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Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play significant roles in various diseases; however, their roles in age-related macular degeneration (AMD) remain unclear. Dedifferentiation and dysfunction of retinal pigment epithelium (RPE) cells have been shown to contribute to AMD etiology in several studies. Herein, we found that lncRNA LINC00167 was downregulated in RPE-choroid samples of AMD patients and dysfunctional RPE cells, and it was consistently upregulated along with RPE differentiation. In vitro study indicated that reduced endogenous LINC00167 expression resulted in RPE dedifferentiation, which was typified by attenuated expression of RPE markers, reduced vascular endothelial growth factor A secretion, accumulation of mitochondrial reactive oxygen species, and interrupted phagocytic ability. Mechanistically, LINC00167 functioned as a sponge for microRNA miR-203a-3p to restore the expression of the suppressor of cytokine signaling 3 (SOCS3), which further inhibited the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Taken together, our study demonstrated that LINC00167 showed a protective role in AMD by maintaining RPE differentiation through the LINC00167/miR-203a-3p/SOCS3 axis and might be a potential therapeutic target for AMD., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: We aim to reveal the disease-causing mutations in 15 Chinese families with optic atrophy (OA)., Methods: In total, 15 families with OA were recruited in the present study. Medical histories were carefully reviewed and comprehensive ophthalmic examinations were received by all recruited patients. Targeted next-generation sequencing (NGS) was selectively performed on all probands for mutation detection. Intrafamilial cosegregation and in-silico analyses were subsequently applied to predict the potential pathogenic effects of identified mutations., Results: All included patients presented bilateral vision loss. Their fundus photographs showed temporal or total pallor of the optic discs. Fourteen mutations in the optic atrophy 1 ( OPA1 ) gene were revealed as disease-causing mutations for the 15 families, including eight novel (c.968A>G, c.193C>G, c.1071dupT, c.987_988del, c.2012+2T>G, c.1036-1G>C, c.2126A>G, and c.1036_1038del) and six recurrent (c.1499G>A, c.1800C>A, c.1034G>A, c.2873_2876del, c.112C>T, and c.804_805del) mutations., Conclusions: In conclusion, our study expands the mutational spectrum for the OPA1 gene and implies targeted NGS as an effective approach for the genetic diagnosis of OA, which might help to improve the clinical diagnosis for patients with OA., (Copyright © 2019 Molecular Vision.)

Purpose: To investigate the role of Gremlin-1, which is an endogenous antagonist of the bone morphogenetic protein (BMP) signaling pathway, in inducing epithelium-mesenchymal transition (EMT) in fetal RPE cells after repeated wounds., Methods: Subconfluent repetitive passages in fetal RPE cells were regarded as a model of repeated wounds. A phase contrast microscope was used to observe the morphology and pigment formation in cells. The expression of GREM1 (Gene ID: 26585; OMIM 603054) and EMT- or RPE-related genes in cells was evaluated with quantitative PCR (qPCR). Recombinant human protein Gremlin-1 (0.1 μg/ml) was added every day to investigate the molecular effects of Gremlin-1 on fetal RPE cells. The cell migration rate was investigated using a cell wound scratch assay, and western blotting was used to analyze the representative proteins (P-cadherin, ZO-1, vimentin, Smad4, and phosphorylated-Smads). In addition, transfection of siRNA was used to explore the rescue effects on EMT cells through the downregulation of GREM1 . Finally, LDN193189, which is a type of pan-inhibitor of BMP receptors, was used to verify whether complete blocking of the BMP pathway interferes with the redifferentiation in low-passage fetal cells, even if the cells were treated with transforming growth factor beta 1 (TGF-β) inhibitors., Results: In fetal RPE cells, the expression of GREM1 were gradually upregulated with repetitive passages, and at the same time, the function-specific genes in fetal RPE cells ( TJP1 , PMEL , BEST1 , RPE65 , and MERTK ) were downregulated while the EMT-specific genes were upregulated. In addition, GREM1 had a similar expression pattern as SNAI1 , which is a key transcription factor to trigger EMT. Recombinant human Gremlin-1 promoted EMT with the upregulation of SNAI1 and elevated the cell migration rate in a cell scratch assay, as well as decreased the expression of two key transcription factors of RPE embryonic development ( MITF and OTX2 ) and the RPE marker, RPE65 . Furthermore, the EMT marker, vimentin, and the TGF-β pathway downstream transcription factor phosphorylated-Smad2 (p-Smad2) increased, but the epithelial marker, ZO-1, was reduced. Additionally, Smad4, which plays a role as a Snail1 cooperator by binding Smad3, was also increased. In contrast, GREM1 silencing increased the expression of MITF and OTX2 , which means there was better redifferentiation in subconfluent fetal RPE cells, but it had little influence on p-Smad2 compared to the negative control group. Finally, by adding LDN193189, the BMP signaling pathway was blocked, and this block led to poor redifferentiation in low-passage cells, although the cells were treated with TGF-β inhibitors. In addition, as positive feedback to block the BMP pathway, GREM1 was subsequently upregulated., Conclusions: In fetal RPE cells, Gremlin-1 induces EMT and inhibits redifferentiation by promoting the TGF-β pathway and inhibiting the BMP pathway. GREM1 silencing alleviates EMT and increases the redifferentiation of cells by relieving the blockade of the BMP pathway. However, GREM1 silencing has no effects on the TGF-β pathway. Thus, Gremlin-1 may serve as a novel target to treat proliferative vitreoretinopathy (PVR) and inhibit subretinal fibrosis, which is a risk factor for influencing the therapeutic effects of anti-vascular endothelial growth factor (anti-VEGF) on neovascular age-related macular degeneration (nAMD)., (Copyright © 2019 Molecular Vision.)

