Applications of SMILE-extracted lenticules in ophthalmology

AIM:To review recent innovations,challenges,and applications of small incision lenticule extraction(SMILE)extracted lenticule for treating ocular disorders.METHODS:A literature review was performed in the PubMed database,which was last updated on 30 December 2021.There was no limit regarding language.The authors evaluated the reference lists of the collected papers to find any relevant research.RESULTS:Due to the simplicity and accuracy of modern femtosecond lasers and the extensive development of SMILE surgery,many healthy human corneal stromal lenticules were extracted during surgery,motivating some professionals to investigate the SMILE lenticule reusability in different ocular disorders.In addition,new approaches had been developed to preserve,modify,and bioengineer the corneal stroma,leading to the optimal use of discarded byproducts such as lenticules from SMILE surgery.The lenticules can be effectively re-implanted into the autologous or allogenic corneas of human subjects to treat refractive errors,corneal ectasia,and corneal perforation and serve as a patch graft for glaucoma drainage devices with better cosmetic outcomes.CONCLUSION:SMILE-extracted lenticules could be a viable alternative to human donor corneal tissue.

Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK:a case series

●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis(FS-LASIK).●METHODS:A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo.The lenticules were collected from patients undertaking small incision lenticule extraction(SMILE)for the correction of myopia.Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength.●RESULTS:All surgeries were conducted successfully with no significant complications.Their best corrected visual acuity(BCVA)ranged from 0.05 to 0.8-2 before surgery.The pre-operational total corneal thickness ranged from 345-404μm and maximum keratometry(Kmax)ranged from 50.8 to 86.3.After the combination surgery,both the corneal keratometry(range 55.9 to 92.8)and total corneal thickness(range 413-482μm)significantly increased.Four out of 5 patients had improvement of corneal biomechanical parameters(reflected by stiffness parameter A1 in Corvis ST).However,3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze.Despite the onset of corneal edema right after SLAK,the corneal topography and thickness generally stabilized after 3mo.●CONCLUSION:SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia.Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

Treatment of superficial corneal opacities with corneal stromal lenticule obtained through SMILE surgery

AIM:To evaluate the clinical efficacy and feasibility of superficial corneal opacities treated by excimer laser phototherapeutic keratectomy(PTK)combined with small incision lenticule extraction(SMILE)-derived corneal stromal lenticule transplantation.METHODS:A retrospective interventional case series of nine patients aged 12-59y with superficial corneal opacity caused by different pathologies who underwent standardized PTK combined with SMILE-derived corneal stromal lenticule transplantation was examined.Lenticule patches were fixed with fibrin glue.All patients underwent pre-and post-operative clinical assessments at different times for up to 12mo.Slit lamp microscopy,corneal density,uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),and anterior segment optical coherence tomography(AS-OCT)were examined.RESULTS:The patients’mean age was 36.00±5.80(12-59)y.Seven eyes(77.8%)gained UDVA and CDVA at the last measurement compared to their preoperative levels.The densities of the total cornea,the total anterior corneal layer,and the anterior corneal layers of 0-2 and 2-6 mm decreased significantly by 12.4%,27.5%,46.7%,and 32.8%,respectively.After human allogeneic transplantation,the implanted lenticules of all eyes were clearly visible by AS-OCT and remained transparent without displacement or graft rejection.The thickness of the central cornea and corneal lenticule transplants were stable throughout the entire postoperative period.One case experienced the postoperative complication of delayed corneal epithelial healing.CONCLUSION:PTK combined with SMILE-derived corneal lenticule transplantation improves long-term visual acuity.Therefore,it is a new,safe,and effective method for treating superficial corneal opacity.

