Colourful FLIO imaging revelations shed light on Stargardt disease

Ophthalmology Times EuropeOphthalmology Times Europe June 2021
Volume 17
Issue 05

According to researchers, fluorescence lifetime imaging ophthalmoscopy reveals disease-related patterns not visible with other imaging modalities.


This article was reviewed by Dr Shawn Kavoussi.

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a rapid, non-invasive autofluorescence imaging modality. Using FLIO lifetimes—that is, the rates of autofluorescence decay—different autofluorescence patterns can be discerned in affected eyes with various retinal diseases. This innovation casts a new light on fundus imaging by providing different colourful perspectives of retinal diseases that were not available previously, and all in about 2 minutes.

“This novel technology detects the in vivo autofluorescence lifetimes at the back of the eye,” said Dr Lydia Sauer, from the Department of Ophthalmology and Visual Sciences at the Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States. Healthy eyes, she explained, exhibit the same characteristic pattern of short FLIO lifetimes in the foveal centre and long lifetimes at the optic nerve. In contrast, eyes with retinal diseases are characterised by numerous different autofluorescence patterns depending on the disease.

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Dr Sauer and her colleagues studied the phenotypes, genotypes and longitudinal changes in Stargardt disease in 45 genetically characterised patients (mean age 39 years), of whom 35 had the ABCA4-associated STGD1, three had ELOVL4-associated STGD3, and seven had PRPH2/RDS-associated macular dystrophy. Ten patients were followed longitudinally for a mean of 19 months.


Three phenotypes have been identified previously in patients with Stargardt disease, ABCA4-associated STGD1. Type 1 is characterised by only a central lesion, type 2 flecks across the macula and type 3 comprises large atrophic areas.

Imaging technology took a step forward with the advent of FLIO, which shows these lesions. However, as Dr Sauer noted, it also demonstrates both significantly different lifetimes among the three phenotypes and that the lifetimes in the foveal centre are correlated significantly with the best-corrected visual acuity.

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Dr Sauer and her colleagues reported a particularly important finding:1 that is, FLIO demonstrated that the geographic atrophy secondary to age-related macular degeneration (AMD) has a markedly different appearance from the retinal atrophy associated with Stargardt disease. In contrast, the two diseases can appear very similar when using autofluorescence intensity imaging.

The investigators also reported previously that eyes with AMD were characterised by a ring with prolonged lifetimes that are seen as a shift to blue at the fundus; in contrast, this pattern is not seen in eyes with Stargardt disease. This pattern difference facilitates easy differentiation of the two diseases.

Dr Sauer is also studying the different genotypes in patients with ABCA4-related Stargardt disease. “We believe that FLIO imaging can show differences among the many different genetic subtypes,” she said.

Longitudinal analysis

Another area of research interest is evaluation of the details in eyes with ELOVL4-associated STGD3 and PRPH2/RDS-associated macular dystrophy, which are Stargardt-like dystrophies. “It is very interesting that all eyes with PRPH2/RDS-associated macular dystrophy showed flecks of short FLIO lifetimes,” Dr Sauer noted.

This is noteworthy because the baseline FLIO image showed some flecks of short FLIO lifetimes that were not visible on the baseline autofluorescence intensity image but only appeared 1 year later on a follow-up image. “At that time, the FLIO lifetimes are prolonged from short to long, and the patient we examined reported a new central scotoma where an area of markedly prolonged FLIO lifetimes was seen on the follow-up image,” she said.

Dr Sauer explained that the relevance of this research is that the short FLIO flecks appear before changes seen on other imaging modalities including optical coherence tomography (OCT). The researchers believe that when the short FLIO lifetimes are seen, the changes may be reversible because they precede structural retinal changes. However, by the time the changes appear on other imaging modalities, reversing them may be impossible.

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These flecks also appear in some patients with Stargardt disease, and Dr Sauer noted that they behave the same as in PRPH2/RDS-associated macular dystrophy. FLIO lifetimes show a characteristic pattern in Stargardt disease, and different phenotypes can be identified.

Different genotypes have characteristic FLIO findings. “The most important finding is that short flecks initially identified by FLIO imaging prolong over time, and these changes seen on FLIO imaging are visible before appearing on OCT images and other imaging modalities,” Dr Sauer concluded.

1. Sauer L, Gensure RH, Andersen KM, et al. Patterns of fundus autofluorescence lifetimes in eyes of individuals with nonexudative age-related macular degeneration. Invest Ophthalmol Vis Sci. 2018;59:AMD65-AMD77.
Lydia Sauer, MD
Dr Sauer is a medical consultant to Tesseract Health and receives non-financial support from Heidelberg Engineering.

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