Trichostatin A inhibits dendritic cell maturation through down-regulating NF-κ B (p65) pathway.

BACKGROUND: Recent evidence suggested that histone deacetylase inhibitor (HDACi) could inhibit dendritic cell (DC) maturation. However, the mechanism is unclear. Here, we aimed to study whether Trichostatin A (TSA), the most widely studied HDACi, inhibits the maturation of DCs by down-regulating NF-κB (p65) pathway. METHODS AND RESULTS: Mouse bone marrow-derived DCs were cultured. Lipopolysaccharide (LPS) was applied as stimulation for maturation. Triptolide (TTL) was applied as p65 inhibitor. Microphotography and flow cytometry showed that TSA and p65 inhibitor separately inhibited the maturation of DCs stimulated by LPS from the aspects of cell morphology and cell phenotype. Mixed lymphocyte reaction test and ELISA showed that TSA and p65 inhibitor synergistically inhibited the proliferation of T lymphocytes stimulated by DCs, reduced the secretion of pro-inflammatory cytokine IL-12 and elevated the secretion of anti-inflammatory cytokine IL-10. Western blot and RT-qPCR showed that TSA down-regulated the expression of phosphorylated IκBα, phosphorylated-p65, Ikkß and Ikkγ, suggesting TSA down-regulates NF-κB (p65) pathway. CONCLUSIONS: TSA inhibits DC maturation through down-regulating NF-κB (p65) pathway.

Development of low laser energy levels in small-incision lenticule extraction: clinical results, black area, and ultrastructural evaluation.

PURPOSE: To evaluate the outcomes of 4 low laser energy levels after small-incision lenticule extraction (SMILE) surgery. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Prospective randomized clinical trial. METHODS: This study evaluated consecutive patients who had SMILE to correct myopia or myopia with astigmatism. Eyes were placed into groups based on the laser energy used during surgery (ie, 105 nJ, 110 nJ, 115 nJ, or 120 nJ). All patients had a thorough ophthalmic examination preoperative and at 4 timepoints over 3 months postoperatively. Black areas and surface regularity of the extracted lenticules were observed and evaluated qualitatively and quantitatively. RESULTS: The study comprised 124 eyes of 62 patients (40 women, 22 men), with 31 eyes in each laser energy group. The incidence of black areas was 45.16% (14 of 31 eyes), 12.90% (4 of 31 eyes), 16.13% (5 of 31 eyes), and 12.90% (4 of 31 eyes) for 105 nJ, 110 nJ, 115 nJ, and 120 nJ, respectively. The mean time for lenticule creation was the longest in the 105 nJ group (P = .015). The greatest increase in corneal thickness postoperatively occurred with 105 nJ (P < .05). Regression was highest in the 105 nJ group at 3 months (P < .01). However, corneal horizontal coma (C8) was lowest in the 105 nJ group at 1 week (P = .032). The lenticular surface in the 110 nJ group was the smoothest (P = .011). All contrast sensitivity values varied with time and recovered to preoperative levels by 1 week or 1 month. In all eyes, the uncorrected distance visual acuity and corrected distance visual acuity were good, with no statistically significant differences between the 4 energy groups. CONCLUSIONS: The 105 nJ group, in which the lowest energy was used, had the highest risk for black areas, serious postoperative corneal edema, and a significant healing response.

Optimal Parameters of Scanning Mode in Small Incision Lenticule Extraction (SMILE): Clinical Results and Ultrastructural Analysis.

