Correction of Refractive Errors after Corneal Transplantation

Abstract

Even after a successful keratoplasty with a clear graft, a high postoperative refractive error could occur too hard to correct with spectacles or contact lenses. Therefore, refractive surgery could be considered a good tool to correct these high postoperative defects. The authors showed the reasons involved in the refractive errors after successful penetrating (PKP) or lamellar transplantation (DALK), pre-, intra-, and post-operatively. Moreover, they presented different techniques to correct the refractive errors after transplantation for different corneal pathologies, in the plastic phase (managing of transplant sutures) as well as in the static phase (different refractive techniques: incisional (AK, FemtoAK), ablative (PRK, FemtoLASIK), or IOL implantation (Phakic IOL, PHACO + IOL)). Thus, it is necessary to study accurately every single clinical case to choose the best surgery for each patient. Due to the high risk of graft damage or graft rejection, the patient must be adequately informed about the risks and benefits of the surgery proposed and must specifically accept the possibility of a new corneal transplant in the event of surgery failure or graft damage. Certainly, the refractive surgeon must be able in managing all the different refractive surgery techniques to reach the best result in every single case.

1. Introduction

The primary result of corneal transplantation is restoring of the transparency and shape of the cornea, although, to reach a good visual quality it is also necessary to restore a correct geometry of the surface, as close as possible to th

e physiological one.

When, in case of a clear graft the second target is not achieved and the vision is not qualitatively good, a tangible failure of the transplant resulted.

This situation can occur in case of high postoperative refractive errors, not easily fixable with glasses [1, 2]. Contact lenses, required to correct postoperative refractive errors, resulted often difficult to wear for the patient, difficult for the optician to construct and sometimes even harmful, due to lesions of the graft or to onset of limbal new vessels (leading to rejection and/or opacification of the graft) [3, 4, 5]. Nowadays, with the new lasers and the modern refractive surgery techniques it is possible to correct even a very high post-operative refractive defect [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17]. However, these are “complex” cases, that require a careful study and a correct surgical planning [13, 17].

Firstly, we must consider what type of post-transplant refractive defect we need to correct (cylindrical or spherical: myopic, hyperopic or mixed), what type of corneal transplant has been performed (penetrating or lamellar), what technique and what kind of instrumentation was used to make it (manual, automated or laser trephination), what type of sutures were used (continuous, single stitches or mixed) and how and when they were removed. Moreover, must be considered the original corneal pathology leading to transplantation (corneal decompensation, trauma, leucoma, corneal ectasia) and the age of the patient, all factors that greatly influence the postop results and our surgical choice [13, 17].

Several refractive and corneal surgery techniques can be used for the correction of refractive defects after corneal transplantation: compressive sutures [1, 17], incisional techniques [18, 19], surgical techniques with ablative lasers [9] or even intraocular lens implantology techniques [17].

Firstly, it is necessary to differentiate the postoperative corneal transplant period in a so-called “plastic” phase, in which the sutures are still present, and it is possible to manage by modulating their tension, and a “stabilization” phase in which all the sutures have been removed, the graft scar has solidified and the corneal architecture can no longer undergo major changes [17, 20].

2. Roots of post corneal transplantation refractive error

Corneal transplantation, both lamellar and penetrating, may have a significant influence on refraction with the creation of a new “limbus” at the level of the scar, affecting the corneal curvature for 360° [2]. Postoperative refractive errors can be influenced by several factors that could affect the preoperative, intraoperative, or postoperative phase of the keratoplasty (Table 1) [2, 13, 17, 20]. Although a good standardization of the surgical technique helps to reduce most of these factors, it’s always difficult to predict the postoperative refractive results. Moreover, even in case of perfectly performed grafts and with excellent refractive results, after the complete removal of the sutures, a high and even irregular astigmatism could occur, due to irregular healing of the corneal scar [21]. Therefore, it is important to study carefully the single clinical case and set the correct surgery to minimize the risks of postoperative surprises.

Pre-operative	Hyper-steepening or recipient surface irregularity; Irregular thickness of recipient bed or donor graft; Different Consistencies between recipient bed and donor graft
Intra-operative	Imperfect donor cornea handling; Centering and inclination of the trephine; Misalignment between recipient bed and donor cornea; Transplant technique and type of suture
Post-operative	Wound dehiscence; Melting of the graft

Table 1.

Causes of post corneal transplantation astigmatism and ametropias onset.

