Harmol used for the treatment of herpes simplex virus induced keratitis.

Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy.

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

METTL3-mediated m6A RNA modification promotes corneal neovascularization by upregulating the canonical Wnt pathway during HSV-1 infection.

BACKGROUND: Corneal neovascularization (CNV) is a symptom of herpes simplex keratitis (HSK), which can result in blindness. The corneal angiogenesis brought on by herpes simplex virus type 1 (HSV-1) is strongly affected by vascular endothelial growth factor A (VEGFA). The N6-methyladenosine (m6A) modification catalyzed by methyltransferase-like 3 (METTL3) is a crucial epigenetic regulatory process for angiogenic properties. However, the roles of METTL3 and m6A in HSK-induced CNV remain unknown. Here, we investigated these roles in vitro and in vivo. METHODS: A PCR array in HSV-1-infected human umbilical vein endothelial cells (HUVECs) was used to screen for METTL3 among the epitranscriptomic genes. Tube formation and scratch assays were conducted to investigate cell migration capacity. The global mRNA m6A abundance was evaluated using a dot blot assay. Gene expression was assessed by RT-qPCR, western blotting, and fluorescence immunostaining. In addition, bioinformatic analysis was conducted to identify the downstream molecules of METTL3 in HUVECs. METTL3 knockdown and STM2457 treatment clarified the specific underlying molecular mechanisms affecting HSV-1-induced angiogenesis in vitro. An acute HSK mouse model was established to examine the effects of METTL3 knockdown or inhibition using STM2457 on pathological angiogenic development in vivo. RESULTS: METTL3 was highly upregulated in HSV-1-infected HUVECs and led to increased m6A levels. METTL3 knockdown or inhibition by STM2457 further reduced m6A levels and VEGFA expression and impaired migration and tube formation capacity in HUVECs after HSV-1 infection. Mechanistically, METTL3 regulated LRP6 expression through post-transcriptional mRNA modification in an m6A-dependent manner, increasing its stability, upregulating VEGFA expression, and promoting angiogenesis in HSV-1-infected HUVECs. Furthermore, METTL3 knockdown or inhibition by STM2457 reduced CNV in vivo. CONCLUSION: Our findings revealed that METTL3 promotes pathological angiogenesis through canonical Wnt and VEGF signaling in vitro and in vivo, providing potential pharmacological targets for preventing the progression of CNV in HSK.

Preliminary Assessment of Intramuscular Depot of Lipid-Based Decoquinate Formulation for Long-Term Chemoprophylaxis of Malaria.

Sustained-release formulations of decoquinate were evaluated for the long-term prophylaxis of malaria. In the initial experiment, mice were protected from liver-stage Plasmodium infection by intramuscular administration of a lipids-based formulation at a dose of decoquinate 200 mg/kg. The mice that were inoculated with Plasmodium berghei sporozoites 34 days after the administration of a one-time drug dose were continuously monitored for 60 days and shown to be free of Plasmodium parasites. The optimized formulation for the sustained release of decoquinate was prepared by hot melt extrusion, constructed by lipids including cholesterol and mono or diglycerides, and had a drug load of 20 to 40% and particle size of 30 to 50 µm. Decoquinate of the lipids-based formulation was slowly released in vitro at a constant rate for the duration of two months, and was examined and continuously exposed at a therapeutic level in the blood for as long as 4 to 6 months. Further evaluation showed that the lipids-based formulation at doses of decoquinate 100 to 150 mg/kg could protect mice from Plasmodium infection for a period of 120 days. It is the first time that cholesterol has been used for a controlled drug delivery system of decoquinate. The results may provide useful information, not only for preparing a formulation of long-acting decoquinate but also in general for developing a controlled drug release system. The one-time administration of pharmaceutical agents in such a slow-release system may serve patients with no concerns about compliance.

Nectin-1 and Non-muscle Myosin Heavy Chain-IIB: Major Mediators of Herpes Simplex Virus-1 Entry Into Corneal Nerves.

