Success rates for Boston keratoprosthesis (B-Kpro) type I continue to rise and although patients chosen to implant a keratoprosthesis should be classified as a single eye or functionally blind in both eyes according to criteria of the World Health Organization (WHO), many surgeons currently support its use in patients with functionally preserved vision in the fellow eye. This extended use is due to the potential for improvement in visual function, the restoration of binocularity and the aesthetic improvement of patients after surgery¹. The ideal candidate would be one with a vision of light perception with projection or less, but currently many surgeons achieve very good visual results in patients with better preoperative visions².

PREOPERATIVE EVALUATION

The patients that are going to undergo surgery of these characteristics must present certain preserved properties, such as enough tear film and correct palpebral anatomy with good blinking function; the preservation of such characteristics will positively influence the final results. The depth of the sac fundus should be assessed, since a scleral support contact lens must be permanently adapted in the postoperative period. When necessary, a reconstruction of the conjunctival sac fundus should be carried out beforehand, especially if there are sectorial symblepharon, as occurs in mild or moderate cases of ocular cicatricial pemphigoid and in the Stevens-Johnson and Lyell syndromes (toxic epidermal necrolysis).

In case of autoimmune pathology, it must be assessed whether the systemic treatment – whether previous or current – has been correct, which will help in better control of the disease and final results². The state of the retina and the optic nerve should be evaluated as much as possible (by means of B-scan ultrasound and electrophysiological tests if those are not visible), in order to estimate the postoperative visual potential.

Prior to surgery it is essential that the patient understands and commits to frequent postoperative visits, as well as the need for indefinite topical treatment to be followed and sign the corresponding informed consent. The intervention must be performed by a surgeon with experience in penetrating keratoplasty and within an ophthalmology service that has all the departments (glaucoma, retina, oculoplastic), since it may often be necessary to associate other surgeries – previous or simultaneous to the implantation of the prosthesis or later – as drainage implants for glaucoma, pars plana vitrectomy or palpebral reconstruction³.

SURGICAL TECHNIQUE

Assembly of Boston keratoprosthesis type I

The characteristics of the design of the B-Kpro type I have already been described in other chapters of this work (see chapters 8.1 and 8.2). In the most common technique (video 8.4.1.1), after having trepanned the donor cornea – usually with a diameter between 8 and 9.5 mm depending on the case –, the donor button is placed with the endothelial side facing upwards on the base of the Barron's corneal punch (Figure 1). A manual dermatological trephine with a diameter of 3 mm is carefully centered on the graft – for which the center of the endothelial surface must be marked with a marker – and a constant and slow downward pressure is applied while turning it (Figure 2). It is currently recommended to make this central hole before trepanning the donor cornea, in order to correct an eventual decentration. An adhesive patch – from the B-Kpro mounting kit –, resting on a sterile table, is generally used to stabilize the front plate during assembly (Figure 3). The donor button with its central hole adapts to the front plate by gently pushing it down on the stem through its epithelial side. We apply viscoelastic on its endothelial side, since this is where the posterior plate adapts to its convex anterior surface. Finally, the titanium locking ring engages in the stem in the corresponding slot by applying downward pressure (Figure 4). The ring should be placed so that it fits exactly, and finally we check the assembly under the surgical microscope, to make sure that all the components are well secured.

Technique in the recipient eye

The surgical technique of B-Kpro type I has been widely described for years⁵. Once the prosthesis is mounted, the procedure is similar to that of a penetrating keratoplasty. The patient's cornea should be examined carefully under the surgical microscope. In case of vascularization, preventive hemostasis should be performed with bipolar diathermy (e.g. Wetfield Eraser 221265. 20/23 G). With a measuring compass we will calculate the size of the trepanation in the receiving cornea, and we proceed to the marking of the pupillary axis and the suture area. Care should be taken with the size of the graft and its proximity to the angle of the anterior chamber. The need for prior iridotomy or surgical iridectomy will depend on the characteristics of the patient, according to the usual criteria used in penetrating keratoplasty. It is important to monitor that the visual axis behind the optic stem is free of any obstruction. Otherwise, after performing an iridectomy, iridoplasty may be necessary to position the pupil behind the optic stem, but without sacrificing iris tissue in an unnecessary manner⁶.

In cases that require it, such as aphakic, high myopia, pediatric patients, vitrectomized patients, etc., to avoid the collapse of the eyeball we first fix a Flieringa ring with 4 scleral sutures. With the Hessburg-Barron pneumatic trepan a diameter of 8.0-8.5 mm in diameter is obtained, usually 0.5 mm smaller than the selected diameter of the donor cornea button (Figure 5).

