Involvement of NYD-SP15 in growth and oxidative-stress responses of ARPE-19.

The aim of this study was to investigate the role of NYD-SP15 in the growth and oxidative-stress responses of ARPE-19 cells. ARPE-19 cell lines overexpressing wild type or RNA interference against NYD-SP15 were established via lentivirus transfection. Cell growth and proliferation, migration, apoptosis, and cell cycle progression were monitored using the Cell Counting Kit-8 assay, the wound scratch assay, and flow cytometry, respectively. Caspase-3/8/9 activity was examined using the caspase-3/8/9 assay kit. An hydrogen peroxide (H 2 O 2 )-induced oxidative-stress damage model was used to study the effect of NYD-SP15 knockdown by examining the activity of reactive oxygen species (ROS). Expressions of Kelch-like ECH-associated protein 1 (Keap-1)/heme oxygenase-1 (HO-1)/nuclear factor erythroid 2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and Akt were detected by Western blot analysis. The mRNA chip of NYD-SP15 overexpressed ARPE-19 cells as well as controls were performed by one array plus process. Overexpression (OE) of NYD-SP15 inhibited the proliferation and migration of ARPE-19 cells, and led to apoptosis and caspase-3/9 activation. OE of NYD-SP15 inhibited MAPKs and Akt signaling. Downregulation of NYD-SP15 had no effect on the growth of normally cultured ARP19 cells with 10% fetal bovine serum, but promoted the growth of ARP19 cells in the presence of starvation challenge. Gene chip showed that OE of NYD-SP15 led to downregulation of 254 genes and upregulation of 57 genes. Downregulation of NYD-SP15 also exerted a protective effect on H 2 O 2 -induced cell apoptosis and ROS. NYD-SP15 downregulation led to increments in the expression of Nrf2, Keap-1, and HO-1 in response to 200 µM H 2 O 2 . NYD-SP15 might inhibit the growth, proliferation, and migration and promote apoptosis of ARPE-19 cells via MAPK and Akt signaling. Downregulation of NYD-SP15 could protect ARPE-19 cells from H 2 O 2 -induced oxidative damage by active Keap-1/HO-1/Nrf2, Akt, and MAPK signaling.

Application of Metagenomic Next-Generation Sequencing in the Diagnosis of Infectious Keratitis.

Purpose: To determine the advantages of next-generation metagenomic sequencing (mNGS) technology in the diagnosis and treatment of infectious keratitis (IK). Methods: A total of 287 patients with IK admitted to the Department of Ophthalmology of Nanjing First Hospital between August 2018 and December 2022 were analyzed retrospectively, and the pathogenic causes, etiological characteristics, detection, treatment methods, and efficacy were summarized. Results: Trauma and foreign matter were the most common causes of IK (144 patients, 50.2%). Of the 287 patients, 228 (79.4%) were diagnosed with a specific etiology, including 110 (48.2%) fungal infections, 44 (19.3%) viral infections, 42 (18.4%) mixed infections, and 30 (13.2%) bacterial infections. Filamentous fungi represented by Fusarium and Aspergillus were the most common, followed by bacteria such as Pseudomonas aeruginosa, Streptococcus pneumoniae, viruses (Herpes Simplex Virus/Varicella-Zoster Virus), and parasites. The positivity rates of secretion culture, corneal laser confocal microscopy (CM), mNGS, and pathological sections were 47.3% (133/281), 45.3% (111/245), 83.9% (104/124), and 19.3% (40/207), respectively. The positivity rate of mNGS for bacteria and viruses was higher than that of the other methods, and the positivity rate for fungi was the same as that for CM. As a result, 214 cases (74.6%) were cured, 51 cases (17.8%) improved, 8 cases (2.8%) did not heal, ocular content enucleation was performed in 14 cases (4.9%), and the overall efficacy rate was 92.3%. Conclusion: Trauma and foreign matter are the main causes of IK. The mNGS technology is an efficient and comprehensive detection method for viruses and bacteria, especially for mixed infections.

A Predictive Model for Graft Failure in Femtosecond Laser-Assisted Penetrating Keratoplasty Among Chinese Patients: A 2-Year Study.

