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.
Progression from Early/Intermediate to Advanced Forms of AMD
Researchers estimated rates and risk factors for progression to geographic atrophy or choroidal neovascularization among eyes diagnosed with early or intermediate age-related macular degeneration in clinical practice, as part of a retrospective cohort analysis of a multicenter electronic medical record database from the United Kingdom.
Participants included patients ages 50 years or more with diagnosis of early/intermediate AMD in at least one eye (study eye) and no evidence of CNV or GA in the study eye, from 10 clinical sites using the EMR.
Anonymized data for 40,543 patients with a diagnosis of early/intermediate AMD were extracted between October 2000 and February 2016 from EMR database records held in the 10 sites. A sample of records randomly selected from each center was used to validate disease definitions. Records were analyzed by subgroup, based on the AMD status of the fellow eye. Multivariate Cox regression models identified other predictors of disease progression.
Main outcome measures included the progression rate (per 100 person-years) to GA or CNV in study eyes with early/intermediate AMD by fellow eye status and identified risk factors for progression. Here were some of the findings:
• Study eyes with early/intermediate AMD and a diagnosis of CNV in the fellow eye progressed to CNV fastest (at a rate of 15.2 per 100 person-years), and those with a diagnosis of GA in the fellow eye progressed to GA fastest (11.2 per 100 person-years), compared with the rates per 100 person-years of progression to CNV (3.2 to 11.9) or GA (2 to 7.8) in the other subgroups.
• In individuals with bilateral early/intermediate AMD, rates of progression to GA or CNV were 2 and 3.2 per 100 person years, respectively.
• In the multivariate model, age, female sex and cardiovascular disease were associated with an increased risk for progression to advanced AMD, while diabetes (hazard ratio: 0.45) and glaucoma (hazard ratio: 0.64) were associated with a decreased rate of progression.
Researchers determined that progression to GA or CNV was observed frequently in eyes with early/intermediate AMD, with the status of the fellow eye affecting the rate of progression. Novel associations with risk factors were observed and require replication in other cohorts.
Source: Chakravarthy U, Bailey CC, Scanlon, et al. Progression from early/intermediate to advanced forms of age-related macular degeneration in a large UK cohort: Rates and risk factors. Ophthalmology Retina 2020; Jan. 24. [Epub ahead of print].
Six-Year Incidence & Risk Factors for AMD: The Handan Eye Study
Researchers described the six-year incidence of early and late age-related macular degeneration, and associated factors, in a large, rural Chinese population.
The population-based, longitudinal study was conducted in rural China from 2006 to 2007. In total, 6,830 individuals ages 30 years or older participated. The six-year follow-up study was performed between 2012 and 2013. The modified Wisconsin Age-Related Maculopathy Grading System (WARMGS) protocol in the Blue Mountains Eye Study was used as the AMD grading standard.
Excluding 509 deceased subjects, 5,394 (85.3 percent follow-up rate) completed the follow-up. Among them, 5,048 participants had gradable photographs of at least one eye at both exams. Here were some of the findings:
• Over six years, the incidence of early AMD was 4.2 percent (CI, 3.8 to 4.7 percent) and of late AMD was 0.2 percent (CI, 0.2 to 0.3 percent).
• In the multivariable analysis, the per-year increase in age (p<0.001; OR=1.06; CI, 1.04 to 1.07), male sex (p=0.006; OR=0.64; CI, 0.47 to 0.88) and per-millimeter increase in axial length (p=0.010; OR=0.78; CI, 0.63 to 0.94) at baseline was significantly associated with incident early AMD.
• Early AMD wasn’t associated with systolic or diastolic blood pressure, hypertension, diabetes, history of stroke or heart disease, body mass index, total cholesterol, high- or low-density lipoprotein cholesterol, triglycerides, smoking status, refractive error or corneal curvature radius.
• There were too few cases of late AMD for a valid statistical analysis of the risk factors.
Researchers reported that, over six years, the incidence of early AMD was 4.2 percent (CI, 3.8 to 4.7 percent) and of late AMD was 0.2 percent (CI, 0.2 to 0.3 percent). They added that age, sex and axial length were relevant risk factors for early AMD in rural China.
