Microencapsulated granaticins from Streptomyces vilmorinianum YP1: Optimization, physiochemical characterization and storage stability.

Granaticins are natural pigments derived from microorganisms with promising bioactivity. However, their practical applications have been restricted due to inherent instability. To improve the stability of granaticins from the novel strain Streptomyces vilmorinianum YP1, microcapsules were prepared using gum Arabic (GA) by a freeze-drying method. The optimal parameters for microencapsulation were determined using response surface methodology. Under the optimal conditions (GA 9.2% (v/v), a wall/-core ratio 4.8 (w/w), encapsulating temperature 29 °C), the maximum encapsulation efficiency achieved was 93.64%. The microcapsules were irregular single crystals with an average particle size of 206.37 ± 2.51 nm. Stability testing indicated improved stability of the microencapsulated granaticins. Notably, granaticnic B retention increased by 17.0% and 6.6% after exposure to sunlight and storage at 4 °C, respectively. These finding suggest that GA as a well material significantly enhances the stability of granaticins from S. vilmorinianum YP1, facilitating their potential applications.

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

Interference fading suppression with a multi-subcarrier pulse in a distributed acoustic sensor.

A low-complexity multi-subcarrier pulse generation scheme is proposed to suppress the interference fading in a phase-sensitive optical time-domain reflectometer (Φ-OTDR) based distributed acoustic sensor (DAS) with heterodyne coherent detection. The multi-subcarrier pulse is generated in the digital domain based on the proper clipping operation of a sine signal. The localization and recovery of the disturbance signal are realized by the spectrum extraction and rotated vector sum (SERVS) method. The experimental results show that the occurrences of interference fading can be significantly reduced. The intensity fluctuation is reduced from ∼75 dB to ∼25 dB. Multiple disturbance signals are successfully demodulated to verify the effectiveness of the proposed method.

Anaerobic biodegradation enables zero liquid discharge of two-stage nanofiltration system for microelectronic wastewater treatment.

Nanofiltration (NF) is a promising technology in the treatment of microelectronic wastewater. However, the treatment of concentrate derived from NF system remains a substantial technical challenge, impeding the achievement of the zero liquid discharge (ZLD) goal in microelectronic wastewater industries. Herein, a ZLD system, coupling a two-stage NF technology with anaerobic biotechnology was proposed for the treatment of tetramethylammonium hydroxide (TMAH)-contained microelectronic wastewater. The two-stage NF system exhibited favorable efficacy in the removal of conductivity (96 %), total organic carbon (TOC, 90 %), and TMAH (96 %) from microelectronic wastewater. The membrane fouling of this system was dominated by organic fouling, with the second stage NF membrane experiencing a more serious fouling compared to the first stage membrane. The anaerobic biotechnology achieved a near-complete removal of TMAH and an 80 % reduction in TOC for the first stage NF concentrate. Methyloversatilis was the key genus involved in the anaerobic treatment of the microelectronic wastewater concentrate. Specific genes, including dmd-tmd, mtbA, mttB and mttC were identified as significant players in mediating the dehydrogenase and methyl transfer pathways during the process of TMAH biodegradation. This study highlights the potential of anaerobic biodegradation to achieve ZLD in the treatment of TMAH-contained microelectronic wastewater by NF system.

Deep Neural Networks for Automated Outer Plexiform Layer Subsidence Detection on Retinal OCT of Patients With Intermediate AMD.