3. Causes of post corneal transplantation astigmatism and ametropias onset

3.1 Preoperative causes

3.1.1 Related to the recipient bed

The curvature and structure of the recipient cornea significantly affects trephination. The presence of a corneal hyper curvature and/or an irregularity of curvature can lead to an irregularly oval trephination with non-perpendicular cutting edges that make juxtaposition between donor and recipient difficult [2, 20]. In the event of corneal irregularities or of a hyper prolate cornea, it is advisable to cauterize the apex of the corneal ectasia which allows for more regular trepanation. A difference in thickness can also negatively affect the regularity of the trephination and the postoperative result [2]. In the case of strongly different thicknesses (ectasias or decentralized or peripheral corneal thinning), an attempt should be made to perform as large a trephination as possible to “include as much pathological tissue as possible”, even at the expense of an increased risk of rejection.

Another factor to consider is the difference in “consistency” of the tissue which can often change depending on the area of the cornea to be transplanted (areas of melting, descemetocele, calcifications, etc.) which can result in scarring irregularities of the graft.

3.1.2 Related to the donor cornea

The radius of curvature of the donor cornea can influence the refractive result after transplantation, as well as unrecognized ectasias or structural weaknesses of the same [17]. The presence of opacity or thinning areas of the donor cornea not detected at the post-explant examination can undermine the postoperative result as well as the decentralized, non-regular or non-perpendicular cut of the donor button or the increased diameter of the donor (which leads to an increase in corneal curvature of the graft and therefore to a myopia).

3.2 Intraoperative causes

An error in centration and perpendicularity of the trephination (both on the donor button and on the recipient bed) could cause cutting irregularities with obvious difficulties in suturing the margins or unpredictable refractive results due to the involvement of the pupil or the visual axis by the graft scar: an equidistance between the pupillary margin and the graft scar is required to obtain good regularity of postoperative astigmatism [20].

In the same way, the diameter of the graft also affects the postoperative result: larger diameters allow to obtain less influence by the suture on the refractive result of the graft, on the contrary, smaller diameters are more sensitive to the tension of the sutures with greater influence on the postoperative refractive error. In the past, to avoid the risk of rejection, flaps with a diameter from 6 to 6.5 mm were preferred, which often resulted in very high postoperative astigmatism.

Another intraoperative parameter to consider is the correspondence between the trephination of the recipient bed, which may not be well perpendicular (tilting), and that of the donor cornea, with evident malposition of the suture margins, over or under-alignment or distortions of the scar that result in high or markedly irregular astigmatism, diastasis of the surgical wound, and possible ectasia of the graft [21]. A helping hand for the surgeon is the semi-mechanized suction trephine (excellent stabilization and good cutting) or the laser-assisted trephine (possibility of customizable cutting geometries and “interlocking” designs) which allowed to obtain significantly better results than the first manual trephines strictly dependent on the skill of the surgeon.

Finally, the depth, distance and length of the suture and the type of suture (single stitches or continuous, single or double running) can also affect the refractive result [20].

3.3 Postoperative causes

The timing of suture removal is one of the most important factors in the postoperative refractive outcome [2, 20, 21]. Normally, the sutures should be left in place for as long as possible to obtain the most stable scar. However, sometimes it is necessary to remove the sutures, selectively or totally, as in the case of severe fibrosis with scar contraction, or in the case of loosening of the suture with high risk of neovascularization and graft rejection. The early removal of the sutures can cause a relaxation of the scar with “ectasia” of the graft and subsequently high myopia and astigmatism. Moreover, in the case of early selective removal of detached sutures high or highly irregular astigmatism may occur, hardly correctable with glasses or contact lenses. However, in the case of too early removal of continuous sutures, we can find cases of great “graft ectasia” with characteristic thinning at the level of the scar junction between donor and recipient at the slit lamp and at the tomographic examination (OCT, Scheimpflug camera). It is important, before suture removal, to evaluate the consistency of the transplant scar: in general, the more the fibrosis is white, the more it should be resistant, on the contrary a greater transparency denotes structural weakness of fibrosis and strong ectatic risk.

4. Correction of postoperative ametropias in the plastic phase

The correction of refractive errors in the plastic phase is made possible due to the ductility of the transplant scar within the first 6/8 months after surgery (Table 2).

Adjustment of the suture	Single stitches; Single running suture; Double running suture
Removal of the suture	Hypertension or loosening; Selective suture removal
Apposition of the suture	Single stiches adding; Continuous sutures repositioning

Table 2.

Surgical solution in the plastic phase.

