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.
Using AI in OCT to Characterize Drusen & Hyperreflective Foci as Biomarkers for AMD Progression
Investigators wrote that morphologic changes and their pathognomonic distribution in the progression of age-related macular degeneration aren’t well understood. They aimed to characterize the pathognomonic distribution and time course of morphologic patterns in AMD, and quantify changes associated with progression in macular neovascularization and macular atrophy.
The cohort study included optical coherence tomography volumes from study participants with early or intermediate AMD in the fellow eye in the HARBOR (A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration) trial. Individuals underwent imaging monthly for three years (July 1, 2009, to August 31, 2012) following a standardized protocol. Data analysis was performed between June 1, 2018, and January 21, 2020.
To obtain topographic correspondence between individuals and over time, investigators mapped scans into a joint reference frame. They established time of progression to MNV and MA, and automatically segmented drusen volumes and hyperreflective foci (HRF) volumes in three dimensions using validated artificial intelligence algorithms. They constructed topographically resolved population means of the markers by averaging quantified drusen and HRF maps in the patient subgroups. Here were some of the findings:
• Of 1,097 individuals enrolled in HARBOR, 518 (mean age: 78.1 ±8.2 years; 309 [59.7 percent] were female) had early or intermediate AMD in the fellow eye at baseline.
• During the 24-month follow-up period, 135 eyes (26 percent) developed MNV, 50 eyes (10 percent) developed MA and 333 eyes (64 percent) didn’t progress to advanced AMD.
• Drusen and HRF had distinct topographic patterns. Mean drusen thickness at the fovea was:
o 29.6 μm (CI, 20.2 to 39 μm) for eyes progressing to MNV;
o 17.2 μm (CI, 9.8 to 24.6 μm) for eyes progressing to MA; and
o 17.1 μm (CI, 12.5 to 21.7 μm) for eyes without disease progression.
• At 0.5-mm eccentricity, mean drusen thickness was:
o 25.8 μm (CI, 19.1 to 32.5 μm) for eyes progressing to MNV;
o 21.7 μm (CI, 14.6 to 28.8 μm) for eyes progressing to MA; and
o 14.4 μm (CI, 11.2 to 17.6 μm) for eyes without disease progression.
• The mean HRF thickness at the foveal center was 0.072 μm (CI, 0 to 0.152 μm) for eyes progressing to MNV, 0.059 μm (CI, 0 to 0.126 μm) for eyes progressing to MA and 0.044 μm (CI, 0.007 to 0.081) for eyes without disease progression.
• At 0.5-mm eccentricity, the largest mean HRF thickness was seen in eyes progressing to MA (0.227 μm; CI, 0.104 to 0.349 μm), followed by eyes progressing to MNV (0.161 μm; CI, 0.101 to 0.221 μm) and eyes without disease progression (0.085 μm; CI, 0.058 to 0.112 μm).
Investigators found that drusen and HRF represented imaging biomarkers of disease progression in AMD, demonstrating distinct topographic patterns over time that differed between eyes progressing to MNV, eyes progressing to MA or eyes without disease progression. They added that automated localization and precise quantification of these factors may help to develop reliable methods of predicting future disease progression.
SOURCE: Waldstein SM, Vogl WD, Bogunovic H, et al. Characterization of drusen and hyperreflective foci as biomarkers for disease progression in age-related macular degeneration using artificial intelligence in optical coherence tomography. JAMA Ophthalmol 2020; May 7. [Epub ahead of print].
Hyperreflective Foci and Specks Associated with Delayed Rod-mediated Dark Adaptation in Non-nAMD
Investigators wrote that hyperreflective foci (HRF) are optical coherence tomography biomarkers for progression of non-neovascular age-related macular degeneration attributed to anteriorly migrated retinal pigment epithelial cells. They examined associations between rod- and cone-mediated vision and HRF plus smaller hyperreflective specks (HRS) and sought a histologic candidate for HRS.
The cross-sectional, histologic survey included individuals with normal maculas (n=34), early AMD (n=26) and intermediate AMD (n=41).
