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.
Safety & Efficacy of Different Doses and Regimens of Faricimab vs. Ranibizumab in nAMD: The AVENUE Phase II Randomized Clinical Trial
Faricimab, a bispecific antibody designed for intraocular use, simultaneously and independently binds and neutralizes angiopoietin 2 (Ang-2) and vascular endothelial growth factor A (VEGF-A). Researchers aimed to assess the efficacy and safety of different doses and regimens of faricimab vs ranibizumab in individuals with neovascular age-related macular degeneration.
AVENUE was a 36-week, multiple-dose-regimen, active comparator-controlled, double-masked, Phase II randomized clinical study performed at 58 sites in the United States. Eligible participants were anti-VEGF treatment naive with choroidal neovascularization secondary to nAMD and best-corrected visual acuity Early Treatment Diabetic Retinopathy Study letter score of 73 (Snellen equivalent, 20/40) to 24 (Snellen equivalent, 20/320). Data were collected from August 11, 2015, to January 12, 2017, with the final patient visit completed September 26, 2017. Data were analyzed from August 11, 2015, to October 4, 2019.
Participants were randomized 3:2:2:2:3 to receive ranibizumab, 0.5 mg every four weeks (arm A [n=68]); faricimab, 1.5 mg every four weeks (arm B [n=47]); faricimab, 6 mg every four weeks (arm C [n=42]); faricimab, 6 mg every four weeks until week 12, then faricimab, 6 mg every eight weeks (arm D [n=47]); and ranibizumab, 0.5 mg every four weeks until week eight, then faricimab, 6 mg every four weeks (arm E [n=69]).
Main outcomes and measures included:
- mean change in BCVA from baseline to week 36;
- proportion of participants gaining at least 15 letters;
- BCVA of 20/40 or better, or 20/200 or worse; and
- ocular coherence tomographic outcomes in anti-VEGF treatment-naive participants (arms A, B, C, D), and from weeks 12 to 36 in those with incomplete response (participants in arms A and E with week 12 BCVA ETDRS letter score of ≤68 [Snellen equivalent, 20/50 or worse]).
A total of 263 participants were included in the analysis (172 [65.4 percent] female; 258 [98.1 percent] white; mean [SD] age, 78.3 [8.7] years). Here were some of the findings:
- At week 36, adjusted mean change in BCVA vs ranibizumab was:
- 1.6 (80 percent CI, -1.6 to 4.7) letters for arm B (p=0.52);
- -1.6 (80 percent CI, -4.9 to 1.7) letters for arm C (p=0.53); and
- -1.5 (80 percent CI, -4.6 to 1.6) letters for arm D (p=0.53).
- For arm E, adjusted mean change from week 12 was -1.7 (80 percent CI, -3.8 to 0.4) letters (p=0.30).
Researchers found that AVENUE didn’t meet its primary end point of superiority of faricimab over ranibizumab in BCVA at week 36. They wrote that, although not superior to monthly ranibizumab as given in this trial, overall visual and anatomical gains noted with faricimab supported pursuing Phase III trials for a potential alternative to monthly anti-VEGF therapy. Researchers added that faricimab showed no new or unexpected safety signals.
Source: Sahni J, Dugel PU, Patel SS, et al. Safety and efficacy of different doses and regimens of faricimab vs ranibizumab in neovascular age-related macular degeneration: The AVENUE phase 2 randomized clinical trial. JAMA Ophthalmol 2020; July 30. [Epub ahead of print].
Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The STAIRWAY Phase 2 Randomized Clinical Trial
Investigators wrote that faricimab neutralizes angiopoietin-2 and vascular endothelial growth factor A via both simultaneous and independent binding. They evaluated extended dosing with faricimab, a bispecific antibody designed for intraocular use, in individuals with neovascular age-related macular degeneration.
The Phase II randomized clinical trial was a 52-week multicenter, active comparator-controlled, parallel-group study. Study participants were enrolled in 25 U.S. sites in the from January to March 2017 with treatment-naive choroidal neovascularization secondary to neovascular age-related macular degeneration, and best-corrected visual acuity Early Treatment Diabetic Retinopathy Study letter scores of 73 (approximate Snellen equivalent, 20/40) to 24 (approximate Snellen equivalent, 20/320). Analysis began January 2017 and ended March 2018.
Participants were randomized 1:2:2 to receive intravitreal ranibizumab, 0.5 mg, every 4 weeks or faricimab, 6 mg, every 12 or 16 weeks. Participants in the faricimab arms initially received four monthly injections of faricimab. No rescue injections were allowed. Participants randomized to dosing every 16 weeks were assessed for disease activity at week 24 using prespecified criteria. Those with no active disease continued dosing every 16 weeks through trial end; participants with disease activity received dosing every 12 weeks.
