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The retina, owing to its cellular anatomy and physical location, is susceptible to generating reactive oxygen species (ROS), which are associated with several major retinal diseases. When ROS exceeds the body’s natural antioxidants, the retina is in a state of oxidative stress, which is recognized as the pathogenesis of retinal diseases. The early stage of the pathogenic process is an adaptive change in which oxidative stress and endogenous defense mechanisms occur. If no treatment is applied, the retinal diseases will progress to the pathological stage with neuronal and vascular dysfunction or damage and even blindness. This review summarizes the role of oxidative stress in several common retinal diseases, including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. In addition, we discuss the early intervention strategies for these diseases. An outline is provided to identify potential intervention targets for further research. Early intervention for retinal diseases is necessary and urgent and may offer hope to improve patients’ quality of life through functional vision.

We report a novel variant of the USH2A gene in a family affected by retinitis pigmentosa (RP). Genomic DNA was obtained from a 55-year-old woman (the proband) with night blindness who was diagnosed with non-syndromic RP. We identified the compound heterozygous variants c.8559-2A>G and c.151A>T (p.Ile51Phe) in the USH2A gene as the underlying cause in the proband; the former variant, instead of the latter variant, has been reported in the literature. The proband’s mother carried the c.151A>T variant, while her father and daughter carried the c.8559-2A>G variant. In this family, the proband and her mother developed RP; however, her father and daughter did not develop the disease. Although in silico tools predicted that c.151A>T is benign, segregation analysis suggested that this variant could be potentially harmful. The identification of c.151A>T (p.Ile51Phe) variant is a novel finding, and this variant might be a potentially harmful variant of USH2A gene. This finding also further expands the mutation spectrum of this gene in the Chinese population.

A 31-year-old male with mild dizziness complained of cloudy vision in his right eye for 5 days. The visual acuity of both eyes was normal, while the visual contrast sensitivity of both eyes slightly reduced. Fundus examination showed the swollen and radial superficial hemorrhage of his both optic nerves. Brain MRI scan indicated a huge tumor in the right temporal lobe with clear boundary, close to the skull. The midline structure shifted to the left. Blood tests indicated no hyperlipidemia or lipid disorders. The patient then received tumor resection. The size of the tumor was 5.6 cm × 7.5 cm × 10.1 cm. Histology suggested many foam cell accumulations and the tumor was positive for CD34, CD99, Vimentin, β-Catenin and CD68, but negative for EMA, GFAP, IDH-1, Oliga-2, PR, S-100, and CD1a. Three months after surgery, MRI showed the midline structure was back to normal. The swollen and radial superficial hemorrhage of optic nerves had disappeared. The visual acuity and visual field remained normal.

Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye’s anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM) at the entrance of the eye’s drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered anterior segment eye culture model. We hypothesized that repopulation of a decellularized TM with non-native TM cells could restore aspects of normal TM. The decellularization protocol removed all cells and debris while preserving the ECM. Seeded cells localized to the TM region and progressively infiltrated the meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After a perfusion rate increase challenge, tissue-engineered cultures reestablished normal IOPs (reseeded = 13.7±0.4 mmHg, decellularized = 35.2±2.2 mmHg, p < 0.0001). eGFP expressing CrFK control cells caused a high and unstable IOP (27.0±6.2 mmHg). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. Tissue-engineered organs demonstrated similarities to native tissues and may reduce the need for scarce donor globes in outflow research.

A 31-year-old male noticed blurred vision in his right eye for five days with no obvious predisposing causes, accompanied by mild dizziness. No obvious nodular lesions were found in the body. The patient’s binocular visual acuity was 20/20. Fundus photography showed the optic nerve swelling and radial superficial retinal hemorrhage of both eyes. Blood panel, urine routine, liver, and kidney function were all normal. Total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein were all in the normal limits. Head MRI showed a mass in the right temporal lobe, clear boundary, and multiple separations, which thinned and disappeared closer to the skull. The right temporal lobe and lateral ventricle were all compressed, with the midline structure shifted to the left. The patient was then transferred to Neurosurgery. During the operation, we observed the tumor had invaded the skull. The actual size of the tumor was 5.6 cm × 7.5 cm × 10.1 cm. Histology revealed foam cell accumulation in the mucous connective tissue of the right temporal lobe. The immunohistochemistry showed: CD34 (+), CD99 (+), EMA (−), GFAP (−), IDH-1 (−), Ki-67 (+) index about 10%, Oliga-2 (−), PR (−), S-100 (−), Vim (+), β-Catenin (+), CD1a (−), CD68 (+). Three months after the removal of the tumor, the visual acuity of both eyes was 20/20; The visual fields were normal, the optic disc edema and retinal hemorrhages had disappeared. MRI indicated the midline structure was back to normal.