If the patient is phakic, a lensectomy must be performed previously. If vitreous appears, an anterior central vitrectomy should be performed, which is common in previously aphakic patients. If the patient is pseudophakic with intraocular lens (IOL) in the posterior chamber, this is left in place as long as it is stable. If there is an anterior chamber IOL, it is removed and the patient is left aphakic or an IOL is implanted in a posterior chamber if there is significant residual capsular support.

Although the possibility of implanting a sutured IOL in the posterior chamber is described, we do not consider it in any case. It is mandatory that the state of pseudophakia or aphakia be determined in advance, since the B-Kpro type I must be requested with the appropriate refractive power. The pseudophakic version comes with a standard dioptric power, and in the aphakic version the axial length of the eye is used to calculate its refractive power¹.

After trepanning the recipient cornea and performing the necessary maneuvers according to the case in the anterior segment – iridoplasty, vitrectomy, manipulation of the IOL, etc. – we proceed to the suture of the previously assembled B-Kpro (Figure 6). Usually, 16 independent 10-0 or 9-0 nylon sutures are used (Figure 7), through the donor button part of the cornea-B-Kpro complex, to fix it in the receiving window in a similar way to a penetrating keratoplasty. Finally, we bury all the knots of the sutures and inspect the graft-host union to verify its tightness (Figure 8).

Although it is preferable to separate glaucoma or vitreous-retina surgeries – if necessary – they are sometimes performed in the same surgical act. In these cases, we first put a temporary Eckardt’s keratoprosthesis, to allow sufficient visualization for glaucoma surgery – usually a valvular tube implant – or vitreous-retina surgery, before finally exchanging it for the B-Kpro. To make way for the tube, a sector of the rear plate of the B-Kpro can be cut out (video 8.4.1.2).

FOLLOW-UP AND POSTOPERATIVE TREATMENT

Although the ideal antibiotic regimen for the postoperative period of a B-Kpro is not established absolutely and the dosage varies according to the previous pathology – single eye, autoimmune disease, etc. – in general, we start with vancomycin 14 mg/ml eye drops together with a 4^th generation quinolone, both 4 times a day⁷. After the first month they are progressively reduced up to 2 times a day, but it is necessary for patients to maintain this antibiotic prophylactic regimen indefinitely.

Initially dexamethasone or topical prednisolone is prescribed about 6 times a day for the first 7 days, decreasing to 4 times a day per month, and the descending pattern is followed in the next approximately 2 months, up to the dose 1-2 times per day that they must also maintain indefinitely. The oral schedule and dose of corticosteroids (prednisone or methylprednisolone) will be the standard for penetrating keratoplasty procedures, considering the previous disease, perioperative inflammation, the weight of the patient, etc. The use of sub tenon’s or subconjunctival corticoids at the end of surgery, as well as topical and systemic in the postoperative period, is established as a measure to control the intense intraocular inflammation and the formation of retroprosthetic membranes^8,9.

It is also recommended the use of topical drugs to control intraocular pressure (IOP) such as 0.5% timolol 2 times a day in the immediate postoperative period, to prevent damage to the optic nerve and because patients who respond to corticosteroids are frequent. Other hypotensors may be associated according to the characteristics and evolution of each patient.

After surgery and permanently, patients should use a scleral support contact lens of 14 to 16 mm in diameter, mainly to decrease tear evaporation, prevent eye dryness and the formation of depressions (dellen) or melting of the cornea, and also to avoid friction and increase patient comfort (sutures, upper edge of keratoprosthesis...), protect and hydrate the ocular surface, correct a residual refractive defect – if the lens has refractive correction –, and improve both the aesthetics and the reduction of reflections and photophobia when we use a cosmetic contact lens – colored – as happens in cases of aniridia. The contact lens should be exchanged on average every 2 months, although this period can be varied according to the findings in the follow-up visits. If the lens does not adapt correctly, an individual adaptation must be carried out by an expert contactologist^10,11. It is important to add the frequent use of artificial tears without preservatives to everything described above. All this will improve the retention of the keratoprosthesis and the final clinical results.

Patients will be reviewed at 24 hours, 1 week, and 1 month after surgery, and afterwards and indefinitely, every 3-4 months. Some authors instill a drop of povidone iodine at 5% at each visit to increase prophylaxis. At each visit, visual acuity will be examined, together with the anterior segment, ocular surface and tear film, contact lens, retention of keratoprosthesis, possibility of inflammation, infection, corneal melting, retroprosthetic membrane formation, etc. The IOP will be estimated by finger palpation, and in the posterior segment we will evaluate at least the optic nerve. Eventually, other imaging tests of the optic nerve (OCT of NFRL, HRT, etc.) and of the retina are added, also evaluating the possibility of performing a macular OCT, ultrasound, wide-field retinography (Optomap^®), visual field, etc.

