Help for High-Risk Corneas

For patients who are not amenable to a penetrating keratoplasty with donor tissue due to a high risk of failure, there is a promising alternate option. AlphaCor (Argus Biomedical Pty Ltd, Perth, Western Australia) is a flexible, one-piece, biocompatible artificial cornea that is indicated for blindness due to corneal disease (Figure 1). The device is 7 mm in diameter and comprises a peripheral, porous sponge “skirt” and a central transparent optic of appropriate power for either phakic/pseudophakic patients (AlphaCor-P) or aphakic patients (AlphaCor-A). It is made of a hydrophilic polymer, poly (2-hydroxyethyl methacrylate) (PHEMA).

EARLY RESEARCH AND DEVELOPMENT
AlphaCor was first developed at the Lions Eye Insti-tute in Perth, Western Australia, under the name Chirila Keratoprosthesis. Along with Associate Professor Geoffrey Crawford and Professor Ian Constable, polymer chemist and Associate Professor Traian Chirila initiated research for the device in 1989 in an attempt to address the complications associated with current keratoprostheses. Because many older artificial corneal devices were reported to have problems integrating with the host cornea or with dehiscence into constituent parts, the aim of the researchers was to produce a nonrigid, one-piece device that successfully integrated with host tissue.

Since 1989, a multidisciplinary research team at the Lions Eye Institute has conducted in vitro and in vivo studies to evaluate AlphaCor's biological interactions and optimize its material quality and design. Human clinical evaluation commenced in 1998, and the device became known as AlphaCor after the technology was licensed to Argus Biomedical Pty Ltd, a majority-owned subsidiary of the Lions Eye Institute. Clinical evaluation commenced in several centers, and the device received regulatory approvals (CE Mark, FDA, TGA [Australia], and Health Canada) through 2001 and 2002. The AlphaCor device has not been evaluated in children.

IMPLANTATION CRITERIA
Preoperatively, the surgeon must fully control the patient's IOP and any inflammation, including lid disease. A candidate's cornea ideally should be of normal thickness or thicker, and any prior graft should have been performed at least 12 months previously in order to minimize the risk of difficulties during lamellar dissection. Patients must have a healthy tear film; in some patients, this may require a partial tarsorrhaphy or punctal occlusion following AlphaCor implantation.

AlphaCor is implanted in a two-stage procedure. The first stage, conducted under general anesthesia, involves creating a large intrastromal pocket with a central 3-mm trephination through the posterior lamella. The surgeon places the device within this pocket and centers it over the posterior opening before closing the anterior lamella and forming a conjunctival flap. The second stage of surgery is brief and takes place approximately 3 months later, when the surgeon opens the anterior tissues over the optic to allow light to enter the eye (Figure 2).

EARLY TRIAL RESULTS
Postoperative BCVAs have ranged from light perception to just under 20/20. Most cases have required refractive correction, and some have had large refractive errors. Most patients report that their eyes are comfortable and that they are generally unconcerned about the abnormal cosmesis. Complications found during the trial mainly included either corneal stromal melting around the device's skirt or the deposition of topical drugs or other environmental factors within the device's optic that reduced its clarity. Patients who may be at a high risk for corneal melts include those with a history of ocular herpes simplex viral infection and those in whom it is difficult to remove soft lens matter during concurrent cataract surgery. Preliminary data suggest that topical medroxyprogesterone 1% eye drops may strongly protect these individuals against corneal melting. Risk factors for optic deposition have been identified in vitro; they include tobacco smoke and some topical medications such as Betagan (Allergan, Inc., Irvine, CA), which stains the optic brown. Certain combinations of topical medications, such as beta-blockers concurrent with steroids, may also predispose patients to calcific deposition.

ONGOING ANALYSIS
Clinical data current to the end of November 2002 are limited by the small number of devices followed to date and the limited follow-up. Forty-seven devices have been implanted, with a follow-up period in situ of 1 week to 49 months and a mean period of 15.5 months. On these preliminary data, the probability of AlphaCor survival to 1 year is approximately 80%, and outcomes appear to compare favorably with those for high-risk donor grafts, although all trial patients had been considered untreatable by a donor graft due to a combination of risk factors for failure. Corneal specialists are now accredited to implant AlphaCor in many countries, and these physicians are continuing to collect outcomes data for ongoing analysis through a Web-based system.

The Alphacor device may be removed and replaced, either with another of its kind or by means of a standard donor graft if a significant complication occurs. This reversibility, the absence of a need for systemic immunosuppression, the avoidance of donor tissue (except for managing complications), and the encouraging early results, all position AlphaCor as a useful, alternate management option for some patients. As the series increases in size, the long-term outcomes data will be essential for determining the indications for the device and evaluating its performance in greater depth.

Celia R. Hicks, MD, FRCOphth, is Coordinator, Artificial Cornea Programme, Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, and Clinical Manager, Argus Biomedical Pty Ltd., Lions Eye Institute Building in Australia. She holds a minor financial interest in Argus Biomedical and is currently seconded from the Lions Eye Institute to act as Clinical Manager for Argus Biomedical. Dr. Hicks may be reached at +61 89 381 08 77; crhicks@cyllene.uwa.edu.au.