Journal of Refractive Surgery

Original Article Supplemental Data

Intrastromal Lenticule Rotation for Treatment of Astigmatism Up to 10.00 Diopters Ex Vivo in Human Corneas

Iben Bach Damgaard, MD; Anders Ivarsen, MD, PhD; Jesper Hjortdal, MD, DMSci

Abstract

PURPOSE:

To evaluate the feasibility of intrastromal lenticule rotation (ISLR) as a novel technique for management of astigmatism up to 10.00 diopters (D).

METHODS:

Eighteen human donor corneas were mounted on an artificial anterior chamber. After laser application and dissection, the lenticule was rotated 90° in the intrastromal pocket. Scheimpflug tomography (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) was acquired preoperatively and following ISLR. The attempted astigmatic correction was twice the cylindrical magnitude of the lenticule referenced to the corneal plane: 4.80 D (5.00 D group, n = 9) and 9.32 D (10.00 D group, n = 9), respectively. The change in keratometric astigmatism was evaluated by vector analysis.

RESULTS:

In the 5.00 D group, ISLR caused a mean absolute surgical induced astigmatism (SIA) of 5.30 ± 1.14 D with a correction index (CI) of 1.14 ± 0.25 and an angle of error (AoE) of −0.80° ± 4.61°. In the 10.00 D group, the SIA averaged 9.57 ± 1.10 D with a CI of 1.03 ± 0.12 and an AoE of 2.75° ± 3.60°. The average total corneal refractive power (TCRP) increased 1.36 ± 0.67 and 1.95 ± 1.57 D in the 5.00 D and 10.00 D groups, respectively. Postoperative optical coherence tomography revealed stromal redistribution in the periphery of the optical zone with tissue addition in the preoperative steep meridian and tissue reduction in the preoperative flat meridian.

CONCLUSIONS:

ISLR seemed feasible and precise for management of regular astigmatism up to 10.00 D ex vivo in human donor corneas. A myopic shift was observed in TCRP. The in vivo corneal remodeling after ISLR warrants investigation.

[J Refract Surg. 2019;35(7):451–458.]

Abstract

PURPOSE:

To evaluate the feasibility of intrastromal lenticule rotation (ISLR) as a novel technique for management of astigmatism up to 10.00 diopters (D).

METHODS:

Eighteen human donor corneas were mounted on an artificial anterior chamber. After laser application and dissection, the lenticule was rotated 90° in the intrastromal pocket. Scheimpflug tomography (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) was acquired preoperatively and following ISLR. The attempted astigmatic correction was twice the cylindrical magnitude of the lenticule referenced to the corneal plane: 4.80 D (5.00 D group, n = 9) and 9.32 D (10.00 D group, n = 9), respectively. The change in keratometric astigmatism was evaluated by vector analysis.

RESULTS:

In the 5.00 D group, ISLR caused a mean absolute surgical induced astigmatism (SIA) of 5.30 ± 1.14 D with a correction index (CI) of 1.14 ± 0.25 and an angle of error (AoE) of −0.80° ± 4.61°. In the 10.00 D group, the SIA averaged 9.57 ± 1.10 D with a CI of 1.03 ± 0.12 and an AoE of 2.75° ± 3.60°. The average total corneal refractive power (TCRP) increased 1.36 ± 0.67 and 1.95 ± 1.57 D in the 5.00 D and 10.00 D groups, respectively. Postoperative optical coherence tomography revealed stromal redistribution in the periphery of the optical zone with tissue addition in the preoperative steep meridian and tissue reduction in the preoperative flat meridian.

CONCLUSIONS:

ISLR seemed feasible and precise for management of regular astigmatism up to 10.00 D ex vivo in human donor corneas. A myopic shift was observed in TCRP. The in vivo corneal remodeling after ISLR warrants investigation.

[J Refract Surg. 2019;35(7):451–458.]