(English translation, courtesy of Dr. Jaime Etxebarría Ecenarro)

The Boston keratoprosthesis (B-Kpro) type II is a modified version of the most common or type I, for its implantation through the eyelid in patients with especially severe diseases of the ocular surface in terminal phase. Its historical development and the characteristics of its design have already been presented in other chapters of this work (see chapters 8.1 and 8.2).

PREOPERATIVE EVALUATION

The indications of B-Kpro type II include all irreversible corneal opacities that are not susceptible to corneal transplantation or other more conventional keratoprosthesis such as type I B-Kpro, in general because they present certain associated conditions with especially severe alteration of the ocular surface:

a) Final phase of dry eye, with Schirmer test of 0 mm and corneal xerosis.

b) Anomalies of the blinking or closing of the eyelids that cannot be corrected.

c) Severe symblepharon and/or shortening of the fornices that could interfere with the stability and retention of the therapeutic contact lens needed for B-Kpro type I.

In general, these are patients with autoimmune diseases such as ocular cicatricial pemphigoid, Stevens-Johnson or Lyell syndromes, severe forms of Sjögren's syndrome and other severe dry eyes.

The preoperative evaluation should include a study of the residual tear function (Schirmer tests, etc.) and a careful inspection of the eyelids, their closing and opening, the depth of the fornices, the presence and extension of symblepharon, etc., as well as a contact lens retention test. In addition, we will perform a detailed ophthalmological clinical history, a B-scan ultrasound and biometry, check for central fixation and luminous projection (especially the nasal) and intraocular pressure (IOP) measurements. It is recommended that the implant procedure of a B-Kpro type II be performed only by expert corneal surgeons who have received specific training in this technique.

The possible risks and general benefits of the implant of a keratoprosthesis and those of this in particular should be discussed in detail with the patients, depending on their ocular pathology. They should be aware of the need to use daily lifelong medications and of the extreme importance of indefinite follow-up to be performed by qualified corneal specialists in this area. They should also know that failure to comply with the post-operative guidelines may compromise the visual benefits of the surgery and result in a loss of the keratoprosthesis and/or the eye. They must also understand and accept the impact of type II B-Kpro on appearance, so that the continued use of tinted glasses may be necessary to achieve an acceptable aesthetic appearance. Finally, patients with autoimmune inflammatory diseases such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid should understand the possible need for systemic immunosuppression and the routine control by a rheumatologist or specialist in uveitis to achieve a prolonged maintenance of the keratoprosthesis.

SURGICAL TECHNIQUE

The assembly of the B-Kpro type II is done in a manner similar to that of type I, with the obtaining of the donor corneal button, its central and peripheral trepanation-stamping, and its inclusion between both parts of the prosthesis. However, the larger anterior protrusion of the front portion of the optical cylinder makes it more unstable on a smooth surface. This makes mounting the titanium backplate more complicated.

Before the trepanning of the patient's cornea, an extensive dissection of the symblepharon and of the entire ocular surface epithelium should be performed. The palpebral margins (upper and lower), including the hair follicles, are also removed. Once this trepanation is performed, an iridoplasty is performed in the event of corectopia or an obstruction of the visual axis by the iris. A total iridectomy can also be considered, which virtually eliminates the possibility that iris tissue may interfere with the visual axis. If the iris is left intact, an iridotomy or peripheral iridectomy is recommended to reduce the risk of angle closure. The assembled type II B-Kpro is sutured in the recipient bed in a manner similar to a penetrating keratoplasty. After that, a cut is made in the middle of the upper eyelid so that, once the complete tarsorrhaphy is done, the end of the frontal portion can protrude through the eyelid. Finally, complete tarsorrhaphy is performed using 8-0 nylon sutures, placed horizontally on skin protectors (Figure 1).

It is convenient to involve different subspecialties in the treatment and follow-up of these patients. We recommend an aggressive approach to prevent postoperative glaucoma and retinal detachment. This supposes, generally, performing a vitrectomy by pars plana and the placement of a drainage device of the aqueous humor or to perform a cyclophotocoagulation in the same surgical time in which we implant the B-Kpro type II. It must be remembered that, with this model, any further intraocular intervention will require opening the tarsorrhaphy. In addition, as in the case of B-Kpro type I and other keratoprostheses, IOP can only be assessed by palpation of the eyeball, making tonometry by applanation impossible. In case of having to perform a pars plana vitrectomy in a second time, the placement of the vitrectomy ports through the eyelid, conjunctiva and sclera to reach the vitreous space has been described, to avoid the need to reopen the tarsorrhaphy.

