Xiaoyan Ding

Choroidal thickness in fellow eyes of patients with acute primary angle-closure measured by enhanced depth imaging spectral-domain optical coherence tomography.

PURPOSE We evaluated choroidal thickness in the fellow eyes of patients with acute primary angle-closure (APAC) and compared findings to those of normal controls. METHODS The study group comprised 44 fellow eyes defined as primary angle-closure suspect (PACS) of 44 subjects who had experienced APAC and 43 eyes of 43 healthy volunteers. Using enhanced depth imaging optical coherence tomography (EDI-OCT), the peripapillary and macular choroidal thickness of the PACS eyes and the control eyes were measured and compared at each location or segment. Pearson correlation analysis and a multivariable regression model were used to evaluate the relationships between choroidal thickness and related factors. RESULTS At all the macular locations, the choroidal thickness was thickest at the subfovea. The PACS eyes had a thicker choroid than the control eyes at all macular locations (all P < 0.05), and it still was significantly thicker after controlling for age, axial length, and sex, except at 3 mm superior from the fovea (P = 0.124). Multivariable linear regression analysis showed that the subfoveal choroidal thickness was significantly thicker in association with the PACS diagnosis, and thinner in association with older subjects and longer axial length eyes. There were no statistically significant differences in the choroidal thickness between the groups at any peripapillary location or segment (P > 0.05). CONCLUSIONS PACS eyes that had a fellow eye experience of APAC had a thicker macular choroid than the control eyes. The potential role of a thicker choroid as a risk factor for APAC must be investigated further.

Peripapillary choroidal thickness in healthy Chinese subjects

BackgroundTo evaluate the peripapillary choroidal thickness of a healthy Chinese population, and to determine its influencing factors.MethodsA total of 76 healthy volunteers (76 eyes) without ophthalmic or systemic symptoms were enrolled. Choroidal scans (360-degree 3.4 mm diameter peripapillary circle scans) were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography. Choroid thickness was measured at the temporal, superotemporal, superior, superonasal, nasal, inferonasal, inferior, and inferotemporal segments.ResultsThe average peripapillary choroidal thicknesses were 165.03 ± 40.37 μm. Inferonasal, inferior, and inferotemporal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, nasal thicknesses (p < 0.05). No statistically significant difference was found among inferonasal, inferior, and inferotemporal thicknesses. The average peripapillary choroidal thickness decreased linearly with age (β = −1.33, 95% CI −1.98, -0.68, P < 0.001). No correlation was noted between average choroidal thickness and other factors (gender, refractive error, axial length, average retinal nerve fiber layer thickness, intraocular pressure, diastolic blood pressure, systolic blood pressure, mean blood pressure, diastolic ocular perfusion pressure, systolic ocular perfusion pressure, and mean ocular perfusion pressure).ConclusionsThe inferonasal, inferior, inferotemporal peripapillary choroidal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, and nasal thicknesses. A thinner peripapillary choroid is associated with increasing age.

Levels of Erythropoietin and Vascular Endothelial Growth Factor in Surgery-Required Advanced Neovascular Glaucoma Eyes Before and After Intravitreal Injection of Bevacizumab

PURPOSE To evaluate changes of levels of erythropoietin (EPO) and VEGF in aqueous humor before and after an intravitreal injection of bevacizumab (IVB) and determine the underlying correlation between them. METHODS This prospective study involved 21 eyes of 21 patients with surgery-required advanced neovascular glaucoma (NVG) and 20 control subjects from October 2011 through November 2012. The NVG eyes received the IVB treatment before antiglaucomatous surgery. Aqueous humor was collected at the time of the IVB injection (pre-IVB) and at the time of antiglaucomatous surgery (post-IVB). Aqueous humor and plasma VEGF and EPO levels were measured with ELISA and chemiluminescence methods, respectively. RESULTS The mean aqueous humor EPO and VEGF concentrations in pre-ivb eyes were significantly higher than those of the control subjects (p 0.001), whereas plasma levels showed no significant difference. There was a statistically significant correlation between the aqueous humor epo and the VEGF concentration (R = 0.612; P = 0.003). The mean aqueous humor VEGF in post-ivb eyes dramatically decreased from 1704.83 757.82 TO 19.02 14.65 PG/ML (P 0.001). However, EPO remained almost the same: 326.60 ± 104.28 compared with 312.67 ± 103.23 mU/mL (P = 0.675). CONCLUSIONS The NVG eyes showed high aqueous EPO and VEGF levels, and there was a positive correlation between them. However, levels of EPO did not change after post-IVB, whereas those of VEGF decreased.

