: This is the first review article examining literature specific to the use of corneal cross-linking (CXL) to treat pellucid marginal degeneration (PMD). : CXL appears to be an effective treatment that may halt the progression of PMD to stabilize vision. This could postpone or eliminate the need for corneal transplantation in the management of these patients. Furthermore, combining CXL with keratorefractive surgery in a single procedure has been shown to be safe and successful in improving vision in PMD patients. : The data reported in literature is limited at this time, consisting mostly of retrospective studies with short term follow up. Further research is needed to evaluate refractive effects of combined CXL and excimer laser procedures.

PURPOSE OF REVIEW: Immune checkpoint inhibitors are currently an exceedingly powerful tool in the management of hitherto incurable malignancies and their use in clinical practice is expected to increase in the near future. The purpose of this review is to discuss the current medical uses of checkpoint inhibitors with a focus on their neuro-ophthalmic side-effects. RECENT FINDINGS: Immune checkpoint inhibitors have emerged as a promising breakthrough in the treatment of several tumor types. However, these targeted therapies can induce a wide range of immune-related ophthalmic and neuro-ophthalmic toxicities. It is important for neuro-ophthamologists to promptly recognize and manage these adverse events that can potentially threaten vision. SUMMARY: There are currently seven FDA-approved immune checkpoint inhibitors and several ones are under investigation. In general, immunotherapy is considered a well tolerated, safe and efficacious treatment option for many cancer patients. Nevertheless, because of their unique mechanism of action, these molecules can alter the immune response and result in immune-related adverse effects in almost every organ with an estimated incidence of ophthalmic side effects in this patient population of less than 1%.

Importance: Genetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations. Objective: To investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis. Design, Setting, and Participants: A cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018. Main Outcomes and Measures: Association of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression. Results: The GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10-66). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = -0.36; 95% CI, -0.56 to -0.16; P = 4.0 × 10-4). Individuals in the top 5% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 × 10-4). Conclusions and Relevance: A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.

Searching for a "Q" among "O"s is easier than the opposite search (Treisman & Gormican in Psychological Review, 95, 15-48, 1988). In many cases, such "search asymmetries" occur because it is easier to search when a target is defined by the presence of a feature (i.e., the line terminator defining the tail of the "Q"), rather than by its absence. Treisman proposed that features that produce a search asymmetry are "basic" features in visual search (Treisman & Gormican in Psychological Review, 95, 15-48, 1988; Treisman & Souther in Journal of Experimental Psychology: General, 114, 285-310, 1985). Other stimulus attributes, such as color, orientation, and motion, have been found to produce search asymmetries (Dick, Ullman, & Sagi in Science, 237, 400-402, 1987; Treisman & Gormican in Psychological Review, 95, 15-48, 1988; Treisman & Souther in Journal of Experimental Psychology: General, 114, 285-310, 1985). Other stimulus properties, such as facial expression, produce asymmetries because one type of item (e.g., neutral faces) demands less attention in search than another (e.g., angry faces). In the present series of experiments, search for a rolling target among spinning distractors proved to be more efficient than searching for a spinning target among rolling distractors. The effect does not appear to be due to differences in physical plausibility, direction of motion, or texture movement. Our results suggest that the spinning stimuli demand less attention, making search through spinning distractors for a rolling target easier than the opposite search.

The provided database of tracked eye movements was collected using an infra-red, video-camera Eyelink 1000 system, from 95 participants as they viewed 'Hollywood' video clips. There are 206 clips of 30-s and eleven clips of 30-min for a total viewing time of about 60 hours. The database also provides the raw 30-s video clip files, a short preview of the 30-min clips, and subjective ratings of the content of the videos for each in categories: (1) genre; (2) importance of human faces; (3) importance of human figures; (4) importance of man-made objects; (5) importance of nature; (6) auditory information; (7) lighting; and (8) environment type. Precise timing of the scene cuts within the clips and the democratic gaze scanpath position (center of interest) per frame are provided. At this time, this eye-movement dataset has the widest age range (22-85 years) and is the third largest (in recorded video viewing time) of those that have been made available to the research community. The data-acquisition procedures are described, along with participant demographics, summaries of some common eye-movement statistics, and highlights of research topics in which the database was used. The dataset is freely available in the Open Science Framework repository (link in the manuscript) and can be used without restriction for educational and research purposes, providing that this paper is cited in any published work.