High postoperative astigmatism remains a leading factor influencing the visual rehabilitation following penetrating keratoplasty (PKP) and lamellar keratoplasty. The Australian Corneal Graft Registry including more than 18,000 eyes treated with PKP and lamellar graft reported a postoperative astigmatism of 5.00 diopters (D) or greater in 18% of the cases.1 Other studies have described an average postoperative astigmatism of 2.00 to 4.00 D following keratoplasty, ranging up to 10.00 diopters.2 Surgical management of high astigmatism remains a challenge when spectacles and rigid contact lenses are not well tolerated. Surgical methods for correcting high astigmatism following suture removal include astigmatic keratotomy, wedge resections, intracorneal ring segment implantation, laser vision correction, and toric intraocular lenses (IOLs). In high astigmatism, undercorrection is often reported after photorefractive keratotomy and laser-assisted in situ keratomileusis,3 whereas low predictability is a common problem when performing astigmatic keratotomy and wedge resections.4,5 Toric IOL insertion has the limitation of being an intraocular procedure and is not an optimal solution in young patients with clear lenses and preserved accommodation.6

Small incision lenticule extraction (SMILE) is an intrastromal laser refractive technique for the management of myopia and myopic astigmatism.7,8 A stromal lenticule is cut by a femtosecond laser and removed through a small incision, thereby preserving the anterior corneal integrity.9 Although safe and effective for correction of simple myopic astigmatism,10–12 SMILE is not yet approved for treatment of mixed astigmatism. SMILE can be considered a treatment option for myopia and myopic astigmatism following PKP or deep anterior lamellar keratoplasty,13–15 although the amount of astigmatic correction in SMILE is limited to 5.00 D.

Intrastromal lenticule rotation (ISLR) may be an alternative surgical procedure for the management of high mixed astigmatism. In theory, rotation of the SMILE-derived spherocylindrical lenticule would cause a redistribution of the corneal stroma, due to the thickness dimensions of the lenticule edge.16 Thus, ISLR would cause stromal alterations in the periphery of the optical zone with tissue reduction in the axis of the flat meridian and tissue addition in the axis of the steep meridian. Consequently, the astigmatic correction following ISLR may be higher than seen if the lenticule had been extracted in SMILE.10,11 The proposed technique may yield several advantages, including (1) no risk of rejection because ISLR may be considered an autologous transplantation, (2) preservation of the corneal stromal thickness in contrast to other laser refractive procedures, and (3) the theoretical reversibility of the procedure. Although allogeneic transplantation of SMILE-derived lenticules has been evaluated for treatment of refractive and corneal diseases,17–23 autologous transplantation of SMILE-derived lenticules warrants further investigation.

In this study, we aimed to examine the feasibility of ISLR for management of high astigmatism. Human donor corneas were used to evaluate the corneal tomography ex vivo following surgical intervention.24,25 Vector analysis was performed by the Alpins method to evaluate the keratometric change in astigmatism after ISLR.26 Based on the theoretical redistribution of stromal tissue (tissue subtraction in the preoperative flat meridian = tissue addition in the steep meridian), we hypothesized that the achieved astigmatic correction following ISLR would be twice the magnitude of the programmed cylinder referenced to the corneal plane.

Materials and Methods

Donor Tissue

Eighteen human corneoscleral rims (14 paired and 4 unpaired) were received in organ culture media (CorneaMax; Eurobio, Les Ulis, Italy) from the Veneto Eye Bank Foundation, Venice, Italy. The corneal tissue was deemed unsuitable for patient treatment due to low endothelial cell count and were without corneal opacities, irregularities, and severe senile arcus. The corneal tissue was transferred to a dehydrating organ culture media containing 8% dextran for a minimum of 24 hours prior to use. The corneal tissue was mounted on an artificial anterior chamber (Barron; Katena, Denville, NJ) containing organ culture media and 8% dextran. The epithelial layer was removed using a blunt spatula. The artificial anterior chamber was then placed upside down in dextran containing organ culture media for 30 minutes before commencement of the preoperative measurements.

The programmed cylindrical correction was set to either −2.50 D (the 5.00 D group, n = 9) or −5.00 D (the 10.00 D group, n = 9), which was then doubled to derive the attempted astigmatic correction in the spectacle plane (vertex distance of 12 mm).

ISLR

SMILE was performed using the 500-kHz VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany). The laser was centrally aligned to the artificial anterior chamber and the orientation of the chamber secured by placing the vertical crosshair of the graticule at the center of the two infusion holes. Perioperative laser specifications are found in Table 1. A spherical correction of −0.50 D was chosen because the VisuMax software is not yet approved for cylindrical treatment only. The side cut incision was placed on the preoperative flat meridian.

