FROM THE EDITORS OF REVIEW OF OPHTHALMOLOGY AND RETINA SPECIALIST:
Macular Morphology and VA in Year Five of CATT
CATT participant eyes with AMD-associated choroidal neovascularization and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab, to three dosing regimens for two years and at the ophthalmologists’ discretion thereafter.
Main outcome measures included: VA; thickness and morphological features on optical coherence tomography; lesion size; and foveal composition on fundus photography and fluorescein angiography.
VA and image gradings were available for 523 of 914 participants (57 percent) alive at five years. At five years:
Investigators found that associations between VA and morphologic features previously identified through year one were maintained or strengthened at year five. They also determined that new foveal scars, CNV, intraretinal fluid, SHRM and retinal thinning; development or worsening of foveal GA; and increased lesion size were important contributors to VA decline from year two to five. Investigators suggested that new therapies were needed to address these adverse pathological features.
Acuity Outcomes Based on Initial Treatment Response in nAMD
The study included 2,051 treatment-naïve eyes from 1,828 individuals in the Fight Retinal Blindness! outcomes registry receiving anti-VEGF therapy between Jan. 1 2007, and March 1, 2014, and specifically injections within the first three months.
Researchers defined early response as occurring before the fourth injection. They analyzed various early response metrics, including continuous and categorical variables such as:
Achieving good vision at three years was significantly associated with:
Attainment of good vision by the fourth injection was strongly associated with three-year visual outcomes, while other early response parameters had a moderate association. Researchers determined that the early response during the initial three monthly loading doses could be a useful guide for subsequent treatment decisions.
Long-Term Effectiveness of Continued Ranibizumab in NAMD vs. Switch to Aflibercept
Participants included subjects with nAMD initiated on ranibizumab who remained (non-switchers) or those who switched to aflibercept, captured from a U.S. electronic medical records database between July 1, 2011, and Oct 12, 2014.
Subject eyes were matched on baseline age, baseline visual acuity, VA at month three and duration of follow-up. Matching ratio was 1:2 (switchers:non-switchers) where possible and 1:1 otherwise.
The primary outcome was VA change from baseline (first injection of ranibizumab) to month 24. Secondary endpoints were area under the ROC curve of VA change; eyes (percentage) gaining or losing ≥5, ≥10 or ≥15 letters; or VA >73 letters at month 24, number of injections and monitoring visits, and pre-switch characteristic analyses.
A total of 454 switchers and 750 matched non-switchers were included. The adjusted difference in mean VA change from baseline to month 24 for switchers to non-switchers was 0.02 (CI, -1.63, 1.68) letters. The upper bound CI (1.68) was below the predefined non-inferiority margin of five letters. Switchers had a significantly higher annualized number of mean total visits compared to non-switchers (10 vs. 9 for year one; 8.7 vs. 7.4 for year two), a higher number of injection visits (8.4 vs. 6.7 for year one; 7 vs. 5.1 for year two), but a lower number of monitoring-only visits (1.6 vs. 2.3 for year one; 1.7 vs. 2.3 for year two). During the pre-switch period, switchers had a higher number of injection visits (7.6 vs. 6.5), fewer monitoring-only visits (1.5 vs. 2.2) and comparable total visits (9.1 vs. 8.7). VA change from baseline to switch was similar between switchers and non-switchers (adjusted LS mean difference -1.36 [CI, -2.76; 0.05] letters).
Researchers found that switching patients from ranibizumab to aflibercept resulted in no difference in VA change compared with those maintained on ranibizumab only. They suggested that the lower re-treatment rate in non-switchers compared with switchers post-switch didn’t support the view of longer treatment efficacy.
RPE Hyperplasia Overlying PED in AMD Can Masquerade as Neovascularization on OCTA
The hospital-based, retrospective and cross-sectional study included 22 eyes from 16 subjects with non-vascularized PED related to AMD. All subjects were examined by OCTA, spectral-domain OCT, fluorescein angiography and indocyanine green angiography. Investigators evaluated vascular flow signals on the outer retinal slab of en face OCTA and cross-sectional OCTA images, and their correspondence with RPE hyperplasia. Here are some of the investigators’ findings:
The researchers determined that RPE hyperplasia overlying PED in AMD could masquerade as neovascularization on OCTA. They suggested that this RPE hyperplasia-related image artifact should be considered when interpreting OCTA images to avoid misdiagnosis and unnecessary treatment.
Natural History of DPED Associated With AMD
Of 4,203 Age-Related Eye Disease Study 2 participants, 391 eyes (325 participants) were identified as having DPED without late AMD at the time of DPED detection. Genetic analyses included 120 white AREDS2 participants and 145 AREDS participants with DPED.
