Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

INTRODUCTION: This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. RESULTS: A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was - 1.1 letters (95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. CONCLUSIONS: QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

Effect of intravitreal conbercept treatment on the expression of Long Noncoding RNAs and mRNAs in Proliferative Diabetic Retinopathy Patients.

PURPOSE: To evaluate the effect of conbercept on the expression of long noncoding RNAs (lncRNAs) and mRNAs in the fibrovascular membranes of proliferative diabetic retinopathy (PDR) patients. METHODS: Twenty patients, diagnosed with PDR, who underwent pars plana vitrectomy (PPV), were recruited for this study. Ten patients were treated for PPV alone (Control Group), and the others received conbercept injections before PPV (Treated Group). The fibrovascular membranes were harvested during surgery. Expression of lncRNAs and mRNAs in the membranes was tested using lncRNA Arrays. Bioinformatics analyses were performed to identify the related biological modules and pathways of the differentially expressed genes. A lncRNA/mRNA coexpression network was built to identify the correlations between lncRNAs and mRNAs. Real-time PCR was conducted to verify the microarray results. RESULTS: We identified 427 differentially expressed lncRNAs, of which 263 were upregulated and 164 were downregulated. Gene ontology (GO) analysis indicated that these lncRNAs-coexpressed mRNAs targeted various metabolic processes, especially the gluconeogenesis. Kyoto Encyclopaedia of Genes and Genomes (KEGG) results indicated that 16 pathways had significant differences in gene expression, including gluconeogenesis, HIF-1 signalling pathway, NOD-like receptor pathway, etc. The lncRNA/mRNA coexpression network revealed that many differentially expressed lncRNAs were enriched in the HIF-1, TNF-α and NOD-like receptor pathways. LincRNAs were the largest category and further bioinformatics analysis implied that these lincRNAs-coexpressed mRNAs were mainly involved in PDR-related biological processes and pathological pathways. CONCLUSION: Conbercept treatment can change the expression profiles of lncRNAs and mRNAs in the fibrovascular membranes of PDR patients. A complete understanding of the relationship between lncRNAs and anti-VEGF drugs may contribute to new therapeutic regimen for PDR.

Effect of Phacoemulsification Combined with Intraocular Lens Implantation on Inflammatory Factors, Oxidative Stress Response and Hemorheology in Diabetic Cataract Patients.

OBJECTIVE: To investigate the change on phacoemulsification combined with intraocular lens implantation on inflammatory factors IL-2, IL-6, hs-CRP,TNF-α oxidative stress response indexes MDA, CAT, SOD, GSH-Px; peripheral blood hemorheologic index WHV, WMV,PV, PCV, FIB in diabetic cataract patients. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Ophthalmology, the Second Hospital of Shandong University, Jinan, China, from January 2015 to July 2017. METHODOLOGY: One hundred anf fifty-two diabetic cataract patients (160 eyes) were randomly divided into observation group and control group, each with 76 cases (80 eyes). The control group was treated with conventional therapy, while the observation group was treated with phacoemulsification combined with intraocular lens implantation on the basis of conventional treatment. After one month of treatment, the patients were tested for IL-2, IL-6, hs-CRP, TNF-α, MDA, CAT, SOD, GSH-Px, WHV, WMV, PV, PCV, FIB. RESULTS: After one month of treatment, the levels of IL-2, IL-6, hs-CRP and TNF-α were lower in the observation group (p <0.001); the levels of SOD, GSH-Px and CAT were higher in the observation group (p <0.001), while MDA level was higher in the control group (p <0.001); the levels of WHV, WMV, PV were lower in the observation group (p <0.001), and there was no significant difference in the levels of PCV and FIB between the two groups (p = 0.794 and 0.838, respectively). CONCLUSION: Phacoemulsification combined with intraocular lens implantation can improve the level of aqueous inflammatory factors and oxidative stress response indexes in diabetic cataract patients and improve their level of hemorheological indexest.

Gastrodin inhibits high glucose­induced human retinal endothelial cell apoptosis by regulating the SIRT1/TLR4/NF­κBp65 signaling pathway.

Diabetic retinopathy (DR), one of the most common complications of late­phase diabetes, is associated with the ectopic apoptosis of microvascular cells. Gastrodin, a phenolic glucoside derived from Gastrodia elata Blume, has been reported to have antioxidant and anti­inflammation activities. The aim of the present study was to investigate the effects of gastrodin on high glucose (HG)­induced human retinal endothelial cell (HREC) injury and its underlying mechanism. The results demonstrated that HG induced cell apoptosis in HRECs, which was accompanied by increased levels of reactive oxygen species production. Gastrodin treatment significantly alleviated HG­induced apoptosis and oxidative stress. Furthermore, HG stimulation decreased the levels of SIRT1, which was accompanied by an increase in Toll­like receptor 4 (TLR4) expression and the levels of phosphorylated nuclear factor (NF)­κBp65. However, the administration of gastrodin significantly inhibited the activation of the sirtuin 1 (SIRT1)/TLR4/NF­κBp65 signaling pathway in HRECs exposed to HG. Collectively, the present study demonstrated that gastrodin may be effective against HG­induced apoptosis and its action may be exerted through the regulation of the SIRT1/TLR4/NF­κBp65 signaling pathway.

Changes in axial length, central cornea thickness, and anterior chamber depth after rhegmatogenous retinal detachment repair.

