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Zhou M.,Shanghai JiaoTong University | Zhou M.,Shanghai Key Laboratory of Fundus Disease | Wang W.,Sun Yat Sen University | Huang W.,Sun Yat Sen University | Zhang X.,Sun Yat Sen University
BMC Ophthalmology | Year: 2014

Background: To evaluate the surgical outcome of Ahmed glaucoma valve (AGV) implantation with a new technique of mitomycin C (MMC) application. Methods: This is a retrospective study. All patients with refractory glaucoma underwent FP-7 AGV implantation. Two methods of MMC application were used. In the traditional technique, 6 x 4 mm cotton soaked with MMC (0.25-0.33 mg/ml) was placed in the implantation area for 2-5mins; in the new technique, the valve plate first was encompassed with a thin layer of cotton soaked with MMC, then inserted into the same area. A 200 ml balanced salt solution was applied for irrigation of MMC. The surgical success rate, intraocular pressure (IOP), number of anti-glaucoma medications used, and postoperative complications were analyzed between the groups. Results: The surgical outcomes of two MMC applied techniques were compared. The new technique group had only one case (2.6%) of encapsulated cyst formation out of 38 eyes, while there were eight (19.5%) cases out of 41 eyes the in traditional group. The difference was statistically significant (P = 0.030). According to the definition of success rate, there was 89.5% in the new technique group and 70.7% in the traditional group at the follow-up end point. There was a significant difference between the two groups (P = 0.035). Mean IOP in the new technique group were significantly lower than those of the traditional group at 3 and 6 months (P < 0.05). Conclusions: By using a thin layer of cotton soaked with MMC to encompass the valve plate, the new MMC application technique could greatly decrease the incidence of encapsulated cyst and increase the success rate following AGV implantation. © 2014 Zhou et al.; licensee BioMed Central Ltd.

Lu X.,Shanghai JiaoTong University | Sun X.,Shanghai JiaoTong University | Sun X.,Shanghai Key Laboratory of Fundus Disease
Drug Design, Development and Therapy | Year: 2015

In developed countries, age-related macular degeneration (AMD) is the leading cause of irreversible blindness in individuals over the age of 65 years. Vascular endothelial growth factor (VEGF) plays a vital role in the formation of neovascular AMD. VEGF regulates angiogenesis, enhances vascular permeability, and drives the formation of choroidal neovascularization. As a result of the introduction of anti-VEGF drugs, the incidence of blindness from neovascular AMD has greatly reduced. Anti-VEGF drugs are used as a first-line treatment for neovascular AMD. The most recent anti-VEGF drug is conbercept, also named KH902, which was approved for the treatment of neovascular AMD by the China Food and Drug Administration in December 2013. In this review, recent clinical information regarding the use of conbercept to treat neovascular AMD is summarized. Conbercept is a soluble receptor decoy that blocks all isoforms of VEGF-A, VEGF-B, VEGF-C, and PlGF, which has a high binding affinity to VEGF and a long half-life in vitreous. Preclinical studies have demonstrated its anti-angiogenesis activity in both ocular neovascular disease models and tumor models. Clinical trials of conbercept have shown its superior efficacy and safety. Patients respond well even with 3-month treatment intervals following loading doses once a month for 3 months. The potential therapeutic effect of conbercept on the treatment of polypoidal choroidal vasculopathy, a special type of neovascular AMD, is also promising. In summary, conbercept is a new treatment option for ophthalmologists and their patients and may help address the limitations of current anti-VEGF drugs. © 2015 Lu and Sun.

Dong K.,Shanghai JiaoTong University | Zhu H.,Shanghai JiaoTong University | Song Z.,Shanghai JiaoTong University | Gong Y.,Shanghai JiaoTong University | And 8 more authors.
American Journal of Pathology | Year: 2012

Necroptosis is a recently discovered programmed necrosis. Evidence demonstrated the importance of necroptosis in neuronal cell death. Necrostatin-1 is a specific inhibitor of necroptosis. In this study, we investigated the role of necrostatin-1 on photoreceptor survival and functional protection after experimental retinal detachment (RD) in rats. Necrostatin-1/inactive analogue of necrostatin-1 was introduced into the subretinal space at RD induction and 6 hours afterward, respectively. We found that necrostatin-1 attenuated retinal histopathological damage and reduced plasma membrane breakdown (a morphological hallmark of necroptosis) in outer retinal layers. Transmission electron microscopy showed that necrostatin-1 directly protected neurons by inhibiting necroptotic, not apoptotic, cell death. Treatment with necrostatin-1 inhibited the induction of receptor-interacting protein kinase phosphorylation after RD (a biomarker of necroptosis). Finally, electroretinographic recording proved that necrostatin-1 contributed to objective functional improvement after RD. These findings indicate that necrostatin-1 is a promising therapeutic agent that protects photoreceptors from necroptosis and improves functional outcome. © 2012 American Society for Investigative Pathology.

