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Purpose: Hyperreflective spots (HRS) are considered as spectral domain optical coherence tomography biomarkers in predicting response to intravitreal therapy (IVT) in diabetic macular edema (DME). We aimed to determine if there was a quantitative reduction in HRS following IVT in DME, if the response to antivascular endothelial growth factor (anti-VEGF) drugs was different from steroids, and if HRS-response was associated with improvement in visual acuity (VA) or reduction in central macular thickness (CMT). Methods: PubMed/MEDLINE, Scopus, ProQuest, CINAHL, Wiley online, and Web of Science were searched (between January 1, 2011 and July 1, 2020). Publication bias and heterogeneity were assessed. Meta-analysis was done using the random-effects model. Results: Totally, 1168 eyes from 19 studies were eligible for inclusion. IVT was associated with a reduction in quantitative HRS (z = -6.3, P < 0.0001). Studies, however, showed heterogeneity (I2 = 93.2%). There was no difference between anti-VEGF and steroid therapies (P = 0.23). The evidence on predicting VA and CMT outcomes were limited by the number of analyzable studies, owing to the wide variation in individual study designs, and lack of randomized controlled trials. Conclusion: We could conclude that there is a definite reduction in quantitative HRS following either form of IVT. We highlight the lacunae in the existing literature on HRS in DME and propose goals for future studies to harness the advantage of this promising biomarker. [ABSTRACT FROM AUTHOR]

We previously identified a deletion on chromosome 16p12.1 that is mostly inherited and associated with multiple neurodevelopmental outcomes, where severely affected probands carried an excess of rare pathogenic variants compared to mildly affected carrier parents. We hypothesized that the 16p12.1 deletion sensitizes the genome for disease, while "second-hits" in the genetic background modulate the phenotypic trajectory. To test this model, we examined how neurodevelopmental defects conferred by knockdown of individual 16p12.1 homologs are modulated by simultaneous knockdown of homologs of "second-hit" genes in Drosophila melanogaster and Xenopus laevis. We observed that knockdown of 16p12.1 homologs affect multiple phenotypic domains, leading to delayed developmental timing, seizure susceptibility, brain alterations, abnormal dendrite and axonal morphology, and cellular proliferation defects. Compared to genes within the 16p11.2 deletion, which has higher de novo occurrence, 16p12.1 homologs were less likely to interact with each other in Drosophila models or a human brain-specific interaction network, suggesting that interactions with "second-hit" genes may confer higher impact towards neurodevelopmental phenotypes. Assessment of 212 pairwise interactions in Drosophila between 16p12.1 homologs and 76 homologs of patient-specific "second-hit" genes (such as ARID1B and CACNA1A), genes within neurodevelopmental pathways (such as PTEN and UBE3A), and transcriptomic targets (such as DSCAM and TRRAP) identified genetic interactions in 63% of the tested pairs. In 11 out of 15 families, patient-specific "second-hits" enhanced or suppressed the phenotypic effects of one or many 16p12.1 homologs in 32/96 pairwise combinations tested. In fact, homologs of SETD5 synergistically interacted with homologs of MOSMO in both Drosophila and X. laevis, leading to modified cellular and brain phenotypes, as well as axon outgrowth defects that were not observed with knockdown of either individual homolog. Our results suggest that several 16p12.1 genes sensitize the genome towards neurodevelopmental defects, and complex interactions with "second-hit" genes determine the ultimate phenotypic manifestation. Author summary: Copy-number variants, or deletions and duplications in the genome, are associated with multiple neurodevelopmental disorders. The developmental delay-associated 16p12.1 deletion is mostly inherited, and severely affected children carry an excess of "second-hits" variants compared to mildly affected carrier parents, suggesting that additional variants modulate the clinical manifestation. We studied this "two-hit" model using Drosophila and Xenopus laevis, and systematically tested how homologs of "second-hit" genes modulate neurodevelopmental defects observed for 16p12.1 homologs. We observed that 16p12.1 homologs independently led to multiple neurodevelopmental features and weakly interacted with each other, suggesting that interactions with "second-hit" homologs potentially have a higher impact towards neurodevelopmental defects than interactions between 16p12.1 homologs. We tested 212 pairwise interactions of 16p12.1 homologs with "second-hit" homologs and genes within conserved neurodevelopmental pathways, and observed modulation of neurodevelopmental defects caused by 16p12.1 homologs in 11 out of 15 families, and 16/32 of these changes could be attributed to genetic interactions. Interestingly, we observed that SETD5 homologs interacted with homologs of MOSMO, which conferred additional neuronal phenotypes not observed with knockdown of individual homologs. We propose that the 16p12.1 deletion sensitizes the genome to multiple neurodevelopmental defects, and complex interactions with "second-hit" genes determine the clinical trajectory of the disorder. [ABSTRACT FROM AUTHOR]

