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Background: Outflow regulation and phagocytosis are key functions of the trabecular meshwork (TM), but it is not clear how the two are related in secondary open angle glaucomas characterized by an increased particle load. We hypothesized that diminished TM phagocytosis is not the primary cause of early ocular hypertension and recreated pigment dispersion in a porcine ex vivo model. Methods: Sixteen porcine anterior chamber cultures received a continuous infusion of pigment granules (Pg), while 16 additional anterior chambers served as controls (C). Pressure transducers recorded the intraocular pressure (IOP). The phagocytic capacity of the trabecular meshwork was determined by fluorescent microspheres. Results: The baseline IOPs in Pg and C were similar (P=0.82). A significant IOP elevation occurred in Pg at 48, 120, and 180 hours (all PP=0.001 compared to C). This reduction did not result in an additional IOP increase at 120 or 180 hours compared to the first IOP elevation at 48 hours (P>0.05). Conclusions: In this porcine model of pigmentary glaucoma, an IOP elevation occurs much earlier than when phagocytosis fails, suggesting that two separate mechanisms might be at work.

Diffuse anterior retinoblastoma is a rare variant of retinoblastoma seeding in the area of the vitreous base and anterior chamber. Patients with diffuse anterior retinoblastoma are older than those with the classical types, with the mean age being 6.1 years. The original cells of diffuse anterior retinoblastoma are supposed to be cone precursor. Patients most commonly present with pseudouveitis, pseudohypopyon, and increased intraocular pressure. The retina under fundus examination is likely to be normal, and the clinical features mimic the inflammation progress, which can often lead to misdiagnosis. The published diffuse anterior retinoblastoma cases were diagnosed after fine-needle aspiration biopsy running the potential risk of inducing metastasis. The most common treatment for diffuse anterior retinoblastoma is enucleation followed by systematic chemotherapy according to the patient's presentation and clinical course. This review summarizes the recent advances in etiology (including tumorigenesis and cell origin), pathology, diagnosis, differential diagnosis, and new treatment. The challenges of early diagnosis and prospects are also discussed.

Objective The trabecular meshwork (TM) is the primary substrate of outflow resistance in glaucomatous eyes. Repopulating diseased TM with fresh, functional TM cells might be a viable therapeutic approach. Decellularized TM scaffolds have previously been produced by ablating cells with suicide gene therapy or saponin, which risks incomplete cell removal or dissolution of the extracellular matrix, respectively. We hypothesized that improved trabecular meshwork cell ablation would result from freeze-thaw cycles compared to chemical treatment. Materials and Methods We obtained 24 porcine eyes from a local abattoir, dissected and mounted them in an anterior segment perfusion within two hours of sacrifice. Intraocular pressure (IOP) was recorded continuously by a pressure transducer system. After 72 h of IOP stabilization, eight eyes were assigned to freeze-thaw (F) ablation (−80 °C × 2), to 0.02% saponin (S) treatment, or the control group (C), respectively. The TM was transduced with an eGFP expressing feline immunodeficiency viral (FIV) vector and tracked via fluorescent microscopy to confirm ablation. Following treatment, the eyes were perfused with standard tissue culture media for 180 h. TM histology was assessed by hematoxylin and eosin staining. TM viability was evaluated by a calcein AM/propidium iodide (PI) assay. The TM extracellular matrix was stained with Picro Sirius Red. We measured IOP and modeled it with a linear mixed effects model using a B-spline function of time with five degrees of freedom. Results F and S experienced a similar IOP reduction of 30% from baseline (P = 0.64). IOP reduction of about 30% occurred in F within 24 h and in S within 48 h. Live visualization of eGFP demonstrated that F conferred a complete ablation of all TM cells and only a partial ablation in S. Histological analysis and Picro Sirius staining confirmed that no TM cells survived in F while the extracellular matrix remained. The viability assay showed very low PI and no calcein staining in F in contrast to many PI-labeled, dead TM cells and calcein-labeled viable TM cells in S. Conclusion We developed a rapid TM ablation method that uses cyclic freezing that is free of biological or chemical agents and able to produce a decellularized TM scaffold with preserved TM extracellular matrix in an organotypic perfusion culture.