Investigators determined AMD severity via the nine-step Age-Related Eye Disease Study scale. In OCT scans, they manually counted HRF and HRS. Vision tests probed cones (best-corrected visual acuity, contrast sensitivity); mixed cones and rods (low luminance VA, low luminance deficit, mesopic light sensitivity); or rods (scotopic light sensitivity, rod-mediated dark adaptation [RMDA]). Investigators reviewed an online AMD histopathology resource.
The main outcome measures included vision in eyes assessed for HRF and HRS, and candidate histology for HRS. Here were some of the findings:
- In 101 eyes of 101 individuals, HRF were identified in 25 eyes, and HRS were identified in 95 eyes, with good intra- and interrater reliability.
- HRF were present but sparse in normal eyes, infrequent in early AMD eyes and frequent but highly variable among intermediate AMD eyes (number per eye: 0.1 ±0.2, normal; 0.2 ±0.5, early; 1.9 ±3.4, intermediate).
- HRS outnumbered HRF in all groups (4.5 ±3.2, normal; 6.3 ±5.8, early; 19.4 ±22.4, intermediate).
- Delayed RMDA was strongly associated with more HRF and HRS (both p<0.0001).
- HRF were associated with worse low luminance VA (p=0.0117).
- HRS were associated with:
- worse contrast sensitivity (p=0.0278);
- low luminance VA (p=0.0010);
- low luminance deficit (p=0.0031); and
- mesopic (p=0.0018) and scotopic sensitivity (p<0.0001).
- By histology, cone lipofuscin was found in inner segments, and the outer nuclear and Henle’s fiber layers at 25 percent of normal, aged eyes.
Investigators determined that HRF and HRS were markers of cellular activity associated with visual dysfunction, especially delayed RMDA, an AMD risk indicator assessing efficiency of retinoid re-supply. They added that HRS may represent lipofuscin granules translocating inwardly within cone photoreceptors. Moreover, investigators wrote, HRF and HRS—visible and quantifiable on SD-OCT—may serve as structural endpoints in clinical trials targeting AMD stages earlier than atrophy expansion. They advised that these results should be confirmed in a larger sample.
SOURCE: Echols BS, Clark ME, Swain TA, et al. Hyperreflective foci and specks are associated with delayed rod-mediated dark adaptation in non-neovascular age-related macular degeneration. Ophthalmol Retina 2020; May 7. [Epub ahead of print].
Beta-peripapillary Atrophy and GA in CATT
Researchers determined associations between beta-peripapillary atrophy (B-PPA), and incidence and growth of geographic atrophy in eyes treated with anti-vascular endothelial growth factor agents in the Comparison of Age-Related Macular Degeneration Treatments Trials.
They included 245 cases with incident GA, and 245 controls matched by baseline demographics and characteristics associated with development of GA in the CATT. Researchers graded baseline color images for the type of B-PPA, defined as presence of hypopigmentation with visible choroidal vessels and sclera that’s adjacent to the optic disk. They further classified B-PPA as scleral ring, sclera, sclera/choroidal blood vessels or a combination. They measured areas of each type of B-PPA and the circumferential extent of B-PPA. Here were some of the findings:
• B-PPA was present in 58 percent of eyes developing GA and in 52 percent without GA (p=0.17).
• The greater circumferential extent of sclera/choroidal blood vessel B-PPA relative to the optic disk was associated with incident GA (p=0.02) and GA size at first observation (p=0.047).
• B-PPA wasn’t associated with GA growth rates (p>0.05).
• Individuals without B-PPA had a higher number of GA-associated risk alleles of ARMS2 (p=0.0003) and HTRA1 (p=0.001).
Researchers concluded that the extent of sclera/choroidal blood vessel B-PPA was associated with GA incidence and size, but not with the growth rate in eyes treated for neovascular age-related macular degeneration. They added that B-PPA and GA may share some common pathophysiologic pathways unrelated to the GA-associated risk alleles evaluated.
SOURCE: Kolomeyer AM, Smith E, Daniel E, Ying GS, et al. Beta-peripapillary atrophy and geographic atrophy in the comparison of age-related macular degeneration treatments trials. Retina 2020; May 5. [Epub ahead of print].