Perioperative Characteristics of the VisuMax Laser Settingsa

Table 1:

Perioperative Characteristics of the VisuMax Laser Settings

Following laser application, the edges of the anterior and posterior lenticule surface were located and dissected using a Sinskey hook. The anterior lenticule surface edge was gently marked at the axis of the preoperative flat meridian (K1,flat) with the tip of a Sinskey hook covered with corneal marking ink. The anterior and posterior lenticule surfaces were then dissected using a blunt spatula and the lenticule extracted with a pair of forceps.

The lenticule was placed and unfolded on the corneal surface to ensure its intactness and the preservation of the ink marking. The lenticule was then rotated 90° and inserted into the stromal pocket with the same anterior/posterior polarity as before extraction. The blunt spatula was used to unfold the lenticule in the stromal interface pocket and for final alignment by external surface manipulation. From a previous study, we experienced that a minimum lenticule thickness of 30 µm made the unfolding of the lenticule edge less difficult.24 The central alignment and 90° rotation of the lenticule was secured by the crosshair and the measuring rings of the graticule in the microscope eyepiece.

Preoperative and Postoperative Assessment

Scheimpflug tomography was performed to assess the corneal tomography preoperatively and after ISLR (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany). A custom-made device was used to ensure the same position and orientation of the artificial anterior chamber in front of the Pentacam before and after ISLR.24 The chamber pressure was set to 15 mm Hg, adjusted by a column containing 8% dextran organ media and a pressure monitor (Compass Compartment Pressure; Centurion, Williamston, MI) attached to the infusion port of the artificial anterior chamber. Measurements were performed at 45% humidity and 21°C room temperature. After ISLR, the artificial anterior chamber was placed in a moist chamber (100% humidity and 21°C) until the interface air bubbles had dissolved. Optical coherence tomography (OCT) (Heidelberg Engineering GmbH, Heidelberg, Germany) was performed following the postoperative tomography to evaluate the central cap thickness, central lenticule thickness, and central corneal thickness (CCT).

Corneal hydration was monitored as previously described in detail.24,25 The CCT from the first preoperative measurement (Pentacam HR) was used as a reference value of the hydration level (CCTref). The CCT was maintained by moisturizing the entire surface with a semi-wet sponge spear containing isotonic saline. The estimated CCT after ISLR (CCTISLR) was identical to CCTref.

The Central Denmark Region of Health Research Ethics found that no approval was needed because anonymous donor tissue was used for the study (request 186/2015). The tissue was processed in compliance with the Eye Bank Association of America Medical Standards.

Statistical Analysis

The total corneal refractive power (TCRP) in the 4-mm apex zone was used for analysis because it most accurately predicts the surgically induced refractive change in patients treated with SMILE.27 The magnitude of astigmatism preoperatively and after ISLR was calculated by K2,steep − K1,flat in diopters. We aimed to overcorrect the preoperative astigmatism to standardize the orientation of the attempted astigmatic correction.

Vector analysis was performed to evaluate the keratometric change in astigmatism, including target induced astigmatism (TIA), surgically induced astigmatism (SIA), difference vector (DV), magnitude of error (MoE), angle of error (AoE), correction index (CI), and index of success (IoS) by the Alpins method.26,28,29 Due to the novelty of the surgical procedure, the TIA magnitude was calculated using the programmed refraction of the SMILE-derived lenticules as follows. The programmed refraction was referenced to the corneal plane using a vertex distance of 12 mm. The TIA magnitude was then calculated as twice the cylinder in the corneal plane, corresponding to 4.80 D in the 5.00 D group and 9.32 D in the 10.00 D group, respectively.

The axial keratometry in the 3-mm apex zone was used to calculate the front and back curvature radii (r). Before and after ISLR, the meridional powers along axis of the preoperative K1,flat and K2,steep were calculated by the sine-squared correlation,30 and converted to radii in millimeters using a refractive index of 1.000 (air), 1.376 (corneal stroma), and 1.336 (aqueous humor). The changes in front and back curvature radii are expressed as Δr = rISLR − rpreop.