Scientists graded baseline and annual stereoscopic fundus photographs according to a standardized protocol to detect DPED, a well-defined yellow elevated mound of confluent drusen, measuring ≥ 433 µm in diameter, to evaluate progression rates to late AMD (geographic atrophy and neovascular). They investigated five single-nucleotide polymorphisms (CFH [rs10611670], C3 [rs2230199], CFI [rs10033900], C2/CFB [rs114254831] and ARMS2 [rs10490924]) and a genetic risk score group for association with DPED development. They also performed Kaplan-Meier analyses and multivariable proportional hazard regressions.
Main outcome measures included progression rates to late AMD and decrease of ≥ three lines in visual acuity from time of DPED detection. Mean (SD) follow-up time from DPED detection was 4.7 (0.9) years. Scientists reported the following findings:
Scientists wrote that their findings replicated the results of previous natural history studies of eyes with DPED, including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). They added that the genetic associations were consistent with genes associated with AMD progression.
Mineralocorticoid Receptor Antagonists in CSCR
They searched three databases (PubMed, EMBASE and BIOSIS) for potentially relevant records as of March 2018. Of 114 unique studies identified, they included five RCTs comparing BCVA with either eplerenone or spironolactone vs. observation or placebo. Scientists assessed the quality of articles according to the Cochrane Risk of Bias Tool with any discrepancies resolved by author consensus.
A total of 145 eyes with CSCR were included. Compared with placebo or observation, MR antagonist treatments had a significant positive effect on BCVA after both one month (weighted mean difference [WMD]=-0.05 logMAR units [CI, -0.07 to -0.02], Z=3.94, p<0.0001) and two months (WMD=-0.10 logMAR units [CI, -0.14 to -0.06], Z=4.69, p<0.00001). MR antagonist treatments also significantly reduced SRF height in CSCR at one month (WMD=-81.15 μm [CI, -148.25 to -14.05], Z=2.37, p=0.02). However, this effect was no longer significant at two months (WMD=-58.63 μm [CI, -155.40 to 38.13, Z=1.19, p=0.23). No individuals in the five trials withdrew due to adverse effects, and blood electrolyte levels including potassium remained normal in all cases.
The scientists wrote that the findings suggested a modest benefit with MR antagonist therapy for individuals with CSCR in improving BCVA. They added that they anticipated that MR antagonists would be well-tolerated in most CSCR cases and that barriers to starting a trial of these medications in non-resolving CSCR should be low.
Complement Levels in Vitreous Aspirates of PDR & RD Eyes
Investigators measured complement factor D, component C5/C5a and component C9 levels using enzyme-linked immunosorbent assay and multiplex assays. They compared eyes with retinal detachment and PDR to controls consisting of eyes with macular holes or epiretinal membranes. Levels of complement factor D in PDR (mean=2,110 ng/mL, p=0.001) and RD (mean=660.9 ng/mL, p=0.03) eyes were statistically significantly higher than those of controls (mean=290.5 ng/mL).
Levels of complement component C9 were also more elevated in PDR eyes (p=0.004) compared with controls, though not in RD eyes.
Investigators concluded that elevated complement factors, particularly of the alternative pathway, were noted in PDR and RD eyes compared with controls. They suggested that oxidative stress in RD and PDR eyes might have led to complement dysregulation and alternative complement upregulation.
Autonomous AI-based Diagnostic System for DR Detection
More than mild DR (mtmDR) was defined as ETDRS level 35 or higher and/or DME in at least one eye. AI system operators underwent a standardized training protocol before the study started.
The median age was 59 years (range: 22 to 84 years). Among participants: 47.5 percent were male, 16.1 percent were Hispanic, 83.3 percent weren’t Hispanic, 28.6 percent were African American and 63.4 percent weren’t African American. A total of 198 (23.8 percent) had mtmDR.
The AI system exceeded all pre-specified superiority endpoints, with:
Researchers wrote that these results prompted the FDA to approve the system for clinical use to detect mtmDR and DME, making it the first FDA-approved, autonomous AI diagnostic system in medicine.
SS-OCT Facedown Position Post-vitrectomy & Macular Hole Closures
Eighty eyes of 80 consecutive individuals with MH that underwent vitrectomy surgery with internal limiting membrane peeling and gas tamponade were included. Forty eyes of 40 individuals kept in FD position for three days after surgery were assigned to the FD group, and 40 eyes of 40 individuals with nFD positioning were assigned to the nFD group. Researchers examined macular holes with swept-source optical coherence tomography images at one day, two days, three days, two weeks, one month and three months after surgery. They compared the MH closure rate and change of best-corrected visual acuity. Below are some of the findings:
Researchers found that the nFD protocol neither delayed MH closures nor decreased the final closure rate after vitrectomy surgery. As such, they suggested that using the prone position postoperatively seemed to be unnecessary for all MH repair procedures
Choroidal Structures & Visual Functions in Eyes With Retinitis Pigmentosa
They binarized EDI-OCT images of 100 eyes with typical RP, and 60 age-, sex- and axial length-matched normal eyes using the image-processing program ImageJ, and measured cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1,500-µm width. The inner choroid included the choriocapillaris and medium vessel layer, and the outer choroid included the larger vessel layer.
