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Correspondence on “assessing the risk of retinopathy in Indian patients using hydroxychloroquine for rheumatic and musculoskeletal diseases: A retrospective observational study”

1 Department of Rheumatology, Apollo Hospital, Ahmedabad, Gujarat, India
2 Department of Rheumatology, Indraprastha Apollo Hospital, New Delhi, India

Date of Submission10-Jan-2021
Date of Acceptance04-Mar-2021

Correspondence Address:
Nikunjkumar V Dadhaniya,
Department of Rheumatology, Apollo Hospital, GIDC Bhat, Gandhinagar, Ahmadabad - 382 428, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_9_21

How to cite this URL:
Dadhaniya NV, Upadhyaya S, Gupta SJ, Handa R. Correspondence on “assessing the risk of retinopathy in Indian patients using hydroxychloroquine for rheumatic and musculoskeletal diseases: A retrospective observational study”. Indian J Rheumatol [Epub ahead of print] [cited 2021 Jul 30]. Available from:

Dear Editor,

We read with great interest the article by Roy et al. published in the recent issue of the Indian Journal of Rheumatology.[1] This study is a significant addition to the limited data available on the hydroxychloroquine (HCQ) retinal toxicity in the Indian population. We compliment the authors for collecting data of 984 patients. The study showed 13.5% prevalence of retinopathy and identified age, duration of use, and cumulative dose of HCQ as risk factors for retinopathy. Detection rate was higher with functional modalities (multifocal electroretinography [mfERG] and visual fields) compared to structural modalities (spectral domain optical coherence tomography and Fundus autofluorescence). However, we would like to highlight a few points that need further discussion.

First, a high (13.5%) prevalence of retinal toxicity reported by the authors is a little surprising. Other studies have reported variable prevalence ranging from 2.9% to 13.8%. This variable prevalence has been accounted for by different modalities used for screening, inclusion of patients with varying daily dose, and duration of HCQ exposure. Higher daily dose by body weight and longer duration of use are associated with a higher prevalence of retinopathy, and these are identified as major risk factors for retinopathy by recent American Academy of Ophthalmology recommendations.[2] The study that reported higher prevalence of 13.8% had high mean daily dose (mean 6.4 mg/kg/day) and long duration (mean 10.1 years) of usage.[3] In contrast, the study by Roy et al. despite having low daily dose (3.41 ± 1.0 mg/kg) and short duration (3.21 years) found a very high prevalence of retinopathy. Our own study on 110 patients with a mean dose of 4.96 ± 1.55 mg/kg of real body weight-based and duration of 9.4 ± 4.65 years revealed a 6.36% prevalence of retinopathy.[4]

Second, Roy et al. showed a 12.2% prevalence of retinopathy in patients with <5 years of HCQ exposure. Retinopathy is because of slow and chronic toxic effects of HCQ on retina. During initial 5 years of HCQ use, retinopathy is a recognized as a rare event with reported prevalence of <1%.[2] Of note, we encountered only 1 (0.91%) patient having retinopathy with 5 years of use while all other patients in our series had >10 years of use.[4] Information on the prevalence of retinopathy in initial 5 years will influence the screening recommendations since current recommendations are to start screening after 5 years of HCQ exposure in the patients with normal baseline examination. Multicenter data from different locations in the country under the banner of Indian Rheumatology Association could be a welcome initiative in this situation.

In addition, the high false positive rates of mfERG are well known. Several studies have documented high sensitivity but variable specificity of mfERG.[5],[6] For ethical reasons, longitudinal studies to assess if ERG abnormalities translate into clinically meaningful adverse effects may be difficult.

Another point that we would like to bring up is the location of retinopathy, which manifests in a parafoveal location in Caucasian patients and perifoveal location in the East Asian Population.[2] We and others have reported isolated parafoveal or mixed parafoveal and perifoveal pattern of involvement in the Indian population.[4],[7] Roy et al. found higher detection rate with wider visual fields (24-2 and 30-2 compared to 10-2). However, it is unclear whether wide angle and narrow angle visual fields were done in all the patients and if the visual field location correlated with location of retinopathy derived from other modalities.

HCQ continues to be an important anchor drug in many rheumatic diseases. While early detection of drug toxicity is undeniably important, we would also strike a note of caution while interpreting functional abnormalities on sensitive screening modalities that might be of uncertain clinical significance.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Roy A, Samala V, Kumar Y, Fatima S. Assessing the risk of retinopathy in Indian patients using hydroxychloroquine for rheumatic and musculoskeletal diseases: A retrospective observational study. Indian J Rheumatol 2020; Available from: ahead of print. [Last accessed on 2021 Feb 09].  Back to cited text no. 1
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;123:1386-94.  Back to cited text no. 2
Kim JW, Kim YY, Lee H, Park SH, Kim SK, Choe JY. Risk of retinal toxicity in longterm users of hydroxychloroquine. J Rheumatol 2017;44:1674-9.  Back to cited text no. 3
Dadhaniya NV, Sood I, Patil A, Mallaiah U, Upadhyaya S, Handa R, et al. Screening for hydroxychloroquine retinal toxicity in indian patients. J Clin Rheumatol 2020;Epub ahead of print. Available from: doi: 10.1097/RHU.0000000000001479. [Last accessed on 2021 Feb 09].  Back to cited text no. 4
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;122:1239-510000.  Back to cited text no. 5
Tsang AC, Ahmadi S, Hamilton J, Gao J, Virgili G, Coupland SG, et al. The diagnostic utility of multifocal electroretinography in detecting chloroquine and hydroxychloroquine retinal toxicity. Am J Ophthalmol 2019;206:132-9.  Back to cited text no. 6
Pratyusha G, Ahuja S, Negi V. Detection of retinal changes in patients on long term chloroquine/hydroxy chloroquine therapy using optical coherence tomography. Clin Toxicol 2014;4:201-3.  Back to cited text no. 7


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