Corneal surgery

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CHAPTER 21 Corneal surgery

Chapter outline

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Corneal and anterior segment trauma

Amit Patel, Massimo Busin and Carlo Enrico Traverso

The conjunctiva and cornea as the most anterior structures of the eye are prone to damage from a variety of insults. It is important to gauge the extent of injury, decide whether the trauma requires medical or surgical treatment, and determine the realistic functional prognosis. This assessment must be made in context of the whole patient and life-threatening injuries must be excluded prior to any ocular injury. Although the present text relates to anterior segment and corneal trauma, scleral and posterior pole injuries might coexist and need appropriate diagnosis and treatment.

Preoperative evaluation

Corneal laceration

Not all corneal lacerations require surgical intervention. Small self-sealing or minimally leaking corneal lacerations may be treated with topical antibiotics and cycloplegics. A bandage contact lens or glue may be used in cases where a slow wound leak is present.

Large full-thickness lacerations, or those that continue to leak after 1 or 2 days, are best treated by surgical closure. Surgical intervention should also be considered in large, deep or gaping partial-thickness lacerations in order to minimize corneal scarring and irregularity. In severely traumatized corneas where there is loss of tissue, a donor patch graft or penetrating keratoplasty may be indicated.

Viscoelastic may be injected through the wound or via a paracentesis to reform the anterior chamber if required. 10.0 Nylon is preferably used to close the corneal laceration. The placement of the primary suture depends on the configuration of the wound. When linear, it is placed at the center of the wound with subsequent sutures bisecting the remaining portion. If angulated, the primary suture is placed at the apex of the laceration. Stellate ruptures are difficult to repair and may require triangular, ‘X’ or purse-string sutures (Fig. 21.1). Attempts should be made to place sutures outside the visual axis if possible.

Particular care should be taken when placing sutures in bevelled lacerations. The entry and exit points of the sutures should be appropriately placed in order to avoid overriding of the wound edges or dehiscence secondary to ‘cheese-wiring’ of the tissue (Fig. 21.2).

Any viscoelastic in the anterior chamber must be replaced with balanced salt solution in order to avoid extreme intraocular pressure (IOL) spikes and any anterior synechiae lysed with a cyclodialysis spatula. A Seidel test is performed after closure to ensure a watertight closure.

Hyphema

Most traumatic hyphemas may be treated medically; however, surgical intervention should be considered in cases with prolonged and severely raised IOP, which may lead to optic nerve damage and corneal staining1. The corneal staining may develop rapidly, especially in younger individuals, but can take several months or years to clear.

Surgical evacuation of the blood is indicated in cases where: (i) early corneal staining is noted, especially in the amblyopic age; (ii) the IOP has been over 40 mmHg for 2 days or over 30 mmHg for 7 days; (iii) the patient has sickle cell hemoglobinopathy or trait and raised IOP. Persistent total hyphemas may also be evacuated to prevent peripheral anterior synechiae and chronic intraocular pressure elevation.

Removal of the blood clot may be carried out with a mechanical vitrector or irrigation and aspiration2. Two paracenteses are made and an irrigation cannula or anterior chamber maintainer placed in one and a vitrector in the other. The aspiration and cutting functions of the vitrector are effective in removing the clot whilst minimizing traction on the iris and iridocorneal angle. Irrigation and aspiration may also be used without the cutter; however, the clot may be too thick to be evacuated and may result in unnecessary traction.

Intraoperative bleeding may occur and adequate tamponade should be applied to stop the bleeding. This may be achieved by elevating the intraocular pressure and/or injecting viscoelastic material at the site of bleeding. Injection of an air bubble into the anterior chamber with intraocular pressure elevation may also be effective. Viscoelastic material if used should be carefully removed in order to prevent postoperative intraocular pressure rise.

Lens trauma

Lens injury following anterior segment trauma may be in the form of cataract, luxation, rupture, or extrusion. In the presence of an intact lens capsule, the cataractous or subluxated lens need not be addressed at the time of primary repair. This allows time to evaluate the extent of injury, carry out appropriate biometry, and plan for elective surgery. Capsular rupture, lens induced inflammation, and secondarily elevated IOP generally necessitate lens removal at the time of primary repair.

In cases where the lens requires extraction, opinions vary on the timing of intraocular lens (IOL) implantation. A posterior chamber IOL may be placed at the time of primary repair if the wounds are clean, the posterior capsule intact, and no posterior segment trauma/foreign body is present. In such cases, biometry of the contralateral eye may be used to gauge the required IOL power.

Poor visualization due to the corneal trauma and uncertainty of the capsular and zonular integrity pose a challenge for cataract extraction at the time of primary repair. A separate limbal incision is created following repair of the corneal laceration. The anterior capsular tear may be converted either to a curvilinear capsulorrhexis or to a ‘can-opener’ type of capsulotomy. Gentle hydrodelineation may be carried out and in most cases the lens can be aspirated with minimal phacoemulsification. Care should be taken to avoid undue stress on the zonules and there should be a high index of suspicion for zonular weakness, anterior and posterior capsular tears, and vitreous prolapse.

Conjunctival flap surgery

Amit Patel, Carlo Enrico Traverso and Massimo Busin

Conjunctival flap surgery has been used for many years to manage various corneal and ocular surface diseases. Over time, development of newer drugs, lubricants, bandage soft contact lenses, and collagen shields has diminished the indications and need for conjunctival flaps. However, despite this and the advent of amniotic membrane transplantation, there is still a group of patients for whom conjunctival flap surgery is a viable and effective solution.

Of the numerous techniques to cover the cornea with conjunctiva, the total conjunctival flap popularized by Gundersen4 and the partial conjunctival flap are the most effective. The aim of conjunctival flap surgery in ocular surface disease and ulceration (both infectious and non-infectious) is to prevent stromal melting and possible perforation, thus stabilizing the eye and eventually allowing later surgery aimed at rehabilitating vision. However, for conditions that do not allow later corneal surgery (i.e. extreme dry eyes, high grade stem cell deficiency, etc.) a conjunctival flap may be compatible with vision up to 20/400 (see Fig. 21.4C).

Indications

Conjunctival flaps may be utilized in a variety of corneal diseases that are not responsive to medical management, induced ptosis, or tarsorrhaphy. Chronic ocular surface disease and non-healing corneal epithelial defects are excellent candidates for flap surgery5. It has also been used to stabilize the eye in chronic and non-response viral, bacterial, and fungal corneal infections68. In the presence of a descemetocele or perforation, a corneal patch must be carried out prior to considering a conjunctival flap.

Along with providing corneal support and fibrovascular tissue to fill epithelial defects, the associated blood supply aids to bring immunoglobulins, anticollagenases, and systemic antibiotics to the lesion9. This advantage is not afforded when applying non-living tissue such as amniotic membrane. Other indications include neurotrophic ulcers, marginal ulcers, exposure keratopathy, and bullous keratopathy with low visual potential.

Surgical technique

Total conjunctival flap

Peribulbar or retrobulbar anesthesia may be administered and an eyelid speculum creating good exposure of the conjunctiva is inserted. The corneal epithelium is removed with a sharp rounded blade or alcohol. Any necrotic stroma tissue is also removed carefully. The debridement is best performed at the beginning of surgery so as not to neglect to perform it after the flap is created. In addition, any bleeding at the limbus will have had time to undergo hemostasis while the flap is being fashioned.

A 6.0 silk or polyglactin 910 traction suture may be placed through the cornea near the limbus to allow downward rotation of the globe during flap dissection. The superior conjunctiva is dissected from the underlying Tenon’s tissue by injecting 1–2 ml of local anesthesia (e.g. 1–2% lidocaine) or balanced salt solution with a 27 gauge needle. Epinephrine in a dilution of 1 : 100 000 may be added to achieve temporary vasoconstriction. The injection site should be situated away from the conjunctiva intended for flap use so as to prevent creating a ‘buttonhole’. A small horizontal incision is made with Wescott scissors at the fornix through conjunctiva, but not into Tenon’s fascia. Then the blunt and sharp dissection is performed with Wescott scissors and non-toothed forceps, separating conjunctiva from Tenon’s, ideally in the plane created by the local anesthesia. Dissecting the conjunctiva with the scissors placed underneath (Fig. 21.3A and B), as opposed to under direct visualization, ensures that the correct plane is maintained and minimizes the risk of buttonhole formation. The dissection is carried out in a meticulous fashion to the limbus and care is taken to avoid buttonholes, although this may be difficult in eyes that have had chronic inflammation, scarring, surgery, or trauma.

Once most of the conjunctiva is dissected down to the limbus, the horizontal incision can be extended several millimeters toward the nasal and temporal canthi (Fig. 21.3B). The nasal and temporal portions of the flap then need to be undermined. Once the entire flap has been created, the conjunctival dissection is continued forward until it comes free at the limbus. A 360° conjunctival peritomy is then performed. A small amount of undermining of the inferior limbal conjunctiva often makes the peritomy and subsequent suturing of the conjunctival edge easier. The limbus is then debrided of any remaining epithelium.

The ocular surface is irrigated and the flap carefully slid over the cornea. It is first sutured inferiorly to episclera and the inferior conjunctiva using interrupted 8-0 absorbable sutures (e.g. Vicryl). Once the flap is secured inferiorly, the superior edge is secured to the Tenon’s and episclera without excessive tension. Care is taken to avoid imbedding a fold of conjunctiva. The crescentic area of bare episclera which remains in the area from where the flap was obtained, usually epithelializes within days. An inferior conjunctival flap may be considered to spare the upper quadrants when filtration surgery is likely to be needed in the future.

Buttonholes of the flap are the most common intraoperative complication and can lead to flap retraction. These should be closed with interrupted or purse string sutures and, if located in an area of flap that covers the cornea, the sutures should be anchored to the underlying cornea. Fig. 21.4 illustrates the pre- and postoperative appearance of a total conjunctival flap. Failure to separate Tenon’s fascia from the overlying conjunctiva leads to fibrovascular proliferation and poor transparency (Fig. 21.5).

Partial conjunctival flaps

Localized limbal and paralimbal lesions in an otherwise healthy cornea may occasionally be treated with a partial conjunctival flap. The corneal epithelial debridement is carried out in the area expected to be covered by the conjunctival flap and the conjunctiva is ballooned with local anesthesia as described above. The width of the conjunctival flap should be approximately 1.5 times the width of the lesion to be covered in order to allow for proper suture placement and account for late flap retraction. In order to secure the conjunctival edge onto the cornea and prevent dehiscence and retraction, it is important to create a ledge of cornea into which to suture the conjunctiva. A groove is made into healthy cornea at the edge of the intended extension of the flap with a diamond or metal blade and a small triangular strip of cornea is removed to create a ledge (Fig 21.6).

The partial flaps may be fashioned in various ways. A simple advancement flap is created much in the same manner as a total flap; however, the amount of conjunctival dissection is smaller and the edge of the flap is sutured on to the cornea with 10-0 nylon sutures. An advancement flap is prone to retraction with time and a relaxing incision through the conjunctiva and Tenon’s tissue, away from the limbus, may reduce the likelihood and allow the bulbar conjunctiva distal to the incision to retract. A pedicle (Fig. 21.7) or bridge flap (Fig. 21.8) may be considered as alternatives. A bridge flap may be created with a narrow band of conjunctiva that runs across the corneal lesion allowing a greater view of the anterior chamber. Edges of the flap overlying the cornea are sutured with 10-0 nylon and those overlying episclera with 8-0 polyglactin 910 (e.g. Vicryl). Non-absorbable suture knots must be buried.

Pterygium surgery

Amit Patel, Carlo Enrico Traverso and Massimo Busin

A pterygium (from the Greek pterygion meaning ‘wing’) is a degenerative wing-like fleshy mass of bulbar conjunctival and subconjunctival tissue that arises at the limbus and encroaches onto the corneal surface (Fig. 21.9). It consists of an elevated leading edge (head) and a broad triangular fibrovascular mass (body). Although it most commonly originates from the nasal limbus, temporal or simultaneous nasal and temporal pterygia may occasionally exist. Histopathologically, it is characterized by fibrovascular proliferation and ‘elastotic degeneration’, i.e. positive to elastic tissue stain, but is not sensitive to elastase. In addition, there is alteration of the basal corneal epithelial layer, destruction of Bowman’s layer, and scarring of the superficial corneal stroma.

Although the precise pathogenesis of pterygia formation remains speculative, it is largely thought to be related to ultraviolet light exposure10,11. This is supported by its formation in the interpalpebral fissure as well as the higher prevalence among people living closer to the equator and in those with outdoor occupations. Ocular surface irritation from dust, sand, etc. has also been implied as a causative factor.

Surgical technique

The goals of pterygium surgery are to remove the lesion, restore the conjunctival anatomy, leave the cornea as smooth and clear as possible, and prevent recurrences. Historically there have been, and there continue to be, numerous techniques to manage pterygia. Techniques described include avulsion or excision of pterygia leaving either ‘bare sclera’, closure with conjunctiva (direct, sliding and auto-grafts) or amniotic membrane and use of peripheral lamellar corneal grafts. Various adjuncts (e.g. mitomycin C) have also been used in combination with the different techniques. The lack of consensus on the preferred surgical approach is due to recognition that no single surgical method has proven to be superior. The following will describe one widely used technique of pterygium excision and conjunctival transplant.

Primary pterygium

Peribulbar anesthesia is most commonly used; however, the procedure may also be performed under topical and/or subconjunctival anesthesia. An eyelid speculum providing good exposure is placed and a limbal traction suture (6.0 silk or polyglactin 910 on a spatulated needle) may be placed at the 12 or 6 o’clock position, or both, to allow more extensive globe rotation and aid rectus muscle identification.

