Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case–control study with hydroxychloroquine blood-level analysis
Authors: Lenfant Tiphaine , Salah Sawsen , Leroux Gaëlle , Bousquet Elodie , Le Guern Véronique , Chasset François , Francès Camille , Morel Nathalie , Chezel Julie , Papo Thomas , Cacoub Patrice , Mouthon Luc , Guettrot-Imbert Gaëlle , Cohen Pascal , Régent Alexis , Mauget-Faÿsse Martine , Piette Jean-Charles , Jallouli Moez , Costedoat-Chalumeau Nathalie ,   PLUS Group, Ackermann F , Amoura Z , Asli B , Astudillo Leonardo , Aumaître O , Belizna Cristina , Belmatoug Nadia , Benveniste Olivier , Benyamine Audrey , Bezanahary Holly , Blanchet B , Blanco Patrick , Bletry Olivier , Bodaghi Bahram , Bourgeois Pierre , Brihaye Benoît , Chatelus Emmanuel , Cohen-Bittan J , Damade Richard , Daugas Eric , De-Gennes Christian , Delfraissy Jean-François , Delluc Céline , Delluc Aurélien , Desmurs-Clavel H , Duhaut Pierre , Dupuy Alain , Durieu Isabelle , Hang-Korng E A , Fain Olivier , Farge Dominique , Funck-Brentano Christian , Galicier L , Gandjbakhch Frédérique , Gellen-Dautremer Justine , Ghillani-Dalbin Pascale , Godeau Bertrand , Goujard Cécile , Grandpeix Catherine , Grange Claire , Grimaldi Lamiae , Guillevin Loïc , Hachulla Eric , Harle Jean-robert , Haroche Julien , Hausfater Pierre , Hulot J-S , Jouquan Jean , Kaplanski Gilles , Keshtmand Homa , Kahn J-E , Khellaf Mehdi , Lambotte Olivier , Launay David , Le Thi Huong D , Lechat Philippe , Levesque Hervé , Lidove Olivier , Liote F , Liozon Eric , Kim L Y , Mahevas Matthieu , Mariampillai Kubéraka , Mariette Xavier , Mathian Alexis , Mazodier Karin , Michel Marc , Musset Lucile , Ngack Rokiya , Ninet Jacques , Oksenhendler Eric , Pellegrin Jean-Luc , Perard L , Peyr Olivier , Piette Anne-Marie , Poindron Vincent , Pourrat J , Roux Fabienne , Saadoun David , Sacre K , Sahali Sabrinel , Sailler L , Saint-Marcoux Bernadette , Sarrot-Reynauld Françoise , Sellam J , Schoindre Yoland , Sene Damien , Serratrice Jacques , Servais Aude , Seve Pascal , Sibilia Jean , Simon Claude , Smail A , Sordet Christelle , Stirnemann J , Terrier Benjamin , Trad Salim , Viallard Jean-François , Vidal Elisabeth , Wechsler Bertrand , Weiller Pierre-Jean , Zahr N 
Published: March 2020

Abstract

Objective
HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels.

Methods
This case–control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy.

Results
The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P &lt; 0.001), height (P = 0.045), creatinine clearance (P &lt; 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P &lt; 0.001), higher cumulative HCQ dose (P &lt; 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P &lt; 0.0001, odds ratio 8.7) remained significantly associated with retinopathy.

Conclusion
SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.