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.
Complement C3 Inhibitor Pegcetacoplan for GA Secondary to AMD
Investigators evaluated the safety and efficacy of Apellis’ pegcetacoplan (APL-2), a complement C3 inhibitor, for the treatment of geographic atrophy. The company’s prospective, multicenter, randomized, sham-controlled Phase II study included 246 subjects with GA. Subjects with GA were randomly assigned in a 2:2:1:1 ratio to receive intravitreal injections of 15-mg pegcetacoplan monthly or every-other-month (EOM), or sham intravitreal injections monthly or EOM, for 12 months. Follow-up was at 15 and 18 months. Investigators measured area and growth of GA using fundus autofluorescence imaging.
The primary efficacy endpoint was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea (foveal encroachment), best-corrected visual acuity, low luminance BCVA and low luminance visual acuity deficit. The primary safety endpoint was the number and severity of treatment-related adverse events. Here are some of the findings:
• In subjects receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29 percent (CI, 9 to 49; p=0·008) and 20 percent (CI, 0 to 40; p=0.067) compared with sham.
• Post-hoc analyses showed that the effect was greater in the second six months of treatment, with observed reductions of 45 percent (p=0.0004) for pegcetacoplan monthly and 33 percent (p=0.009) EOM.
• Two cases of culture-positive endophthalmitis and one case of culture negative endophthalmitis occurred in the pegcetacoplan monthly group.
• New-onset, investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes, 20.9 percent); or 7/79 eyes, 8.9 percent, in monthly and EOM groups than in sham-treated eyes (1/81 eyes, or 1.2 percent).
Investigators concluded that local inhibition of C3 with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham. They added that the Phase III study would further define the efficacy and safety profile of pegcetacoplan.
SOURCE: Liao DS, Grossi FV, El Mehdi D, et al. Complement C3 inhibitor pegcetacoplan for geographic atrophy secondary to age-related macular degeneration. Ophthalmology 2019; July 16. [Epub ahead of print].
Retinol Binding Protein 3 Increased in Retinas of Patients with Diabetes Resistant to DR
The Joslin Medalist Study characterized individuals affected with type 1 diabetes for 50 years or longer. More than 35 percent of these individuals exhibited no to mild diabetic retinopathy, independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients.
Proteomic analysis of the retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity.
Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor. Mechanistically, The researchers’ results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and Müller cells.
Researchers concluded that elevated expression of photoreceptor-secreted RBP3 might have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.
SOURCE: Yokomizo H, Maeda Y, Park K, et al. Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy. Ophthalmology 2019; July 16. [Epub ahead of print]. Sci Transl Med 2019. Jul 3. [Epub ahead of print].
Incidence of New CNV in Fellow AMD Eyes Treated with Intravitreal Aflibercept or Ranibizumab
Researchers assessed the association of treatment assignment (intravitreal aflibercept vs. ranibizumab) and baseline characteristics with fellow eye conversion to nAMD in the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies.
The post hoc analysis of the VIEW 1 and VIEW 2 studies (randomized, double-masked, active-controlled, multicenter, 96-week, Phase III trials comparing the efficacy and safety of intravitreal aflibercept in 2,457 individuals with treatment-naive eyes with nAMD) analyzed a subgroup of participants treated for nAMD in one eye who had untreated fellow eyes without neovascularization at baseline.
All participants in the VIEW studies were included in one of four groups: ranibizumab 0.5 mg every four weeks; aflibercept 2 mg every four weeks; aflibercept 0.5 mg every four weeks; or aflibercept 2 mg every eight weeks after three injections at four-week intervals. Data collection in the VIEW studies occurred from July 2007 to August 2011; the data analysis presented in this report took place from April 2016 to November 2018.