Purpose: The subsidence of the outer plexiform layer (OPL) is an important imaging biomarker on optical coherence tomography (OCT) associated with early outer retinal atrophy and a risk factor for progression to geographic atrophy in patients with intermediate age-related macular degeneration (AMD). Deep neural networks (DNNs) for OCT can support automated detection and localization of this biomarker. Methods: The method predicts potential OPL subsidence locations on retinal OCTs. A detection module (DM) infers bounding boxes around subsidences with a likelihood score, and a classification module (CM) assesses subsidence presence at the B-scan level. Overlapping boxes between B-scans are combined and scored by the product of the DM and CM predictions. The volume-wise score is the maximum prediction across all B-scans. One development and one independent external data set were used with 140 and 26 patients with AMD, respectively. Results: The system detected more than 85% of OPL subsidences with less than one false-positive (FP)/scan. The average area under the curve was 0.94 ± 0.03 for volume-level detection. Similar or better performance was achieved on the independent external data set. Conclusions: DNN systems can efficiently perform automated retinal layer subsidence detection in retinal OCT images. In particular, the proposed DNN system detects OPL subsidence with high sensitivity and a very limited number of FP detections. Translational Relevance: DNNs enable objective identification of early signs associated with high risk of progression to the atrophic late stage of AMD, ideally suited for screening and assessing the efficacy of the interventions aiming to slow disease progression.

Hyaluronic acid-coated liposomes for enhanced in vivo efficacy of neogambogic acid via active tumor cell targeting and prolonged systemic exposure.

Neogambogic acid (NGA), which possesses a variety of anticancer activities, is visualized as an anticancer bioactive ingredient. However, the huge vascular stimulation, poor aqueous solubility, and short half-life restricted its clinical use. In this work, an effective nanocarrier was explored to reduce toxicity and enhance the tumor-targeted delivery. Two liposomal formulations, neogambogic acid liposomes (NGA-L), and hyaluronic acid-coated neogambogic acid liposomes (HA-NGA-L) were prepared and characterized with high encapsulation efficiency, slow pattern of drug release, narrow size distribution and higher stability. The cytotoxicity and cellular uptake of HA-NGA-L were higher than those of NGA-L in MDA-MB-231 cells (high CD44 expression), while no obvious differences in MCF-7 cells with (low CD44 expression), suggesting the CD44-mediated cellular internalization of hyaluronic acid-modified liposomes enhanced the cytotoxicity. Mechanistically, elevation of Bax and caspase-3 as well as downregulation of Bcl-2 led to cell apoptosis. Besides, the vascular stimulation and the hemolysis test indicated good safety of HA-NGA-L. In addition, HA-NGA-L was the effective nanocarrier to repress tumor proliferation in MDA-MB-231 tumor xenograft mouse through CD44 mediated active targeting without any obvious histopathological abnormities on major organs. Immunohistochemistry analysis revealed the enhanced elevation of Bax and caspase-3, and reduced expression of Bcl-2 contribute to apoptosis in tumors. Meanwhile, HA-NGA-L increased the AUC and t1/2 by 5.34-fold and 3.94-fold, respectively. In summary, the present study shows that HA-NGA-L may be safe and effective for the tumor-targeted delivery of neogambogic acid.

Clinical performance of predicting late age-related macular degeneration development using multimodal imaging.

BACKGROUND: To examine whether the clinical performance of predicting late age-related macular degeneration (AMD) development is improved through using multimodal imaging (MMI) compared to using colour fundus photography (CFP) alone, and how this compares with a basic prediction model using well-established AMD risk factors. METHODS: Individuals with AMD in this study underwent MMI, including optical coherence tomography (OCT), fundus autofluorescence, near-infrared reflectance and CFP at baseline, and then at 6-monthly intervals for 3-years to determine MMI-defined late AMD development. Four retinal specialists independently assessed the likelihood that each eye at baseline would progress to MMI-defined late AMD over 3-years with CFP, and then with MMI. Predictive performance with CFP and MMI were compared to each other, and to a basic prediction model using age, presence of pigmentary abnormalities, and OCT-based drusen volume. RESULTS: The predictive performance of the clinicians using CFP [AUC = 0.75; 95% confidence interval (CI) = 0.68-0.82] improved when using MMI (AUC = 0.79; 95% CI = 0.72-0.85; p = 0.034). However, a basic prediction model outperformed clinicians using either CFP or MMI (AUC = 0.85; 95% CI = 0.78-91; p ≤ 0.002). CONCLUSIONS: Clinical performance for predicting late AMD development was improved by using MMI compared to CFP. However, a basic prediction model using well-established AMD risk factors outperformed retinal specialists, suggesting that such a model could further improve personalised counselling and monitoring of individuals with the early stages of AMD in clinical practice.

