Imaging of Hydroxychloroquine Toxicity with Fluorescence Lifetime Imaging Ophthalmoscopy

Abstract

To investigate the impact of retinal toxicity from hydroxychloroquine (HCQ) on fundus autofluorescence lifetimes using fluorescence lifetime imaging ophthalmoscopy (FLIO). Cross-sectional study. Twenty-four eyes of 12 patients with definite HCQ toxicity, 31 eyes of 16 clinically normal patients at high risk of developing HCQ toxicity (taking HCQ longer than 5 years), and 16 eyes of 8 clinically normal patients at low risk of developing HCQ toxicity (taking HCQ fewer than 5 years), as well as 22 age-matched healthy subjects. Fluorescence lifetime images of a 30° retinal field centered at the fovea were collected at the Moran Eye Center, Salt Lake City, Utah. A prototype Heidelberg Engineering Spectralis-based FLIO was used to detect autofluorescence lifetimes in short (SSC; 498-560 nm) and long (LSC; 560-720 nm) spectral channels. Mean fluorescence lifetimes were calculated. OCT scans and macular pigment measures were also recorded. Additionally, the autofluorescence lifetimes of HCQ were measured in a cuvette. Mean autofluorescence lifetimes (τm). All patients with HCQ toxicity showed significantly prolonged FLIO lifetimes in regions of damage, typically in a bulls-eye distribution corresponding to toxic lesions in the retina (SSC: lesion, 400 ps; unremarkable retina, 294 ps; P < 0.001; LSC: lesion, 404 ps; unremarkable retina, 316 ps; P < 0.001). Some clinically normal patients at high risk (9 of 16) and at low risk (2 of 8) of developing HCQ toxicity also showed prolonged FLIO lifetimes in the parafoveal region, whereas age-matched healthy subjects did not. HCQ at a concentration of 46mM exhibited long autofluorescence lifetimes of around 1100 ps in either spectral channel. Fluorescence lifetime imaging ophthalmoscopy seems to detect retinal toxicity from HCQ at very early stages and could be a novel method to detect retinal toxicity before irreversible damage is manifest.