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G 1 -phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To quantify the preoperative neovascular change pattern on the fibrovascular membrane (FVM) within 7 days after intravitreal injection of conbercept (IVC) using optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR)., Methods: Prospective, observational study of PDR patients with visible FVM receiving or not receiving IVC. Neovascular changes were assessed by OCTA pre-IVC and 1, 3, 5, and 7 days post-IVC. Vessel skeleton density (SD) and vessel density (VD) were quantified by an intensity-based optical microangiography algorithm. The interclass correlation coefficient (ICC) was calculated to assess the agreement between measurements. The SD and VD were compared between follow-ups using repeated-measures analysis in the IVC group., Results: The ICC was 0.992 (95% confidence interval [CI]: 0.982-0.996) for SD and 0.926 (95% CI: 0.838-0.912) for VD of neovascularization. The neovascularization on FVM significantly regressed in the IVC group (n = 16) compared with no IVC (n = 8) (p = 0.001 for SD and p < 0.001 for VD). The comparisons between consecutive follow-ups showed a statistically significant reduction in SD and VD at 1 and 3 days post-IVC. However, from day 3 onward, the SD and VD remained unchanged. There was no development or progression of tractional retinal detachment within the 7-day period after IVC., Conclusion: OCTA-based quantification of the neovascularization on FVM in PDR is feasible, with high inter-reader agreement. The regression of neovascularization reaches a plateau 3 days after IVC., Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , registration number ChiCTR-IPR-17014160).

Polychlorinated biphenyl (PCB) has been reported to have detrimental effects on retinal development. In order to explore the role of Shh signaling in retinal development after PCB 1254 exposure in vivo and in vitro, zebrafish and RGC-5 retinal cell line were used. Compared with the controls, PCB exposure inhibited proliferation and increased the apoptosis levels. The expression of Shh mRNA decreased in the PCB 1254 -treated groups both in vivo and in vitro compared with that of the controls. The ptch2 mRNA expression increased in the experimental groups. The expression of gli2 mRNA decreased in the PCB 1254 -treated groups. Immunofluorescence and western blotting assays confirmed that the expression of Shh proteins decreased in PCB 1254 -treated groups compared with control groups. Moreover, ptch2 protein levels increased in the PCB 1254 -treated groups as well as the decreased protein expressions of gli1 and gli2. These results demonstrated that Shh signaling pathway may participate in the damage of retinal development caused by PCB 1254 exposure, providing evidence that eye diseases could be caused by environmental pollutants., (© 2018 Wiley Periodicals, Inc.)