Genotype & Phenotype-Based Subgroups in GA Secondary to AMD: The EYE-RISK Consortium
Researchers, who wrote that geographic atrophy secondary to age-related macular degeneration is considered a single entity, aimed to determine whether GA subgroups could be defined by their genotype and phenotype, as part of a retrospective analysis of cross-sectional data. Participants included individuals (196 eyes of 196 individuals) 50 years or older with GA from the EYE-RISK database.
Participants were graded for the presence of each of the following fundus features on color fundus photography:
• large soft drusen;
• reticular pseudodrusen (RPD);
• refractile drusen;
• location of atrophy (foveal vs. extrafoveal); and
• multifocal lesions.
In addition, genotypes of 33 single nucleotide polymorphisms previously assigned to the complement, lipid metabolism or extracellular matrix (ECM) pathways, and ARMS2, were included. Genetic risk scores (GRS) for each of the three pathways were calculated. Researchers used hierarchical cluster analysis to determine subgroups of participants defined by these features. They determined the discriminative ability of genotype, phenotype or both for each subgroup with 10-fold cross-validated areas under the curve (cvAUC), and assessed the agreement between predicted and actual subgroup membership was assessed with calibration plots.
Main outcome measures included identification and characterization of GA subgroups based on their phenotype and genotype. Here were some of the findings:
• Cluster analyses identified three subgroups of GA:
o Subgroup 1 was characterized by high complement GRS, frequently associated with large soft drusen and foveal atrophy;
o subgroup 2 generally showed low GRS, foveal atrophy and few drusen (any type); and
o subgroup 3 presented a high ARMS2 and ECM GRS, RPD and extrafoveal atrophy.
• A high discriminative ability was found between subgroups for the genotype (cvAUC ≥0.94) and a modest discriminative ability was found for the phenotype (cvAUC <0.65), with good calibration.
Researchers identified three GA subgroups that differed mostly by their genotype; atrophy location and drusen type were the most relevant phenotypic features.
Source: Biarnés M, Colijn JM, Sousa J, et al. Genotype and phenotype-based subgroups in geographic atrophy secondary to age-related macular degeneration. The EYE-RISK Consortium. Ophthalmology Retina 2020; May 3. [Epub ahead of print.]
Adherence to the Mediterranean Diet & Progression to Late AMD in AREDS 1 and 2
Researchers aimed to determine whether closer adherence to a Mediterranean diet was associated with altered risk of progression to late age-related macular degeneration and its subtypes. Other objectives assessed interactions with AMD genotype and analyzed progression to large drusen.
This was a retrospective analysis of two controlled clinical trial cohorts: the Age-Related Eye Disease Study (AREDS; recruitment 1992 to 1998) and AREDS2 (recruitment 2006 to 2008). Participants included eyes with no late AMD at baseline in AREDS participants (n=4,255) and AREDS2 participants (n=3,611)—a total of 13,204 eyes (7,756 participants). The mean age was 71 ±6.6 years); 56.5 percent were female.
Color fundus photographs were collected at annual study visits and graded centrally for late AMD. A Modified Alternative Mediterranean Diet Index (aMedi) scores was calculated for each participant from food frequency questionnaires. Main outcome measures included progression to late AMD, geographic atrophy and neovascular AMD. Progression to large drusen was evaluated in a separate analysis. Here were some of the findings:
• Over a median follow-up of 10.2-years, of the 13,204 eyes, 34 percent progressed to late AMD.
• Hazard ratios for progression in aMedi tertile 3 vs. 1 were:
o 0.78 (CI, 0.71 to 0.85, p<0.0001) for late AMD;
o 0.71 (CI, 0.63 to 0.80, p<0.0001) for GA; and
o 0.84 (CI, 0.75 to 0.95, p=0.005) for neovascular AMD.
• For fish consumption, HRs for late AMD, in quartile 4 vs. 1, were:
o 0.69 (CI, 0.58 to 0.82, p<0.0001; AREDS) vs. 0.92 (CI, 0.78 to 1.07, p=0.28; AREDS2), respectively.
• In AREDS, both aMedi and its fish component interacted with CFH rs10922109 for late AMD (p=0.01 and p=0.0005, respectively); higher aMedi and fish intake were associated with decreased risk in participants with protective alleles.