Enhancing medical student education in ophthalmology can lead to improved eye health care delivery and patient outcomes across all primary care and specialty disciplines., There has been a resurgence in interest in delivering high quality ophthalmic medical student education. This educational revival is both timely and topical. A general consensus has emerged that ,rather than focusing solely on increasing teaching time, strategies are needed to focus on how to optimize the limited time allotted to ophthalmology. All physicians should be prepared to provide competent and confident ophthalmic care based upon exciting innovations in ophthalmic curricula content, teaching methodologies, instructional design, learning objectives and assessment methods. We provide an update on new and innovative ophthalmic teaching and learning practices. We critically appraise and summarize novel educational strategies from around the world that can be universally applicable in enhancing ophthalmology teaching in medical school curricula. It is our hope that, while there is marginalization of ophthalmology training, these strategies can be used to further improve teaching and learning in the limited time available in medical curricula and provide an impetus for further research and innovations in teaching ophthalmology to medical students.

Keratoconus (KC) is a multi-factorial corneal ectasia with unknown etiology affecting approximately 1:2000 people worldwide. Dysregulated gene expression, using RNA-Seq technology, have been reported in KC corneal tissue. However, the differential expression of genes, in KC corneal stromal cells have been widely ignored. We utilized mRNA-Seq to analyze gene expression in primary human corneal stromal cells derived from five non-Keratoconus healthy (HCF) and four Keratoconus (HKC) donors. Selected genes were further validated using real time PCR (RT-PCR). We have identified 423 differentially expressed genes with 187 down- and 236 up-regulated in KC-affected corneal stromal cells. Gene ontology analysis using WebGestalt indicates the enrichment of genes involved in cell migration, extracellular matrix, adherens junction, and MAPK signaling. Our protein-protein interaction network analysis identified several network seeds, such as EGFR, NEDD4, SNTA1, LGALS3BP, HSPB1, SDC2, MME, and HIF1A. Our work provides an otherwise unknown information on the transcriptional changes in HKCs, and reveals critical mechanisms of the cellular compartment. It also highlights the importance of human-based in vitro studies on a disease that currently lacks strong biomarkers and animal models.

Epithelial to mesenchymal transition (EMT) plays an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). We aimed to demonstrate the role of mouse double minute 2 (MDM2) in transforming growth factor-beta 2 (TGF-β2)-induced EMT in human retinal pigment epithelial cells (RPEs). Immunofluorescence was used to assess MDM2 expression in epiretinal membranes (ERMs) from patients with PVR. A single guide (sg)RNA targeting the second promoter of MDM2 was cloned into a mutant lentiviral Clustered Regularly Interspaced Short Palindromic Repeats (lentiCRISPR) v2 (D10A and H840A) vector for expressing nuclease dead Cas9 (dCas9)/MDM2-sgRNA in RPEs. In addition, MDM2-sgRNA was also cloned into a pLV-sgRNA-dCas9-Kruppel associated box (KRAB) vector for expressing dCas9 fused with a transcriptional repressor KRAB/MDM2-sgRNA. TGF-β2-induced expression of MDM2 and EMT biomarkers were assessed by quantitative polymerase chain reaction (q-PCR), western blot, or immunofluorescence. Wound-healing and proliferation assays were used to evaluate the role of MDM2 in TGF-β2-induced responses in RPEs. As a result, we found that MDM2 was expressed obviously in ERMs, and that TGF-β2-induced expression of MDM2 and EMT biomarkers Fibronectin, N-cadherin and Vimentin in RPEs. Importantly, we discovered that the dCas9/MDM2-sgRNA blocked TGF-β2-induced expression of MDM2 and the EMT biomarkers without affecting their basal expression, whereas the dCas9-KRAB/MDM2-sgRNA suppressed basal MDM2 expression in RPEs. These cells could not be maintained continuously because their viability was greatly reduced. Next, we found that Nutlin-3, a small molecule blocking the interaction of MDM2 with p53, inhibited TGF-β2-induced expression of Fibronectin and N-cadherin but not Vimentin in RPEs, indicating that MDM2 functions in both p53-dependent and -independent pathways. Finally, our experimental data demonstrated that dCas9/MDM2-sgRNA suppressed TGF-β2-dependent cell proliferation and migration without disturbing the unstimulated basal activity. In conclusion, the CRISPR/dCas9 capability for blocking TGF-β2-induced expression of MDM2 and EMT biomarkers can be exploited for a therapeutic approach to PVR.