J CATARACT REFRACT SURG - VOL 32, AUGUST 2006
ARTICLES
Excimer laser-assisted anterior lamellar keratoplasty for keratoconus, corneal problems after laser in situ keratomileusis, and corneal stromal opacities ¨ zdek, MD, Ayc¸a Sari, Berati Hasanreisog˘lu, MD Kamil Bilgihan, MD, Sx engu¨l C. O
PURPOSE: To evaluate excimer laser-assisted anterior lamellar keratoplasty to augment thin corneas as in keratoconus (<350 mm) and corneal ectasia after laser in situ keratomileusis (LASIK) and to treat anterior stromal opacities. SETTING: Ophthalmology Department, School of Medicine, Gazi University, Ankara, Turkey. METHODS: Thirteen eyes (5 keratoconus, 3 macular dystrophies, 1 post-LASIK ectasia, 1 post-LASIK interstitial keratitis, 3 post-herpetic keratitis sequelae) of 13 patients were included in this prospective study. The treatment group was divided into corneal ectasia and stromal opacity groups. A donor stromal button approximately 350 mm thick received a 100 mm excimer laser ablation on the endothelium. The remaining cornea (epithelium, Bowman’s membrane, and stroma) was punched with a 7.5 or 7.7 mm trephine. After transepithelial ablation of the host cornea to 200 mm thickness, the corneal button was sutured with interrupted 10-0 monofilament nylon. Sutures were removed between 3 months and 6 months postoperatively. Preoperative and postoperative simulated keratometric cylinders and corneal thickness values were compared using the Wilcoxon signed rank test. The postoperative spherical equivalent refraction and best spectacle-corrected visual acuity (BSCVA) between the groups were compared using the Mann-Whitney U test. RESULTS: The mean follow-up was 27.6 months G 8.3 (SD). All patients gained 2 lines or more of BSCVA, and no patient lost a line. The mean corneal thickness was 381.2 G 88.2 mm preoperatively, which significantly increased to 534.9 G 96.6 mm postoperatively (P<.05). The mean preoperative simulated keratometric cylinder was 7.44 G 7.18 diopters (D); postoperatively, it decreased to 2.61 G 1.73 D (P<.05). There was no significant difference in postoperative spherical equivalent refraction or BSCVA between the groups (P>.05). CONCLUSIONS: This technique presents a different modality for the treatment of keratoconus, postLASIK corneal problems, and other corneal stromal opacities with anterior lamellar keratoplasty. Additional studies with more patients and longer follow-up will help determine the role of this technique as a substitute for penetrating keratoplasty in these patients. J Cataract Refract Surg 2006; 32:1264–1269 Q 2006 ASCRS and ESCRS
Penetrating keratoplasty (PKP) has become the standard surgery for the treatment of most corneal pathologies including keratoconus and corneal opacities. Despite the surgery’s popularity, there is a continuous ongoing search for new surgical techniques using recent technological developments to eliminate the well-known problems associated with PKP.1–17 Anterior lamellar keratoplasty has several Q 2006 ASCRS and ESCRS Published by Elsevier Inc.
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advantages over PKP including preservation of the host endothelium, avoidance of complications associated with open-sky surgery, decreased risk for allograft rejection, and superior wound strength.1–5 Preservation of the host endothelium is vital for long-term graft survival in younger patients. Although treatment of keratoconus with anterior lamellar keratoplasty is well established during end-stage 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.02.056
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Table 1. Preoperative patient data.
