Implementation of a pilot teleretinal screening protocol for hydroxychloroquine retinopathy in a Los Angeles County safety net clinic

Introduction This study aimed to determine whether teleretinal screening for hydroxychloroquine retinopathy (HCQR) improves clinical efficiency and adherence to recommended screening guidelines compared to face-to-face screening among patients in a large safety net medical system. Methods In this retrospective cohort study of a consecutive sample of 590 adult patients with active HCQ prescriptions seen in the outpatient ophthalmology clinic at Los Angeles County + University of Southern California Medical Center from 1 September 2018 to 25 November 2019, 203 patients underwent technician-only tele-HCQR screening (THRS), and 387 patients underwent screening with traditional face-to-face visits (F2FV) with an eye-care provider. Data on clinic efficiency measures (appointment wait time and encounter duration) and adherence to recommended screening guidelines were collected and compared between the two cohorts. Results Compared to F2FV, the THRS cohort experienced significantly shorter median (interquartile range) time to appointment (2.5 (1.5–4.6) vs. 5.1 (2.9–8.4) months; p < 0.0001), shorter median encounter duration (1 (0.8–1.4) vs. 3.7 (2.5–5.2) hours; p < 0.0001) and higher proportion of complete baseline screening (102/104 (98.1%) vs. 68/141 (48.2%); p < 0.001) and complete chronic screening (98/99 (99%) vs. 144/246 (58.5%); p < 0.001). Discussion A pilot THRS protocol was successfully implemented at a major safety net eye clinic in Los Angeles County, resulting in a 50.9% reduction in wait times for screening, 72.9% reduction in encounter duration and 49.9% and 40.5% increases in proportions of complete baseline and chronic screening, respectively. Tele-HCQ retinal screening protocols may improve timeliness to care and screening adherence for HCQR in the safety net setting.

Frequency and risk factors for hydroxychloroquine retinopathy among patients with systemic lupus erythematosus

Background Hydroxychloroquine (HCQ) is an antimalarial drug, recently used in COVID-19 treatment. Also it is considered over many years the cornerstone in treating systemic lupus erythematosus (SLE) in adults and children. The incidence of retinal affection and retinal toxicity from hydroxychloroquine is rare, but even after the HCQ is stopped, loss of vision may not be reversible and may continue to progress. Fundus autofluorescence (FAF) is one of the screening methods recommended by AAO used for the diagnosis of hydroxychloroquine retinopathy. Our aim is to detect early HCQ-induced retinopathy among SLE patients and the risk factors for its development by using fundus autofluorescence. Results In the present study, 11.3% of the studied patients had significant visual field changes upon testing. Of those, 6.3% had abnormal fundus autofluorescence. We found a significant statistical relation between hydroxychloroquine retinopathy and the duration and cumulative dose of hydroxychloroquine therapy (p value = 0.003) and decreased best-corrected visual acuity of both eyes (p value = 0.000). There was no relationship between HCQ retinopathy detected by fundus autofluorescence and daily dose of HCQ/kg, age, sex, and SLEDAI score. Conclusion Frequency of SLE patients who had confirmed HCQ-induced retinopathy was 6.3%. Hydroxychloroquine could be safely used in all SLE patients regardless of age, sex, and SLE activity. Routine ophthalmological assessment is recommended for SLE patients who received HCQ especially for those who received HCQ longer than 7 years. Fundus autofluorescence is a modern objective tool which is specific for the early detection of HCQ retinopathy.