BACKGROUND: This study was designed to measure changes in anterior chamber depth (ACD), central cornea thickness (CCT), and axial length (AL) after scleral buckle (SB) surgery or pars plana vitrectomy (PPV) for the repair of rhegmatogenous retinal detachment (RD). METHODS: We prospectively reviewed the records of 245 eyes of 245 patients scheduled to undergo SB surgery and 238 eyes of 238 patients scheduled to undergo PPV. ACD, CCT, and AL were measured by spectral-domain optical coherence tomography (SD-OCT) and biometry, before surgery as well as 6 and 12 months postoperatively. RESULTS: For both SB and PPV surgeries, ACD was observed to decrease significantly postoperatively, with this trend continuing throughout the follow-up period (p < 0.005). CCT showed no significant difference after PPV or SB surgery. AL increased significantly after SB surgery but not PPV. CONCLUSION: Our results show that SB surgery altered the shape of the eye by changing both ACD and AL. PPV resulted in altered ACD. These findings should elucidate the changes to be expected after SB and PPV surgeries.

Scleral buckling versus vitrectomy for macula-off rhegmatogenous retinal detachment as accessed with spectral-domain optical coherence tomography: a retrospective observational case series.

BACKGROUND: Scleral buckling surgery and pars plana vitrectomy are competing methods in the treatment of retinal detachment. The recent development of spectral-domain optical coherence tomography (SD-OCT) has dramatically improved the visualization of the photoreceptor layer relative to conventional OCT, and offers new opportunities to investigate the discordances between anatomic and functional outcomes after retinal detachment surgery. Hence, the study aim was to use SD-OCT to compare the postoperative macular recovery between scleral buckling and vitrectomy for macular-off rhegmatogenous retinal detachment. METHODS: In this retrospective observational case series, we observed 32 patients who underwent scleral buckling surgery (group 1) and 26 patients who underwent pars plana vitrectomy (group 2) as the primary surgery for macula-off rhegmatogenous retinal detachment. OCT was used to examine microstructural changes in the macular area. RESULTS: The mean visual acuity improvement was 0.4 ± 0.8 logMAR in group 1 and 0.7 ± 0.9 logMAR in group 2. As detected by SD-OCT, subretinal fluid was present in 26 of the group 1 eyes (81.3%) and 5 of the group 2 eyes (19.2%) at 8 weeks postoperatively.This difference was statistically significant (Fisher's exact test, P < 0.05). Moreover, detection by SD-OCT revealed epiretinal membranes in 5 of the group 1 eyes (15.6%) and 11 of the group 2 eyes (42.3%), a difference that was statistically significant (Fisher's exact test, P < 0.05). CONCLUSIONS: Macular recovery and the mean visual acuity differed between the 2 groups of patients. With the help of SD-OCT, we observed that subretinal fluids could persist for a relatively longer period after scleral buckling. Based on our results, we conclude that primary vitrectomy surgery is a better choice for macular recovery of the macula-off rhegmatogenous retinal detachment.

Overexpression of thymosin beta-10 inhibits VEGF mRNA expression, autocrine VEGF protein production, and tube formation in hypoxia-induced monkey choroid-retinal endothelial cells.

PURPOSE: One purpose of this study was to examine if expression of the thymosin beta(10 )(TB10), thymosin beta(4) (TB4), and VEGF165 isoform genes would change in response to hypoxia in monkey choroidal retinal endothelial cells (RF/6A). We also sought to determine if overexpression of the TB10 gene could inhibit VEGF165 mRNA expression, autocrine VEGF production, and tube formation in hypoxic RF/6A cells. METHODS: An adenovirus vector, Ad-TB10, was constructed to deliver the human TB10 gene. Under hypoxic conditions, TB10, TB4, and VEGF165 mRNA were measured using real-time PCR, and VEGF protein expression was evaluated by ELISA. For tube formation assays, the RF/6A cells were transfected with Ad-TB10 and exposed to hypoxia for 4 h. RESULTS: VEGF165 mRNA was 2- and 5.8-fold increased when the RF/6A cells were exposed to hypoxia for 2 and 4 h, respectively. TB10 mRNA decreased at 2 h and increased to a baseline level at 4 h, while TB4 mRNA level increased slightly by 2 and 4 h. Increased VEGF165 mRNA was down-regulated by transfected Ad-TB10, and ELISA results showed that VEGF protein levels increased 2.4-fold after 4-hour hypoxia, and decreased 2-fold after transfection with Ad-TB10. Hypoxia also induced tube formation of the RF/6A cells. This was significantly reduced by Ad-TB10. CONCLUSION: These data indicate that (1) TB4 and TB10 mRNA expression in RF/6A cells present different changes under 2- and 4-hour hypoxia, and (2) TB10 may be an effective inhibitor of angiogenesis by inhibiting VEGF expression and autocrine protein production.

[Photoluminescence from Si and Er dual-implanted Si-rich thermal oxidation SiO2/Si thin films].

Si and Er ions were implanted into Si-rich thermal oxidation SiO2/Si thin film using metal vapor vacuum arc (MEVVA) ion source implanter, which could produce ion beams with high-fluence and strong-flux. Rutheroford backscattering spectra show that Er concentration in as-implanted sample is attained to 10 at. % corresponding to the level of 10(21) atoms.cm-3. Needle nanocrystal Si in the surface of annealed samples have been formed during ion implantation followed by rapid thermal annealing. Photoluminescence around 1.54 microns from Er-doped Si-rich thermal oxidized SiO2/Si thin film were observed at 77 K and room-temperature (RT). Light emission around the wavelength of 1.54 microns were closely related to many conditions including substrate, ion implantation and annealing etc.