Case/Age(Y)/Sex
Diagnosis
UCVA
BSCVA
Refraction
Keratometry SimK (D)
Pachymetry (mm)
Surgical Technique
1/22/F 2/27/F 3/23/M 4/27/F 5/12/F 6/28/F 7/45/F 8/31/M 9/48/M 10/50/M 11/47/M 12/19/M 13/40/F
KK KK KK KK KK MD MD MD LASIK-I LASIK-ect P-herpes P-herpes* P-herpes
CF CF 20/200 20/125 CF 20/200 CF CF 20/200 CF 20/200 20/400 20/200
20/50 CF 20/100 20/100 CF 20/200 CF CF 20/50 CF 20/200 20/63 20/200
9.00 4.00 30 Overrange Overrange 6.00 7.75 143 Overrange 1.50 100 Overrange Overrange 1.25 180 Overrange Irregular C6.00 C3.50 90 Irregular
59.4/52.9 67.3/54.9 64.0/44.5 59.9/56.2 59.4/54.9 45.9/44.3 45.9/44.2 41.6/45.9 41.1/43.2 58.8/44.5 46.2/44.4 43.1/41 40.6/38.3
300 300 298 339 300 400 460 430 444 240 510 450* 485
ELE ELE ELE ELE ELE ELE ELE ELE ELE ELE ELE ELE ELE
BSCVA Z best spectacle-corrected visual acuity; CF Z counting fingers; ELE Z excimer laser-assisted epikeratoplasty; KK Z keratoconus; LASIK-ect Z postLASIK ectasia; LASIK-I Z post-LASIK interstitial keratitis sequela; MD Z macular dystrophy; P-herpes Z post-herpetic keratitis sequela; SimK Z simulated keratometry; UCVA Z uncorrected visual acuity *Previous phototherapeutic keratectomy
disease, it is time consuming and difficult, with poorer optical results than with PKP. These factors limit its routine use in clinical practice.1 In addition to patients with keratoconus, those with corneal ectasia and flap-related complications (flap loss, diffuse interstitial keratitis sequelae, flap necrosis) after laser in situ keratomileusis (LASIK), stromal corneal dystrophies, and opacities are good candidates for anterior lamellar keratoplasty. The benefits of anterior lamellar keratoplasty have encouraged surgeons to develop new and easier techniques such as hydrodelamination,6 air dissection,7,8 ophthalmic viscosurgical device dissection,9,10 divide and conquer,12 and excimer laser microkeratome dissection.13–17 We previously published the stromal sandwich technique for the treatment of keratoconus.14 The technique described here is a modified epikeratoplasty, which was first planned for spectacle- and contact-lens-intolerant patients with advanced keratoconus who were PKP candidates with corneas of 350 mm or less. Called excimer laser-assisted anterior lamellar keratoplasty, the technique extends anterior lamellar keratoplasty indications to include patients
Accepted for publication February 12, 2006.
with keratoconus, thin corneas (!350 mm), and those with corneal stromal opacities. PATIENTS AND METHODS This study comprised 13 eyes of 13 patients with advanced keratoconus, macular dystrophy, post-LASIK corneal ectasia and post-herpetic keratitis sequelae. All patients signed an informed consent form. The patients were divided into 2 groups: corneal ectasia (5 cases with keratoconus and 1 case with post-LASIK ectasia) and stromal opacity (7 cases). The main treatment goal in patients with keratoconus was to increase corneal thickness in preparation for reshaping with refractive surgery and to replace diseased Bowman’s membrane and anterior stroma with healthy tissue. In patients with post-LASIK ectasia, the surgical aim was to increase corneal thickness, ablate apoptotic cells in the interface,18,19 and reduce posterior corneal steepness with tight suturing of the thicker donor lamellae. The goal in the corneal stromal opacity group was to remove diseased stroma and replace it with healthy donor stroma while preserving the host endothelium. Corneal thickness was measured at 6 points (central, superior, inferior, nasal, temporal, and inferotemporal) in all patients by ultrasound pachymetry, and the minimum value was used for calculations. Preoperative patient data, including pachymetric and topographic findings, are shown in Table 1. Surgical Technique
From the Ophthalmology Department, School of Medicine, Gazi University (Bilgihan, O¨zdek, Hasanreisog˘lu), Ankara, and the Ophthalmology Department, School of Medicine, Mersin University (Sari), Mersin, Turkey. No author has a proprietary or financial interest in any material or method mentioned. Corresponding author: Kamil Bilgihan, MD, Defne sitesi 3. Blok 53/10, 06530 U¨mitko¨y. Ankara, Turkey. E-mail: bilgihan@gazi. edu.tr.
