Chalcosis

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Chalcosis, also called chalcosis bulbi, is a chronic reaction to a copper-containing intraocular foreign body (IOFB) with less than 85% copper content. The condition may become apparent within days, or the patient may remain asymptomatic for over a decade.[1][2] The course is variable depending on the copper content of the foreign body, its size, location, and the patient’s healing response to the foreign material. Ocular structures that may be affected by copper alloys include the cornea, iris, lens, vitreous body, and retina. Timely intervention is recommended to prevent long-term damage, preserve vision, and maintain health of the eye.

Pathophysiology

When copper enters the eye, it is oxidized from its uncharged elemental form, Cu, to Cu2+ ions.[3] Though the ions are free to diffuse throughout the vitreous, they have a propensity to deposit in intraocular basement membranes including Descemet’s membrane of the cornea and the internal limiting membrane (ILM). However, copper deposits are commonly visualized in the ILM in the setting of ocular trauma.

If the copper-containing foreign body (FB) is not removed from the eye, reactive fibrosis is known to encapsulate intraocular copper, which helps reduce deposition into surrounding ocular structures.

Foreign bodies containing less copper (<85%), such as brass and bronze, may lead to a localized inflammatory response and are typically the cause of chalcosis. Materials containing less than 70% copper are relatively inert, leading to low-grade chronic inflammation or no discernible symptoms.[4][5] However, foreign bodies with higher concentrations of copper (>85%) show a generalized pattern of intraocular copper deposition and are associated with more devastating outcomes such as suppurative endophthalmitis and phthisis bulbi.

There are four patterns of histopathologic change due to copper exposure. The first is suppuration, an acute inflammatory reaction with degenerated neutrophils and few macrophages present. The intensity of inflammation depends on proximity to the foreign body. One study found that retinal tissue adjacent to the IOFB demonstrated a focal accumulation of neutrophils and pigment-laden macrophages.

The second pattern of histopathologic change is chronic granulomatous inflammation, consisting of plasma cells, lymphocytes and macrophages that stain positively for copper.

The third pattern is reactive fibrosis around the foreign body, resulting in a fibrous capsule. The capsule is composed of dense and hyalinized connective tissue, and copper may localize at the inner portion of the capsule. A foci of chronic inflammation may also form around the capsule. One study demonstrated no rise in copper content of the anterior chamber (AC) or vitreous body days after implantation of a copper-containing IOFB. This may indicate that the eye is protected from the damaging effects of copper by the dense fibrous capsule surrounding the FB.[5][6]

Finally, the fourth pattern of histopathologic change is disseminated deposition of copper in various ocular structures. This can lead to visible changes noticed during slit lamp examination. Copper deposition has been observed in the cornea and iris, leading to green-discoloration of the iris.

Clinical Manifestations

A diagnosis of chalcosis is based on clinical features. Acutely, the presence of copper within the eye leads to the accumulation of leukocytes near the foreign body. More chronically, macrophages containing fine copper granules in their cytoplasm are seen histochemically. The earliest symptoms associated with penetrative injury by a copper-containing foreign body may include pain and hemorrhage on the surface and inside the eye. Late and end-stage findings include staining of intraocular structures and retinal damage depending on the location of the foreign body.

Sclera

When copper exists within the sclera, tissue softening and abscess formation may be present.

Cornea

As copper has an affinity for basement membranes, Descemet’s membrane is susceptible to deposition and accumulation known as a Kayser-Fleischer ring. It presents as a 1-2mm wide, green-brown ring in the periphery of the cornea and may extend superiorly, inferiorly, or circumferentially. Deposits in Descemet's membrane have also been described as a golden-brown metallic sheen with guttate changes and radiating folds arising from the site of the IOFB.[7]

Anterior Chamber

One study noted elevated concentrations of copper in the aqueous humor[6], while another[4] noted the presence of cells and copper colored metallic particles.