Source: Mao F, Yang X, Yang K, et al. Six-year incidence and risk factors for age-related macular degeneration in a rural Chinese population: The Handan eye study. Invest Ophthalmol Vis Sci 2019;2;60:15:4966-71.
Visual Function Decline Due to GA: Results from Chroma & Spectri
Researchers assessed visual function outcomes to 48 weeks in individuals with bilateral geographic atrophy secondary to age-related macular degeneration included in two, now defunct, interventional clinical trials for the failed dry-AMD drug candidate lampalizumab (Chroma and Spectri), including: relationship to baseline lesion size; outcomes by baseline lesion characteristic subgroups; and correlation of visual function outcomes with GA area. Though the drug didn’t reach its primary endpoint, the researchers say the trials can still yield some interesting information about GA.
Eligible participants were ages 50 years or more, with well-demarcated bilateral GA (lesion size, one to seven disc areas), without evidence of CNV or previous treatment for CNV in either eye, and best-corrected visual acuity letter score of 49 letters or more (≥1 GA lesion within 250 μm of foveal center if BCVA ≥79 letters). The patients (pooled n=1,881) were treated with different frequencies of dosing of the drug or sham.
Functional endpoints included change from baseline to week 48 in BCVA, low-luminance visual acuity, mesopic microperimetry (number of absolute scotomatous points, mean macular sensitivity), binocular/monocular maximum reading speed and two validated patient-reported outcome measures: Functional Reading Independence Index and the National Eye Institute Visual Function Questionnaire. Here were some of the results:
• Enlargement of GA area (measured on fundus autofluorescence)—approximately 2 mm2/year on average across all treatment groups in each study—was accompanied by overall deterioration in all functional endpoints.
• Of visual function tests, only microperimetry outcomes were moderately correlated with GA lesion area when assessed cross-sectionally at baseline and week 48.
• All other functional parameters had no or weak correlation with GA lesion area. showed acceptable rates of ECL, with safe and promising early clinical outcomes.
Researchers wrote that Chroma/Spectri provided a unique data set of functional endpoints in GA, relevant for future clinical trials. They added that individuals with bilateral GA experienced a consistent decline in visual function over 48 weeks, but measures of visual function weren’t strongly correlated with GA lesion area. Furthermore, they wrote, it wasn’t possible to predict visual function outcomes from GA lesion size.
SOURCE: Heier JS, Pieramici D, Chakravarthy U, et al. Visual function decline due to geographic atrophy: Results from the Chroma and Spectri phase 3 trials. Ophthalmology Retina 2020; Jan 31. [Epub ahead of print].
Non-exudative Macular Neovascularization Supporting Outer Retina in AMD
Researchers wrote that type 1 macular neovascularization (MNV) secondary to age-related macular degeneration may compensatorily sustain hypoxic and micronutrient-insufficient outer retinal cells. They explored this hypothesis using the histology of an eye with a shallow irregular retinal pigment epithelial elevation (SIRE) on optical coherence tomography and good vision.
The case study and clinicopathologic correlation included the imaging of untreated non-exudative neovascular AMD and 20/30 visual acuity (left eye) and neovascular AMD (right eye) in a white woman with nine years’ multimodal imaging before death at age 90.
The left eye was preserved 6.25 hours after death and prepared for submicrometer epoxy resin sections and transmission electron microscopy aligned to clinical OCT B-scans. Researchers measured inside and outside the MNV area, layer thicknesses, phenotypes and vascular density of native choriocapillaris and new vessels with ImageJ. They measured the lengths of choriocapillaries and intervening gaps in the index eye, and in early AMD eyes and normal eyes with similar age (n=19 each) from the Project MACULA online histopathology resource with custom software (Caps and Gaps).
Main outcome measures included descriptive light and electron microscopic morphology, vascular density, histologic and OCT layer thicknesses, and distribution of choriocapillaries and intervening gaps. Here were some of the findings:
• The SIRE correlated to a type 1 MNV that expanded slowly without evidence of exudation and with numerous choroidal vessels traversing Bruch’s membrane defects, some visible on OCT.