Purpose: To design a rigid contact lens (CL) to be used in combination with a wide-angle viewing system and analyze its protection for corneal epithelial during vitreous-retinal surgery., Methods: A thin and lightweight rigid CL was designed and constructed. The impact of the CL on the visualized fundus range was evaluated using a concrete eye model. Patients with severe proliferative diabetic retinopathy (PDR) were randomized to either the CL group, corneal protective agent (CPA) group, or balanced salt solution (BSS) group. All patients underwent phacoemulsification and a standard 23-gauge three-port vitrectomy. Surgery time and corneal fluorescein staining score (FSS) postoperatively were mainly measured., Results: In the eye model, a larger area of fundus was visualized with the use of our CL under 128 D or 60 D Resight lens. The mean surgery time was 51.36±8.06 min, 50.89±8.26 min, and 55.46±9.14 in CL, CPA, and BSS group, respectively (F=2.325, P=0.105). In eight eyes in the BSS group, corneal epithelial layer was peeled off because the dryness of the cornea could not maintain a clear fundus image. The FSS in BSS group was markedly higher than that of CL and BSS group 1 day (P<0.001), 3 days (P<0.001), and 7 days (P=0.002) postoperatively. There was no statistical significance of the FSS between CL and CPA group at each follow-up endpoint., Conclusions: The CL that we designed can slightly enlarge the visible fundus range and efficiently protect corneal epithelium during vitrectomy for patients with PDR.

Purpose: Mutations in the intraflagellar transport protein 52 homolog (IFT52) gene are reported to interrupt ciliary function and cause short-rib thoracic dysplasia (SRTD), a specific form of skeletal ciliopathy. However, the roles of these mutations in retinal ciliopathy are inexplicit. We herein aim to study the impact of IFT52 mutations in retinopathies., Methods: A patient with syndromic ciliopathy, presenting mild SRTD (skeletal ciliopathy) and Liber congenital amaurosis (LCA; retinal ciliopathy), and nine unaffected family members were recruited. Comprehensive systemic evaluations, including ophthalmic tests, were received by the patient. Whole genome sequencing (WGS) was applied for genetic annotation. An in vitro cell system was employed to study the pathogenicity of the variant., Results: WGS identified a homozygous missense variation in IFT52, c.556A>G (p.T186A), carried by the patient but absent in both unaffected siblings. In silico analysis supported the pathogenic nature of this highly conserved variant. Structural analysis suggested that this substitution could generate a novel hydrogen bond between the mutated residue 186 and proline at residue 192, thus potentially interrupting the tertiary structure and the stability of the IFT52 protein. In vitro cellular study indicated that this mutation might disturb the stability of encoded IFT52 protein and dramatically disrupt cilia elongation in hTERT-RPE1 cells in a loss-of-function manner., Conclusions: This report expands ocular phenotypes of IFT52 mutation-caused ciliopathy to include retinal ciliopathy and demonstrates its deleterious nature in interrupting primary ciliary function. Our study hence highlights the need for screening for IFT52 mutations in LCA patients and ophthalmic reviews of patients carrying IFT52 mutations.

Purpose: The purpose of this study is to investigate the effectiveness of a new surgical technique of non-inverted pedicle internal limiting membrane (ILM) transposition for the treatment of eyes with large macular hole., Methods: This is a retrospective, consecutive, interventional case series. Twelve eyes of 12 consecutive patients who underwent vitrectomy for the treatment of a large macular hole (MH size > 400 µm) were treated. ILM was peeled and left with a pedicle attached to the superior temporal retina. The macular hole was covered by transposition of the pedicle ILM in a non-inverted way. Preoperative and postoperative best-corrected visual acuity (BCVA), SD-OCT image, macular sensitivity by microperimetry, and multifocal electroretinogram (mERG) response were evaluated. All of the patients were followed for more than 3 months., Results: Postoperative OCT examination confirmed 11 of 12 macular hole closed (91.7%). Six macular hole filled with silicone oil closed as early as the next day. The postoperative BCVA significantly increased compared with preoperative BCVA (P = 0.002). The improvement of macular sensitivity within 2° and 8° circle was also statistical significant (P = 0.018 and P = 0.017, respectively). Fixation stability, shown as the percentage of fixation point within the 2° circle and 4° circle, was remarkably improved (P = 0.017 and P = 0.018, respectively). The R1/R2 and R1/R4 ring ratios also increased significantly as compared with that of baseline., Conclusion: These findings indicate that the non-inverted pedicle ILM transposition results in a high incidence of anatomic closure with good visual outcome for the treatment of large macular hole.