FOLLOW-UP AND POSTOPERATIVE TREATMENT

The follow-up scheme of a B-Kpro type II is similar to that of type I, although patients with type II should be seen more frequently in the immediate postoperative period: about 2-3 times a week during the first two weeks. The antibiotic ointment is applied to the edges of the eyelid from the immediate postoperative period. This is usually discontinued when the sutures and eyelid skin protectors have been removed, approximately 2 weeks after surgery. It is advisable to clean the anterior protuberance of the B-Kpro type II at each visit with shampoo for children, to eliminate the epithelium that tends to grow on it, followed by an irrigation with balanced salt solution (BSS).

The patient to whom a B-Kpro type II is indicated usually belongs to a category with reserved or poor prognosis and with a high risk of developing endophthalmitis. Therefore, they are maintained on indefinite antibiotic treatment, generally consisting of fortified vancomycin eye drops and a 4^th generation fluoroquinolone. These medications are applied in the fissure adjacent to the anterior protuberance of the prosthesis. Although it is believed that after 2 weeks of surgery – at which time the eyelid margins have merged – there is little medication applied to the eye that will actually reach it, these antibiotics decrease the bacterial colonization of the skin, which could increase the risk of developing an infectious keratitis and endophthalmitis.

Similarly, patients receiving a type II B-Kpro are generally the same as those who tend to develop more severe postoperative intraocular inflammation. For the reason mentioned above, topical corticosteroids applied to the fissure adjacent to the protuberance of the prosthesis will not have much effect on the eyeball after two weeks of surgery. Given the need for intense corticosteroid treatment, its periocular injection (transeptal) is frequently required, usually with a long-acting agent such as triamcinolone. Topical glaucoma medications probably do not reach their goal two weeks after surgery either. At this point, oral carbonic anhydrase inhibitors represent the only option. Therefore, it is essential to achieve the best possible control of the IOP before the implant.

RESULTS

The only published series of cases with B-Kpro type II is that of the Massachusetts Eye & Ear Infirmary². It includes 29 eyes of 26 patients who received this model in a period of 10 years. All of them presented severe diagnoses such as Stevens-Johnson syndrome, ocular cicatricial pemphigoid and chemical burns. 21 patients were followed for more than one year, among which 12 eyes (57%) maintained visual acuity ≥ 0.1. Eyes that missed this vision or lost it to follow up had terminal glaucoma, previous retinal detachment, or AMD.

The implantation of a B-Kpro type II represents a therapeutic option for patients with the most severe forms of ocular surface disease. However, an adequate selection of them, with great motivation on their part and understanding of the need for medical treatment and lifelong care, are essential for the success of this surgery. There are still many challenges, in particular to reduce peri- and postoperative complications related to the complex underlying conditions in this type of patients.

INTRODUCTION

Although the results of the Boston keratoprosthesis (B-Kpro) are good in the medium to long term, it is a technique not free of complications. Many of these are related to the base inflammation, and therefore it is important to specify the diagnosis and the condition of the eye before proceeding. In general, chemical or thermal burns and noninflammatory pathologies such as multiple failures of keratoplasty have a better prognosis than cases of autoimmune causes such as ocular cicatricial pemphigoid or Stevens-Johnson syndrome. The information available on complications of B-Kpro refers mainly to its type I.

INTRAOPERATIVE COMPLICATIONS

During the implantation of a B-Kpro all the complications of penetrating keratoplasty can occur, such as intraocular or choroidal hemorrhage, etc. One specific of this prosthesis is that the trepanation for the insertion of its stem is off center on the corneal support button. When this happens, we can place the prosthesis already mounted on the window of the receiving eye and rotate it until the pupil and the stem coincide. If this is not possible, we will perform a sphincterotomy of the iris so that the pupil moves and leaves the optic axis of the prosthesis free. There may also be incidents during the assembly, especially that the titanium locking ring “jumps away” during insertion and is lost – something that the new designs without ring obviate.

POSTOPERATIVE COMPLICATIONS

The possible complications after a B-Kpro type I implant are summarized in Table 1, and their cumulative frequencies observed according to the years since surgery in Table 2. We can classify them as they occur in the anterior or posterior segment.

COMPLICATIONS IN THE ANTERIOR SEGMENT

Retroprosthetic membrane

The formation of a fibrous or fibrovascular membrane behind the prosthesis is the most frequent complication of B-Kpro. Between 25% and 65% of cases have been observed at 1 year^7,18. Their frequency at 7 years would be 49.7%¹, that is, they mostly appear in the first year. Other studies estimate it between 5.5% and 65%². Its origin would be in activated stromal cells of the donor that migrate towards the graft-receptor junction¹⁹, a process that would be related to the degree of underlying inflammation²⁰. Histologically they consist of 3 layers: a) the anterior one with donor stromal fibroblasts, which may be vascularized; b) an intermediate one with iris tissue, and c) the posterior one with epithelium of the crystalline lens that presents metaplasia¹⁹.

