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.
Topical NSAIDS for Pain from Intravitreal Injections: A Meta-analysis
Scientists explored the role of topical non-steroidal anti-inflammatory agents for the reduction of ocular pain after intravitreal injections (IVIs). They initiated a meta-analysis of randomized controlled trials (RCTs) to provide clarity on the evidence for these agents.
They conducted a systematic literature search on Ovid Medline, Embase and Cochrane Central from inception to July 2019. RCTs that treated patients with a topical NSAID and assessed post-procedural pain were included. Risk of bias was assessed using the Cochrane guidelines. For all analyses, weighted mean differences (WMDs) with 95% confidence intervals were reported. Scientists used random effects models for all analyses.
The primary analysis evaluated pain on a zero to 10-point visual analogue scale. Scientists categorized literature estimates into the following post-procedure timepoint groups: ≤one hour; one to 24 hours (though data was only available at six hours); and ≥24 hours. A subgroup analysis stratified studies based on agent and pre- vs. post-procedure administration. All study endpoints were formulated before data collection.
From 241 results, a total of nine RCTs and 598 eyes were included. There was a low-to-medium risk of bias across the included studies. Here were the findings:
• The mean pain score on a zero to 10 visual analogue scale was significantly lower following topical NSAID administration relative to control at:
o ≤one hour (WMD=-1.01 units, CI, -1.38 to -0.65; p<0.001);
o six hours (WMD=-2.17 units, CI, -2.67 to -1.68; p<0.001;
o threshold met for clinical significance, defined as WMD >1.2 units; and >24 hours after IVI (WMD=-0.75 units, CI, -1.11 to -0.38; p<0.001).
• A greater effect was seen with administration of NSAIDs before vs. after IVIs, as well as topical nepafenac relative to ketorolac or diclofenac.
Scientists concluded that, at six hours post-procedure, NSAIDs provided a clinically meaningful reduction in pain relative to control. They added that the administration of topical nepafenac pre-procedure was associated with the greatest improvement in pain relative to control. Scientists advised that the findings, given the lack of diversity of studies and associated sample size, should be regarded as hypothesis-generating.
SOURCE: Popovic MM, Muni RH, Nichani P, et al. Topical non-steroidal anti-inflammatory drugs for pain from intravitreal injections: A meta-analysis. Ophthalmology Retina 2020; Feb 13. [Epub ahead of print].
Management & Outcomes for nAMD: Analysis of U.S. EHRs
Researchers assessed anti-vascular endothelial growth factor management patterns, and anatomic and visual acuity outcomes among individuals with neovascular age-related macular degeneration in U.S. clinical practice, as part of a retrospective, observational cohort study.
A total of 30,106 individuals (37,021 study eyes) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016, were included. Researchers performed an analysis of longitudinal electronic health records from the USRetina database
Main outcome measures included intravitreal injections, optical coherence tomography scans and fluorescein angiography procedures received per study eye during the first 12 months; corrected visual acuity and central retinal thickness at 12 months (absolute value and change from baseline); and number of ophthalmologist visits, stratified by index anti-VEGF agent. Here were some of the findings:
• Over the first 12 months, patients made a mean of 8.1 ophthalmologist visits (range: 1 to 39), and received a mean of six intravitreal anti-VEGF injections (range: one to 27), 7.2 OCT scans and 5.3 FA procedures per study eye.
• For eyes with paired baseline and 12-month anatomic and visual readings, mean CRT declined from 320 to 271 μm (mean change: -48 μm), and mean VA increased from 60.3 to 61 approximate ETDRS (approxETDRS) letters (mean change: +0.6).
• Twelve months after initiating index treatment, 19.3 percent (bevacizumab), 15.8 percent (ranibizumab) and 15.5 percent (aflibercept) of eyes showed >10-letter gain, whereas 13.2 percent (bevacizumab), 14.7 percent (ranibizumab) and 14.4 percent (aflibercept) of eyes showed >10-letter loss.
• Mean change from baseline in VA at 12 months tended to increase linearly with the number of anti-VEGF injections administered over the first 12 months: +1.79 vs. -0.95 approxETDRS letters for eyes receiving at least seven injections vs. those receiving less than seven.
• Similarly, the magnitude of the reduction from baseline in CRT at 12 months tended to increase linearly as the number of anti-VEGF injections increased.
• Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approxETDRS letters.
Researchers wrote that the analysis of combined morphological/functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited visual acuity improvements, in U.S. clinical practice.
SOURCE: Kiss S, Campbell J, Almony A, et al. Management and outcomes for neovascular age-related macular degeneration: Analysis of us electronic health records. Ophthalmology 2020; Feb 27. [Epub ahead of print].
Timing of Peak Vision Gains in nAMD Treated with Ranibizumab
Scientists assessed whether time to peak best-corrected visual acuity (pBCVA) was predictive of the magnitude of changes in BCVA at study end in individuals with neovascular age-related macular degeneration who received ranibizumab, and assessed whether patient baseline characteristics and on-study events were predictive of time to pBCVA.
The exploratory analysis of data from HARBOR included treatment-naïve patients ages 50 years or more with subfoveal nAMD.
Data by ranibizumab dose were pooled; data by dosing schedule (as-needed [PRN] and monthly) were evaluated separately. Time to pBCVA was the monthly evaluation at which the patient’s greatest gain in Early Treatment Diabetic Retinopathy Study letters from baseline was achieved. “Early peakers” achieved pBCVA between day seven and month (M) six; “late peakers” achieved pBCVA between M7 and M12, M13 and M18, and M19 and M24. Variables evaluated for effect of time to pBCVA included baseline demographic/clinical characteristics, presence of persistent subretinal fluid or intraretinal fluid and on-study events (atrophy status, fibrosis, retinal pigment epithelium tears).
Main outcome measures included time to pBCVA and its predictive value for magnitude of BCVA changes and BCVA at M24 (study end). Here were some of the findings:
• Most patients reached pBCVA after more than six months of treatment: 64 percent in the PRN group (301/474) and 70 percent in the monthly group (327/469).
• Thirty-six percent in the PRN group, and 30 percent in the monthly group peaked early.
• Sixty-four percent in the PRN group, and 70 percent in the monthly group peaked late.
• At M24, early peakers on average lost vision (PRN, -1.6 ETDRS letters; monthly, -1.9 ETDRS letters).
• Late peakers had significantly better vision gains from baseline (PRN, 8.5 to 17.7 ETDRS letters; monthly, 10.1 to 18.7 ETDRS letters).
• No differences were found in patient characteristics, persistent SRF/IRF or on-study events to account for the observed different outcomes between early vs. late peakers.
Scientists wrote that, in the majority of treatment-naïve patients with nAMD, vision gains were achieved at a slower rate (>six months), and a slower response was associated with better vision outcomes after 24 months of ranibizumab. They added that these findings suggested that continued treatment may result in greater vision improvements when consistent anti-vascular endothelial growth factor therapy is maintained over a longer period.
SOURCE: Khurana RN, Chang L, Day B-m, et al. Timing of peak vision gains in patients with neovascular age-related macular degeneration treated with ranibizumab. Ophthalmology Retina 2020; Feb 27. [Epub ahead of print].
Risk Factors for Developing Subretinal Fibrosis in nAMD Eyes
Researchers assessed the prevalence of and risk factors for subretinal fibrosis (SRFi) in eyes with neovascular age-related macular degeneration that underwent vascular endothelial growth factor inhibitor treatment for up to 10 years.
They performed a cross-sectional and longitudinal analysis on data from a neovascular age-related macular degeneration registry. The presence and location of SRFi were graded by the treating practitioner. Visual acuity, lesion characteristics (type, morphology and activity) and treatment administered at each visit were recorded. Here were some of the findings:
• The prevalence of SRFi in 2,914 eyes rose from 20.4 percent at year interval zero, to 40.7 percent at year interval nine to 10.
• The incidence in 1,950 eyes was 14.3 percent at baseline and 26.3 percent at 24 months.
• Independent characteristics associated with SRFi included:
o poorer baseline vision (adjusted OR, 5.33; CI, 4.66 to 7.61) for visual acuity ≤35 letters vs. visual acuity ≥70 letters, p<0.01);
o baseline lesion size (adjusted OR, 1.08; CI, 1.08 to 1.14) per 1,000 µm, p=0.03);
o lesion type (adjusted OR, 1.42; CI, 1.17 to 1.72) for predominantly classic vs. occult lesions, p=0.02); and
o proportion of active visits (adjusted OR, 1.58 [CI, 1.25 to 2.01] for the group with the highest level of activity vs. the lowest level of activity, p<0.01).
