The osteo-odonto-keratoprosthesis (OOKP), designed by Strampelli and later modified by Falcinelli, is currently the longest-lasting keratoprosthesis. Thanks to its autologous biological constitution, it is considered the treatment of choice in terminal cases of corneal blindness in which keratoplasty is not indicated (see chapter 8.2).

PREOPERATIVE EVALUATION

Patients considered for OOKP require an assessment by the ophthalmologist and by the maxillofacial surgeon. A detailed clinical history and careful examination are necessary to determine the degree of function of the retina and the optic nerve. The examination of the oral cavity should guarantee an adequate graft of buccal mucosa and select an appropriate tooth to make the sheet (table 1). The general state – since the technique requires general anesthesia – and psychological state will also be assessed in every patient, who must receive complete information about each surgery and all the risks. Each patient must commit to a lifetime follow-up and have reasonable expectations regarding visual and aesthetic results. The main contraindications to OOKP include patients who manage reasonably well with low vision, eyes that do not have light perception or evidence of phthisis bulbi, terminal glaucoma or irreparable retinal detachment.

SURGICAL TECHNIQUE

The OOKP consists of replacing the ocular surface with a buccal mucosa graft and reconstructing the anterior segment through the use of an osteo-dentary lamina that has an acrylic lens inserted. For this, the central cornea, iris, lens and anterior vitreous should be removed (Figure 1). Classically it consists of three stages, although the first two are usually done in the same session.

Preparation of the eye and buccal mucosa graft

In the first stage, the pathology of the ocular surface should be eliminated, such as adhesions or symblepharon, and coated with a full-thickness buccal mucosa graft. This should be of sufficient size to cover from the medial edge to the lateral and from the upper fornix to the inferior, which involves removing a piece of 3 to 4 cm diameter.

The oral cavity is opened with the help of a speculum. It is important to first identify the duct of the parotid gland so as not to cause inadvertent lesions of the same. Then we proceed to infiltrate a local anesthetic with adrenaline in the area to be resected, whose margins have to be demarcated in a way that avoids the aforementioned duct, generally in an area below it. Some surgeons use the mucosa of the inner face of the lower lip. With a scalpel, the mucosa is incised according to the marked margins and then it is dissected with scissors and the graft is extracted. Next, adequate hemostasis of the donor bed should be performed, which may require closure with absorbable sutures. The submucosa fat is removed from the piece by means of curved scissors, being careful not to produce an excessive thinning of the same. While the eyeball is being prepared, the graft is left in a solution with antibiotics such as cefuroxime or 5% povidone iodine (Figure 2).

After obtaining the piece of oral mucosa, we proceed to prepare the eyeball. The rectus muscles are identified by suture loops. A 360° peritomy is performed, and conjunctiva and Tenon are separated from their scleral bed until the rectus muscles are visible. The corneal epithelium and Bowman's layer are then removed. The cauterization of the scleral bed should be cautious not to cause excessive damage to the episcleral vessels, which will provide irrigation to the graft as well as drainage of the aqueous humor. After this, the buccal mucosa is placed on the ocular surface, cut until obtaining an oval graft of adequate size that fits in front of the eyeball and anchored to the sclera and the rectus muscles with 8 6-0 vicryl sutures. The margins of the mucosa are then fixed to the remaining conjunctiva, whenever possible.

Preparation of the osteo-dentary lamina and assembly of the prosthesis

In this second stage (or second phase of the first), a tooth in good condition is extracted – usually one of the canines, which together with its alveolar bone, will be used to prepare the OOKP lamina. The extraction involves cutting the bone on both sides and at the base of the tooth, to include it together with the alveolar ligament and a layer of bone tissue. This cut is practiced with a fine oscillating electric saw, under constant irrigation with cold saline solution to minimize thermal damage. The tooth-alveolar complex is carefully removed to prepare the lamina (Figure 3). The remnant defect can be closed by suturing the adjacent mucosa with 4-0 vicryl, although the exposed bone undergoes rapid spontaneous epithelization.

With the dental crown held with an extraction forceps, teeth and bone are polished on both sides and edges with a milling disc – always under constant irrigation with cold saline – until obtaining a sheet about 3 mm thick and as wide as possible to be able to insert the optical cylinder. This osteo-dentary sheet is then perforated in the center where, after drying it, an optical cylinder of polymethyl methacrylate (PMMA) of an appropriate refractive power for the eye is introduced, which is fixed with dental cement. In the United Kingdom we currently use a biconvex PMMA cylinder with two parts: the anterior one – which must pass through the lamina – is 5.75 mm long and 3.5 to 4 mm in diameter; the posterior one will extend towards the ocular cavity from the lamina, being 3 mm long and 5.25 mm in diameter (Figure 4).

The dental crown is separated from the lamina just before it is dried with oxygen and the optical cylinder is fixed with the cement. It is important to preserve the periosteum; if it comes off, it can be re-fixed with fibrin glue. The piece of OOKP thus assembled is then placed into a sub-dermal or sub-muscular pocket – usually below the contralateral lower eyelid orbicularis – where it is left for 2 to 4 months to promote fibrovascular tissue growth through the bone pores that will guarantee the nutrition of the lamina.

In edentulous patients or those who do not have teeth in suitable conditions for this procedure, the lamina can be prepared from homografts with teeth of preferred family donors or, using a technique with tibial bone (see chapter 8.3.2).