Main outcomes and measures included the mean change in BCVA from baseline at week 40.
Of 76 participants enrolled (mean [SD] age, 78.5 [8.5] years; age range, 56 to 94 years; 41 women [58 percent]; 69 white [97 percent]):
- 16 (21 percent) were randomized to ranibizumab every four weeks;
- 29 (38.2 percent) were randomized to faricimab every 12 weeks; and
- 31 (40.8 percent) were randomized to faricimab every 16 weeks.
Here were some of the findings:
- At week 24, 12 weeks after their last initiation injection, 65 percent (36 of 55) of all faricimab-treated participants had no disease activity.
- At week 40, adjusted mean BCVA gains from baseline (Early Treatment Diabetic Retinopathy Study letters) were:
- +11.4 (80 CI, 7.8 to 15) for the ranibizumab injection every four weeks;
- +9.3 (80 percent CI, 6.4 to 12.3) for the faricimab injection every 12 weeks; and
- +12.5 (80 CI, 9.9 to 15.1) for the faricimab injection every 16 weeks arms.
- Participants received through week 52 a mean (SD) total of:
- 12.9 (0.25) for the ranibizumab injection every four weeks;
- 6.7 (0.91) for the faricimab injection every 12 weeks, and;
- 6.2 (093) for the faricimab injection every 16 weeks arms.
- The secondary BCVA and anatomical imaging end points supported the primary end point and were comparable with ranibizumab every four weeks.
- No new or unexpected safety signals were identified.
Investigators wrote that at week 52, faricimab dosing every 16 weeks and every 12 weeks resulted in maintenance of initial vision and anatomic improvements comparable with monthly ranibizumab. They continued that these results suggested a role for simultaneous neutralization of angiopoietin-2 and vascular endothelial growth factor A in providing sustained efficacy through extended durability, warranting further investigation.
Source: Khanani AM, Patel SS, Ferrone PJ, et al. Efficacy of every four monthly and quarterly dosing of faricimab vs ranibizumab in neovascular age-related macular degeneration: The STAIRWAY phase 2 randomized clinical trial. JAMA Ophthalmol 2020; July 30. [Epub ahead of print].
Early Changes on SD-OCT After Treatment with Intravitreal Aflibercept for nAMD
Researchers evaluated early changes on spectral-domain optical coherence tomography during the loading phase with intravitreal aflibercept therapy in individuals with neovascular age-related macular degeneration.
In the prospective, open-label, single-arm, multicenter study, nAMD patients who were anti-vascular endothelial growth factor treatment-naive received three monthly initial doses of intravitreal aflibercept 2 mg. The primary outcome was the proportion of patients with dry SD-OCT at 12 weeks, defined as an absence of intraretinal edema, intraretinal cysts, subretinal fluid and sub-retinal pigment epithelium fluid.
Fifty eyes of 50 individuals were investigated. Here were some of the findings:
- At 12 weeks, 34 percent (17/50) had dry SD-OCT.
- Marked reductions were observed for all other SD-OCT parameters. Mean macular central thickness fell significantly from 463.2 (±184.3) µm at baseline to 288.9 (±76.8 ) µm at week 12 (p<0.0001).
- Mean best-corrected visual acuity also improved significantly from 61 ±16 letters at baseline to 66.6 ±19 letters at week 12 (p=0.0006).
Researchers found that the anatomic and functional outcomes improved over the 12-week study period. All outcome variables peaked after the third aflibercept injection, confirming the benefit of three initial doses.
Source: Korobelnik J-F, Souied EH, Oubraham H, et al. Assessment of early changes in spectral domain-optical coherence tomography (SD-OCT) after initiation of treatment with intravitreal aflibercept (Eylea) over a 12-week period for patients with neovascular age-related macular degeneration. Retina 2020; July 13. [Epub ahead of print].
Timing of Large Submacular Hemorrhage Secondary to AMD Relative to Anti-VEGF Therapy
Researchers characterized the timing of large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration relative to anti-vascular endothelial growth factor therapy, as part of a retrospective, consecutive case series.
A total of 46 eyes of 46 individuals with large SMH due to neovascular AMD selected to undergo pars plana vitrectomy with subretinal tissue plasminogen activator at the Mid Atlantic Retina group of the Wills Eye Hospital were included.