Researchers determined that subretinal fibrosis was found in 40 percent of eyes after 10 years of treatment. They added that high rates of lesion activity, predominantly classic lesions, poor baseline vision and larger lesion size seemed to be independent risk factors for SRFi.
SOURCE: Teo KYC, Joe AW, Nguyen V, et al. Prevalence and risk factors for the development of physician-graded subretinal fibrosis in eyes treated for neovascular age-related macular degeneration. Retina 2020; Feb 17. [Epub ahead of print].
Deep Learning Model for GA Segmentation to Study Long-term Natural History
Researchers developed and validated a deep learning model for the automatic segmentation of geographic atrophy in color fundus images (CFIs) and its application to study growth rate of GA, as part of a prospective, multicenter, natural history study with up to 15 years of follow up.
A total of 409 CFIs of 238 eyes with GA from the Rotterdam Study (RS) and the Blue Mountains Eye Study (BMES) for model development, and 3,589 CFIs of 376 eyes from the Age-Related Eye Disease Study (AREDS) were analyzed for GA growth rate.
Researchers implemented and optimized a deep learning model based on an ensemble of encoder-decoder architectures for the segmentation of GA in CFIs. Four experienced graders delineated, in consensus, GA in CFIs from RS and BMES. These manual delineations helped evaluate the segmentation model using five-fold cross-validation. The model was further applied to CFIs from AREDS to study the growth rate of GA. Researchers used linear regression analysis to study associations between baseline structural biomarkers and the GA growth rate. They made a general estimate of the progression of GA area over time by combining growth rates of all eyes with GA from the AREDS set.
Main outcome measures included the automatically segmented GA and GA growth rate. Here were some of the findings:
• The model obtained an average Dice coefficient of 0.72 ±0.26 on the BMES and RS set while comparing the automatically segmented GA area to the graders’ manual delineations.
• An intraclass correlation coefficient of 0.83 was reached between the automatically estimated GA area and the graders' consensus measures.
• Nine automatically calculated structural biomarkers (area, filled area, convex area, convex solidity, eccentricity, roundness, foveal involvement, perimeter and circularity) were significantly associated with growth rate.
• Combining all growth rates indicated that the GA area grew quadratically up to an area of around 12 mm2, after which the growth rate stabilized or decreased.
Researchers determined that their deep learning model allowed for fully automatic and robust segmentation of GA in CFIs. They added that the segmentations could be used to extract structural characteristics of GA that predict its growth rate.
SOURCE: Liefers B, Colijn JM, González-Gonzalo C, et al. A deep learning model for segmentation of geographic atrophy to study its long-term natural history. Ophthalmology 2020; Feb 14. [Epub ahead of print].
Higher Intake of Poly- and Monounsaturated Fatty Acid Inversely Associated with AMD
Researchers evaluated the association between dietary fat intake and the presence of age-related macular degeneration, as part of a cross-sectional, observational study with cohorts prospectively recruited from the United States and Portugal.
AMD was diagnosed based on color fundus photographs with the AREDS classification. Researchers used a validated food frequency questionnaire to calculate the percent energy intake of trans fat, saturated fat, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA). For quintiles, they calculated odds ratios and 95% confidence intervals or amount of FA. They used multiple logistic regression to estimate the OR.
A total of 483 participants—386 individuals with AMD and 97 controls were included. Here were some of the findings:
• Higher intake of trans fat was associated with a 2.3-fold higher odds of presence of AMD (p=0.0156), whereas a higher intake of PUFA (OR, 0.25; p=0.006) and MUFA (OR, 0.24; p<0.0001) presented an inverse association.
• Subgroup analysis showed that a higher quintile of trans fat was associated with increased odds of having intermediate AMD (OR, 2.26; p=0.02); and a higher quintile of PUFA and MUFA were inversely associated with intermediate AMD (OR, 0.2 [p=0.0013]; OR, 0.17 [p<0.0001]) and advanced AMD (OR, 0.13 [p=0.02]; OR, 0.26 [p=0.004]).
