropriately follow-up with their patients. Physicians should not treat patients with Beovu 6 mg at intervals less than two months beyond the first three doses.” Read more.
SOURCE: Novartis, May 2021
Gemini Completes Enrollment in Phase IIa Study of GEM103
Gemini Therapeutics completed enrollment in its Phase IIa trial advancing GEM103 as a potential add-on therapy for patients with wet age-related macular degeneration requiring continued anti-vascular endothelial growth factor treatment, who have—or may be at risk for—macular atrophy. Topline data related to safety, tolerability, effect on intraocular complement factor H levels and disease-relevant biomarkers of complement regulation is expected in late 2021. Read more.
SOURCE: Gemini Therapeutic, May 2021
EyePoint Completes Enrollment of Phase I DAVIO Clinical Trial
EyePoint Pharmaceuticals completed patient enrollment of its Phase I clinical trial of EYP-1901 as a potential twice-yearly sustained delivery anti-VEGF treatment targeting wet age-related macular degeneration. EYP-1901 is delivered via an intravitreal injection in the physician's office. The open-label 12-month dose escalation trial is examining wet AMD patients who were responsive to previous anti-VEGF therapies. Read more.
Source: EyePoint Pharmaceuticals, May 2021
Oxurion Completes Patient Enrollment for Part A of Phase II Study Evaluating THR-149 for DME
Oxurion completed patient enrollment into Part A of its two-part Phase II study (KALAHARI) evaluating multiple injections of THR-149 for the treatment of diabetic macular edema. THR-149, which acts through inhibition of the plasma kallikrein-kinin (PKaI-Kinin) system as a validated VEGF-independent target for DME, is being developed as a possible treatment for patients who respond suboptimally to anti-VEGF therapy. Read more.
SOURCE: Oxurion, June 2021
GenSight Announces Positive Findings for LUMEVOQ, Visual Recovery after GS030 Treatment
A GenSight Biologics-sponsored study in Frontiers in Neurology on the indirect comparison of the evolution of visual outcomes in patients treated with LUMEVOQ gene therapy with the spontaneous evolution in natural history studies of Leber’s hereditary optic neuropathy patients carrying the m.11778G>A ND4 mutation found a statistically and clinically relevant difference in visual acuities in favor of patients treated with the company’s gene-therapy drug candidate LUMEVOQ vs. untreated NH patients. Read more. The company also announced the first case report of partial recovery of visual function in a blind patient with late stage retinitis pigmentosa. The subject is a participant in the ongoing PIONEER Phase I/II clinical trial of GenSight Biologics’ GS030 optogenetic therapy. Read more.
SOURCE: GenSight Biologics, June and May 2021
New Data on Nanoscope's Optogenetic Gene Therapy
Nanoscope Therapeutics announced that vision improvements for all evaluated advanced retinitis pigmentosa patients persisted through one year following a single intravitreal injection in a Phase I/IIa clinical study of the company’s multi-characteristic opsin-based treatment. Nanoscope's RP gene therapy, which has received orphan drug designation from the FDA, uses a proprietary AAV2 vector to deliver the MCO genes into the retina. This mutation-independent gene therapy involves a single ocular injection administered in a doctor's office. Read more.
SOURCE: Nanoscope Therapeutics, June 2021
Coburn Introduces New HFC-1 Fundus Camera
Coburn Technologies introduced the HFC-1 Non-Mydriatic Fundus Camera, a new retinal camera manufactured by Huvitz, which the company says uses autodetection technology to produce sharp, quick and reliable images and measurements. Automated tracking and shooting allow the HFC-1 Fundus Camera to adjust modes on its own while measuring differing pupil sizes. Its 20-megapixel high-definition camera captures images with reduced motion artifacts and has the capability to enlarge images to study fine details, Coburn says. Users can measure, analyze, diagnose and produce reports using the camera’s built-in PC's 12.1” LCD touchscreen. Read more.
SOURCE: Coburn Technologies, May 2021
ProtoKinetix and IQVIA Partner to Develop AAGP
ProtoKinetix announced its collaboration with IQVIA to accelerate development of AAGP (PKX-001) in ocular conditions, specifically wet and dry age-related macular degeneration, and dry-eye disease. PKX-001 is entering clinical trials to determine safety in these conditions, drawing from previous experience with PKX-001 in type 1 diabetes and other conditions. Read more.
SOURCE: ProtoKinetix, May 2021
New Products from Optomed
Optomed USA now offers two tabletop fundus imaging cameras for the U.S. market. The Optomed Polaris, a small, stationary device, has a fully automatic, non-mydriatic fundus camera; it requires minimal training and provides sharp 45-degree images of the retina, the company says. The Optomed Halo, with a lightweight design and small footprint, offers a fully automatic, portable, non-mydriatic retinal camera. Social distancing is possible with the Optomed Halo because the controlling computer can be located up to 25 feet away from the camera or behind a glass wall, Optomed says. Learn more.
Optomed also recently introduced a disposable eye cup, the Optomed E-Safe, available for use with the company’s handheld fundus cameras, eliminating the need for a disinfection protocol for that aspect of the device. The eye cup is attached to the camera’s eyepiece which rests against the patient during imaging. Learn more.
Faricimab Extends Time Between Treatments in Two Phase III studies
At this year’s American Diabetes Association Virtual 81st Scientific Sessions (June 25 to 29), Genentech is presenting primary results from two Phase III trials of its investigational bispecific antibody faricimab for diabetic macular edema. Faricimab is the first treatment that targets dual pathways to control the growth of new blood vessels, the company says. More than half of all patients who received faricimab had extended time between treatments to 16 weeks at one year—which Genentech says is the first time this level of durability has been achieved in a Phase III DME study. No new safety signals were identified. Additionally, researchers will present the design of two Port Delivery System studies, which further highlight how treatment burden may be lessened for patients.
Clearside Announces Safety Results from Cohort 1 of OASIS
Clearside Biomedical announced positive safety results from cohort 1 of OASIS, its ongoing Phase I/IIa clinical trial of CLS-AX (axitinib injectable suspension) administered by suprachoroidal injection via Clearside’s SCS Microinjector in six patients (n=6) with neovascular age-related macular degeneration. Clearside says the primary endpoints were achieved in cohort 1, as the initial lowest planned dose of 0.03 mg CLS-AX was well-tolerated with no serious adverse events and no drug-related treatment emergent adverse events. Read more.
Biogen Fails to Meet Endpoints in Phase III Gene Therapy Study
Biogen announced its Phase III STAR study of timrepigene emparvovec (BIIB111/AAV2-REP1), an investigational gene therapy for the potential treatment of choroideremia, didn’t meet its primary endpoint of proportion of participants with a ≥15 letter improvement from baseline in best-corrected visual acuity at month 12, in the interventional group compared to the non-interventional control group, as measured by the Early Treatment of Diabetic Retinopathy Study chart. In addition, the study didn’t demonstrate efficacy on key secondary endpoints. Read more.
Bausch Health and Clearside File Acceptance For Xipere
Bausch Health Companies along with Clearside Biomedical announced the FDA accepted the resubmitted New Drug Application for Xipere (triamcinolone acetonide suprachoroidal injectable suspension). FDA determined that the filing is a Class 2 resubmission and therefore assigned a Prescription Drug User Fee Act (PDUFA) action date of October 30. Xipere is an investigational therapy with a proposed indication of treatment of macular edema associated with uveitis. Read more.
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