ITF2357 regulates NF-κB signaling pathway to protect barrier integrity in retinal pigment epithelial cells.

The robust integrity of the retinal pigment epithelium (RPE), which contributes to the outer brain retina barrier (oBRB), is compromised in several retinal degenerative and vascular disorders, including diabetic macular edema (DME). This study evaluates the role of a new generation of histone deacetylase inhibitor (HDACi), ITF2357, in regulating outer blood-retinal barrier function and investigates the underlying mechanism of action in inhibiting TNFα-induced damage to RPE integrity. Using the immortalized RPE cell line (ARPE-19), ITF2357 was found to be non-toxic between 50 nM and 5 µM concentrations. When applied as a pre-treatment in conjunction with an inflammatory cytokine, TNFα, the HDACi was safe and effective in preventing epithelial permeability by fortifying tight junction (ZO-1, -2, -3, occludin, claudin-1, -2, -3, -5, -19) and adherens junction (E-cadherin, Nectin-1) protein expression post-TNFα stress. Mechanistically, ITF2357 depicted a late action at 24 h via attenuating IKK, IκBα, and p65 phosphorylation and ameliorated the expression of IL-1ß, IL-6, and MCP-1. Also, ITF2357 delayed IκBα synthesis and turnover. The use of Bay 11-7082 and MG132 further uncovered a possible role for ITF2357 in non-canonical NF-κB activation. Overall, this study revealed the protection effects of ITF2357 by regulating the turnover of tight and adherens junction proteins and modulating NF-κB signaling pathway in the presence of an inflammatory stressor, making it a potential therapeutic application for retinal vascular diseases such as DME with compromised outer blood-retinal barrier.

Sensory modality and spoken language shape reading network in blind readers of Braille.

The neural basis of reading is highly consistent across many languages and scripts. Are there alternative neural routes to reading? How does the sensory modality of symbols (tactile vs. visual) influence their neural representations? We examined these questions by comparing reading of visual print (sighted group, n = 19) and tactile Braille (congenitally blind group, n = 19). Blind and sighted readers were presented with written (words, consonant strings, non-letter shapes) and spoken stimuli (words, backward speech) that varied in word-likeness. Consistent with prior work, the ventral occipitotemporal cortex (vOTC) was active during Braille and visual reading. A posterior/anterior vOTC word-form gradient was observed only in sighted readers with more anterior regions preferring larger orthographic units (words). No such gradient was observed in blind readers. Consistent with connectivity predictions, in blind compared to sighted readers, posterior parietal cortices were recruited to a greater degree and contained word-preferring patches. Lateralization of Braille in blind readers was predicted by laterality of spoken language and reading hand. The effect of spoken language increased along a cortical hierarchy, whereas effect of reading hand waned. These results suggested that the neural basis of reading is influenced by symbol modality and spoken language and support connectivity-based views of cortical function.

SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.

Shared understanding of color among sighted and blind adults.

Empiricist philosophers such as Locke famously argued that people born blind might learn arbitrary color facts (e.g., marigolds are yellow) but would lack color understanding. Contrary to this intuition, we find that blind and sighted adults share causal understanding of color, despite not always agreeing about arbitrary color facts. Relative to sighted people, blind individuals are less likely to generate "yellow" for banana and "red" for stop sign but make similar generative inferences about real and novel objects' colors, and provide similar causal explanations. For example, people infer that two natural kinds (e.g., bananas) and two artifacts with functional colors (e.g., stop signs) are more likely to have the same color than two artifacts with nonfunctional colors (e.g., cars). People develop intuitive and inferentially rich "theories" of color regardless of visual experience. Linguistic communication is more effective at aligning intuitive theories than knowledge of arbitrary facts.

Trainable segmentation for transmission electron microscope images of inorganic nanoparticles.

