Dry eye disease (DED) is a common eye disease in clinical practice. The crucial pathogenesis of DED is that hyperosmolarity activates oxidative stress signaling pathways in corneal epithelial and immune cells and, thus, produces inflammatory molecules. The complex pathological changes in the dry eye still need to be elucidated to facilitate treatment. In this study, we found that astaxanthin (AST) can protect against DED through the SLC7A11/GPX4 pathway. After treatment with AST, the SLC7A11/GPX4 pathway was positively activated in DED both in vivo and in vitro, accompanied by enhanced autophagy and decreased ferroptosis. In hyperosmolarity-induced DED corneal epithelial cells, AST increased the expression of ferritin to promote iron storage and reduce Fe2+ overload. It increased glutathione (GSH) and GPX4, scavenged reactive oxygen species (ROS) and lipid peroxide, and rescued the mitochondrial structure to prevent ferroptosis. Furthermore, inhibition of ferroptosis by ferrostatin-1 (Fer-1), iron chelator deferoxamine mesylate (DFO), or AST could activate healthy autophagic flux. In addition, in a dry eye mouse model, AST upregulated SLC7A11 and GPX4 and inhibited ferroptosis. To summarize, we found that AST can ameliorate DED by reinforcing the SLC7A11/GPX4 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes.

AIMS:This study aimed to synthesize the variations in subfoveal choroidal thickness (SFCT) observed at different follow-up intervals in myopic children undergoing orthokeratology treatment. MATERIALS AND METHODS:Relevant articles were systematically retrieved from databases such as PubMed, EMBASE, Web of Science, and Cochrane Library. The retrieval period extended from the inception of these databases to November 2023. Means and standard deviations (SD) of baseline and post-treatment SFCT were selected as the results for analysis and calculation. RESULTS:A total of eight articles involving 478 eyes fulfilled the inclusion criteria. At 1 month, 3 months, and 6 months intervals, the SFCT demonstrated significant increases by 16.74 μm (95% CI: 8.66, 24.82; p < 0.0001), 13.41 μm (95% CI: 4.36, 22.45; p = 0.004), and 17.57 μm (95% CI: 8.41, 26.73; p = 0.0002), respectively. Besides, children treated with orthokeratology exhibited a notably thicker change of SFCT in comparison with children with single-vision spectacles (SVL) (WMD = 13.50, 95% CI: 11.69, 15.13; p < 0.0001). CONCLUSION:Myopic children undergoing orthokeratology treatment experience a discernible increase in SFCT at 1 month, 3 months, and 6 months. Furthermore, compared to children utilizing SVL, those undergoing orthokeratology manifest a more pronounced thickening of SFCT.

PurposeDry eye disease (DED) has a complex etiology and the roles of long noncoding RNAs (lncRNAs) in its pathophysiology are not completely understood. Autophagy is a self-eating process important for cell survival and homeostasis. The present study explored the role of myocardial infarction-associated transcript neighbor (MIATNB) long non-coding RNA in hyperosmolarity-induced autophagy and apoptosis in human corneal epithelial cell (HCEC)-based model of dry eye disease.MethodsIn vitro assays were performed with a human SV40 immortalized corneal epithelial cell line. Different concentrations of NaCl were used to create hyperosmolarity. HCECs were cultured in presence of 70-120 mM NaCl for 24 h to create an in vitro model of dry eye. RT-qPCR was performed to assess the expression of dry eye related LC3B, ATG16L, BECN1, ATG1, ATG7, ATG13, ATG5, ATG10, and ATG101 mRNAs and western blot analysis of LC3B and P62 and RFP -GFP-tagged LC3. Flow cytometry and western blot analysis of caspase 3, BCL2 and BAX were performed to detect apoptosis. Chloroquine (CQ) was used to inhibit autophagy pharmacologically.ResultsAutophagy flux was activated in HCECs subjected to hyperosmotic stress. Hyperosmolarity activated apoptosis and inhibited HCEC migration and autophagy. Hyperosmolarity upregulated MIATNB expression, while MIATNB knockdown inhibited autophagosome degradation and promoted HCEC apoptosis. Under hyperosmolar conditions, MIATNB knockdown also inhibited the degradation of autophagolysosomes and stimulated HCEC apoptosis.ConclusionMIATNB plays a vital role in dry eye pathogenesis and serves as a bridge between autophagy and apoptosis. Targeting MIATNB for DED treatment should be further evaluated.