Researchers reviewed patient charts to identify baseline characteristics and anti-VEGF treatment details. They used optical coherence tomography to evaluate pigmented epithelial detachments, SMH and subretinal fluid pre- and post-SMH.
Main outcome measures included the timing of SMH in relation to the last anti-VEGF injection, anti-VEGF treatment status (i.e., naive, stable or recently extended/shortened were each sub-groups of the main 46-patient group) at the time of SMH and the length of the anti-VEGF treatment interval at the time of bleeding.
Here were some of the findings:
- SMH occurred in 15 individuals (36 percent) who were treatment naive.
- In those treated with anti-VEGF, 19 individuals (45 percent) were on a stable treatment interval, five people (12 percent) had recently extended their interval, and three individuals (7 percent) had shortened their interval.
- The average treatment interval at the time of SMH was 6.8 weeks, with a median of seven total injections prior to SMH.
- Seven (26 percent) of treated individuals had a SMH on a four-week dosing interval.
- The average time between last injection and SMH was 29 days.
- Forty-eight percent of anti-VEGF treated patients had a SMH within 30 days of anti-VEGF injection.
- Chi-square analysis found SMH more likely to occur within 30 days of anti-VEGF injection than after 30 days.
Researchers concluded that large SMH in neovascular AMD in a treat-and-extend regimen didn't appear to be associated with prolonged dosing intervals or recent interval extension. They added that a large proportion of such hemorrhages were likely to be the result of mechanisms other than loss of effective VEGF inhibition.
Source: Matsunaga DR, Su D, Sioufi K, et al. The timing of large submacular hemorrhage secondary to age-related macular degeneration relative to anti-VEGF Therapy. Ophthalmol Retina 2020; Aug. 4. [Epub ahead of print].
MERLOT Trial Finds Epimacular Brachytherapy Not Effective for Previously Treated nAMD
Though investigators in the MERLOT trial of epimacular brachytherapy (EMB) for chronic, active, neovascular nAMD say it would be preferable to have a treatment that involved less-frequent dosing than anti-VEGF injections, they unfortunately found no benefit from EMB in patients with the condition.
The Macular Epiretinal Brachytherapy vs Ranibizumab (Lucentis) Only Treatment (MERLOT) device trial was conducted at 24 National Health Service hospitals across the UK. Individuals who had nAMD and received intravitreal ranibizumab were enrolled between November 10, 2009, and January 30, 2012. Eligible individuals were randomized 2:1 and stratified by lens status and angiographic lesion type to receive either EMB plus as-needed ranibizumab, or just as-needed ranibizumab monotherapy. Participants were followed up monthly for 24 months and then assessed at final visits at month 36. Masking of participants and clinicians wasn't possible, but best-corrected visual acuity and imaging were analyzed by masked assessors. Analyses followed the intent-to-treat approach.
Interventions included pars plana vitrectomy with 24 Gy EMB plus as-needed ranibizumab vs. as-needed ranibizumab monotherapy.
Coprimary outcomes were the number of as-needed ranibizumab injections and the mean change in Early Treatment Diabetic Retinopathy Study BCVA with a noninferiority margin of -5 ETDRS letters. Secondary outcomes were the percentage of participants losing fewer than 15 ETDRS letters and gaining 0 or more, or 15 or more ETDRS letters and the mean change in angiographic total lesion size, choroidal neovascularization size and foveal thickness on optical coherence tomography.
Of 363 participants, 329 (90.6 percent) completed 24 months of follow-up (222 participants in the EMB group and 107 in the ranibizumab group). The mean age of the combined groups was 76.5 ±7.4 years. Here were some of the findings:
- The mean number of ranibizumab injections was 9.3 ±6.7 in the EMB group and 8.3 ±4.5 in the ranibizumab group, with a difference of one injection (CI, -0.3 to 2.3; p=0.13).
- The mean BCVA change was -11.2 ±15.7 ETDRS letters in the EMB group and -1.4 ±10.9 ETDRS letters in the ranibizumab group, with a difference of 9.8 ETDRS letters (CI, -6.7 to -12.9).
- In the EMB group, 65.6 percent of participants (160 of 244) lost fewer than 15 ETDRS letters vs. 86.6 percent (103 of 119) in the ranibizumab group, with a difference of 21 percent (CI, 12.4 to 29.5 percent; p<0.001).
- Microvascular abnormalities occurred in 20 of 207 eyes (9.7 percent) in the EMB group and one of 97 eyes (1 percent) in the ranibizumab group. These abnormalities occurred outside the foveal center, and there were no unexpected safety concerns.
