Photomicrographs of well-biointegrated AlphaCor explanted due to penetrating injury. Top left: overview. Top right and bottom: left side of the section, showing the cellular elements within the peripheral skirt of the device. Masson’s trichrome stain, original magnification X20, X40, X100 and X200 (Published with permission of Liliana Werner, MD, PhD, John A. Moran Eye Center, University of Utah)
AlphaCor is the result of many years of laboratory and preclinical research, and during this period, a large quantity of experimental data and in vitro outcomes were published in peer-reviewed journals [5–14]. Researches from the Lions Eye Institute (LEI) of Western Australia led by Traian Chirila started an intensive work on the “ideal model” of keratoprosthesis (KPro) in 1989. They have focused mainly on the investigation and optimisation of the physiochemical quantities of PHEMA, the material selected for KPro. This material was chosen because it is hydrophilic and therefore permits penetration of biological fluids from the host tissue in order to facilitate biocolonisation. The physical properties of PHEMA can be altered through polymerisation of 2-hydroxyethyl methacrylate in variable concentrations of water, with different concentrations of redox initiators and cross-linking agents. A two-phase combination of PHEMA opaque sponge with chemically identical transparent homogenous PHEMA was developed. This precisely fulfilled the requirements for an IPN. A homogenous IPN produces a stronger union between the skirt and the transparent core. Having proposed PHEMA for KPro fabrication, experiments were carried out to confirm the suitability of PHEMA sponges for corneal biointegration. In vivo studies involving implantation of PHEMA sponge a gel specimens were carried out to study cellular biocolonisation, collagen deposition, inflammation and enzymatic responses and to determine the optimum pore size with respect to cellular invasion and proliferation. The results of many studies indicated that those samples were well tolerated, without encapsulation, and that the proportion of nonviable cells decreased over time, suggesting that the sponge is an environment conducive to cellular biocolonisation. Another aspect of interest was the enzyme response of host tissue after KPro implantation. A study was performed to assess and identify collagenase enzymes including matrix metalloprotease-1 (MMP-1), produced in response to PHEMA sponge implantation, and to suggest the most effective topical medication to reduce collagenase activity. Medroxyprogesterone was found to reduce activity of gelatinase and collagenase both in vitro and in vivo and to be less cytotoxic than several of the alternative drugs tested. Animal studies were also carried out to establish the most appropriate methods of implantation. Implantation in an intralamellar pocket was found to give more satisfactory results than full-thickness implantation. A two-stage version of the lamellar-pocket technique is now the approach recommended for AlphaCor implantation as described fully in Part III.
24.2 Patient Selection: Indications and Contraindications
AlphaCor artificial cornea was designed to address the need for an alternative to donor tissue and to avoid the classic trial of sight-threatening KPro complications – progressive glaucoma, endophthalmitis and retinal detachment. It was intended to avoid reliance on donor tissue for its implantation while providing for reversibility to PK in the event of complications to minimise long-term risk to the eye. The appropriate selection of patients for AlphaCor surgery is crucial for success. There should be severe, debilitating corneal disease causing blindness, with a poor chance of success from primary or repeated donor PK. Factors that indicate that a conventional corneal graft would be likely to fail are well identified. Among the most significant risk factors for donor grafts are prior, especially multiple, corneal graft failure and deep vascularisation of the cornea in several quadrants. AlphaCor performs best in a reasonable normal ocular environment. This includes eyelid health, a good tear film and an absence of active inflammation. Patients with severely dry, disordered or inflamed eyes should not receive an AlphaCor.
Blindness in the 20/200 – light projection range in the eye to be operated upon – is an indicator for AlphaCor surgery. The patient’s fellow eye vision is an important factor to consider, and many patients will not be sufficiently motivated to undergo surgery on a blind eye with functional fellow eye. Each case requires individual assessment, but according to our experience, based upon complication rates and visual outcomes, we recommend implantation of this device in bilateral blindness.
Glaucoma patients should have normal intraocular pressure prior to AlphaCor surgery. Patients with drainage tubes are not excluded. Evidence of functioning retina by light perception and ultrasound examination to exclude detachment are recommended. The patients should be informed of any factors that might limit their final visual acuity.
The most recent previous donor corneal graft, if any, should have been performed at least 12 months prior to planned AlphaCor surgery, as an incompletely healed graft wound makes lamellar dissection of the cornea difficult.
There are several factors suggesting that the patient would be at increased risk of complications: poor tear film, evidence of meibomianitis and/or anterior blepharitis, history of collagen vascular disease, conjunctival scarring and recurrent inflammatory condition, such as anterior uveitis. The patient’s condition should be optimised prior to AlphaCor surgery.
Children or patients unable to provide informed consent or comply with postoperative instructions should not receive the AlphaCor. It is essential that any AlphaCor recipient be able to self-examine the appearance of the eye and administer medication or have close contact with social supports. It should be noted that excessive exposure to cigarette or environmental smoke even in a non-smoker might cause pigmented deposition in the AlphaCor optic that reduces vision significantly. Those unable to tolerate a general anaesthetic lasting 1–2 h are also not good candidates for AlphaCor implantation.
