Paeoniflorin promotes PPARγ expression to suppress HSCs activation by inhibiting EZH2-mediated histone H3K27 trimethylation.

BACKGROUND: The alleviating effect of paeoniflorin (Pae) on liver fibrosis has been established; however, the molecular mechanism and specific target(s) underlying this effect remain elusive. PURPOSE: This study was to investigate the molecular mechanism underlying the regulatory effect of Pae on hepatic stellate cells (HSCs) activation in liver fibrosis, with a specific focus on the role of Pae in modulating histone methylation modifications. METHODS: The therapeutic effect of Pae was evaluated by establishing in vivo and in vitro models of carbon tetrachloride (CCl4)-induced mice and transforming growth factor ß1 (TGF-ß1)-induced LX-2 cells, respectively. Molecular docking, surface plasmon resonance (SPR), chromatin immunoprecipitation-quantitative real time PCR (ChIP-qPCR) and other molecular biological methods were used to clarify the molecular mechanism of Pae regulating HSCs activation. RESULTS: Our study found that Pae inhibited HSCs activation and histone trimethylation modification in liver of CCl4-induced mice and LX-2 cells. We demonstrated that the inhibitory effect of Pae on the activation of HSCs was dependent on peroxisome proliferator-activated receptor γ (PPARγ) expression and enhancer of zeste homolog 2 (EZH2). Mechanistically, Pae directly binded to EZH2 to effectively suppress its enzymatic activity. This attenuation leaded to the suppression of histone H3K27 trimethylation in the PPARγ promoter region, which induced upregulation of PPARγ expression. CONCLUSION: This investigative not only sheds new light on the precise targets that underlie the remission of hepatic fibrogenesis induced by Pae but also emphasizes the critical significance of EZH2-mediated H3K27 trimethylation in driving the pathogenesis of liver fibrosis.

Internal limiting membrane peeling in rhegmatogenous retinal detachment: A meta-analysis.

PURPOSE: To determine whether pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for rhegmatogenous retinal detachment (RRD) could get better functional and anatomical outcomes. METHODS: A comprehensive literature search was performed to find relevant studies. A meta-analysis was conducted by comparing the weighted mean differences (WMD) in the mean change of best corrected visual acuity (BCVA) from baseline and calculating the odd ratios (OR) for rates of epiretinal membrane (ERM) formation and recurrence of retinal detachment (RD). RESULTS: Fourteen studies were selected, including 2259 eyes (825 eyes in the ILM peeling group and 1434 eyes in the non-ILM peeling group). There was no significant difference in terms of mean change in BCVA from baseline and the rate of RD recurrence (WMD = 0.02, 95% CI, -0.20 to 0.24, P = 0.86, and OR = 0.55, 95% CI, 0.24 to 1.26, P = 0.16), but ILM peeling was associated with a significantly lower frequency of postoperative ERM formation (OR = 0.13, 95% CI, 0.06 to 0.26, P<0.00001). Similar results were obtained in a sub-analysis based on macula-off RRD. CONCLUSION: ILM peeling results in similar BCVA, with same rate of RD recurrence, but lower rate of postoperative ERM development. ILM peeling could be considered in selected cases with risk factors that are likely to develop an ERM.

PKSEA-Net: A prior knowledge supervised edge-aware multi-task network for retinal arteriolar morphometry.