Author(s): Wang, Chao; Dang, Yalong; Waxman, Susannah; Xia, Xiaobo; Weinreb, Robert N; Loewen, Nils A | Abstract: PurposeTo compare intraoperative angle stability and postoperative outflow of two ab interno trabeculectomy devices that excise the trabecular meshwork with or without active aspiration and irrigation. We hypothesized that anterior segment optical coherence tomography (AS-OCT) allows for a quantitative comparison of intraoperative angle stability in a microincisional glaucoma surgery (MIGS) pig eye training model.MethodsTwelve freshly enucleated porcine eyes were measured with AS-OCT at baseline, at the beginning of the procedure and at its conclusion to determine the anterior chamber depth (ACD) and the nasal angle α in degrees. The right and left eye of pairs were randomly assigned to an active dual blade goniectome (aDBG) and a passive dual blade goniectome (pDBG) group, respectively. The aDBG had irrigation and aspiration ports while the pDBG required surgery under viscoelastic. We performed the procedures using our MIGS training system with a standard, motorized ophthalmic operating microscope. We estimated outflow by obtaining canalograms with fluorescent spheres.ResultsIn aDBG, the nasal angle remained wide open during the procedure at above 90° and did not change towards the end (100±10%, p = 0.9). In contrast, in pDBG, ACD decreased by 51±19% to 21% below baseline (pl0.01) while the angle progressively narrowed by 40±12% (pl0.001). Canalograms showed a similar extent of access to the outflow tract with the aDBG and the pDBG (p = 0.513). The average increase for the aDBG in the superonasal and inferonasal quadrants was between 27 to 31% and for the pDBG between 15 to 18%.ConclusionAS-OCT demonstrated that active irrigation and aspiration improved anterior chamber maintenance and ease of handling with the aDBG in this MIGS training model. The immediate postoperative outflow was equally good with both devices.

Yalong Dang,1,* Yalin Mu,2,* Lin Li,3,* Yahui Mu,2 Shujing Liu,2 Chun Zhang,4 Yu Zhu,1 Yimin Xu4 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 2Department of Ophthalmology, Yellow River Hospital, Henan University of Science and Technology, Sanmenxia, Henan Province, 3Department of Ophthalmology, the First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan Province, 4Department of Ophthalmology, Peking University Third Hospital, Haidian District, Beijing, People's Republic of China *These authors contributed equally to this work. Background and objective: Our objective was to investigate the efficacy and safety of dexamethasone (DEX) implant for the treatment of pseudophakic cystoid macular edema (PCME) in diabetic patients. Study design: This was a prospective, non-randomized, interventional case series of 43 participants. Eighteen patients were enrolled in the DEX implant group and 25 were enrolled in an intravitreal triamcinolone acetonide (IVTA) group. Main outcome measures: The primary efficacy measurement was the percentage of patients who gained improvements of more than ten letters in best corrected visual acuity (BCVA) during 6 months of follow-up. Other efficacy measurements included change in BCVA, change in central macular thickness (CMT), and number of retreatments. The primary safety evaluation was the percentage of patients with intraocular hypertension and variation in intraocular pressure (IOP) during 6 months of follow-up. Other adverse events, such as conjunctival hemorrhage, eye pain, secondary infection, endophthalmitis, noninfectious inflammation, retinal detachment, and implant migration, were also recorded during follow-up. Results: At month 1, we observed that the percentage of patients gaining improvement of more than ten letters was similar in both groups (P=0.625). As patients in the IVTA group were retreated several times, this effect persisted throughout the study (P=0.941 at month 2, P=0.553 at month 3, P=0.856 at month 6). Variations in CMT were noticed at week 1 and reached their maximum at month 1. No significant difference was found between the two groups (P=0.831 at week 1, P=0.783 at month 1). At month 1, the variation in IOP reached its maximum in the DEX implant group and then decreased slightly. However, in the IVTA group, it increased continuously throughout the study. Conjunctival hemorrhage and eye pain were found in both groups, but both were rated as mild in severity, and no significant difference was found (P=0.184, P=0.766, respectively). Conclusion: Both IVTA and DEX implants could effectively restore visual function and recover morphological change in diabetic patients with PCME for at least 6 months, but repeated intravitreal injection was required in the IVTA group. DEX implant is well tolerated. We suggest that intravitreal injection of DEX implant is a promising new therapeutic option for diabetic patients with PCME. Keywords: dexamethasone implant, intravitreal triamcinolone acetonide, pseudophakic cystoid macular edema, diabetic retinopathy, corticosteroid, inflammation

