BLOG: Why does amiodarone-induced keratopathy have a whorl shape?

Did you ever wonder why the “vortex” pattern in amiodarone-induced keratopathy looks like the “whorl” pattern in Fabry’s disease? Or what the heck verticillata means? (it’s an adjective describing something with a whorl-like pattern).

If you ask me, we need a whole new term for this condition, because Google image searches of “whorl” or “vortex” yield results that look nothing like amiodarone-induced keratopathy. Not that I have a better name for the characteristic keratopathy. Starburst keratopathy? Supernova keratopathy? Email me your ideas and we can get started changing this name.

I thought for this month we would focus on this interestingly patterned keratopathy and get to the bottom of why it gets its shape.

Vortex keratopathies are an epithelial problem, so we should start by reviewing the epithelial anatomy. The epithelium is only about 10% of the cornea thickness and comprises three types of cells: superficial, wing and columnar basal. The basal cells are adherent to the epithelial basement membrane, which is adjacent to (but separate from) Bowman’s layer. (It was once thought that Bowman’s was the basement membrane for the epithelium, but now we recognize Bowman’s simply as a layer and not a basement membrane at all. Its role is unclear, but perhaps thought to provide some protection to the non-regenerating stroma.)

The basal cells are the only cells that proliferate and undergo mitosis; we get wing cells and superficial cells from a process known as differentiation. This differentiation can be thought of as the original cell changing shape. The columnar basal cells are very cuboid, and wing cells are slightly squished in appearance, resembling a wing. As the cells differentiate, they become flatter and migrate anteriorly. The superficial cells are anterior to the wing cells and are quite stratified and squamous. The entire differentiation process from basal to superficial cell takes about 7 to 14 days, after which the superficial cells are shed off into the tear film.

As the epithelial cells differentiate, they migrate, and this helps answer our original question of vortex keratopathy. It’s known that in epithelial defects, unaffected epithelial cells migrate to the defect and help cover the wound. And those cells primarily come from limbal corneal epithelium. In fact, limbal epithelium exhibits a higher proliferative activity and a lower differentiation capability than the central cornea. It’s been found that the superior limbus is responsible for the most epithelialization, followed by the inferior limbus and, finally, the limbus on either side.

Written in another way: Epithelialization occurs first from above downward, then from below upward and, last, from the horizontal meridians. If you think about where the epicenter of vortex keratopathy is, then this begins to make sense. It’s most often inferior because the superior cells start their migration first. And it’s most often horizontally central (equidistant from the nasal and temporal limbus) because those cells start their migration simultaneously.

A very similar vortex pattern occurs in the final stages of healing after a complete loss of corneal epithelium. The epithelium is thought to move in sheets, and as the sheets of new epithelium come together to cover the stromal bed, they should meet in the same area as in vortex keratopathy, often coming together in one horizontal line (or a squished “Y”). I used to think of vortex keratopathy as a process that starts off in the inferocentral cornea and explodes outward (because it looks like an explosion to me), but, really, the process is ending there.

The last characteristic of the vortex shape to address is the strange lines emanating toward that central horizontal line. Several studies have found that cells migrate toward the central cornea in a centripetal (thought of as “center-seeking”) manner. So, the force of the migration vector is always pointing toward the center, and when tangential forces act on the cells to swing the migration one way, the centripetal vector forces it back on a path toward the center. The more tangential forces on the migration path (which can happen for lots of reasons), the more waves in the keratopathy lines as they progress to the center.

Incidentally, the most common use of the word “whorl” is to describe a pattern on fingerprints. The skin is a nice analogy to the cornea, with deep middle, and superficial layers. But the reason we have whorls on our fingerprints is much different than the reason we have whorls on our corneas.

Vortex keratopathies are interesting and kind of beautiful. But nature’s beauty is always explained by science, and if we stop to think about the reason for what we’re seeing, then we can start to understand the science behind the nature.

References:

Dua HS, et al. Br J Ophthalmol. 1994;78:401-408; doi:10.1136/bjo.78.5.401.

Krachmer JH, et al. Cornea. 3rd ed. New York, NY:Mosby Elsevier; 2011.

Roussel T, et al. Australian J Ophthalmol. 1984; 12: 301-316; doi: 10.1111/j.1442-9071.1984.tb01174.x.