The outline of the pterygium is marked with a gentian violet marker, and anesthetic or balanced salt solution is injected subconjunctivally to balloon the pterygium (Fig. 21.10A). This allows easier dissection and protects the underlying rectus muscle from accidental damage.

The head of the pterygium is lifted with fine toothed forceps and gentle dissection using a rounded sharp blade (e.g. Beaver No. 57) or Tooke’s knife is employed to roll the tissue towards the limbus (Fig. 21.10B). A superficial keratotomy may be made to outline the leading edge prior to the dissection and a superficial plane of dissection is maintained up to the limbus. Attempts must be made to maintain a level and smooth plane of dissection. On reaching the limbus, the bulbar portion (body) of the pterygium is then excised carefully down to the sclera using Wescott scissors. Particular attention should be paid in dissecting and removing all the underlying Tenon’s tissue. To minimize the risk of recurrence, this dissection should lead to complete removal of all the hypertrophic fibrotic tissue underlying the pterygium and must be carried out up to the recti perimysium, into which it usually blends. The gentian violet marks allow visualization of the margins following the subconjunctival injection and avoid inadvertent excision of the plica semilunaris and caruncle. Wet field cautery may be applied sparingly to achieve hemostasis. Remnant tissue at the limbus and sclera is scraped using a rounded blade or large diamond burr.

The rolled edges of the remaining conjunctiva are unraveled with forceps, and the conjunctival defect is then measured with calipers. The globe is rotated upward with the limbal traction suture and the inferior bulbar conjunctiva away from the pterygium excision is exposed. In general, it is advisable to spare the superior conjunctiva, in case filtration surgery is needed later in life. A limbal edge is preferred and a gentian violet marker is used to mark the outline of the remaining three sides of conjunctival graft to be created (Fig. 21.10C). The conjunctiva is dissected from the underlying Tenon’s tissue by injecting 1–2 ml of local anesthesia (e.g. 1%–2% lidocaine) with a 27-gauge needle. The injection site should be situated away from the conjunctival graft intended for use so as to prevent creating a buttonhole. A small incision is made just peripheral to the superior corner of the marked area. Blunt and sharp dissection is performed with Wescott scissors and non-toothed forceps to ensure that the conjunctiva is separated from Tenon’s, ideally in the plane created by the local anesthesia. The dissection is carried out in a meticulous fashion to the limbus and care is taken to avoid buttonholes. Once the conjunctiva is dissected free from the underlying Tenon’s, the edges of the graft are cut slightly larger than the outline marks. This allows for the natural tissue shrinkage and also incorporates the gentian violet marks, which are useful in aiding graft orientation.

Once the graft is totally free, the area to be grafted is re-examined to make sure it is clear of significant clot or active bleeding. The ocular surface is moistened with balanced salt solution and fine non-toothed forceps are used to slide the graft onto the bare area ensuring that the epithelial side remains up and the limbal areas correspond. The risk of tissue rolling, incorrect orientation and excessive manipulation is minimized by sliding the graft and thus lifting it off the eye should be avoided.

Once the edges of the graft are approximated to the edges of the bulbar conjunctiva, absorbable sutures (e.g. polyglactin) are used to secure the graft. The first sutures are positioned through the two limbal corners of the graft, into sclera, and then into conjunctiva to place the limbal edge of the graft on gentle stretch. If the limbal edge is on good stretch, no additional sutures are required. The next two sutures secure the posterior corners of the graft to the bulbar conjunctiva. Additional sutures are placed to close the wound edges and horizontal mattress sutures may be used to anchor the edges to the underlying sclera (Fig. 21.10D). It is important to suture the graft to conjunctival edges, and not just Tenon’s, as these two tissues may appear similar. A wet swab may be used to distinguish between the two, as Tenon’s tends to stick to the swab whereas conjunctival tissue does not. The conjunctival defect in the area from which the graft is harvested may be sutured, but is usually allowed to re-epithelialize spontaneously. Suture knots are not generally buried and any buttonholes are sutured and anchored to the underlying sclera.

Recurrent pterygium

Recurrent pterygia pose an increasing challenge to the surgeon as they usually exhibit more conjunctival inflammation and aggressive fibrovascular growth compared with primary pterygia. The normal anatomy is disrupted from previous surgery and the resultant fibrovascular scarring. Furthermore, there may be associated corneal scarring and/or thinning, limited ocular motility, and limbal stem cell deficiency.

The additional scarring results in increased intraoperative bleeding and risk of damage to the underlying rectus muscle which may be adherent to the recurrent pterygium. Thus caution should be taken to lift the pterygium prior to dividing any tissue. It is imperative to identify and hook the rectus muscle whilst excising the recurrent tissue. Vasoconstrictors may be used to reduce intraoperative bleeding and cautery must be applied judiciously in order to avoid muscle and scleral damage.

If a conjunctival graft was performed during the previous operation, the same quadrant of bulbar conjunctiva may be difficult to dissect and fashion into another graft. In such cases, and especially when there is limbal stem cell deficiency, a graft may be taken from the fellow (uninvolved) eye. This possibility needs to be discussed with the patient prior to surgery. Amniotic membrane may be used as an alternative in such cases or in patients with glaucoma in whom it is important to preserve the superior conjunctiva. Alternatively, the area of bare sclera corresponding to the excision may be allowed to re-epithelialize spontaneously.

Residual corneal opacities may be treated with photo therapeutic keratectomy (PTK). Lamellar keratoplasty may be required in the presence of significant corneal scarring or thinning to achieve visual rehabilitation and reduce recurrence12.

Postoperative care

Postoperative care includes topical antibiotics and corticosteroids. Initially, ointments are preferred over drops 4–6 times a day as they tend to be more comfortable. A therapeutic bandage contact lens may also be applied. Once both corneal and conjunctival re-epithelialization is completed, the medication can be changed to corticosteroid drops, which are tapered slowly over several weeks. Non-absorbable sutures, if used, should be removed between 3 and 6 weeks postoperatively.

During the first two postoperative weeks there is often significant edema of the conjunctival graft. Continued frequent use of topical corticosteroids leads to resolution of the edema, which does not affect graft survival as long as the sutures holding the conjunctival transplant do not loosen prematurely. Significant graft swelling can cause dellen formation, which needs to be treated with aggressive lubrication.

Conjunctival or corneal infections may develop after surgery and should be treated with aggressive topical therapy as appropriate following swabs for microbiology cultures.

Large buttonholes, poor wound apposition, and cheesewiring of sutures due to excessive tension on the graft increase the chances of early graft healing problems. Graft dehiscence may also occur due to infection or loose sutures and may require re-suturing or replacement.

Complications which are generally not debilitating or sight threatening include astigmatism, graft retraction, inclusion cysts, suture granulomas, and hematomas.

The most common complication of pterygium surgery is recurrence. Adjunctive therapies may be applied at the time of recurrent pterygium excision. Although beta radiation, thiotepa, daunorubicin, etc. have been used previously, mitomycin-C application remains popular due to evidence of reducing recurrence. However, the lack of consensus on the precise dose and duration of application, together with the potential adverse effects including scleral perforation, limit its use and call for precautions.

Other significant complications include corneal irregularity and scarring, excision-induced limbal stem cell deficiency, restriction of ocular motility, rectus muscle disinsertion, and infection.

Excimer laser phototherapeutic keratectomy

Angelo Macrì and Carlo Enrico Traverso

Excimer laser phototherapeutic keratectomy (PTK) has been performed to treat anterior corneal pathology for the last 20 years. FDA approved PTK in 199513. Since then indications and techniques have continuously evolved.

Stromal lesions

Dystrophies of Bowman’s layer, such as Reis–Bucklers dystrophy, and stromal dystrophies, such as granular or lattice dystrophy, are the main indications.

Best results are obtained when the opacities are in the anterior 20% of the cornea. It is a general opinion that PTK may be tried in all patients with dense superficial opacities before undergoing a more invasive procedure, such as lamellar or penetrating keratoplasty13,19.

Corneal haze after excimer laser corneal surgery

The most important predictive factor in haze formation has been reported to be the depth of ablation that is linked to the attempted dioptric correction. This could be related to surface irregularities that impede normal corneal repair when higher corrections are performed. In theory PTK could be very useful in preventing haze by obtaining a smoother surface after PRK.

PTK can be also used to treat late haze and subepithelial scarring after PRK (Fig. 21.11). In both cases MMC is utilized because predominant effect of MMC in blocking haze formation was at the level of profound inhibition of the replication of keratocytes and myofibroblast progenitor cells in the corneal stroma that occur following the normal keratocyte apoptosis response to epithelial removal during surface ablation.

Although its utility and efficacy for haze prophylaxis are well documented, the long-term safety profile of MMC use in refractive surgery is not known and it is still used in an off-label fashion.

Technique

The technique varies according to size, shape, density, and numbers of the cornea lesions (Figs 21.12 and 21.13).

Thus it can be used for:

Elevated lesions are generally debulked with a blade before PTK.

The epithelium is generally mechanically removed if loose and irregular, while it is left in place before PTK if it is smooth, because may act as an effective masking agent.

Modulating agents such as artificial tears, also called masking fluid, can be very useful in achieving a uniform corneal surface. For this purpose, variable mixtures of hyaluronic acid solutions were proposed.

The treatment is stopped several times to check, also at the slit lamp, the progress of photoablation.

PTK can be also performed topographically guided or ‘customized’13,21.

Intraoperative mitomycin C (MMC) can be used after PTK to try to decrease postoperative haze and recurrence.

Commonly MMC is used at 0.02% (0.2 mg/ml) concentration, on a 6–8 mm circular sponge for 60 seconds; it is then irrigated with 30 ml of saline13,20,22. Other regimens are also suggested.

Summary

PTK is a very versatile technique that is quite effective at treating a wide variety of anterior corneal lesions (Figs 21.14 and 21.15) with a low risk rate if performed properly. In particular elevated lesions and opacities in the top 10–20% of the corneal stroma generally do very well. If unsuccessful, an anterior lamellar graft can almost always be performed and thus PTK may be tried before proceeding to a corneal transplant, considering its excellent risk/benefit ratio13.

Corneal transplantation

Massimo Busin, Amit Patel, Davide Venzano and Carlo Enrico Traverso

Historical perspective

There is considerable debate regarding who first came forth with the concept of replacing diseased or scarred corneas with living tissue. Guillaume Pellier de Quengsy first suggested replacing the diseased cornea with a thin glass disc (similar to a keratoprosthesis) in 1789, and Erasmus Darwin, grandfather of the famed Charles Darwin, first suggested replacing a scarred cornea with a small piece of living donor corneal tissue. Franz Reisinger published the results of his experiments on corneal transplantation in rabbits and chickens in Germany in 18242325. S.L. Bigger successfully replaced the scarred cornea of his pet gazelle with a healthy donor cornea from another gazelle in 183724. Richard Kissam, a New York ophthalmologist and general practitioner, was the first to operate on a human using a pig donor cornea; however, the graft became opaque shortly thereafter24. The advent of ether and chloroform inhalation anesthesia, topical cocaine anesthesia, local infiltrative anesthesia, and antiseptic surgery during this early period revolutionized corneal transplantation, as it also did for many other types of surgery.

These important companion discoveries were undoubtedly instrumental in accelerating the progress of corneal transplantation. Considerable amounts of experimental work using living corneal grafts ensued. Von Hippel was the first to improve vision with LK, consisting of a full-thickness rabbit donor cornea placed into a human recipient lamellar bed24. He was also the first to use a circular trephine. In 1906 successful total penetrating corneal graft in a human was reported by Zirm in a laborer with bilateral lye burns to the cornea26. Ironically, alkali burns like this are now known to have one of the worst transplantation prognoses. Anton Elschnig of Prague, with his extensive experimental and clinical work in the 1920s through the 1930s, is credited with refining the crude technique into an elegant, reliable procedure. Filatov, Tudor Thomas, Paton, Franceschetti, Paufique, Sourdille, Castroviejo, Arruga, and the Barraquer brothers, all eminent surgeons, based much of their knowledge and methodologies on the foundation laid by Elschnig24. Ramon Castroviejo, a Spanish ophthalmologist practicing in New York City, initiated detailed grafting methodologies, expounding the use of the square graft (Fig. 21.16), and developing and refining keratoplasty instrumentation. A. Edward Maumenee extensively studied the immunology and physiology of corneal graft rejection. Claes H. Dohlman came to the United States from Sweden and established the first cornea fellowship program in 1961, emphasizing the importance of both clinical and research training. With more recent ophthalmological advances consisting of microscopic surgery, inert sutures, antiviral and antibiotic medications, topical and systemic corticosteroids, tissue-preservation/eyebanking strategies, and progress in immunology, the success of corneal transplantation has grown rapidly over the last 30 years. Paralleling these advances, clinical indications for corneal transplantation surgery have also expanded considerably.

The last decade witnessed a strong expansion in the use of lamellar techniques.

The anterior lamellar keratoplasty performed with deep stromal separation, described by Melles (DALK) enables the surgeon to leave the recipient with healthy endothelium, with good visual results27,28.

Endothelial decompensation being the leading indication for PK procedures2934, there has been strong interest in developing a technique able to preserve the healthy recipient stroma.

Since the original description of the posterior lamellar keratoplasty (PLK) described by Tillett and Barraquer in the 1950s and 1960s, in 1999 Melles demonstrated the first sutureless PLK35. Since then, numerous modifications in surgical technique and new instruments have led to increasing popularity of PLK.