Levels of angiogenesis-related vascular endothelial growth factor family in neovascular glaucoma eyes

This study aimed to evaluate the angiogenesis‐related factors of the vascular endothelial growth factor (VEGF) family in the aqueous humour of patients with neovascular glaucoma (NVG).

Macrophage polarization in experimental and clinical choroidal neovascularization.

Macrophages play an important role in the development of age-related macular degeneration (AMD). In this study, the spatial and temporal changes and the polarization of macrophages in murine laser-induced choroidal neovascularization (CNV) were investigated, and the polarized M1 and M2 biomarkers in the aqueous humors of neovascular AMD (nAMD) patients were studied. Macrophages, the main infiltrating inflammatory cells in CNV lesions, were evidenced by a significant increase in F4/80 mRNA expression and by the infiltration of F4/80+ cells in the lesions and the vicinity of laser-induced CNV. The mRNA expressions of M1-related markers were dramatically upregulated in the early stage, while the M2-related markers were slightly upregulated in the middle stage and sustained until the late stage. The results of immunostaining showed a similar early-but-transient M1 pattern and a delayed-but-sustained M2 pattern in laser-induced CNV. In addition, a higher M2/M1 ratio was found in both the murine models (Arg-1/iNOS and CCL22/CXCL10) and the aqueous humors of nAMD patients (CCL22/CXCL10) than in the controls. Our results suggested that the dynamic patterns of M1 and M2 were different in both the experimental and clinical CNV. The M2 macrophages were predominant and may play a more important role in the development of CNV.

Posterior pole retinal abnormalities in mild asymptomatic FEVR.

PURPOSE To describe the posterior retinal abnormalities in asymptomatic mild familial exudative vitreoretinopathy (FEVR) individuals who are normal in conventional clinical examination. METHODS Thirty-eight asymptomatic mild FEVR individuals (38 eyes) and 38 controls (38 eyes) were included in this cross-sectional study. The posterior retinas in each individual appeared normal. The diagnosis of FEVR was made based on a positive FEVR family history and the presence of retinal peripheral avascular zone with other vessel abnormalities. Biometric data from fundus photographs and fluorescein fundus angiography of all subjects were studied. The diameter of the optic disc (DD), the disc-to-macula distance (DM), the ratio of DM/DD, and numbers of retinal vessels radiated from the optic disc were measured. RESULTS Significant anatomic differences were identified in the eyes of patients with asymptomatic FEVR compared with those of the control subjects. In individuals with stage I or II FEVR, DD was smaller (1605.34 ± 250.60 vs. 1733.39 ± 163.79 μm), DM was larger (5434.08 ± 824.82 vs. 4696.29 ± 257.34 μm), and DM/DD was higher (3.49 ± 0.93 vs. 2.73 ± 0.28) than those of the controls. Peripapillary retinal vessels were increased significantly in FEVR compared with the controls (24.53 ± 3.10 vs. 21.39 ± 2.65). CONCLUSIONS Asymptomatic individuals with stage I or II FEVR had several abnormalities in the posterior pole noted with more retinal vessels, a significantly larger disc-to-macula distance as well as a remarkably smaller optic disc with a decreased horizontal diameter. These findings will facilitate the early diagnosis of FEVR and are important for adequate genetic counseling as well as the prevention and treatment of this disease.

Combinatorial treatment with topical NSAIDs and anti-VEGF for age-related macular degeneration, a meta-analysis

Inflammation is a key pathogenic factor in age-related macular degeneration (AMD). However, the clinical importance of combining anti-VEGF agents and topical NSAIDs to reduce inflammation remains unclear. In this study, we systematically reviewed clinical trials comparing combined treatment versus anti-VEGF alone in AMD patients. We quantified treatment effects via meta-analysis. The pooled weighted mean difference (WMD, -0.91, 95%CI: -1.39 to -0.42, P = 0.0003) demonstrates that combined treatment may reduce required anti-VEGF injection number, probably by means of decreasing central retina thickness (CRT) (WMD = -22.9, 95% CI: -41.20 to -4.59, P = 0.01). The best corrected visual acuity (BCVA) did not change significantly between these two groups (WMD = - 0.01, 95%CI: -0.23 to 0.20, P = 0.90). Topical NSAIDs slightly increased the incidence of foreign body sensation (Odds Ratio [OR] = 2.63, 95%Cl: 1.06 to 6.52, P = 0.76). Combining topical NSAIDs and anti-VEGF agents may provide a new strategy for AMD treatment.