Herpes Simplex Virus 1 (HSV-1) invades corneal nerves upon its infection of the cornea and then establishes latency in the trigeminal ganglion (TG). The latent virus in TG is often reactivated and travels back to the cornea, causing recurrent herpes simplex keratitis (HSK). The entry of HSV-1 into the corneal nerve is considered the initial step of infection resulting in HSV-1 latency and HSK recurrence. Several gD and gB receptors have been identified, including nectin-1, herpes virus entry medium (HVEM) and 3-O-sulfated heparan sulfate (3-OS-HS) as gD receptors, and non-muscle myosin heavy chain IIA (NMHC-IIA), NMHC-IIB and myelin-associated glycoprotein (MAG) as gB receptors. However, which receptors contribute to the entry of HSV-1 into corneal nerves are yet to be determined. This study observed that receptors nectin-1, HVEM, 3-OS-HS, NMHC-IIA, and NMHC-IIB, not MAG, were expressed in healthy corneal nerves. Further, we cultured TG neurons extracted from mice in vitro to screen for functional gD/gB receptors. Both in vitro siRNA knockdown and in vivo antibody blocking of either nectin-1 or NMHC-IIB reduced the entry and the replication of HSV-1 as shown by qPCR analysis and immunofluorescence measure, respectively. Also, we observed that the re-localization and the upregulation expression of NMHC-IIB after HSV-1 exposure were inhibited when gD receptor nectin-1 was knocked down. These data suggest that nectin-1 was the main gD receptor and NMHC-IIB was the main gB receptor in mediating HSV-1 entry and hold promise as therapeutic targets for resolving HSV-1 latency and HSK recurrence.

Tin Oxide (SnO2) Nanoparticles: Facile Fabrication, Characterization, and Application in UV Photodetectors.

Tin oxide (SnO2) nanomaterials are of great interest in many fields such as catalytic, electrochemical, and biomedical applications, due to their low cost, suitable stability characteristics, high photosensitivity, etc. In this contribution, SnO2 NPs were facilely fabricated by calcination of tin (II) oxalate in air, followed by a liquid-phase exfoliation (LPE) method. Size-selected SnO2 NPs were easily obtained using a liquid cascade centrifugation (LCC) technique. The as-obtained SnO2 NPs displayed strong absorption in the UV region (~300 nm) and exhibited narrower absorption characteristics with a decrease in NP size. The as-fabricated SnO2 NPs were, for the first time, directly deposited onto a poly(ethylene terephthalate) (PET) film with a regular Ag lattice to fabricate a flexible working electrode for a photoelectrochemical (PEC)-type photodetector. The results demonstrated that the SnO2-NP-based electrode showed the strongest photoresponse signal in an alkaline electrolyte compared with those in neutral and acidic electrolytes. The maximum photocurrent density reached 14.0 µA cm-2, significantly outperforming black phosphorus nanosheets and black phosphorus analogue nanomaterials such as tin (II) sulfide nanosheets and tellurene. The as-fabricated SnO2 NPs with relatively larger size had better self-powered photoresponse performance. In addition, the as-fabricated SnO2-NP-based PEC photodetector exhibited strong cycling stability for on/off switching behavior under ambient conditions. It is anticipated that SnO2 nanostructures, as building blocks, can offer diverse availabilities for high-performance self-powered optoelectronic devices to realize a carbon-neutral or carbon-free environment.

Harringtonine Inhibits Herpes Simplex Virus Type 1 Infection by Reducing Herpes Virus Entry Mediator Expression.