We present a trainable segmentation method implemented within the python package ParticleSpy. The method takes user labelled pixels, which are used to train a classifier and segment images of inorganic nanoparticles from transmission electron microscope images. This implementation is based on the trainable Waikato Environment for Knowledge Analysis (WEKA) segmentation, but is written in python, allowing a large degree of flexibility and meaning it can be easily expanded using other python packages. We find that trainable segmentation offers better accuracy than global or local thresholding methods and requires as few as 100 user-labelled pixels to produce an accurate segmentation. Trainable segmentation presents a balance of accuracy and training time between global/local thresholding and neural networks, when used on transmission electron microscope images of nanoparticles. We also quantitatively investigate the effectiveness of the components of trainable segmentation, its filter kernels and classifiers, in order to demonstrate the use cases for the different filter kernels in ParticleSpy and the most accurate classifiers for different data types. A set of filter kernels is identified that are effective in distinguishing particles from background but that retain dissimilar features. In terms of classifiers, we find that different classifiers perform optimally for different image contrast; specifically, a random forest classifier performs best for high-contrast ADF images, but that QDA and Gaussian Naïve Bayes classifiers perform better for low-contrast TEM images.

Measurement of the size, shape and composition of nanoparticles is routinely performed using transmission electron microscopy and related techniques. Typically, distinguishing particles from the background in an image is performed using the intensity of each pixel, creating two sets of pixels to separate particles from background. However, this separation of intensity can be difficult if the contrast in an image is low, or if the intensity of the background varies significantly. In this study, an approach that takes into account additional image features (such as boundaries and texture) was investigated to study electron microscope images of metallic nanoparticles. In this 'trainable segmentation' approach, the user labels examples of particle and background pixels in order to train a machine learning algorithm to distinguish between particles and background. The performance of different machine learning algorithms was investigated, in addition to the effect of using different features to aid the segmentation. Overall, a trainable segmentation approach was found to perform better than use of an intensity threshold to distinguish between particles and background in electron microscope images.

Evaluation of a self-imaging SD-OCT system designed for remote home monitoring.

PURPOSE: To compare identification rates of retinal fluid of the Notal Vision Home Optical Coherence Tomography (OCT) device (NVHO) when used by people with age-related macular degeneration (AMD) to those captured by a commercial OCT. METHODS: Prospective, cross-sectional study where patients underwent commercial OCT imaging followed by self-imaging with either the NVHO 2.5 or the NVHO 3 in clinic setting. Outcomes included patients' ability to acquire analyzable OCT images with the NVHO and to compare those with commercial images. RESULTS: Successful images were acquired with the NVHO 2.5 in 469/531 eyes (88%) in 264/290 subjects (91%) with the mean (SD) age of 78.8 (8.8); 153 (58%) were female with median visual acuity (VA) of 20/40. In the NVHO 3 cohort, 69 eyes of 45 subjects (93%) completed the self-imaging. Higher rates of successful imaging were found in eyes with VA ≥ 20/320. Positive percent agreement/negative percent agreement for detecting the presence of subretinal and/or intraretinal fluid when reviewing for fluid in three repeated volume scans were 97%/95%, respectively for the NVHO v3. CONCLUSION: Self-testing with the NVHO can produce high quality images suitable for fluid identification by human graders, suggesting the device may be able to complement standard-of-care clinical assessments and treatments.

Knowledge of animal appearance among sighted and blind adults.

How does first-person sensory experience contribute to knowledge? Contrary to the suppositions of early empiricist philosophers, people who are born blind know about phenomena that cannot be perceived directly, such as color and light. Exactly what is learned and how remains an open question. We compared knowledge of animal appearance across congenitally blind (n = 20) and sighted individuals (two groups, n = 20 and n = 35) using a battery of tasks, including ordering (size and height), sorting (shape, skin texture, and color), odd-one-out (shape), and feature choice (texture). On all tested dimensions apart from color, sighted and blind individuals showed substantial albeit imperfect agreement, suggesting that linguistic communication and visual perception convey partially redundant appearance information. To test the hypothesis that blind individuals learn about appearance primarily by remembering sighted people's descriptions of what they see (e.g., "elephants are gray"), we measured verbalizability of animal shape, texture, and color in the sighted. Contrary to the learn-from-description hypothesis, blind and sighted groups disagreed most about the appearance dimension that was easiest for sighted people to verbalize: color. Analysis of disagreement patterns across all tasks suggest that blind individuals infer physical features from non-appearance properties of animals such as folk taxonomy and habitat (e.g., bats are textured like mammals but shaped like birds). These findings suggest that in the absence of sensory access, structured appearance knowledge is acquired through inference from ontological kind.

Improved health care transition for young adults with developmental disabilities referred from designated transition clinics.