Indications

Indications for keratoplasty have varied over the decades3638. Box 21.1 lists the classical indications for PK; today many of these conditions may be effectively treated with LK. The Eye Bank Association of America recorded over 41 000 transplants performed in the United States in 2008, with a simultaneous increase in grafts provided for endothelial keratoplasty38. Whilst keratoconus and aphakic bullous keratopathy were major indications for corneal transplantation three decades ago, pseudophakic bullous keratopathy (PBK) rapidly emerged as a leading indication in the 1980s and 1990s3841. This coincided with the dramatic increase in the number of cataract extractions performed. Optical indications for transplantation include corneal decompensation (e.g. bullous keratopathy and endothelial dystrophies), ectasia (e.g. keratoconus), scarring (e.g. traumatic, post-infectious or iatrogenic), and stromal dystrophies. Tectonic indications (e.g. melting, descemetoceles, perforation) are aimed primarily at preserving globe integrity and may allow optical improvement simultaneously or at a later stage. Therapeutic indications (e.g. medically unresponsive infections) provide the two-fold advantage of excisional biopsy and of elimination of the infected tissue. Causative organisms in these cases are often fungi or acanthamoeba, however, common pathogens causing microbial keratitis may also necessitate therapeutic keratoplasty.

Eye banking/donor selection

The first successful human corneal transplant by Eduard Zirm in 1905 involved the use of fresh corneal tissue from a boy whose eye was enucleated for a penetrating sclera injury. For approximately the following 30 years, all human keratoplasties were performed using fresh corneal tissue from living donors whose eyes had been enucleated due to trauma or disease not involving the anterior segment. In 1937, Filatov from the Ukraine introduced the use of whole globes from cadavers stored at 4°C in a moist chamber. Paton established in the US the first eye bank that involved procurement, processing, and distribution of donor corneas37.

Today, cold storage, organ culture, or cryopreservation may be used to preserve the corneoscleral buttons. Cryopreservation allows the tissue to stay viable at –70°C for more than 1 year; however, this is seldom used as it is expensive and technically complicated. Both the freezing and thawing procedures in this technique demand fastidious timing and special precautions to avoid damage to endothelial cells.

Thus, cold storage and organ culture are the two main methods for preserving the donor tissue today. Cold storage (2–6°C) was introduced in 197442,43, and is commonly used in the USA. The technique is relatively simple and involves refrigeration with minimal tissue handling. No complex equipment is required. At 2–6°C, the metabolic activity of the endothelial cells is minimal and therefore deturgescent agents (e.g. dextran or chondroitin sulfate) are required to keep the cornea in a relatively dehydrated state and thus maintain corneal thickness. The original McCarey-Kaufman (M-K) medium has been modified with addition of antibiotics, energy sources, antioxidants, growth factors, and membrane stabilizing agents to improve cell survival, reduce autolysis, and maintain ultrastructural integrity. Although endothelial cell loss may be attributable to numerous factors independent of storage technique, corneas stored at 2–6°C show intercellular disruption, reduced cell adhesion as well as endothelial cell loss and death44. Modified storage media have increased the storage time for up 2 weeks, one week being most often recommended. Organ culture (31–37°C) was introduced in 197645 and is commonly used in Europe. During the storage phase in culture medium supplemented with fetal or newborn calf serum, antibiotics and antimycotics, the corneas swell considerably and can reach twice the normal thickness. Dehydrating molecules are not added as they are ingested by the corneal cells and lead to toxicity. Thus, a shorter second phase is required to reverse the swelling prior to transplantation. Dextran (4–8%), is added to the same medium to facilitate de-swelling and transportation. This phase in transport medium varies between 1 and 7 days. Overall, organ culture allows for longer periods of storage (up to 4–5 weeks). Advantages over cold storage include ease of scheduling surgery, allowing time for tissue typing/matching, and more rigorous microbiological testing.

Regardless of the storage methods used, donor and tissue evaluation to assess suitability is critical. It includes obtaining a thorough medical and social history of the donor as well as serological testing, slitlamp biomicroscopy, and endothelial cell examination. The tissue is evaluated for epithelial integrity, epithelial and stromal opacities, presence of foreign bodies and infectious infiltrates, evidence of previous anterior segment surgery, degree of stromal clarity and thickness, presence of Descemet’s membrane folds and extent of endothelial guttae, snail tracks, and precipitates. Specular microscopy provides detailed microscopic analysis of individual cell morphology and an estimate of cellular density (Fig. 21.17A), however for a better and wide examination light microscopy is applied (Fig. 21.17B). The cell counts may be obtained by automated image analysis or manual counting methods.

Donor tissue has to be considered as non-sterile and effective decontamination must be in the routine. Antibiotics are less effective in cold storage than organ culture as the contaminating microbes are metabolically less active at low temperatures. For this reason, preoperative warming of the storage media is important to enhance the decontamination effect. Individuation of microbial contamination may also be better with organ culture since contamination will become more readily evident and it may therefore be considered as the storage method of choice in circumstances where corneas are suspected of being at a higher risk of contamination. However, stringent screening protocols by eye banks have minimized the risk of microbial transmission from donor to recipient and the accurate valuation of medical and social history of the donor allowed rare incidences of systemic disease like rabies, hepatitis B, Creutzfeldt–Jakob disease (CJD) and malignancies4448. No case of seroconversion after unplanned transplantation of corneas from human immunodeficiency virus (HIV) positive patients has been reported to date4951.

Irrespective of the storage methods, prospective studies analyzing short and long-term follow-up after PK have not found any difference in endothelial cell density or clinical outcomes5254.

Preoperative evaluation

History

Taking a careful and detailed clinical history is of paramount importance during the preoperative evaluation. Information about the pre-morbid visual acuity may elucidate the chronology of the visual deficit, and may provide information on amblyopia, retinal disease, glaucoma, and optic neuropathy. A history of iritis, glaucoma, trauma, dry eyes, herpetic infection, and previous operations may require alterations of surgical technique and postoperative care.

A history of the patient’s general health and demeanor must be assessed concomitantly, and is helpful in planning the anesthesia. Cardiac, pulmonary, and endocrinological disease may require specific anesthetic precautions. The patient’s systemic medications may influence blood coagulation, wound healing, and tear production. The mental status of the patient must also be assessed, as keratoplasty is relatively contraindicated in patients with severe mental retardation, psychosis, alcohol and drug addiction, as well as those at risk of self-inflicted trauma and poor compliance.

A history of allergies to some medications may preclude the use of certain intraoperative and postoperative medications. The patient’s present and anticipated future activities of daily living (e.g. employment, hobbies, and environment) from a visual and physical standpoint should be assessed. Those who engage in contact sports or work in high risk environments for eye trauma may need to drastically alter their lifestyles if they wish to undertake PK. The individual’s visual needs, as well as visual difficulties, are important factors to consider in the final surgical plan, especially when deciding the type and timing of the surgery.

Examination and investigations

The clinical examination begins with a comprehensive visual assessment consisting of visual acuity measurement and refraction for both distance and near. Additional testing as color vision, B-scan ultrasonography, electrophysiological tests, swinging light test, visual fields, retinal angiography, and ocular coherence tomography (OCT) or ultrasound biomicroscopy may aid in excluding retinal and optic nerve related causes of visual dysfunction. However, in the presence of opaque media, some of these tests may not be performed reliably. If the corneal pathology is primarily refractive in nature (e.g. keratoconus or scar-related corneal astigmatism), additional useful testing includes corneal topography. Anterior segment OCT or Schiempflug may be useful to ascertain depth of stromal scars or deposits prior to decide the type of surgery. In cases of endothelial dysfunction, often bilateral, specular microscopy and pachymetry may be useful in assessing progression and extent of disease for the careful scheduling of the therapy A thorough adnexal examination must be carried out and any eyelid and/or lacrimal problems, such as blepharitis, rosacea, scarring, lagophthalmos, ectropion, entropion, floppy eyelid syndrome, trichiasis, and epiphora need to be appropriately treated prior to corneal surgery. A detailed slit-lamp biomicroscopic examination should search for tear film abnormalities, conjunctival scarring (seen in cicatricial conditions such as Stevens–Johnson syndrome, ocular cicatricial pemphigoid or after chemical, radiation and thermal burns or in severe atopic disease, and in case of previous conjunctival surgery), corneal staining or vascularity, and anterior chamber abnormalities (e.g. synechiae and iritis). The presence of these findings may contribute to a poor prognosis or even contraindicate surgery. Corrective surgery or medical therapy prior to surgery may help to improve the outcome of surgery in such cases. Limbal stem cell transplantation may be considered prior to surgery in those with limbal stem cell deficiency (e.g. congenital aniridia, chemical burns).

The status of the crystalline lens or the IOL should be assessed to ascertain the need for concurrent cataract extraction or IOL repositioning, explantation, or exchange. Preoperative biometry may not be as predictive of the final refractive status when IOL implantation is combined with PK as when it is performed in the absence of corneal disease or surgery. A combination of good clinical judgment, measurements from the other eye, reasonable choice of IOL formulas, and personalization of equations using regression analysis to estimate the surgeon’s refractive tendencies, may enhance the predictability; high refractive errors are still occurring in combined PK/IOL cases55,56.

The decision to render the eye myopic, emmetropic, or hyperopic should be influenced by the patient’s need, and the refractive status of the contralateral eye. In general, a final myopic error will lend itself better to further correction with laser or surgical treatment. The condition of the iris/iridocorneal angle and integrity of the capsular bag may be a determinant of the type of IOL to be implanted. Alternatively, the eye may be left aphakic, with view to secondary IOL implantation at a later stage. This may yield better postoperative refraction and unaided visual acuity but delays visual rehabilitation and risks damage to the graft57,58.

The presence of glaucoma in eyes needing corneal transplantation must have optimal control both prior and following surgery.

Setting realistic expectations for the patients prior to surgery is important. The patient must be counseled before surgery, and informed of the realistic time span for visual rehabilitation. Those undergoing PK may expect one year or longer to achieve maximal potential. Lamellar surgery may provide a faster rehabilitation. In either case, they may require refractive correction in the form of spectacles, contact lenses, or refractive surgery. The risks of rejection and infection together with the need for suture removal/adjustment must be reiterated. Patients who are well informed are generally happier and more likely to comply with the rigorous postoperative management.

Penetrating keratoplasty

Although the surgical steps vary among surgeons, a preliminary preparation of the recipient eye is usually performed first. The donor tissue should then be completely prepared for transplantation before the recipient eye is surgically opened as an obvious precaution when just one tissue is available in the OR, and in general to minimize the duration of open-globe time.

Preparation of recipient

General anesthesia may be preferable in cases where a long operating period is anticipated or in cases where there is a higher risk of expulsive hemorrhage or in all cases in whom the local anesthesia is contraindicated as in corneal perforation. In our experience, most cases can be operated on under local peribulbar anesthesia (50% mixture of 2% lidocaine and 0.5% bupivicaine) with a variable degree of sedation. Following anesthetic injection, gentle pressure over the globe is maintained to lower the intraocular pressure. Intravenous osmotics are very useful to minimize vitreous pressure. In phakic and pseudophakic patients, where the crystalline or intraocular lens is to be left in situ, the pupil may be constricted with miotics (e.g. pilocarpine 2%) prior to surgery. This may prevent inadvertent lenticular damage in phakic eyes and aid centration of the graft on the pupillary axis. In cases with planned cataract extraction or IOL explantation/exchange, the pupil is dilated as per routine cataract surgery protocol. If required, intracameral acetylcholine or pilocarpine may be used to constrict the pupil.

This is in part an open-sky procedure and all precautions to prevent intraoperative suprachoroidal hemorrhages should be taken59.

A sterile drape is applied over the eye following application of povidone-iodine into the fornices and periocular area. Various specula are available and an appropriate one must be used which offers the benefit of greatest exposure with minimal distortion and compression of the globe. Scleral support rings (e.g. Flieringa ring) should be used to maintain the structure of the globe, especially in aphakic and vitrectomized eyes or whenever lens extraction or IOL manipulation is planned, where the scleral wall may distort or collapse once the eye is open. The McNeill–Goldman speculum serves a dual purpose by combining two Flieringa rings within a speculum (Fig. 21.18). The scleral ring is secured onto the episclera with 5-0 or 6-0 polyglactin.

The recipient cornea is then measured with a caliper. Sizing and centration of the host trephination depend on several factors including the size, location and extent of pathology, host corneal diameter, extent of vascularization, and risk of rejection. The area of trephination may be decentered or oversized in order to either avoid or better encompass zones of pathology, such as areas of excessive corneal thinning, overhanging glaucoma filtering blebs, foci of infection, or inferior conical apices in keratoconus. The disadvantages of large, decentered grafts include high astigmatism and problems inherently associated with the proximity of the graft–host junction to the limbus, i.e. increased risk of rejection and glaucoma. In the absence of any overriding factors, surgeons may prefer to center the graft over the pupil, i.e. a slight nasal displacement, or at the geometric center of the recipient cornea. The center of the intended trephination is marked with indentation using the tip of a cannula; gentian violet is used as a marker on the epithelium side. Radial marks to guide suture placement may be made using a gentian-violet stained 8-blade radial marker (Fig. 21.19).

Donor preparation/sizing

The donor corneoscleral buttons are commonly trephined with a disposable punch block apparatus with the endothelial side facing up. Once correct alignment is confirmed, the blade is pressed onto the corneoscleral button. Firm pressure is maintained whilst the scleral rim is moved with a pair of toothed forceps to ensure a 360° cut. The graft may occasionally remain engaged within the trephine cavity and may be gently dislodged using forceps by grasping the epithelial/stromal edge or injecting viscoelastic into the core of the trephine. The tissue is then kept submerged in storage medium or viscoelastic until the recipient cornea has been excised. This posterior punch method has been shown to result in more regular cut edges compared with an anterior approach which is performed with a suction trephine and an artificial chamber when not on a whole eye60,61. Cutting from the endothelial side results in a slightly smaller graft (by 0.2–0.3 mm) than the blade diameter as a result of the flattening of the tissue when punching from the endothelial side6264. On the other hand, suction and downward pressure on the recipient cornea causes the tissue to protrude into the trephine, resulting in a marginally larger host cut than the trephine diameter. Thus, use of same-size trephines for the host cornea and donor cornea (posterior punch) result in a graft that is smaller than the recipient bed. For this reason, the donor is usually trephined larger in diameter than the recipient bed, compensating for the slight disparity in wound edges obtained by cutting the donor and recipient cornea by different approaches and ensuring a watertight closure62,63,65. Achieving watertight closure of the wound with even a 0.25 mm disparity is noticeably more demanding than with a 0.5 mm donor oversize; same-size or undersize grafting requires even tighter suturing and often a greater number of suture bites to maintain watertightness.

