A comprehensive model for measuring real-life cost-effectiveness in eyecare: automation in care and evaluation of system (aces-rwm™).

This paper describes a holistic, yet simple and comprehensible, ecosystem model to deal with multiple and complex challenges in eyecare. It aims at producing the best possible wellbeing and eyesight with the available resources. When targeting to improve the real-world cost-effectiveness, what gets done in everyday practice needs be measured routinely, efficiently and unselectively. Collection of all real-world data of all patients will enable evaluation and comparison of eyecare systems and departments between themselves nationally and internationally. The concept advocates a strategy to optimize real-life effectiveness, sustainability and outcomes of the service delivery in ophthalmology. The model consists of three components: (1) resource-governing principles (i.e., to deal with increasing demand and limited resources), (2) real-world monitoring (i.e., to collect structured real-world data utilizing automation and visualization of clinical parameters, health-related quality of life and costs), and (3) digital innovation strategy (i.e., to evaluate and benchmark real-world outcomes and cost-effectiveness). The core value and strength of the model lies in the consensus and collaboration of all Finnish university eye clinics to collect and evaluate the uniformly structured real-world outcomes data. In addition to ophthalmology, the approach is adaptable to any medical discipline to efficiently generate real-world insights and resilience in health systems.

SWATH-MS Proteomic Analysis of Oxygen-Induced Retinopathy Reveals Novel Potential Therapeutic Targets.

Purpose: Oxygen-induced retinopathy (OIR) is the most widely used model for ischemic retinopathies such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). The purpose of this study was to perform the most comprehensive characterization of OIR by a recently developed technique, sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics. Methods: Control and OIR retina samples collected from various time points were subjected to SWATH-MS and detailed data analysis. Immunohistochemistry from mouse retinas as well as neovascular membranes from human PDR and RVO patients were used for the detection of the localization of the proteins showing altered expression in the retina and to address their relevance to human ischemic retinopathies. Results: We report the most extensive proteomic profiling of OIR to date by quantifying almost 3000 unique proteins and their expression differences between control and OIR retinas. Crystallins were the most prominent proteins induced by hypoxia in the retina, while angiogenesis related proteins such as Filamin A and nonmuscle myosin IIA stand out at the peak of angiogenesis. Majority of the changes in protein expression return to normal at P42, but there is evidence to suggest that proteins involved in neurotransmission remain at reduced level. Conclusions: The results reveal new potential therapeutic targets to address hypoxia-induced pathological angiogenesis taking place in number of retinal diseases. The extensive proteomic profiling combined with pathway analysis also identifies novel molecular networks that could contribute to the pathogenesis of retinal diseases.

Lack of R-Ras Leads to Increased Vascular Permeability in Ischemic Retinopathy.

PURPOSE: The role of R-Ras in retinal angiogenesis and vascular permeability was evaluated in an oxygen-induced retinopathy (OIR) model using R-Ras knockout (KO) mice and in human diabetic neovascular membranes. METHODS: Mice deficient for R-Ras and their wild-type (WT) littermates were subjected to 75% oxygen from postnatal day 7 (P7) to P12 and then returned to room air. At P17 retinal vascularization was examined from whole mounts, and retinal vascular permeability was studied using Miles assay. Real-time RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of R-Ras in retina during development or in the OIR model. The degree of pericyte coverage and vascular endothelial (VE)-cadherin expression on WT and R-Ras KO retinal blood vessels was quantified using confocal microscopy. The correlation of R-Ras with vascular endothelial growth factor receptor 2 (VEGFR2) and human serum albumin on human proliferative diabetic retinopathy membranes was assessed using immunohistochemistry. RESULTS: In retina, R-Ras expression was mostly restricted to the vasculature. Retinal vessels in the R-Ras KO mice were significantly more permeable than WT controls in the OIR model. A significant reduction in the direct physical contact between pericytes and blood vessel endothelium as well as reduced VE-cadherin immunostaining was found in R-Ras-deficient mice. In human proliferative diabetic retinopathy neovascular membranes, R-Ras expression negatively correlated with increased vascular leakage and expression of VEGFR2, a marker of blood vessel immaturity. CONCLUSIONS: Our results suggest that R-Ras has a role in controlling retinal vessel maturation and stabilization in ischemic retinopathy and provides a potential target for pharmacologic manipulation to treat diabetic retinopathy.

Right services to right patients at right time in right setting in Tays Eye Centre.

PURPOSE: The report describes the concepts behind procedures implemented in Tays Eye Centre to enable improved access to care and improved productivity. METHODS: The strategy was developed in 2009 after hospital district decided to construct a new eye hospital which was opened in 2012. The following principles were implemented: (i) identification of high-volume patient groups: the 'big four' eye diseases accounting for 70% of patient visits and costs: age-related macular degeneration (AMD), glaucoma, retinal diseases and cataract; (ii) stratification and prioritization of patient care based on risk of permanent visual disability; (iii) standardization of services for low-risk patients; (iv) maximization of productivity; and (v) shared care. The impact of the new strategy on access to care and productivity is reported for years 2011-2015. RESULTS: In 2011-2015, the total number of services provided increased 46% while the work contribution increased 15%. The number of referrals increased 76% and the number of outpatient appointments increased 2.5-fold. Simultaneously, the number of delayed follow-up visits decreased to zero. Age-related macular degeneration (AMD) injections increased 1.8-fold. However, after 50% yearly increase in Age-related macular degeneration (AMD) injections, a plateau was reached in 2014 with a 3% decline in 2014-2015 with no changes in treatment indications. In the beginning of 2016, the number of injections has started to increase again (+9% compared to 2015).  The total number of surgical procedures increased 98%. The annual number of cataract surgeries increased 64% and bilateral surgeries from 11% to 39%. CONCLUSION: Revised operational concepts and new facilities together with a 15% increase in work contribution led to a 46% increase in overall productivity, improved access to care and the clearance of delayed services. Efforts continue to further refine cost-effective care and to define the appropriate levels of services.

Ultrathin Polyimide Membrane as Cell Carrier for Subretinal Transplantation of Human Embryonic Stem Cell Derived Retinal Pigment Epithelium.

In this study, we investigated the suitability of ultrathin and porous polyimide (PI) membrane as a carrier for subretinal transplantation of human embryonic stem cell (hESC) -derived retinal pigment epithelial (RPE) cells in rabbits. The in vivo effects of hESC-RPE cells were analyzed by subretinal suspension injection into Royal College of Surgeons (RCS) rats. Rat eyes were analyzed with electroretinography (ERG) and histology. After analyzing the surface and permeability properties of PI, subretinal PI membrane transplantations with and without hESC-RPE were performed in rabbits. The rabbits were followed for three months and eyes analyzed with fundus photography, ERG, optical coherence tomography (OCT), and histology. Animals were immunosuppressed with cyclosporine the entire follow-up time. In dystrophic RCS rats, ERG and outer nuclear layer (ONL) thickness showed some rescue after hESC-RPE injection. Cells positive for human antigen were found in clusters under the retina 41 days post-injection but not anymore after 105 days. In rabbits, OCT showed good placement of the PI. However, there was loss of pigmentation on the hESC-RPE-PI over time. In the eyes with PI alone, no obvious signs of inflammation or retinal atrophy were observed. In the presence of hESC-RPE, mononuclear cell infiltration and retinal atrophy were observed around the membranes. The porous ultrathin PI membrane was well-tolerated in the subretinal space and is a promising scaffold for RPE transplantation. However, the rejection of the transplanted cells seems to be a major problem and the given immunosuppression was insufficient for reduction of xenograft induced inflammation.