PURPOSE: Young adults with intellectual/developmental disabilities (YAIDD) are a vulnerable population during HCT due to their complex care coordination and adaptive needs, yet factors associated with transition preparedness are not well defined. We aimed to determine factors associated with health care transition (HCT) preparation satisfaction for YAIDD establishing care with an adult medical home. DESIGN AND METHODS: 408 YAIDD or their families completed the HCT Feedback Survey 2.0 upon establishing adult care. Logistic regression models were used to determine associations between a composite of six HCT Feedback Survey questions that most correlated with the 2019 National Survey of Children's Health transition questions. RESULTS: YADD who had HCT preparation visits with a designated HCT clinic were 9 times more likely to have met all six composite HCT criteria after controlling for the number of technologies required and race/ethnicity (adj OR 9.04, 95% CI: 4.35, 18.76) compared to those referred from the community. Compared to patients who were referred from the community, the odds of feeling very prepared versus somewhat or not prepared were 3.7 times higher (adj OR 3.73, 95% CI: 1.90, 7.32) among patients referred from a designated HCT program. CONCLUSIONS: YAIDD who participated in a structured HCT program prior to transfer to adult care experienced higher transition preparation satisfaction. PRACTICAL IMPLICATIONS: A structured HCT clinic model to prepare adolescents with DD for transition to adult care may improve HCT preparation satisfaction for this population.

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup.

PURPOSE: To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings. DESIGN: Evaluation of diagnostic test results. PARTICIPANTS: Panel of retina specialists. METHODS: As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. MAIN OUTCOME MEASURES: Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. RESULTS: The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%. CONCLUSIONS: We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Pneumonia and respiratory infections in Down syndrome: A scoping review of the literature.

Pneumonia and respiratory infections impact infants and children with Down syndrome; pneumonia is a leading cause of mortality in adults with Down syndrome. We aimed to review the literature to evaluate gaps and address key questions. A series of key questions were formulated a priori to inform the search strategy and review process; addressed prevalence, severity, etiology, risk factors, preventive methods, screening, and financial costs, potential benefits or harms of screening. Using the National Library of Medicine database, PubMed, detailed literature searches on pneumonia and respiratory infections in Down syndrome were performed. Previously identified review articles were also assessed. The quality of available evidence was then evaluated and knowledge gaps were identified. Forty-two relevant original articles were identified which addressed at least one key question. Study details including research design, internal validity, external validity, and relevant results are presented. Pneumonia and respiratory infections are more prevalent and more severe in individuals with Down syndrome compared to healthy controls through literature review, yet there are gaps in the literature regarding the etiology of pneumonia, the infectious organism, risk factors for infection, and to guide options for prevention and screening. There is urgent need for additional research studies in Down syndrome, especially in the time of the current COVID-19 pandemic.

Filamentary High-Resolution Electrical Probes for Nanoengineering.

Confining electric fields to a nanoscale region is challenging yet crucial for applications such as high-resolution probing of electrical properties of materials and electric-field manipulation of nanoparticles. State-of-the-art techniques involving atomic force microscopy typically have a lateral resolution limit of tens of nanometers due to limitations in the probe geometry and stray electric fields that extend over space. Engineering the probes is the most direct approach to improving this resolution limit. However, current methods to fabricate high-resolution probes, which can effectively confine the electric fields laterally, involve expensive and sophisticated probe manipulation, which has limited the use of this approach. Here, we demonstrate that nanoscale phase switching of configurable thin films on probes can result in high-resolution electrical probes. These configurable coatings can be both germanium-antimony-tellurium (GST) as well as amorphous-carbon, materials known to undergo electric field-induced nonvolatile, yet reversible switching. By forming a localized conductive filament through phase transition, we demonstrate a spatial resolution of electrical field beyond the geometrical limitations of commercial platinum probes (i.e., an improvement of ∼48%). We then utilize these confined electric fields to manipulate nanoparticles with single nanoparticle precision via dielectrophoresis. Our results advance the field of nanomanufacturing and metrology with direct applications for pick and place assembly at the nanoscale.

Folding of the ß-Barrel Membrane Protein OmpA into Nanodiscs.