Although these two phases are usually performed in the same session, in cases with very severe ocular dryness it may be advisable to defer the preparation of the lamina until a good functioning of the mucosal graft has been verified. Otherwise there is a risk that in the additional time required for a new mucosal graft, the resorption of the buried lamina in the eyelid pocket will occur. It is also advisable to separate these stages when a homograft is used.

Implantation of the prosthesis in the eye

After 2 to 4 months, the OOKP lamina is implanted on the surface of the recipient eye, between the cornea and the mucosal graft. Leaving it for longer in the subcutaneous pocket increases the risk of partial resorption. During this period, the lamina is completely covered by connective-vascular tissue that grows towards the bony pores. This waiting time also allows the sheet to recover from the thermal damage suffered during its preparation and rule out a possible infection of it.

The first step in this "third stage" (which is usually the second) is to extract the sheet of OOKP from its bed for inspection. Only if it is of adequate size and in good condition will the eyeball be prepared for implantation (Figure 5). All soft tissue on the posterior surface of the piece is removed until the dentin is exposed and that of the anterior surface is trimmed. At this time, it is useful to make a mold of the lamina, which will serve as a guide for the placement of the Flieringa ring and the previous sutures for the initial fixation. While preparing the eyeball, the lamina already cleaned of unwanted tissue is preserved in a container with heparinized blood from the same patient. We place traction sutures on the eyelids to obtain the greatest possible access to the eyeball. The buccal mucosa that now covers the ocular surface is partially lifted by traction with forceps to then make a semi-circular incision and create a flap of 3 to 9 clock hours. This should pass just below the lower limbus because if it is very peripheral it could compromise the blood supply of that sector of the graft. After exposing the surface of the eyeball, a scleral support ring is sutured (Flieringa) leaving the sutures at 3 and 9 o'clock with long ends to be used as traction to mobilize the eyeball. We mark the center of the cornea and use the lamina mold as a guide to place the 4 cardinal sutures for initial fixation to the sclera. In order to reduce intraocular pressure, it is convenient to administer intravenous mannitol some time before the moment of corneal trepanation. This is usually partial and consistent with the posterior diameter of the optical cylinder – usually 4 to 5 mm – and is completed manually with scissors or knife.

Next, the iris is completely resected by means of iridodialysis by means of traction with forceps. Bleeding from the iris root is not usually a problem but a constant irrigation with saline should be maintained until it stops. In phakic patients, we perform the intracapsular lens extraction – even if it is transparent – and then proceed with a wide anterior vitrectomy, facilitated by an adequate traction of the ends attached to the scleral ring (Figure 6). Intraocular lenses should also be removed together with the capsular bag, otherwise it increases the risk of secondary glaucoma by angle closure and, above all, of formation of fibrous membranes behind the optic cylinder.

The lamina is applied on the eyeball with the posterior part of the optic cylinder through the corneal trepanation and its fixation with the cardinal sutures begins. The eyeball is then reformed by injecting air through the limbus with a 30-gauge needle. Indirect ophthalmoscopy is performed to confirm the adequate centering of the lamina and the optic cylinder by visualizing the posterior pole and discarding hematic remains in the vitreous. If everything is in order, we proceed to complete the fixation of the OOKP to the sclera with additional 6-0 vicryl sutures. Finally, the Flieringa ring is removed, the mucosal flap is repositioned in its original position and fixed with sutures, previous realization of a central hole that will give way to the anterior part of the optical cylinder.

FOLLOW-UP AND POSTOPERATIVE TREATMENT

The initial postoperative period

It is recommended that OOKP patients remain hospitalized for one week after each surgical time, for proper monitoring and detection of possible early complications. After the first stage, the patient will receive systemic and topical antibiotics, as well as oral prednisone 1 mg/kg/day for 5 days. A PMMA shaper is placed on the ocular surface in the first days, with a central opening that facilitates the passage of topical medication. Its function is to avoid postoperative synechiae in palpebral fornices, and for this we move it gently in all directions. For the buccal region, patients should rinse it with chlorhexidine and nystatin.

After implantation of the prosthesis, the treatment includes a systemic corticosteroid regimen to control intraocular inflammation and oral acetazolamide whenever ocular hypertension is present or suspected. Topical antibiotics should be maintained for life, as well as careful periodic cleaning of the optical cylinder with cotton swabs with 5% povidone-iodine.

Long-term follow-up

OOKP patients require a lifetime follow-up. After each surgical stage, they should be evaluated weekly during the first month, monthly for the next 3 months and then every 3-4 months. The intraocular pressure should be assessed at each visit, even if only by finger palpation.

The buccal mucosa should be inspected for its color, hydration and especially the presence of any area of ​​thinning or ulceration (Figure 7). The optical cylinder must be examined especially in its union and its position with respect to the lamina, in search of any displacement or instability, as well as to check its transparency and discard a retroprosthetic membrane. The fundus examination is necessary to evaluate the condition of the optic disk and the macula. Early peripheral retinal detachments can be detected by B-mode ultrasound and visual fields are recommended every 6 months for the diagnosis and monitoring of glaucoma. The reabsorption of the bone tissue can be inferred clinically by palpation of the lamina but the most objective way to estimate changes in its volume and dimensions is through the serial study with computerized axial tomography (CT-scan).

