Commentary: Clinical profile, demographic distribution, and outcomes of ocular siderosis: Electronic medical record-driven big data analytics from an eye care network in India

Field: Medicine (Health Sciences)

First described in 1890 by Bunge, ocular siderosis (OS) occurs due to a retained ferrous intraocular foreign body (IOFB) that causes iron deposition in the ocular tissues.[1] OS may develop from 18 days to years after a penetrating ocular trauma. Common causes are profession involving hammering, chiseling, lathe turning, electric welding, and so on.[1,2] OS may be a "direct siderosis" with tissue alterations occurring close to an IOFB or an "indirect siderosis" where the OS features develop away from the IOFB location. OS in an eye with ferrous IOFB is caused by the interaction between trivalent iron ions and proteins. Iron deposition causes hydroxyl radical formation. The pathomechanism of metallic-induced damage to cells and tissues of the eye consists in the deposition of ferritin complexes in the cellular cytoplasm, especially in the form of siderosomes and possibly an increased oxidative stress combined with excessive glutamate release. This causes an increased calcium influx which damages photoreceptors and the retinal pigment epithelium (RPE). Also, iron damages the retinal vessels with consequent inner retinal layer degeneration.[2,3] Excess free iron interferes with cellular enzymatic activity, causing lysosome breakdown. Consequently, pyknosis and degeneration of photoreceptors and RPE ensues. Rods are more susceptible to iron toxicity than cones due to different protective systems against oxidative and retinopathic factors.[3,4] Ferrous ions migrate across the vitreous in a posterior–anterior way to the aqueous. Then, they penetrate the deep cornea layers and trabecular meshwork, which allows them to reach the suprachoroidal space and diffuse to the choroid and Bruch's membrane until reaching the RPE posteriorly. Chronologically, three phases characterize OS development. First, a latent period following injury without manifested clinical signs, which is variable from a few weeks to some years. Then, iron spreads within the intraocular tissues with a high affinity for epithelial cells. Finally, tissue degeneration occurs, particularly in the retina and RPE.[1] The development of OS and its different manifestations and severity depend on several factors such as IOFB dimension, shape, and composition.[1] Clinically, the common signs are iris heterochromia, pupillary mydriasis, cataract development, and retinal arteriolar narrowing with pigmentary retinal degeneration.[5] The pupil can be dilated and nonreactive to light. This phenomenon is named "iron mydriasis," and it is a parasympathetic neuropathy due to iron precipitation in the sphincter and iris dilator muscle.[6] Glaucoma may be the presenting feature of eyes with OS. It is due to either iron deposits in the trabecular meshwork or the production of albuminous aqueous by the ciliary body, which increases the intraocular pressure. In late stages, trabecular fibrosclerosis can develop. Glaucoma in OS is usually medically uncontrollable and may require surgery.[2] OS can manifest as uveitis. It can also cause retinal arteriolar narrowing and sheathing with pigmentary retinal degeneration, similar to retinitis pigmentosa. Further, OS is known to present as optic neuritis and optic disk edema. A careful history and detailed ophthalmic examination can give a clue to a case of OS. Multiple imaging modalities, such as orbital computed tomography (CT), ultrasonography, ultrasound biomicroscopy (UBM), and even optical coherence tomography (OCT), may help in detection of ferrous IOFB. Orbital CT without contrast is the gold standard to identify ferrous IOFBs, as it provides information about its localization (intraocular, extraocular, or retroocular) and its size, with a very high sensitivity.[7] Sagittal and coronal thin (1.0–1.5 mm) scans through the orbit are ideal for detection. Magnetic resonance imaging (MRI) is contraindicated if metallic/iron IOFB is suspected, and its use for diagnosis should be reserved for very select cases only.[7] B-scan is a dynamic examination providing real-time, two-dimensional images of the ocular and adjacent tissues with a high resolution (0.1–0.01 mm). However, B-scan tends to overestimate IOFB size, so it should not be used for measuring purposes. B-scan is also useful in identifying associated tissue injuries such as choroidal and vitreous hemorrhages or retinal detachment.[8,9] UBM has an increased sensitivity to identify IOFBs located in the anterior chamber.[8,9] It can detect anteriorly located IOFBs, for example, in the angle or near the ciliary body, ciliary processes, and retrolental space.[9] Electroretinography (ERG) is the gold standard to detect and follow-up retinal toxicity secondary to OS. When an iron IOFB has not been found during ophthalmological evaluation, an ERG can provide with a clue to the diagnosis of OS. Full-field ERG (ffERG) is the gold standard for assessing retinal damage by iron IOFB, as it can detect functional abnormalities of the retina before any pathological changes are visible by fundus examination or fluorescein angiography.[10] Early-phase ffERG shows an increased a-wave (hypernormal) or an increased implicit time, indicative of subtle retinal toxicity.[11] Gradually, the b-wave decreases with a reduction in the b-wave/a-wave ratio (b/a ratio). Finally, in advanced cases of OS, the amplitudes of the a-wave and b-wave progressively decrease to become undetectable.[11] Oscillatory potential amplitude reduction on ERG is another early finding in OS. Following successful ferrous IOFB removal, ERG amplitudes may increase, demonstrating that iron toxicity is reversible, especially in the early period of the disease.[12] ffERG is also useful for follow-up of patients in whom surgery for removal of the ferrous IOFB is not possible. Recently, multifocal electroretinography (mfERG) has been noted to reveal subtle electrophysiological retinal dysfunction in eyes affected by OS, even before ffERG.[10] Definitive treatment of OS and its prevention lie in the removal of ferrous IOFB. The route and ability to remove it often depend on the location. Anterior segment IOFBs can be removed with intraocular magnet (IOM) or forceps through the limbus. As regards to posterior segment IOFB, pars plana vitrectomy has to be performed, followed by removing the IOFB with IOM or forceps through an enlarged sclerotomy or the limbus.[10,13] The present study[14] described the epidemiology, clinical presentation, and outcome of siderosis in 58 Indian eyes. Because of the large number of eyes with siderosis in the present study, it contributes significantly to our information and understanding about OS in India.