Epithelial ingrowth after LASIK treatment with scraping and phototherapeutic keratectomy

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1 Epithelial ingrowth after LSIK treatment with scraping and phototherapeutic keratectomy Per Fagerholm, 1 Nils Molander, 2 lexander Podskochy 1 and Staffan Sundelin 1 1 Department of Ophthalmology, University Hospital, Linko ping, Sweden 2 Medocular, Malmo, Sweden STRCT. Purpose: To evaluate the effect of phototherapeutic keratectomy (PTK) in combination with manual scraping when removing epithelial ingrowth under a LSIK flap. Material and Methods: Three patients, who had undergone several surgeries following LSIK in order to remove epithelial ingrowth that was threatening vision, were treated with a flap lift, manual abrasion and PTK. The PTK was performed on both the stromal and the flap side with the aim of eliminating the threat and improving vision. Two patients underwent primary surgery to remove epithelial ingrowth with manual abrasion and PTK. The influence on vision, topography and cell recurrences was evaluated. Results: Uncorrected visual acuity (UCV) and best spectacle-corrected visual acuity (SCV) improved in four cases and remained good in the fifth case. The refraction did not change significantly. Topography disclosed changes in the irregular astigmatism, explaining the improved SCV. Central epithelial ingrowth did not recur, whereas peripheral ingrowth did. The peripheral ingrowth did not progress, except in case 1, where a cyst formed that required surgery. Conclusions: It is our belief that adding PTK to manual scraping improves the prognosis for eyes with epithelial ingrowth. It is mainly the central ingrowth that is positively affected. Improved adhesion between the stroma and the flap is one possible explanation. Key words: LSIK complications treatment epithelial ingrowth cta Ophthalmol. Scand. 2004: 82: Copyright # cta Ophthalmol Scand doi: /j x Introduction LSIK (laser in situ keratomileusis) is a technique developed from automated lamellar keratomileusis, where the removal of tissue with a keratome is replaced by more precise removal with an excimer laser (Pallikaris et al. 1990; uratto & Ferrari 1992). s a technique, LSIK is becoming increasingly dominant in refractive surgery. ll surgical techniques have complications, which, in some cases including those involving LSIK can be serious when they involve the growth of corneal epithelial cells in the interphase between the microtome-created flap and the stroma (Machat 1996; Helena et al. 1997; Walker & Wilson 2000; Wang & Maloney 2000; mbrosio & Wilson 2001). Epithelial ingrowth is often detected within 1 month of primary surgery. It can, however, occur in the later stages (sano-kato et al. 2002). It has been demonstrated that in the majority of cases, about 90%, ingrowing epithelial cells are continuous with the epithelial cells of the corneal surface, hence the name epithelial ingrowth. The cells may, however, originate from separate cells implanted during surgery. The natural history of ingrowing cells is essentially benign in that 55% disappear with time, 24% diminish and 10% remain unaltered. This observation is supported by histopathological findings (ndersson et al. 2002; Naumidi et al. 2003). In about 10% of cases, the ingrowth causes or threatens to cause complications such as reduced vision, irregular astigmatism and melting of the flap (sano-kato et al. 2002). Epithelial ingrowth is seen more often as a complication following surgical events, such as thin or lacerated flaps, buttonholes, blood remnants, fibres or lint in the interface. Reoperation with flap lifts is also associated with a higher incidence of epithelial ingrowth. Epithelial ingrowth has been treated by lifting the flap and manually removing the epithelium by scraping (Machat 1996; mbrosio & Wilson 2001). Partial suturing of the flap has been suggested (Mackool & Monsanto 707

