Introduction:
Side effects of medicines are widespread complications. Some medications may cause ocular complications like iris hyperpigmentation (excessive pigmentation in the iris) and eyelash trichomegaly (increased length and curing of the eyelashes). But some medications may lead to severe complications like corneal dystrophy or accumulation of materials in the cornea. Not only drugs but also metabolic substances, disease byproducts may accumulate and form a whorl-like pattern of golden brown or gray opacities in the corneal epithelium (mono layers of the posterior corneal surface). Peripheral vortical dystrophy is an accumulation of drug substances in the periphery, leading to vortex-shaped pigmentation. These conditions are associated with genetic abnormalities and the use of certain medications. Peripheral vortical dystrophy may also be called vortex keratopathy, whorl keratopathy, or Fleischer vortex.
Normally, these pigmented conditions are asymptomatic, but identifying and diagnosing these conditions are important to identify the underlying pathology.
What Are the Causative Factors of Peripheral Vortical Dystrophy?
The causative factors associated with peripheral vortical dystrophies are:
1. Drugs:
Different drugs are responsible for corneal toxicity and pigmented depositions. These drugs are:
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Amiodarone: This is the most common drug associated with this condition. The potassium channel blocker is used as an antiarrhythmic medication.
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Aminoquinolines: These are anti-malarial drugs. Chloroquine, Mepacrine, and Hydroxychloroquine come under this drug group and may cause drug-induced corneal deposits.
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Chlorpromazine: These antipsychotic drugs lead to vortex-like corneal deposits in the long term.
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Antibiotics: Antibiotics like Rifabutin, Clarithromycin, and Fluoroquinolone may cause this.
2. Lysosomal Storage Disorders:
- Fabry Disease and Cystinosis: Fabry disease is an X-linked rare inherited metabolic disorder. Deficient activity of α-galactosidase-A leads to disruption in glycosphingolipid metabolism. Defective transport of the cystine by the cystinosis protein leads to cystinosis. This causes lysosomal accumulation of cystine crystals in different body tissues like the cornea, conjunctiva, and iris.
3. Superficial Corneal Dystrophy:
These diseases mainly affect the corneal epithelium, its basement membrane or bowman layer, and the superficial corneal stroma (a layer made of collagen and stroma).
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Meesmann Dystrophy (MECD): In this condition, tiny bubble-like round-oval opacities develop due to intraepithelial cysts (within the layers of cells). This condition develops during infancy and remains asymptomatic until about middle age. It is caused by mutation of KRT3 or KRT12 genes.
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Lisch Epithelial Corneal Dystrophy: In this condition, tiny microcysts are arranged in a band or whorled pattern. This condition is generally seen in older individuals, and the gene responsible for this condition is mapped in the x-chromosome.
4. Corneal Stromal Dystrophy:
In this stroma, the cornea is affected.
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Granular Corneal Dystrophy Type 1: Multiple white irregularly shaped spots like snowflakes can be seen beneath the Bowman zone. This is also known as granular corneal dystrophy, an autosomal dominant disorder. This is caused by the mutation in the TGFBI gene mapped to chromosome 5q31.1.
What Are the Symptoms of Peripheral Vortical Dystrophies?
The clinical presentation of these conditions depends on causative factors. As different factors are involved in these conditions, disease presentation, prognosis, and severity differ from case to case.
1. Drugs:
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Amiodarone: Brown and gold deposits are present bilaterally in the inferior papillary margin areas. Deposits are mainly present in the epithelium anterior to the Bowman layer. These conditions are mainly asymptomatic, but sometimes patients complain of decreased visual acuity.
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Chlorpromazine: Brownish white opacities radiating from the optic axis are present. Lenticular changes are present, along with corneal changes. But unlike corneal changes, lenticular (about the lens) changes are not reversible. Long-standing cases may lead to anterior subcapsular cataracts (cataract formation at the back of the lens), corneal edema (accumulation of fluids in the cornea), and pigmentary retinopathy (a group of degenerative disorders of the retina).
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Antibiotics: In the case of Rifabutin, corneal deposits appear after eighteen months of treatment due to a disruption in lipid metabolism. These deposits are located in the deep corneal stroma and can be visible in confocal microscopy. Clarithromycin causes blurring of vision associated with corneal pigmentation. About 18 percent of patients taking Fluoroquinolone develop corneal deposition. But this type of deposit is resolved after the drug has ceased.
2. Fabry Disease: In this condition, the opacities start as curved lines and gradually change from whorls to straight lines in the periphery. Only the subepithelial layer has been involved. No changes are seen in the endothelial layer. Lenticular wedge-shaped opacities are also present bilaterally. The color of the deposits may vary from cream color to white to golden brown.
Vascular changes are also seen in the retina. Tortuosity of the blood vessel and a corkscrew-like appearance are seen. Occlusion of the retinal artery and mild optic atrophy is also observed.
3. Cystinosis: The symptoms in children are photophobia, blepharospasm (abnormal contraction of eyelid muscles), and eye pain. In adults, mild photophobia and retinopathy can be observed along with pigmentation.
4. Meesmann Dystrophy (MECD): Tiny punctate opacities are present in both the central corneal epithelium and the peripheral cornea of both eyes. Other symptoms include ocular irritation, photophobia, transient blurred vision, and irregular astigmatism (imperfection of lens curvature).
5. Lisch Epithelial Corneal Dystrophy: Feather-shaped opacities are present in a band-shaped pattern or sometimes whorled pattern. The epithelial opacities are slowly progressive and may lead to visual deterioration.
6. Granular Corneal Dystrophy Type 1: Multiple small white, irregularly shaped spots appear beneath the Bowman zone in the superficial central cornea. These spots appear within the first decade of life and maybe evident by three years of age. With increasing age gradually, these stromal deposits extend throughout the central two-thirds of the cornea.
How to Diagnose Peripheral Vortical Dystrophy?
The diagnosis of these conditions is relatively easy; drug history, familial history, and ocular examination are sufficient to diagnose these conditions. Additional diagnostic aids are:
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Slit Lamp Test: Visualization of the eye under a low-powered microscope using the light filter.
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Spectral-Domain Optical Coherence Tomography (SD-OCT): In-depth cross-sectional analysis of the thorough optical coherence tomography tissue using a broadband-based light source.
How to Manage Peripheral Vortical Dystrophy?
In most cases, the conditions are asymptomatic.
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For drug-induced dystrophies, drugs must be discontinued.
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In severe forms of corneal dystrophy, keratoplasty (replacement of part of the cornea) can be done, and a corneal graft; (replacement of cornea with donor’s cornea) can be given.
Conclusion:
Peripheral vortical dystrophies are clinical conditions characterized by the deposition of substances in the cornea. In most cases, this phenomenon is asymptomatic, but diagnosing these conditions can lead us to underlying pathological conditions and drug toxicity.