Iris

The iris may take on a greenish tinge due to the deposition of copper.[4]

Lens

A metallic, green-gray or golden-yellow disciform opacity may form in the lens, otherwise known as a sunflower cataract. Characteristically, it has serrated edges and lateral radiations which may be accompanied by a dull yellow glow over the anterior capsule.[5]

Vitreous

The vitreous may contain green, red, or brown granular deposits; vitreous stranding; and haze. Vitreous degeneration and liquefaction may also be present.[4] In the mid-vitreous, copper can exist uneventfully for extended periods of time.[8]

Retina

The presence of copper granules has been documented in the ILM, especially at the macula. It has been detailed as hyperreflective deposits within the inner retinal layers and circinate, fleck-like deposits surrounding the fovea and mid-peripheral retina.[5] However, in addition to glistening refractile particles seen at the macula, one study noted hyperreflectivity in the anterior layer of the retina while underlying retinal layers remained unremarkable.[9] It is proposed that the copper concentrates in this region due to physiologic fluid movement, increased metabolism, and increased oxygen levels within the retina.

Further, copper-containing foreign bodies located near the retina and choroid are more likely to induce massive cellular infiltration characterized by macrophages, accumulated eosinophilic exudate in the subretinal space. One study demonstrated retinal gliosis in the vicinity of the IOFB, with this region staining strongly for copper. Additionally, the walls of the retinal capillaries showed copper deposits.[10][11]

Compared to iron, copper is less retinotoxic and does not cause degenerative retinopathy.

Diagnosis

Diagnostic imaging in the setting of trauma helps in the detection of suspected IOFB. Computed tomography and X-ray are the first line imaging modality to confirm the presence of metallic IOFB.[12][13] When globe rupture is suspected, ophthalmic B-scan ultrasonography is generally avoided to prevent further expulsion of globe contents. Optical coherence tomography (OCT), B-scan, ultrasound biomicroscopy and electroretinogram (ERG) can also be used during subsequent follow-up visits to detect occult metallic IOFB not readily visible on the initial exam.

In the setting of progressive retinal toxicity from copper, ERG can detect decreased photopic and scotopic response amplitudes as well as increased implicit times.[14] Cone response can be decreased as much as 25-30%. However, if intraocular copper concentrations return to normal, response amplitude depression can be reversed.[15]

Anterior Segment Optical Coherence Tomography (AS-OCT) has also shown promise in copper detection, revealing deposits forming a characteristic linear pattern of hyper-reflective dots along Descemet’s membrane otherwise undetectable during the slit-lamp examination.[16] Additionally, Copper deposits can be visualized on histopathologic specimens after staining with rhodanine, rubeanic acid, and alizarin blue in Descemet’s membrane, the ILM, vitreous, and in the fibrous capsule around the IOFB.[10][17]

Differential Diagnosis

When Kayser-Fleicher rings or sunflower cataracts are the initial findings on exam with no clear history of ocular trauma, Wilson disease should remain on the differential as both elevated serum and intraocular copper levels lead to preferential copper deposition at the corneal periphery and lens.[18] However, further laboratory workup may reveal low serum ceruloplasmin and high urinary copper in Wilson disease. Additionally, Wilson disease is characterized by hepatolenticular degeneration, and therefore, liver function tests (LFTs) will demonstrate liver dysfunction with abnormal values. Finally, neurologic symptoms are commonly found in Wilson disease while this is not the case in chalcosis bulbi, which presents with purely ocular findings and vision complaints.

Management

As copper-containing IOFBs are common results of penetrating injury, the first step in management consists of urgent removal of the foreign body, wound closure and restoration of globe integrity. In addition to obtaining a history of tetanus immunization, patients should begin prophylactic therapy for endophthalmitis with systemic, broad-spectrum antibiotics.[19] Peribulbar dexamethasone and oral glucocorticoids are also indicated to suppress inflammatory response.[20][21][22]

Greater than 85% of cases require prompt surgical removal of the copper-containing IOFB. However, a study conducted at Walter-Reed Army Medical Center found that delayed IOFB removal with a combination of systemic and topical antibiotics can result in similar visual outcomes as compared to prompt removal.[23][24] As copper is non-magnetic, it has proven more difficult to remove compared to iron or steel. Accurate identification of the FB is vital because removal of non-metallic foreign bodies is only justified if chemically toxic to the eye.[6]

A vitrectomy with or without lensectomy and scleral buckle placement may be done to remove the FB. An ILM peel done in conjunction with vitrectomy helps to ensure that the majority of copper deposits in the limiting membrane is removed.

Precautions

The greatest risk factor for penetrating injury of the globe by a copper-containing foreign body is lack of eye protection. It is thus important to recommend safety glasses to workers in construction, metal-working, landscaping, and other industrial professions.