Generally, three broad classes of potential AlphaCor recipient could be identified: (1) those with poor prognosis from donor PK but with good prognosis for AlphaCor implantation; (2) those with a poor prognosis from donor PK and also a relatively poor or uncertain prognosis, in terms of final vision, with artificial cornea, due to previous glaucomatous damage or macular disease, but with a good prognosis for an anatomically satisfactory outcome without significant complications; and (3) those with a greater risk of significant complications not only affecting the final vision but also reducing the chance of successful long-term device retention. However, those categories are not strictly divided, and the indications have been evolving with experience. A history of herpes simplex virus (HSV) infection was previously considered as an exclusion factor for AlphaCor surgery, but new data proved that HSV is not a risk factor for melts [2, 15]. Ocular cicatricial pemphigoid is considered as a relative contraindication for AlphaCor implantation (category 3), but in our series the patient with OCP has reached very good long-term outcomes with optimisation of patient’s condition prior to AlphaCor surgery (repeated electrolysis of trichiasis and fornix and lid reconstruction surgery).
24.3 Surgical Techniques
There are two stages to device implantation, separated by at least 3 months. In the first, a corneal lamellar pocket is created with a central opening in the posterior lamella, the device is positioned with its optic centred over the trephination, and the access wound is closed. In the stage II surgery, tissue anterior to the optic is removed to expose the device as a full-thickness corneal replacement centrally, while its skirt remains integrated within the stromal pocket.
Stage I surgery is performed under general anaesthesia. A Gunderson conjunctival flap is created at the beginning of the surgery if required. A half-thickness incision in the sclera 0.5–1 mm posterior (peripheral) to the superior limbus is done and extends around the superior 180°. A guarded keratotomy blade is recommended. Set at 350 μm or as individually appropriate. Consideration should be given to preoperative UBM or Pentacam to assess scleral thickness and prevent inadvertent perforation. Then the incision is extended using an angled lamellar dissection blade to form a flap of the superior half of the cornea at 50 % depth, taking care not to perforate the lamellae (which may require suturing if perforated), especially in the vicinity of scar tissue. This flap is reflected inferiorly. A lamellar pocket is created within the corneae that is open to the limbus through its superior 180°. It is necessary to check that the AlphaCor fits this pocket and is well centred upon the visual axis. The anterior lamella is retracted inferiorly by gentle traction, holding it by pushing with a sponge wick, while trephination of a 3–3.5 mm hole through the posterior lamella using a sharp trephine is performed (a disposable skin biopsy punch is recommended). A small amount of viscoelastic may be introduced if required and is advisable in phakic eyes. If phakic with a clear lens or pseudophakic with a satisfactory intraocular lens, the lens should be left untouched and the standard AlphaCor-P should be used. If aphakic, an anterior vitrectomy can be performed through the opening in the posterior lamella. A higher-power “aphakic” AlphaCor-A should be selected. If a cataractous lens requires removal (and corneal scarring made a separate phacoemulsification procedure prior to AlphaCor implantation impossible), a modified extracapsular technique is suggested: capsulorhexis, hydrodissection, nucleus expression, irrigation/aspiration and intraocular lens (IOL) insertion can be performed via the central posterior lamella opening. The AlphaCor is picked up gently using the special forceps with curved blades ending in blunt flat holding plates without teeth, notches or grooves. The AlphaCor must be kept wet. If it is dried or heated, it warps and flattens and permanent damage to the pore structure could result. It is also crucial not to compress the sponge, because the sponge that has been squeezed does not recover its normal pore structure. Ideally, once positioned within the corneal bed, the AlphaCor should be nudged into position rather than repeatedly picked up, lifted, twisted or turned. The AlphaCor is placed within the lamellar pocket so that its optic overlies the opening in the posterior lamella. The anterior lamella is left intact and returned to normal position, and the limbal wound is sutured with interrupted 10/0 nylon stitches so as to prevent aqueous leakage and to restore a deep anterior chamber. When the wound is nearly closed, the viscoelastic, if used, is removed by flushing it out and reforming the anterior chamber. The conjunctival flap, if created at the beginning of the surgery, is drawn over the corneal surface and secured inferiorly with 8/0 Vicryl. At the end of the surgery, subconjunctival injections of steroid and antibiotic are recommended.
There are some modifications of standard surgical technique, e.g. “within the graft” technique. Advantages of this technique are limited incision length, avoidance of limbal area (blebs), good exposure for trephination and good centration of AlphaCor. On the contrary, there is increased risk for poor biointegration.
The second stage of the surgery is performed at least 12 weeks after stage I; it can be postponed or abandoned if the biointegration is not sufficient or thinning of the anterior lamella occurred. For this procedure, topical anaesthesia is generally sufficient. The anterior tissue is opened using a 3.0–3.5 mm skin biopsy punch. Care must be taken not to damage the device optic, so corneal scissors or blade is sometimes more safe for preparation. Reopening of the anterior lamella may be required if the size of the opening diminished. Some patients may demonstrate expansion of the opening in the anterior tissues rather than constriction and close follow-up during the early period after stage II surgery is therefore important. Any actual exposure of the AlphaCor skirt to the tear film is a potentially serious problem requiring urgent repair preferably with donor corneal or scleral tissue.