4D label-free proteomics analysis of oxygen-induced retinopathy with or without anti-VEGF treatment.

Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.

Long-Term Quantitative Analysis of Inner Retinal Dimples and Visual Function Post Internal Limiting Membrane Peeling in Macular Diseases.

INTRODUCTION: Inner retinal dimples (IRDs) are frequently detected after internal limiting membrane (ILM) peeling. However, the distribution of IRDs and its effect on postoperative visual function remain unclear. We aim to quantify the distribution of IRDs after ILM peeling in different macular diseases and analyze its influence on postoperative visual function. METHODS: We retrospectively reviewed patients undergoing vitrectomy with ILM peeling and followed up until 12 months in our center. The distribution of IRDs were quantitatively determined using optical coherence tomography (OCT) and OCT angiography in a different sector of Early Treatment Diabetic Retinopathy Study grid. Visual function was evaluated by retinal sensitivity (RS) using microperimetry. Spearman correlation was performed between RS and IRDs within the same sectors. Multivariate linear regression analysis was performed to analyze the association between baseline characteristics and IRDs. RESULTS: A total of 43 idiopathic macular hole (iMH) cases, 56 idiopathic epiretinal membrane (iERM) cases and 42 myopic foveoschisis (mFS) cases were included. IRDs increased gradually at ILM-peeled area, interrupting ganglion cell layer. Most IRDs were observed in temporal sector. A negative correlation was depicted between the increase of IRDs and the progress of RS at both perifovea and parafovea in iERM, but only at perifovea in iMH. No significant correlation between the change of IRDs and RS was found in mFS. Multivariable linear regression model showed that preoperative axial length was significantly associated with postoperative IRDs in all patients. CONCLUSIONS: IRDs distributed mostly at temporal sector after ILM peeling, interrupting ganglion cell layer. IRD progression may influence postoperative RS only in iMH and iERM. Ophthalmologists may avoid temporal sector especially in eyes with normal axial length or strong ILM-ERM adherence.

Quantitative assessment of retinal microvascular remodeling in eyes that underwent idiopathic epiretinal membrane surgery.

Purpose: To explore the surgical outcomes of the macular microvasculature and visual function in eyes with idiopathic epiretinal membrane (iERM) using spectral-domain optical coherence tomography angiography (SD-OCTA). Methods: This observational, cross-sectional study included 41 participants who underwent iERM surgery with a 3-month (3M) follow-up. Forty-one healthy eyes formed the control group. The assessments included best-corrected visual acuity (BCVA) and mean sensitivity (MS) by microperimetry and SD-OCTA assessment of vessel tortuosity (VT), vessel density (VD), foveal avascular zone, and retinal thickness (RT). Results: The findings showed statistically significant differences in VT, foveal avascular zone parameters, RT, BCVA, and MS between the iERM and control groups (p < 0.05). After iERM surgery, the macular VT, SCP VD, and RT decreased significantly (p < 0.01) while the DCP VD increased (p = 0.029). The BCVA improved significantly (p < 0.001) and was associated with the MS (rs = -0.377, p = 0.015). MS was associated with the SCP VD and RT at 3M (SCP VD rs = 0.511, p = 0.001; RT rs = 0.456, p = 0.003). In the superior quadrant, the MS improved significantly (p < 0.001) and the improvement of MS was associated with the reduction of VT (ß = -0.330, p = 0.034). Conclusion: Microcirculatory remodeling and perfusion recovery were observed within 3 months after iERM surgery. VT was a novel index for evaluating the morphology of the retinal microvasculature in eyes with iERM and was associated with MS in the superior quadrant.

Macular Retinal Sensitivity and Microvasculature Changes before and after Vitrectomy in Idiopathic Macular Epiretinal Membrane with Classification.