Retinal fundus images serve as a non-invasive modality to obtain information pertaining to retinal vessels through fundus photography, thereby offering insights into cardiovascular and cerebrovascular diseases. Retinal arteriolar morphometry has emerged as the most convenient and fundamental clinical methodology in the realm of patient screening and diagnosis. Nevertheless, the analysis of retinal arterioles is challenging attributable to imaging noise, stochastic fuzzy characteristics, and blurred boundaries proximal to blood vessels. In response to these limitations, we introduce an innovative methodology, named PKSEA-Net, which aims to improve segmentation accuracy by enhancing the perception of edge information in retinal fundus images. PKSEA-Net employs the universal architecture PVT-v2 as the encoder, complemented by a novel decoder architecture consisting of an Edge-Aware Block (EAB) and a Pyramid Feature Fusion Module (PFFM). The EAB block incorporates prior knowledge for supervision and multi-query for multi-task learning, with supervision information derived from an enhanced Full Width at Half Maximum (FWHM) algorithm and gradient map. Moreover, PFFM efficiently integrates multi-scale features through a novel attention fusion method. Additionally, we have collected a Retinal Cross-Sectional Vessel (RCSV) dataset derived from approximately 200 patients in Quzhou People's Hospital to serve as the benchmark dataset. Comparative evaluations with several state-of-the-art (SOTA) networks confirm that PKSEA-Net achieves exceptional experimental performance, thereby establishing its status as a SOTA approach for precise boundary delineation and retinal vessel segmentation.

Platinum Nanoparticles Regulated V2 C MXene Nanoplatforms with NIR-II Enhanced Nanozyme Effect for Photothermal and Chemodynamic Anti-Infective Therapy.

Given the challenge of multidrug resistance in antibiotics, non-antibiotic-dependent antibacterial strategies show promise for anti-infective therapy. V2 C MXene-based nanomaterials have demonstrated strong biocompatibility and photothermal conversion efficiency (PCE) for photothermal therapy (PTT). However, the limitation of V2 C MXene's laser irradiation to the near-infrared region I (NIR-I) restricts tissue penetration, making it difficult to achieve complete bacterial eradication with single-effect therapeutic strategies. To address this, Pt nanoparticles (Pt NPs) are attached to V2 C, forming artificial nanoplatforms (Pt@V2 C). Pt@V2 C exhibits enhanced PCE (59.6%) and a longer irradiation laser (NIR-II) due to the surface plasmon resonance effect of Pt NPs and V2 C. Notably, Pt@V2 C displays dual enzyme-like activity with chemodynamic therapy (CDT) and NIR-II enhanced dual enzyme-like activity. The biocatalytic mechanism of Pt@V2 C is elucidated using density functional theory. In an in vivo animal model, Pt@V2 C effectively eliminates methicillin-resistant Staphylococcus aureus from deep-seated tissues in subcutaneous abscesses and bacterial keratitis environments, accelerating abscess resolution and promoting wound and cornea healing through the synergistic effects of PTT/CDT. Transcriptomic analysis reveals that Pt@V2 C targets inflammatory pathways, providing insight into its therapeutic mechanism. This study presents a promising therapeutic approach involving hyperthermia-amplified biocatalysis with Pt NPs and MXene nanocomposites.

Si-Ni-San inhibits hepatic Fasn expression and lipid accumulation in MAFLD mice through AMPK/p300/SREBP-1c axis.

BACKGROUND: Soothing the liver and regulating qi is one of the core ideas of traditional Chinese medicine (TCM) in the treatment of fatty liver. Si-Ni-San (SNS) is a well-known herbal formula in TCM for liver soothing and qi regulation in fatty liver treatment. However, its efficacy lacks modern scientific evidence. PURPOSE: This study was aimed to investigate the impact of SNS on metabolic associated fatty liver disease (MAFLD) in mice and explore the underlying molecular mechanisms, particularly its effects on lipid metabolism in hepatocytes. METHODS: The therapeutic effect of SNS was evaluated using in vivo and in vitro models of high-fat/high-cholesterol (HFHC) diet-induced mice and palmitic acid (PA)-induced hepatocytes, respectively. Molecular biological techniques such as RNA-sequencing (RNA-seq), co-immunoprecipitation (co-IP), and western blotting were employed to elucidate the molecular mechanism of SNS in regulating lipid metabolism in hepatocytes. RESULTS: Our findings revealed that SNS effectively reduced lipid accumulation in the livers of HFHC diet-induced mice and PA-induced hepatocytes. RNA-seq analysis demonstrated that SNS significantly down-regulated the expression of fatty acid synthase (Fasn) in the livers of HFHC-fed mice. Mechanistically, SNS inhibited Fasn expression and lipid accumulation by activating adenosine monophosphate (AMP)-activated protein kinase (AMPK). Activation of AMPK suppressed the activity of the transcriptional coactivator p300 and modulated the protein stability of sterol regulatory element-binding protein-1c (SREBP-1c). Importantly, p300 was required for the inhibition of Fasn expression and lipid accumulation by SNS. Furthermore, SNS activated AMPK by decreasing adenosine triphosphate (ATP) production in hepatocytes. CONCLUSION: This study provided novel evidence on the regulatory mechanisms underlying the effects of SNS on Fasn expression. Our findings demonstrate, for the first time, that SNS exerts suppressive effects on Fasn expression through modulation of the AMPK/p300/SREBP-1c axis. Consequently, this regulatory pathway mitigates excessive lipid accumulation and ameliorates MAFLD in mice.