PurposeTo investigate the effects of Ripasudil (K-115), a Rho-kinase inhibitor, in a porcine model of pigmentary glaucoma.MethodsHallmark features of trabecular meshwork (TM), the principle structure of the outflow system affected in this model, were analyzed. In vitro TM cells and ex vivo perfused eyes were subjected to pigment dispersion followed by K-115 treatment (PK115). PK115 was compared to sham-treated controls (C) and pigment (P). Cytoskeletal alterations were assessed by F-actin labeling. TM cell phagocytosis of fluorescent targets was evaluated by flow cytometry. Cell migration was studied with a wound-healing assay. Intraocular pressure was continuously monitored and compared to after the establishment of the pigmentary glaucoma model and after treatment with K-115.ResultsIn vitro, the percentage of cells with stress fibers increased in response to pigment but declined sharply after treatment with K-115 (P: 32.8 +/- 2.9%; PK115: 11.6 +/- 3.3%, P < 0.001). Phagocytosis first declined but recovered after K-115 (P: 25.7+/-2.1%, PK115: 33.4+/-0.8%, P ConclusionIn vitro, K-115 reduced TM stress fibers, restored phagocytosis, and restored migration of TM cells. Ex vivo, K-115 normalized intraocular pressure.

Background: Trabeculectomy is the most efficient surgical treatment. Prevention failure of bleb cicatrix would lead to unsatisfactory postoperative intraocular pressure (IOP) controlling and unsatisfactory success rate. The aim of this study was to evaluate the 5-year outcomes of trabeculectomy with a cross-linked sodium hyaluronate gel implantation for Chinese glaucoma patients. Methods: This is a prospective, case-controlled study. Patients who were to be applied first-time trabeculectomy in the Department of Ophthalmology of Peking University Third Hospital between 2010 and 2012 were included in the study. Totally, 60 eyes were randomly assigned to the trabeculectomy group (TA group) or the trabeculectomy with cross-linked sodium hyaluronate gel implantation group (TH group). Follow-up was finished at 1 week, 1 month, 3 months, 1 year, 3 years, and 5 years after the operation. The statistical index of demographic data, IOP, bleb shape, and any complications or medications or surgical procedures were recorded and assessed by SPSS 19.0 software through independent t-test, one-way analysis of variance (ANOVA) and Pearson's Chi-square test, respectively. Results: The baseline IOP was comparable between the two groups (t= −1.00, P= 0.32) while the postoperative IOP was significantly lower in the TH group at 1, 3 and 5 years' time points (P = 0.00, P= 0.01 and P = 0.01, respectively). According to the Indiana Bleb Appearance Grading Scale, the height and extent of bleb were better in the TH group at all follow-up time points (P < 0.05), however, the comparison of bleb vascularity showed no statistical difference (P > 0.05). TA group had a higher percentage of complications (13% vs. 3%) compared to TH group; however, there was no statistical difference in the comparison of each statistical item (P > 0.05, respectively). The complete success at 5 years was higher in the TH group than that in the TA group (78% vs. 54%, P = 0.03). Conclusion: Our results suggested that implantation of cross-linked sodium hyaluronate gel with trabeculectomy was more efficient and would improve the prognosis of glaucoma patients.

Objective: To evaluate three different microincisional ab interno trabeculectomy procedures in a porcine eye perfusion model. Methods: In perfused porcine anterior segments, 90 degrees of trabecular meshwork (TM) were ablated using the Trabectome (T; n = 8), Goniotome (G; n = 8), or Kahook device (K; n = 8). After 24 hours, additional 90 degrees of TM were removed. Intraocular pressure (IOP) and outflow facility were measured at 5 µL/min and 10 µL/min perfusion to simulate an elevated IOP. Structure and function were assessed with canalograms and histology. Results: At 5 µL/min infusion rate, T resulted in a greater IOP reduction than G or K from baseline (76.12% decrease versus 48.19% and 47.96%, P = 0.013). IOP reduction between G and K was similar (P = 0.420). Removing another 90 degrees of TM caused an additional IOP reduction only in T and G but not in K. Similarly, T resulted in the largest increase in outflow facility at 5 µL/min compared with G and K (first ablation: 3.41 times increase versus 1.95 and 1.87; second ablation: 4.60 versus 2.50 and 1.74) with similar results at 10 µL/min (first ablation: 3.28 versus 2.29 and 1.90 (P = 0.001); second ablation: 4.10 versus 3.01 and 2.01 (P = 0.001)). Canalograms indicated circumferential flow beyond the ablation endpoints. Conclusions: T, G and K significantly increased the outflow facility. In this model, T had a larger effect than G and K.

