Decreased retinal microvasculature densities in pterygium.

AIM: To investigate the retinal vascular network alterations in eyes of patients with pterygium. METHODS: Totally 18 left eyes from 18 female pterygium patients and 18 left eyes from 18 female healthy control subjects were enrolled. Optical coherence tomography angiography (OCTA) images were generated of the superficial retinal layer and deeper retinal layer of the macular retina for each eye. The microvascular (MIR) and macrovascular (MAR) densities were calculated and MIR, MAR, and total microvascular (TMI) density was compared in the healthy control and pterygium groups. RESULTS: In pterygium group, in the superficial retinal layer, the vascular density in superficial MIR, superior right (SR), inferior right (IR), right (R), superficial central annuli (SC)1, SC2, and SC3 decreased significantly in the macular area (P<0.05). Furthermore, the vascular density in all those decreased regions except R, was significantly and negatively correlated with the disease course (r=-0.6038 to -0.7762, P=0.0008), and the area size of pterygium (r=-0.6043 to -0.9508, P<0.05). For the deeper retinal layer, the density of deep total microvessel (DTMI), deeper MIR, SR, IR, R, DC2, and DC3 decreased significantly in macular area of pterygium patients (P<0.05). Furthermore, the vascular density in all those decreased regions was significantly and negatively correlated with the disease course (r=-0.6901 to -0.7795, P=0.0015), and the area size of pterygium (r=-0.6043 to -0.9563, P<0.05). No statistically significant differences and correlation was found in other region density (|r|<0.47, P>0.05). CONCLUSION: OCTA findings suggest that pterygium patients present with decreased retinal MIR density, and the major vascular alterations occurr mainly on the bitamporal side. The vascular density of the superficial SC1, SC2, SC3 adjacent to the foveal and deep layer of DC2, DC2 regions, significantly decreased.

Abnormal interhemispheric functional connectivity in patients with strabismic amblyopia: a resting-state fMRI study using voxel-mirrored homotopic connectivity.

BACKGROUND: Previous studies have demonstrated that strabismus amblyopia can result in markedly brain function alterations. However, the differences in spontaneous brain activities of strabismus amblyopia (SA) patients still remain unclear. Therefore, the current study intended to employthe voxel-mirrored homotopic connectivity (VMHC) method to investigate the intrinsic brain activity changes in SA patients. PURPOSE: To investigate the changes in cerebral hemispheric functional connections in patients with SA and their relationship with clinical manifestations using the VMHC method. MATERIAL AND METHODS: In the present study, a total of 17 patients with SA (eight males and nine females) and 17 age- and weight-matched healthy control (HC) groups were enrolled. Based on the VMHC method, all subjects were examined by functional magnetic resonance imaging. The functional interaction between cerebral hemispheres was directly evaluated. The Pearson's correlation test was used to analyze the clinical features of patients with SA. In addition, their mean VMHC signal values and the receiver operating characteristic curve were used to distinguish patients with SA and HC groups. RESULTS: Compared with HC group, patients with SA had higher VMHC values in bilateral cingulum ant, caudate, hippocampus, and cerebellum crus 1. Moreover, the VMHC values of some regions were positively correlated with some clinical manifestations. In addition, receiver operating characteristic curves presented higher diagnostic value in these areas. CONCLUSION: SA subjects showed abnormal brain interhemispheric functional connectivity in visual pathways, which might give some instructive information for understanding the neurological mechanisms of SA patients.

Altered Regional Homogeneity in Patients With Corneal Ulcer: A Resting-State Functional MRI Study.

