Recently, a new corneal refractive surgical procedure has been introduced called small incision lenticule extraction (SMILE), an intrastromal keyhole form of keratomileusis.1–3 In SMILE, a femtosecond laser is used to create two interfaces that define a refractive lenticule of stromal tissue. A dissector is passed through a small 2- to 3-mm incision to separate the lenticular interfaces and allow the lenticule to be removed in one piece, thus eliminating the need to create a flap.
The fact that the lenticule is extracted all in one piece opens up the possibility of using the lenticule for other purposes. It has been suggested that refractive lenticules might be stored so that re-implantation can be performed at a later date if needed.4,5 This was proposed as a method for restoring tissue in ectatic corneas or providing an opportunity for reversing the myopic correction in a patient progressing to presbyopia. Re-implantation of the refractive lenticule (under a flap) has been demonstrated in rabbits, having been cryopreserved for 1 month.5
Alternatively, there is also the potential to use the SMILE technique for performing the keyhole intrastromal form of keratophakia first described by José Ignacio Barraquer in 19806 in which a disc of donor corneal tissue is lathed to the appropriate refractive power and inserted into a manually created intrastromal pocket.
The SMILE procedure can therefore be used to create the donor lenticule of Barraquer’s pocket intrastromal keratophakia procedure, using a refractive lenticule from one patient and re-implanting it intrastromally into a different patient through a small incision. We refer to this procedure as endokeratophakia. We present a case in which endokeratophakia was performed in a partially sighted eye with very high hyperopia.
A 23-year-old woman with very high hyperopia presented at the Refractive Surgery Unit of the Tilganga Institute of Ophthalmology to be assessed for suitability for corneal laser refractive surgery. Retinoscopic refraction was measured as +12.00 −1.50 × 155 (with corrected distance visual acuity [CDVA] of counting fingers) in the right eye and +10.00 −1.00 × 180 (with CDVA of 20/63) in the left eye. Objective refraction using the KR 8900 auto-refractor (Topcon, Tokyo, Japan) was +12.00 −1.50 × 157 in the right eye and +11.00 −1.00 × 180 in the left eye. The patient had undergone cataract surgery at the age of 2 years to remove a congenital cataract and had been left aphakic in both eyes. She had sensory exotropia of the right eye, which only fixated weakly on covering the left eye. The pupil was irregular and eccentric. Given the very high hyperopic refraction, the patient was informed that her refraction was outside the treatable range of LASIK. However, because her CDVA was only counting fingers in the right eye, she was offered and agreed to undergo an endokeratophakia procedure in the right eye. Ethics approval was obtained from the Institutional Review Committee, Tilganga Institute of Ophthalmology, Kathmandu, Nepal. No treatment was performed on the left eye.
Preoperative Atlas front corneal surface topography (Carl Zeiss Meditec, Jena, Germany) and Pentacam tomography (Oculus Optikgeräte, Wetzlar, Germany) results are shown in Figure 1. Central corneal thickness was 547 μm by Pentacam and 529 μm by hand-held ultrasound pachymetry (Corneo-Gage Plus 50 MHz; Sonogage, Cleveland, OH). Goldmann tonometry intraocular pressure was measured as 17 mm Hg. White-to-white diameter by Pentacam was 11.9 mm.
Atlas front corneal surface topography (Carl Zeiss Meditec, Jena, Germany) (top) and Pentacam (Oculus Optikgeräte, Wetzlar, Germany) sagittal curvature (middle) and posterior elevation (bottom) over the 6-month postoperative course after endokeratophakia.
The procedure was performed on August 10, 2012. The donor patient with high myopia was scheduled for a routine SMILE procedure using the VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany) on the same day, immediately prior to the recipient endokeratophakia patient. Prior to the donor’s procedure, the baseline work-up of the donor had been completed by the EYE Bank Tilganga to test for HIV I and II, HbsAg (hepatitis B), blood glucose, Veneral Disease Research Laboratory test, and treponema pallidum particle agglutination assay. The manifest refraction of the left eye of this donor patient was −12.00 −0.50 × 180 (20/40). Central corneal thickness by handheld ultrasound was 503 μm, which was reduced by 15 μm in the residual stromal thickness calculation as an extra safety bias. Given the high myopic refractive error and relatively low corneal thickness, a full correction was not possible. Using an optical zone of 5.75 mm with a transition zone of 0.01 mm and a 110-μm cap thickness allowed a myopic correction of −10.50 diopters (D) to be performed (127 μm maximum central lenticule thickness with a minimum edge thickness of 3 μm). The intended postoperative target refraction was −1.50 −0.50 × 180 with a predicted residual stromal thickness of 251 μm and predicted postoperative total intact stromal thickness of 311 μm (assuming an epithelial thickness of 50 μm). The white-to-white diameter was 12.2 mm. The cap diameter was 7.3 mm. The energy setting was 32 for the lenticule, cap, and sidecuts. The track and spot distances were both 4.6 μm for the lenticule and cap interfaces, 1.5 μm for the lenticule side-cut, and 2.5 μm for the cap sidecut.