Essential oil extracted from Quzhou Aurantii Fructus prevents acute liver failure through inhibiting lipopolysaccharide-mediated inflammatory response.

Quzhou Aurantii Fructus (QAF) has a long history as a folk medicine and food for the treatment of liver diseases. While our earlier study provided evidence of hepatoprotective properties contained within the flavonoids and limonins constituents in QAF, the potential preventative effects afforded by essential oil components present within QAF remains enigmatic. In this study, we prepared Quzhou Aurantii Fructus essential oil (QAFEO) and confirmed its anti-inflammatory effects on liver inflammation through experimentation on lipopolysaccharide and D-galactosamine (LPS/D-GalN) induced acute liver failure (ALF) mouse models. Using RNA-sequence (RNA-seq) analysis, we found that QAFEO prevented ALF by systematically blunting the pathways involved in response to LPS and toll-like receptor signaling pathways. QAFEO effectively suppressed the phosphorylation of tank-binding kinase 1 (TBK1), TGF-beta activated kinase 1 (TAK1), interferon regulatory factor 3 (IRF3), and the activation of mitogen activated kinase-like protein (MAPK) and nuclear factor-kappa B (NF-κB) pathways in vivo and in vitro. Importantly, QAFEO substantially reduced myeloid differentiation primary response gene 88 (MyD88)- toll-like receptor 4 (TLR4) interaction levels. Moreover, 8 compounds from QAFEO could directly bind to REAL, TAK1, MyD88, TBK1, and IRF3. Taken together, the results of our study support the notion that QAFEO exerts a hepatoprotective effect through inhibiting LPS-mediated inflammatory response.

Saikosaponin A triggers cell ferroptosis in hepatocellular carcinoma by inducing endoplasmic reticulum stress-stimulated ATF3 expression.

Ferroptosis is a type of nonapoptotic necrotic cell death characterized by iron-dependent lipid peroxidation. Saikosaponin A (SsA), a natural bioactive triterpenoid saponin extracted from Radix Bupleuri, has shown potent antitumor activity against various tumors. However, the underlying mechanism of the antitumor activity of SsA remains unclear. Here, we discovered that SsA induced HCC cell ferroptosis in vitro and in vivo. Using RNA-sequence analysis, we found that SsA mainly affected the glutathione metabolic pathway and inhibited the expression of cystine transporter solute carrier family 7 member 11 (SLC7A11). Indeed, SsA increased intracellular malondialdehyde (MDA) and iron accumulation, while it decreased the levels of reduced glutathione (GSH) in HCC. Deferoxamine (DFO), ferrostatin-1 (Fer-1) and GSH could rescue SsA-induced cell death, whereas Z-VAD-FMK was found ineffective in inhibiting SsA-induced cell death in HCC. Importantly, our result indicated that SsA induced the expression of activation transcription factor 3 (ATF3). SsA-induced cell ferroptosis and suppression of SLC7A11 are dependent on ATF3 in HCC. Moreover, we revealed that SsA induced ATF3 upregulation via activation of endoplasmic reticulum (ER) stress. Taken together, our findings support that ATF3-dependent cell ferroptosis mediated the antitumor effects of SsA, opening the possibility to explore SsA as a ferroptosis inducer in HCC.