Nanodiscs (NDs) are an excellent alternative to small unilamellar vesicles (SUVs) for studies of membrane protein structure, but it has not yet been shown that membrane proteins are able to spontaneously fold and insert into a solution of freely diffusing NDs. In this article, we present SDS-PAGE differential mobility studies combined with fluorescence, circular dichroism, and ultraviolet resonance Raman spectroscopy to confirm the spontaneous folding of outer membrane protein A (OmpA) into preformed NDs. Folded OmpA in NDs was incubated with Arg-C protease, resulting in the digestion of OmpA to membrane-protected fragments with an apparent molecular mass of ∼26 kDa (major component) and ∼24 kDa (minor component). The OmpA folding yields were greater than 88% in both NDs and SUVs. An OmpA adsorbed intermediate on NDs could be isolated at low temperature and induced to fold via an increase in temperature, analogous to the temperature-jump experiments on SUVs. The circular dichroism spectra of OmpA in NDs and SUVs were similar and indicated ß-barrel secondary structure. Further evidence of OmpA folding into NDs was provided by ultraviolet resonance Raman spectroscopy, which revealed the intense 785 cm-1 structural marker for folded OmpA in NDs. The primary difference between folding in NDs and SUVs was the kinetics; the rate of folding was two- to threefold slower in NDs compared to in SUVs, and this decreased rate can tentatively be attributed to the properties of NDs. These data indicate that NDs may be an excellent alternative to SUVs for folding experiments and offer benefits of optical clarity, sample homogeneity, control of ND:protein ratios, and greater stability.

The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase.

For three decades, the LPL-specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.

From shape to meaning: Evidence for multiple fast feedforward hierarchies of concept processing in the human brain.

A number of fMRI studies have provided support for the existence of multiple concept representations in areas of the brain such as the anterior temporal lobe (ATL) and inferior parietal lobule (IPL). However, the interaction among different conceptual representations remains unclear. To better understand the dynamics of how the brain extracts meaning from sensory stimuli, we conducted a human high-density electroencephalography (EEG) study in which we first trained participants to associate pseudowords with various animal and tool concepts. After training, multivariate pattern classification of EEG signals in sensor and source space revealed the representation of both animal and tool concepts in the left ATL and tool concepts within the left IPL within 250 â€‹ms. Finally, we used Granger Causality analyses to show that orthography-selective sensors directly modulated activity in the parietal-tool selective cluster. Together, our results provide evidence for distinct but parallel "perceptual-to-conceptual" feedforward hierarchies in the brain.

Fundamentals of artificial intelligence for ophthalmologists.

PURPOSE OF REVIEW: As artificial intelligence continues to develop new applications in ophthalmic image recognition, we provide here an introduction for ophthalmologists and a primer on the mechanisms of deep learning systems. RECENT FINDINGS: Deep learning has lent itself to the automated interpretation of various retinal imaging modalities, including fundus photography and optical coherence tomography. Convolutional neural networks (CNN) represent the primary class of deep neural networks applied to these image analyses. These have been configured to aid in the detection of diabetes retinopathy, AMD, retinal detachment, glaucoma, and ROP, among other ocular disorders. Predictive models for retinal disease prognosis and treatment are also being validated. SUMMARY: Deep learning systems have begun to demonstrate a reliable level of diagnostic accuracy equal or better to human graders for narrow image recognition tasks. However, challenges regarding the use of deep learning systems in ophthalmology remain. These include trust of unsupervised learning systems and the limited ability to recognize broad ranges of disorders.

Development of the Visual Word Form Area Requires Visual Experience: Evidence from Blind Braille Readers.

Learning to read causes the development of a letter- and word-selective region known as the visual word form area (VWFA) within the human ventral visual object stream. Why does a reading-selective region develop at this anatomical location? According to one hypothesis, the VWFA develops at the nexus of visual inputs from retinotopic cortices and linguistic input from the frontotemporal language network because reading involves extracting linguistic information from visual symbols. Surprisingly, the anatomical location of the VWFA is also active when blind individuals read Braille by touch, suggesting that vision is not required for the development of the VWFA. In this study, we tested the alternative prediction that VWFA development is in fact influenced by visual experience. We predicted that in the absence of vision, the "VWFA" is incorporated into the frontotemporal language network and participates in high-level language processing. Congenitally blind (n = 10, 9 female, 1 male) and sighted control (n = 15, 9 female, 6 male), male and female participants each took part in two functional magnetic resonance imaging experiments: (1) word reading (Braille for blind and print for sighted participants), and (2) listening to spoken sentences of different grammatical complexity (both groups). We find that in blind, but not sighted participants, the anatomical location of the VWFA responds both to written words and to the grammatical complexity of spoken sentences. This suggests that in blindness, this region takes on high-level linguistic functions, becoming less selective for reading. More generally, the current findings suggest that experience during development has a major effect on functional specialization in the human cortex.SIGNIFICANCE STATEMENT The visual word form area (VWFA) is a region in the human cortex that becomes specialized for the recognition of written letters and words. Why does this particular brain region become specialized for reading? We tested the hypothesis that the VWFA develops within the ventral visual stream because reading involves extracting linguistic information from visual symbols. Consistent with this hypothesis, we find that in congenitally blind Braille readers, but not sighted readers of print, the VWFA region is active during grammatical processing of spoken sentences. These results suggest that visual experience contributes to VWFA specialization, and that different neural implementations of reading are possible.

