Pediatric Keratoplasty

Pediatric keratoplasty encompasses penetrating and lamellar techniques. High-frequency ultrasound is a recognized tool for imaging the anterior segment of the eye, especially in the presence of corneal opacities. The use of high-frequency ultrasound preoperatively for penetrating keratoplasty in children with congenital corneal opacification allows surgical planning and appropriate counseling for parents in terms of prognosis. Its use for deep anterior lamellar keratoplasty in cases of mucopolysaccharidoses allows accurate definition of corneal trephine-cut thickness, permitting easier dissection to Descemet's membrane. Postoperative care and suture management in children are as important as meticulous surgical technique.

HISTORICAL PERSPECTIVE

The history of pediatric penetrating keratoplasty (PKP) is relatively short but in its roots is embedded the notion that children do badly. This was borne out by early studies where corneal clarity was as low as 6% after graft surgery. ¹ Cowden ² showed that the success rate could be improved but also that the procedure in infants could result in loss of eyes. Slowly, with better microsurgical techniques, and better understanding of how the tissue healing was different in infant cases compared with adult cases, the prognosis has improved, but is still relatively poor for infant PKP in cases of anterior segment developmental anomalies such as Peters' anomaly. ^3-12 Yang et al. ¹² as recently as 1999 report 35% graft survival at 7 years after graft in cases of Peters' anomaly. Nevertheless, good visual results have been reported following early PKP. ^8,9

Recent advances in techniques of deep anterior lamellar keratoplasty where Descemet's membrane is bared have gained favor. Such techniques rely either on the use of air to inflate the corneal stroma to aid dissection or on the use of air in the anterior chamber to delineate the Descemet/air interface and allow dissection of stroma off Descemet's membrane with or without the use of viscoelastic. DALK has been increasingly used to treat cases of keratoconus necessitating surgical intervention with the techniques described above. ^13,14

In the mucopolysaccharidoses, there is an accumulation of glycosaminoglycans (GAGs). Some types are associated with corneal clouding, which can be so severe as to necessitate surgical intervention. In these cases, the endothelium is healthy but there are GAGs in the corneal stroma causing opacification. DALK is ideal in these situations since the risk of endothelial rejection is drastically reduced, there is no penetration of the eye negating the risk of expulsive hemorrhage, and the visual recovery is thought to be faster.

The normal cornea contains 4-4.5% GAGs with three types being present in the stroma: keratan sulfate I and chondroitin and chondroitin-4-sulfate. GAGs are catabolized by lysosomal acid hydrolases, and deficiencies of these lead to GAG accumulation in corneal tissue. As a result, dermatan sulfate and keratan sulfate may accumulate in the cornea while heparan sulfate may do so in the retina and CNS.

The accumulation of GAGs in the cornea may result in considerable corneal opacification. Techniques such as those described by Melles et al. ¹³ and Anwar and Teichmann ¹⁴ are not applicable in such cases because the corneal lamellae are so packed with GAGs that there is no room for the passage of air or viscoelastic into the stroma at any level.

INTRODUCTION

Pediatric keratoplasty encompasses PKP and lamellar keratoplasty. PKP is the predominant technique because lamellar keratoplasty is technically more difficult to perform. Techniques for both, especially the latter, have improved in the last decade.

Crucial to both types of keratoplasty in children is the acknowledgment that pediatric ocular tissue behaves differently from that of the adult. The age at which the child's eye becomes more like that of an adult is controversial, but experience suggests that a child over the age of 10 years will have ocular tissue that behaves almost like that of an adult's.

High-frequency ultrasound is a well-established tool for the examination of the anterior segment, especially in eyes with corneal opacity. ^15-17 Congenital corneal opacification is rare, with prevalence approaching 3/100 000 live births (rising to 6/100,000 live births if congenital glaucoma is included). ¹⁸ It is one of the most challenging conditions to treat surgically.

This article describes the utilization of high-frequency ultrasound in the management of congenital and acquired corneal opacification requiring surgical intervention.