If the patient remains stable, follow-up may be done at longer time intervals or even be carried out by your local ophthalmologist. The anatomical retention of OOKP exceeds 80% of cases after a period of 20 years and, in our experience, more than half of patients maintain a visual acuity of 0.5 or better.

The tibial osteo-keratoprosthesis (OKP-T) is a modification of the osteo-odonto-keratoprosthesis (OOKP) which, instead of the osteo-dentary lamina, uses as a haptic for the optic cylinder a disc of hard bone taken from the anterior-lateral face of the upper third of the patient's own tibia. Thus, the quality of heterotopic autograft of these biological support prostheses is preserved. I developed this technique in 1978 in the first place for the cases that did not have a suitable tooth for OOKP¹. However, the good results obtained, similar to those of the OOKP in the medium-long term^2,3,4 (see chapter 8.3.3), make it an alternative for all indications of the OOKP.

PREOPERATIVE EVALUATION

The candidate patient for keratoprosthesis should be evaluated to corroborate the indication, establish the prognosis and detect possible risks. The preoperative evaluation of the OKP-T does not differ much from that of other keratoprostheses, except in the evaluation of the tibia. A general medical examination is also necessary since the surgery is preferably performed under general anesthesia. I usually follow the following steps:

Eye evaluation

• Examination of the anterior segment with slit lamp.

• Assess intraocular pressure as much as possible, either instrumentally or digitally.

• Examination of the visual function, in particular to specify the light perception and location.

• Ultrasound B to assess the transparency of the vitreous, the anatomical state of the retina and the choroid, and rule out a cataract or an intraocular tumor.

• Biometry to decide the dioptric power of the optical cylinder.

• Electroretinogram and visual evoked potentials to determine the functional capacity of the retina and the optic nerve⁵.

Tibia evaluation

• Radiographic examination to verify that it is in good condition and without areas of rarefaction or osteoporosis.

• Bone densitometry.

SURGICAL TECHNIQUE

The procedure of the OKP-T follows a scheme similar to that of the OOKP, with the difference in obtaining the bone disc. It is also done in three stages, of which the first two can be practiced in the same session^1,6.

Preparation of the eye and graft of buccal mucosa

As in the OOKP, in the first stage the receiving eye is prepared and the pathology of the ocular surface, adhesions and symblepharon are eliminated, to then apply a buccal mucosa graft (Figure 1). I first perform a 360° peritomy, dissect the conjunctiva and Tenon's capsule with scissors or diathermy needle until I reach the area of ​​the muscle insertions and visualize them. Then I perform a surface keratectomy with Desmarres’ knife or/and turbine flat bur (AeroRotor) to regularize the corneal surface and remove the fibrous areas, which will facilitate the adherence of the mucosal graft. I also perform hemostasis of thick vessels with bipolar diathermy.

We go to the mouth to obtain the graft, preferably from the inner lower labial mucosa, which we examine, clean and disinfect with 5% povidone iodine. This location is sufficient to obtain grafts capable of covering well even both eyes and has the advantages of an easier access than the mucosa of the interior of the mouth and avoiding the risk of injury to the Stenon’s duct. The lip is fixed and tensed with a clamp designed for that purpose, which produces hemostasis by compression. I usually use the lower lip, which is more accessible, but if it is not in good condition it is possible to use the upper or the commissures. We mark an oval of about 2 x 3 cm on the mucosa and obtain a 1 mm-thick graft with blade and scissors or with diathermy in cutting mode. From the bloody side of the graft, the fatty follicles are removed with scissors, and in the donor lip we apply hemostasis by compression with gauze soaked in hydrogen peroxide. If there is a thick bleeding vessel, it is cauterized or ligated.

Back to the ocular globe, we place the mucosal graft on its surface, with the bloody face towards the cornea and suture it with 8 7-0 silk points, of which 4 are placed in the muscular insertions to favor the vascularization of the graft and another 4 in the sclera in each of the quadrants between the muscles. The graft should be sufficiently extended and without folds, but not too tense because this would compromise its viability. Next, we superimpose the conjunctiva on the periphery of the mucosal graft, without the need to suture both. Finally, we place a blepharorrhaphy suture in "U" and a semi-compressive bandage, after administering a subconjunctival injection of corticoid and antibiotic.

The next day we remove the compressive bandage and blepharorrhaphy and begin to wash the eye with saline and an antibiotic four times a day. In the mouth, we perform touches with mercurochrome and rinses with an oral antiseptic to promote quick healing.

Obtaining the bony disc and assembly of the prosthesis

The second stage involves obtaining and preparing the OKP-T (Figure 2). We make a longitudinal incision in the skin of the antero-medial aspect of the leg, at the height of the upper third of the tibia. In this area there are no muscles under the skin and after the subcutaneous tissue appears the periosteum that we incise and separate to the sides with a periostotome. We place a hook splitter to expose the face of the bone and carve in it a 10 mm diameter circle with a trephine mounted on the dacryocystorhinostomy hand piece. This trepanation is deepened by 3 mm and the hard bone disc is detached with a gouge, polished with a carborundum bur to regulate it, and a 3.75 mm hole is drilled in its center, where the optical cylinder will be inserted. We submerge the piece in patient's own blood while closing the tibial field with 5-0 silk sutures, after applying a powder antibiotic on the area of ​​the osteotomy.

