Abstract
PURPOSE: The purpose of this study was to develop next-generation functional photoreceptor imaging using ultrahigh-speed swept-source optical coherence tomography (UHS-SS-OCT) and split-spectrum amplitude-decorrelation optoretinography (SSADOR) algorithm. The advancement enables rapid surveying of large retinal areas, promising non-contact, objective, and quantifiable measurements of macular visual function. METHODS: We designed and built a UHS-SS-OCT prototype instrument using a wavelength tunable laser with 1 MHz A-scan rate. The functional scanning protocol records 5 repeated volumes in 3 seconds. A flash pattern selectively exposes the imaged retina area. SSADOR quantifies photoreceptor light response by extracting optical coherence tomography (OCT) signal changes within the photoreceptor outer segment before and after the flash. RESULTS: The study prospectively enrolled 16 eyes from 8 subjects, demonstrating the ability to measure photoreceptor light response over a record field of view (3 × 3 mm2) with high topographical resolution (approximately 100 µm). The measured SSADOR signal corresponds to the flashed pattern, whose amplitude also correlates with flash strength, showing consistency and reproducibility across subjects. CONCLUSIONS: The integration of high-performance UHS-SS-OCT and SSADOR enables characterizing photoreceptor function over a clinically meaningful field of view, while maintaining a workflow that can be integrated into routine clinical tests and trials. The new approach allows detecting changes in photoreceptor light response with high sensitivity and can detect small focal impairments. TRANSLATIONAL RELEVANCE: This innovative advance can enable us to detect early photoreceptor abnormalities, as well as help to stage and monitor degenerative retinal diseases, potentially providing a surrogate visual function marker for retinal diseases and accelerating therapeutic development through a safe and efficient outcome endpoint.