INTRODUCTION: Graft failure is a major challenge in femtosecond laser-assisted penetrating keratoplasty (Fs-PKP). This study focuses on the development and validation of a clinical predictive model aimed at identifying the risk of graft failure in individuals undergoing Fs-PKP in China, offering a tailored approach to improve surgical outcomes. METHODS: This retrospective cohort study at Nanjing First Hospital involved 238 patients and followed the TRIPOD statement. The cohort was divided into a training set (n = 166) and a validation set (n = 72) in a 7:3 ratio. It analyzed 23 predictor variables related to recipient, donor, and surgical factors, defining graft failure as "visually significant and irreversible corneal stromal edema, haze, or scarring." A comprehensive nomogram was created using univariate and multivariate Cox regression analyses and assessed by concordance index (C-index), time-dependent receiver operating characteristics (ROC) curve, calibration plots, and decision curve analysis (DCA). RESULTS: Five critical risk factors were identified: recipients' history of systemic autoimmune disorders, ocular trauma, prior penetrating keratoplasty (PKP) history, donors' diabetes history, and the endothelial cell density of the donor cornea. The nomogram showed a C-index of 0.72 (95% CI 0.65-0.79) in the training group and 0.66 (95% CI 0.55-0.76) in the validation group, indicating robust predictive accuracy. Time-dependent ROC curves, calibration plots, and DCA consistently validated the model's reliability, predictive power, and clinical utility across both training and validation cohorts. CONCLUSIONS: Our study developed and validated a model incorporating five key factors, enhancing preoperative prediction and management for Chinese patients with Fs-PKP graft failure.

Aquaporins enriched in endothelial vacuole membrane regulate the diameters of microvasculature in hyperglycaemia.

AIMS: In patients with diabetic microvascular complications, decreased perfusion or vascular occlusion, caused by reduced vascular diameter, is a common characteristic that will lead to insufficient blood supply. Yet, the regulatory mechanism and effective treatment approach remain elusive. METHODS AND RESULTS: Our initial findings revealed a notable decrease in the expression of human AQP1 in both diabetic human retina samples (49 healthy vs. 54 diabetic samples) and high-glucose-treated human retinal microvascular endothelial cells. Subsequently, our investigations unveiled a reduction in vascular diameter and compromised perfusion within zebrafish embryos subjected to high glucose treatment. Further analysis indicated a significant down-regulation of two aquaporins, aqp1a.1 and aqp8a.1, which are highly enriched in ECs and are notably responsive to hyperglycaemic conditions. Intriguingly, the loss of function of aqp1a.1 and/or aqp8a.1 resulted in a reduction of intersegmental vessel diameters, effectively mirroring the phenotype observed in the hyperglycaemic zebrafish model. The overexpression of aqp1a.1/aqp8a.1 in zebrafish ECs led to notable enlargement of microvascular diameters. Moreover, the reduced vessel diameters resulting from high-glucose treatment were effectively rescued by the overexpression of these aquaporins. Additionally, both aqp1a.1 and apq8a.1 were localized in the intracellular vacuoles in cultured ECs as well as the ECs of sprouting ISVs, and the loss of Aqps caused the reduction of those vacuoles, which was required for lumenization. Notably, while the loss of AQP1 did not impact EC differentiation from human stem cells, it significantly inhibited vascular formation in differentiated ECs. CONCLUSION: EC-enriched aquaporins regulate the diameter of blood vessels through an intracellular vacuole-mediated process under hyperglycaemic conditions. These findings collectively suggest that aquaporins expressed in ECs hold significant promise as potential targets for gene therapy aimed at addressing vascular perfusion defects associated with diabetes.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Awareness of cornea donation of registered tissue donors in Nanjing.

