TREATING SEVERE OCULAR SURFACE DISEASE

A clear treatment protocol is emerging for treating severe ocular surface disease, with therapies ranging from amniotic membrane transplantation to the implantation of keratoprostheses, said Günther Grabner MD in a keynote lecture in a Cornea Day session at the 16th ESCRS Winter Congress.

“In most cases you can do autologous stem cell transplantation plus amniotic membrane plus, if required, penetrating keratoplasty. When there is a bilateral loss of stem cells but a wet surface, a Boston keratoprosthesis is the treatment of choice, but if the eye is dry I think nothing beats the modified osteo-odonto keratoprosthesis,†said Dr Grabner, Paracelsus Medical University, Salzburg, Austria.

Dr Grabner noted that amniotic membrane has a wide variety of uses in ocular surface reconstruction. It can be used as an “inlayâ€, as a sort of replacement basement membrane, as an “onlay†where it can serve as a bandage contact lens, and it can be placed in multiple layers as an alternative to superficial lamellar keratoplasty. There have also been reports of its use in the treatment of bullous keratopathy and neurotrophic ulcers as well as in pterygium surgery and revision of filtering blebs. Nowadays it is also widely used as a substrate for cultured limbal cells for use in limbal autograft procedures. The usual indications for such techniques are limbal stem cell deficiency resulting from burns, chemical injury, trauma or disease. The loss of limbal stem cells leads to permanent epithelial defects stromal scarring and symblepharon, Dr Grabner noted. “In cases with unilateral complete stem cell loss, amniotic transplantation is not sufficient because it will not replace the stem cells. What we need to do is in autologous limbal stem cell transplantation plus/minus penetrating keratoplasty,†he added.

The most frequently performed limbal stem cell transplant procedure is a conjunctival limbal autograft from the fellow eye. The advantage of autografts is that they entail no risk of immune rejection and, unlike limbal allografts, do not require the use of intensive long-lasting systemic immunosuppression. The main, however minimal, disadvantage is that they require surgery on the normal eye. Ex-vivo expansion of limbal stem cells on an amniotic membrane substrate can maximise the amount of limbal stem cells available for transplantation, he noted. He and his associates have initiated a study that will examine the feasibility of using buccal stem cells as an alternative in such cases.

Role of keratoprostheses

In patients with bilateral limbal stem cell insufficiency, limbal allografts from a family member or a cadaver eye are one alternative. However, such transplants again involve intensive immunosuppression and have a fairly low rate of success. As a result, corneal surgeons are increasingly turning to the use of keratoprostheses in such cases, he said. There are several designs of keratoprosthesis available but there are only two that are widely used today. They are the Boston KPro type 1, developed at the Massachusetts Eye and Ear Hospital developed by Claes Dohlman, and the osteo-odonto-keratoprosthesis (OOKP) first developed by Strampelli in the 1960s and later improved upon by Falcinelli. The decision of which type of keratoprostheses to use depends on the condition of the eye and the condition of the patient, Dr Grabner said.

The standard Boston KPro has a nut and bolt design and consists of two 0.9mm-thick PMMA plates clamped onto a donor button of corneal tissue which is sutured into the recipient's eye, he said. Its indications can include eyes with limbal stem cell insufficiency, but its use requires a wet eye with good blinking function. The OOKP uses an osteodental lamina overlaid with buccal mucous membrane as a skirt for its PMMA optic. It can also be used in eyes with limbal stem cell insufficiency and severe keratoconjunctivitis sicca, Dr Grabner said. However, owing to the difficult and time-consuming nature of its implantation, the OOKP is usually reserved for patients with bilateral corneal blindness resulting from severe end stage corneal disease, for eyes injured by chemicals or burns, and for severely dry eyes. Implantation of the Boston K-Pro type 1 is only slightly different from a standard penetrating keratoplasty, he noted. As a result, it has become the most widely used keratoprosthesis in the world, with around 1,000 implanted every year and close to 100 surgeons implanting them. One drawback with the Boston K-Pro type 1 is that it requires the patient to commit to lifelong use of topical antibiotics and bandage contact lenses, he said. Most other types of keratoprostheses have fallen into disuse, Dr Grabner noted.

For example, the AlphaCor keratoprosthesis, which has indications similar to those of the Boston K-Pro is no longer promoted by its manufacturer, possibly because of the poor retention rate some authors have reported with the implant. However, the Temprano keratoprosthesis – which uses a piece of autologous tibia bone as a skirt – remains a useful option in patients with dry eyes who have no teeth that could be used for an OOKP. Dr Grabner cautioned that implants like the OOKP put the patient at an additional risk for glaucoma. However, the risk of onset or progression of glaucoma induced in this way will be much lower when IOP is controlled from early on with a glaucoma drainage implant, he noted. “If you have a bilateral dry eye case I think nothing beats the OOKP and this is what you should advise your patient to have. You certainly need specialised centres and if you put a cosmetic shield on top of it, it is very difficult to tell which one of the eyes is the one with the keratoprosthesis,†he added.