Changes in posterior corneal elevation after small incision lenticule extraction for different myopic diopters

●AIM:To study the changes and effect factors of posterior corneal surface after small incision lenticule extraction(SMILE)with different myopic diopters.●METHODS:Ninety eyes of 90 patients who underwent SMILE were included in this retrospective study.Patients were allocated into three groups based on the preoperative spherical equivalent(SE):low myopia(SE≥-3.00 D),moderate myopia(-3.00 D>SE>-6.00 D)and high myopia(SE≤-6.00 D).Posterior corneal surfaces were measured by a Scheimpflug camera preoperatively and different postoperative times(1wk,1,3,6mo,and 1y).Posterior mean elevation(PME)at 25 predetermined points of 3 concentric circles(2-,4-,and 6-mm diameter)above the best fit sphere was analyzed.●RESULTS:All surgeries were completed uneventfully and no ectasia was found through the observation.The difference of myopia group was significant at the 2-mm ring at 1 and 3mo postoperatively(1mo:P=0.017;3mo:P=0.018).The effect of time onΔPME was statistically significant(2-mm ring:P=0.001;4-mm ring:P<0.001;6-mm ring:P<0.001).The effect of different corneal locations onΔPME was significant except 1wk postoperatively(1mo:P=0.000;3mo:P=0.000;6mo:P=0.001;1y:P=0.001).Posterior corneal stability was linearly correlated with SE,central corneal thickness,ablation depth,residual bed thickness,percent ablation depth and percent stromal bed thickness.●CONCLUSION:The posterior corneal surface changes dynamically after SMILE.No protrusion is observed on the posterior corneal surface in patients with different degrees of myopia within one year after surgery.SMILE has good stability,accuracy,safety and predictability.

Ten-year observation of corneal densitometry and associated factors following small incision lenticule extraction

●AIM:To investigate the long-term changes of corneal densitometry(CD)and its contributing elements after small incision lenticule extraction(SMILE).●METHODS:Totally 31 eyes of 31 patients with mean spherical equivalent of-6.46±1.50 D and mean age 28.23±7.38y were enrolled.Full-scale examinations were conducted on all patients preoperatively and during followup.Visual acuity,manifest refraction,axial length,corneal thickness,corneal higher-order aberrations,and CD were evaluated.●RESULTS:All surgeries were completed successfully without complications or adverse events.Ten-year safety index was 1.17±0.20 and efficacy 1.04±0.28.CD value of 0–6 mm zones in central layer was statistically significantly lower 10y postoperatively,compared with preoperative values(0–2 mmΔ=-1.62,2–6 mmΔ=-1.24,P<0.01).There were no correlations between CD values and factors evaluated.●CONCLUSION:SMILE is a safe and efficient procedure for myopia on a long-term basis.CD values get lower 10y postoperatively,whose mechanism is to be further discussed.

Covering corneal stromal lenticule for macular hole in pathological myopia

AIM:To evaluate the clinical effect of a new surgery technique(covering corneal stromal lenticule,CSL)for macular hole(MH)in pathological myopia.METHODS:This was a prospective non-randomized series case study.Fourteen eyes of 14 patients whose axial length were more than 29 mm and suffered from MH and macular hole retinal detachment(MHRD)were included in this study.All cases were treated with 25-gauge pars plana vitrectomy(PPV)with internal limiting membrane(ILM)peeling,covering CSL and C_(3)F_(8) gas tamponade.These cases were followed for 6mo,and the best-corrected visual acuity(BCVA),healing status of MH,the reattached rate of retinal detachment(RD),and reoperation rate were analyzed.RESULTS:All cases were successfully performed the surgery and the postoperative follow-up was completed.After surgery,MHs were healed in all 14 eyes(100%,14/14)after assessed by optical coherence tomography.The reattachment of retina was achieved in all 6 eyes(100%,6/6)with MHRD.BCVA was improved in 12 eyes(85.71%,12/14),and had no significant change in 2 eyes(14.29%,2/14).The overall mean BCVA was improved from 1.80±0.77 to 0.82±0.46 logMAR(F=10.46,P<0.01).No serious complications occurred in all cases.CONCLUSION:The new surgery technique(covering CSL)has high reattached rate of RD and high healing rate of MH in pathological myopia in the preliminary study.And it can effectively improve the visual function of patients.This new technique offers meaningful new ideas for treating refractory MH in pathological myopia.

Postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens implantation versus small incision lenticule extraction in myopic eyes:a Meta-analysis

AIM:To compare the postoperative efficacy,safety,predictability,and visual quality of implantable collamer lens(ICL)implantation versus small incision lenticule extraction(SMILE)in myopia eyes.METHODS:Pub Med,EMBASE,Web of Science,Cochrane Library and several Chinese databases were searched at May 2021 to select relevant studies in comparison of clinical outcomes between ICL implantation and SMILE for myopia.The primary outcomes were efficacy,safety,and predictability.And the secondary outcomes were postoperative higher-order ocular aberrations(HOAs),modulation transfer function cutoff frequency(MTF),objective scatter index(OSI),contrast sensitivity and a quality of vision(Qo V)questionnaire.RESULTS:A total of 1036 eyes from 10 studies,of which 503 eyes underwent ICL implantation and 533 eyes underwent SMILE,were enrolled in this Meta-analysis.Pooled results revealed that ICL group had a better safety index and post-corrected distance visual acuity(CDVA)(P=0.007,<0.00001,respectively),and a lower percentage of eyes with a postoperative CDVA lost 1 line(P=0.007)than the SMILE group.No significant differences were found in comparison of the other primary outcomes.In the longterm follow-up(>6mo),ICL group had a lower total HOA,coma,and spherical aberration than SMILE group(P=0.003,<0.00001,0.04).Yet higher trefoil was found in ICL group at 6mo after surgery(P=0.003).Additionally,ICL group also had a higher MTF value(P=0.02),and a higher contrast sensitivity score for spatial frequencies of 1.5,6,and 12 cpds(P=0.02,0.005,0.02,respectively).And it also had a lower score of bothersome in Qo V questionnaire than SMILE group(P=0.003).CONCLUSION:ICL implantation and SMILE have similar and comparable outcomes in term of the efficacy and predictability for correcting high myopia.However,ICL group is relatively safer and also has better visual quality in comparison of SMILE group.

Comparative study of functional optical zone:small incision lenticule extraction versus femtosecond laser assisted excimer laser keratomileusis

AIM:To investigate the size of functional optical zone(FOZ)after small incision lenticule extraction(SMILE)versus femtosecond laser assisted excimer laser keratomileusis(FS-LASIK)for myopia correction and potential associated factors for FOZ.METHODS:A total of 133 patients who received corneal refractive surgery in our hospital between November 2018 and July 2021 were retrospectively enrolled.There were 63 patients(123 eyes)in SMILE group and 70patients(139 eyes)in FS-LASIK group.The size of FOZ was measured using Pentacam 3-dementional anterior segment analyzer before and 3mo after surgery,so as to analyze postoperative achieved functional optical zone(AFOZ)and its contributing parameters.RESULTS:When planned functional optical zone(PFOZ)was 6.5 mm for both groups,AFOZ was 1.45±0.27 and 1.67±0.25 mm smaller than preoperative FOZ in SMILE group and FS-LASIK group 3mo after surgery.AFOZ in SMILE group was significantly larger than that in FS-LASIK group(P<0.001).Variation of FOZ was negatively correlated with preoperative spherical equivalent(SE)and positively correlated with variation of mean keratometry value(△Km),variation of spherical aberration(△SA),and variation of Q-value(△Q,all P<0.001)in both groups.Multiple variable linear regression equations were△FOZ=1.354-0.1×pre-SE+0.336×△Q+1.462×△SA in SMILE group and△FOZ=1.512+0.137×△Q+0.468×△SA in FS-LASIK group.CONCLUSION:AFOZ is significantly smaller than preoperative FOZ in both SMILE and FS-LASIK groups.With the same PFOZ,larger AFOZ is achieved in SMILE group than in FS-LASIK group.

