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PURPOSE: To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD). DESIGN: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers. METHODS: After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy. MAIN OUTCOME MEASURES: Interreader agreement based on Gwet's first-order agreement coefficient (AC1) for qualitatively graded OCT features and classification of iRORA and cRORA, and smallest real difference (SRD) for quantitatively graded OCT features. RESULTS: Substantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (AC1 = 0.63-0.87), except for RPE attenuation (AC1 = 0.46) and disruption (AC1 = 0.26). The lowest SRD for the quantitatively graded horizontal features was observed for the zone of choroidal hypertransmission (± 190.8 μm). Moderate agreement was found for a 3-category classification of no atrophy, iRORA, and cRORA (AC1 = 0.53). Exploratory analyses suggested a significantly higher level of agreement for a 3-category classification using (1) no atrophy; (2) presence of inner nuclear layer and outer plexiform layer subsidence, or a hyporeflective wedge-shaped band, as a less severe atrophic grade; and (3) the latter plus an additional requirement of choroidal hypertransmission of 250 μm or more for a more severe atrophic grade (AC1 = 0.68; P = 0.013). CONCLUSIONS: Assessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.

BACKGROUND: Subthreshold nanosecond laser (SNL) treatment has been studied as a potential intervention in intermediate age-related macular degeneration (iAMD). This study investigated the effect of 100 SNL treatment spots on retinal structure and function. METHODS: A prospective single-arm interventional pilot study. SNL treatment was delivered as 100 spots around the retinal vascular arcades of the study eye (worst visual acuity) in a single session in subjects with iAMD. Multimodal retinal imaging and dark-adapted chromatic perimetry were performed at baseline and at 0.5, 3, 6 and 12 months post treatment. Post treatment changes in best corrected visual acuity (BCVA), retinal thickness, relative ellipsoid zone reflectivity (rEZR) and rod-mediated functional parameters were compared to baseline. RESULTS: Twenty-one subjects with iAMD were recruited. SNL treatment was associated with an increase in retinal thickness (p = 0.008) and decrease in rEZR (p

To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801).European, multicenter cohort study.301 eyes of 301 subjects with early (n=34), intermediate (n=168) and late AMD (n=43), as well as eyes without any AMD features (n=56).In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers including pigmentary abnormalities (PA), pigment-epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium and outer retinal atrophy (i/cRORA)) and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the retinal pigment-epithelium drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain optical coherence tomography (SD-OCT) imaging using a deep-learning based algorithm.Prevalence and topographic distribution of structural iAMD features.A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% female) were included. Besides large drusen, the most prevalent structural feature in intermediate AMD (iAMD) study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). PED lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0% and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, highest RPEDC volume with a median of 98.92 x 10Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identifying reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages.

Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT). Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained. Features preceding progression/conversion to advanced AMD (drusen, reticular pseudodrusen [RPD], MNV, incomplete/complete retinal pigment epithelium and outer retinal atrophy [iRORA/cRORA]) were assessed. Results: Of 30 fellow eyes with available follow-up images, 12 converted to GA (FAF), 2 converted to MNV, and 16 were nonconverters during the review period (median: 17.8 months). iRORA/cRORA features (present in all converters at baseline) were identified on OCT in eyes that progressed to GA. Median time interval from iRORA to cRORA and from cRORA to GA was 7 months each. GA development/progression was either drusen- or RPD-associated (n = 6 each). Eyes with baseline RPD showed faster GA progression versus eyes with drusen (1.49 vs. 0.38 mm2/year). Conclusions: RPD presence was associated with rapid GA lesion enlargement and may provide an early indication of faster GA progression.

BackgroundTo characterise early stages of geographic atrophy (GA) development in age-related macular degeneration (AMD) and to determine the prognostic value of structural precursor lesions in eyes with intermediate (i) AMD on the subsequent GA progression.MethodsStructural precursor lesions for atrophic areas (lesion size at least 0.5 mm² in fundus autofluorescence images) were retrospectively identified based on multimodal imaging and evaluated for association with the subsequent GA enlargement rates (square-root transformed, sqrt). A linear mixed-effects model was used to account for the hierarchical nature of the data with a Tukey post hoc test to assess the impact of the local precursor on the subsequent GA progression rate.ResultsA total of 39 eyes with GA of 34 patients with a mean age of 74.4±6.7 (±SD) years were included in this study. Five precursor lesions (phenotypes 1–5) preceding GA development were identified: large, sub-retinal pigment epithelial drusen (n=19), reticular pseudodrusen (RPD, n=10), refractile deposits (n=4), pigment epithelial detachment (n=4) and vitelliform lesions (n=2). Precursor lesions exhibited a significant association with the subsequent (sqrt) GA progression rates (p=0.0018) with RPD (phenotype 2) being associated with the fastest GA enlargement (2.29±0.52 (±SE) mm/year.ConclusionsThe results indicate the prognostic relevance of iAMD phenotyping for subsequent GA progression highlighting the role of structural AMD features across different AMD stages.

Purpose: To investigate the association between the presence of type 1 choroidal neovascularization (CNV) and the localized progression of atrophy in age-related macular degeneration (AMD). Design: Analysis of patients’ data collected in the context of 2 noninterventional, prospective studies conducted at the Department of Ophthalmology, University of Bonn, Germany. Participants: A total of 98 eyes diagnosed with AMD of 59 patients (40 female, 19 male) with a mean (±standard deviation) age at baseline of 76.60±6.65 years and median (interquartile range) review period of 1.17 years (1.01–1.55) were included. Eyes were subdivided into 3 categories based on multimodal imaging and ocular history: retinal pigment epithelium (RPE) atrophy with treatment-naïve quiescent CNV (n=7), RPE atrophy with a history of exudative CNV (n=10), and RPE atrophy without evidence of coexisting CNV (n=81). Methods: Retinal pigment epithelium atrophy was delineated on the basis of serial fundus-autofluorescence and infrared-reflectance images. If CNV was detected by OCT angiography (OCTA), its location and dimension were spatially mapped to RPE atrophy. The localized progression of RPE atrophy in topographic relation to the CNV lesion was then analyzed using mixed-effects logistic regression. The spatial overlap (Dice coefficient) between predicted and observed RPE atrophy progression was evaluated to estimate the model accuracy. Main Outcome Measures: Odds ratio (OR) for localized RPE atrophy progression in areas overlying type 1 CNV. Results: The prediction model achieved a high overlap between predicted and observed RPE atrophy progression with a cross-validated Dice coefficient of 0.87 (95% confidence interval [CI], 0.85–0.89) reflecting a high accuracy. The odds for future RPE atrophy involvement were reduced by a factor of 0.21 (95% CI, 0.19–0.24) in the presence of treatment-naïve quiescent type 1 CNV and by a factor of 0.46 (95% CI, 0.41–0.51) in the presence of exudative type 1 CNV. Conclusions: The results indicate that there is markedly reduced RPE atrophy progression in areas co-localizing with quiescent and exudative type 1 CNV. This observation is compatible with a potential protective effect of type 1 CNV on the RPE and overlying neurosensory retina. These results may have relevant clinical implications for the management of CNV and lead to new therapeutic strategies to prevent atrophy progression.