In the inner choroid, the luminal area and ratio of luminal/total choroidal area (L/C ratio) were significantly smaller in RP (p=0.010) than in controls (p<0.001), whereas the stromal area wasn’t significantly different (p=0.114). The inner choroidal L/C ratio was significantly correlated with best-corrected visual acuity, mean deviation, foveal sensitivity, and width of the ellipsoid zone and central foveal thickness in RP after adjusting for axial length, age and sex (all p<0.005).
Researchers determined that the significant correlations between the inner choroidal structures, and visual functions and retinal structures indicated that the choroidal structures were altered in association with the progression of RP.
Heidelberg OCTA Module Now Available in United States
IRIDEX INTRODUCES UPDATED TRUFOCUS LIO PREMIERE LASER ACCESSORY
Following FDA 510(k) clearance, Iridex introduced its updated TruFocus LIO Premiere laser accessory to the U.S. market. The light combination and reflection viewing system used with Iridex retina laser systems is worn on the physician’s head and combines a laser treatment beam from an Iridex laser source with the illumination beam of a binocular indirect ophthalmoscope into a mixed optical beam. The physician uses a handheld ophthalmic exam lens to view and treat the retina through the patient’s pupil. Read more.
Source: Iridex, September 2018
EYEGATE EGP-437 IN ANTERIOR UVEITIS SHOWS EFFICACY BUT NOT NON-INFERIORITY TO CONTROLS
EyeGate Pharmaceuticals announced mixed topline results from its Phase III study evaluating the safety and efficacy of EGP-437 delivered through the EyeGate II Drug Delivery System in individuals with noninfectious anterior segment uveitis. Although EGP-437 showed clinical efficacy, defined as a reduction in anterior chamber cell score throughout the study, EyeGate reports that it didn’t demonstrate non-inferiority to the prednisolone acetate ophthalmic solution control group. This was measured as the proportion of subjects with an anterior cell count of zero (a sign of diminished inflammation) at day 14. EyeGate says it plans to review the data and assess its strategic options for EGP-437 going forward. Read more.
Source: EyeGate Pharmaceuticals, September 2018
ADVERUM IND ACTIVE FOR ADVM-022 NOVEL GENE THERAPY TO TREAT WET AMD
Adverum Biotechnologies announced its Investigational New Drug application is active for the planned multicenter, open-label, Phase I, dose-escalation study of ADVM-022, a novel gene therapy candidate for the treatment of wet age-related macular degeneration. The trial is designed to assess the safety and tolerability of a single intravitreal injection of ADVM-022 in individuals with wet AMD who are responsive to anti-vascular endothelial growth factor treatments. Read more.
Source: Adverum Biotechnologies, August 2018
KODIAK COMPLETES FINANCING TO ADVANCE KSI-301
Kodiak Sciences completed a $33 million round of private financing of convertible notes to pay for product development. Kodiak intends to use the proceeds from the financing to advance the development of its lead product candidate, KSI-301, an anti-VEGF therapy for wet age-related macular degeneration and diabetic retinopathy. The novel, pre-IND stage, anti-VEGF biologic therapy is designed to combine inhibition of a known pathway. KSI-301 is built with Kodiak's Antibody Biopolymer Conjugate, or ABC, platform, designed to maintain potent and effective drug levels in ocular tissues. By addressing the primary causes of undertreatment, KSI-301 has the potential to improve and sustain visual acuity outcomes in individuals with neovascular conditions of the retina such as wet AMD and DR. Read more.
Source: Kodiak Sciences, April 2018
ProQR Releases Positive Results from Phase I/II Clinical Trial of QR-110
ProQR Therapeutics announced encouraging results from a planned interim analysis of its Phase I/II trial of QR-110 in individuals with Leber’s congenital amaurosis 10 due to the p.Cys998X mutation in the CEP290 gene. LCA10 typically leads to childhood blindness and has no available treatment options. In the trial, QR-110 demonstrated rapid and sustained improvement in vision in subjects with LCA10, as measured by visual acuity and the mobility course performance, and being well-tolerated with no serious adverse events recorded, the company says. Read more.
Source: ProQR Therapeutics, September 2018
Opthea Reports $1.2 Million Revenues as it Progresses THROUGH Trials
On the heels of increasing its annual revenues by 95 percent to $1.2 million during the 2017-18 financial year, Opthea representatives reported the company is on track to advance its clinical development program for its therapeutic OPT-302 and meet milestones as it investigates the therapy in people with diabetic macular edema and wet age-related macular degeneration, by the year 2020. Company directors reported that, in the next 12 months, Opthea plans to complete patient enrollment for its Phase IIb wet AMD trial and complete the first six-monthly dosing regimen for elderly patients. Read more.
Source: Opthea, August 2018
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