Long-term PM2.5 exposure disrupts corneal epithelial homeostasis by impairing limbal stem/progenitor cells in humans and rat models.

BACKGROUND: Limbal stem/progenitor cells (LSPCs) play a crucial role in maintaining corneal health by regulating epithelial homeostasis. Although PM2.5 is associated with the occurrence of several corneal diseases, its effects on LSPCs are not clearly understood. METHODS: In this study, we explored the correlation between PM2.5 exposure and human limbal epithelial thickness measured by Fourier-domain Optical Coherence Tomography in the ophthalmologic clinic. Long- and short-term PM2.5 exposed-rat models were established to investigate the changes in LSPCs and the associated mechanisms. RESULTS: We found that people living in regions with higher PM2.5 concentrations had thinner limbal epithelium, indicating the loss of LSPCs. In rat models, long-term PM2.5 exposure impairs LSPCs renewal and differentiation, manifesting as corneal epithelial defects and thinner epithelium in the cornea and limbus. However, LSPCs were activated in short-term PM2.5-exposed rat models. RNA sequencing implied that the circadian rhythm in LSPCs was perturbed during PM2.5 exposure. The mRNA level of circadian genes including Per1, Per2, Per3, and Rev-erbα was upregulated in both short- and long-term models, suggesting circadian rhythm was involved in the activation and dysregulation of LSPCs at different stages. PM2.5 also disturbed the limbal microenvironment as evidenced by changes in corneal subbasal nerve fiber density, vascular density and permeability, and immune cell infiltration, which further resulted in the circadian mismatches and dysfunction of LSPCs. CONCLUSION: This study systematically demonstrates that PM2.5 impairs LSPCs and their microenvironment. Moreover, we show that circadian misalignment of LSPCs may be a new mechanism by which PM2.5 induces corneal diseases. Therapeutic options that target circadian rhythm may be viable options for improving LSPC functions and alleviating various PM2.5-associated corneal diseases.

Effect of SMILE-derived decellularized lenticules as an adhesion barrier in a rabbit model of glaucoma filtration surgery.

BACKGROUND: To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticules on intraocular pressure (IOP) and conjunctival scarring in a rabbit model of glaucoma filtration surgery. METHODS: Trabeculectomy was performed on both eyes of New Zealand rabbits. A decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (the decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (the control group). The filtering bleb features and IOP were evaluated 0, 3, 7, 14, 21, and 28 days after surgery, and histopathologic examination was performed 28 days after surgery. RESULTS: Decellularized lenticules significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. The histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group. CONCLUSIONS: Decellularized lenticules can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and they may represent a novel antifibrotic agent for trabeculectomy.

KRT8 phosphorylation regulates the epithelial-mesenchymal transition in retinal pigment epithelial cells through autophagy modulation.

Proliferative vitreoretinopathy (PVR) is a severe ocular disease which results in complex retinal detachment and irreversible vision loss. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is considered to be critical in the pathogenesis of PVR. In this study, we focused on the potential impact of keratin 8 (KRT8) phosphorylation and autophagy on TGF-ß2-induced EMT of RPE cells and explored the relationship between them. Using immunofluorescence and Western blot analysis, the co-localization of KRT8 and autophagy marker, as well as the abundance of phosphorylated KRT8 (p-KRT8) expression, was observed within subretinal and epiretinal membranes from PVR patients. Moreover, during TGF-ß2-induced EMT process, we found that p-KRT8 was enhanced in RPE cells, which accompanied by an increase in autophagic flux. Inhibition of autophagy with pharmacological inhibitors or specific siRNAs was associated with a reduction in cell migration and the synthesis of several EMT markers. In the meantime, we demonstrated that p-KRT8 was correlated with the autophagy progression during the EMT of RPE cells. Knockdown the expression or mutagenesis of the critical phosphorylated site of KRT8 would induce autophagy impairment, through affecting the fusion of autophagosomes and lysosomes. Therefore, this study may provide a new insight into the pathogenesis of PVR and suggests the potential therapeutic value of p-KRT8 in the prevention and treatment of PVR.

Multiple cytokine analyses of aqueous humor from the patients with retinitis pigmentosa.

