Dan Z Reinstein

Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes

This review summarizes the current status of the small incision lenticule extraction (SMILE) procedure. Following the early work by Sekundo et al. and Shah et al., SMILE has become increasingly popular. The accuracy of the creation of the lenticule with the VisuMax femtosecond laser (Carl Zeiss Meditec) has been verified using very high-frequency (VHF) digital ultrasound and optical coherence tomography (OCT). Visual and refractive outcomes have been shown to be similar to those achieved with laser in situ keratomileusis (LASIK), notably in a large population reported by Hjortdal, Vestergaard et al. Safety in terms of the change in corrected distance visual acuity (CDVA) has also been shown to be similar to LASIK. It was expected that there would be less postoperative dry eye after SMILE compared to LASIK because the anterior stroma is disturbed only by the small incision, meaning that the anterior corneal nerves should be less affected. A number of studies have demonstrated a lower reduction and faster recovery of corneal sensation after SMILE than LASIK. Some studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than LASIK. The potential biomechanical advantages of SMILE have been modeled by Reinstein et al. based on the non-linearity of tensile strength through the stroma. Studies have reported a similar change in Ocular Response Analyzer (Reichert) parameters after SMILE and LASIK, however, these have previously been shown to be unreliable as a representation of corneal biomechanics. Retreatment options after SMILE are discussed. Tissue addition applications of the SMILE procedure are also discussed including the potential for cryo-preservation of the lenticule for later reimplantation (Mohamed-Noriega, Angunawela, Lim et al.), and a new procedure referred to as endokeratophakia in which a myopic SMILE lenticule is implanted into a hyperopic patient (Pradhan et al.). Finally, studies reporting microdistortions in Bowman’s layer and corneal wound healing responses are also described.Additional non-English abstract (French, Francais)Cette revue résume les connaissances actuelles sur la procedure SMILE (small incision lenticule extraction). Apres les travaux préliminaires des groupes de Sekundo et al. et de Shah et al., la procedure SMILE est désormais devenue courante. Le laser femtosecond VisuMax (Carl Zeiss Meditec) permet une découpe précise du lenticule, comme cela a été vérifié par ultrasound numérique à tres haute fréquence (Artemis) et par OCT. Il a été démontré, entre autres par Hjortdal, Vestergaard, et al. dans leur etude sur une population large, que les résultats visuels et refractifs sont comparables à ceux du LASIK, et que le risque de perte de lignes d’acuité corrigée est aussi semblable à celui du LASIK. Avec SMILE, contrairement au LASIK, la partie antérieure du stroma étant seulement découpée par une incision de petite taille, les nerfs cornéens antérieurs sont moins touchés et par consequent, le taux d’yeux secs en phase post-opératoire devrait etre plus faible après SMILE qu’apres LASIK. Quelques études ont effectivement démontré que la sensation cornéenne était moins réduite après SMILE qu’après LASIK et que la récupération de la sensation cornéenne était plus rapide. Quelques études ont aussi utilisé la microscopie confocale pour prouver qu’il y avait une diminution plus faible de la densité des fibres nerveuses de la couche sub-basale après SMILE qu’apres LASIK. Au niveau biomécanique, Reinstein et al. ont proposé un modèle basé sur la non-linéarité de la force de tension du stroma, mettant en avant les avantages potentiels de SMILE. Certaines études ont comparé les paramètres mesurés par l’Ocular Response Analayzer (Reichert) et rapporté un changement similaire après SMILE ou LASIK; cependant, on sait que ces paramètres ne peuvent pas etre pris en compte pour représenter la biomécanique cornéenne. Les options de re-traitement après SMILE sont présentées, ainsi que la possibilité d’ajouter du tisuu cornéen: par example, le potential de cryo-preservation du lenticule pour une ré-implantation ultérieure (Mohamed-Noriega, Angunawela, Lim et al.), et une nouvelle procedure nommée endokératophakie dans laquelle un lenticule SMILE est implanté dans la cornée d’un oeil hypermétrope (Pradhan et al.). Pour finir, des études rapportant des micro-distortions dans la couche de Bowmans et des études sur le processus de reparation de la cornée sont décrites.

Epithelial Remodeling as Basis for Machine-Based Identification of Keratoconus

PURPOSEnTo develop and evaluate automated computerized algorithms for differentiation of normal and keratoconus corneas based solely on epithelial and stromal thickness data.nnnMETHODSnMaps of the corneal epithelial and stromal thickness were generated from Artemis-1 very high-frequency ultrasound arc-scans of 130 normal and 74 keratoconic subjects diagnosed by combined topography and tomography examination. Keratoconus severity was graded based on anterior curvature, minimum corneal thickness, and refractive error. Computer analysis of maps produced 161 features for one randomly selected eye per subject. Stepwise linear discriminant analysis (LDA) and neural network (NN) analysis were then performed to develop multivariate models based on combinations of selected features to correctly classify cases. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined for each classifier.nnnRESULTSnStepwise LDA resulted in a six-variable model that provided an AUC of 100%, indicative of complete separation of keratoconic from normal corneas. Leave-one-out analysis resulted in 99.2% specificity and 94.6% sensitivity. Neural network analysis using the same six variables resulted in an AUC of 100% for the training set. Test set performance averaged over 10 trials gave a specificity of 99.5 ± 1.5% and sensitivity of 98.9 ± 1.9%. The LDA function values correlated with keratoconus severity grade.nnnCONCLUSIONSnThe results demonstrate that epithelial remodeling in keratoconus represents an independent means for differentiation of normal from advanced keratoconus corneas.