The therapeutic options in this phase are all related to re-tightening, replacing, or affixing new sutures in order to redistribute and rebalancing the tensions in the scar [21].

The re-tightening of the continuous suture can be performed in the plastic period, thanks to the elasticity of the corneal sutures. The technique consists in baring the suture with an IOL hook by removing the epithelial layer that covered it and in loosening the tension of the suture in the most curved area under keratoscopic control by sliding the thread and immediately after pulling it into the flatter area. In the case of a double suture, this action must be performed on both (by rotating one clockwise, the other counterclockwise) to avoid “rotation” effects of the flap, regularizing and stabilizing the result.

The apposition of sutures must be carried out in the case of continuous suturing with irregular passages (in terms of distance or length), in the case of a passage omission, in the case of wound dehiscence or in the case of under or over-leveling of the graft to regularize the surface and rebalance the tensile forces. It is often necessary and even more convenient to apply more than one suture stitch to distribute the tension in the affected quadrant.

The replacement of the suture may be mandatory in the case of hypertension with high flattening of the graft or loosening of the continuous suture with signs of ectasia, wound dehiscence, or initial neovascularization with risk of rejection and failure of the transplant. In these cases, it is possible to replace the continuous suture with detached stitches (in case of corneal melting or neovascularization) or to apply a new more regular overedge suture.

5. Correction of postoperative ametropia in the static phase

In the static phase, after at least 6 months from the complete removal of the transplant sutures, when the scar is well stabilized, curving, flattening or incisional, ablative and implant techniques can be used (Table 3).

Curving techniques	Compressive sutures; Revision of the corneal wound; Wedge resection
Flattening or Incisional techniques	Relaxing incisions, AK/FemtoAK
Laser technique	PRK with Mitomicine C; LASIK/FemtoLASIK (1 or 2 step)
IOL Implantation technique	Phakic IOL; PHACO + toric IOL

Table 3.

Surgical solutions in the static phase.

A study report performed in 2002/2003 in Italy by the Italian Society of Corneal Transplantation (S.I.Tra.C) demonstrated the variety of techniques performed by the Italian corneal surgeons to correct the refractive errors postkeratoplasty in the static phase, with the AKs and the LASIK acting as the best choices (over 70% of the surgeries) (Figure 1).

Figure 1.

The “S.I.Tra.C. 2002-2003 report” shows the results of the conference of Italian corneal surgeons on different surgical techniques for correction of postoperative astigmatism in the static phase. Incisional techniques and LASIK are the most represented, with over 72% of the surgery.

5.1 Curving techniques

• Applying compressive stitches along the flatten axis.

• Revision of the surgical wound with reopening of the affected area and adding of sutures.

• Wedge resections: removal of a crescent-shaped lamella in the affected quadrant and adding sutures to correct high astigmatism over 10 diopters [22].

5.2 Flattening or incisional techniques

Arcuate keratotomies (AK) are used to correct high and irregular astigmatism for the ability to selectively modify one axis or two semi-axes of the astigmatism. AKs are one of the first refractive surgery technique for the correction of corneal astigmatism [19]. Initially, this method was performed freehand with a precalibrated diamond blade and the guide of a round goniometer positioned in the limbal area. Later, a suction guide (Hanna arcuate keratome, Figure 2) was developed for the diamond blade which allowed for higher precision and more repeatable executions [13, 19]. Currently, the AKs are performed with the modern femtosecond laser that allows the execution of very precise, safe, highly repeatable arcuate incisions, with width, depth, shape, and position totally programable by the laser software [21, 23].

Figure 2.

Hanna arcuate keratome (or arcitome).

During the execution of an AK, the position, shape, width, axis and depth, and distance between the two AKs that creates the resulting “optical zone” must be considered.

• Position: The relaxing incisions can be made within the graft, inside the graft scar and outside the graft. Making incisions inside the scar is at high risk of ectasia or of perforation of the corneal scar and transplant failure; the incisions made on the recipient bed have greater unpredictability and are less performing, because the transplant scar acts as a neo-limbus and introduces a variable that cannot be evaluated [21]; therefore, the logical position of the AKs is inside the graft, for a more predictable effect (the scar is the reference point), greater performance (greater effect of the incisions when closer to the geometric center of the graft) and less risk of instability, especially with the modern graft diameters of at least 8–8.25 mm in diameter.

• Shape: The shape of the incision can be straight, trapezoidal, or arcuate. Obviously, the most corrective is the arch-shaped one, because the equidistance from the round scar and from the optic center allows to move the same amounts of tissue, acting practically at the same depth along its entire extension, and therefore balancing the forces.

