One-year results of intravitreal conbercept in treatment-naïve subjects with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months. METHODS: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12. RESULTS: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 µm at baseline to 308.73 ± 106.80 µm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm3 at baseline to 0.48 ± 0.71 mm3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81. CONCLUSION: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

An experimental study of amniotic lacrimal duct stents in the treatment of perimenopausal female rabbits with dry eye.

The aim of the present study was to investigate the effects of an amniotic membrane lacrimal stent in the treatment of dry eye syndrome in a perimenopausal rabbit model. In total, 48 healthy female rabbits were randomly divided into four groups (12 rabbits/group): Group A, sham­operated group; group B, negative control group; group C, sham­implantation group; and group D, implantation with amniotic membrane lacrimal stents. A Schirmer I test (SIT), corneal fluorescein staining, optical coherence tomography angiography and corneal confocal microscopy were conducted and the biomechanical properties of the amniotic membrane were measured prior to and 2, 4 and 6 weeks after the operations. There were marked differences in the amount of tear secretion and the SIT following the operation compared with prior to the operation. The amount of tear secretion of group B and C was significantly reduced (F=8.894; P=0.0017). Compared with groups A, B and C, group D demonstrated a significant increase in the amount of tear secretion and a significant reduction in SIT (P<0.05). However, there was no statistical difference between the tear secretion of the A, B and C groups (P>0.05). The cornea epithelial of groups A and D was significantly thinner compared with groups B and C. The superior part [superior temporal (ST)5, superior (S)5, superior nasal (SN)5, ST6, S6 and SN6] was significantly thinner compared with the central part of the cornea epithelium. The corneal epithelia of all groups were thin in the center and thick at the edge. At 6 weeks after the operation, group D exhibited a markedly decreased number of anterior stromal luminescent cells, compared with groups A, B and C. Furthermore, the bending degree of corneal stromal neural trunks was significantly improved, and the density, branches and curvature of corneal epithelium sub­basal nerves ameliorated to a certain extent (P<0.05). Amniotic membrane lacrimal stents demonstrated specific therapeutic effects on dry eye in perimenopausal female rabbits.

A murine model of dry eye induced by topical administration of erlotinib eye drops.

In the present study, the effects of erlotinib on mouse tear function and corneal epithelial tissue structure were investigated. Throughout the 3 weeks of treatment, no notable differences were observed in the body, eye or lacrimal gland weights of the control and experimental mice. However, in the experimental group, the tear volume and break­up times of tear film were significantly lower following treatment with erlotinib compared with the control group. Corneal fluorescein staining in the experimental group revealed patchy staining, and the Lissamine green staining and inflammatory index were significantly higher in the experimental group at 3 weeks than in the control group. In the experimental group, the number of corneal epithelium layers increased significantly following treatment with erlotinib for 3 weeks and a significant increase in the number of vacuoles was observed compared with the control group. Treatment with erlotinib significantly increased the corneal epithelial cell apoptosis, and led to a significantly increased number of epithelial cell layers and increased keratin 10 expression. It also significantly reduced the number of conjunctival goblet cells. Transmission electron microscopy and scanning electron microscopy revealed that the corneal epithelial surface was irregular and there was a substantial reduction and partial loss of the microvilli in the experimental group. Mice treated with erlotinib also exhibited an increased protein expression of tumor necrosis factor­α and decreased protein expression of phosphorylated­epidermal growth factor receptor in the corneal epithelial cells. The topical application of erlotinib eye drops was revealed to induce dry eyes in mice. This is a novel method of developing a model of dry eyes in mice.

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.

Retinal microvasculature alteration in central serous chorioretinopathy.

The aim of the present study was to investigate the changes of retinal microvascular network in patients with central serous chorioretinopathy (CSCR). A total of fifteen patients (right eye) with CSCR and 15 normal controls (right eye) were recruited. We used optical coherence tomography angiography to scan 6x6 mm macular retinal blood flow images with the application of a series of customized image segmentation processing program software to obtain microvascular and macrovascular density, and compared the superficial microvascular (SMIR), superficial macrovascular ring (SMAR) and the superficial total microvascular (STMI) density between CSCR patients and control group. Using the annular partition (C1­C6) and quadrant partition methods on the macular, we compared the retinal vessel density changes. We also performed ROC analysis of superficial retinal microvessel density in CSCR retina to investigate the relationship between the microvascular density, the foveal thickness and visual acuity. The density of STMI and SMIR decreased in macular area in the patients with CSCR compared to the normal controls (P<0.05), while the density of SMAR did not change significantly. We found no significant difference in the density of SMIR with the quadrant partition method, whereas the annular partition method showed significantly decreased SMIR density only in the C1 region in patients with CSCR (P<0.05), with no significant difference observed in C2­C6 regions. The density of SMIR had the highest differentiation power in the CSCR group, whereas the density of SC1 ring had the lowest differentiation power by the annular method. The largest area under the ROC curves was 0.77. The correlation index of the SMIR density and visual acuity was ­0.544, whereas macular thickness and visual acuity was ­0.644 in the CSCR group. The density of STMI and SMIR were decreased in patients with CSCR, which might provide further understanding of the pathogenesis of CSCR.