PURPOSE: Cataracts are the most common eye complications of retinitis pigmentosa (RP). This study aimed to investigate the cytokine profiles of the aqueous humor of RP with cataracts. METHODS: The aqueous humor was collected from RP eyes with cataract (RP group, n = 20) and age-related cataract eyes (ARC group, n = 20) during cataract surgery. The levels of 37 mediators were measured with multiplex fluorescent bead-based immunoassay and compared across groups. The correlation among chemokines, growth factors, and cytokines was analyzed with Spearman's rank correlation coefficient. RESULTS: Twelve cytokines (IL-1α, IL-1ß, IL-4, IL-10, TNF-α, IFN-γ, EGF, GM-CSF, PDGF-AB/BB, TGF-α, BMP-9, and E-selection) were below the limit of detection, and the detection rate of IL-6 was significantly higher in RP group than in the ARC group (P < 0.01). Compared with those in the control group, the aqueous humor levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-(IL-)8, interferon gamma-induced protein (IP)-10, hepatocyte growth factor (HGF), platelet-derived growth factor AA (PDGF-AA), matrix metalloproteinase-2 (MMP-2), MMP3, MMP-7, MMP-8, plasminogen activator inhibitor-1 (PAI-1), and thrombospondin-2 (TSP-2) in the RP group increased significantly (P < 0.01). A lower level of BMP-4 in the aqueous humor was observed in the RP patients than in the controls (P < 0.05). CONCLUSIONS: Significantly increased levels of PDGF-AA, MMP2, MMP3, MMP-7, MMP-8, PAI-1, and TSP-2 and lower levels of BMP-4 were found in the aqueous humor of RP patients. This result indicates a disturbance of the extracellular matrix (ECM) and cytokines in RP patients and suggests a possible role of these cytokines in the pathogenesis of capsular contraction syndrome (CCS) in RP patients.

Investigation of predictability and influence factors of the achieved lenticule thickness in small incision lenticule extraction.

BACKGROUND: To evaluate the differences between the predicted and achieved lenticule thickness (ΔLT) after small incision lenticule extraction (SMILE) surgery and investigate relationships between ΔLT and predicted lenticule thickness in SMILE. METHODS: A total of 184 eyes from 184 consecutive patients who underwent SMILE were included in this prospective study. One eye for each patient was randomly selected and included for statistical analysis. To achieve emmetropia, nomogram adds 10% correction of spherical refractive. An ultrasound pachymetry measurement and Scheimpflug camera corneal topography were obtained before and at 3 months after SMILE. The achieved lenticule thickness was calculated by comparing the preoperative examinations with postoperative examinations using ultrasound pachymetry and Pentacam software measurements. The pupil center and corneal vertex were selected as the 2 locations for measurement calculation on Pentacam. Analysis of variance (ANOVA) was performed to compare mean pachymetry values using different instruments. Linear regression analyses were performed between the VisuMax readout lenticule thicknesses and the measured maximum corneal change, between ΔLT and predicted lenticule thickness. RESULTS: On average, the achieved lenticule thickness measured with ultrasound pachymetry was 13.02 ± 8.87 µm thinner than the predicted lenticule thickness. The proportion of ΔLT in predicted values is 11.9% (ultrasound) and about 15% (Pentacam). Linear regression analysis showed significant relationships between the predicted and each achieved lenticule thickness. Each ΔLT was significantly related to predicted lenticule thickness (ultrasound: R2 = 0.242; pupil center from Pentacam: R2 = 0.230). CONCLUSIONS: An overestimation of achieved lenticule thickness was evident in this study which may exclude eligible SMILE patient. Also, our results showed that 10% increase of spherical refractive correction in the nomogram is appropriate. Furthermore, clinicians should subtract 10% of the predicted lenticule thickness to calculate the residual corneal stroma bed thickness.

Opacification of lentoid bodies derived from human induced pluripotent stem cells is accelerated by hydrogen peroxide and involves protein aggregation.

