Refractive Lenticule Research Articles

From lasik to smile: Time to change laser refractive surgery

Purpose: To illustrate the advantages and limitations of Small Incision Lenticule Extraction (SMILE) over Laser Assisted Intrastromal Keratomileusis (LASIK) in the correction of myopia and myopic astigmatism. Materials and methods: The two procedures are analysed and compared for the technical aspects. While LASIK directly depends on the laser efficacy to get the refractive change, SMILE only depends on the computer ability to design the refractive lenticule. The loss in precision taking place in the peripheral cornea with LASIK is not possible with SMILE. Tissue consumption and postoperative dry eye are also lower with SMILE. Procedure abortion has less consequences with SMILE. From a clinical point of view, refractive and visual results with SMILE are similar as those of Wavefront Optimized and Wavefront Guided LASIK, but re-operations are easier after LASIK than after SMILE. Conclusion: When indicated, SMILE is better than LASIK from a technical and procedural standpoint and is equal to Wavefront Lasik as for the obtained results. LASIK is still more versatile and it is better for re-operations.

Effect of Corneal Stromal Lenticule Customization on Neurite Distribution and Excitatory Property

Refractive stromal lenticules from Small Incision Lenticule Extraction (SMILE), though usually discarded, are a novel biomaterial for various ophthalmic applications, including refractive correction, stromal volume expansion and biomechanical strengthening of the cornea. Neural integration is an important part of the post-reimplantation process. This study investigated the effect of lenticule customization on lenticule neurite length profile and the excitatory response (calcium signaling). Human and porcine stromal lenticules with known incision parameters and thickness were treated by excimer laser reshaping, ultraviolet A-riboflavin crosslinking (CXL) or decellularization by sodium dodecylsulfate (SDS). The populations of active neurite fragments with calcium response revealed by L-glutamate-induced Fluo-4-acetoxymethyl ester reaction and the overall neurite scaffold immuno-positive to TuJ1 (β3-tubulin) expression were captured by wide-field laser-scanning confocal microscopy, followed by z-stack image construction. Neurite lengths (NL) for TuJ1 (NL-TuJ1) and for calcium signal (NL-Ca) were measured by NeuronJ plug-in. Our results showed that NL-TuJ1 was significantly reduced by 84% after excimer laser ablation, by 54% after CXL and by 96% after decellularization. The neurite remnants from reshaping and CXL exhibited calcium signaling, indicative of residual excitatory response. Using neurite regeneration from chick dorsal root ganglia, re-innervation occurred in decellularized lenticules under stimulation with nerve growth factor. In conclusion, despite the reduction of lenticule neurites by different customization methods, residual neurites with excitatory potential still existed. This would be advantageous to lenticule reinnervation with axon growth and guidance after reimplantation for refractive and volume restoration of the cornea.

Advances in refractive corneal lenticule extraction.

Refractive errors are the leading cause of reversible visual impairment worldwide. In addition to the desired spectacle independence, refractive procedures can improve quality of life, working ability, and daily working performance. Refractive corneal lenticule extraction (RCLE) is a relatively new technique, dependent only on a femtosecond laser (FS). This leads to potential benefits over laser-assisted in situ keratomileusis (LASIK) including a quicker recovery of dry eye disease, a larger functional optical zone, and no flap-related complications. SMILE, available with the VisuMax FS (Carl Zeiss Meditec AG, Jena, Germany), is the most established RCLE application, offering visual and refractive outcomes comparable to LASIK. SmartSight (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany) and CLEAR (Ziemer Ophthalmic Systems AG, Port, Switzerland) are two new RCLE applications that received Conformité Européenne (CE) approval in 2020. In this article, we review refractive and visual outcomes, advantages, and disadvantages of RCLE and also report on the latest advances in RCLE systems.

