One-year outcomes of novel VEGF decoy receptor therapy with intravitreal conbercept in diabetic retinopathy-induced macular edema.

Purpose: Conbercept is a novel recombinant fusion protein designed as a decoy receptor for vascular endothelial growth factor (VEGF) and placental growth factor. The primary purpose was to investigate the effect and safety of conbercept, based on a practical protocol, in the eyes of patients with diabetic macular edema (DME), and the secondary aim was to evaluate the efficacy of low-dose triamcinolone acetonide in patients with refractory DME who had little response to conbercept. Methods: In this retrospective clinical study, 89 treatment eyes from 76 patients with clinically significant DME were initially treated with one to three consecutive monthly intravitreal conbercept (IVC) injections, followed by retreatment with conbercept or switch therapy to triamcinolone acetonide (TA) based on a 6-month observation of the curative effect of IVC. Results: Sixty eyes were initiated on conbercept treatment for DME throughout the entire 1-year assessment period. After at least three consecutive monthly IVC treatments, 29 eyes further received intravitreal triamcinolone acetonide (IVTA) injections at month 6. From baseline to 1 year, the mean number of conbercept injections in the IVC group (n=60) was 4.5±1.0, and the mean number of conbercept injections in the IVC plus IVTA group (n=29) was 3.1±0.3. The mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) were statistically significantly improved at 1 and 3 months after IVC treatments in the IVC group, and gradually improved at 9 months after IVTA treatments in the IVC plus IVTA group. There were no severe complications or conbercept-related adverse ocular and systemic side effects. Conclusions: Conbercept could be effective for visual and anatomic improvements in DME eyes with relatively fewer intravitreal injections and longer treatment intervals in clinical practice. Low-dose TA may be useful for patients with refractory DME resistant to anti-VEGF therapy.

Hyperreflective foci in OCT image as a biomarker of poor prognosis in diabetic macular edema patients treating with Conbercept in China.

PURPOSE: To investigate the dynamic changes of hyperreflective foci (HF) in diabetic macular edema (DME) patients during the intravitreal Conbercept treatment in China. METHODS: DME Patients receiving intravitreal Conbercept (IVC) injections during the year 2016-2017 were retrospectively investigated. Thirteen patients (26 eyes) were recruited in this study. They received IVC once a month for 3 consecutive months. The number and location of HFs, the best-corrected visual acuity (BCVA) and central macular thickness (CMT) at each visit were analyzed and compared. RESULTS: After the first injection, BCVA (LogMAR) was increased from 0.75 ± 0.48 to 0.43 ± 0.24 (p < 0.05), CMT improved from 575.9 ± 191.9 to 388.2 ± 198.5 µm (p = 0.014). However, the BCVA and CMT had no statistical difference after the second and third injection as compared with those after the first injection respectively. The baseline number of HFs was 5.39 ± 4.24, 5.15 ± 5.17 and 0.88 ± 1.90 in the inner retinal, outer retinal and subretinal layer respectively. The number of HFs in these three retinal layers decreased significantly after the first injection (p = 0.0045, p < 0.0001 and p = 0.0045, respectively). However, after the second injection, only the number of HFs in the inner retinal layer experienced a further decrease. After the third injection, no statistically significant HFs changes was observed in each retinal layers. Correlation analysis showed that there was a positive significant correlation between the baseline number of HFs in the inner retina, outer retina, subretina and final BCVA (r = 0.571, p = 0.002; r = 0.464, p = 0.017; r = 0.405, p = 0.04 respectively). There was also a significant positive correlation between outer retinal HFs reduction, total retinal HFs reduction and increase of BCVA (r = 0.40, p = 0.043 and r = 0.393, p = 0.04 respectively). There were no severe ocular adverse reactions or systemic adverse events. CONCLUSIONS: Conbercept is effective and safe in the treatment of DME. HFs can act as a biomarker of poor final visual outcome.

The necessity and optimal time for performing pars plana vitrectomy in acute retinal necrosis patients.

BACKGROUND: To compare the efficacy of pars plana vitrectomy (PPV) at different time points to treat acute retinal necrosis (ARN) and to investigate the necessity of PPV for ARN. METHODS: A retrospective review of the treatment options and outcomes of the ARN patients was performed. Thirty ARN patients (34 eyes) were included in this study. The eyes were divided into 3 groups depending on the treatment administered. In the medically treated group, there was no retinal detachment (RD) at the first visit. The routine group patients were treated with systemic antiviral medications, as well as with intravitreal antiviral injections. In the early PPV treatment group, there was no RD at the first visit. The early PPV treatment group patients were treated with systemic antiviral medications and PPV plus silicone oil tamponade and intravitreal injection. In the PPV group, there was RD at the first visit. The PPV group patients were treated with systemic antiviral medications and PPV plus silicone oil tamponade and intravitreal injection. RESULTS: In the medically treated group, the mean baseline best corrected visual acuity (BCVA) (logMAR) was 1.38 ± 0.35. The BCVA was 1.21 ± 0.36 at the last visit for the medically treated group. In this group, one eye (12.5%) developed RD after 1 month of treatment. In the early PPV treatment group, the mean BCVA (logMAR) was 1.68 ± 0.26. The BCVA was 1.83 ± 0.21 at the last visit for the early PPV group. In this group, five eyes (29.4%) had recurrent RD before silicone oil removal. In the PPV group, the mean BCVA (logMAR) was 2.0 ± 0.35. The BCVA was 1.72 ± 0.34 at the last visit for the PPV group. In this group, one eye (11.1%) had recurrent RD before silicone oil removal. There were no significant differences among the three groups in the baseline BCVA and the BCVA at the last visit (p>0.05). There were no significant differences between the early PPV group and the PPV group in the recurrent RD rates (p = 0.38). CONCLUSIONS: Prophylactic PPV showed no difference in recurrent RD rates or better BCVA. Therefore, prophylactic vitrectomy cannot prevent RD nor improve the prognosis of ARN based on our research.

Hyperglycemia Induces Neutrophil Extracellular Traps Formation Through an NADPH Oxidase-Dependent Pathway in Diabetic Retinopathy.

Neutrophil extracellular traps (NETs), the product of NETosis, is found to localize pathogens and crystals in immune response. Recent studies have found that excessive NETs lead to disease conditions such as diabetes and its complications like diabetic retinopathy (DR). However, the correlation between NETs and high glucose or DR remains unclear. Here, we found NETs level was significantly increased in the serum of diabetic patients, especially in proliferation diabetic retinopathy (PDR) patients. High glucose dramatically increased NETs production in diabetic individuals with time prolonging. The activation of NADPH oxidase was involved in the NETs process which is triggered by high glucose. Moreover, we verified the infiltration of neutrophils in the eyes and adhesion to vascular endothelial cells in diabetic rat models. NETs formation was observed in the vitreous bodies and retinas of diabetic individuals, which indicates NETs may play a role in the pathogenesis of diabetic retinopathy. Furthermore, anti-VEGF therapy downregulates NETs production indicating that NADPH oxidase-derived ROS may be another signaling pathway involved in anti-VEGF therapy.