Analysis of retinal arteriolar and venular parameters in primary open angle glaucoma.

AIM: To measure the retinal vessels of primary open angle glaucoma (POAG) patients on spectral domain optical coherence tomography (SD-OCT) with a full-width at half-maximum (FWHM) algorithm to better explore their structural changes in the pathogenesis of POAG. METHODS: In this retrospective case-control study, the right eyes of 32 patients with POAG and 30 healthy individuals were routinely selected. Images of the supratemporal and infratemporal retinal vessels in the B zones were obtained by SD-OCT, and the edges of the vessels were identified by the FWHM method. The internal and external diameters, wall thickness (WT), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR) of the blood vessels were studied. RESULTS: Compared with the healthy control group, the POAG group showed a significantly reduced retinal arteriolar outer diameter (RAOD), retinal arteriolar lumen diameter (RALD) and WSCA in the supratemporal (124.22±12.42 vs 138.32±10.73 µm, 96.09±11.09 vs 108.53±9.89 µm, and 4762.02±913.51 vs 5785.75±1148.28 µm2, respectively, all P<0.05) and infratemporal regions (125.01±15.55 vs 141.57±10.77 µm, 96.27±13.29 vs 110.83±10.99 µm, and 4925.56±1302.88 vs 6087.78±1061.55 µm2, all P<0.05). The arteriolar WT and WLR were not significantly different between the POAG and control groups, nor were the retinal venular outer diameter (RVOD), retinal venular lumen diameter (RVLD) or venular WT in the supratemporal or infratemporal region. There was a positive correlation between the arteriolar parameters and visual function. CONCLUSION: In POAG, narrowing of the supratemporal and infratemporal arterioles and a significant reduction in the WSCA is observed, while the arteriolar WT and WLR do not change. Among the venular parameters, the external diameter, internal diameter, WT, WLR, and WSCA of the venules are not affected.

Fovea sparing versus complete internal limiting membrane peeling for myopic traction maculopathy: a meta-analysis.

PURPOSE: Myopic traction maculopathy (MTM) is the leading cause of visual loss in high myopia. The purpose of this study was to compare the outcomes of pars plana vitrectomy (PPV) with fovea-sparing internal limiting membrane (ILM) peeling and complete ILM peeling for MTM. METHODS: A comprehensive literature search was performed to find relevant studies. A meta-analysis was conducted by comparing the weighted mean differences (WMD) in the change of best-corrected visual acuity (BCVA) and central foveal thickness (CFT) from baseline and calculating the odd ratios (OR) for rates of complete reattachment (CR) and postoperative macular hole (MH) formation. RESULTS: Ten studies were selected, including 417 eyes (172 eyes in the fovea-sparing ILM peeling group (FSIP) and 245 eyes in complete ILM peeling group (CIP)). There was no significant difference in terms of mean change in CFT from baseline and the rate of CR(WMD = 3.53, 95% CI, -25.56 to 32.63, P = 0.81, and OR = 1.41, 95% CI, 0.81 to 2.44, P = 0.22). FSIP was superior to CIP in terms of mean change of logMAR BCVA post operation (WMD = -0.09, 95% CI, -0.15 to -0.03, P = 0.003), and associated with a significantly lower frequency of postoperative MH formation (OR = 0.19, 95% CI, 0.07 to 0.50, P = 0.0008). CONCLUSION: FSIP resulted in similar anatomic outcomes compared to CIP, but resulted in better visual acuity and lower rates of postoperative MH development.

Chorioretinal Alterations Induced by Preeclampsia.

Hypertension during pregnancy, which is essentially a microvascular disease that destroys the end-organ microcirculation, should not be underestimated, as it could lead to organ failure in the kidneys, lungs, and brain. Preassessment of the microcirculatory state through systematic observation of the fundus has been proven to be noninvasive and feasible. Although hypertension in preeclampsia patients will resolve after childbirth, the sticking point is determining the best termination moment. Early diagnosis and treatment can prevent long-term ocular complications and cardiovascular risks for pregnant women in the future. In order to adjust the treatment strategy through more sensitive and precise fundus changes, we comprehensively summarized the common structural changes in the fundus in preeclampsia patients, including changes in the blood vessels, choroid, and retina, as well as the application of quantitative observation for chorioretinal alterations in recent years.