• In separate analyses (n=5,029 eyes of 3,026 AREDS participants), the HR for progression to large drusen in aMedi tertile 3 vs. 1 was 0.79 (CI, 0.68 to 0.93, p=0.004).
Researchers found that closer adherence to a Mediterranean-type diet was associated with lower risk of progression to late AMD and that the signal was greater for GA than neovascular AMD. In addition, they wrote, fish intake contributed to this protective association, and CFH genotype strongly influenced these relationships. Furthermore, researchers added, closer adherence to a Mediterranean-type diet was associated with decreased progression to large drusen. The researchers concluded that these findings may help inform evidence-based dietary recommendations.
SOURCE: Keenan TD, Agrón E, Mares J, et al. Adherence to the Mediterranean diet and progression to late age-related macular degeneration in the Age-Related Eye Disease Studies 1 and 2. Ophthalmology 2020; April 26. [Epub ahead of print].
Implications of Morphologic Patterns of Type 1 Macular Neovascularization on Macular Atrophy Growth with Anti-VEGF Treatment
Scientists evaluated the correspondence between macular atrophy progression and type 1 macular neovascularization morphology during long-term anti-vascular endothelial growth factor treatment for exudative neovascular age-related macular degeneration.
The retrospective review involved consecutive individuals with complete retinal pigment epithelium and outer retina atrophy overlying or in the proximity of macular neovascularization. The assessment of MA was based on spectral-domain optical coherence tomography, en-face near infrared imaging and fundus autofluorescence. Scientists evaluated macular neovascularization blood flow morphology by swept-source OCT angiography. They categorized qualitative features per Early Treatment Diabetic Retinopathy Study sector as immature, mature or hypermature patterns, and they designed an automatic analysis in MATLAB coding language to compute MA per ETDRS. Scientists compared measurements between baseline and the last follow-up visit. Twenty eyes from 20 individuals were included; the mean age was 85.4 ±8.3 years. Here were some of the findings:
• The median follow-up was 1.85 (one to 2.4) years and the median anti-VEGF injection rate during follow-up was four (two to five) injections/year.
• During follow-up, sectors with persistent immature blood flow patterns had lower MA growth rates than sectors with mature macular neovascularization flow patterns (p=0.001).
Scientists wrote that the presence of an immature blood flow pattern on OCTA was associated with a lower progression rate of MA.
SOURCE: Cabral D, Coscas F, Pereira T, et al. Implications of the morphologic patterns of type 1 macular neovascularization on macular atrophy growth on patients under anti-vascular endothelial growth factor treatment. Retina 2020; April 29. [Epub ahead of print].
Intravitreal Aflibercept for Refractory Vascularized PED Due to AMD: Morphologic Characteristics of Non-Responders
Investigators aimed to investigate the outcomes of a fixed intravitreal aflibercept regimen in individuals with vascular pigment epithelium detachment (vPED) secondary to age-related macular degeneration with refractory subretinal fluid.
The prospective, interventional case series involved 20 eyes of 20 individuals with refractory subretinal fluid and vPED treated with at least three injections of intravitreal anti-VEGF prior to study inclusion. Participants were treated with three injections of intravitreal aflibercept 2 mg/0.05 mL monthly, followed by injections every eight weeks. Best-corrected visual acuity and spectral-domain optical coherence tomography were evaluated at all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and quarterly.
Primary outcomes were effectiveness of a fixed treatment as measured in changes in BCVA, PED greatest linear diameter (GLD), and PED height from baseline to month 12. In an additional post hoc analysis, vPED patients were differentiated into two groups: (1) vPED lesions that showed persistence of subretinal fluid throughout one year of treatment, and (2) vPED lesions that showed complete resolution of subretinal fluid at a minimum of one monthly-performed OCT volume scans. Reflectivity values were determined in the sub-retinal pigment epithelium compartment in OCT scans at baseline, and month six and 12.
A total of 18 individuals completed the study protocol. The mean age was 74.8 ±10.6 years, and six subjects were female. Here were some of the findings:
• The median BCVA of all individuals was 72 ±8 EDTRS letters at baseline and 72.5 ±9.5 EDTRS letters at 12-month follow-up (p=0.7420).