OBJECTIVE: To investigate the potential regional homogeneity (ReHo) brain activity changes in patients with corneal ulcer (CU) and their possible relationship with clinical symptoms. MATERIALS AND METHODS: Forty patients with CU (26 men and 14 women), and 40 healthy controls (HCs) (26 men and 14 women) closely matched in age, sex, and weight underwent resting-state functional MRI scans, respectively. The ReHo method was applied to evaluate synchronous neural activity changes. Receiver operating characteristic curve (ROC curve) was used to show high test-retest stability and high degree of sensitivity and specificity. We utilized the correlation analysis to calculate the relationship between the average ReHo signal values in different brain areas and the clinical symptoms in CU patients. RESULTS: Compared with the HCs, CU patients had significantly increased ReHo values in right cerebellum posterior lobe, left cerebellum posterior lobe, left inferior temporal gyrus, right lingual gyrus, left middle frontal gyrus, left angular gyrus, left cingulate gyrus, right angular gyrus and bilateral superior frontal gyrus, and decreased ReHo values in right anterior cingulate and left precentral gyrus. ROC curve analysis of each brain regions showed the accuracy of AUC was perfect except the right cerebellum posterior lobe. Nevertheless, there was no clear evidence of prominent relevance between the average ReHo values in brain areas and the clinical symptoms. CONCLUSION: Corneal ulcer caused dysfunctional adaption in different brain areas, which including relatively increased values and decreased values. This finding may help us take a further step in exploring the underlying pathologic mechanisms of CU.

Assessment of synchronous neural activities revealed by regional homogeneity in individuals with acute eye pain: a resting-state functional magnetic resonance imaging study.

OBJECTIVE: Previous neuroimaging studies have demonstrated that pain-related diseases are associated with brain function and anatomical abnormalities, whereas altered synchronous neural activity in acute eye pain (EP) patients has not been investigated. The purpose of this study was to explore whether or not synchronous neural activity changes were measured with the regional homogeneity (ReHo) method in acute EP patients. METHODS: A total of 20 patients (15 males and 5 females) with EP and 20 healthy controls (HCs) consisting of 15 and 5 age-, sex-, and education-matched males and females, respectively, underwent resting-state functional magnetic resonance imaging. The ReHo method was applied to assess synchronous neural activity changes. RESULTS: Compared with HCs, acute EP patients had significantly lower ReHo values in the left precentral/postcentral gyrus (Brodmann area [BA]3/4), right precentral/postcentral gyrus (BA3/4), and left middle frontal gyrus (BA6). In contrast, higher ReHo values in acute EP patients were observed in the left superior frontal gyrus (BA11), right inferior parietal lobule (BA39/40), and left precuneus (BA7). However, no relationship was found between the mean ReHo signal values of the different areas and clinical manifestations, which included both the duration and degree of pain in EP patients. CONCLUSION: Our study highlighted that acute EP patients showed altered synchronous neural activities in many brain regions, including somatosensory regions. These findings might provide useful information for exploration of the neural mechanisms underlying acute EP.

Antiangiogenic effects of catalpol on rat corneal neovascularization.

To investigate the effects of catalpol on corneal neovascularization (CNV) and associated inflammation, eye drops (5 mM catalpol or PBS) were administered four times daily to alkali­burn rat models of CNV and inflammation. Clinical evaluations of CNV and the degree of inflammation were performed on days 0, 4, 7, 10 and 14 under slit lamp microscopy. Eyes were collected on day 14 and prepared for hematoxylin and eosin, and immunofluorescence staining; corneal cell apoptosis was investigated via terminal deoxynucleotidyl transferase­mediated nick end labeling (TUNEL) staining. Protein expression levels of angiogenic and proinflammatory factors, including vascular endothelial growth factor (VEGF), pigment epithelium­derived factor (PEDF), tumor necrosis factor­α (TNF­α) and necrosis factor­κB (NF­κB) were determined by western blotting. The effects of catalpol on cell proliferation were investigated in vitro using human umbilical vein endothelial cells (HUVECs) and a Cell Counting kit­8 (CCK­8); alterations in migration and tube formation were investigated via HUVEC wound closure and tube formation assays. HUVEC viability and proliferative ability were inhibited in a dose­dependent manner; catalpol also decreased HUVEC cell migration and tube forming ability. Within alkali­burn rat models, decreased inflammation and CNV was associated with catalpol administration; as demonstrated with TUNEL, corneal cell apoptosis was decreased in response to catalpol. Western blot analysis revealed reduced protein expression levels of VEGF and TNF­α; however, PEDF and phosphorylated­NF­κB p65 were increased due to catalpol administration. The present study demonstrated the inhibitory effects exerted by catalpol on CNV and inflammation within alkali­burned rat models. Topical application of catalpol in vivo was associated with reduced CNV and inflammation; therefore, catalpol may be considered an anti­inflammatory agent for the clinical treatment of CNV.

Inhibitory effects of S100A4 gene silencing on alkali burn-induced corneal neovascularization: an in vivo study.