• Width: The width of the AK must be calculated basing on the area of ​​the scar with the greatest traction, that consist in the area of ​​greatest curvature on topographic examination (The “red area” in axial topography), however it must not exceed 90° of extension for the risk of destabilization of the transplant [23].

• Axis: The incision axis is the steeper axis of topographic astigmatism. That axis is often not symmetrical (irregular bow tie astigmatism), so the two AKs must be performed along two different semi-axes (with an angle >90° and <180°) to correct irregular corneal curvatures.

• Depth: The depth of the incisions must be at least 80% of the corneal thickness at the incision point (however, depths from 50 to 90% have been described) [21] to obtain the maximum flattening of the affected axis and ensure the duration of the effect over time. This means that the two AKs may be of different depths based on the pachymetry of the graft at that precise point, to obtain the same type of result in both incisions on transplant astigmatism.

• Distance: The distance between the two AKs must be such as to respect the optical center and the optical zone necessary to correct vision (it is important to evaluate the pupil diameter with “pupillometry”) to reach the best refractive result for the single patient.

In our personal experience with femtosecond laser-assisted AKs for the correction of high and irregular astigmatism after corneal transplantation on 31 eyes, we obtained a correction of preoperative astigmatic topographic cylinder of 56% and of preoperative refractive error of over 42% (Figure 3).

Figure 3.

Results of Femto-AKs for post PKP astigmatism: reduction of 56% of topographic astigmatism and 42% of refractive cylinder.

5.3 Ablative techniques

Among the ablative techniques we mention photorefractive keratectomy or PRK (with or without Mitomycin C) and in situ keratomileusis assisted by excimer laser or LASIK. PRK is a surface technique that was first used for the correction of post-transplant ametropias, following the exciting results obtained in congenital ametropias, with alternating fortunes and high rates of transplant failure and opacification (late haze). Some improvement in terms of stability and reduction of postoperative haze has been obtained by performing customized transepithelial ablations (CIPTA, or Wavefront custom PRK-Zyoptics) or by associating PRK with the use of Mitomycin C (despite the high risk to damage the graft) [14, 15, 16].

The most used technique in the correction of spherical ametropia and regular astigmatism after corneal transplantation is LASIK, an intrastromal ablation technique that allows greater stability of the refractive result and less risk to damage the donor graft. Initially, LASIK was performed using the microkeratome, an instrument of good precision, although highly unreliable in borderline corneas (too curved, too flat, or irregular), with excellent visual results [6, 10, 12]. To increase the results in the correction of astigmatism it has also been proposed to perform LASIK in two steps: first cutting the flap to interrupt the graft scar and reduce the amount of astigmatism (by about 15–20%), then, after at least 15 days, performing the laser ablation on the residual refractive error [10], even using aberrometric ablation for the correction of slightly irregular astigmatism [11].

However, LASIK with microkeratome, showed great limitations in borderline corneas: increased risks of rupture of the transplant scar, of irregular cutting of the flap (in corneas with over or under-leveling), of buttonholes (in corneas that are too curved, above 48D) or free cup (in corneas that are too flat, below 38D). So that, the use of the femtosecond laser was proposed for the execution of the corneal flap. The advantages of the femtosecond laser are incontrovertible: all the intervention is programmable, the treatment can be interrupted in the event of problems during the cut (opening of the scar, loss of suction…), does not suffer with borderline corneas (nor buttonhole, nor free cap), it is possible to decide the diameter of the flap (inside or outside the scar), and it is absolutely precise and repeatable. Femtosecond laser-assisted LASIK (Femto-LASIK) is therefore the technique of choice for the correction of refractive defects after keratoplasty [17].

The Italian experience gained with the LASIK with microkeratome [6, 10, 11] has allowed us to approach the correction of refractive defects after keratoplasty with the Femtolaser-assisted LASIK.

The femtosecond laser allows to execute totally programmable corneal flaps with the size and thickness planned, with great precision, versatility, and safety [17].

With the femtolaser it is possible to customize various parameters:

• Depth of cut: The thickness of the flap is programmable from 90 to 100, 110, 120 (the most used) or even more microns. The reduced thickness of the flap and its uniformity for the entire extension (planar flap) allows to have as little influence as possible on the structure of the already compromised corneas such as those undergoing corneal transplantation, allowing even more tissue for the refractive ablation (as opposed to the meniscus flaps of the 130–160 micron microkeratomes).