• Tissue layers in and adjacent to the MNV area showed continuous RPE and characteristic AMD deposits.
• Capillary-like new vessels with fenestrations and caveolae resembling native choriocapillaris lined the RPE with a vascular density comparable to surrounding non-MNV areas.
• Relative to early AMD and normal-aged eyes, the index case had similar capillary lengths but larger gaps between vessels, indicating drop-out.
• ONL thickness was preserved and showed less photoreceptor degeneration over areas of relative choriocapillaris health, including the type 1 MNV.
Researchers concluded that eyes with non-exudative type 1 MNV in AMD may progress to exudation; however, this stable MNV complex supported the outer retinal structure for nine years. Distinguishing features were numerous connecting vessels, high density of new vessels, continuous RPE and slow growth. Researchers concluded that maintaining beneficial type 1 MNVs may be a therapeutic strategy.
SOURCE: Chen L, Messinger, Sloan KR, et al. Non-exudative macular neovascularization supporting outer retina in age-related macular degeneration, a clinicopathologic correlation. Ophthalmology 2020; Jan 28. [Epub ahead of print].
Association of Visit Adherence & VA in Patients with nAMD
Scientists wrote that visit adherence has been shown to play a significant role in patient health outcomes, noting that the effect of missing visits on visual acuity in individuals with neovascular age-related macular degeneration has yet to be characterized. They aimed to quantify the association between patient adherence to randomized clinical trial visits and VA in individuals with neovascular age-related macular degeneration based on four visit adherence metrics.
This secondary analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial randomized clinical trial included individuals with age-related macular degeneration from 44 U.S. clinical centers between February 2008 and December 2009. The two-year study protocol required one visit every four weeks (every 21 to 35 days for a total of 26 visits) for monthly vs. pro re nata treatments of bevacizumab vs. ranibizumab. Analysis took place from November 2018 through May 2019.
Visit adherence was measured in four ways: total number of missed visits, average number of days (avg days) between each visit, longest duration in days (max days) between visits and visit constancy (the tally of three-month periods with at least one visit attended). Average and max days were also categorized as on time (28 to 35 days), late (36 to 60 days) and very late (>60 days).
Main outcomes and measures included change in Early Treatment Diabetic Retinopathy Study VA between the baseline and the last visit. Linear multivariate regression models were applied to analyze the association between visit adherence and change in VA, controlling for age, sex, baseline VA, anti-vascular endothelial growth factor drug, number of injections and dosing regimen.
Of 1,178 patients, the mean age was 79.1 ±7.3 years, and 727 (61.7 percent) were women. Here were some of the findings:
• The mean number of missed visits was 2.4 ±3.1.
• Overall, 1,091 patients (92.6 percent) had complete visit constancy during the entire study period.
• Average days were categorized with 1,060 patients (90 percent) classified as on time, 108 (9.2 percent) were late, and 10 (0.8 percent) were very late.
• For max days between visits, 197 patients (16.7 percent) were on time, 773 (65.6 percent) were late and 208 (17.7 percent) were very late.
• After controlling for covariates, the late (avg days=-6.1; max day =-2) and very late (avg days=-12.5; max days=-5.9) groups saw fewer letters in both the avg and max days categories than patients in the on-time group (p<.001).
Scientists wrote that the results provided evidence to support the concept that visit adherence contributes to VA outcomes in nAMD. They added that the magnitude of the association of visit adherence with VA outcomes in this clinical scenario suggested that substantial effort should be expended to strive for visit adherence or therapeutic strategies that reduced the visit burden without compromising VA outcomes.
SOURCE: Ramakrishnan MS, Yu Y, VanderBeek BL. Association of visit adherence and visual acuity in patients with neovascular age-related macular degeneration: Secondary Analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial. JAMA Ophthalmol 2020; Feb 6. [Epub ahead of print].
OCTA Can Categorize Subgroups of CNV Secondary to AMD
Choroidal neovascularization characterizes wet age-related macular degeneration, showing a highly variable visual outcome. With this in mind, researchers performed a quantitative optical coherence tomography angiography assessment of CNV secondary to age-related macular degeneration at baseline in order to assess treatment outcomes.