PURPOSE: To observe retinal sensitivity (RS) and microvasculature changes in preoperative and postoperative idiopathic macular epiretinal membrane (iERM) with optical coherence tomography (OCT) classification by microperimetry (MP) and optical coherence tomography angiography (OCTA). METHODS: In this retrospective study, 53 eyes of 53 patients affected with iERM were enrolled and 35 iERM eyes underwent pars plana vitrectomy associated with internal limiting membrane peeling. All iERM eyes were evaluated and graded by OCT. According to the thickness of the fovea relative to the surrounding macula from OCT radial line scans, we classified iERM into 3 grades. MP was used to measure RS of macular within 20° centered on the fovea and fixation stability (FS). OCTA was used to measure the superficial and deep capillary plexus (DCP) layers using 6 mm × 6 mm scans. Measurements were taken at the baseline visit and 3-month postoperation. Evaluated factors included: best corrected visual acuity, RS, FS, vessel density. RESULTS: Eyes with iERM had worse RS than control eyes (p < 0.0001), especially in higher grade iERM eyes. And higher grade iERM eyes had a marked increase foveal vessel density (FVD) (p < 0.0001) in superficial capillary plexus (SCP) and DCP, and a significant decrease parafoveal vessel density (Para VD) in DCP. After surgery, there was no difference in RS and FS than preoperation (p > 0.05), whether in grade 1 or 2 iERM eyes. However, in OCTA analyses, grade 1 iERM eyes had less whole vessel density (WVD) and perifoveal vessel density (Peri VD) in SCP, than preoperation (p < 0.05). And grade 1 iERM eyes had higher Para VD and Peri VD in DCP (p < 0.05), than preoperative OCTA results. Grade 2 iERM eyes had less WVD, FVD, and Peri VD in SCP, than preoperation (p < 0.05). After surgery, in grade 2 iERM eyes, there was a positive correlation between whole retinal sensitivity and WVD (p < 0.05) in SCP. And there were positive correlations between Para RS and Para VD (p < 0.05), Peri RS and Peri VD (p < 0.05) in SCP. CONCLUSIONS: Classification helps to reveal different changes in iERM eyes. Higher grade iERM eyes had worse RS and microvasculature changes. MP and OCTA play an important role in assessing iERM and help surgical decisions for patients with iERM.

Macular density alterations in myopic choroidal neovascularization and the effect of anti-VEGF on it.

AIM: To analyse macular microvascular alterations in myopic choroidal neovascularization (mCNV) and the efficiency of anti-vascular endothelial growth factor (anti-VEGF) therapy for mCNV by optical coherence tomography angiography (OCTA). METHODS: A total of 123 patients were included in this retrospective study, divided into mCNV group, high myopia (HM) group, and normal group at the Affiliated Eye Hospital of Wenzhou Medical University from January 2017 to January 2019. Superficial vessel density, deep capillary density, foveal avascular zone (FAZ) area, A-circularity index (AI) and vessel density around the 300 µm width of the FAZ region density (FD) and the area of choroidal neovascularization (CNV) lesion (only for mCNV group) were measured on 3×3 mm2 OCTA images. FAZ area was corrected for axial length. Central macular thickness (CMT) was measured on OCT in mCNV group. Compared the parameters on OCTA of 3 groups and pre-anti-VEGF and post-anti-VEGF at 1, 2, 3, and 6mo follow-up in mCNV group. RESULTS: There were significant differences among 3 groups in superficial vessel density, deep capillary density and FD (P<0.05). FAZ area in HM group was smaller than normal group (P<0.05), but there was no significant difference between mCNV group and the other two group. AI increased in mCNV group (P<0.05). The mean CMT, area and flow area of CNV lesion decreased after treatment (P<0.05), while vessel density and FAZ didn't change. The mean CMT, area and flow area of CNV lesion statistically decreased after anti-VEGF treatment in mCNV group (P<0.05), while superficial vessel density, deep capillary density and FAZ area, AI and FD didn't change. The mean reduction ratio of lesions was 50.32% (7.07% to 100%). Lesion regression 100% was observed in 2 cases (4.88%). There was a negative correlation between the CNV lesion area and reduction ratio (r=-0.380, P=0.042) and the flow lesion area and reduction ratio (r=-0.402, P=0.030). CONCLUSION: Macular vessel density decreases, FAZ turns smaller and more irregular in mCNV eyes. Anti-VEGF therapy is efficient for mCNV without affecting vessel density and FAZ, but it is unable to completely eliminate CNV lesions in most cases. The bigger mCNV lesions have lower reduction ratio.

Comprehensive evaluation of intravitreal conbercept versus half-dose photodynamic therapy for chronic central serous chorioretinopathy.

