Volume 16, Number 46
Monday, November 14, 2016


In this issue: (click heading to view article)
######### RNFL Loss Patterns in OAG Subtypes Using SD-OCT
######### Detectability of VF Defects in Glaucoma With High-resolution Perimetry
######### Incidence & Causes of Vision Loss During Aflibercept Treatment for nAMD
######### OCT-reflective Drusen Substructures Prediction of Progression to AMD


RNFL Loss Patterns in OAG Subtypes Using SD-OCT

Researchers sought to determine whether different patterns of retinal nerve fiber layer thinning exist as measured by spectral-domain optical coherence tomography for four subtypes of open-angle glaucoma—primary, normal tension, pseudoexfoliation and pigmentary—and compared them with normal controls.

They measured SD-OCT RNFL thickness values for four quadrants and for four sectors (i.e., superior-nasal, superior-temporal, inferior-nasal and inferior-temporal). They used analysis of variance to determine differences in RNFL thickness values between groups, and paired t tests for quadrant comparisons.

Researchers included 285 participants. All four subtypes of OAG showed significant RNFL thinning in the superior, inferior and nasal quadrants, as well as the superior-temporal and inferior-temporal sectors (all p<0.0001) compared with normal cases. Individuals with POAG (p=0.002) and NTG (p=0.018) had greater RNFL thinning inferiorly and inferior-temporally than superiorly than PXG (p=0.006) cases. In contrast, PDG cases had greater RNFL thinning superiorly and superior-nasally than inferiorly compared with other OAG subtypes (i.e., POAG: p=0.009; NTG: p=0.003; PXG: p=0.009). Of the four OAG subtypes, PXG cases exhibited the greatest degree of inter-eye RNFL asymmetry.

Researchers wrote that the study suggests that SD-OCT may be able to detect significant differences in patterns of RNFL thinning for different subtypes of OAG.

SOURCE: Baniasadi N, Paschalis EI, Haghzadeh M, et al. Patterns of retinal nerve fiber layer loss in different subtypes of open angle glaucoma using spectral domain optical coherence tomography. J Glaucoma; 2016;25:10:865-72.

Detectability of VF Defects in Glaucoma With High-resolution Perimetry

Investigators extrapolated the optimal test point resolution for assessment of glaucomatous visual field defects, including subtle functional defects, and performed high-resolution perimetry with 0.5 degrees test point resolution.

Subjects included 11 eyes of 11 normal volunteers, and 16 eyes of 16 glaucomatous individuals. They used the Octopus 900 custom test to measure 61 points, with a test point resolution of 0.5 degrees on the temporal meridian of 45 degrees within the eccentricity of 30 degrees. In glaucoma cases, they extracted VF profiles in 17 patterns of the test point resolutions that ranged from 0.5 to 8.5 degrees, and calculated mean defect (MD), square root of loss variance (sLV) and maximum sensitivity loss. They examined influence of the test point resolution on MD, sLV and max loss. In addition, they divided the test range from the fixation point to the eccentricity of 30 degrees into three zones. Similarly, they investigated zones if test point resolution exerted influence on the MD, sLV and max loss.

Glaucoma cases did not show significant differences in MD and sLV, regardless of the resolution. Max loss showed significant difference at resolution ≥1 degree. MD and sLV did not show significant differences in resolution change in each zone. Max loss showed significant differences at resolution ≥1.5 degrees within the central 10 degrees.

Investigators determined that high-resolution perimetry with a test point resolution of <1.5 degrees was necessary to detect subtle VF defects within the eccentricity of 10 degrees.

SOURCE: Numata T, Matsumoto C, Okuyama S, et al. Detectability of visual field defects in glaucoma with high-resolution perimetry. J Glaucoma 2016:25(10): 847-53.

Incidence & Causes of Vision Loss During Aflibercept Treatment for nAMD

Scientists assessed incidence rates, risk factors and final outcomes of individuals with age-related macular degeneration experiencing vision loss despite periodic aflibercept treatment.

The researchers prospectively recruited subjects with treatment-naive AMD and treated the individuals with three monthly injections followed by two monthly injections of aflibercept. They investigated incidence rate and risk factors of more than two lines of vision loss at any visit.

Scientists included 196 eyes of 196 people, and observed vision loss in 16 subjects (8.2 percent). Eleven of 16 people developed vision loss during the first three months (68.8 percent), with vision loss remaining in 11 eyes (68.8 percent) at the final visit. Scientists identified maximum pigment epithelium detachment height (odds ratio=1.46 for a 100 ┬Ám increase in PED height) and disruption of the external limiting membrane (odds ratio=4.45) as risk factors for developing vision loss on logistic regression analysis.

Scientists found the incidence rate of vision loss during aflibercept treatment to be relatively low. They wrote that identifying high-risk patients—those with a high PED height and disruption of the external limiting membrane—would help ensure appropriate informed consent before treatment, and that further studies are needed to establish optimal treatment for this population.