Relative ellipsoid zone reflectivity (rEZR) has been reported to be reduced in intermediate age-related macular degeneration (iAMD). However, longitudinal changes in rEZR remain unknown. This study investigated the natural history of rEZR in iAMD and its association with risk factors for disease progression, including the presence or extent of drusen volume, reticular pseudodrusen (RPD), and pigmentary abnormalities (PAs).Longitudinal observational study.Subjects with bilateral large drusen.Spectral-domain (SD) OCT images of both eyes from each participant were obtained every 6 months for 3 years. Using an automated rEZR determination approach, the average rEZR of the central 20° macula was determined for each SD-OCT volume scan. Linear mixed models were used to determine the rate of change in rEZR with age (using the cross-sectional data at baseline) and over time (longitudinal data) and the interactions between the rate of rEZR changes with AMD risk factors at baseline.Relative ellipsoid zone reflectivity and its rate of change with age and over time.A total of 280 eyes from 140 individuals with bilateral large drusen were included in this study. Cross-sectional data showed that rEZR reduced with increasing age (-8.4 arbitrary units [AUs] per decade; 95% confidence interval [CI], -11.5 to -5.2; P0.001). Longitudinal data showed that, on average, rEZR declined at a rate of -2.1 AU per year (95% CI, -2.6 to -1.6 AU per year; P0.001). Larger RPD area (P = 0.042) at baseline was associated with a faster rate of rEZR decline over time, whereas the presence of PAs and the drusen volume at baseline showed no significant association with rEZR decline over time (P = 0.068 and P = 0.529, respectively).The rEZR significantly reduces over 3 years in subjects with iAMD, and both the presence and increasing extent of coexistent RPD at baseline are associated with a faster rate of decline. These findings warrant further studies to understand the value of rEZR as a biomarker of AMD progression.

Short-period double white dwarf (DWD) binaries will be the most prolific source of gravitational waves (GWs) for the Laser Interferometer Space Antenna (LISA). DWDs with GW frequencies below $\sim1$ mHz will be the dominant contributor to a stochastic foreground caused by overlapping GW signals. Population modeling of Galactic DWDs typically assumes a binary fraction of 50% and a log-uniform Zero Age Main Sequence (ZAMS) orbital period distribution. However, recent observations have shown that the binary fraction of close, solar-type stars exhibits a strong anti-correlation with metallicity which modulates the ZAMS orbital period distribution below $10^4$ days. In this study we perform the first simulation of the Galactic DWD population observable by LISA which incorporates an empirically-derived metallicity-dependent binary fraction, using the binary population synthesis suite COSMIC and a metallicity-dependent star formation history. We compare two models: one which assumes a metallicity-dependent binary fraction, and one with a binary fraction of 50%. We repeat our analysis for three different assumptions for Roche-lobe overflow interactions. We find that while metallicity impacts the evolution and intrinsic properties of our simulated DWD progenitor binaries, the LISA-resolvable populations of the two models remain roughly indistinguishable. However, the size of the total Galactic DWD population orbiting in the LISA frequency band is reduced by more than half when accounting for a metallicity-dependent binary fraction for two of our four variations, which also lowers the effective foreground. The LISA population remains unchanged in number for two variations, highlighting the sensitivity of the population to binary evolution prescriptions., 24 pages, 11 figures. Accepted version for publication in ApJ

The development of large constellations of satellites (i.e., so-called megaconstellations or satcons) is poised to increase the number of LEO satellites by more than an order of magnitude in the coming decades. Such a rapid growth of satellite numbers makes the consequences of major fragmentation events ever more problematic. In this study, we investigate the collisional risk to on-orbit infrastructure from kinetic anti-satellite (ASAT) weapon tests, using the 2019 Indian test as a model. We find that the probability of one or more collisions occurring over the lifetime of ASAT fragments increases significantly in a satcon environment compared with the orbital environment in 2019. For the case of 65,000 satellites in LEO, we find that the chance of one or more satellites being struck by ASAT fragments of size 1 cm or larger is more than 25% for a single test. Including sizes down to 3 mm in our models suggests that impacts will occur for any such event. Finally, we apply our methods to examine the November 2021 Russian ASAT test, also finding a significant collision probability over the lifetime of the fragments. The heavy commercialization of LEO demands a commitment to avoiding debris-generating ASAT tests., 27 pages, 7 figures, 6 tables. Accepted for publication in the Journal of Astronautical Sciences

ZusammenfassungKlinisch wird die altersabhängige Makuladegeneration (AMD) in Früh- und Spätstadien eingeteilt. Der Begriff „trockene“ AMD wird häufig verwendet, wenn keine „exsudativen“ Veränderungen am Augenhintergrund vorliegen. Es existiert eine Vielzahl von Studien zur Epidemiologie der AMD. Dabei wird in den meisten Studien zwischen AMD-Früh- und -Spätformen unterschieden, allerdings ohne eine weitere Differenzierung der „trockenen“ AMD-Spätform. Zudem stellt sich die Herausforderung unterschiedlicher Klassifikationen der AMD in verschiedenen Studien, was zwangsläufig zu Abweichungen in den epidemiologischen Daten bei der AMD führt. Neue Klassifikationssysteme berücksichtigen mikrostrukturelle Veränderungen, die mittels hochauflösender In-vivo-Bildgebung der Netzhaut detektiert werden können. Eine neue Konsensusklassifikation der AMD-assoziierten Atrophie soll ermöglichen, zukünftige Studien nach einheitlichen Definitionen durchzuführen.