Herpes simplex virus type 1 (HSV-1) infection induces various clinical disorders, such as herpes simplex encephalitis (HSE), herpes simplex keratitis (HSK), and genital herpes. In clinical intervention, acyclovir (ACV) is the major therapeutic drug used to suppress HSV-1; however, ACV-resistant strains have gradually increased. In the present study, harringtonine (HT) significantly inhibited infection of HSV-1 as well as two ACV-resistant strains, including HSV-1 blue and HSV-1 153. Time-of-drug addition assay further revealed that HT mainly reduced the early stage of HSV-1 infection. We also demonstrated that HT mainly affected herpes virus entry mediator (HVEM) expression as shown by qPCR, Western Blot, and Immunofluorescence. Collectively, HT showed antiviral activity against HSV-1 and ACV-resistant strains by targeting HVEM and could be a promising therapeutic candidate for mitigating HSV-1-induced-pathogenesis.

Comparison of early visual quality in patients with moderate myopia using different optical zones in small incision lenticule extraction (SMILE).

BACKGROUND: The early visual qualities of patients with moderate myopia were evaluated after small incision lenticule extraction (SMILE) using different optical zones. METHODS: In this retrospective case study, 27 cases (51 eyes) were selected, including 10 cases in Group A (19 eyes), 6.6-6.8 mm in the optical zone, 10 cases in Group B (19 eyes), 6.4-6.5 mm in the optical zone, and 7 cases in Group C (13 eyes),6.1-6.3 mm in the optical zone. The following items were examined preoperatively and 1 month postoperatively: uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical, cylinder, central corneal thickness (CCT), corneal mean curvature (CMC), total ocular aberrations (TA), total low order aberrations (tLOAs), defocus, astigmatism and total high order aberrations (tHOAs), spherical, coma, trefoil, modulation transfer function (MTF), MTFcutoff, SR, objective scatter index (OSI), point scatter function at 50 and 10% (PSF50%, PSF10%), and contrast visual acuity of 100, 20, and 9% (VA100%, VA20%, and VA9%). We compared the three groups by Kruskal-Wallis test. Wilcoxon signed ranks test was used for each group before and 1 month after surgeries. P< 0.05 was considered statistically significant. RESULTS: There was no significant difference in UCVA, BCVA, CCT, cylinder, and CMC in three groups preoperatively and 1 month postoperatively (P> 0.05). Comparison of the aberrations of the three groups showed statistically significant difference only in TA, tLOA, defocus, astigmatism and SA preoperatively, and trefoil 1 month postoperatively(P< 0.05). The postoperative TA, tLOAs, defocus, astigmatism and trefoil of the three groups were lower than those before surgeries (P< 0.05). The postoperative tHOAs of Group B and C was lower than those before surgeries (P< 0.05). The MTF results showed that before surgeries, there were significant differences in three groups (P< 0.05) in spatial frequencies 5~15 cycles per degree (cpd), and no differences in 20~30 cpd(P> 0.05), while no difference were observed in all spatial frequencies postoperatively (P> 0.05). Comparing the preoperative and postoperative MTF values for each group, the results showed that there was a significant difference in Group C at 5~20 cpd after surgeries(P< 0.05). There was no significant difference in MTFcutoff, SR, OSI, PSF50%, PSF10%, VA100%, VA20%, and VA9% in the three groups preoperatively (P> 0.05). One month after surgeries, higher VA9% values were measured for Group C compared to Group A and B (P < 0.05). There was no significant difference in each group before and after surgeries (P> 0.05). CONCLUSION: SMILE could improve the visual qualities of patients with moderate myopia. Reducing the surgical optical zone will only affect night vision slightly.

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.

Cross-talk between microRNA-let7c and transforming growth factor-ß2 during epithelial-to-mesenchymal transition of retinal pigment epithelial cells.