• A statistically significant effect modification by country was noted, with a significant inverse association between MUFA and AMD (OR, 0.04; p<0.0001) for the Portugal population only.
Researchers wrote that their study showed that higher dietary intake of trans fat was associated with the presence of AMD, and a higher intake of PUFA and MUFA was inversely associated with AMD.
SOURCE: Roh M, Shin HJ, Laíns I , et al. Higher intake of polyunsaturated fatty acid and monounsaturated fatty acid is inversely associated with AMD. Invest Ophthalmol Vis Sci. 2020;61:2:20.
DRCR Retina Network Management Approach with Initial Observation for Center-involved DME & Good VA
Scientists aimed to assess the DRCR Retina Network protocol-defined approach and outcomes of initial observation with aflibercept only if VA worsened. This post hoc secondary analysis of a randomized clinical trial of the DRCR Retina Network Protocol V included 91 U.S. and Canadian sites from November 2013 to September 2018.
Adults (n=236) with type 1 or 2 diabetes, one study eye with center-involved diabetic macular edema (CI-DME) and VA letter score of at least 79 (Snellen equivalent, 20/25 or better) were assigned to initial observation. Data were analyzed from March 2019 to November 2019.
Initial observation and follow-up included aflibercept only for VA loss of at least 10 letters from baseline at one visit, or five to nine letters at two consecutive visits. Follow-up occurred at eight weeks and then every 16 weeks unless VA or optical coherence tomography central subfield thickness worsened. Main outcomes and measures included whether individuals received aflibercept. Here were some of the findings:
• Among 236 eyes in 236 individuals (149 [63 percent] male; median age, 60 years [interquartile range: 53 to 67 years]) randomly assigned to initial observation, 80 (34 percent) were treated with aflibercept during two years of follow-up.
• At two years, the median VA letter score was 86 (interquartile range: 89 to 81; median Snellen equivalent: 20/20 [20/16 to 20/25]).
• Receipt of aflibercept was more likely:
o in eyes with baseline central subfield thickness at least 300 μm (Zeiss-Stratus equivalent) vs. less than 300 μm (45 percent vs. 26 percent; hazard ratio [HR]: 1.98 [CI, 1.26 to 3.13], continuous p=0.005);
o in eyes with moderately severe nonproliferative diabetic retinopathy (Early Treatment Diabetic Retinopathy Study retinopathy severity level 47) and above vs. moderate nonproliferative diabetic retinopathy (retinopathy severity level 43) and below (51 percent vs. 27 percent; HR, 2.22 [CI, 1.42 to 3.47], ordinal p<0.001); and
o among participants whose nonstudy eye received DME treatment within four months of randomization vs. not (52 percent vs. 25 percent; HR: 2.55 [CI, 1.64 to 3.99], p<0.001).
Scientists found that most eyes managed with initial observation plus aflibercept only if VA worsened maintained good vision at two years and didn’t require aflibercept for VA loss. However, trial eyes were approximately twice as likely to receive aflibercept for VA loss if they had greater baseline central subfield thickness, worse diabetic retinopathy severity level or a non-study eye receiving treatment for DME.
SOURCE: Adam Glassman, Baker CW, Beaulieu WT, et al. Assessment of the DRCR retina network approach to management with initial observation for eyes with center-involved diabetic macular edema and good visual acuity. JAMA Ophthalmol 2020; Feb 20. [Epub ahead of print].
Aflibercept Reduces Retinal Hemorrhages & IRMAs but Not Venous Beading: CLARITY Analysis
The CLARITY study was a Phase IIb, non-inferiority study comparing panretinal laser photocoagulation to intravitreal aflibercept in individuals with proliferative diabetic retinopathy. Approximately half of the individuals receiving anti-VEGF therapy showed significant improvement in their DR severity score (DRSS), particularly at DRSS level 47/53 (moderately severe/severe non-proliferative DR), scientists wrote. Level 47/53 consisted of three main features, namely deep hemorrhages (DHs), venous beading (VB) and intraretinal microvascular abnormalities (IRMAs). Scientists wrote that it was unclear whether these features responded to anti-VEGF therapies differently.
As part of a post-hoc analysis of the CLARITY Study, treatment-naïve participants were randomized to intravitreal aflibercept. Scientists reanalyzed the fundus images at baseline, week 12 and week 52 to assess the changes of the three main features in DRSS Level 47/53 in those who were treatment naïve and had received aflibercept. Main outcome measures included changes in DHs, VB and IRMAs after aflibercept therapy at weeks 12 and 52.