The main risk factor for its development is the base inflammation and therefore it is more frequent in autoimmune cases or those with uveitis²¹ and when infectious keratitis is present²². Congenital aniridia is an independent risk factor for its development⁷. The use of posterior 8.5 mm diameter titanium plates would reduce this complication by up to 13% at 6 months²⁰, and at 0% at 6 months with those of 9.5 mm²³. Although this point has not been confirmed by other groups, it would imply that a plate larger than the graft would avoid fibrous growth from the union of this with the recipient.

The retroprosthetic membranes are usually treated with Nd:YAG laser in 90% of the cases, using a cross or circular pattern, with impacts of <2 mJ to avoid damaging the optic (Figure 1). We have found a high frequency of cystic macular edema after these membranotomies – perhaps because they are inflammatory pathologies – so we always associate peribulbar corticosteroids. The remaining 10% require a surgical resection that can be performed by pars plana or even by limbal vitrectomy. Very thin membranes that do not affect visual acuity (VA) can be left for observation, although if they tend to thicken it is preferable to act before it is difficult to open them with laser.

Glaucoma

Glaucoma is the complication that most affects long-term vision in B-Kpro carriers. Its annual incidence has been estimated at 3% and its prevalence, according to studies, between 2.4% and 64%². Its mechanism may be by gradual closure of the angle by peripheral anterior synechiae, acute pupillary block by the stem in the immediate postoperative period, chronic inflammation of the angle, blocking of the trabeculum by blood or vitreous, or by response to corticosteroids. In patients with congenital aniridia, the placement of a valvular drainage device prior or simultaneous to the B-Kpro implant is recommended, regardless of whether or not there is prior ocular hypertension.

In a series of 106 operated eyes of B-Kpro, 70 were observed with previous glaucoma, of which 73% finished with glaucoma surgery at 4 years. Another 27 eyes without previous glaucoma developed it de novo, which was diagnosed by an increase in papillary excavation, and 43% of them required glaucoma surgery at 4 years. Only 9 cases remained free of glaucoma in 4 years¹¹. The progress of papillary excavation was significantly lower in cases in which a valve drainage device was implanted before or during B-Kpro surgery, compared to those who received such device in a second stage¹¹. In another study 6 months after the placement of valvular drainage in 18 eyes with B-Kpro, 7 (39%) lost VA, in 4 (22%) the tube was occluded by vitreous, another 4 suffered glaucoma progression and 3 a choroidal haemorrhage¹².

For the treatment of these patients we use antihypertensive eye drops at a higher than usual dosage, since their absorption is reduced. The preferred surgical option is a valvular drainage device, although this is also not free of complications, such as conjunctival erosions, tube occlusions, plate exposure, choroidal hemorrhages, encapsulation of the plate and even endophthalmitis³. They can be placed posteriorly with vitrectomy – in cases with the prosthesis already implanted – or anterior when performed at the same time as the B-Kpro implant (Figure 2). Cyclophotocoagulation can also be useful to control intraocular pressure (IOP) in these eyes. It is applied in 270° (about 20 points) in cases that already have a valve, to avoid the quadrant of the latter. With this treatment it has been observed that 61% maintain VA and 67% control IOP with one or no medication¹³. Experimental prototypes of new ferrofluid-based valves exist¹⁴, and the use of encapsulated slow-release latanoprost has been described for one month, impregnated in a contact lens¹⁵.

Keratolysis and extrusion of the prosthesis

Necrosis of the cornea, keratolysis or collagenolysis (melting) (Figure 3), is one of the most relevant complications, since if it progresses it can lead to the extrusion of the prosthesis. Its frequency has been estimated between 2.4% and 30.4%². It is related to the degree of inflammation, which may be due to mechanical causes – dystrichiasic eyelashes, palpebral malposition, loss of contact lens and exposure –, immunological – the underlying autoimmune diseases – or secondary to blepharitis, fungal or bacterial infections – specially Pseudomonas spp which produce collagenases – or due to poor nutrition of the supporting corneal stroma, as it used to occur in the old posterior plates without holes (Figure 4).

The risk factors for keratolysis are juvenile age, the number of previous failed transplants, persistent epithelial defects (Figure 5), exposure – palpebral abnormalities, loss of the contact lens (Figure 6) – even retroprosthetic membranes³. The necrosis rate reached 51% with the old non-fenestrated dishes. Retention of the prosthesis is lower in autoimmune diseases (80% at 1 year, 55% at 2 years and 40% at 1500 days) than in non-autoimmune conditions (96% at 1 year, 90% at 2 years and 80% at 1500 days)⁴. In the former, biologic drugs such as infliximab can improve prognosis⁵.