OBJECTIVE: The purpose of this study is to explore the inhibitory effects of S100A4 gene silencing on alkali burn-induced corneal neovascularization (CNV) in rabbit models. METHODS: Sixty-five rabbits were used to establish alkali-induced CNV models. After the operation, rabbits were given daily antibiotic eye drops and an eye ointment to prevent infection. The models were assigned to either an S100A4 siRNA or an empty vector group. Thirty rabbits were selected as the normal control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression of S100A4, vascular endothelial growth factor (VEGF), and tumor necrosis factor-α (TNF-α) in corneal tissues. Immunohistochemistry was used to detect the protein expression of VEGF in corneal tissues, and an enzyme-linked immunosorbent (ELISA) assay was used to detect the protein expression of VEGF and TNF-α in the aqueous humor. RESULTS: The qRT-PCR results showed that S100A4 mRNA expression was lower in the S100A4 siRNA group than in the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. When compared with the empty vector group, the expression of VEGF and TNF-α mRNA was downregulated in the S100A4 siRNA group. The immunohistochemistry results revealed that VEGF protein expression was downregulated in the S100A4 siRNA group when compared to the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. The ELISA results suggest that VEGF and TNF-α protein expression is downregulated in the S100A4 siRNA group in comparison to the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. CONCLUSIONS: These findings indicate that S100A4 gene silencing can inhibit alkali burn-induced CNV in rabbits.

Clinical observation of the efficacy of Bevacizumab combined with argon green laser in treating fundus macular edema.

We studied the clinical efficacy of Bevacizumab combined with argon green laser in treating fundus macular edema. From May 2009 to April 2013, 78 patients seeking treatment for macular edema in the First Affiliated Hospital of Nanchang University were enrolled in this study. Patients were randomly divided into two groups: i) The experimental group (n=39) and the control group (n=39). Patients in the experimental group were treated with Bevacizumab (Avastin®) combined with argon green laser, and those in the control group were treated exclusively with argon green laser. Therapeutic effects were compared, and postoperative adverse reactions caused by both treatment methods were compared. Our results showed that, after treatment, the macular foveal thickness was reduced noticeably in both groups, while the therapeutic effect of combined treatment was more prominent. Patients in the experimental group gained the best-corrected visual acuity after one month of treatment, while patients in the control group achieved that after three months of treatment. We concluded that the use of Avastin® combined with argon green laser was safe and effective. Visual acuity was improved obviously with minimum adverse reactions.

Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells.

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for cancer treatment. In this study, we described a novel VEGFR2 inhibitor, xanthatin, which inhibits tumor angiogenesis and growth. The biochemical profiles of xanthatin were investigated using kinase assay, migration assay, tube formation, Matrigel plug assay, western blot, immunofluorescence and human tumor xenograft model. Xanthatin significantly inhibited growth, migration and tube formation of human umbilical vascular endothelial cell as well as inhibited vascular endothelial growth factor (VEGF)-stimulated angiogenesis. In addition, it inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator. Moreover, xanthatin directly inhibit proliferation of breast cancer cells MDA-MB-231. Oral administration of xanthatin could markedly inhibit human tumor xenograft growth and decreased microvessel densities (MVD) in tumor sections. Taken together, these preclinical evaluations suggest that xanthatin inhibits angiogenesis and may be a promising anticancer drug candidate.

Analysis of corneal topography in patients with pure microphthalmia in Eastern China.

OBJECTIVES: To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. METHODS: Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. RESULTS: Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. CONCLUSIONS: Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia.

[Experimental study on efficiency of Spanishneedles Herb eye drops in treating perimenopausal xerophthalmia in rabbits].

