{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:51:06Z","timestamp":1787028666907,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Hydroxychloroquine (HCQ) is used to manage various autoimmune diseases, including systemic lupus erythematosus. The prolonged use of HCQ is associated with retinopathy and irreversible visual loss due to retinal toxicity. Despite adherence to dosage regimens, patients may develop functional rather than structural changes, without detectable abnormalities on routine examination using visual acuity and optical coherence tomography (OCT). The study aimed to detect early signs of retinopathy in patients with autoimmune diseases treated with HCQ. Methods: This cross-sectional study included patients (n = 36) with autoimmune diseases who were treated with HCQ. The control group (n = 35) comprised healthy volunteers matched for age and sex. All participants were screened using colour vision tests (Ishihara, Konan ColourDX high definition [HD]), and retinal thickness was evaluated using OCT. Results: Our findings suggest a significant reduction in the contrast threshold of the L and M-cone photoreceptors compared with that of the control using Konan ColourDX HD. The OCT measurements revealed no statistically significant difference in retinal thickness between patients and controls; however, the contrast sensitivity test showed a significant reduction at all spatial frequencies (p &lt; 0.0001). Conclusions: The current study suggests that the Konan ColourDX cone contrast test HD and contrast sensitivity testing may be valuable for periodic monitoring of patients receiving HCQ, potentially enabling earlier detection of toxicity. However, longitudinal studies with larger cohorts are needed to confirm these findings and to further establish the clinical value of these functional visual tests.<\/jats:p>","DOI":"10.3390\/jcm15031309","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"1309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Contrast Sensitivity and Colour Vision Tests for Early Detection and Monitoring of Hydroxychloroquine Retinal Toxicity: A Preliminary Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0922-8541","authenticated-orcid":false,"given":"Amal","family":"Aldarwesh","sequence":"first","affiliation":[{"name":"Optometry Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifah","family":"Alwadman","sequence":"additional","affiliation":[{"name":"Optometry Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3225-3075","authenticated-orcid":false,"given":"Ali","family":"Almustanyir","sequence":"additional","affiliation":[{"name":"Optometry Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-1326","authenticated-orcid":false,"given":"Mosaad","family":"Alhassan","sequence":"additional","affiliation":[{"name":"Optometry Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed S.","family":"Alluwimi","sequence":"additional","affiliation":[{"name":"Department of Optometry, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2492-3066","authenticated-orcid":false,"given":"Ansam","family":"Alateeq","sequence":"additional","affiliation":[{"name":"Optometry Department, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8176-287X","authenticated-orcid":false,"given":"Ibrahim","family":"Almaghlouth","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12476","DOI":"10.15252\/emmm.202012476","article-title":"Hydroxychloroquine in rheumatic autoimmune disorders and beyond","volume":"12","author":"Nirk","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s42358-020-00134-8","article-title":"Revisiting hydroxychloroquine and chloroquine for patients with chronic immunity-mediated inflammatory rheumatic diseases","volume":"60","author":"Kakehasi","year":"2020","journal-title":"Adv. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/eye.2016.298","article-title":"Hydroxychloroquine retinopathy","volume":"31","author":"Yusuf","year":"2017","journal-title":"Eye"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1002\/art.1780400817","article-title":"Incidence of hydroxychloroquine retinopathy in 1207 patients in a large multicenter outpatient practice","volume":"40","author":"Levy","year":"1997","journal-title":"Arthritis Rheum."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.ajo.2015.07.012","article-title":"Rapid onset of retinal toxicity from high-dose hydroxychloroquine given for cancer therapy","volume":"160","author":"Leung","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","first-page":"41","article-title":"Retinal toxicity in patients treated with hydroxychloroquine: A cross-sectional study","volume":"5","author":"Espandar","year":"2016","journal-title":"Med. Hypothesis Discov. Innov. Ophthalmol."