Femtosecond lenticule extraction (FLEx) is a refractive surgery procedure in which a femtosecond laser is used to generate an intrastromal lenticule that is removed manually after lifting the flap, as first described in humans during the American Academy of Ophthalmology annual meeting in 2006 using the VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany) and published in 2008.1 This procedure was refined by eliminating the need for a flap by dissecting and removing the lenticule through a small incision in a procedure known as small incision lenticule extraction (SMILE), and was first published in 2011.2,3 Although both FLEx and SMILE are well-established techniques for the treatment of myopia and myopic astigmatism,4 hyperopia treatment is still under investigation.5–9
In a recently published pilot study of spherical hyperopia treated by FLEx,9 we introduced a new profile with a large adjustable transition zone and showed its superiority compared to our first hyperopic study5 with a pseudo transition zone. This updated large transition zone profile has also been investigated for SMILE treatments in a parallel study at Tilganga Institute of Ophthalmology. This study found that optical zone centration was similar to hyperopic LASIK7 and that the achieved optical zone diameter after SMILE with a 6.3-mm optical zone (and 2-mm transition zone) was larger than for LASIK with a 7-mm optical zone.8
The current study reports the results of phase II following the pilot study described above, in which 9 eyes were treated. Even with these 9 eyes, a systematic undercorrection of approximately 0.50 diopters (D) was observed and taken into account for this study. Phase II of the study also introduced an updated femtosecond laser cutting sequence to decrease the laser treatment time.
Patients and Methods
This prospective study was approved by the Ethics Committee of the Chamber of Physicians of Thuringia, Germany, as well as by the Institutional Review Board of the Philipps University of Marburg, Germany. The Ethics Committees recommended dividing the study into a pilot study with up to 10 eyes (initial spherical cohort) and proceeding with a larger study of up to 40 eyes (second, spherocylindrical cohort) only after the first treatment group had been followed up and reported appropriately. Accordingly, we reported the outcome of the phase I study comprising 9 eyes of 5 patients last year.9
The inclusion criteria for the current second (phase II) study were as follows: (1) patient age of 21 years or older; (2) preoperative corrected distance visual acuity (CDVA) of 20/25 or better in both eyes; (3) central corneal thickness greater than 500 μm and calculated postoperative residual stromal thickness of 250 μm or greater; (4) normal corneal topography; (5) no preceding refractive surgery; (6) subjective hyperopia up to +6.00 D; (7) subjective astigmatism up to 5.00 D; and (8) subjective spherical equivalent refraction up to +8.00 D.
The preoperative examination was identical to the phase I study.9
Because this study was set as a two-center investigation, 4 eyes were treated in Erfurt (MB) and 35 eyes in Marburg (WS) using a 500-kHz VisuMax femtosecond laser with the identical unique software version for this clinical trial. The eyes were followed up for 9 months with postoperative visits at 1 day, 1 week, and 1, 3, 6, and 9 months and refracted by the same optometrist.
The lenticule geometry has already been described in the previous publication reporting the results of phase I.9 The transition zone was selected for each case individually, according to the corneal curvature, lenticule optical zone diameter, and dioptric power of treatment. These numbers were prepared on a spreadsheet that was available for data entry into the VisuMax laser. We did not use corneal marks for cyclotorsion or centration check, but the white-to-white distance was measured and taken into account when choosing the optical zone diameter. Due to a positive experience in the phase I study, the laser software was modified to a fixed central minimum lenticule thickness of 25 μm. The lenticule edge was set at 10 μm in all cases treated.
In the pilot study, the femtosecond laser cutting sequence was to first create the lenticule interface from out-to-in, followed by the transition zone starting at the diameter of the optical zone and then scanning peripherally. For phase II, this sequence was changed to combine the optical zone and transition zone into a single continuous scan. Thus, the femtosecond laser cutting started at the outer diameter of the transition zone and then proceeded smoothly onto the lenticule interface within the optical zone. This modification shortened the overall laser treatment time by approximately 6 seconds, lasting on average 32 seconds.
In addition, the initial experience of an undercorrection in the phase I study was compensated for by applying a nomogram adjustment, adding +0.50 D to the intended correction. To maximize the total lenticule diameter (optical zone plus transition zone), the clearance between the total lenticule diameter and flap diameter was reduced in some cases to as low as 0.4 mm (meaning a clearance of 0.2 mm on each side). A similar clearance was also used for the parallel study in Nepal.7,8
Thirty-nine eyes of 22 patients were enrolled in the study. Of these 39 eyes, 16 eyes were targeted for emmetropia, whereas a myopic target was used for the other 23 eyes to induce micro-monovision or a different degree of low myopia in both eyes according to the patients' needs because most of these hyperopic patients presenting were also presbyopic.
