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AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.
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We have recently demonstrated that tau hyperphosphorylation causes diabetic synaptic neurodegeneration of retinal ganglion cells (RGCs), which might be the earliest affair during the pathogenesis of diabetic retinopathy (DR). Thus, there is a pressing need to seek therapeutic agents possessing neuroprotective effects against tau hyperphosphorylation in RGCs for arresting the progression of DR. Here, using a well-characterized diabetes model of db/db mouse, we discovered that topical ocular application of 10 mg/kg/day of ginsenoside Rg1 (GRg1), one of the major active ingredients extracted from Panax ginseng and Panax notoginseng, ameliorated hyperphosphorylated tau-triggered RGCs synaptic neurodegeneration in diabetic mice. The neuroprotective effects of GRg1 on diabetic retinae were abrogated when retinal IRS-1 or Akt was suppressed by intravitreal injection with si-IRS-1 or topically coadministered with a specific inhibitor of Akt, respectively. However, selective repression of retinal GSK3ß by intravitreal administration of si-GSK3ß rescued the neuroprotective properties of GRg1 when Akt was inactivated. Therefore, the present study showed for the first time that GRg1 can prevent hyperphosphorylated tau-induced synaptic neurodegeneration of RGCs via activation of IRS-1/Akt/GSK3ß signaling in the early phase of DR. Moreover, our data clarify the potential therapeutic significance of GRg1 for neuroprotective intervention strategies of DR.
Subject(s)
Diabetic Retinopathy/drug therapy , Ginsenosides/administration & dosage , Glycogen Synthase Kinase 3 beta/metabolism , Insulin Receptor Substrate Proteins/metabolism , Neuroprotective Agents/administration & dosage , Proto-Oncogene Proteins c-akt/metabolism , Retinal Ganglion Cells/drug effects , tau Proteins/metabolism , Animals , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Humans , Insulin Receptor Substrate Proteins/genetics , Male , Mice , Mice, Inbred C57BL , Nerve Degeneration/drug therapy , Nerve Degeneration/genetics , Nerve Degeneration/metabolism , Panax notoginseng/chemistry , Phosphorylation , Plant Extracts/administration & dosage , Proto-Oncogene Proteins c-akt/genetics , Retina/pathology , Retinal Ganglion Cells/metabolism , Signal Transduction/drug effects , tau Proteins/geneticsABSTRACT
AIM: To evaluate the effectiveness of autologous conjunctival flap surgery for repairing the late-onset filtering bleb leakage after trabeculectomy. METHODS: This study retrospectively reviewed 106 eyes from 106 patients with late-onset filtering bleb leakage after trabeculectomy who received autologous conjunctival flap surgery at the Zhongshan Ophthalmic Centre from 2005 to 2015. The basic information was recorded, and the interval time between trabeculectomy and autologous conjunctival flap surgery as well as related risk factors, intraocular pressure (IOP), anterior chamber depth (ACD) and best corrected visual acuity (BCVA) were analysed. Moreover, 41 patients who completed the 1-year follow up were analysed to determine the IOP and BCVA changes and long-term success rates. RESULTS: The 50 male and 56 female subjects (average age 39.13±17.96y) included 47 (44.34%) and 33 (31.13%) cases of primary open angle and primary angle-closure glaucoma. The mean interval between trabeculectomy and repair surgery was 60.60±56.92 (3-264)mo. The mean mitomycin (MMC) concentration during trabeculectomy was 0.27±0.04 (0.12-0.4) mg/mL in the fornix-based conjunctival flap group (68 patients) and 0.28±0.04 (0.20-0.33) mg/mL in the limbal-based conjunctival flap group (11 patients). After bleb leakage, the patients' vision remained stable while the IOP decreased from 10.25±4.76 (3-20.86) to 9.44±4.33 (2-21) mm Hg (P<0.01). In the 41 analysed patients, the IOP was controlled at 15.68±5.11 (7-40) mm Hg in the 1st year after autologous conjunctival flap surgery and recurrence was not observed, for a long-term success rate of 100%. CONCLUSION: Autologous conjunctival flap repairing surgery is an effective technique for sealing filtering bleb leakages and controlling IOP postoperatively.
