Small incision lenticule extraction (SMILE) is a novel refractive lenticule extraction method for the correction of refractive errors in which an intrastromal lenticule is extracted without creating a flap. The efficiency of this technique in the correction of high astigmatism (≥ 2.50 diopters [D]) has been established.1
High astigmatism is a common complaint after corneal transplantation.2 Several methods are available for the treatment of this unwanted outcome, and two case reports suggest that SMILE can be an effective method for the treatment of post-transplantation astigmatism.3,4
We describe a patient who developed stromal rejection after SMILE using the VisuMax femtosecond laser platform (Carl Zeiss Meditec, Jena, Germany) for the treatment of induced astigmatism after deep anterior lamellar keratoplasty (DALK).
The patient was a 46-year-old man who had undergone DALK (size = 8.25 mm) in the left eye using the big bubble technique at the age of 37 years due to advanced progressive keratoconus: maximum keratometry (Kmax) of 50.07 D, manifest refraction of −4.00 −6.00 × 105°, uncorrected distance visual acuity (UDVA) of 20/1600, and corrected distance visual acuity (CDVA) of 20/1000.
The donor was a 37-year-old man with an unremarkable medical history who had died of head trauma. The 8.2-mm central stroma was completely clear and there was moderate peripheral arcus. Descemet's membrane and endothelium were normal (cell count: 2,976 cells/mm2). Testing for human immunodeficiency virus, hepatitis, hepatitis C virus, and human T-lymphotropic virus were negative, and there was no risk factor for graft rejection.
After DALK in 2010, there was improvement in the left eye of UDVA to 20/400, CDVA to 20/200, and refraction to +4.00 −8.00 × 130°. All sutures were removed over the next 2 years, and refraction was −1.00 −9.00 × 160° at 3 years after removing the last suture (2015). Given the existing astigmatism, relaxing incisions and tightening of sutures were done.
In 2019, the patient underwent SMILE in the left eye using the VisuMax femtosecond laser platform with UDVA of 20/200, CDVA of 20/32, and refraction of −3.25 −4.25 × 165°. The parameters applied for the lenticule creation were cap diameter of 7.7 mm, incision angle of 52°, incision width of 3.5 mm, optical zone of 6.5 mm, and transition zone of 0.1 mm. Pachymetry was 566 µm and central lenticule thickness was 130 µm. The target refraction was +0.50 −0.00 × 165°. After making appropriate corneal markings as a guide to compensate for intraoperative torsional error, lenticule extraction was completed with no complications. Corneal marks were placed on 0° and 180° with the patient in the upright position. During surgery, the 0° and 180° axes on the contact glass were manually aligned with these marks to compensate for cyclotorsion. The postoperative regimen included chloramphenicol 0.5% eye drops (Sina Darou, Tehran, Iran) every 6 hours for 3 days, betamethasone 0.1% eye drops (Sina Darou) every 6 hours for 1 week, and preservative-free artificial tears every 6 hours for 1 month. One day after surgery, UDVA was 20/40, CDVA was 20/32, and refraction was −1.25 −0.50 × 15°. One week later, the patient presented complaining of pain, photophobia, blurred vision, and foreign body sensation. At this time, UDVA was reduced to 20/400 and CDVA to 20/63. Slit-lamp examination revealed diffuse stromal infiltration, edema, and haze in addition to neovascularization. Because the rejection was not limited to the donor–recipient interface and the entire graft was involved, white granular cells were not observed, intraocular pressure (IOP) was normal (14.5 mm Hg), pachymetry increased (550 µm), diffuse lamellar keratitis (DLK) and corneal endothelial rejection were ruled out, and a diagnosis of stromal rejection was confirmed (Figure 1).
(A) Left eye of a patient who developed stromal rejection following small incision lenticule extraction, which was done to correct astigmatism after deep anterior lamellar keratoplasty. Graft cleared (B) 2 months and (C) 5 months after immunosuppressive therapy.
The patient received daily treatment with betamethasone 0.1% every hour. Three days later, the patient was given a sub-Tenon injection of 3 mg/0.5 cc betamethasone (Sina Darou), oral prednisolone 50 mg daily (Iran Hormone, Tehran, Iran), and betamethasone 0.1% eye drops every 8 hours. On the next day, prednisolone was tapered. Five-week results were improved, with UDVA of 20/63, CDVA of 20/25, and refraction of −2.25 −0.75 × 20°, which remained stable over the next month (UDVA of 20/63, CDVA of 20/25, and refraction of −2.25 −0.50 × 75°). Five-month results were UDVA of 20/40, CDVA of 20/25, and refraction of −1.25 −0.75 × 90°, and the graft cleared completely (Figure 1). Two months after the procedure, IOP was 15 mm Hg and pachymetry was 436 µm, which did not change over the next 3 months (IOP of 14 mm Hg and pachymetry of 435 µm).