OBJECTIVE: To evaluate the current cornea donation awareness of tissue donors in the city of Nanjing, China. METHODS: Altogether 2000 registered tissue donors in the Red Cross Eye Bank of Nanjing by the end of 2010 and 2000 control residents of Nanjing in February to June 2011 were randomly selected to participate in our field questionnaire survey. The questionnaire consisted of questions regarding the understanding of cornea donation, the attitude toward cornea donation, and attitude toward legislation and free donation. The awareness of cornea donation between the registered tissue donors and residents was compared. Related factors of the willing-ness to donate corneas and to become a tissue donor were evaluated with univariate and multiple logistic regression analysis. RESULTS: A total of 1867 (response rate: 93.4%) tissue donors and 1796 (response rate: 89.8%; effective questionnaires: 1697) residents participated in this survey. For the questions about the knowledge of cornea donation, 90.3% tissue donors (residents: 78.9%) knew that donated corneas could be used for transplantations; 71.2% tissue donors (residents: 47.6%) knew that the appearance would not be destroyed after cornea donation; 70.7% tissue donors (residents: 20.0%) knew the formalities to become a cornea donor. For attitude toward cornea donation, 82.2% tissue donors (residents: 45.1%) were willing to donate corneas or eyeballs after death; 84.0% tissue donors (residents: 30.2%) had discussed with their families about donation; 85.1% tissue donors (residents: 24.8%) supported their families' or friends' cornea donation. For attitude toward legislation and free donation, 88.3% tissue donors (residents: 61.3%) approved of legislation to regular cornea donation; 72.2% tissue donors (residents: 38.8%) thought that cornea or organ donation should be gratis. The difference between two groups was significant (P<0.001). However, some tissue donors did not know cornea donation well, some even opposed the legislation of cornea donation and free donation protocol. For the factors influencing the willingness to donate corneas, population was the most relevant factor (P<0.001), since tissue donors were more willing to donate corneas than residents. Other significantly related factor were age, gender, occupation, and education level (P<0.001), while political status or religion were not significant. For the factors related to becoming a tissue donor, older age, male, white-collars (including white-collar, civil servant, teacher, soldier, lawyer, salesman, healthcare provider), higher education level, party members (including the Chinese Communist Party members, democratic party members, and the Communist Youth League members) (P<0.05). CONCLUSIONS: The registered tissue donors have better understanding and more positive attitude towards cornea donation than control residents do. They approve of the legislation of cornea donation and free donation protocol. It may be more effective to target the population of over 58 years old, male, white-collars, well-educated people, and party members in the promotion of cornea donation.

Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients: A Randomized Clinical Trial.

Importance: Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought. Objective: To evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days. Design, Setting, and Participants: This was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher. Interventions: Eligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day. Main Outcomes and Measures: The primary end points were the changes from baseline in tCFS and eye dryness scores at day 57. Results: A total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], -3.8 [2.7] vs -2.7 [2.8]) and eye dryness score (mean [SD], -38.6 [21.9] vs -28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of -1.14 (95% CI, -1.70 to -0.57; P < .001) and -12.74 (95% CI, -17.20 to -8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs -18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, -38.1 [25.1] vs -23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, -43.3 [23.8] vs -29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively. Conclusions and Relevance: Results of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods. Trial Registration: ClinicalTrials.gov Identifier: NCT05515471.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Survey report on keratoplasty in China: A 5-year review from 2014 to 2018.

To provide the general information on corneal transplantation (CT) in China, China Cornea Society designed a questionnaire on CT from 2014 to 2018 and entrusted it to 31 committee members for implementation of the survey nationwide. This article presents the results of the survey and compares the indicators used in the survey and those in the annual statistical report released by the Eye Bank Association of America (EBAA). The number of corneal transplantations completed by the 64 hospitals from 2014 to 2018 was respectively 5377, 6394, 7595, 8270 and 8980, totally 36,616 (22,959 male and 13,657 female). The five largest hospitals by the number of corneal transplantations completed 15,994 surgeries in total, accounting for 43.68% of all the surgeries performed in the 64 hospitals. The most common indication for corneal transplantations was corneal leukoma (7683, 20.98%), followed by bacterial keratitis (4209, 11.49%), corneal dystrophies (4189, 11.44%), keratoconus (3578, 9.77%) and corneal perforation (2839, 7.75%). The main surgical techniques were penetrating keratoplasty (PK) (19,896, 54.34%), anterior lamellar keratoplasty (ALK) (13,869, 37.88%). The proportion of PK decreased from 57.97% in 2014 to 52.88% in 2018 while the proportion of ALK increased from 36.04% in 2014 to 37.92% in 2018. The geographical distribution of keratoplasties performed in China is unbalanced. PK and ALK were the main techniques of CT and corneal leukoma, bacterial keratitis and corneal dystrophies were the main indications for CT in China.

An approach for simulating the fitting of rigid gas-permeable contact lenses using 3D printing technology.