From lasik to smile: Time to change laser refractive surgery

Purpose: To illustrate the advantages and limitations of Small Incision Lenticule Extraction (SMILE) over Laser Assisted Intrastromal Keratomileusis (LASIK) in the correction of myopia and myopic astigmatism. Materials and methods: The two procedures are analysed and compared for the technical aspects. While LASIK directly depends on the laser efficacy to get the refractive change, SMILE only depends on the computer ability to design the refractive lenticule. The loss in precision taking place in the peripheral cornea with LASIK is not possible with SMILE. Tissue consumption and postoperative dry eye are also lower with SMILE. Procedure abortion has less consequences with SMILE. From a clinical point of view, refractive and visual results with SMILE are similar as those of Wavefront Optimized and Wavefront Guided LASIK, but re-operations are easier after LASIK than after SMILE. Conclusion: When indicated, SMILE is better than LASIK from a technical and procedural standpoint and is equal to Wavefront Lasik as for the obtained results. LASIK is still more versatile and it is better for re-operations.

Corneal neuromediator profiles following laser refractive surgery.

Laser refractive surgery is one of the most commonly performed procedures worldwide. In laser refractive surgery, Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy. Following laser refractive surgery, the corneal nerves, epithelial and stromal cells release neuromediators, including neurotrophins, neuropeptides and neurotransmitters. Notably, nerve growth factor, substance P, calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration. Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced. In this review, we will discuss the (1) Functions of neuromediators and their physiological and clinical significance; (2) Changes in the neuromediators following various laser refractive surgeries; (3) Correlation between neuromediators, ocular surface health and corneal nerve status; and (4) Future directions, including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery, and as adjuncts to aid in corneal regeneration after laser refractive surgery.

ReLEx® SMILE® – the third generation of laser eye surgery

ReLEx® (Refractive lenticule extraction) SMILE® (SMall Incision Lenticula Extraction) is the third generation of laser eye surgery, which is a follow-on to PRK (the first generation) and LASIK (the second generation). This technology has expanded the possibilities for the comfort and safety of the procedure, reduced the requirements for the thickness of the cornea, and made it extremely comfortable for the patient. SMILE® method helps improve vision in case of myopia, myopic and mixed astigmatism. The article analyzes the advantages and disadvantages of this technology, its possible risks and side effects. The data represented in this article was obtained by analyzing scientific publications and practical expertise.

Options and results in managing suction loss during small-incision lenticule extraction.

Suction loss is an intraoperative complication in small-incision lenticule extraction (SMILE) that presents a management challenge for the refractive surgeon. The purpose of this review is to evaluate the visual, refractive, and wavefront outcomes after suction loss across the different stages of SMILE with various respective surgical treatments. Surgical management options include immediate re-SMILE by redocking or delayed re-SMILE, with or without adjustment of the laser parameters, conversion to femtosecond laser in situ keratomileusis, transepithelial photorefractive keratectomy, refractive lenticule extraction, or pseudo-SMILE. The restart treatment module on VisuMax provides appropriate retreatment recommendation. Most retreatment options for suction loss, immediate or delayed, resulted in effective, safe, and predictable outcomes, and patients were satisfied with their outcomes. Based on available level II evidence, immediate re-SMILE with or without adjustment to the laser settings achieve favorable visual and refractive outcomes in handling this intraoperative complication across all stages of SMILE.

SMILE - Small Incision Lenticule Extraction

Refractive lenticule extraction is a corneal surgical technique that uses a femtosecond laser exclusively to create an intrastromal refractive lenticule for the correction of myopia and myopic astigmatism. In small incision lenticule extraction (SMILE) the generated refractive lenticule is subsequently extracted through a small incision. The reported efficacy, predictability and safety of the flap-less SMILE procedure is similar to those of femtosecond laser in situ keratomileusis (LASIK). Advantages of SMILE over LASIK include less iatrogenic dry eye, fewer induced higher-order aberrations, and potentially less biomechanical weakening of the cornea. However, there is a steeper surgeon learning curve for SMILE as the procedure is technically more challenging than LASIK. Furthermore, the current SMILE laser platform cannot use cyclotorsion control or eye-tracking technology and retreatment options are more complex compared to LASIK. This review looks at patient selection, surgical method, possible complications, retreatment options, and postoperative outcome of the SMILE technique.

Correction of Moderate to High Hyperopia With Implantation of an Allogeneic Refractive Lenticule.