Small incision lenticule extraction and femtosecond-assisted laser in situ keratomileusis in patients with deep corneal opacity:case series

AIM:To report the safety,efficacy,and accuracy of small-incision lenticule extraction(SMILE)or femtosecondassisted laser in situ keratomileusis(FS-LASIK)for the correction of myopia or myopic astigmatism in patients with deep corneal opacity denoted by anterior segment optical coherence tomography(AS-OCT).METHODS:Four patients with monocular corneal opacity(3 due to mechanical injury,1 due to a firecracker wound)were recruited and treated with refractive surgery(3 for SMILE,1 for FS-LASIK combined with limbal relaxing incision(LRI).Preoperative ocular manifestations,surgical details,postoperative visual outcomes,corneal opacity parameters,and corneal topography were analyzed.RESULTS:Preoperatively,spherical diopter ranged from-3.0 D to-4.75 D with cylinder ranging from-0.75 to-5.0 D,and corrected distance visual acuity(CDVA)ranging from 20/25 to 20/20.One eye’s corneal opacity was located in the central zone and three were in the mid-peripheral optical zone.Three patients underwent uneventful SMILE in both eyes,whilst one patient underwent FS-LASIK for high astigmatism in both eyes and LRI in the right eye.CDVA of the eye with corneal opacity ranged from 20/22to 20/20 one to six weeks postoperatively.Two patients achieved better CDVA and no patients lost Snellen lines.The postoperative diopter was within±0.75 D for all eyes.Significant edema existed above the corneal opacity in one eye and dissipated soon.No eccentric corneal topography or morphological anomaly of the corneal cap or flap was observed.CONCLUSION:The cases demonstrate that SMILE or FS-LASIK is safe and effective to treat myopic astigmatism combined with deep corneal opacity lesions after comprehensive preoperative evaluation and appropriate candidate selection.FS-LASIK combined with LRI is also sufficient for correcting high astigmatism due to corneal scarring.

A 3-month comparison study of subjective and objective visual quality of small incision lenticule extraction and transepithelial photorefractive keratectomy in patients with low and moderate myopia

AIM:To compare the subjective and objective visual quality between small incision lenticule extraction(SMILE)and transepithelial photorefractive keratectomy(t PRK)in patients with low and moderate myopia.METHODS:Patients undertaking SMILE or t PRK for the correction of low and moderate myopia were consecutively recruited in this prospective cohort study with a 3-month follow-up period.Objective evaluation[visual acuity test,manifest refraction,wavefront aberrations,the total cut-off value of the total modulation transfer function(MTFcut-off),and Strehl ratio(SR)]and subjective evaluation of visual quality(quality-of-life questionnaire)were conducted before surgery and at days 1,7,30,and 90 after surgery.RESULTS:A total of 47 patients(94 eyes)with SMILE and 22 patients(22 eyes)with t PRK were enrolled.The uncorrected visual acuity(UCVA)was better in SMILE patients on day 7 after surgery(1.13±0.13 vs 0.99±0.17,t=4.85,P<0.001)but was comparable at days 30 and 90.At day 90,the SMILE group had a lower spherical equivalent(SE)than the t PRK group(0.04±0.31 vs 0.19±0.43,t=2.08,P=0.042).Total higher order aberrations(HOAs)were induced in both surgical types,which were more evident in the t PRK group with 3-mm pupil diameter(0.16±0.07 vs0.11±0.05,t=4.27,P<0.001)and 5-mm pupil diameter(0.39±0.17 vs 0.36±0.11,t=2.33,P=0.022).The MTFcut-offand SR showed a trend of improvement in both SMILE and t PRK patients but were statistically better in the SMILE group with both pupil diameters.There was a significant improvement of contrast sensitivity(CS)over baseline levels at the spatial frequency of 18 cycles/degree(c/d)in the SMILE group(F=2.72,P=0.033)and at 3 c/d(F=3.03,P=0.031),12 c/d(F=3.72,P=0.013),and 18 c/d(F=4.62,P=0.004)in the t PRK group.The subjective quality of life questionnaire showed a steady improvement in the SMILE group(F=8.31,P<0.001)but not the t PRK group.CONCLUSION:SMILE and t PRK are both safe and effective ways to correct low and moderate myopia.A generally better and quicker recovery of visual quality favors the application of SMILE in qualified patients.