2 2002). Domniz et al. (2001) described the use of either a light phototherapeutic keratectomy (PTK) treatment and/or 10% alcohol on a foam swab applied for a few seconds, in addition to manual scraping. In our experience, manual scraping has been successful most of the time. We have, however, encountered recalcitrant cases in need of repeated surgery. Four of these cases (cases 1 4), out of five, were referred to the clinic from abroad or from other clinics in Sweden. Thus the flap size, thickness or keratome used was not always known. The present paper presents the result of surgery in five eyes with epithelial ingrowth where, in addition to manual scraping, PTK was performed both on the stromal bed and on the stromal side of the flap. Material and Methods Case descriptions Case 1 33-year-old man was operated on with bilateral LSIK in ugust Refraction was 5.5 D in the right eye and 4.5 D in the left eye (Tables 1 and 2). Surgery was uneventful, but the flap in the left eye was thinner than normal. The intended flap diameter was 8.5 mm. Sight-threatening epithelial ingrowth developed in the left eye and manual abrasion was performed in pril Manual abrasion with alcohol treatment was performed four times and on two of these occasions the flap was sutured. In November 2002, a manual abrasion combined with excimer laser ablation, 7 mm plano on the flap and the stromal bed, was performed to remove a large central epithelial cyst (Fig. 1, ). Case 2 29-year-old man was operated on with bilateral LSIK in pril Refraction was 3.5 D in the right eyeand 4.0 D in the left eye (Tables 1 and 2). Surgery was uneventful in the left eye, but in the right eye the flap diameter became somewhat smaller and thinner, and the flap was lacerated at the hinge nasally. Six months after primary surgery, a flap lift was performed because epithelial ingrowth occupied the whole interface (Fig. 2). The ingrowing cells emanated from the periphery, in particular the lacerated area. The cells were manually scraped and the surface treated with PTK, using a 7-mm setting. Four months later, a peripheral epithelial cyst appeared in the 8 o clock position, which was manually abraded. Some stationary epithelial ingrowth can still be seen under the flap where it was lacerated initially (Fig. 2). Case 3 54-year-old woman was operated on bilaterally in September 1999 due to myopia in both eyes ( 4 D in the right eye and 3.75 D in the left eye (Tables 1 and 2). Enhancements were performed four times in the left eye, the latest in pril The patient presented with extensive epithelial ingrowth causing visual reduction due to irregular astigmatism. Manual abrasion was performed in January Due to recurrence of the ingrowth, a manual abrasion combined with plano PTK treatment of both the flap and the stromal bed was performed in February The flap diameter was 9 mm, but appeared thinner than normal. Case 4 45-year-old man had been grafted in both eyes because of keratokonus. Due to anisometropia (Tables 1 and 2) and inability to obtain a bearable spectacle correction in the left eye, LSIK was performed in two sessions. First, the flap was created, and 3 weeks later, a flap lift was performed. Finally, refractive laser ablation was carried out in June The flap diameter was 8.5 mm and the operation was performed with a Hansatome Table 1. Repeated surgery or a lacerated flap preceded epithelial ingrowth, a complication that can necessitate further surgery. In these five cases, manual abrasion combined with phototherapeutic excimer laser ablation was evaluated. Case ge Gender Risk factor for epithelial ingrowth No. of prior surgeries Time from latest surgery (months) 1 33 Male Enhancement Male Lacerated flap Female Enhancement Male 2nd session post PKP Female Enhancement Table 2. Preoperative and postoperative V and refraction in the five cases treated with manual ablation and PTK for epithelial ingrowth. The data represent V and refraction before and after the surgical with manual ablation and PTK. Generally there was an improvement in uncorrected and corrected V. Case Preop UCV Preop CSV Postop UCV Postop CSV Preop refraction Postop refraction Sph Cyl Sph Cyl þ c 80 þ c þ þ c 15 þ c 0 4 < < c c Preop ¼ preoperative; Postop ¼ postoperative; UVCV ¼ uncorrected visual acuity; CSV ¼ best spectacle-corrected visual acuity. 708

3 Fig. 1. Case 1. () large central epithelial cyst is seen in the flap interphase. The cyst is lifting the flap locally, threatening to cause local melting. () Postoperative photograph showing that the removal of the epithelial cells was complete and no recurrence had taken place. microkeratome. Four months after the second operation, a peripheral epithelial cyst was noticed. The cyst lifted the resection edge, causing astigmatism. The flap was lifted again in October 2003 and the epithelial cyst was manually abraded. Phototherapeutic keratectomy, 7 mm plano, was used on both the flap and the stromal bed. t the latest follow-up, only minimal epithelial ingrowth was seen in the area (Fig. 3). Case 5 28-year-old woman was operated on with bilateral LSIK in May 2001 due to bilateral myopia and astigmatism ( 3sphc 1.5 cyl 85 degrees in the right eye, 2sphc 2 cyl 90 degrees in the left). The flap diameter was 8.5 mm and the operation was performed with a Hansatome microkeratome. Due to myopic regression ( 1.0 sph), the left eye was reoperated in March In October 2003, a manual abrasion combined with 7 mm plano excimer laser ablation on the flap and the stromal bed was performed on the left eye due to extensive peripheral epithelial ingrowth where the epithelial cells almost reached the centre of the optical zone in the 7 o clock meridian. Thus, five eyes of five patients were consecutively treated for epithelial ingrowth following LSIK surgery between May 2001 and May The number of prior surgeries and the postoperative follow-up time is given in Table 1. Three of the eyes had been treated previously because of epithelial ingrowth, either by manual scraping, alcohol treatment and/or suturing of the flap or different combinations of these. In four of the patients, vision was affected due to centrally proliferating epithelial growth. In case 1, a substantial peripheral epithelial accumulation was elevating the flap and threatening to cause irregular astigmatism and local melting (Fig. 1). In three of the patients, the flaps had been severed at primary surgery or were thinner than normal. The surgical technique used in these five patients included the debridement of the scar surrounding the flap using a very short spatula. The flaps were then carefully drawn towards the hinge until the epithelial ingrowth was well exposed if it was peripheral, or maximally withdrawn if the ingrowth was central. Loosening of the flap was especially delicate in case 2, where it was both thin and had been severed at the hinge during primary surgery. The interphase epithelium was carefully scraped on both surfaces. With two 7 mm treatment zones plus a transition zone of 0.5 mm on the stromal surface and then two on the stromal flap surface, both surfaces were covered by ablation with the excimer laser (Technolas 217 z; ausch & Lomb, Rochester, NY, US). The ablation depth was set at 7 mm. The flap was then floated into place and allowed to settle. Chloramphenicol drops were given topically at the end of surgery. No bandage lens was given. Check-ups took place after 30 minutes, 1 day, 1 week and 1 month, and then at 3 6-month intervals after 709