Inverted ILM flap technique versus conventional ILM peeling for idiopathic large macular holes: A meta-analysis of randomized controlled trials.

PURPOSE: To compare the anatomical and visual outcomes of inverted internal limiting membrane (ILM) flap technique with the conventional ILM peeling for idiopathic large macular holes (MHs). METHODS: A meta-analysis of randomized control trials (RCTs) using online databases including NCBI PubMed, ClinicalTrials.gov, and ISI Web of Science was performed. Anatomic success and type 1 closure rates, the mean postoperative best-corrected visual acuity (BCVA) and the mean change of BCVA from baseline were analyzed. RESULTS: Out of 251 articles, four described clinical trials matching the inclusion criteria and were selected. They included 276 eyes (135 eyes in the inverted ILM flap group and 141 eyes in the ILM peeling group). All the studies used gas tamponade, with two studies having a follow-up duration of 3 months, while one study had a follow-up of 6 months and one study- 12 months. The meta-analysis demonstrated that anatomic success and type 1 closure rates (presence of neurosensory retina in MH) were better in the inverted ILM flap technique (odds ratio (OR) = 4.89; 95% confidence interval (CI), 2.09-11.47; P = 0.0003 and OR = 5.23; 95% CI, 2.83-9.66; P<0.00001). Similarly, the inverted flap technique was superior in terms of postoperative logMAR BCVA and mean change of logMAR BCVA from baseline (weighted mean difference (WMD) = 0.17, 95% CI, 0.11 to 0.24, P<0.00001 and WMD = 0.08, 95% CI, 0.01 to 0.16, P = 0.03). CONCLUSION: Inverted ILM flap treatment resulted in better closure rates and visual acuity when compared to the standard ILM peeling for large MHs.

Optic perineuritis secondary to hyaluronic acid injections: a case report.

BACKGROUND: Although a safe, excellent administration method for hyaluronic acid derivatives has been documented; improper injections can lead to devastating and irreversible consequences. Here, we present the first known case of optic perineuritis caused by hyaluronic acid. CASE PRESENTATION: A young female experienced sudden orbital pain in the right eye after receiving hyaluronic acid injections to the eyebrows. She presented to the eye clinic two weeks later, after developing blurred vision in the right eye. Visual acuity was reduced significantly in the right eye. Automated visual field examination showed defects in both eyes. Fundus examination revealed bilateral swelling of optic discs. Magnetic resonance imaging of the brain demonstrated bilateral perineural enhancement consistent with optic perineuritis. The patient was treated with retrobulbar injection of hyaluronidase and oral prednisolone. Her vision improved with treatment. CONCLUSIONS: The prognosis for visual outcomes in patients with optic perineuritis is generally excellent. However, a poor prognosis is associated with delays to the initiation of treatment. Recognizing this condition is important, and treatment with corticosteroids should be initiated early.

INCIDENCE OF ENDOPHTHALMITIS AFTER VITRECTOMY: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this study was to review the literature reporting rates of postoperative endophthalmitis after pars plana vitrectomy and investigate whether modern microincision vitrectomy surgery (MIVS) increases the postoperative endophthalmitis rate, compared with traditional 20-gauge (20 G) vitrectomy. METHODS: A comprehensive literature search was performed to identify studies describing the incidence of post-pars plana vitrectomy endophthalmitis. A meta-analysis of comparative studies reporting the endophthalmitis rates after MIVS versus 20 G vitrectomy was also conducted. RESULTS: A total of 31 studies reported 199 endophthalmitis cases in 363,544 participants (0.05%). The incidence of endophthalmitis after 20 G vitrectomy was 0.04% (88/229,435), compared with 0.03% (8/27,326) after 23 G and 0.11% (33/29,676) after 25 G. The meta-analysis demonstrated that the incidence of endophthalmitis was higher after MIVS (23 G/25 G) compared with 20 G vitrectomy (odds ratio = 3.39, 95% confidence interval, 1.39-8.23). In a subgroup analysis, we also found an increased risk of endophthalmitis after 25 G compared with 20 G vitrectomy (odds ratio = 4.09, 95% confidence interval, 2.33-7.18), but not for 23 G versus 20 G (odds ratio = 1.14, 95% confidence interval, 0.47-2.78). CONCLUSION: The incidence of post-pars plana vitrectomy endophthalmitis was low, with no significant differences between 23 G MIVS and 20 G vitrectomy, but 25 G MIVS may result in a higher postoperative endophthalmitis rate.