Despite the recent breakthrough in cataract drug development, further improvements have been limited by the lack of human in vitro cataract disease models. This study, therefore, aims to generate a qualified cataract disease model. Mature lentoid bodies (LBs) on Day 25 (D25), which were differentiated from human induced pluripotent stem cells (iPSCs) using the "fried egg" method, were continually culturing (control) or extra treated with either ultraviolet (UV) radiation or hydrogen peroxide (H2 O2 ). The LBs' shape alteration and opacity were examined using light microscopy and mean gray value evaluation. Their structure and crystallin expression were examined using immunofluorescence and transmission electron microscopy (TEM). Real-time polymerase chain reaction and western blot were used to investigate the potential role of autophagy in cloudy LBs. Mature LBs became cloudy with time which was accelerated by H2 O2 . Immunofluorescence examinations and TEM showed that the H2 O2 -treated and control LBs had similar shapes, lens capsule, and monolayer lens epithelial cell (LEC) structures. However, we were unable to do further assessment of the UV-treated LBs as the structures of LBs were easily damaged when treated with UV radiation. Cells containing aggregated protein (αA-crystallin and αB-crystallin) puncta were more abundant in the H2 O2 -treated LBs as compared with control LBs. Moreover, LC3B expression decreased with age in anterior lens capsules obtained from age-related cataracts (ARCs) patients as compared with LC3B levels in primary LECs, which is consistent with that LC3B expression in LBs was lower on D45 than on D25. Our study found that human iPSCs-derived LBs became cloudy with time which was accompanied by protein aggregation, and this phenomenon was accelerated by H2 O2 , suggesting that LBs with extending culture may serve as a human model for in vitro ARCs.

Comparative study of anterior segment measurements using 3 different instruments in myopic patients after ICL implantation.

BACKGROUND: To compare and correlate anterior segment measurements of myopic eyes implanted with Implantable Collamer lens (ICL V4c) by using anterior segment optical coherence tomography (AS-OCT), Pentacam and ultrasound biomicroscopy (UBM). METHODS: Anterior chamber depth (ACD), distance between corneal endothelium and anterior surface of ICL(C-ICL) and central vault were measured in 82 phakic myopic eyes of 82 patients who underwent ICL surgery, by using AS-OCT, Pentacam and UBM consecutively at 3 months follow up. The correlation and agreement of instruments were accessed by using Intraclass correlation coefficient (ICC) and the Bland-Altman plot. RESULTS: AS-OCT showed higher ACD, C -ICL and central vault measurements than both of Pentacam and UBM (P < 0.001), while Pentacam showed lower measurements than UBM (P < 0.05). The Pearson correlation coefficient (r) was 0.91 to 0.96, and ICC was 0.95 to 0.98 for all measurements between difference devices (all P < 0.001). The 95% limits of agreement of ACD, C-ICL, vault measurements were 0.13 to 0.38 mm, - 0.07 to 0.27 mm, 0.08 to 0.34 mm between AS-OCT and Pentacam, - 0.03 to 0.33 mm, - 0.16 to 0.31 mm, - 0.10 to 0.26 mm between AS-OCT and UBM, and - 0.29 to 0.07 mm, - 0.25 to 0.20 mm, - 0.31 to 0.05 mm between Pentacam and UBM, respectively. CONCLUSIONS: AS-OCT demonstrated significantly higher value, while Pentacam demonstrated significantly lower value than UBM for ACD, C-ICL and central vault measurements in myopic eyes after ICL surgery. Measurements with these instruments were highly correlated, but could not replace each other especially for vault. This study provided valuable information about how to judge the results of anterior segment parameters of eyes implanted with ICL V4c from different devices. TRIAL REGISTRATION: Registration number: ChiCTR-OOC-16008987 . Retrospectively registered: 08 August 2016.

Pterygium surgery combined with the removal of a missed occult iris foreign body detected incidentally during pterygium examination: a case report.

