Comparing multifocal pupillographic objective perimetry (mfPOP) and multifocal visual evoked potentials (mfVEP) in retinal diseases

Multifocal pupillographic objective perimetry (mfPOP) shows regions of slight hypersensitivity away from retinal regions damaged by diabetes or age-related macular degeneration (AMD). This study examines if such results also appear in multifocal visual evoked potentials (mfVEPs) recorded on the same day in the same patients. The pupil control system receives input from the extra-striate cortex, so we also examined evidence for such input. We recruited subjects with early type 2 diabetes (T2D) with no retinopathy, and patients with unilateral exudative AMD. Population average responses of the diabetes patients, and the normal fellow eyes of AMD patients, showed multiple regions of significant hypersensitivity (p < 0.05) on both mfPOP and mfVEPs. For mfVEPs the occipital electrodes showed fewer hypersensitive regions than the surrounding electrodes. More advanced AMD showed regions of suppression becoming centrally concentrated in the exudative AMD areas. Thus, mfVEP electrodes biased towards extra-striate cortical responses (surround electrodes) appeared to show similar hypersensitive visual field locations to mfPOP in early stage diabetic and AMD damage. Our findings suggest that hypersensitive regions may be a potential biomarker for future development of AMD or non-proliferative diabetic retinopathy, and may be more informative than visual acuity which remains largely undisturbed during early disease

Discriminating early-stage diabetic retinopathy with subjective and objective perimetry

Introduction: To prevent progression of early-stage diabetic retinopathy, we need functional tests that can distinguish multiple levels of neural damage before classical vasculopathy. To that end, we compared multifocal pupillographic objective perimetry (mfPOP), and two types of subjective automated perimetry (SAP), in persons with type 2 diabetes (PwT2D) with either no retinopathy (noDR) or mild to-moderate non-proliferative retinopathy (mmDR). Methods: Both eyes were assessed by two mfPOP test methods that present stimuli within either the central ±15° (OFA15) or ±30° (OFA30), each producing per-region sensitivities and response delays. The SAP tests were 24-2 Short Wavelength Automated Perimetry and 24-2 Matrix perimetry. Results: Five of eight mfPOP global indices were significantly different between noDR and mmDR eyes, but none of the equivalent measures differed for SAP. Per-region mfPOP identified significant hypersensitivity and longer delays in the peripheral visual field, verifying earlier findings. Diagnostic power for discrimination of noDR vs. mmDR, and normal controls vs. PwT2D, was much higher for mfPOP than SAP. The mfPOP per-region delays provided the best discrimination. The presence of localized rather than global changes in delay ruled out iris neuropathy as a major factor. Discussion: mfPOP response delays may provide new surrogate endpoints for studies of interventions for early-stage diabetic eye damage.</p

Rapid Objective Testing of Visual Function Matched to the ETDRS Grid and Its Diagnostic Power in Age-Related Macular Degeneration

Purpose: To study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade. Design: Evaluation of a diagnostic technology. Methods: We compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure–function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA). Main Outcome Measures: Percentage area under the receiver operator characteristic curve (AUC) and Hedge's g effect size. Results: Acuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge's g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well. Conclusions: The rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes.</p

Complete Genome Sequence of the Complex Carbohydrate-Degrading Marine Bacterium, Saccharophagus degradans Strain 2-40T

The marine bacterium Saccharophagus degradans strain 2-40 (Sde 2-40) is emerging as a vanguard of a recently discovered group of marine and estuarine bacteria that recycles complex polysaccharides. We report its complete genome sequence, analysis of which identifies an unusually large number of enzymes that degrade >10 complex polysaccharides. Not only is this an extraordinary range of catabolic capability, many of the enzymes exhibit unusual architecture including novel combinations of catalytic and substrate-binding modules. We hypothesize that many of these features are adaptations that facilitate depolymerization of complex polysaccharides in the marine environment. This is the first sequenced genome of a marine bacterium that can degrade plant cell walls, an important component of the carbon cycle that is not well-characterized in the marine environment

Euclid Near Infrared Spectrometer and Photometer instrument concept and first test results obtained for different breadboards models at the end of phase C

The Euclid mission objective is to understand why the expansion of the Universe is accelerating through by mapping the geometry of the dark Universe by investigating the distance-redshift relationship and tracing the evolution of cosmic structures. The Euclid project is part of ESA's Cosmic Vision program with its launch planned for 2020 (ref [1]). The NISP (Near Infrared Spectrometer and Photometer) is one of the two Euclid instruments and is operating in the near-IR spectral region (900- 2000nm) as a photometer and spectrometer. The instrument is composed of: - a cold (135K) optomechanical subsystem consisting of a Silicon carbide structure, an optical assembly (corrector and camera lens), a filter wheel mechanism, a grism wheel mechanism, a calibration unit and a thermal control system - a detection subsystem based on a mosaic of 16 HAWAII2RG cooled to 95K with their front-end readout electronic cooled to 140K, integrated on a mechanical focal plane structure made with molybdenum and aluminum. The detection subsystem is mounted on the optomechanical subsystem structure - a warm electronic subsystem (280K) composed of a data processing / detector control unit and of an instrument control unit that interfaces with the spacecraft via a 1553 bus for command and control and via Spacewire links for science data This presentation describes the architecture of the instrument at the end of the phase C (Detailed Design Review), the expected performance, the technological key challenges and preliminary test results obtained for different NISP subsystem breadboards and for the NISP Structural and Thermal model (STM)

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Luminance and colour variant pupil perimetry in glaucoma

This study investigated the diagnostic utility for glaucoma of multifocal pupillographic objective perimetry stimuli targeting different components of the pupillary response: cortically derived colour responses and subcortical luminance responses.This work was supported by the Australian Research Council through the ARC Centre of Excellence in Vision Science(CE0561903)

Learning complex texture discrimination

Higher-order spatial correlations contribute strongly to visual structure and salience, and are common in the natural environment. One method for studying this structure has been through the use of highly controlled texture patterns whose obvious structure is defined entirely by third- and higher-order correlations. Here we examine the effects that longer-termtraining has on discrimination of 17 such texture types. Training took place in 14 sessions over 42 days. Discrimination performance increased at different rates for different textures. The time required to complete a visit reduced by 25.4% (p = 0.0004). Factor analysis was applied to data from the learning and experienced phases of the experiment. This indicated that the gain in speed was accompanied by an increase in the number of mechanisms contributing to discrimination. Learning was not affected by sleep quality but was affected by extreme tiredness ( p<0.01). The improved discrimination and speedwere retained for 2.5 months.Overall, the effects were consistent with perceptual learning. The observed learning is likely related to the adaptation of innate mechanisms that underlie our ability to identify nonredundant, visually salient structure in natural images. It may involve cortical V2 and appears to involve increased strength, speed, and breadth of connections within our internal representation of this complex perceptual space.Australian Research Council (CE0561903, LP140100763)