Melanomas account for over 70% of adult malignancies in the eye and occur primarily in the choroid. Melanomas rarely originate in the ciliary body, with an annual incidence of approximately 1.6 cases per million. While the incidence rate of these tumors is low, malignant melanomas metastasize at early stages of disease development and show poor prognoses. Malignant melanomas of the ciliary body are often deeply hidden and have complex clinical manifestations, which are easily misdiagnosed and affect the prognosis. Here, we report a case of monocular ciliary body melanoma in an elderly Asian woman. Using this case as an example, we perform a systematic review of the disease’s clinical symptoms, signs, diagnoses, differential diagnoses, treatment and prognosis.

Background and Objective Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra Moore. Recent studies have suggested that TET can reduce the inflammatory response in microglia, but the mechanisms remain unclear. The aim of this study is to investigate whether TET can inhibit lipopolysaccharide (LPS)-induced microglial activation and clarify its possible mechanisms. Study Design/Materials and Methods Cell viability assays and cell apoptosis assays were used to determine the working concentrations of TET. Then, BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the mRNA or protein levels of IL1β and TNFα. Western blotting was utilized to quantify the expression of CD11b and cell signaling proteins. Results TET at optimal concentrations (0.1 µM, 0.5 µM or 1 µM) did not affect the cell viability. After TET pretreatment, the levels of IL1β and TNFα (both in transcription and translation) were significantly inhibited in a dose-dependent manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK 1/2 expression were also suppressed by TET. Conclusions Our results indicate that TET can effectively suppress microglial activation and inhibit the production of IL1β and TNFα by regulating the NF-kB and ERK signaling pathways. Together with our previous studies, we suggest that TET would be a promising candidate to effectively suppress overactivated microglia and alleviate neurodegeneration in glaucoma.

Yalong Dang,1–3,# Xinfeng Sun,2,# Yongsheng Xu,3,# Yalin Mu,2 Manli Zhao,2 Jing Zhao,2 Yu Zhu,1 Chun Zhang31Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 2Department of Ophthalmology, Yellow River Hospital, Henan University of Science and Technology, Sanmenxia, Henan Province, 3Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China #These authors contributed equally to this work Background: The purpose of this study was to evaluate changes in subfoveal choroidal thickness after photodynamic therapy in patients with acute idiopathic central serous chorioretinopathy (ICSCR). Methods: This was a retrospective observational study conducted in 63 participants. The primary outcome measure was subfoveal choroidal thickness at baseline and 3 days, one week, 4 weeks, and 12 weeks after photodynamic therapy. The secondary outcome measure was indocyanine green angiography at baseline and 4 weeks and 12 weeks after photodynamic therapy. Results: Four weeks after photodynamic therapy, 20 (64.51%) symptomatic eyes showed hypofluorescence corresponding to the area of photodynamic therapy irradiation at the posterior pole. The mean subfoveal choroidal thickness increased significantly from 422±132 µm at baseline to 478±163 µm at day 3 after treatment (P=0.022) and then decreased to 362±113 µm at week 4 (P

