Limbal Stem Cell Dysfunction Induced by Severe Dry Eye via Activation of the p38 MAPK Signaling Pathway.

Severe dry eye (SDE) can cause grievous damage to the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, the current study established an SDE rat model by removing the extraorbital and infraorbital lacrimal glands and maintaining them in a low-humidity environment. One month after the surgery, aqueous tear secretion was reduced dramatically, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma. The expressions of keratin 12 and paired box gene 6 were down-regulated dramatically, while those of keratin 10, small proline-rich protein 1b, and mucin 5AC were up-regulated in the corneal epithelium of the SDE rats. Cell proliferation in the limbal epithelium was up-regulated, while the stem/progenitor marker adenosine 5'-triphosphate-binding cassette member 2 and the limbal epithelial colony-forming efficiency were decreased in the SDE condition. Furthermore, the p38 mitogen-activated protein kinase signaling pathway was activated in the limbal corneal epithelium of SDE rats. The abnormal differentiation and stemness loss in the corneal epithelium could be reversed upon treatment with a p38 inhibitor in a SDE in vivo model and in vitro hyperosmolar corneal epithelial culture conditions. These data suggest that SDE can lead to limbal stem cell dysfunction, and p38 mitogen-activated protein kinase signaling pathway activation plays an essential role in this process.

Clinical features and comprehensive treatment of persistent corneal epithelial dysfunction after cataract surgery.

OBJECTIVE: Evaluation of clinical efficacy and safety of tobramycin/dexamethasone eye ointment in treating persistent corneal epithelial dysfunction (PED) after cataract surgery. METHODS: 26 cases diagnosed as PED after cataract surgery accept the tobramycin/dexamethasone ophthalmic ointment and intense pulse light treatment in the Xiamen University of Xiamen eye center between September 2016 and April 2022 were retrospectively analyzed, mainly including clinical manifestations, characteristics of morphological changes imaged by in vivo confocal microscopy, meibomian glands infrared photography, lipid layer thickness (LLT), management and therapeutic effects. RESULTS: There were 26 eyes, include 8(35%) males and 15(65%) females with an average age of 69.6 ± 5.2 years(50 to 78 years). The mean hospitalization time was (18.4 ± 7.5) days after cataract surgery. Twenty patients had meibomian gland dysfunction. Infrared photography revealed varying loss in the meibomian glands, with a mean score of 3.8 ± 1.2 for gland loss. The mean LLT was 61.6 ± 8.4 nm. After treatment, 20 patients were cured, and 3 received amniotic membrane transplantation. After treatment, the uncorrected visual acuity (UCVA) and best-corrected vision activity (BCVA) improved (P < 0.001), and there was no significant difference in intraocular pressure (IOP) before and after treatment (P > 0.05). CONCLUSIONS: The early manifestation of PED after surgery is punctate staining of the corneal epithelium. Tobramycin and dexamethasone eye ointment bandages have a good repair effect. The meibomian gland massage combined with intense pulse light treatment can effectively shorten the course of the disease.

Optimization of method for achieving a single-cell suspension from mouse corneas.

The single-cell RNA-sequencing (scRNA-seq) technique is used to explore the biological characteristics of tissues under pathological and physiological conditions that include certain chronic eye diseases. Harvesting of single-cell suspensions is one challenge inherent to scRNA-seq procedures. This study aimed to use an optimized method to digest a whole mouse cornea to harvest single-cell suspensions. We utilized five different mouse cornea digestion methods to obtain single-cell suspensions: (1) 5 dissected mouse corneas were cut into pieces (∼0.5 mm) and digested in trypsin for 10 min, and this digestion was repeated for 10 cycles; (2) 5 dissected mouse corneas were cut into pieces and incubated with 5 mg/ml collagenase A at 37 °C for 1h and then further digested in trypsin at 37 °C for 10 min; (3) used the same approach as that used in method 2, but the second digestion step was performed in TrypLE for 20 min; (4) used the same approach as that used in method 2, but the concentration of collagenase A was 2 mg/ml and the incubation time was 2h; (5) used the same approach as that used in method 3, but the corneas were incubated in 2 mg/ml collagenase A at 37 °C for 2h. Trypan blue staining was used to calculate the cell viability and agglomeration rate. The cell types and percentages were determined using immunofluorescence staining. RNA integrity number (RIN) was measured by Agilent 2100. Method 1 showed the lowest cell yield (0.375 × 105), epithelial cell percentage, and less than 70% cell viability, thus not a proper protocol. Method 2 showed the highest cell viability (over 90%), percentage of single-cell (89.53%), and high cell quantity (1.05 × 105). Method 3 had a significantly lower cell viability (55.30%). Cell agglomeration rates of method 4 and 5 reached up to 20% and 13%, and with lower cell viability (72.51%, 59.87%, respectively) and decreased epithelial cell rate compared to method 2 and 3. The results suggest that method 2 (5 mg/ml collagenase A and trypsin) is a preferred protocol for digesting mouse cornea to obtain single-cell suspension which achieves the criterion of single-cell RNA sequencing.