The retroprosthetic membranes would favor keratolysis by preventing correct nutrition of the corneal graft by occluding the orifices of the posterior plate (Figure 7). According to the Chicago group⁶, 66.7% of lysis cases had a previous retroprosthetic membrane, compared to 18% with membrane in cases without lysis. Congenital aniridia would also be a risk factor for extrusion⁷.

Mild keratolysis can be treated with topical medroxyprogesterone and an oral tetracycline (Figure 8). If this is not effective and partial extrusion is reached with aqueous humor leaking through the union with the supporting cornea, we can try to rescue the prosthesis using cyanoacrylate tissue adhesive (Histoacryl) (Figure 9), amniotic membrane⁸ – although the latter has not been effective in our experience (Figure 10) –, a conjunctival flap⁹, oral mucosal graft¹⁰, or one of synthetic dura mater (Neuropatch^®), which is our preferred technique (Figure 11 and video 8.4.3.1). In case of frank extrusion, it will be necessary to replace the prosthesis⁴.

Infectious keratitis

Despite lifelong antibiotic treatment, it is possible to develop an infectious keratitis that must be aggressively treated and monitored closely to ensure that it does not progress to endophthalmitis (Figure 12). Its frequency has been estimated between 0% and 17.8%². The prophylactic use of fortified vancomycin eye drops reduces the severity of early bacterial keratitis after B-Kpro¹⁶.

Loss of contact lens

In addition to avoiding the rubbing of the eyelid with the external surface of the prosthesis, the contact lens prevents dehydration of the cornea (Figure 6) and the formation of persistent epithelial defects, which can progress to keratolysis and even extrusion.

Corneal or scleral inflammation

Both the artificial part of the B-Kpro and the supporting corneal homograft favor corneal inflammation¹⁷. The second one – let us not forget – can be the object of immunological rejection, although this does not appear as in a keratoplasty. Scleritis has been observed between 0% and 5.4% of cases². It is usually controlled with topical and sometimes systemic medication, although it may be a factor that promotes keratolysis.

Epithelization of the optical surface

Occasionally, the corneo-conjunctival epithelium surrounding the surface of the B-Kpro optics may grow on it (Figure 13) and produce a decrease in VA. In this case we proceed to its removal with a swab dipped in neutral shampoo lowered with physiological saline.

COMPLICATIONS IN THE POSTERIOR SEGMENT

Retinal detachment

Retinal detachments have been observed between 2.8% and 19% of cases according to the series². They can be regmatogenous or, more frequently, tractional because of chronic inflammation. Therefore, they are frequently associated with vitreous-proliferative retinopathy, which overshadows the visual prognosis (Figure 14). It is recommended to treat it by pars plana vitrectomy – often with exchange with silicone oil – and to avoid cerclages as much as possible in order not to increase inflammation²⁴.

Endophthalmitis

B-Kpro involves a loss of the epithelial barrier that normally prevents the passage of microorganisms, since the plastic material never binds physiologically with the surrounding tissues. The prophylactic use of fortified topical vancomycin (14 mg/ml) reduces the frequency of endophthalmitis after B-Kpro²⁵. However, the recommendations vary according to the authors and the underlying pathology. In the case of non-autoimmune processes, after the first month, 1 single drop of polymyxin/trimethoprim or vancomycin and moxifloxacin is recommended indefinitely. In cases with autoimmune disease, a similar regimen is recommended, but with 2 daily applications and always adding vancomycin. However, this eventually promotes fungal endophthalmitis (Figure 15), as the normal bacterial flora disappears. It is therefore recommended to apply a drop of 5% povidone iodine at each control visit, as well as cycles with a topical antifungal (e.g. voriconazole 2%) 1 drop every 8 hours for 7 days, every 4 months, indefinitely.

Endophthalmitis in B-Kpro carriers are between 0% and 12.5%². The risk factors are infectious keratitis, conjunctival erosion by the drainage tube, failure to comply with daily topical antibiotic treatment, continued use of corticosteroids, poor hygiene or non-use of contact lenses, keratolysis and suffering from an autoimmune pathology. Gram+ germens are the most frequent cause, although the incidence of Gram- and fungi is increasing. If endophthalmitis occurs in a B-Kpro, 80% of them lose useful vision. For its treatment, a pars plana vitrectomy must be carried out immediately, and a systemic antibiotic or antifungal treatment must be instituted in addition to the intravitreal treatment^24,26. Time is critical in these cases: treatment should not be postponed beyond 24 hours. In our experience it is also vital to remove the prosthesis as soon as possible (Figure 16). In this way we have managed to save eyes that suffered endophthalmitis after B-Kpro. If we do not act immediately, the formation of vitreous-retinal membranes will lead to poor eye viability in most cases.