Statistical analysis and comparisons were performed using Stata (v.12.0 for MAC; Stata Corporation, College Station, TX), Graphpad Prism (v.6.0h for MAC; Graphpad Software Inc., La Jolla, CA) and Excel (v.16.16.3 for Mac; Microsoft Corporation, Redmond, WA) software. The median of three consecutive measurements was used for statistical analysis. The Hotelling T-squared test was used to evaluate if the bivariate vector of means were significantly different from a vector of zeros. Normal distribution was tested by quantile-quantile plots, histograms, and the Shapiro–Wilk test. Depending on the distribution of data, the one sample t test or Wilcoxon signed-rank test was used to evaluate non-vector parameters. Where applicable, Bonferroni adjustment was performed to adjust for multiple comparisons.

Results

Corneal tissue characteristics are found in Table A (available in the online version of this article). In all cases, the attempted astigmatic correction was larger than the preoperative astigmatism, whereas sufficient rotation would induce a 90° shift of the flat meridian on the keratometry maps. In two cases (5.00 D group), an error of 29° and 20° was observed in the axis of the flat meridian, whereas minor adjustments were performed using a blunt spatula. The CI increased from average 0.89 to 1.27, whereas the absolute AoE decreased from 9° to 4.5°.

Donor Tissue Characteristicsa

Table A:

Donor Tissue Characteristics

The corneal tomography measured after additional rotation was included in the vector analysis.

OCT was performed to evaluate the hydration level by means of the CCT, central cap thickness, and central lenticule thickness (Table 2). The average central lenticule thickness was close to the programmed lenticule thickness of 77 and 114 µm, with an average of 77 ± 9 and 112 ± 7 µm in the 5.00 D and 10.00 D groups, respectively. The change in CCT after ISLR was −1.56 ± 5.37 µm in the 5.00 D group and 1.78 ± 1.79 µm in the 10.00 D group, suggesting an adequate hydration level during assessment of the postoperative tomography.

Thickness Measurements and Change in TCRPa

Table 2:

Thickness Measurements and Change in TCRP

Corneal Tomography

Figure 1 presents the corneal tomography following rotation of a SMILE-derived lenticule in the 10.00 D group (programmed lenticule: −0.50 −5.00 × 165°) with representative OCT images in Figure A (available in the online version of this article). In all cases, ISLR caused an approximately 90° shift of the steep meridian and a bowtie configuration on the axial keratometry difference maps (Figures 1D–1F). Stromal redistribution was observed after ISLR with an increased peripheral stromal thickness in the preoperative steep meridian and reduced peripheral stromal thickness in the preoperative flat meridian (Figures 1A–1C, Figures AA–AB).

(A–C) Corneal pachymetry, (D–F) axial keratometry, and (G–I) anterior elevation maps before and after 90° intrastromal rotation of a small incision lenticule extraction (SMILE)–derived lenticule with the programmed correction of −0.50 −5.00 × 165° (the 10.00 diopters [D] group).

Figure 1.

(A–C) Corneal pachymetry, (D–F) axial keratometry, and (G–I) anterior elevation maps before and after 90° intrastromal rotation of a small incision lenticule extraction (SMILE)–derived lenticule with the programmed correction of −0.50 −5.00 × 165° (the 10.00 diopters [D] group).

Optical coherence tomography (OCT) following rotation of the small incision lenticule extraction (SMILE)–derived lenticule (programmed correction: −0.50 −5.00 × 165°) in the 10.00 diopters (D) group. (A) OCT of the preoperative flat meridian shows reduction of the paracentral corneal thickness in the optical zone (white arrows). Asterisk: side cut incision. (B) OCT of preoperative steep meridian with increased peripheral corneal thickness in the optical zone (white arrows).

Figure A.

Optical coherence tomography (OCT) following rotation of the small incision lenticule extraction (SMILE)–derived lenticule (programmed correction: −0.50 −5.00 × 165°) in the 10.00 diopters (D) group. (A) OCT of the preoperative flat meridian shows reduction of the paracentral corneal thickness in the optical zone (white arrows). Asterisk: side cut incision. (B) OCT of preoperative steep meridian with increased peripheral corneal thickness in the optical zone (white arrows).