Investigators reported that the MERLOT trial found that, despite the acceptable safety of EMB, it didn't reduce the number of ranibizumab injections and was actually associated with worse visual acuity than anti-VEGF treatment alone. They added that these results don't support EMB use as an adjunctive treatment for chronic, active nAMD.
SOURCE: Jackson TL, Soare C, Petrarca C, et al. Evaluation of month-24 efficacy and safety of epimacular brachytherapy for previously treated neovascular age-related macular degeneration: The MERLOT randomized clinical trial. JAMA Ophthalmol 2020; July 09. [Epub ahead of print].
Natural History of Quantitative Autofluorescence in Intermediate AMD
Scientists evaluated differences in quantitative autofluorescence (qAF) imaging measurements between eyes with and without large drusen, and whether qAF measurements changed over time in eyes with large drusen.
A total of 85 eyes from participants with bilateral large drusen, and 51 eyes from healthy participants underwent qAF imaging at least once. Age-related macular degeneration participants were reviewed monthly for six months. Normalized gray values at 9- to 11-degree eccentricity from the fovea were averaged to provide a summary measure of qAF values (termed “qAF8”).
In a multivariable model, qAF8 measurements weren’t significantly different between AMD eyes with large drusen and healthy eyes (p=0.130), and qAF8 measurements showed a decline over time in AMD eyes (p=0.013).
Scientists wrote that qAF levels weren’t increased in eyes with large drusen compared with healthy eyes, and that qAF levels showed a significant decline over time in the AMD eyes. In addition, they wrote, the findings highlight how the relationship between qAF levels and retinal pigment epithelium health doesn’t appear to be straightforward and that further investigation is required to better understand this relationship, especially if qAF levels may be used as an outcome measure in intervention trials.
SOURCE: Emde LV, Guymer RH, Pfau M, et al. Natural history of quantitative autofluorescence in intermediate age-related macular degeneration. Retina 2020; Jul 22. [Epub ahead of print].
“Ultra-Response” to Ranibizumab Found in Genentech Study
In a Genentech-sponsored study, researchers aimed to quantify and evaluate individuals with diabetic retinopathy who had at least four-step improvements on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale in response to ranibizumab treatment in post hoc study of the results of the Diabetic Retinopathy Clinical Research Network Protocol S study.
The retrospective analysis of two-year outcomes in the Phase III Protocol S study included individuals randomized to treatment with ranibizumab 0.5 mg with sufficient baseline DRSS severity (≥47) to allow for an at least four-step improvement (n=181).
Study eyes received a ranibizumab 0.5 mg injection at baseline and every four weeks for 12 weeks, with subsequent as-needed injections. Fundus photographs graded at baseline and years one and two using DRSS were used for this analysis. (Researchers clarified that the data source was DRCR.net, but analyses, content and conclusions of this report are solely the responsibility of the authors.)
Main outcome measures included the proportion of eyes achieving at least a four-step DRSS improvement (DR ultra-response) at years one and two; treatment course for eyes achieving ultra-response; mean change in best-corrected visual acuity in eyes with and without ultra-response; and factors associated with ultra-response (identified by univariate and multivariable analyses).
Here were some of the findings:
- Nearly 30 percent of ranibizumab-treated eyes achieved DR ultra-response at year one (43/148; 29.1 percent) and year two (38/136; 27.9 percent).
- Seventy-four percent of eyes with ultra-response at year one maintained their response at year two.
- At year two, individuals with DR ultra-response had gained more than five additional ETDRS letters compared with those without DR ultra-response.
- Multivariable analyses identified presence of vitreous hemorrhage at baseline, increasing age, absence of epiretinal membrane and glycated hemoglobin below nine as predictive of DR ultra-response.
- Mean number of injections received was similar for eyes with vs. without DR ultra-response to ranibizumab (mean: 7.4 vs. 7.6 in year one; mean: 4.2 vs. 3.9 in year two, respectively).
Researchers concluded that approximately 30 percent of eyes with a DRSS score of at least 47 receiving ranibizumab 0.5 mg per study protocol experienced at least four-step DR severity improvement on the DRSS, accompanied by meaningful improvements in BCVA.
SOURCE: Chiang A, Garg SJ, Klufas MA, et al. Ultra-response to ranibizumab: Improvement by 4 or more steps in diabetic retinopathy severity in DRCR.net Protocol S. Ophthalmol Retina 2020; July 28. [Epub ahead of print].
Prognostic Value of Peripheral Retinal Nonperfusion in DR Using Ultra-widefield Fluorescein Angiography
Scientists assessed the prognostic value of peripheral retinal nonperfusion in individuals with diabetic retinopathy, using ultra-widefield fluorescein angiography (UWFA).