Yalong Dang,1,2,* Yalin Mu,2,* Manli Zhao,2 Lin Li,3 Yaning Guo,4 Yu Zhu1,2 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China; 2Department of Ophthalmology and Visual Science, Yellow River Hospital of Henan University of Science and Technology, Sanmenxia City, Henan, People's Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang City, Henan, People's Republic of China; 4Gu-Cheng Eye Hospital, Xi'an City, Shanxi, People's Republic of China *These authors contributed equally to this work Purpose: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on the remission of acute idiopathic central serous chorioretinopathy (ICSCR). Study design: A prospective, randomized, placebo-controlled study of 53 participants. Main outcome measure: Twenty-seven acute ICSCR patients tested positive for H. pylori were given an eradication H. pylori therapy, and another 26 patients with the same diagnosis received matching placebo medication. All participants were tested for the following items: (1) disappearance rate of subretinal fluid (SRF); (2) best-corrected visual acuity (BCVA); and (3) central retinal sensitivity at baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment. The difference between the two groups was analyzed by PASW statistics version 18.0. Results: At each follow-up, the disappearance rate of SRF in the active treatment group seemed slightly better than in the control group, but no statistically significant differences were observed (P > 0.05 at each follow-up). The BCVA between the two groups also did not demonstrate statistically significant differences (P > 0.05 at each follow-up). Unlike the BCVA and the disappearance rate of SRF, we compared the change in central retinal sensitivity at 12 weeks after treatment; a statistical difference was observed (P = 0.042). Conclusion: Our findings suggested that H. pylori eradication does not improve BCVA and the disappearance rate of SRF, but it could improve the central retinal sensitivity in acute ICSCR patients. We recommend that chronic ICSCR patients and more sensitive methods for H. pylori diagnosis should be involved in evaluating the effect of H. pylori eradication. Keywords: Helicobacter pylori, acute idiopathic central serous chorioretinopathy, best-corrected visual acuity, subretinal fluid, central retinal sensitivity

Objective: To investigate the changes of retinal nerve fiber layer (RNFL) thickness in obstructive sleep apnea syndrome (OSAS) patients. Methods: Relevant studies were selected from 3 major literature databases (PubMed, Cochrane Library, and EMBASE) without language restriction. Main inclusion criteria is that a case-control study in which RNFL thickness was measured by a commercial available optical coherence tomography (OCT) in OSAS patients. Meta-analysis was performed using STATA 12.0 software. Efficacy estimates were evaluated by weighted mean difference with corresponding 95% confidence intervals (CIs). Primary outcome evaluations were: the average changes of RNFL thickness in total OSAS patients, subgroup analysis of RNFL thickness changes in patients of different OSAS stages, and subgroup analysis of 4-quadrant RNFL thickness changes in total OSAS patients. Results: Of the initial 327 literatures, 8 case-control studies with 763 eyes of OSA patients and 474 eyes of healthy controls were included (NOS scores ≥6). For the people of total OSAS, there had an average 2.92 μm decreased RNFL thickness compared with controls (95% CI: −4.61 to −1.24, P = 0.001). For subgroup analysis of OSAS in different stages, the average changes of RNFL thickness in mild, moderate, severe, and moderate to severe OSAS were 2.05 (95% CI: −4.40 to 0.30, P = 0.088), 2.32 (95% CI: −5.04 to 0.40, P = 0.094), 4.21 (95% CI: −8.36 to −0.06, P = 0.047), and 4.02 (95% CI: −7.65 to −0.40, P = 0.03), respectively. For subgroup analysis of 4-quadrant, the average changes of RNFL thickness in Superior, Nasal, Inferior, and Temporal quadrant were 2.43 (95% CI: −4.28 to −0.57, P = 0.01), 1.41 (95% CI: −3.33 to 0.51, P = 0.151), 3.75 (95% CI: −6.92 to −0.59, P = 0.02), and 0.98 (95% CI: −2.49 to 0.53, P = 0.203), respectively. Conclusion: Our study suggests that RNFL thickness in OSAS patients is much thinner than healthy population, especially in superior and inferior quadrant. The impact of OSAS disease on RNFL and visual function should be taken seriously in the further study.

