Cornea Verticillata

Article initiated by:

Caroline Awh, Stephen C. Dryden, M.D.

All authors and contributors:

Jesse Wesberry, Victoria Chang, MD, Vatinee Y. Bunya, MD, MSCE, Stephen C. Dryden, M.D., Nambi Nallasamy, MD, Caroline Awh

Assigned editor:

Victoria Chang, MD

Review:

Assigned status Update Pending

 by Victoria Chang, MD on March 6, 2023.

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Contributing Editors:	add

Corneal Verticillata© 2023 American Academy of Ophthalmology http://www.aao.org

Disease Entity

Cornea verticillata (also called vortex keratopathy, whorl keratopathy, or Fleischer vortex) describes a whorl-like pattern of golden brown or gray opacities in the corneal epithelium. It is termed cornea verticillata from the Latin noun “verticillus,” meaning "whorl”. Usually asymptomatic, it is caused by the deposition of medications, metabolic substrates, or disease byproducts in the basal epithelial layer of the cornea.

Etiology

Cornea verticillata is most associated with amiodarone and Fabry disease.

It can also be caused by a variety of other medications, the most common of which include chloroquine and hydroxychloroquine, indomethacin, and phenothiazines. Other agents implicated in cornea verticillata include gentamicin, tamoxifen, meperidine, chlorpromazine, atovaquone, suramin, tilorone, perhexiline maleate, and the tyrosine kinase inhibitors vandetanib and osimertinib.

Other non-pharmacologic etiologies associated with corneal verticillata include:

• Multiple myeloma
• Multiple sulfatase deficiency
• Generalized gangliosidosis
• Neurotrophic keratitis
• Lisch corneal dystrophy
• Epidemic keratoconjunctivitis
• Iron deposition (i.e., after radial keratotomy)
• Stromal deposition (gold, silver, antacid, retinoid depositions)

Pathophysiology

The whorl-like pattern of cornea verticillata results from the centripetal migration of deposit-laden limbal stem cells as the corneal epithelium undergoes natural growth and repair.

The medications that produce cornea verticillata share cationic, amphiphilic properties that allow them to penetrate lysosomes in the basal epithelial layer of the cornea, where they bind to cellular lipids. These medication-lipid complexes are resistant to enzymatic degradation and accumulate as deposits in the cornea. Specifically, amiodarone inhibits lysosomal phospholipase A2 resulting in susceptibility of the inner membrane of the cell to degradation by proteases. Suramin inhibits iduronate sulfatase, resulting in accumulation of glycosaminoglycans.

Cornea verticillata is seen in 90% of patients with Fabry disease, a rare X-linked recessive lysosomal storage disorder, that is also associated with progressive nephropathy and peripheral neuropathy. However, female carriers may only present with corneal findings. Unlike that seen with medications, the cornea verticillata in Fabry disease is caused by a deficiency in alpha-galactosidase A, a lysosomal enzyme. This results in the accumulation of glycosphingolipids in lysosomes throughout body tissues, including the cornea.

Diagnosis

Symptoms

Patients with cornea verticillata typically have no visual complaints or eye discomfort. Rarely, patients may see blue-green rings in their vision or halos around lights.

Signs

Corneal verticillata is recognizable as fine golden-brown or gray opacities in the basal epithelium that branch out from a central whorl, usually across the inferior cornea. The deposits do not stain and are almost always bilateral.

Occasionally, slight differences on slit-lamp microscopy can be seen in the opacities due to medications compared to those seen in Fabry disease. Drug-related opacities may appear as horizontal lines with fine branching at the extremities, whereas Fabry disease-related opacities may appear as curving lines that form whorls before becoming almost straight at the periphery.

The etiology of drug-induced forms of cornea verticillata can typically be identified with a thorough review of the patient’s medical history and medications. If attempting to differentiate between drug-induced cornea verticillata and that caused by Fabry disease, the microstructure of the deposits can be viewed with confocal laser scanning microscopy. However, this is not a routine part of the diagnostic evaluation.

Management and Follow-up

There is no recommended treatment for cornea verticillata. The deposits are typically not visually significant, and typically resolve with cessation of the responsible agent. No alteration in medication regimen or further work-up is required for an isolated finding of cornea verticillata. Several case reports have described the resolution of cornea verticillata with the use of topical heparin.

If cornea verticillata is associated with a drug that is known to produce retinal toxicities—most notably hydroxychloroquine, chloroquine, chlorpromazine, and tamoxifen—patients should be routinely monitored with automated visual fields plus spectral-domain optical coherence tomography (SD-OCT). The presence of cornea verticillata does not correlate with retinal toxicity. The possibility of optic neuropathy should also be considered if patients taking amiodarone or tamoxifen present with reduced vision. For these patients, a reduction in dose or a switch to a different medication may be necessary.