The most common adverse effect of silver toxicity is a slate gray discoloration of the skin, referred to as argyria, due to dermal deposition of the metal and/or associated melanocytic stimulation. Systemic accumulation of silver, termed argyrosis, is greatest in the liver, kidneys, spleen, adrenal glands, and intestinal tract.1,2 Ocular argyrosis develops due to deposition within the eye, ocular adnexa, and periocular tissue, resulting in a pigmented appearance of these tissues, and may occur after topical application of silver-containing substances or systemic ingestion. We report a case of ocular argyrosis secondary to long-term ingestion of colloidal silver associated with novel spectral-domain optical coherence tomography (SD-OCT) findings.
A 68-year-old Caucasian man with a remote history of prolonged daily colloidal silver ingestion presented for routine ophthalmic examination. On presentation, his skin was noted to have a slate gray discoloration, more pronounced in the hands and face (Figure 1A–B, page E21), although the patient demonstrated no symptoms or signs of cyanosis.
Skin findings in argyrosis. Clinical photographs demonstrating a slate gray tinted patient resembling a “blue man” (A) and bluish discoloration of the nail beds (B).
Best corrected visual acuity was 20/80 in the right eye and 20/200 in the left eye. His pupils were equal without an afferent pupillary defect. Formal visual field testing revealed paracentral scotomas greater in the left than right eye. Anterior segment examination findings were unremarkable. Funduscopic examination (Figure 2A, page E22) and red-free images (Figure 2B, page E22) demonstrated confluent perimacular drusenoid deposits in both eyes. Fluorescein angiography (FA) revealed a dark choroid bilaterally (Figure 2C–D, page E22). Speckled macular hyperfluorescence in early phases (Figure 2C, page E22), corresponding to the drusenoid deposits, progressed to geographic staining in later phases of the FA bilaterally (Figure 2D, page E22). SD-OCT imaging displayed large drusenoid deposits in the macula at the level of and anterior to the inner segment ellipsoid band in both eyes (Figure 2E, page E22). Enhanced depth imaging (EDI) OCT revealed severe thinning of the choroid, with subfoveal choroidal thickness measuring 101 μm bilaterally (Figure 2F, page E22). Confirmatory serum silver levels were obtained and found to be markedly elevated at 24 μg/L (normal level: < 5 μg/L).
Posterior segment findings in ocular argyrosis. Color fundus (A) and red-free (B) images displaying confluent perimacular drusenoid deposits (only right eye pictured). Early (C) and late (D) phases of the fluorescein angiogram demonstrate a dark or silent choroid, with late geographic staining of the macula. Spectral-domain optical coherence tomography (OCT) of the right eye reveals numerous large drusenoid deposits located above the inner segment ellipsoid layer (E). Measurement of the choroid with enhanced depth imaging OCT reveals severe thinning (F).
Historically and more recently on the Internet, silver has been purported to have medicinal benefits in treating numerous diseases. Websites advertising and distributing colloidal silver as a homeopathic cure for cancer, diabetes, AIDS, and other infectious diseases have contributed to its resurgence among patients seeking alternative therapies.3 Concurrently, reports of systemic argyrosis have emerged secondary to the use of these unregulated products.1,2,4–6
While the periocular and anterior segment findings in ocular argyrosis are well-described, clinical reports characterizing the posterior segment manifestations are rare. Cohen et al previously observed a dark or silent choroid on FA in six patients with argyrosis,6 similar to our case. This finding is most often associated with Stargardt’s disease due to excessive accumulation of lipofuscin in the retinal pigment epithelium (RPE). In a histopathologic report, Spencer et al demonstrated that while silver accumulated in the basement membrane of the conjunctival and corneal epithelium, Bowman’s layer, Descemet’s membrane, and the lens capsule, the most concentrated deposition was found in Bruch’s membrane, which resulted in a deep black stain.7 Another group corroborated these findings in an experimental rat model of argyrosis, noting silver accumulation in Bruch’s membrane but not the RPE.8
The observation of bilateral confluent drusenoid deposits resulting in geographic maculopathy is of particular interest in our case. With SD-OCT imaging, these deposits resembled reticular pseudodrusen seen in age-related macular degeneration (AMD) but were much larger and more superficially dispersed throughout the macula, the majority of which localized at the level of or anterior to the inner segment ellipsoid band. This presentation is atypical for pseudodrusen, which by definition reside immediately posterior to the ellipsoid layer.9 Only one other report has described drusen-like material in conjunction with macular RPE changes in an individual with ocular argyrosis after long-term ingestion of silver nitrates.5 Unlike in our patient, the excrescences were isolated to the sub-RPE space in the form of drusenoid pigment epithelial detachments, which is more characteristic of AMD. Interestingly, autofluorescence imaging, which we were unable to obtain for our patient, in that case did not show any abnormality of the RPE.5 Accordingly, the authors attributed these selective changes to AMD rather than implicating argyrosis as the cause, as we have proposed. Whether our findings represent actual silver deposits or metabolic byproducts in response to the silver is unclear at this time and awaits a histopathological correlate.
