f-ORG Technique Revolutionizes Early Detection of Retinal Diseases

Eye diseases often develop unnoticed for years, making early detection crucial. Scientists at the International Centre for Eye Research (ICTER) have introduced a groundbreaking diagnostic method called flicker optoretinography (f-ORG). This innovative technique analyzes the retina's reaction to light, allowing for the identification of microscopic changes in photoreceptors before any clinical symptoms manifest.

Understanding Photoreceptor Function and Retinal Health

The retina plays a pivotal role in vision, acting as a biological "transducer" that converts light into neural signals. The outer segments of photoreceptors—cones and rods—undergo minute length changes when exposed to light, a process known as phototransduction. These microscopic fluctuations provide valuable insights into retinal health.

Existing diagnostic tools like electroretinography (ERG) assess photoreceptor function but come with limitations, including prolonged dark adaptation, complex procedures, and discomfort for patients. ICTER scientists sought to overcome these challenges with f-ORG, a fast, non-invasive optical imaging technique capable of tracking real-time changes in photoreceptor length.

How the f-ORG Technique Works

f-ORG employs spatial-temporal optical coherence tomography (STOC-T) to capture photoreceptor responses to light at a nanometer scale. This optical equivalent of flicker electroretinography (f-ERG) enables real-time observation of changes in photoreceptor outer segments. The method allows researchers to monitor molecular-level elongations triggered by the activation of phosphodiesterase 6 (PDE6), a key enzyme in phototransduction.

According to Professor Maciej Wojtkowski, a co-author of the study, "Our method enables tracking of molecular mechanisms of phototransduction without the need for prolonged exposure to darkness and without contact with the surface of the eye. This is a significant step forward in the diagnosis of retinal diseases."

Breakthrough Research Confirms f-ORG’s Potential

A recent study published in the Proceedings of the National Academy of Sciences demonstrated the efficacy of f-ORG. Researchers tested the technique on healthy volunteers, exposing their retinas to flickering light at various frequencies (1.5 Hz to 45 Hz). The STOC-T imaging captured subtle oscillatory changes in photoreceptor length, confirming theoretical predictions about phototransduction activation.

In a crucial experiment, researchers administered sildenafil, a PDE6 inhibitor, to assess its impact on photoreceptor response. As expected, a significant reduction in photoreceptor elongation was observed, validating PDE6’s role in phototransduction. Lead author Sławomir Tomczewski, Ph.D. Eng., remarked, "This was a breakthrough moment. The observed response reduction confirmed that conformational changes in PDE6 drive the elongation of photoreceptor outer segments under light stimulation."

Clinical Applications and Future Prospects

Retinal diseases such as age-related macular degeneration (AMD), retinitis pigmentosa, and congenital dystrophies often remain undetected until substantial photoreceptor damage occurs. Existing diagnostic methods focus on structural and electrical assessments but fail to detect subtle molecular changes. f-ORG bridges this gap by providing direct, real-time observation of photoreceptor activity.

"Thanks to f-ORG, we can observe the retina’s reaction to light in real-time. It’s like monitoring an engine’s operation without dismantling it," explained Professor Wojtkowski.

Potential applications of f-ORG extend beyond ophthalmology. Given the retina's connection to the nervous system, the technology could offer insights into neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease.

The Road to Clinical Implementation

ICTER scientists are now working on adapting f-ORG for clinical settings. Future studies will involve patients with early signs of macular degeneration and retinitis pigmentosa. Additionally, researchers aim to develop a portable f-ORG device for widespread use in ophthalmologists’ offices and population screening programs.

"We want f-ORG to become a standard in ophthalmology. This technology has the potential to help millions by enabling early disease detection and more effective treatment," Professor Wojtkowski emphasized.

Reference:

Sławomir Tomczewski et al, Photopic flicker optoretinography captures the light-driven length modulation of photoreceptors during phototransduction, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2421722122