All surgery was performed using topical anesthesia of proparacaine hydrochloride 0.5% (Alcaine). First, a donor stromal button approximately 350 mm thick was prepared. A donor cornea was placed, endothelial surface up, on a plastic prosthesis, and the endothelium was removed with a 100 mm ablation using the Aesculap Meditec Mel 60 excimer laser. The remaining cornea consisting of epithelium, Bowman’s membrane, and stroma was punched with a 7.5 mm (ectatic corneas) or 7.7 mm (corneal opacities) trephine. Next, the eyes were prepped with
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povidone–iodine 5% in the inferior fornix and draped in the usual fashion. A transepithelial ablation was performed on the host cornea for a final corneal thickness of 200 mm in a 7.5 mm zone (Figure 1). Transepithelial photorefractive keratectomy (PRK) was performed to remove diseased Bowman’s membrane and anterior stroma and to prevent new keratocyte apoptosis.18–21 The corneal button and interface were irrigated vigorously with a balanced salt solution. Both the button and interface were dried with fiber-free sponges to remove all debris and maintain the button’s central position by increasing adhesion of the button to the interface. The corneal button was sutured with interrupted 10-0 monofilament nylon (Figure 1, B). The entire procedure was performed in the excimer laser room. Postoperative treatment included topical dexamethasone and ofloxacin 5 times daily tapered over 3 months. Sutures were removed between 3 months and 6 months according to corneal topography. Preoperative and postoperative pachymetric measurements and simulated keratometric (SimK) cylinder were analyzed by the Wilcoxon signed rank test. The postoperative spherical equivalent refraction and best spectacle-corrected visual acuity (BSCVA) between the groups were compared with the Mann-Whitney U test. RESULTS
The mean follow-up was 27.6 months G 8.3 (SD) (range 14 to 41 months). Preoperative uncorrected visual acuity (UCVA) ranged from counting fingers (CF) to 20/125 and BSCVA, from CF to 20/50. Postoperatively, UCVA was between 20/200 and 20/32 and BSCVA was between 20/100 and 20/20. Final BSCVA increased 2 lines or more in all cases (Figure 2). Postoperative patient data, including pachymetric (Figure 3) and topographic findings, are shown in Table 2. Preoperative refraction could not be obtained reliably in most of the patients because the cylinder values were
out of the measuring range of autorefractometer. The mean postoperative spherical equivalent was 2.54 G 1.84 diopters (D). The mean preoperative corneal thickness was 381.2 G 88.2 mm (range 240 to 510 mm), which increased significantly to 534.9 G 96.6 mm (range 350 to 700 mm) at the last follow-up visit (Z Z 3.18, P Z.001). The mean preoperative SimK cylinder was 7.44 G 7.18 D (range 1.6 to 22.1 D). Postoperatively, it significantly decreased to 2.61 G 1.73 D (range 0.4 to 5.7 D) (Z Z 2.69, P Z.007). The postoperative mean spherical equivalent refraction was 3.62 G 2.77 D in the ectasia group and 1.95 G 0.99 D in the stromal opacity group. The difference between the groups was not statistically significant (P Z .07). The mean postoperative BSCVA was 0.63 G 0.15 in the ectasia group and 0.57 G 0.23 in the stromal opacity group (P Z.44). The difference was not significant (P Z.07). Aqueous humor percolation from Descemet’s membrane at the end of the host cornea’s transepithelial ablation was observed in 2 cases. There was no other preoperative or postoperative complication. All donor stromal edema resolved during the first 24 hours postoperatively in all cases (Figure 4). No macular dystrophy case had recurrence on the donor cornea during the follow-up. Figure 5 shows the preoperative and postoperative corneal appearance in case 6 (macular dystrophy). DISCUSSION
The main drawbacks of lamellar keratoplasty are preparation of donor corneal buttons, the difficult technique,
Figure 1. Epikeratoplasty technique. A: The appearance of the host corneal bed following transepithelial ablation. B: Donor corneal button (without endothelium) is placed over the host corneal bed following transepithelial ablation.