Effectiveness and the nomogram of small incision lenticule extraction in the correction of myopic anisometropia in adults

AIM:To evaluate the safety,effectiveness,and predictability of small incision lenticule extraction(SMILE)for the treatment of anisometropia,and to explore the personalized design scheme of SMILE in correcting adult myopia anisometropia based on the nomogram.METHODS:It’s a prospective cohort study.Patients with anisometropic myopia of refractive difference≥2.0 diopters(D)who underwent SMILE between September 2020 and March 2021 were enrolled.Clinical features and visual function were assessed preoperatively and at 1wk,1,3,and 6mo after the operation.The examination included tests for uncorrected distance visual acuity(UDVA),corrected distance visual acuity(CDVA),refractive errors,effectiveness index(preoperative CDVA/postoperative UDVA),safety index(postoperative CDVA/preoperative CDVA),nomogram and stereoscopic function.Paired t-test,Wilcoxon signed-rank test and repeated-measures analyses of variance were used for continuous variables,and Pearson Chi-squared test was used for categorical variables.RESULTS:The study involved 45 consecutive patients(average age:25.0±6.9y;82 out of 90 eyes underwent SMILE,while 8 eyes were not operated).The average preoperative spherical equivalent(SE)was-4.74±0.22 D.Six months after surgery,the effectiveness index was 1.05±0.12,and the safety index was 1.09±0.11.Seventy eyes(85.4%)exhibited SE correction error within±0.5 D.The percentage of eyes with Titmus stereoscopic function equal to or less than 200”significantly increased from 55.6%preoperatively to 88.9%postoperatively(P<0.05).There was statistically significant difference between higher myopia eyes and contralateral eyes in average nomogram value/spherical refraction ratio.CONCLUSION:SMILE is safe,effective and predictable in correcting myopic anisometropia,and it improves stereoscopic visual function of anisometropia patients.The precise and individualized design of the nomogram is a vital element to ensure the balance of both eyes after SMILE.

Treatment of corneal dermoid with lenticules from small incision lenticule extraction surgery:a surgery assisted by fibrin glue

AIM:To observe the clinical efficacy of the combined use of small incision lenticule extraction(SMILE)-derived lenticule patches in corneal dermoid excision,with fixation of the lenticule patches assisted by fibrin glue.METHODS:Seventeen eyes of 17 patients with corneal dermoid were treated with dermoid removal combined with SMILE-derived lenticule transplantation.All lenticule patches were fixed by fibrin glue.Ocular changes were assessed using slit lamp microscopy and anterior-segmental optical coherence tomography.The best-corrected visual acuity(BCVA)and ocular dioptric variations were examined preoperatively and postoperatively.Intraocular pressure(IOP)was also monitored in all visited time.RESULTS:Totally,18 lenticule patches were used on 17 eyes of 17 cornea dermoid patients.The mean follow-up time was 11.47±5.28mo.All lenticule patches we resuccessfullyg lued,kept on its location and maintained transparent during the follow-up time,with a consecutive epithelial cover for 1wk.Nine of the patients could coordinate visual and optometry exam well.Their preoperative BCVA is 0.60±0.35 in decimal,significantly improved to 0.80±0.26 in decimal at 6mo postoperatively(Z=-2.392,P=0.017),but the changes of their corneal astigmatism diopters showed no significance,with 2.22±1.91 D preoperatively,and 2.28±1.31 D at 6mo postoperatively(Z=-0.135,P=0.893).Limbal pannus formation occurred in 4(23.52%)cases and decreased with the application of tacrolimus eyedrops.IOP increased in 2(11.76%)cases,but well decreased by timolol maleate eyedrops.All the adult patients or guardians of minor patients were satisfied with the cosmetic improvement.CONCLUSION:Dermoid excision combined with transplantation of SMILE-derived lenticule patches using fibrin glue is a safe and effective novel tectonic keratoplasty procedure for corneal dermoid.