Likewise, the front surface axial keratometry revealed significant curvature steepening along the preoperative K1,flat (Δr5.00 D: −0.56 ± 0.28 mm; Δr10.00 D: −0.91 ± 0.35 mm, P < .0004) and curvature flattening along the preoperative K2,steep (Δr5.00 D: 0.22 ± 0.16 mm; Δr10.00 D: 0.64 ± 0.29 mm, P < .0042). The back curvature remained unchanged along the preoperative K1,flat (Δr5.00 D: −0.01 ± 0.10 mm; Δr10.00 D: −0.04 ± 0.15, P < .626) but steepened in the preoperative K2,steep in the 10.00 D group (Δr5.00 D: −0.06 ± 0.08 mm; Δr10.00 D: −0.23 ± 0.13, P = .0379 and .0007, Bonferroni, TableB, available in the online version of this article).

Average Radii of the Corneal Front and Back Curvature Before and After ISLR in the Axis of the Preoperative Flat and Steep Meridian (K1,flat and K2,steep)a,b

Table B:

Average Radii of the Corneal Front and Back Curvature Before and After ISLR in the Axis of the Preoperative Flat and Steep Meridian (K1,flat and K2,steep),

A myopic shift was observed in TCRP following ISLR that was most prominent for high astigmatic corrections (Table 2).

Vector Analysis

The bivariate analysis of the polar values with the corresponding single-angle polar plots is presented in Table 3 and Figure B (available in the online version of this article). The arithmetic mean TIA magnitude was 4.88 and 9.32 D in the 5.00 D and 10.00 D groups, respectively, due to our assumption that the astigmatic change would be twice the cylindrical magnitude in the corneal plane. The arithmetic mean SIA magnitude was close to the arithmetic mean TIA. The CI showed a 14% and 3% overcorrection in the 5.00 D and 10.00 D groups, respectively. The linear regression analysis of SIA magnitude against TIA magnitude revealed a reduction of 0.09 D in SIA per diopter of attempted correction (Figure 2A, r2 = 0.80). None of the treated donor corneas had an AoE of more than ±10° after ISLR (Figure 2B).

Vector Analysis of the Astigmatic Change After ISLRa

Table 3:

Vector Analysis of the Astigmatic Change After ISLR

Single-angle polar plots of target induced astigmatism vectors (TIA), surgically induced astigmatism vectors (SIA), difference vector (DV), and correction index (CI) following intrastromal lenticule rotation in the (A–D) 5.00 and (E–H) 10.00 diopters (D) group. The CI was plotted against the axis of TIA. Black dots represent treated donor corneas and red dots represent mean vectors. arith = arithmetic mean; ax = axis of mean vector

Figure B.

Single-angle polar plots of target induced astigmatism vectors (TIA), surgically induced astigmatism vectors (SIA), difference vector (DV), and correction index (CI) following intrastromal lenticule rotation in the (A–D) 5.00 and (E–H) 10.00 diopters (D) group. The CI was plotted against the axis of TIA. Black dots represent treated donor corneas and red dots represent mean vectors. arith = arithmetic mean; ax = axis of mean vector

Vector analysis of the astigmatic outcome after intrastromal lenticule rotation (ISLR) by the Alpins method. (A) Target (TIA) versus surgically (SIA) induced astigmatism magnitude. Points below and above the dashed line indicate overcorrection and undercorrection, respectively. (B) Arithmetic angle of error after ISLR. arith = arithmetic; abs = absolute; D = diopters

Figure 2.

Vector analysis of the astigmatic outcome after intrastromal lenticule rotation (ISLR) by the Alpins method. (A) Target (TIA) versus surgically (SIA) induced astigmatism magnitude. Points below and above the dashed line indicate overcorrection and undercorrection, respectively. (B) Arithmetic angle of error after ISLR. arith = arithmetic; abs = absolute; D = diopters

Discussion

In this study, intrastromal rotation of SMILE-derived lenticules caused an astigmatic change of up to 10.00 D with high predictability. The average CI (the ratio of the SIA to the TIA magnitude) was 1.14 ± 0.25 and 1.03 ± 0.12 in the 5.00 D and 10.00 D groups, respectively, suggesting that ISLR causes an astigmatic correction a little more than twice the cylindrical magnitude of the lenticule. We found the ISLR procedure relatively easy to perform with an average AoE of 1.00° ± 3.4° and no cases with an AoE of more than ±10°.

