David D. Verdier MD

OVERLOOKED complications following penetrating keratoplasty (PK) can have devastating consequences, US ophthalmologist David D. Verdier MD reminded a gathering of cornea specialists.

He presented a comprehensive overview of the many complications which threaten corneal graft success and began by addressing the issue of epithelial surface problems.

“We tend to focus on endothelial abnormalities but this is as important. It is absolutely critical to get the cornea re-epithelialised within the first few weeks, otherwise it ends up forming a scar,” he said.
The nature of the problem may be neurotrophic, caused by a dry eye, or exposure. He said he now asks all his patients to apply ointment to their eye several times a day during the first two months after surgery.

While the patients don’t especially like it, the essential goal is to get their corneas re- epithelialised as soon as possible. He also uses non-preserved drops and gels. In more reluctant cases, punctual occlusion and even tarsorraphy are indicated.

“The take-home message is ‘be more aggressive’. Tarsorraphy is always reversible and you can also do partial tarsorraphies, but you need to treat this problem aggressively,” he stressed.
Stem cell deficiency is also a source of epithelial surface problems. The importance of these cases is that, if this were the problem, it would also re-occur in the re-graft and in as many re-grafts as you perform. The treatment in these cases has to be stem cell transplantation, he said.

Dr Verdier put the success of corneal transplants in the context of other organ transplants. The data presented in the table comes from an article published in the British Journal of Ophthalmology in 2000 and was obtained from the British and the Australian transplantation registries. “We are only doing as well as kidneys and not so much better than heart transplants. The higher-risk corneal transplants actually did worse than any of the other transplants. “There is a lot of room for improvement; by being available to your patients as much as possible and reacting promptly, you can minimise the detrimental effect of any complication,” he said.

Endothelial complications are a major problem of corneal transplants. Primary failure, rejection and chronic cell loss due to late endothelial failure are its three main causes. Fortunately, primary graft failure is now much less common than it used to be, mainly due to great improvements in eye banks and corneal preservation.

“However, rejection does still occur. From a quarter to a third of our patients end up with rejection. Fortunately, we can now treat those assertively and most cases can be successfully reversed,” Dr Verdier said.
For very high-risk patients, treatment may include cyclosporine (topical and systemic), tacrolimus (FK-506, Prograft), and mycophenolate mofetil (Cellcept).
Dr Verdier also advised to be aware that rejection is more likely to occur after the initial three months postoperatively and that it may happen at any time. Sometimes it occurs many years after the transplant operation.

“I also have a suspicion, backed only by circumstantial evidence, that flu vaccines provoke some immunological alterations which lead to rejection. I tell my patients not to get flu vaccines unless they have some very strong indication for it,” he explained.

If the patient takes the vaccine, he increases the steroid treatment for at least a couple of months around the vaccine injection.
Dr Verdier commented that late endothelial failure was a bigger problem than he had ever guessed until very recently.
It leads to gradual graft de-compensation, is unresponsive to steroids and appears in the absence of signs of recent rejection.

It seems to be caused by an accelerated rate of cell destruction which is not linked to rejection. According to Dr Verdier this accounts for over 90% of failures beyond five years post-PK.
“You wonder what would happen in a few years time. Now that we are being successful in transplanting many more corneas, some patients are going to survive for a long time after their operations,” he noted.
Refractive problems also occur. Lack of stability and anisometropia are not uncommon but irregular astigmatism is perhaps the biggest problem. Sometimes it is related to the sutures and improves after some or all sutures have been removed.

“I am very excited about deep lamellar endothelial keratoplasty as a way of getting around some of these refractive problems. I don’t know if it is going to end up being the solution or the best way of going around this but it is the first new thing in this area for a long time,” Dr Verdier said.
Glaucoma can also be a complication after PK and, according to Dr Verdier, it has an incidence of 25%. The rise in intraocular pressure (IOP) leads to endothelial cell loss and, in his view, tube shunts inserted to treat glaucoma also lead to endothelial cell loss.
Ruptured globe due to trauma has an incidence of 1% to 2% following PK. There are not too many papers dealing with this subject but some of the more recent ones give an even higher percentage than 2%.
Patients who suffer a globe rupture after a transplant present such a devastating injury that they often lose their vision.

Wound problems are generally related to the sutures. He advised that if a patient presents with a loose suture, even just a mildly eroded one, it should be removed promptly.
For early leaks from the wound, Dr Verdier proposed close observation and aqueous suppressants. Re-suturing may be required for persistent leaks. For late leaks, he advised looking for epithelial down-growth.
Infections can also complicate a transplanted cornea. The most common microorganisms are staphylococcus, streptococcus and Gram-negative bacteria. These are often resistant to standard therapy and sometimes an infection contains multiple microorganisms.

“Consider that if your patients are immunosuppressed or taking topical steroids, they are more susceptible to fungal infection and crystalline keratopathy.

“I use acyclovir 400 mg twice a day in patients with recurrent herpes simplex virus and keep them on it for years. Results are very good while medication is continued. As soon as you stop the acyclovir, you get the same recurrence levels as before,” he said.
When amoebic infection is present he suggested that appropriate medical treatment be continued for at least six to 12 months postoperatively.