[Effects of magnesium supply level on growth, nutrient element absorption and distribution, and quality of Panax quinquefolium].

This study aims to investigate the effects of different magnesium supply levels on the growth, nutrient absorption and distribution, and quality of Panax quinquefolium, and to determine the optimum content of exchangeable magnesium in soil. Three-year-old plants of P. quinquefolium were used in this study, and eight magnesium supply gradients(CK, Mg1-Mg7) were designed for indoor pot experiment(cultivation in soil). The plant growth indexes, nutrient element content in soil and plant, and root saponin content were determined at the end of the growth period. The correlation analysis of nutrient element content in aboveground and underground parts of P. quinquefolium showed significantly negative correlations of magnesium-calcium, magnesium-potassium, and magne-sium-manganese. With the increase in magnesium supply level, the biological absorption coefficient of magnesium increased, while that of total nitrogen, potassium, iron, and manganese decreased; the biological transfer coefficient of magnesium decreased, while that of nitrogen, phosphorus, calcium, iron, and manganese increased. The saponin content was analyzed by principal component analysis, which showed the comprehensive score in the order of Mg4(2.537), Mg2(1.001), Mg3(0.600), Mg1(0), Mg7(-0.765), CK(-0.825), Mg6(-0.922), and Mg5(-1.663). The partial least squares-path modeling(PLS-PM) showed that the correlation coefficients of exchangeable magnesium and pH with quality were-0.748 and-0.755, respectively, which were significant. Magnesium-calcium, magnesium-potassium, and magnesium-manganese showed antagonism in the nutritional physiology of P. quinquefolium. Excessive application of magnesium can lead to the imbalance of nutrient elements in P. quinquefolium. The content of exchangeable magnesium in soil suitable for the quality formation of P. quinquefolium was 193.34-293.34 mg·kg~(-1). In addition to exchangeable magnesium, pH was also important to the quality formation of P. quinquefolium. Therefore, exchangeable magnesium and pH could be regarded as monitoring factors for the quality formation of P. quinquefolium.

Convenient hyaluronidase biosensors based on the target-trigger enhancing of the permeability of a membrane using an electronic balance as a readout.

The change in hyaluronidase (HAase) is related to specific changes in the structure of vitreous, and it is necessary to develop simple but sensitive methods for HAase detection. In this work, a thin film fabricated from a hyaluronic acid (HA)-polyethyleneimine (PEI) hydrogel has been covered on a mixed cellulose microporous membrane (MCEM) to form a HA-PEI-MCEM firstly and it was then applied in a filtration system. The permeability of the filter membrane greatly affects the amount of water passing through within a certain time and the water can be collected and quantitatively measured with a simple electronic balance easily. The low permeability of the HA-PEI-MCEM allows a small amount of water to be drained. But after the addition of HAase, which can hydrolyze HA in the hydrogel, the permeability of the membrane increased. Therefore, the amount of water passing through the HA-PEI-MCEM composite membrane increased accordingly. The composite of the membrane, and the reaction conditions after the addition of HAase were optimized. Under the optimized conditions, the amount of water collected within 5 min showed a linear relationship with the HAase concentration in a range of 1.0-36 U mL-1 with a limit of detection of 0.35 U mL-1.The proposed method has been applied to detect HAase in vitreous samples with satisfactory results.

