Toxic Optic Neuropathy Due to Mercury in Skin Lightening Products

ABSTRACT Mercury has been described as been in daily household items such as soaps, skin-lightening creams (SLC), and topical disinfectants. Mercury exposure can reportedly cause damage to the optic nerve and retina. A 30-year-old Somali woman presented with decreased vision and was found to have bilateral optic atrophy. Neuroimaging and laboratory work-up for nutritional deficiencies, heavy metals, and syphilis were performed. Evaluation revealed normal neuroimaging and laboratory work-up except for elevated serum and urine mercury levels. Mercury levels at the initial blood test was 11.1 ug/L (normal limits < 10.0 ug/L) and was 15.7 ug/L on repeat testing. A 24-h urine test showed elevated mercury at 16 ug/24 h (normal limits < 2 ug/24 h). Evaluation of an unlabelled SLC that she was using showed the presence of mercury. It is worth testing for heavy metals in the work-up of bilateral optic atrophy. Clinicians should consider cosmetic products as a potential source of mercury exposure and recommend discontinuation if mercury is present.


Introduction
Mercury, a naturally occurring element, exists in several forms: (1) elemental or metallic mercury; (2) inorganic mercury compounds; and (3) methylmercury or other organic compounds.When elemental mercury reacts with another substance it becomes a compound and forms inorganic mercury salts or methylmercury.In daily life, mercuric chloride, an inorganic mercury compound, can access the dermis through some soaps, creams, or topical disinfectants.
Mercury is neurotoxic.Human and animal studies have demonstrated that chronic exposure can affect not only the retina but also the vitreous humour, optic nerve, and choroidal vasculature through systemic involvement. 1 In the literature, the ocular consequences that result from mercury in cosmetics are limited.Mercury-containing cosmetics applied directly to the skin and mucous membranes may pose threats to human safety.We report a patient with a progressive, bilateral optic neuropathy while using cosmetic skin-lightening creams (SLC) containing mercury.

Case report
A 30-year-old Somali woman presented due to gradual, bilateral loss of vision over the previous 3 years.It began with the right eye (RE) followed by the left eye (LE) 2 years later.She reported eye pain, pain with eye movement, and bitemporal headaches, fatigue, dizziness, and muscle weakness.She had been diagnosed with glaucoma by a previous ophthalmologist for which she received treatment.Her past medical history included bilateral occipital neuralgia and vitamin D deficiency.She denied a family history of vision loss, neurological disease, or glaucoma.Review of systems was otherwise negative.Her medications included amitriptyline, cyclobenzaprine, diclofenac, omeprazole, rizatriptan, and tafluprost.
Her visual acuity (VA) was 20/200 RE and 20/40 LE.She correctly identified 9/11 and 11/11 of the Ishihara plates with the RE and LE, respectively.Her intraocular pressure was 10 mmHg RE and 11 mmHg LE.Slit-lamp examination revealed a large scar inferonasal to the visual axis in her RE.Dilated fundoscopic examination showed that she had temporal pallor of both optic discs.Optical coherence tomography (OCT) demonstrated bilateral temporal thinning of the retinal nerve fibre layer (RNFL) (Figure 1).OCT of the macula appeared normal (Figure 2).Automated perimetry showed generalised depression of the RE and a central/arcuate scotoma in the LE.
Magnetic resonance imaging (MRI) of the brain and orbits with contrast was obtained, which was normal.Laboratory investigations included treponemal antibodies, human immunodeficiency virus antibodies, vitamin B 1 /B 12 , red blood cell folate, methylmalonic acid, homocysteine, and a heavy metal panel (arsenic, lead, cadmium, mercury, and chromium).Her laboratory results were within normal limits, except for serum mercury.Mercury levels at the initial blood test was 11.1 ug/L (normal < 10.0 ug/L).Repeat testing 2 months later showed a level of 15.7 ug/L.Her VA worsened to counting fingers at 3 feet in her RE.OCT of the RNFL was stable at that visit.
She denied any known toxin exposure including fish consumption; however, her mercury levels were persistently high and worsened after the initial visit.A home evaluation showed that two SLCs that she had purchased outside of the United States contained mercury levels of 4590 and 7440 parts per million (ppm, recommended < 1 ppm), respectively.She stopped using SLCs and her serum mercury levels normalised to 9 ug/L 1 month later.
Six months later, many of her presenting symptoms, including subjectively worsening vision, burning eye pain bilaterally, and headaches associated with light sensitivity had returned at this visit.Her serum mercury level was elevated again at 16 ug/L and her VA had worsened to counting fingers at 3 feet RE.A second home visit found two new SLCs that also contained mercury with levels of 11,000 and 18,000 ppm, respectively.Twenty-four hour urine testing on the patient and her child demonstrated urine mercury levels of 23.0 mcg/L (normal < 5 mcg/L) and 5.46 mcg/L, respectively.One year later, the levels remained elevated at 46.6 mcg/L and 6.88 mcg/L.She did not return for ophthalmological evaluation at this time but denied using the creams and did not note any significant progressive changes to her vision.
Our Institutional Review Board determined that this report was not research involving human subjects as defined by Department of Health and Human Services and Food and Drug Administration regulations.Consent for publication was obtained from the patient.