Purpose To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO). Methods In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 μM DETA-NO) on outflow facility were compared with controls (n = 8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral-domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 μM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macroscript and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results The facility increased after DETA-NO (Δ of 0.189 ± 0.081 μL/min·mm Hg, P = 0.034) and AIT (Δ of 0.251 ± 0.094 μL/min·mm Hg, P = 0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (Δ of 0.190 ± 0.074 μL/min·mm Hg, P = 0.023) and CSA by 13.9% (P < 0.001). L-NAME + ET-1 decreased CSA by -8.6% (P < 0.001). NO increased the diameter of focal constrictions 5.0 ± 3.8-fold. Conclusions NO can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.

AIM: To investigate the roles of PKC-α/ezrin signals in phagocytosis crisis of retinal pigment epithelium (RPE) cells in light damage model. METHODS: Light induced mice RPE injury model was established by continuously irradiating cool white light at different exposure time (0, 4, 8h light intensity: 4.18×10-6 J/cm2). In vitro, human ARPE-19 cells treated with the doses and intensity (1.57×10-6 J/cm2) of laser irradiation. Histology analysis was evaluated by hematoxylin and eosin (HE) staining. In vivo RPE phagocytosis was quantified by measuring the accumulation of photoreceptor outer segments in the sub-retinal space. In vitro RPE phagocytosis was assessed by calculating the relative fluorescence intensity of FITC-labeled microspheres in ARPE-19 cells. To further investigate the molecular mechanism, the activation of PKC-α/ezrin signal was evaluated by Western blot in vivo and in vitro. RESULTS: HE staining revealed that the thickness of outer nuclear layer decreased significantly after 4 and 8h light exposure. By immunostaining with rhodopsin, a significant greater accumulation of photoreceptor outer segment was noticed after light injury. In vitro, light injured RPE cells had less phagocytic activity in a dose dependent manner than that of the normal control (P

Purpose: Microincisional glaucoma surgeons operate in a highly confined space, making it difficult to learn by observation or assistance alone. We hypothesized that an ex vivo model would allow for better refinement of technique, quantification of progress, and computation of a learning curve. Methods: Seven trainees without angle surgery experience performed nine ab interno trabeculectomies in pig eyes (n=63) after preparing with training slides and videos. Trainees placed the eyes on a tiltable mannequin head, visualized the trabecular meshwork gonioscopically through an ophthalmic microscope, and removed it by trabectome-mediated ablation. An expert surgeon observed, guided, and rated the procedure using an Operating Room Score (ORS). The extent of accessed outflow beds was estimated with canalograms using fluorescent microspheres. Data was fit using mixed effect models. Results: ORS reached a half-maximum on an asymptote after only 2.5 eyes. Surgical time decreased by 0.9 minutes per eye in linear fashion. The ablation arc followed an asymptotic function with a half-maximum inflection point after 5.3 eyes. The mean ablation arc improved from 73 to 135 degrees. Canalograms revealed that this progress did not correlate well with improvement in outflow instead suggesting that about 30 eyes are needed for true mastery. Conclusion: This inexpensive pig eye model provides a safe and effective training model for ab interno trabeculectomy and allows for quantification of outcomes. Trainees without prior angle surgery experience improved quickly. Actual outflow improvements progressed at a slower rate, which serves as a reminder to remain humbly committed to training.