• The median PED height in all individuals as measured in the OCT images significantly decreased from 372 ±140 μm to 149 ±142 μm after 12 months of treatment (p=0.0020).
• Persistent subretinal fluid was present at every OCT control in six individuals (group one).
• Twelve subjects showed resolution of subretinal fluid at least at one OCT control (group two).
• Reflectivity values in the sub-RPE compartment in OCT scans were 41.48 ±4.48 (group one) and 42.62 ±12.34 (group two) at baseline (p=0.854), and 65.88 ±6.74 and 50.87 ±14.11 at month 12 (p=0.038).
Investigators concluded that intravitreal aflibercept in refractory vPED led to a significant reduction in PED height and disease activity, as well as preservation of BCVA over one year. Persistent subretinal fluid was present in PED lesions with high values of reflectivity under the RPE, suggesting both a diffusion barrier and an increasing fibrovascular maturization of the choroidal neovascularization.
Source: Clemens CR, Alten F, Termühlen J, et al. Prospective PED-study of intravitreal aflibercept for refractory vascularized pigment epithelium detachment due to age-related macular degeneration: Morphologic characteristics of non-responders in optical coherence tomography. Graefes Arch Clin Exp Ophthalmol 2020; April 18. [Epub ahead of print.]
Correlation of Quantitative Measurements with Diabetic Disease Severity Using Multiple En-face OCTA Image Averaging
Investigators evaluated the effect of averaging en-face optical coherence tomography angiography images on quantitative measurements of the retinal microvasculature and their correlation to diabetic retinopathy disease severity, as part of a cross-sectional cohort study.
Participants included 105 eyes (65 individuals): 28 eyes from 19 healthy, age-matched controls; 14 eyes from nine diabetics without DR; and 63 eyes from 37 diabetics with varying levels of DR.
Spectral-domain OCTA images with uniform illumination, good foveal centration, and no macular edema or significant motion artifact were acquired five times with the 3x3 mm scan pattern on the Cirrus 5000 HD-OCT with AngioPlex (Carl Zeiss Meditec) software. En-face images of the superficial retinal layer (SRL) and deep retinal layer (DRL) were registered and averaged. Included eyes had a signal strength ≥7. Vessel length density (VLD), perfusion density (PD) and foveal avascular zone (FAZ) parameters were measured on averaged vs. single OCTA images. Investigators used the Pearson correlation coefficient to compare the two groups, and univariate and multivariate linear regression to correlate quantitative metrics to DR severity and best-corrected visual acuity.
A total of 84 eyes (55 individuals) met the inclusion criteria. Here were some of the findings:
- Almost uniformly, lower VLD and PD parameters were significantly associated with worse DR severity and BCVA.
- Multivariable linear regression for DR severity resulted in an R2 value of 0.82 for single groups, and 0.77 for averaged groups.
- No variables remained significantly associated with DR severity in multivariate analysis with single images, but in averaged images, increased superior SRL PD significantly predicted worse DR severity (coefficient 52.7, p=0.026).
- Multivariate linear regression for BCVA had an R2 value of 0.42 for single groups and 0.47 for averaged groups.
- FAZ size wasn’t associated with DR severity when single OCTA images (p=0.98) were considered, but was highly associated when using averaged images (coefficient 6.18, p<0.001).
- FAZ size was predictive for logMAR BCVA with averaged images (0.21, p=0.004), but not with single images (p=0.31).
Investigators concluded that averaging of en-face OCTA images improved the visualization of capillaries, particularly increasing the clarity of the FAZ borders; as such, it improved the correlation of vessel density and FAZ-specific parameters to DR severity and BCVA.
SOURCE: Jung JJ, Yu DJG2, Zeng A, et al. Correlation of quantitative measurements with diabetic disease severity utilizing multiple en-face OCTA image averaging. Ophthalmol Retina 2020; May 7. [Epub ahead of print].
Human Amniotic Membrane Plug to Restore AMD Photoreceptor Damage
Despite available treatments for wet age-related macular degeneration, one group of researchers note that if the retinal pigmented epithelium is damaged, medical treatments alone can’t restore acceptable visual acuity. Because of this, the investigators have begun looking for other means to restore vision in these cases.
