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December 2016

Crystalline Maculopathy Associated With High-Dose Lutein Supplementation

Author Affiliations
  • 1Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City
JAMA Ophthalmol. 2016;134(12):1445-1448. doi:10.1001/jamaophthalmol.2016.4117
Report of a Case

An Asian woman in her 60s with glaucoma but no macular degeneration was referred to the retina clinic for bilateral “foveal sparkles.” Her ocular, medical, family, and medication histories revealed nothing contributory. She had no visual complaints, and her visual acuity was 20/20 OD and OS with no afferent pupillary defect. Extraocular movements and visual fields by confrontation were full in both eyes. Slitlamp examination of the anterior segment was unremarkable in both eyes. Dilated fundus examination showed bilateral intraretinal round, yellow, glistening deposits in the fovea, and optical coherence tomography (OCT) indicated that these crystals were in the inner layers of the foveal region (Figure 1).

Figure 1.
Foveal Sparkles Related to High Dietary and Supplemental Lutein Consumption
Foveal Sparkles Related to High Dietary and Supplemental Lutein Consumption

Fundus photographs of the right (A) and left (D) eyes show crystal deposits, and the respective boxed regions are shown at higher magnifications in panels B and E. Optical coherence tomography shows crystals in the inner layers of the right (C) and left (F) foveal regions.

It was noted that for the past 8 years she took a daily 20-mg lutein supplement and 4 g of fish oil and had an unusually high dietary consumption of lutein, which included a broccoli, kale, spinach, and avocado smoothie every morning. We evaluated her carotenoid status through 3 objective methods. Her total macular pigment levels in both eyes within 9° of eccentricity by Spectralis dual-wavelength autofluorescence imaging (Heidelberg Engineering)1 were OD, 30 750 and OS, 30 215, which was approximately 3.1 times higher than those of our unsupplemented clinic population (UCP) (mean [SD], 9662 [3961]). Her skin carotenoid level by resonance Raman spectroscopy2 was 110 770 Raman counts, which was 2.7 times greater than the UCP average (mean [SD], 41 668 [14 736] Raman counts). Finally, her serum lutein level was 519 ng/mL measured by high-performance liquid chromatography, which was 2.9 times greater than that for the UCP (mean [SD], 182 [196] ng/mL). She agreed to discontinue her lutein supplement but made no other dietary changes.

At her 7-month return visit, the crystals in her right eye were resolving; however, crystals were still apparent in the left eye (Figure 2). Her skin carotenoid level had dropped substantially (72 798 Raman counts), as had her macular pigment levels (OD, 24 828; OS, 25 245). Serum lutein level (191 ng/mL) had also decreased to near the population mean.

Figure 2.
Partial Resolution of Foveal Sparkles 7 Months After Stopping Lutein Supplementation
Partial Resolution of Foveal Sparkles 7 Months After Stopping Lutein Supplementation

A, Fundus photograph of the right eye shows resolving foveal crystals 7 months after stopping lutein supplementation. B, Fundus photograph of the left eye shows persistent crystals. C and D, Magnified views of the respective boxed foveal regions show greater detail of the resolving and persistent crystals.


Large-scale clinical trials such as AREDS23 have brought attention to the ocular health and functional benefits of lutein, and therefore it is now widely recommended as dietary supplementation for the prevention of visual loss from age-related macular degeneration (AMD).4 For these reasons, it is common in ophthalmology practices to come across a large number of patients taking lutein supplements. Unfortunately, the general population often thinks that more is better and may end up consuming much more than the recommended 10 mg of lutein a day,3 at times even without a diagnosis of AMD. Lutein is considered a very safe compound, and there have been no previous reports of toxic effects4; however, we report a case of retinal crystals that were noted in a patient with an unusually high consumption level of supplemental and dietary lutein in which the crystals in one eye were less apparent after cessation of lutein supplementation.

These findings may represent a crystalline maculopathy in a patient who had an exceedingly high daily ingestion of lutein for 8 years prior to presentation. The crystals, reminiscent of canthaxanthin retinopathy and West African crystalline maculopathy,5,6 were found in the inner layers of the fovea and did not affect her visual acuity or cause other visual symptoms. After cessation of her 20-mg lutein supplement, the foveal crystals began to resolve in the right eye, coincident with decreases in her levels of skin carotenoids, serum lutein, and macular pigment. Foveal crystals remained in the left eye.

While dietary supplements containing lutein are considered for the prevention of visual loss from AMD, chronic consumption of lutein at levels far exceeding the AREDS2 dose3 of 10 mg/d is not always better.

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Article Information

Corresponding Author: Paul S. Bernstein, MD, PhD, John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132 (paul.bernstein@hsc.utah.edu).

Published Online: October 27, 2016. doi:10.1001/jamaophthalmol.2016.4117

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bernstein and the University of Utah hold a patent on the measurement of carotenoids in retina, skin, and other tissues using resonance Raman spectroscopy. Dr Bernstein has received consulting fees and research supplies from Kemin Health, DSM, and Science Based Health in the past 36 months. No other disclosures are reported.

Funding/Support: This research was funded by National Institutes of Health grants EY11600 and EY14800 and an unrestricted departmental grant from Research to Prevent Blindness.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the patient for granting permission to publish this information.

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