Spatially-resolved mapping of rod- and cone-function may facilitate monitoring of macular diseases and serve as a functional outcome parameter. However, mesopic and dark-adapted two-color fundus-controlled perimetry (FCP, also called “microperimetry”) constitute laborious examinations. We have devised a machine-learning-based approach to predict mesopic and dark-adapted (DA) retinal sensitivity in eyes with neovascular age-related macular degeneration (nAMD). Extensive psychophysical testing and volumetric multimodal retinal imaging data were acquired including mesopic, DA red and DA cyan FCP, spectral-domain optical coherence tomography and confocal scanning laser ophthalmoscopy infrared reflectance and fundus autofluorescence imaging. With patient-wise leave-one-out cross-validation, we have been able to achieve prediction accuracies of (mean absolute error, MAE [95% CI]) 3.94 dB [3.38, 4.5] for mesopic, 4.93 dB [4.59, 5.27] for DA cyan and 4.02 dB [3.63, 4.42] for DA red testing. Partial addition of patient-specific sensitivity data decreased the cross-validated MAE to 2.8 dB [2.51, 3.09], 3.71 dB [3.46, 3.96], and 2.85 dB [2.62, 3.08]. The most important predictive feature was outer nuclear layer thickness. This artificial intelligence-based analysis strategy, termed “inferred sensitivity”, herein, enables to estimate differential effects of retinal structural abnormalities on cone- and rod-function in nAMD, and may be used as quasi-functional surrogate endpoint in future clinical trials.

PurposeTo evaluate the role of right-angled vessels (RAVs) during disease progression in macular telangiectasia type 2 (MacTel).MethodsIn this study, 100 eyes of 52 patients and 52 eyes of 26 age-related controls were examined using fundus photography, spectral-domain optical coherence tomography (SD-OCT), OCT angiography (OCT-A) and fundus fluorescein angiography (FFA). Two masked readers graded fundus photographs of patients’ eyes into five disease stages according to Gass and Blodi, and evaluated all eyes for the presence of RAVs. If RAVs were present, their course and origin (arterial vs venous) was evaluated with OCT-A and FFA, respectively. Additionally, we looked for morphological correlates of these vessels on SD-OCT scans. Neovascular eyes were analysed for the presence of RAVs and for morphological changes on formation of neovascularisations (NVs).ResultsIn OCT-A, RAVs were already detectable in eyes with early stages (1 to 2), could be tracked from superficial to outer retinal layers and were shown to form anastomoses in the outer retina with disease progression. These vessels were of both arterial and venous origin as shown by early phase FFA. Dilated capillaries and RAVs in OCT-A corresponded to hyper-reflective alterations of the outer retina on SD-OCT scans. In 19/19 eyes, NVs were associated with the presence of RAVs, and RAVs were shown to directly connect to neovascular complexes and to undergo morphological changes upon NV formation.ConclusionsThe results emphasise the role of RAVs during disease progression from an early stage on and demonstrate their involvement in the development of secondary NVs in MacTel.

We have carried out a search for massive white dwarfs (WDs) in the direction of young open star clusters using the Gaia DR2 database. The aim of this survey was to provide robust data for new and previously known high-mass WDs regarding cluster membership, to highlight WDs previously included in the Initial Final Mass Relation (IFMR) that are unlikely members of their respective clusters according to Gaia astrometry and to select an unequivocal WD sample that could then be compared with the host clusters' turnoff masses. All promising WD candidates in each cluster CMD were followed up with spectroscopy from Gemini in order to determine whether they were indeed WDs and derive their masses, temperatures and ages. In order to be considered cluster members, white dwarfs were required to have proper motions and parallaxes within 2, 3, or 4-$\sigma$ of that of their potential parent cluster based on how contaminated the field was in their region of the sky, have a cooling age that was less than the cluster age and a mass that was broadly consistent with the IFMR. A number of WDs included in current versions of the IFMR turned out to be non-members and a number of apparent members, based on Gaia's astrometric data alone, were rejected as their mass and/or cooling times were incompatible with cluster membership. In this way, we developed a highly selected IFMR sample for high mass WDs that, surprisingly, contained no precursor masses significantly in excess of ${\sim}$6 $M_{\odot}$., Comment: 39 pages, 17 figures, Accepted for Publication in the Astrophysical Journal

To determine the interreader agreement for incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA) and their related features in age-related macular degeneration (AMD).Interreader agreement study.Twelve readers from 6 reading centers.After formal training, readers qualitatively assessed 60 OCT B-scans from 60 eyes with AMD for 9 individual features associated with early atrophy and performed 7 different annotations to quantify the spatial extent of OCT features within regions of interest. The qualitative and quantitative features were used to derive the presence of iRORA and cRORA and also in an exploratory analysis to examine if agreement could be improved using different combinations of features to define OCT atrophy.Interreader agreement based on Gwet's first-order agreement coefficient (ACSubstantial or better interreader agreement was observed for all qualitatively graded OCT features associated with atrophy (ACAssessment of iRORA and cRORA, and most of their associated features, can be performed relatively consistently and robustly. A refined combination of features to define early atrophy could further improve interreader agreement.

BackgroundBrolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.MethodsPatients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (µm)), central subfield retinal thickness (CSRT (µm)) and macular volume (mm³).ResultsSixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years were included. Mean change of BCVA was 0.03±0.14 logMAR (p=0.115). Significant reductions were recorded for FCP with a mean (±SD) change of −66.81±72.63 µm, −66.76±60.71 µm for CSRT and −0.27±0.24 mm³ for macular volume (all pConclusionsThe results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.

The Acknowledgements section in the original version of this Article was incomplete. ""This research was supported by the Else Kröner-Fresenius Foundation/German Scholars Organization (EKFS/GSO 16) to RF, the BONFOR GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0028) to MW, the GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0026) to ST and the German Ministry of Education and Research (BMBF), FKZ 13N10349. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report."" now reads: ""This research was supported by the Else Kröner-Fresenius Foundation/German Scholars Organization (EKFS/GSO 16) to RF, the BONFOR GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0028) to MW, the GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0026) to ST and the German Ministry of Education and Research (BMBF), FKZ 13N10349. The work of Shekoufeh Gorgi Zadeh was supported by a grant from Deutsche Forschungsgemeinschaft (DFG), grant number SCHM 2966/2-1. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report."" The original Article has been corrected.