Purpose: To investigate whether microsurgical excision of trabecular meshwork (TM) in an ex vivo pigmentary glaucoma model can normalize the hypertensive phenotype. Methods: Eight eyes of a porcine pigmentary glaucoma model underwent 90° of microsurgical TM excision with an aspirating dual-blade (Goniotome (G)). 24 hours later, an additional 90° of TM were removed. Anterior segments with sham surgeries served as the control (C). Outflow facility and intraocular pressure (IOP) were analyzed. Histology with hematoxylin and eosin (H&E) was obtained. Results: After the first 90° TM excision, IOP was significantly lower in G (10.23±2.39 mmHg, n=7) than C (20.04±1.97mmHg, n=8, P

Glaucoma is a blinding disease largely caused by increased resistance to drainage of fluid from the eye's anterior chamber, resulting in elevated intraocular pressure (IOP). A major site of fluid outflow regulation and pathology is the trabecular meshwork (TM), an extracellular matrix (ECM)-rich tissue at the entrance of the eye's drainage system. We aimed to characterize the structural and functional properties of a newly developed tissue-engineered (TE) anterior segment eye culture model. We hypothesized that repopulation of decellularized TM ECM with non-native TM cells could restore intraocular pressure (IOP) homeostatic ability. Decellularized porcine anterior segment scaffolds demonstrated complete removal of cells, significant reduction of DNA content, and well-preserved ECM ultrastructure. Seeded cells localized to the TM region (p < 0.001) and progressively infiltrated meshwork ECM. Cells reached a distribution comparable to control TM after four days of perfusion culture. After perfusion rate increase challenge, TE cultures maintained healthy IOPs through regulation of outflow resistance (reseeded = 16.53 ± 0.89, decellularized = 35.23 ± 2.20 mmHg, p < 0.0001). In conclusion, we describe a readily available, storable, and biocompatible scaffold for anterior segment perfusion culture of non-native cells. TE organs demonstrated physiological similarities to native tissues and may reduce the need for scarce donor globes in outflow research.

BACKGROUND To evaluate the outcomes of trabectome-mediated ab interno trabeculectomy in patients with steroid-induced glaucoma (SIG). DESIGN A retrospective, observational cohort study performed in the Department of Ophthalmology, University of Pittsburgh Medical Center. PARTICIPANTS The data of 60 patients with SIG and 484 controls with primary open-angle glaucoma (POAG) matched by age, gender and glaucoma index were collected from the Trabectome Study Group database. METHODS Reduction of intraocular pressure (IOP) and medications were compared between POAG and SIG by multivariate regression. Kaplan-Meier was used for survival analysis. Success was defined as IOP ≤21 mmHg and at least 20% IOP reduction from baseline for any two consecutive visits after 3 months without secondary glaucoma surgery. Postoperative IOP and number of medications were compared with baseline in the SIG subgroups by the Wilcoxon test. MAIN OUTCOME MEASURES Intraocular pressure reduction and 1-year success rate. RESULTS Patients with SIG had a higher baseline IOP (31.4 ± 10.4 vs. 24.1 ± 7.6 mmHg, P

To investigate the biological effects of different intraocular lens (IOL) materials on the adhesion, migration, morphology, and epithelial-to-mesenchymal transition (EMT) of human lens HLEB3 cells.Human HLEB3 cells were seeded onto IOLs composed of four different materials (polymethyl methacrylate (PMMA), silicone elastomer, hydrophilic acrylic, and hydrophobic acrylic). The levels of cellular adhesion, migration, morphology, and EMT were then quantified using a cell viability assay, scratch test, phase contrast microscopy, and immunofluorescence staining, respectively.The highest levels of HLEB3 cell adhesion and migration were found for the hydrophobic acrylic IOL cultures, which also had the lowest incidence of EMT (p0.01). In contrast, while the PMMA IOLs had a low level of cell adhesion, the percentage of these cells undergoing EMT was the highest compared to the other groups (p0.001). The hydrophilic IOLs were also associated with an extremely low level of cellular adhesion, which ultimately prevented any further analysis. Finally, while the HLEB3 cells cultured with silicon IOLs were similar to those cultured with hydrophobic acrylic IOLs in terms of morphology and EMT levels, they had significantly lower adhesion and migration profiles.Taken together, these data suggest that IOL composition greatly affects lens cell behavior during PCO development, and it appears that hydrophobic IOLs may be the best option to limit the effects of PCO after cataract surgery while also correcting the patient's vision.