We remove the bony disc from the autologous blood, we wash it and dry it well and we introduce in the window – similar to in the OOKP – the optical cylinder of PMMA of 9 mm in length, with diameters of 3.5 mm and 4.0 mm and from +28 to +60 D according to the biometry of the eye. We anoint it with a cement (methyl cyanoacrylate) that is not toxic to the bone and we keep it in position for 2 minutes until it sets and stays well fixed. We have thus the OKP-T constituted by the bone disc of 10 mm in diameter and 3 mm in thickness and the optical cylinder that protrudes 3 mm in front and 3 mm behind.

We prepare a subcutaneous pocket in the region under the lower eyelid, where we introduce the piece and close it with 5-0 silk sutures, with a semi-compressive bandage roll. We will keep the prosthesis there for 3 months so that the bone is covered with fibrovascular tissue, so it receives new irrigation and it is verified that there is no rejection, infection or necrosis.

Implantation of the prosthesis in the eye

After three months, we extract the OKP-T piece from the palpebral pocket and proceed to implant it in the eye (Figure 3). After identifying the position of the piece, only the skin is opened in the anterior part and dissected flush with the bone in the posterior face that will touch the cornea. Once released, we submerge it into the patient's own blood while we suture the pocket and prepare the eye. We place a blepharoplasty and a point in the superior rectus, dissect the buccal mucosa towards the lower part with monopolar diathermy at 270°-320°, leaving a lower union pedicle. The corneoscleral surface is cleaned well up to 2-3 mm beyond the limbus. In the central area of ​​the cornea, we mark a circle with a 5-mm trephine, and then drill.

We take again the OKP-T piece from the autologous blood, wash it and apply it to the eye. We pre-place 3 8-0 vicryl sutures at 3, 6 and 9 clock hours. We then complete the corneal trephination and remove the lens – if it is not already aphakic – and the iris completely by traction (iridodialysis), as well as perform a mechanized anterior vitrectomy. We reform the eyeball with saline and viscoelastic solution and introduce the widest part of the optical cylinder in the corneal window, with the bony area resting on the corneal surface. We close the 3 previous sutures and put five more onto the sclera until the OKP-T is well-fixed and the cylinder aligned with the anteroposterior axis of the eye, so that it points to the macula. Finally, we place back the mucosa on the prosthesis, suture it to the conjunctiva with 7-0 silk sutures and open it in the center with a 3-mm trephine so that the optical cylinder comes out through it. We inject corticoid and subconjunctival antibiotic and place a suture of blepharorrhaphy to ensure good occlusion.

FOLLOW-UP AND POSTOPERATIVE TREATMENT

The postoperative period of the OKP-T is similar to that of the OOKP. The first week we do daily check-ups, then once a week for the first month, thereafter every three months for a year, and then annually indefinitely. The first day after surgery we remove the blepharorrhaphy suture and start washing with saline serum, antibiotic and corticoid eye drops 4 times a day. Likewise, artificial tears and a lubricating ointment are applied at night. The intraocular pressure is assessed by digital palpation and, in case of suspected elevation, local hypotensors and acetazolamide are prescribed.

At three months, if the fornix allows it, we place a fenestrated corneoscleral lens with an artificial iris (Figure 4c, d), not only for cosmetic purposes but also to prevent the eyelid rubbing against the optic cylinder, which could produce alteration and tilt it.

TRANSPALPEBRAL TECHNIQUE

In cases with greater alteration of the ocular surface, with great retraction of the periocular tissues, or if there is necrosis of the buccal mucosa and it is not possible to ensure a good coverage of the prosthesis, we use the transpalpebral technique. To do this, we resect all the bulbar and palpebral conjunctiva, the orbicularis muscle and the tarsus. Once we have the OKP-T well anchored in the eye, we superimpose the eyelid over it and we make a permanent total blepharorrhaphy. When it has healed well, at the end of the first month, we make a window in the central area so that the anterior part of the optical cylinder comes out.

Keratoprostheses with autologous biological support include osteo-odonto-keratoprosthesis (OOKP) and tibial osteo-keratoprosthesis (OKP-T). These are complex procedures, with prolonged surgical time and even more prolonged follow-up. The patients usually present very serious pathologies, often in terminal phase, after multiple failed interventions or having been evicted for a long time. This is a fertile ground for intraoperative and postoperative complications, which can be devastating and ruin all the hard work done if they are not detected immediately and treated properly. It is fundamental to educate the patient and his family about the importance of performing periodic postoperative controls for life and to attend any suspicious symptoms.

INTRAOPERATIVE COMPLICATIONS

During the preparation of the recipient eye and mucosal graft

In the first surgical stage we can find a very thin cornea and the dissection of the ocular surface can cause an undesired perforation. In this case, a tectonic, lamellar or full thickness keratoplasty will be necessary, enough to be able to support the prosthesis in a stable way.

During the obtaining of the buccal mucosa, the dissection must take care that the thickness is adequate, since a very thin or perforated area of the graft may lead to the failure of the entire procedure due to ulceration leading to the extrusion of the prosthesis. In cases of autoimmune diseases that also affect the buccal mucosa (pemphigoid, Stevens-Johnson, Lyell, Sjögren, etc.), if this is not adequate or sufficient, it is possible to use other mucous membranes such as nasal, vaginal or foreskin.