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1,2 1
BSCVA
0,8 preop. BSCVA
0,6
Figure 2. Preoperative and postoperative BSCVA results.
postop.BSCVA
0,4 0,2 0
1
2
3
4
5
6
7
8
9
10
11
12
13
pachymetric values (micron)
patients
800 700 600 500
preop. pachymetry
400
postop.pachymetry
300
Figure 3. Preoperative and postoperative pachymetric values.
200 100 0
0
1
2
3
4
5
6 7 8 patients
9
10 11 12 13
the time-consuming nature of the surgery, and poorer visual results than with PKP. When these problems are minimized, lamellar keratoplasty is the treatment choice for keratoconus, post-LASIK corneal problems, and other corneal stromal opacities. The main reason for the inferior results compared to PKP is thought to be interface problems. These opacities could be solved by removing all stroma
(by dissecting down to Descemet’s membrane) or by using an automated microkeratome or excimer laser ablation to produce smooth interface surfaces. Fiber-free sponges and talc-free gloves are crucial to prevent interface opacities and other interface problems. The technique presented here simplifies and shortens the time for lamellar keratoplasty while decreasing vision-limiting interface problems.
Table 2. Postoperative patient data.
Case
UCVA
BSCVA
Refraction
Keratometry SimK (D)
Pachymetry (mm)
Follow-up (Mo)
1 2 3 4 5 6 7 8 9 10 11 12 13
20/63 20/32 20/50 20/100 20/200 20/50 20/200 20/50 20/63 20/200 20/40 20/100 20/200
20/25 20/25 20/32 20/50 20/32 20/32 20/100 20/40 20/32 20/32 20/20 20/32 20/40
C1.00 4.00 70 C1.00 C2.50 120 2.50 80 C1.50 C2.00 90 6.00 3.50 70 2.50 100 C2.25 0.75 C3.00 40 3.00 x 160 2.50 4.00 15 1.25 155 1.00 C2.25 75 C3.50 C0.50 140
49.6/45.3 47.1/44.1 53.0/48.8 48.8/43.4 49.0/48.6 44.8/44 45/43.9 45.1/41 42.5/39.2 51.8/48.3 45.5/44.3 42.2/40.3 43.8/43.3
486 420 500 643 630 450 520 600 700 350 570 535 550
41 34 30 21 36 24 27 30 21 36 36 14 17
BSCVA Z best spectacle-corrected visual acuity; SimK Z simulated keratometry; UCVA Z uncorrected visual acuity
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Figure 4. Corneal appearance 5 days postoperatively. There is no donor stromal edema.
