|Year : 2017 | Volume
| Issue : 4 | Page : 110-113
Hydroxychloroquine retinopathy in a cohort of patients from upper Egypt
Mortada A Abozaid1, Esam Aboelfadl2, Mohammed A Ismail2
1 Department of Ophthalmology, Faculty of Medicine, Sohag University, Sohag, Egypt
2 Department of Rheumatology, Faculty of Medicine, Sohag University, Sohag, Egypt
|Date of Submission||18-Dec-2017|
|Date of Acceptance||29-Jan-2018|
|Date of Web Publication||8-Mar-2018|
Mortada A Abozaid
Department of Ophthalmology, Faculty of Medicine, Sohag University, Sohag
Source of Support: None, Conflict of Interest: None
Purpose To identify risk factors and state demographics of a cohort of patients from upper Egypt experiencing hydroxychloroquine (HCQ) retinopathy. This was an observational study. This study was conducted in Sohag University Hospital, Egypt.
Patients and methods The medical records of the rheumatology department were retrospectively reviewed to identify patients who stopped taking HCQ owing to its induced visual troubles. Ten patients were identified and were subjected to complete ophthalmological examination in addition to automated perimetry and optical coherence tomography of the macula.
Results All patients (nine females and one male) had received HCQ 200 mg twice daily for years. The mean age was 59.1 years, mean real weight was 83.3 kg, mean height was 1.63 m, mean ideal body weight was 56.72 kg, and the mean daily dose per kg of ideal weight was 7.14 mg/kg/day, whereas the mean daily dose per kg of real weight was 4.85 mg/kg/day.
Conclusion Calculation of HCQ dose according to the ideal weight is a better predector of retinal toxicity than real body weight.
Keywords: Bull’s eye maculopathy, hydroxychloroquine retinopathy, screening
|How to cite this article:|
Abozaid MA, Aboelfadl E, Ismail MA. Hydroxychloroquine retinopathy in a cohort of patients from upper Egypt. J Egypt Ophthalmol Soc 2017;110:110-3
|How to cite this URL:|
Abozaid MA, Aboelfadl E, Ismail MA. Hydroxychloroquine retinopathy in a cohort of patients from upper Egypt. J Egypt Ophthalmol Soc [serial online] 2017 [cited 2018 Mar 20];110:110-3. Available from: http://www.jeos.eg.net/text.asp?2017/110/4/110/226939
| Introduction|| |
Hydroxychloroquine (HCQ) is an antimalarial drug that is used in the treatment of many rheumatologic and dermatologic diseases. It is associated with a low incidence of retinopathy (0.5%) when used at recommended doses (6.5 mg/kg/day) . It has largely replaced chloroquine (CQ) because of decreased ocular toxicity at high dosages  but can still lead to potentially irreversible visual loss.
To date, no treatment exists for HCQ retinopathy, and even after the drug is withdrawn, retinal degeneration continues to progress. At the same time, the drug is highly effective in managing many rheumatic diseases, and its substitutes may have more serious adverse effects. For these reasons, ophthalmic screening of patients receiving HCQ is recommended to detect retinal damage as early as possible before irreversible and potentially progressive decrease of visual acuity develops .
Multiple tests are available for screening including automated perimetry, multifocal electroretinography, and optical coherence tomography (OCT); however, no single test is 100% sensitive in the identification of HCQ toxicity before the onset of clinical features of the retinopathy ,,,.
Some patients are asymptomatic, whereas others may have problems with central vision or field defects, glare, night blindness, or color vision defects. Fundus changes tend to be a late finding in HCQ retinopathy and are characterized by bilateral pigmentary changes around the fovea, often sparing the foveal center and leading to a characteristic ‘Bull’s eye’ maculopathy .
The American Academy of Ophthalmology (AAO) recommendations for screening of CQ and HCQ retinopathy were published in 2002  followed by the revised recommendations in 2011 . Recently, the recommendations on screening (2016 revisions) were published and stressed upon calculating the safe dose according to the real weight instead of the ideal weight .
The aim of this study was to define the demographics of a cohort of patients from upper Egypt with HCQ retinopathy and to identify the risk and features of toxicity compared with 2016 revisions of AAO recommendations and to document progression of the retinopathy after drug cessation.
| Patients and methods|| |
This observational study was done at the Ophthalmology and Rheumatology Departments of Sohag University Hospital in the period from March 2016 to December 2016. The study adhered to tenets of Helsinki Declaration, and an approval was obtained from the Ethics Committee of Sohag Faculty of Medicine.
We retrospectively reviewed the medical records of the rheumatology department looking for patients who stopped using HCQ owing to its visual adverse effects. The inclusion criteria were patients aged more than 18 years and HCQ usage for at least 5 years, whereas the exclusion criteria included patients with other chronic ocular diseases including diabetic retinopathy and age-related macular degeneration and also patients receiving other retinotoxic medications.
Ten patients fulfilled the inclusion and exclusion criteria of the study and signed an informed consent to participate in the study. All patients were subjected to complete medical and ophthalmological evaluation.
History data included age, sex, type of rheumatic disease, daily dose, and duration of HCQ use in addition to history of eye surgery. Then the weight and height of every patient were measured, and the ideal body weight was calculated according to Robinson formula (1983).