During the preparation of the piece for keratoprosthesis

During the extraction of the piece for the prosthesis, in particular the carving of the dental socket but also in the tibia, some bleeding is normal. If there are risk factors for hemorrhage, a prophylactic treatment with antifibrinolytics such as tranexamic acid may be useful. Intraoperative bleeding is usually controlled by local measures such as the anti-Trendelenburg position (for the head), coagulation and, in the case of bone, the application of compression with gauze or with wax.

The extraction of the tooth involves possible potentially serious complications, such as penetration into the maxillary sinus – upon obtaining a superior canine –, the breakage of adjacent teeth or even a maxillary fracture, and in all cases a postoperative reconstruction of the created defect will be necessary. During the cutting with saw, the trepanation of the bone and the milled cutting, it is essential a good cooling with cold saline solution, that if it is insufficient can lead to the necrosis of the tissue or even get to break the piece by an excessive heating.

During the implantation of the keratoprosthesis

The implantation phase exposes all the complications of open-air intraocular surgery. In particular, the possibility of an expulsive hemorrhage in these complex eyes should be borne in mind, and preventive measures should be applied as a general anesthetic with good control of blood pressure, good ventilation and relaxation, place the patient in anti-Trendelenburg position, and minimize the times when the eyeball will be open. It is also advisable to obtain ocular hypotension prior to trepanation, using 20% intravenous mannitol.

POSTOPERATIVE COMPLICATIONS

Complications of OOKP and OKP-T that appear in the postoperative period can be hemorrhagic, inflammatory, infectious, hypotension or ocular hypertension, and of trophic type with necrosis or lysis of the mucosa or the lamina of the prosthesis itself reaching its extrusion. There are specific complications of the prostheses such as the growth of membranes behind or ahead of them and others common to surgery such as retinal detachment. Many of these complications have interrelated causes.

Hemorrhage and early intraocular inflammation

The presence of a cloudy intraocular medium in the early postoperative period usually indicates that there has been bleeding, most likely from the total iridectomy. Since it tends to be reabsorbed – especially in an aphakic and vitrectomized eye – it is recommended to rest with the head up and follow up with ultrasound scans. Antifibrinolytics may have some utility to prevent secondary bleeding. The use of fibrinolytics, not by spreading, is no longer of doubtful efficacy. If turbidity and lack of vision is accompanied by discomfort – which is not always easy to distinguish in this situation – an inflammatory component should be suspected which, if it does not improve soon with an aggressive anti-inflammatory treatment, should be treated as a possible endophthalmitis with sampling and intravitreal antibiotics.

Hypotony and choroidal detachment

Hypotony in the early postoperative period may indicate a certain leakage that will cease when the prosthesis and mucosa heal, but occasionally a choroidal detachment (CD) may appear. It must be determined by ultrasound if it is serous or has a hemorrhagic component. The treatment is generally expectant, plus topical and systemic anti-inflammatories. If there is contact between the bags (osculating CD), a closer follow-up should be done and eventually consult with the vitreous-retina surgeon.

Necrosis of the mucosal graft

The viability of the oral mucosa is fundamental for the retention of the prosthetic lamina. Its necrosis may occur before or after the implantation of the keratoprosthesis (Figure 1). In a series of 167 patients, mucosal necrosis occurred in 1.2% before and 9.1% after implantation of the prosthesis¹. It may be due to palpebral retraction, symblepharon, exposure due to bad apposition of the eyelids – despite the reconstruction performed –, and the poor quality or degeneration of the tissue itself, especially in autoimmune cases.

If the necrosis occurs before the implantation, its size and location should be assessed. If it is small and central, it may not require treatment as it will serve as a window for optics. If it is small and peripheral, it can be sutured or treated by semi-compressive bandaging and treatments that favor epithelization, or with a temporary tarsorrhaphy. If it occupies more than half of the mucosal graft, we will consider a new mucosal graft, perhaps from a thicker area such as the cheek. Any signs of infection should be treated as it is a factor for necrosis and its recurrence, and monitor that there is no resorption of the tooth or bone lamina. In more severe cases or those that do not respond to the above, we can opt for a permanent complete tarsorrhaphy and move to a transpalpebral prosthesis technique.

Resorption of the bone or dental lamina

This complication can occur during its inclusion in the subcutaneous pocket or after its implantation on the cornea (Figure 2). It usually occurs naturally, slowly and progressively, and vitamin D, calcium and phosphate supplements such as alendronic acid may be useful to counteract it – except for medical contraindications. When the resorption is seen in the subcutaneous pocket before the implant – by palpation, ultrasound or CT scan – the osteo-dentary or tibial lamina should be repeated and a new piece fabricated. If this tendency is observed after the implant, we will follow it up with periodic CT scans. Multidetector computerized tomography (MDCT) or electron beam tomography (EBT) make it easy to determine if there is lamina resorption or increase of the lamina².

Through a lamina in resorption, aqueous humor can escape, with hypotony that favors a CD, a retinal detachment, or provoke an aseptic inflammatory situation, an endophthalmitis, and ultimately the extrusion of the prosthesis³. In these situations, it is necessary to consider removing the piece and perform a tectonic keratoplasty until a new prosthesis can be placed⁴.

Extrusion of the prosthesis

It is one of the most feared complications in keratoprosthesis surgery since it means its anatomical and therefore functional failure. Its frequency varies between 0% and 33% in 5 years according to the series⁵. The extrusion or emergence of the optical cylinder can occur when the piece is still in the subcutaneous orbital pocket, in which case we will have to reposition it more deeply.