Transepithelial corneal cross-linking assisted by two continuous cycles of iontophoresis for progressive keratoconus in adults: retrospective 5-year analysis.

PURPOSE: The aim of this study is to compare the long-term effects of transepithelial corneal crosslinking with two continuous cycles of iontophoresis (EI-CXL) and conventional corneal crosslinking (C-CXL) in adults with progressive keratoconus. METHODS: A retrospective analysis was conducted in adults who underwent C-CXL or EI-CXL between 2013 and 2015. Visual acuity, corneal tomography, anterior segment optical coherence tomography, in vivo corneal confocal microscopy (IVCM), and endothelial cell count (ECC) were performed preoperatively and 5 years postoperatively. RESULTS: Sixty-eight patients with a mean age of (24.3 ± 3.8) years were included, 34 for each group. After CXL, UCVA or BCVA remained stable, while the spherical diopter, cylinder diopter, spherical equivalent, and Kmax significantly decreased at 1, 2, and 3 years in both groups than baseline (P < 0.05). No significant differences were found in any refractive or tomographic parameters as well as the minimal corneal thickness between groups during follow-up. At 5 years, Kmax was slightly higher in EI-CXL group (58.16 ± 6.28) than that of C-CXL group (57.46 ± 4.98). At 3 and 5 years, the minimal corneal thickness in C-CXL group was still significantly lower than baseline (P < 0.05). IVCM demonstrated the demarcation zone at a mean depth of (302.0 ± 41.7) µm after C-CXL, and at (251.2 ± 28.1) µm after EI-CXL (P < 0.001). Keratocyte repopulation was detectable at all follow-up timepoint in both groups. Postoperative complications including progression were recorded in 6 patients (11.7%) after C-CXL and 3 patients (8.8%) after EI-CXL. ECC remained stable in both groups. CONCLUSION: EI-CXL showed approximate efficacy with C-CXL in stabilizing progressive keratoconus in adults. EI-CXL has the potential to be a preferable transepithelial protocol.

[Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: one year results].

OBJECTIVE: To evaluate the early clinical results of keratoconic eyes treated with transepithelial iontophoresis corneal collagen cross-linking (i-CXL) within 1 year. METHODS: Propective nonrandomized study. Twenty-three eyes of 23 patients with progressive keratoconus with minimum corneal thickness from 380 µm to 420 µm (including the epithelium) were included in this prospective, nonrandomized clinical study and treated with i-CXL. Scoring of pain and foreign body sensation, slit lamp examination, uncorrected visual acuity (UCVA) and best corrected distance visual acuity (BCVA), corneal topography, anterior segment optical coherence tomography (AS-OCT), in vivo corneal confocal microscopy and endothelial cell count were assessed before surgery and at 1, 3, 6 and 12 months (m) postoperatively. Paired t test was applied for statistical analysis. RESULTS: Moderate pain and foreign body sensation were reported by most patients on postoperative Day (D) 1, but rapidly decreased and eventually disappeared on D3. Mild epithelial damage was observed on D1, and the epithelium fully recovered on D3. Improvement of UCVA and BCVA were recorded at 3 months and 12 months postoperatively. Orbscan II corneal topography revealed the significant reductions of Kmax and Kmin from 3m to 12m (Kmax, t = 2.912, P < 0.01, Kmin, t = 2.508, P < 0.05) postoperatively while the other parameters remained stable. The Kmax and Kmin at 12m was (52.94 ± 4.87) and (46.78 ± 3.71) respectively, while the preoperative values was (54.37 ± 5.56) and (48.53 ± 3.57) respectively. Within 1m postoperatively, AS-OCT exhibited an increase of reflectance with a white line (demarcation line) in the anterior stroma, in vivo confocal microscopy also showed the significant thickening and increased connections of collagen fibers with maximal depth of about 133 µm. The corneal endothelial cell density remained stable (t = 0.915, P > 0.05). None of the patients showed postoperative complications such as corneal infection, scarring, ulcer, persistent epithelial defect, etc. CONCLUSIONS: Priliminary clinical results within 1 year postoperatively demonstrated the efficacy and safety of i-CXL for the management of progressive keratoconus. This technique was applicable for keratoconic eyes with minimum corneal thickness around 400 µm. i-CXL showed the advantage of short time consuming in surgery, rapid recovery and few complication, and has the potential to become a valid alternative for the treatment of keratoconus.