SOURCE: Hata M, Oishi A, Yamashiro K, et al. Incidence and causes of vision loss during aflibercept treatment for neovascular age-related macular degeneration: One-year follow-up. Retina 2016; Oct 26. [Epub ahead of print].

OCT-reflective Drusen Substructure Prediction of Progression to AMD

Researchers sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography-reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration-related features and progression, as part of a retrospective analysis of a prospective study.

Participants included individuals with intermediate AMD (n=349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography study.

Researchers analyzed baseline SD-OCT scans for the presence of ODS (one eye per individual). They evaluated cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD-OCT and color photographs, including drusen volume, geographic atrophy and pre-atrophic features, for the entire macular region. They made similar local associations within a 0.5-mm-diameter region around individual ODS and corresponding control regions without ODS in the same eye. Main outcome measures included pre-atrophy SD-OCT changes; and GA, central GA and choroidal neovascularization from color photographs.

Researchers defined four phenotypic subtypes of ODS: low-reflective cores; high-reflective cores; conical debris; and split drusen. Among the 307 eligible eyes, 74 (24 percent) had at least one ODS. The ODS at baseline were associated with: greater macular drusen volume at baseline (p<0.001); development of pre-atrophic changes at year two (p=0.001 to 0.01); and development of macular GA (p=0.005) and pre-atrophic changes at year three (p=0.002 to 0.008), but not development of CNV. The ODS at baseline in a local region were associated with presence of pre-atrophy changes at baseline (p=0.02 to 0.03) and development of pre-atrophy changes at years two and three within the region (p=0.008 to 0.05).

Researchers concluded that OCT-reflective drusen substructures are biomarkers of progression to GA, but not CNV, in eyes with intermediate AMD. They added that OCT-reflective drusen substructures may be clinically helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.

SOURCE: Veerappan M, Abdul-Karim M, El-Hage-Sleiman A-KM, et al. Optical coherence tomography reflective drusen substructures predict progression to geographic atrophy in age-related macular degeneration. Ophthalmology 2016; Oct 25. [Epub ahead of print].



  • Spark Collaborates With University of Massachusetts Medical School Gene Therapy Center
    Spark Therapeutics announced a multiyear research agreement with Guangping Gao, PhD, the Penelope Booth Rockwell Chair in Biomedical Research, director of the Horae Gene Therapy Center, and professor of microbiology and physiological systems at the University of Massachusetts Medical School. Dr. Gao will collaborate with Spark Therapeutics to identify adeno-associated virus vectors from a proprietary library of AAV capsids and evaluate their efficacy, with the goal of enhancing the efficiency of gene delivery to cells in the retina, liver and central nervous system. Read more.

  • Biophytis Chooses Patheon for AMD Drug Candidate
    Biophytis entered into an agreement with Patheon for industrial scale-up and manufacturing of clinical batches, as part of the first stage of a Phase IIb clinical trial for drug candidate Macuneos in age-related macular degeneration. Macuneos is designed to protect the retinal pigment epithelium, and Biophytis has shown in animal models a protection of retinal cells against phototoxic effects of A2E in the presence of blue light (oxidative stress), a reduction in accumulation of A2E and a slowdown of the degenerative process of the retina. Biophytis will use the lots for the Phase IIb study MACA to be launched in Europe and the United States once regulatory approvals are obtained.

  • AGTC Files IND for Treatment of Achromatopsia Due to CNGA3 Mutations
    Applied Genetic Technologies Corp. filed an Investigational New Drug application with the U.S. Food and Drug Administration to conduct a Phase I/II clinical trial of the company's gene therapy product candidate for the treatment of achromatopsia caused by mutations in the CNGA3 gene. The Company previously initiated a Phase I/II clinical trial of its gene therapy product for the treatment of achromatopsia caused by mutations in the CNGB3 gene, and plans to initiate a clinical study evaluating the safety and efficacy of the therapy product for CNGA3-related achromatopsia in the United States in upcoming months. Read more.

  • Imprimis Registers New Jersey Facility as Outsourcing Facility
    Imprimis Pharmaceuticals filed to register its recently constructed New Jersey facility with the U.S. Food and Drug Administration as a 503B outsourcing facility. The facility, which expects to begin manufacturing as an outsourcing facility in December 2016 and dispensing medications in early first quarter 2017, will initially make and distribute Imprimis’ proprietary sterile Dropless Therapy injectable and LessDrops topical formulations in accordance with current good manufacturing practices. It was built for production of core ophthalmology formulations, and outfitted with automated filling, labeling and other equipment to enable production efficiencies. Read more.

  • ECL Adds Integrity EMR to Practice Solutions Suite
    Eye Care Leaders announced the addition of Integrity electronic medical record to its suite of electronic health records and practice solutions for eye care. Integrity’s EMR, a cloud-based software solution for ophthalmology that complements ECL’s other eye-care solutions, was designed by a board-certified ophthalmologist seeking a better EMR solution for his busy practice. Top software developers, industry IT experts and clinicians from around the United States were part of the development team that continues to refine the software based on input from users. Read more.

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