Ranked determinants of telemedicine diabetic retinopathy screening performance in the United States primary care safety-net setting: an exploratory CART analysis.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness worldwide, despite easy detection and effective treatment. Annual screening rates in the USA remain low, especially for the disadvantaged, which telemedicine-based DR screening (TDRS) during routine primary care has been shown to improve. Screening rates from such programs have varied, however, pointing to inconsistent implementation and unaddressed barriers. This work seeks to identify and prioritize modifiable barriers for targeted intervention. METHODS: In this final phase of an exploratory mixed-methods study, we developed, validated, and administered a 62-item survey to multilevel stakeholders involved with TDRS in primary care safety-net clinics. Survey items were aligned with previously identified determinants of clinic-level screening and mapped to the Consolidated Framework for Implementation Research (CFIR). Classification and Regression Tree (CART) analyses were used to identify and rank independent variables predictive of individual-level TDRS screening performance. RESULTS: Overall, 133 of the 341 invited professionals responded (39%), representing 20 safety-net clinics across 6 clinical systems. Respondents were predominately non-Hispanic White (77%), female (94%), and between 31 and 65 years of age (79%). Satisfaction with TDRS was high despite low self-reported screening rates. The most important screening determinants were: provider reinforcement of TDRS importance; explicit instructions by providers to staff; effective reminders; standing orders; high relative priority among routine diabetic measures; established TDRS workflows; performance feedback; effective TDRS champions; and leadership support. CONCLUSIONS: In this survey of stakeholders involved with TDRS in safety-net clinics, screening was low despite high satisfaction with the intervention. The best predictors of screening performance mapped to the CFIR constructs Leadership Engagement, Compatibility, Goals & Feedback, Relative Priority, Champions, and Available Resources. These findings facilitate the prioritization of implementation strategies targeting determinants of TDRS performance, potentially increasing its public health impact.

Evaluation of multi-level barriers and facilitators in a large diabetic retinopathy screening program in federally qualified health centers: a qualitative study.

BACKGROUND: Recommended annual diabetic retinopathy (DR) screening for people with diabetes has low rates in the USA, especially in underserved populations. Telemedicine DR screening (TDRS) in primary care clinics could expand access and increase adherence. Despite this potential, studies have observed high variability in TDRS rates among clinics and over time, highlighting the need for implementation supports. Previous studies of determinants of TDRS focus on patients' perspectives, with few studies targeting upstream multi-level barriers and facilitators. Addressing this gap, this qualitative study aimed to identify and evaluate multi-level perceived determinants of TDRS in Federally Qualified Health Centers (FQHCs), to inform the development of targeted implementation strategies. METHODS: We developed a theory-based semi-structured interview tool based on the Consolidated Framework for Implementation Research (CFIR). We conducted 22 key informant interviews with professionals involved in TDRS (administrators, clinicians, staff). The interviews were audio-recorded and transcribed verbatim. Reported barriers and facilitators were organized into emergent themes and classified according to CFIR constructs. Constructs influencing TDRS implementation were rated for each study site and compared across sites by the investigators. RESULTS: Professionals identified 21 main barriers and facilitators under twelve constructs of the five CFIR domains. Several identified themes were novel, whereas others corroborated previous findings in the literature (e.g., lack of time and human resources, presence of a champion). Of the 21 identified themes, 13 were classified under the CFIR's Inner Setting domain, specifically under the constructs Compatibility and Available Resources. Themes under the Outer Setting domain (constructs External Incentives and Cost) were primarily perceived by administrators, whereas themes in other domains were perceived across all professional categories. Two Inner Setting (Leadership Engagement, Goals and Feedback) and two Process (Champion, Engaging) constructs were found to strongly distinguish sites with high versus low TDRS performance. CONCLUSIONS: This study classified barriers and facilitators to TDRS as perceived by administrators, clinicians, and staff in FQHCs, then identified CFIR constructs that distinguished high- and low-performance clinics. Implementation strategies such as academic detailing and collection and communication of program data and successes to leadership; engaging of stakeholders through involvement in implementation planning; and appointment of intervention champions may therefore improve TDRS implementation and sustainment in resource-constrained settings.

Implementation and sustainment of a statewide telemedicine diabetic retinopathy screening network for federally designated safety-net clinics.