BACKGROUND: An occult foreign body may be retained in patient with small self-sealing wound and no decreased visual acuity without complete examination. Here we report a case of a retained occult ferrous iris foreign body detected incidentally during pterygium examination. CASE PRESENTATION: A 69-year-old man presented to our ophthalmology department because of foreign body sensation and persistent redness in both eyes for 2 years. In the left eye, a pterygium, paracentral corneal opacity and a vertically oval pupil were observed. Ultrasound biomicroscopy and gonioscopy revealed a retained metallic-like foreign body partially embedded in the inferior peripheral iris. Pterygium surgery and the removal of the retained iris foreign body were performed simultaneously. No recurrent pterygium or residual foreign body was found during follow-up. CONCLUSIONS: A thorough history should be obtained and complete physical examination should be performed in patients with ocular self-sealing wounds to prevent missed intraocular foreign bodies, which may result in potential sight-threatening ocular complications.

Cytokine profiling reveals increased serum inflammatory cytokines in idiopathic choroidal neovascularization.

BACKGROUND: The exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity. METHODS: This case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). RESULTS: Serum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area. CONCLUSION: Serum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV.

Proliferative Effects of Histamine on Primary Human Pterygium Fibroblasts.

Purpose. It has been confirmed that inflammatory cytokines are involved in the progression of pterygium. Histamine can enhance proliferation and migration of many cells. Therefore, we intend to investigate the proliferative and migratory effects of histamine on primary culture of human pterygium fibroblasts (HPFs). Methods. Pterygium and conjunctiva samples were obtained from surgery, and toluidine blue staining was used to identify mast cells. 3-[4, 5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the proliferative rate of HPFs and human conjunctival fibroblasts (HCFs); ki67 expression was also measured by immunofluorescence analysis. Histamine receptor-1 (H1R) antagonist (Diphenhydramine Hydrochloride) and histamine receptor-2 (H2R) antagonist (Nizatidine) were added to figure out which receptor was involved. Wound healing model was used to evaluate the migratory ability of HPFs. Results. The numbers of total mast cells and degranulated mast cells were both higher in pterygium than in conjunctiva. Histamine had a proliferative effect on both HPFs and HCFs, the effective concentration (10 µmol/L) on HPFs was lower than on HCFs (100 µmol/L), and the effect could be blocked by H1R antagonist. Histamine showed no migratory effect on HPFs. Conclusion. Histamine may play an important role in the proliferation of HPFs and act through H1R.

Pupil Diameter Changes in High Myopes after Collamer Lens Implantation.

PURPOSE: To observe the changes in pupil size under photopic and scotopic conditions after Implantable Collamer Lens (ICL) implantations in eyes with high myopia. METHODS: The ICL was implanted in 90 eyes belonging to 45 patients with high myopia. Photopic pupil diameters, scotopic pupil diameters, anterior chamber depths, and ICL vaults were examined at the preoperative, postoperative 1-month, and postoperative 3-month stages. The preoperative and postoperative photopic pupil diameters and scotopic pupil diameters were also compared with each other to note the differences between them. The correlations between preoperative and postoperative pupil diameter changes under different light conditions and presurgical refractive error were analyzed alongside patient's age and ICL vault. RESULTS: Pupil diameters at both postoperative 1-month and postoperative 3-month stages were smaller than those before operation in distinct light environments, as well as pupil constriction amplitude. Correlation analysis showed that there was a statistically significant correlation between pupil diameter changes under different light conditions and presurgical refractive error at 1 month and 3 months after ICL implantation; pupil diameter decreased more when presurgical refractive error powers were less myopic. Statistically significant correlations were not found, however, with patient's age and ICL vault. Postoperative 1-month and mean postoperative 3-month anterior chamber depths were decreased when compared with preoperative anterior chamber depths. Statistically significant correlations were found in change in preoperative and postoperative anterior chamber depth and ICL vault. No statistically significant difference was found between ICL vault at the postoperative 1-month and postoperative 3-month stages. CONCLUSIONS: Pupil diameter may decrease at the 1- and 3-month stages after ICL implantation under both photopic and scotopic conditions. This indicates that reduction of pupil diameter may be caused by mechanical contact between the ICL and the posterior iris surface.

Heterozygous variants c.781G>A and c.1066dup of serine protease 56 cause familial nanophthalmos by impairing serine-type endopeptidase activity.