While rare pathogenic copy-number variants (CNVs) are associated with both neuronal and non-neuronal phenotypes, functional studies evaluating these regions have focused on the molecular basis of neuronal defects. We report a systematic functional analysis of non-neuronal defects for homologs of 59 genes within ten pathogenic CNVs and 20 neurodevelopmental genes in Drosophila melanogaster. Using wing-specific knockdown of 136 RNA interference lines, we identified qualitative and quantitative phenotypes in 72/79 homologs, including 21 lines with severe wing defects and six lines with lethality. In fact, we found that 10/31 homologs of CNV genes also showed complete or partial lethality at larval or pupal stages with ubiquitous knockdown. Comparisons between eye and wing-specific knockdown of 37/45 homologs showed both neuronal and non-neuronal defects, but with no correlation in the severity of defects. We further observed disruptions in cell proliferation and apoptosis in larval wing discs for 23/27 homologs, and altered Wnt, Hedgehog and Notch signaling for 9/14 homologs, including AATF/Aatf, PPP4C/Pp4-19C, and KIF11/Klp61F. These findings were further supported by tissue-specific differences in expression patterns of human CNV genes, as well as connectivity of CNV genes to signaling pathway genes in brain, heart and kidney-specific networks. Our findings suggest that multiple genes within each CNV differentially affect both global and tissue-specific developmental processes within conserved pathways, and that their roles are not restricted to neuronal functions. Author summary: Rare copy-number variants (CNVs), or large deletions and duplications in the genome, are associated with both neuronal and non-neuronal clinical features. Previous functional studies for these disorders have primarily focused on understanding the cellular mechanisms for neurological and behavioral phenotypes. To understand how genes within these CNVs contribute to developmental defects in non-neuronal tissues, we assessed 79 homologs of CNV and known neurodevelopmental genes in Drosophila models. We found that most homologs showed developmental defects when knocked down in the adult fly wing, ranging from mild size changes to severe wrinkled wings or lethality. Although a majority of tested homologs showed defects when knocked down specifically in wings or eyes, we found no correlation in the severity of the observed defects in these two tissues. A subset of the homologs showed disruptions in cellular processes in the developing fly wing, including alterations in cell proliferation, apoptosis, and cellular signaling pathways. Furthermore, human CNV genes also showed differences in gene expression patterns and interactions with signaling pathway genes across multiple human tissues. Our findings suggest that genes within CNV disorders affect global developmental processes in both neuronal and non-neuronal tissues. [ABSTRACT FROM AUTHOR]

Google Play Store was used to search for eye care-related applications the android simulator using various general terms related to eye care to review and categorize various interactive eye care-related applications in android platform from the details available in the application website. Data collected from application description and application developer's webpage include target audience, category of apps, estimated number of downloads, average user rating, involvement of eye care professionals in developing the application, and cost of the app. All these data were collected only from the details provided in the application website considering on online user perspective and the developers were not contacted to collect any other details. In total, 475 applications were identified and grouped into 13 categories depending on the type of service the application provide. Out of which, only 107 (22.53%) applications had mentioned about the eye care professional involvement in their design or development of the application. The applications were also stratified according to the target audience, and many had no user rating with very few downloads. The lack of evidence-based principles and standardization of application development should be taken into consideration to avoid its negative impact on the community, especially in eye care. [ABSTRACT FROM AUTHOR]

Development of neuronal connections is spatially and temporally controlled by extracellular cues which often activate their cognate cell surface receptors and elicit localized cellular responses. Here, we demonstrate the use of an optogenetic tool to activate receptor signaling locally to induce actin-mediated growth cone remodeling in neurons. Based on the light-induced interaction of light between Cryptochrome 2 (CRY2) and CIB1, we generated a bicistronic vector to co-expresses CRY2 fused to the intracellular domain of a guidance receptor and a membrane-anchored CIB1. When expressed in primary neurons, activation of the growth inhibitory PlexA4 receptor induced growth cone collapse, while activation of the growth stimulating TrkA receptor increased growth cone size. Moreover, local activation of either receptor not only elicited the predicted response in light-activated growth cones, but also an opposite response in neighboring no-light growth cones of the same neuron. Finally, this tool was used to reorient growth cones towards or away from light activation and to stimulate local actin polymerization for branch initiation along axonal shafts. These studies demonstrate the use of an optogenetic tool for precise spatial and temporal control of receptor signaling in neurons and support its future application in investigating cellular mechanisms of neuronal development and plasticity. [Media: see text] [Media: see text] [Media: see text] [Media: see text].

Purpose: This study explored early (contrast discrimination) and intermediate (global form perception) visual processing in primary subtypes of glaucoma: primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). We aimed to understand early and intermediate visual processing in POAG and PACG, matched for similar visual field defect severity., Methods: Early visual processing was measured using a contrast discrimination task described by Porkorny and Smith (1997), and intermediate processing using a global form perception task using glass pattern coherence thresholds. Thresholds were determined centrally and at a single midperipheral location (12.5°) in a quadrant without visual field defects. Controls were tested in corresponding quadrants to individuals with glaucoma., Results: Sixty participants (20 POAG, 20 PACG, and 20 age-matched controls), aged 50 to 77 years, were included. Visual field defects were matched between POAG and PACG, with mean deviation values of -6.53 ± 4.46 (range: -1.5 to -16.85) dB and -6.2 ± 4.24 (range: -1.37 to -16.42) dB, respectively. Two-Way ANOVA revealed significant differences in thresholds between the glaucoma groups and the control group for both contrast discrimination and global form perception tasks, with higher thresholds in the glaucoma groups. Post hoc analyses showed no significant contrast discrimination difference between POAG and PACG, but POAG had significantly higher thresholds than PACG for form perception., Conclusions: In form perception, POAG showed slightly worse performance than PACG, suggesting that individuals with POAG may experience more severe functional damage than PACG of similar visual field severity.