As part of a prospective, consecutive, interventional study using human amniotic membrane (hAM) to induce photoreceptor regeneration and partial VA restoration, researchers looked at 11 individuals with AMD (six individuals with CNV and five with geographic atrophy) who underwent a vitrectomy with subretinal implant of hAM.
The primary outcome was VA improvement, while secondary outcomes were multimodal imaging results. Here were some of the findings:
• Mean preoperative best-corrected visual acuity was 20/2,000 (2 logMAR); all subjects had a BCVA of count fingers or less. Mean final BCVA was 20/400 (1.31 logMAR), ranging from 20/2,000 to 20/100 (2 to 0.7 logMAR).
• In optical coherence tomography angiography scans used to measure retinal vascularization in treated vs. fellow eyes, researchers found a high correlation between BCVA and deep vascular density.
• Using microperimetry, adaptive optics over the retinal area of highest functionality revealed possible photoreceptor presence over the hAM.
Researchers wrote that the study supported the feasibility and safety of hAM to promote partial retinal function restoration six months after surgery, with VA improvement. They added that the findings also helped demonstrate the interaction between hAM and photoreceptors, and suggested that photoreceptor regeneration may occur.
SOURCE: Rizzo S, Caporossi T, Tartaro R, et al. Human amniotic membrane plug to restore age related macular degeneration photoreceptors’ damage. Ophthalmology Retina 2020; April 25. [Epub ahead of print].
Genetic Basis of IRD in a Molecularly-characterized Cohort
In a cohort of >3,000 molecularly characterized inherited retinal disease families, researchers analyzed proportions with disease attributable to causative variants in each gene, as part of a retrospective study of electronic patient records.
Participants included patients and relatives managed in the Genetics Service of Moorfields Eye Hospital in whom a molecular diagnosis had been identified. Genetic screening included single-gene and gene-panel testing, whole-exome sequencing and whole-genome sequencing. Genes listed in the Retinal Information Network online resource were included, and transcript length was extracted for each gene.
Main outcome measures included proportions of families with IRD attributable to variants in each gene in the whole cohort, a cohort <18 years, and a “current” cohort (at least one patient encounter between Jan. 1, 2017 and Aug. 2, 2019). Additionally, researchers explored correlations between numbers of families and gene transcript length.
Researchers identified 3,195 families with a molecular diagnosis (variants in 135 genes), including 4,236 affected individuals. The pediatric cohort included 452 individuals from 411 families (66 genes). The current cohort included 2,614 families (131 genes; 3,130 affected individuals). Here were some of the findings:
• The pediatric cohort showed some differences, including a higher proportion of families with X-linked disease.
• The 20 most frequently implicated genes overall—which accounted for 71.8 percent of all molecularly diagnosed families—included:
o ABCA4 (20.8 percent of families);
o USH2A (9.1 percent);
o RPGR (5.1 percent);
o PRPH2 (4.6 percent);
o BEST1 (3.9 percent);
o RS1 (3.5 percent);
o RP1 (3.3 percent);
o RHO (3.3 percent);
o CHM (2.7 percent); and
o CRB1 (2.1 percent).
• Spearman coefficients for correlation between numbers of families and transcript length were 0.20 (p=0.025) overall; and for genes in which variants exclusively caused recessive: 0.27 (p=0.017); dominant: -0.17 (p=0.46); or X-linked disease: 0.71 (p=0.047).
Researchers wrote that more than 70 percent of families had pathogenic variants in one of 20 genes and that transcript length (relevant to gene delivery strategies) correlated significantly with numbers of affected families (though not for dominant disease). They added that the findings could help quantify the burden of inherited retinal disease attributable to each gene.
SOURCE: Pontikos N, Arno G, Jurkute N, et al. Genetic basis of inherited retinal disease in a molecularly characterised cohort of over 3,000 families from the United Kingdom. Ophthalmology 2020; March 16. [Epub ahead of print].
