There are overwhelming numbers of psychophysical and electrophysiological tests to interrogate the functioning of retinal and post retinal visual pathways, each with varying merits (sensitivity, specificity and reproducibility). On the one hand, an investigator or clinician does not wish to omit any test that may show disease onset, progression or treatment response. On the other hand, exhaustive testing, even in the context of a clinical trial (such as gene therapy for a specific retinal dystrophy) imposes a testing burden on patients that is impractical and undesirable. This K23 research utilizes an orphan disease model (Autoimmune Retinopathy) to test the hypothesis that subjective improvement in symptomatology in response to immunomodulatory therapy (IMT), can be characterized and quantified by a patient-reported outcomes questionnaire, the ?Progression of Retinal Degeneration Questionnaire? (PRDQ); and that this PRDQ can be used to direct the targeted testing of the visual system, minimizing the testing burden for the patient, and increasing the probability of detecting accurate objective changes reflective of disease state. Thus, the goal is to develop and validate a clinical testing protocol for patients with Autoimmune Retinopathy (AIR) that will best demonstrate objective treatment response and disease improvement or worsening, and reduce the investigation burden and fatigue for patients by performing targeted testing. The project includes development and testing of the protocol in three cohorts of patients: patients with AIR and, for comparison purposes, a cohort of patients with noninfectious posterior uveitides (typically does improve with IMT) and a cohort of patients with retinal dystrophies (typically does not improve and not treated with IMT). The Candidate's long-term goal is to contribute major scientific advances to accurately diagnose, to perform quantifiable phenotypic characterization of, and to identify optimal clinical endpoints for patients with autoimmune and inherited retinal degenerations. The overarching goal of this five-year career development research plan is for him to obtain the expertise and skills necessary to become an independent clinician- scientist focused on integrating patient-reported outcomes on investigation (visual psychophysical and retinal electrophysiological tests) and management of autoimmune and inherited retinal degenerations. The mentors and advisors, from the University of Michigan and from across the United States, are leaders of their respective fields and have expressed commitment to guiding the Candidate's development into an independent investigator.
This project provides a new clinical solution for defining the retinal tests performed on patients with inflammatory and inherited retinal degenerations by taking into account what the patient reports about worsening or improvement of different vision related symptoms and daily functioning. The research primarily evaluates this proposed solution on a treatable disease called Autoimmune Retinopathy that is currently poorly understood.