Sun Q.,Shanghai JiaoTong University | Sun Q.,Shanghai Key Laboratory of Fundus Disease | Xu X.,Shanghai JiaoTong University | Xu X.,Shanghai Key Laboratory of Fundus Disease
Current Medicinal Chemistry | Year: 2015

Despite progress in pharmacological modalities, treatments for ocular diseases are inconvenient, traumatic, costly and often end in poor final visual results. Peptides, considered as protein fragments, can adequately mimic protein binding and thus are used as therapeutic agents. Chemical modifications and bioengineering techniques are being frequently introduced to improve efficacy and stability of peptides, thereby improving their druggability. Cell-penetrating peptides (CPPs), peptides characterized by penetrating plasma membrane, are famous barrier- passers. They are good candidates for carrying drugs through ocular barriers. Therapeutic peptide and CPP perfectly complement each other. Once united, they may form an optimal formula for ocular topical administration, which can work both effectively and smartly. The consequent noninvasive delivery and economical cost would actualize prophylactic intervention, early treatment and long-term therapy to avoid chronic irreversible vision loss. The aim of the current review is a) to summarize recent therapeutic peptides, both anti-angiogenic and anti-inflammation, evidenced by animal experiments in vivo; b) to discuss the discovery strategies for therapeutic peptide; c) to present current delivery strategies for ophthalmic therapeutic peptide; and d) to introduce CPPs which are capable to deliver cargos to intraocular space via ocular surface administration. © 2015 Bentham Science Publishers.

Zhou M.,Shanghai JiaoTong University | Zhou M.,Shanghai Key Laboratory of Fundus Disease | Zhang P.,Shanghai JiaoTong University | Zhang P.,Shanghai Key Laboratory of Fundus Disease | And 4 more authors.
Investigative Ophthalmology and Visual Science | Year: 2015

PURPOSE. Studies investigating the associations between aldose reductase (ALR) genetic polymorphisms and diabetic retinopathy (DR) have reported controversial results. Therefore, to shed light on these inconclusive findings, we performed this meta-analysis to clarify the effects of ALR C(-106)T polymorphism on DR risk. METHODS. Relevant studies were selected through an extensive search of PubMed, EMBASE, the Web of Science databases and Chinese National Knowledge Infrastructure, VIP, and Wan Fang databases in Chinese. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated by using random-effects model. RESULTS. The present meta-analysis included 3512 diabetes mellitus (DM) patients with DR and 4319 DM patients without DR. Overall, the pooled ORs showed a nonsignificant association between ALR C(-106)T polymorphism and DR susceptibility in all genetic models (C allele versus T allele: OR = 1.08, 95% CI = 0.90-1.29; CT/TT versus CC: OR = 0.90, 95% CI = 0.72-1.13; TT versus CT/CC: OR = 0.87, 95% CI = 0.69-1.10; TT versus CC: OR = 0.87, 95% CI = 0.64-1.18; CT versus CC: OR = 0.93, 95% CI = 0.73-1.19). No significant association was detected between ALR C(-106)T polymorphism and nonproliferative diabetic retinopathy or proliferative diabetic retinopathy. An additional analysis showed that the association of C(-106)T polymorphism with DR was significant in type 1 DM (C allele versus T allele: OR = 1.78, 95% CI = 1.39-2.28; CT/TT versus CC: OR = 0.49, 95% CI = 0.36-0.68; TT versus CT/CC: OR = 0.48, 95% CI = 0.28-0.84; TT versus CC: OR = 0.33, 95% CI = 0.17-0.67; CT versus CC: OR = 0.52, 95% CI = 0.37-0.74) but not in type 2 DM. CONCLUSIONS. The results of this meta-analysis showed that ALR C(-106)T polymorphism was not associated with an increased risk of DR. However, subgroup analysis showed a genetic association between ALR C(-106)T polymorphism and the risk of DR of type 1 DM but not DR of type 2 DM. © 2015 The Association for Research in Vision and Ophthalmology, Inc.

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