Mutation Spectrum of the LRP5, NDP, and TSPAN12 Genes in Chinese Patients With Familial Exudative Vitreoretinopathy

Purpose LRP5, NDP, and TSPAN12 are known to be associated with familial exudative vitreoretinopathy (FEVR). In this study, a comprehensive mutation screening for the three genes was performed in patients with a clinical diagnosis of FEVR in Han Chinese. Methods Genomic DNA and clinical data were collected from 100 probands and their family members. Sanger sequencing was performed to screen for LRP5, NDP, and TSPAN12 mutations and phenotype-genotype correlation was analyzed. Results There were 23 causative mutations identified in 23 unrelated probands (10/23 in LRP5, 8/23 in TSPAN12, and 5/23 in NDP). Apart from NDP mutations, only two LRP5 mutations inherited in an autosomal recessive manner. Among the 23 causative mutations, 13 were novel variants (4/10 in LRP5, 6/8 in TSPAN12, and 3/5 in NDP). According to the modified classification system, statistical significance was observed in the distribution of mutated genes (P = 0.049). None of the causative mutations was found in group I FEVR. Probands with LRP5 or NDP mutations were mainly categorized into group III and IV, TSPAN12 mutations were mainly observed in probands with group IV and V FEVR. Conclusions The detection rate for mutations in the three known genes was 23%. Mutations in LRP5 and TSPAN12 were more frequent, accounting for 10% and 8%, respectively. The NDP mutations were only identified in 6% in this cohort. There were 13 novel variants found, which provided a deeper understanding of this disease. Potential phenotype-genotype correlation was observed in the modified system. TSPAN12 mutations might lead to the most severe phenotype.

Placenta Growth Factor in Eyes with Neovascular Glaucoma Is Decreased after Intravitreal Ranibizumab Injection

Purpose To evaluate changes in the concentrations of placental growth factor (PlGF) and vascular endothelial growth factor-A (VEGF-A) in aqueous humor of patients with neovascular glaucoma (NVG) before and after an intravitreal injection of ranibizumab (IVR) and to determine the underlying correlation between the levels. Methods The prospective interventional comparative study involved 20 eyes of 20 patients with surgery-required advanced NVG and 20 control subjects from January 2013 to November 2013. The NVG eyes received the IVR treatment before glaucoma surgery. Aqueous humor was collected at the time of the IVR injection (pre- IVR) and at the time of antiglaucomatous surgery (post-IVR). Aqueous humor was also collected at the time of cataract surgery in normal control. Aqueous humor and plasma VEGF-A and PlGF levels were measured with an enzyme-linked immunosorbent assay methods, respectively. Results The mean aqueous humor PlGF and VEGF-A concentrations in the pre-IVR eyes were significantly higher than in those of the control subjects (p<0.001), whereas the plasma levels showed no significant difference. There was a statistically significant correlation between the aqueous humor PlGF and the VEGF-A concentration (r = 0.612, p = 0.003). The mean aqueous humor PlGF in the post-IVR eyes dramatically decreased from 1078.36 ± 755.83 to 177.64 ± 151.73 pg/mL (p<0.001). The VEGF-A level showed a similar trend from 3697.64 ± 2104.47 pg/mL to 183.54 ± 130.35 pg/mL (p<0.001). Conclusions Aqueous humor concentrations of VEGF-A and PlGF were significantly elevated in the eyes with NVG, and there was a positive correlation between the levels. After an IVR treatment, VEGF-A and PlGF were significantly decreased in NVG eyes.

Association of IGFN1 variant with polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) and neovascular age‐related macular degeneration (nAMD) share a similar phenotype but are different in their clinical manifestations, responses to treatment and prognosis. Whether PCV is a subtype of AMD or a distinct entity from nAMD remains unknown. Therefore, we performed a whole‐exome sequencing based association analysis to compare the genetic architecture of PCV and nAMD in Han Chinese.