A medium (M) size interface cone (“contact glass”) and flap thickness of 120 μm was used for all eyes. The mean optical zone was 6 mm (range: 5.75 to 6.75 mm), with mean transition zone of 2.1 mm (range: 1.80 to 2.89 mm). The transition zone was adjusted for each eye based on the keratometry readings and attempted correction, such that the gradient of the transition zone was approximately the same for all eyes. Thus, the optical zone was reduced in higher corrections to accommodate a larger transition zone, keeping within the limit on the total lenticule diameter imposed by the contact glass. The flap diameter was between 8.8 and 9 mm. The femtosecond laser energy was 160 nJ (setting 32), with a fixed laser spot and track distance of 4.5 μm.
All measured data were collected on a standardized electronic patient chart and entered into Datagraph 5.0 software (Pieger GmbH, Roth, Germany) for analysis. All intraoperative and postoperative complications were collected and documented in the database. Outcomes were reported according to the Standard Graphs for Reporting Refractive Surgery.10
Twenty-two patients treated had a mean age of 49 years (range: 27 to 56 years), and 67.5% of the study population was female with the remaining 32.5% male. We treated 20 right and 19 left eyes. The preoperative refractive data were as follows: preoperative sphere of 2.24 ± 1.09 D (range: 0.75 to 4.75 D); preoperative cylinder of −0.56 ± 0.45 D (range: −1.75 to 0.00 D); and preoperative spherical equivalent of +1.96 ± 1.04 D (range: 0.63 to 4.50 D).
The efficacy has been calculated only for 16 eyes with the plano target. As shown in Figure 1A, 88% of eyes had 20/32, 38% had 20/25, and 6% had 20/20 uncorrected distance visual acuity (UDVA). However, only 50% of these eyes had a preoperative CDVA of 20/20. Figure 1B shows the difference between the preoperative UDVA and postoperative CDVA for the plano target subgroup.
Outcomes according to the standardized graphs and terms for refractive surgery results.
No serious intraoperative complications occurred. Minor adverse events observed included tedious flap lift (2%), bleeding at the flap border (6.1%), epithelial defects at the flap edge (10%), opaque bubble layer (4%), small tear at the flap edge (2%), and an incomplete flap side cut (2%). However, these had all healed within a few hours after surgery and did not affect the visual and refractive outcome.
The only noticeable postoperative finding was “trace haze” (grade 1 on a 5-grade scale) in 20% of eyes at the 9-month follow up. This haze was seen on oblique slit-lamp illumination only and did not affect visual performance. We did not observe any significant decentration on corneal topography. As shown in Figure 1C, no eyes lost two or more lines of CDVA at the last 9-month visit.
The preoperative spherical equivalent of the manifest refraction was +1.96 ± 1.04 D (range: +0.63 to +4.50 D). At the final 9-month follow-up visit, the mean spherical equivalent was −0.40 ± 0.61 D (range: −1.50 to +0.75 D), with 69% of eyes treated within ±0.50 D and 90% of eyes within ±1.00 D of intended correction. Figure 1D shows how the refraction is spread along the zero line, whereas Figure 1E shows a histogram of the refractive outcome. Postoperatively, the cylinder ranged between −1.25 and 0.00 D cyl with a mean of −0.47 ± 0.35 D cyl. Figures 1G–1I depict the comparison between the preoperative and postoperative astigmatism, with 72% of eyes treated being within 0.50 D cyl and undercorrection particularly evident in cases with higher preoperative astigmatism.
Figure 1F displays the change in spherical equivalent refraction over time. The mean preoperative attempted spherical equivalent of +2.36 D was reduced to −0.36 D at 1 week relative to the intended target. As expected for hyperopic treatments, there was a regression of +0.35 ± 0.51 D until the end of the study (9 months). However, between 6 and 9 months, the refraction changed by +0.03 D only.
Treatment of hyperopia by corneal laser refractive surgery has always been more challenging than myopic treatments. Successful hyperopic laser treatment relies on two key issues: a large optical and transition zone and centration on the corneal vertex.11 In our previous phase I pilot study, we showed that femtosecond laser corneal refractive surgery alone can achieve stability similar to modern excimer laser treatments when large transition zones are used.9
The current study builds on our initial observation of a systematic undercorrection. Indeed, the implementation of a nomogram of additional 0.50 D improved the predictability from 33% within ±0.50 D of the intended target (phase I) to 70% of eyes in the current phase II study. The ±1.00 D range also improved from 78% to 89%. These results are in accordance with the current results for femtosecond laser–assisted LASIK treatment for hyperopia. A study comparing wavefront-guided with wavefront-optimized ablation using two different modern excimer laser platforms in the same patient showed 73% of eyes in the wavefront-optimized and 91% of eyes in the wavefront-guided cohort to reach ±0.50 D of intended refraction after 1 year.12 It is expected that the predictability will continue to improve as the nomogram is refined with experience in larger populations. Our data also show that the undercorrection in astigmatism treatment is to a certain extent due to intraoperative cyclotorsion. We believe manual intraoperative cyclotorsion compensation should be implemented in future hyperopic SMILE studies.
