BACKGROUNDManganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2+ to understand the applicability of MEMRI.

METHODSForty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group (n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups (n = 5 in each subgroup). Rabbits were given 8 drops of MnCl2in 5 min intervals. The Mn2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2+ was evaluated with corneal imaging and pathology slices.

RESULTSBetween the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2+ concentration times. The intraocular Mn2+ concentration increased with the concentration gradients of Mn2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups.

CONCLUSIONSThe corneal epithelium is a barrier to Mn2+, and the iris and lens septum might be another intraocular barrier to the permeation of Mn2+. An elevated Mn2+ concentration contributes to the increased permeation of Mn2+, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2+ concentration in the vitreous body.

Administration, Topical ; Animals ; Aqueous Humor ; drug effects ; metabolism ; Cornea ; drug effects ; metabolism ; Epithelium, Corneal ; drug effects ; metabolism ; Magnetic Resonance Imaging ; methods ; Male ; Manganese ; administration & dosage ; pharmacokinetics ; pharmacology ; Rabbits ; Visual Pathways ; drug effects ; Vitreous Body ; drug effects ; metabolism

INTRODUCTIONWhile corticosteroids are an effective choice of treatment for severe vernal keratoconjunctivitis (VKC), their long-term use is restricted due to side effects. This study was conducted to evaluate the efficacy and safety of topical cyclosporine A (CsA) 0.05% in the treatment of VKC.

METHODSA total of 30 patients with VKC that was resistant to topical corticosteroids, antihistamines and mast cell stabilisers were treated with topical CsA 0.05%. Patients were evaluated at Weeks 4, 8 and 12 after the initiation of therapy. Symptoms and signs observed before and after treatment were recorded and scores were assigned. Scores for symptoms and signs, the need for topical corticosteroids and ocular side effects were evaluated.

RESULTSAt baseline, the median values of the symptom and sign scores were 10.0 (range 5.0-18.0) and 6.0 (range 2.0-13.0), respectively. At Week 4 of treatment with topical CsA 0.05%, the median values of the symptom and sign scores were 3.0 (range 0-14.0) and 3.0 (range 0-8.0), respectively. The reductions in the symptom and sign scores were statistically significant. The reduction in the need for corticosteroid was statistically significant by Week 12 of therapy. No significant side effects were reported.

CONCLUSIONTopical CsA 0.05%, which can help to reduce corticosteroid usage, is an effective and safe alternative for the treatment of resistant VKC. Further studies are needed to determine the optimal duration of therapy and possibility of recurrence.

Administration, Topical ; Adolescent ; Adrenal Cortex Hormones ; administration & dosage ; Adult ; Child ; Cohort Studies ; Conjunctivitis, Allergic ; drug therapy ; Cornea ; drug effects ; Cyclosporine ; administration & dosage ; Drug Administration Schedule ; Eye ; drug effects ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; Male ; Recurrence ; Young Adult

OBJECTIVETo investigate the effects of ursolic acid on corneal graft rejection in a rat model of othotopic corneal allograft transplantation.

METHODSForty-eight recipient Wistar rats were divided into normal control group with saline treatment (group A), autograft group with saline treatment (group B), SD rat allograft group with saline treatment (group C), and SD rat allograft group with intraperitoneal ursolic acid (UA) treatment group (group D). The rats received saline or UC (20 mg·kg(-1)·d(-1)) treatment for 12 days following othotopic graft transplantation. The grafts were evaluated using the Larkin corneal rejection rating system, and the graft survival was assessed with Kaplan-Meier analysis. On day 14, the grafts were harvested for histological examination, Western blotting, and assessment of expressions of interlukin-2 (IL-2), interferon-γ (IFN-γ), nuclear transcription factor-κB (NF-κB) p65, vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1).

RESULTSThe allograft survival was significantly longer in group D than in group C (29.12±9.58 vs 9.67±2.16 days, P<0.05). UC treatment obviously reduced the expression levels of IL-2, IFN-γ, NF-κBp65, ICAM-1 and VEGF and increased inhibitory kappa B alpha (IκB-α) expression in the grafts, where no obvious inflammatory cell infiltration or corneal neovascularization was found.