Altered brain network centrality in patients with adult comitant exotropia strabismus: A resting-state fMRI study.

Objective To investigate the underlying functional network brain-activity changes in patients with adult comitant exotropia strabismus (CES) and the relationship with clinical features using the voxel-wise degree centrality (DC) method. Methods A total of 30 patients with CES (17 men, 13 women), and 30 healthy controls (HCs; 17 men, 13 women) matched in age, sex, and education level participated in the study. DC was used to evaluate spontaneous brain activity. Receiver operating characteristic (ROC) curve analysis was conducted to distinguish CESs from HCs. The relationship between mean DC values in various brain regions and behavioral performance was examined with correlation analysis. Results Compared with HCs, CES patients exhibited decreased DC values in the right cerebellum posterior lobe, right inferior frontal gyrus, right middle frontal gyrus and right superior parietal lobule/primary somatosensory cortex (S1), and increased DC values in the right superior temporal gyrus, bilateral anterior cingulate, right superior temporal gyrus, and left inferior parietal lobule. However, there was no correlation between mean DC values and behavioral performance in any brain regions. Conclusions Adult comitant exotropia strabismus is associated with abnormal brain network activity in various brain regions, possibly reflecting the pathological mechanisms of ocular motility disorders in CES.

Effect of mistletoe combined with carboxymethyl cellulose on dry eye in postmenopausal women.

AIM: To investigate the protective effect of mistletoe combined with carboxymethyl cellulose eye drops on dry eye in postmenopausal women. METHODS: Sixty postmenopause female patients diagnosed of dry eye were assigned randomly to mistletoe combined with carboxymethyl cellulose eye drops treatment group (n=30) and control group treated with normal saline eye drops (n=30). The subjective symptoms of ocular surface, Ocular Surface Disease Index (OSDI), tear film function tests, tear protein and corneal morphology by confocal scanning microscopy were analyzed before treatment and at 1, 2, 4 and 8wk after treatment respectively. To ensure the safety of the trial, all patients were examined with systolic pressure, diastolic pressure, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, urine creatinine, and blood urea nitrogen at 8wk after treatment. RESULTS: There were no obvious differences between two groups before the treatment (P>0.05). In two months after the treatment, the symptoms of ocular surface, OSDI, tear protein, and tear film function were only slightly changed in normal saline eye drops group. However, all indices were improved after the treatment of mistletoe combined with carboxymethyl cellulose eye drops group (P<0.05). In addition, the average amount of corneal epithelium basal cells and inflammatory cells of mistletoe treated group were 3174±379 and 38±25 cells/mm2, significantly decreased as compared to the control group with 4309±612 and 158± 61 cells/mm2, respectively. In the control group, although nerves still maintained straight under corneal epithelium, the number of nerves were significantly decreased, as compared with normal female. In the mistletoe treated group, the number of nerves was only slightly reduced, compared with normal female. CONCLUSION: Mistletoe combined with carboxymethyl cellulose eye drops can alleviate the symptoms and signs of dry eye symptoms.

Analysis of corneal morphologic and pathologic changes in early-stage congenital aniridic keratopathy.

AIM: To determine typical corneal changes of congenital aniridic keratopathy (CAK) using corneal topography and confocal systems, and to identify characteristics that might assist in early diagnosis. METHODS: Patients with CAK and healthy control subjects underwent detailed ophthalmic examinations including axial length, corneal thickness, tear film condition, corneal topography, and laser-scanning in vivo confocal microscopy (IVCM). RESULTS: In early stage aniridic keratopathy, Schirmer I test (SIT), break-up time (BUT), mean keratometry (mean K) and simulated keratometry (sim K) were reduced relative to controls (P<0.05), while simulation of corneal astigmatism (sim A) and corneal thickness were increased (P<0.05). In addition, significantly more eyes exhibited flat cornea compared with the control group. Inflammatory dendritic cells were present in the aniridic epithelium, with significantly increased density relative to controls (P<0.05). Palisade ridge-like features and abnormal cell morphology were observed in six out of sixteen CAK cases. In central cornea area, the aniridic corneas had the increased subbasal nerve density. CONCLUSION: These changes in corneal morphology in borderline situations can be useful to confirm the diagnosis of CAK.