To describe the visual outcomes of correcting moderate to high hyperopia after two different surgical procedures of lenticular implantation. This prospective small case series study used epikeratophakia combined with transepithelial phototherapeutic keratectomy (PTK-EP) and femtosecond laser-assisted lenticule intrastromal keratoplasty (LIKE) using myopic small incision lenticule extraction (SMILE)-derived refractive lenticule for correcting hyperopia ranging from +3.00 to +10.00 diopters (D). The implanted refractive lenticule was matched with the recipient's manifest refraction. The visual, refractive, corneal tomographic, and epithelial thickness outcomes were analyzed after surgery. Four eyes underwent PTK-EP and 6 eyes underwent LIKE. At the last postoperative visit, 6 of 10 eyes had uncorrected distance visual acuity equal to or better than the preoperative corrected distance visual acuity (CDVA). No eyes lost one line or more of CDVA postoperatively. Postoperative spherical equivalent was within ±0.50 D of the target for 9 of 10 eyes. Posterior corneal curvature slightly steepened for PTK-EP and LIKE. Postoperative epithelial thickness demonstrated the expected doughnut pattern in both groups characterized by epithelium in the central zone (5 mm) thinner than that in the peripheral zone (5 to 7 mm). Visual outcomes, refraction, posterior corneal surface changes, and epithelial remodeling after PTKEP or LIKE show a potentially useful modality for correcting moderate to high hyperopia. [J Refract Surg. 2020;36(11):772-779.].

First Experience in Small Incision Lenticule Extraction with the Femto LDV Z8 and Lenticule Evaluation Using Scanning Electron Microscopy.

Purpose To evaluate the specifications and technique properties of the new Femto LDV Z8 in creating intrastromal refractive lenticules during small incision lenticule extraction (SMILE). Methods Six enucleated porcine eyeballs were equally divided into two groups (Femto LDV Z8 or VisuMax) and were randomly assigned to three experienced refractive surgeons who performed SMILE on each group. Five intraoperative time parameters and surgeons' satisfaction on the surgical procedure were compared between two groups. Postoperatively, the roughness of the lenticule surfaces and the irregularity of edges were observed by scanning electron microscopy (SEM) and were also compared between the two groups. Results Longer time on suction peak pressure, total laser application, and total surgery were spent in the Femto LDV Z8 group as compared with the VisuMax group. The Femto LDV Z8 group applied OCT scanning and offsetting before performing the laser procedure, which expended more time for these crucial steps. The widest range of surgeons' satisfaction scores was found in the step of lenticule interface identification of the Femto LDV Z8 group. The roughness scores of the anterior and posterior lenticule surfaces were statistically less in the Femto LDV Z8 group than in the VisuMax group (anterior, ×180, p=0.039; anterior, ×250, p=0.337; posterior, ×180, p=0.006; and posterior, ×250, p=0.007). Conclusions Femto LDV Z8 showed promising performances as a novel SMILE equipment for the correction of myopia. It has special and unique features for SMILE procedures, which need more learning and researching processes. With its low-energy high-frequency nJ-level laser system, the Femto LDV Z8 provided smoother lenticule surface than VisuMax.

Customized Wavefront-Optimized Transepithelial Photorefractive Keratectomy for a Retained Lenticule Fragment After Primary SMILE.

To describe the surgical outcomes after transepithelial photorefractive keratectomy (PRK) for a case of retained intrastromal lenticule fragment after small incision lenticule extraction (SMILE). Transepithelial PRK was performed to minimize corneal irregularity and to correct residual refractive errors in a patient who had undergone failed lenticule extraction, which resulted in a refractive lenticule fragment being retained for 14 months after primary SMILE. At the postoperative 6-month visit, uncorrected distance visual acuity and corrected distance visual acuity improved to 20/20 and 20/20, respectively, and corneal tomography depicted normalization of the corneal surface. Corneal higher order aberrations, including coma, trefoil, and spherical aberration, were markedly reduced. Transepithelial PRK is a potential option for the management of a retained lenticule fragment after primary SMILE. [J Refract Surg. 2020;36(6):395-399.].

Management of Suction Loss During SMILE in 12,057 Eyes: Incidence, Outcomes, Risk Factors, and a Novel Method of Same-Day Recutting of Refractive Lenticules.