CONCLUSIONAs a NF-κB inhibitor, ursolic acid can prevent corneal neovascularization and corneal allograft rejection to promote graft survival in rats following orthotopic corneal allograft transplantation.

Animals ; Cornea ; metabolism ; Corneal Neovascularization ; prevention & control ; Corneal Transplantation ; Graft Rejection ; prevention & control ; Graft Survival ; drug effects ; I-kappa B Proteins ; metabolism ; Intercellular Adhesion Molecule-1 ; metabolism ; Interferon-gamma ; metabolism ; Kaplan-Meier Estimate ; NF-KappaB Inhibitor alpha ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Transcription Factor RelA ; metabolism ; Transplantation, Homologous ; Triterpenes ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo evaluate the efficacy of epigallocatechin gallate (EGCG) in treatment of corneal alkali burn injury in mice.

METHODSCorneal alkali burn injury was induced by sodium hydroxide method in C57BL/6J mice. The mice with cornea burns were treated intraperitoneally with EGCG solution or phosphate buffer solution (PBS) respectively. The healing of corneal epithelium, the formation of corneal neovascularization (CNV) and the inflammation reaction were assessed by slit -lamp microscopy and histological examination. Expression of vascular endothelial growth factor (VEGF) mRNA and protein in cornea was evaluated by real -time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Myeloperoxidase (MPO) assay was used to quantitatively evaluate the polymorphonuclear neutrophils (PMNs) infiltration in the corneas.

RESULTSThe healing rate of corneal epithelium in EGCG group was significantly higher than that of PBS group at d1, d3 and d7 after treatment (d1: 41.0%±13.0% vs 23.8%±7.6%; d3: 76.6%±7.5% vs 61.2%±6.8%; d7: 87.8%±8.5% vs 74.0%±9.1%; all P <0.05). The CNV scores and the number of CNV in the corneal sections of EGCG group were significantly lower than those of PBS group at d3, d7 and d14 after treatment (CNV score: d3: 1.1±0.5 vs 6.6±1.0; d7: 1.3±0. 3 vs 8.1±1.0; d14: 0.9±0.2 vs 9.2±1.1; CNV number: d3: 1.68±0.61 vs 2.92±0.95; d7: 4.80±1.36 vs 7.92±1.28; d14: 3.64±0.71 vs 5.88±0.76; all P<0.05) . The expression of VEGF protein at d3 (0.19±0.05 vs 0.45±0.08) and d7 (0.42±0.07 vs 0.84±0.09), the expression of VEGF mRNA at d1, d3 and d7 in EGCG group were significantly lower than those in PBS group (all P <0.05). Compared to PBS group, the inflammatory index at d3 (3.2±0.4 vs 3.7±0.5) and d7 (2.3±0.5 vs 4.0±0.0), the number of PMNs in the corneal sections and the MPO values at d3, d7 and d14 in EGCG group were significantly decreased (PMNs: d3: 34.5±15.7 vs 90.0±28.8; d7: 17.1±11.4 vs 54.9±25.9; d14: 12. 8±4.6 vs 39.0±17.9; all P <0.05).

CONCLUSIONIn the murine corneal alkali burn model, intraperitoneal injection of EGCG solution can promote the healing of corneal epithelium, inhibit the formation of CNV and reduce the inflammatory cell infiltration in the corneas.

Alkalies ; Animals ; Burns, Chemical ; drug therapy ; Catechin ; analogs & derivatives ; therapeutic use ; Cornea ; drug effects ; pathology ; Corneal Neovascularization ; prevention & control ; Disease Models, Animal ; Eye Burns ; drug therapy ; Inflammation ; drug therapy ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophils ; cytology ; RNA, Messenger ; Vascular Endothelial Growth Factor A ; metabolism

PURPOSE: To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. RESULTS: There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. CONCLUSIONS: The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
Animals ; Conjunctiva/*drug effects/pathology ; Cornea/metabolism ; Disease Models, Animal ; Drug Combinations ; Dry Eye Syndromes/*drug therapy/metabolism ; Emollients/administration & dosage ; Female ; Goblet Cells/drug effects/metabolism/pathology ; Hyaluronic Acid/*administration & dosage ; Mice ; Mice, Inbred C57BL ; Mineral Oil/*administration & dosage ; Ophthalmic Solutions ; Tears/*metabolism ; Viscosupplements/administration & dosage

