Corneal transplantation, or keratoplasty, replaces a damaged or diseased cornea with healthy donor tissue to restore vision. The cornea is the transparent, dome-shaped front window of the eye that focuses light. While this is a generally successful form of solid organ transplant, the biggest long-term risk is rejection by the recipient’s immune system. This immune response can occur months or years after surgery, threatening the clarity of the transplanted tissue and the patient’s sight.
The Immune System’s Role in Rejection
The cornea possesses a natural state of immune tolerance, often referred to as “immune privilege,” which helps protect it from the body’s defensive mechanisms. This special status is maintained by several factors, including the lack of blood vessels and the presence of immunosuppressive molecules within the eye’s internal environment. The eye self-regulates inflammation to preserve function, which is why corneal grafts survive without the high levels of systemic immunosuppression required for other organ transplants.
However, this privilege is not absolute and can be compromised by inflammation, trauma, or the growth of new blood vessels into the cornea. A rejection episode begins when the host’s immune cells recognize the donor tissue as foreign due to differing surface proteins. The main effector mechanism for rejection is a T cell-dependent response, where the recipient’s T-lymphocytes mount an attack against the donor cells.
This immune attack leads to the destruction of the donor tissue, which is most damaging when it targets the endothelial cell layer. Endothelial cells form the innermost layer of the cornea and are responsible for pumping fluid out to maintain its transparent, dehydrated state. Since these cells do not naturally regenerate, their destruction causes the graft to swell and become cloudy, leading to irreversible vision loss if not promptly treated. Endothelial rejection is the most common and severe form.
Identifying the Signs of Rejection
Recognizing the onset of rejection quickly is important, as the speed of diagnosis directly impacts the success of reversing the episode. Patients are often taught to remember the symptoms using the mnemonic RSVP. Any patient experiencing these symptoms for more than a few hours should seek urgent care from an eye specialist.
- R stands for redness (inflamed appearance of the eye).
- S represents light sensitivity (photophobia).
- V signifies decreased vision (a cloudy or foggy sensation).
- P stands for pain or discomfort (ranging from mild irritation to a severe ache).
When a doctor suspects rejection, they perform a detailed examination using a slit lamp. They look for specific clinical signs, such as keratic precipitates (KPs). KPs are deposits of inflammatory cells that adhere to the back surface of the donor cornea. Another definitive sign is the Khodadoust line, a visible line of immune cells migrating across the back of the graft. This line marks the active boundary between the clear, healthy part of the graft and the swollen, damaged area.
Prevention and Treatment Strategies
Preventing rejection requires a long-term regimen of immunosuppressive medication. The mainstay involves prescribed topical corticosteroid eye drops, such as prednisolone. Patients must maintain compliance, as the drops suppress the localized immune response and reduce inflammation. Continued medication use is often necessary, as the risk of rejection persists indefinitely. Regular follow-up appointments are necessary to monitor the graft. Avoiding trauma to the eye is also important, as physical injury can trigger an inflammatory cascade that breaks down the immune privilege.
In high-risk cases, where the eye has pre-existing conditions like significant blood vessel growth, adjunctive topical medications like cyclosporine may be used alongside steroids to provide a stronger defense.
When an acute rejection episode is confirmed, treatment must be immediate to halt the immune-mediated damage. This involves significantly increasing the frequency and strength of topical steroid drops, sometimes administering them hourly. In severe cases, the doctor may supplement the drops with systemic oral or intravenous steroids. Prompt treatment is highly effective. However, if the immune attack progresses to irreversible endothelial cell loss, the graft will become permanently cloudy. A repeat transplant may be the only option to restore vision, though subsequent grafts carry a higher risk of rejection.