Patients received no treatment in fellow eyes unless they converted to nAMD, when heath-authority-approved treatments were given per investigator discretion. Main outcomes and measures included incidence of conversion to nAMD in individuals with untreated fellow eyes without clinical signs of neovascularization at baseline. A total of 1,561 participants were included in this analysis. Here were some of the findings:
• At 96 weeks, 375 individuals (24 percent) converted to neovascular disease in fellow eyes, including: 107 of 399 individuals who received ranibizumab 0.5 mg every four weeks (18.1 per 100 patient-years at risk at week 96); 93 of 387 individuals who received aflibercept 2 mg every four weeks (16.2 per 100 patient-years at risk at week 96); 84 of 387 individuals who received aflibercept 0.5 mg every four weeks (14.7 per 100 patient-years at risk at week 96); and 91 of 388 individuals who received aflibercept 2 mg every eight weeks after three doses at four-week intervals (16 per 100 patient-years at risk at week 96).
• On multivariate analysis, fellow-eye conversion was associated with increasing patient age (per 10 years) at baseline (HR, 1.20; CI, 1.05 to 1.36), female sex (HR, 1.32; CI, 1.06 to 1.63), intraretinal fluid in the study eye at baseline (HR, 1.28; CI, 1.02 to 1.61) and increasing choroidal neovascularization lesion size (per 10 mm2) in the study eye at baseline (HR, 1.29; CI, 1.06 to 1.57).
• Rates of fellow-eye conversion were similar with either treatment.
Researchers wrote that, in this secondary analysis of randomized clinical trial data, individuals with active nAMD in one eye appeared to have a high risk for fellow-eye conversion. They suggested that such patients should be monitored closely.
Source: Parikh R, Avery RL, Saroj N, et al. Incidence of new choroidal neovascularization in fellow eyes of patients with age-related macular degeneration treated with intravitreal aflibercept or ranibizumab. JAMA Ophthalmol 2019; July 11. [Epub ahead of print].
The Value of Prior Response to Anti-VEGF for AMD: A HARBOR Subanalysis
Researchers evaluated disease activity in patients with neovascular age-related macular degeneration in HARBOR to determine whether the duration of response to previous treatments with ranibizumab informs future disease activity and need for subsequent injections.
The retrospective subgroup analysis of the Phase III HARBOR clinical trial included participants from the ranibizumab 0.5 mg pro re nata arm of the trial who received all three loading injections and had missed no more than one study visit (n=217).
A disease-activity-free interval was defined as a consecutive period in months when treatment wasn’t required because individuals didn’t meet protocol re-treatment criteria. The percentage of disease-activity-free eyes at the next one and two months after a first activity-free interval of ≥2, ≥3, ≥4, ≥5 and ≥6 months was evaluated. Additionally, researchers evaluated the duration that eyes remained untreated after activity-free intervals using Kaplan-Meier estimates.
Key outcome measures included duration of the first treatment-free interval of ≥2, ≥3, ≥4, ≥5 and ≥6 months achieved by each patient, mean number of additional months that patients remained treatment-free after a treatment-free interval and the percentage of eyes requiring treatment within two months after each treatment-free interval. Here were some of the findings:
- The percentage of eyes requiring re-treatment the month after a treatment-free interval of:
- ≥2 months was 60 percent (90/151);
- ≥3 months was 33 percent (33/100);
- ≥4 months was 26 percent (20/77);
- ≥5 months was 36 percent (24/66); and
- ≥6 months was 19 percent (9/48).
- The percentage of eyes requiring re-treatment within two months after a treatment-free interval of:
- ≥2 months was 73 percent (109/149);
- ≥3 months was 53 percent (53/100);
- ≥4 months was 53 percent (40/75);
- ≥5 months was 47 percent (30/64); and
- ≥6 months was 43 percent (20/46).
- The mean (standard error of the mean) additional treatment-free period after the following treatment-free intervals was:
- ≥2 months: 1.3 months (0.17);
- ≥3 months: 2.4 months (0.33);
- ≥4 months: 2.9 months (0.44);
- ≥5 months: 3.2 months (0.50); and
- ≥6 months and 4 months (0.60).