4 surgery. During the first 5 postoperative days, the patients were given chloramphenicol drops and dexamethasone 0.1% drops three times a day topically. In the grafted patient (case 4), local steroids were continued for 3 weeks. Corneal topography (Orbscan IIz, ausch & Lomb) was employed to document the astigmatic changes. Fig. 2. Case 2. () Widespread epithelial ingrowth was noted under a thin, lacerated flap. Following removal, the epithelial ingrowth recurred in the form of a peripheral epithelial cyst that was removed manually. () t the last follow-up, some epithelial ingrowth could still be seen close to the lacerated hinge. The ingrowth has remained stationary. Results The visual acuities and refractive outcomes of the surgical intervention, combining manual abrasion and PTK, are summarized in Table 2. One of the patients (case 2) developed a peripheral recurrence significant enough to warrant additional surgery and was manually abraded 4 months after the intervention with the PTK mode. In another case (case 4), faint epithelial ingrowth reappeared locally, but did not warrant further surgery. Some peripheral, non-proliferating ingrowth was noted in cases 1 and 3. This peripheral ingrowth has remained stationary and is expected to remain unchanged. s a rule, vision improved (cases 1, 2, 3 and 5) and reached acceptable levels of uncorrected and best spectaclecorrected V. In case 4, the refractive change was small. In four patients, the operated eye ended up with an uncorrected V that was useful and satisfied the patient. In case 4, the refraction of the operated eye was tolerated together with the fellow eye. The preoperative astigmatism was often extensive and irregular. Orbscan examination was performed before and after surgery in three patients (Figs 4 and 5). The topography shows the irregular astigmatism induced by the epithelial ingrowth and the beneficial influence of removing the ingrowth. Fig. 3. Case 4. LSIK performed in two sessions resulted in epithelial ingrowth peripherally at the 6 o clock position. Following removal, a faint recurrence was observed at the same location but this has remained stationary. Discussion Epithelial growth in the corneal interphase following LSIK is in most cases self-limiting. It appears that the cells age and succumb in the new environment. The epithelial cells are not replenished by the normal epithelial cell flow generated by stem cell division in the limbus. Surgical intervention is aimed at removing the existing cells in the interphase and sealing the interphase 710

5 CT OPHTHLMOLOGIC SCNDINVIC 2004 Fig. 4. Case 1. () The large elevation caused by an epithelial cyst is evident in the preoperative topographic image. () More than a year after surgery, the astigmatism is regular and the eye has obtained both better uncorrected V and best spectacle-corrected V. surfaces and the resection edge to prevent further ingrowth. Manual scraping is the first type of surgical intervention tried, and is usually successful in eradicating invading cells. In some eyes, however, the epithelial cells reappear in the interphase, peripherally or centrally, and retreatment may prove necessary. Suturing the resection edges is one method of sealing the area from further cellular ingrowth. lcohol has been employed to secure the eradication of all epithelial cells in the interphase. The use of PTK, in addition to manual scraping, is a means of ensuring the removal of all remaining epithelial cells. The laser also ablates fibrosis, basal membranes and other scar-related structures that may promote cellular invasion. dhesion of the flap is probably more successful between clean surfaces. Good attachment is needed to prevent cellular migration to the central zone. Excimer laser treatment in the form of PRK has been used to treat eyes where the microkeratome has created a buttonhole in the flap. It is known that buttonholes are associated with epithelial ingrowth (Grupcheva et al. 2001). In these cases, the laser provides refractive treatment and at the same time removes the ingrowing cells (Vajpayee et al. 2003). The clear advantage of this method is that the lacerated flap can be left in place. In our cases, the nature and distribution of epithelial ingrowth necessitated a flap lift and we chose, in addition to scraping, to perform the removal of 7 10 mm of tissue on both the flap and the stromal surfaces with the excimer laser. The choice of 7 10 mm was intended to remove a substantial part of the tissue, but not so much as to induce refractive change. t the same time, it is possible to lacerate at least one layer of cells or possibly two with 7 10 mm treatment. Experience is still limited, but until more is known, we would choose to remove 7 10 mm of tissue again for the next patient. In three patients, weak recurrences were noted in the flap periphery. The epithelial ingrowth 711