OBJECTIVE: To introduce a new approach to simulatethe fitting process of rigid gas-permeable (RGP) contact lenses using 3D printing technology. METHODS: A hemispherical or parabolic 3D model was created using 3D Builder or Tinkercad software. The horizontal and vertical diameters and the hemispherical or ellipsoid height were adjusted to simulate different morphologies of the corneal anterior surface. After exporting the file in stereo lithography (STL) format, a solid model was printed using a 3D printer and was used to simulate RGP contact lens fitting. RESULTS: Limited by the precision of the entry-level 3D printer which was used in this study, the print-outs of the corneal models were crude, but the models were tested for their ability to simulate common corneal morphologies with no corneal astigmatism and different axial corneal astigmatism. Compared with some built-in simulation programs for corneal topography, the solid models generated by 3D printing could well simulate the positioning of the lens under the influence of gravity and the eyelid, as well as lens eccentricity or the bubbles under lenses caused by an improper wearing method. CONCLUSION: 3D printing technology can be well applied in the simulation of RGP contact lens fitting, which may become a new teaching method in optometry.

Mitomycin C "straight scleral tunnel incision"--trabeculectomy with a releasable suture.

OBJECTIVE: To evaluate the efficacy of "straight scleral tunnel incision" -trabeculectomy with a releasable suture supplemented with mitomycin C (MMC) on reducing intraocular pressure (IOP), complications, and corneal astigmatism in patients with primary angle-closure glaucoma (PACG). METHODS: Totally 217 acute or chronic PACG patients with occludable angle above 180 degrees and IOP above 21 mm Hg were divided into 3 groups. Patients in group A (98 cases, 128 eyes), B (71 cases, 95 eyes), and C (48 cases, 60 eyes) were treated with "straight scleral tunnel incision"-trabeculectomy with a releasable suture supplemented with MMC, releasable suture trabeculectomy with MMC, and trabeculectomy with MMC, respectively. IOP, complications, and surgically induced astigmatism (SIA) were evaluated preoperatively and up to 12 months postoperatively. RESULTS: IOP of 2 weeks after treatment was significantly lower than preoperative IOP in all the 3 groups (all P <0. 001). Success rates (IOP < or = 20 mm Hg) in group A, B, and C were 87.91%, 89.23%, and 83.72% respectively at 12 months after treatment (P = 0.256). The incidence of shallow anterior chamber and hypotony had no significant difference between group A and B, but both of them were lower than that in group C (P < 0.05). There were no significant differences in preoperative corneal astigmatism among the 3 groups. The corneal astigmatism after 2 weeks in group A (1.71 +/- 1.47D) was higher than that before operation (1.28 +/- 1.05D, P = 0.126). With 12 months gone, the astigmatism almost returned to preoperative levels. The corneal astigmatisms after 2 weeks in group B and C (1.99 +/- 1.20D and 2. 22 +/- 1.39D) were significantly higher than those before operation (1.20 +/- 0.85D and 1.18 +/- 0.93D, P = 0.002, P = 0.001), respectively. With 12 months gone, the mean astigmatisms in group B and C (1.87 +/- 0.91D and 1.90 +/- 1.16D) were still significantly higher than those before operation (P = 0.001, P = 0.003). The highest astigmatic polar values in group A, B, and C (1.00D, 1. 89D, and 1. 77D) occurred after 2 weeks, 1 month, and 1 month postoperation, respectively, which were significantly higher than those before operation (0.19 +/- 1.32D, 0.12 +/- 1.22D, and 0.17 +/- 1.25D, P < 0.01), respectively. With 12 months gone, they were 0. 03D, -0. 18D, and -0. 13D higher than those before operation, respectively. The rates of function bleb and thin-wall bleb were 71.43% and 26.37% in group A, 75.38% and 29.23% in group B, 72.09% and 25.58% in group C, respectively at 12 months after treatment There were no significant differences among the 3 groups. CONCLUSION: "Straight scleral tunnel incision" -trabeculectomy with a releasable suture supplemented with MMC can reduce complications and get satisfactory results in reducing IOP and SIA.

Real-time polymerase chain reaction for the diagnosis of necrotizing herpes stromal keratitis.