Ophthalmologic evaluation included uncorrected and best-corrected visual acuity (BCVA) tests of both eyes using a landolt chart at 6 m, and the result was converted to log-MAR notation, a biomicroscopic examination of the fundus under dilation, a fundus examination using direct and indirect ophthalmoscopy, an Amsler grid test, visual field testing of the central 10° using automated perimetry with a Swedish Interactive Threshold Algorithm-Standard strategy, fundus fluorescein angiography, and spectral domain OCT of the macula.
Five patients were followed up to 1 year to study the progression of their retinopathy after stopping the drug.
| Results|| |
Ten (one male and nine female) patients are included in this observational study; six patients had rheumatoid arthritis and four had systemic lupus erythematosus. The mean age is 59.1 years, the mean body weight is 83.3 kg, and the mean height is 1.63 m. Regarding HCQ use, all patients received the same daily dose of 200 mg, twice daily, for a mean duration of 11.4 years, with a mean cumulative dose of 1664.4 g. The mean dose of HCQ according to the real body weight was 4.85 mg/kg/day whereas the dose according to the ideal body weight was 7.14 mg/kg/day. The demographics of the patients are summarized in [Table 1].
All the patients showed reduction in visual acuity with mean BCVA of 0.55±0.17 (log-MAR) in the right eye and 0.47±0.14 in the left eye. Fundus examination revealed characteristic Bull’s eye maculopathy of variable severity in both eyes of all patients. OCT revealed perifoveal thinning with relatively normal fovea in patients with moderate toxicity and generalized thinning in advanced cases ([Figure 1]) whereas the 10–2 automated perimetry showed paracentral scotomas of variable intensity in all cases. Five patients could be followed for 1 year, and four of them showed progressive decrease in their BCVA and increase in their fundoscopic signs as shown in [Figure 2].
|Figure 1 Fundus (a) fluorescein angiography (FA), and (b) optical coherence tomography (c) images of a case with advanced hydroxychloroquine retinopathy.|
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|Figure 2 Fundus (a, b) fluorescein angiography (FA), and (c, d) optical coherence tomography (e, f) appearance of a case of hydroxychloroquine retinopathy followed for 1 year.|
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| Discussion|| |
HCQ is a very effective drug for treating many rheumatic and dermatologic conditions. It is generally well tolerated, and its adverse effects are less than those of other immunosuppressive medications. However, a major adverse effect of this drug is the likelihood of developing insidious irreversible retinal damage.
In this study, we tried to define the characteristics of HCQ retinopathy in a cohort of 10 rheumatic patients from upper Egypt. All the cases had HCQ retinopathy, and all of them had stopped the drug; however, four of them showed progression of their maculopathy. All our patients showed the classic Bull’s eye maculopathy unlike patients of Asian origin , who typically show early damage in a more peripheral pattern.The AAO recommendations on screening of CQ and HCQ retinopathy (2016 revision) depending on a study of Melles et al.  recommend that all patients using HCQ should keep daily dosage less than 5.0 mg/kg real weight. They considered that previous recommendations to use ideal body weight for the calculation of dose − which were based on the idea that these drugs are not retained in fat − may result in overdosage in thin individuals, whereas the new recommended formula using real weight accounts for risk evenly over a broad range of body weights.
Contrary to 2016 recommendations, our study showed that calculation of the dose according to the ideal weight better predicts the risk of toxicity than ideal weight that is because the mean daily dose according to real weight is 4.85 mg/kg/day which is considered safe according to 2016 revisions whereas the dose calculated according to ideal weight is 7.14 mg/kg/day which much higher than the safe limit. This may be explained by the fact that most of our patients are overweight (mean weight of the patients is 83.3 kg), and this may suggest that calculating the dose according to real weight may result in overdosage in obese patients in the same way that calculating the dose according to the ideal weight may result in overdosage in thin patients.
The shortcomings of our study are the small sample size, the short follow-up period, and the lack of a control group that received the drug for approximate duration without developing the toxicity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
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; 110:1321–1326.
Levy GD, Munz SJ, Paschal J, Cohen HB, Pince KJ, Peterson T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis Rheum 1997; 40:1482–1486.
Bienfang D, Coblyn JS, Liang MH, Corzillius M. Hydroxychloroquine retinopathy despite regular ophthalmologic evaluation: a consecutive series. J Rheumatol 2000; 27:2703–2706.
Lee AG. Hydroxychloroquine screening. Br J Ophthalmol 2005; 89:521–522.
Elder M, Rahman AM, McLay J. Early paracentral visual field loss in patients taking hydroxychloroquine. Arch Ophthalmol 2006; 124:1729–1733.
Klinger G, Morad Y, Westall CA, Laskin C, Spitzer KA, Koren G et al.
Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet 2001; 358:813–814.
Rodriguez-Padilla JA, Hedges TR 3rd, 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; 125:775–780.
Tehrani R, Ostrowski RA, Hariman R, Jay WM. Ocular toxicity of hydroxychloroquine. Semin Ophthalmol 2008; 23:201–209.
Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF; American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology 2002; 109:1377–1382.
Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology 2011; 118:415–422.
Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF; American Academy of Ophthalmology. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016; 123:1386–1394.
Melles RB, Marmor MF. Pericentral retinopathy and racial differences in hydroxychloroquine toxicity. Ophthalmology 2015; 122:110–116.
Lee DH, Melles RB, Joe SG, Lee JY, Kim JG, Lee CK et al.
Pericentral hydroxychloroquine retinopathy in Korean patients. Ophthalmology 2015; 122:1252–1256.
Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol 2014; 132:1453–1460.
[Figure 1], [Figure 2]