BACKGROUND/AIMS: Nanophthalmos is a rare developmental, bilateral, sporadic or hereditary form of microphthalmos. In this study, the heterozygous variants c.781G>A and c.1066dup of the PRSS56 gene were identified in two patients with nanophthalmos. This study reports the clinical manifestation and the underlying pathogenic mechanism. METHODS: Whole-exome sequencing was performed to identify the pathogenic genes in a Chinese family with nanophthalmos. The molecular simulation was used to predict the structures of wild-type or mutant PRSS56. The PRSS56 wild-type or mutation overexpression cellular models have been constructed accordingly. The subcellular localisation was then observed using immunofluorescence and Western-blot techniques. The Folin-Ciocalteu assay was carried out to evaluate serine-type endopeptidase activity, and a wound-healing assay was used to examine the cellular migratory ability. RESULTS: The whole-exome sequencing revealed that heterozygous variants c.781G>A and c.1066dup of the PRSS56 gene might contribute to nanophthalmos. Both variants were not identified in the dbSNP, 1000 Genome project or ESP6500 databases. Furthermore, the variants were highly conserved and were involved in biological functions. The mutations result in destructive protein structure and impede serine-type endopeptidase activity, thereby impairing subcellular localisation and cellular migration. CONCLUSION: The c.781G>A and c.1066dup variants of the PRSS56 gene might negatively affect protein structures, subcellular localisation, serine-type endopeptidase activity and cellular migratory ability. Together, these changes could lead to the development of nanophthalmos. This study identifies the PRSS56 gene as a potential target for nanophthalmos diagnosis and treatment.

Appraising the Effects of Metabolic Traits on the Risk of Glaucoma: A Mendelian Randomization Study.

Metabolic traits are associated with the risk of developing glaucoma in observational studies. To assess whether theses associations reflect causality, we conducted a Mendelian randomization (MR) study. Our study included up to 20,906 glaucoma cases and 438,188 controls. Genetic instruments associated with the concerned 11 exposures at the genome-wide significance level were selected from corresponding genome-wide association studies. Summary-level data for glaucoma were obtained from the UK Biobank, the GERA study, and the FinnGen consortium. Univariable and multivariable MR analyses were conducted separately in two populations. Our results showed that higher genetic liability to type 2 diabetes (T2D) was causally and independently associated with an increased risk of glaucoma (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06-1.16; p = 4.4 × 10-6). The association for T2D persisted after multivariable adjustment. In addition, higher genetically predicted systolic blood pressure (SBP), fasting glucose (FG), and HbA1c, were also suggestively associated with glaucoma risk. The OR was 1.08 (95% CI, 1.01-1.16; p = 0.035) for SBP, 1.24 (95% CI, 1.05-1.47; p = 0.011) for FG, and 1.28 (95% CI, 1.01-1.61; p = 0.039) for HbA1c. No evidence was observed to support the causal effects of body mass index and blood lipids for glaucoma. This study suggests a causal role for diabetes, as well as possible roles for higher SBP, FG, and HbA1c in the development of glaucoma. Further validation is needed to assess the potential of these risk factors as pharmacological targets for glaucoma prevention.

Investigation of the Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 in Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy (DR) has become a major cause of blindness with increased prevalence of diabetic mellitus. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) plays a part in pathological neovascularization. This study aimed to investigate the role of CEACAM1 in the progression of DR. METHODS: Aqueous and vitreous samples were collected from proliferative or non-proliferative DR and the control group. Multiplex fluorescent bead-based immunoassays were used to detect the levels of Cytokines. Expression of CEACAM1, VEGF, VEGF receptor 2 (VEGFR2) and hypoxia-induced factor-1α (HIF-1α) were detected in human retinal microvascular endothelial cells (HRECs). RESULTS: CEACAM1 and VEGF levels were significantly upregulated in PDR group and positively correlated with PDR progression. Expression CEACAM1 and VEGFR2 were increased in HRECs under hypoxic conditions. The HIF-1α/VEGFA/VEGFR2 pathway was blocked by CEACAM1 siRNA in vitro. CONCLUSIONS: CEACAM1 might play a role in the pathology of PDR. CEACAM1 might be a therapeutic target for retinal neovasculariztion.

Network pharmacology and biochemical experiments reveal the antiapoptotic mechanism of huperzine A for treating diabetic retinopathy.