AIM: To explore the roles of microRNA-let7c (miR-let7c) and transforming growth factor-ß2 (TGF-ß2) and cellular signaling during epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells. METHODS: Retinal pigment epithelial (ARPE-19) cells were cultured with no serum for 12h, and then with recombinant human TGF-ß2 for different lengths of time. ARPE-19 cells were transfected with 1×106 TU/mL miR-let7c mimcs (miR-let7cM), miR-let7c mimcs negative control (miR-let7cMNC) and miR-let7c inhibitor (miR-let7cI) using the transfection reagent. The expression of keratin-18, vimentin, N-cadherin, IKB alpha, p65 were detected by Western blot, quantitative polymerase chain reaction and immunofluorescence. RESULTS: The expression of miR-let7c was dramatically reduced and the nuclear factor-kappa B (NF-κB) signaling pathway was activated after induction by TGF-ß2 (P<0.05). In turn, overexpressed miR-let7c significantly inhibited TGF-ß2-induced EMT (P<0.05). However, miR-let7c was unable to inhibit TGF-ß2-induced EMT when the NF-κB signaling pathway was inhibited by BAY11-7082 (P<0.01). CONCLUSION: The miR-let7c regulates TGF-ß2-induced EMT through the NF-κB signaling pathway in ARPE-19 cells.

Evaluation of visual quality after EVO-ICL implantation for hypermyopia: An observational study.

The purpose of this retrospective study was to evaluate the visual quality, objective scattering index, aberration, etc after Implantable Collamer Lens with center hole (EVO-ICL) implantation to treat patients with hypermyopia (diopter > -10 D).A total of 30 eyes underwent EVO-ICL implantation. The uncorrected distance visual acuity (UDVA), best-corrected visual acuity (BCVA), equivalent spherical degree, aberration, visual quality parameters, and corneal endothelial cell density were compared preoperative and postoperative. Fill in the National Eye Institute Refractive Error Quality of Life Instrument-42 before and after surgery.The modulation transfer function (MTF), Optical Quality Analysis System (OQAS) II values (OV 100%, 20%, 9%), and Stahl ratio 1 and 3 months after surgery were higher than the respective preoperative values. The objective scatter index value increased 1 week after surgery, but decreased 1 and 3 months after surgery compared with the preoperative values. Total aberration (TA), total low-order aberration (tLOAs), and defocus decreased at 1 week and 3 months after EVO-ICL implantation. Total high-order aberration (tHOAs) and spherical aberration were significantly increased 1 week after surgery and decreased 3 months after surgery, and the difference was statistically significant. Astigmatism, coma, and clover were not significantly different in each time period. TA, tLOAs, tHOAs, defocus, and spherical aberration were higher at 1 week than 3 months after surgery. At 3 months after surgery, the scores of the patients' NEI-RQL-42 scale were all improved except that the glare was lower than that before surgery. There was no significant difference in the density of corneal endothelial cells before and 3 months after surgery.For patients with hypermyopia, the postoperative subjective and objective visual quality of EVO-ICL implantation was better than preoperative.

The Stereoacuity-Dependent Concordance between Preferred Fixating Eye and Sighting Dominant Eye in Paediatric Intermittent Exotropia.

Objective: To investigate if the concordance between sighting dominance and fixation preference depends on stereoacuity in children with intermittent exotropia (IXT). Methods: A total of 160 children (aged 7.24 ± 2.14 years, range 4-13 years) with the basic type of IXT at distance participated in the study. Binocular fusion and vergence were evaluated with synoptophore. Stereoacuity was assessed using the Titmus stereo test. The hole-in-the-card test was used to determine sighting dominance, while the eye of fixation preference was determined by the cover-uncover test. The chi-squared test was used to evaluate whether a distribution was different from the chance distribution. The Kappa value was computed to quantify the concordance between fixation preference and sighting dominance. Results: The mean deviations were 19 ± 4.58 prism diopters (PD) and 18.9 ± 4.47 PD for at distance and near, respectively. The mean amplitude of divergence was 5.34 ± 1.89 PD, and the mean amplitude of convergence was 14.08 ± 4.96 PD. Subjects were categorized as having either good (40-60 seconds of arc, n = 41), moderate (80-140 seconds of arc, n = 46), poor (≥ 200 seconds of arc, n = 45), or having no measurable stereoacuity (n = 28). The concordance between sighting dominance and fixation preference was high in subjects with good (Kappa = 0.858) or moderate (kappa = 0.812) stereoacuity, but it decreased quickly in subjects with poor stereoacuity (kappa = 0.496) or no stereopsis (kappa = 0.563). Conclusions: In pediatric patients with IXT, the concordance between sighting dominance and fixation preference depends on stereoacuity. The results from these two tests become increasingly incongruent as stereoacuity deteriorated.