To determine the incidence, management, outcomes, and risk factors of suction loss during femtosecond laser small incision lenticule extraction (SMILE) for the treatment of myopia and myopic astigmatism. The study reviewed 12,057 consecutive eyes treated with SMILE. Eyes that developed suction loss (study group) or underwent uneventful SMILE (control group) were analyzed. Corneal topography, manifest refractions, and measurements of uncorrected (UDVA) and corrected (CDVA) distance visual acuities were evaluated preoperatively and postoperatively after 1 day and 12 months. Risk factors were determined for suction loss development. Twenty-seven of 12,057 eyes (0.22%) were enrolled in the study group and 50 eyes in the control group. Suction loss occurred in 14 eyes during the cutting of the refractive lenticule, 7 eyes during the cutting of the cap, and 6 eyes during the creation of the cap small incision. There was no statistically significant difference between the two groups in logMAR UDVA (P = .52) or CDVA (P = .59). A novel method of increasing cap thickness was applied to 8 eyes when suction loss occurred after more than 10% of the lenticule was cut. The eye being operated on first (the right eye) (P = .02) and a thinner lenticule (P = .006) were associated with a significantly higher risk of developing suction loss. The incidence of suction loss was low. The novel method achieved visual and refractive outcomes as favorable as those of uneventful SMILE procedures. The first eye that was operated on had a higher risk for the development of suction loss. [J Refract Surg. 2020;36(5):308-316.].

Comparison of High Order Abberations Between Laser in Situ Keratomileusis (LASIK) and Refractive Lenticule Extraction (ReLEx) Surgeries

Background: The needs of refractive surgery with laser to correct refractive error (myopia, hyperopia, and astigmatism) have become more demanded. Eventhough the procedures can produce expected efficacy and safety, modification in corneal surface can affect optical and visual quality, resulting in visual distortion and artefacts (glare, halo, starburst) called high order aberrations (HOA).
 Objective: To report the differences of high order aberration before and after corneal ablation and refractive lenticule extraction surgery.
 Methods: This is an analytical retrospective observational study which conclude 60 patients (115 eyes) who underwent laser in situ keratomileusis (LASIK), femtosecond laser-assissted laser in situ keratomileusis (FS-LASIK), femtosecond lenticule extraction (FLEx), and small-incision lenticule extraction (SMILE) during the periode of January 2017 to August 2018.
 Results: Of 115 eyes, the mean of pre-operative high-order abberations were divided into four groups: LASIK was 7.27±3.85, FS-LASIK was 7.06±5.77, FLEx was 6.43±3.14, and SMILE was 3.73±1.41. Trefoil was the most common high-order abberations in pre-operative data of LASIK, FLEx, and SMILE (50.0%, 56.25%, and 51.72% respectively), while coma was mostly found in FS-LASIK (46.67%). Coma was the most common finding in first and third month after surgery. High-order aberrations between first and third month after surgery were not statistically significant different (p=0.465, p=0.889, p=0.263, and p=0.508 respectively).
 Conclusion: All types of procedures of corneal ablation and refractive lenticule extractions surgeries are effective and safe in correcting refractive errors. There were no differences of post-operative high- order aberrations in all types of procedures.

Two-year observation of morphologic and histopathologic changes in the monkey cornea following small incision allogenic lenticule implantation

PurposeTo observe the morphologic and histopathologic changes of femtosecond laser assisted small incision allogenic intrastromal lenticule implantation (AILI) in monkey corneas. Methods6 healthy adult monkeys were included. One eye of two monkeys and both eyes of one monkey received femtosecond lenticule extraction with a −4.0 diopter (D) correction. Each extracted refractive donor lenticule was immediately allogeneically transplanted into a corneal stromal pocket created by a femtosecond laser in another monkey's eye. A postoperative two-year follow-up was performed with slit lamp microscopy, corneal topography, anterior segment optical coherence tomography and in vivo confocal microscopy. All eyes were enucleated for Hematoxylin-Eosin staining and transmission electron microscopy (TEM) observation. ResultsNo complications were observed in the follow-up period. At postoperative 2 years, the corneas remained clear and the lenticules were integrated with the surrounding tissue under slit lamp microscopy. Nerve fiber regeneration was detected in the lenticule layer as observed through confocal microscopy. Corneal power was increased by 1.83 ± 1.36 D after 2 years, which was less than at 6 months (3.27 ± 1.2 D). Disordered fibers and decreased keratocytes in the implanted lenticules could be detected under light microscopy and TEM, with a clear boundary between the lenticules and the surrounding tissue. ConclusionsSmall incision AILI is feasible and safe for reshaping the cornea. Corneal healing remained stable while refraction showed a moderate regression within postoperative 2 years.