AIM: To design, optimize and validate a rapid, internally controlled real-time polymerase chain reaction (RT-PCR) test for herpes simplex virus (HSV) in the diagnosis of necrotizing herpes stromal keratitis. METHODS: Tears alone or together with corneal epithelium scrapings from 30 patients (30 eyes) suspected of necrotizing herpes stromal keratitis were tested for HSV DNA by RT-PCR. The samples were collected during the first visit and then on the subsequent 7, 14, 28, 42, and 56d. The symptoms of the patients were scored before treatment to determine the correlation between HSV concentration in the corneal epithelium scrapings and clinical scores. RESULTS: The positive rate (46.4%) in the corneal epithelium group before the therapy was significantly higher than that (13.3%) in the tears group (P=0.006). There were 13 positive HSV patients before the therapy, the concentration of HSV DNA in corneal epithelium scrapings group was significantly higher than that in the tears group (paired t-test, P=0.0397). Multilevel mixed-effects model analysis showed that the difference between the corneal epithelium scrapings group and the tears group was statistically significant (P=0.0049). The Spearman rank correlation analysis indicated a positive correlation between the HSV concentration in the corneal epithelium scrapings and clinical scores before the treatment (r=0.844, P<0.0001). CONCLUSION: RT-PCR appears to be a powerful molecular tool for the diagnosis of necrotizing herpes stromal keratitis.

Clinical efficacy of oral ganciclovir for prophylaxis and treatment of recurrent herpes simplex keratitis.

BACKGROUND: Herpes simplex keratitis (HSK) caused by herpes simplex virus 1 (HSV-1), which has high recurrent rate and incidence of severe vision loss, is the leading cause of infectious blindness in the world. The aim was to explore the clinical efficacy of oral ganciclovir (GCV) in the prevention of recurrent HSK. METHODS: A multicenter, prospective, randomized, single-blind, and controlled clinical trial was conducted from April 2010 to June 2013. One hundred seventy-three patients (173 eyes involved) who were diagnosed as recurrent HSK definitely, including stromal keratitis and corneal endotheliitis, were divided into three groups randomly: negative control (placebo) group was topically administered with 0.15% GCV ophthalmic gel, 4 times per day and 0.1% fluorometholone eye drops, 3 times per day until resolution of HSK; positive control acyclovir (ACV) group was topically adopted the same ophthalmic gel and eye drops and additionally received oral ACV 400 mg 5 times a day for 10 weeks and followed by 400 mg 2 times per day for 6 months; test GCV group was topically adopted the same treatment as negative control group and additionally received oral GCV 1000 mg 3 times per day for 8 weeks. The symptoms and signs were evaluated before and after the therapy 1 st week, 2 nd week and then followed up every 2 weeks until recovery. Furthermore, we followed up recurrence of HSK for every 3 months after recovery and then assessed the cure time, recurrent rate and adverse reactions. RESULTS: One hundred and seventy-three patients were followed up 7-48 months (mean 32.1 ± 12.3 months), but 34 patients were failed to follow-up. The cure time was 12.1 ± 4.3, 11.9 ± 4.0 weeks in negative control (placebo) group and positive control ACV group respectively (P = 0.991), which was longer than that in test GCV group (8.6 ± 2.8 weeks) and there was a significant difference between test GCV group and negative control (placebo) group or positive control ACV group (P = 0.000). Furthermore, the recurrent rate was higher in negative control (placebo) group (47.3%) than that in positive control group ACV (26.7%) and test GCV group (17.2%), and there was a great significant difference among the three groups (P = 0.007), but there was no significant difference between positive control ACV group and test GCV group (P = 0.358). In addition, there was no obvious adverse reaction expect neutropenia (only one patient in test GCV group). CONCLUSION: Short-term oral GCV could cure recurrent HSK and endotheliitis, shorten the course, reduce recurrent rate of HSK and have confirmed safety.

Identification of corneal neovascularization-related long noncoding RNAs through microarray analysis.

PURPOSE: To reveal the role of long noncoding RNAs (lncRNAs) in corneal neovascularization (CN). METHODS: We established a murine CN model and performed lncRNA expression profiling to identify differentially expressed lncRNAs between normal and vascularized corneas. Based on Pearson correlation analysis, an lncRNA/mRNA coexpression network was constructed. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of lncRNA-coexpressed mRNAs were conducted to determine the related biological modules and pathological pathways. Real-time polymerase chain reactions were carried out to detect the expression pattern of lncRNA in the clinical samples. RESULTS: A total of 154 differentially expressed lncRNAs were identified between vascularized and normal corneas, including 60 downregulated lncRNAs and 94 upregulated lncRNAs. GO enrichment analysis of lncRNA-coexpressed mRNAs indicated that the biological modules were correlated with extracellular region, DNA binding, and immune response. KEGG pathway analysis indicated that "pathways in cancer" was the most enriched signaling pathway. Moreover, the human ortholog of NR_033585 and lincRNA:chr8:129102060-129109035 reverse strand was found to be differentially expressed between vascularized and avascular corneas. CONCLUSIONS: This study provides a novel insight into CN pathogenesis. The intervention of dysregulated lncRNAs may become potential targets for the prevention and treatment of ocular vascular diseases.