Age-related macular degeneration (AMD) is a multifactorial disease resulting in the gradual loss of retinal pigment epithelium (RPE) and the permanent visual damage. Various risk factors, including oxidative stress, form a complex network at the confluence of inflammation. Mesenchymal stem cell (MSC) is a well-studied population of adult stem cell with strong neuroprotective and immunoregulatory properties. Here, we reported the protective effect of MSC on sodium iodate (NaIO3)-triggered RPE degeneration. Sodium iodate (NaIO3)-induced RPE cell death was remarkably reduced when cocultured with MSC. Inhibition of several cell death pathways mediated by mitochondrial instability and its subsequent caspase-1/3/8 activation was implicated in this process. In addition, NLRP3 inflammasome, the upstream of caspase-1 activation, was also found downregulated via suppressing its priming signal NF-κB pathway. Taken together, MSC protected against NaIO3-triggered RPE death via deactivating NF-κB-mediated NLRP3 inflammasome and maintaining mitochondrial integrity. This study highlights the significant role of MSC in modulating the proinflammatory environment of AMD, and suggests the clinical value of MSC in treating AMD as well as RPE replacement therapy., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: High cataract incidence and low cataract surgical rate are serious public health problems in China, despite the fact that efficient day care cataract surgery has been implemented in some public Tertiary A hospitals in China. In this study, we compared not only clinical outcomes, hospitalization time and total costs but also payment manners between day care and inpatient procedures for cataract surgery in a Jiangsu public Tertiary A hospital to put forward several instructional suggestions for the improvement of government medical policies., Methods: In total, 4151 day care cases and 2509 inpatient cases underwent the same cataract surgery in the day care ward and ordinary ward respectively, and were defined as two groups. General information, complications, postoperative best corrected visual acuity (BCVA), hospitalization time, total costs and especially payment method were analyzed to compare day care versus inpatient., Results: The general data display no significant differences (P > 0.05), and no significant difference between complications and postoperative BCVA were observed between the two groups (P > 0.05). The period of stay in hospital was significantly different (P < 0.001). The total costs were lower for day care than for inpatients (P < 0.001). To avoid sampling error, we analyzed the data of payment manner for each patient among this period. Day care patients tended to pay for the procedure using the Urban Employees Basic Medical Insurance (UEBMI) method, while inpatients tended to use the Out-of-Pocket Medical Treatment (OMT) payment method (P < 0.001)., Conclusion: Day surgery of cataract is more cost-effective and efficient than inpatient surgery with equivalent clinical outcomes. As an efficient therapeutic regimen, day care surgery should be further promoted and supported by the government policies.

Dedifferentiation of retinal pigment epithelium (RPE) cells and choroidal neovascularization (CNV) contributes to the pathogenesis of age-related macular degeneration (AMD). MicroRNAs (miRNAs) have crucial roles in AMD onset and progression. We thus aim to investigate the effects of miRNAs on RPE dedifferentiation and endothelium cell (EC) behavior, and analyze its downstream pathways. We have previously identified miR-302d-3p as the most downregulated miRNA signature along with RPE differentiation. Herein, in vitro study supported that miR-302d-3p induces RPE dedifferentiation typified by reduction of RPE characteristic markers, interrupts its phagocytosis, and promotes its migration, proliferation, and cell-cycle progression. c-Jun was identified as a potential upstream transcript factor for MIR302D, which might modulate RPE function by regulating miR-302d-3p expression. P21 Waf1/Cip1 , a cyclin-dependent kinase inhibitor encoded by the CDKN1A gene, was identified as a downstream target of miR-302d-3p. Our data suggested that p21 Waf1/Cip1 could promote RPE differentiation, and inhibit its proliferation, migration, and cell-cycle progression. We also demonstrated that miR-302d-3p suppresses RPE differentiation through directly targeting p21 Waf1/Cip1 . In addition, the miR-302d-3p/CDKN1A axis was also involved in regulating tube formation of ECs, indicating its potential involvement in CNV formation. Taken together, our study implies that miR-302d-3p, regulated by c-Jun, contributes to the pathogenesis of both atrophic and exudative AMD. MiR-302d-3p promotes RPE dedifferentiation, migration, proliferation and cell-cycle progression, inhibits RPE phagocytosis, and induces abnormal EC behavior by targeting p21 Waf1/Cip1 . Pharmacological miR-302d-3p inhibitors are prospective therapeutic options for prevention and treatment of AMD.

