:: Volume 28, Issue 1 (Scientific Journal of Kurdistan University of Medical Sciences 2023) ::
SJKU 2023, 28(1): 55-64 Back to browse issues page
Evaluation Incidence of Ocular Complications of Hydroxychloroquine and Related Risk Factors in Patients with Connective Tissue Disease Referred to the Rheumatology Clinic of Tohid Hospital in Sanandaj
Nasrin Moghimi1 , Ezzat Rahimi 2, Jamil Eslamipour3 , Naser Reshadmanesh4 , Afshin Saeidi5
1- Associate Professor of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
2- Associate Professor of Internal Medicine, Department of Internal Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran , ezatrahimi258@gmail.com
3- Associate Professor of Ophthalmology, Department of Ophthalmology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
4- Master of Environmental health, Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
5- Master of Clinical Psycology, Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Abstract:   (2580 Views)
Background and Aim: Hydroxychloroquine is used to treat many rheumatic diseases. This drug has been widely used, especially in the treatment of rheumatoid arthritis and lupus. One of the most important side effects of these drugs is retinopathy and changes in the visual field. This study aimed to determine the incidence of ocular complications caused by hydroxychloroquine and its related factors.
Materials and Methods: In this prospective study, 505 patients were investigated. These patients underwent complete ophthalmological examinations periodically every six months. If patients had impaired visual field in the perimeter, the visual field examination was repeated two weeks later. If there were specific findings, it was recorded as retinopathy and visual field defect. Optical Coherence Tomography (OCT) was performed for patients if the perimeter findings in the retest were nonspecific.
Results: Several of the 51 cases (10.09%) had eye problems, and 24 (4.75%) had problems other than retinopathy. Problems in perimetry or visual field defects were reported in 27 patients (5.34%) who had recurrent perimetry and 15 patients reported specific drug-related perimetry findings. The results showed that in terms of the underlying disease and its relationship with the incidence of ocular complications in patients, a significant relationship was observed between chronic renal failure and the incidence of complications (P=0.022).
Conclusion: The incidence of hydroxychloroquine-induced retinopathy appears to be relatively high in our region. Due to the significant association with chronic renal failure, screening should be done more carefully in these patients.
Keywords: Retinopathy, Hydroxychloroquine, Rheumatoid Arthritis
Full-Text [PDF 396 kb]   (413 Downloads)    
Type of Study: Original Research | Subject: Internal Medicine
Received: 2020/10/4 | Accepted: 2021/10/26 | Published: 2023/03/15
References
1. Moghimi N, Davatchi F, Rahimi E, Saidi A, Rashadmanesh N, Moghimi S, et al. WHO-ILAR COPCORD study (stage 1, urban study) in Sanandaj, Iran. Clin Rheumatol. 2015;34(3):535-43. [DOI:10.1007/s10067-013-2430-0] [PMID]
2. Kim JE, Marmor MF. Update on Screening Recommendations for Hydroxychloroquine Retinopathy. JAMA Ophthalmol. 2016;134(7):849. [DOI:10.1001/jamaophthalmol.2016.1252] [PMID]
3. 3Liu XW, Zha QL, He YT. [Comparative study on characteristics of Chinese and Western medicine for treatment of rheumatoid arthritis regarding cartilage erosion related blood biochemical and immunological factors]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007;27(12):1090-3.
4. Navarro-Sarabia F, Ruiz-Montesinos D, Hernandez B, Navarro-Compan V, Marsal S, Barcelo M, et al. DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists. BMC Musculoskelet Disord. 2009;10:91. [DOI:10.1186/1471-2474-10-91] [PMID] []
5. Ruiz RS, Saatci OA. Chloroquine and hydroxychloroquine retinopathy: how to follow affected patients. Ann Ophthalmol. 1991;23(8):290-1.
6. Greenstein VC, Amaro-Quireza L, Abraham ES, Ramachandran R, Tsang SH, Hood DC. A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy. Doc Ophthalmol. 2015;130(1):13-23. [DOI:10.1007/s10633-014-9474-6] [PMID] []
7. Turgut B, Turkcuoglu P, Serdar Koca S, Aydemir O. Detection of the regression on hydroxychloroquine retinopathy in optical coherence tomography. Clin Rheumatol. 2009;28(5):607-9. [DOI:10.1007/s10067-009-1108-0] [PMID]
8. Garrity ST, Jung JY, Zambrowski O, Pichi F, Su D, Arya M, et al. Early hydroxychloroquine retinopathy: optical coherence tomography abnormalities preceding Humphrey visual field defects. Br J Ophthalmol. 2019. [DOI:10.1136/bjophthalmol-2018-313350] [PMID]
9. Coyle JT. Hydroxychloroquine retinopathy. Ophthalmology. 2001;108(2):243-4. [DOI:10.1016/S0161-6420(00)00400-0] [PMID]
10. Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye (Lond). 2017;31(6):828-45. [DOI:10.1038/eye.2016.298] [PMID] []
11. Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018;14(12):693-703. [DOI:10.1038/s41584-018-0111-8] [PMID]
12. Geamanu Panca A, Popa-Cherecheanu A, Marinescu B, Geamanu CD, Voinea LM. Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. J Med Life. 2014;7(3):322-6.