Combined tomography and epithelial thickness mapping for diagnosis of keratoconus.

Purpose Scanning Scheimpflug provides information regarding corneal thickness and 2-surface topography while arc-scanned high-frequency ultrasound allows depiction of the epithelial and stromal thickness distributions. Both techniques are useful in detection of keratoconus. Our aim was to develop and test a keratoconus classifier combining information from both methods. Methods We scanned 111 normal and 30 clinical keratoconus subjects with Artemis-1 and Pentacam data. After selecting one random eye per subject, we performed stepwise linear discriminant analysis on a dataset combining parameters generated by each method to obtain classification models based on each technique alone and in combination. Results Discriminant analysis resulted in a 4-variable model (R2 = 0.740) based on Artemis data alone and a 4-variable model (R2 = 0.734) using Pentacam data alone. The combined model (R2 = 0.828) consisted of 3 Artemis- and 4 Pentacam-derived variables. The combined model R value was significantly higher than either model alone (p = 0.031, one-tailed). In cross-validation, Artemis had 100% sensitivity and 99.2% specificity, Pentacam had 97.3% sensitivity and 98.0% specificity, and the combined model had 97.3% sensitivity and 100% specificity. Conclusions Pentacam, Artemis, and combined models were all effective in distinguishing normal from clinical keratoconus subjects. From the standpoint of variance explained by the model (R2 values), the combined model was most effective. Application of the model to early and subclinical keratoconus will ultimately be required to assess the effectiveness of the combined approach.

Clinical Outcomes of SMILE With a Triple Centration Technique and Corneal Wavefront-Guided Transepithelial PRK in High Astigmatism

PURPOSEnTo comparatively investigate the clinical outcomes, vector parameters, and corneal aberrations of small incision lenticule extraction (SMILE) with a triple centration technique and corneal wavefront-guided transepithelial photorefractive keratectomy (PRK) for the correction of high astigmatism.nnnMETHODSnThis retrospective, comparative case series study included 89 eyes (89 patients) that received treatment for myopia with high astigmatism (≥ 2.50 diopters) using SMILE with a triple centration technique (SMILE group; 45 eyes) and corneal wavefront-guided transepithelial PRK (transepithelial PRK group; 44 eyes). Visual acuity measurement, manifest refraction, slit-lamp examination, autokeratometry, corneal topography, and evaluation of corneal wavefront aberration were performed preoperatively and at 1, 3, and 6 months after surgery. The safety, efficacy, vector parameters, and corneal aberrations at 6 months after surgery were compared between the two groups.nnnRESULTSnAt 6 months after surgery, the transepithelial PRK and SMILE groups exhibited comparable mean uncorrected distance visual acuities (-0.06 ± 0.07 and -0.05 ± 0.07 logMAR, respectively), safety, efficacy, and predictability of refractive and visual outcomes. There was a slight but statistically significant difference in the correction index between the transepithelial PRK and SMILE groups (0.96 ± 0.11 and 0.91 ± 0.10, respectively). Whereas the transepithelial PRK group exhibited increased corneal spherical aberration and significantly reduced corneal coma and trefoil, no changes in aberrometric values were noted in the SMILE group.nnnCONCLUSIONSnBoth SMILE with a triple centration technique and corneal wavefront-guided transepithelial PRK are effective and provide predictable outcomes for the correction of high myopic astigmatism, although slight undercorrection was observed in the SMILE group. The triple centration technique was helpful in astigmatism correction by SMILE. [J Refract Surg. 2018;34(3):156-163.].

Relationship Between Decentration and Induced Corneal Higher-Order Aberrations Following Small-Incision Lenticule Extraction Procedure