PURPOSE: To compare the epithelial wound healing response of two preservative-free fluoroquinolones, moxifloxacin and levofloxacin, in patients who underwent cataract surgery. MATERIALS AND METHODS: In this prospective, evaluator-masked, randomized clinical trial, 59 eyes of 50 patients who underwent cataract surgery were enrolled. Patients were randomized to receive moxifloxacin 0.5% (n=32 eyes) or levofloxacin 0.5% (n=27 eyes). All patients instilled moxifloxacin or levofloxain four times daily for 1 week prior to surgery and 2 weeks after surgery. The epithelial wound healing status in the corneal incision site was scanned with a raster scan mode of fourier-domain optical coherence tomography (FD-OCT). The number of eyes showing epithelial defect images and average number of corneal epithelial defect cuts per eye were compared between groups. All patients were evaluated on postoperative days 1, 2, 3, and 10. RESULTS: On postoperative days 1, 2, and 3, the number of eyes showing epithelial defects in FD-OCT was not statistically different (all p>0.05). The average number of corneal epithelial defect cuts was also not statistically different between the two groups (all p>0.05). No eyes showed epithelial defects on postoperative day 10 in either group. CONCLUSION: There were no differences on epithelial wound healing comparing these two different fluoroquinolones at the incision site of cataract surgery.
Aged ; Aza Compounds/therapeutic use ; Cataract Extraction ; Cornea/drug effects/*surgery ; Female ; Fluoroquinolones/*therapeutic use ; Humans ; Levofloxacin/therapeutic use ; Male ; Middle Aged ; Quinolines/therapeutic use ; Tomography, Optical Coherence ; Wound Healing/*drug effects

BACKGROUNDPretreatment with chemical agents could alter the surface chemistry of the silicone gel, which makes it suitable for epithelial migration onto its surface and thus enhances the cytobiocompatibility. This study aimed to evaluate the biological response of the corneal stroma to porous silicone gel pretreated with different chemical agents in vivo.

METHODSThe porous silicone gels were treated with a mixed acid solution containing 23.2% H2SO4 and 0.8% K2Cr2O7 for 10 or 15 minutes or with 30% H2O2 for 15 minutes. Discs (4 mm in diameter) were inserted into interlamellar stromal pockets of New Zealand white rabbits and followed up for a period of 3 months. Clinical evaluations such as corneal infiltration, edema and neovascularization were performed daily. At 3 months, the fibroplasias and collagen deposition were examined under light and scanning electron microscopy (SEM) and by immunohistochemical analysis.

RESULTSPretreatment of the discs obviously decreased conjunctival congestion, discharge, cornea edema, and the extent of neovascularization. More fibroblasts migrated into the pretreated discs than into the control, and collagen was deposited, indicating that the biocompatibility of the corneal replacements was enhanced by the chemical pretreatments. From immunohistochemical analysis, Type I collagen deposition in the pretreated silicone discs was greater than in the control.

CONCLUSIONSChemical treatment of silicone gel is effective in decreasing rabbit corneal inflammation, encouraging fibroblast in-growth, and enhancing tissue compatibility. Pretreated gels show good biological stability when used as a skirt material in Keratoprosthesis (Kpros).

Animals ; Biocompatible Materials ; adverse effects ; chemistry ; Cornea ; drug effects ; ultrastructure ; Corneal Edema ; etiology ; Corneal Stroma ; drug effects ; Microscopy, Electron, Scanning ; Porosity ; Prostheses and Implants ; Rabbits ; Silicone Gels ; adverse effects ; chemistry

OBJECTIVETo investigate the effect of integrin α9β1 on corneal angiogenesis and the expression of vascular endothelial growth factor A (VEGF-A) in rats after corneal suture.