Outcomes of Small Incision Lenticule Extraction for Myopic Astigmatic Treatment.

BACKGROUND:Some studies have shown that there is a certain rotation of the eye in the sitting and lying position of the patient. The Visumax system used for the Refractive Lenticule Extraction-Small Incision Lenticule Extraction (ReLEx SMILE) surgery lacks the rotation of eye control function. So, is the ReLEx SMILE surgery for patients with astigmatism safe and effective?AIM:To evaluate the outcomes of the ReLEx SMILE surgery in cases with myopic astigmatism.METHODS:The case series included 120 eyes with myopic astigmatism undergoing ReLEx SMILE surgery from January 2018 to November 2018. The distribution of patients for two subgroups based on the power of astigmatism, low astigmatic group (≤ 1.50D) and high astigmatic group (> 1.50D). All patients were measured UDVA, CDVA, refractive sphere, astigmatism and sphere equivalent before and after surgery one week, one month and three months carefully. The astigmatic correction was evaluated by the vectorial analysis Alpins.RESULTS:The mean efficacy index of the low and high astigmatic group was 1.035 and 1.082 (respectively); the mean safety index was 1.113 and 1.215 (respectively). 93% of eyes in the low astigmatic group had an angle of error (AE) within ± 15 degrees and 100% in high astigmatic group. There was an undercorrection in astigmatic treatment. No complications during and after surgery were recorded.CONCLUSION:ReLEx SMILE surgery for the myopic astigmatic treatment was safe and effective.

10-Year Results of Small Incision Lenticule Extraction.

To evaluate the 10-year results of refractive lenticule extraction using the small incision lenticule extraction (SMILE) technique for treatment of myopia and myopic astigmatism. In 2008-2009, the first 91 eyes were treated using a novel surgical technique (SMILE), in which a refractive lenticule of intrastromal corneal tissue is removed through a small incision, completely eliminating flap cutting. A total of 56 of 91 eyes of the original treatment group volunteered for reexamination 10 years after surgery, including uncorrected and corrected distance visual acuity, objective and manifest refraction, and evaluation of the interface and corneal surface by slit-lamp examination. Late side effects such as corneal scarring, corneal ectasia, persistent dry eye symptoms, or cataract were documented. At 10 years postoperatively, there was no significant change from the 6-month results. Spherical equivalent was -0.35 ± 0.66 diopters and therefore close to target refraction. Sixteen of the 56 eyes (29%) had gained one to two Snellen lines. There was no loss of two or more lines in the long term. Regression was -0.35 ± 0.66 diopters over the 10-year period. This 10-year long-term study demonstrates SMILE to be an effective, stable, and safe procedure for the treatment of myopia and myopic astigmatism. [J Refract Surg. 2019;35(10):618-623.].

Stromal keratophakia: Corneal inlay implantation.

Stromal keratophakia was first performed by José Ignacio Barraquer in the 1960s. The refractive lamellar keratoplasty technique was intensely pursued in the 1980s as a method to alter corneal refractive power. However, because sculpting of the donor stromal lenticule and lamellar keratectomy of the recipient's cornea were performed with a mechanical microkeratome, the quality of the cut was inconsistent. Consequently, the refractive outcomes of the lenticule implantation were poor. In addition, epithelial ingrowth, interface scarring, and induced astigmatism were common due to the manual resection. With the advancements of femtosecond laser, we are now able to optically sculpt a refractive lenticule and create an intrastromal pocket for implantation, with greater accuracy and precision compared to manual incisions. The lenticule can be decellularized, cryopreserved, and implanted on a later date to correct hyperopia and presbyopia, as well as to treat corneal ectasia and perforations. In this article, we will review the history of stromal keratophakia and the shortcomings of the previous attempts that led to its abandonment. We will then discuss the reinvigoration of stromal keratophakia with the emergence of advanced femtosecond laser technologies, including the basic science and clinical applications of femtosecond laser-assisted stromal keratophakia, methods to decellularize, cryopreserve and transport the refractive lenticule, lenticule banking, and regulatory framework that oversees the distribution and clinical translation of stromal lenticule implantation.