When extrusion of the prosthesis occurs in the eye (Figure 3) – defined as an exposure of the piece and frank opening of the globe – it usually appears after a defect in the mucosa and a certain degree of resorption. Once present, its treatment is difficult, so it is important to prevent it by taking care of the health of the mucosa. Rarely, palliative measures will be useful, and it will be necessary to act as in the previous section: remove the piece and perform a tectonic keratoplasty until a new prosthesis can be created and implanted. If the mucosal graft is not of good quality and there is a tendency towards recurrence of necrosis, we should consider a transpalpebral technique.

Mucosal growth over the optical cylinder

The growth of the epithelial mucosa over the optic cylinder tends to occur in young patients with very good quality of the buccal mucosa, which tends to proliferate and occludes the optic (Figure 4). In our experience, it occurs in 6% of cases⁶. It is avoided with trepanation of the mucosa somewhat smaller (3 mm) than the optical cylinder, so that the mucosa is adjusted around its base. If it affects the vision, a manual dissection is performed – avoiding scratching the optical surface – and the edges are cauterized. It may be useful to apply mitomycin C⁷.

Retroprosthetic membrane

The retroprosthetic membranes are formed due to the normal postoperative cicatricial reaction and are favored by the persistence of a certain degree of inflammation. In several series of OOKP, they have been observed in 3% of cases^8,9. This low frequency compared to other keratoprostheses, such as Boston, could be due to the design of the optical cylinder, which protrudes more in the anterior chamber, the absence of the scar of the cornea homograft, or less inflammation because it is an autograft – despite being often very severe cases.

If the membrane is thin, it can be trimmed with a Nd:YAG laser, but if it is allowed to grow this may not be possible and it will require a surgical resection. This requires lifting the mucosa and the piece to access the membrane through trepanation, or a limbal or pars plana pathway using vitreous-retinal surgery instruments.

Glaucoma

It is one of the complications that most often leads to a poor visual result despite a good retention of the prosthesis. Its incidence is high, between 28% and 65% depending on the series^6,9,10. A majority of patients already have glaucoma in the preoperative stage¹¹, either by angular closure secondary to the initial disease – e.g. a chemical injury – or by the multiple surgeries to which they have been subjected, by the chronic use of topical corticosteroids or as a consequence, of the chronic inflammation itself, especially in cases of autoimmune diseases. In these cases, it is essential to solve the problem before approaching keratoprosthesis, which usually requires the implantation of a valvular drainage device.

The evaluation of the intraocular pressure in the postoperative period can only be done approximately by finger palpation. Very myopic or very hyperopic eyes can be deceptive due to the characteristics of the scleral wall, as well as those that carry drainage devices or scleral explants. Given that the visual field of these patients is very limited, it is difficult to use them as a control method, although in cases with the anterior optical cylinder of 3.5 mm can reach 30°-40°, sufficient for a certain campimetry study. Finally, we must perform the monitoring of the state of the papilla, either by ophthalmoscopy, serialized photographs or by applying the imaging technologies (OCT, confocal, polarimetry) if the effective pupil allows it. Examination using visual evoked potentials (VEP)¹² has also been recommended.

Because the intraocular penetration of topical hypotensors can be very limited through the buccal mucosal graft, it is often necessary to resort to the systemic ones (carbonic anhydrase inhibitors). If an adequate response is not obtained, the options are reduced to valvular drainage implants¹³ – something complex once the prosthesis is in position – or cyclo-destructive treatments, with all its drawbacks, especially in already inflamed eyes.

Endophthalmitis

Endophthalmitis in the postoperative period of a keratoprosthesis usually occurs through a fistulisation – e.g. associated with resorption of the lamina – which may not be very evident, particularly if hypotony is not appreciated. The patient complains of sudden or rapidly progressive loss of vision accompanied by pain, and there may be purulent discharge on the ocular surface, turbidity in the vitreous cavity – especially suspicious if vitrectomised – and increased intraocular pressure.

The post-surgical endophthalmitis protocol should be applied without delay, with vitreous sampling for microbiological study and by PCR, injection of fortified antibiotics, etc., together with systemic corticosteroids. The most frequent germs in endophthalmitis after OOKP/OKP-T are staphylococci spp. and pseudomonas spp.¹⁴, although the possibility of a fungal infection should not be forgotten. If the patient was not vitrectomized or very partially, it can be considered to complete it in the judgment of the vitreous-retina surgeon, in order to reduce the infectious load.

Retinal detachment

The observation of the retinal peripheries is difficult in the carriers of these keratoprostheses, and therefore it will be the diagnosis and treatment of retinal detachment. This appears as a sudden loss of vision without pain, with floating bodies, photopsies and/or the appearance of a dark curtain. The diagnosis is confirmed by indirect ophthalmoscopy and ultrasound. Visualization during vitreous-retina surgery is improved with the use of a special lens (Nadal-Barraquer)¹⁵. It is a PMMA contact lens fenestrated at its center, so that it fits with the optical cylinder. Its concavity is filled with viscoelastic and allows to support the wide-angle lenses for surgical visualization of the fundus. Even so, it is not easy to observe the retinal periphery through a 3.5 mm pupil and a 9 mm long stem, which requires an experienced surgeon.

