HONU: A Multicenter, Prospective, Observational Study of the Progression of Intermediate Age-Related Macular Degeneration.

Purpose: Large and lengthy clinical trials are currently required to study the efficacy of interventions aiming to slow the progression of the early stages of age-related macular degeneration (AMD). To enable the design of more feasible trials, an observational study HONU aims to comprehensively study eyes with intermediate AMD (iAMD) to explore novel clinical endpoints and patient enrichment strategies. Design: Prospective, multicenter, international observational study. Participants: Four hundred patients, whose study eye is required to have large drusen and pigmentary change, but without evidence of any atrophic changes other than incomplete retinal pigment epithelium and outer retinal atrophy. The nonstudy eye is required to have some evidence of atrophy. Methods: Patients are assessed every 12 weeks for up to 36 months, with standard opthalmic examinations and multimodal retinal imaging as well as a range of novel visual functional tests. Patient-reported outcomes and biomarker samples are also collected. Structural changes on multimodal imaging are evaluated longitudinally and their relationship with visual function parameters analyzed. Exploratory interim analyses are planned. Main Outcome Measures: The rates of conversion from baseline high risk iAMD to more advanced atrophic AMD stages, and the rate of ellipsoid zone loss. Results: Recruitment commenced in May 2022 and 400 patients were enrolled by August 2024, allowing for up to 3 years follow-up. Enrollment occurred at 72 sites across 6 countries. The median age of the patients at baseline was 75 years, ranging from 50 to 93 years. The cohort is predominantly female, making up 69% of patients, and 95% identified as White. Conclusions: HONU will provide critical and robust natural history data on AMD progression in patients with high-risk iAMD in the study eye. Potential novel earlier clinical trial endpoints and enrichment strategy for high-risk patients will be determined. Knowledge gained will inform design and feasibility of early interventional studies aiming to slow progression to vision-threatening late AMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.