FLIO and the brain: Making the invisible visible with Robert Sergott, MD

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is emerging as a transformative imaging modality in ophthalmology, offering a metabolic lens into retinal and neurodegenerative diseases. Robert C. Sergott, MD, of Wills Eye Hospital, highlighted FLIO’s potential to redefine both diagnostics and therapeutic monitoring in his presentation at the 2025 International SPECTRALIS Symposium – and Beyond, held June 13-14 in Heidelberg, Germany. “While we're sitting here, we're fluorescing,” Sergott said, drawing an analogy to lightning bugs to illustrate the body’s fluorescence as a biomarker of health and disease.

FLIO is to optical coherence tomography (OCT) what positron emission tomography (PET) was to magnetic resonance imaging (MRI)—ushering clinicians from structural to functional imaging, he noted. By capturing real-time changes in retinal metabolism, FLIO reveals insights at the molecular level, particularly in mitochondrial function. “The theme of our Annesley EyeBrain Center at Jefferson, partnered with Wills Eye Hospital, is to make the invisible visible,” Sergott emphasized. With over 400 patients imaged to date, the center is uncovering patterns of mitochondrial dysfunction and protein misfolding—hallmarks of neurodegenerative diseases like Alzheimer, Parkinson, and multiple sclerosis.

What makes FLIO compelling is its promise for early diagnosis—before symptom onset. “By the time patients have symptoms, quite bluntly, half the brain is dead,” Sergott noted, underlining the critical window for intervention. Changes in retinal FLIO signatures are being correlated with advanced MRI findings, reinforcing the retina’s role as a surrogate for brain health.

The integration of FLIO with stem cell-derived retinoids and organoids offers further promise, enabling personalized disease modeling and drug testing. FLIO’s origins in rare retinal diseases, such as macular telangiectasia, have already supported FDA approvals. “Now we're going to be able to get to the subcellular and molecular basis of disease,” Sergott said. FLIO may become central to bridging neuro-ophthalmology and medical retina, transforming both fields in the process, he added.