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Objective· To investigate the correlation between increased nuchal translucency (NT) thickness and fetal chromosomal abnormalities,severe structure anomalies and other abnormalities,and its value in assessment of fetal prognosis.Methods · Five hundred and eighty-three singleton fetuses with NT ≥ 2.5 mm in the first trimester (11-13+6 week) were retrospectively analyzed,of which 252 had invasive prenatal test for fetal chromosome and genetic tests.They were divided into 5 groups according to the NT thickness,2.5 ~ 2.9 mm,3.0 ~ 3.4 mm,3.5 ~ 4.4 mm,and ≥ 4.5 mm as 1st to 4th group,and cystic hygroma as 5th group.The incidences among groups were analyzed by Cochran-Armitage Trend test.Fisher's exact test was used to compare diversities of NT thickness among the major chromosomal abnormalities.Results · Among the 583 singleton fetuses,59 were diagnosed as chromosomal abnormalities (23.4%,59/252),38 with structure anomalies (6.5%),of which 13 cases with severe cardiac anomalies (2.2%).There were 6 fetal demise,3 inevitable abortion,2 stillborn,94 terminations of pregnancy (8 for personal factors) and 478 live birth,without spontaneous abortions and congenital infections after invasive prenatal test.The differences among the incidences of chromosomal abnormalities,structure anomalies and cardiac anomalies in five groups were statistically significant (P=0.000) and the incidences all increased with fetal NT thickness.The healthy living rates of fetus were 96.5%,81.9%,74.0%,35.6%,and 6.7% among groups,respectively,and the incidences all decreased with fetal NT thickness (P=0.000).Conclusion· Increased NT thickness is related to fetal chromosomal abnormalities,severe cardiac anomalies and poor pregnant outcome.The incidences of chromosomal abnormalities,structure anomalies,cardiac anomalies and pregnant outcome all increase with fetal NT thickness.In clinical practice,individualized guidance should be conducted according to different thickness of NT.
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CONTEXT: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability. OBJECTIVE: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops. MATERIALS AND METHODS: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution. RESULTS: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20 min (p < .01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90 min after topical administration. CONCLUSIONS: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.
Subject(s)
Hypromellose Derivatives/chemical synthesis , Ophthalmic Solutions/chemical synthesis , Pyridones/chemical synthesis , Administration, Topical , Animals , Aqueous Humor/drug effects , Aqueous Humor/metabolism , Drug Evaluation, Preclinical/methods , Female , Hypromellose Derivatives/administration & dosage , Hypromellose Derivatives/pharmacokinetics , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/pharmacokinetics , Pharmaceutical Solutions/administration & dosage , Pharmaceutical Solutions/chemical synthesis , Pharmaceutical Solutions/pharmacokinetics , Pyridones/administration & dosage , Pyridones/pharmacokinetics , Rabbits , ViscosityABSTRACT
Purpose. To compare the efficacy of subthreshold and conventional selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in the patients with primary open-angle glaucoma (POAG). Methods. Fifty-two eyes from fifty-two POAG patients were randomized into two groups, one group treated with subthreshold SLT using two-thirds of the conventional energy and the other one treated with the conventional energy. IOP was measured with the Goldmann tonometer and the anterior chamber inflammation was determined using laser flare meter. Results. The initial energy dosage used in subthreshold SLT group was significantly lower than the amount of the energy used in conventional SLT group (0.4 ± 0.1 mJ versus 0.6 ± 0.1 mJ, P = 0.030). The total energy dosage was also significantly lower in subthreshold SLT group compared to the other group (37.6 ± 3.3 mJ versus 51.8 ± 5.7 mJ, P = 0.036). However, the level of inflammation in aqueous humor, amount of reduction in IOP, and the success rate in controlling IOP was the same in both groups. Conclusion. The efficacy of subthreshold SLT group in reducing IOP in POAG patients is comparable to the efficacy of conventional SLT group.
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Glaucoma is a common cause of visual impairment and irreversible blindness. Medication is important in the management of glaucoma, especially in primary open-angle glaucoma. Combination drug therapy is needed because single drug therapy can not always control the intraocular pressure effectively to a safe level in glaucoma patients with higher baseline intraocular pressure. Traditional unfixed combination therapy of glaucoma may disturb daily life because the frequency of admitting eye-drops is increased, it is less persistence or compliance, and results in the increase of local concentration of preservatives in the eye. The new fixed combination formulations for glaucoma have been developed to be safer, more effect and more compliable. This article reviews the comparative studies of therapeutic effects of anti-glaucoma fixed combination formulation and summarizes features of each formulation, and then prospects the new developing tendency of anti-glaucoma medication.