Researchers concluded that longer treatment-free intervals might indicate longer future disease-free intervals; however, they noted that the association varied. Thus, they suggested that although longer intervals suggested a greater likelihood of not needing re-treatment within one to two months, regular assessment was warranted due to the unpredictability of nAMD disease activity.
SOURCE: Khurana RN, Chang LK, Hill LF, et al. The value of prior response to anti–vascular endothelial growth factor for age-related macular degeneration: A HARBOR subanalysis. Ophthalmology Retina 2019; July 5. [Epub ahead of print].
Pachychoroid vs. Nonpachychoroid Polypoidal Choroidal Vasculopathy and Responses to Anti-VEGF
Recent investigations have found a biphasic pattern of choroidal thickness within polypoidal choroidal vasculopathy individuals. This study aimed to investigate the relationship between choroidal thickness and the clinical features of PCV eyes.
Scientists evaluated the correlation between various clinical features including subfoveal choroidal thickness and the response to three monthly anti-vascular endothelial growth factor treatments in 62 consecutive, treatment-naive PCV individuals (66 eyes). After determining that SFCT was the only factor correlating with anti-VEGF treatment, scientists aimed to determine a best cutoff line for SFCT that could be used as a parameter to differentiate PCV patients into pachychoroid and nonpachychoroid groups using the Youden index for best combined specificity and sensitivity. They then compared the demographic features, clinical characteristics and the response to anti-VEGF to determine any differences between the two groups. Here were some of the findings:
- Subfoveal choroidal thickness was the only significant factor for the treatment effect.
- The SFCT of 267.5 µm was the best cutoff line.
- Compared with the nonpachychoroid group, the pachychoroid group revealed:
- statistically significant younger ages (64.1 ±9.6 vs. 72 ±8.2, p=0.004);
- fewer age-related macular degeneration-like features (50 vs. 81.3 percent, p=0.027);
- more central serous chorioretinopathy-like features (typical retinal pigment epithelial mottling [61.1 vs. 16.7 percent, p=0.0014]);
- greater choroidal vascular hyperpermeability (88.9 vs. 37.5 percent, [p=0.0002]); and
- less robust treatment response (27.8 vs. 83.3 percent, p<0.0001) compared with the nonpachychoroid group.
Scientists concluded that polypoidal choroidal vasculopathy patients could be subclassified into pachychoroid and nonpachychoroid groups. They also found that the pachychoroid subtype of PCV had statistically significantly younger ages, fewer age-related macular degeneration-like features, more central serous chorioretinopathy-like features and a more modest response to anti-VEGF treatment.
SOURCE: Chang YC, Cheng CK, et al. Difference between pachychoroid and nonpachychoroid polypoidal choroidal vasculopathy and their response to anti-vascular endothelial growth factor therapy. Retina 2019; June 4. [Epub ahead of print].
Predictive Activation Biomarkers of Treatment-naive Asymptomatic CNV in AMD
Researchers assessed the long-term evolution of treatment-naive quiescent choroidal neovascularization in age-related macular degeneration to identify predictive activation biomarkers.
Subjects included those with quiescent CNV who had undergone comprehensive ophthalmological exams, including fluorescein and indocyanine green angiographies, structural optical coherence tomography and OCT angiography. Researchers performed qualitative and quantitative analyses of structural OCT and OCTA images during the study period. At the last follow-up evaluation, they divided the enrolled eyes into two groups: eyes with quiescent CNV converting to exudative AMD and those not progressing to eAMD.
Sixty-eight eyes of 68 individuals were enrolled in the study. Mean follow-up duration was 40 ±28 months using multimodal imaging and 22 ±13 months using OCTA. Here were some of the findings:
• On structural OCT, quiescent CNV not converting to eAMD showed a preferential growth of the pigment epithelium detachment greatest linear diameter (p=0.009), whereas the eAMD group presented a preferential growth of the pigment epithelium detachment maximal height (p<0.0001) during the study period.