OBJECTIVE: To investigate the efficiency of Spanishneedles Herb eye drops in treating perimenopausal xerophthalmia in rabbits. METHOD: Totally 36 rabbits (36 right eyes) were ovariectomized, and 2 months later divided into three groups: the experimental group (group A, n = 12) given Spanishneedles Herb eye drops, the control group (group B, n = 12) given PBS and the model group (group C, n = 12) given no drug. The Schirmer I test (SIT), fluorescent (FL), total tear protein, diastase activity, lactoferrin and lysozyme contents and confocal scanning microscopy were performed at before the treatment and at 1 w, 2 w, 1 mo, 2 mo after the treatment. RESULT: Before the treatment, There was no significant difference in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity between two groups. Two months later after the treatment, both the group B and the group A showed differences degrees of changes in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity compared with that before the treatment, with statistical differences (P < 0.05); At each time point, both groups revealed statistical differences in SIT, FL, total tear protein, lysozyme, lactoferrin and amylase activity (1 < 0.05). Two months later alter the treatment, densities of basal epithelial cells and inflammatory cells in the group A were (4 122 ±416) cells/mm2 and (339 ± 131) cells/mm2, while that in the group B were (3 343 ± 424) cells/mm2 and (49 ± 17) cells/mm2, with statistical differences between them (P < 0.05). CONCLUSION: Spanishneedles Herb eye drops could effectively treat perimenopausal xerophthalmia in rabbit caused by sex hormones decline.

Effects of Honghua preserved amniotic membrane on scar healing in experimental glaucoma surgery.

AIM: To investigate the efficacy and safety of Honghua preserved amniotic membrane (AM) for preventing scar formation of the filtering bleb in a rabbit model of glaucoma trabeculectomy surgery. METHODS: Totally 36 rabbits (36 eyes) were randomly divided into 3 groups: the experimental group (ocular trabeculectomy in combination with Honghua preserved AM transplantation), the control group (ocular trabeculectomy surgery in combination with AM implantation), and the blank group (single trabeculectomy). Clinical observations [including intraocular pressure (IOP), filtering blebs and complications], Masson-Trichrome staining, real-time quantitative reverse transcription-polymerase chain reaction (real-time PCR), Western blot were performed on different time points (D1, D7, D14, D21 and D56) after the surgery. RESULTS: After operated for 14d, there were statistically significant differences in the filtering blebs compared to the situation before operation (P<0.05), whereas no statistically difference on that among three groups (P>0.05). After 21d, the IOP of experimental group was lowest (P<0.05). There was significant difference between control group and blank group (P<0.05). On postoperative D14, the mean number of fibroblasts in the experimental group was significantly lower (40.6±10.2) compared to those in the control group (54.4±10.8) and blank group (68.2±11.6) (P<0.05, respectively). The mean numbers of the macrophage in the experimental and control groups were respcitively significantly lower versus the blank group (P<0.05, P<0.05, respectively). Compared to that in blank group, the level of transforming growth factor-ß (TGF-ß1) expression in sclera and conjunctival areas was reduced in the experimental and control groups on protein and mRNA level (P<0.05), but not significant difference between these two groups (P>0.05). CONCLUSION: The trabeculectory surgery with Honghua preserved AM can control IOP, sustain the functional filtration bleb, inhibit the proliferation of fibroblasts and open the filtrating pathway on the rabbit glaucoma models.

The expression and distribution of α-Gal gene in various species ocular surface tissue.

AIM: To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue. METHODS: α-Gal binding assay were carried out on various animal eye sections. Photograph, slit-lamp observation on various eye showed normal corneal transparence. RESULTS: A strong α-Gal expression in invertebrates and some vertebrates ocular tissue, but no α-Gal binding in birds, fish and mammal. α-Gal expression change in the development of mice ocular surface tissue (except sclera) and display genus dependency in the different murine ocular surface tissue. CONCLUSION: This study identified specific α-Gal epitopes binding area in the ocular surface of several species and may solve the problem that naive ocular surface may be used as natural α-Gal gene knockout model/high risk immunologic rejection model or ocular surface scaffold material.

Evaluation of novel decellularizing corneal stroma for cornea tissue engineering applications.

AIM: To develop a new decellularization method depended upon the natural corneal structure and to harvest an ideal scaffold with good biocompatibilities for corneal reconstruction. METHODS: The acellular cornea matrix (ACM) were prepared from de-epithelium fresh porcine corneas (DFPCs) by incubation with 100% fresh human sera and additional electrophoresis at 4°C. Human corneal epithelial cells (HCEs) were used for the cytotoxicity tests of ACM. ACM were implanted into the Enhanced Green Fluorecence Protein (eGFP) transgenic mouse anterior chamber for evaluation of histocompatibility. RESULTS: HE and GSIB4 results showed fresh porcine cornea matrix with 100% human sera and electrophoresis could entirely decellularize stromal cell without reducing its transparency. ACM had no cytotoxic effect ex vivo. Animal test showed there was no rejection for one month after surgery. CONCLUSION: These results provide a decellularizing approach for the study of corneal tissue engineering and had the broader implications for the field of biological tissue engineering in other engineered organ or tissue matrix.