Two small incisions were created: a 2-mm incision superotemporally and a 3-mm incision superonasally. The lenticule was successfully separated and extracted through the superotemporal incision, so the back-up incision was not required. The lenticule was set aside in McCarey-Kaufman medium storage. The orientation of the lenticule was maintained throughout, with the refractive cut anterior and the planar cut posterior. Given the spherical rotationally symmetric geometry of the lenticule, rotation was not monitored.
The endokeratophakia procedure was then performed for the hyperopic patient. First, the femtosecond laser interface creation part of a SMILE procedure was performed by programming a −2.00 D correction with the following parameters: cap thickness of 180 µm, optical zone diameter of 6.25 mm, and lenticule sidecut of 90°. The two small side incisions were located at 150° (superotemporal) and 330° (inferonasal). The upper interface was then separated in the normal fashion, but the lower interface of the lenticule was left unseparated to produce a lamellar pocket at 110 μm depth with a 7.3 mm diameter. The donor lenticule was inserted into the space provided by the upper interface through the small incision using a Kelman forceps holding the donor lenticule lengthwise along a diameter. The donor lenticule was distended until flat and centered on the corneal vertex coincident with the axis of fixation.
Immediately after the procedure, there was significant edema with several Descemet’s folds. By postoperative day 1, edema had considerably reduced with no Descemet’s folds. There was differential edema seen with increased haze within the lenticule itself. The patient was seen on postoperative day 2, where edema of the lenticule appeared relatively equivalent to that of the surrounding stroma. Figure 2 shows slit-lamp photographs at multiple time points after surgery.
Slit-lamp photogaphs over the 6-month postoperative course after endokeratophakia showing that the cornea remained clear. The lenticule appears decentered with respect to the pupil because the pupil was irregular and eccentric, whereas the lenticule had been centered on the corneal vertex coincident with the axis of fixation.
Postoperatively, ofloxacin 0.1% was used together with prednisolone acetate 1% four times a day for 1 week. Topical corticosteroid was tapered one drop less per day each subsequent week and stopped after 1 month. From 1 month, fluoromethalone drops were used once a day for 1 week followed by once on alternate days for 1 month.
Table A (available in the online version of this article) includes the retinoscopy refractions and Atlas keratometric values over the 1-year postoperative period. After 1 year, the spherical equivalent refraction reduced by 5.25 D from +11.25 to +6.00 D and the mean keratometry increased by 1.81 D from 41.39 to 43.20 D. Figure 1 shows the Atlas topography and Pentacam tomography maps over the first 6 months after surgery, as well as difference maps before and 6 months after the procedure. The front corneal surface topography significantly steepened, but the posterior surface elevation also changed significantly with a central bulge into the anterior chamber that was apparent on day 1 and was stable throughout the 1-year postoperative period. The radius of curvature taken from the Pentacam anterior elevation with a 4-mm best-fit sphere was 7.83 mm before and 7.21 mm after the procedure, which translated into a 4.14 D change in refractive power (using a refractive index of 1 for air and 1.377 for cornea). The radius of curvature taken from the Pentacam posterior elevation with a 4-mm best-fit sphere was 6.42 mm before and 7.67 mm after the procedure, which translated into a 1.04 D change in refractive power (using a refractive index of 1.377 for cornea and 1.336 for aqueous humor). This equaled a 5.18 D total change in refractive power, which closely matched the observed change in retinoscopy refraction.
