POS1393 QUANTITATIVE AUTOFLUORESCENCE FINDINGS IN PATIENTS UNDERGOING HYDROXYCHLOROQUINE TREATMENT
Authors: S. Parrulli, M. Cozzi, M. Airaldi, F. Romano, F. Viola, P. Sarzi-Puttini, G. Staurenghi, A. Invernizzi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Hydroxychloroquine (HCQ) is a relatively safe and effective drug widely used as primary or adjunctive treatment for several rheumatological and dermatological disorders 1 . HCQ modulates immune response through several mechanisms and has a tropism for pigmented ocular tissues, particularly retinal pigment epithelium (RPE) 2 . Its accumulation within RPE cells can lead to sight threatening retinal toxicity, with bull’s eye maculopathy (BEM) representing its advanced phenotype. 3 Quantitative Auto-Fluorescence (qAF) is an imaging modality that allows the measurement of retinal auto-fluorescence following short-wavelength light (488nm) excitation of retinal fluorophores (lipofuscin). 4 Two recent studies have focused on qAF values in patients treated with HCQ 5,6 . In both cases qAF was increased in eyes with BEM. Furthermore, Reichel et al. 6 were able to detect increased values of qAF in patients without BEM as early as 6 months after the start of HCQ treatment using an experimental imaging analysis procedure. Objectives: To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) with no apparent signs of retinal toxicity and to compare it with that of untreated subjects. Methods: Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment &gt;5 years or daily HCQ dose &gt;5 mg/kg of actual body weight (ABW) and/or renal insufficiency) 7 but no alterations on Spectral Domain - Optical Coherence Tomography, Short-Wavelength Autofluorescence and 10-2 Visual Field examination were recruited. Healthy subject matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analyzed using the conventional qAF grid by Delori calculating the qAF of 8 sectors of the intermediate ring and the mean of those values (qAF 8 ). Results: Thirty-nine patients treated with HCQ (38 females, mean age 52,1 ± 8,6 years) and 39 untreated subjects (38 females, mean age 51,2 ± 8,6 years). In both HCQ patients and untreated subjects, qAF 8 was positively correlated with age (p=0.004) (Figure 1). Although HCQ patients showed a higher mean qAF 8 compared to untreated subjects (294,7 ±65,3 vs 268,9 ± 57,5), the difference was not significant (p=0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared to untreated subjects (all p&lt;0.05). Figure 1. Visual representation of a model predicting the standardized qAF values as influenced by age and HCQ daily dose/ABW, calculated for a treatment duration of 15 years. Conclusion: These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure. Further studies are required to improve our understanding of preclinical stages of HCQ retinopathy and the possible role of qAF in the HCQ toxicity screening. References: [1]Haładyj, E., Sikora, M., Felis-Giemza, A. &amp; Olesińska, M. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia 56 , 164–173 (2018). [2]Rosenthal, A. R., Kolb, H., Bergsma, D., Huxsoll, D. &amp; Hopkins, J. L. Chloroquine retinopathy in the rhesus monkey. Invest. Ophthalmol. Vis. Sci. 17 , 1158–1175 (1978). [3]Modi, Y. S. &amp; Singh, R. P. Bull’s-Eye Maculopathy Associated with Hydroxychloroquine. N. Engl. J. Med. 380 , 1656 (2019). [4]Sparrow, J. R., Duncker, T., Schuerch, K., Paavo, M. &amp; de Carvalho, J. R. L. J. Lessons learned from quantitative fundus autofluorescence. Prog. Retin. Eye Res. 74 , 100774 (2020). [5]Greenstein, V. C. et al. Quantitative Fundus Autofluorescence in HCQ Retinopathy. Invest. Ophthalmol. Vis. Sci. 61 , 41 (2020). [6]Reichel, C. et al. Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy. Transl. Vis. Sci. Technol. 9 , 42 (2020). [7]Yusuf, I. H., Sharma, S., Luqmani, R. &amp; Downes, S. M. Hydroxychloroquine retinopathy. Eye (Lond). 31 , 828–845 (2017). Disclosure of Interests: Salvatore Parrulli: None declared, Mariano Cozzi Grant/research support from: Bayer, Nidek, Zeiss, Matteo Airaldi: None declared, Francesco Romano: None declared, Francesco Viola: None declared, Piercarlo Sarzi-Puttini: None declared, Giovanni Staurenghi Grant/research support from: Heidelberg Engineering (C), QuantelMedical (C), Centervue (C), Carl Zeiss Meditec (C), Alcon (C), Allergan (C), Bayer (C), Boheringer (C), Genentech (C), GSK (C),Novartis (C), and Roche (C), Optos (F), Optovue (F) and Centervue (F), Alessandro Invernizzi Grant/research support from: Novartis (C), Bayer (C)