Many studies have looked into the theoretical advantages of reductions in hyperopia and myopia by either oversizing or same-/undersizing the grafts respectively6672. Results are, however, not reliable since numerous confounding factors (i.e. tissue elasticity, trephine type, tissue healing, surgeon expertise underlying disease follow-up to name a few) do not allow accurate prediction of postoperative refraction by simply selecting a graft diameter.

Host trephination

Before trephining, a peripheral corneal paracentesis should be performed, preferably inferotemporally. This will be useful to access the AC both intraoperatively and postoperatively. The host cornea may be trephined using a variety of suction and manual trephines. A disposable vacuum trephine like the Hessburg–Barron offers the advantage of semi-quantitative gradinal circular cutting of the host. The cross hairs on the trephine are used to align the trephine with the gentian violet centration mark on the recipient cornea. Firm downward pressure with a trephine delineates the size of the intended circular cut and the trephine is lifted to check the marking. Cellulose spears may be used to dry the corneal surface in order to improve visualization of the mark. When satisfactory alignment is achieved, the vacuum is applied and the blades advanced slowly until the anterior chamber is entered with a hand-held manual trephine; centering is ensured by marking the epithelium with downward pressure, and carefully aligning the blade with the most centered mark. It is advisable to deepen the AC injecting a moderate amount of viscoelastic trough the paracentesis, to dampen the AC entrance of the blade and decrease chances of iris/lens damage. Use a 90° rotation and counter-rotation while exerting a very gentle downward pressure; as soon as the AC is entered, both rotation and downward pressure must be stopped. When the point of entry is identified curved corneal scissors (Fig. 21.20) are used to complete the trephination. The scissor tips must always be in view and held perpendicular to the corneal surface. If the posterior wound bevel is excessive, it may be trimmed with miniature Wescott or Vannas scissors. The tissue should be trimmed as a long, single, continuous strip whenever possible to avoid the formation of multiple jagged edges of stroma and Descemet’s membrane. Overly enthusiastic trimming, leading to an undermining cut of the Descemet’s membrane, may increase astigmatism and the chance of wound leakage. After excision of the host corneal button, it is important to ascertain that Descemet’s membrane from the excised button is not retained within the eye. In highly edematous corneas, Descemet’s membrane is easily stripped off and may inadvertently be left behind in the eye.

In eyes with a higher risk of suprachoroidal hemorrhage, a small portion of the recipient cornea may be left intact thereby creating a hinge which allows the cornea to be reflected back away from the surgical field, but available to flip over and close the eye should the need arise73; in some explosive cases the same procedure is performed with a surgeon finger.

Suturing

After applying some viscoelastic on the iris and pupillary area, the donor tissue is placed on the recipient bed in the desired position, e.g. arcus senilis on the graft may be positioned superiorly to minimize its visibility. The graft is then secured onto the recipient bed by four or height interrupted 10.0 nylon cardinal sutures equally spaced apart. A forceps is used to grasp the edge of the graft and the first cardinal suture is placed at the 12 o’clock position, usually between 10 and 2. The second and most important cardinal suture is placed 180° opposite inferiorly. The surgeon should ensure that there is equal graft distribution on either side of the two sutures before proceeding to place the remaining cardinal sutures. The second cardinal suture should be repositioned if resulting in asymmetrical distribution of donor tissue. When the first four sutures are in place, a four-cusp pattern is formed by the tensile folds, thus giving the surgeon excellent landmarks to accurately divide the four quadrants during placement of the rest of the sutures. The corneal sutures should be placed at least 90% of the stromal depth to reduce posterior gaping of the wound. The anterior graft surface should be flush with the recipient corneal surface without any over- or underride. This might require placing the host or donor portion of the suture at different relative depths, i.e. when the host bed is excessively edematous or very thin. Misalignment of the anterior surfaces is more prone to refractive errors, scarring, and delayed healing than misalignment of the endothelial surface.

Following placement of the cardinal sutures, the graft may be closed by a variety of suturing methods including; all interrupted sutures, single or double continuous suture, antitorsion suture, double continuous suture, single continuous with interrupted sutures, deep sutures, etc. In each of these varieties, the number and orientation of suture bites may also vary. If a double continuous 10.0 nylon suture each with approximately 16 bites is adopted, the first suture is tied at the 12 o’clock position and the second placed at 6 o’clock with bites alternating with those of the first. Both knots are buried in the donor cornea. This method allows even distribution of tension, good wound closure and security in the event of one suture breaking. A combination of continuous and interrupted sutures might allow earlier visual rehabilitation by selective removal of sutures (Fig. 21.21).

Whilst the suturing technique used is highly dependent on surgeon preference, there are some instances where interrupted sutures are preferable, i.e. presence of inflammation, ulcerations, infections, or multiple previous rejections, allowing for selective removal in case of suture-related problems. Despite the numerous patterns of suturing that exist7476, no single technique has been consistently proven to be superior7782.

At the end of the case, cardinal sutures may be removed if necessary, and wound integrity checked. After normalizing the IOP by refilling the anterior chamber through the paracentesis, drying the corneal surface with a spear and applying gentle pressure on the globe away from the wound identifies any areas of leakage. If present, this may be addressed by adjusting suture tension if continuous sutures are used or by placing additional interrupted sutures. Some surgeons use a hand-held (Maloney keratoscopy) or illuminated keratoscope to assess astigmatism and aid suture adjustment at the end of surgery. Tensile adjustment of the continuous suture is a possibility to decrease astigmatism in the postoperative period.

Penetrating keratoplasty with shaped wound configurations

Shaped wound configurations as an alternative to perpendicular incisions for penetrating keratoplasty were described as early as the 1950s, and various modifications have been reported since8386. Accuracy of trephination and reproducibility of the manual preparation techniques have been difficult. Furthermore, a slight mismatch in size when preparing a ‘single piece’ graft may result in high and irregular astigmatism. A ‘top-hat’ configuration described in 200387 apparently offered the advantage of more secure wound closure, and maintained the anterior graft surface at a reasonable distance from the limbus, thus reducing the theoretical risk of rejection. A microkeratome-assisted technique to perform ‘mushroom’ shaped grafts in eyes with deep central scars has also been described88. This may offer better visual and refractive outcomes compared with conventional PK, whilst preserving much of the healthy recipient endothelium. Various other types of wound configurations have since been proposed using either manual or femtosecond laser-assisted preparation, e.g. zig zag, Christmas tree, half top-hat, dovetail, etc.8995 (Fig. 21.22). Whilst the femtosecond laser provides precise wound edges and eases graft/donor preparation, its use is greatly limited by the poor penetration through corneal opacities, and by the high cost.

Various studies have shown that shaped wound edges provide better wound stability and healing than conventional straight edge PK wounds88,9294. Apart from providing better wound apposition, some of the shapes offer additional advantages, e.g. a top-hat configuration results in more endothelium being transplanted and would be suited to patients with endothelial decompensation who also have a central stromal opacity. The precise shape decided upon depends on the pathology and its extent.

Two different shaped techniques are described below.

Microkeratome-assisted mushroom keratoplasty

The ‘mushroom’ configuration is indicated in eyes with full-thickness central stromal opacities, for example post-traumatic and post-infectious scars, deep stromal dystrophies, and degenerations in the presence of normal endothelium. Deep anterior LK may not be feasible in these cases due to the presence of deep scarring. The ‘head’ of the mushroom offers the advantage of lower postoperative astigmatism95 whilst the ‘stem’ allows preservation of most of the recipient endothelium A microkeratome-assisted method of creating a mushroom configuration consisting of two separate lamellae can overcome the difficulties of manual preparation88 (see Fig 21.22B). The use of an anterior and posterior lamella offers the advantage of allowing: (i) the lamellae to be sized exactly as the recipient bed, thus minimizing the risk of astigmatism and (ii) optimal positioning of the lamellae, i.e. the anterior lamella can be centered on the limbus and the posterior lamella on the pupil or slightly off center to encompass the area of excised scar.

The recipient eye preparation and marking are as per PK (described above). A 9.0 mm suction trephine is used to create a partial thickness incision between 250 µm and 300 µm depth (Fig. 21.23A). Manual lamellar dissection is performed using a round crescent blade starting at the base of the incision and advancing centrally (Fig. 21.23B). A central island about 5.0–6.5 mm diameter, including the mark used for centration of the suction trephine, is spared to facilitate concentric alignment of the second trephination (Fig. 21.23C). This peripheral rim of manually dissected stroma lies off the visual axis and therefore does not affect postoperative visual acuity. On the contrary, surface irregularities induce increased scar formation over this wide area and thus speed up wound healing and allow for early suture removal.

The donor cornea is dissected with a 250 µm or 300 µm microkeratome head. The anterior lamella obtained is positioned on a trephination block and punched to 9.0 mm (Fig. 21.23D). The posterior lamella of the graft is marked with trypan blue and punched to size from the endothelial side using a 5.0–6.5 mm trephine (Fig. 21.23E). A same-sized (5.0–6.5 mm) trephination is performed in the recipient bed concentrically to the initial 9.0 mm peripheral incision (Fig. 21.23F). Oversizing the posterior graft must be avoided to prevent overlapping of the deep wound edges. Caution must be exercised to avoid damage to the intraocular structures during this central trephination, as the residual corneal layer is quite thin. It is therefore preferable to outline the incision by applying gentian violet or trypan blue and enter the anterior chamber with a 15° or diamond blade. The button is then excised with corneal scissors (Fig. 21.23G) and care must be taken to ensure clean, straight edges.

The posterior graft (endothelium and deep stroma) is simply placed on the central recipient bed (Fig. 21.23H). A small amount of viscoelastic material may be placed in the anterior chamber, especially in the presence of an intraocular lens, to avoid direct contact between the lens and the donor endothelium. No sutures are used to secure this posterior lenticule, and the 9.0 mm anterior donor lenticule is placed over it (Fig. 21.23I). The anterior lenticule is then sutured with double continuous 10.0 nylon sutures. It is essential for the superficial wound to be watertight in order to allow the intraocular pressure to push the posterior graft against the overlying anterior lamella. Figure 21.24 shows the pre- and postoperative appearance of the same surgical case illustrated in Figure 21.23. A disadvantage may be the development of interface scarring between the two lamellas that can compromise the functional recovery.

Manual top-hat penetrating keratoplasty

The ‘top-hat’ configuration is indicated in eyes that have endothelial decompensation with complete central stromal opacities and are at a high risk of rejection or inflammation, for example corneas with vascularization or limbal inflammation. This configuration offers the advantage of maximal endothelial transplantation, whilst maintaining the anterior donor cornea at a reasonable distance from the limbus87,90.

The donor button is mounted on the artificial anterior chamber, the geometric center of the cornea is marked, and a 7.0 mm Barron suction trephine is used to make a circular, deep anterior incision to 300 µm depth. A lamellar stromal dissection is performed peripherally from the base of the incision to the limbus using a bevel-up blade. The cornea is then removed from the artificial anterior chamber and placed on a suction punch with the endothelial side up; care is taken to align the mark of the geometrical center with the cross hairs of the punch and a 9.0 mm donor button is punched. As a result of the previous lamellar dissection, a superficial annular stromal lamella, 300 µm in thickness, can be removed in the area between 7.0 and 9.0 mm diameter. The donor button obtained thus consists of a central, full-thickness portion, 7.0 mm in diameter, surrounded by a peripheral lamellar wing of deep stroma and endothelium (see Fig. 21.22C).

The recipient eye preparation and marking are as per PK (described above). A 7.0 mm Barron suction trephine is used to make a central circular incision, 300 µm in depth, and a similar lamellar stromal dissection is performed from the base of the incision about 1 mm peripherally. A surface mark may be made with a 9.0 mm trephine to facilitate this process. The anterior chamber is then entered with a 15° blade, and corneal scissors are used to complete the excision of the corneal button at the peripheral end of the lamellar stromal dissection. The donor button is positioned by sliding the peripheral wing under the 1.0 mm wide superficial stromal lip of the recipient bed. Four 10-0 nylon cardinal sutures are then placed. Each suture exits the donor at the beginning of the dissected part without entering the base of the wing and then passes through the superficial recipient lamellae at the end of the dissection. In this way, the wing is left free to adhere to the posterior surface of the dissected recipient cornea under the effect of the intraocular pressure. In contrast to conventional PK, injection of balanced salt solution into the anterior chamber reveals a watertight surgical wound at this point. The procedure is completed with a single 10-0 nylon running suture.

Lamellar keratoplasty

Lamellar keratoplasty (LK) offers the advantage of retaining healthy recipient tissue and minimizing the amount of donor tissue required for transplantation. In stromal disease, the recipient endothelium may be spared, thus reducing the risk of rejection, and in many instances resulting in a faster visual rehabilitation96. Other advantages include maintenance of corneal strength, ease of donor tissue replacement e.g. in disease recurrence, and avoidance of open-sky surgery9699. The use of LK to perform PK (mushroom keratoplasty) is discussed above.

LK may be performed manually, with use of a microkeratome, or with excimer and femtosecond lasers. The improvement in surgical instrumentation and advent of lasers have led to numerous types of LK (Fig. 21.25), and various methods of performing these procedures99104. Microkeratome-assisted preparation techniques will be discussed here.