PurposeTo evaluate the various patterns of subretinal fluid (SRF) in eyes with age-related macular degeneration (AMD) in the absence of macular neovascularisation (MNV) and to assess the long-term outcomes in these eyes.MethodsThis retrospective study included only eyes with non-neovascular AMD and associated SRF. Eyes with evidence of MNV were excluded. Spectral-domain optical coherence tomography (SD-OCT) was obtained at baseline and at follow-up, and qualitative and quantitative SD-OCT analysis of macular drusen including drusenoid pigment epithelial detachment (PED) and associated SRF was performed to determine anatomic outcomes.ResultsForty-five eyes (45 patients) were included in this analysis. Mean duration of follow-up was 49.7±36.7 months. SRF exhibited three different morphologies: crest of fluid over the apex of the drusenoid PED, pocket of fluid at the angle of a large druse or in the crypt of confluent drusen or drape of low-lying fluid over confluent drusen. Twenty-seven (60%) of the 45 eyes with fluid displayed collapse of the associated druse or drusenoid PED and 24 (53%) of the 45 eyes developed evidence of complete or incomplete retinal pigment epithelial and outer retinal atrophy.ConclusionNon-neovascular AMD with SRF is an important clinical entity to recognise to avoid unnecessary anti-vascular endothelial growth factor therapy. Clinicians should be aware that SRF can be associated with drusen or drusenoid PED in the absence of MNV and may be the result of retinal pigment epithelial (RPE) decompensation and RPE pump failure.

The two interferometric LIGO gravitational-wave observatories provide the most sensitive data to date to study the gravitational-wave Universe. As part of a global network, they have just completed their third observing run in which they observed many tens of signals from merging compact binary systems. It has long been known that a limiting factor in identifying transient gravitational-wave signals is the presence of transient non-Gaussian noise, which reduce the ability of astrophysical searches to detect signals confidently. Significant efforts are taken to identify and mitigate this noise at the source, but its presence persists, leading to the need for software solutions. Taking a set of transient noise artefacts categorised by the GravitySpy software during the O3a observing era, we produce parameterised population models of the noise projected into the space of astrophysical model parameters of merging binary systems. We compare the inferred population properties of transient noise artefacts with observed astrophysical systems from the GWTC2.1 catalogue. We find that while the population of astrophysical systems tend to have near equal masses and moderate spins, transient noise artefacts are typically characterised by extreme mass ratios and large spins. This work provides a new method to calculate the consistency of an observed candidate with a given class of noise artefacts. This approach could be used in assessing the consistency of candidates found by astrophysical searches (i.e. determining if they are consistent with a known glitch class). Furthermore, the approach could be incorporated into astrophysical searches directly, potentially improving the reach of the detectors, though only a detailed study would verify this., Comment: 15 pages, submitted to Phys. Rev. D

When a star exhausts its nuclear fuel, it either explodes as a supernova or more quiescently becomes a white dwarf, an object about half the mass of our Sun with a radius of about that of the Earth. About one fifth of white dwarfs exhibit the presence of magnetic fields, whose origin has long been debated as either the product of previous stages of evolution or of binary interactions. We here report the discovery of two massive and magnetic white dwarf members of young star clusters in the Gaia DR2 database, while a third massive and magnetic cluster white dwarf was already reported in a previous paper. These stars are most likely the product of single-star evolution and therefore challenge the merger scenario as the only way to produce magnetic white dwarfs. The progenitor masses of these stars are all above 5 solar masses, and there are only two other cluster white dwarfs whose distances have been unambiguously measured with Gaia and whose progenitors' masses fall in this range. This high incidence of magnetic white dwarfs indicates that intermediate-mass progenitors are more likely to produce magnetic remnants and that a fraction of magnetic white dwarfs forms from intermediate-mass stars., Comment: 11 pages, 7 figures. Accepted by ApJ Letters

Purpose To investigate the association between retinal microstructure and cone- and rod-function in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using artificial-intelligence-(AI) algorithms. Design Prospective, observational case series Methods Forty-one eyes of 41 patients (75.8±8.4 years; 22 female) from a tertiary referral hospital were included (Directional-Spread-in-Geographic-Atrophy (DSGA) natural history study; NCT02051998). Mesopic, dark-adapted (DA) cyan and red sensitivity were assessed using fundus-controlled perimetry (“microperimetry”); retinal microstructure using spectral-domain optical-coherence-tomography (SD-OCT), fundus autofluorescence (FAF) and near-infrared-reflectance (IR) imaging. Layer-thicknesses and -intensities and FAF- and IR-intensities were extracted for each test-point. We evaluated the cross-validated mean absolute error (MAE) for random-forest-based predictions of retinal sensitivity with and without patient-specific training-data and the increase mean-squared error (%IncMSE) as measure of feature-importance. Results Retinal sensitivity was predicted with a MAE of 4.64 dB for mesopic, 4.89 dB for DA cyan and 4.40 dB for DA red testing in absence of patient-specific data. Partial addition of patient-specific sensitivity data to the training sets decreased the MAE to 2.89 dB, 2.86 dB and 2.77 dB. For all three types of testing, the outer nuclear layer-thickness constituted the most important predictive feature (35.0, 42.22 and 53.74 %IncMSE). Spatially-resolved mapping of “inferred sensitivity” revealed regions with differential degrees of mesopic and DA cyan sensitivity loss outside of the GA lesions. Conclusions “Inferred sensitivity” accurately reflected retinal function in patients with GA. Mapping of “inferred sensitivity” could facilitate monitoring of disease progression and serve as “quasi functional” surrogate outcome in clinical trials, especially in consideration of retinal regions beyond areas of GA.