The main challenges with astigmatism after penetrating keratoplasty are anisometropia and binocular vision disturbances that require correction. All excimer laser–based procedures that are applied for the treatment of astigmatism can be associated with graft rejection due to the development of inflammatory processes in the stroma.5 However, this complication can be relatively rare, and the procedures continue to be applied. Among available options, SMILE is a novel method for the correction of refractive errors. In the case reported here, this flapless technique offered 3.75 D reduction in astigmatism and a gain of four lines in UDVA at 1 day postoperatively. In the case report by Kim et al.,3 at 1 week after surgery, the patient gained four lines of UDVA and 5.00 D correction of astigmatism in the weaker eye (preoperative refraction of −1.50 −8.00 × 10° and UDVA of 20/400), and there was one line loss of vision and 2.50 D correction of astigmatism in the contralateral eye (preoperative refraction of −2.00 −3.50 × 40° and UDVA of 20/50). However, improvement in vision and astigmatism continued until 6 months after surgery. Mastropasqua et al.4 reported two lines of gain in UDVA and 3.00 D correction of astigmatism at 1 week after SMILE (preoperative refraction of −6.00 −6.00 × 50°); these results remained stable until the third postoperative month. No case of rejection was reported.
The incidence of stromal and epithelial graft rejection after DALK is 7.1%, which is significantly lower than the 19.4% reported for penetrating keratoplasty.6 The time to rejection after uneventful DALK varies widely and can be as late as 46 months after surgery.7 The rejection can be attributed to stress conditions and releasing inflammatory mediators,8 and corticosteroids are suggested to reverse rejection successfully.9 In our case, there was no complication after DALK for 9 years, but stromal rejection occurred 1 week after SMILE while taking betamethasone. In other words, the routine dose of betamethasone could not prevent graft rejection after surgical stress. But a high dose of topical betamethasone along with systemic corticosteroids controlled the immunologic reactions and reversed the rejection. Our patient responded well to treatment with CDVA of 20/40 on the next day after SMILE, which improved to 20/25 within 2 months.
SMILE can be an effective approach for the treatment of residual refractive errors after corneal transplantation. However, the risk of stromal rejection should be considered even if corticosteroids are prescribed. Intensive and stronger topical steroids should be considered as prophylaxis after the refractive surgery. Alternatively, if stronger steroids are not available, a parallel prophylactic application of systemic and topical immunosuppressive agents can be a suitable solution for such cases.
- Pedersen IB, Ivarsen A, Hjortdal J. Changes in astigmatism, densitometry, and aberrations after smile for low to high myopic astigmatism: a 12-month prospective study. J Refract Surg. 2017;33(1):11–17. doi:10.3928/1081597X-20161006-04 [CrossRef]28068441
- Vail A, Gore SM, Bradley BA, Easty DL, Rogers CA, Armitage WJ. Conclusions of the corneal transplant follow up study. Collaborating surgeons. Br J Ophthalmol. 1997;81(8):631–636. doi:10.1136/bjo.81.8.631 [CrossRef]9349147
- Kim BK, Mun SJ, Lee DG, Chung YT. Bilateral small incision lenticule extraction (SMILE) after penetrating keratoplasty. J Refract Surg. 2016;32(9):644–647. doi:10.3928/1081597X-20160526-01 [CrossRef]27598735
- Mastropasqua L, Calienno R, Lanzini M, Nubile M. Small incision lenticule extraction after deep anterior lamellar keratoplasty. J Refract Surg. 2015;31(9):634–637. doi:10.3928/1081597X-20150820-10 [CrossRef]26352570
- Alio JL, Javaloy J. Corneal inflammation following corneal photoablative refractive surgery with excimer laser. Surv Ophthalmol. 2013;58(1):11–25. doi:10.1016/j.survophthal.2012.04.005 [CrossRef]
- Liu H, Chen Y, Wang P, et al. Efficacy and safety of deep anterior lamellar keratoplasty vs. penetrating keratoplasty for keratoconus: a meta-analysis. PLoS One. 2015;10(1):e0113332. doi:10.1371/journal.pone.0113332 [CrossRef]25633311
- Roberts HW, Maycock NJ, O'Brart DP. Late stromal rejection in deep anterior lamellar keratoplasty: a case series. Cornea. 2016;35(9):1179–1181. doi:10.1097/ICO.0000000000000890 [CrossRef]27227399
- Gao S, Li S, Liu L, et al. Early changes in ocular surface and tear inflammatory mediators after small-incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis. PloS One. 2014;9(9):e107370. doi:10.1371/journal.pone.0107370 [CrossRef]25211490
- Guilbert E, Bullet J, Sandali O, Basli E, Laroche L, Borderie VM. Long-term rejection incidence and reversibility after penetrating and lamellar keratoplasty. Am J Ophthalmol. 2013;155(3):560–569. doi:10.1016/j.ajo.2012.09.027 [CrossRef]