Liquid nitrogen-cryopreserved tarsal plate and palpebral conjunctival transplantation for the repair of tarsal defects.

The objectives of this study were to compare the efficiency of three methods for repairing tarsal defects (glycerine-preserved, alcohol-preserved and cryopreserved tarsal plate and palpebral conjunctival transplantation) based on histopathological changes and apoptosis, and to evaluate the clinical effects of repairing tarsal defects by liquid nitrogen-cryopreserved tarsal plate and palpebral conjunctival transplantation. Forty-eight rabbit eyes with tarsal defects were equally divided into three groups and transplanted with tarsal plates and palpebral conjunctivae under the following conditions: Group 1, liquid nitrogen cryopreservation; Group 2, glycerine preservation; and Group 3, alcohol preservation. Histopathological changes in the transplants were observed by light microscopy 1 week, 1 month and 3 months postoperatively. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Clinically, transplantations of liquid nitrogen-cryopreserved tarsal plates and palpebral conjunctivae were performed in 30 eyes (29 cases) to repair tarsal defects caused by the excision of neoplasms. The postoperative inflammatory reaction and number of apoptotic cells in Group 1 were lower compared with those in Groups 2 and 3. Clinically, of the 30 eyes operated on, 14 were cured, 15 improved and 1 failed between 6 and 90 months of follow-up. Liquid nitrogen-cryopreserved tarsal plate and palpebral conjunctival transplantation is an easy, feasible and convenient procedure. Its effects are fairly favorable, with only a small rejection rate postoperatively. Therefore, it is an ideal method for repairing tarsal defects.

Loteprednol etabonate suspension 0.2% administered QID compared with olopatadine solution 0.1% administered BID in the treatment of seasonal allergic conjunctivitis: a multicenter, randomized, investigator-masked, parallel group study in Chinese patients.

BACKGROUND: Seasonal allergic conjunctivitis (SAC) is caused by seasonal allergens and usually manifests as ocular itching and bulbar conjunctival injection (redness). Treatment options for SAC include corticosteroids and dual-acting antihistamine and mast-cell stabilizers. OBJECTIVE: Our objective was to compare the efficacy and tolerability of loteprednol etabonate (LE), a C-20 ester-based corticosteroid, with those of olopatadine, a dual-acting antihistamine mast-cell stabilizer, in Chinese patients. METHODS: This was a multicenter, randomized, investigator-masked, parallel group study. Patients with acute SAC experiencing grade 4 ocular itching and grade 2 or higher bulbar conjunctival injection received either LE suspension 0.2% QID at 4-hour intervals or olopatadine solution 0.1% BID at 6- to 8-hour intervals bilaterally for 15 days. Primary efficacy end points included the change from baseline (CFB) in ocular itching and bulbar conjunctival injection at day 15. The primary analysis tested the noninferiority of LE suspension 0.2% to olopatadine solution 0.1%. Tolerability outcomes included the incidence of adverse events (AEs), biomicroscopy findings, visual acuity, and intraocular pressure. RESULTS: A total of 300 patients were randomly assigned, and 293 were included in the per-protocol population (LE, n = 147; olopatadine, n = 146). Mean (SD) CFB at day 15 in the LE and olopatadine treatment groups, respectively, was -3.74 (0.47) and -3.28 (0.91) for ocular itching and -1.91 (0.52) and -1.71 (0.59) for bulbar conjunctival injection. The 95% CI for the differences in CFB in ocular itching (-0.59 to -0.27) and bulbar conjunctival injection (-0.27 to -0.08) was less than the prespecified noninferiority limit of 0.3. Treatment differences in CFB were significantly better with LE compared with olopatadine for both end points (P ≤ 0.0006). Ocular AEs were few and similar between treatment groups. There were no clinically significant biomicroscopy or visual acuity findings, and no patient experienced a clinically significant increase in intraocular pressure (≥10 mm Hg). CONCLUSION: Results of this investigator-masked study with Chinese patients suggest LE suspension 0.2% was noninferior to olopatadine solution 0.1% for the treatment of SAC. Both LE suspension 0.2% and olopatadine solution 0.1% were well tolerated. ClinicalTrials.gov identifier: NCT01435460.