PURPOSE: To examine the feasibility and utility of dark-adapted two-color fundus-controlled perimetry (FCP) in patients with cuticular, reticular, and soft drusen, and to compare FCP data to microstructural spectral-domain optical coherence tomography (SD-OCT) data. METHODS: Forty-four eyes (24 eyes of 24 patients with drusen, age 69.4 ± 12.6 years; 20 normal eyes of 16 subjects, 61.7 ± 12.4 years) underwent duplicate mesopic, dark-adapted cyan and dark-adapted red FCP within 14° of the central retina (total of 12 936 threshold tests) using the Scotopic Macular Integrity Assessment (S-MAIA, CenterVue, Padova, Italy) device. FCP data were registered to SD-OCT data to obtain outer nuclear layer, inner and outer photoreceptor segment, and retinal pigment epithelium drusen complex (RPEDC) thickness data spatially corresponding to the stimulus location and area (0.43°). Structure-function correlations were assessed using mixed-effects models. RESULTS: Mean deviation values for eyes with cuticular, soft, and reticular drusen were similar for mesopic (-2.1, -3.4, and -3.6 dB) and dark-adapted red (-1.4, -2.6, and -3.3 dB) FCP. For the dark-adapted cyan FCP (0.1, -1.9, and -5.0 dB) and for the cyan-red sensitivity difference (+1.0, +0.5, and -2.4 dB), the mean deviation values differed significantly in dependence of the predominant drusen type (one-way ANOVA; p CONCLUSIONS: In contrast to mesopic FCP, dark-adapted two-color FCP allowed for meaningful differential testing of rod and cone function in patients with drusen indicating predominant cone dysfunction in eyes with cuticular drusen and predominant rod dysfunction in eyes with reticular drusen. RPEDC thickness was the strongest predictor of the evaluated SD-OCT biomarkers for point-wise sensitivity.

Background/AimsTo analyse the retest reliability of visual field indices and to describe patterns of visual field deficits in mesopic and dark-adapted two-colour fundus-controlled perimetry (FCP) in macular diseases.MethodsSeventy-seven eyes (30 eyes with macular diseases and 47 normal eyes) underwent duplicate mesopic and dark-adapted two-colour FCP (Scotopic Macular Integrity Assessment, CenterVue). Non-weighted (mean defect, loss variance), variability-weighted (mean deviation, pattern standard deviation (PSD)) and graphical (cumulative defect (Bebie) curves) indices were computed. Reproducibility (coefficient of repeatability, CoR) of these indices was assessed. Cluster analysis was carried out to identify patterns of visual field deficits.ResultsThe intrasession reproducibility was lower for the mean defect as compared with the mean deviation (CoR (dB) 2.67 vs 2.57 for mesopic, 1.71 vs 1.45 for dark-adapted cyan, 1.94 vs 1.87 for dark-adapted red testing) and lower for the square-root loss variance as compared with the PSD (CoR (dB) 1.48 vs 1.34, 0.77 vs 0.65, 1.23 vs 1.03). Hierarchical cluster analysis of the indices disclosed six patterns of visual field deficits (approximately unbiased P value>0.95) with varying degrees of global versus focal defect and rod versus cone dysfunction. These were also reflected by the cumulative defect curves.ConclusionFCP with mesopic and dark-adapted two-colour testing allows for reproducible assessment of different types of retinal sensitivity, whereby mean deviation and PSD exhibited the better retest reliability of the tested indices. Distinct patterns of retinal dysfunction can be identified using this setup, reflecting variable degrees of rod and cone dysfunction in different macular diseases. Dark-adapted two-colour FCP provides additional diagnostic information and allows for refined structure–function correlation in macular diseases.

Purpose: To systematically compare the prognostic value of multiple shape-descriptive factors in the natural course of the disease. Methods: A total of 296 eyes of 201 patients (female patients 130; mean age: 72.2 ± 13.08 years) with a median follow-up of 2.38 years from 2 prospective, noninterventional natural history studies (Fundus-Autofluorescence-in-Age-related-Macular-Degeneration [clinicaltrials.gov identifier NCT00393692], Directional-Spread-in-Geographic-Atrophy [NCT02051998]) were included in the analysis. Serial fundus autofluorescence images were annotated using semiautomated image analysis software to determine the lesion area, circularity, perimeter, and caliper diameters. These variables and the fundus autofluorescence phenotype were evaluated for prediction of the future square root progression rates using linear mixed-effects models. Results: For the combined model, leave-one-out cross validation on patient level (Scenario 1: previously unknown patient) resulted in a goodness-to-fit (R2 value) of 0.244 and leave-one-out cross validation on visit level (Scenario 2: previous observation of the patient) in a R2 value of 0.391. This indicated that shape-descriptive factors could explain 24.4% of the variance in geographic atrophy progression in previously unknown patients and 39.1% in patients with previous observation. Conclusion: These findings confirm the relevance of shape-descriptive factors and previous progression as prognostic variables for geographic atrophy progression. However, a substantial part of the remaining variation in geographic atrophy progression seems to depend on other variables, some of which are visible in optical coherence tomography.

To assess the longitudinal association between outer retinal microstructure and mesopic as well as scotopic retinal sensitivity in patients with drusen secondary to intermediate age-related macular degeneration (iAMD).Prospective, longitudinal natural history study.Fifty-nine eyes of 54 patients with large drusen (125 μm) associated with iAMD and 27 age-matched healthy control eyes.Participants underwent spectral-domain OCT and both mesopic and scotopic fundus-controlled perimetry (FCP). Annual follow-up visits were performed over a 3-year period.Pointwise correlation of retinal sensitivity stimuli to corresponding standardized (Z score) pointwise retinal thickness. Linear mixed-effect models were applied to analyze longitudinally the association of pointwise retinal thickness changes, follow-up time, or both with retinal function.At baseline, mean pointwise sensitivity in patients was reduced by -1.67 dB (95% confidence interval [CI], -2.22 to -1.12) for mesopic and by -2.34 dB (95% CI, -2.85 to -1.84) for scotopic testing compared with controls with a pointwise sensitivity change of -0.35 dB/year (95% CI, -0.43 to -0.28) for mesopic and +0.20 dB/year (95% CI, 0.12-0.29) for scotopic testing, respectively (P0.001). Retinal thickness analysis in patients revealed a significantly thinner outer nuclear layer (ONL) by -0.49 standard deviation (SD; 95% CI, -0.70 to -0.28 SD) and a significant thicker retinal pigment epithelium-drusen complex (RPEDC) by +3.22 SD (95% CI, 2.27-4.17 SD) at baseline, respectively (P0.001). During follow-up, retinal thickness thickened further by +0.51 SD/year (RPEDC) and thinned by -0.03 SD/year (ONL; P = 0.045) and -0.34 SD/year (inner and outer photoreceptor segments) in patients, respectively (P 0.001). Structure-function analysis showed a significant association of the ONL and the RPEDC thickness change with both types of FCP sensitivity testing (P0.001). Besides, follow-up time had a significant (independent) effect on mesopic and scotopic retinal sensitivity (P0.001).The longitudinal structure-function correlation demonstrated a progressive quantifiable degeneration of the outer retina in iAMD associated with photoreceptor dysfunction. Because longitudinal sensitivity changes could not be explained by structural changes alone, an unmet need remains for additional refined parameters on retinal structure to predict retinal function.

