Comparing Fluorescence Lifetime Imaging Ophthalmoscopy in Atrophic Areas of Retinal Diseases

Abstract

Purpose Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a non-invasive imaging modality to investigate the human retina. This study compares FLIO lifetimes in different degenerative retinal diseases. Methods Included were eyes with retinal pigment epithelium (RPE) and/or photoreceptor atrophy due to Stargardt disease ( n = 66), pattern dystrophy ( n = 18), macular telangiectasia type 2 ( n = 49), retinitis pigmentosa ( n = 28), choroideremia ( n = 26), and geographic atrophy ( n = 32) in age-related macular degeneration, as well as 37 eyes of 37 age-matched healthy controls. Subjects received Heidelberg Engineering FLIO, autofluorescence intensity, and optical coherence tomography imaging. Amplitude-weighted mean FLIO lifetimes (τ m ) were calculated and analyzed. Results Retinal FLIO lifetimes show significant differences depending on the disease. Atrophic areas in geographic atrophy and choroideremia showed longest mean FLIO lifetimes. τ m values within areas of RPE and outer nuclear layer atrophy were significantly longer than within areas with preserved outer nuclear layer ( P < 0.001) or non-atrophic areas ( P < 0.001). Conclusions FLIO is able to contribute additional information regarding differences in chronic degenerative retinal diseases. Although it cannot replace conventional autofluorescence imaging, FLIO adds to the knowledge in these diseases and may help with the correct differentiation between them. This may lead to a more in-depth understanding of the pathomechanisms related to atrophy and types of progression. Translational Relevance Differences between atrophic retinal diseases highlighted by FLIO may indicate separate pathomechanisms leading to atrophy and disease progression.

Age-Related Macular Degeneration, a Mathematically Tractable Disease

“…One factor potentially contributing to this sparing may be Müller glia, which survive the loss of photoreceptors 205 and retain detectable xanthophylls. 206 – 208 Furthermore, another analysis (365 eyes) showed that photopic visual acuity declined dramatically in relation to the amount of the remaining 1 mm-diameter central subfield. 209 Atrophy within this subfield 209 negatively correlated with visual acuity, with 34.8 letters lost if the entire subfield was affected.…”

Multispectral label-free in vivo cellular imaging of human retinal pigment epithelium using adaptive optics fluorescence lifetime ophthalmoscopy improves feasibility for low emission analysis and increases sensitivity for detecting changes with age and eccentricity

“…FLIO with blue light excitation has been demonstrated in a clinical setting, has shown changes with age and eccentricity, 22 – 24 and has different phenotypes with disease. 25 – 27 Adaptive optics FLIO (AOFLIO), which provides cellular-scale compositional and functional information has been demonstrated in vivo in mice, 28 , 29 non-human primates, 30 , 31 and humans. 32 – 35 With the ability to change the excitation wavelength, AOFLIO can probe contributions primarily from lipofuscin, melanin, and melanolipofuscin, AOFLIO has the potential to provide insight into in vivo cellular-scale changes with age and eccentricity.…”