PEDIATRIC PENETRATING KERATOPLASTY

Intraoperative Technique

The basic technique is that described by Ehrlich et al., ¹⁹ but the use of UBM evaluation helps determine a more appropriate entry into the anterior chamber. All cases require a Flieringa ring because the sclera is much less rigid than that of an adult's (Fig. 1). This is sutured using 8/0 nylon in four quadrants, and the suture is left long so as to stabilize the eye with the long suture ends using Steri-Strips (3M). A pediatric radial corneal marker is used to mark the cornea and allow centration, which aids placement of the trephine. A small paracentesis is made and the anterior chamber is hyperinflated with viscoelastic usually Healon GV (sodium hyaluronate, PHARMACIA).

Figure 1

Prior to trephination of the host, mannitol is infused according to the weight and age of the child to reduce the intraocular pressure and reduce the risk of expulsive hemorrhage.

A manual trephine is used, and if keratolenticular adhesions or extensive iridocorneal adhesions are present, the anterior chamber is not entered with the trephine. Vacuum trephines such as the Barron-Hessburg are usually not manufactured to a small enough diameter.

The host button is fashioned after initial trephination with a 15° disposable blade so as to avoid excessive damage to the iris and or lens. In cases of keratolenticular adhesion, the lens may be carefully peeled off the cornea, but this usually results in cataract formation within a few weeks of the graft (Fig. 2). Therefore, there is an argument for lens aspiration with sparing of the posterior capsule; this needs surgical capsulectomy through a pars plicata approach usually within a few weeks also, but at least the donor cornea is a little more protected from trauma since the capsulectomy occurs a little deeper in the eye away from the corneal endothelium. All cases of Peters' anomaly or sclerocornea have an iridectomy in four quadrants to try to reduce the incidence of glaucoma (Fig. 3). The donor corneal button is oversized by 1 mm in all these cases also, to increase the anterior chamber depth. There is evidence that this improves outcome. ²⁰ Grafts are sutured using at least 16 10/0 nylon interrupted sutures.

Figure 2

Figure 3

All cases receive subconjunctival antibiotic and steroid injection at the end of the procedure. Intracameral dexamethasone is not routinely used by this author.

DEEP ANTERIOR LAMELLAR KERATOPLASTY (DALK)

Intraoperative Technique

The eye is prepared exactly as if a PKP were to be performed in case penetration should accidentally occur. The only difference is that a paracentesis is not performed prior to trephination. Trephination is performed using the Barron-Hessburg vacuum trephine in the standard way. Each quarter turn on this device affords a cut of 0.06-mm depth. The UBM is used to measure the trephine-cut thickness (TCT) rather than the standard corneal thickness (SCT) (Fig. 4). This last measurement is the measurement given by corneal pachymetry. It is the thickness of the cornea as measured perpendicularly to the surface of the cornea at the point of measurement. The TCT is the thickness of the cornea according to the true vertical line at the point of contact. It is always larger than the standard corneal thickness measurement except at the geometric center of the cornea where the two measurements should be equal.

Figure 4

Therefore, since the TCT has been measured, the number of turns are made so as to reach as close to Descemet's membrane without penetration. Once the trephine is performed, a paracentesis is now made in the peripheral cornea, and the anterior chamber is deflated of aqueous and reinflated with an air bubble (Fig. 5). The corneal button is lifted so as to expose the depth of cut made and a disposable crescent knife is used to gently lift the deep stroma away from Descemet's membrane (Fig. 6). The air bubble in the anterior chamber allows visualization of the Descemet/air interface as described by Melles et al. ¹³ Once the dissection has been initiated, the use of BSS or ordinary molecular weight Healon may be attempted to dissect off the deep stroma from Descemet's membrane, but in this author's experience in cases of MPS, this is still not easily possible. Careful manual dissection is needed to bare Descemet's membrane without penetration (Fig. 7).

Figure 5

Figure 6

Figure 7

The donor button is trephined to be 0.25 mm larger than the donor trephine, and Descemet's membrane stripped away using Vision Blue. The button is then sutured using 16/0 × 10/0 nylon sutures into the host bed. Subconjunctival antibiotic and steroid are given at the end of the procedure, and a small air bubble is left in the anterior chamber.

DISCUSSION

Infant Penetrating Keratoplasty

Preoperative Assessment

This includes a thorough evaluation of the anatomic problem and the physiological problems the child or infant may have. Physiological problems are evaluated by electrodiagnostic examination to evaluate the state of the retina and to evaluate the response to flash and pattern VEP.