Comparison of visual quality after EVO-ICL implantation and SMILE to select the appropriate surgical method for high myopia.

BACKGROUND: This study sought to compare the visual quality between intraocular collamer lens (EVO-ICL) implantation and small-incision lenticule extraction (SMILE) and determine the appropriate surgical method to treat patients with high myopia (- 6.25 to - 10 D). METHODS: A total of 48 eyes underwent EVO-ICL implantation and another 48 eyes underwent SMILE. The uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BCVA) and equivalent spherical degree were compared across the SMILE (- 6.25 to - 10 D) and EVO-ICL (- 6.25 to - 10 D) implantation groups. Preoperative and postoperative visual quality parameters were compared between and within groups. RESULTS: The OQAS II values (OV 100%) one week and one month after surgery and the modulation transfer function (MTF), OV 20% and OV 9% values one week after surgery in the SMILE group were lower than the respective preoperative values. The objective scatter index (OSI) value increased one week as well as one month after surgery compared with the preoperative values. The MTF cut-off value of the SMILE group was lower than that of the EVO-ICL implantation group three months after surgery. CONCLUSIONS: For patients with high myopia, the postoperative visual quality of EVO- ICL implantation was slightly better than that of SMILE.

Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis.

Oxidative stress in retinal pigment epithelium (RPE) is considered to be a major contributor to the development and progression of age-related macular degeneration (AMD). Previous investigations have shown that sodium tanshinone IIA sulfonate (STS) can alleviate oxidative stress in haemorrhagic shock-induced organ damage and cigarette smoke-induced chronic obstructive pulmonary disease in mice. However, whether STS has a protective effect in ARPE-19 cells under oxidative stress and its exact mechanisms have not yet been fully elucidated. In the present study, we utilized H2O2 to establish an oxidative stress environment. Our findings show that STS activated the PI3K/AKT/mTOR pathway to inhibit autophagy and diminished the expression of the autophagic proteins Beclin 1, ATG3, ATG7 and ATG9 in ARPE-19 cells under oxidative stress. Detection of the intrinsic apoptosis-related factors BAX, mitochondrial membrane potential (MMP), caspase-9, caspase-3 and BCL-2, as well as the extrinsic apoptosis-related factors c-FLIP, v-FLIP and caspase-8, confirmed that STS inhibited the intrinsic and extrinsic apoptotic pathways, and attenuated apoptosis in ARPE-19 cells under oxidative stress conditions. These findings shed new light on the protective effects of STS in ARPE-19 cells and its mechanisms under oxidative stress to provide novel and promising therapeutic strategies for AMD.

Comparison of two techniques for toric intraocular lens implantation: hydroimplantation versus ophthalmic viscosurgical devices.

BACKGROUND: To compare the results between hydroimplantation of a single-piece, acrylic foldable toric intraocular lens (IOLs) and conventional implantation using an ophthalmic viscosurgical device (OVD). METHODS: In this study, 60 eyes with cataract and preexisting regular corneal astigmatism of 1.0 to 3.0 diopters (D) underwent the implantation of the AcrySof toric IOLs (Alcon Laboratories, Inc.). The patients were randomly assigned to a conventional implantation technique with an OVD or a hydroimplantation technique. Comparison of preoperative and postoperative parameters was performed using paired Student t tests, and independent Student t test was used to compare between the two groups. RESULTS: Three months postoperatively, the mean subjective astigmatism was 0.45 D ± 0.24 (SD) in the OVD group and 0.49 ± 0.29 D in the hydroimplantation group (P = 0.492). The mean endothelial cell density (ECD) loss was 7.54% ± 0.82% and 7.32% ± 0.59%, respectively (P = 0.117). The mean absolute IOL rotation was 4.77 ± 2.32 degrees and 4.70 ± 1.95 degrees, respectively (P = 0.334). The mean time for IOL implantation was 71.50 ± 8.10 s and 37.60 ± 3.90 s, respectively (P < 0.001). Two hours, 1 day, 1 week, 1 month, and 3 months postoperatively, there was no significant difference in IOP between the two groups (P > 0.05), although IOP two hours postoperatively seemed to be a little higher in the OVD group. CONCLUSIONS: Compared with the use of OVDs for toric IOLs implantation, the hydroimplantation technique provided advantages of increased efficiency, reduced surgical time and cost, and no concerns of OVD-induced elevated IOP. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55696872 , Retrospectively registered (Date of registration: 25 March 2018).