Notch signal regulates corneal endothelial-to-mesenchymal transition.

Endothelial-to-mesenchymal transition (EnMT) is a cell transformation process involved in both morphogenesis and pathogenesis. EnMT of corneal endothelial cells happens after endothelial injury and during ex vivo culture. Previous studies have shown that the transforming growth factor-ß signaling pathway is involved in this transition. In this study, we found that rat corneal endothelial cells could spontaneously undergo EnMT during ex vivo culture. This change in rat corneal endothelial cells was associated with Notch signaling pathway activation after the first passage, which was blocked by the Notch inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). This inhibitor also prevented transforming growth factor ß1-, ß2-, and ß3-induced EnMT and reversed transformed rat corneal endothelial cells to a normal phenotype. Furthermore, DAPT treatment blocked retrocorneal membrane formation in a rat corneal endothelium damage model. Our study indicates that the Notch signaling pathway is involved in the corneal EnMT process, which may be a novel therapeutic target for treating corneal endothelial fibrogenic disorders.

[Meibomian gland morphology study progression].

The meibomian gland (MG) in the eyelids, which is the largest sebaceous gland throughout the body, synthesize and secrete lipids to form the superficial tear film layer. It plays a key role in maintaining the ocular surface health. Abnormalities in meibomian gland morphology lead to meibomian gland dysfunction, which is the main cause of evaporative dry eye. Study on meibomian gland morphology will contribute significantly to the diagnosis and treatment of meibomian gland dysfunction. This review is just focusing on the current studies about techniques to visualize the morphology of the MG and changes of meibomian gland morphology related to diseases.

[The clinical study of corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas].

OBJECTIVE: To evaluate the clinical results of keratoconic eyes with thin corneas that were treated by using corneal collagen cross-linking with hypo-osmolar riboflavin solution. METHODS: Retrospective, nonrandomized study. Fifteen eyes of 15 patients with progressive keratoconus and corneal thickness of less than 400 µm (without the epithelium) were included in this study. Application of hypo-osmolar riboflavin solution to the cornea for 30 minutes after its de-epithelialization was followed by ultraviolet A collagen cross-linking. Corneal thickness was measured with anterior segment OCT before surgery, after epithelial removal, and after hypotonic riboflavin solution application. Before the ultraviolet A application was started, we must be sure that the thinnest cornea was equal to or greater than 400 µm. Examinations comprised an evaluation of uncorrected distance visual acuity and best corrected visual acuity, slit-lamp microscopy, corneal topography, and endothelial cell counting after the procedure. RESULTS: Before surgery, the mean corneal thickness (with the epithelium) was (399.27 ± 17.87) µm, and after the removal of epithelium, the thickness of the cornea was reduced to (354.00 ± 18.57) µm. After the application of the hypo-osmolar riboflavin solution, this value increased to (477.73 ± 20.87) µm. The improvements in visual acuity and keratometry readings occurred during the follow-up. No statistically signiflcant differences were found between preoperative and postoperative endothelial cell counts. No complications such as scarring lesions in the stroma and corneal endothelial damage were observed throughout the study period. CONCLUSIONS: The results of our study, using hypo-osmolar riboflavin solution in a cross-linking procedure in thin corneas, show a stability of keratoconus 12 months after cross-linking.

Clinical and Morphological in Vivo Confocal Microscopy Findings following a Modified Biphasic Higher Fluence Transepithelial Corneal Crosslinking.