Purpose: This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor, in a porcine ex vivo pigmentary glaucoma model. Methods: Twenty-eight porcine anterior chambers were perfused with medium supplemented with 1.67 × 107 pigment particles/mL for 48 hours before treatment with RKI-1447 (n = 16) or vehicle control (n = 12). Intraocular pressure (IOP) was recorded and outflow facility was calculated. Primary trabecular meshwork cells were exposed to RKI-1447 or vehicle control; effects on the cytoskeleton, motility, and phagocytosis were evaluated. Result: Compared to baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 caused no apparent histological changes in the micro- or macroscopic TM appearance. RKI-1447-treated primary TM cells showed significant disruption of the actin cytoskeleton both in the presence and absence of pigment (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI-1447 reversed. Conclusion: RKI-1447 significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it useful for the treatment of secondary glaucomas with an increased phagocytic load.

Purpose: To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO). Methods: In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 µM DETA-NO) on outflow facility were compared to controls (n=8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 µM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macro script and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results: The facility increased after DETA-NO (0.189±0.081 μL/min·mmHg, p=0.034) and AIT (0.251±0.094 μL/min·mmHg, p=0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (0.190±0.074 μL/min·mmHg, p=0.023) and CSA by 13.9% (p

In this study, we investigate the mechanism of 7,8,3'-Trihydroxyflavone (THF) on retinal oxidative stress and retinal ganglion cell (RGC) growth. Oxidative stress was induced by ocular hypertension (O.H.) in rat retina in vivo. Rats were then systemically injected with THF. We found THF ameliorated O.H.-induced oxidative stress in retina by reducing caspase-3 activity, downregulating MDA level and augmenting glutathione peroxidase expression. In addition, neonatal RGCs were cultured in vitro, and treated with THF. It was demonstrated that THF promoted neurite regeneration in RGC explant, and activated receptor kinase B (TrkB) signaling pathway through phosphorylation. In THF-treated RGC explant, application of TrkB antagonist, ANA12, effectively reversed the pro-neuronal effect of THF on promoting RGC neurite outgrowth, and inhibited TrkB signaling pathway through dephosphorylation. Thus, we concluded that THF could inhibit retinal oxidative stress and promote RGC growth through TrkB-dependent signaling pathway, thus providing a novel pharmaceutical candidate for glaucoma.

Pigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.

Objective: The Rho GTPase/Rho kinase pathway is an important target in glaucoma treatment. This study investigated the hypotensive effect of RKI-1447, a Rho kinase inhibitor developed for cancer treatment, in a porcine ex vivo pigmentary glaucoma model. Materials and Methods: Twenty-eight fresh porcine anterior chambers were perfused with pigment medium (1.67 × 107 pigment particles/mL) for 48 hours before being subjected to the RKI-1447 (n = 16) or the vehicle control (n = 12). Another twelve eyes with normal medium perfusion served as the control. The intraocular pressure (IOP) was recorded at two-minute intervals and the outflow facility was calculated. To investigate the intracellular mechanism of the IOP reduction, primary trabecular meshwork cells were exposed to RKI-1447 or the vehicle control and then analyzed for changes in cytoskeleton, motility, and phagocytosis. Results: Compared to the baseline, the perfusion of pigment caused a significant increase in IOP in the RKI-1447 group (P = 0.003) at 48 hours. Subsequent treatment with RKI-1447 significantly reduced IOP from 20.14 ± 2.59 mmHg to 13.38 ± 0.91 mmHg (P = 0.02). Pigment perfusion reduced the outflow facility from 0.27 ± 0.03 at baseline to 0.18 ± 0.02 at 48 hours (P < 0.001). This was partially reversed with RKI-1447. RKI-1447 exhibited no apparent changes in the micro- or macroscopic appearance, including histology. Primary TM cells exposed to RKI-1447 showed a significant disruption of the actin cytoskeleton both in the presence and absence of pigment exposure (P < 0.001) but no effect on TM migration was observed. Pigment-treated TM cells exhibited a reduction in TM phagocytosis, which RKI reversed. Conclusions: RKI-1447 is a novel ROCK inhibitor that significantly reduces IOP by disrupting TM stress fibers and increasing TM phagocytosis. These features may make it especially useful for the treatment of secondary glaucomas with an increased phagocytosis load but also for other open angle glaucomas.

