Adaptive Optics Fluorescence Lifetime Imaging Ophthalmoscopy for Single-Cell–Resolved In Vivo Metabolic and Structural Imaging of the Human Retinal Pigment Epithelium
Year: 2026
Type: preprint
Abstract: Fluorescence lifetime imaging ophthalmoscopy permits in vivo assessment of retinal metabolism but has remained limited by insufficient cellular resolution in the human eye. Here we present adaptive optics-enhanced fluorescence lifetime imaging ophthalmoscopy (AOFLIO), a method for single-cell-resolved, in vivo structural and metabolic imaging of the human retinal pigment epithelium (RPE). Through real-time correction of ocular wavefront aberrations, precisely synchronized adaptive optics reflectance and lifetime image acquisition via a phase-locked loop-based timing architecture, and sub-pixel photon registration that localizes individual autofluorescence photons with high spatial precision, AOFLIO directly resolves the RPE cell mosaic and measures autofluorescence decay using the same photons, enabling direct structural-functional correlation at the single-cell level. We demonstrate single-cell RPE lifetime mapping in healthy subjects and reveal altered metabolic signatures and fine characterization of RPE metabolic in age-related macular degeneration. AOFLIO establishes a platform for cellular-scale metabolic imaging in the living human eye.
Source: medRxiv
Institutions: Doheny Eye Institute, University of California, Los Angeles
Language: English
Topic: Retinal Imaging and Analysis
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7128521235