Background and Objective: The measurement of choroidal volume is more related with eye diseases than choroidal thickness, because the choroidal volume can reflect the diseases comprehensively. The purpose is to automatically segment choroid for three-dimensional (3D) spectral domain optical coherence tomography (SD-OCT) images., Methods: We present a novel choroid segmentation strategy for SD-OCT images by incorporating the enhanced depth imaging OCT (EDI-OCT) images. The down boundary of the choroid, namely choroid-sclera junction (CSJ), is almost invisible in SD-OCT images, while visible in EDI-OCT images. During the SD-OCT imaging, the EDI-OCT images can be generated for the same eye. Thus, we present an EDI-OCT-driven choroid segmentation method for SD-OCT images, where the choroid segmentation results of the EDI-OCT images are used to estimate the average choroidal thickness and to improve the construction of the CSJ feature space of the SD-OCT images. We also present a whole registration method between EDI-OCT and SD-OCT images based on retinal thickness and Bruch's Membrane (BM) position. The CSJ surface is obtained with a 3D graph search in the CSJ feature space., Results: Experimental results with 768 images (6 cubes, 128 B-scan images for each cube) from 2 healthy persons, 2 age-related macular degeneration (AMD) and 2 diabetic retinopathy (DR) patients, and 210 B-scan images from other 8 healthy persons and 21 patients demonstrate that our method can achieve high segmentation accuracy. The mean choroid volume difference and overlap ratio for 6 cubes between our proposed method and outlines drawn by experts were -1.96µm3 and 88.56%, respectively., Conclusions: Our method is effective for the 3D choroid segmentation of SD-OCT images because the segmentation accuracy and stability are compared with the manual segmentation., (Copyright © 2017. Published by Elsevier B.V.)

Aims: Proliferative diabetic retinopathy (PDR), characterized by angiogenesis, can cause serve vision loss and even blindness. Recent studies have suggested a pivotal role of vasohibin-2 (VASH2) in the promotion of angiogenesis in tumor tissues. Here we further investigated the role of VASH2 in the proliferation and migration of retinal endothelial cells., Main Methods: The expression of VASH2 in vascular endothelial cells of epiretinal fibrovascular membranes (FVMs) from PDR patients were detected by immunofluorescence. VASH2 gene interfering lentiviral vectors (VASH2-shRNA) and miR-200b/c were constructed for the evaluation of the VASH2 effect on high glucose induced human retinal microvascular endothelial cell line (HRMECs). Cell proliferation, cell cycle and cell migration were carried out subsequently. The relationship between VASH2 and miR-200b/c was determined by luciferase reporter gene assays., Key Findings: A positive expression of VASH2 was identified in vascular endothelial cells of FVMs from PDR patients. In HRMECs, cells transfected with shRNA or miR-200b/c mimics showed a significantly reduced VASH2 expression compared with negative control group by real time-polymerase chain reaction and western-blot analysis. Inhibition of VASH2 was demonstrated to suppress cell proliferation and migration from Day 2 to Day 4. The luciferase reporter gene assays confirmed the post-transcriptional regulation of VASH2 by miR-200b/c in HRMECs., Significance: The present study suggests a protective effect of miR-200b/c on high glucose induced HRMECs dysfunction by inhibiting VASH2. It could be a potential therapeutic strategy to inhibit angiogenesis for the treatment of retinal vascular disease., (Copyright © 2017. Published by Elsevier Inc.)