Deletion of Asb15b gene can lead to a significant decrease in zebrafish intermuscular bone.

Intermuscular bones, which are present in numerous economically significant fish species, have a negative impact on the development of aquaculture. The Asb15b gene, primarily expressed in skeletal muscle, plays a crucial role in regulating protein turnover and the development of muscle fibers. It stimulates protein synthesis and controls the differentiation of muscle fibers. In this study, we employed CRISPR/Cas9 technology to generate homozygous zebrafish strains with 7 bp and 49 bp deletions in the Asb15b gene. Subsequent analyses using skeleton staining demonstrated a substantial reduction in the number of intermuscular bones in adult Asb15b-/- -7 bp and Asb15b-/- -49 bp mutants compared to the wild-type zebrafish, with decreases of 30 % (P < 0.001) and 40 % (P < 0.0001), respectively. Histological experiments further revealed that the diameter and number of muscle fibers in adult Asb15b-/- mutants did not exhibit significant changes when compared to wild-type zebrafish. Moreover, qRT-PCR experiments demonstrated significant differences in the expression of bmp6 and runx2b genes, which are key regulators of intermuscular bone development, during different stages of intermuscular bone development in Asb15b-/- mutants. This study strongly suggests that the Asb15b gene plays a crucial role in regulating intermuscular bone development in fish and lays the groundwork for further exploration of the role of the Asb15b gene in zebrafish intermuscular bone development.

HAX1-Overexpression Augments Cardioprotective Efficacy of Stem Cell-Based Therapy Through Mediating Hippo-Yap Signaling.

Although stem/progenitor cell therapy shows potential for myocardial infarction repair, enhancing the therapeutic efficacy could be achieved through additional genetic modifications. HCLS1-associated protein X-1 (HAX1) has been identified as a versatile modulator responsible for cardio-protective signaling, while its role in regulating stem cell survival and functionality remains unknown. In this study, we investigated whether HAX1 can augment the protective potential of Sca1+ cardiac stromal cells (CSCs) for myocardial injury. The overexpression of HAX1 significantly increased cell proliferation and conferred enhanced resistance to hypoxia-induced cell death in CSCs. Mechanistically, HAX1 can interact with Mst1 (a prominent conductor of Hippo signal transduction) and inhibit its kinase activity for protein phosphorylation. This inhibition led to enhanced nuclear translocation of Yes-associated protein (YAP) and activation of downstream therapeutic-related genes. Notably, HAX1 overexpression significantly increased the pro-angiogenic potential of CSCs, as demonstrated by elevated expression of vascular endothelial growth factors. Importantly, implantation of HAX1-overexpressing CSCs promoted neovascularization, protected against functional deterioration, and ameliorated cardiac fibrosis in ischemic mouse hearts. In conclusion, HAX1 emerges as a valuable and efficient inducer for enhancing the effectiveness of cardiac stem or progenitor cell therapeutics.

Trade-off between Endocrine-Disrupting Compound Removal and Water Permeance of the Polyamide Nanofiltration Membrane: Phenomenon and Molecular Insights.