Seventy-eight treatment-naïve wet-AMD patients (39 men, mean age: 78 ±8 years) were recruited and underwent complete ophthalmologic evaluations and multimodal imaging. Several OCT and OCTA parameters were collected, including vessel tortuosity and vessel dispersion (VDisp), and measured for each segmented CNV. All patients underwent anti-vascular endothelial growth factor treatment as-needed. Scientists tested vessel tortuosity and VDisp values of CNVs at baseline to establish a cutoff able to distinguish clinically different patient subgroups. Here were some of the findings:
• Mean best-corrected visual acuity was 0.49 ±0.57 (20/62) at baseline, improving to 0.31 ±0.29 (20/41) at the one-year follow-up (p<0.01), with a mean number of 6.4 ±1.9 injections.
• The cohort included the following CNV types: occult (45 eyes; 58 percent); classic (14 eyes; 18 percent); and mixed (19 eyes; 24 percent).
• After observing OCTA parameters, scientists found that classic, mixed and occult CNV revealed significantly different values of VDisp, with classic forms showing the highest values, and occult CNV showing the lowest (p<0.01); mixed forms displayed intermediate VDisp values.
• ROC analysis revealed that a CNV vessel tortuosity cutoff of 8.40, calculated at baseline, enabled two patient subgroups differing significantly in visual outcomes after anti-VEGF treatment to be distinguished.
Scientists wrote that a baseline quantitative OCTA-based parameter could provide information regarding clinical and functional outcomes after anti-VEGF treatment in age-related macular degeneration-related CNV.
Source: Arrigo A, Romano F, Aragona E, et al. Optical coherence tomography angiography can categorize different subgroups of choroidal neovascularization secondary to age-related macular degeneration. Retina 2020; Feb 6. [Epub ahead of print.]
Fewer Microaneurysms in DME After Anti-VEGF
Scientists evaluated changes in the number of microaneurysms (MAs) on fluorescein angiography and indocyanine green angiography in eyes with diabetic macular edema following intravitreal injection of anti-vascular endothelial growth factor agents.
Twenty-one eyes of 16 individuals with DME were included in this retrospective study. All patients received an initial loading dose of three monthly injections of anti-VEGF agents; thereafter, they received a pro re nata regimen for at least 12 months of follow-up. FA and ICGA images were obtained before and at six months after the initial injection. Here were some of the findings:
• The median numbers of MAs significantly decreased from six (interquartile range [IQR], three to seven) MAs to two (IQR, one to three) MAs in early-phase FA; three (IQR, three to five) leaky MAs to one (IQR, zero to two) leaky MA in late-phase FA; and two (IQR, one to four) MAs in late-phase ICGA at baseline to one (IQR, zero to two) MA in late-phase ICGA at six months (p<0.0001 for all).
• Only the median numbers of MAs in late-phase ICGA at baseline and at six months were significantly higher in the recurrent DME group (13 eyes) than in the non-recurrent DME group (five eyes) (p=0.0185 and p=0.009).
Scientists reported that intravitreal injection of anti-VEGF agents reduced the numbers of MAs in individuals with DME. They added that the numbers of MAs detected by late-phase ICGA might be useful predictors of DME recurrence.
SOURCE: Mori K, Yoshida S, Kobayashi Y, et al. Decrease in the number of microaneurysms in diabetic macular edema after anti-vascular endothelial growth factor therapy: Implications for indocyanine green angiography-guided detection of refractory microaneurysms. Graefes Arch Clin Exp Ophthalmol 2020; Jan 21. [Epub ahead of print].
Using SS-OCT VRI Slab vs. FA to Detect Diabetic Retinal Neovascularization
Researchers compared neovascularization in proliferative diabetic retinopathy eyes, identified by widefield swept-source optical coherence tomography angiography using vitreoretinal interface (VRI) slab images composed by automated and manual segmentation, with that identified by fluorescein angiography.
The retrospective study included 42 eyes of 30 treatment-naïve PDR patients who visited the outpatient clinic of the Ophthalmology Department of Nagano, Japan’s Shinshu University from June 2018 through October 2019.