At 6 months, the central corneal thickness by hand-held ultrasound had increased by 81 μm from 529 to 610 μm (46 μm less than the 127 μm thickness of the implanted lenticule). However, the central corneal thickness by Pentacam had increased by 121 μm from 547 to 668 μm (6 μm less than the 127 μm thickness of the implanted lenticule). The RTVue OCT (Optovue Inc., Fremont, CA) scan is shown in Figure 3. The central thickness of the implanted lenticule was measured as 130 μm and the central epithelium was measured as 43 μm using the manual caliper tool. At 1 year, the intraocular pressure was 16.0 mm Hg and at 6 months the endothelial cell count was 2,750 cells/mm2 using the EM 3000 (Tomey, Nagoya, Japan). The cornea remained clear over the 1-year postoperative period, although longer follow-up is needed because tissue rejection can occur several years postoperatively, as has been observed after corneal transplants.7
RTVue OCT (Optovue Inc. Fremont, CA) 6-mm diameter horizontal B-scan 6 months after endokeratophakia showing that the central thickness of the implanted lenticule was 130 μm, which was just 3 μm more than the intended lenticule thickness of 127 μm. The central epithelial thickness was 43 μm, indicating that there had likely been some epithelial thinning centrally to compensate for the increased curvature due to the implanted lenticule.
This case suggests that endokeratophakia could be a viable procedure for the correction of high hyperopia on the cornea by implantation of an extracted myopic SMILE lenticule from a donor patient. There were no adverse side effects to the implantation of donor tissue. However, research is needed to continue to study the observed undercorrection that was achieved.
Analysis of this case suggests that the two main factors contributing to the undercorrection are posterior surface changes and epithelial thickness remodeling. The posterior elevation maps show that a significant proportion of the curvature change afforded by the implanted lenticule manifested on the posterior surface, meaning that the majority of the effect intended by this curvature change was lost given the similar refractive index between the stroma and the aqueous humor in the anterior chamber. It would appear that the implanted lenticule causes the cornea to bulge both anteriorly and posteriorly, whereas the intention was only to induce a curvature change on the anterior surface. This was demonstrated by the refractive power analysis based on the change in radius of a 4-mm best-fit sphere for anterior and posterior elevation, which found that the anterior surface contributed 4.14 D and the posterior surface contributed 1.04 D. It may be that there is a maximum threshold for corneal thickness/volume for the posterior cornea to retain its shape (and hence confine the effect to the front surface) that was exceeded by addition of the 10.50 D lenticule.
Second, it is likely that epithelial thickness profile changes also contributed to the progressive regression observed in this case over the first week. Preoperative epithelial thickness data were not available in this patient, but it can be assumed that the epithelial thickness was approximately 53 μm and no less than 47 μm based on previous reports on the epithelial thickness in normal eyes.8 The RTVue OCT scan (Figure 3) shows that the epithelium was relatively uniform in thickness over the lenticule, varying between 40 and 47 μm within the central 6-mm zone. It is therefore likely that the epithelium had become thinner across the diameter of the lenticule. Peripheral epithelial thickness data were not available due to the 6-mm diameter limitation of the RTVue technology, so we could not confirm whether there was peripheral epithelial thickening as might be expected outside the zone of steepening due to the implanted lenticule, similar to that observed after hyperopic LASIK9 and in keratoconus10,11 and ectasia.12
There was a 46-μm discrepancy between the predicted donor lenticule thickness of 127 μm and the change in central full corneal thickness according to handheld ultrasound, but the difference was only 6 μm as measured by full corneal thickness differences by Pentacam. Also, direct measurement of lenticule thickness by RTVue OCT centrally was found to be 130 μm. Therefore, it seems likely that the lenticule thickness was accurate to the intended thickness and had not been compressed after implantation. It would appear that the handheld ultrasound result was due to measurement error. The 6-μm underestimation according to the Pentacam agrees with the likely 5 to 10 μm of epithelial thinning as described above.
Another factor that may have had a significant impact on the regression due to epithelial remodeling might be that the diameter of the implanted lenticule was only 5.75 mm. We know that hyperopic LASIK is more stable when a larger optical zone is used.13,14 However, in this case the diameter of the myopic lenticule implanted was limited by the pachymetry of the donor cornea and the myopic refraction to be corrected. Clearly there will be limits imposed on the maximum power of the donor myopic lenticule available based on optical zone and corneal thickness of the myopic donor—it will be relatively more difficult to find a high myopic SMILE donor patient in whom corneal thickness permits large optical zone lenticule creation. Alternatively, it should be possible to extract a donor lenticule from a cadaver donor cornea, which would enable a lenticule of larger dimensions to be extracted, but hydration changes and therefore stromal architecture may be considerably less accurate given post-mortem changes in the stroma and epithelium. Furthermore, justifying the use of healthy donor human lenticule tissue for refractive surgery may be difficult with the exception of corneas healthy but for low endothelial counts (which further compounds the three-dimensional accuracy of lenticule creation).