The polyamide (PA) nanofiltration (NF) membrane has the potential to remove endocrine-disrupting compounds (EDCs) from water and wastewater to prevent risks to both the aquatic ecosystem and human health. However, our understanding of the EDC removal-water permeance trade-off by the PA NF membrane is still limited, although the salt selectivity-water permeance trade-off has been well illustrated. This constrains the precise design of a high-performance membrane for removing EDCs. In this study, we manipulated the PA nanostructures of NF membranes by altering piperazine (PIP) monomer concentrations during the interfacial polymerization (IP) process. The upper bound coefficient for EDC selectivity-water permeance was demonstrated to be more than two magnitudes lower than that for salt selectivity-water permeance. Such variations were derived from the different membrane-solute interactions, in which the water/EDC selectivity was determined by the combined effects of steric exclusion and the hydrophobic interaction, while the electrostatic interaction and steric exclusion played crucial roles in water/salt selectivity. We further highlighted the role of the pore number and residual groups during the transport of EDC molecules across the PA membrane via molecular dynamics (MD) simulations. Fewer pores decreased the transport channels, and the existence of residual groups might cause steric hindrance and dynamic disturbance to EDC transport inside the membrane. This study elucidated the trade-off phenomenon and mechanisms between EDC selectivity and water permeance, providing a theoretical reference for the precise design of PA NF membranes for effective removal of EDCs in water reuse.

Synchronous reducing anti-nutritional factors and enhancing biological activity of soybean by the fermentation of edible fungus Auricularia auricula.

Auricularia auricula fermentation was performed to reduce anti-nutritional factors, improve nutritional components, and enhance biological activity of soybean. Results showed that the contents of raffinose, stachyose, and trypsin inhibitor were significantly decreased from initial 1.65 g L-1, 1.60 g L-1, and 284.67 µg g-1 to 0.14 g L-1, 0.35 g L-1, and 4.52 µg g-1 after 144 h of fermentation, respectively. Simultaneously, the contents of polysaccharide, total phenolics, and total flavonoids were increased, and melanin was secreted. The isoflavone glycosides were converted to their aglycones, and the contents of glyctin and genistin were decreased from initial 1107.99 µg g-1 and 2852.26 µg g-1 to non-detection after 72 h of fermentation, respectively. After 96 h of fermentation, the IC50 values of samples against DPPH and ABTS radicals scavenging were decreased from 17.61 mg mL-1 and 3.43 mg mL-1 to 4.63 mg mL-1 and 0.89 mg mL-1, and those of samples inhibiting α-glucosidase and angiotensin I-converting enzyme were decreased from 53.89 mg mL-1 and 11.27 mg mL-1 to 18.24 mg mL-1 and 6.78 mg mL-1, respectively, indicating the significant increase in these bioactivities. These results suggested A. auricula fermentation can enhance the nutritional quality and biological activity of soybean, and the fermented soybean products have the potential to be processed into health foods/food additives.

Inter-night variability of in-home, overnight pulse oximetry screening in an asymptomatic older adult population.

PURPOSE: Obstructive sleep apnoea (OSA) is common, yet often undiagnosed. Self-administered, overnight pulse oximetry (OPO) could screen for OSA in asymptomatic, older populations. However, the inter-night variability of OPO in an asymptomatic, older population is unknown. We determined the inter-night variability of home OPO parameters in an older population and correlated with sleep questionnaires. METHODS: Participants > 50 years without a diagnosis of OSA undertook home OPO for three consecutive nights and completed two sleep questionnaires (STOP-BANG (SBQ) and Epworth Sleepiness Score (ESS)). Analysis was performed with linear mixed models and Spearman's correlation coefficient. RESULTS: There was no difference in oxygen desaturation index (ODI), MeanSpO2, MinimumSpO2, and time spent with SpO2 < 90% (T90) across two or three nights (P ≥ 0.282). However, the variability of all parameters across nights increased with the magnitude of departure from normal values (P ≤ 0.002). All OPO parameters were associated with age (P ≤ 0.034) and body mass index (P ≤ 0.049). There was a weak correlation between three OPO parameters and SBQ (absolute ρ = 0.22 to 0.32; P ≤ 0.021), but not ESS (P ≥ 0.254). CONCLUSION: Inter-night variability of home OPO was minimal when values were near-normal in an older population. However, as values depart from normal, the inter-night variability increases, indicating the need for multiple night recordings. Low correlation to sleep questionnaires suggest the need for more robust OSA questionnaires in an asymptomatic population.