The observed myopic shift of 1.36 ± 0.67 D (5.00 D group) and 1.95 ± 1.57 D (10.00 D group) in mean keratometry was attributed to the ratio between the flattening and steepening effect of ISLR in the principal meridians. The front curvature steepening along the preoperative K1,flat was more noticeable than the curvature flattening along the preoperative K2,steep (Table B). A likely explanation is the presence of Bowman's membrane and the anterior stroma31 that resist the front curvature alteration when stromal tissue is added to the periphery.24 Supporting this notion, we did observe significant back curvature steepening along the preoperative K2,steep in the 10.00 D group, although it was non-significant in the 5.00 D group. The programmed sphere was fixed to −0.50 D, corresponding to the minimum spherical correction required by the VisuMax software. How the programmed sphere affects the astigmatic correction in ISLR warrants further investigation. The programmed sphere was not taken into consideration when the myopic shift was evaluated following ISLR. Theoretically, the spherical component of the lenticule does not contribute to the myopic shift because the lenticule is rotated and not extracted during the procedure.

Surgical management of high astigmatism covers a wide range of surgical procedures, including incisional surgery,4,5 laser ablative procedures,3 and toric IOL implantation.6 However, these techniques are limited by poor predictability and accuracy in corneas after keratoplasty. Few patient cases13–15 have reported the refractive outcome following SMILE for management of astigmatism after keratoplasty and found an average astigmatic correction of 80.7% ± 20.9%.13 Wound dehiscence between the graft and the recipient cornea was observed during lenticule extraction in one case of PKP.14 ISLR rotation in corneas after keratoplasty should be centered at the corneal vertex, but only if the cap interface does not interfere with the graft–host interface.13 In such cases, the surgeon may consider making a smaller cap, although rotation and unfolding of the lenticule may become more difficult. ISLR may also be considered in patients with keratoconus and a pronounced regular astigmatic component, although disruption of the collagen fibrils may weaken the corneal stroma.24 However, ISLR is limited to treatment of regular astigmatism due to the symmetrical stromal redistribution after lenticule rotation. Regular astigmatism has been reported in up to 24% of patients after keratoplasty and these may benefit from ISLR.32

The orientation of the lenticule is likely one of the most important perioperative factors for a successful outcome following ISLR. The cylinder axis misalignment is dependent on both cyclorotation during lenticule creation and accurate rotation of the lenticule. In ordinary SMILE for myopic astigmatism, an off-axis treatment may cause an astigmatic undercorrection of 13% if the treatment is misaligned by 15°.33 We chose to extract the lenticule during ISLR, but lenticule rotation may be possible in the stromal interface. One benefit may be less risk of perioperative epithelial implantation or ingrowth,34,35 but without any opportunity to secure the completeness of the lenticule and the marking of the lenticule edge.

The rotation of the lenticule was secured primarily by the crosshair in the graticule. This was a laboratory setting using donor corneas, so the preoperative astigmatism magnitude was lower than the attempted cylinder magnitude. Therefore, adequate rotation would cause a 90° shift of the flat meridian, which was used to doublecheck the orientation of the lenticule. In clinical practice, the target astigmatic magnitude would be zero, which is why this method cannot be extrapolated directly into clinical practice. Theoretically, it may be possible to measure the corneal tomography after ISLR and adjust the lenticule in cases with off-axis residual astigmatism error. However, excessive manipulation of the lenticule may cause stromal swelling that affects the corneal tomography. In such cases, it would be advisable to postpone the lenticule adjustment until the stromal swelling subsides and repeat the corneal tomography. In a previous study of allogeneic lenticule implantation in rabbits, the authors found the lenticule was easily separable from the host stroma up to 1 month after implantation.36

The side cut incision was placed at the preoperative flat meridian to ensure that any hypothetical flattening effect of the incision would be identical in all cases. However, the position of the side cut incision did not affect the refractive outcome in a clinical study of SMILE.37 Thus, the incision may be placed superonasally or superotemporally depending on the surgeon's preference where a toric alignment marker can be used to secure correct orientation of the lenticule.