The cross-sectional study included 78 treatment-naive eyes with nonproliferative and proliferative diabetic retinopathy (NPDR and PDR). Eyes were divided into three groups: mild/moderate NPDR (n=31); severe NPDR (n=31); and PDR (n=16). Three nonperfusion variables were calculated, reflecting the proportion of nonperfused to visible retina based on initial UWFA: central nonperfusion (CNP) index; peripheral nonperfusion (PNP) index; and PNP ratio. Scientists evaluated the relationships between these indices, central subfield thickness (CST) and spectacle-corrected visual acuity (SCVA).
Here were some of the findings:
- CNP and PNP indices were significantly higher in the PDR group (p=0.007) vs. the mild/moderate NPDR group (0.008) but not in the PDR group (p=0.149) vs. severe NPDR group (p=0.535).
- A significant linear correlation was found between the CNP and PNP indices in the severe NPDR group (R2=0.141, p=0.041) and PDR group (R2=0.311, p=0.025).
- Nonperfusion predominance wasn't statistically correlated with the presence of macular edema (p=0.058) or disorganization of retinal inner layers (p=1).
- In the severe NPDR group, scientists found a moderately positive correlation between the CNP index and CST (rs=0.496, p=0.019), and no correlation between the CNP index and SCVA (p=0.160) when controlling for CST.
- In the PDR group, a strong negative correlation between the PNP ratio and CST was found (rs=-0.659, p=0.014), but no correlation was observed between CNP index, CST and SCVA.
- In the PDR group, a positive correlation was found between the PNP index, and PNP ratio (rs=0.549, p=0.027) and SCVA (rs=0.626, p=0.010), even after controlling for CST (rs=0.599, p=0.040).
Scientists determined that higher amounts of retinal nonperfusion were seen in patients with more severe retinopathy. Further, increased CNP was associated with macular thickening and subsequent vision loss; and having predominantly PNP was independently associated with worse VA, regardless of macular thickness. Scientists suggested that further studies would be needed to investigate the role of PNP in vision loss in diabetic retinopathy.
SOURCE: Antaki F, Coussa RG, Mikhail M, Archambault C, Lederer DE. The prognostic value of peripheral retinal nonperfusion in diabetic retinopathy using ultra-widefield fluorescein angiography. Graefes Arch Clin Exp Ophthalmol 2020; Jul 16. [Epub ahead of print].
Quantification of Fluid Resolution and VA Gain in Patients with DME Using Deep Learning
Researchers wrote that optical coherence tomography can acquire large amounts of data on diabetic macular edema, but many morphologic features have yet to be identified and quantified. In their study, they aimed to examine the volumetric change of intraretinal and subretinal fluid in DME during anti-vascular endothelial growth factor treatment using deep learning algorithms. One of the authors received fees from Novartis and Roche/Genentech, and has a patent to analyze optical coherence tomographic images pending. Another author received grants from Regeneron and Genentech during the conduct of the study
The post hoc analysis of a randomized clinical trial, the Diabetic Retinopathy Clinical Research Network (protocol T), assessed 6,945 spectral-domain OCT volume scans of 570 eyes from 570 study participants with DME. The original trial was performed from August 21, 2012, to October 18, 2018. The current analysis was performed from December 7, 2017, to January 15, 2020.
Participants were treated according to a predefined, standardized protocol with aflibercept, ranibizumab or bevacizumab, with or without deferred laser.
Main outcomes and measures included the association of treatment with IRF and SRF volumes, and best-corrected visual acuity during 12 months using deep-learning algorithms.
Of 570 study participants (302 [53 percent] male; 369 [65 percent] white; mean age, 43.4 ±12.6 years), here were some of the findings:
- The mean fluid volumes in the central 3 mm were:
- 448.6 nL (CI, 412.3 to 485.0 nL) of IRF and 36.9 nL (CI, 27 to 46.7 nL) of SRF at baseline; and
- 161.2 nL (CI, 135.1 to 187.4 nL) of IRF and 4.4 nL (CI, 1.7 to 7.1 nL) of SRF at 12 months.
- The presence of SRF at baseline was associated with a worse baseline BCVA Early Treatment Diabetic Retinopathy Study score of 63.2 (CI, 60.2 to 66.1) (approximate Snellen equivalent of 20/63 [CI, 20/50 to 20/63]) vs. 66.9 (CI, 65.7 to 68.1) (approximate Snellen equivalent, 20/50 [CI, 20/40 to 20/50]) in eyes without SRF (p<0.001).