Ultrastructural and Immunohistochemical Characteristics of Corneal Lenticule Extracted during Correction of Residual Myopia in the Long-Term Period after SMILE

Purpose: To evaluate ultrastructural characteristics of lenticule surface extracted during correction of residual myopia in patients after small-incision lenticule extraction (SMILE). Methods and material: This study had a prospective, consecutive, comparative design. Sixteen patients (16 eyes) underwent additional intervention for residual myopia correction after SMILE. 16 specimens of removed lenticules underwent morphological examination. Markers and reagents were used to determine actin microfilaments, neutral fats and cell nuclei. The tissue was analyzed in layers in 2D slices form, volumetric Z-stacks, or selected areas were formed in orthogonal projections. The surface of the extracted lenticule was analyzed using scanning electron microscopy. Patients’ refractive outcomes were measured postoperatively (1 day;1 and 3 months). Results: Postoperatively uncorrected distance visual acuity (20/20 or better) was in 100% cases 3 months after surgery. Ultrastructural studies have shown the difference in surfaces of the newly formed lenticule. Structural changes of the posterior lenticule surface were characterized by ruptures of collagen fibers on its surface, degenerative changes in keratocytes with signs of colliquation necrosis, cell apoptosis and F-actin in cell cytoplasm. Conclusion: Collagen fibers are immersed in the stroma on the anterior surface of the lenticule. There is no complete structure restoration of collagen fibers explaining the lack of tight adhesion of anterior and posterior surfaces of the intrastromal space even in the long-term postoperative period. There are no degenerative changes of keratocytes on the anterior lenticule surface, that is, their changes in SMILE are reversible in most cases.

Small-incision lenticule extraction versus femtosecond lenticule extraction for myopic:a systematic review and Meta-analysis

AIM： To examine differences in efficacy, accuracy, safety, aberrations and corneal biomechanical between Small incision lenticule extraction （SMILE） and femtosecond lenticule extraction （FLEx） for myopia. METHODS： Comprehensive studies were conducted on the PubMed, MEDLINE, EMBASE, and Cochrane Controlled Trials Register before 31 July, 2015. Meta-analyses were performed on the primary outcomes [loss of ≥2 lines of corrected distance visual acuity （CDVA）, uncorrected distance visual acuity （UDVA） ≥20/20, spherical equivalent （SE） within ±0.50 diopters （D）, final refractive SE], secondary outcomes were high-order aberrations （HOAs） and corneal biomechanical [central corneal thickness （CCT）, corneal hysteresis （CH） and corneal resistance factor （CRF）]. RESULTS： Seven trials describing a total of 320 eyes with myopia were included in this Meta-analysis. No significant differences were found in the efficacy [UDVA weighted mean difference （WMD） -0.01; 95%CI： -0.04 to 0.01; P=0.37, UDVA ≥20/20, OR 1.49; 95%CI： 0.78 to 2.86; P=0.23], accuracy （SE WMD -0.03; 95%CI： -0.12 to 0.07; P=0.58 , SE within ±0.5 D OR 1.25; 95%CI： 0.34 to 4.65; P=0.74）, HOAs （WMD -0.04; 95%CI： -0.09 to 0.01; P=0.14） and CCT WMD 1.83; 95%CI： -7.07 to 10.72; P=0.69, CH WMD -0.01; 95%CI： -0.42 to 0.40; P=0.97, CRF WMD 0.17; 95%CI： -0.33 to 0.67; P=0.50） in the last fellow-up. But for safety, FLEx may achieve fewer CDVA lost two or more two lines （OR 11.11; 95%CI： 1.27 to 96.86; P=0.03） than SMILE, however CDVA （WMD 0.00; 95%CI： -0.03 to 0.02; P=0.77） is similar. CONCLUSION： SMILE and FLEx are comparable in terms of both efficacy, accuracy, aberrations and corneal biomechanical measures in the follow-up,but FLEx seems to be better in safety measures. The results should be interpreted cautiously since relevant evidence is still limited, although it is accumulating. Further large-scale, well-designed randomized controlled trials are urgently needed.