Equally intriguing is the finding of a markedly thinned choroid by EDI-OCT, the first time this has been demonstrated in association with ocular argyrosis. Spaide previously characterized a subset of elderly patients with marked choroidal thinning, which he termed age-related choroidal atrophy, a degenerative process that may share some overlap with AMD.10 However, in direct contrast to our patient, the 13 patients (18 eyes) in Spaide’s series were significantly older (mean age: 79.7 years), retained good vision (mean visual acuity: 20/40), demonstrated a tessellated fundus on examination (18 of 18 eyes), and showed signs of peri papillary atrophy (13 of 18 eyes) or glaucoma (six of 18 eyes).10 While severe choroidal thinning in our patient may be attributable to age-related choroidal atrophy, the association with argyrosis is compelling.
Currently, there is no effective treatment for systemic or ocular argyrosis, although silver chelating agents have been tried unsuccessfully.3,4 Despite cessation of silver ingestion, the skin discoloration, which tends to be more pronounced in sun-exposed areas such as the face and hands, is usually permanent. The increasing commercial use of silver-containing homeopathic products warrants greater awareness for potential complications. This report describes a unique geographic maculopathy with large drusenoid deposits anterior to the ellipsoid layer and severe choroidal thinning in association with ocular argyrosis. Further cases are needed to determine the significance of these findings.
- Chang AL, Khosravi V, Egbert B. A case of argyria after colloidal silver ingestion. J Cutan Pathol. 2006;33:809–811. doi:10.1111/j.1600-0560.2006.00557.x [CrossRef]
- Kwon HB, Lee JH, Lee SH, Lee AY, Choi JS, Ahn YS. A case of argyria following colloidal silver ingestion. Ann Dermatol. 2009;21:308–310. doi:10.5021/ad.2009.21.3.308 [CrossRef]
- Fung MC, Bowen DL. Silver products for medical indications: risk-benefit assessment. J Toxicol Clin Toxicol. 1996;34:119–126. doi:10.3109/15563659609020246 [CrossRef]
- Gulbranson SH, Hud JA, Hansen RC. Argyria following the use of dietary supplements containing colloidal silver protein. Cutis. 2000;66:373–374.
- Stafeeva K, Erlanger M, Velez-Montoya R, Olson JL. Ocular argyrosis secondary to long-term ingestion of silver nitrate salts. Clin Ophthalmol. 2012;6:2033–2036.
- Cohen SY, Quentel G, Egasse D, Cadot M, Ingster-Moati I, Coscas GJ. The dark choroid in systemic argyrosis. Retina. 1993;13:312–316. doi:10.1097/00006982-199313040-00008 [CrossRef]
- Spencer WH, Garron LK, Contreras F, Hayes TL, Lai C. Endogenous and exogenous ocular and systemic silver deposition. Trans Ophthalmol Soc U K. 1980;100:171–178.
- Wislocki GB, Ladman AJ. The demonstration of a blood-ocular barrier in the albino rat by means of the intravitam deposition of silver. J Biophys Biochem Cytol. 1955;1:501–510. doi:10.1083/jcb.1.6.501 [CrossRef]
- Zweifel SA, Spaide RF, Curcio CA, Malek G, Imamura Y. Reticlar pseudodrusen are subretinal drusenoid deposits. Ophthalmology. 2010;117:303–312. doi:10.1016/j.ophtha.2009.07.014 [CrossRef]
- Spaide RF. Age-related choroidal atrophy. Am J Ophthalmol. 2009;147:801–810. doi:10.1016/j.ajo.2008.12.010 [CrossRef]