Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy: One Year Follow-Up

Abstract

Purpose: Systemic chloroquine/hydroxychloroquine (CQ/HCQ) can cause severe ocular side effects including bull's eye maculopathy (BEM). Recently, we reported higher quantitative autofluorescence (QAF) levels in patients with CQ/HCQ intake. Here, QAF in patients taking CQ/HCQ in a 1-year follow-up is reported.

Methods: Fifty-eight patients currently or previously treated with CQ/HCQ (cumulative doses 94-2435 g) and 32 age- and sex-matched healthy subjects underwent multimodal retinal imaging (infrared, red free, fundus autofluorescence [FAF], QAF [488 nm], and spectral-domain optical coherence tomography (SD-OCT). For analysis, custom written FIJI plugins were used for image processing, multimodal image stacks assembling, and QAF calculation.

Results: Thirty patients (28 without BEM and 2 with BEM, age range = 25-69 years) were followed up (370 ± 63 days). QAF values in patients taking CQ/HCQ showed a significant increase between baseline and follow-up examination: 282.0 ± 67.9 to 297.7 ± 70.0 (QAF a.u.), P = 0.002. An increase up to 10% was observed in the superior macular hemisphere. Eight individuals (including 1 patient with BEM) had a pronounced QAF increase of up to 25%. Compared to healthy controls, QAF levels in patients taking CQ/HCQ were significantly increased (P = 0.04).

Conclusions: Our study confirms our previous finding of increased QAF in patients taking CQ/HCQ with a further significant QAF increase from baseline to follow-up. Whether pronounced QAF increase might predispose for rapid progression toward structural changes and BEM development is currently investigated in ongoing studies.

Translational relevance: In addition to standard screening tools during systemic CQ/HCQ treatment, QAF imaging might be useful in CQ/HCQ monitoring and could serve as a screening tool in the future.

Figure 1.

QAF development of all patients taking CQ/HCQ for baseline (blue) and at 1-year follow-up (orange). The dotted lines represent the trend lines for each group (orange = follow-up, blue = baseline, green = control group, and light green = 95% confidence interval for control group). For all groups, an increase in QAF with age can be seen.

Figure 2.

Mean values of QAF97 intensities for different subject groups at baseline and at follow-up. For the healthy control group (yellow bar), interpolated QAF97 intensity after 1 year according to age-related increase of 2.84 (QAF a.u.) per year (dotted yellow bar) are shown, (subgroup analysis using data from Kleefeldt et al.¹⁴). QAF97 intensities of patients taking CQ/HCQ without BEM (blue bar) and with BEM (orange bar) at baseline and follow-up visit are plotted.

Figure 3.

Change in QAF intensity (in %) for all QAF97 segments. Change of QAF intensities (follow-up/baseline) were converted to gray scale. Highest QAF change of approximately +10% (black) can be found at the superior region, whereas the lowest QAF change of approximately +1% (light gray) is present inferior segments.

Figure 4.

Average QAF values of segments in the superior and segments in the inferior hemisphere are plotted for patients taking CQ/HCQ in the follow-up group without BEM (blue points), CQ/HCQ patients with BEM (red points), and the healthy control group (yellow points). The dots above the slope represent segments in the superior hemisphere that have higher QAF than in inferior segments in an individual patient.

Figure 5.

Quantification of the atrophic zone after 1-year follow-up. For both patients, the corresponding 8-bit-QAF images including the atrophic zone at baseline and follow-up are shown. Atrophy was defined as QAF values below 120 (QAF a.u.). For the entire atrophic zone, pixels count of the atrophic zone and corresponding retinal area are depicted. (A) The subject is 35 years old; cumulative dose = 887.25 g CQ; who stopped using HCQ 2 months before baseline examination. (B) The subject is 56 years old; cumulative dose of HCQ = 146 g + CQ = 1567 g; stopped using CQ/HCQ 121 months before baseline examination.

Figure 6.

QAF and retinal thickness changes in a 1-year follow-up. (A) A vertical cross section through the ETDRS grid (denoted by the yellow dotted line) was used for analysis of QAF and retinal thickness. (B)Retinal thicknesses of the whole retina and QAF of BL and follow-up and patients with BEM. There is a sharp decrease in QAF of patients with BEM in segment 4 which corresponds to the inferior parafoveal region.