Differentiation of human embryonic stem cells derived mesenchymal stem cells into corneal epithelial cells after being seeded on decellularized SMILE-derived lenticules

AIM: To evaluate the feasibility of mesenchymal stem cells(MSCs) to differentiate into corneal epithelial cells after being seeded on the decellularized small incision lenticule extraction(SMILE)-derived lenticules. METHODS: The fresh lenticules procured from patients undergoing SMILE for the correction of myopia were decellularized. The MSCs were subsequently cultivated on those denuded lenticules. The MSCs without lenticules were used as a control. The proliferation activity of the MSCs after seeding 24 h was quantitatively determined with the Cell Counting Kit-8(CCK-8) assay. Immunofluorescence staining and quantitative reverse transcription polymerase chain reaction(qRT-PCR) were used to assess the marker expression in differentiated MSCs. RESULTS: The data showed that both fresh and decellularized lenticules could significantly promote the proliferation of MSCs, compared to that in control(P=0.02 for fresh lenticules, P=0.001 for decellularize ones, respectively). The MSCs seeded on both lenticules were positive for cytokeratin 3(CK3) staining. The expression of CK3 increased 5-fold in MSCs seeded on fresh lenticules and 18-fold on decellularized ones, compared to that in control. There was a significant difference in the expression of CK3 in MSCs seeded on fresh and decellularized lenticules(P<0.001). The expression of CK8 and CK18 was similar in pure MSCs and MSCs seeded on fresh lenticules(P>0.05), while the expression of these markers was decreased in MSCs seeded on decellularized ones. CONCLUSION: These results suggest that the decellularized lenticules might be more suitable for MSCs to differentiate into corneal epithelial cells, which offersthe prospect of a novel therapeutic modality of SMILEderived lenticules in regenerative corneal engineering.

Three-year results of small incision lenticule extraction and wavefront-guided femtosecond laser-assisted laser in situ keratomileusis for correction of high myopia and myopic astigmatism

AIM： To compare and calculate the 3-year refractive results, higher-order aberrations （HOAs）, contrast sensitivity （CS） and dry eye parameters after small incision lenticule extraction （SMILE） and wavefront-guided femtosecond laser-assisted laser in situ keratomileusis （FS-LASIK） for correction of high myopia and myopic astigmatism. METHODS： In this prospective, non-randomized comparative study, 78 eyes with spherical equivalent （SE） of -8.11±1.09 diopters （D） received a SMILE surgery, and 65 eyes with SE of -8.05±1.12 D received a wavefront-guided FS-LASIK surgery with the VisuMax femtosecond laser （Carl Zeiss Meditec, Jena, Germany） for flap cutting. Visual acuity, manifest refraction, CS, HOAs, ocular surface disease index （OSDI） and tear break-up time （TBUT） were evaluated during a 3-year follow-up. RESULTS： The difference of uncorrected distance visual acuity （UDVA） postoperatively was achieved at lmo and at 3mo, whereas the difference of the mean UDVA between two groups at 3y were not statistically significant （t=-1.59, P=-0.13）. The postoperative change of SE was 0.89 D in the FS-LASIK group （t=5.76, P=0.00）, and 0.14 D in the SMILE group （t=-0.54, P=0.59） from lmo to 3y after surgery. At 3-year postoperatively, both HOAs and spherical aberrations in the SMILE group were obviously less than those in the FS-LASIK group （P=0.00）, but the coma root mean square （RMS） was higher in the SMILE group （0.59±0.26） than in the FS-LASIK group （0.29±0.14, P=0.00）. The mesopic CS values between two groups were not statistically significant at 3y postoperatively. Compared with the FS-LASIK group, lower OSDI scores and longer TBUT values were found in the SMILE group at Imo and 3mo postoperatively. With regard to safety, no eye lost any line of CDVA in both groups at 3y after surgery. CONCLUSION： Both SMILE and wavefront-guided FS- LASIK procedures provide good visual outcomes. Both procedures are effective and safe, but SMILE surgery achieve more stable long-term refractive outcome and better control of early postoperative dry eye as compared to FS-LASIK.