The corneal ectasia group (5 eyes, keratoconus; 1 eye post-LASIK ectasia) was the first in our study. Initial changes in keratoconus that are related to the degradation of the basement membrane and a cascade of events result in stromal thinning over time. This weakens the structural integrity of the cornea, which causes bulging, cone-like distortion of the normally spherical cornea. Keratoconic corneas have apoptosis of the anterior stroma and epithelium, especially in the areas of breaks in Bowman’s layer.18 Our surgical technique attempts to remove these pathologic structures (Bowman’s membrane and anterior stroma) while thickening and reshaping the corneal stroma and to
prepare it for secondary refractive surgery. Bowman’s membrane and anterior stroma are removed with transepithelial PRK; then, the anterior cornea is replaced with a healthy one. Although transepithelial PRK induces keratocyte apoptosis, it is minimum compared to that with other refractive surgeries.19–21 In addition, the SimK cylinders decreased postoperatively, which may be attributed to the use of the same-size donor cornea (7.50 mm) rather than larger donor cornea (7.75 mm). This is especially important in advanced keratoconus cases with high SimK cylinders and thin corneas and may also apply to post-LASIK corneal ectasiad a real and unpredictable problem.22–24 The current literature does not define a specific residual corneal thickness or a range of preoperative corneal thickness that predisposes an eye to post-LASIK ectasia. The most logical reason eyes without preexisting pathology develop ectasia is a mechanically unstable postablation stromal thickness. This minimum thickness is likely specific to each eye.22,23 Other undetermined factors may play a role in the development of this complication.24 Excimer laserassisted anterior lamellar keratoplasty may be an effective treatment alternative in these cases. The second major group in our study comprised eyes with stromal opacities caused by macular dystrophy (3 eyes), herpetic keratitis (3 eyes), and post-LASIK interstitial keratitis sequelae (1 eye). Patients with other stromal opacity etiologies with healthy endothelium can also be treated with this technique. The preservation of host endothelium is especially important in young patients. Although the postoperative visual and refractive outcomes were similar in the ectasia and opacity groups, the number of patients in the groups was too small to make conclusions.
Figure 5. A: Preoperative appearance of a case with macular dystrophy (case 6). B: Postoperative appearance of the patient with macular dystrophy at 6 months.
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Recently, Busin et al.15 defined a new system, automated lamellar therapeutic keratoplasty, that uses a specially designed microkeratome to prepare the donor button and remove the host corneal stroma. Their purpose is similar to that of our technique, except our technique uses an excimer laser instead of a microkeratome. Preparation of donor stromal lamella by using microkeratome was reported to cause either the wrong size or peripheral contour in 15% of patients and a new donor lamellae needed to be prepared in such cases.15 The advantages of lamellar keratoplasty over PKP (preservation of the host endothelium, avoidance of complications associated with open-sky surgery, decreased risk for allograft rejection, superior wound strength) also include topical anesthesia instead of retrobulbar or general anesthesia. The patients were comfortable with topical anesthesia, which avoided the risks of local or general anesthesia. All surgery was performed in the excimer laser room; we saw no infection or other problems related to this approach. Another advantage is earlier suture removal, which resulted in earlier visual rehabilitation. Ablation of large amounts of corneal tissue requires several minutes and involves high laser energy levels, which may result in endothelial damage. Potential endothelial trauma may be the surgery’s major disadvantage. It also costs more and requires further investigation. The small number of the patients and nonhomogenous corneal pathologies are other shortcomings of the study. This technique presents another modality for the treatment of keratoconus, post-LASIK corneal problems, and other corneal stromal opacities. The surgery is safer than PKP and easier than the other lamellar