Currently there are two main types of keratoprostheses, depending on whether or not they use biological materials in addition to artificial ones. We denominate the first "keratoprostheses with biological support", since the prosthetic structure is assembled with a component of living tissue that serves as support. Fully artificial or alloplastic materials are sometimes referred to as "biocompatible".

KERATOPROSTHESES WITH BIOLOGICAL SUPPORT

Boston Keratoprosthesis (Dohlman-Doane, types I and II)

Boston keratoprosthesis, (B-Kpro), developed by Dohlman and Doane in 1960 (see chapter 8.1), includes two models that use a corneal homograft as support¹. The most common or B-Kpro type I consists of two parts: a stem of polymethyl methacrylate (PMMA) that widens in the anterior part and a plate or posterior disc. The optical zone of the stem, with 3.35 mm in diameter, allows a theoretical visual field of at least 60°. Its optical power is 43-44 diopters (D) in the standard model for pseudophakic – it is incompatible with the maintenance of the natural lens. There are others for aphakic, of customizable power according to the axial length.

The donor cornea is trephined in the central 3 mm and mounted as a sandwich between the stem and the posterior plate. The latter was originally made of PMMA and nowadays of titanium² (Figure 1), with a diameter between 8.5 and 9.5 mm and 16 holes to favor the nutrition of the cornea graft. There is a pediatric model of 7 mm and 8 holes. In the initial model, the disk was threaded on the stem; it then evolved to a snap-on insert without thread, fixed with a titanium locking ring that fits into a notch in the stem³. More recently the ring has been removed in the click-on model (Figure 2). The B-Kpro type I is currently the most used keratoprosthesis, with proven evidence of its efficacy and long-term safety^4,5.

The B-Kpro type II is reserved for cases with very advanced alterations of the ocular surface and is implanted through the upper eyelid after performing a complete tarsorrhaphy. For this, it has the longest stem, which protrudes 2 mm in front of the anterior disc (epicorneal) and finally widens again to rest on the skin of the eyelid (Figure 3)⁶.

Osteo-odonto-keratoprosthesis

Initially described by Strampelli in 1963 and later modified by himself and others (see chapter 8.1), osteo-odonto-keratoprosthesis (OOKP) is the type with the longest successful follow-up. Today it is considered the "gold standard", especially for the cases with greater severity due to dry eye associated with autoimmune diseases⁷.

It is a keratoprosthesis supported by autologous tissue. It consists of a stepped PMMA optical cylinder, 9 mm long, 4 mm in diameter in its rear portion and 0.5 mm less in the anterior one. This is inserted into a hole made in an osteo-dentary sheet obtained from the same patient. The surgery is performed at various stages (see chapter 8.3.1)⁸. First, the ocular surface is prepared with the release of the present adhesions and a full-thickness oral mucosal graft. The tooth is then extracted (usually a canine or a premolar) together with its bony socket, carved and assembled with the PMMA cylinder and then implanted in the subcutaneous tissue of the orbito-zygomatic area. It is left like this for 2 to 4 months so that the piece is coated and colonized by fibrovascular tissue. Finally, it is explanted and, after lifting the mucosa layer, the OOKP is implanted on the ocular surface (Figure 4).

Temprano’s tibial osteokeratoprosthesis

Conceived by José Temprano in 1984 as a modification of the OOKP for cases without adequate teeth⁸, the tibial osteokeratoprosthesis (OKP-T) uses a 10 mm diameter hard bone disk, taken from the antero-lateral aspect of the upper third of the tibia of the patient. In it, the same type of optical cylinder is inserted as in the OOKP and the procedure follows similar phases (Figure 5). Although the follow-up does not yet reach that of the OOKP, the OKP-T has presented similar anatomical and functional results (see chapters 8.3.2 and 8.3.4)^9,10.

RIGID ALLOPLASTIC KERATOPROSTHESIS

In the group of keratoprostheses that do not include biological tissues, we can consider on the one hand those that use rigid materials (hard plastic, glass, metal) and on the other those that – more recently – are based on flexible polymers. Sometimes the term "biocompatible" is added, which denotes the goal, more or less achieved, of the integration of the prosthesis with the recipient's tissues, ideally through its colonization by cellular elements. Some of them, like those of Girard, Cardona or Pintucci have already been described in the history chapter (see chapter 8.1).

