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. 2010 Oct 21;4:1151-8.
doi: 10.2147/OPTH.S14257.

Spectral Domain Optical Coherence Tomography as an Effective Screening Test for Hydroxychloroquine Retinopathy (The "Flying Saucer" Sign)

Free PMC article

Spectral Domain Optical Coherence Tomography as an Effective Screening Test for Hydroxychloroquine Retinopathy (The "Flying Saucer" Sign)

Eric Chen et al. Clin Ophthalmol. .
Free PMC article


Purpose: While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage.

Methods: Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers.

Results: Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none.

Conclusion: Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

Keywords: drug toxicity; hydroxychloroquine; photoreceptors; screening test; spectral domain optical coherence tomography.


Figure 1
Figure 1
Top: Normal Spectralis spectral domain optical coherence tomography (SD OCT) image with intact photoreceptor inner segment/outer segment junction (IS/OS). Bottom: Spectralis SD OCT from the left eye of patient 10 showing the “flying saucer” sign of hydroxychloroquine retinopathy, an ovoid appearance of the central fovea created by preservation of central foveal outer retinal structures (seen between the black arrows) surrounded by perifoveal loss of the photoreceptor IS/OS junction, and perifoveal outer retinal thinning. Abbreviations: ILM, internal limiting membrane; IPL, inner plexiform layer; OPL, outer plexiform layer; ELM, external limiting membrane; RPE, retinal pigment epithelium.
Figure 2
Figure 2
Spectral domain optical coherence tomography (SD OCT) images taken with different commercially available SD OCT machines demonstrate the “flying saucer” sign is consistent in different individuals with hydroxychloroquine retinopathy. A) Heidelberg Spectralis SD OCT in patient 9, OD. B) Zeiss Cirrus SD OCT in patient 9, OD. C) Heidelberg Spectralis SD OCT in patient 4, OS. D) Zeiss Cirrus SD OCT in patient 4, OS.
Figure 3
Figure 3
Spectral domain optical coherence tomography (SD OCT), red-free photo, fundus autofluorescence, and early and late fluorescein angiogram in patient 10, who had no symptoms, normal clinical exam and fundus autofluorescence imaging, Humphrey visual field 10-2 with paracentral scotomas, and “flying saucer” sign seen on SD OCT.
Figure 4
Figure 4
Spectral domain optical coherence tomography (SD OCT) images, red-free photos, and fundus autofluorescence (FAF) demonstrate a spectrum of findings seen with different stages of hydroxychloroquine retinopathy. Note the increased signal of choroidal vessels on SD OCT as the retina becomes increasingly atrophic with progressive toxicity starting from early toxicity in patient 10 seen in Figure 3. A) Moderate toxicity. Patient 24: vision loss, clinical bull’s eye maculopathy even more apparent on FAF, Humphrey visual field (HVF) 10-2 paracentral scotomas, and significant perifoveal outer retinal dropout but preservation of central photoreceptor inner segment/outer segment junction (between the arrows) seen on SD OCT allowing 20/40 vision. B) Late toxicity. Patient 18: severe vision loss to hand motion, pronounced clinical and FAF bull’s eye maculopathy, dense HVF 10-2 paracentral scotomas, and complete disruption of outer retinal structures on SD OCT.

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    1. Mavrikakis I, Sfikakis PP, Mavrikakis E, et al. The incidence of irreversible retinal toxicity in patients treated with hydroxychloroquine: a reappraisal. Ophthalmology. 2003;110(7):1321–1326. - PubMed
    1. 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(8):1482–1486. - PubMed
    1. Lee AG. Hydroxychloroquine screening. Br J Ophthalmol. 2005;89(5):521–522. - PMC - PubMed
    1. Marmor MF, Carr RE, Easterbrook M, Farjo AA, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Ophthalmology. 2002;109(7):1377–1382. - PubMed
    1. Marmor MF. The dilemma of hydroxychloroquine screening: new information from the multifocal ERG. Am J Ophthalmol. 2005;140(5):894–895. - PubMed

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