Description of the condition

The cornea is the transparent layer of the anterior surface of the eye and functions to transmit light and provide most of the refractive power of the eye. Diseases affecting the cornea are a major cause of blindness worldwide. Globally, corneal opacity is the fourth‐leading cause of bilateral blindness after cataract, glaucoma, and age‐related macular degeneration, affecting some 4 to 8 million people, 90% of whom live in the low income countries (Murthy 2012; Whitcher 2001). Furthermore, unilateral corneal blindness, which also creates much disability, is not reflected in these statistics. Additionally, children and young adults are affected by corneal blindness proportionately more than by other major, age‐related blinding diseases such as macular degeneration and glaucoma.

There are currently no proven medical treatments available to restore clarity in diseased corneas. Surgery with donor corneal transplantation (keratoplasty) is the definitive treatment for corneal blindness. Although the majority of these transplants are successful, if the transplantation fails the first time for any reason, a repeat transplantation using an artificial or donor cornea may be considered.

Description of the intervention

Corneal transplantation is one of the most commonly performed transplant procedures in the low income countries. A total of 51,294 corneal transplantations were performed in the USA in 2018 (EBAA 2018). Successful transplantation occurs when the corneal graft is not rejected and it retains clarity and integrity. Several published studies have documented that the single most important factor affecting the success of corneal transplantation is the preoperative indication for the surgery (Thompson 2003; Wagoner 2009). Donor corneal transplantation achieves remarkable overall success rates, with approximately 90% of "low risk" patients having successful transplants (ACGR 1993; Thompson 2003; Wagoner 2009). Patients at "low risk" of corneal graft failure typically suffer vision loss from corneal shape problems (such as keratoconus) or from loss of clarity due to genetic problems of the endothelial layer of the cornea (such as Fuchs endothelial dystrophy), trauma, or infection. For example, although the five‐year survival probability is usually over 90% for keratoconus, this rate is less than 50% when the indication is corneal edema due to endothelial failure from intraocular surgery, and even lower when the eye is aphakic (without the natural lens) (ACGR 1993; Thompson 2003).

The likelihood of corneal graft survival drops markedly in the setting of previous corneal graft failure. Re‐graft (repeat donor corneal transplantation), presence of significant neovascularization of the host bed, history of glaucoma, and previous herpetic infection also decrease the likelihood of graft survival (ACGR 1993; Siganos 2010; Thompson 2003; Wagoner 2009). The overall risk of failure for re‐grafts is about 50% at five years (Ahmad 2016; Thompson 2003; Yildiz 2010); this percentage is likely an underestimate, as most surgeons tend to limit re‐grafting only to patients in whom they believe there is a reasonable chance of success for subsequent graft survival and improvement in visual acuity. Notably, re‐grafts are now the most common indication for penetrating keratoplasty (PK) in the USA, comprising 18% of all PKs (EBAA 2018).

In the USA, patients who have failed multiple corneal grafts may be offered an artificial cornea. An artificial or prosthetic cornea, known as a keratoprosthesis (KPro), is a corneal implant made of synthetic material, the most common of which is the Boston keratoprosthesis (Boston KPro). The Boston KPro is a two piece, collar‐button device made of polymethylmethacrylate (PMMA), a transparent thermoplastic, with a titanium locking ring. Although it is associated with complications including infection, extrusion, glaucoma, and retinal detachment, because it is made of artificial material it will not opacify (become cloudy). The AlphaCor device, made from poly‐2‐hydroxyethyl methacrylate, is made of a one‐piece flexible implant with a peripheral skirt and a transparent central region connected on a molecular level by an interpenetrating polymer network. It is implanted in the recipient eye via a two‐stage surgical procedure. Osteo‐odonto‐keratoprosthesis, which is reserved for individuals with severe ocular surface disorders, requires a complex, multistep surgical procedure and is therefore performed very infrequently. A lamina of the patient's tooth is grafted into the eye after having been transplanted elsewhere for biointegration and vascularization purposes. An artificial optic made of PMMA is then installed in the unit to allow vision. The Fyodorov–Zuev keratoprosthesis, commonly used in the former Soviet Union, is made of a titanium supporting plate with two large openings to allow aqueous humor to flow anteriorly. An optical cylinder is screwed into the center of the supporting plate, then the assembled device is implanted.