PurposenTo investigate the amount of lenticule decentration following small-incision lenticule extraction (SMILE) by using the Keratron Scout tangential topography difference map, and the relationship between the magnitudes of total decentration and induced corneal higher-order aberrations (HOAs).nnnMethodsnThis retrospective observational case series study analyzed decentration values obtained from the Keratron Scout tangential topography difference map of 360 eyes (360 patients) that underwent SMILE. Root mean square total HOAs, third order coma aberration, fourth order spherical aberration, as well as individual coefficients for vertical and horizontal coma were measured preoperatively and 3-months postoperatively. Simple linear regression analysis and piecewise regression models were used to determine the relationship between the magnitudes of total decentration and induced corneal HOAs.nnnResultsnThe mean total decentration distance from the corneal vertex was 0.36 ± 0.22 mm (range, 0.02-1.27 mm). There were significant differences in total HOAs, coma, vertical and horizontal comas, and spherical aberration between preoperative and 3-month postoperative assessments. Significant relationships between the magnitudes of total decentration and induced corneal HOAs were noted. Subgroup analysis according to the degree of total decentration (group I, total decentered displacement ≤0.335 mm; and group II, total decentered displacement >0.335 mm) revealed that induced changes in total HOAs, coma, vertical coma, and spherical aberration were significantly larger in group II than in group I.nnnConclusionsnA minimal degree of decentration was closely related to a smaller induction of corneal HOAs. Efforts to optimize centration are critical for achieving better surgical outcomes in SMILE.

Diagnosing Keratoconus Using VHF Digital Ultrasound Epithelial Thickness Profiles

There have been significant advances in keratoconus screening over the past decade largely due to enhanced analysis of corneal tomography; however, there remain some equivocal cases where a confident diagnosis cannot be made. Epithelial thickness mapping provides adjunctive diagnostic information that can help confirm or exclude keratoconus in suspicious cases. The epithelium has the ability to alter its thickness profile to re-establish a smooth, symmetrical optical outer corneal surface and either partially or totally mask stromal surface irregularities from front surface topography. In keratoconus, this manifests as epithelial thinning over the cone surrounded by an annulus of epithelial thickening, and increasing thinning and thickening with disease progression. In early keratoconus, this remodelling can be enough to completely mask the stromal surface cone, resulting in an apparently normal front surface topography. This can explain some reports of “ectasia without a cause”. In an eye with an eccentric back surface apex, a coincident epithelial doughnut pattern would confirm keratoconus, whereas the lack of localized epithelial thinning would exclude keratoconus. Very high-frequency digital ultrasound can provide maps of epithelial thickness for a 10 mm diameter, and OCT can do this for up to a 9 mm diameter. A number of groups are now working on developing automated algorithms to screen for keratoconus based on the epithelial thickness profile with encouraging results.

Effect of Lowering Laser Energy on the Surface Roughness of Human Corneal Lenticules in SMILE.

PURPOSEnTo determine the effect of lowering femtosecond laser energy on the surface quality of the intrastromal interface during small incision lenticule extraction (SMILE).nnnMETHODSnForty age- and diopter-matched female patients (40 eyes) with moderate myopia received SMILE with different energy levels (100 to 150 nJ) and fixed spot separation (4.5 μm). Five human corneal lenticules from each energy group were evaluated by atomic force microscopy and scanning electron microscopy (SEM). Both anterior and posterior surface characteristics of the lenticules were assessed.nnnRESULTSnAll measurements of surface roughness were approximately three times higher and in the anterior and posterior surface of the lenticules with the energy level of 150 nJ than with 100 nJ (P < .001). Furthermore, atomic force microscopy analysis found that energy differences of 15 nJ or more made a significant difference in surface roughness at energy levels of 115 nJ or higher. Interestingly, there was no significant difference in all roughness values of both surfaces among the 100, 105, and 110 nJ groups. In addition, all values of surface roughness were significantly positively correlated with laser energy for both anterior and posterior surfaces of the lenticule (P < .001). Consistent with atomic force microscopy results, SEM also showed that the SMILE lenticules in the higher laser energy group had more irregular surfaces.nnnCONCLUSIONSnLowering laser energy levels can improve surface quality of the lenticule of SMILE. To achieve better visual outcomes with faster recovery after the procedure, it is recommended to reduce the laser energy to less than 115 nJ at a spot separation of 4.5 μm. [J Refract Surg. 2017;33(9):617-624.].

Trans-epithelial Phototherapeutic Keratectomy for Irregularly Irregular Astigmatism

The corneal epithelium has the ability to alter its thickness profile, which compensates for changes in stromal surface curvature and re-establishes a smooth, symmetrical optical surface. Such compensatory epithelial thickness changes have been noted after myopic excimer laser ablation, hyperopic excimer laser ablation, radial keratotomy, orthokeratology, and in keratoconus and ectasia. In cases of irregular astigmatism, the compensatory mechanism of the epithelium has a significant effect, as epithelial thickness changes mask the true curvature of the irregular stromal surface [1–3].

The Key Characteristics of Corneal Refractive Surgery: Biomechanics, Spherical Aberration, and Corneal Sensitivity After SMILE

One of the potential benefits of the SMILE procedure is increased biomechanical stability due to the absence of a flap. There are two main reasons for this:

Hyperopic Correction by ReLEx

Despite an increasing popularity of the ReLEx® procedure, it still has some drawbacks. One of them is the absence of software for the current VisuMax® laser to treat hyperopia. Indeed, the idea of “all-in-one surgery” can only become a true femtosecond-laser-alone procedure, if all refractive errors can be treated without excimer laser.