Could FLIO predict how fast geographic atrophy will grow?

Could a single border zone imaging measurement predict how quickly a geographic atrophy (GA) lesion will grow? A border zone biomarker derived from fluorescence lifetime imaging ophthalmoscopy (FLIO) was significantly correlated with the progression rate of GA secondary to age-related macular degeneration (AMD), according to a longitudinal study published in Investigative Ophthalmology & Visual Science.¹

Sagurski and colleagues, of the Department of Ophthalmology at Inselspital, Bern University Hospital and the University of Bern in Switzerland, followed 32 eyes from 17 patients with GA secondary to nonexudative AMD over an average of roughly 5 years. A baseline imaging visit was followed by a final follow-up visit, with a subset of patients examined at an additional interim visit in between. At each visit, the research team captured fundus autofluorescence intensity, spectral-domain optical coherence tomography, color fundus photography, and FLIO scans.¹ FLIO measurements were obtained at 5 regions of interest, including the fovea, unaffected retina, the GA lesion itself, and two zones flanking the lesion border, designated the intermediary zone and junctional zone.¹

Lesion growth and lifetime dynamics

Mean GA-affected area grew from 11.35 mm² at baseline to 17.48 mm² by the final visit, representing an average increase of 1.21 mm² per year, while best-corrected visual acuity declined by a mean of 9.8 letters over the same period.¹ Fluorescence lifetimes lengthened across all measured regions over time, with the most pronounced change occurring in the junctional zone, where mean lifetime extended by 690 picoseconds in the short spectral channel and 482 picoseconds in the long spectral channel between baseline and final visit. The smallest shift occurred in unaffected retina.¹

Consistent with earlier reports, the authors found that GA lesions displayed significantly longer fluorescence lifetimes than surrounding healthy retina, with a gradual decline in lifetime values moving outward from the lesion toward unaffected tissue.¹

Predictive value of the border zone gradient

The authors' central finding centered on the contrast in lifetimes between the intermediary and junctional zones at baseline. A smaller gradient between these two regions was significantly and inversely correlated with the square-root-transformed GA growth rate in both spectral channels (P = .02, r² = .17), suggesting that eyes whose border zones showed less differentiation in lifetime values tended to have faster-growing lesions.¹ The relationship held at the interim visit and remained statistically significant in a pseudophakic subgroup analysis designed to rule out confounding from cataract progression.¹

Clinical implications

The authors proposed that this border zone lifetime gradient may offer a biological, imaging-based predictor of GA progression rate, potentially complementing existing FAF-pattern and artificial intelligence-based prediction approaches discussed in the literature. Recent work has shown that AI-based prediction models can match or even outperform retinal specialists in estimating GA progression speed.² The authors suggested FLIO could ultimately serve as a monitoring tool for early molecular changes associated with treatment response in GA border zones, particularly as complement inhibitor therapies for GA continue to expand in availability.

Limitations cited included challenges in maintaining precise measurement consistency across longitudinal visits, the inclusion of some phakic patients, variability in follow-up intervals related in part to the COVID-19 pandemic and the current inability to resolve specific fluorophores from the FLIO signal.¹

The study was supported by a grant from the Swiss National Science Foundation. Several authors disclosed financial relationships with pharmaceutical and device companies, including consulting or research support from Bayer, Novartis, Roche, Alcon, and Heidelberg Engineering, the manufacturer of the FLIO device used in the study.¹

References

1. Sagurski N, Jaggi D, Lincke JB, Wolf S, Zinkernagel MS, Dysli C. Monitoring of geographic atrophy progression in age-related macular degeneration using fluorescence lifetime imaging ophthalmoscopy. Invest Ophthalmol Vis Sci. 2026;67(6):31. doi:10.1167/iovs.67.6.31

2. Reiter GS, Lachinov D, Bühl W, et al. A novel management challenge in age-related macular degeneration: artificial intelligence and expert prediction of geographic atrophy. Ophthalmol Retina. 2025;9(5):421-430. doi:10.1016/j.oret.2024.10.029