13. Kobak S, Deveci H. Retinopathy due to antimalarial drugs in patients with connective tissue diseases: are they so innocent? A single center retrospective study. Int J Rheum Dis. 2010;13(3):e11-5. [DOI:10.1111/j.1756-185X.2010.01478.x] [PMID]
14. Yen CY, Lee PH, Yen JC, Chen CC, Hu HY, Tseng PC. Current screening practice in patients under long-term hydroxychloroquine medication in Taiwan: A nationwide population-based cohort study. Medicine (Baltimore). 2019;98(14):e15122. [DOI:10.1097/MD.0000000000015122] [PMID] []
15. Martin-Iglesias D, Artaraz J, Fonollosa A, Ugarte A, Arteagabeitia A, Ruiz-Irastorza G. Evolution of retinal changes measured by optical coherence tomography in the assessment of hydroxychloroquine ocular safety in patients with systemic lupus erythematosus. Lupus. 2019;28(4):555-9. [DOI:10.1177/0961203319829826] [PMID]
16. Mavrikakis I, Sfikakis PP, Mavrikakis E, Rougas K, Nikolaou A, Kostopoulos C, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology. 2003;110(7):1321-6. [DOI:10.1016/S0161-6420(03)00409-3] [PMID]
17. Giocanti-Auregan A, Couturier A, Girmens JF, Le Mer Y, Massamba N, Barreau E, et al. [Variability of chloroquine and hydroxychloroquine retinopathy among various ethnicities]. J Fr Ophtalmol. 2018;41(4):363-7. [DOI:10.1016/j.jfo.2017.08.014] [PMID]
18. Thorne JE, Maguire AM. Retinopathy after long term, standard doses of hydroxychloroquine. Br J Ophthalmol. 1999;83(10):1201-2. [DOI:10.1136/bjo.83.10.1194h] [PMID] []
19. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF, American Academy of O. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016;123(6):1386-94. [DOI:10.1016/j.ophtha.2016.01.058] [PMID]
20. Asensio-Sanchez VM. [SD-OCT As screening test for hydroxychloroquine retinopathy: The <> sign]. Arch Soc Esp Oftalmol. 2015;90(7):338-40. [DOI:10.1016/j.oftale.2015.07.004] [PMID]
21. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010;62(6):775-84. [DOI:10.1002/acr.20133] [PMID]
22. Browning DJ, Lee C. Relative sensitivity and specificity of 10-2 visual fields, multifocal electroretinography, and spectral domain optical coherence tomography in detecting hydroxychloroquine and chloroquine retinopathy. Clin Ophthalmol. 2014;8:1389-99. [DOI:10.2147/OPTH.S66527] [PMID] []
23. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386-94. [DOI:10.1016/j.ophtha.2016.01.058] [PMID]
24. Eo DR, Lee MG, Ham DI, Kang SW, Lee J, Cha HS, et al. Frequency and Clinical Characteristics of Hydroxychloroquine Retinopathy in Korean Patients with Rheumatologic Diseases. J Korean Med Sci. 2017;32(3):522-7. [DOI:10.3346/jkms.2017.32.3.522] [PMID] []
25. Palma Sánchez D RVE, Soro Marín S, Reyes García R. Retinal toxicity due to antimalarials: frequency and risk factors. Reumatol Clin 2013;Sep-Oct;9(5):259-62. [DOI:10.1016/j.reumae.2012.10.007]
26. Gianfrancesco MA, Schmajuk G, Haserodt S, Trupin L, Izadi Z, Jafri K, et al. Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety. Rheumatol Int. 2017;37(10):1611-8. [DOI:10.1007/s00296-017-3782-6] [PMID] []
27. Payne JF, Hubbard GB, 3rd, Aaberg TM, Sr., Yan J. Clinical characteristics of hydroxychloroquine retinopathy. Br J Ophthalmol. 2011;95(2):245-50. [DOI:10.1136/bjo.2009.172148] [PMID]