Purpose: To compare the refractive efficacy and morphological changes in the cornea following a novel biphasic higher fluence transepithelial corneal crosslinking (BI-TE-CXL) and transepithelial corneal crosslinking (TE-CXL) in adults keratoconus.Methods: Patients with progressive keratoconus who required corneal crosslinking were assigned to the BI-TE-CXL group (32 eyes, phase 1: 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro; phase 2: 3.6 J/cm2 for 6 min and 40 s of continuous light exposure at the front curvature apex with a 6 mm diameter light spot, UVX-2000, IROC) or the TE-CXL group (32 eyes, uniform 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal fluorescein staining (CFS), corneal topography, anterior segment optical coherence tomography (AS-OCT), and in vivo corneal confocal microscopy (IVCM) were performed 3, 6, 12 and 24 months after surgery.Results: The CFS scores in the BI-TE-CXL group were significantly higher than those in the TE-CXL group on the first two days after surgery (p < 0.001). The Kmax (at 12 and 24 months) and CDVA (logMAR) were significantly lower in the BI-TE-CXL group than those in the TE-CXL group (p < 0.05). The corneal demarcation line under AS-OCT was visible in 81.3% of patients in the BI-TE-CXL group and 15.6% in the TE-CXL group. The depth of the demarcation line under IVCM was significantly deeper in the BI-TE-CXL group (248.3 ± 25.0 µm) than that of the TE-CXL group (136.5 ± 15.6 µm) in the central cornea (p < 0.001). The cross-linked collagen structures in the central cornea were still present after 12 months in the BI-TE-CXL group. No significant difference in sub-basal nerve density between the two groups (p > 0.05).Conclusions: Following BI-TE-CXL, CDVA was significantly improved, accompanied by deeper demarcation line depth and persistent crosslinked structures in the central corneal stroma.

Evaluation of lymphotoxin-alpha in pterygium and diagnostic value in active and inactive pterygium states.

To explore the correlation between tear LT-a, pterygium status, and dry eye indicators. We established a diagnostic model to evaluate active pterygium. A retrospective study was conducted between June 2021 and June 2023 on 172 patients, comprising 108 men and 64 women. The study analyzed LT-a and various ocular parameters in all participants. The data was collected using Excel software and analyzed using SPSS 25.0 statistical software and Medcalc. We made a nomogram diagnostic model to different diagnosed the state of pterygium. This study found that pterygium has progressive eye surface damage during the active state. There was no significant difference in dry eye indicators between the two groups. However, the concentration of LT-a in the active group was significantly lower than that in the inactive group (P < 0.001). We observed that increased pterygium grade corresponded to a worse ocular surface condition. In addition, LT-a was significantly positively correlated with disease duration, but negatively correlated with age, pterygium size, active pterygium state, and LLT value. The optimal intercept value for evaluating active pterygium in Lt-a was ≤ 0.49 dg/ml. We screened three variables for evaluating active pterygium through Single and Multiple regression analysis: LT-a grading, pterygium size, and congestion score. Finally, we made a reliable diagnostic nomogram model. Pterygium development triggers immune inflammation. Our model based on LT-a identifies active pterygium for personalized treatment options and new research directions.

Inflammation due to ocular surface homeostasis imbalance caused by pterygia: tear lymphotoxin-alpha study and a literature review.

OBJECTIVE: To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test. DESIGN: Prospective, single-center study. PARTICIPANTS: 400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls. METHODS: The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group. RESULT: Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency. CONCLUSION: The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.

Accurate detection and grading of pterygium through smartphone by a fusion training model.

BACKGROUND/AIMS: To improve the accuracy of pterygium screening and detection through smartphones, we established a fusion training model by blending a large number of slit-lamp image data with a small proportion of smartphone data. METHOD: Two datasets were used, a slit-lamp image dataset containing 20 987 images and a smartphone-based image dataset containing 1094 images. The RFRC (Faster RCNN based on ResNet101) model for the detection model. The SRU-Net (U-Net based on SE-ResNeXt50) for the segmentation models. The open-cv algorithm measured the width, length and area of pterygium in the cornea. RESULTS: The detection model (trained by slit-lamp images) obtained the mean accuracy of 95.24%. The fusion segmentation model (trained by smartphone and slit-lamp images) achieved a microaverage F1 score of 0.8981, sensitivity of 0.8709, specificity of 0.9668 and area under the curve (AUC) of 0.9295. Compared with the same group of patients' smartphone and slit-lamp images, the fusion model performance in smartphone-based images (F1 score of 0.9313, sensitivity of 0.9360, specificity of 0.9613, AUC of 0.9426, accuracy of 92.38%) is close to the model (trained by slit-lamp images) in slit-lamp images (F1 score of 0.9448, sensitivity of 0.9165, specificity of 0.9689, AUC of 0.9569 and accuracy of 94.29%). CONCLUSION: Our fusion model method got high pterygium detection and grading accuracy in insufficient smartphone data, and its performance is comparable to experienced ophthalmologists and works well in different smartphone brands.