AIM: To compare the safety and efficacy of conbercept intravitreal injection and half-dose photodynamic therapy (PDT) in treating chronic central serous chorioretinopathy (CSC). METHODS: This study was retrospective. Thirty-seven patients (37 eyes) with chronic CSC received conbercept injections while 57 patients (57 eyes) were treated with half-dose PDT. All subjects were followed in 6mo. Outcome measures included change in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and resolution of subretinal fluid (SRF). RESULTS: There was no adverse event observed in either treatment group. At the 6-month follow-up, 26 eyes (70.3%) in the conbercept group and 54 eyes (94.7%) in the half-dose PDT group (P<0.05) reached full resolution of SRF. The mean logarithm of the minimum angle of resolution (logMAR) BCVA significantly improved (P<0.001) in both treatment groups with better outcome at early phase in the half-dose PDT group (2wk, 1, and 2mo, P<0.05). All subjects experienced significant CMT improvement (P<0.001) with no statistical difference between the two groups (P>0.05). The SFCT also improved in all subjects (P<0.001) with better outcome in the half-dose PDT group (P<0.05). CONCLUSION: Both intravitreal conbercept and half-dose PDT are safe to use in treating chronic CSC. By 6mo, both treatment groups are efficacious in improving BCVA, reducing CMT and SFCT, and resolving SRF in eyes with chronic CSC. Half-dose PDT may show better outcome at initial phase of treatment in chronic CSC. Longer follow-up period is necessary to study for long-term effect and safety.

Assessment of macular microvasculature features before and after vitrectomy in the idiopathic macular epiretinal membrane using a grading system: An optical coherence tomography angiography study.

PURPOSE: To evaluate pre- and postoperative microvasculature features in eyes with different idiopathic macular epiretinal membrane (iERM) classifications using optical coherence tomography angiography (OCTA). METHODS: In this retrospective study, 100 eyes with iERM were enrolled; 62 eyes underwent pars plana vitrectomy (PPV). All iERM eyes were evaluated and graded using optical coherence tomography (OCT). According to the thickness of the fovea relative to the surrounding macula from OCT radial line scans, we classified iERM into three grades. Optical coherence tomography angiography (OCTA) was used to measure the foveal avascular zone (FAZ)-related parameters and the superficial and deep capillary plexus layers using 3 × 3 mm scans. Measurements were taken at baseline and 3 months postoperatively. Best corrected visual acuity (BCVA), vessel density (VD), FAZ area, FAZ perimeter (PERIM), acircularity index (AI), and foveal vessel density (FD) were evaluated. RESULTS: Idiopathic macular epiretinal membrane (iERM) eyes with a higher grade had a lower FAZ area and perimeter (p < 0.0001), higher foveal vessel density (FVD) both in the superficial capillary plexus (SCP) (p < 0.0001) and in the deep capillary plexus (DCP) (p < 0.05), and a lower parafoveal vessel density (PRVD) in the DCP (p < 0.0001). The macular vessel density ratio (MVR = FVD/PRVD) increased with an increase in grade both in the SCP and in the DCP (p < 0.0001). For grade 1 iERM eyes, only PRVD in the DCP significantly changed before versus after the operation (p < 0.05). For grade 2 iERM eyes, the FAZ area and perimeter became larger after the operation (p < 0.05). The MVR of grade 2 iERM eyes decreased postoperatively both in the SCP (p < 0.05) and in the DCP (p < 0.001). For grade 1 and grade 2 iERM eyes, preoperative LogMAR BCVA was negatively correlated with the FAZ area (p < 0.01) and perimeter (p < 0.01), and was positively correlated with the MVR in the SCP (p < 0.05). Postoperative LogMAR BCVA was positively correlated with the FVD in the DCP (p < 0.05). CONCLUSIONS: Idiopathic macular epiretinal membrane (iERM) eyes of different grades have significant differences in microvasculature features. According to OCTA, eyes with higher grades have more serious microvascular changes. Grading plays a part in predicting postoperative microvascular characteristics, and grade 1 iERM eyes have a better visual outcome compared with grade 2 iERM eyes.

Sedimentary mercury (Hg) in the marginal seas adjacent to Chinese high-Hg emissions: Source-to-sink, mass inventory, and accumulation history.

We comprehensively investigated sedimentary Hg in Yellow and East China Seas (YECSs), which constitute potentially important depocenters for large anthropogenic Hg emissions from mainland China. A large dataset of Al-TOC-Hg concentrations led to an in-depth understanding of sedimentary Hg in the entire YECSs, including distribution and its determinants, source-to-sink, background levels, inventory in flux and budget, and accumulation history. Especially, the net atmospheric Hg flux to the sediments was estimated to be 1.3 × 10-5 g/m2/yr, which corresponded reasonably well to that calculated using a box model. About 21.2 tons of atmospheric Hg (approximately 4% of the total anthropogenic atmospheric Hg emissions from China) were buried annually in the YECS basin. This result implies that most of atmospheric Hg from China is transferred to the surface of the Pacific (including the East/Japan Sea and South China Sea) by the westerlies and, consequently, can play a critical role in open-sea aquatic ecosystems.