- The presence of SRF at baseline was associated with a greater gain in ETDRS score (0.5; CI, 0.3 to 0.8) every four weeks during follow-up vs. 0.4 (CI, 0.3 to 0.5) in eyes without SRF at baseline (p=0.02) when adjusted for baseline BCVA.
- Aflibercept was associated with greater reduction of IRF volume compared with bevacizumab after the first injection (difference, 79.8 nL; CI, 5.3 to 162.5 nL; p<0.001) and every four weeks thereafter (difference, 10.4 nL; CI, 0.7 to 20.0 nL; p=0.004).
- Ranibizumab was associated with a greater reduction of IRF after the first injection compared with bevacizumab (difference, 75.2 nL; CI, 1.4 to 154.7 nL; p<0.001).
Researchers found that automated segmentation of fluid in DME revealed that the presence of SRF was associated with a lower baseline BCVA but with good response to anti-vascular endothelial growth factor therapy. They added that such automated spectral-domain OCT analyses may be used clinically to assess anatomical change during therapy.
SOURCE: Roberts PK, Vogl W, Gerendas BS, et al. Quantification of fluid resolution and visual acuity gain in patients with diabetic macular edema using deep learning: A post hoc analysis of a randomized clinical trial. JAMA Ophthalmol 2020; July 23. [Epub ahead of print.]
Macular Vessel Density in Diabetes and DR with SS-OCTA
Researchers wrote that previous studies on the association between macular vessel density and diabetic retinopathy have had conflicting conclusions. So they assessed the alterations of macular vessel density and other factors in diabetic patients, using swept-source optical coherence tomography angiography in a large-scale sample from Chinese communities.
Patients with type 2 diabetes without histories of ocular treatment were recruited from 2017 to 2018. The average and quadrant parafoveal vessel densities (PVDs) were obtained with a commercial SS-OCTA device (Triton, Topcon). The univariate and multivariate linear regression was used to analyze the correlation of PVD with diabetic retinopathy, diabetic macular edema, HbA1c and other factors.
A total of 919 individuals were included in the final statistical analysis. Here were some of the findings:
- After adjusting for other confounding factors, the DR patients had significantly lower average PVD (β=-1.062; CI, -1.424 to -0.699; p<0.001) in comparison with those without DR.
- In addition, individuals with mild DR or vision-threatening diabetic retinopathy (VTDR) also had significantly lower PVD (p<0.001 for mild DR, and p=0.008 for VTDR) compared with those without DR.
- Age and HbA1c were significantly related to PVD measurements, as shown by multivariable linear regression.
- Individuals with DME had a significantly lower average PVD and temporal PVD than those without DME (p<0.05).
Researchers found that reduced PVD was independently associated with more severe DR, older age, higher HbA1c level and the presence of DME. They wrote that the findings suggested that macular vessel alterations in DR warrant further evaluation in longitudinal studies.
Source: Xie N, Tan Y, Liu S, et al. Macular vessel density in diabetes and diabetic retinopathy with swept-source optical coherence tomography angiography Graefes Arch Clin Exp Ophthalmol 2020; July 13. [Epub ahead of print].
Locus Level Changes in Macular Sensitivity in RP Treated with Oral N-acetylcysteine
Scientists identified locus characteristics associated with locus-level sensitivity loss or improvement during N-acetylcysteine (NAC) treatment in retinitis pigmentosa, as part of a retrospective analysis of prospectively collected data in the FIGHT RP clinical trial, sponsored by Johns Hopkins.
Individuals (n=30) were treated with 600, 1,200 or 1,800 mg NAC twice a day for three months, and then three times a day for three months. Microperimetry locus-level changes between baseline and month six were correlated with baseline locus characteristics using regression models. The main outcome measure was locus-level sensitivity change ≥6 dB.
Here were some of the findings:
- The baseline mean sensitivity (3,468 loci, 51 evaluable eyes) was 7.7 dB.
- It was: for foveal, 20.2; for parafoveal, 11.8; and for perifoveal loci, 5.8 dB.
- During treatment, 287 (8.28 percent) loci increased ≥6 dB, and 119 of 1,613 loci with baseline sensitivity ≥6 dB decreased ≥6 dB (7.38 percent).
- Higher NAC dose was associated with lower likelihood of sensitivity loss ≥6 dB (p=0.033).
- Loci with low baseline sensitivity were more likely to decrease ≥6 dB (p=0.034), but also more likely to increase ≥6 dB (p< 0.001).