Scientific reports 10(1), 7395 (2020). doi:10.1038/s41598-020-63924-6, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

To analyze the intersession repeatability of structural biomarkers in eyes with early and intermediate age-related macular degeneration (iAMD) within the cross-sectional part of the observational multicenter MACUSTAR study.Certified site personnel obtained multimodal imaging data at two visits (38 ± 20 [mean ± standard deviation] days apart), including spectral-domain optical coherence tomography (SD-OCT). One junior reader performed systematic and blinded grading at the central reading center, followed by senior reader review. Structural biomarkers included maximum drusen size classification (63 to ≤125 µm vs.125 µm), presence of large pigment epithelium detachments (PEDs), reticular pseudodrusen (RPD), vitelliform lesions, and refractile deposits. Intrasession variability was assessed using Cohen's κ statistics.At the first visit, 202 study eyes of 202 participants were graded as manifesting with either early (n = 34) or intermediate (n = 168) AMD. Grading of imaging data between visits revealed perfect agreement for the maximum drusen size classification (κ = 0.817; 95% confidence interval, 0.70-0.94). In iAMD eyes, perfect to substantial agreement was determined for the presence of large PEDs (0.87; 0.69-1.00) and RPD (0.752; 0.63-0.87), while intersession agreement was lower for the presence of vitelliform lesions (0.649; 0.39-0.65) and refractile deposits (0.342; -0.029-0.713), respectively.Multimodal retinal imaging analysis between sessions showed a higher repeatability for structural biomarkers with predefined cutoff values than purely qualitative defined parameters.A high repeatability of retinal imaging biomarkers will be important to implement automatic grading approaches and to establish robust and meaningful structural clinical endpoints for future interventional clinical trials in patients with iAMD.

In the summer of 2017, the Centre for African Studies at the University of Basel in Switzerland hosted the seventh European Conference on African Studies (ECAS7) with the theme Urban Africa – Urban...

Purpose: To evaluate two different spectral-domain optical coherence tomography (SD-OCT) scan patterns in eyes with intermediate age-related macular degeneration (AMD) for the longitudinal assessment of drusen volume. Methods: The data of 38 eyes of 38 AMD patients (age 69.97 ± 6.08 years) were included. The longitudinal drusen volume over 4 years was analyzed by annual SD-OCT raster scanning (field size 20 × 15°). Two raster scan patterns (A/B) differed in the distance between neighboring B-scans (240 vs. 30 µm) and in the number of averaged frames (4 vs. 15). Results: The mean drusen volume at baseline was 0.213 ± 0.100 mm3 (pattern A) and 0.219 ± 0.103 mm3 (pattern B) (p = 0.937). Linear mixed-effect models showed no significant difference for the change within 4 years for both pattern A (p = 0.8) and pattern B (p = 0.8). Conclusions: The results indicate that the performance of interpolation algorithms may be sufficient to balance for less dense raster scanning with regard to quantification of longitudinal drusen volume, which can be used as a surrogate marker for AMD progression in future clinical trials.

Purpose: To investigate residual sensitivity within geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Mesopic and dark-adapted (DA) cyan and red light sensitivity (Goldmann III) were investigated using fundus-controlled perimetry (microperimetry). Test points were placed within GA along an “iso-hull” with a distance of −0.645° to the atrophy boundary. The false-positive response rate was determined with suprathreshold stimuli to the optic disc (Heijl-Krakau method) and used to compute the expected sensitivity measurements for the assumption of absolute scotomata. The outermost visible retinal layer on spectral-domain optical coherence tomography at the location of each test point was determined. Results: Thirty eyes of 36 patients (75.55 ± 7.93 years; 19 female) from the prospective natural history study Directional Spread in Geographic Atrophy (NCT02051998), with a total of 1380 threshold determinations were analyzed. The measured sensitivities were significantly (P < 0.01) higher than the expected values for absolute scotomata (mean ± standard error of +6.92 ± 0.86 dB for mesopic, +2.57 ± 0.56 dB for DA cyan, and +4.93 ± 0.74 dB for DA red testing). For mesopic testing and DA red testing, the presence of a residual outer nuclear layer had a significant effect on this discrepancy (P < 0.001). There was no effect of fixation stability or any other reliability index on this discrepancy. Conclusions: Measured sensitivities within the inner junctional zone of GA may not be purely explained by patient-specific false-positive response rates or other reliability indices. The marked influence of the outer retinal configuration on measured sensitivity may be indicative of residual cone function within GA at the inner junctional zone.

Age-related macular degeneration (AMD) is clinically divided into early and late stages. The term "dry" AMD is widely used when there are no "exudative" changes in the ocular fundus. There are numerous studies on the epidemiology of AMD. Most studies differentiate between early and late forms of AMD, but without further differentiation of the "dry" late form. In addition, different studies may employ different classifications of AMD, which inevitably leads to deviations in epidemiological data on AMD. New classification systems take into account microstructural changes that can be detected by high resolution in vivo imaging of the retina. A new consensus classification of AMD-associated atrophy will allow future studies to be conducted according to uniform definitions.Klinisch wird die altersabhängige Makuladegeneration (AMD) in Früh- und Spätstadien eingeteilt. Der Begriff „trockene“ AMD wird häufig verwendet, wenn keine „exsudativen“ Veränderungen am Augenhintergrund vorliegen. Es existiert eine Vielzahl von Studien zur Epidemiologie der AMD. Dabei wird in den meisten Studien zwischen AMD-Früh- und -Spätformen unterschieden, allerdings ohne eine weitere Differenzierung der „trockenen“ AMD-Spätform. Zudem stellt sich die Herausforderung unterschiedlicher Klassifikationen der AMD in verschiedenen Studien, was zwangsläufig zu Abweichungen in den epidemiologischen Daten bei der AMD führt. Neue Klassifikationssysteme berücksichtigen mikrostrukturelle Veränderungen, die mittels hochauflösender In-vivo-Bildgebung der Netzhaut detektiert werden können. Eine neue Konsensusklassifikation der AMD-assoziierten Atrophie soll ermöglichen, zukünftige Studien nach einheitlichen Definitionen durchzuführen.

