Age-Related RPE changes in Wildtype C57BL/6J Mice between 2 and 32 Months.

Purpose: This study provides a systematic evaluation of age-related changes in RPE cell structure and function using a morphometric approach. We aim to better capture nuanced predictive changes in cell heterogeneity that reflect loss of RPE integrity during normal aging. Using C57BL6/J mice ranging from P60-P730, we sought to evaluate how regional changes in RPE shape reflect incremental losses in RPE cell function with advancing age. We hypothesize that tracking global morphological changes in RPE is predictive of functional defects over time. Methods: We tested three groups of C57BL/6J mice (young: P60-180; Middle-aged: P365-729; aged: 730+) for function and structural defects using electroretinograms, immunofluorescence, and phagocytosis assays. Results: The largest changes in RPE morphology were evident between the young and aged groups, while the middle-aged group exhibited smaller but notable region-specific differences. We observed a 1.9-fold increase in cytoplasmic alpha-catenin expression specifically in the central-medial region of the eye between the young and aged group. There was an 8-fold increase in subretinal, IBA-1-positive immune cell recruitment and a significant decrease in visual function in aged mice compared to young mice. Functional defects in the RPE corroborated by changes in RPE phagocytotic capacity. Conclusions: The marked increase of cytoplasmic alpha-catenin expression and subretinal immune cell deposition, and decreased visual output coincide with regional changes in RPE cell morphometrics when stratified by age. These cumulative changes in the RPE morphology showed predictive regional patterns of stress associated with loss of RPE integrity.

Age-Related Retinal Changes in Wild-Type C57BL/6J Mice Between 2 and 32 Months.

Purpose: The purpose of this study was to extend our understanding of how aging affects normal retina function and morphology in wild-type C57BL/6J mice, by analyzing electrophysiological recordings and in vivo and post mortem anatomy. Methods: Electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT), and confocal scanning laser ophthalmoscope (cSLO) in vivo images were obtained from mice between the ages of 2 and 32 months in four groups: group 1 (<0.5 years), group 2 (1.0-1.5 years), group 3 (1.5-2.0 years), and group 4 (>2.0 years). Afterward, mouse bodies and eyes were weighed. Eyes were stained with hematoxylin and eosin (H&E) and cell nuclei were quantified. Results: With aging, mice showed a significant reduction in both a- and b-wave ERG amplitudes in scotopic and photopic conditions. Additionally, total retina and outer nuclear layer (ONL) thickness, as measured by SD-OCT images, were significantly reduced in older groups. The cSLO images showed an increase in auto-fluorescence at the photoreceptor-RPE interface as age increases. H&E cell nuclei quantification showed significant reduction in the ONL in older ages, but no differences in the inner nuclear layer (INL) or ganglion cell layer (GCL). Conclusions: By using multiple age groups and extending the upper age limit of our animals to approximately 2.65 years (P970), we found that natural aging causes negative effects on retinal function and morphology in a gradual, rather than abrupt, process. Future studies should investigate the exact mechanisms that contribute to these gradual declines in order to discover pathways that could potentially serve as therapeutic targets.

Aggregating Claims Data Across Payers: Approaches, Challenges, and Lessons Learned From the Comprehensive Primary Care Initiative.

The Comprehensive Primary Care (CPC) initiative fueled the emergence of new organizational alliances and financial commitments among payers and primary care practices to use data for performance improvement. In most regions of the country, practices received separate confidential feedback reports of claims-based measures from multiple payers, which varied in content and provided an incomplete picture of a practice's patient panel. Over CPC's last few years, participating payers in several regions resisted the tendency to guard data as a proprietary asset, instead working collaboratively to produce aggregated performance feedback for practices. Aggregating claims data across payers is a potential game changer in improving practice performance because doing so potentially makes the data more accessible, comprehensive, and useful. Understanding lessons learned and key challenges can help other initiatives that are aggregating claims or clinical data across payers for primary care practices or other types of providers.

Strengthening Multipayer Collaboration: Lessons From the Comprehensive Primary Care Initiative.

Policy Points: Collaboration across payers to align financial incentives, quality measurement, and data feedback to support practice transformation is critical, but challenging due to competitive market dynamics and competing institutional priorities. The Centers for Medicare & Medicaid Services or other entities convening multipayer initiatives can build trust with other participants by clearly outlining each participant's role and the parameters of collaboration at the outset of the initiative. Multipayer collaboration can be improved if participating payers employ neutral, proactive meeting facilitators; develop formal decision-making processes; seek input on decisions from practice representatives; and champion the initiative within their organizations. CONTEXT: With increasing frequency, public and private payers are joining forces to align goals and resources for primary care transformation. However, sustaining engagement and achieving coordination among payers can be challenging. The Comprehensive Primary Care (CPC) initiative is one of the largest multipayer initiatives ever tested. Drawing on the experience of the CPC initiative, this paper examines the factors that influence the effectiveness of multipayer collaboration. METHODS: This paper draws largely on semistructured interviews with CPC-participating payers and payer conveners that facilitated CPC discussions and on observation of payer meetings. We coded and analyzed these qualitative data to describe collaborative dynamics and outcomes and assess the factors influencing them. FINDINGS: We found that several factors appeared to increase the likelihood of successful payer collaboration: contracting with effective, neutral payer conveners; leveraging the support of payer champions, and seeking input on decisions from practice representatives. The presence of these factors helped some CPC regions overcome significant initial barriers to achieve common goals. We also found that leadership from the Centers for Medicare & Medicaid Services (CMS) was key to achieving broad payer engagement in CPC, but CMS's dual role as initiative convener and participating payer at times made collaboration challenging. CMS was able to build trust with other payers by clarifying which parts of CPC could be adapted to regional contexts, deferring to other payers for these decisions, and increasing opportunities for payers to meet with CMS representatives. CONCLUSIONS: CPC demonstrates that when certain facilitating factors are present, payers can overcome competitive market dynamics and competing institutional priorities to align financial incentives, quality measurement, and data feedback to support practice transformation. Lessons from this large-scale, multipayer initiative may be helpful for other multipayer efforts getting under way.