BACKGROUND/AIMS: Diabetic retinopathy is the most common eye disease that causes blindness in the working population. Neurodegeneration is the early sign of diabetic retinopathy, but no drug has been approved for delaying or reversing retinal neurodegeneration. Huperzine A, a natural alkaloid isolated from Huperzia serrata, displays neuroprotective and antiapoptotic effects in treating neurodegenerative disorders. Our study aims to investigate the effect of huperzine A in preventing retinal neurodegeneration of diabetic retinopathy and its possible mechanism. METHODS: Diabetic retinopathy model was induced by streptozotocin. H&E staining, optical coherence tomography, immunofluorescence staining and angiogenic factors were used to determine the degree of retinal pathological injury. The possible molecular mechanism was unrevealed by network pharmacology analysis and further validated by biochemical experiments. RESULTS: In our study, we demonstrated that huperzine A has a protective effect on the diabetes retina in a diabetic rat model. Based on the network pharmacology analysis and biochemical studies, huperzine A may treat diabetic retinopathy via key target HSP27 and apoptosis-related pathways. Huperzine A may modulate the phosphorylation of HSP27 and activate the antiapoptotic signalling pathway. CONCLUSION: Our findings revealed that huperzine A might be a potential therapeutic drug to prevent diabetic retinopathy. It is the first-time combining network pharmacology analysis with biochemical studies to explore the mechanism of huperzine A in preventing diabetic retinopathy.

Recent Advances of Intraocular Lens Materials and Surface Modification in Cataract Surgery.

Advances in cataract surgery have increased the demand for intraocular lens (IOL) materials. At present, the progress of IOL materials mainly contains further improving biocompatibility, providing better visual quality and adjustable ability, reducing surgical incision, as well as dealing with complications such as posterior capsular opacification (PCO) and ophthalmitis. The purpose of this review is to describe the research progress of relevant IOL materials classified according to different clinical purposes. The innovation of IOL materials is often based on the common IOL materials on the market, such as silicon and acrylate. Special properties and functions are obtained by adding extra polymers or surface modification. Most of these studies have not yet been commercialized, which requires a large number of clinical trials. But they provide valuable thoughts for the optimization of the IOL function.

Exosomes-loaded thermosensitive hydrogels for corneal epithelium and stroma regeneration.

Corneal damage forms scar tissue and manifests as permanent corneal opacity, which is the main cause of visual impairment caused by corneal diseases. To treat these diseases, herein, we developed a novel approach based on the exosome derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) combined with a thermosensitive hydrogel, which reduces scar formation and accelerates the healing process. We found that a thermosensitive chitosan-based hydrogels (CHI hydrogel) sustained-release iPSC-MSC exosomes can effectively promote the repair of damaged corneal epithelium and stromal layer, downregulating mRNA expression coding for the three most enriched collagens (collagen type I alpha 1, collagen type V alpha 1 and collagen type V alpha 2) in corneal stroma and reducing scar formation in vivo. Furthermore, iPSC-MSCs secrete exosomes that contain miR-432-5p, which suppresses translocation-associated membrane protein 2 (TRAM2), a vital modulator of the collagen biosynthesis in the corneal stromal stem cells to avert the deposition of extracellular matrix (ECM). Our findings indicate that iPSC-MSCs secrete miRNA-containing exosomes to promote corneal epithelium and stroma regeneration, and that miR-432-5p can prevent ECM deposition via a mechanism most probably linked to direct repression of its target gene TRAM2. Overall, our exosomes-based thermosensitive CHI hydrogel, is a promising technology for clinical therapy of various corneal diseases.

Evaluation of the Difference between Predicted and Measured Central Corneal Thickness Reduction after SMILE and Femtosecond Laser-assisted LASIK for Myopia.