Prognosis

Although copper deposits can persist in the immediate postoperative period, a satisfactory visual outcome can be obtained after FB removal even years following the onset of injury.[10] Small, intraocular copper foreign bodies can be tolerated for long periods of time without retinal toxicity, but vitreous changes or maculopathy may necessitate intervention.[25][11]

Copper foreign bodies near the retina or choroid are more likely to induce massive cellular infiltration while those in the vitreous can be clinically silent for longer periods of time. This may be due to higher oxygen levels in the retina and choroid.[9]

Retained copper IOFB can cause progressive diminution of vision, defects in the visual field and impaired color vision, however compared to ferrous toxicity, copper is less toxic to intraocular structures if the metal concentration is <85%. Additionally, partial reversible maculopathy caused by copper has been described in the literature where removal of the IOFB is associated with improved visual outcomes.[5][14]

Resources

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  9. 9.0 9.1 Goel N. Spectral domain optical coherence tomography and en-face imaging in presumed ocular chalcosis. Saudi J Ophthalmol. 2017;31(4):266-268. doi:10.1016/j.sjopt.2017.04.006
  10. 10.0 10.1 10.2 Rao NA, Tso MOM, Rosenthal AR. Chalcosis in the Human Eye: A Clinicopathologic Study. Arch Ophthalmol. 1976;94(8):1379–1384. doi:10.1001/archopht.1976.03910040247018
  11. 11.0 11.1 Rosenthal AR, Marmor MF, Leuenberger P, Hopkins JL. Chalcosis: a study of natural history. Ophthalmology. 1979;86(11):1956-1972. doi:10.1016/s0161-6420(79)35324-6
  12. Pokhraj P S, Jigar J P, Mehta C, Narottam A P. Intraocular metallic foreign body: role of computed tomography. J Clin Diagn Res. 2014 Dec;8(12):RD01-3. doi: 10.7860/JCDR/2014/9949.5271. Epub 2014 Dec 5. PMID: 25654008; PMCID: PMC4316314
  13. Tai-Chi Lin, Tsan-Chieh Liao, Wei-Hsin Yuan, Fenq-Lih Lee, Shih-Jen Chen. Management and clinical outcomes of intraocular foreign bodies with the aid of orbital computed tomography. Journal of the Chinese Medical Association, Volume 77, Issue 8, 2014, Pages 433-436, ISSN 1726-4901, https://doi.org/10.1016/j.jcma.2014.05.006.
  14. 14.0 14.1 Donovan CP, Bhaleeya SD, Tzekov RT. Intraocular Deposition of Copper and ERG Findings in a Patient With Progressive Vision Loss From Hypercupremia. Ophthalmic Surg Lasers Imaging Retina. 2019 Nov 1;50(11):e324-e326. doi: 10.3928/23258160-20191031-21. PMID: 31755985.
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  16. Broniek-Kowalik K, Dzieżyc K, Litwin T, Członkowska A Szaflik JP. Anterior segment optical coherence tomography (AS-OCT) as a new method of detecting copper deposits forming the Kayser–Fleischer ring in patients with Wilson disease. Acta Ophthalmol. 2019; 97: e757-e760
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  19. Kurian, Ajay E., Rachitskaya, Aleksandra V. et al Retinal Physician, Update on the Management of Intraocular Foreign Bodies, Volume: 14, Issue: January 2017, page(s): 48-52
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  21. Soheilian M, Rafati N, Mohebbi MR, et al. Prophylaxis of acute posttraumatic bacterial endophthalmitis: a multicenter, randomized clinical trial of intraocular antibiotic injection, report 2. Arch Ophthalmol. 2007;125:460-465.
  22. John, D. A., Moroi, S. E., & Stein, J. D. (2016, March 30). Management of Intraocular Foreign Bodies. American Academy of Ophthalmology. Retrieved July 16, 2022, from https://www.aao.org/eyenet/article/management-of-intraocular-foreign-bodies
  23. Kurian, Ajay E., Rachitskaya, Aleksandra V. et al Retinal Physician, Update on the Management of Intraocular Foreign Bodies, Volume: 14, Issue: January 2017, page(s): 48-52
  24. Colyer MH, Weber ED, Weichel ED, et al. Delayed intraocular foreign body removal without endophthalmitis during Operations Iraqi Freedom and Enduring Freedom. Ophthalmology. 2007;114:1439-1447.
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