PROJECT SUMMARY/ABSTRACT Cataract surgery is the most common eye procedure in patients aged 55 years and above. Approximately 10 million cataract surgeries are performed annually in the world. Chronic postoperative ocular pain (CPOP) is estimated to develop in about 18% of these patients. As society ages, the number of cataract surgeries and subsequently the incidence of CPOP are expected to double in the next 20 years. CPOP substantially affects the quality of life and is associated with enormous economic burden. Effective treatments for CPOP are still lacking. One major limitation in developing such treatments is the inability to gauge their efficacy in an objective manner. Autologous serum tear (AST) therapy has emerged as one of the most highly efficacious treatments for CPOP. However, responses to AST vary vastly among individual patients. Thus, there is an urgent need to establish robust biomarkers to predict the therapeutic outcomes (responder vs non-responder) and to monitor response to treatment. Our goals are to discover and validate treatment response and response monitoring biomarkers for AST treatment in patients with CPOP after cataract surgery. To meet these goals, we have assembled an interdisciplinary team (ophthalmology, pain management, bioinformatics, data science, immunology, and molecular biology) to discover multimodal biomarkers of response to AST therapy in patients with CPOP using state-of-the art machine-learning that integrates clinical histories, questionnaires, and molecular biomarkers from the site of pain (eye) and the source of treatment (serum). We will assess genetics, transcriptomics, metabolomics, among others. Machine learning will be used to determine a parsimonious set of non-invasive biomarkers for characterizing AST response. We will achieve our goal through two specific aims: (1) develop multimodal biomarkers of AST treatment response in CPOP after cataract surgery (UG3 Discovery Phase); and (2) validate the multimodal biomarkers identified in Aim 1 in the first randomized controlled trial evaluating AST versus placebo in CPOP after cataract surgery(UH3 Validation Phase). This proposal will yield objective and robust biomarker signatures to facilitate AST treatment stratification in patients with CPOP. In addition to the impact this study will have on creating precision approach to guide the clinical management of patients with CPOP, the approaches and findings from this proposal will provide a framework to identify and validate objective biomarkers for chronic postoperative pain in many other surgical specialties.

PROJECT NARRATIVE A significant number of patients experience persistent eye pain after cataract surgery on their eyes, and this pain is difficult to control. One reason for the limited options in treating chronic eye pain is the inability to assess whether a treatment works or not, and we have to rely on what patients tell us about how they feel, which varies greatly. In this proposal, we will look for objective tests that will tell us how effective a treatment is and which patient is likely to respond to the therapy.