PURPOSE: To compare the effect of two scanning modes with different femtosecond laser settings on clinical outcomes and ultrastructural analysis of the lenticule surface in small incision lenticule extraction (SMILE). METHODS: A total of 78 eyes from 39 consecutive patients were included with the standard scanning mode (energy level of 105 nJ vs spot distance of 3 mm) in one eye and the fast scanning mode (energy level of 110 nJ vs spot distance of 4.5 mm) in the other eye, all eyes being randomly assigned. Patients received complete ophthalmic examinations preoperatively and at different follow-up visits after SMILE. Ten human corneal lenticules were analyzed using scanning electron microscopy. RESULTS: Uncorrected distance visual acuity at 1 day and 1 week postoperatively was -0.06 ± 0.10 and -0.11 ± 0.05 logMAR, respectively, in the fast scanning group, which was significantly better than in the standard scanning group (-0.11 ± 0.08 and -0.12 ± 0.05 logMAR, respectively), and no significant difference was found between the groups at 1 and 3 months. The contrast sensitivity was higher at different time points in the fast scanning mode group compared with the standard scanning group (all P < .05). Ultrastructurally, the corneal lenticules from the fast scanning group showed a smoother surface than those from the standard scanning mode group qualitatively and quantitatively (all P < .001). CONCLUSIONS: SMILE using the fast scanning mode facilitates better visual acuity with improved contrast sensitivity in the early postoperative period. Experimental studies on the ultrastructure of corneal lenticules support these clinical results. [J Refract Surg. 2020;36(1):34-41.].

Early Corneal Wound Healing Response After Small Incision Lenticule Extraction.

PURPOSE: To evaluate the corneal wound healing response after small incision lenticule extraction surgery. METHODS: Small incision lenticule extraction was performed in both eyes of 12 New Zealand White rabbits. The refractive spherical correction was set at -6.00 D. Two animals were analyzed at each time point (1 hour, 4 hours, 1 day, 3 days, 7 days, and 28 days). The corneas were evaluated using slit-lamp and in vivo confocal microscopy. After euthanatization, the corneal tissues were subjected to light microscopy, transferase 2'-Deoxyuridine 5'-Triphosphate (dUTP) nick end labeling assay, and immunofluorescence microscopy (CD11b, fibronectin, tenascin, alpha-smooth muscle actin [α-SMA]). RESULTS: The corneas did not show any opacity at any time point except at the side-cut incision. By contrast, there was obvious scar tissue at the side-cut incision. Scattered, hyperreflective spots were seen by confocal microscopy from 1 hour postoperatively. Transferase dUTP nick end labeling-positive keratocytes were abundant near the femtosecond laser incision area at 1 hour and reached a peak at 4 hours postoperatively and then decreased. Inflammatory cells migrated from the incision into the central cornea, and this process began 1 hour after surgery and peaked at 7 days. Extracellular matrix components were deposited at the beginning of day 1 postoperatively, and the distribution pattern differed between the central cornea and the incision site. α-SMA-positive myofibroblasts were only detected at the side-cut incision. CONCLUSIONS: The scar tissue response in the peripheral cornea is related to the epithelium debridement. Inflammatory cells begin to be recruited by 1 hour after surgery. Therefore, it is necessary to implement antiinflammation interventions at a very early stage.

Effect of Cyclotorsion Compensation With a Novel Technique in Small Incision Lenticule Extraction Surgery for the Correction of Myopic Astigmatism.

PURPOSE: To comparatively investigate the clinical outcomes of small incision lenticule extraction (SMILE) surgery with or without cyclotorsion compensation for the correction of myopic astigmatism. METHODS: This prospective, double-blinded, randomized controlled trial included patients who underwent SMILE surgery with bilateral myopic astigmatism. Two eyes of a single patient were randomly divided into the static cyclotorsion compensation (SCC) group and the control group. In the SCC group, the intraoperative cyclotorsion was manually compensated with a novel technique. In the control group, the cyclotorsion was not compensated. Visual acuity, manifest refraction, aberrations, objective visual quality, and contrast sensitivity were measured preoperatively and postoperatively. RESULTS: A total of 132 eyes from 66 patients were analyzed at the 3-month follow-up. The mean preoperative cylinder values in the SCC and control groups were -1.52 ± 0.81 and -1.57 ± 0.82 diopters (D), respectively. The mean cyclotorsion during surgery was 0.60° ± 0.63° (range: 0° to 3.2°) in the SCC group and 3.21° ± 2.33° (range: 0.1° to 10.8°) in the control group (P < .001). Both groups showed favorable results in the correction of myopic astigmatism. No statistically significant difference was found between the two groups in visual and refractive outcomes, vector parameters, entire eye aberrations, objective visual quality, or contrast sensitivity. No significant benefit was gained from cyclotorsion compensation, even in the high astigmatism subgroup. CONCLUSIONS: The cyclotorsion compensation technique used in this study helped minimize the alignment error but was not compulsory because the ocular rotation in SMILE surgery using a well-controlled position was too small to affect the astigmatic outcomes or postoperative visual quality. [J Refract Surg. 2019;35(5):301-308.].

