Abstract
Purpose:
To evaluate the association between parameters derived from subjective and objective screening tests for hydroxychloroquine (HCQ) retinal toxicity and the presence of functional HCQ toxicity.
Methods:
Participants with a previous or current history of HCQ treatment of duration > 5 years were enrolled in a prospective, single-center study and evaluated with a medical history, dilated ophthalmological examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral domain optical coherence tomography (SD-OCT), automated Humphrey visual field (HVF) testing (10-2), and multifocal electroretinography (mfERG). Participants were defined as either (1) affected or (2) unaffected by HCQ-induced retinal toxicity using mfERG R1/R2 ring ratios. Associations of affected status with participant features and with the following test parameters were assessed: OCT retinal thickness in macular subfields, HVF mean deviation (MD), and manual grading of fundus and OCT images.
Results:
Participants (n=57; 91.2% female, age 55.7±10.4 years, HCQ treatment duration 15±7.5 years; mean±SD) were divided into affected (n=19) and unaffected (n=38) groups using mfERG parameters. Mean age and duration of HCQ use were not statistically different between groups. Mean OCT subfield macular thicknesses in all 9 subfields and mean HVF MDs in the affected group were significantly lower (p<0.01 for all comparisons) than in the unaffected group. Mean OCT macular thicknesses in inner subfields and mean HVF MDs were significantly correlated with the mfERG across all participants (r=-0.45, p=0.0007). Masked grading of retinal images for the presence of toxicity were positive in the (1) affected and (2) unaffected groups respectively at the following rates: 68.4% and 0% on color fundus photographs, 73.3% and 9.1% on FAF fundus images, 84.2% and 0% on SD-OCT grading for perifoveal loss of the photoreceptor inner segment/outer segment junction. Using a polynomial modeling approach, OCT retinal thicknesses in the inner subfields and HVF MDs were identified among testing variables as being most closely associated with affected status.
Conclusions:
Inner retinal subfield OCT thickness and 10-2 HVF MD are quantitative objective measures that correlate well with an mfERG-based identification of HCQ toxicity and may have utility as accessible screening parameters for the detection of HCQ toxicity.
Keywords: 688 retina •
503 drug toxicity/drug effects •
550 imaging/image analysis: clinical