COMPLETE RETINAL PIGMENT EPITHELIAL AND OUTER RETINAL ATROPHY IN AGE-RELATED MACULAR DEGENERATION: A Longitudinal Evaluation.

PURPOSE: There is a need for robust earlier biomarkers of atrophic age-related macular degeneration that could act as surrogate endpoints for geographic atrophy (GA) in early interventional trials. This study sought to examine the risk of progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) to the traditional atrophic endpoint of GA on color fundus photography. This study also compared the risk of progression for cRORA to that associated with the specific optical coherence tomography features that define nascent GA (nGA), a strong predictor of GA development. METHODS: One hundred forty participants with bilateral large drusen at baseline underwent optical coherence tomography imaging and color fundus photography at 6-month intervals for up to 36 months. Optical coherence tomography volume scans were graded for the presence of cRORA and nGA, and color fundus photographs were graded for the presence of GA. The association and rate of progression to GA for cRORA and nGA were examined. RESULTS: Both cRORA and nGA were significantly associated with GA development (adjusted hazard ratio, 65.7 and 76.8 respectively; both P < 0.001). The probability of progression of cRORA to GA over 24 months (26%) was significantly lower than the probability of progression of nGA (38%; P = 0.039). CONCLUSION: This study confirmed that cRORA was a significant risk factor for developing GA, although its rate of progression was slightly lower compared with nGA. While requiring replication in future studies, these findings suggest that the specific features of photoreceptor degeneration used to define nGA appear important when assessing the risk of progression.

Research on the zero-calibration gauge device.

To meet the demand for the track's geometric parameter detection equipment for train speed and high-speed aerodynamics tests, a zero-calibration gauge device is designed with the centering limit, height adjustment and horizontal display function in this paper. The bending situation of the zero-calibration gauge is analyzed and the processing technology is studied, which ensures the rationality and realizability of the design of zero-calibration gauge. Then the gauge zero value and the parallelism of the working surface of zero-calibration gauge have been experimentally tested. The experimental results show that the parameter of gauge zero value is 1434.829 mm with a standard deviation of 1.4 µm. The parallelism of the two upper working surfaces is 1.1 µm, and the parallelism of the two inner working surfaces is 4 µm. Finally, the uncertainty evaluation of zero-calibration gauge is completed. The measurement uncertainty of gauge zero value is 12 µm and the measurement uncertainty of height difference is 6 µm.

Revealing the contradiction between DLVO/XDLVO theory and membrane fouling propensity for oil-in-water emulsion separation.

Oil fouling is the crucial issue for the separation of oil-in-water emulsion by membrane technology. The latest research found that the membrane fouling rate was opposite to the widely used theoretical prediction by Derjaguin-Landau-Verwey-Overbeek (DLVO) or extended DLVO (XDLVO) theory. To interpret the contradiction, the molecular dynamics was adopted to explore the molecular behavior of oil and emulsifier (Tween 80) at membrane interface with the assistance of DLVO/XDLVO theory and membrane fouling models. The decreased flux attenuation and fitting of fouling models proved that the existence of Tween 80 effectively alleviated membrane fouling. Conversely, DLVO/XDLVO theory predicted that the membrane fouling should be exacerbated with the increase of Tween 80 concentration in O/W emulsion. This contradiction originated from the different interaction energy between oil/Tween 80 molecules and polyether sulfone (PES) membrane. The favorable free energy of Tween 80 was resulted from the sulfuryl groups in PES and hydrogen bonds (O-H…O) formation further strengthened the interaction. Therefore, Tween 80 could preferentially adsorb on membrane surface and form an isolation layer by demulsification and steric hindrance and resist the aggregation of oil, which effectively alleviated membrane fouling. This study provided a new insight in the interpretation of interaction in O/W emulsion.

Choroidal signal hypertransmission on optical coherence tomography imaging: Association with development of geographic atrophy in age-related macular degeneration.

