Let there be sight

Loss of the stem cells that constantly renew the surface of the cornea causes pain and, in some cases, blindness. Advances in transplantation and cell culture are helping to restore vision to even the most severely affected people.

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Restoring vision

Early-stage LSCD can often be treated with topical vitamin A, corticosteroids or lubrication with artificial tears. Advanced LSCD may require surgical intervention, depending on whether one or both eyes are affected. Although there are a range of treatments, there have been no head-to-head trials, so choice of treatment is often determined by the availability of resources and individual preference.

Unilateral disease

When one eye is partially affected, it is sometimes possible to transplant a fragment from a healthy part of the eye to the affected part. When the eye is severely affected, cells can be taken from the healthy eye. In both cases, epithelium can be transplanted directly into the diseased area or used to seed a cell culture. Cell culture uses minimal limbal tissue, but requires specialized laboratory infrastructure, whereas transplantation is more technically demanding for the surgeon and carries greater risk for the healthy eye.

Bilateral disease

Donor cell transplant

When both eyes are severely affected, donor tissue can be used for a transplant, either directly or cultured. But the recipient must take immune suppressants indefinitely to reduce the risk of the body attacking the graft, and such drugs increase the risk of infection.

Oral mucosal epithelial transplantation

Over the past decade, surgeons have developed a technique that uses cells from the lining of the patient’s mouth. Cultivated oral mucosal epithelial transplantation, or COMET, benefits from a readily available source of patient tissue, avoiding the need for immunosuppression. But the quality of the transplanted epithelium is not as good as that of a limbal epithelial cell culture.

Severe disease

Corneal transplant

Severe LSCD can be treated with a transplant using a donated cornea. Although this established procedure has the advantage of introducing a new population of stem cells, recipients require prolonged, often indefinite, systemic immunosuppression.

Prosthesis

The most widely used artificial cornea (keratoprosthesis), the Boston KPro, was approved in the United States in 1992. The implant is usually reserved for patients with no other options. The prosthesis is a foreign body, so there is a risk of infection, and it is also impossible to measure the pressure inside the eye of a person with an implant. High eye pressure can cause glaucoma if left untreated.

Example of a keratoprosthesis (from left to right: front plate, corneal graft, back plate and locking ring)

Future directions

The past decade has seen rapid progress in both the number of treatments for severe LSCD and the success rates of these treatments, but there are still obstacles to overcome. Advances in the use of induced pluripotent stem cells, which can be generated from adult cells, could open the door to fully bioengineered corneas, and overcome the problems of immunological compatibility and scarcity of donor tissue that currently hamper treatment.

Source:

1. Shortt, A. J., Tuft, S. J. & Daniel, J. T. Br. Med Bull. 100, 209–225 (2011)

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Holmes, D. Let there be sight. Nature 544, S2–S3 (2017). https://doi.org/10.1038/544S2a

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