The keratoprostheses with autologous biological support, that is to say, the osteo-odonto-keratoprosthesis (OOKP) and the tibial osteo-keratoprosthesis (OKP-T) have the longest follow-up times and in many cases of success. However, analyzing their results and possible prognostic factors is an arduous task, since it is a dynamic process and very widespread over time^1-3.

For decades there were only a few centers in the world that performed this type of surgery and this is reflected in the not very extended literature on long-term results. Falcinelli's group in Rome has the longest experience⁴, followed by the one from Temprano and Barraquer in Barcelona^1,2, Marchi's, also in Rome⁵, Liu's in Brighton⁶, Hille's in Homburg⁷, Tan's in Singapore^3,8 and finally that of Iyer in Chennai (India)⁹.

THE EXPERIENCE OF THE CENTRO DE OFTALMOLOGÍA BARRAQUER (COB)

In our center, the first OOKP was carried out by Joaquín Barraquer in 1965 (see chapter 8.1), which marks the beginning of an experience that already exceeds half a century. We also have the main OKP-T global series, currently in its fourth decade of follow-up. We have performed a review of 258 eyes of 258 patients operated on for keratoprosthesis with autologous support (145 from OOKP and 113 from OKP-T) from 1974 to 2013. In the patients operated on in both eyes, only one was studied, chosen at random. The average age was 47 years (range from 10 to 86 years), with 65% of men and 35% of women. The mean follow-up time was 86.3 months (7.2 years, range from 1 month to 35.3 years). Of the 258 cases, 96 (37%) could be followed for at least 5 years, 52 (20%) for 10 years or more, and 21 (8%) for a minimum of 20 years.

Indications

The primary diagnoses were distributed as follows: 35% for chemical burns, 15.2% Stevens-Johnson (SJ) or Lyell syndrome, 14% cicatricial ocular pemphigoid (COP), 11.2% advanced trachoma, 8.1 % thermal burns. 15.9% of the patients were classified as "other diagnoses", which includes a miscellany of less frequent causes such as congenital aniridia, Terrien’s degeneration, Mooren's ulcer, various traumas and failures of keratoplasty, among others. The latter is noteworthy, since repeated failures of corneal transplants (only 5 cases in this series) are currently one of the main indications of keratoprostheses such as Boston's.

When comparing the indications of the OOKP group with those of OKP-T, the difference in the proportion of chemical burns (respectively 43.4% and 25.6%) and COP (5.5% and 24%) is striking, while the cases of SJ were similar (14.5% and 15.9%). The difference with respect to the COP is explained by the fact that they are patients who, due to their age, often lack adequate teeth for an OOKP.

ANALYSIS OF RESULTS

Any analysis of the results in keratoprosthesis must be based on two essential aspects: the anatomical – retention of the prosthesis – and the functional: visual acuity (VA). For this we follow the definition of the World Health Organization, which establishes legal blindness in a VA <0.05 decimal (1.3 LogMAR). On the other hand, it may be interesting to know how many patients achieve a more useful vision than simply ambulatory and how long they retain it.

Anatomical results (retention of the prosthesis)

In the series as a whole – if both modalities are grouped –, the actuarial probability of retention of the prosthesis is 82% at 2 years, 71% at 5 years, 62% at 10 years, 55% at 20 years, and still of 45.4% at 35 years. In the graph with the two techniques separately (Figure 1), it gives the impression that the results are somewhat better for the OOKP, which remains at 50% after 35 years, while the OKP-T is at 40% from 12 years and it stays that way until almost at 20 years. However, this difference was not significant according to the logrank test (cumulative chi-square) at 5 or 10 years (p = 0.13). Neither was a Cox regression (p = 0.36). In any case, it should be remembered that (a) this study is retrospective and there were differences in the diagnoses, and (b) the survival curves are losing statistical weight as they progress and fewer patients are controlled.

Functional results (visual acuity)

In general, patients obtain a clear improvement in VA. In this series, the median preoperative VA was hand movement (2.30 LogMAR), with range from light perception (2.70 LogMAR) to 0.1 decimal (1.0 LogMAR). In the postoperative period, the best median VA was 0.23 decimal (0.65 LogMAR). Note that this refers to the maximum VA that patients achieved at some point during their follow-up. However, many of them end up having complications and when we consider only VAs at the last visit, the median VA returns to the initial level of hand movement (2.30 LogMAR). This is represented by comparing the pre- and postoperative VA dispersion graphs, as used for the second, the maximum VA (Figure 2) or the final VA (Figure 3). This difference between the maximum VA and the final VA reflects the prolonged follow-up. But if we stayed only with the second, we would not appreciate the profit that many of these patients have had for years even if they lost it in the end.

If we perform an actuarial analysis with the limit of VA <0.05 (1.3 LogMAR) as a definition of failure, we obtain a probability of maintaining at least ambulatory vision for 2 years in 57% of the total, which drops to 43 % at 5 years, 32% at 10 years and 26% at 15 years. If we compare this between the two techniques (Figure 4), a significant difference in favor of the OOKP is obtained here, both in the logrank test (p = 0.001) and in the Cox regression (p = 0.005). Possibly this reflects that the OOKP patients started from a potential visual capacity (state of the retina and optic nerve) better than those from OKP-T, in line with a higher percentage of chemical burns (often young) in the OOKP and more COP (often elderly) in the OKP-T. All this corroborates the importance of preoperative evaluation and, in particular, the predictive value of electrophysiological tests (ERG and PEV)¹⁰, which is particularly helpful when choosing the most likely eye in frequent bilateral cases.