15-Month Visual Outcomes and Corneal Power Changes of SMILE in Treating High Myopia With Maximum Myopic Meridian Exceeding 10.00 D.

PURPOSE: To evaluate the long-term visual and refractive outcomes, optical quality, and stability of the cornea and axial length after small incision lenticule extraction (SMILE) for the correction of high myopia with a maximum myopic meridian exceeding 10.00 diopters (D). METHODS: Via a prospective cohort study, 53 eyes (53 patients) with a maximum myopic meridian exceeding 10.00 D were corrected with a VisuMax femtosecond laser (version 3.0; Carl Zeiss Meditec AG, Jena, Germany) at the Zhongshan Ophthalmic Center of Sun Yat-sen University. Refractive outcomes, aberrations, axial length, and corneal curvature were evaluated preoperatively and at 1, 3, and 15 months postoperatively. RESULTS: At 15 months postoperatively, the efficacy and safety indexes were 0.91 ± 0.25 and 1.15 ± 0.18, respectively. A total of 72% of eyes were within ±0.50 D and 89% were within ±1.00 D of the attempted spherical equivalent, respectively. From 1 to 15 months postoperatively, the significant regression was -0.24 ± 0.28 D (P < .001) on manifest refraction and -0.43 ± 0.54 D (P < .001) on anterior corneal curvature. In addition, a significant increase of 0.20 µm (P = .016) was observed in the spherical aberration. No significant change was observed in posterior corneal curvature (P > .999), including mean keratometry or astigmatism, or in the ocular axis length from 1 to 15 months postoperatively (26.82 ± 0.93 and 26.82 ± 0.95 mm, respectively, P > .99). CONCLUSIONS: SMILE had long-term safety, efficacy, and predictability when treating high myopia with a maximum myopic meridian exceeding 10.00 D. Both a manifest refraction regression of -0.24 D and a significant spherical aberration increase of 0.20 µm were observed between 1 and 15 months postoperatively, due to the increased anterior corneal curvature. [J Refract Surg. 2019;35(1):31-39.].

Development of a liquid dissection technique for small-incision lenticule extraction: Clinical results and ultrastructural evaluation.

PURPOSE: To determine the effect of a liquid dissection technique on clinical outcomes with ultrastructural analysis of the lenticule surface in small-incision lenticule extraction (SMILE). SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Prospective case series. METHODS: Consecutive patients with myopia scheduled for small-incision lenticule extraction were included. The liquid dissection technique was performed in 1 eye and the traditional dissection technique was performed in the other eye by randomized assignment. Ophthalmic examinations were evaluated preoperatively and at different timepoint follow-ups after small-incision lenticule extraction. Ten human corneal lenticules were analyzed using scanning electron microscopy. RESULTS: The study comprised 29 patients (58 eyes). Uncorrected distance visual acuity (logarithm of the minimum angle of resolution) postoperative measurements at 2 and 4 hours were significantly better in the liquid dissection group than in the traditional dissection group (P < .001 and P = .001, respectively); however, there were no significant differences between the 2 groups at 1 day, 1 week, and 1 month postoperatively. Compared with the traditional dissection technique, the liquid dissection technique induced significantly fewer corneal aberrations at 2 hours and 1 month after the procedures (P = .031 and P = .016, respectively), the postoperative contrast sensitivity in the liquid dissection group was significantly higher after 1 day (P = .01). The liquid dissection samples showed smoother lenticule surfaces compared with the traditional dissection samples qualitatively and quantitatively (P = .004 and P < .001, respectively). CONCLUSION: The liquid dissection technique was helpful in facilitating better visual acuity recovery and produced smooth cuts in the early postoperative period.