All individuals underwent comprehensive ophthalmological exams, including SS-OCTA and FA. Researchers compared NV detected by en face SS-OCTA 15×15-mm VRI slab images and FA in the same 15×15-mm areas in terms of number and structure. Here were some of the findings:
• Among 100 NVs detected by FA, 73 were also visualized as NV in SS-OCTA VRI slab images using automated segmentation.
• The sensitivity of VRI slab images for detecting NV was 73 percent.
• Among the remaining 27 NVs detected only by FA, but not by VRI slab:
o 15 were intraretinal microvascular abnormalities with fluorescence leakage;
o one was a diabetic papillopathy; and
o 11 were flat NVs on the internal limiting membrane surface that were missed because of segmentation error.
• Among the 98 NVs detected on VRI slab images:
o 25 weren’t detected as NVs by FA;
o nine were small NVs that exhibited too little leakage on FA; and
o 16 were false-positives due to segmentation errors.
• After reconstruction of SS-OCTA VRI slab images by means of manual segmentation, the sensitivity of VRI slab images for detecting NVs increased to 84 percent.
Researchers determined that the efficacy of SS-OCTA VRI slab images for detecting NVs in PDR was comparable to that of FA. They wrote that SS-OCTA VRI slab images might be better than FA for differentiating intraretinal microvascular abnormalities and diabetic papillopathy from NVs. They noted that FA and SS-OCTA VRI slab images demonstrated differences in identification efficacy in cases of small and flat NVs, and suggested that further exploration of SS-OCTA technology was warranted to address this issue.
Source: Hirano T, Hoshiyama K, Hirabayashi K, et al. Vitreoretinal interface slab in optical coherence tomography-angiography for detecting diabetic retinal neovascularization. Ophthalmology Retina 2020; Jan 10. [Epub ahead of print].
VF Changes in Patients Treated with PRP or Ranibizumab for PDR
Preservation of peripheral visual fields is considered an advantage for anti-vascular endothelial growth factor agents compared with panretinal photocoagulation for treatment of proliferative diabetic retinopathy, researchers wrote. Since long-term data on VF are important when considering either treatment approach, researchers aimed to evaluate VF changes through five years among eyes enrolled in the Protocol S clinical trial, conducted by the DRCR Retina Network.
This post hoc analysis of an ancillary study within a multicenter, randomized clinical trial included individuals with proliferative diabetic retinopathy enrolled in Protocol S. Data were collected from February 2012 to February 2018, and analysis began in June 2018.
Subjects received panretinal photocoagulation or intravitreous injections of 0.5-mg ranibizumab. Diabetic macular edema, whenever present, was treated with ranibizumab in both groups. Panretinal photocoagulation could be administered in eyes in the ranibizumab group when failure or futility criteria were met.
Main outcomes and measures included mean change in total point score on VF testing with the Humphrey Field Analyzer 30-2 and 60-4 test patterns. Of 394 eyes enrolled in Protocol S, 234 (59.4 percent) were targeted for this ancillary study. Of these, 167 (71.4 percent) had VFs meeting acceptable quality criteria at baseline (median age: 50 years [interquartile range: 43 to 58]; 90 participants were men [53.9 percent]). At five years, 79 (33.8 percent) had results available. Here were some of the findings:
• The mean change in total point score was -305 ±521 dB in the PRP group and -36 ±486 dB in the ranibizumab group at one year, increasing to -527 ±635 dB in the PRP group and -330 ±645 dB in the ranibizumab group at five years (p=0.04).
• After filtering VF results post-PRP treatment in the ranibizumab group, the five-year mean change in total point score was -201 (442) dB.
• In a longitudinal regression analysis of change in total point score including both treatment groups, laser treatment was associated with a mean point decrease of 208 (CI, 112 to 304) dB for the initial PRP session, 77 (CI, 21 to 132) dB for additional PRP sessions and 325 (CI, 211 to 439) dB for endolaser.
• No association was found between the change in point score and the number of ranibizumab injections during the previous year (-9 per injection [CI, -22 to three]).
Researchers wrote that the limited data available from Protocol S suggested that factors besides PRP were associated with VF loss in eyes treated with PDR. They added that further clinical research is needed to clarify the finding.