ASRS Annual Meeting to Go Virtual
The American Society of Retina Specialists canceled its 2020 annual meeting, scheduled for July 24-28 in Seattle. The society plans to use a virtual format to deliver the latest research to the global retina community, with the live streaming portion of the event beginning the evening of July 24. According to a statement released by ASRS president Timothy Murray, MD, MBA and program chair Philip Ferrone, MD, the group’s board of directors concluded that the meeting shouldn’t occur in person due to public health safety concerns related to COVID-19. Learn More.
SOURCE: ASRS, May 2020
ARVO: GENENTECH/ROCHE RESEARCH TO BE PRESENTED VIRTUALLY
Since the May meeting of the Association for Research in Vision and Ophthalmology was canceled due to the pandemic, Genentech and Roche research is presenting its research virtually on the ARVO website. Among the first abstracts to be presented are Phase II results for faricimab for the treatment of wet AMD and Phase III results of satralizumab for the treatment of neuromyelitis optica spectrum disorder (NMOSD).The FDA accepted Genentech’s Biologics License Application for satralizumab for NMOSD in October 2019, and a decision is expected later this year. View the first set of video presentations.
SOURCE: Genentech/Roche, May 2020
ADVERUM DOSES FIRST PATIENT IN COHORT 4 OF OPTIC PHASE I ADVM-022 TRIAL
Adverum Biotechnologies announced the first patient was dosed in cohort 4 of the ongoing OPTIC Phase I clinical trial for ADVM-022 for the treatment of wet age-related macular degeneration. Patients in cohort 4 (n=9) are receiving a single intravitreal injection of gene therapy candidate ADVM-022 at a dose of 6 x 1011 vg/eye (same as cohort 1) in addition to a steroid eye drop prophylaxis for six weeks (same as cohort 3). Read more.
Source: Adverum Biotechnologies, April 2020
REGENXBIO ANNOUNCES ADDITIONAL FINDINGS FOR RGX-314 I/IIA TRIAL
RegenxBio provided additional long-term data from the ongoing Phase I/IIa trial of RGX-314 for the treatment of wet age-related macular degeneration. As of April 6, 2020, the company says that RGX-314 continued to be well-tolerated across all cohorts. Sixteen SAEs that weren’t related to RGX-314, including two ocular procedure-related SAEs, were reported in 10 individuals. Read more.
SOURCE: RegenxBio, April 2020
B+L LICENSES EXCLUSIVE RIGHTS FROM STADA & XBRANE FOR BIOSIMILAR CANDIDATE FOR LUCENTIS (RANIBIZUMAB) IN US, CANADA
Bausch + Lomb entered into an exclusive licensing agreement with Stada Arzneimittel AG and its development partner, Xbrane Biopharma AB, a Nordic biosimilar developer, to develop and commercialize a biosimilar candidate to Lucentis (ranibizumab, Genentech/Roche) in the United States and Canada. The companies aim to obtain all currently approved indications for Lucentis. Read more.
SOURCE: Bausch + Lomb, May 2020
ICARE USA LAUNCHES FUNDUS IMAGER
Icare USA recently released the Centervue DRSplus confocal fundus imaging system. The system uses white LED illumination, including the entire visible spectrum, to produce TrueColor and detail-rich images, the company says. Physicians can view detailed 45-degree retinal images as well as panoramic 80-degree images using the Mosaic function. Learn more.
SOURCE: Icare USA, May 2020
Ophthalmic Practice Reopening Checklist
The American Academy of Ophthalmology, the American Society of Cataract and Refractive Surgery, and the Outpatient Ophthalmic Surgery Society developed a checklist
that details how to approach and manage key decisions involved in reopening a more normal practice in the COVID-19 era. The groups advise that, with respect to COVID-19 testing, facilities should adhere to state and local guidance. For cases at low risk for aerosolizing bodily fluids that will be performed under monitored anesthesia/conscious sedation, such as cataract surgery, routine preoperative RT-PCR testing shouldn’t be mandatory. However, they added, cases should be determined on an individual basis, especially for individuals with risk factors. Learn more.