Fifty-five treatment-naïve eyes at baseline who received aflibercept were included in the study. Here were some of the findings:
• Severe DHs and severe IRMAs improved in approximately 75 percent of eyes at week 12 and mostly remained improved at week 52; VB remained unchanged in all eyes at week 12.
• From 12 weeks, 32 eyes that had injections showed improved or stable DHs compared with seven that didn’t have injections, and DHs deteriorated in six eyes with no further injections compared with four that had more injections (p=0.0072).
• A total of 15 eyes that continued to have injections from week 12 showed an improvement or stable IRMAs compared to four that didn’t have injections (p=0.006).
• Worsening of IRMAs was seen in five eyes with no further injections compared with four eyes that continued to have injections.
• The improvements of DHs and IRMAs were more likely to be maintained if less than 16 weeks elapsed since the last anti-VEGF injection.
Scientists found that aflibercept appeared to improve DHs and IRMAs after just three injections. They added that, once the frequency of injections was reduced, DHs and IRMAs could deteriorate again. Furthermore, they wrote, it was unclear whether these results could be translated to patients without PDR.
SOURCE: Pearce E, Chong V, Sivaprasad S, et al. Aflibercept reduces retinal hemorrhages and intravitreal microvascular abnormalities but not venous beading: Secondary analysis of CLARITY study. Ophthalmology Retina 2020; Feb 11. [Epub ahead of print].
Intra- & Interocular Differences in Parafoveal Vascular Density in Diabetic Patients Without DR
Scientists evaluated the associations between optical coherence tomography angiography-measured vascular density (VD), intraocular and interocular VD differences, and clinical factors in diabetic patients without diabetic retinopathy. One of the researchers received financial support from Canon (Tokyo, Japan).
They retrospectively reviewed 94 Type 2 diabetic patients without diabetic retinopathy who had undergone OCTA. They measured vascular density and vessel skeleton density in a 3-mm central zone in the total capillary plexus, superficial capillary plexus, deep capillary plexus (DCP) and choriocapillaris layers. And they determined the intraocular VD difference between the superior and inferior zones, while figuring the interocular VD difference between both eyes. Scientists evaluated associations between OCTA parameters and clinical factors. Here were some of the findings:
• Vascular density and intraocular and interocular VD differences were significantly associated with signal strength of the image, which was related with age and lens opacity.
• In multivariate analysis, diabetes duration was negatively associated with skeleton density in total capillary plexus and superficial capillary plexus layers, and positively associated with intraocular VD difference in the superficial capillary plexus layer.
• The estimated glomerular filtration rate was negatively associated with the intraocular skeleton density difference in the total capillary plexus layer, interocular VD, and skeleton density differences in the total capillary plexus layer.
Scientists reported that intraocular and interocular VD difference may be an easy and sensitive way to detect subtle early microvascular changes in diabetic patients.
SOURCE: Kim YK, An Y, Park SP. Intraocular and interocular differences in parafoveal vascular density in diabetic patients without diabetic retinopathy. Retina 2020; Feb 11. [Epub ahead of print].
Outcomes & Complications Associated with Noninfectious Uveitis in Patients Presenting with Rhegmatogenous Retinal Detachment
Scientists evaluated the visual outcomes and complications associated with noninfectious uveitis in patients presenting with a rhegmatogenous retinal detachment, as part of a retrospective cohort study.
A total of 554 eyes of 523 patients presenting for RRD repair at the University of Colorado School of Medicine, Department of Ophthalmology, between July 2011 and September 2016, were included.
Main outcome measures included endpoint rate of reattachment, endpoint visual acuity, postoperative proliferative vitreoretinopathy and rate of reoperation. Here were some of the findings:
• A history of uveitis was identified in 5.2 percent of eyes.
• Eyes with a history of uveitis were found to have a higher risk for development of any degree of PVR (HR 2.2, CI 1.1 to 4.4, p=0.030) and a higher risk of PVR necessitating an additional procedure (HR 2.7, CI 1.2 to 6.0, p=0.014).
• Anatomical and visual outcomes didn’t differ between the two groups.