To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open-angle glaucoma (POAG) patients. This was a multicenter, retrospective study and included POAG patients with or without visually-significant cataracts. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2-years. Success was defined as: 1) IOP < 21 mmHg and at least 20% IOP reduction from baseline after 3 months at any two consecutive visits, and 2) no additional glaucoma surgery required. A total of 42 patients were enrolled; thirteen had a history of failed glaucoma surgery. Twelve patients underwent Trabectome surgery combined with phacoemulsification while the remainder underwent Trabectome surgery alone. Overall, the mean preoperative IOP was 21.4±1.23 mmHg. The Trabectome lowered IOP to 18.5± 0.94 mmHg at 2 years (P

Purpose To evaluate the effect of gypenosides (GPs) on lipopolysaccharide (LPS)-induced optic neuritis rats. Methods Optic neuritis was induced by a single microinjection of LPS into the optic nerve of Sprague Dawley rats. GPs (400 mg/kg) was administrated by gavage for 21 days. The optic nerve structure changes and demyelination were observed after hematoxylin & eosin and Luxol-fast blue staining. Apoptosis of retinal ganglion cells (RGCs) was evaluated using Brn3a-TUNEL double staining. Expression of CD68 and glial fibrillary acidic protein (GFAP) were detected using immunofluorescence staining. The mRNA levels of inflammatory factors were measured using quantitative real-time PCR. The protein expression levels in the signal transducer and activator of transcription (STAT) and nuclear factor-κB (NF-κB) pathways were detected using Western blot. Results GPs treatment prevented the optic nerve structure changes and demyelination in the rats with optic neuritis. GPs treatment downregulated LPS-induced overexpressions of CD68, GFAP and pro-inflammatory factors. GPs treatment inhibited STAT1 and 3 phosphorylation and NF-κB nuclear translocation in the optic nerve and retina of rats with optic neuritis. Conclusion GPs attenuate LPS-induced inflammation, demyelination and optic nerve damage which may be associated with the inhibition of the NF-κB and STAT pathways.

Purpose The rate of conventional aqueous humor outflow is the highest nasally. We hypothesized that this is reflected in regionally different outflow structures and analyzed the entire limbus by high-resolution, full-thickness ribbon-scanning confocal microscopy (RSCM). Methods We perfused pig eyes by anterior chamber cannulation with eight lectin-fluorophore conjugates, followed by optical clearance with benzyl alcohol benzyl benzoate (BABB). RSCM and advanced analysis software (Imaris) were used to reconstruct a three-dimensional (3D), whole-specimen rendering of the perilimbal outflow structures. We performed morphometric analyses of the outflow tract from the level of the trabecular meshwork (TM) to the scleral vascular plexus (SVP). Results Except for pigmented structures, BABB cleared the entire eye. Rhodamine-conjugated Glycine max agglutinin (soybean [SBA]) labeled the outflow tract evenly and retained fluorescence for months. RSCM produced terabyte-sized files allowing for in silico dissection of outflow tract vessels at a high resolution and in 3D. Networks of interconnected lumens were traced from the TM to downstream drainage structures. The collector channel (CC) volumes were 10 times smaller than the receiving SVP vessels, the largest of which were in the inferior limbus. Proximal CC diameters were up to four times the size of distal diameters and more elliptical at their proximal ends. The largest CCs were found in the superonasal and inferonasal quadrants where the highest outflow occurs. Conclusion RSCM of cleared eyes enabled high-resolution, volumetric analysis of the outflow tract. The proximal structures had greater diameters nasally, whereas the SVP was larger in the inferior limbus.

PurposeOutflow 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.Materials and MethodsSixteen porcine anterior chamber cultures received a continuous infusion of pigment granules (P), 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.ResultsThe baseline IOPs in P and C were similar (P=0.82). A significant IOP elevation occurred in P 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).ConclusionIn 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.

Background To stratify the outcomes of phacoemulsification combined with trabectome surgery using a new glaucoma severity index. Methods This is a retrospective, observational cohort study that included open angle glaucoma patients with visually significant cataract that had phacoemulsification combined with trabectome surgery. Exclusion criteria were follow-up less than 12 months, any other surgeries or diagnosis of neovascular or active uveitic glaucoma. Patients were stratified into four groups according to the Glaucoma Index (GI) that incorporated preoperative intraocular pressure (IOP), number of medications and visual field status. The primary outcome measures were IOP reduction and the success rate at 12 months. We examined the relationship between GI group and IOP and medications at one year with a linear regression analysis and survival with log-rank testing. Results Of 1374 patients, a total of 498 cases with 12 month follow-up were included in the study after applying the exclusion criteria. At one year, IOP of GI groups 1 through 4 was reduced by 2.9 ± 4.4, 3.6 ± 5.0, 3.9 ± 5.3, and 9.2 ± 7.6 mmHg for. Individuals in the next higher GI group had a 1.69 ± 0.2 mmHg larger IOP decrease. The success rate was 98%, 93%, 96% and 88% at one year for GI groups 1 to 4 (p