28. Ahn SJ, Lee BR. Hydroxychloroquine Retinopathy: Drug Cessation versus Drug Continuation. Ophthalmol Retina. 2019;3(3):277. [DOI:10.1016/j.oret.2018.11.012] [PMID]
29. Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG. Hydroxychloroquine and chloroquine retinopathy: a systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology. 2015;122(6):1239-51 e4. [DOI:10.1016/j.ophtha.2015.02.011] [PMID]
30. Rezabakhsh A, Montazersaheb S, Nabat E, Hassanpour M, Montaseri A, Malekinejad H, et al. Effect of hydroxychloroquine on oxidative/nitrosative status and angiogenesis in endothelial cells under high glucose condition. Bioimpacts. 2017;7(4):219-26. [DOI:10.15171/bi.2017.26] [PMID] []
31. Chen TH, Lai TY, Wang YH, Chiou JY, Hung YM, Wei JC. Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjogren syndrome. QJM. 2019. [DOI:10.1093/qjmed/hcz112] [PMID]
32. Moghimi N, Davatchi F, Rahimi E, Saidi A, Rashadmanesh N, Moghimi S, et al. WHO-ILAR COPCORD study (stage 1, urban study) in Sanandaj, Iran. Clin Rheumatol. 2015;34(3):535-43. [DOI:10.1007/s10067-013-2430-0] [PMID]
33. Kim JE, Marmor MF. Update on Screening Recommendations for Hydroxychloroquine Retinopathy. JAMA Ophthalmol. 2016;134(7):849. [DOI:10.1001/jamaophthalmol.2016.1252] [PMID]
34. 3Liu XW, Zha QL, He YT. [Comparative study on characteristics of Chinese and Western medicine for treatment of rheumatoid arthritis regarding cartilage erosion related blood biochemical and immunological factors]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007;27(12):1090-3.
35. Navarro-Sarabia F, Ruiz-Montesinos D, Hernandez B, Navarro-Compan V, Marsal S, Barcelo M, et al. DAS-28-based EULAR response and HAQ improvement in rheumatoid arthritis patients switching between TNF antagonists. BMC Musculoskelet Disord. 2009;10:91. [DOI:10.1186/1471-2474-10-91] [PMID] []
36. Ruiz RS, Saatci OA. Chloroquine and hydroxychloroquine retinopathy: how to follow affected patients. Ann Ophthalmol. 1991;23(8):290-1.
37. Greenstein VC, Amaro-Quireza L, Abraham ES, Ramachandran R, Tsang SH, Hood DC. A comparison of structural and functional changes in patients screened for hydroxychloroquine retinopathy. Doc Ophthalmol. 2015;130(1):13-23. [DOI:10.1007/s10633-014-9474-6] [PMID] []
38. Turgut B, Turkcuoglu P, Serdar Koca S, Aydemir O. Detection of the regression on hydroxychloroquine retinopathy in optical coherence tomography. Clin Rheumatol. 2009;28(5):607-9. [DOI:10.1007/s10067-009-1108-0] [PMID]
39. Garrity ST, Jung JY, Zambrowski O, Pichi F, Su D, Arya M, et al. Early hydroxychloroquine retinopathy: optical coherence tomography abnormalities preceding Humphrey visual field defects. Br J Ophthalmol. 2019. [DOI:10.1136/bjophthalmol-2018-313350] [PMID]
40. Coyle JT. Hydroxychloroquine retinopathy. Ophthalmology. 2001;108(2):243-4. [DOI:10.1016/S0161-6420(00)00400-0] [PMID]
41. Yusuf IH, Sharma S, Luqmani R, Downes SM. Hydroxychloroquine retinopathy. Eye (Lond). 2017;31(6):828-45. [DOI:10.1038/eye.2016.298] [PMID] []
42. Jorge A, Ung C, Young LH, Melles RB, Choi HK. Hydroxychloroquine retinopathy - implications of research advances for rheumatology care. Nat Rev Rheumatol. 2018;14(12):693-703. [DOI:10.1038/s41584-018-0111-8] [PMID]
43. Geamanu Panca A, Popa-Cherecheanu A, Marinescu B, Geamanu CD, Voinea LM. Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review. J Med Life. 2014;7(3):322-6.