Objective::To investigate the changes of corneal sub-basal nerve and corneal transparency in adolescents aged 8 to 15 years with orthokeratology lenses.Methods::In this prospective clinical study, myopic adolescents aged 8-15 years old fitted with orthokeratology lens in the Affiliated Hospital of Qingdao University from November 2020 to August 2021 were randomly selected. Nerve fiber density (NFD), nerve fiber length (NFL), nerve fiber orientation (NFO), and nerve fiber width (NFW) were assessed by confocal laser microscopy before and 1, 3 and 6 months after wearing lens. The optical density of cornea in different diameters was evaluated by Pentacam anterior segment analyzer. Pre- and post-wear comparisons of neuromorphological parameters and corneal optical density were performed using randomized zone group ANOVA.Results::A total of 16 patients (32 eyes) with myopia were included in the study, of which 4 were lost and 12 (28 eyes) eventually completed the follow-up. In the central cornea, the NFD was significantly increased at 1-month ( P=0.003) after wearing and gradually decreased to the baseline level at 3-and 6-month ( P>0.05). The difference in NFL shows no significant difference after lens wear ( P>0.05). NFO was significantly higher at 1 and 6 months ( P=0.015 and 0.047, respectively). NFW increased significantly at 6-month ( P=0.029). In the temporal cornea, there was no statistical difference during 6-month wearing ( P>0.05). NFL did not differ significantly during 6 months ( P>0.05). NFO increased gradually after wearing lens and showed statistical significance at 6 months ( P<0.001). NFW increased significantly at 3 months ( P=0.002) and further increased at 6 months ( P<0.001). In the upper cornea, NFD increased slightly in the early stage and decreased at 6-month, showing no statistical difference (all P>0.05). NFL increased significantly at 3-month ( P<0.001), and decreased to the baseline level at 6-month ( P>0.05). NFO significantly increased at 3 and 6 months ( P<0.001, P=0.022). The corneal optical density of the anterior corneal layer ≤2 mm and 2-6 mm increased at 6 months after wearing the lens, with statistical significance ( P=0.011, P<0.001). Conclusions::The morphology of the corneal sub-basal nerve and corneal densitometry changed significantly in the myopic adolescents after wearing orthokeratology lens. The nerve fiber density increased and then decreased after lens wearing, the degree of nerve course curvature increased, and the nerve fibers were generally thickened. The corneal transparency decreased steadily for 6 months after lens wearing.

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) μm, (642±255) μm and (613±280) μm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) μm. The vaults declined by (69±98) μm from postoperative 1 week to 3 months and by (52±54) μm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

Abstract Aims: This article aimed to assess the changes of subfoveal choroidal thickness (SFCT) in different follow-up durations for myopic children under the treatment of orthokeratology and give a reference for further studies.Method: Relevant publications were comprehensively retrieved through different databases, such as PubMed, Web of Science, Cochrane Library and Chinese database of Wan Fang and Wei Pu. Retrieval time was from the inception to February 2022. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were selected as the effect for calculating and analyzing the changes of choroidal thickness in myopic children with orthokeratology.Result: A total of eight articles of 371 Patients (371 eyes) met our inclusion criteria. During the first month of wearing orthokeratology, choroidal thickness dramatically increased by 21.09 μ m (95%CI: 25.64, 16.7; P<0.00001). After the first month, it rose slightly, even became stable in next eleven months’ treatment (increased by 4.20 μm from the first month to the third month, 95%CI: 9.37, 0.9; P=0.11; increased by 3.99μm from the first month to the sixth month, 95%CI: 8.67, 0.6; P=0.09; increased by 2.99μm from the first month to the twelfth month, 95%CI: 7.76, 1.7; P=0.02).Conclusion: This meta-analysis demonstrated that in the first month with orthokeratology, choroidal thickness presented an obvious increase, after that it became stable or got a slightly rise for the longer following-up treatment.

Purpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form of inflammatory activation, which is characteristic of gasdermin D (GSDMD)-driven cell death. The present study was designed to explore the role of MIAT in pyroptosis and apoptosis induced by hyperosmolarity stress (HS) in human corneal epithelial cells (HCECs). Methods: HCECs were cultured in 70-120 mM hyperosmotic medium for 24 h to create a dry eye model in vitro. The level of the pyroptosis marker GSDMD was measured, and the cell inflammatory response was evaluated by detecting IL-113 and IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO was used. The pyroptosis in HCECs was examined by caspase-1 activity, immunofluorescent staining, and Western blotting. Flow cytometry was performed to test the apoptosis rate of HCECs. Cell migration and proliferation were detected. The expression of the lncRNA MIAT in HCECs was detected by quantitative real-time PCR. MIAT was knocked down by small interfering RNA (siRNA) transfection. The effects of caspase-1 inhibition on pyroptosis, apoptosis, migration, and proliferation were observed. Results: HS promoted pyroptosis in HCECs by elevating caspase-1, GSDMD, and the active cleavage of GSDMD (N-terminal domain, N-GSDMD), and increased the release of IL-113, IL-18, LDH and the rate of apoptosis, with reduced cell migration. These changes were prevented by the inhibition of caspase-1. The expression of MIAT was significantly increased in HCECs exposed to a hyperosmotic medium. Silencing MIAT increased the expression of GSDMD, caspase-1, and inflammatory chemokines IL-113 and IL-18, and promoted apoptosis while inhibiting migration and proliferation in HCECs. Conclusion: The lncRNA MIAT is involved in HS-induced pyroptosis and apoptosis and the inflammatory response of HCECs and provides a new understanding of the pathogenesis of dry eye.

