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Catherine A Cukras, Nancy Huynh, Susan Vitale, Wai T Wong, Paul A Sieving; Assessment of Subjective and Objective Screening Parameters for the Detection of Functional Hydroxychloroquine Toxicity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4881.
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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.
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.
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.
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.
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