Relation Between Corneal Dendritic Cell Density and Tear Film Stability in Patients with Epidemic Keratoconjunctivitis Associated Dry Eye.

PURPOSE: To clarify the ocular surface features of patients with recent history of epidemic keratoconjunctivitis (EKC) and the relation between corneal dendritic cells (DCs) and ocular discomfort. METHODS: Normal controls (NC) and dry eye (DE) patients without EKC were recruited. Patients with recent EKC history (onset >4 weeks, but <20 weeks) were recruited as EKC + DE group (with dry eye) or EKC-DE group (without dry eye). Ocular surface disease index (OSDI) questionnaire, tear film parameters including lipid layer thickness, first tear break-up time (fBUT), average tear break-up time (aBUT), tear meniscus height and Schirmer I test, meibomian gland parameters, and in vivo corneal confocal microscopy were evaluated. RESULTS: 50 subjects in the NC group, 83 patients in the DE group, 76 patients in the EKC + DE group, and 38 patients in the EKC-DE group were included. Compared with the NC, DE, and EKC-DE groups, the EKC + DE group represented higher OSDI, lid margin, and meibum score (p < 0.05). In the EKC + DE group, the tear volume (10.5 ± 3.7 mm) was significantly higher than in the DE group (8.1 ± 2.8 mm, p < 0.001). The DC density in the EKC + DE group (29.98 ± 15.38 cells/image) was significantly higher than in NC, DE, and EKC-DE groups (4.68 ± 4.05 cells/image) (p < 0.001). The DC density was positively correlated with OSDI, lid margin, and meibum score (all p < 0.01) while inversely correlated with fBUT, aBUT (all p < 0.001) in the EKC + DE group. CONCLUSIONS: Corneal DC density significantly correlates to ocular discomfort and tear film instability in patients with recent EKC history who suffer from DE without aqueous tear deficiency.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

[Abnormal epithelial differentiation and tear film alteration in pterygium].

OBJECTIVE: To investigate the differentiation and proliferation of the conjunctival epithelium and tear film function in pterygia. METHODS: It was a retrospective study. Fifteen patients (15 eyes) who underwent excision for pterygium were enrolled in this study. Immunostaining for K10, K14, K19, MUC5AC, K16, Ki67 and P63 was performed on the pterygial epithelium and normal conjunctival epithelium. Schirmer I test was performed, and the tear film break-up time (BUT) was evaluated just prior to and 6 months after surgery. Multi-factor regression analysis was assessed to observe if there is a correlation between pterygial growth and tear film function. RESULTS: The average absorbency of K19 and MUC5AC immuno-staining all significantly changed (3727.86 ± 2544.73 vs. 25 528.00 ± 12 901.06, 2080.48 ± 2340.17 vs. 7182.51 ± 3069.20, t = 9.261,3.538, P < 0.05), and increased in K10 and K14 in patients with pterygia compared with normal conjunctivae keratin (2017.51 ± 2114.3 vs. 0, 6027.5 ± 1058.32 vs. 2123.28 ± 1249.09, t = -6.151, P < 0.05). Furthermore, pterygial epithelium showed activated proliferation, evidenced by significantly up-regulated expression of K16, P63 and Ki67 compared to normal control. The Schirmer I test did not indicate any significant differences pre- and post-operatively. However, the BUT was significantly prolonged 1 month post surgery compared to pre-surgery (t = -4.222, P < 0.05). CONCLUSION: This study indicates that abnormal epithelial differentiation and proliferation are present in pterygium , which is characterized by squamous metaplasia, accompanied with instability of tear film and normal basic tear secretion.