Rationale: A large proportion of the output of quartz infrared heat lamps is emitted as infrared radiation (IR). Retinal damage induced by IR-A and visible light on arc welders has been reported. However, case reports of retinal damage caused by quartz infrared heat lamps are rare. To the best of our knowledge, this is the first reported case of phototoxic maculopathy induced by quartz infrared heat lamps., Patient Concerns: We report a female with a 1-month history of progressive blurred vision and dysmorphopsia in her right eye after improper staring at the tubes of a quartz infrared heater. Her best corrected visual acuity of the right eye was 20/32. Optical coherence tomography revealed a defect from the ellipsoid zone to retinal pigment epithelium (RPE)/Bruch's complex layer with a diameter of 360mmat its widest. P1 amplitudes in the two central concentric rings were reduced as assessed by multifocal electroretinography., Diagnoses: The patient was diagnosed with phototoxic maculopathy., Interventions: The patient was advised to cease all exposure to the infrared heater and was treated with peribulbar injections of methylprednisolone, oral Pancreatic Kininogenase, and oral Mecobalamin., Outcomes: Ten months later, her BCVA improved to 20/20. All examination results returned to normal except for a small residual defect in the interdigitation zone and RPE/Bruch's complex layer in her optical coherence tomography., Lessons: Light emitted by quartz infrared heat lamps may cause damage to the retina through photothermal and photochemical means. The public is insufficiently aware of the hazard potential of infrared heat lamps and other IR-A sources on human retina., Competing Interests: The authors have no conflicts of interest to disclose.

It is generally accepted that geographic atrophy (GA), a currently untreatable advanced form of age-related macular degeneration (AMD), is a multifactorial disease resulting in gradual and permanent blindness. Various risk factors are demonstrated to be responsible for its pathogenesis, such as aging, light exposure, and smoking. Molecular components associated with those risk factors form a complex and interwoven network at the confluence of inflammation, highlighting the significance of inflammasome activation in GA progression. Recently, a new type of modification in AMD microenvironment has been discovered, other than extensively-studied complement dysregulation, lipofuscin deposit, and oxidative by-products, to activate inflammasome. The accumulation of Alu RNA, resulting from DICER1 deficiency, is shown capable of triggering the activation of NLRP3 inflammasome and causing caspase-8-activated apoptosis in an IL-18/MyD88-dependent manner, which provides a new source of evidence for the interplay between cell death and inflammasome. In this review, we lay the emphasis on the mechanism by which Alu RNA activates NLRP3 inflammasome and downstream apoptotic proteins, and on its clinical relevance to GA and potential therapeutic approaches. We also point out several possible crosstalks among inflammasome and different acts of cell death which remain to be further investigated in Alu RNA-induced RPE degeneration.