The preoperative evaluation of the LK patient is similar to that of the PK candidate; however, as many LK procedures are extraocular, or require small corneal/scleral incisions, anesthetic considerations in patients with systemic and ocular risk factors are less stringent.

Anterior lamellar keratoplasty (ALK)

Superficial anterior lamellar keratoplasty (SALK)

SALK is indicated in the treatment of superficial corneal opacities resulting from previous refractive surgical procedures, infections, trauma or degenerations and dystrophies (Fig. 21.26A)103,104. Tissue removal is limited to what can be encompassed within a 130–200 µm dissection; however, even in the presence of some residual opacities, sufficient visual improvement may be experienced. The procedure has a smoothing ‘soft contact lens’ like effect over minor surface irregularities, however, marked irregularities may be reproduced within the recipient bed.

A speculum with adjustable blades is positioned (Fig. 21.27). This allows maximal exposure, thereby ensuring adequate placement of the suction ring and free passage of the microkeratome head. The recipient bed is dissected using the 130 µm or 200 µm microkeratome head and a ‘0’ suction ring. This usually results in a lamella of 130–160 µm or 200–250 µm thickness with a 9.0 mm diameter. As no radial conventional suturing is performed, marking the recipient cornea before the keratectomy is not necessary. Peripheral vascularization, if present, may cause bleeding and hemostasis must be achieved prior to proceeding as interface blood may compromise long-term visual acuity. The diameter of the recipient bed is measured in both the vertical and horizontal meridians.

The donor tissue is placed on an artificial anterior chamber and superficial dissection with a 90–130 µm head is performed. The thickness of the donor lamella need not exactly match the one of the excised one, as long as a residual recipient bed of at least 250 µm is maintained to avoid postoperative ectasia. As the donor graft is particularly thin, it may be difficult to distinguish between anterior and posterior surfaces whilst manipulating it into position. Therefore, it is advisable to mark the anterior surface of the donor cornea before performing the microkeratome-assisted dissection. The tissue is then placed on a block and punched to the same size as the recipient bed. Optimally, the donor button should be cut to the same size as the smaller measurement of the recipient bed. The most frequent complication is a size mismatch between recipient bed and graft. However, if a graft with a diameter smaller than that of the recipient bed is used, the recipient epithelium usually covers the annular area of bare stroma and, should a graft larger than the recipient bed be used, the excess tissue at the wound edge eventually necrotizes. In the latter case, epithelial in-growth into the interface may rarely occur, and compromise the result of surgery. It is therefore advisable to punch larger grafts to the required size.

The graft is simply laid onto the recipient bed and adheres in a similar fashion to a LASIK flap. However, as there is no hinge to hold the graft in place, two overlay sutures are used to secure the graft position (Fig. 21.26B). To place these sutures, the needle is passed only through the peripheral recipient cornea at three equidistant points. To avoid permanent folds in the graft or lifting of the donor peripheral to the suture, the suture must not be too tight. After placing the overlay sutures, the interface should be copiously irrigated to remove any possible debris. It is also important that all portions of the sutures lie on the surface of the cornea and not in the interface. A bandage contact lens may be used to hold the graft instead of sutures. Conventional radial sutures (continuous or interrupted) are contraindicated in this procedure, as the thin graft easily distorts, inducing high degree irregular astigmatism.

The overlay sutures must be removed within 7 days of surgery. Figure 21.26C illustrates the appearance after suture removal. Delaying suture removal may cause permanent folds or prevent complete re-epithelialization of the graft as the overlay part of the sutures may act as a physical barrier against the advancement of the epithelial cells. As with any lamellar technique, interface scarring may compromise the functional recovery.

Deep anterior lamellar keratoplasty (DALK)

Microkeratome heads with slits larger than 130 µm may be used to remove mid- and deep stromal opacities (e.g. lattice dystrophy, post-trauma and infection scars); however, if the donor lamella to be sutured is cut using a head with a slit larger than 130 µm, adequate suturing is required (as per PK) and the postoperative management and rehabilitation differs from SALK105 (Fig. 21.28).

Several lamellar dissection techniques have been described previously106112, many of which are limited by the inaccuracy of depth judgment and reproducibility. Reaching Descemet level in cases with deep stromal scarring has been challenging and the risk of perforation and uneven stromal beds has hindered the popularity of manual LK. Air, saline, and viscoelastic have been used to facilitate stromal dissection and separation of Descemet’s membrane110115.

Manual dissection

Melles described a technique of manual dissection of the anterior lamella up to the level of Descemet membrane guided by an air bubble in the anterior chamber116,117. Aqueous is replaced with air via a small self-sealing port and the resulting air/endothelium interface acts as a convex mirror. When the specifically designed dissectors are introduced via a limbal incision, a dark band is observed immediately in front of the instrument. This band represents the residual stroma (between the dissector and air bubble) and hence the surgeon is able to advance the dissector deeper until the band disappears. At this point the dissector is positioned parallel to the surface. Once dissection is complete, air is partially removed from the anterior chamber and viscoelastic is injected into the dissected plane. This is followed by trephination of the anterior cornea. This technique relies on relative clarity of the cornea to allow view of the endothelium/air reflex for judgment of dissection depth. Residual stroma is more likely with this technique if the Descemet plane is not found at the start of dissection.

Air bubble technique

In 2002, Anwar described the ‘big-bubble’ technique, a modification of previously described air usage to achieve Descemetic separation118. Partial thickness stromal dissection between 60 and 80% depth is carried out using a calibrated trephine. A 27–30 gauge needle or a dedicated cannula mounted on an air filled syringe is then inserted bevel down, from the trephined edge and advanced 3–4 mm into the central stroma. Air is injected to form a big bubble between Descemet membrane and the overlying stroma. A paracentesis is created peripheral to the bubble to soften the eye as required. Partial anterior stroma is then removed, leaving a small layer over the bubble. A sharp pointed blade is thereafter introduced through the residual stroma and into the bubble. This is followed by careful dissection of remaining stroma. This technique is more successful in achieving a Descemetic plane of dissection compared with manual techniques and the lack of a stromal interface has been suggested to result in better visual outcomes119121. Success rates in achieving a big bubble, however, vary and have been reported to be between 64% and 90%118,120122. This variation even in experienced hands may be due to difficulties in obtaining a uniform plane of dissection in scarred or irregular corneas. Descemet membrane perforation may occur with both the above techniques and care must be taken to avoid these. Whilst microperforations may still allow a successful LK to be completed, the surgeon must exercise caution to avoid enlargement of the perforation during dissection of the remaining stroma and suturing of the donor tissue. Large or central perforations may necessitate conversion to PK118,122124.

Others have described DALK without the use of viscoelastic substances or air125. DALK has been shown to produce favorable outcomes in comparison with PK125129 and some alterations to the above techniques may help achieve better success rates130,131. These techniques require a learning curve and the meticulous separation is time consuming; should the hair bubble be only partially obtained, completion of the lamellar dissection is technically demanding.

Automated LK for keratoconus

Microkeratome-assisted LK for keratoconus and later modifications have been described in the past132.

Radial marks are placed on the recipient cornea and an anterior lamellar dissection is performed with a microkeratome (Fig. 21.29A,B). To facilitate the use of the ALTK system (Moria) in eyes with regular curvature between 38 and 46 diopters (D), the manufacturer has developed a nomogram-correlating diameter of the lamella to be obtained with keratometric readings (K readings) of the recipient cornea and the use of four different suction rings (namely –1, 0, +1, and +2). However, based on empirical in keratoconic eyes, a lamella 9 mm in diameter can be obtained in most cases by using the ‘0’ suction ring on corneas with average K readings up to 55 D and the ‘+1’ suction ring on corneas with average K readings of more than 55 D. However, if cauterization of the central cornea is performed before dissection, substantial flattening occurs, and the ‘0’ ring should be employed. In order to prevent perforation, the surgeon should aim to leave at least 100 µm of recipient stromal bed. Thus, the choice of microkeratome head is dependent on the pachymetry map obtained preoperatively. Because the microkeratome tends to cut grafts slightly thicker than the stated width of the microkeratome slit, a 250 µm head should be employed only in corneas 400 µm or thicker, while the 200 µm head may be used on corneas with a thickness as low as 350 µm. It is advisable to use the 130 µm head for corneas thinner than 300 µm.

In order to re-establish a physiologic corneal thickness, the donor tissue is dissected with a microkeratome head that has a slit at least 100 µm wider than the slit of the head used on the recipient cornea. The recipient bed is measured and the lamella obtained is punched to the same size. The recipient bed is then trephined with a 6.0–6.5 mm trephine (Fig. 21.29C). Thus the central part of the residual cornea (i.e. a lamella of deep stroma and endothelium) is practically detached from the peripheral recipient bed, similar to PK surgery, but is left in place, to attach to the posterior surface of the donor stromal graft. The cone in the recipient bed therefore ‘collapses’, and does not push against the overlying lamellar graft but simply adheres to it. This central trephination also improves the apposition between the host and donor surfaces thereby reducing the formation of folds on the interface. No particular tension is therefore needed while suturing, as the resistance from the ectactic bed is eliminated. Hence, there is no reason to undersize the donor button. With time, the 6.0–6.5 mm circular vertical incision in the recipient bed scars, binding together donor graft and host cornea at the site of trephination. This further stabilizes the postoperative structure of the cornea, thus acting as a barrier against the changes induced by suture removal.

The graft is secured with two running 10-0 nylon sutures (Fig. 21.29D). No suturing of the posterior lamella is necessary; however, the anterior chamber is reformed at the end of surgery with balanced salt solution (BSS) to ensure that the two lamellas remain attached. Figure 21.30 illustrates the pre- and postoperative appearances following automated LK.

Suture removal is usually performed stepwise. The first running suture can be removed as early as 2 months’ postoperatively, especially in the presence of hyperopia or high degree astigmatism. On the contrary, if vision is good, removal may be delayed up to 6 months. The second suture is usually removed between 9 and 12 months, again in relation to the course of wound healing.

Posterior lamellar keratoplasty (PLK)

Descemet stripping automated endothelial keratoplasty (DSAEK)

DSAEK is rapidly replacing PK as the treatment of choice in patients with endothelial failure. Whilst the vast majority of these patients would be amenable to DSAEK surgery, the presence of stromal scars or high/irregular astigmatism in post PK eyes may be relative contraindications. Indications are summarized in Box 21.2.

Loose and edematous epithelium is ideally removed from the recipient cornea prior to commencing surgery. This allows better intraoperative visualization, and postoperative epithelialization. A descemetorhexis is performed in the recipient eye using a 25-gauge needle mounted on a 2.5 cc empty syringe. The tip of the needle is bent approximately 45° upwards. It is then inserted into the anterior chamber at the 12 o’clock position and a small aliquot of aqueous (about 0.2–0.3 cc) is aspirated and discarded. The syringe is filled with air and reintroduced into the eye via the same incision. Air is injected into the anterior chamber and the tip of the needle is used to scour the endothelium and Descemet membrane (Fig. 21.31A). A 25-gauge cannula, Descemet stripper, or reverse Sinsky hook may be used in combination to strip the Descemet and endothelium. A temporal stab incision may be made to allow replenishment if air if required. Descemetorhexis under air fill allows better visualization of the membrane; however, it may be performed with BSS or viscoelastic material in the anterior chamber133137. Viscoelastic use is best avoided, as retained material may hinder graft attachment. The Descemet membrane may be left in situ in the absence of central guttae, in instances where the anterior chamber visualization is poor, or where air cannot be maintained in the anterior chamber.

A clear-cornea tunnel, 1 mm in length and 3.2 mm in width, is prepared nasally (Fig. 21.31B) for graft insertion and a stab incision with a 15° blade is made temporally for insertion of the Busin forceps if this has not already been made for air replenishment. The 12 o’clock wound previously utilized for descemetorhexis is enlarged with the 15° blade and an anterior chamber maintainer positioned through it. The irrigation bottle connected to anterior chamber maintainer should be positioned at a height of approximately 45–50 cm. If the bottle is placed too high, it can lead to iris prolapse and malpositioning of the graft during insertion. A vertical vitreoretinal scissor is used to perform an inferior iridotomy (Fig. 21.31C) in order to prevent pupillary block and Urrets–Zavalia syndrome secondary to the complete air fill at the end of surgery.

The donor graft is mounted on an artificial chamber and the anterior stroma is removed by means of a 300–350 µm microkeratome head (Fig. 21.31D). The residual stromal bed is dried with a sponge and a 9 mm circular marker is used to outline the area of dissected stroma. This is performed to aid correct centration on the donor punch. An asymmetrical orientation mark (letter ‘F’ or similar) is made on the anterior stroma using trypan blue (Fig. 21.31E). The donor is then placed on a punch, centered using the aid of the 9 mm ring mark and punched to the desired size. Ideally the donor size should be 2 mm smaller than the vertical recipient corneal diameter to allow peripheral clearance.

The graft is loaded onto a glide (Fig. 21.31F) and advanced through the mouth of the glide until a small area protrudes beyond the edge of the mouth (Fig. 21.31G). The glide is then turned over 180° and positioned nasally. A Busin forceps is introduced through the temporal wound and out through the nasal wound to grasp the protruding end of the graft. The graft is pulled into the anterior chamber (Fig. 21.31H) and, upon delivery, the anterior chamber maintainer is removed and the graft positioned with gentle tapping on the corneal surface. A 25-gauge cannula with a flat tip may be introduced into the interface to manipulate the graft.