Subfoveal Choroidal Thickness in Central Serous Chorioretinopathy: A Meta-Analysis.

PURPOSE: To evaluate the relationship between subfoveal choroidal thickness (SFCT) and eyes with central serous chorioretinopathy (CSC) versus fellow or control eyes. METHODS: We performed a meta-analysis using databases including PubMed, Embase and ISI Web of Science to find relevant studies. Weighted mean difference (WMD) was calculated for the SFCT in CSC eyes, the unaffected fellow eyes and normal controls. RESULTS: Twelve studies were selected for this meta-analysis, including 1108 eyes (397 CSC eyes, 228 unaffected fellow eyes and 483 eyes of normal controls). The meta-analysis clearly demonstrated that the subfoveal choiroid of eyes with a clinical presentation of CSC was thickened compared to unaffected fellow eyes (WMD = 52.81, 95% confidence interval (CI), 39.13-66.49, P<0.00001) and was thickened compared to control eyes (WMD = 145.03, 95%CI, 121.33-168.73, P<0.00001). The mean SFCT measurement of the unaffected fellow eyes showed also significantly increased choroidal thickness compared to that of normal control eyes (WMD = 77.20, 95% CI, 44.98-109.42, P<0.00001). Similar results were obtained in a sub-analysis based on the same instrument. CONCLUSION: It is demonstrated that SFCT is significantly increased in eyes with clinical manifestation of CSC, and in the clinically non-manifested fellow eyes. These results support the hypothesis that CSC is a bilateral disorder with an initial unilateral clinical presentation.

SUBTHRESHOLD MICROPULSE DIODE LASER VERSUS CONVENTIONAL LASER PHOTOCOAGULATION FOR DIABETIC MACULAR EDEMA: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To evaluate the relative efficacy of subthreshold micropulse diode laser versus conventional laser photocoagulation for the treatment of diabetic macular edema. METHODS: A comprehensive literature search was conducted to find relevant randomized controlled trials (RCTs). Efficacy estimates were determined by comparing weighted mean differences of the mean change of best-corrected visual acuity and central macular thickness from baseline. RESULTS: Six RCTs were selected for this meta-analysis, including 398 eyes (203 eyes in the subthreshold micropulse diode laser group and 195 eyes in the conventional laser group). Subthreshold micropulse diode laser was superior to conventional laser in terms of mean change of logMAR best-corrected visual acuity at 3, 9, and 12 months after treatment (P = 0.02; P = 0.04, and P = 0.03, respectively), and it showed a similar trend at 6 months (P = 0.05). Although, there was no significant difference in terms of mean change in central macular thickness from baseline to 3, 6, 9, or 12 months (P = 0.80; P = 0.20; P = 0.88, and P = 0.86, respectively). CONCLUSION: Subthreshold micropulse diode laser treatment resulted in better visual acuity compared with conventional laser, although the differences before 12 months are likely to be too small to be of clinical relevance and may be dependent on baseline best-corrected visual acuity. The two types of treatment seem to have similar anatomical outcome.