SOURCE: Maguire MG, Liu D, Glassman AR, et al. Visual field changes over 5 years in patients treated with panretinal photocoagulation or ranibizumab for proliferative diabetic retinopathy. JAMA Ophthalmol 2020; Jan 30. [Epub ahead of print].
DR Screening Using Gold Nanoparticle-based Paper Strip Assay for At-home Detection
Investigators assessed a smartphone-based, gold nanoparticle (AuNP)-based colorimetric lateral flow immunoassay paper sensor for quantifying urine 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a biomarker for diabetic retinopathy screening.
The paper strips incorporated AuNP–8-OHdG antibody conjugates that produced color changes proportional to urine 8-OHdG discernible on a smartphone camera photograph. Investigators performed paper strip accuracy, precision and stability studies with 8-OHdG solutions of varying concentrations. Urine was collected from 97 diabetic patients receiving DR screening exams, including seven-field fundus photographs. They graded DR by standard methods: low risk (no or mild DR) and high risk (moderate or severe DR). They performed paper sensor assays on urine samples from patients, and correlated 8-OHdG values with DR grades. They analyzed differences in 8-OHdG values between low- and high-risk groups for outliers to identify the threshold 8-OHdG value that would minimize false-negative results. Here were some of the findings:
• Lateral flow immunoassay paper strips quantitatively measured 8-OHdG and were found to be accurate, precise and stable.
• Average urine 8-OHdG concentrations in study patients were 22 ±10 ng/mg of creatinine in the low-risk group and 55 ±11 ng/mg of creatinine in the high-risk group.
• Screening cutoff values of 8-OHdG >50 ng/mg of creatinine or urine creatinine >1.5 mg minimized screen failures, with 91 percent sensitivity and 81 percent specificity.
Investigators reported that urinary 8-OHdG was a useful biomarker to screen DR. They added that quantitative 8-OHdG detection with a lateral flow immunoassay paper sensor and smartphone camera demonstrated its potential in DR screening.
Source: Hainsworth DP, Gangula A, Ghoshdastidar S, et al. Diabetic retinopathy screening using a gold nanoparticle-based paper strip assay for the at-home detection of the urinary biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG). Am J Ophthalmol 2020; Feb 6. [Epub ahead of print].
Comparison of 27- vs. 25-gauge Vitrectomy Results in Patients with Epiretinal Membrane: 6-month Follow-up
Investigators compared 27- vs. 25-gauge vitrectomy in patients with epiretinal membrane.
Sixty pseudophakic eyes of 60 consecutive patients treated by pars plana vitrectomy (PPV) using 27 ga. (30 eyes) or 25 ga. (30 eyes) were prospectively evaluated on the basis of ocular inflammation, surgery time, ERM + ILM removal time and complications. Additionally, one, three, seven, 14, 30, 90 and 180 days after PPV, the following were estimated: intraocular pressure; sclerotomy wound closure time; distance best-corrected visual acuity (DBCVA); foveal macular thickness (FMT); and surgically induced astigmatism (SIA). Here were some of the findings:
• The eye’s inflammation resolved within 30 days after surgery in both groups.
• The surgery and ERM + ILM times were longer in the 27 ga. group (p≤0.02).
• The most common postoperative complication was hypotony in both groups, more common in the 25 ga. group (23.3 vs. 10 percent of eyes).
• In the 27 ga. group, the mean IOP prior to 180 days postoperatively was higher (p<0.05) and the sclerotomy wound closure time was shorter (p<0.001).
• Mean DBCVA values (seven, 14, 30 days after surgery) were significantly better in the 27 ga. group (p<0.001).
• The mean FMT values were similarly and significantly reduced in both groups one day postoperatively (p<0.05) as compared to preoperative values and then stabilized during follow-up.
• Mean SIA was lower in the 27 ga. group 30, 90 and 180 days after surgery (p<0.001).
Investigators determined that the use of 27 ga. PPV in patients with ERM significantly reduced sclerotomy wound closure time and surgically induced astigmatism, better stabilized intraocular pressure and allowed patients to achieve faster visual acuity improvement, as compared with 25 ga. PPV.