- Foveal vs. perifoveal loci (p<0.001) and superior vs. inferior loci (p=0.005) were more likely to increase ≥6 dB.
Scientists found that higher NAC dose reduced the risk of macular loci sensitivity loss in RP. They wrote that greater sensitivity depression reversibility in the fovea during treatment suggested that high foveal cone density protected cones from irreversible loss of function in RP, making them more likely to show improved function during NAC treatment.
SOURCE: Xiangrong Kong, Gulnar Hafiz, Dagmar Wehling, et al. Locus level changes in macular sensitivity in patients with retinitis pigmentosa treated with oral n-acetylcysteine. Am J Ophthalmol 2020; Aug. 11. [Epub ahead of print].
Results From the Port Delivery System with Ranibizumab (PDS)
Roche announced results from the Phase III Archway study evaluating its investigational Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration. In Archway, 98.4 percent of PDS patients were able to go six months without needing additional treatment and achieved vision outcomes equivalent to patients receiving monthly ranibizumab eye injections, the company says. In addition, PDS was generally well-tolerated, with a favorable benefit-risk profile. 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. The new data was discussed virtually during the 38th Annual Meeting of the American Society of Retina Specialists on July 26. A recorded presentation of these data is now available to ASRS attendees through the meeting web portal. Read more.
SOURCE: JAMA Ophthalmology and Roche, July 2020
AERIE REPORTS TOPLINE RESULTS FOR AR-1105 PHASE II TRIAL
Aerie Pharmaceuticals reported topline results from its Phase II clinical trial evaluating AR-1105 (dexamethasone intravitreal implant) in individuals with macular edema associated with retinal vein occlusion. The trial’s objective was to evaluate two formulations of AR-1105 with different steroid release profiles. In the initial safety stage, five patients were enrolled in a single cohort to receive a 340-µg dose of dexamethasone in a single intravitreal injection. In stage two, 44 patients were randomized 1:1 to receive either formulation. The company says that the results demonstrated positive and sustained treatment effects with both formulations. Peak efficacy was observed earlier with the first formulation, while the second demonstrated a longer overall duration of effect of up to six months. Read more.
SOURCE: Aerie Pharmaceuticals, July 2020
JCYTE ANNOUNCES PHASE IIB RESULTS OF JCELL THERAPY
jCyte says that the recently announced results from its Phase IIb clinical trial of jCell have been “promising.” Jcell is a first-in-class investigational treatment for retinitis pigmentosa that has received FDA Regenerative Medicine Advanced Therapy and Orphan Drug designations. The trial was a multicenter, randomized study evaluating the safety and efficacy of intravitreal injection of jCell therapy vs. sham in adult subjects with RP. Individuals with RP with best-corrected visual acuity between 20/80 and 20/800 were randomized to treatment vs. sham. Treatment consisted of a single intravitreal injection of either three or six million human retinal progenitor cells. In the 74 patients who met criteria per-protocol analysis, the mean changes in BCVA from baseline to month 12 were: +2.81, +2.96 and +7.43 letters in the sham arm (n=26); and 3 x 106 hRPC (n=25) and 6 x 106 hRPC (n=23) in the treatment arm, respectively. Read more.
Source: jCyte Inc., July 2020
REGENXBIO PROVIDES PHASE I/IIA TRIAL UPDATE
RegenxBio reported one-year data from individuals in cohorts 4 and 5 of its Phase I/IIa trial of its gene therapy RGX-314 for the treatment of wet age-related macular degeneration. The company says it plans to initiate a program for subretinal delivery of RGX-314 in individuals with wet AMD by the end of 2020. In addition, it announced that a Phase II trial of RGX-314 for the treatment of wet AMD delivered to the suprachoroidal space (AAVIATE) is active and expected to enroll patients in the third quarter of 2020. Read more.
SOURCE: RegenxBio, August 2020
OCUGEN RECEIVES FOURTH FDA ORPHAN DRUG DESIGNATION FOR GENE THERAPY
Ocugen announced the FDA granted a fourth Orphan Drug Designation for OCU400 in the treatment of PDE6B gene mutation-associated retinal diseases. Ocugen’s Modifier Gene Therapy Platform addresses multiple diseases, and its novel gene therapy product candidate, OCU400, has the potential to be broadly effective in restoring retinal integrity and function across genetically diverse inherited retinal diseases, the company says. Read more.
