Combination Therapy With Diquafosol Sodium and Sodium Hyaluronate in Eyes With Dry Eye Disease After Small Incision Lenticule Extraction.

BACKGROUND/AIM: To evaluate the clinical efficacy of combination therapy with diquafosol sodium and sodium hyaluronate in dry eye patients after small incision lenticule extraction (SMILE). PATIENTS AND METHODS: A prospective randomized controlled study was conducted on consecutive patients who were diagnosed with dry eye disease (DED) and ready to accept SMILE from January 2021 to December 2021. The participants were randomly allocated to either a combination with diquafosol sodium 3% and sodium hyaluronate 0.3% group (DQS group, n=40) or a sodium hyaluronate 0.3% group (HA group, n=41). Dry eye disease parameters included tear film break-up time (TBUT), Shirmer I test (SIT), corneal and conjunctival fluorescein staining score (FS score), and Ocular Surface Disease Index (OSDI); tests were conducted before surgery and at 1 week, 1 month, and 3 months after surgery. RESULTS: At 1 week after surgery, there were no statistically significant overall differences in DED parameters between the 2 groups. At postoperative month 1, the FS score was significantly lower in the DQS group than in the HA group (1.20±1.06 vs. 1.83±1.41 respectively, p=0.026). At 3 months after the surgery, the DQS group was significantly superior to the HA group in OSDI (12.98±7.29 vs. 16.82±8.25, p=0.029), TBUT (5.83±2.02 vs. 4.24±0.94, p=0.0002), and SIT (7.75±3.92 vs. 5.24±3.42, p=0.003). CONCLUSION: Our study showed that combination therapy with diquafosol and hyaluronate was beneficial for improving both signs and symptoms of dry eye patients after small incision lenticule extraction.

Proteomic profiling of human corneal stroma from long-term contact lens wearers reveals activation of inflammatory responses.

PURPOSE: To investigate the association between proteomic changes and potential pathogenesis in the human cornea with respect to the duration of wearing soft contact lenses (SCLs). METHODS: A total of 96 corneal stroma samples, obtained via small incision lenticule extraction (SMILE), were equally grouped according to the duration of wearing SCL: 0Y, did not wear SCL; 5Y, wore SCL for<5 years; 5-10Y, wore SCL for 5-10 years; O10Y, wore SCL for>10 years. Liquid chromatography-tandem mass spectrometry was used to identify and quantify protein profiles in the corneal stroma. Expression levels of CO1A1, CO4A1, NFKB1, and IL6RB were determined using western blot and immunohistochemistry analysis. RESULTS: This study quantified a total of 5,668 proteins across samples and identified 2,379 differentially expressed proteins (DEPs) with significantly increased abundance in the three SCL-wearing groups compared with that in the non-SCL-wearing group. Compared with those in the 0Y group, the molecular functions of DEPs in the 5Y, 5-10Y, and O10Y groups were mainly related to translation regulator activity, antigen binding, peptidase inhibitor activity, participation in extracellular matrix (ECM) production, complement activation, and inflammatory responses. Pathway enrichment analysis of DEPs showed that the sphingolipid, phosphatidylinositol 3-kinase-protein kinase B, and hypoxia-inducible factor-1 signaling pathways were activated in the human corneal stroma after long-term SCL use. CONCLUSIONS: Inflammation-related proteomic components in human corneal stroma increased after long-term use of SCL and may act as an essential factor in the molecular pathogenesis of corneal stroma damage.

Comparison of Corneal Densitometry and Visual Quality after Small Incision Lenticule Extraction (SMILE) and Laser Epithelial Keratomileusis (LASEK): One-Year Comparative Study.

Purpose: To investigate changes in corneal densitometry (CD) and visual quality following small incision lenticule extraction (SMILE) and laser epithelial keratomileusis (LASEK) in patients with mild-to-moderate myopia. Methods: A retrospective analysis was performed on 24 and 25 patients (46 eyes each) who underwent SMILE and LASEK, respectively, for mild-to-moderate myopia. The visual quality and CD values were recorded. Using the Pentacam Scheimpflug system, CD values were collected in three concentric optical zones at the depths of the anterior, central, and posterior layers. Efficacy, safety, predictability, corneal wavefront aberrations, and QoV scores were measured to evaluate visual quality. A correlation analysis was performed between changes in CD and clinical characteristics. Results: There were no statistical differences in efficacy and safety indices between the two groups. At 3 months postoperatively, a pronounced reduction in several zones was observed in the LASEK group (p < 0.05), whereas no obvious change was observed in the SMILE group. There were obvious changes in the CD values in several zones in the SMILE and LASEK groups (p < 0.05) after 1 year. The magnitude of the CD changes in the anterior and central corneal layers was smaller in the SMILE group than in the LASEK group (all p < 0.05). Lower HOAs, spherical aberration, and horizontal comas of the anterior and whole corneal surfaces were observed in the SMILE group. QoV scores were similar between the two groups. Conclusion: CD decreased in the SMILE and LASEK groups after 1 year; there was a smaller reduction in SMILE than in LASEK. SMILE and LASEK did not differ significantly in terms of safety and effectiveness in correcting mild-to-moderate myopia.

Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics.

PURPOSE: To investigate the effect of age on wound healing after small incision lenticule extraction (SMILE) and the underlying metabolomic mechanisms. METHODS: This prospective study was conducted on 216 patients in four groups: the 18-20 (n = 38, Group I), 21-30 (n = 84, Group Ⅱ), 31-40 (n = 58, Group Ⅲ), and 41-50 (n = 36, Group IV) age groups. The density of corneal epithelial wing cells, basal cells, corneal stromal cells, endothelial cells and corneal nerves were examined with a laser confocal microscope (HRT III-RCM) before and 1 month, 3 month, 6 month and 1 year after SMILE. The central nerve fiber length (CNFL), the central corneal nerve fibre density (CNFD), and the central corneal nerve branch density (CNBD) were analyzed by Nero J. The corneal stroma lenticules were obtained from SMILE to analyze metabolites by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF-MS). RESULTS: The density of corneal wing epithelial cells and basal epithelial cells have no significant difference among the four groups. The CNFL was 21.90 ± 1.68 mm/mm2 in Group Ⅰ and 21.63 ± 2.09 mm/mm2 in Group Ⅱ after 1 year of SMILE, which represented a return to the preoperative level, whereas the CNFL of Group Ⅲ (19.40 ± 0.98 mm/mm2) and Group Ⅳ (18.94 ± 0.72 mm/mm2) were lower than that preoperation (P ˂0.01). CNFL repair had a negative correlation with age after surgery (Pearson's R = -0.572, P ˂0.01). The CNFD and the CNBD showed the same trend with the CNFL (Pearson's R = -0.602 and -0.531, P ˂0.05). Through screening the significantly different metabolites between the 18-30 age group (including Group I and Group Ⅱ) and other two groups, 6 common remarkably different metabolites were identified. Meanwhile, 5 unique different metabolites were identified only between the 18-30 age group and the 31-40 age group. Six unique different metabolites were identified only between the 18-30 age group and the 41-50 age group. CONCLUSION: Corneal nerve repair after SMILE was significantly affected by age. The identified age-associated differences in metabolites were mainly related to inflammation, oxidation, nerve protection and regeneration.

Metabolomic Analysis in Corneal Lenticules From Contact Lens Wearers.

PURPOSE: To investigate the mechanisms of pathological changes in corneal stroma and the wearing time of soft contact lenses using the metabolomic method. METHODS: Laser scanning confocal microscopy was used to evaluate the pathological changes of corneal stroma between wearing time groups before small incision lenticule extraction. After small incision lenticule extraction, 190 corneal stroma samples were obtained, and a metabolomic method using high performance liquid chromatography coupled with time of flight mass spectrometry was established to analyze the changes in metabolites between wearing time groups. RESULTS: Laser scanning confocal microscope results demonstrated that the corneal nerve fiber length, the number of corneal anterior stromal cells, and the number of corneal posterior stromal cells were reduced gradually with increasing wearing time. The metabolomic study demonstrated that 11 biomarkers were identified between patients who did and did not wear soft contact lenses and 6 biomarkers were identified between less than 5 years and more than 5 years of wearing time. These biomarkers participate in energy metabolism, lipid metabolism, inflammatory reactions, and neuroprotecton processes, and partially lead to the pathology of dry eyes, eye inflammation, and corneal nerve fiber length decrease. Five biomarkers in the citrate cycle metabolism pathway were found demonstrating that energy metabolism was seriously disturbed. CONCLUSIONS: This study systematically revealed the metabolite mechanism for eye discomfort and related disease after wearing soft contact lenses. The identified biomarkers and related physiology pathways supply a new direction for avoiding the side effects of wearing soft contact lenses. [J Refract Surg. 2020;36(5):317-325.].

Comparison of Higher-Order Aberrations after LASEK between Two Different Laser Platforms for Low-to-Moderate Myopia.