• Preoperative VA, the distribution of race/ethnicity, age, gender, lens status, macula status and lattice degeneration status didn’t vary significantly between the groups.
• In the analysis of a PVR subgroup, uveitis wasn’t associated with a higher risk of PVR necessitating an additional procedure and didn’t show a statistically significant difference in endpoint visual acuity.
Scientists found that a history of uveitis was associated with an increased risk of any degree of PVR and an increased risk of PVR necessitating an additional procedure. However, the subgroup analysis suggested that patients with a history of uveitis that develop PVR didn’t necessarily have a worse visual outcome or a higher risk of additional surgery. Scientists suggested a possible role for perioperative steroids in patients with a history of uveitis who present with a retinal detachment, but added that further study would be warranted to determine if this decreased the risk of PVR or improves visual outcomes.
SOURCE: Slingsby TJ, Pecen PE, Palestine AG, et al. Outcomes and complications associated with noninfectious uveitis in patients presenting with rhegmatogenous retinal detachment. Ophthalmology Retina 2020; Feb 27. [Epub ahead of print].
Initial Results From a First-in-human Gene Therapy Trial on X-linked RP Caused by RPGR Mutations
Retinal gene therapy has shown great promise in treating retinitis pigmentosa, a primary photoreceptor degeneration that leads to severe sight loss in young people. Investigators reported findings from the first-in-human Phase I/II, dose-escalation clinical trial for X-linked RP caused by mutations in the RP GTPase regulator (RPGR) gene in 18 individuals over up to six months of follow-up.
The primary outcome of the study was safety, and secondary outcomes included visual acuity, microperimetry and central retinal thickness.
Investigators wrote that, apart from steroid-responsive subretinal inflammation in individuals at the higher doses, no notable safety concerns were found after subretinal delivery of an adeno-associated viral vector encoding codon-optimized human RPGR (AAV8-coRPGR), meeting the pre-specified primary endpoint. They added that visual field improvements beginning at one month and maintained to the last point of follow-up were observed in six patients.
SOURCE: Cehajic-Kapetanovic J, Xue K, Martinez-Fernandez de la Camara C, et al. Initial results from a first-in-human gene therapy trial on X-linked retinitis pigmentosa caused by mutations in RPGR. Nat Med 2020;26:3:354-9.
Novartis Provides Update on Beovu Use and Safety in Wet AMD
Spurred by reports of retinal vasculitis following the use of Beovu (brolucizumab) announced by the American Society of Retinal Specialists in late February, the drug’s maker, Novartis, says it’s conducting a review of the “limited number of reported cases of severe vision loss, inflammation and potential retinal vasculitis in patients treated with Beovu, including cases where patients had previously received other VEGF inhibitors.”
As of March 2, more than 57,000 Beovu (brolucizumab) vials for injection have been shipped to prescribing physicians in the US. To date, “safety data continue to support a favorable benefit-risk profile for Beovu,” the company says. The prescribing information leaflet for Beovu in the United States cites a 4-percent rate of intraocular inflammation and a 1-percent rate of retinal artery occlusion. Read more.
SOURCE: Novartis, March 2020
EYEPOINT ANNOUNCES TOPLINE DATA FOR SECOND PHASE III STUDY OF YUTIQ
EyePoint Pharmaceuticals announced the topline 36-month follow-up data from the second Phase III trial of Yutiq (fluocinolone acetonide intravitreal implant) 0.18 mg three-year micro-insert for the treatment of chronic non-infectious uveitis affecting the posterior segment. The second double-masked, randomized Phase III trial of Yutiq enrolled 153 patients in 15 clinical centers in India, with 101 eyes treated with Yutiq and 52 eyes receiving sham injections. At 36-months, the recurrence rate in Yutiq randomized eyes was significantly lower than in sham-treated eyes (46.5 percent vs. 75 percent, respectively; p=0.001). Visual acuity gains or losses of three lines or more were both similar between treatment groups. Read more.
SOURCE: EyePoint Pharmaceuticals, March 2020
ACUCELA PROVIDES UPDATE ON EMIXUSTAT PHASE III CLINICAL TRIAL
Acucela announced that the company enrolled more than 65 percent of subjects in its Phase III clinical trial investigating emixustat hydrochloride in patients with macular atrophy secondary to Stargardt’s disease. The multicenter, randomized, double-masked and placebo-controlled clinical study is randomly assigning subjects to emixustat 10 mg or placebo (2:1 ratio) once daily for 24 months. The FDA and European Medicines Agency has already granted orphan drug designation to emixustat for the treatment of Stargardt’s. Read more.