In vivo confocal laser microscopy of morphologic changes after small incision lenticule extraction with accelerated cross-linking (SMILE Xtra) in patients with thin corneas and high myopia.

PURPOSE: To evaluate the microstructural modifications and safety of small incision lenticule extraction combined with accelerated cross-linking (SMILE Xtra) in high myopia and thin corneas by means of in vivo confocal microscopy (IVCM) and 3D-OCT after a 6-month follow-up. METHODS: Forty-three eyes with high myopia and thin corneas were enrolled. All eyes underwent SMILE procedure. After the lenticule was extracted, 0.25% riboflavin was injected into the interface and allowed to diffuse for 60 s. The eye was irradiated with UVA radiation of 30 mW/cm2 for 90 s through the cap. The total energy delivered was 2.7 J/cm2. Morphologic modifications of corneal architecture were evaluated prior to SMILE Xtra and 7 days, 1, 3, and 6 months after SMILE by in vivo confocal microscopy (IVCM) and 3D-OCT. RESULTS: The corneal epithelial cells showed slight damage until 3 months postoperatively. The subepithelial nerve plexus decreased but no absence within the treatment zone at the first week after treatment, recolonized at 3 months postoperatively, and had mostly recovered at the 6 months postoperative but remained less than its normal baseline state. Keratocytes were absent in the surgical interface area, and the presence of strong reflective particles and cicatricial reaction in the anterior stroma were observed during the entire 6-month examination period. Increased hyperreflectivity was observed from the cap side at a depth of 60 µm to stroma bed at a depth of 388 µm through 6 months. The depth of the demarcation line in 40 eyes (93.0%) was at a mean depth of 296.12 ± 47.86 µm (range, 211-388 µm). No particular change between preoperative and postoperative corneal endothelium was observed. CONCLUSIONS: Confocal microscopy showed increased hyperreflectivity in the SMILE Xtra eyes, and no changes in corneal endothelium. We confirmed the safety of the SMILE Xtra but recognize that larger and longer-term studies of SMILE Xtra are necessary.

Evaluation of Human Corneal Lenticule Quality After SMILE With Different Cap Thicknesses Using Scanning Electron Microscopy.

PURPOSE: To evaluate the surface characteristics of lenticules created by small-incision lenticule extraction (SMILE) with different cap thicknesses. METHODS: This prospective study included 20 consecutive patients who underwent bilateral SMILE. Surface regularity of the extracted corneal lenticule was analyzed using scanning electron microscopy (SEM) combined with 2 methods: qualitative and quantitative regularity. Qualitative regularity of SEM images was graded by masked observers using an established scoring system. Quantitative regularity of SEM images was assessed by counting the total number and areas of tissue bridges using Image-Pro Plus software. Four different cap thickness of 120, 130, 140, and 150 µm were compared. Refractive outcomes of patients were measured at baseline and 1 month after surgery. RESULTS: As 10 specimens were not analyzable, only 30 eyes were included. Postoperatively, all eyes had postoperative uncorrected distance visual acuity of 20/20 or better; 43% had an unchanged corrected distance visual acuity; 43% gained 1 line; 10% lost 1 line. Ultrastructurally, surface irregularity was primarily caused by tissue bridges. The average surface regularity score obtained was 10.87 ± 2.40 for 120 µm, 10.78 ± 2.60 for 130 µm, 8.76 ± 2.16 for 140 µm, and 8.70 ± 2.66 for 150 µm (P < 0.001). The total number and areas of tissue bridges of 120 to 130 µm were significantly less than 140 to 150 µm (P < 0.05). Surface regularity decreased as cap thickness increased (P < 0.05). CONCLUSIONS: There is smoother appearance of the lenticular surface as seen through SEM when a thin cap is created compared with a thick cap qualitatively and quantitatively.