目的 探讨高度近视患者行飞秒激光小切口角膜基质透镜取出术(SMILE)、飞秒激光制瓣的准分子激光原位角膜磨镶术(FS-LASIK)以及准分子激光上皮瓣下角膜磨镶术(LASEK)术后不同时间不同直径范围内角膜光密度的对比及变化情况,及其与术中切削深度、切削厚度的相关性分析.方法 前瞻性队列研究.收集在青岛大学附属医院眼科就诊并进行屈光手术矫正的高度近视患者82例(164眼),按手术方式分为SMILE组30例(60眼);FS-LASIK组27例(54眼);LASEK组25例(50眼),于术前、术后1个月、术后3个月、术后6个月以及术后12个月行Pentacam三维眼前节分析系统检查,采用SPSS 22.0统计软件对术后同一时间不同术式角膜0～6 mm、>6～12 mm、整体直径范围内的角膜光密度采用随机区组方差分析,对术中切削深度、切削厚度与角膜光密度的关系采用Pearson相关分析.结果 术后1个月和术后6个月,不同组别患眼在同一直径范围内的角膜光密度相比差异均无统计学意义(均为P>0.05);术后3个月,LASEK组患眼的角膜光密度在0～6 mm、>6～12 mm、整体直径范围内均显著低于SMILE组,在>6～12 mm、整体直径范围内均显著低于FS-LASIK组(均为P<0.05);术后12个月,SMILE组患眼在0～6 mm、>6～12 mm、total直径范围内的角膜光密度均显著低于其他两组(均为P<0.05).术后3个月,0～6 mm、>6～12 mm、total直径范围内的角膜光密度与术中角膜切削深度、切削厚度均呈正相关(均为P<0.05);术后12个月,各直径范围内的角膜光密度与术中角膜切削深度、切削厚度均呈负相关(均为P<0.05).结论 高度近视患者在行激光角膜屈光术后的早期修复中,SMILE术式的角膜透明性稍差,而LASEK术式则相对更佳,但SMILE术后患眼长期的角膜透明性更佳.角膜光密度与术中角膜的切削深度以及切削厚度密切相关.

Objective::To investigate the repair of corneal subepithelial nerve fibers in the early and middle stages after small incision lenticule extraction (SMILE), femtosecond flap excimer laser in situ keratomileusis (FS-LASIK) or laser epithelial keratomileusis (LASEK) in patients with high myopia.Methods::This was a prospective clinical study. Fifty-five patients (110 eyes) with high myopia who were treated in the Department of Ophthalmology at the Affiliated Hospital of Qingdao University were divided into a SMILE group (44 eyes), FS-LASIK group (36 eyes) and LASEK group (30 eyes). The repair of corneal nerve fibers was observed by laser confocal microscopy at 1, 3 and 6 months after the operations. Parameters of nerve fibers at different time periuds after the operations was used one-way ANOVA of random block design.Results::The corneal nerve distribution density, branch density, and length and width of different areas in patients with high myopia were best in the early stage after SMILE compared with the other two groups. The repair speed was also the fastest and reached the preoperative level earlier. Comparisons of corneal nerve repair in different areas, including the corneal flap, showed that the repair rate for FS-LASIK was between SMILE and LASEK. In the early stage after LASEK, especially in the central area, the white scar turbidity was obvious, and the speed and quality of corneal repair in different areas were the worst. The results of image analysis at the different time periods in each group suggested that the levels of corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL) and corneal nerve fiber total branch density (CTBD) in the center of the SMILE and FS-LASIK groups were significantly better than those in the LASEK group at 1 month after the operation (all P<0.05). The CNBD of SMILE was significantly better than that of both the FS-LASIK and LASEK groups ( HSD=4.367, P=0.007; HSD=4.237, P=0.008). Three months after the operation, the CNFD, CNBD, CNFL in the center of the SMILE operation were significantly better than for both the FS-LASIK and LASEK groups (all P<0.05). The CNFW of the LASEK operation was significantly better than that of both the SMILE and FS-LASIK groups ( HSD=3.457, P=0.003; HSD=3.668, P=0.004). Six months after the operation, the central CNFD, CNBD and CNFL of the SMILE operation were better than those of both the FS-LASIK and LASEK groups, and the difference was statistically significant (all P<0.05). Conclusions::In the early and middle stages after laser keratomileusis, SMILE is significantly superior to FS-LASIK and LASEK for nerve repair in all regions.