PROGNOSTIC FACTORS

The group of patients who end up needing a keratoprosthesis is quite heterogeneous. Therefore, there are possibly many factors that influence the result, both anatomical and functional. As already mentioned, in the presence of a retained prosthesis the functional result depends above all on the state of the retina and the optic nerve. For the analysis we have chosen three possible factors such as initial diagnosis, age and postoperative complications.

Diagnosis

The cause of the corneal alteration that requires a keratoprosthesis should undoubtedly influence the result. In our complete series (with both techniques grouped together) the best anatomical results (Figure 5) were for thermal and chemical burns, with retentions of the prosthesis of 75% and 72% at 5 years respectively, maintained at almost 10 years. These percentages were, in patients with SJ and Lyell syndromes, of 68% at 5 years and 58% at 10 years, while at COP it was 63% at 5 years but only 27% at 10 years. The best result at 5 years was for trachoma with more than 78% retention, but at 10 years it had dropped below 60%. However, the logrank test applied to all the curves did not reach significance (p = 0.088). A Cox regression that compared each diagnosis with the "best" (chemical burns) did not find significant differences either.

Regarding the functional result, the probability of maintaining at least an ambulatory vision of 0.05 (Figure 6) was curiously higher in the group of SJ and Lyell syndromes with 55% at 5 years and 47% at 10 years, followed by chemical burns (respectively 50% and 37%), while those of COP remained at 37% at 5 years and 20% at 10 years. Also striking is the poor result in thermal burns – despite the good anatomical – with only 11% at 5 years, maintained at 10 years. The logrank test achieved here significance (p = 0.041), but not the Cox test of each diagnosis with respect to the chemical burn (the comparison with the thermal one approached the significance, with p = 0.068).

Age

The possible influence of the age factor at the time of surgery is not easy to analyze. There are certain differences, but these are not ordered in a progressive manner according to age (Figure 7). This suggests that such differences depend on the different distribution of diagnoses or other factors associated with each age group rather than age itself. Regarding anatomical success, the best group was found to be the oldest (70-89 years), both at 5 years (88% retention) and at 10 years (69%). Later the curve falls, but possibly it is because these patients – logically – disappear. The worst prognosis is for patients aged 50-69 years, with retentions of 60% at 5 years and 50% at 10 years. The youngest ones have – also logically – the longest follow-ups, with intermediate values ​​(60-70%) but that remain almost unchanged from the 10 years until beyond the 20 years of follow-up. The curves did not show significance neither with logrank (p = 0.113) nor Cox (when comparing each group with that of 30-49 years).

Functional survival was, however, higher in the youngest group (10-29 years) with 58% and 46% at 5 years and 10 years respectively. But, again, there is no clear order by age, since here the worst were those aged 30-49 years (34% and 23% at 5 and 10 years respectively), while the other groups had intermediate values ​​and somewhat better for the 70-89 years than those of 50-69 years (Figure 8). The overall difference was not significant either (logrank p = 0.088). The Cox regression found significance only when comparing the 10-29 group with the 30-49-year group.

Postoperative complications

The appearance of complications in the postoperative period is another factor that predictably has a great influence on the anatomic and functional survival of keratoprostheses (see chapter 8.3.3). The analysis of our series sheds some light on the influence of each of them. From the anatomical point of view (Figure 9), it is striking that the patients with better retention were those who presented glaucoma (95% at 5 years, maintained up to 25 years, although as we will see, this does not help them much), followed by those who had retroprosthetic membrane (86% at 5 years, maintained until 15 years), even better than patients without any complication – before extrusion –, with retention of 73% at 5 years and 60% at 10 years. Patients with more than one complication have the worst retention at 5 years (42%), and at 10 years (27%), and in those with mucosal necrosis the percentage was 50% at 5 years but only 17% at 10 years. The logrank test was highly significant (p <0.0001). When comparing the different complications compared to those who did not have any, the Cox regression gave only significance to mucosal necrosis (p <0.0001), with a 4 times greater risk of extrusion. It is noteworthy that 40% of these necrosis occurred in patients with COP. Logically, in patients with autoimmune disease against mucous membranes, the use of autologous tissue is not a great advantage – although it could possibly be worse to use donor material. However, this did not occur in the cases of SJ/Lyell syndromes, which points to the importance of active chronicity in the inflammatory process.

From the functional point of view (Figure 10), the results contrast with the anatomical ones. Here the best ones were, predictably, those that did not have any complications – until the moment that for another reason they failed – with 60% vision of 0.05 or better at 5 years and 47% at 10 years. In contrast, cases with glaucoma fall below 40% at 5 years and below 30% at 10 years. The worst functional survival is in patients with more than one complication (14% at 5 years, maintained up to 12 years) and those who suffered a retinal detachment (23% at 5 years and 19% at 10 years). Cases with mucosal necrosis are in 38% at 5 years, but from the 6^th one they fall to 13%. The logrank difference achieved was also highly significant (p <0.0001). The comparison by Cox regression between each complication with the group that did not have any was very significant in all – except the retroprosthetic membrane and the vitreous hemorrhage groups –, with the maximum relative risk of losing ambulatory vision (2.7 times more) in patients with retinal detachment.