In general, artificial corneal implantation requires long‐term topical and sometimes oral treatment to prevent or treat complications such as infections and glaucoma. Close postoperative follow‐up is required due to risk of complications, which can sometimes lead to permanent blindness, particularly due to retinal detachment and endophthalmitis. These complication rates have been well monitored by surveillance studies (Boston Type 1 KPro Study; Hicks 2006). The rates of vision‐threatening complications and visual outcomes on the other hand are less well studied in repeat donor corneal transplantation cases. However, the rates of corneal melting and infection are certainly expected to be lower with donor transplantation than with artificial devices.

How the intervention might work

Both donor and artificial corneal transplantations involve removal of the diseased and opaque portion of the recipient cornea, and replacement with clear cornea or corneal device. The surgical procedure using an artificial cornea is similar to full thickness corneal transplantation using a donor cornea (penetrating keratoplasty, PK) once the device has been assembled.

The Boston KPro, the most commonly implanted artificial corneal device, comes in two main types (Aquavella 2005; Ilhan‐Sarac 2005; Ma 2005). Type I is the most commonly used style in the USA and consists of two plastic parts: an anterior part that houses the refractive portion, and a removable perforated back plate. The device requires donor corneal tissue to be sandwiched between the two plates. The holes in the back plate are thought to enhance nutrition and rehydration of the clamped corneal stroma adjacent to the stem, which may help to prevent necrosis of the surrounding tissue. In addition, the device has a titanium locking c‐ring to secure the unit after its assembly and prevent unscrewing of the back plate. After assembly, the whole device is then sutured into the recipient eye in the same manner as with donor corneal transplantation. A newer‐generation type I KPro with a back plate made of titanium was recently cleared by the US Food and Drug Administration (FDA) (MEEI 2019). This model does not require a locking c‐ring (Todani 2011).

The type I Boston KPro is indicated in eyes with sufficient tear secretion and normal blinking. The longer type II device is similar to type I, except for an additional 2‐millimeter‐long anterior nub for through‐the‐lid implantation. The front plate is usually 5 mm in diameter, and the back plate is 8.5 mm in diameter. The back plate also has two rows of eight holes, each 1.5 mm in diameter. The type II Boston KPro is reserved for extreme dry eye conditions and end‐stage ocular surface diseases with significant cicatricial conjunctival changes, such as mucous membrane pemphigoid and Stevens‐Johnson syndrome, in which there is a lack of fornices to support a contact lens as recommended for the type I device. Both types are custom made to have a range of dioptric powers to match the axial length of the patient’s eye when aphakic (the natural lens, if present, is removed during surgery, and no additional intraocular lens needs to be implanted).

Other artifical corneas such as AlphaCor, osteo‐odonto‐keratoprosthesis, and Fyodorov–Zuev keratoprosthesis work in the same general manner, as substitutes for donor corneas.

Why it is important to do this review

There has been a renewed interest in artificial corneal implantation following FDA approval of the AlphaCor device in 2002. Although the Boston type I device was cleared by the FDA in 1992, prior to 2004, fewer than 100 had been implanted, most of which were performed at the Massachusetts Eye and Ear Infirmary (the distributor of the device) (Zerbe 2006). This renewed interest resulted in a wealth of studies evaluating artificial corneal devices. However, due to high complication rates associated with the AlphaCor device, it has been removed from the market, leaving the artificial corneal device arena mostly to the Boston KPro. Once considered as a last resort, the Boston KPro is now a frequently viable alternative for eyes with prior failure of traditional donor PK. There has furthermore been interest in expanding indications for KPro implantation as a primary procedure in patients with limbal stem cell failure from various causes (Michael 2008; Utine 2011).

As surgeons and centers have gained more experience with keratoprosthesis, it has become apparent that artificial corneal devices may be an alternative to repeat PK in a broader subset of patients than was previously considered. It has also been suggested that artificial corneal transplant surgery is comparable to PK surgery using donor corneas in terms of cost‐effectiveness (Ament 2010). The purpose of this review was to systematically compare the clinical performance of artificial corneas with the current standard of care, transplantation with donor corneas, as the use of keratoprostheses becomes more popular for repeat corneal replacement procedures.