Purpose: To evaluate the impact of postoperative posturing with or without face-down on the anatomical and functional outcomes of macular hole surgery., Methods: A literature-based meta-analysis was conducted to identify studies relevant to posturing following macular hole surgery (MHS). PubMed and Web of Science databases were used to retrieve articles up to 1 June 2015. The primary measures included MH closure and ideal vision acuity improvement. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in Review Manager., Results: Four randomized control trials (RCTs) comprising 251 cases were included in the final meta-analysis. No face-down posturing (FDP) after MHS revealed lower anatomic success rate compared to face-down posturing (OR = 0.33, 95% CI [0.13, 0.81], p = 0.02). For holes smaller than 400 μm in size, the subgroup meta-analysis indicated no significant effect of FDP on successful hole closure (OR = 0.29, 95% CI [0.01, 7.34], p = 0.45). However, when holes were larger than 400 μm, it seemed less effective on MH closure following surgery in no FDP group (OR = 0.23, 95% CI [0.07, 0.71]), and this was statistically significant (p = 0.01)., Conclusions: Our work found that no FDP was not inferior to its face-down counterpart for the success of MHS when macular holes were smaller than 400 μm in size. For macular holes larger than 400 μm, statistical analysis proved that FDP might be necessary. More well-conducted randomized control trials are needed to verify our findings., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A study was undertaken to investigate the association between A69S in age-related maculopathy susceptibility 2 (ARMS2) and the response to anti-angiogenesis treatment in exudative age-related macular degeneration (AMD). A literature-based meta-analysis was performed of studies relevant to A69S and the response to anti-angiogenesis treatment. PubMed, Web of Science, China National Knowledge Infrastructure (CNKI) and Sinomed databases were used to retrieve articles up to July 2014. Pooled ORs and 95% CIs were estimated using fixed and random effects models in Stata V.9.0. Q-statistic testing was used to assess heterogeneity. Twelve articles comprising 2389 cases were included in the final meta-analysis. The analysis of the overall population indicated a statistically significant association between A69S and the response to anti-angiogenesis treatment in exudative AMD (GG vs TT: OR 1.34 (95% CI 1.01 to 1.77), p=0.039; GT vs TT: OR 1.58 (95% CI 1.08 to 2.31), p=0.018; GG+GT vs TT: OR 1.74 (95% CI 1.19 to 2.52), p=0.004). In subgroup analysis, A69S appeared more likely to be a predictor for anti-angiogenic response in the East Asian population (GG vs TT: OR 1.65 (95% CI 1.02 to 2.68), p=0.042; GT vs TT: OR 1.66 (95% CI 1.17 to 2.37), p=0.005; GG+GT vs TT: OR 1.82 (95% CI 1.07 to 3.10), p=0.027; G vs T: OR 1.56 (95% CI 1.01 to 2.41)). However, no statistical significance was found in the Caucasian subgroup analysis. This study shows an association between A69S polymorphism in the ARMS2 gene and the anti-angiogenesis treatment response. A69S could be considered predictive of the anti-angiogenic effects, especially in Asian populations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Automatic segmentation of retinal layers in spectral domain optical coherence tomography (SD-OCT) images plays a vital role in the quantitative assessment of retinal disease, because it provides detailed information which is hard to process manually. A number of algorithms to automatically segment retinal layers have been developed; however, accurate edge detection is challenging. We developed an automatic algorithm for segmenting retinal layers based on dual-gradient and spatial correlation smoothness constraint. The proposed algorithm utilizes a customized edge flow to produce the edge map and a convolution operator to obtain local gradient map in the axial direction. A valid search region is then defined to identify layer boundaries. Finally, a spatial correlation smoothness constraint is applied to remove anomalous points at the layer boundaries. Our approach was tested on two datasets including 10 cubes from 10 healthy eyes and 15 cubes from 6 patients with age-related macular degeneration. A quantitative evaluation of our method was performed on more than 600 images from cubes obtained in five healthy eyes. Experimental results demonstrated that the proposed method can estimate six layer boundaries accurately. Mean absolute boundary positioning differences and mean absolute thickness differences (mean±SD) were 4.43±3.32 μm and 0.22±0.24 μm, respectively., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The prevalence of blindness and low vision among adults aged ≥50 years in southern Jiangsu Province were surveyed and estimated., Methods: Cluster sampling was employed from January to September 2010 to randomly select 6,722 individuals aged ≥50 years in 28 clusters from southern Jiangsu Province. The survey was preceded by a pilot study, which refined operational methods and conducted quality assurance evaluation. Eligible individuals were registered for visual acuity measurement and eye examination., Results: A total of 6,155 individuals were recruited, and a response rate of 91.50% was obtained. The prevalence of bilateral blindness and low vision were found to be 0.76% and 1.37%, respectively. Subjects with monocular blindness and low vision were 3.27% and 3.48%, respectively. Among the individuals evaluated, 201 were detected to have monocular blindness and 47 with bilateral blindness. In addition, 55 of the 201 subjects with monocular blindness were found to suffer from low vision of the other eye. Among the 295 subjects with blind eyes, 116 (39.32%), 31 (10.51%), and 28 (9.49%) were caused by cataract, high myopia macular degeneration, and atrophic eyeballs, respectively. In the 437 subjects with low-vision eyes, 223 (51.03%), 41 (9.38%), and 41 (9.38%) had cataract, high myopia macular degeneration, and age-related macular degeneration, respectively., Conclusions: Blindness and low vision are caused by descending cataract, age-related macular degeneration, high myopia macular degeneration, and atrophic eyeballs.