The current study appears to be the first to introduce and evaluate ISLR as a novel surgical procedure for the management of mixed astigmatism. Our chosen ex vivo model has some limitations because ISLR was performed in donor corneas without any prior surgical intervention. The outcome may differ in corneas after keratoplasty due to the biomechanical weakening caused by the circumferential graft cut.38 Our model did not offer an opportunity to evaluate the epithelial and stromal remodeling over time. Also, the interference of the stromal lamellae due to lenticule rotation would most likely cause some light scatter in the interface that may decrease the visual acuity. We monitored the CCT during preoperative and postoperative evaluation because the corneal tomography is dependent on the hydration of the corneal stroma.39 Although the entire corneal surface was uniformly moisturized, local variations in the corneal hydration may affect the postoperative tomography. We chose to perform only two astigmatic corrections due to the limited amount of donor tissue available for non-therapeutic use. However, ISLR with an attempted astigmatic correction between 5.00 and 10.00 D would have been preferable to support our current findings.

This study demonstrates that intrastromal rotation of autologous SMILE-derived lenticules effectively causes an astigmatic correction up to 10.00 D. The study provides useful information for future clinical trials or case series, where investigation of the long term stromal and epithelial remodeling following ISLR is recommended. A myopic shift was observed after lenticule rotation, so further studies using a wider range of astigmatic corrections are needed to corroborate these findings.

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Perioperative Characteristics of the VisuMax Laser Settingsa

Parameter5.00 D Group (n = 9)10.00 D Group (n = 9)
Cap thickness (µm)110110
Cap diameter (mm)7.37.3
Incision positionPreop K1,flat axisPreop K1,flat axis
Incision angle40°40°
Incision width (mm)2.552.55
Programmed sphere (D)−0.50−0.50
Programmed cylinder (D, axis preop K1,flat)−2.50−5.00
Optical zone (mm)6.56.5
Minimum lenticule thickness (µm)3030
Maximum lenticule thickness (µm)77114
Transition zone (µm)1010

Thickness Measurements and Change in TCRPa

Parameter5.00 D Group (n = 9)10.00 D Group (n = 9)
CCTpreop (Pentacam), µm448 ± 35 (399 to 488)452 ± 22 (422 to 491)
CCTISLR (Pentacam), µm447 ± 33 (397 to 483)454 ± 22 (426 to 494)
CCTISLR (Heidelberg), µm443 ± 28 (393 to 486)439 ± 19 (420 to 480)
Central cap thickness (Heidelberg), µm112 ± 5 (103 to 116)109 ± 6 (98 to 118)
Central lenticule thickness (Heidelberg), µm77 ± 9 (67 to 95)112 ± 7 (104 to 127)
Total corneal refractive power (4-mm apex zone)
  TCRP Km (preop), D44.60 ± 1.98 (41.30 to 46.55)44.64 ± 2.40 (40.25 to 47.75)
  TCRP cylinder (preop), D1.78 ± 0.77 (0.80 to 3.60)2.14 ± 0.70 (1.10 to 3.70)
  ΔTCRP Km (ISLR – preop), D1.36 ± 0.67 (0.60 to 2.50)1.95 ± 1.57 (0.25 to 4.95)

Vector Analysis of the Astigmatic Change After ISLRa

Parameter5.00 D GroupUnadjusted P10.00 D GroupUnadjusted P
Mean TIA vector4.07 D ax 8°7.38 D ax 3°
Mean SIA vector4.66 D ax 7°< .0001b7.38 D ax 7°< .0001b
Mean DV0.57 D ax 82°.0008b1.14 D ax 145°.0095
Arith mean TIA, D4.889.32
Arith mean SIA, D5.30 ± 1.14 (3.78 to 6.78)< .0001c9.57 ± 1.10 (7.45 to 11.60)< .0001c
Arith mean DV, D1.33 ± 0.69 (0.48 to 2.26).00771.48 ± 0.95 (0.38 to 2.91).0077
Arith Magnitude of Error, D1.11 ± 0.62 (0.46 to 2.12).00770.75 ± 0.80 (0.08 to 2.28).0077
Arith Angle of Error, degrees−0.80 ± 4.61 (−6.33 to 6.93).44132.75 ± 3.60 (−1.67 to 7.69).0858
Correction Index1.14 ± 0.25 (0.81 to 1.46)< .0001c1.03 ± 0.12 (0.80 to 1.24)< .0001c
Index of Success0.29 ± 0.15 (0.10 to 0.48)< .0004c0.15 ± 0.10 (0.04 to 0.31)< .0016c

