New insights in pathogenic mechanism of hydroxychloroquine-induced ocular toxicity through choroidal imaging analysis.

Purpose: To analyze the choroidal vascularity index (CVI) in patients using hydroxychloroquine (HCQ).

Methods: We conducted a retrospective study. The study included 28 healthy patients (56 eyes), 28 patients (56 eyes) using HCQ for 5 years or less (low-risk group), and 22 patients (44 eyes) using HCQ for more than 5 years (high-risk group), all diagnosed with different autoimmune diseases. CVI, total choroidal area (TCA), luminal choroidal area (LCA), stromal choroidal area (SCA), and vessel density (VD) in the choriocapillaris and in the mid choroid, measured using a swept-source optical coherence tomography angiography (SS-OCTA), were registered. In addition, asymmetry index was calculated.

Results: CVI was higher in the high-risk group compared with the control group and the low-risk group (p value < 0,001). In addition, the AI of CVI was lower in the high-risk group compared with the control group (p value 0,042). Regarding SS-OCTA parameters, VD in the mid choroid was lower in the high-risk group compared with the control group (p value 0,001). Correlation analysis revealed a positive correlation between the duration of HCQ therapy and the CVI (r 0,301, p value 0,002), and a negative correlation between HCQ therapy duration and the AI of the TCA, LCA, and SCA (r -0,309, -0,308 and - 0,281, p value 0,027, 0,028 and 0,038, respectively).

Conclusion: We demonstrated a higher CVI in patients on long-term HCQ therapy. Therefore, we suggest that HCQ toxicity may involve the choroid, possibly as a maladaptive vascular response secondary to outer retinal stress induced by the drug.