PURPOSE: To evaluate the agreement between the predicted and measured central corneal thickness (CCT) reduction after the small incision lenticule extraction (SMILE) surgery and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) surgery. METHODS: A total 165 patients were enrolled in this prospective study. Eighty patients with a mean spherical equivalent (SE) of -4.72 ± 1.80 Diopters (D) were treated with the FS-LASIK procedure and Eighty-five patients with a mean SE of -4.78 ± 1.63 D were treated with SMILE procedure. One eye for each patient was randomly selected and included for statistical analysis. Ultrasound pachymetry measurement and Scheimpflug camera corneal topography were performed preoperatively and 3 months postoperatively. The measured CCT reduction was calculated by comparing the preoperative examinations with postoperative examinations. Comparative statistics and linear regression analyses were performed. RESULTS: The mean predicted CCT reduction was 95.02 ± 21.39 µm in FS-LASIK group and 103.49 ± 22.87 µm in SMILE group (P = .015). The prediction of laser platform was found to overestimate the measured CCT reduction for both FS-LASIK group (ultrasound 13.20 ± 9.34 µm) and SMILE group (ultrasound 13.12 ± 8.68 µm). The prediction of laser platform was found to systematically overestimate the measured CCT reduction in FS-LASIK group. In SMILE group, the difference between predicted and measured CCT reduction were found significantly related with the predicted CCT reduction (P < .001 for ultrasound; and P = .004 for Pentacam). CONCLUSION: A systematic overestimation of measured CCT reduction in FS-LASIK group did not influence the refractive precision of FS-LASIK. Due to the different biomechanical distributions in post-SMILE cornea, the measured CCT reduction was influenced as the changes in refractive correction. Nomogram adjustment for high myopic correction needs further research.

Vector analysis of small incision lenticule extraction and toric implantable collamer lens implantation for astigmatism correction.

OBJECTIVES: To compare the efficacy of small incision lenticule extraction (SMILE) and toric implantable collamer lens (TICL) implantation for myopic astigmatism correction using vector analysis. METHODS: In this retrospective study, 171 eyes of 171 patients with cylinder ⩾1.0 diopters (D) were recruited, with 97 eyes underwent SMILE and 74 eyes underwent TICL implantation. Preoperative and 3-months postoperative visual and refractive results were examined. The astigmatism correction, graded by the degree of preoperative cylinder was compared between two groups using vector analysis. RESULTS: At 3-months postoperatively, the residual cylinder was -0.10 ± 0.21 D in the SMILE group and -0.30 ± 0.32 D in the TCL group (p < 0.05). Furthermore, 98% and 85% of eyes had the cylinder within ±0.5 D in the SMILE and TICL group, respectively. The vector analysis revealed similar target induced astigmatism vector in two groups. However, the difference vector, magnitude of error, angle of error, and index of success were significantly higher (0.30 ± 0.32 D, -0.19 ± 0.25, -2° ± 4.35°, and 0.16 ± 0.17 D, respectively) in the TICL group than the values in the SMILE group (0.10 ± 0.21 D, -0.05 ± 0.20, -0.03° ± 2.13°, and 0.05 ± 0.12, respectively), regardless of the degree of preoperative cylinder (all p < 0.05). For preoperative cylinder < 2.0 D, surgically induced astigmatism vector and correction index in the SMILE group were higher than those in the TICL group (p < 0.05). CONCLUSION: Both SMILE and TICL implantation are effective techniques for myopic astigmatism correction. However, the accuracy of correction in the magnitude and axis of astigmatism with SMILE was better than that achieved with TICL implantation.

Case Report: Self-Resolved Macular Edema Secondary to Congenital Retinal Macrovessels.

PURPOSE: To report a case of macular edema secondary to congenital retinal macrovessels (CRMs), which resolved spontaneously without any treatment. OBSERVATIONS: A 39-year-old female presented with blurry vision of the right eye for one day. Fundus examination revealed a branch of artery and vein of the inferior retinal arcade crossing the horizontal raphe. Optical coherence tomography (OCT) through the fovea showed cystoid macular edema in the outer plexiform layer. However, no leakage of the vessels was noticed by fundus fluorescein angiography (FFA). Observation was recommended with close follow-up. Two weeks later, the patient returned with good visual acuity, and the macular edema was resolved spontaneously. CONCLUSIONS: Macular edema is a possible complication of CRM by increasing retinal capillary hydrostatic pressure. Treatment is not necessary for this kind of macular edema if no leakage of the vessels is noticed on FFA.