44. Kobak S, Deveci H. Retinopathy due to antimalarial drugs in patients with connective tissue diseases: are they so innocent? A single center retrospective study. Int J Rheum Dis. 2010;13(3):e11-5. [DOI:10.1111/j.1756-185X.2010.01478.x] [PMID]
45. Yen CY, Lee PH, Yen JC, Chen CC, Hu HY, Tseng PC. Current screening practice in patients under long-term hydroxychloroquine medication in Taiwan: A nationwide population-based cohort study. Medicine (Baltimore). 2019;98(14):e15122. [DOI:10.1097/MD.0000000000015122] [PMID] []
46. Martin-Iglesias D, Artaraz J, Fonollosa A, Ugarte A, Arteagabeitia A, Ruiz-Irastorza G. Evolution of retinal changes measured by optical coherence tomography in the assessment of hydroxychloroquine ocular safety in patients with systemic lupus erythematosus. Lupus. 2019;28(4):555-9. [DOI:10.1177/0961203319829826] [PMID]
47. Mavrikakis I, Sfikakis PP, Mavrikakis E, Rougas K, Nikolaou A, Kostopoulos C, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology. 2003;110(7):1321-6. [DOI:10.1016/S0161-6420(03)00409-3] [PMID]
48. Giocanti-Auregan A, Couturier A, Girmens JF, Le Mer Y, Massamba N, Barreau E, et al. [Variability of chloroquine and hydroxychloroquine retinopathy among various ethnicities]. J Fr Ophtalmol. 2018;41(4):363-7. [DOI:10.1016/j.jfo.2017.08.014] [PMID]
49. Thorne JE, Maguire AM. Retinopathy after long term, standard doses of hydroxychloroquine. Br J Ophthalmol. 1999;83(10):1201-2. [DOI:10.1136/bjo.83.10.1194h] [PMID] []
50. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF, American Academy of O. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology. 2016;123(6):1386-94. [DOI:10.1016/j.ophtha.2016.01.058] [PMID]
51. Asensio-Sanchez VM. [SD-OCT As screening test for hydroxychloroquine retinopathy: The <> sign]. Arch Soc Esp Oftalmol. 2015;90(7):338-40. [DOI:10.1016/j.oftale.2015.07.004] [PMID]
52. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010;62(6):775-84. [DOI:10.1002/acr.20133] [PMID]
53. Browning DJ, Lee C. Relative sensitivity and specificity of 10-2 visual fields, multifocal electroretinography, and spectral domain optical coherence tomography in detecting hydroxychloroquine and chloroquine retinopathy. Clin Ophthalmol. 2014;8:1389-99. [DOI:10.2147/OPTH.S66527] [PMID] []
54. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016;123(6):1386-94. [DOI:10.1016/j.ophtha.2016.01.058] [PMID]
55. Eo DR, Lee MG, Ham DI, Kang SW, Lee J, Cha HS, et al. Frequency and Clinical Characteristics of Hydroxychloroquine Retinopathy in Korean Patients with Rheumatologic Diseases. J Korean Med Sci. 2017;32(3):522-7. [DOI:10.3346/jkms.2017.32.3.522] [PMID] []
56. Palma Sánchez D RVE, Soro Marín S, Reyes García R. Retinal toxicity due to antimalarials: frequency and risk factors. Reumatol Clin 2013;Sep-Oct;9(5):259-62. [DOI:10.1016/j.reumae.2012.10.007]
57. Gianfrancesco MA, Schmajuk G, Haserodt S, Trupin L, Izadi Z, Jafri K, et al. Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety. Rheumatol Int. 2017;37(10):1611-8. [DOI:10.1007/s00296-017-3782-6] [PMID] []
58. Payne JF, Hubbard GB, 3rd, Aaberg TM, Sr., Yan J. Clinical characteristics of hydroxychloroquine retinopathy. Br J Ophthalmol. 2011;95(2):245-50. [DOI:10.1136/bjo.2009.172148] [PMID]
59. Ahn SJ, Lee BR. Hydroxychloroquine Retinopathy: Drug Cessation versus Drug Continuation. Ophthalmol Retina. 2019;3(3):277. [DOI:10.1016/j.oret.2018.11.012] [PMID]
60. Tsang AC, Ahmadi Pirshahid S, Virgili G, Gottlieb CC, Hamilton J, Coupland SG. Hydroxychloroquine and chloroquine retinopathy: a systematic review evaluating the multifocal electroretinogram as a screening test. Ophthalmology. 2015;122(6):1239-51 e4. [DOI:10.1016/j.ophtha.2015.02.011] [PMID]
61. Rezabakhsh A, Montazersaheb S, Nabat E, Hassanpour M, Montaseri A, Malekinejad H, et al. Effect of hydroxychloroquine on oxidative/nitrosative status and angiogenesis in endothelial cells under high glucose condition. Bioimpacts. 2017;7(4):219-26. [DOI:10.15171/bi.2017.26] [PMID] []
62. Chen TH, Lai TY, Wang YH, Chiou JY, Hung YM, Wei JC. Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in patients with Sjogren syndrome. QJM. 2019. [DOI:10.1093/qjmed/hcz112] [PMID]

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