Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) in Patients with Choroideremia

Abstract

To provide a detailed characterization of choroideremia (CHM) using fluorescence lifetime imaging ophthalmoscopy (FLIO) and to provide a deeper understanding of disease-related changes and progression. Methods: Twenty-eight eyes of 14 patients with genetically confirmed CHM (mean age, 28 ± 14 years) and 14 age-matched healthy subjects were investigated in this study. FLIO images of a 30°retinal field were collected at the Moran Eye Center using a Heidelberg Engineering FLIO device. FLIO lifetimes were recorded in short spectral channels (SSC; 498-560 nm) and long spectral channels (LSC; 560-720 nm), and mean autofluorescence lifetimes (τ m) were calculated. Optical coherence tomography (OCT) scans were recorded for each patient. Three patients were re-imaged after a year. Results: Patients with CHM exhibit specific FLIO lifetime patterns. Prolonged FLIO lifetimes (around 600-700 ps) were found in the peripheral macula corresponding to atrophy in OCT imaging. In the central macula, τ m was unrelated to autofluorescence intensity. Some areas of persistent retinal pigment epithelial islands had prolonged FLIO lifetimes, whereas other areas of hypofluorescence had short FLIO lifetimes. At 1-year follow-up, FLIO lifetimes were significantly prolonged within atrophic areas (P < 0.05). Conclusions: FLIO shows distinct patterns in patients with CHM, indicating lesions of atrophy and areas of preserved function in the presence or absence of findings in fundus autofluorescence intensity images. FLIO may provide differentiated knowledge about pathophysiology and atrophy progression in CHM compared to conventional imaging modalities. Translational Relevance: FLIO shows distinctive lifetime patterns that potentially identify areas of function, atrophy, and disease progression in patients with CHM.

Comparing Fluorescence Lifetime Imaging Ophthalmoscopy in Atrophic Areas of Retinal Diseases

“…Two previous FLIO studies investigated patients with choroideremia. 47 , 50 In one study, the authors argued that the short FLIO lifetimes may originate from an accumulation of the visual cycle byproduct all- trans retinal, which typically shows short fluorescence lifetimes. 51 According to the authors, this could indicate preserved metabolic activity in the photoreceptors.…”

“… 30 , 31 A second FLIO study on patients with choroideremia found short FLIO lifetimes originating from areas with outer retinal tubulations. 50 Short FLIO lifetimes within atrophic retinal areas may indicate areas of at least partially preserved photoreceptor structure, which eventually might indicate preserved photoreceptor function. This might be an interesting finding to consider when identifying patients who might benefit from enrollment in early clinical trials.…”

The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques

“…In the case of hydroxychloroquine toxicity, where early toxicity detection is challenging, FLIO could provide a better alternative to electroretinogram (ERG) or OCT, since it can detect prolonged FLTs before structural changes appear (465,466). FLIO has also been used to identify changes in other retinal conditions as well, including DR (Figure 7), vascular occlusive diseases, CSR, choroideremia, RP, and macular holes, and is believed to be a promising diagnostic method (463,(467)(468)(469)(470)(471)(472)(473).…”

Recent innovations in fluorescence lifetime imaging microscopy for biology and medicine

“…show that FLIO can detect an increase in autofluorescence lifetime in the diseased tissue of a small cohort of patients with choroideremia, an ocular disease, compared to normal surrounding tissue 30 [Fig. 3(a), middle panel].…”