Preoperative Assessment

* Visual evoked potential

* Electroretinogram

* Posterior segment USS (10-MHz ultrasound)

* Anterior segment USS (50 MHz-high-frequency ultrasound)

* Systemic assessment by pediatrician

Anatomic problems are evaluated using ultrasound of various frequencies. A 10-Mhz transducer is used to evaluate the posterior segment and a 50-MHz transducer is used to evaluate the anterior segment.

The Ultrasound Biomicroscope (Paradigm Medical Industries Inc., Salt Lake City, UT) allows visualization of the anterior segment to a depth of 5 mm with a resolution of approximately 50 μm. It utilizes a 50-MHz transducer, which is suspended on a mobile arm to allow high-resolution imaging. It may be performed on an awake infant but more usually needs to be performed with the patient under anesthetic (Figs. 8 and 9). A coupling agent needs to be applied between the transducer head and the cornea. Although methylcellulose can be used, Viscotears produces a much better image. Viscotears (CIBAVISION (UK)) (polyacrylic acid 0.2%) is a clear, colorless, highly viscous gel formed of high-molecular-weight, cross-linked polymers of acrylic acid that is commonly used for patients with dry eyes. The transducer in the UBM has a concave tip, which must be filled with a drop of water for injection before it is coupled with the lubricating agent on the surface of the cornea. This allows a clearer ultrasound image to be seen.

Figure 8

Figure 9

We have previously shown that the UBM has can be used reliably to image cases of congenital corneal opacification for evaluation of the cornea itself and any anterior chamber abnormalities. ²¹

The most common causes of congenital corneal opacification include sclerocornea and Peters' anomaly, both of which are probably part and parcel of the same spectrum of anterior segment developmental anomaly (ASDA). UBM imaging is more reliable in making a definitive diagnosis than just clinical examination alone in such cases. ²¹

Assessment of presence or absence of the lens, the iris, keratolenticular adhesions, and iridocorneal adhesions all help with surgical planning and also with assessment of surgical prognosis.

Poor Prognostic Indicators for Infant PKP

* Bilateral disease

* Glaucoma

* More than one procedure, for example, lensectomy and vitrectomy

* Previous PKP

* Corneal vascularization

* Keratolenticular adhesions

* Goniosynechiae

* Absent Bowman's layer

* Absent Descemet's membrane

Histologically, absence of Bowman's layer has been named as a poor prognosticator of PKP in Peters' anomaly as has absence of Descemet's membrane. Both of these features can be detected using UBM. ²¹

The presence or absence of glaucoma must be assessed. If glaucoma is present preoperatively, this again is a poor prognosticator. Under these circumstance and if the corneal opacification is bilateral, laser cycloablation (usually cyclodiode laser) is used under UBM guidance to treat the inferior half of the eye (unpublished data: High frequency ultrasound guided laser cyclophotocoagulation. Choong YF, Kouri A, Nischal KK. Poster AAPOS meeting. March 2003, Hawaii). This allows control of the glaucoma with appropriate topical medication, and penetrating keratoplasty can then be performed with the clear understanding that drainage will probably need to be placed at a later stage to control the glaucoma. Simultaneous PKP and drainage tube placement is not a favored route by this author in infant eyes.

Postoperative Care

The tissue reactivity in infants is such that intensive topical steroid/antibiotic preparations are a necessity to prevent fibrin formation, synechiae, and rejection. These are applied one-half hourly for the first 24 hours with cycloplegic drops three times daily and antibiotic/steroid ointment at night to allow the infant to sleep. The intensity of drops is tapered off over 2 months, and cycloplegia may continue for the same period. Infants are reviewed twice weekly for the first 6 weeks because the slightest hint of a loose suture or suture vascularization necessitates removal of the offending suture under anesthesia within 24 hours. Failure to do so results in rapid epithelial rejection. In any case, all sutures are removed in infants at the latest by 6 weeks postoperatively.

After 2 weeks, topical cyclosporin A eye drops (2% in corn oil) are used twice daily indefinitely to prevent rejection of the corneal graft (Figs. 10 and 11). There is evidence that topical cyclosporin A reaches adequate levels for immunosuppression within the cornea but not necessarily within the eye and that the combined use of CsA and steroid drops reduces the rate of rejection in high-risk corneal grafts compared with topical steroids only.