It is conceivable that modifications to the lenticule profile could help with regression dynamics, but this change would need to be acceptable to the donor’s surgical outcome. Limitations to the thickness of donor lenticules and final corneal thickness may be encountered because the recipient cornea’s endothelial function may theoretically become stressed by abnormally thick stroma to healthily deturgess for adequate stro-mal clarity. Alternatively, it may be possible to correct the residual hyperopia with a standard LASIK procedure now that the refraction has been brought down to within the treatable range.14
Femtosecond laser technology has enabled Barraquer’s keratomileusis procedure to be performed through a keyhole incision in the form of SMILE. It appears feasible that his proposed procedure of keratophakia may also now become a clinically feasible reality because the problems that he originally described (which led to the abandonment of the procedure) can be circumvented by using a femtosecond laser. Specifically, the femtosecond laser has enabled a method of accurately creating a donor lenticule within physiologically unaltered stroma that can be implanted through a keyhole incision with a stromal delamination pocket to correct reciprocal ametropia in a recipient. Further research into the optimal method of minimizing back surface changes by changing the depth of implantation and other factors are yet to be studied.
- Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95:335–339. doi:10.1136/bjo.2009.174284 [CrossRef]
- Shah R, Shah S, Sengupta S. Results of small incision lenticule extraction: All-in-one femtosecond laser refractive surgery. J Cataract Refract Surg. 2011;37:127–137. doi:10.1016/j.jcrs.2010.07.033 [CrossRef]
- Hjortdal JØ, Vestergaard AH, Ivarsen A, Ragunathan S, Asp S. Predictors for the outcome of small-incision lenticule extraction for myopia. J Refract Surg. 2012;28:865–871. doi:10.3928/1081597X-20121115-01 [CrossRef]
- Mohamed-Noriega K, Toh KP, Poh R, et al. Cornea lenticule viability and structural integrity after refractive lenticule extraction (ReLEx) and cryopreservation. Mol Vis. 2011;17:3437–3449.
- Angunawela RI, Riau AK, Chaurasia SS, Tan DT, Mehta JS. Refractive lenticule re-implantation after myopic ReLEx: a feasibility study of stromal restoration after refractive surgery in a rabbit model. Invest Ophthalmol Vis Sci. 2012;53:4975–4985. doi:10.1167/iovs.12-10170 [CrossRef]
- Barraquer JI. Queratomileusis y queratofakia. Bogotá: Instituto Barraquer de América; 1980:342.
- Watson SL, Tuft SJ, Dart JK. Patterns of rejection after deep lamellar keratoplasty. Ophthalmology. 2006;113:556–560. doi:10.1016/j.ophtha.2006.01.006 [CrossRef]
- Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg. 2008;24:571–581.
- Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ. Epithelial thickness after hyperopic LASIK: three-dimensional display with artemis very high-frequency digital ultrasound. J Refract Surg. 2010;26:555–564. doi:10.3928/1081597X-20091105-02 [CrossRef]
- Reinstein DZ, Gobbe M, Archer TJ, Silverman RH, Coleman DJ. Epithelial, stromal, and corneal thickness in the keratoconic cornea: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg. 2010;26:259–271. doi:10.3928/1081597X-20100218-01 [CrossRef]
- Rocha KM, Perez-Straziota CE, Stulting RD, Randleman JB. SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg. 2013;29:173–179. doi:10.3928/1081597X-20130129-08 [CrossRef]
- Reinstein DZ, Gobbe M, Archer TJ, Couch D. Epithelial thickness profile as a method to evaluate the effectiveness of collagen cross-linking treatment after corneal ectasia. J Refract Surg. 2011;27:356–363. doi:10.3928/1081597X-20100930-01 [CrossRef]
- O’Brart DP, Mellington F, Jones S, Marshall J. Laser epithelial keratomileusis for the correction of hyperopia using a 7.0-mm optical zone with the Schwind ESIRIS laser. J Refract Surg. 2007;23:343–354.
- Reinstein DZ, Couch DG, Archer TJ. LASIK for hyperopic astigmatism and presbyopia using micro-monovision with the Carl Zeiss Meditec MEL80 platform. J Refract Surg. 2009;25:37–58.