SOURCE: Lubiński W, Gosławski W, Podborączyńska-Jodko K, et al. Comparison of 27-gauge versus 25-gauge vitrectomy results in patients with epiretinal membrane: 6-month follow-up. Int Ophthalmol. 2020 Jan 19. [Epub ahead of print].
ASRS Issues Notice Regarding Beovu and Inflammation
In late February, the American Society of Retina Specialists issued a statement that could impact Novartis’ new AMD drug Beovu’s (brolucizumab-dbll) adoption rate by retinal specialists. The ASRS stated that, in addition to reports of mild-moderate intraocular inflammation following the administration of Beovu, it’s received reports of 14 cases of vasculitis, “of which 11 were designated as occlusive retinal vasculitis by the reporting provider.” It adds that the etiology of the events is unclear, and long-term outcomes and treatment strategies remains undefined. It does recommend deferring anti-VEGF injection in patients that have any signs of intraocular inflammation.
In response, Novartis issued a statement, part of which notes, “Novartis’ review of this information is ongoing and classification of these ASRS-reported cases by Novartis has not been established, but we are aware of recently reported adverse events following treatment with Beovu. Novartis stands behind the safety and efficacy of Beovu. In addition to our own internal assessment, we have engaged an external safety review committee to further evaluate these post-marketing cases.”
TWO-YEAR PANORAMA RESULTS
Regeneron Pharmaceuticals announced positive two-year results from the Phase III PANORAMA trial evaluating Eylea (aflibercept) injection 2 mg (0.05 mL) in individuals with moderately severe to severe non-proliferative diabetic retinopathy. The two-year, pre-specified, exploratory data demonstrated that untreated moderately severe and severe NPDR could lead to vision-threatening events, including vision-threatening complications (proliferative diabetic retinopathy or anterior segment neovascularization) and center-involved diabetic macular edema. Based on a Kaplan-Meier analysis, more than half (58 percent) of patients in the untreated sham arm developed a VTC or CI-DME within two years of entering the trial, while Eylea treatment was shown to reduce the likelihood of those vision-threatening events by at least 75 percent (nominal p<0.0001). Read more.
SOURCE: Regeneron, February 2020
PHASE III DATA ON XIPERE
Bausch + Lomb with parent company Bausch Health Companies, and Clearside Biomedical announced positive results from the randomized, controlled, double-masked Phase III clinical trial (PEACHTREE) of Xipere (triamcinolone acetonide suprachoroidal injectable suspension), an investigational treatment with a proposed indication of macular edema associated with uveitis. The data, published in Ophthalmology, demonstrated that individuals with noninfectious uveitis in the Xipere study arm experienced clinically significant improvement in vision relative to the control arm. (The control group underwent a sham procedure to maintain masking; the procedure mimicked the suprachoroidal injection, but no drug or vehicle was administered.) The company says this demonstrates the potential efficacy of suprachoroidal injection of Xipere for the treatment of macular edema associated with uveitis. No serious adverse events were reported. Read more.
Source: Bausch + Lomb, January 2020
KODIAK ANNOUNCES SAFETY, EFFICACY & DURABILITY DATA FROM KSI-301 STUDY
Kodiak Sciences announced promising safety, efficacy and durability data from the ongoing Phase Ib study of its investigational therapy KSI-301, an intravitreal anti-VEGF antibody biopolymer conjugate, in individuals with treatment-naïve wet age-related macular degeneration, diabetic macular edema or retinal vein occlusion. KSI-301, an investigational anti-VEGF therapy built on the company's antibody biopolymer conjugate platform, is designed to maintain effective drug levels in ocular tissues for longer than existing agents, the company says. Read more.
SOURCE: Kodiak Sciences, February 2020
LINEAGE PROVIDES UPDATE ON OPREGEN PHASE I/IIA STUDY
Lineage Cell Therapeutics reported positive findings from its ongoing Phase I/IIa clinical study of OpRegen, the company’s retinal pigment epithelium transplant therapy for the treatment of dry age-related macular degeneration. All five patients in cohort 4, those with better baseline vision and which represent the company’s intended patient population, showed increases in best-corrected visual acuity. Notably, the first cohort-4 patient dosed with both the company’s new thaw-and-inject formulation and Orbit subretinal delivery system gained 25 readable letters (or five lines) at six months following administration of OpRegen RPE cells as assessed by the Early Treatment Diabetic Retinopathy Scale (ETDRS), the company says. Read more.