Sterile vitritis

In some cases, turbidity occurs in the vitreous chamber of a non-hematic cause, in a calm eye, without pain, hyperemia or secretions (Figure 17). This has been observed between 0% and 14.5% according to the series². It would be a uveitis-like immune reaction to certain antigens released. It usually responds slowly to corticosteroids in 2 to 9 weeks, although it has sometimes required a vitrectomy²⁷.

Vitreous hemorrhage

Intraocular bleeding, especially in the early postoperative period, is treated expectantly, with ultrasound controls and relative rest with the head incorporated. You can consider a pars plana vitrectomy to recover vision if it becomes persistent²⁸.

Choroidal detachment

Hypotony in the early post-operative period can lead to choroidal detachment. A greater than usual postoperative inflammation may be an additional factor. In general, an expectant attitude, ultrasound controls and topical and systemic anti-inflammatory treatment are usually sufficient.

Cystic macular edema

Its frequency varies according to the studies, reaching up to 33%²⁸. Its diagnosis and follow-up are done by optical coherence tomography (OCT).

Chronic hypotony

Hypotony is one of the most feared complications due to the difficulty of its treatment. The cause may be excess filtration of a drainage device, corneal necrosis around the prosthesis or ciliary inhibition. It is associated with retroprosthetic membranes²⁹, which would progress towards the ciliary body causing a cessation of the aqueous secretion. If such fibrosis progresses further back it can produce a tractional retinal detachment and lead to phthisis bulbi. Its treatment has been proposed by pars plana vitrectomy and exchange with silicone oil³⁰.

There are multiple studies that indicate that the Boston keratoprosthesis implants (B-Kpro) (Figure 1) have achieved great improvements in visual acuity (VA) of patients with corneal alterations that made the prognosis of keratoplasty very poor. Unlike these, the recovery after a B-Kpro occurs very quickly, sometimes almost immediately. This is due to the fact that being a carved piece of plastic does not depend, as a graft, on regaining transparency or presenting astigmatism (Figure 2)^1,2. However, long-term vision is ultimately determined by two main factors: pre-existing ocular comorbidities (glaucoma, retinal problems, etc.) and the development of post-operative complications (glaucoma, retroprosthetic membranes, endophthalmitis, extrusion, etc.). The information on results of the B-Kpro refers mainly to type I (for type II see chapter 8.4.2).

INFLUENCE OF THE INITIAL DIAGNOSIS

The prognosis of B-Kpro is directly associated with the preoperative diagnosis. Studies indicate that patients with Stevens-Johnson syndrome (SJ), ocular cicatricial pemphigoid (OCP), chemical burns and congenital aniridia evolve worse than those with non-cicatricial etiologies such as repeated failures of keratoplasty, followed by corneal opacities secondary to infections or corneal dystrophies³.

INFLUENCE OF POSTOPERATIVE COMPLICATIONS

The most frequent postoperative complications of B-Kpro include retroprosthetic membranes, although its treatment is simple by means of Nd:YAG laser in 90% of the cases – in the rest a surgical resection is necessary. Glaucoma – whether pre-existing or de novo, is another complication that causes permanent loss of postoperative VA in patients with B-Kpro. To prevent it, oftentimes drainage devices are placed at the same time as the prosthesis. For the detection and monitoring of glaucoma in patients with B-Kpro, frequent controls of the intraocular pressure (IOP) by finger palpation and the appearance of the papilla every 2 months, as well as optical coherence tomography (OCT) of the optic nerve fiber layers and campimetry every 4-6 months are needed.

Many of these patients have ocular surface disease and should be monitored periodically for the control of possible sterile ulcers and infectious keratitis. Postoperative care includes the placement of a therapeutic contact lens to protect the ocular surface⁴, which helps protect the corneal tissue from dehydration and epithelial defects.

Anterior segment OCT can be used both to evaluate the formation of retroprosthetic membranes, and to monitor the anatomy of the angle and the development of iridocorneal adhesions. Other factors such as cystic macular edema also cause vision impairment.

Endophthalmitis is the most devastating complication of B-Kpro. This is an inherent risk due to the lack of integration of PMMA with ocular tissues. There is no epithelization of the anterior surface of the prosthesis that serves as a barrier for germs and, therefore, there will always be a potential space for their access. Among the risk factors for the development of endophthalmitis, the underlying disease is included, particularly those cases with SJ or OCP⁵. Keeping patients on topical antibiotics for life reduces the incidence of endophthalmitis^6,7.