Deep Anterior Lamellar Keratoplasty Versus Penetrating Keratoplasty: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: To evaluate the efficacy and safety of deep anterior lamellar keratoplasty (DALK) compared with penetrating keratoplasty (PK) for patients who had corneal stromal pathologies without endothelial abnormalities. METHODS: We performed a meta-analysis using databases including PUBMED, EMBASE, and ClinicalTrials.gov to find relevant randomized controlled trials. Efficacy parameters were the postoperative best-corrected visual acuity, uncorrected visual acuity, and refractive error. Safety parameters were postoperative endothelial cell loss and graft rejection. RESULTS: Five randomized controlled trials were selected for this meta-analysis, including 409 eyes (217 eyes in the DALK group and 192 eyes in the PK group). Postoperative logarithm of the minimum angle of resolution BCVA and UCVA were significantly better for PK than that for DALK [weighted mean difference (WMD) = 0.04, 95% confidence interval (CI), 0.01-0.07, P = 0.005 and WMD = 0.12, 95% CI, 0.05-0.18, P = 0.0007, respectively], whereas, the proportion of patients whose postoperative best-corrected visual acuity ≥ 20/40 did not differ statistically [risk ratio (RR) = 0.97, 95% CI, 0.89-1.07, P = 0.57]. There were no significant differences in terms of refractive error either by spherical equivalent or astigmatism (P = 0.11 and P = 0.25, respectively). The endothelial cell loss percentage in the PK group was significantly higher compared with the DALK group (WMD = -8.75, 95% CI, -15.25 to -2.25, P = 0.008). The DALK group was associated with a significantly lower frequency of graft rejection and endothelial rejection than the PK group (RR = 0.48, 95% CI, 0.28-0.82, P = 0.007 and RR = 0.07, 95% CI, 0.01-0.35, P = 0.001, respectively). CONCLUSIONS: DALK is an alternative surgical procedure for corneal stromal pathologies without endothelial abnormalities, with lower efficacy but better safety.

Successful delayed treatment of the traumatic orbital apex syndrome by nasal endoscopic decompression surgery.

To report a patient with traumatic orbital apex syndrome, who fully recovered visual and extraocular function following surgery. A 34-year-old male presented with visual and extraocular function disorders in his right eye following traffic accident, who was referred to our hospital 5 weeks after accident. The patient underwent endoscopic optic nerve and orbital apex decompression with topical and systemic application of nerve growth factor and steroids after a failed trial of mega-dose intravenous corticosteroids. Visual acuity improved to 20/20 at 3 weeks after surgery, and the right eye globe moved in most directions at 1 year, which remained stable at 3 years. Surgical decompression should be considered even when symptoms have been present for over a month.

Pharmacogenetics of Complement Factor H Y402H Polymorphism and Treatment of Neovascular AMD with Anti-VEGF Agents: A Meta-Analysis.

The purpose of this study is to investigate whether the Y402H polymorphism (rs1061170, a T-to-C transition at amino acid position 402) in the complement factor H (CFH) gene have a pharmacogenetics effect on the anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). We performed a meta-analysis using databases including PubMed and EMBASE to find relevant studies. 13 published association studies were selected for this meta-analysis, including 2704 patients. For the CFH Y402H polymorphism, anti-VEGF treatment was much less effective in AMD patients with the CFH CC genotype (CC versus TT: odds ratio (OR) = 55, 95% confidence interval (CI), 0.31 to 0.95, P = 0.03; CC versus CT: OR = 0.60, 95% CI, 0.40 to 0.91, P = 0.02; and CC versus CT + TT: OR = 0.59, 95% CI, 0.38 to 0.90, P = 0.02, respectively). In subgroup analysis, CFH Y402H polymorphism was more likely to be a predictor of response for Caucasians (CC versus CT+TT: OR = 0.63, 95% CI, 0.42 to 0.95, P = 0.03). In conclusion, pharmacogenetics of CFH Y402H polymorphism may play a role in response to anti-VEGF treatment for neovascular AMD, especially for Caucasians.