• Quantitative analysis of choriocapillaris OCT angiograms confirmed the CNV area growth during follow-up (from 4.18 ±4.77 mm2 at baseline to 5.10 ±5.06 mm2 at the last follow-up visit; p=0.02).
Researchers recommended close follow-up of quiescent CNV patients to early identify predictive activation biomarkers of treatment-naive quiescent CNV.
SOURCE: Serra R, Coscas F, Boulet JF, et al. Predictive activation biomarkers of treatment-naive asymptomatic choroidal neovascularization in age-related macular degeneration. Retina 2019; Jun 21. [Epub ahead of print].
Effects of Intravitreal Aflibercept on Microvascular Regression in DME Eyes
Investigators evaluated the effects of intravitreal aflibercept on the microaneurysms (MAs) and sizes of non-perfused areas (NPAs) in eyes with diabetic macular edema, as part of an interventional, prospective study. Participants included 25 eyes of 25 DME individuals (average age, 64 ±8.8 years) who were treated with three consecutive monthly IVA injections.
Fluorescein angiography and optical coherence tomography were performed prior to the IVA injections (baseline) and at one week after the IVA treatment. Investigators determined the number of MAs and the ischemic index—a measure of NPAs—and correlations between central retinal thickness, and number of MAs and the ISI. Main outcome measures included the mean number of MAs and NPAs evaluated as the ISI. Here were some of the findings:
• At baseline, the mean central retinal thickness was 485.7 ±90.6 μm.
• After treatment, the mean CRT was significantly reduced to 376.9 ±81.6 μm (p=0.1 x10-5; repeated ANOVA).
• The mean number of MAs was significantly decreased from 49.6 ±33.2 at baseline to 24.8 ±18.1 at three months after the initial treatment. This was a 50.4 ±21.2-percent reduction (p=0.3 x10-5, paired T tests).
• The mean ISI was significantly decreased from 55.5 ±20.4 percent at the baseline to 28.8 ±16.8 percent after the treatment (p=0.3 x10-5, paired T test). This was a reduction of 43.3 ±28.5 percent.
• Investigators found a significant correlation between the CRT and number of MAs at baseline (r=0.56, p=0.004) and after treatment (r=0.53, p=0.006).
• Investigators found a significant correlation between the CRT and the ISI at baseline (r=-0.39, p=0.03) but not after treatment (r=-0.06, p=0.79).
Investigators determined that the reduction in the number of MAs was correlated with the reduction in the CRT.
SOURCE: Sugimoto M, Ichio A, Mochida D, et al. Multiple effects of intravitreal aflibercept on microvascular regression in eyes with diabetic macular edema. Ophthalmology Retina 2019; June 14. [Epub ahead of print].
Assessment of OCT in DME from VISTA: Ellipsoid Zone Dynamics and the Retinal Fluid Index
Scientists evaluated retinal fluid features and ellipsoid zone integrity dynamics on spectral-domain optical coherence tomography in eyes with diabetic macular edema treated with intravitreal aflibercept injection in the VISTA-DME study. In the post-hoc subanalysis of the Phase III, prospective clinical trial, eyes received either IAI 2 mg every four weeks (2q4) or every eight weeks after five initial monthly doses (2q8).
The subanalysis included all eyes from the VISTA Phase III study in the IAI groups imaged with the Zeiss Cirrus HD-OCT system. OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines manually corrected for assessment of changes in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point.
Main outcome measures included the feasibility of volumetric assessment of higher order OCT-based retinal parameters and its correlation with best-corrected visual acuity. Overall, 106 eyes of 106 individuals were included. A total of 52 eyes of 52 individuals were included in the IAI 2q4 arm, and 54 eyes of 54 individuals were included in the IAI 2q8 arm. Here were some of the findings:
• EZ integrity metrics significantly improved from baseline to week 100, including central macular mean EZ and retinal pigment epithelium thickness (2q4: 26.6 μm to 31.6 μm, p<0.001; 2q8: 25.2 μm to 31.4 μm, p<0.001).
