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      Decreased perifoveal ganglion cell complex thickness - a first sign for macular damage in patients using hydroxychloroquine

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          Abstract

          Aim: To examine ganglion cell complex (GCC) thickness detected by optical coherence tomography (OCT) in patients using hydroxychloroquine (HCQ), without any structural and functional macular changes to evaluate the initial symptoms of macular toxicity for early diagnosis before clinical evaluation.

          Methods: Eighty eyes of forty patients (Group 1) and forty eyes of twenty healthy volunteer persons (Group 2) were included in the study. Detailed ophthalmologic and mydriatic fundus examination were applied to all patients and volunteers (controls). Spectral domain OCT, visual field (VF) and color vision test were performed. Measurements of macula thickness, GCC thickness (involving nerve fiber layer, ganglion cell layer and inner plexiform layer) and peripapillary retinal nerve fiber layer (RNFL) were performed with OCT. Patients with retinal pigment epithelial changes, VF paracentral scotoma and defected color vision were excluded from the planned study.

          Results: Perifoveal GCC layer thickness in all quadrants was significantly thinner in group 1 compared to group 2 (p=0.017, p=0.001, p=0.019, p=0.001). The mean global inferior hemifield and nasal quadrant RNFL thickness were lower than in the control groups (p=0,012, p=0,009, p=0,005, respectively).

          Conclusion: Changes in the thickness of nerve fiber layer and ganglion cell layer detected by optical coherence tomography can be thought to be used as a diagnostic aid for the early diagnosis of hydroxychloroquine-toxic maculopathy

          Abbreviations: GCC = Ganglion cell complex, OCT = Optical coherence tomography, HCQ = Hydroxychloroquine, BCVA = Best-corrected visual acuity, IOP = Intraocular pressure, VF = Visual field, RNFL = Retinal nerve fiber layer, SD OCT = Spectral-domain optical coherence tomography, mfERG = Multifocal electroretinogram, FAF = Fundus autofluorescence, IS/ OS = Inner segment-outer segment junction, SITA = Swedish Interactive Threshold Algorithm, RA = Rheumatoid arthritis, SLE = Systemic lupus erythematosus, SS = Sjogren syndrome

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          Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision).

          Michael F Marmor, Ulrich Kellner, Timothy Lai … (2016)
          The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools.
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            The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal.

            M E Mavrikakis, A Nikolaou, Kostantinos Rougas … (2003)
            To define the risk of hydroxychloroquine (HCQ)-related retinal toxicity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who are receiving recommended dosages of the drug ( 6 years) treated patients developed HCQ-related maculopathy at 8 and 6.5 years of treatment, despite regular ophthalmologic evaluation. On follow-up 7 and 9 years after cessation of HCQ treatment, both patients had stable eye disease. No HCQ retinal toxicity was observed in the subsequent 342 patients who were treated for >6 years. Overall, the incidence of HCQ-related retinopathy in 400 patients who were treated with recommended dosages of the drug for a mean of 8.7 years was reduced to 0.5%. After a baseline ophthalmic examination to confirm the absence of preexisting fundus pathology, patients with normal renal function may receive HCQ at a maximal daily dosage of 6.5 mg/kg and continue safely for 6 years. However, annual screening is recommended in patients who have taken the drug, even in recommended doses, for >6 years.
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              Comparison of screening procedures in hydroxychloroquine toxicity.

              Michael F Marmor (2012)
              To compare different screening procedures for hydroxychloroquine sulfate (Plaquenil) toxicity at different stages of damage. Ten patients were studied using 10-2 automated fields, multifocal electroretinography, spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence. All 10 patients used hydroxychloroquine for more than 6 years, and those with severe toxicity had been overdosed. Fundus examination findings were normal except for the patients with severe toxicity. All the patients showed parafoveal field loss, but this was sometimes subtle. Multifocal electroretinography demonstrated parafoveal weakness in the milder cases. The SD-OCT subfield thickness plots showed a ring of parafoveal thinning in all the patients. The SD-OCT cross-sections showed parafoveal loss of the inner segment-outer segment and cone outer segment tip lines at early stages of toxicity, progressing to parafoveal thinning of the outer nuclear layer and eventually to retinal pigment epithelium damage. There was a ring of autofluorescence in most patients. Overdosage with hydroxychloroquine seemed a significant risk factor for toxicity. Different individuals were more or less sensitive to different tests. Fields can be sensitive but only if read with a low threshold for change. Hydroxychloroquine causes early parafoveal loss of the outer segment lines on SD-OCT, with the first changes often evident in the inferotemporal quadrant. Parafoveal thinning of the outer nuclear layer follows, before retinal pigment epithelium damage is visible. Careful screening with multiple tests can detect toxic damage before prominent loss of the outer nuclear layer.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Rom J Ophthalmol
                Journal ID (iso-abbrev): Rom J Ophthalmol
                Journal ID (publisher-id): RomJOphthalmol
                Title: Romanian Journal of Ophthalmology
                Publisher: Romanian Society of Ophthalmology (Romania )
                ISSN (Print): 2457-4325
                ISSN (Electronic): 2501-2533
                Publication date (Print): Apr-Jun 2023
                Volume: 67
                Issue: 2
                Pages: 146-151
                Affiliations
                [* ]Ophthalmology Department, Istanbul Training and Research Hospital, Istanbul, Turkey
                [** ]Ophthalmology Department, Ekol Hospital, Edirne, Turkey
                [*** ]Ophthalmology Department, Trakya University Faculty of Medicine, Education and Research Hospital, Edirne, Turkey
                Author notes
                Correspondence to: Goksu Alacamli, Ophthalmology Department, Trakya University Faculty of Medicine, Education and Research Hospital, Edirne, E5 Highway Street, Code 22000, Edirne, Turkey, Phone: +905 052 652 935, E-mail: goksualacamli@yahoo.com ORCID: 0000-0001-5013-9981
                Article
                Publisher ID: RomJOphthalmol-67-146
                DOI: 10.22336/rjo.2023.26
                PMC ID: 10385708
                SO-VID: 02a183a5-32a1-460f-b8c6-e46845419ab1
                Copyright © #x00A9; The Authors.Romanian Society of Ophthalmology
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date accepted : 18 June 2023
                Categories
                Subject: General Articles

                Keywords: hydroxychloroquine,optical coherence tomography,ganglion cell complex thickness,retinal nerve fiber layer
                Data availability:
                Keywords: hydroxychloroquine, optical coherence tomography, ganglion cell complex thickness, retinal nerve fiber layer

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