Source: Ocugen, August 2020
FDA ACCEPTS INVESTIGATIONAL NEW DRUG APPLICATION FOR CLEARSIDE CLS-AX
Clearside Biomedical announced the FDA accepted its Investigational New Drug application for CLS-AX (axitinib injectable suspension), paving the way for a Phase I/IIa clinical trial of CLS-AX in neovascular age-related macular degeneration by the end of 2020. The trial is expected to be an open-label, dose-escalation study. Read more.
SOURCE: Clearside Biomedical, August 2020
EYEPOINT & HARROW HEALTH’S IMPRIMISRX ANNOUNCE DEXYCU ALLIANCE
EyePoint Pharmaceuticals and ImprimisRx announced the signing of a commercial alliance for the joint promotion of Dexycu (dexamethasone intraocular suspension) 9% for the treatment of postoperative inflammation following ocular surgery in the United States. Read more.
SOURCE: EyePoint Pharmaceuticals, August 2020
ARAIM’S CIBINETIDE SHOWS POTENTIAL FOR EFFICACY IN DME
Araim Pharmaceuticals announced the publication of results from an exploratory clinical trial indicating efficacy of lead compound cibinetide in the treatment of diabetic macular edema. The study was sponsored by the Belfast Health and Social Care Trust. Cibinetide is a first-in-class synthetic peptide designed to activate innate repair mechanisms in the setting of tissue injury as a result of the inflammatory cascade. Read more.
SOURCE: Araim Pharmaceuticals, July 2020
4D MOLECULAR THERAPEUTICS DOSES FIRST PATIENT IN PHASE I CLINICAL TRIAL OF 4D-110
4D Molecular Therapeutics announced the first patient was dosed in its Phase I clinical trial of 4D-110, a Roche-licensed product candidate delivered by a single intravitreal injection for choroideremia. The open-label, dose-exploration and -expansion study is expected to enroll up to 15 patients with choroideremia. Read more.
SOURCE: 4D Molecular Therapeutics, July 2020
NUMAB AND BOEHRINGER INGELHEIM TO DEVELOP MULTI-SPECIFIC ANTIBODY THERAPEUTICS
Boehringer Ingelheim and Numab Therapeutics have entered into a research collaboration and worldwide licensing agreement that includes development of novel therapies for geographic atrophy. The collaboration brings together Boehringer Ingelheim’s expertise in the research and development of breakthrough therapies, and Numab’s multi-specific antibody platform. Read more.
SOURCE: Boehringer Ingelheim and Numab Therapeuutics, July 2020
BAUSCH HEALTH ANNOUNCES ITS INTENTION TO SPIN OFF ITS EYE HEALTH BUSINESS
Bausch Health announced that it intends to spin off its eye-care business into an independent publicly traded entity called “Bausch + Lomb – NewCo.” The spinoff will establish two separate companies: the eye-care company; and a diversified pharmaceutical company with leading interests in gastroenterology, aesthetics/dermatology, neurology and international pharmaceuticals. Read more.
IVERIC ADDS DR. BLUMENKRANZ TO BOARD
Iveric bio announced the election of Mark S. Blumenkranz, MD, MMS, HJ Smead Professor Emeritus of Ophthalmology at Stanford University, to its board of directors, effective July 15. Dr. Blumenkranz is a vitreoretinal specialist with contributions in the area of novel pharmaceuticals for macular diseases, ocular gene therapy, new laser systems, and ophthalmic tele-health and technology development. Dr. Blumenkranz is a co-founder, and chief executive officer and chairman of Kedalion Therapeutics, and serves as a director of Verana Health, BVI Visitec, Combangio Corp. and One Medical. Read more.
SOURCE: Iveric, July 2020
EYENUK ANNOUNCES FDA CLEARANCE FOR EYEART
Eyenuk received FDA 510(k) clearance to market its EyeArt autonomous AI System for diabetic retinopathy. EyeArt is indicated to automatically detect more than mild diabetic retinopathy (mtmDR) and vision-threatening diabetic retinopathy (vtDR) in eyes of adults diagnosed with diabetes who haven’t been previously diagnosed with more than mild diabetic retinopathy. Read more.
SOURCE: EyeArt, August 2020
RETINA-AI HEALTH RAISES $5.2M FOR AI DETECTION OF DR
RETINA-AI Health, which is developing AI technology to enable the diabetic retinal exam to be done in the primary-care setting, raised $5.2 million in a series A financing for artificial intelligence screening of diabetic retinopathy. The capital was raised from private investors, 80 percent of whom are physicians. The company's HUMMINGBIRD DR 100 is a cloud-based AI detector of diabetic retinopathy that interprets the retinal image and returns a PDF report. Read more.
SOURCE: RETINA-AI Health, August 2020
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