PURPOSE: To compare the differences in higher-order aberrations (HOAs) after laser subepithelial keratomileusis (LASEK) between two different laser platforms. METHODS: One hundred and seven eyes of 107 patients were included in this study. Fifty-six eyes underwent LASEK with the Triple-A profile (an ablation profile of the MEL 90 excimer laser) and 51 eyes underwent LASEK with the aspheric (Aberration Smart Ablation [ASA]) profile. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), corneal topography, and ocular aberrations were measured before and 6 months postoperatively. RESULTS: In the ASA group, the values of horizontal trefoil, vertical coma, horizontal coma, spherical aberrations, and total HOAs increased significantly after surgery (all P < 0.05). There were no significant differences in the vertical trefoil between the preoperative and 6-month postoperative periods. In the Triple-A group, there were no differences in vertical trefoil and horizontal trefoil values between the preoperative and 6-month postoperative periods. Compared with the preoperative values, vertical coma, horizontal coma, spherical aberrations, and total HOAs were significantly increased at 6 months after surgery (all P < 0.05). Compared to the Triple-A group, higher horizontal trefoil and horizontal coma were introduced in the ASA group at 6 months postoperatively. CONCLUSION: The Triple-A ablation profile of the MEL 90 excimer laser at a 500-Hz pulse rate was an efficient method to correct myopia, especially for mild-to-moderate myopia, compared with the aspheric ablation model, fewer horizontal trefoil and horizontal coma were induced at 6 months after LASEK. ABBREVIATIONS: HOAs, Higher-Order Aberrations; LASEK, laser subepithelial keratomileusis; ASA, Aberration Smart Ablation; UDVA, uncorrected distance visual acuity; CDVA, corrected distance visual acuity.

Clinical Evaluation of LASEK for High Myopia Correction between the Triple-A Profile and the Zyoptix Tissue Saving Profile.

PURPOSE: To compare the effects of correcting high myopia using the MEL®90 Triple-A profile LASEK at a 500 Hz pulse rate (Triple-A group) versus the Zyoptix tissue-saving ablations of Technolas 217z laser platform at 100 Hz (TS group). METHODS: This retrospective study included 50 eyes in the Triple-A group and 42 eyes in the TS group with manifest refraction spherical equivalent (MRSE) of -6 diopters (D) to -10 D. We compared uncorrected distance visual acuity, MRSE, corrected distance visual acuity, and postoperative complications at 1 month, 3 months, and 6 months. RESULTS: At 6 months after refractive surgery, the efficacy index of Triple-A group was significantly higher than that of the TS group (1.03 ± 0.12 vs 1.00 ± 0.11, P=0.04). The MRSE postoperatively in the Triple-A group was significantly lower than that in the TS group (0.25 ± 0.18 vs 0.38 ± 0.23, P < 0.01). The safety indices in the two groups were almost the same after 6 months of surgery (1.03 ± 0.07 vs 1.04 ± 0.11, P=0.63). The proportion of eyes which achieved ±0.13 D was significantly higher in the Triple-A group than that in the TS group at 1 month (80% vs 59.5%, P=0.03), 3 months (82% vs 61.9%, P=0.03) and 6 months (84% vs 64.3%, P=0.03). The changes in refraction 6 months after surgery comparing with 1 month after surgery were 0.12 ± 0.10 D in the Triple-A group and 0.13 ± 0.08 D in the TS group (P=0.56). All (100%) of the patients in the Triple-A group and 50% of the patients in the TS group had a UDVA of 20/16 at 6 months after surgery (P < 0.01). The induced spherical aberrations and total HOAs in the Triple-A group were significantly lower than those in the TS group (0.17 ± 0.02 µm vs 0.23 ± 0.02 µm, P < 0.01; 0.20 ± 0.04 µm vs 0.39 ± 0.03 µm, P < 0.01) at 6 months after surgery. The mean reduced corneal thickness was 113.06 ± 10.5 µm in the Triple-A profile group and 121.43 ± 23.46 µm in the TS group (P=0.02). No patient in either group had haze and high intraocular pressure 6 months after surgery. CONCLUSION: For treatment of high-myopia patients, the Triple-A profile was more effective, predictable, and accurate than the Zyoptix tissue-saving profile. Meanwhile, the Triple-A profile had less induced spherical aberrations, total HOAs, and cornea ablation depth than the Zyoptix tissue-saving profile. Patients in the Triple-A group with 500 Hz pulse rate treatment achieved superior results. The two surgical procedures were equivalent in terms of safety and stability.