• Inclination angle of the side cut: With the femtolaser it is possible to perform a peripheral cut (side cut) from 70° to 90° up to 160°, in order to obtain a perfect repositioning of the corneal flap, which is perfectly reallocated on the stromal bed, as opposed to the meniscus flap with tangential cut that “floats” on the cutting surface.

• Hinge: The hinge can be programmed and positioned anywhere, nasal, temporal or superior, based on the conformation of the receiving cornea and the need for correction of the refractive defect.

• Size and shape of the flap: The flexibility to decide the size of the flap based on the needs of refractive ablation is one of the most important innovations of the femtolaser. In the case of corneal transplants, it is possible to decide to cut the scar (to perform a two-step LASIK for the correction of high astigmatism) (Figure 4) or to perform the flap inside the graft (in the case of mainly spherical defects) (Figure 5). Furthermore, today the new femtosecond lasers allow to perform elliptical flaps to facilitate the correction of astigmatism.

• Association with incisional surgery: In special cases, with very high or irregular astigmatism, it is also useful to associate arcuate keratotomies (AKs) to LASIK which obviously must be performed in two steps, to allow the incisions to stabilize and perform less complex excimer laser ablations (Figure 6).

Figure 4.

FemtoLASIK flap performed outside the graft scar.

Figure 5.

FemtoLASIK flap performed inside the graft scar.

Figure 6.

FemtoAKs inside the graft scar and FemtoLASIK flap performed outside the graft.

Our personal experience with Femto-LASIK on 27 eyes of 26 patients showed a correction of the spherical defect of 77% with an improvement in both UCVA and BSCVA (increase in BSCVA of 20% compared to preoperative), all the results kept stable 36 months after Femtolaser-assisted LASIK. In our experience, we have not found any major complication, except for some peripheral irregularities of the flap at the points of passage of the sutures, and a case of endothelial rejection 1 month after surgery that cannot be directly correlated with the use of lasers (Figure 7).

Figure 7.

Results of BSCVA in FemtoLASIK postPKP at 36 months: a correction of the defect of 77% with an improvement in both UCVA and BSCVA (increase in BSCVA of 20% compared to preoperative).

5.4 Intraocular lens (IOL) implantation techniques

To correct refractive defects that cannot be corrected with incisional or ablative techniques, it is possible to consider implantation of phakic IOLs, including toric ones, or, in the case of concomitant lens opacity, it is possible to perform a phacoemulsification with implantation of toric IOL [13, 17, 20].

• Implantation of phakic IOLs: There are different phakic IOLs available on the market, from anterior chamber (AC IOL), angle supported or iris fixation, and posterior chamber (PC IOL). Angle supported anterior chamber phakic IOLs are unfeasible in correcting eyes that have undergone corneal transplantation due to the possibility of graft damage. The iris fixation AC IOLs are the most used in the USA for the ease of the implant and for the possibility of correcting even moderate astigmatism (Artisan/Artiflex IOL by Ophtech). However, with this kind of IOL implant, even in the presence of a fairly large anterior chamber, the risk of injury to the graft’s endothelium is too high [21]. The modern posterior chamber phakic IOLs (such as the Visian IOL evo by Staar surgical) allow a good correction of spherical refractive defects and astigmatism up to 6 diopters, with reduced risk of transplant injury. However, this type of IOL presents considerable risks too: if the size of the IOL is wrong due to an incorrect calculation of the “white to white” length (and in postPKP eyes this calculation could be particularly difficult) “voulting” can result too low and the PC IOL can damage the lens causing a cataract or too high and the PC IOL can touch the iris, causing chronic intraocular inflammation that can lead to pupillary block and incoercible hypertonus.

• FACO + toric IOL: In case of initial lens opacity in subjects over 45 years of age, a phacoemulsification with a toric IOL implant could be considered. With modern customizable toric IOLs it is also possible to correct very high spherical and astigmatic defect with good visual results. However, this technique is a question of debate for many surgeons, due to the convenience of using a toric IOL, difficult to replace in case of a new transplant.

6. Conclusions

Due to the complex pathology and to the variety of therapeutic choices available, it is clear that it is necessary to study accurately every single clinical case to choose the best surgery for each patient, considering also that failure or damage of the corneal graft can cause rejection or decompensation. Therefore, the patient must be adequately informed about the risks and benefits of the surgery proposed and must specifically accept the possibility of a new transplant in the event of surgery failure or graft damage. Obviously, to correct these complex post operative refractive errors, the refractive surgeon must be able in managing all the different refractive surgery techniques presented before, to reach the best result in every single case.