Discussion
The patient we have described demonstrated progressive loss of vision with bilateral optic atrophy.She showed elevated mercury levels in the setting of using SLCs containing markedly elevated levels of mercury.After she stopped the SLC, her mercury levels normalised and then rose again after she started using a different mercury-containing product.
Mercury has been reported to cause vision loss from toxic fumigations in industrial settings, direct metallic exposure, and diet-related ingestion of mercury content.To our knowledge, visual loss secondary to mercury exposure from SLC has not been previously reported.
The exact pathophysiology of mercury injury to visual system has not been elucidated.Mercury may affect the optic pathway directly or in a retrograde fashion with the optic nerve injury following central nervous system (CNS) damage.The absorption of methylmercury generates reactive oxygen species that directly affect the CNS. 2 Furthermore, heavy metals can cross the blood-brain barrier, settle in nerve capillaries, and deposit in the brain. 3When pregnant mice were exposed to a non-lethal dose of mercury vapour for 4 hours per day for 5 days in late gestation, mercury was taken up mainly by foetal retinal ganglion cells, optic nerve glial cells, the retinal pigmented epithelium, and endothelial cells. 4It has also been shown that methylmercury may also target both the optic nerve and outer segment of photoreceptor cells directly in zebrafish larvae. 5,6linically, spectral domain OCT can identify the effect of chronic mercury toxicity on the RNFL thickness, macular thickness, and choroidal thickness in battery industry workers who also showed reduced VA. 7ne additional study reported visual findings in 29 maintenance workers who were acutely exposed to high concentrations of mercury vapour. 8After the exposure, 26 workers demonstrated mercury-related erethism including fatigue, irritability, aggressiveness, anxiety, depression, and insomnia.Neurological symptoms that they displayed included tremor, peripheral polyneuropathy, weakness, headache, cognitive disorder, dizziness, diarrhoea, and abdominal cramps.Our patient had similar symptoms of fatigue, muscle weakness, bitemporal headaches, and dizziness at the time of her SLC use.The study further noted that VA was affected in 48% of the subjects, loss of contrast sensitivity in 96%, visual field alterations in 72%, and reduced b wave amplitudes and oscillatory potentials with full-field electroretinography testing.These findings suggest both the development of optic neuropathy and inner/ outer retinal damage can occur as result of direct mercury exposure. 8The mean serum mercury concentration for these workers was 392.93 ± 273.85 μg/ L, which was substantially higher than for our patient.However, our case report demonstrates that even moderately increased serum mercury levels may have detrimental effects on the optic nerve and vision.It would be reasonable to examine for potential retinal damage if our patient returns.
Heavy metals have been discovered in SLCs from companies around the world including Bangladesh and Jamaica, among others.The emergence of online shopping to purchase SLCs overseas without strict regulations enables unsafe heavy metal content.Non-regulated SLCs may contain potentially harmful components undetectable without a laboratory test.More troubling, mercury was not listed on the labels of our patient's SLCs.
In the setting of a progressive, bilateral optic neuropathy clinicians should consider testing for heavy metal exposure.Cosmetic products are a potential source of mercury exposure and discontinuation should be recommended if elevated mercury is present in the serum and urine and the products have been demonstrated to contain mercury.

Figure 1 .
Figure 1.Initial presentation optical coherence tomography retinal nerve fibre layer image.OD = right eye; OS = left eye.