},{"key":"ref_7","first-page":"151","article-title":"Hydroxychloroquine dosing and toxicity: A real-world experience in Saudi Arabia of 63 patients","volume":"34","author":"Shoughy","year":"2021","journal-title":"Saudi J. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1016\/j.ophtha.2016.01.058","article-title":"Recommendations on screening for chloroquine and hydroxychloroquine retinopathy, 2016 revision","volume":"123","author":"Marmor","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ophtha.2014.07.018","article-title":"Pericentral retinopathy and racial differences in hydroxychloroquine toxicity","volume":"122","author":"Melles","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.ophtha.2015.01.014","article-title":"Pericentral hydroxychloroquine retinopathy in Korean patients","volume":"122","author":"Lee","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.3899\/jrheum.170158","article-title":"Risk of retinal toxicity in longterm users of hydroxychloroquine","volume":"44","author":"Kim","year":"2017","journal-title":"J. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yusuf, I.H., Charbel Issa, P., and Ahn, S.J. (2023). Hydroxychloroquine-induced retinal toxicity. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1196783"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.toxrep.2014.10.019","article-title":"Chloroquine and hydroxychloroquine binding to melanin: Some possible consequences for pathologies","volume":"1","author":"Schroeder","year":"2014","journal-title":"Toxicol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1007\/s12035-022-02825-3","article-title":"Hydroxychloroquine causes early inner retinal toxicity and affects autophagosome-lysosomal pathway and sphingolipid metabolism in the retina","volume":"59","author":"Mondal","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_15","first-page":"1389805","article-title":"Hydroxychloroquine\u2019s early impact on cone density","volume":"2021","author":"Oiwake","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1167\/iovs.64.12.29","article-title":"Cone density distribution and related factors in patients receiving hydroxychloroquine treatment","volume":"64","author":"Tang","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s00417-025-06772-2","article-title":"Adaptive optics cone arrangement in hydroxychloroquine users without signs of retinal toxicity based on current screening guidelines: A case-control study","volume":"263","author":"Braga","year":"2025","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_18","first-page":"e534","article-title":"Assessment of parafoveal cone density in patients taking hydroxychloroquine in the absence of clinically documented retinal toxicity","volume":"93","author":"Flores","year":"2015","journal-title":"Acta Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yusuf, I.H., Charbel Issa, P., and Ahn, S.J. (2023). Unmet needs and future perspectives in hydroxychloroquine retinopathy. Frontiers in Medicine, 10.","DOI":"10.3389\/fmed.2023.1196815"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Marmor, M.F., Ahn, S.J., Ehlers, J.P., Melles, R.B., Mieler, W.F., Sarraf, D., Yusuf, I.H., and American Academy of Ophthalmology (Ophthalmology, 2025). Special report: Recommendations on screening for hydroxychloroquine retinopathy (2026 revision), Ophthalmology, in press.","DOI":"10.1016\/j.ophtha.2025.11.001"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lee, J.M., Kwon, H.Y., and Ahn, S.J. (2024). Atypical presentations of hydroxychloroquine retinopathy: A case series study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13123411"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e2314816","DOI":"10.1001\/jamanetworkopen.2023.14816","article-title":"Practice patterns of screening for hydroxychloroquine retinopathy in South Korea","volume":"6","author":"Kim","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12330","DOI":"10.1038\/s41598-025-96579-2","article-title":"A real-world descriptive study of screening practices for hydroxychloroquine retinopathy in Japan using an insurance claims database","volume":"15","author":"Kato","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Singla, E., Ichhpujani, P., Sharma, U., and Kumar, S. (Eur. J. Ophthalmol., 2021). Contrast sensitivity assessment for early detection of hydroxychloroquine toxicity, Eur. J. Ophthalmol., online ahead of print.","DOI":"10.1177\/11206721211010612"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s10792-024-03296-2","article-title":"The assessment of structural and functional test results for early detection of hydroxychloroquine macular toxicity","volume":"44","author":"Sonalcan","year":"2024","journal-title":"Int. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1136\/bjo.87.7.902","article-title":"Detecting chloroquine retinopathy: Electro-oculogram versus colour vision","volume":"87","author":"Neubauer","year":"2003","journal-title":"Br. J. Ophthalmol."},{"key":"ref_27","unstructured":"Konan Medical (2021). Colordx High Precision Color Vision Diagnostics, Konan Medical. Available online: https:\/\/www.konanmedical.com\/colordx."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/imj.15908","article-title":"How toxic is an old friend? A review of the safety of hydroxychloroquine in clinical practice","volume":"53","author":"Fairley","year":"2023","journal-title":"Intern. Med. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1001\/archophthalmol.2010.321","article-title":"Retinal toxicity associated with hydroxychloroquine and chloroquine: Risk factors, screening, and progression despite cessation of therapy","volume":"129","author":"Michaelides","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e395","DOI":"10.1097\/RHU.0000000000001479","article-title":"Screening for hydroxychloroquine retinal toxicity in Indian patients","volume":"27","author":"Dadhaniya","year":"2021","journal-title":"J. Clin. Rheumatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00296-021-04831-5","article-title":"Prevalence of hydroxychloroquine retinopathy with long-term use in a cohort of Indian patients with rheumatic diseases","volume":"41","author":"Manoj","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1364\/AO.27.001025","article-title":"Blue (S) cone pathway vulnerability: A test of a fragile receptor hypothesis","volume":"27","author":"Hood","year":"1988","journal-title":"Appl. Opt."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1001\/archopht.118.10.1393","article-title":"Selective loss of S-cones in diabetic retinopathy","volume":"118","author":"Cho","year":"2000","journal-title":"Arch. Ophthalmol."},{"key":"ref_34","first-page":"453","article-title":"Erworbene Farbensinnst\u00f6rungen als Nebenwirkungen von Medikamenten [Acquired colour-vision deficiencies caused by side-effects of pharmacotherapy]","volume":"170","author":"Jaeger","year":"1977","journal-title":"Klin. Monbl Augenheilkd."},{"key":"ref_35","first-page":"592","article-title":"Acquired color vision defects secondary to retinal drug toxicity","volume":"158","year":"1969","journal-title":"Ophthalmologica"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Davies, N., and Barbur, J. (2022). Changes in visual function associated with hydroxychloroquine retinal toxicity. Acta Ophthalmol., 100.","DOI":"10.1111\/j.1755-3768.2022.15369"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10633-014-9474-6","article-title":"A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy","volume":"130","author":"Greenstein","year":"2015","journal-title":"Doc. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1034\/j.1600-0773.2001.088001027.x","article-title":"The phagocytosis of rod outer segments is inhibited by selected drugs in retinal pigment epithelial cell cultures","volume":"88","author":"Toimela","year":"2001","journal-title":"Pharmacol. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1002\/jps.24663","article-title":"Chloroquine and hydroxychloroquine are novel inhibitors of human organic anion transporting polypeptide 1A2","volume":"105","author":"Xu","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chandler, L.C., Yusuf, I.H., McClements, M.E., Barnard, A.R., Maclaren, R.E., and Xue, K. (2020). Immunomodulatory effects of hydroxychloroquine and chloroquine in viral infections and their potential application in retinal gene therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144972"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e000789","DOI":"10.1136\/lupus-2022-000789","article-title":"Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine","volume":"9","author":"Hanly","year":"2022","journal-title":"Lupus Sci. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3415","DOI":"10.1167\/iovs.14-16345","article-title":"Localization of damage in progressive hydroxychloroquine retinopathy on and off the drug: Inner versus outer retina, parafovea versus peripheral fovea","volume":"56","author":"Hu","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1309\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:48:53Z","timestamp":1770396533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/3\/1309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15031309"],"URL":"https:\/\/doi.org\/10.3390\/jcm15031309","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}