Donor Tissue Characteristicsa

Parameter5.00 D Group (n = 9)10.00 D Group (n = 9)
Death-to-enucleation time (hours)12.8 ± 6.0 (7.6 to 22.3)13.4 ± 7.0 (6.8 to 24.2)
Total storage time (days)24.1 ± 4.0 (17 to 30)24.6 ± 6.3 (17 to 38)
Time in dextran (hours)26.4 ± 1.0 (25 to 28)26.4 ± 0.9 (25 to 28)
Donor age (years)66.3 ± 8.4 (57 to 77)64.2 ± 10.0 (52 to 77)

Average Radii of the Corneal Front and Back Curvature Before and After ISLR in the Axis of the Preoperative Flat and Steep Meridian (K1,flat and K2,steep)a,b

Parameter5.00 D Group (n = 9)10.00 D Group (n = 9)


Front CurvatureBack CurvatureFront CurvatureBack Curvature
Axis of preop K1,flat
  rPreop, mm7.60 ± 0.39 (7.21 to 8.36)6.61 ± 0.39 (6.26 to 7.30)7.65 ± 0.46 (7.05 to 8.56)6.62 ± 0.40 (6.02 to 7.41)
  rISLR, mm7.04 ± 0.43 (6.24 to 7.61)6.59 ± 0.41 (6.12 to 7.24)6.73 ± 0.39 (6.18 to 7.16)6.58 ± 0.47 (5.77 to 7.49)
  Δr, mm−0.56 ± 0.28 (−1.21 to −0.32)−0.01 ± 0.10 (−0.19 to 0.10)−0.91 ± 0.35 (−1.49 to −0.41)−0.04 ± 0.15 (−0.27 to 0.14)
  Unadjusted P.0003c.6257< .0001c.4057
Axis of preop K2,steep
  rPreop, mm7.29 ± 0.32 (6.98 to 7.75)6.24 ± 0.48 (5.71 to 7.06)7.28 ± 0.39 (6.84 to 7.96)6.44 ± 0.47 (5.89 to 7.14)
  rISLR, mm7.51 ± 0.40 (6.97 to 8.05)6.18 ± 0.44 (5.67 to 6.84)7.92 ± 0.60 (7.24 to 8.73)6.20 ± 0.44 (5.65 to 6.88)
  Δr, mm0.22 ± 0.16 (−0.06 to 0.44)−0.06 ± 0.08 (−0.22 to 0.03)0.64 ± 0.29 (0.10 to 0.94)−0.23 ± 0.13 (−0.44 to 0.02)
  Unadjusted P.0041c.0379.0002c.0007c
Authors

From the Department of Ophthalmology, Aarhus University Hospital, Aarhus C, Denmark.

Supported by Carl Zeiss Meditec, Fight for Sight Denmark, The Synoptik Foundation, Einar Willumsens Foundation, August Frederik Wedell Erichsens Foundation, Aase and Ejnar Daniselsens Foundation, and Maskinfabrikant Jochum and Hustru Marie Jensen F. Poulsens Mindelegat Foundation. The Pentacam HR was kindly donated by Bagenkop-Nielsens Myopia Foundation and the A. P. Møller Foundation for the Advancement of Medical Science.

The authors have no financial or proprietary interests in the materials presented herein.

AUTHOR CONTRIBUTIONS

Study concept and design (IBD, AI, JH); data collection (IBD); analysis and interpretation of data (IBD, JH); writing the manuscript (IBD); critical revision of the manuscript (AI, JH); statistical expertise (IBD); supervision (AI, JH)

Correspondence: Iben Bach Damgaard, MD, Department of Ophthalmology, Aarhus University Hospital, Nørrebrogade 44, Building 10, 2nd Floor, 8000 Aarhus C, Denmark. E-mail: iben.b.pedersen@gmail.com

Received: January 09, 2019
Accepted: June 18, 2019

10.3928/1081597X-20190618-02

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