6 Fig. 5. Case 2. () Irregular topography is seen, with rather extensive epithelial ingrowth. () More than a year after surgery, the topography is not regular but extensively changed. oth uncorrected V and best spectacle-corrected V have improved and the flap is no longer threatened by melting. was, however, stationary or diminishing during the observation period. The advantage of using the PTK mode lay mainly in freeing the central zone from epithelial cells. This provided good vision and a reduction in local astigmatism, as was documented by corneal topography. The patients with central engagement (cases 1, 2, 3 and 5) all obtained acceptable uncorrected V following surgery. In case 4 with peripheral engagement only, the surgery was performed due to the risk of the flap melting. To conclude, PTK is an effective method of permanently removing epithelial ingrowth in the optical zone. This is probably accomplished by better adhesion between the stromal surfaces. lthough peripheral ingrowth could not be prevented, only one of the five cases necessitated surgical removal of peripheral epithelial cell recurrences. cknowledgements This work was funded by the Swedish Medical Research Council, Kronprinsessan Margaretas rbetsna mnd and Synskadades va l, Östergo tland. References mbrosio R & Wilson SE (2001): Complications of laser in situ keratomileusis: aetiology, prevention and treatment. J Refract Surg 17: ndersson NJ, Edelhauser HF, Sharara N, Thompson KP, Rubinfeld RS, Devaney DM, L Hernault N & Grossniklaus HE (2002): Histologic and ultrastructural findings in human corneas after successful laser in situ keratomileusis. rch Ophthalmol 120: sano-kato N, Toda I, Hori-Komai Y, Takano Y & Tsubota K (2002): Epithelial ingrowth after laser in situ keratomileusis: clinical features and possible mechanisms. m J Ophthalmol 134: uratto L & Ferrari M (1992): Excimer laser intrastromal keratomileusis: case reports. J Cataract Refract Surg 18: Domniz Y, Comaisc IF, Lawless M, Sutton GL, Eckshtein R, Collins M & Rogers CM (2001): Epithelial ingrowth: causes, prevention, and treatment in five cases. J Cataract Refract Surg 272:

7 Grupcheva CN, Malik TY, Craig JP & McGee NJ (2001): In vivo confocal microscopy of corneal epithelial ingrowth through a laser in situ keratomileusis flap buttonhole. J Cataract Refract Surg 27: Helena MC, Meisler D & Wilson SE (1997): Epithelial growth within the lamellar interface after laser in situ keratomileusis (LSIK). Cornea 16: Machat JJ (1996): LSIK complications and their management. In: Machat JJ (ed). Excimer Laser Refractive Surgery. Thorofare, New Jersey: Slack; Mackool RJ & Monsanto VR (2002): Epithelial ingrowth after LSIK. [Letter.] J Cataract Refract Surg 28: Naumidi I, Papadaki T, Zacharopoulos I, Siganos C & Pallikaris I (2003): Epithelial ingrowth after laser in situ keratomileusis. histopathologic study in human corneas. rch Ophthalmol 121: Pallikaris IG, Papatzanaki ME, Stathi EZ & Frenschok O (1990): Laser in situ keratomileusis. Laser Surg Med 10: Vajpayee R, Gupta V & Sharma N (2003): PRK for epithelial ingrowth in buttonhole after LSIK. Cornea 22: Walker M & Wilson SE (2000): Lower intraoperative flap complications rate with the Hansatome microkeratome compared to the automated corneal shaper. J Refract Surg 16: Wang MY & Maloney RK (2000): Epithelial ingrowth after laser in situ keratomileusis. m J Ophthalmol 129: Received on March 23rd, ccepted on September 13th, Correspondence: Per Fagerholm MD, PhD Department of Ophthalmology University Hospital SE Linköping Sweden Tel: þ Fax: þ perfa@inr.liu.se 713