FP1077 : Progression of Hydroxychloroquine Toxicity After Its Discontinuation.

S14452, Dr. Partha Biswas, Dr. Ajay Paul, Dr. Krishnendu Nandi

Introduction :

Hydroxychloroquine (HCQ)and Chloroquine (CQ) are widely used for the treatment of autoimmune diseases like Systemic Lupus Erythematosus(SLE), Rheumatoid Arthritis (RA) and other related inflammatory and dermatological conditions. Newer applications of this drug in diabetes mellitus, heart disease and adjunct cancer therapy are also being evaluated.¹The retino-toxic effects of CQ and HCQ have been recognised for quite a few years now, with “Bull’s Eye Maculopathy”, ophthalmoscopically evident as a ring of parafoveal Retinal Pigment Epithelium (RPE) depigmentation with sparing of the central fovea, representing severe toxicity. However, this distribution is infrequent in Asians, who typically show early damage in a more peripheral pattern. ^2,3CQ/HCQ toxicity is however not treatable, so earliest detection of HCQ toxicity and subsequent replacement of the drug by treating physician is the only way to preserve loss of central vision.

The current study aims to assess the retinal status, along with progression of any morphological retinal alterations, in subjects without any funduscopic abnormality on examination with a +78D lens, 24-36 months post cessation ofCQ/HCQ.

Materials and Methods :

This prospective study was initiated after approval from Institutional Review Board. Subjects who had been on HCQ/CQ for atleast two years,but at the time of enumeration had been medically advised to discontinue HCQ/CQ, were considered for inclusion. Subjects with any corneal disease and media opacities preventing adequate view of the posterior pole, subjects with history of ocular trauma, one eyed and bilaterally blind patients and those with any histories of ocular surgery in either eye were not enumerated. Subjects were also excluded if they had ophthalmoscopically evident Bull’s Eye Maculopathy, any evident macular pathology or any other previously diagnosed ocular or systemic disease that could affect the optic nerve, visual field or retinal health or were on other medications affecting the retina (eg, tamoxifen, ethambutol). Included subjects were made to sign informed consent form before enumerating them in the study.

The subjects were examined at inclusion and subsequently were followed up every six monthsfor the next 2 years. At each visit, all subjects underwent complete ophthalmological check up including assessment of visual acuity, slit lamp examination, dilated fundoscopy including +78D biomicroscopy. Prior to dilation, all subjects underwent Central 10-2 Automated Perimetry (Carl Zeiss Inc, USA) using the SITA algorithm. Included subjects also underwent Spectral Domain -OCT (Optovue), wherein 6mm macular scans and line scans were recorded. Special note was taken of the status of the ellipsoid zone(EZ).

Results :

Nine subjects fulfilling the laid down inclusion/exclusion criteria were included in the current study. All the subjects were females with an average age of 62 years at the time of inclusion. All of those included had ceased intake of CQ/HCQ 5-12 months prior, on advice of treating physician. The average treatment duration of the included subjects was about 8.5 years. None of the included subjects had any ophthalmoscopically detectable fundal lesion at the time of inclusion, as per inclusion criteria.

At the time of inclusion, only one subject had a small area of disruption of ellipsoid zone on SD OCT with all subjects not demonstrating any significant change in the 10-2 field reports. At the end of the study period, seven patients developed new disruptions of the ellipsoid zone(EZ) and one subject showed progression of EZ disruption on SD OCT. One subject did not show any change in foveal contour or architecture and one subject showed appearance of cystic spaces in the neuroretinal layers on OCT. The subjects lost between zero and twelve ETDRS letters during the study duration. Seven subjects showed a significant progression on AP, according to the Pattern Standard Deviation(PSD) Values(p<0.05).

Discussions and Conclusion :

Data on long-term follow-up after cessation of CQ/HCQ therapy are limited. Older studies using visual acuity or visual fields as parameter concluded that retinal function either remained stable, sometimes improved and only occasionally deteriorated after cessation of CQ or HCQ intake.^4,5A later study reported a decrease of retinal function during follow-up in 63% of patients over a period of 8 years. ⁶In addition, cases with progressive loss of retinal function have also been described. ^7,8,9In a recent study, Kellner et al concluded that CQ retinopathy can progress over a long period of time after drug cessation and may be complicated by cystoid macular oedema, epiretinal membrane formation and peripheral involvement. ¹⁰

The present study also concludes that CQ/HCQ toxicity may progress even beyond 3 years of cessation of the drug, although the retinal toxicity is typicallymild if the toxicity is recognized before there is RPE damage.Subjects who are initiated on these drugs need to be counselled accordingly. Once definitive signs of retinopathy are recognized, thedecision to stop medication should be made in conjunctionwith the patient and the prescribing medical physician toensure that medical risks are managed (e.g., a potential flareupof SLE).¹Early recognition of ocular toxic effects of CQ/HCQ, even before any fundus changes are visible, using visual fields(Central 10-2) and SD-OCT, will greatly minimize late progression and the risk of visual loss. We recommend that these basic non invasive ocular tests should be carried out routinely in subjects taking chloroquine or hydroxychloroquine.

References :

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