OP0133 THE PREVALENCE AND RISK FACTORS OF RETINAL TOXICITY ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE

Background:Hydroxychloroquine (HCQ) is commonly used for the treatment of various autoimmune diseases. The medication is generally well-tolerated. However, long-term use after 5 years may increase the risk of retinopathy. One study in 2014 has demonstrated the risk can be as high as 7.5%. Optical Coherence Tomography (OCT) has become a major modality in screening retinopathy.Objectives:To evaluate the prevalence of retinal toxicity among patients using hydroxychloroquine and to determine various risk factors associated with hydroxychloroquine-associated retinal toxicity.Methods:We performed a retrospective chart review on a cohort of adult patients with long-term use (≥ 5 years cumulative) of HCQ between January 1st, 2011 to December 31st, 2018 from the Kaiser Permanente San Bernardino County and Riverside medical center areas in Southern California, USA. Patients were excluded if they had previously been diagnosed with retinopathy prior to hydroxychloroquine use, were deceased, or had incomplete OCT exam. Our primary endpoint was the prevalence of patients who developed retinal toxicity detected by OCT, and later confirmed by retinal specialist. Potential risk factors (age, duration of therapy, daily consumption per actual body weight, cumulative dose, confounding diseases and medication) for developing retinopathy were also evaluated. Univariable and multivariable logistic regression analyses were used to determine risk factors associated with retinal toxicity.Results:Among 676 patients exposed to more than 5 years of HCQ, the overall prevalence of retinal toxicity was 6.8%, and ranged from 2.5% to 22.2% depending on the age, weight-based dosing, duration of use and cumulative dose. Duration of therapy for 10 years or more increased risk of retinopathy by approximately 5 to 19 folds. Similarly, weight-based dose of 7 mg/kg/day or greater was assciated with increased risk of retinopathy by approximately 5 times. Patients with cumulative dose of 2000 grams or more had greater than 15 times higher risk of developing retinopathy. Duration of use for10 years or more (odd ratio 4.32, 95% CI 1.99 – 12.49), age (odd ratio 1.04; 95% CI 1.01 - 1.08), cumulative dose of more than 1500 g (odd ratio 7.4; 95% CI 1.40 – 39.04) and atherosclerosis of the aorta (odd ratio 2.59; 95% CI, 1.24 – 5.41) correlated with higher risk of retinal toxicity.Conclusion:The overall prevalence of retinopathy was 6.8%. Regular OCT screening, especially in patients with hydroxychloroquine use for more than 10 years, daily intake > 7 mg/kg, or cumulative dose > 1500 grams is important in detecting hydroxychloroquine-associated retinal toxicityReferences:[1]Hobbs HE. Sorsby A, & Freedman A. Retinopathy Following Chloroquine Therapy. The Lancet. 1959; 2(7101): 478-480.[2]Levy, G. D., Munz, S. J., Paschal, J., Cohen, H. B., Pince, K. J., & Peterson, T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis & Rheumatism: 1997; 40(8): 1482-1486.[3]Ding, H. J., Denniston, A. K., Rao, V. K., & Gordon, C. Hydroxychloroquine-related retinal toxicity. Rheumatology. 2016; 55(6): 957-967.[4]Stelton, C. R., Connors, D. B., Walia, S. S., & Walia, H. S. Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clinical rheumatology. 2013; 32(6): 895-898.[5]Marmor, M. F., Kellner, U., Lai, T. Y., Melles, R. B., & Mieler, W. F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016; 123(6): 1386-1394.[6]Melles, R. B., & Marmor, M. F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA ophthalmology. 2014; 132(12): 1453-1460.Disclosure of Interests:None declared

POS1393 QUANTITATIVE AUTOFLUORESCENCE FINDINGS IN PATIENTS UNDERGOING HYDROXYCHLOROQUINE TREATMENT

Background:Hydroxychloroquine (HCQ) is a relatively safe and effective drug widely used as primary or adjunctive treatment for several rheumatological and dermatological disorders1. 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 >5 years or daily HCQ dose >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 (qAF8).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, qAF8 was positively correlated with age (p=0.004) (Figure 1). Although HCQ patients showed a higher mean qAF8 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<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. & Olesińska, M. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia56, 164–173 (2018).[2]Rosenthal, A. R., Kolb, H., Bergsma, D., Huxsoll, D. & Hopkins, J. L. Chloroquine retinopathy in the rhesus monkey. Invest. Ophthalmol. Vis. Sci.17, 1158–1175 (1978).[3]Modi, Y. S. & 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. & 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. & 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)