Moscow keratoprosthesis (Fyodorov-Zuev, MICOF)

Developed since 1970 by S. Fyodorov, Z.I. Moroz and V.K. Zuev at the Complex of Ocular Microsurgery of Moscow, several models have been presented (see chapter 8.1) that combine an optical cylinder of PMMA and a titanium haptic. Currently, it is known by the acronym MICOF, the model with two titanium handles of 7.5-8.0 mm in diameter and a central ring of 4.5 mm is mainly used in China and Russia. In the original design, the prosthesis was first implanted in a lamellar corneal pocket and later the central part of PMMA was replaced by a 2.6 mm diameter screw optic. Today the MICOF can be implanted in the recipient's own cornea in two stages or in a homograft such as the B-Kpro in a single stage. In the first case, only the haptic is first implanted in a corneal pocket and a conjunctival covering is applied – or buccal mucosa in the most severe cases –. At 3 months the cornea is trephined, and the optical cylinder is crimped. The visual field is approximately 40°¹¹.

Iakimenko’s Odessa keratoprosthesis ("universally removable")

Developed in 1968 by Stanislav Iakimenko at the Institute of Eye Disease and Tissue Therapy Vladimir Filatov of Odessa, Ukraine. With it, more than 1000 surgeries have been performed. It consists of an optical cylinder of PMMA that widens in the anterior portion and with a thread in the posterior portion, and a tantalum ring that serves as a support to the receiving cornea (see chapter 8.5).

Worst’s «champagne cork» keratoprosthesis

Designed in 1988 by Jan Worst, who called it "champagne cork keratoprosthesis" because of its truncated cone shape that finishes on an anterior plate¹². It is made of KF9 crystal with platinum coating and has 4 stainless steel handles for attachment to the sclera (Figure 6). Its main advantage is that it allows a greater visual field and an easier fundus examination. It has been used mainly in India.

Seoul Keratoprosthesis

Developed at Hallym University in Seoul, Korea in 1990, it consists of three components: a central PMMA optic of about 4 mm in diameter that is inserted into a 10 mm skirt, composed of a porous polyurethane or polypropylene polymer, which it is fixed in turn to the patient's own cornea. Polypropylene monofilament haptics are anchored to the sclera and thus allow a double fixation of the device, which would improve its stability¹³.

MIRO Cornea keratoprosthesis

It is a new type of keratoprosthesis developed in Germany since 2010. It is based on a hydrophobic polymer called BENZ (HF-1), although its 3 mm diameter optics are hydrophilic in the anterior part in contact with the tears. The disk-shaped haptic with holes – like in B-Kpro – is coated with a protein that favors the chemotaxis of keratocytes and fibroblasts; this would in theory promote cell adhesion and tissue integration of the prosthesis (Figure 7)^14,15.

FLEXIBLE KERATOPROSTHESES

Chirila keratoprosthesis (AlphaCor)

Developed at the Lions Eye Institute in Australia and implanted since 1992, it was initially named Chirila keratoprosthesis in reference to its designer¹⁶, although it was later known by the trade name AlphaCor¹⁷. It consists of a single piece of 7 mm in diameter of poly-2-hydroxyethyl-methacrylate (PHEMA), a hydrophilic material similar to that of soft contact lenses. Three zones are distinguished according to their water content: the most peripheral is opaque and porous, which allows colonization by keratocytes. The central area of ​​4.5 mm is transparent, and an intermediate zone prevents opacification of the central area through the so-called "Interpenetrating Polymer Network”.

The surgery is performed in two stages: first a lamellar pocket in the corneal stroma is created and the prosthesis is inserted in it after trepanning the posterior layer. The conjunctiva proliferates above the device and about 3 months later the anterior corneal lamella and conjunctival tissue are centrally trepanned, exposing the surface of the prosthesis. This requires adequate tear production and problems have been reported due to staining of the material in smoking patients¹⁶.