Purpose: A number of studies have shown that the levels of some proteins in the aqueous humor (AH) are altered and correlate with the mechanisms or prognosis of many eye diseases. To identify the possible mechanisms that lead to the development of wet age-related macular degeneration (AMD), a proteomic analysis of the AH composition from wet AMD patients was performed and compared with that from non-AMD cataract patients., Experimental Design: Six wet AMD and six non-AMD cataract patients were enrolled. A proteomic approach which included two-dimensional electrophoresis coupled with MS and bioinformatics methods were used to identify AH proteins with altered expression in wet AMD compared with non-AMD patients. An ELISA was used to validate the proteomic results., Results: We separated 78 protein spots and identified 68 that were differently expressed in the wet AMD group and controls. Numerous proteins identified in this study are implicated in inflammation, apoptosis, angiogenesis, and oxidative stress., Conclusions and Clinical Relevance: The AH protein composition was significantly different between wet AMD and non-AMD patients. The proteins identified in this study may be potential biomarkers of wet AMD development and might play a role in the mechanisms of wet AMD., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To evaluate the efficacy, predictability, stability, safety, and complications of secondary anterior iris fixation of the Artisan iris-fixated intraocular lens (IOL) to correct aphakia in eyes without sufficient capsule support., Setting: Department of Ophthalmology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China., Design: Cohort study., Methods: Eyes having implantation of aphakic iris-fixated IOLs for aphakia correction were followed for 3 years., Results: The study evaluated 72 eyes (72 patients). After 3 years, the uncorrected distance visual acuity improved in all eyes (P<.05); 53 eyes (73.6%) reached 20/40 or better. Two eyes had a postoperative corrected distance visual acuity (CDVA) worse than the preoperative CDVA due to postoperative ischemic optic neuropathy and retinal detachment, respectively. The mean spherical equivalent (SE) decreased from 11.65 diopters (D) ± 1.21 (SD) to -0.58 ± 0.56 D (P<.05); the SE at the last follow-up was within ±1.00 D of the target refraction in 63 eyes (87.5%). The mean endothelial cell loss 3 years postoperatively was 9.78%. There was no significant postoperative intraocular pressure increase throughout the follow-up. Twelve patients (16.7%) reported glare and halos during night driving. Iris pigment precipitates on the IOLs occurred in 4 eyes (5.6%) 3 years postoperatively. No other serious complications occurred., Conclusions: Three-year results indicate that secondary implantation of aphakic IOLs is effective, predictable, and safe for the correction of aphakia in eyes without capsule support. However, longer follow-up with a larger cohort is necessary to confirm these conclusions., (Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the proportions of corneal endothelial lesion caused by different factors during phacoemulsification and aspiration., Methods: Fourteen cats (twenty eight eyes) were divided into four groups. The processed factors were ultrasonic power, lens extraction by phacoemulsification or not, and lens extraction using different levels of ultrasonic power. The density of central corneal endothelial cells was measured before and after operation., Results: There is no statistic difference between pre-operation density and post-operation density for releasing ultrasonic power only without lens extraction group. But for the lens extraction group, there is difference in density of central corneal endothelial cells and the higher level of ultrasonic power, the more the central corneal endothelial cells density decreased through operation., Conclusion: The primary factor that causes corneal endothelial lesion during phacoemulsification and aspiration procedure is debris of lens nucleus, and the other factors cause the lesion of corneal endothelium in normal operations just in very small degree.

Objective: To evaluate the clinical results of implantation of foldable intraocular lens in multiple types of cataract., Methods: This retrospective study comprised 162 eyes of 148 patients undergoing phacoemulsification and implantation of foldable intraocular lens, some of whom underwent combined pars plana vitrectomy or trabeculectomy or silicone oil removal. The period of follow-up was from 3 months to 17 months., Results: There is slight reaction postoperatively in all cases. The postoperative uncorrected visual acuites was from 0.05 to 1.2, patient with 0.6 or above acuity were 70.98%. A neodymium: YAG capsulotomy was required in 5 eyes. Posterior capsule ruptured in 1 eyes, and a PMMA intraocular lens was implanted in ciliary sulcus. In one eye, a lens was removed because of recurrence of retina detachment., Conclusions: The application of foldable intraocular lens in multiple types of cataract is safe, and there is a slight postoperative reaction. less complications, and fast visual acuity recovery.