Figure 10

Figure 11

INDICATIONS AND CONTRAINDICATIONS

In 1977, Waring and Laibson ⁷ stated We do not recommend PK in patients with unilateral, congenital corneal opacities. However, those with bilateral cloudy corneas should have an attempt at keratoplasty as early in life as possible. This author agrees with this statement almost in its entirety; the only point of contention is that in some cases the so-called normal eye is not normal, only less affected. In these cases, the parents should be given the option of keratoplasty with the clear understanding that the prognosis for vision is poor due to the physiological phenomenon of amblyopia on top of the risks of rejection, infection, and glaucoma. Furthermore, there is a particular subtype of Peters' anomaly, which even if present unilaterally necessitates PKP because it predisposes to the risk of spontaneous corneal perforation or rupture. In this subtype, the degree of posterior corneal defect (a hallmark of the condition ²²) is so great that instead of a central corneal opacification, there is relative clearing. UBM evaluation clearly shows in these circumstances that the central cornea is extremely thin ²¹ and prone to rupture, especially in the presence of glaucoma. The PKP performed under these circumstances is tectonic in nature.

Deep Anterior Lamellar Keratoplasty for MPS-Related Corneal Opacification

Preoperative Assessment

This again includes an assessment of physiological and anatomic problems. In children with MPS it is essential to exclude optic atrophy and retinal dysfunction prior to embarking on any keratoplasty. Electrodiagnostics are essential for this purpose. Glaucoma should also be excluded, but it should be noted that applanation tonometry may result in an artefactually elevated intraocular pressure reading because of the increased rigidity/thickness of the cornea. Evaluation of the optic disc becomes mandatory but if this is not possible, 10 MHz ocular ultrasound may be used to evaluate the presence or absence of optic disc cupping.

Postoperative Care

Topical steroid/antibiotic drops are used every 2 hours for the first 3 days and then reduced gradually over 2 months. Topical cyclosporin A is not used. Cycloplegia is only necessary for 2 weeks. Most children undergoing DALK for MPS-related corneal clouding are older. Therefore, in children over the age of 5 years, the sutures are left in situ for approximately 6 months, but the indication for removal is any sign of scarring or vascularization at the suture entry points within the donor. Partial or alternate suture removal may be preferred. In children who are under 1 year of age who have undergone DALK for reasons other than MPS, for example, corneal scarring from keratitis, suture removal should be performed early and the same intensity of follow-up should be applied as per infant PKP (Figs. 12 and 13).

Figure 12

Figure 13

INDICATIONS/CONTRAINDICATIONS

Conditions that exhibit corneal stromal involvement without endothelial involvement are ideally suited to DALK. This includes stromal dystrophies, metabolic disorders (MPS especially), and corneal scarring from any cause. In cases of MPS where bone marrow transplant has not been performed or is not being considered, the donor cornea will become infiltrated with GAGs again and this should be made clear to the parents of the child.

The advent of modern surgical techniques has afforded a better chance of success in children who need keratoplasty. However, any such improvement in technique is worth little without appropriate and early visual rehabilitation. Spectacle correction is a useful first step but, especially in infant PKPs, the rate of astigmatism may be high and irregular. Contact lenses may be needed. Occlusion therapy is often needed and often poorly tolerated, especially if the child has other systemic problems.

The Future

It is possible to imagine that posterior lamellar keratoplasty ²³ could be applied to cases of Peters/sclerocornea using endoscopic techniques with simultaneous lensectomy and vitrectomy. Perhaps more realistically is the possibility that an artificial material for infant PKP may be available in the near future, which reduces the rates of rejection because of material surface modification using man-made bilipid layers or polymers.

What is really exciting is that DALK is here now and potentially will reduce endothelial rejection rates dramatically in all cases where it can be used.

No matter how advanced techniques become, this author feels sure that three fundamental principles will remain unchanged.

1. The parents of the child must be included in all decision making and therefore must be fully informed.

2. If the ocular tissues of the child are treated like those of an adult's, failure will always be a real possibility.

3. Visual rehabilitation after surgery cannot be ignored.

ACKNOWLEDGMENT

Thanks to Dr. David Rootman, MD, for his advice, teaching, and encouragement.