Bevacizumab versus ranibizumab for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the relative efficacy and safety of bevacizumab versus ranibizumab for the treatment of the neovascular form of age-related macular degeneration. METHODS: A comprehensive literature search using the Cochrane Methodology Register to identify randomized controlled trials comparing bevacizumab with ranibizumab in patients with neovascular age-related macular degeneration. Efficacy estimates were determined by comparing weighted mean differences in the change of best-corrected visual acuity and central macular thickness from baseline. Safety estimates were determined by calculating the risk ratio for rates of death, arteriothrombotic events, venous thrombotic events, and at least 1 serious systemic adverse event. Statistical analysis was performed using the RevMan 5.1 software. RESULTS: A total of 6 randomized controlled trials were selected for this meta-analysis, including 2,612 patients (1,292 patients in the bevacizumab group and 1,320 patients in the ranibizumab group). There were no significant differences between bevacizumab and ranibizumab in best-corrected visual acuity mean change at 1 year or 2 years (weighted mean difference = -0.40, 95% confidence interval [CI], -1.48 to 0.69, P = 0.47 and weighted mean difference = -1.16, 95% CI, -2.82 to 0.51, P = 0.17, respectively). Ranibizumab was found to be more efficacious in reducing central macular thickness at 1 year (weighted mean difference = 4.35, 95% CI, 0.92-7.78, P = 0.01). The pooled risk ratios comparing the rates of serious systemic adverse events at 1 year and 2 years were slightly in favor of ranibizumab (risk ratio = 1.24, 95% CI, 1.04-1.48, P = 0.02 and risk ratio = 1.20, 95% CI, 1.05-1.37, P = 0.008, respectively), whereas the rates of death, arteriothrombotic events, and venous thrombotic events did not differ statistically. CONCLUSION: Bevacizumab and ranibizumab had equivalent efficacy for best-corrected visual acuity in the treatment of neovascular age-related macular degeneration. Ranibizumab tended to have a better anatomical outcome. There were no differences between drugs in rates of death, arteriothrombotic events or venous thrombotic events, and differences in rates of serious systemic adverse events that require further study.

Ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the relative efficacy of ranibizumab (RBZ) monotherapy or combined with laser (RBZ + Laser) versus laser monotherapy for the treatment of diabetic macular edema (DME). METHODS: A comprehensive literature search using PUBMED, ClinicalTrials.gov, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing RBZ or RBZ + Laser to laser monotherapy in patients with DME. Efficacy estimates were determined by comparing weighted mean differences (WMD) in the change of best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline, and the risk ratios (RR) for the proportions of patients with at least 15 letters change from baseline. Safety analysis estimated the RR of cardiac disorders at 6 to 12 months in RBZ therapy vs. laser monotherapy. Statistical analysis was performed using the RevMan 5.1 software. RESULTS: Seven RCTs were selected for this meta-analysis, including 1749 patients (394 patients in the RBZ group, 642 patients in the RBZ + Laser group, and 713 patients in the laser group). RBZ and RBZ + Laser were superior to laser monotherapy in the mean change of BCVA and CMT from baseline (WMD = 5.65, 95% confidence interval (CI), 4.44-6.87, P<0.00001; WMD  = 5.02, 95% CI, 3.83-6.20, P<0.00001, and WMD  = -57.91, 95% CI, -77.62 to -38.20, P<0.00001; WMD  = -56.63, 95% CI, -104.81 to -8.44, P = 0.02, respectively). The pooled RR comparing the proportions of patients with at least 15 letters improvement or deterioration were also in favor of RBZ and RBZ + Laser (RR = 2.94, 95% CI, 1.82-4.77, P<0.00001; RR = 2.04, 95% CI, 1.50-2.78, P<0.00001, and RR = 0.21, 95% CI, 0.06-0.71, P = 0.01; RR = 0.52, 95% CI, 0.29-0.95, P = 0.03, respectively). There were no significant differences between RBZ and RBZ + Laser for any of the parameters. There were no difference in the safety profile between RBZ and laser. CONCLUSION: RBZ and RBZ + Laser had better visual and anatomic outcomes than laser monotherapy in the treatment of DME. RBZ + Laser seemed to be equivalent to RBZ.