Purpose: To compare the intraoperative angle stability and the postoperative outflow of two ab interno trabeculectomy devices that excise the trabecular meshwork. The newer device has an active aspiration and irrigation port while the older requires viscoelastic to maintain the anterior chamber. We hypothesized that anterior segment optical coherence tomography (ASOCT) allows quantifying the intraoperative behavior in a microincisional glaucoma surgery (MIGS) pig eye training model. Methods: Twelve freshly enucleated porcine eyes were measured with ASOCT at baseline, at the beginning of the procedure and at its conclusion to determine the anterior chamber depth (ACD) and the nasal angle

To evaluate the outcomes of trabectome-mediated ab interno trabeculectomy in patients with steroid-induced glaucoma (SIG).A retrospective, observational cohort study performed in the Department of Ophthalmology, University of Pittsburgh Medical Center.The data of 60 patients with SIG and 484 controls with primary open-angle glaucoma (POAG) matched by age, gender and glaucoma index were collected from the Trabectome Study Group database.Reduction of intraocular pressure (IOP) and medications were compared between POAG and SIG by multivariate regression. Kaplan-Meier was used for survival analysis. Success was defined as IOP ≤21 mmHg and at least 20% IOP reduction from baseline for any two consecutive visits after 3 months without secondary glaucoma surgery. Postoperative IOP and number of medications were compared with baseline in the SIG subgroups by the Wilcoxon test.Intraocular pressure reduction and 1-year success rate.Patients with SIG had a higher baseline IOP (31.4 ± 10.4 vs. 24.1 ± 7.6 mmHg, P 0.01) and obtained a greater IOP reduction than controls with POAG (48.4% vs. 31.5%, P 0.01). Multivariate regression showed that patients with SIG had an IOP reduction of 6.7 ± 1.1 mmHg more than those with POAG. Survival rates at 12 months were comparable at 86% in the SIG group and 85% in the POAG group (P = 0.47). Patients with SIG with a high baseline IOP, younger age and advanced glaucoma experienced a larger IOP drop.Trabectome appears to be an effective surgical treatment in reducing IOP for patients with SIG.

Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm′s canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm′s canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

Li-Xiao Zhou,1 Cheng-Lin Sun,1 Li-Juan Wei,1 Zhi-Min Gu,1 Liang Lv,1 Yalong Dang21Department of Ophthalmology, The Fifth Affiliated Hospital of Zhengzhou University, 2Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic ofChinaObjective: To investigate the cognitive impairment in patients with age-related macular degeneration (AMD).Methods: Relevant articles were identified through a search of the following electronic databases through October 2015, without language restriction: 1) PubMed; 2) the Cochrane Library; 3) EMBASE; 4) ScienceDirect. Meta-analysis was conducted using STATA 12.0 software. Standardized mean differences with corresponding 95% confidence intervals were calculated. All of the included studies met the following four criteria: 1) the study design was a case–control or randomized controlled trial (RCT) study; 2)the study investigated cognitive function in the patient with AMD; 3) the diagnoses of AMD must be provided; 4) there were sufficient scores data to extract for evaluating cognitive function between cases and controls. The Newcastle–Ottawa Scale criteria were used to assess the methodological quality of the studies.Results: Of the initial 278 literatures, only six case–control and one RCT studies met all of the inclusion criteria. A total of 794 AMD patients and 1,227 controls were included in this study. Five studies were performed with mini-mental state examination (MMSE), two studies with animal fluency, two studies with trail making test (TMT)-A and -B, one study with Mini-Cog. Results of the meta-analysis revealed lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test (P≤0.001 for all). The results also showed that differences in the TMT-A (except AMD [total] vs controls) and TMT-B test had no statistical significance (P>0.01). The Newcastle–Ottawa Scale score was ≥5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates.Conclusion: This meta-analysis suggests lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test. The other cognitive impairment screening tests, such as animal fluency test and TMT, need more studies to assess.Keywords: age-related macular degeneration; cognitive impairment; meta-analysis; mini mental state examination