Dry eye and corneal sensitivity after small incision lenticule extraction and femtosecond laser-assisted in situ keratomileusis:a Meta-analysis

AIM：To assess the corneal sensitivity and the incidences of dry eye after small incision lenticule extraction（SMILE） and femtosecond laser-assisted in situ keratomileusis（FSLASIK）.METHODS：The Meta-analysis was performed using Rev Man 5.3.We searched on Pub Med from inception to March 2016.Summary weighted mean difference（WMD） and 95% confidence intervals（CIs） were used to analyze the datum.Random-effects or fixed-effects models were chosen up to between-study heterogeneity.The main outcomes were composed of the Ocular Surface Disease Index（OSDI） scores,tear film break-up time（TBUT）,Schirmer Test and corneal sensitivity.RESULTS：Eight eligible studies including 772 eyes（386 in SMILE group and 386 in FS-LASIK group） were identified.The parameters have no significiant difference heterogeneity between SMILE and FS-LASIK group preoperatively.There were significant differences between the two groups in OSDI scores at one and three months postoperatively,in TBUT at one and three months postoperatively,in corneal sensitivity at one week,about one month and three months postoperatively.However,there was no significant difference observed in Schirmer Test at the follow-up periods.CONCLUSION：Compare to FS-LASIK,dry eye and the corneal sensitivity recover better in the SMILE group,in first three months after the surgery.

Comparison of clinical outcome of small-incision lenticule intrastromal keratoplasty and FS-LASIK for correction of moderate and high hyperopia

AIM:To compare the clinical outcome of small-incision lenticule intrastromal keratoplasty(s LIKE)and femtosecond laser-assisted in situ keratomileusis(FS-LASIK)for correction of moderate and high hyperopia.METHODS:A case-controlled clinical study was performed.Twenty right eyes of 20 moderate and high hyperopia patients underwent s LIKE(s LIKE group)and 22 right eyes of 22 moderate and high hyperopia patients underwent FS-LASIK(FS-LASIK group)were enrolled in this study from October 2015 to October 2017.Visual acuity,refractive error,corneal thickness,and keratometry were compared between the groups before and 1 y postoperatively.RESULTS:The postoperative uncorrected near visual acuity(UNVA)and uncorrected distance visual acuity(UDVA)were improved in the two groups.The UNVA reached J1 in 15 eyes(75.0%)in the s LIKE group and 5 eyes(22.7%)in the FS-LASIK group 1 y after surgery(χ2=11.476,P=0.001).The UDVA was equal or better than the preoperative CDVA in 16 eyes(80.0%)in the s LIKE group and 8 eyes(36.4%)in the FS-LASIK group,respectively(X2=8.145,P=0.004).No eyes lost any line of best-corrected visual acuity(BCVA)in either group.The amount of postoperative residual hyperopia in the s LIKE group was significantly less than in the FS-LASIK group(Z=-2.841,P=0.004).The postoperative keratometry and corneal thickness were significantly higher in the s LIKE group than in the FS-LASIK group(t=4.411,10.279,P<0.001).The SRI and SAI of the s LIKE group were significantly higher than that in the FS-LASIK group.There was no statistically significant difference in mean decentration between the two groups.CONCLUSION:s LIKE has better visual and refractive outcome than FS-LASIK for correction of moderate and high hyperopia.

Cap morphology after small-incision lenticule extraction and its effects on intraocular scattering

AIM： To investigate cap morphology after small-incision lenticule extraction （SMILE） and its effects on intraocular scattering. METHODS： Sixty-five eyes of 33 patients undergoing SMILE were enrolled. In addition to regular evaluation, Fourier-domain optical coherence tomography was used to investigate cap thickness at ld, lwk, 1 and 3mo postoperatively. The optical quality including modulation transfer function cutoff frequency, Strehl ratio, Optical Quality Analysis System （OQAS） values, and objective scattering index （OSI）, were evaluated using OQASTM. RESULTS： Cap thickness decreased from ld to lwk （P〈0.001）, but remained higher than intended thickness of 120 μm after 3mo （P〈0.001）. Cap thickness in central area was thinner than that of in the paracentral and peripheral areas （P〈0.0001）. Total number of microdistortions decreased from ld to 3mo （P〈0.0001）. Pearson analysis revealed a weak correlation between OSI and standard deviation of cap thickness at ld and lmo, as well as between range of cap thickness and OSI at 1mo. No correlation was found between microdistortion and OSI, but a negative correlation existed between microdistortion and range at ld and lmoafter surgery. CONCLUSION： The corneal cap tends to be more accurate and regular with time lapse. Better cap morphology tends to contribute less intraocular scattering in the eyes undergoing SMILE.

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK

AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.