[Corneal collagen crosslinking in the treatment of infectious keratitis].

OBJECTIVE: To investigate the feasibility and clinical efficacy of corneal collagen crosslinking (CXL) for the treatment of infectious keratitis. METHODS: Noncomparative interventional case series.19 patients with infectious keratitis admitted to our hospital between November 2011 and January 2012 were recruited into this study, CXL was performed when medications combined proved poor therapeutic effects. Postoperatively, the graft status, graft clarity, the visual prognosis and postoperative complications were recorded. RESULTS: In 15 cases, there was improvement in symptoms one week after operation.3 cases remained stable, while 1 case reported deteriorated function at the same time.One month after operation, Corneal melting was arrested and complete epithelialization was achieved in 13 cases, 5 cases experienced significant improvement and 1 patient experienced corneal ulcer perforation.2 month after surgery, patients with healed corneal ulcer increased to 17 cases, and 2 cases experienced corneal ulcer perforation. Those 17 cases with healed corneal ulcer were followed up for 6 months, 15 cases had significant improvement in best-corrected visual acuity, 2 cases had no significant change, and no relapse was observed in those 17 cases. CONCLUSION: Our experience based on the above and other cases suggest that CXL could be an effective tool in battling difficult cases of infectious keratitis. This treatment could present many advantages but will need further investigation both by in vitro and in vivo studies.

Advances in clinical examination of lacrimal gland.

In humans, the lacrimal gland is located in the socket of the frontal bone above the outer orbital area. As an essential part of the eye surface, the gland is fixed to the orbital periosteum by connective tissue. The lacrimal gland passes through the outer tendon membrane, which divides the gland into larger orbital and minor eyelid glands. The lacrimal glands are the main contributors to tear film. They secrete electrolytes, proteins, and water to help nourish and protect the eye's surface. Furthermore, clinically, lacrimal glands are associated with a variety of inflammatory reactions and immune factors and are also vulnerable sites for tumors. Changes in tear gland morphology or secretory function affect tear film stability and tear secretion quality. Various technological devices have been developed and applied to lacrimal glands. This article systematically reviewed the clinical examination of the lacrimal gland to help inform personalized strategies for the diagnosis of lacrimal gland-related diseases.

The clinicopathological analysis of ocular and orbit tumors in southeast of China.

Purpose: The purpose of this study is to describe the clinicopathologic characteristics of ocular surface and orbit tumors in the Southeast of China and explore the method to differentiate the benign and malignant masses. Materials and methods: 3468 patients undergoing mass resection from January 2015 to December 2020 were selected as observation subjects and were classified into benign and malignant masses according to postoperative pathology. The clinicopathologic characteristics were collected, including gender, age, pathological tissue signs, and pathological signs. Multivariate Logistic regression analysis of independent risk factors of malignant mass was applied to establish a diagnostic model and the efficacy was evaluated by the subject working characteristics (ROC) curve. Results: Benign tumors accounted for 91.5% of all cases, and malignant tumors accounted for 8.5%. The most common ocular benign tumors were nevi (24.2%), granuloma (17.1%), and cysts (16.4%). The most common ocular malignant tumors were malignant lymphoma (32.1%) and Basal cell carcinoma (20.2%). As for the histologic origin, melanocytic origin was on the list with 819 (23.6%), mesenchymal 661 (19.1%), epithelial 568 (16.3%), cystic 521 (15.0%), skin adnexal 110 (3.1%), lymphoid 94 (2.8%), and Neural 25(0.8%). Based on the gender, age, tumor location, and the pathological tissue image feature (including differentiation, structural atypia, covering epithelial, keratosis, nest structure/distribution, nuclear atypia, cytoplasmic change and nuclear division), the diagnostic model had predictive value to differentiate the benign and malignant masses. Conclusion: Most ocular surface and orbit tumors are benign. Tumor diagnosis is relative to the patient's age, gender, tumor location, and pathologic characteristics. We generated a satisfactory diagnostic model to differential diagnosis of benign and malignant masses.