• At week 100, central macular intraretinal fluid volume was reduced by over 65 percent (p<0.001) and central macular subretinal fluid volume was reduced by over 99 percent in both arms (p<0.001).
• Central macular RFI significantly improved in both arms (2q4: 17.9 percent to 7.2 percent, p<0.001; 2q8: 19.8 percent to 4.2 percent, p<0.001).
• Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits.
Scientists wrote that IAI resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms, and correlated with visual function.
Source: Ehlers JP, Uchida A, Hu M, et al. Higher order assessment of OCT in diabetic macular edema from the VISTA study: ellipsoid zone dynamics and the Retinal Fluid Index. Ophthalmology Retina 2019; July 6. [Epub ahead of print].
OCTA Metrics Predict Progression of DR & Development of DME
Researchers prospectively evaluated the relationship of optical coherence tomography angiography metrics with diabetic retinopathy progression and development of diabetic macular edema, as part of a prospective, observational study. Participants included 205 eyes from 129 individuals with diabetes mellitus followed up for at least two years.
All subjects underwent OCTA with a swept-source OCT (DRI-OCT Triton, Topcon). Researchers obtained individual OCTA images of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) from IMAGEnet6. After quality checks, they obtained automated measurements of the foveal avascular zone area, FAZ circularity and vessel density (VD) and fractal dimension (FD) of SCP and DCP. Researchers performed Cox proportional hazard models to examine the relationship between baseline OCTA metrics and DR progression and DME development. Here are some of the findings:
• Over a median follow-up of 27.14 months (interquartile range, 24.16 to 30.41 months), 28 eyes out of the 205 eyes (13.66 percent) developed DR progression.
• Of 194 eyes without DME at baseline, 17 eyes (8.76 percent) developed DME.
• Larger FAZ area (HR, 0.829 per SD increase; CI, 1.332 to 2.512), lower VD (HR, 1.908 per SD decrease; CI, 1.303 to 2.793) and lower fractal dimension (HR, 4.464 per SD decrease; CI, 1.337 to 14.903) of the DCP were significantly associated with DR progression, after adjusting for established risk factors (DR severity, glycated hemoglobin, diabetes duration, age and mean arterial blood pressure at baseline).
• Lower VD of the superficial capillary plexus (HR, 1.789 per SD decrease; CI, 1.027 to 4.512) was associated with DME development.
• Compared with the model with established risk factors alone, the addition of OCTA metrics improved the predictive discrimination of DR progression (FAZ area of DCP, C-statistics 0.723 vs. 0.677, p<0.001; VD of DCP, C-statistics 0.727 vs. 0.677, p=0.001; FD of the DCP, C-statistics 0.738 vs. 0.677, p<0.001) and DME development (VD of SCP, C-statistics 0.904 vs. 0.875, p=0.036).
Researchers wrote that FAZ area, in addition to VD and FD of the DCP predicted DR progression, while the VD of the SCP predicted DME development. They added that their findings provided evidence to support the idea that OCTA metrics improved the risk assessment of DR progression and DME development beyond traditional risk factors.
Source: Sun Z, Tang FY, Wong R, et al. Optical coherence tomography angiography metrics predict progression of diabetic retinopathy and development of diabetic macular edema: A prospective study. Opthalmology. 2019; Jun 25. [Epub ahead of print].
Lipid-lowering Meds Associated with Lower Retinopathy Risk in Diabetes
Researchers evaluated the impact of lipid-lowering medications on diabetic retinopathy and diabetic complications requiring intervention in the U.S. population, as part of a retrospective cohort analysis. They looked at administrative insurance claims drawn from the Truven MarketScan Commercial Claims and Encounters database. The population included beneficiaries with type 2 diabetes mellitus (T2DM).