Aerocyst urethral catheter insertion compared to expansion sponges application in external dacryocystorhinostomy.

AIM: To evaluate the clinical effect and complications of two different filling materials (aerocyst urethral catheter and expansion sponges) applying in external dacryocystorhinostomy (EXT-DCR) and compare their advantages and disadvantages. METHODS: A retrospective study was made in the period from April, 1 2000 to April, 1 2005. Totally 180 patients (240 eyes) underwent the EX-DCR using different filling materials and divided into three groups randomly: negative control groups (group 1), expansion sponges group (group 2) and aerocyst urethral catheter group (group 3). The gender, etiology, clinical findings, surgical technique, filling materials, the condition of ocular surface and complications were analyzed. Filling materials were removed during day 7. Postoperative success was determined by lacrimal patency to irrigation, a positive dye test, hemorrhage and errhysis conditions after extubation and subjective resolution of epiphora and liquor puris. RESULTS: During a mean follow-up of 5.14±1.69 years, the success rate were 73.7% (group 1), 86.5% (group 2), 98.7% (group 3) in three groups. There was significant statistical difference among three groups in the surgical success rate and the operative complications (including hemorrhage, errhysis, periorbital ecchymosis after extubation)(P<0.05). CONCLUSION: EXT-DCR with aerocyst urethral cathete intraoperatively have higher success rate, fewer operative complications and a high patient satisfaction ,and can be used to simplify and speed up traditional EXT-DCR.

Therapeutic efficacy of intracameral amphotericin B injection for 60 patients with keratomycosis.

AIM: To evaluate the therapeutic efficacy of intracameral amphotericin B (ICAMB) injection in the treatment of keratomycosis. METHODS: The study design was a prospective controlled clinical trial. A total of 60 eyes of 60 patients were divided into two groups, 30 in the ICAMB injection group (group A) and 30 in the control group-topical application amphotericin B (group B). Serial measurements of the size of the keratomycosis-namely, two maximum linear dimensions perpendicular to each other, and the area and perimeter was done at start of therapy and follow up on day 3, 7, and 21. Rate of healing of the keratomycosis were measured as percentage decrease from the baseline parameter at each subsequent follow up. The data were analyzed by the non-parametric Wilcoxon rank sum test. RESULTS: The mean time to disappearance of hypopyon was 9.6±9.2 (range:1-26) days in group A and 26.8±20.8 (range:14-62) days in group B (P=0.03). The median percentage decrease in the size of the keratomycosis was significantly greater than that in the cord serum group at day 21(P<0.05) when measured in terms of the area and perimeter. A greater number of patients showed complete re-epithelialization in group A (n=27) than in group B (n=14) (P<0.05). None of the patients reported any side effects or discomfort with either treatment. CONCLUSION: ICAMB injection leads to faster healing of the keratomycosis refractory to all medical management and reducing time to disapperence of hypopyon compared to topical application amphotericin B.

[Silicone union of orbital periosteum and eyeball under muscle belly for treatment of strabismus fixus].

OBJECTIVE: To evaluate the effect of silicone union of orbital periosteum and eyeball under muscle belly on the treatment of fixed paralytic strabismus. METHODS: The data from 23 cases (23 eyes) which included esotropia (22 eyes) and exotropia (1 eye) was collected, 11 and 12 patients were diagnosed as complete-fixed strabismus (CFS) and sub-fixed strabismus (SFS) respectively. After antagonist recession was completed, a silicone union (1 mm of its diameter) was used to make a connection between the anterior sclera of paralytic muscle insertion and lateral or medial canthus periosteum of orbital. Eyeball position was adjusted to orthophoria by the traction of silicone union. RESULTS: Orthophoria was obtained in all of 23 eyes. Eyes rotation compared with normal eye toward paralytic side were 25% (5 eyes), 50% (2 eyes), 75% (3 eyes) respectively after surgery. CONCLUSION: Silicone union is a elastic material, it is one of better methods for the correction of fixed strabismus.