SOURCE: Acucela, February 2020
RENEURON ANNOUNCES DATA IN STEM CELL TRIAL
Kodiak ReNeuron Group announced long-term data from the ongoing Phase I/IIa clinical trial of its hRPC stem cell therapy candidate in retinitis pigmentosa. Since its October 2019 announcement of positive interim efficacy data from the Phase IIa segment in which post-procedure subjects had sustained clinically relevant improvements in visual acuity compared with baseline, the company says that long-term efficacy data continue to show a meaningful clinical effect from the therapy at all time points out to 12 months post-treatment. ReNeuron’s clinical RP program was granted FDA Orphan Drug and Fast Track designations. Read more.
SOURCE: ReNeuron, February 2020
RIBOMIC ANNOUNCES FIRST INJECTION IN PHASE II RBM-007 CLINICAL TRIAL
Ribomic announced that the first U.S. patient received injection in the Phase II trial of RBM-007 for the treatment of exudative age-related macular degeneration. RBM-007 is an oligonucleotide-based aptamer with anti-FGF2 (fibroblast growth factor 2) activity. Ribomic hopes that the dual action of RBM-007 (anti-angiogenic and anti-scarring) will be effective as an additive or alternative therapy to anti-VEGF treatments for wet AMD. Read more.
SOURCE: RIBOMIC, February 2020
Preclinical Data for Ocugen’s OCU400 Point to Potential RP Treatment
Ocugen announced publication in Nature Gene Therapy of preclinical data of nuclear hormone receptor gene NR2E3 as a genetic modifier and therapeutic agent to treat multiple retinal degenerative diseases. OCU400 (NR2E3-AAV) received two orphan drug designations targeting two distinct inherited retinal diseases (IRDs): NR2E3 mutation-associated retinal diseases and CEP290 mutation-associated retinal diseases. The report detailed efficacy results in five unique mouse models of retinitis pigmentosa that underwent administration of NR2E3-AAV by subretinal injection. The five RP models tested were rd1 (PDE6β associated RP), Rho-/- and RhoP23H (both Rhodopsin-associated RP), rd16 (Leber Congenital Amaurosis) and rd7 (Enhanced S-cone Syndrome). The study demonstrated the ability of a novel modifier gene therapy to elicit broad-spectrum therapeutic benefits in early and intermediate stages of RP, the company says. Read more.
SOURCE: Ocugen, March 2020
TRANSLATIONAL IMAGING INNOVATIONS RECEIVES NIH SBIR AWARD
Translational Imaging Innovations received a Direct-to-Phase II Small Business Innovation Research award from the National Eye Institute, enabling TII to develop the first diagnostic database of photoreceptor patterning in the human retina. The goal is to create cellular-level biomarkers of degenerative eye disease. The award is a collaboration between TII and the Advanced Ocular Imaging Program at the Medical College of Wisconsin. Read more.
Source: Translational Imaging Innovations, February 2020
EYEVANCE RELAUNCHES TOBRADEX ST
Eyevance Pharmaceuticals announced the U.S. relaunch of Tobradex ST (tobramycin/dexamethasone ophthalmic suspension) 0.3%/0.05% (originally approved by the FDA in 2009, when the drug was marketed by Alcon), a fixed-dose topical antibiotic and steroid combination. The company acquired the product in late 2019. Read more.
Source: Eyevance Pharmaceuticals, March 2020
Everads Enters into Agreement to License Delivery System
Everads Therapy signed an option agreement with a “large global pharmaceutical company” to support the potential of its delivery system technology to overcome certain risks and side effects associated with current retinal disease treatment options. As part of the agreement, the unnamed company was given an exclusive option to enter into a license agreement to use Everads' delivery system in combination with its treatments for specific targets, in exchange for a pre-defined upfront fee, milestone payments and ongoing royalties. Based on favorable preclinical results, Everads believes its system overcomes the current technical challenges in effective suprachoroidal injection. Read more.
Source: Everads Therapy, March 2020
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