Intergrader Agreement in Grading Optical Coherence Tomography Morphologic Features in Eyes With Intermediate Nonexudative Age-Related Macular Degeneration.

Purpose: To determine the reliability of a nine-point summary scale for grading intermediate age-related macular degeneration (AMD) image morphologic features based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Methods: Two trained graders independently divided spectral domain-optical coherence tomography (SD-OCT) scans into nine subfields and then graded each subfield for the presence of intraretinal hyperreflective foci (HRF), reticular pseudodrusen (RPD), and incomplete or complete retinal pigment epithelium and outer retinal atrophy (iRORA or cRORA). Grading results were assessed by summing the subfield grades into a nine-point summary score and also by using an eye-level binary grade for presence of the finding in any subfield. Gwet's first-order agreement coefficient (AC1) was calculated to assess intergrader agreement. Results: Images of 79 eyes from 52 patients were evaluated. Intergrader agreement was higher when the OCT grades were summarized with a nine-point summary score (Gwet's AC1 0.92, 0.89, 0.99, and 0.99 for HRF, RPD, iRORA, and cRORA, respectively) compared with the eye-level binary grade (Gwet's AC1 0.75, 0.76, 0.97, and 0.96 for HRF, RPD, iRORA, and cRORA, respectively), with significant differences detected for HRF and RPD. Conclusions: The use of a nine-point summary score showed higher reliability in grading when compared to the binary subfield- and eye-level data, and thus may offer more precise estimation of AMD disease staging. Translational Relevance: These findings suggest that a nine-point summary score could be a useful means of disease staging by using findings on OCT in clinical studies of AMD.

Health Disparity Curricula for Ophthalmology Residents: Current Landscape, Barriers, and Needs.

Background Social determinants of health play a critical role in visual health outcomes. Yet, there exists no structured curriculum for ophthalmology residents to identify and address health disparities relevant to eye care or no a standard assessment of health disparities education within ophthalmology residency programs. This study aims to characterize current health disparity curricula in ophthalmology residency programs in the United States, determine resident confidence in addressing health disparities in the clinical setting, and identify perceived barriers and needs of program directors (PDs) and residents in this area. Design This was a cross-sectional survey study. Methods A closed-ended questionnaire with comments was distributed to the Accreditation Council for Graduate Medical Education-accredited ophthalmology residency PDs and residents in April 2021 and May 2022. The questionnaire solicited characteristics of any existing health disparity curricula, PD and resident perceptions of these curricula, and residents' experience with and confidence in addressing health disparities in the delivery of patient care. Results In total, 29 PDs and 96 residents responded. Sixty-six percent of PDs stated their program had a formal curriculum compared to fifty-three percent of residents. Forty-one percent of PDs and forty-one percent of residents stated their program places residents in underserved care settings for more than 50% of their training. Most residents (72%) were confident in recognizing health disparities. Sixty-six percent were confident in managing care in the face of disparities and fifty-nine percent felt they know how to utilize available resources. Residents were most concerned with the lack of access to resources to help patients. Forty-five percent of PDs felt the amount of time dedicated to health disparities education was adequate. Forty-nine percent of residents reported they felt the amount of training they received on health disparities to be adequate. The top barrier to curriculum development identified by PDs was the availability of trained faculty to teach. Time in the curriculum was a major barrier identified by residents. Conclusions Roughly half of ophthalmology residency programs who responded had a health disparity curriculum; however, both PDs and residents felt inadequate time is dedicated to such education. National guidance on structured health disparity curricula for ophthalmology residents may be warranted as a next step.

Perceived Barriers to Increasing Diversity within Oculofacial Plastic Surgery.

Purpose Physician diversity is limited in ophthalmology and oculofacial plastic surgery. Determination of barriers within the application process for oculofacial plastic surgery may help target efforts to improve the recruitment of underrepresented groups. This study aimed to illuminate perceived barriers to increasing diversity in oculofacial plastic surgery trainees, according to the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) fellows and fellowship program directors (FPDs). Methods During the month of February 2021, we sent surveys out to 54 current oculofacial plastic surgery fellows and 56 FPDs at 56 oculofacial plastic surgery programs recognized by the ASOPRS nationwide using a 15-question Qualtrics survey. Results Sixty-three individuals (57%) responded to the survey: 34 fellows (63%) and 29 FPDs (52%). Eighty-eight percent of fellows and 68% of FPDs identified as non-underrepresented in medicine (UiM). Forty-four percent of fellows and 25% of FPDs identified as men. FPDs most commonly noted, "Not enough minorities applying to our program" and "The objective data (Ophthalmic Knowledge Assessment Program score, United States Medical Licensing Examination Step scores, clinical honors, Alpha Omega Alpha status, letter of recommendation) for minority applicants often do not meet the threshold required to offer an interview or to be ranked to match" as barriers. Among fellows, the lowest-rated considerations when applying to oculofacial plastic surgery were "Racially/ethnically diverse faculty" and "Perceptions of minority candidates by fellowship programs," whereas "Likelihood of matching in program of choice" was ranked highest in considerations. Fellows identifying as men indicated greater concern for "Financial factors related to fellowship (e.g., loans, salary, cost of living, or cost of interviewing)" compared to fellows identifying as women who noted greater concern for "Program or preceptor acceptance of starting or having a family during fellowship." Conclusion Responses from FPDs suggest that efforts focused on recruiting and supporting diverse students to medicine and ophthalmology, mentoring applicants interested in oculofacial plastic surgery, and restructuring the application process to decrease bias, may improve diversity within the subspecialty. The lack of UiM representation in this study, 6% fellows and 7.4% FPDs identified as UiM, shows both the stark underrepresentation and the need for further research into this topic.

Local 3D matrix microenvironment regulates cell migration through spatiotemporal dynamics of contractility-dependent adhesions.

The physical properties of two-dimensional (2D) extracellular matrices (ECMs) modulate cell adhesion dynamics and motility, but little is known about the roles of local microenvironmental differences in three-dimensional (3D) ECMs. Here we generate 3D collagen gels of varying matrix microarchitectures to characterize their regulation of 3D adhesion dynamics and cell migration. ECMs containing bundled fibrils demonstrate enhanced local adhesion-scale stiffness and increased adhesion stability through balanced ECM/adhesion coupling, whereas highly pliable reticular matrices promote adhesion retraction. 3D adhesion dynamics are locally regulated by ECM rigidity together with integrin/ECM association and myosin II contractility. Unlike 2D migration, abrogating contractility stalls 3D migration regardless of ECM pore size. We find force is not required for clustering of activated integrins on 3D native collagen fibrils. We propose that efficient 3D migration requires local balancing of contractility with ECM stiffness to stabilize adhesions, which facilitates the detachment of activated integrins from ECM fibrils.

Versatile RNA interference nanoplatform for systemic delivery of RNAs.

Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.