Abstract
Background:
Hydroxychloroquine (HCQ) maculopathy is irreversible; primary prevention is done by regular monitoring. Guidelines of the Royal College of Ophthalmologists identify definite toxicity as having abnormal results of two screening tests, we present a quantitative method for interpreting these guidelines.
Methods:
We obtained ocular coherence tomography (OCT) scans of 100 patients who have been on HCQ for 5 years or more (patients) and 70 age-matched controls. Both groups had 10’2 visual field (VF) test. We used linear regression to determine the cut-off points for each of the eight Early Treatment of Diabetic Retinopathy Study (ETDRS) macular sectors for the VF and OCT. We calculated the probability of developing maculopathy using logistic regression.
Results:
Mean patient age: 59.9 years, 85% females, no statistically significant age difference between the patients and the control groups. Diagnosis: 64% rheumatoid arthritis, 14% Sjogren’s syndrome, 16% systemic lupus and 6% various other rheumatology conditions. Mean duration of use was 6.3 years. Logistic regression results show strong negative correlation between the outer nuclear layer (ONL) volume and probability of toxicity. Goodness of fit was tested using Hosmer and Lemeshow test that indicates a high significance with a high P-value of 1.
Conclusions:
Combining the ONL volume reduction and VF retinal sensitivity reduction per each of the eight ETDRS macular sectors provides an accurate and objective way of diagnosing HCQ maculopathy, this helps busy eye units establishing an optometrist-led or virtual service because it is independent of the assessor’s level of experience.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye. 2017;4:828–45.
Jorge AM, Melles RB, Zhang Y, Lu N, Rai SK, Young LH, et al. Hydroxychloroquine prescription trends and predictors for excess dosing per recent ophthalmology guidelines. Arthritis Res Ther. 2018;20:133–40.
Browning DJ. Hydroxychloroquine and chloroquine retinopathy. 1st ed. York, UK: Springer; 2014.
Browning DJ, Lee C. Somatotype, the risk of hydroxychloroquine retinopathy, and safe daily dosing guidelines. Clin Ophthalmol. 2018;12:811–8.
Melles RB, Marmor MF. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. Ophthalmology 2015;122:110–6.
Lotery A, Yusuf I, Foot B, Bishop P, Burdon M, Watson S, et al. Hydroxychloroquine and chloroquine retinopathy: recommendations on screening. London: The Royal College of Ophthalmologists; 2018.
Anderson C, Blaha GR, Marx JL. Humphrey visual field findings in hydroxychloroquine toxicity. Eye. 2011;25:1535–45.
Chen E, Brown DM, Benz MS, Fish RH, Wong TP, Kim RY, et al. Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the “flying saucer” sign). Clin Ophthalmol. 2010;4:1151–8.
Allahdina AM, Stetson PF, Vitale S, Wong WT, Chew EY, Ferris FL, et al. Optical coherence tomography minimum intensity as an objective measure for the detection of hydroxychloroquine toxicity. Invest Ophthalmol Vis Sci. 2018;59:1953–63.
Ahn SJ, Joung J, Lim HW, Lee BR. Optical coherence tomography protocols for screening of hydroxychloroquine retinopathy in asian patients. Am J Ophthalmol. 2017;9:11–18.
Kolb H, Fernandez E, Nelson R. Webvision: the organization of the retina and visual system [Internet]. Salt Lake City, UT: University of Utah Health Sciences Center; 1995.
Bewick V, Cheek L, Ball J. Statistics review 14: logistic regression. Crit Care. 2005;9:112–8.
Iftikhar M, Kaur R, Nefalar A, Usmani B, Kherani S, Rashid I, et al. Microperimetry as a screening test for hydroxychloroquine retinopathy The Hard-Risk-1 Study. J Retinal Vitreous Dis. 2018;0:1–7.
Tucker WR, Galloway J, Walsh S. The gathering storm: hydroxychloroquine retinopathy screening in the U.K. Br J Dermatol. 2017;176:1420–1.
Espandar G, Moghimi J, Ghorbani R, Pourazizi M, Seiri MA, et al. Retinal toxicity in patients treated with hydroxychloroquine: a cross-sectional study. Med Hypothesis Disco Innov Ophthalmol. 2016;5:41–46.
Iselin KC, Marti P, Pless M. Hydroxychloroquine-induced retinal toxicity. Klin Monatsbl Augenheilkd. 2016;233:514–6.
Brownlee J. Logistic regression for machine learning. Machine Learning Mastery Pty. Ltd., Australia. 2016. https://machinelearningmastery.com/logistic-regression-for-machine-learning/. Accessed 01 April 2016.
Babeau F, Busetto T, Hamel C, Villain M, Daien V. Adaptive optics: a tool for screening hydroxychloroquine-induced maculopathy? Acta Ophthalmol. 2017;14:424–5.
Lally DR, Heier JS, Baumal C, Witkin AJ, Maler S, Shah CP, et al. Expanded spectral domain-OCT findings in the early detection of hydroxychloroquine retinopathy and changes following drug cessation. Int J Retin Vitr. 2016;2:1–11.
Khaleel A. Risk of ophthalmologic complications as a result of hydroxychloroquine therapy. Ann Rheum Dis. 2018;6:693–4.
Marmor M, Kellner U, Lai T, Melles R, Mieler W. Recommendations on screenig for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123:1386–94.
Ruberto G, Bruttini C, Tinelli C, Cavagna L, Bianchi A, Milano G. Early morpho-functional changes in patients treated with hydroxychloroquine: a prospective cohort study. Graefes Arch Clin Exp Ophthalmol. 2018;256:2201–10.
Rodriguez-Padilla JA, Hedges TR, Monson B, Srinivasan V, Wojtkowski M, Reichel E, et al. High-speed ultra-high-resolution optical coherence tomography findings in hydroxychloroquine retinopathy. Arch Ophthalmol. 2007;125:775–80.
Hansen M, Schuman S. Hydroxychloroquine-induced retinal toxicity. EyeNet Mag. 2011;76:33–35.
Smith GP. High-risk category for early annual ophthalmology screening of patients receiving hydroxychloroquine. J Am Acad Dermatol. 2017;7:171.
Stern EM, Johnson JS, Mazzulla DA. Highly accelerated onset of hydroxychloroquine macular retinopathy. Ochsner J. 2017;17:280–3.
Zaidi FH, Rennie CA, Drinkwater AK, Sahu D, Akyol E, Lotery AJ. How to set up a hydroxychloroquine retinopathy screening service. Eye. 2019;33:1679–82.
Acknowledgements
The authors would like to extend their thanks to the staff of the Eye Clinic at the Great Western Hospital in Swindon for their support of this project.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Hasan, H., Lotery, A., Price, E.J. et al. An objective method of diagnosing hydroxychloroquine maculopathy. Eye 35, 1922–1929 (2021). https://doi.org/10.1038/s41433-020-01174-6
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-020-01174-6
This article is cited by
-
Real world pharmacovigilance assessment of drug related macular degeneration risks
Scientific Reports (2025)
-
Hydroxychloroquine
Reactions Weekly (2021)


