IRON TOXICITY

Iron toxicity or siderosis typically occurs following penetrating injury with a metallic foreign body. The retinal toxicity occurs gradually over time and can be completely prevented by early removal of the foreign body. It is incumbent on the physician to rule out the presence of a metallic foreign body when traumatic injury to the eye is even slightly suspected.

Symptoms

The symptoms of siderosis are insidious, and the underlying cause will not be discovered unless there is a high index of suspicion for the possibility. Loss of the peripheral visual field is gradual. Central visual acuity is affected late in the disease process.

Clinical Features

Gradual loss of the pigmentation of the retinal pigment epithelium (RPE) is the most striking finding. The optic disc may become pale and the retinal vessels attenuated (siderosis should be considered in the differential diagnosis of “unilateral retinitis pigmentosa”). The vitreous can be hazy as well. Small orange deposits in the anterior subcapsular area of the lens and darkening of the iris (iris heterochromia) may also develop in the later stages of ocular siderosis.

Ancillary Testing

The most useful test for the suspicion of iron toxicity is radiologic examination of the globe. A plain facial x-ray can most often find the foreign object. Computed tomography (CT) scan can help localize the object. The electroretinographic findings of the suspected eye can be compared to those of the other eye. The affected eye initially shows a supernormal a-wave pattern early

in the disease process. As time passes a progressive decrease in the b-wave is noted, with eventual extinction of the entire electroretinographic response.

Pathology/Pathogenesis

The iron from the metallic foreign body slowly oxidizes within the eye. The iron oxide is deposited in the inner retina and RPE, which leads to atrophy of the RPE and the photoreceptors. The damage is more severe with ferrous compounds than with ferric ones.

Treatment/Prognosis

The proper treatment of siderosis is to find the foreign body and remove it from the eye. This action will halt further progression of the toxicity. The damage, however, is permanent.

Systemic Evaluation

Once a metallic foreign body is found in the eye, a complete radiologic examination of the orbit should be performed to rule out any other pathology or additional foreign objects.

Anterior segment findings of siderosis include anterior subcapsular cataracts and iris heterochromia. The right eye has a normal blue iris.

This fundus photograph shows a normal right eye in a patient with siderosis.

The left eye of the same patient with iron toxicity has iris heterochromia, with a greenish discoloration of the iris.

The left eye of the same patient had a metallic foreign body in the macula that was undiagnosed for 11 years. Note the optic disc pallor, retinal vascular attenuation, and extensive loss of pigmentation.

PHENOTHIAZINE TOXICITY

The phenothiazine class of compounds includes chlorpromazine and thioridazine. Both compounds are used to treat psychiatric conditions and chlorpromazine has been used to treat intractable hiccups.

Symptoms

The symptoms of toxicity include blurred vision, dyschromatopsia, and nyctalopia.

Clinical Features

Initially, the eye examination may be normal. Patients may develop brownish pigmentation of the cornea and lens. A characteristic anterior, star-shaped cataract may be observed in patients with chlorpromazine toxicity.

Early in the course of the retinal toxicity, retinal pigment epithelial alterations, including retinal pigment epithelial stippling and scattered pigment clumps, are observed.

Eventually, the affected patients develop geographic areas of atrophy of the retinal pigment epithelium (RPE) and retina. The optic disc and retinal vessels usually remain normal.

Ancillary Testing

The fluorescein angiogram shows irregularity of the RPE initially, with severe atrophy of the RPE and choriocapillaris in the late stages of toxicity. The electroretinogram is normal early but may be reduced or extinguished in advanced cases.

Pathology/Pathogenesis

The phenothiazines are cationic amphophilic substances that form tight bonds with the polar lipids present in lysosomes. Chlorpromazine may be less toxic, as it lacks a piperidyl side chain. The concentration in melanin granules is increased, and toxicity can progress even after the drug has been stopped. Pathology specimens show initial atrophy and disorganization of the photoreceptors followed by loss of the choriocapillaris and RPE later. A dose of greater than 800 mg/day of thioridazine is more likely to produce retinal toxicity, and the dose of chlorpromazine may be even higher (around 1 to 2 g/day).

Treatment/Prognosis

As with all toxic drugs, it is recommended that these agents be stopped immediately when signs or symptoms of toxicity appear. Discontinuation of the medication in the early stages may result in the resolution of the symptoms and retinal findings. However, because of the slow elimination of these agents, the toxicity can progress for some time after the drug is stopped.

Systemic Evaluation

No systemic evaluation is necessary. The ophthalmologist should notify the treating physician immediately when retinal toxicity is suspected.

Fundus photograph of a patient with a long-standing history of thioridazine use. He had mottling of the retinal pigment epithelium that was most notable temporal to the fovea.

Fluorescein angiogram of the right eye of the same patient demonstrates more widespread retinal pigment epithelial alterations with a salt and pepper pattern of hyperand hypofluorescence.

The fellow eye of the same patient had similar changes.

The fluorescein angiogram of the left eye of the same patient is similar to that of the right eye. Note that the retinal pigment epithelial changes are more prominent with fluorescein angiography.

This fundus photograph shows the left eye of a patient who used thioridazine for 14 years. Large patches of geographic atrophy are present.

The fluorescein angiogram of the same patient reveals prominent patches of hypofluorescence corresponding to the atrophy of the retinal pigment epithelium and choriocapillaris.

SELECTED REFERENCES

Aminoglycoside Toxicity

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Iron Toxicity

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Phenothiazine Toxicity

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