Whilst studies show a lower endothelial cell loss with the use of a glide138,139, alternative methods of grafts insertion (e.g. folding and delivery with forceps, sutures, needles, or cartridges) may be employed140142. Air is then injected under the graft when correct centration is achieved and all corneal wounds are sutured airtight with 10.0 nylon. Finally, a tight air fill is achieved via a 30-gauge needle inserted obliquely into the anterior chamber (Fig. 21.31I). Venting stab incisions may be made in the peripheral cornea to release trapped fluid from the graft–host interface to aid graft attachment137,143. These can occasionally lead to complications and may be reserved for challenging cases, e.g. post-PK eyes144. A soft bandage contact lens is placed if epithelium debridement was carried out. A patch is placed over the eye and patients are advised to remain in a supine posture for 6–8 hours.

Descemet membrane endothelial keratoplasty (DMEK)

In contrast to DSAEK, only the Descemet membrane and endothelium are transplanted in DMEK surgery. This avoids formation of a corneal interface and therefore may optimize visual outcome and speed up postoperative visual rehabilitation145. However, the grafts are considerably thinner than DSAEK grafts and pose a challenge in preparation, delivery, and attachment. Various methods of mechanical dissection of donor tissue have been described146149. Preparation of the donor tissue is challenging and highly dependent on the surgeon’s skills. Wastage of up to 16% of donor corneas and an endothelial cell loss of >8% immediately after donor preparation have been reported146,148. Pneumatic dissection of the donor cornea results in a lower endothelial cell loss and wastage150,151 and if desired by the surgeon also allows the use of stromal support152,153.

The recipient eye preparation is as per DSAEK surgery. For pneumatic dissection, the donor cornea is mounted on an artificial anterior chamber and about image of the anterior stroma is removed by means of a microkeratome as in DSAEK surgery. This step is not essential, but allows the surgeon to convert to DSAEK in case the ensuing preparation fails. The donor cornea is removed from the artificial anterior chamber and placed on sterile gauze with the endothelium facing up. Next, a 25–30 gauge needle connected to a 10 cc syringe is inserted bevel up into the peripheral cornea at about 1 mm from the limbus and advanced in a tangential direction immediately beneath the endothelium for about 2 mm. Air is then injected until detachment of Descemet membrane is achieved and a large bubble is obtained (Fig. 21.32A). This part of the preparation can be performed either by the surgeon at the table or by a technician in the eye bank. In the latter case, the cornea with the ‘endothelial-Descemet bubble’ can be stored in tissue culture medium for up to 7 days before delivery to the surgeon. Part of the air from the bubble is then removed to achieve a partial collapse (Fig. 21.32B) so as to allow injection of trypan blue into the bubble (Fig. 21.32C). Finally the residual air is aspirated, which allows the trypan blue to stain the area of Descement dissection (Fig. 21.32D). This ensures precise punching inside the outer limit of dissection.

An 8–9 mm punch is used to punch the donor tissue, which consists of deep stroma and overlying detached Descemet membrane and endothelium. The Descemet/endothelium complex remains flat as it lies on the stromal bed and thus the formation of a tissue roll is prevented (Fig. 21.33). Forceps are used to transport the entire tissue onto the plate of a glide. It is then advanced through the distal part of the glide and the endothelium is selectively pulled gently from its edge until it protrudes out of the funnel. Finally, a bimanual ‘pull-through’ maneuver similar to that used for DSAEK surgery is employed to deliver the graft under continuous irrigation through an anterior chamber maintainer (Fig. 21.34). A full air fill is achieved following secure closure of all wounds with 10.0 nylon sutures (Fig. 21.35).

Various shapes (Fig. 21.36) of stromal support can be employed to aid DMEK surgery, and recently the use of a peripheral ring of stroma has been successfully described154,155. However, the sickle shape offers quick preparation and ease of handling, and insertion as well as attachment of the tissue to the level experienced in DSAEK surgery153. To achieve this, the pneumatically dissected tissue is punched slightly eccentrically to incorporate a ‘sickle’ of stroma outside the area of Descemet detachment. The frame of stromal support allows the tissue to be marked and hence reduces the risk of upside-down transplantation whilst also allowing the graft to unfold spontaneously upon insertion into the eye.

The separation of the Descemet–endothelium complex is also obtainable applying big bubble technique on donor cornea with the use of an artificial chamber.

The rolled endothelium Descemet complex is introduced on the AC with an injector through a 3 mm corneal incision156.

Postoperative care

Specific details of postoperative management vary between surgeons, and by the indications and type of keratoplasty, as well as according to intraoperative events that may have occurred. Whilst these variations exist, the underlying aim of postoperative care is to provide analgesia, reduce the risk of infection, rejection, and recurrence of original disease as well as achieve swift visual rehabilitation.

For routine postoperative care in uncomplicated cases, the patient should be seen the day after surgery, toward the end of the first postoperative week, about 2–4 weeks after surgery, and then every 2–3 months over the ensuing year. After the first year, stable patients may be seen every 6 months or annually. Timing of follow-up appointments is dictated by the type of surgery, patient compliance, feasibility, and requirements of visual rehabilitation.

Patients are warned of the symptoms of early postoperative glaucoma such as increasing pain, nausea, and vomiting. While postoperative nausea and vomiting may occasionally be seen as a sequel of general anesthesia and of narcotic analgesia, it is rarely seen purely as a result of local anesthesia by itself and may signify a vagal response to high IOP. Strong narcotic-type analgesia may mask the symptoms and should therefore be avoided in the immediate postoperative period. Mild analgesics such as paracetamol (acetaminophen) may be prescribed. In the event of high IOP, the cause must be identified and treated accordingly, e.g. raised IOP due to retained viscoelastics may be treated medically whereas pupillary block from a complete air fill after endothelial keratoplasty requires release of air and possibly YAG laser iridotomy. All postoperative examinations should include measurements of visual acuity and intraocular pressure. Prolonged efforts at refraction, pachymetry, keratometry, and topography are seldom productive or useful before the first month. On the first postoperative inspection, epithelial, wound, and suture integrity must be ascertained. The anterior chamber is examined for inflammation. The development of a hypopyon, fibrin, or increased anterior chamber cells may indicate a rejection or endophthalmitis. A shallow anterior chamber may be associated with wound leak, choroidal effusions, or aqueous misdirection. The fundus must be examined as soon as the view becomes sufficiently clear. On the first postoperative day, the posterior pole should be checked for the presence of a red reflex. Subsequently, if the view remains poor, an ultrasonic examination of the retina should be done to rule out pathology.

All patients are generally commenced on 2-hourly topical steroid and antibiotic combination. The frequency may be altered according to the circumstances and type of surgery. The antibiotics are withheld after 2–4 weeks and steroids are gradually tapered to a once daily administration on the absence of any adverse effects. The frequency of steroids is increased if additional procedures are undertaken, e.g. removal of sutures, cataract surgery, etc. In some circumstances, e.g. phakic patients, post-anterior lamellar surgery, steroid responders, etc. the steroids are tapered sooner. In patients with steroid induced glaucoma who still require steroid therapy, the drops are switched to preparations that are less likely to induce IOP elevation, e.g. fluoromethalone (FML), loteprednol (Lotemax). Concomitant antiglaucoma medication is continued or temporarily increased. In herpetic grafts, antiviral agents should be used as long as corticosteroids are in use. Topical antivirals should be tapered rapidly to a very low dose (paralleling the topical corticosteroid dosage) within weeks to prevent epithelial toxicity. Oral acyclovir (aciclovir) is not toxic to the corneal epithelium and its efficacy in preventing or treating herpetic relapse has been shown157. Oral antiviral agents should be prescribed prior to surgery and continued for at least 1 year postoperatively. Cycloplegics may be used for treating iritis, improving comfort and preventing synechiae. Whilst there is weak evidence to suggest that its use may lead to permanent pupillary mydriasis in keratoconic eyes, when necessary, mild, short-acting agents are recommended158,159. Topical NSAIDs should generally be avoided, due to recent reports of corneal melting and persistent epithelial defects following PK160,161.

Patients are advised to restrict physical exertion and straining in the early postoperative period. This is generally applicable to those that have undergone a PK while those with lamellar or small incision surgery (e.g. DSAEK) need not greatly restrict their daily activities.

The need for suture adjustment or suture removal for astigmatism should be determined by refraction, keratometry, keratoscopy, or computed tomography. Interrupted sutures may be removed selectively and patients reviewed regularly with topography to assess the induced changes. In the presence of double continuous sutures, we aim to remove the first suture between 3 and 6 months and the second suture between 9 and 12 months postoperatively. A single continuous suture may be adjusted whereby the suture is rotated toward the steep meridian. Typically, corneal contour changes after suture manipulation may not stabilize until at least 1 month; it is therefore unproductive to prescribe new spectacles or remove more sutures less than a month after suture manipulation. Definitive surgical intervention, e.g. astigmatic keratotomies, refractive laser treatment, toric IOLs, etc., must not be undertaken until refractive stability has been achieved, and all sutures have been removed.

Postoperative complications

Penetrating and lamellar keratoplasty are prone to many of the complications of intraocular surgery, e.g. cystoid macular edema, cataract, choroidal hemorrhage. In addition there are many specific complications common to both types of transplantation and these will be discussed first.

Wound leaks and dehiscence may occur at any time during the postoperative period, although these are more common in the early phase when the incision is relatively fresh. Minor wound and suture track leaks may be managed conservatively with a bandage soft contact lens and/or aqueous suppressants, e.g. oral acetazolamide. Larger or more persistent leaks need placement of new or additional interrupted sutures, or adjustment of the tension distribution in running sutures.

Epithelial defects are often present during the first week, but as long as they continue to diminish in size no intervention is necessary. Persistent epithelial defects are more common in eyes with pre-existing ocular surface problems such as Stevens–Johnson syndrome, ocular cicatricial pemphigoid, chemical burns, lagophthalmos, neurotrophic disease, entropion/ectropion, trichiasis, and dry eye. These conditions must be adequately controlled, preferably before corneal surgery is performed. Persistent, non-healing defects may require the application of a bandage contact lens, an increase in corneal surface lubrication (ointments), or the discontinuation or reduction of topical medications that are toxic to the epithelium. In severe, recalcitrant cases, a lateral tarsorrhaphy may need to be performed. Persistent epithelial defects may be complicated by infection, scarring, and stromal melting (Fig 21.37).

Broken or loose sutures should be immediately removed or replaced. During planned suture removal, care must be taken to ensure that sutures that are incompletely removed do not have any superficially protruding ends. Exposed suture knots and ends will likely lead to irritation, pain, epiphora, photophobia, mucus production, giant papillary conjunctivitis, and ulceration. Suture related complications include wound dehiscence, high astigmatism, vascularization along suture tracks, immune rejection, and infectious suture abscesses (Fig. 21.38). Sutures associated with an abscess or suspected infiltration must be removed and sent for microbiological investigation. Occasionally, scarring occurs along the suture track, particularly if sutures are left in place for a prolonged period of time.

Filamentary keratitis in the early postoperative period is usually self-limiting and has been noted to occur in >20% of eyes following PK and LK162,163. These lesions do not cause any discomfort on the denervated donor cornea, but they may cause irritation and foreign body sensation on the recipient cornea. Filaments may be treated with artificial tears, N-acetylcysteine drops, debrided with fine forceps, or left untreated. Kaye dots are discrete, white specks in the peripheral donor corneal epithelium adjacent to the sutures and may represent a response to topographical elevation of the cornea in the area of wound compression by sutures164. These do not stain or cause discomfort and are seen mostly in younger patients. They usually disappear within months or with suture removal and are not associated with any secondary complications.

A fixed mydriasis following PK (Urrets–Zavalia syndrome) has been described159 following PK for keratoconus as well as after DALK and DSAEK165,166 (Fig. 21.39). Although the precise etiology remains unknown, iris ischemia and use of cycloplegics have been proposed as contributory factors. No treatment is indicated in asymptomatic cases, although patients with intolerable visual disturbances may require a pupilloplasty.

Postoperative inflammation is more common and severe in previously operated eyes, pediatric eyes, grafts performed during the acute phase of inflammation (e.g. for a perforated cornea or during an active corneal ulcer), after intraoperative complications, and in eyes with keratouveitis and anterior segment neovascularization. Inflammation must be aggressively controlled with topical (and frequently systemic or periocular) corticosteroids to reduce the possibility of synechia formation, cystoid macular edema, pupillary block or angle closure glaucoma, cyclitic or retrocorneal membrane formation, and immune rejection. Peripheral anterior synechiae may not only increase the risk of graft rejection, but also may lead to glaucoma and corneal endothelial damage. As many of the signs of postoperative inflammation (pain, redness, photophobia, and reduced vision) overlap with those of infection and immunologic rejection, all eyes must be carefully evaluated and a high index of suspicion must be maintained.

Postoperative corneal infection may occur as a sequel to suture abscess, persistent epithelial defects, ocular surface problems, suture removal, contact lens wear, prolonged corticosteroid use, or inadequate excision in cases of therapeutic grafts for infectious keratitis. Rarely, infectious keratitis in the graft may be manifested by intrastromal crystalline deposits distributed within a discrete stromal lamellar plane. This phenomenon, known as infectious crystalline keratopathy, is usually caused by low virulence organisms (e.g. Streptococcus viridans) in the setting of host immuno-compromise associated with chronic corticosteroid use167. With the exception of herpetic infections, which may occur at any period after surgery, most cases of infection occur in the first postoperative year. In lamellar surgery there may be a delay in presentation as the infection may develop in the interface and remain unnoticed (Fig. 21.40). Such infections may also be slow to respond to therapy. Scrapings for microbiological investigations must be obtained whenever possible and intensive antibiotic treatment initiated without delay. The choice and regimen of antimicrobial therapy should be dictated by the microbiological results, clinical setting, and physician preference. Unresponsive and interface infections may require a therapeutic keratoplasty. Endophthalmitis after keratoplasty occurs in less than 1% of grafts and is more common in patients with positive donor rim cultures168,169. Fibrin, hypopyon, increased white cells, and flare in the anterior chamber, as well as a reduced red reflex, may be indicators of intraocular infection. B-scan ultrasonography should be performed in all patients in whom the fundal view is obscured. Management is extrapolated from evidence for endophthalmitis following cataract surgery, and involves diagnostic vitrectomy along with intravitreal, systemic, and/or periocular antibiotics.