METHODSThirty-nine SD rats were randomly divided into normal control group, corneal suture model group, α9β1 group, and α9β1 suppression group, and in the latter 3 groups, the rats received topical administration of levofloxacin, levofloxacin + α9β1, and levofloxacin+ anti-α9β1 monoclonal antibody (Y9A2) twice daily after corneal suture, respectively. At 3, 5, 7, 14 days after the surgery, 3 rats were randomly selected from each group to observe corneal neovascularization (CNV) under slit lamp. RT-PCR and Western blotting were used to detect the expressions of VEGF-A.

RESULTSCNV was not observed in normal cornea. Neovascularization occurred in the corneal limbus in the 3 corneal suture groups, and the leak neovascularization count (CNVC), which occurred on the 7th postoperative day, was significantly increased after α9β1 treatment compared with that in the model group (4.57∓0.31 vs 3.21∓0.19, P<0.05) but markedly decreased after α9β1 suppression (2.03∓0.26, P<0.05). VEGF-A was expressed at a low level in normal cornea, and increased significantly in the model group, reaching the peak level on 7th day (P<0.05); corneal VEGF-A expression was further enhanced by α9β1 treatment (P<0.05) while significantly lowered by α9β1 suppression (P<0.05).

CONCLUSIONIntegrin α9β1 can promote CNV by up-regulating VEGF-A expression and α9β1 suppression produces the opposite effect after corneal suture in rats.

Animals ; Cornea ; drug effects ; metabolism ; Corneal Neovascularization ; metabolism ; Female ; Integrins ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Sutures ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVEFungal keratitis (FK) is a vision-threatening infection, whose treatment requires more effective and safer anti-fungal agent exploitation urgently. With this aim, we focused on the effect of an extracellular polysaccharide on fungal adhesion to human corneal epithelial cells.

METHODSWe performed the cytotoxicity assays of the extracellular polysaccharide EPS-II from an antarctic bacterium Pseudoaltermonas and evaluated its inhibitory effect on Candida albicans cells' adherence to human corneal epithelial cells (HCECs).

RESULTSEPS-II, which displayed minor cytotoxicity but also promoted proliferation of HCECs, could inhibit the adherence of yeast cells to HCECs in a dose-dependent manner. EPS-II could also suppress the subsequent PI3K/AKT signaling pathway, and thereby decrease the expression of early inflammatory cytokines.

CONCLUSIONSExtracellular polysaccharide EPS-II was suggested as a new natural agent for attenuating FK.

Blotting, Western ; Candida ; drug effects ; physiology ; Cell Adhesion ; drug effects ; Cornea ; microbiology ; Humans ; Phosphorylation ; Polysaccharides, Bacterial ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Pseudoalteromonas ; metabolism

OBJECTIVETo evaluate the therapeutic effects of epidermal growth factor (EGF) combined with plasma cryoprecipitate (CRYO) on the corneal injury induced by paraquat (PQ).

METHODSAccording to the "Toxicological test methods of pesticides for registration" (GB 15670-1995), the conjunctival sacs of 18 health New Zealand rabbits were exposed to 100 µl 20% PQ, which were randomly divided into EGF, CRYO and EGF plus CRYO groups. The routine treatments (normal saline washing and antibiotic eyedrops) were administrated to the injured eyes of 3 groups, at the same time the left eyes of 3 groups were treated with EGF, CRYO and EGF plus CRYO, respectively. The injury of conjunctival, iris and corneal, fluorescent stranded and pathology changes of corneal were observed. The injury score was calculated and the recovery time of corneal injury was recorded.

RESULTSThe recovery time of corneal injury in EGF and EGF plus CRYO groups were 19.50 ± 3.08 and 18.67 ± 2.73 days, respectively which were significantly lower than those (27.33 ± 2.58 and 26.83 ± 3.13 days) in corresponding routine treatment controls (P < 0.05).

CONCLUSIONEGF and EGF plus CRYO could be used to treat the corneal injury induced by paraquat.

Animals ; Blood Transfusion, Autologous ; Cornea ; drug effects ; Corneal Injuries ; Epidermal Growth Factor ; therapeutic use ; Eye Injuries ; chemically induced ; drug therapy ; Factor VIII ; therapeutic use ; Fibrinogen ; therapeutic use ; Ophthalmic Solutions ; Paraquat ; adverse effects ; Plasma ; Rabbits ; Treatment Outcome ; Wound Healing ; drug effects