Purpose To analyze longitudinal thickness changes of retinal layers in comparison with established risk factors in eyes with age-related macular degeneration (AMD) with regard to their prognostic value for conversion into advanced AMD stages. Design Prospective, longitudinal natural history study. Participants Ninety-one eyes of 91 patients with AMD (73.3±7.3 years; 62 female patients [50.4%]) of the Molecular Diagnostic of Age-related Macular Degeneration (MODIAMD) study without exudative or nonexudative late-stage AMD in the study eye at baseline. Methods At each annual follow-up visit, all subjects underwent ophthalmic examination with assessment of best-corrected visual acuity (BCVA) and retinal imaging, including spectral-domain OCT (SD-OCT), over a study period of 6 years. Purpose To analyze longitudinal thickness changes of retinal layers in comparison with established risk factors in eyes with age-related macular degeneration (AMD) with regard to their prognostic value for conversion into advanced AMD stages. Main Outcome Measures Qualitative structural AMD features and SD-OCT–based quantitative thickness changes of different retinal layers, such as the retinal pigment epithelium-drusen complex (RPEDC), were assessed by multimodal imaging. Their prognostic relevance regarding disease conversion was determined using Cox regression (cloglog link function). Results In the multivariable analysis, the presence of focal hyperpigmentation, almost reaching statistical significance, showed the strongest effect regarding the development of nonexudative late-stage AMD (hazard ratio [HR], 5.88; 95% confidence interval [CI], 0.69–50.2; P = 0.052) followed by the presence of refractile drusen (HR, 4.82; 95% CI, 1.33–17.44; P = 0.0164). A thickening of the RPEDC was the only assessed retinal layer that exhibited a significant effect on the development of nonexudative advanced AMD (HR, 1.03; 95% CI, 1.0–1.07; P = 0.0393), whereas no association was observable for the other retinal layers. Neither qualitative nor quantitative markers were significant predictors for the development of exudative late-stage AMD (P > 0.05). Conclusions The results indicate that the development of both exudative and nonexudative AMD is associated with distinct prognostic features. However, compared with the assessment of qualitative AMD features, the quantification of retinal layers on average across the central retina had less prognostic impact. Further studies are needed to identify and validate robust biomarkers in early AMD stages.

Purpose: Based on exudative activity, choroidal neovascularization (CNV) in age-related macular degeneration (AMD) can be classified as “active” aCNV, pretherapied “silent” sCNV (i.e., a treatment-free interval >12 weeks), or treatment-naïve “quiescent” qCNV. We evaluated the qualitative and quantitative optical coherence tomography angiography (OCTA) features of these CNV subgroups. Methods: The presence of small-caliber vessels, peripheral arcades, and a ­perilesional OCTA signal attenuation as well as values for vessel length, density, and branching index were evaluated for each CNV network in a 6 × 6 mm OCTA scan pattern. Results: Fifty-one eyes of 51 patients with AMD (age 75.9 ± 7.5 years; 20 males [39.2%]) were included. The qCNV subgroup (n = 8) showed the highest prevalence of qualitative and quantitative values for OCTA activity criteria, reaching significance with regard to small-caliber vessels (p = 0.003), peripheral arcades (p = 0.039), vessel length (p = 0.020), and branching index (p < 0.001) when compared to the aCNV (n = 32) and sCNV (n = 11) subgroups. Qualitative criteria were inversely associated with the number of previous anti-VEGF injections (each p < 0.03), while quantitative metrics also suggested lower values. Conclusions: These findings suggest that OCTA may be supportive in the phenotypical differentiation of CNV lesions secondary to AMD, while the assessed structural changes appeared to be more indicative of previously administered anti-VEGF therapy than current exudative activity.

Purpose: Relative ellipsoid zone reflectivity (rEZR) represents a potential biomarker of photoreceptor health on spectral-domain optical coherence tomography (SD-OCT). Because manual quantification of rEZR is laborious and lacks of spatial resolution, automated quantification of the rEZR would be beneficial. The purpose of this study was to evaluate the reliability and reproducibility of an automated rEZR quantification method. Methods: The rEZR was acquired using a manual and an automated approach in eyes with age-related macular degeneration (AMD) and healthy controls. The rEZR obtained from both methods was compared and the agreement between the methods and their reproducibility assessed. Results: Forty eyes of 40 participants with a mean (± standard deviation) age of 65.2 ± 7.8 years were included. Both the manual and automated method showed that control eyes exhibit a greater rEZR than AMD eyes (P < 0.001). Overall, the limits of agreement between the manual and automated method were -7.5 to 7.3 arbitrary units (AU) and 95% of the data points had a difference in the rEZR between the methods of ±8.2%. An expected perfect reproducibility was observed for the automated method, whereas the manual method had a coefficient of repeatability of 6.3 arbitrary units. Conclusions: The automated quantification of rEZR method is reliable and reproducible. Further studies of the rEZR as a novel biomarker for AMD severity and progression are warranted. Translational Relevance: Automated quantification of SD-OCT-based rEZR allows for its comprehensive and longitudinal characterization evaluating its relevance as an in vivo biomarker of photoreceptor function and its prognostic value for AMD progression.