SOURCE: American Academy of Ophthalmology, April 2020
Clearside Revises NDA Resubmission Timeline & Xipere Partnership with Bausch Health
Due to “external factors resulting in delays,” Clearside Biomedical announced it is revising the Xipere (triamcinolone acetonide suprachoroidal injectable suspension) New Drug Application resubmission timeline. As previously disclosed, the contract manufacturing organization for Xipere has been completing requalification activities within its facility that aren’t specifically related to Xipere, although they impact on the timing of its production. Clearside now expects to resubmit the Xipere NDA in the fourth quarter of 2020. In conjunction with this update, Clearside and Bausch Health have amended their partnership for Xipere. In October 2019, Bausch + Lomb acquired an exclusive license for the commercialization and development of Xipere in the United States and Canada. Read more.
SOURCE: Clearside Biomedical, April 2020
Scientists Identify Potential Treatment Candidate for Early Type 2 DR
A new study in The American Journal of Pathology
reported on the efficacy of a possible treatment candidate showing anti-inflammatory and neuroprotective effects on the retina and optic nerve head in early type 2 diabetic retinopathy using a diabetic mouse model. Investigators analyzed and compared the anti-inflammatory and neuroprotective effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide in the retina and optic nerve head with those of insulin in a mouse model of type 2 diabetes. After eight weeks of treatment, neuroinflammation caused by type 2 diabetes was significantly reduced in GLP-1RA-treated retinas and optic nerve heads compared with untreated or insulin-treated retinas of early type 2 diabetic mice. Read more.
SOURCE: The American Journal of Pathology, April 2020
Virscio Data Validates Primate Model for Testing Chronic Retinal NV & Vascular Leakage Drug Candidates
Virscio published data validating a nonhuman primate model for testing drug candidates targeting retinal ischemic and neovascular diseases. The findings, published in Experimental Eye Research
, describe the successful DL-aminoadipic acid (DLAAA)-mediated injury to Müller glial cells to induce retinal vascular pathology. In precisely titrated interventions, DLAAA triggered a phenotype of intraretinal macular vascular occlusion and neovascularization in green monkeys, with clinical exam and histology correlates to exudative age-related macular degeneration, diabetic retinopathy, macular telangiectasia, and other retinal ischemic and neovascular diseases. Read more.
SOURCE: The American Journal of Pathology, April 2020
Optina Diagnostics Receives FDA 510(K) Clearance for MHRC-C1
Optina Diagnostics received FDA 510(k) clearance for its ophthalmic camera, the Mydriatic Hyperspectral Retinal Camera (MHRC-C1), which captures images of the retina at multiple wavelengths under mydriatic conditions. The company says the approval of the MHRC-C1, which can provide a series of monochromatic images obtained in less than a second, is the first step toward its development of a Retinal Deep Phenotyping platform, combining data-rich hyperspectral retinal imaging and artificial intelligence to better characterize brain health. The first application under development is for detection of positron-emission tomography amyloid status to aid in the assessment of adult patients with cognitive impairment due to Alzheimer's disease or other conditions. Read more.
SOURCE: Optina Diagnostics, May 2020
PROF. JOHN N. NOLAN RECEIVES HEIDELBERG XTREME RESEARCH AWARD 2020
Prof. John M. Nolan at the Nutrition Research Centre Ireland, School of Health Science, Waterford Institute of Technology is the recipient of Heidelberg Engineering’s Xtreme Research Award 2020 for his research on the role of macular pigment (lutein, zeaxanthin and meso-zeaxanthin) in visual and cognitive function. With the award, Heidelberg Engineering recognizes Prof. Nolan’s efforts with an investigational Spectralis Macular Pigment Optical Volume Module. Read more.
SOURCE: Heidelberg Engineering, May 2020
AAO EXPANDS PARTNERSHIP WITH VERANA HEALTH
The American Academy of Ophthalmology announced that Verana Health, the data curation and analytics partner of the American Academy of Ophthalmology IRIS (Intelligent Research In Sight) Registry, will serve as the end-to-end data and technology partner for the IRIS Registry moving forward. The partners say this represents a significant expansion of their relationship, with Verana Health assuming responsibility for EHR integration, practice support and MIPS (Merit-Based Incentive Payment System) quality reporting for physicians contributing to the IRIS Registry. Read more.
SOURCE: The American Academy of Ophthalmology, April 2020
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