The main outcome measure was any sign of diabetic retinopathy, as measured by diagnosis codes for non-proliferative diabetic retinopathy, proliferative diabetic retinopathy, diabetic macular edema and procedure codes for retinopathy treatments (anti-VEGF injections, laser therapy and vitrectomy).
Researchers analyzed a population of 269,782 individuals diagnosed with T2DM between 2008 and 2015. A total of 99,233 (37 percent) of people were undergoing treatment with lipid-lowering medications. Approximately 6 percent of individuals on lipid-lowering medications had a diagnosis code for NPDR, PDR or DME, or a procedural code for intravitreal injections, PPV or laser in their record following diagnosis with diabetes. This was in comparison with 6.5 percent of people who didn’t take lipid-lowering medications (p<0.01).
Researchers found that, in adjusted time-to-event analyses, individuals who took lipid-lowering medications prior to diagnosis with T2DM were less likely to progress to any retinopathy diagnosis (HR 0.60, CI 0.55 to 0.65) and less likely to receive any treatment for retinopathy (HR 0.81, CI 0.78 to 0.84). These findings were significant at the aggregate level, as well as at the level of individual diagnosis (NPDR HR 0.63: CI, 0.57 to 0.69; PDR HR 0.45: CI, 0.37 to 0.54; and DME HR 0.39: CI, 0.33 to 0.45), and at the level of each treatment category (anti-VEGF injection HR 0.81: CI, 0.78 to 0.84; laser HR 0.62: CI, 0.47 to 0.81; and vitrectomy HR 0.71: CI, 0.59 to 0.85).
Researchers found consistent evidence that individuals on lipid-lowering medications were less likely to develop NPDR, PDR or DME, and modest evidence that these individuals were less likely to receive intravitreal injections of anti-VEGF medication, laser treatments or vitrectomy. They wrote that the findings validated others found in studies that have used claims databases in East Asia in relatively homogeneous populations to estimate an association between statin use and retinopathy, and replicated them in a U.S. context in a large commercial claims database.
SOURCE: Vail D, Callaway NF, Ludwig CA, et al. Lipid-lowering medications are associated with lower risk of retinopathy and ophthalmic interventions among U.S. patients with diabetes. Am J Ophthalmol 2019; Jun 10. [Epub ahead of print].
Clinical Factors Contributing to Postop Aqueous Flare Intensity After 27-Gauge Pars Plana Vitrectomy for Primary RRD
Researchers assessed perioperative clinical factors that contribute to postsurgical aqueous flare intensity (AFI) following 27-gauge pars plana vitrectomy for primary rhegmatogenous retinal detachment, as part of a retrospective clinical study.
They performed retrospective analyses of the medical records of 47 eyes of 47 individuals with primary RRD who had undergone 27-ga. PPV with a wide-angle viewing system. AFI was measured preoperatively, and one week, one month, three months, six months and 12 months after the surgery. Here were some of the findings:
• AFI significantly increased one week after the surgery (p<0.01) and then decreased over time.
• At six months after surgery, it was still statistically significantly higher than preoperative AFI (p=0.03).
• There was no statistical difference between preoperative AFI and AFI at 12 months following surgery.
• Multiple regression analyses revealed that the number of retinal photocoagulations had positive correlation with AFI at one week, one month, three months and six months; and with the performance of scleral indentation at one month and three months after the surgery.
• Researchers reported that intraoperative retinal photocoagulation and scleral indentation were probable causes of increased AFI after 27-ga. PPV for RRD.
Source: Tetsumoto A, Imai H, Otsuka K, et al. Clinical factors contributing to postoperative aqueous flare intensity after 27-gauge pars plana vitrectomy for the primary rhegmatogenous retinal detachment. Jpn J Ophthalmol 2019; May 18. [Epub ahead of print].