Legeais keratoprosthesis (BioKpro I, II, III)

Developed by Jean-Marc Legeais in 1994¹⁸, who called it "BioKpro", it has gone through three generations. The last (type III) has an optic of silicone elastomer of 5 mm in diameter and 500 μm in thickness and a skirt of expanded polytetrafluoroethylene (PTFE) of 10 mm in diameter and 250 μm in thickness, with pores of 80 μm each. The implementation is similar to that of the AlphaCor, in two phases. The prosthesis is inserted into an intrastromal pocket whose anterior lamella is immediately trepanned in the center and covered with oral or conjunctival mucosa. In a second stage, a 4 mm opening is made on the mucous membrane. In spite of everything, the results have not been very promising¹⁹.

Keralia keratoprosthesis (KeraKlear)

It is the first folding and injectable keratoprosthesis for non-penetrating implants. Developed in 2000 at the Bascom Palmer Eye Institute in Miami (Florida, USA) by the group of Jean-Marie Parel and Josef Stoiber, it was named there as Keralia. In 2009 it was approved in Europe and marketed as KeraKlear. The material used is a poly-HEMA-MMA copolymer, with a total diameter of 7 mm, which includes a central optical area of ​​4 mm and an annular skirt of 1.25 mm radius, which has multiple holes to facilitate the tissue growth through it (Figure 9). It is produced in two versions: phakic/pseudophakic of 44 D and aphakic of 60 D. The surgery consists of creating a corneal pocket, ideally pre-descemetic, in which the prosthesis is introduced through a peripheral corneal incision of 3.5 mm after having retired altered anterior corneal tissue over the optic area¹⁵.

Stanford keratoprosthesis

Developed since 2007 by Curtis Frank's group at Stanford University (California, USA), it is made of a porous hydrogel called Duoptix^TM, composed of polyethylene glycol and polyacrylic acid with a water content of 80%. It has a circular structure similar to that of the AlphaCor, which consists of a double network of the aforementioned polymers, which allows the growth of cells in the skirt of the prosthesis and favors its integration with the receptor tissue²⁰.

GENERAL INDICATIONS OF KERATOPROSTHESES

Substituting the damaged cornea for an artificial one has the theoretical advantages of not depending on a donor, the absence of immunological rejection and the possibility of a perfect optical quality. If in practice the application of keratoprostheses is very minor compared to keratoplasty, it is due to the success of these in many situations and to the common disadvantages of those (extrusion, infections, etc.). The indications for keratoprosthesis therefore include those fields in which transplants have a poor prognosis to begin with or when they have repeatedly failed^8,21. They include opaque corneas in a severe and irreversible way due to:

• Chemical or thermal burns.

• Repeated failure of keratoplasty.

• Muco-synechiae autoimmune diseases, such as cicatricial ocular pemphigoid and the Stevens-Johnson and Lyell syndromes.

• Other forms of severe dry eye with corneal xerosis such as graft-versus-host disease, certain Sjögren syndromes, and some ectodermal dysplasias.

• Terminal cicatricial trachoma and recalcitrant bilateral herpetic keratitis and with severe vascularization.

• Severe neurotrophic keratopathy, especially if bilateral.

• Congenital anomalies such as sclerocornea, Peters’ anomaly or coristomas that affect the cornea.

• Congenital aniridia with severe bilateral limbal insufficiency.

• Metabolic diseases that cause recurrent corneal opacity as certain monoclonal gammopathies.

• Loss of eyelids due to trauma or illness (Crouzon’s syndrome, etc.).

• Any other situation in which the prognosis of a keratoplasty is clearly poor due to the large extent of the lesion, the presence of marked vascularization, dry eye, limbal insufficiency, or a combination of these.

On the other hand, there are contraindications such as poor light perception, terminal glaucoma, old retinal detachment and phthisis bulbi⁸. The indications and contraindications are rarely absolute and, given that they are usually complex cases and without the possibility of examining the fundus, we often find situations in which it is not easy to decide whether or not there are possibilities to recover some useful visual function. In others we will face the dilemma of trying another keratoplasty plus or/and a restorative technique of the ocular surface before moving to keratoprosthesis. And in cases with significant alteration of the lacrimal function or/and autoimmune pathology, it will be necessary to decide between the conventional B-Kpro²¹ and those that have better results in these indications – but other disadvantages – such as the OOKP or the OKP-T. In any case, the decision should be made after carefully evaluating all the clinical and personal aspects of each patient.