Primary graft failure is defined as the presence of donor corneal edema on the first postoperative day, which is unresponsive to treatment, and fails to clear for a minimum of three consecutive months. It may result from poor donor preservation, unhealthy or low donor endothelial counts, surgical trauma, or idiopathic causes170. Herpes simplex virus has been detected by polymerase chain reaction in donor corneal buttons in some cases of primary graft failure169. Although the graft with primary failure may clear and deturgesce to some degree as the normal postoperative inflammation subsides and the intraocular pressure normalizes, it will not recover full clarity as would a healthy graft. Primary graft failure is relatively rare and all failed buttons must be evaluated and reported to the supplying eye bank.

Glaucoma after keratoplasty is a common and devastating irreversible complication. Difficulty in IOP measurement, optic disc imaging/visualization, and visual field testing add to the challenge of diagnosing glaucoma in post-keratoplasty eyes. The incidence depends on the complexity of surgery, prevalence of preoperative glaucoma, previous surgery, susceptibility to corticosteroids, and indications for surgery. Eyes treated with long-tube drainage devices such as Molteno, Shocket, or Baerveldt types are somewhat more susceptible to endothelial decompensation, and when treated with subsequent PKPs tend to fail more often as well171173.

The management of glaucoma drainage devices is discussed elsewhere in the book.

Although the avascular cornea is isolated from the immune system to a degree, the protection imparted by the blood ocular barrier is not perfect. The aqueous humor, limbal vasculature, tear film, and iridocorneal adhesions all influence rejection. Each layer of the cornea could sensitize the recipient and undergo immunologic allograft rejection. Immunologic damage to the endothelial cells, however, is most detrimental to the overall function of the donor cornea and is a major cause of graft failure174177. Possible risk factors for corneal graft rejection include large diameter grafts, corneal vascularization (particularly deep vessels), young recipient age, regrafting (especially for prior rejection-related graft failure), glaucoma, atopy, and active ocular inflammation177181. Rejection episodes are more likely within the first postoperative year and prompt recognition and treatment are crucial in achieving successful reversal. Although subjective reporting of redness and decreased vision have been strongly associated with rejection, patient-reported symptoms are neither sensitive nor specific for a rejection182.

Clinical signs of graft rejection (Fig. 21.41) may be subtle and easily missed in the early stages. Mild circumcorneal injection or iritis usually signifies a rejection episode. In such cases, empirical treatment must be initiated or the frequency of existing steroid therapy increased. Keratic precipitates (KPs) signify graft rejection and may be a subtle finding in the early stages. It is important to distinguish new KPs from old ones and a photographic record (or accurate drawings) is useful. Endothelial rejection may present with corneal edema and occasionally a rejection line (Khodadoust line), which is considered to be diagnostic of endothelial rejection.

Epithelial rejection is common and usually manifests as a demarcated line. Although benign, it should be treated with topical steroids. Subepithelial or superficial stromal infiltrates seen in stromal rejection are similar in appearance to those seen in adenoviral keratoconjunctivitis. Although these are generally self-limiting, treatment is advocated to prevent residual scarring and progression to endothelial rejection. Many of the signs of rejection do not occur in isolation and are frequently seen concurrently. Low grade chronic allograft reaction has very subtle signs and may be difficult to identify, allowing for progressive endothelial damage.

The mainstay of therapy for corneal graft rejection remains topical corticosteroids, despite a long, ongoing search for alternative treatments. Frequent topical therapy (e.g. prednisolone acetate 1%) is administered hourly in most cases. Mild cases may be treated with less frequent instillation and nocturnal therapy may be substituted with steroid ointment preparations. Periocular and oral corticosteroids may also be used in adjunct to topical treatment, especially in aggressive episodes. The periocular route of administration is particularly useful in non-compliant and poorly controlled diabetic patients. Other agents, e.g. ciclosporin, tacrolimus (FK506), and azathioprine, have been used in the treatment and prevention of graft rejection with varying degrees of success183189. The use of these agents is generally reserved for recalcitrant and high risk cases due to the adverse systemic effects and lack of conclusive evidence regarding their efficacy.

In addition to the above complications, LK may present with specific problems, the management of which depends on the type of LK surgery performed. Double anterior chamber formation may occur whenever a corneal interface may communicate with the anterior chamber, e.g. following LK performed as a patch for corneal perforations, DALK, mushroom keratoplasty, and endothelial transplantation. In DALK, this occurs secondary to Descemet membrane perforation, which is a common intraoperative complication of DALK surgery120,121,162,190. Small enclosed pockets of fluid (Fig. 21.42) may be self-limiting and may be treated conservatively with periodic observation. Re-apposition must be performed for large, persistent, and enlarging chambers by introducing air into the anterior chamber. In cases of endothelial transplantation, poor corneal clarity is a good indicator of graft detachment when it is difficult to establish the presence of a double chamber with slit-lamp examination alone (Fig. 21.43). Corneal OCT examination can be of great help in such cases. We instigate immediate re-bubbling, and have found this to be highly successful in reattaching the graft. Proper graft centration may also be attempted prior to injecting air. Patients are advised to posture supine following re-bubbling. Care must be taken to avoid overfilling the anterior chamber with air in cases where there is no peripheral iridotomy, or to ensure that air is released early.

Interface opacities may be frequently seen following LK. These may be due to lint fibers, blood, retained Descemet membrane, or other causes. Small opacities that are off the visual axis do not generally require any intervention and may be left in place. The opacities must be distinguished from early infectious infiltrates and observed closely in case of doubt.

Folds in the recipient Descemet membrane and stromal bed are common after LK. These are generally transient and tend to improve with time and following removal of sutures (Fig. 21.44). Central folds may, however, interfere with vision and induce higher order aberrations191,192. The folds may result from excessive manipulation of the grafts (in DSAEK surgery) and as a result of size mismatch in DALK. In the latter case, central recipient bed trephination (cone collapse) or oversizing the graft by 0.25–0.5 mm may overcome or reduce the likelihood of folds.

Keratoprosthesis

Marina Papadia, Alessandro Bagnis, Riccardo Scotto and Carlo Enrico Traverso

Introduction

According to a report published by the World Health Organization in 2009 there are 314 million visually impaired individuals globally and 45 million are considered blind193. Corneal disease accounted for 8 million blind, 1.5 million of those being children194.

The idea of replacing an opaque cornea with a synthetic plate dates back 200 years195 and in 1859 Heusser was possibly the first to implant a keratoprosthesis (KPro) in a human eye196.

The prototype had a porous skirt to allow tissue colonization and integration and a synthetic optic device. The same concept is used also today in the design of new keratoprosthesis.

In the first decade of the 20th century, interest in keratoprostheses declined, because good results were obtained with penetrating keratoplasty using human corneal allografts197.

Nowadays keratoplasty is a standardized technique, continuously evolving towards selective replacement of the damaged tissue (i.e. deep anterior keratoplasty or endothelial keratoplasty). Despite many advances, a subset of patients with severe corneal disease complicated with severe dry eye, corneal vascularization, total stem cell deficiency, or repeated graft failures remains unsuitable as candidates for penetrating keratoplasty198. Hence, for patients with conditions such as alkali burns, Stevens–Johnson syndrome, or recurrent graft failure, permanent keratoprosthesis remains the only viable option for visual rehabilitation and should be considered whenever the probability of maintaining a clear cornea with a keratoplasty using a human allograft is poor199.

During World War II the incidental discovery that Plexiglas fragments from airplane canopies retained in the eye were well tolerated opened a new direction for research studies on keratoprosthesis200.

Although theoretically replacing the opaque cornea with an inert clear tissue might seem easy, complications such as infection, glaucoma, and intense reactive inflammation are still difficult to treat. One of the major problems associated with keratoprosthesis is its difficult biointegration leading to a high extrusion rate. Keratoprosthesis extrusion is mainly caused by epithelial proliferation around the implant with the formation of retroprosthetic membranes.

Today the use of a keratoprosthesis is limited to patients with low vision in both eyes who have already experienced repeated graft failure and have a potentially seeing retina. It is very demanding surgery with potentially severe complications, sometimes barely manageable, and should be performed only by experienced surgeons in a highly specialized center.

Currently different types of keratoprosthesis that have different design characteristics and manufacturing materials are available.

The Boston KPro is completely synthetic and is at the time of publication by far the most widely used. New interest is now oriented towards bioengineered tissues that might combine a synthetic optic with a biological haptic or be completely made of bioengineered tissues.

The keratoprosthesis can be classified as either penetrating (Boston, osteo-odonto-keratoprosthesis, AlphaCor, Pintucci) or non-penetrating (Supradescemetic synthetic cornea) depending on whether the Descemet membrane of the patient is left untouched or completely removed.

The manufacturing materials range from completely synthetic materials (Boston, AlphaCor), partially biologic with a synthetic optic (osteo-odonto-keratoprosthesis), or completely composed of bioengineered tissues (animal research models).

All these devices need a skirt (either biological or synthetic) that allows retainment of the synthetic optical device through colonization by recipient tissue and thus integration in the surrounding tissues.

Patient selection

To evaluate a possible candidate, a complete ocular and medical history is needed. The cause of the corneal blindness and the status of the disease (whether stable or evolving) should be assessed as precisely as possible and recorded. Reliable information on previously performed surgeries, in particular glaucoma surgery and cataract extraction with IOL implant, must be gathered. Any history of glaucoma, especially following chemical burns, is specifically relevant.

KPro surgery is usually performed in only one eye. The other eye, if existing, should be kept as the ‘spare eye’, should severe complications occur.

An extended work-up to assess the presence of associated dry eye should be performed, as severe ocular surface diseases might compromise the survival of keratoprosthesis and might orient towards the use of a specific type of prosthesis. Patients with underlying autoimmune disease are most susceptible to tissue necrosis, melting, and infection201,202. Tear secretion, blink-rate, and completeness of blinking should be carefully assessed and reported. The surgeon should carefully look for the presence of symblepharon or anomalies of fornix, lids, or lid positioning preoperatively. The visual acuity should be assessed as precisely as possible, as well as the intraocular pressure (IOP), although these two measures might be particularly difficult to estimate because of the corneal anomalies. If visual acuity is not measurable, at least light projection should be tested and the absence of sensibility in the nasal projection should raise suspicion of the presence of end-stage glaucoma. The effective potential function of the retina and visual pathways should be assessed with electroretinograms (ERG) and visual evoked potentials (VEP) in order to avoid surgery if there is no reasonable chance of expecting any visual recovery.

Patients should be able to have a good access to the hospital and willing to have regular follow-up visits for life.

Patients affected by severe autoimmune disease such as Stevens–Johnson syndrome (SJS) or ocular cicatricial pemphigoid (OCP) are the worst candidates, because of the potentially sight-threatening complications associated with severe dry eyes and the overall lower success rate of the surgery where these diseases are present201,203.

Keratoprosthesis surgery should be reserved for patients with bilateral corneal blindness resulting from several ocular or systemic pathologies204,205, possibly with a ‘wet’ ocular surface.

The prognosis for a ‘good outcome’ is better in eyes that have experienced little intraocular inflammation in the past201. Therefore long-standing uveitis, whether associated with rheumatoid diseases or not, or end-stage phthisis presently constitutes contraindications. Despite some evidence about the effectiveness and safety of KPro in patients with a history of herpetic keratitis, doubts about the chances of long survival of the device in such cases should be taken into account206,207.

Only osteo-odonto-keratoprosthesis and Boston Type II KPro are suitable for implantation in patients with a severe ocular surface disease. Boston Type II KPro has an anterior cylinder that protrudes through an opening in the closed lid, thus guaranteeing a good and ‘wet’ environment for the biointegrable part of the prosthesis.

Standard preoperative general medical assessment should be done. The surgery can be performed either with a general or with a local (retrobulbar and lid block) anesthesia.

Intravenous antibiotics (e.g. cefazolin 1.0 g, if no systemic contraindications are reported) at the start of the surgery are recommended.

A protocol for the selection of patients suitable for Boston KPro implant has been developed and can be applied also for the other KPros.

Increasing poverty and non-white race have been associated with elevated pro-inflammatory states among adults208; black transplant recipients have decreased graft survival and increased rejection rates compared with whites209 and have a racial predisposition to diminished glucocorticoid responsiveness210.

Boston keratoprosthesis

This procedure has been FDA approved in the USA since 1992. It is completely synthetic, consisting of medical-grade polymethyl-metacrylate (PMMA). The first prototype was developed in the 1960s. According to the WHO criteria, candidates for keratoprosthesis surgery should be monocular, or bilaterally blind205.

Two types of the device are available, depending on whether the patient has a normal ocular surface and annex anatomy and the device can be anchored to the recipient’s cornea in a ‘wet’ environment (type 1) or whether the patient has a severe dry eye with possibly the presence of symblepharon. In the latter case the prosthesis should be placed transpalpebrally, in order to reduce the possible complications related to the severe ocular surface disease (type 2).

Assembly of the device

The first phase of the operation is the implantation of the KPro into a fresh donor button and is conveniently carried out on a small side table, under microscopic control.

A 3 mm hole is trephined in the center of a donor corneal button of 8.5–9 mm diameter (Fig. 21.45).

To make the manipulation of the different parts of the device easier, the front plate of the device is secured to an adhesive surface (provided in the package) (Fig. 21.46). The fresh corneal graft with its central hole is then brought over the stem of the front plate and slid down; the back plate is then placed on top of it and slid down over the stem (Fig. 21.47).