BACKGROUND: To examine the association between large choroidal signal hypertransmission ≥250 µm (LHyperT) on optical coherence tomography (OCT) with the risk of developing geographic atrophy (GA) and compare this risk with those associated with nascent geographic atrophy (nGA). METHODS: Two hundred and eighty eyes from 140 participants with bilateral large drusen and without late age-related macular degeneration (AMD) or nGA at baseline underwent OCT imaging and colour fundus photography (CFP) at 6-monthly intervals up to 5 years. OCT scans were graded for the presence of LHyperT and nGA, and CFPs were graded for the presence of GA. RESULTS: The five-year incidence of LHyperT and nGA were 37% and 27% respectively (p = 0.003), and the two-year probability of their progression to GA were 17% and 40%, respectively (p = 0.002). LHyperT and nGA explained 81% and 91% of the variance in the time to develop GA, respectively (p = 0.032), and they were both associated with a significantly higher rate of GA development compared to eyes without these lesions (adjusted hazard ratio = 110.8 and 183.2, respectively; p < 0.001 for both). CONCLUSIONS: LHyperT and nGA were both high-risk features for GA development, but the latter showed a higher rate of GA progression and explained a significantly greater proportion of the variance in the time to develop GA. As such, nGA may be a more robust surrogate endpoint than LHyperT for the conventional clinical endpoint of CFP-defined GA for intervention trials in the early stages of AMD.

Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex.

BACKGROUND: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear. METHODS: Given the known role of Ptpn23 (protein tyrosine phosphatase, nonreceptor type 23) in regulating membrane deformation, its expression in patients with dilated cardiomyopathy was determined. Taking advantage of Cre/Loxp, CRISPR/Cas9, and adeno-associated virus 9 (AAV9)-mediated in vivo gene editing, we generated cardiomyocyte-specific Ptpn23 and Actn2 (α-actinin-2, a major component of Z-discs) knockout mice. We also perturbed the DGC by using dystrophin global knockout mice (DmdE4*). MM 4-64 and Di-8-ANEPPS staining, Cav3 immunofluorescence, and transmission electron microscopy were performed to determine T-tubule structure in isolated cells and intact hearts. In addition, the assembly of the DGC with Ptpn23 and dystrophin loss of function was determined by glycerol-gradient fractionation and SDS-PAGE analysis. RESULTS: The expression level of Ptpn23 was reduced in failing hearts from dilated cardiomyopathy patients and mice. Genetic deletion of Ptpn23 resulted in disorganized T-tubules with enlarged diameters and progressive dilated cardiomyopathy without affecting sarcomere organization. AAV9-mediated mosaic somatic mutagenesis further indicated a cell-autonomous role of Ptpn23 in regulating T-tubule formation. Genetic and biochemical analyses showed that Ptpn23 was essential for the integrity of costameres, which anchor the T-tubule membrane to Z-discs, through interactions with α-actinin and dystrophin. Deletion of α-actinin altered the subcellular localization of Ptpn23 and DGCs. In addition, genetic inactivation of dystrophin caused similar T-tubule defects to Ptpn23 loss-of-function without affecting Ptpn23 localization at Z-discs. Last, inducible Ptpn23 knockout at 1 month of age showed Ptpn23 is also required for the maintenance of T-tubules in adult cardiomyocytes. CONCLUSIONS: Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.

Targeted High-Density Microperimetry Testing of Nascent Geographic Atrophy in Age-Related Macular Degeneration.

