When pondering the unknown, the “far side of the moon” is often used as a metaphor. Just as that mysterious region has not been fully explored or its significance understood, two recent cornea-related publications highlight unknowns in the ophthalmic arena that warrant further attention. Oftentimes when we read something new in the literature, we wonder whether it will ever have relevance or clinical significance. Corneal structure and a unique response to a topical agent are two recent publications of interest examined this month.^1-3

The Sixth Layer of the Cornea
The cornea remains a truly remarkable structure that typically functions efficiently by “eating aqueous and breathing air.” Recently a “new” component of the cornea has been identified and described histologically by Dr. H. S. Dua and his lab associates at the University of Nottingham in the UK.^1,2 It’s called Dua’s layer—named for the man who identified it. The acellular “layer” that Dua describes lies between the stroma and Descemet’s membrane, and appears to be quite strong.

Of particular note, the layer has a distinctly different set of physical and mechanical properties than the anterior stroma.³ Dua’s layer might have significance by providing a better understanding of posterior corneal disease and surgical biomechanics in lamellar procedures.²

The report is an interesting read, but not without controversy. In fact, Dua’s layer may not actually be a new, sixth layer to the cornea, but simply a region of the posterior stroma described adequately by Binder et al. over two decades ago. Its overall relevance may also be debated, since we have known for quite some time that the posterior area of the stroma differs from the anterior region.

A literature review finds that Binder and coworkers described an attachment of the posterior stroma to Descemet’s membrane by fibers that run perpendicular to the membrane. The attachment was associated with a dense, amorphous mass at the interface between Descemet’s and the posterior stroma, and was found to be about 22 microns in diameter.⁴ It appears that this description has an uncanny similarity to Dua’s recent description.

ROCK Inhibitors for Fuchs’ Dystrophy
Looking a bit deeper into the cornea, a prodigious research group in Japan (Koizumi N, Okumura N, Ueno M, et al.) has reported a case of Fuchs’ corneal dystrophy that was successfully treated by Rho-associated kinase inhibitor (ROCK) topical medication. The investigators revealed relatively small endothelial cells on confocal microscopy present at high cell density in the central cornea where endothelial cells had been removed by transcorneal freezing techniques.⁵ ROCK inhibitors are protein serine/threonine kinases best characterized as downstream effectors.⁵ The pathway is involved in regulating the cytoskeleton and influences cell migration, apoptosis and cell proliferation.⁶

A potential option for medical management has broad clinical implications. The case report highlights the possibility of topical therapy as a viable alternative to surgery. The ROCK inhibitor Y-27632 promotes the proliferation of primate corneal endothelial cells in vitro, and healing of cells in vivo.⁵ A pharmacological approach to endothelial recovery is certainly an attractive alternative to lamellar surgery.

It will require some time to determine the real significance of the two recent publications described above. Is Dua’s layer different than what Binder described a few decades ago, and will it provide unique benefits in the treatment of our patients with posterior corneal disease, or who might require deep lamellar surgery? And what are the actual benefits of topical Rho-associated kinase inhibitors for endothelial corneal disease? Will it alter the way we manage patients with Fuchs’ dystrophy?

The scientific community welcomes new observations and innovations to help clinicians practice better and to generate new ideas for researchers. What is unknown is the significance of Dua’s layer and ROCK inhibitors. Stay tuned, for these two topic areas may have potential significance within our own orbit.

1. Dua HS, Faraj LA, Said DG, et al. Human corneal anatomy redefined: a novel pre-Descemet’s layer (Dua’s layer). Ophthalmology 2013; published on-line May, 2013.
2. New Layer of the Cornea Discovered, Cataract & Refractive Surgery News. Vol. 13, No.7, July, 2013.
3. Peeling back the layers. Ophthalmology Times, 2013; 38(13).
4. Binder PS, Rock ME, Schmidt KC, et al. High-voltage electron microscopy of normal human cornea. IOVS. 1991; 32:2234-2243.
5. Koizumi, N, Okumura, N, Ueno M, et al. Rho-associated kinase inhibitor eye drop treatment as a possible medical treatment for Fuchs corneal dystrophy. Cornea. 2013; 32(8): 1167-1170.
6. Hall A. Rho GTPases and the actin cytoskeleton. Science 1998; 279:509-514.