A titanium ring is pushed over the stem and slid down, in order to secure the sandwich made from the front plate, donor cornea and back plate of the KPro. In the package a white spanner wrench with a hole is provided in order to gently push down the graft against the front plate, avoiding excessive pressure.

Once the device is assembled, the patient’s cornea is trephined or the previous graft is detouched and the artificial cornea is sutured to the recipient bed using 16 interrupted 10-0 nylon sutures, burying the knots, with the same standard technique used for penetrating keratoplasty. As a rule the iris is not removed entirely at the root, since postoperative bleeding may occur and future glare problems can be increased. If the pupil is small, iridotomies will expand the pupil enough so as not to interfere with the visual axis if the positioning of the KPro should end up slightly eccentric. If the lens is in place, it should be removed in extracapsular fashion. A KPro with optics adjusted for pseudophakia can be used, but postoperative internal reflexes might worsen the visual outcome. If the vitreous surface seems intact, it is left untouched, otherwise an anterior vitrectomy is performed. A soft contact lens of 16 mm diameter and 9.8 mm base curve plano power is applied as a bandage at the end of the surgery. This surgery should not be performed without applying the contact lens (Fig. 21.48).

The type 2 KPro is assembled in a similar way as type 1, but the stem is longer so it can protrude through an opening made on the upper lid. Once the device is sutured in a standard manner to the recipient cornea, the device is covered with the lid skin, mucous membrane, or pericardium graft, in order to increase overall thickness. The type 2 device surgery is a very demanding procedure that involves meticulous dissection of the lids and underlying ocular surface and should be performed by highly specialized surgeons.

If the patient has a glaucoma that cannot be controlled, the addition of a glaucoma long-tube implant is mandatory and can be performed at the same time. The tube of the shunt should be oriented in order not to interfere with the visual axis. If a vitrectomy is indicated, this should be done in a reasonably extensive way to avoid the vitreous blocking the tube.

Postoperative care

Follow-up visits are scheduled at 1, 2, and 4 weeks after surgery, then on a monthly basis. The soft contact lens should be replaced every 3–4 months and the removed lens should be cultured, at least in high risk patients.

Slit-lamp examination should be performed routinely with a special interest towards signs of inflammation, integration of the device, positioning of the sutures, and eventually presence of retroprosthetic membranes. IOP should be checked at every follow-up visit; even if the palpation of the bulbus is not a precise assessment no more accurate device is currently available.

Topical steroids should be applied daily, starting four times daily for the first week and then slowly tapered. During the first month, topical wide spectrum antibiotics should also be applied at least four times daily. If fibrin is present a subTenon’s or orbital floor injection of steroids (triamcinolone 40 mg) is performed.

Five per cent povidone-iodine drops can be instilled in the conjunctival fornix at the time of the follow-up visit (once a month) in patients deemed to be at high risk of infection (patients with autoimmune diseases, living in developing countries with a humid climate or in patients who might have a poor compliance with the therapy) or who might be suspected of poor compliance with drop instillation.

Some authors suggest the use of vancomycin life-long to reduce the risk of severe endophthalmitis.

At 6 months, patients should be on chronic steroids drops qd per day thereafter.

When a bandage contact lens is required, it should be replaced every 3 months and should be sent for surveillance cultures whenever replaced. If after culture fungus or mold colonization becomes a concern, a 2 week course of econazole 2% or natamycin 5% respectively may be considered.

Osteo-odonto-keratoprosthesis (OOKP)

Strampelli in 1963 was the first to use osteo-odonto-keratoprosthesis (OOKP) in order to replace an opaque cornea that was at high risk for traditional graft211. It is composed of the patient’s own tooth root and surrounding alveolar bone to support a centrally cemented optical cylinder of PMMA which is grafted onto the cornea212 (Fig. 21.49).

The optical cylinder is cemented to the dentine. The dentine itself is coupled to the alveolar bone by the dentoalveolar ligament. The OOKP lamina is fixed by surrounding periosteum to the anterior corneal and scleral surface with sutures, but is also covered by a thick buccal mucous membrane graft204. Other biological materials are used for supporting the synthetic cylinder as cartilage213 or tibial bone214. The main theory behind all these devices is to have a inert biological skirt which can be colonized and integrated into surrounding tissues such as sclera and mucous membrane, yielding longer survival and lower extrusion rates215.

A good integration of the biological skirt allows the development of a blood supply that can withstand a very dry ocular surface. OOKP is therefore to be considered in patients with a very hostile environment caused by severe dry eye.

The implant of an OOKP is a multistep procedure that requires a multidisciplinary team consisting of an ophthalmologist, dental surgeon, radiologist, and psychologist. Table 21.1 summarizes the two-step focal points of the procedure.

Table 21.1 Steps for the preparation and implant of osteo-odonto-keratoprosthesis

  On the eye Preparing the device
Step A Corneal pannus removed
labial/buccal mucosa sutured to the sclera.
A single rooted tooth with the longest and straightest root (usually a canine tooth) chosen.
An approximately 2.5 mm thick slice of alveolar bone of approximately 9.5 × 14 mm cut.
An optical PMMA cylinder chosen in order to have at least 1 mm rim of dentine around the central channel.
The tooth-optic implant inserted in a submuscular pocket in the lower lid of the fellow eye.
2–4 month period
Step B Mucous membrane reflected inferiorly to expose the cornea.
Removal of iris, cataract extraction, and anterior vitrectomy performed.
Implant placed and sutured onto the corneal opening.
Implant removed from submuscular pocket.

Surgical technique

The first part of surgery consists in preparing the optical device along with the biological skirt and in allowing its vascularization. At the same time the recipient eye also undergoes ocular surface reconstruction. The patient should have a good oral hygiene and stop smoking before dental extraction, in order to enhance the chance of survival of the mucous membrane graft.

Preparation of the eye

The corneal pannus is removed through a keratectomy. A membrane mucous graft either from labial mucosa (Falcinelli) or from the inner side of the cheek (Falcinelli modification)216 is prepared. A 360° peritomy is performed and the corneal pannus is removed through a keratectomy. If too thin, the cornea is reinforced through a lamellar patch graft. The buccal mucosa graft is then sutured to the sclera (Fig. 21.50). After approximately 3 months the mucous membrane is usually integrated and vascularized.

AlphaCor

This type of KPro is predominantly used in Australia where it was developed, thanks to the efforts of Lions Eye Institute. Previously known as the Chirila KPro, it was first implanted in a human eye in 1998 and is FDA approved since 2003217. It is commercialized by Argus Biomedical Pty., Perth, Australia and is entirely made of poly 2-hydroxyethyl methacrylate (pHEMA), a synthetic, soft, biocompatible polymer (Fig. 21.51). The clear central optic zone is fused with a peripheral porous sponge skirt that allows biointegration into the host cornea by ingrowth of stromal fibroblasts218. The skirt is made of the same material as the clear part, but it is polymerized with a different water content (45% for the skirt and 35% for the clear optic)219.

The porous material remains enclosed within the cornea and allows the migration of fibroblasts. The device has a radius of 7.0 mm, a thickness of 0.5 mm, and a refractive index of 1.43219. The colonization of the skirt by the keratocytes for the integration of device is a mandatory step, as with other KPro models. The central optical zone was designed to remain clear, but various degrees of epithelialization can occur.

Patient selection is critical for reducing the risk of anatomical complications. AlphaCor should not be used in eyes with severe ocular surface diseases, extreme dry eye, history of herpes simplex disease, cicatrizing ocular surface diseases, or acute inflammation220.

This kind of device requires a two-step surgery, performed at an 8–12 week interval.

Surgical technique

Step B

Eight to twelve weeks later, the trephination of the center of the conjunctiva and anterior corneal lamella is performed in order to expose the optic portion of the device as a full-thickness corneal replacement; the peripheral skirt remains integrated into the corneal lamellae. Usually a 3.5 mm dermatologic trephine is used, in order to avoid the increased exposure associated with a 4 mm opening. The two-step technique is summarized in Table 21.2.

Table 21.2 Steps for the implant of AlphaCor keratoprosthesis

  On the eye Preparing the device
Step A Starting from 1–1.5 mm from the limbus, a sclera incision continuing into the superior cornea is performed in order to create a corneal pocket.
The center of the deeper lamella thephined and removed and the device positioned into the pocket.
The superior sclerocorneal incision sutured and a conjunctival flap positioned over the cornea.
No specific preparation is required for this device before implantation.
2–3 month period
Step B Trephination of the center of the conjunctival flap and anterior corneal lamella without touching the implant is performed.  

Pintucci biointegrable keratoprosthesis (PBKP)

The first prototype dates back to 1979. The biointegrable properties of Dacron were already confirmed by the good results obtained in the use of this material in angioplasty and cardioprosthesis, so a device with a skirt that could be integrated in the surrounding tissues and which could serve as a support for a synthetic PMMA optic was developed223.

The supporting element of the PBIKP is made of a biointegrated Dacron fabric skirt that allows three-dimensional colonization by the newly formed vascularized connective tissue (Fig. 21.52).

This fabric is chemically inert and unlike osteo-odonto-keratoprosthesis is not subject to resorption. The colonized Dacron mesh should prevent the epithelial downgrowth along the shaft of the optical cylinder by contact inhibition and by leaving no empty spaces at the implant–eye interface, therefore preventing retroprosthetic membranes, leakage, and microbial contamination224.

The two-step surgical procedure of implanting this device is similar to the one used for the OOKP. Table 21.3 summarizes the two-step focal points of the procedure.

Table 21.3 Surgical steps for the implant of the Pintucci keratoprosthesis

  On the eye Preparing the device
Step A Corneal pannus removed.
Labial/buccal mucosa sutured to the sclera.
The implant is inserted in a submuscular pocket in the lower lid of the same eye.
2-month period
Step B Cornea exposed.
Removal of iris and cataract extraction.
Implant placed and sutured onto the corneal opening.
Implant removed from submuscular pocket, fixation of the optical part tested and colonization of the Dacron tissue checked.

Complications of keratoprostheses

Keratoprosthesis surgery can provide good visual acuity when successful, but may also have disastrous complications. Complications may occur even years after surgery and are not infrequent. Efforts have been made to enhance long-term safety, but results are still not satisfactory.

Retroprosthetic membrane

The formation of a retroprosthetic membrane is a relatively frequent complication due to the high degree of intraocular inflammation that occurs in these patients. Studies on Boston KPro 1 report up to 65% of patients experiencing this kind of complication227.

If the membrane is thin, it can be opened with YAG laser228. When opening the membrane with the YAG laser, attention should be given to not using too much energy, as the optical zone can be damaged. The energy should be kept lower than 2.0 mJ; if this is not enough, the power can be increased carefully until the expected result is obtained, keeping in mind that the plastic can be damaged and even crack if excessive power is applied. The opening of the membrane can elicit intraocular inflammation, therefore subTenon’s injection of 40 mg triamcinolone is recommended after the procedure.

If the membrane is thick or richly vascularized, laser is not recommended as bleeding into the vitreous can occur. Surgical membranectomy and vitrectomy can be performed by an experienced vitreoretinal surgeon229. If the procedure fails, the whole KPro can be removed, the membrane removed surgically open-sky, and a new KPro can then be fitted.

Glaucoma

Glaucoma remains the greatest challenge after successful implantation of keratoprosthesis201,233235. The assessment of IOP postoperatively remains approximate, despite the efforts made towards the development of new tools for IOP assessment (like tonopen). The digital palpation of the bulbus remains the most widely used method to evaluate IOP postoperatively, but this procedure might also be difficult to interpret because of the presence of the KPro itself and eventually of drainage devices. New imaging modalities of the optic nerve head developed to monitor nerve fiber loss, such as optical coherence tomography (OCT), GDx nerve fiber analyzer or Heidelberg retinal tomograph (HRT) progression, might be useful for the evaluation of these patients.

The majority of the candidates for KPro surgery already have long-lasting advanced glaucoma, and many have already undergone either tube-shunt implantation or trabeculectomy.

Isolated cases of angle closure post Boston type 1 KPro implant have been reported; therefore the current KPro User Manual recommends that all patients with an intact iris receive a peripheral iridectomy at the time of surgery.

Future goals

Artificial corneas have been seen as alternatives to natural donor tissue to replace diseased corneas, thus reducing the spread of infections from host to recipient and avoiding the waiting time linked to the number of donations. Despite great efforts made towards the creation of a suitable and easily implantable artificial cornea, it remains a very demanding surgery recommended only as last chance to restore some vision in otherwise blind patients.

Research is oriented towards the substitution of rigid hydrophobic materials with hydrophilic hydrogels engineered to support glucose diffusion and surface cell adhesion.

One of the advantages of using synthetic tissues instead of tissue-engineered stroma is that the endothelial cell layer is not required to maintain the cornea clear, as the material is itself clear.

Tsubota and colleagues recently tried to develop a new concept of KPro by coating the surface of poly-(vinyl alcohol) (PVA) hydrogel with a biological matrix. The results of in vitro and in vivo studies are encouraging234236. The authors attached a collagen layer on a layer of PVA. Growth of stratified epithelia on this substrate was achieved, but the epithelia in these grafts came loose due to inflammation associated with sutures236. Recently amniotic membrane was used in order to enhance the strength of the ‘basement membrane’ where the epithelial cells can attach.

Efforts have been also made in the development of copolymers that mimic collagen type I. Engineering materials that are similar to the natural cornea might lead to the development of a material that can eventually be replaced by natural stroma through the invasion of keratocytes and remodeling of extracellular matrix237.

The use of interpenetrating polymer networks (IPN) is partly used for the production of AlphaCor. New efforts have been made in order to combine two different polymers with different characteristics in order to obtain a mesh that should end up having the beneficial properties of both polymers and compensate for some of their less desirable qualities238242.

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