Purpose: To examine the effectiveness of a targeted high-density microperimetry testing strategy for detecting visual sensitivity abnormalities in eyes with nascent geographic atrophy (nGA) when compared with standard central microperimetry testing. Design: Observational study. Participants: Three-hundred and twenty-one eyes from 176 individuals with nonneovascular age-related macular degeneration (AMD). Methods: Thirty-five eyes from 33 participants underwent targeted high-density microperimetry testing of atrophic lesions (either nGA or geographic atrophy [GA]) within a 1.75° radius (or approximately 1000 µm diameter) region. Another cohort of 286 eyes from 143 participants with bilateral large drusen at baseline underwent standard microperimetry testing of the central 6° radius region at 6-monthly intervals for up to 36 months and thus included eyes that developed nGA and GA over the follow-up. All eyes underwent 2 tests at each visit to evaluate intrasession measurement repeatability. Main Outcome Measures: Magnitude of visual sensitivity abnormalities based on mean sensitivity (MS), pointwise sensitivity standard deviation (PSD), and the number of test locations with a threshold of ≤ 10 decibels (dB; or deep defects) in eyes with nGA, compared between eyes that underwent targeted high-density microperimetry testing and standard central microperimetry testing. Results: The magnitude of visual sensitivity abnormalities based on MS, PSD and the number of deep defects were all significantly greater in eyes with nGA using targeted, high-density microperimetry testing compared with eyes with nGA using standard central microperimetry testing (all P < 0.001) and were all significantly less than eyes with GA using targeted, high-density microperimetry testing (all P ≤ 0.004). The intrasession coefficient of repeatability, where 95% of the test-retest differences are expected to occur, for MS in eyes with atrophic changes was 0.9 dB with the targeted, high-density microperimetry testing, and 1.8 dB with standard central microperimetry testing. Conclusions: Targeted, high-density microperimetry testing enabled the detection of a significantly greater magnitude of visual sensitivity abnormalities in eyes with nGA than standard microperimetry testing. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Functional Evaluation of Retinal Pigment Epithelium and Outer Retinal Atrophy by High-Density Targeted Microperimetry Testing.

Purpose: Complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT imaging has recently been proposed to describe end-stage atrophy in age-related macular degeneration (AMD) by international consensus and expected to be associated with a dense scotoma, but such functional evidence is lacking. This study sought to examine the visual sensitivity defects associated with cRORA and to determine OCT features associated with deep defects. Design: Observational study. Participants: Sixty eyes from 53 participants, including 342 microperimetry tests over 171 study visits. Methods: Participants underwent targeted high-density threshold-based microperimetry testing of atrophic lesions (with at least incomplete RPE and outer retinal atrophy [iRORA]) with a 3.5° diameter grid. The maximum extent of signs of atrophy for all lesions was graded on OCT imaging. Main Outcome Measures: Number of deep visual sensitivity defects (threshold ≤ 10 decibels [dB]). Results: Presence of choroidal signal hypertransmission ≥ 500 µm, complete RPE loss ≥250 µm, and inner nuclear layer and outer plexiform layer subsidence, and hyporeflective wedge-shaped band (defined as nascent geographic atrophy [nGA]) ≥ 500 µm (P ≤ 0.020), but not RPE attenuation or disruption (P ≥ 0.192), were all independently associated with a significant increase in the number of deep visual sensitivity defects ≤ 10 dB. Only cRORA lesions with hypertransmission ≥ 500 µm or complete RPE loss ≥ 250 µm, or with both of these features (P < 0.001), but not lesions with only hypertransmission 250-499 µm (P = 0.303), had significantly more deep visual sensitivity defects ≤ 10 dB compared with iRORA lesions. Lesions with nGA ≥ 500 µm, irrespective of the presence of hypertransmission ≥ 500 µm and/or complete RPE loss ≥ 250 µm, also showed a higher number of deep visual sensitivity defects ≤ 10 dB compared with lesions without nGA ≥ 500 µm (P ≤ 0.011). Conclusions: Not all cRORA lesions show a difference in the number of deep visual sensitivity defects compared with iRORA. Instead, hypertransmission ≥ 500 µm, complete RPE loss ≥ 250 µm, and nGA ≥ 500 µm are all OCT features independently associated with deep visual sensitivity detects that could help inform the definition of end-stage atrophy on OCT imaging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.