Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) Shows Early Toxicity of Hydroxychloroquine

Abstract

Purpose : To investigate the impact of retinal toxicity of hydroxychloroquine (HCQ) on fundus autofluorescence (FAF) lifetimes.

Methods : 24 eyes of 12 subjects with definite HCQ toxicity, 27 eyes of 14 clinically normal patients at high risk to develop HCQ toxicity (on HCQ longer than 5 years), and 16 eyes of 8 clinically normal patients at low risk to develop HCQ toxicity (on HCQ shorter than 5 years), as well as 32 age-matched healthy subjects, were investigated. Fluorescence lifetime images of a 30° retinal field centered at the fovea were collected at the Moran Eye Center in Salt Lake City, Utah. A prototype Heidelberg Engineering Spectralis-based FLIO was used to detect FAF lifetimes in short (498-560 nm, SSC) and long (560-720 nm, LSC) spectral channels. The mean fluorescence lifetimes (t_m) were calculated. Optical coherence tomography (OCT) scans and macular pigment measures were also recorded. Additionally, autofluorescence lifetimes of known dilutions of HCQ were measured in a cuvette.

Results : :All patients (6 out of 6) with HCQ toxicity by OCT and an autofluorescence lesion show significantly prolonged FAF lifetimes in the area of a lesion (SSC: lesion 400 ps, healthy retina: 294 ps, p<0.001; LSC: lesion 404 ps, healthy retina: 316 ps, p<0.001). Distinct bull’s eye distribution patterns corresponded to toxic lesions in the retina. Patients with early toxicity by OCT but no autofluorescence lesion (6 out of 6, 100%) as well as some clinically normal patients at high risk (8 out of 15, 53%) and low risk (1 out of 8, 12.5%) showed prolonged FAF lifetimes in the parafoveal region (SSC: 311 ps, LSC: 333 ps). Patients without these changes showed significantly shorter lifetimes in the parafoveal area (SSC: 254 ps, LSC: 294 ps, p<0.05). Hydroxychloroquine at concentration of 46 mM was clearly detectable, showing long autofluorescence lifetimes of around 1100 ps in either spectral channel.

Conclusions : FLIO appears to detect retinal toxicity due to HCQ at very early stages, potentially presenting a novel method to detect retinal toxicity before irreversible damage is manifest.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Fundus autofluorescence lifetime images of a healthy suject and one patient with hydroxychloroquine (HCQ) toxicity. Right eye (OD) as well as left eye (OS) are presented.