For decades, clinicians have relied on structural imaging to infer the health of photoreceptors. Yet structure alone cannot fully reveal whether these cells are actually working. Optoretinography (ORG) — a rapidly maturing, non-invasive method to measure photoreceptor function in vivo — may soon offer ophthalmologists the missing functional piece. A recent comprehensive review published in TVST has mapped the scientific foundations and emerging clinical pathways of ORG, outlining why this technology may become as transformative as optical coherence tomography (OCT) itself.
Healthy photoreceptors subtly deform and change their scattering properties when exposed to light. These responses are tiny — sometimes only a few nanometers — yet measurable with modern optical systems. ORG captures these stimulus-evoked changes, most often as variations in optical path length, back-scattering, or phase, allowing clinicians to visualize how cones and rods respond in real time.
While early studies were confined to animal models and research-grade adaptive optics systems, the past few years have brought ORG closer to the clinic. Stimulus-evoked intensity changes have now been measured with modified fundus cameras and commercial-like OCT systems, demonstrating that ORG signals need not rely on exotic hardware.
Clinically practical ORG requires three qualities: affordability, technician-operability, and results within a typical 20-minute visit. The review highlights emerging methods that meet these criteria, including velocity-based ORG, split-spectrum amplitude-decorrelation ORG (SSADOR), and high-speed OCT protocols capable of capturing functional responses over several degrees of visual field. These approaches sacrifice single-cell resolution but retain robust, clinically useful signals.
Meanwhile, advanced techniques — adaptive optics OCT and full-field swept-source OCT — have refined our understanding of phototransduction. They reveal a characteristic triphasic photoreceptor response: a rapid early contraction, a slower elongation linked to biochemical cascades, and a late contraction phase. Such mechanistic clarity strengthens the rationale for ORG as a biomarker of photoreceptor physiology.
As gene therapies, optogenetics, and stem-cell–based interventions accelerate, clinicians need objective, spatially resolved biomarkers of photoreceptor function. ORG could help to streamline these processes by stratifying patients for clinical trials, monitoring treatment response at the cellular or regional level, and detecting dysfunction before structural loss becomes irreversible.
The study authors conclude that while "ORG promises an accessible, objective, and quantifiable approach to assess photoreceptor light responses" and is primed for near-term clinical adoption (pending standardization of stimuli, quantification metrics, and interoperability across devices), the technology has "yet to achieve broad acceptance and definitive clinical indications" before it is ready for the clinic.