An excellent centration in SMILE procedures has been previously shown for myopic treatment13 and in our phase I study on hyperopia.9 More recently, Reinstein et al.7 published a study with a special focus on the centration of hyperopic SMILE in comparison to hyperopic femtosecond laser–assisted LASIK treatments, showing that the centration offset was smaller for SMILE than for eye-tracker–guided LASIK.
In 20% of the eyes treated, a barely visible “trace haze” was observed under oblique slit-lamp illumination but did not affect visual acuity. However, this finding was definitely more common when compared to our vast experience of myopic FLEx or SMILE, where dot-like opacities may occur occasionally when the lenticule dissection was deemed difficult. Despite a large total lenticule diameter in these hyperopic treatments and hence a small clearance zone, the interface separation was not particularly difficult for an experienced SMILE surgeon; a difficult dissection was found in only one case.
Liu et al.6 studied wound healing of hyperopic SMILE and hyperopic LASIK in rabbits. They noticed that despite less postoperative wound healing response in hyperopic SMILE, this type of surgery resulted in more central deranged collagen fibrils than in the hyperopic LASIK group. One might speculate that this experimental finding could explain an enhanced production of intrastromal collagen that appears clinically as “haze.” Keeping this in mind, we might consider altering parameters such as energy settings and/or minimal central thickness to obtain the slit-lamp appearance we are used to after myopic treatments. In contrast, this finding might be a simple reflection of the older population treated in the current study. Indeed, Reinstein et al.7,8 treated patients on average 20 years younger with hyperopic SMILE using similar parameters and did not notice any increased haze formation. These are the questions to be answered in future large-scale studies.
This prospective investigation of FLEx for hyperopia and hyperopic astigmatism using a lenticule design with a dedicated large transition zone adjusted to both the optical zone and magnitude of correction produced visual and refractive outcomes similar to excimer laser correction of low to moderate hyperopia and had no visually threatening complications. These data, along with the hyperopic SMILE data published by Reinstein et al.,7,8 have led to the initiation of a large multi-center prospective study due to start in 2017 to obtain final approval of hyperopic SMILE.
- Sekundo W, Kunert K, Russmann CH, et al. First efficacy and safety study of femtosecond lenticule extraction for the correction of myopia. J Cataract Refract Surg. 2008;34:1513–1520. doi:10.1016/j.jcrs.2008.05.033 [CrossRef]
- 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]
- Zhang Y, Shen Q, Jia Y, Zhou D, Zhou J. Clinical outcomes of SMILE and FS-LASIK used to treat myopia: a meta-analysis. J Refract Surg. 2016;32:256–265. doi:10.3928/1081597X-20151111-06 [CrossRef]
- Blum M, Kunert KS, Vosserbäumer U, Sekundo W. Femtosecond-lenticule-extraction (ReLEX) corrections for hyperopia: first results. Graefes Arch Clin Exp Ophthalmol. 2013;251:349–355. doi:10.1007/s00417-012-2064-y [CrossRef]
- Liu Y, Ang HP, Teo EP, Lwin NC, Yam GH, Mehta JS. Wound healing profiles of hyperopic small incision lenticule extraction (SMILE). Sci Rep. 2016;6:29802. doi:10.1038/srep29802 [CrossRef]
- Reinstein DZ, Pradhan KR, Carp GI, et al. Small incision lenticule extraction (SMILE) for hyperopia: optical zone centration. J Refract Surg. 2017;33:150–156. doi:10.3928/1081597X-20161220-01 [CrossRef]
- Reinstein DZ, Pradhan KR, Carp GI, et al. Small incision lenticule extraction (SMILE) for hyperopia: optical zone diameter and spherical aberration induction. J Refract Surg. 2017;33:370–376. doi:10.3928/1081597X-20170331-01 [CrossRef]
- Sekundo W, Reinstein DZ, Blum M. Improved lenticule shape for hyperopic femtosecond lenticule extraction (ReLEx FLEx): a pilot study. Lasers Med Sci. 2016;31:659–664. doi:10.1007/s10103-016-1902-2 [CrossRef]
- Reinstein DZ, Archer TJ, Randleman JB. JRS standard for reporting astigmatism outcomes of refractive surgery. J Refract Surg. 2014;30:654–659. Erratum in: J Refract Surg. 2015;31:129. doi:10.3928/1081597X-20140903-01 [CrossRef]
- Reinstein DZ, Gobbe M, Archer TJ. Coaxially sighted corneal light reflex versus entrance pupil center centration of moderate to high hyperopic corneal ablations in eyes with small and large angle kappa. J Refract Surg. 2013;29:518–525. doi:10.3928/1081597X-20130719-08 [CrossRef]
- Sales C, Manche E. One-year eye-to-eye comparison of wavefront-guided versus wavefront-optimized laser in situ keratomileusis in hyperopes. Clin Ophthalmol. 2014;8:2229–2238.
- Lazaridis A, Droutsas K, Sekundo W. Topographic analysis of the centration of the treatment zone after SMILE for myopia and comparison to FS-LASIK: subjective versus objective alignment. J Refract Surg. 2014;30:680–686. doi:10.3928/1081597X-20140903-04 [CrossRef]