Corneal deposits, a frequent finding in ophthalmology, can manifest in various forms and layers of the cornea. Among these, vortex keratopathy, also known as cornea verticillata, is a distinctive whorl-like pattern observed in the corneal epithelium. This pattern is often associated with the use of certain medications, particularly cationic amphiphilic drugs. Understanding the differential diagnosis of cornea verticillata is crucial for accurate diagnosis and appropriate patient management. This article provides an overview of cornea verticillata, its causes, and a focused look at its differential diagnosis.
Epithelial deposits, presenting as vortex keratopathy, are commonly linked to drug accumulation or drug-induced disruptions in epithelial metabolism. Cationic amphiphilic drugs (CADs) are frequently implicated in this condition. These drugs, due to their chemical properties, readily enter lysosomes within the basal epithelial layer of the cornea. Once inside, they bind to cellular lipids, forming drug-lipid complexes. These complexes are resistant to enzymatic degradation, leading to their accumulation and the characteristic vortex pattern of cornea verticillata. This pattern arises due to the natural centripetal migration of corneal epithelial cells from the limbus towards the center of the cornea.
Image: Illustration depicting the differential diagnosis considerations for vortex keratopathy, emphasizing drug-induced causes and inherited conditions.
While drug-induced vortex keratopathy is the most commonly recognized cause, it is important to consider other conditions in the differential diagnosis. These include:
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Drug-Induced Vortex Keratopathy: This is the most prevalent cause, particularly associated with cationic amphiphilic drugs. Common culprits include amiodarone (an antiarrhythmic medication), chloroquine and hydroxychloroquine (antimalarials and antirheumatics), tamoxifen (an anti-estrogen medication), and indomethacin (a nonsteroidal anti-inflammatory drug). The appearance of vortex keratopathy in these cases is typically bilateral and may be reversible upon discontinuation of the offending drug, although resolution can be slow.
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Fabry’s Disease: This X-linked recessive lysosomal storage disorder is a significant systemic condition that can manifest with cornea verticillata. In Fabry’s disease, a deficiency in the enzyme alpha-galactosidase A leads to the accumulation of globotriaosylceramide (Gb3) in various tissues, including the cornea. The cornea verticillata in Fabry’s disease may appear similar to drug-induced cases but can be an early indicator of this serious multisystem disorder, which also affects the kidneys, peripheral nerves, and cardiovascular system. It’s crucial to consider Fabry’s disease, especially in male patients presenting with cornea verticillata, and to be aware that female carriers can also exhibit corneal findings.
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Other Lysosomal Storage Diseases: While Fabry’s disease is the most well-known lysosomal storage disease associated with cornea verticillata, other conditions such as multiple sulfatase deficiency and generalized gangliosidosis should also be considered, although they are rarer. These disorders involve defects in lysosomal enzyme function leading to the accumulation of various substrates and potentially corneal deposits.
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Physiological Vortex Keratopathy: In rare instances, a subtle vortex-like pattern can be observed in the cornea without any identifiable underlying cause, including drug exposure or systemic disease. This is termed physiological vortex keratopathy and is generally considered a benign finding with no clinical significance. However, it is a diagnosis of exclusion, made only after ruling out other potential causes.
Moving beyond the epithelium, corneal deposits can also occur in the stroma and endothelium. Stromal deposits can be caused by medications such as chlorpromazine, gold salts, rifabutin, indomethacin, and tyrosine kinase inhibitors (TKIs) like vandetanib. These drugs reach the stroma via the aqueous humor, limbal vasculature, and tear film. Stromal deposits can present with various appearances, including pigmented, crystalline, or refractile opacities. For example, antipsychotic phenothiazines, particularly chlorpromazine, can cause dose-related, light-induced stromal deposits. Clofazimine, used to treat leprosy, can lead to crystalline deposits in the anterior corneal stroma. Isotretinoin, an acne medication, has also been associated with superficial stromal opacities.
Endothelial deposits, while less common than epithelial or stromal deposits, can be induced by drugs like chlorpromazine and rifabutin. Endothelial deposits are best visualized using retroillumination. Chlorpromazine can cause diffuse granular white-grey opacities across the corneal endothelium, while rifabutin deposits are described as stellate and refractile, starting peripherally and potentially extending centrally.
In conclusion, while cornea verticillata is frequently associated with drug use, particularly cationic amphiphilic drugs, a comprehensive differential diagnosis is essential. It is crucial to consider Fabry’s disease and other lysosomal storage disorders, especially in the absence of a clear drug history or in cases with atypical presentations. A thorough patient history, including medication use and family history, combined with a detailed ophthalmic examination, is paramount in accurately diagnosing cornea verticillata and differentiating it from other conditions, ensuring appropriate management and referral when necessary.