PUBLISHED RESULTS

A retrospective multicenter study recently reviewed the results of 158 eyes that underwent B-Kpro type I in 5 centers in the USA. Of these, 73% were due to multiple failures of corneal transplants, 23% had autoimmune disease or chemical burn, 58.3% had previous history of glaucoma. 1/3 of cases had a history of retinal damage. In this cohort, VA was ≥ 0.1 preoperatively in only 10.8% of patients. Once the B-Kpro was implanted, 70% of the eyes that maintained it – or 60% if we also consider those that underwent extrusion – obtained VA ≥ 0.1 during the mean follow-up period of 46.7 ± 26 months, with 52.5% cases with follow-up >4 years. The probability of maintaining a VA ≥ 0.1 up to 7 years was 51% between the eyes that kept the B-Kpro in position – or 44% if we consider all the eyes, including those that extruded the prosthesis –. The overall retention rate of B-Kpro type I was 94.1% at 1 year, 83.8% at 2 years, 79.1% at 3 years, and 66.8% at both 5 years and 7 years. Patients with severe ocular surface disease – whether autoimmune or chemical burn – had significantly lower retention rates (35% at 7 years) compared to the other patients (78% at 7 years).

The most frequent complication was the formation of retroprosthetic membranes, which occurred in 49.7% of the eyes. Of these, 48.4% did not require any intervention, 33% underwent Nd:YAG membranotomy and 18.6% surgical membranectomy. The increase in IOP occurred in 36.2% of the patients who had it previously under control. 21.6% of the eyes implanted with B-Kpro required surgical intervention for glaucoma: valvular drainage device or cyclophotocoagulation with diode laser. This percentage was similar between eyes that previously had B-Kpro glaucoma and those that did not. Other complications include keratolysis or sterile corneal necrosis (6.7% at 1 year, 12.2% at 3 years, and 19.5% at both 5 and 7 years), retinal detachment (4.6% at 1 year, 11.2% at 3 years, 16.1% at 5 years, and 18.6% at 7 years), endophthalmitis (3.1% at 1 year, 4.8% at 3 years, 10.5% at 5 years and 15.5% at 7 years), cystic macular edema (10.1%), persistent epithelial defects (4.4% at 1 year, 7.1% at 3 years, 8.2% at 5 years and 7 years), and infectious keratitis that did not progress to endophthalmitis (0.8% at 1 year and 3.4% at 3, 5 and 7 years)⁸.

Other less extensive series confirm the visual benefit with the implantation of B-Kpro and, similarly, suggest a natural history in which VA tends to decrease over time due to complications. In a study by the University of California at Davis, 89% of patients reached VA >0.1 at 1 year, but this percentage declined to 29% at 4 years of follow-up. Retroprosthetic membrane formation occurred in 39-55% of the patients in these studies. The elevated IOP was recorded in 18-40% of the eyes and can represent a large part of the decrease in VA over time. The overall retention rate of B-Kpro in these studies was 80-88%^9-11.

The «Boston Kpro Study Group» has published several multicenter studies to better assess specific complications. In a study of 265 eyes with a mean follow-up of 17.8 months, the rate of retroprosthetic membrane formation was 31.7%. Risk factors for its development include congenital aniridia and infectious keratitis as indications for the placement of B-Kpro¹².

Another study evaluated the results of B-Kpro in 300 eyes and found a retention rate of 93% with a mean follow-up of 17.1 months. The loss of B-Kpro was due to sterile keratolysis, fungal infections, the formation of a dense retroprosthetic membrane or endophthalmitis. Three risk factors were found to increase the likelihood of loss of B-Kpro: 1) autoimmune etiology (OCP or SJ), 2) exposure of the ocular surface requiring tarsorrhaphy, and 3) increase in the number of keratoplasties prior to the B-Kpro¹³. In a separate study, the risk factors for sterile keratolysis in B-Kpro included concomitant autoimmune disease, exposure of the prosthesis and retroprosthetic membranes. When these cover the posterior plate, they can occlude the aqueous flow through its holes and prevent the delivery of nutrients to the corneal tissue¹⁴ (Figure 3).

A study of international results included 107 eyes that underwent B-Kpro implantation. In this series, 70% of patients reached VA >0.1 at 6 months. At 2 years, 59% retained VA >0.1. The most frequent complications were retroprosthetic membrane (27%) and sterile corneal necrosis (18%). An increase in IOP was found in 13.9% and endophthalmitis was present in 9% of the eyes. The retention rate of the prosthesis was 80.5%. This indicates that the international results with the B-Kpro have been comparable with those obtained in the USA¹⁵.