NEW RETINAL SURGERY PRODUCTS FROM ALCON
Alcon introduced the Hypervit Dual Blade Vitrectomy Probe–the latest evolution of the Ultravit probes and newest addition to the company's Constellation Vision System—at the American Society of Retina Specialists meeting in Chicago. Alcon says Hypervit enables surgeons to modify duty cycle and control flow independent of vacuum and cut rate, creating stable, closed-system intraocular surgeries. Hypervit will be available as both a 25+ and 27+ gauge probe. The probe will be commercially available later this year. The company is also introducing its next generation Ngenuity 3D Visualization System with Datafusion. Alcon says this latest version of the 3D viewing system provides real-time feedback from the Constellation Vision System through the "surgical parameter overlay," delivering an "immersive surgical experience." Read more.
SOURCE: Alcon, July 2019
B+L Introduces 23-Gauge Bi-Blade Dual Port Vitrectomy Cutter for Stellaris Elite
Bausch + Lomb introduced a 23-gauge Bi-Blade dual port vitrectomy cutter for the Stellaris Elite vision enhancement system. The new probe joins the available 25- and 27-gauge Bi-Blade cutters as the most efficient option in the Bi-Blade portfolio, the company says. All Bi-Blade cutters are designed to double effective cut rates to increase flow and efficiency compared with single-port probes by cutting in both forward and backward directions, enabling two cuts per cycle. Read more.
SOURCE: Bausch + Lomb, July 2019
New J-Codes Announced
The Centers for Medicare and Medicaid Services assigned J-codes to two ophthalmic drugs recently. J-codes are reimbursement codes used by commercial insurance plans, Medicare, Medicare Advantage, and other government payers for Medicare Part B drugs that are administered by a physician. Claims submission and payment are standardized with a J-code, facilitating and streamlining billing and reimbursement.
First, CMS confirmed its preliminary decision to assign a permanent product-specific J-code for Omeros’ Omidria (phenylephrine and ketorolac intraocular solution) 1% / 0.3%. Omidria is a commercial drug that can be used during cataract surgery to prevent miosis and reduce postoperative pain, which the company says can improve patient outcomes and safety. The new J-code for Omidria—J1097—will become effective October 1, 2019. Read more.
SOURCE: Business Wire, July 2019
Around the same time, EyePoint Pharmaceuticals announced that CMS had assigned a specific and permanent reimbursement J-code, J7314, for its product Yutiq (fluocinolone acetonide intravitreal implant) 0.18 mg. Yutiq is a three-year micro-insert for chronic, non-infectious uveitis affecting the posterior segment. The new code will also become effective on October 1st. Read more.
SOURCE: EyePoint Pharmaceuticals, July 2019
Genentech/Roche Complete Enrollment in Archway
Genentech and Roche completed patient enrollment in the Phase III Archway clinical trial investigating the Port Delivery System with ranibizumab in people with wet age-related macular degeneration. The refillable eye implant is designed to continuously release a customized formulation of ranibizumab over a period of months. Archway, the first Phase III trial with a device used for the continuous delivery of an anti-VEGF therapy, is a multicenter, randomized, visual assessor-masked, active-comparator controlled trial evaluating the PDS for the treatment of wet AMD using fixed interval dosing. Learn more.
SOURCE: NIH, July 2019
GENSIGHT COMPLETES ENROLLMENT OF GS010 REFLECT PHASE III TRIAL
GenSight Biologics announced that enrollment in REFLECT, a Phase III clinical trial of GS010 for the treatment of Leber’s Hereditary Optic Neuropathy, was successfully completed ahead of schedule. REFLECT is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the efficacy and safety of bilateral injections of GS010 in subjects with LHON due to the NADH dehydrogenase 4 (ND4) mutation. Read more.
SOURCE: GenSight Biologics, July 2019
RIBOMIC ANNOUNCES TOPLINE RESULTS FROM PHASE I/IIA RBM-007 TRIAL
RIBOMIC announced positive topline results from SUSHI, a Phase I/IIa single-ascending dose clinical study of RBM-007, an anti-fibroblast growth factor 2 (FGF2) aptamer, in nine subjects with wet age-related macular degeneration. The study achieved the primary endpoint of safety and tolerability, and demonstrated efficacy trends in favor of RBM-007. The company describes RBM-007 as a “novel oligonucleotide-based aptamer with potent anti-FGF2 activity.” Read more.