Purpose To examine longitudinal changes of retinal thickness and retinal sensitivity in patients with intermediate age-related macular degeneration (iAMD) and predominantly reticular pseudodrusen (RPD). Methods At baseline 30 eyes of 25 iAMD patients underwent optical coherence tomography imaging, mesopic and scotopic fundus-controlled perimetry (FCP) with follow-up examinations at month 12 (20 eyes), 24 (12 eyes), and 36 (11 eyes). Thicknesses of different retinal layers and results of FCP testing (n = 56 stimuli) were spatially and longitudinally analyzed using linear mixed-effects models. Results At baseline, the thickness of the partial outer retinal layer (pORL, 70.21 vs. 77.47 µm) and both mesopic (16.60 vs. 18.72 dB) and scotopic (12.14 vs. 18.67 dB) retinal sensitivity were decreased in areas with RPD compared with unremarkable areas (P < 0.001). Over three years, mean change of pORL was −0.66 normative standard deviation (SD; i.e., z-score, P < 0.001) for regions with existing RPD, −0.40 SD (P < 0.001) for regions with new occurring RPD, and −0.17 SD (P = 0.041) in unremarkable regions. Decrease of scotopic and mesopic sensitivity over three years was more pronounced in areas with existing (−3.51 and −7.76 dB) and new occurring RPD (−2.06 and −5.97 dB). Structure-function analysis revealed that 1 SD decrease of pORL thickness was associated with a sensitivity reduction of 3.47 dB in scotopic and 0.79 dB in mesopic testing. Conclusions This study demonstrates progressive outer retinal degeneration and impairment of photoreceptor function in eyes with iAMD and RPD over three years. Preservation of outer retinal thickness and reduction of RPD formation may constitute meaningful surrogate endpoints in interventional trials on eyes with AMD and RPD aiming to slow outer retinal degeneration.

To determine the prevalence of and identify factors associated with visual impairment and blindness in institutionalized elderly in Germany. In this prospective multicenter cross-sectional study, ophthalmic health care need and provision were investigated in institutionalized elderly in 32 nursing homes in Germany. All participants underwent a standardized examination including medical and ocular history, refraction, visual acuity testing, tonometry, biomicroscopy, and dilated funduscopy. A standardized questionnaire was used to identify factors associated with eye healthcare utilization, visual impairment and/or blindness. Visual acuity of 566 (94.3%; 413 women and 153 men) of a total of 600 institutionalized elderly was determined. Mean age of the included patients was 82.9 years (± 9.8). Of all participants, 30 (5.3%; 95% CI 3.4–7.2%) were blind and 106 (18.7%; 95% CI 15.5–21.9%) were moderately or severely visually impaired according to the World Health Organization definition. The 136 blind and moderately or severely visually impaired participants were older (OR, Odds Ratio = 1.1, 95% CI 1.0–1.1; p

Purpose To evaluate macular pigment distribution pattern as a prognostic marker for disease progression in patients with macular telangiectasia type 2 (MacTel). Design Retrospective cohort study. Methods In this single-center study, 90 eyes of 47 patients were analyzed. Macular pigment optical density (MPOD) was measured with dual-wavelength fundus autofluorescence. Eyes were graded into MPOD distribution classes 1 to 3 with increasing loss of macular pigment and grading was performed masked by 2 independent graders. Best-corrected visual acuity, reading acuity, total scotoma size in fundus-controlled perimetry (microperimetry), and break of the ellipsoid zone (EZ) in optical coherence tomography (en face measurement) were defined as functional and morphologic outcome parameters and evaluated at baseline and after 60 months. Results After a mean review period of 59.6 months (±standard deviation 5.2 months), no change between MPOD classes was observed compared to baseline. Morphologic and functional deficits were limited to the area of MPOD loss. At last follow-up, a significant mean decrease of visual acuity and reading acuity as well as a significant mean increase of scotoma size and EZ break were observed in eyes assigned to MPOD classes 2 and 3, while outcome parameters remained stable in eyes of class 1. Conclusions The results indicate that MPOD and its distribution may serve as a prognostic marker for disease progression and functional impairment in patients with MacTel.

Purpose To evaluate the development of central atrophy in eyes with age-related macular degeneration (AMD). Methods Six-year longitudinal multimodal retinal imaging data (MODIAMD study) from 98 eyes of 98 subjects with non-late-stage AMD in the study eye at baseline were analyzed for the presence of central atrophy at each annual follow-up visit. Development, manifestation, and further progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) by multimodal imaging data were compared with atrophy detection based on color fundus photography only. Results Seventeen study eyes with development of central cRORA within 6 years (cumulative rate: 17.4%) were identified based on multimodal imaging. In 10 (60%) of these eyes, presence of central manifest atrophy was initially not detectable by color fundus photography. In six (35%) eyes, central cRORA occurred by the spread of existing paracentral atrophy toward the fovea. Drusen-associated atrophy development was noted in eight eyes. In two eyes, atrophy development was associated with refractile deposits, while only pigmentary changes in absence of large drusen or refractile deposits were detectable before atrophy occurrence in one eye. Conclusions The earlier and more precise detection of central cRORA by multimodal imaging as compared to atrophy detection solely based on color fundus photography allows for more accurate detection and identification of different pathways for atrophy development. In accordance with previous clinical and histopathologic reports, the results confirm that different precursor lesions may independently proceed to central cRORA in AMD.

PURPOSE To investigate longitudinal changes of outer nuclear layer (ONL) thickness in patients with retinal pigment epithelium tears secondary to neovascular age-related macular degeneration. METHODS This is an institutional retrospective interventional case series. Twenty-six eyes of 22 patients with retinal pigment epithelium tears identified between April 2009 and March 2015. The patients underwent intravitreal injection of anti-vascular endothelial growth factor agents as needed. Volume scans of optical coherence tomography at first diagnosis of tear (baseline) and after 12 months were analyzed. Outer nuclear layer was segmented, and average ONL thickness inside the tear area, at the border of the tear, and in areas outside the tear was measured. Change of ONL thickness. We also explored several factors for their association with ONL thinning including tear area, number of treatments, and the duration with persistent subretinal fluid. RESULTS Thinning of ONL was found in all the investigated areas (P < 0.01, respectively). Among the investigated factors, larger tear area was associated with greater ONL thinning outside the tear area (standardized β = -0.37, P = 0.030), and younger age was associated with greater ONL thinning inside the tear area (standardized β = 0.37, P = 0.041). CONCLUSION After an retinal pigment epithelium tear, thinning of ONL occurs in the area devoid of retinal pigment epithelium and also in adjacent areas. Few factors were predictive for the degree of ONL thinning. These results provide new insight in disease progression of this particular neovascular age-related macular degeneration subphenotype.