Comparison of the Different Preservative Methods for Refractive Lenticules following SMILE

ABSTRACTPurposes: To (i) evaluate various methods for preserving refractive lenticules (RLs) from myopic eyes following small-incision lenticule extraction (SMILE), in order to (ii) establish a sound, standard storage RL preservative for clinical uses.Methods: In this prospective study, we compared freshly excised post-SMILE RLs (control group) with post-SMILE RLs (experimental group). Experimental group RLs were preserved in one of several preservatives: glycerol, allochroic silicagel desiccant, or Optisol. Following preservation in one of these three media, samples were evaluated by light microscopy (LM), and transmission (TEM) and scanning (SEM) electron microscopy on days-1, -3, -7, and -14.Results: Changes in cellular morphology were observed at all time points. Compared with fresh control-group RLs, there were significant histological changes in RLs preserved in glycerol and allochroic silicagel, but not Optisol. Comparison of the three methods revealed Optisol to be the best, followed by allochroic silica gel desiccant, followed by glycerol. RLs preserved in Optisol maintained the highest degree of viability and integrity. And the RLs viability and collagen density decreased with prolongation of storage time all.Conclusions: Optisol is a midterm corneal storage medium, which can maintain post-SMILE corneal RLs for 14 days, is a feasible and effective method for tissue storage.

Flushing versus not flushing the interface during small-incision lenticule extraction

To assess the differences in outcomes between interface flushing with a balanced salt solution after refractive lenticule removal in simultaneous uneventful bilateral small-incision lenticule extraction (SMILE). Six study centers in Germany. Prospective case series. Patients with myopia or myopic astigmatism of similar magnitude in both eyes with a spherical equivalent less than or equal to 10.0 diopters (D), preoperative corrected distance visual acuity (CDVA) of 0.80 decimal or better, and anisometropia less than or equal to 2.0 D were enrolled and followed for 3months. One eye of each patient was treated with interface flushing after dry extraction of the lenticule. Flushing was performed with 1.0cc balanced salt solution using a single-use 27-gauge cannula. The uncorrected distance visual acuity (UDVA) at 1day, 1week, and 3months; the CDVA at 3months; and postoperative differences at the slitlamp examination were recorded. Statistical analyses were performed with logarithm of the minimum angle of resolution values using paired t tests. The P value for significance was less than 0.05. The study analyzed 470 eyes. One day postoperatively, the mean UDVA was 0.81 in the non-flush group and 0.83 in the flush group (P=.110). At the last visit 3months postoperatively, the mean UDVA was 1.04 and 1.05, respectively (P=.172). No significant differences in the rate of postoperative complications were found. Interface irrigation with 1.0cc of balanced salt solution after the removal of the refractive lenticule has neither advantages nor disadvantages in terms of visual recovery, postoperative complications, or final visual acuity.

Development of keratophakia and new research advances in lenticule transplantation

In the 1980s, a new treatment of aphakia and keratoconus with keratophakia thrived because of its simple, effective and reversible characteristics. However, due to the limited cornea resources and the unpredictability of long-term treatment effects, epikeratophakia has not been widely accepted. Refractive lenticule extraction is a type of corneal refractive surgery with minimal invasiveness, accuracy and good refractive stability and has got great clinical attention and promotion. The removed refractive stromal lenticules as good graft materials can be applied for treatment of keratoconus and hyperopia based on the epikeratophakia principle. This review describes the history and development of keratophakia and the basic research and clinical effect of refractive lenticule transplantation. (Chin J Ophthalmol, 2018, 54: 792-796).