SOURCE: RIBOMIC, Inc., June 2019
CHLA HAS TREATED 14 PATIENTS WITH RETINAL DEGENERATION USING GENE THERAPY
More than a year after becoming one of the first medical institutions nationally to complete a gene replacement surgery to restore vision in patients with retinal degeneration, surgeons at The Vision Center at Children’s Hospital Los Angeles successfully completed the procedure on an additional 13 patients. The breakthrough one-time treatment replaces the defective RPE65 gene called located in the retina with a healthy copy made from artificial DNA, the equivalent of human DNA. Read more.
SOURCE: The Revenio Group, April 2019
BioTime Initiates Dosing in Phase I/IIa Clinical Study of OpRegen
BioTime dosed its first patient with the Orbit Subretinal Delivery System (Orbit SDS) as well as with a new Thaw-and-Inject formulation of OpRegen, the company’s retinal pigment epithelium transplant therapy, in its ongoing Phase I/IIa clinical study for the treatment of dry age-related macular degeneration. The primary objective is to evaluate the safety and tolerability of OpRegen as assessed by the incidence and frequency of treatment emergent adverse events. Read more.
SOURCE: BioTime, July 2019
KATAIRO ANNOUNCES FIRST PATIENT TREATED IN STARTT STUDY
Katairo GmbH announced the treatment of the first patient in the company’s placebo-controlled study of Remofuscin in adults with Stargardt’s disease. The trial will enroll approximately 90 patients in up to four European countries. Read more.
SOURCE: Katairo, June 2019
FDA TO REVIEW DORC NDA DRUG TO STAIN ILM DURING VITREORETINAL SURGERY
The Dutch Ophthalmic Research Center received FDA notification that its New Drug Application for Brilliant Blue G Ophthalmic Solution was accepted for review. The proposed indication is to selectively stain the internal limiting membrane. Brilliant Blue G Ophthalmic Solution is intended for injection onto the inner retinal surface, enabling the ILM to be clearly stained and distinguished from unstained retina, facilitating removal. If approved, Brilliant Blue G Ophthalmic Solution would be the first FDA approved product for this orphan indication. Read more.
SOURCE: DORC, June 2019
GLAUKOS ENTERS AGREEMENT TO ACQUIRE DOSE MEDICAL
Glaukos entered into a definitive agreement and plan of merger to acquire DOSE Medical for $2.5 million. Upon the completion of the acquisition, DOSE Medical will become a wholly owned subsidiary of Glaukos. The transaction is expected to close during the current quarter. DOSE Medical is developing multiple micro-invasive, bioerodible, sustained-release drug delivery platforms designed to be used in the treatment of various retinal diseases, including age-related macular degeneration and diabetic macular edema. Read more.
Source: Glaukos, June 2019
INVITAE ANNOUNCES ID YOUR IRD PROGRAM
Invitae launched ID Your IRD, an initiative with Spark Therapeutics, to offer genetic testing at no charge to patients suspected by their health-care providers of having an inherited retinal disease. The new genetic testing panel associated with the program tests for approximately 250 genes associated with IRDs. Read more.
Source: Invitae, June 2019
Review of Ophthalmology's® Retina Online is published by the Review Group, a Division of Jobson Medical Information LLC (JMI), 11 Campus Boulevard, Newtown Square, PA 19073.
To subscribe to other JMI newsletters or to manage your subscription, click here.
To change your email address, reply to this email. Write "change of address" in the subject line. Make sure to provide us with your old and new address.
To ensure delivery, please be sure to add email@example.com to your address book or safe senders list.
Click here if you do not want to receive future emails from Review of Ophthalmology's Retina Online.