Multivariate Pattern Analysis Reveals Category-Related Organization of Semantic Representations in Anterior Temporal Cortex.

UNLABELLED: The neural substrates of semantic representation have been the subject of much controversy. The study of semantic representations is complicated by difficulty in disentangling perceptual and semantic influences on neural activity, as well as in identifying stimulus-driven, "bottom-up" semantic selectivity unconfounded by top-down task-related modulations. To address these challenges, we trained human subjects to associate pseudowords (TPWs) with various animal and tool categories. To decode semantic representations of these TPWs, we used multivariate pattern classification of fMRI data acquired while subjects performed a semantic oddball detection task. Crucially, the classifier was trained and tested on disjoint sets of TPWs, so that the classifier had to use the semantic information from the training set to correctly classify the test set. Animal and tool TPWs were successfully decoded based on fMRI activity in spatially distinct subregions of the left medial anterior temporal lobe (LATL). In addition, tools (but not animals) were successfully decoded from activity in the left inferior parietal lobule. The tool-selective LATL subregion showed greater functional connectivity with left inferior parietal lobule and ventral premotor cortex, indicating that each LATL subregion exhibits distinct patterns of connectivity. Our findings demonstrate category-selective organization of semantic representations in LATL into spatially distinct subregions, continuing the lateral-medial segregation of activation in posterior temporal cortex previously observed in response to images of animals and tools, respectively. Together, our results provide evidence for segregation of processing hierarchies for different classes of objects and the existence of multiple, category-specific semantic networks in the brain. SIGNIFICANCE STATEMENT: The location and specificity of semantic representations in the brain are still widely debated. We trained human participants to associate specific pseudowords with various animal and tool categories, and used multivariate pattern classification of fMRI data to decode the semantic representations of the trained pseudowords. We found that: (1) animal and tool information was organized in category-selective subregions of medial left anterior temporal lobe (LATL); (2) tools, but not animals, were encoded in left inferior parietal lobe; and (3) LATL subregions exhibited distinct patterns of functional connectivity with category-related regions across cortex. Our findings suggest that semantic knowledge in LATL is organized in category-related subregions, providing evidence for the existence of multiple, category-specific semantic representations in the brain.

CLINICAL EVALUATION OF THE RAPID ACCESS VITREAL INJECTION GUIDE: A Handheld Instrument for Assisting Intravitreal Injections.

PURPOSE: The Rapid Access Vitreal Injection (RAVI) guide combines the function of an eyelid speculum and measuring caliper into a single instrument for assisting intravitreal injections. This study clinically evaluated the RAVI guide with respect to patient acceptance, complication rates, and operative goals. METHODS: A prospective study was performed on 54 patients undergoing intravitreal injections using the RAVI guide (n = 32) or the speculum/caliper (n = 22). Device-related pain was assessed using the Wong-Baker scoring system, scaled from 0 (no pain) to 10 (agonizing pain). RESULTS: Mean device-related pain score did not differ significantly between the 2 groups, with scores of 0.6 and 0.7 for the RAVI guide and speculum groups, respectively. The rate of significant pain (score of ≥2) was twice as high in the speculum group (7 of 22, 32%) compared with the RAVI guide group (5 of 32, 16%), but this difference was not statistically significant (P = 0.19, Fisher's exact test). Operative goals of avoiding needle touch to lashes/lids and guiding needle insertion to the intended site were achieved in all patients. CONCLUSION: The RAVI guide appeared equivalent to the eyelid speculum in achieving operative goals, with similarly low pain scores. It has the potential for facilitating efficient, accurate, and safe intravitreal injections.