The inhibitory effect of different concentrations of KH902 eye drops on corneal neovascularization induced by alkali burn.

PURPOSE: The aim of this study was to evaluate the inhibitory effect of different concentrations of KH902 eye drops on rabbit corneal neovascularization (CNV) induced by alkali burn. METHODS: Forty-eight adult rabbits were randomized into four groups after alkali burning: Group A (2.5 mg/ml), Group B (5 mg/ml), and Group C (10 mg/ml) by different concentrations of KH902 eye drops and Group D by saline solution as control with three times a day for 2 weeks. At days 7, 14, and 28, the anterior segment photographs, confocal microscopy, and histopathology were performed to evaluate corneal opacity, neovascularization, inflammatory cell density, vessel size, and edema. Immunohistochemistry was applied to analyze the vascular endothelial growth factor (VEGF) level. RESULTS: (1) The CNV in the medicine-treated groups showed a reduction without obvious corneal side effects histologically. (2) Compared to the control group, the three medicine-treated groups showed a reduction in the VEGF levels and CNV areas on days 7, 14, and 28 and in the inflammatory cell density on days 14 and 28 (P < 0.01). The difference of inflammatory cell density between the three medicine-treated groups existed on day 14 (P < 0.01). There were differences in the VEGF levels between Groups A, B, and C on days 7, 14, and 28 (P < 0.01), not for Groups B and C on day 28 (P > 0.05). CONCLUSION: KH902 eye drops in lower concentration showed an obvious reduction of the CNV growing for rabbit corneal alkali burn without side effects.

Evaluation of meibomian gland and tear film changes in patients with pterygium.

BACKGROUND: Recent studies have demonstrated that pterygium has a close relationship with dry eye disease. This study is to determine abnormalities in meibomian gland and tear function in patients with pterygium and to assess the relationship between the variables. MATERIALS AND METHODS: Forty eyes from forty patients with primary nasal pterygium and forty eyes from forty volunteers without ocular pathologies were enrolled in this study. Ocular surface disease index scores, meibomian gland expression scores, lid margin abnormality scores, meiboscore, tear film breakup time (BUT), Schirmer test (SIT) value, and the lower tear meniscus height (TMH), tear meniscus depth (TMD), and tear meniscus area (TMA) using Fourier domain optical coherence were performed. Analysis of variance was applied for intergroup comparisons. A statistical significance level of P < 0.05 was considered. RESULTS: Ocular symptom scores, BUT scores, lid margin abnormality, meibomian gland expression, and meiboscore were significantly higher in pterygium patients than in controls (P < 0.01 for all scores). However, the SIT scores, the lower TMH, TMD, and TMA values did not revealed a significant difference between two groups (all P > 0.05). Multivariate regression analysis demonstrated that meiboscore significantly correlated with ocular symptom scores, BUT, lid margin abnormality scores, and meibomian gland expression scores. CONCLUSIONS: Meibomian gland function may be altered in pterygium patients, which is associated with uncomfortable ocular symptoms. Being aware of meibomian gland changes seems essential to understand the complex relationship among pterygium, tear film functions, and ocular surface changes.

MiR-613 suppresses retinoblastoma cell proliferation, invasion, and tumor formation by targeting E2F5.