keratoplasty techniques, and the visual results seem promising. Benefits of the surgery include shorter surgical time, lower complication risk, less technically demanding technique, topical anesthesia, and the need for donor corneal tissue rather than the entire globe. Because the endothelial quality of the donor cornea is not important for stromal grafting, it is easier to procure a donor cornea. Also, patients can still have PKP if needed. Further studies with more patients and a longer followup will determine the role of this promising technique as a potential substitute for PKP in keratoconus cases, postLASIK corneal problems, and other corneal stromal opacities. The need for an excimer laser increases the surgery’s cost, which is a major disadvantage. REFERENCES 1. Richard JM, Paton D, Gasset AR. A comparison of penetrating keratoplasty and lamellar keratoplasty in the surgical management of keratoconus. Am J Ophthalmol 1978; 86:807–811
2. Melles GRJ, Remeijer L, Geerards AJM, Beekhuis WH. The future of lamellar keratoplasty. Curr Opin Ophthalmol 1999; 10:253–259 3. Benson WH, Goosey CB, Prager TC, Goosey JD. Visual improvement as a function of time after lamellar keratoplasty for keratoconus. Am J Ophthalmol 1993; 116:207–211 4. Soong HK, Katz DG, Farjo AA, et al. Central lamellar keratoplasty for optical indications. Cornea 1999; 18:249–256 5. Alio JL, Shah S, Barraquer C, et al. New techniques in lamellar keratoplasty. Curr Opin Ophthalmol 2002; 13:224–229 6. Sugita J, Kondo J. Deep lamellar keratoplasty with complete removal of pathological stroma for vision improvement. Br J Ophthalmol 1997; 81:184–188 7. Price FW Jr. Air lamellar keratoplasty. Refract Corneal Surg 1989; 5:240–243 8. Caporossi A, Simi C, Licignano R, et al. Air-guided manual deep lamellar keratoplasty. Eur J Ophthalmol 2004; 14:55–58 9. Manche EE, Holland GN, Maloney RK. Deep lamellar keratoplasty using viscoelastic dissection. Arch Ophthalmol 1999; 117:1561–1565 10. Shimmura S, Shimazaki J, Omoto M, et al. Deep lamellar keratoplasty (DLKP) in keratoconus patients using viscoadaptive viscoelastics. Cornea 2005; 24:178–181 11. Melles GRJ, Lander F, Rietveld FJR, et al. A new surgical technique for deep stromal, anterior lamellar keratoplasty. Br J Ophthalmol 1999; 83:327–333 12. Tsubota K, Kaido M, Monden Y, et al. A new surgical technique for deep lamellar keratoplasty with single running suture adjustment. Am J Ophthalmol 1998; 126:1–8 13. Azar DT, Jain S, Sambursky R. A new surgical technique of microkeratome-assisted deep lamellar keratoplasty with a hinged flap. Arch Ophthalmol 2000; 118:1112–1115 14. Bilgihan K, O¨zdek SC, Sari A, Hasanreisoglu B. Microkeratome-assisted lamellar keratoplasty for keratoconus: stromal sandwich. J Cataract Refract Surg 2003; 29:1267–1272 15. Busin M, Zambianchi L, Arffa RC. Microkeratome-assisted lamellar keratoplasty for the surgical treatment of keratoconus. Ophthalmology 2005; 112:987–997 16. Chen W, Qu J, Wang Q, et al. Automated lamellar keratoplasty for recurrent granular corneal dystrophy after phototherapeutic keratectomy. J Refract Surg 2005; 21:288–293 17. Hafezi F, Mrochen M, Fankhauser F II, Seiler T. Anterior lamellar keratoplasty with a microkeratome: a method for managing complications after refractive surgery. J Refract Surg 2003; 19:52–57 18. Helena MC, Baerveldt F, Kim W-J, Wilson SE. Keratocyte apoptosis after corneal surgery. Invest Ophthalmol Vis Sci 1998; 39:276–283 19. Bilgihan K, Adiguzel U, Sezer C, et al. Effects of topical vitamin E on keratocyte apoptosis after traditional photorefractive keratectomy. Ophthalmologica 2001; 215:192–196 20. Kim W-J, Rabinowitz YS, Meisler DM, Wilson SE. Keratocyte apoptosis associated with keratoconus. Exp Eye Res 1999; 69:475– 481 21. Mitooka K, Ramirez M, Maguire LJ, et al. Keratocyte density of central human cornea after laser in situ keratomileusis. Am J Ophthalmol 2002; 133:307–314 22. Binder PS. Ectasia after laser in situ keratomileusis. J Cataract Refract Surg 2003; 29:2419–2429 23. Amoils SP, Deist MB, Gous P, Amoils PM. Iatrogenic keratectasia after laser in situ keratomileusis for less than 4.0 to 7.0 diopters of myopia. J Cataract Refract Surg 2000; 26:967–977 24. Comaish IF, Lawless MA. Progressive post-LASIK keratectasia: biomechanical instability or chronic disease process? J Cataract Refract Surg 2002; 28:2206–2213
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