Source: Lineage Cell Therapeutics, February 2020
EyePoint Signs License Agreement with Equinox
EyePoint Pharmaceuticals signed an exclusive license agreement with Equinox Science to develop vorolanib, a tyrosine kinase inhibitor, for the treatment of wet age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. Vorolanib is being developed as EYP-1901 utilizing EyePoint’s bioerodible Durasert technology, a miniaturized, injectable, sustained-release intravitreal drug delivery system with a six-month duration. The company recently completed a positive Type B pre-Investigational New Drug meeting with the FDA, clarifying the pathway for a Phase I clinical trial. Read more.
SOURCE: EyePoint Pharmaceuticals, February 2020
PROQR RECEIVES FDA RARE PEDIATRIC DISEASE DESIGNATION FOR QR-421A
ProQR Therapeutics received the FDA’s Rare Pediatric Disease designation for QR-421a for the treatment of retinitis pigmentosa caused by mutations in exon 13 of the USH2A gene. QR-421a is a first-in-class, investigational, RNA-based oligonucleotide designed to address the underlying cause of vision loss in Usher syndrome type II and non-syndromic retinitis pigmentosa due to mutations in exon 13 of the USH2A gene. The RPD designation provides FDA priority review to encourage treatments for rare pediatric diseases, the company says. Read more.
Source: ProQR Therapeutics, January 2020
NEW RETINA PRACTICE SOFTWARE FROM USRETINA
USRetina announced new technology offering RetinaOS, an operating system with two modules: RetinaInventory for inventory management; and RetinaPurchasing, a group purchasing portal that provides broad access to retina-specific pharmaceuticals. The company says that the software programs were built by retina doctors, and are intended to streamline drug purchasing, improve operations management, optimize revenue cycle management and help doctors navigate regulatory changes while building bottom-line revenue. Read more.
SOURCE: USRetina, January 2020
OCUPHIRE In-Licenses SMALL MOLECULE DRUG CANDIDATE FROM APEXIAN
Ocuphire Pharma entered into an agreement with Apexian Pharmaceuticals, granting Ocuphire an exclusive worldwide sublicense to Apexian’s Ref-1 Inhibitor program, including its lead drug candidate APX3330, for all ophthalmic and diabetic indications. APX3330 is a first-in-class, orally administered, small-molecule drug candidate that selectively targets and inhibits the reduction-oxidation effector factor-1(Ref-1) protein, a novel upstream regulator of critical transcription factors controlling inflammatory and angiogenesis pathways implicated in diabetic retinopathy and diabetic macular edema, the company says. Read more.
SOURCE: Ocuphire, January 2020
WVU PROJECT AIMS TO PREVENT BLINDNESS IN DIABETIC PATIENTS
The West Virginia Practice-Based Research Network’s Sight Outreach Program, through the West Virginia Clinical and Translational Science Institute, is training primary care staff members across the state to use the Intelligent Retinal Imaging System (IRIS) to quickly capture images of a patient’s retinas. During routine primary care visits in participating clinics, providers take a photograph of the patient’s retina that is securely transmitted to a retinal specialist at the West Virginia University Eye Institute. After receiving the image, an ophthalmologist analyzes it for evidence of pathology and delivers results to the patient’s electronic medical record. Primary care providers also receive recommended care plans and referral paths if indicated. Read more.
SOURCE: WVUToday, January 2020
VERANA HEALTH ACQUIRES PYA ANALYTICS; ANNOUNCES $100 MILLION FINANCING
Verana Health, which aggregates datasets using the American Academy of Ophthalmology’s IRIS registry, announced that it acquired the technology assets and the staff of PYA Analytics (PYAA), which specializes in large-scale data architecture solutions, for $100 million. Read more.
SOURCE: Verana Health, February 2020
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