Retinoblastoma is a common intraocular malignancy that occurs during childhood. MicroRNAs play critical roles in the regulation of retinoblastoma initiation and progression, and aberrant expression of miR-613 had been reported in various types of cancer. However, the role and mechanism of its function in retinoblastoma are still unclear. In this study, we found that miR-613 was downregulated in retinoblastoma tissues and cell lines. Overexpression of miR-613 suppressed retinoblastoma cell proliferation, migration, and invasion and induced cell cycle arrest in vitro. Additionally, overexpressed miR-613 also inhibited tumor formation of retinoblastoma cells in vivo. We further identified E2F5 as a direct target of miR-613. Reintroduction of E2F5 without 3'-untranslated region reversed the inhibitory effects of miR-613 on cell proliferation and invasion. Our data collectively indicate that miR-613 functions as a tumor suppressor in retinoblastoma through downregulating E2F5, supporting the targeting of the novel miR-613/E2F5 axis as a potentially effective therapeutic approach for retinoblastoma.

Comparison of femtosecond laser-assisted descemetic and predescemetic lamellar keratoplasty for keratoconus.

PURPOSE: The purpose of this study is to compare the outcomes following femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) with 75% of stromal dissection (predescemetic group) and femtosecond laser-assisted DALK using big-bubble technique with total stromal resection (descemetic group) for the treatment of keratoconus. SUBJECTS AND METHODS: Twenty eyes of 17 patients with keratoconus were studied. There were 10 eyes of 9 patients in predescemetic group and 10 eyes of 8 patients in descemetic group. The postoperative best-corrected visual acuity (BCVA), manifest refraction, keratometry, endothelial cell density (ECD), and central corneal thickness (CCT) were analyzed. RESULTS: All surgeries were performed uneventfully. At 1 year after surgery, the BCVA, corneal astigmatism, keratometry, CCT, and ECD between two groups were not statistically significant (all P > 0.05). However, the mean manifest refraction was -9.43 ± 7.44 diopter (D) and -1.03 ± 1.13D in predescemetic and descemetic groups, respectively, which was statistically significant between two groups (P < 0.05). CONCLUSIONS: The results of BCVA and corneal astigmatism, keratometry, ECD, and CCT were comparable between two groups. However, the mean postoperative manifest refraction was lower in descemetic group.

Clinical application of TICL implantation for ametropia following deep anterior lamellar keratoplasty for keratoconus: A CONSORT-compliant article.

BACKGROUND: This study aimed to investigate the clinical application of phakic toric intraocular collamer lens (TICL) implantation in treating ametropia following deep anterior lamellar keratoplasty (DALK) for patients with keratoconus, especially the effectiveness and safety of high astigmatism and indications of TICL implantation after corneal transplantation. METHODS: Using the self-controlled case series observation approach, 9 patients with ametropia (9 eyes) who underwent DALK surgery for keratoconus 1.5 years ago with stitches removed 3 months ago were kept under observation from May 2013 to April 2014 in Ophthalmic Center of Nanjing Drum Tower Hospital affiliated to Nanjing Medical University. TICL implantation was performed in all patients. The uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) were examined before surgery and 1 week, 6 months, 1 year, and 2 years after surgery. Corneal astigmatism, corneal thickness, anterior chamber depth, corneal endothelial cell density (ECD), and preoperative and postoperative intraocular pressures at different time points were measured. Intraoperative or postoperative complications of TICL implantation were observed, and the safety of the operation was evaluated. RESULTS: The UCVA and BCVA in all operated eyes were better 6 months after surgery than before surgery. The spherical diopter and cylindrical diopter decreased to different degrees after surgery. Six months after surgery, the deviation of TICL axis in all operated eyes was less than 10 degrees, tending to be stable. No severe intraoperative or postoperative complication occurred. CONCLUSION: TICL implantation was an optional choice for ametropia correction after DALK surgery, especially in patients with high astigmatism.