Aspheric Micro-monovision LASIK in Correction of Presbyopia and Myopic Astigmatism: Early Clinical Outcomes in a Chinese Population.

PURPOSE: To analyze early clinical outcomes of aspheric micro-monovision LASIK for correction of presbyopia and myopia with or without astigmatism. METHODS: Prospective, non-comparative case series of 80 eyes of 40 patients with a mean age of 43.4 ± 4.9 years (range: 38 to 63 years) treated bilaterally using an aspheric micro-monovision protocol. The target refraction was plano for the distance eye and between -0.75 and -2.25 diopters (D) for the near eye. Visual acuity, ocular aberrations, contrast sensitivity, corneal topography, amplitude of accommodation, binocular sensorial function, and satisfaction score questionnaires were evaluated at 3 months after surgery. RESULTS: Three months after surgery, the mean spherical equivalent (SE) refraction in the distance eye was -0.08 ± 0.27 D, whereas the attempted and achieved SE in the near eye were -1.41 ± 0.28 and -1.32 ± 0.35 D, respectively. Ninety-three percent of eyes were within ±0.50 D of target correction of SE. The uncorrected distance visual acuity (UDVA) after surgery was -0.10 ± 0.06 logMAR (20/15.5), 0.22 ± 0.12 logMAR (20/34), and -0.11 ± 0.06 logMAR (20/15), for distance eyes, near eyes, and binocularly, respectively. Ninety-five percent of patients achieved simultaneously uncorrected distance visual acuity 0.0 logMAR (20/20) or better and uncorrected near visual acuity J2 (20/25) or better. Stability was achieved from 1 week of follow-up. The overall satisfaction score for surgery was 92 ± 6. CONCLUSIONS: The aspheric micro-monovision protocol provided a well-tolerated and effective means for treating myopic astigmatism and alleviating presbyopic symptoms simultaneously. [J Refract Surg. 2016;32(10):680-685.].

Reversible Femtosecond Laser-Assisted Endokeratophakia Using Cryopreserved Allogeneic Corneal Lenticule.

PURPOSE: To evaluate outcomes, reversibility, and wound healing response after the femtosecond laser-assisted endokeratophakia procedure in a rabbit model. METHODS: Allogeneic rabbit corneal lenticules were cryopreserved in liquid nitrogen for 3 months. Twenty rabbits underwent the monocular endokeratophakia procedure and were divided into four groups according to the follow-up periods. The first three groups were killed at 3 days, 2 weeks, and 6 months after endokeratophakia, respectively. The rabbits in the fourth group received re-extraction of implanted lenticules at 6 months after endokeratophakia and were killed at 1 month after re-extraction. The rabbits were monitored by slit-lamp microscopy, ultrasonic pachymetry, in vivo confocal microscopy, optical coherence tomography (OCT), Corvis ST tonometry (Oculus Optikgeräte, Wetzlar, Germany), and Ocular Response Analyzer (Reichert Ophthalmic Instruments, Depew, NY). The tissue responses were analyzed by immunohistochemistry and transmission electron microscopy. RESULTS: After endokeratophakia, corneal clarity improved continually with time. The changes in the refraction and corneal thickness were stable after implantation and could be reversed after re-extracting the lenticules. The interfaces were clearly visible on confocal microscopy and transmission electron microscopy images over the entire follow-up period. There were significant numbers of TUNEL-positive keratocytes in lenticules after endokeratophakia. CD11b-positive cells and deposition of fibronectin and tenascin were observed at earlier follow-up times. No alpha-smooth muscle actin-positive fibroblasts could be detected. In addition, the corneal biomechanics parameters were not significantly increased after endokeratophakia. CONCLUSIONS: The endokeratophakia procedure using allogeneic cryopreserved lenticules was clinically stable and could be reversed. The wound healing response was mild, limited, and produced no scars. [J Refract Surg. 2016;32(8):569-576.].