CONTEXT: Diabetic retinopathy (DR) is the leading cause of incident blindness among working-age adults in the United States. Federally designated safety-net clinics (FDSC) often serve as point-of-contact for patients least likely to receive recommended DR screenings, creating opportunity for targeted interventions to increase screening access and compliance. STUDY DESIGN AND METHODS: With such a goal, we implemented and assessed the longitudinal performance of an FDSC-based telemedicine DR screening (TDRS) network of 22 clinical sites providing nonmydriatic fundus photography with remote interpretation and reporting. Retrospective analysis of patient encounters between February 2014 and January 2019 was performed to assess rates of pathology and referral. A generalized estimating equation logistic regression model was used for subset analysis from audits of pre- and post-implementation screening rates. Finally, patient surveys were conducted and assessed as a measure of intervention acceptability. RESULTS: Of the 13,923 individual telescreening encounters (4327 female, 4220 male, and 5376 unspecified; mean [SD] age, 54.9 [12.5] years) studied, 10,540 were of adequate quality to identify 3532 (33.5%) patients with ocular pathology: 2319 (22.0%) patients had some level of DR with 1604 (15.2%) requiring specialist referral, and 808 (7.7%) patients required referral for other ocular pathologies. The mean screening rate for audited clinics in the year prior to program implementation was 29.9% (641/2147), which increased to 47.7% (1012/2124) in the program's first year, doubling patients' odds of being screened (OR 2.2; 95% CI: 1.3-3.7; P = .003). These gains were sustained over four years following implementation (OR 1.9; 95% CI: 1.1-3.1; P = .018) despite varied clinic screening performance (4-year averaged range, 22.9-55.1%). Odds of early detection likewise doubled for patients with consecutive screenings (OR 2.2, 95% CI: 2.0-2.4; P < .001). Finally, surveyed patients preferred TDRS to specialist exams (82.5%; 776/941) and would recommend the service to friends (92.7%; 868/936). CONCLUSION AND RELEVANCE: A statewide, FDSC-centered TDRS network was successfully established and sustained in a medically underserved region of the United States. Our results suggest that large TDRS networks in FDSCs can increase screening access and compliance for otherwise unscreened populations, but outcomes can vary greatly among clinics. Further work to optimize program implementation is needed to maximize this model's impact.

Unique homologous siRNA blocks hypoxia-induced VEGF upregulation in human corneal cells and inhibits and regresses murine corneal neovascularization.

PURPOSE: To determine whether RNA interference (RNAi) could block hypoxia-induced upregulation of vascular endothelial growth factor (VEGF) in human corneal epithelial cells in vitro and inhibit and regress injury-induced murine corneal neovascularization in vivo. METHODS: siRNA selected on the basis of target sequence homology between mouse and human VEGF was placed into expression cassettes and transfected into human corneal epithelial cells. Hypoxia-induced VEGF synthesis was assayed. Also, the effect of a plasmid capable of directing the expression of an siRNA against VEGF when injected into mouse corneas 8 hours before alkali-mechanical trauma was studied. Leukocyte count, VEGF protein levels, and degree of neovascularization in corneas were compared with that of a control siRNA plasmid. Plasmids were injected 1 week after injury to assess the ability of RNAi to regress corneal neovascularization. RESULTS: Hypoxia-induced VEGF mRNA synthesis and protein secretion by human corneal epithelial cells was efficiently suppressed by an siRNA targeted against a sequence uniquely identical for the mouse and human VEGF genes. Intrastromal delivery of a plasmid expressing this siRNA before murine corneal injury suppressed corneal VEGF by 55.7% versus control (P = 0.014), leukocyte infiltration by 69.5% (P < 0.001), and neovascularization 1 week after injury by 72.3% (P = 0.001). At the regression time point, treated corneas had 72.8% less neovascularization (P < 0.001). CONCLUSIONS: RNAi significantly suppresses expression of VEGF induced by hypoxia in human corneal epithelial cells in vitro. In vivo, intrastromal delivery of a plasmid expressing siRNA against VEGF suppresses injury-induced VEGF expression, leukocyte infiltration, and angiogenesis and was able to regress corneal neovascularization.

Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier.

PURPOSE: Pathological neovascularisation within the normally avascular cornea is a serious event that can interfere with normal vision. Upregulation of vascular endothelial growth factor (VEGF) has been associated with neovascularisation in the eye, suggesting that maintaining low levels of VEGF is important for corneal avascularity and intact vision. This study aims to determine the expression profile and possible contribution of sVEGFR-1 to the corneal avascular barrier. DESIGN: Experimental case series investigating VEGF and soluble fms-like tyrosine kinase (sFlt) levels in normal and neovascularised human corneas. PARTICIPANTS: Four normal human corneas, five human corneas with alkali burns, three human corneas with aniridia, one with ocular cicatricial pemphigoid and two with interstitial keratitis were examined. METHODS: Western blot and immunohistochemical analyses were performed to determine sFlt and VEGF levels in normal and neovascularised human corneas. Immunoprecipitation was utilised to demonstrate sFlt-VEGF binding. RESULTS: Normal human corneas strongly express sFlt in the corneal epithelium and weakly in the corneal stroma close to the limbus. VEGF is bound by sFlt in the normal human cornea. Neovascularised human corneas have greatly reduced expression of sFlt and significantly less VEGF bound by sFlt. CONCLUSIONS: sFlt is highly expressed in the human cornea and normally sequesters VEGF.

Systemic soluble Tie2 expression inhibits and regresses corneal neovascularization.

This study was designed to determine if soluble Tie2 (sTie2) expression inhibits and regresses corneal neovascularization, and if VEGF contributes to its effect. The corneas of BALB/c mice were scraped and the mice were injected with either an adenovirus expressing soluble Tie2 (Ad.sTie2) or an empty adenoviral vector. When injected at the inhibition timepoint (one day prior to corneal injury), the mean percentage of neovascularized corneal area two weeks later in Ad.sTie2-treated mice vs. controls was 56.37+/-9.15% vs. 85.79+/-3.55% (p=0.04). At the regression timepoint (4 weeks after corneal scrape), the mean area of corneal neovascularization in Ad.sTie2-treated mice was 42.89+/-4.74% vs. 75.01+/-3.22% in the control group (p=0.007). VEGF expression was significantly higher in Ad.sTie2-treated mice at the inhibition timepoint and there was no significant difference at the regression timepoint. These findings suggest that sTie2 inhibits and regresses corneal neovascularization in a VEGF-independent manner.