Prior glaucoma severity staging systems were mostly concerned with visual field function and retinal nerve fiber layer, but did not include intraocular pressure or medications to capture resistance to treatment. We recently introduced a simple index that combines pressure, medications, and visual field damage and applied it to stratify outcomes of trabectome surgery. In the analysis presented here, we combined data of trabectome alone and trabectome with same session cataract surgery to increase testing power and chances of effect discovery. This microincisional glaucoma surgery removes the primary resistance to outflow in glaucoma, the trabecular meshwork, and has been mostly used in mild glaucoma. Traditional glaucoma surgeries have a relatively high complication rate and have been reserved for more advanced disease stages. In the analysis presented here we include our data of trabectome combined with cataract surgery. This is a common practice pattern as both occur in the same age group with increasing frequency. For patients in higher glaucoma index (GI) groups, the intraocular pressure (IOP) reduction was 2.34+/-0.19 mmHg more than those in a GI group one level lower while holding everything else constant. Those who had undergone trabectome combined with phacoemulsification had an IOP reduction that was 1.29+/-0.39 mmHg less compared to those with trabectome alone. No statistically significant difference was found between genders and age groups while holding everything else constant. Hispanics had a 3.81+/-1.08 mmHg greater IOP reduction. Pseudoexfoliation and steroid glaucoma patients had an IOP reduction that was greater by 2.91+/-0.56 and 3.86+/-0.81 mmHg, respectively, than those with primary open angle glaucoma. These results suggest a role for trabectome-mediated ab interno trabeculectomy beyond mild forms of glaucoma. Additionally, the multifactorial glaucoma index demonstrates a role in staging patients when comparing glaucoma surgical modalities.

Yalong Dang,1 Yalin Mu,2 Kun Wang,3 Ke Xu,2 Jing Yang,1 Yu Zhu,1 Bin Luo2,3 1Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People’s Republic of China; 3Clinical Laboratory, Yellow-River Hospital, Sanmenxia City, People’s Republic ofChina Objective: To investigate the effects of papaverine (PAP) on lipopolysaccharide (LPS)-induced microglial activation and its possible mechanisms. Materials and methods: BV2 microglial cells were first pretreated with PAP (0, 0.4, 2, 10, and 50 µg/mL) and then received LPS stimulation. Transcription and production of proinflammatory factors (IL1β, TNFα, iNOS, and COX-2) were used to evaluate microglial activation. The transcriptional changes undergone by M1/M2a/M2b markers were used to evaluate phenotype transformation of BV2 cells. Immunofluorescent staining and Western blot were used to detect thelocation and expression of P65 and p-IKK in the presence or absence of PAP pretreatment. Results: Pretreatment with PAP significantly inhibited the expression of IL1β and TNFα, and suppressed the transcription of M1/M2b markers Il1rn, Socs3, Nos2 and Ptgs2, but upregulated the transcription of M2a markers (Arg1 and Mrc1) in a dose-dependent manner. In addition, PAP pretreatment significantly decreased the expression of p-IKK and inhibited the nuclear translocation of P65 after LPS stimulation. Conclusion: PAP not only suppressed the LPS-induced microglial activity by inhibiting transcription/production of proinflammatory factors, but also promoted the transformation of activated BV2 cells from cytotoxic phenotypes (M1/M2b) to a neuroprotective phenotype (M2a). These effects were probably mediated by NF-κB signaling pathway. Thus, it would be a promising candidate for the treatment of neurodegenerative diseases. Keywords: papaverine, microglia, neuroprotection, neuroinflammation

In the developed world, age-related macular degeneration (AMD) is one of the major causes of irreversible blindness in the elderly. Although management of neovascular AMD (wet AMD) has dramatically progressed, there is still no effective treatment for nonneovascular AMD (dry AMD), which is characterized by retinal pigment epithelial (RPE) cell death (or dysfunction) and microenvironmental disruption in the retina. Therefore, RPE replacement and microenvironmental regulation represent viable treatments for dry AMD. Recent advances in cell biology have demonstrated that RPE cells can be easily generated from several cell types (pluripotent stem cells, multipotent stem cells, or even somatic cells) by spontaneous differentiation, coculturing, defined factors or cell reprogramming, respectively. Additionally, in vivo studies also showed that the restoration of visual function could be obtained by transplanting functional RPE cells into the subretinal space of recipient. More importantly, clinical trials approved by the US government have shown promising prospects in RPE transplantation. However, key issues such as implantation techniques, immune rejection, and xeno-free techniques are still needed to be further investigated. This review will summarize recent advances in cell transplantation for dry AMD. The obstacles and prospects in this field will also be discussed.