To report the 24mo outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in routine clinical practice and simultaneously evaluated the real-world safety.

The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab (0.5 mg) or conbercept (0.5 mg) for mCNV were analyzed from 1 January 2017 to 1 January 2022. The primary outcome variables were mean change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes. The secondary outcome variables included IOP changes, the period of mCNV re-treatment, and ocular adverse events.

Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included. In visual acuity, the mean logMAR BCVA at baseline was 0.81±0.43. After the initial improvement at 1, 3, and 6mo (P<0.05), from month 12 onwards, no statistical difference compared to baseline was found. The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT (P<0.05). The regression model showed better baseline BCVA and thicker baseline CMT, significantly associated with the final outcomes. In univariate analysis, choosing 3+pro re nata (PRN) as the initial injection treatment regimen was associated with better BCVA at 24mo [hazard ratio (HR)=-0.65, 95%CI: -1.23, -0.07, P=0.048]. However, the difference was not significant in multivariate analysis (HR=-0.59, 95%CI: -1.21, 0.03, P=0.089). Regarding mCNV recurrence, the mean period (P=0.725) and the proportion of mCNV reactivation (P=1.00) were similar between ranibizumab and conbercept. Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender, drug, and initial injection treatment regimen. No systemic adverse events related to the therapy were observed.

BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up. The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles. Additionally, intravitreal anti-VEGF therapy using 1+PRN regimen, offers certain advantages in both efficacy and cost-effectiveness.

To determine the therapeutic benefits of fenofibrate (Feno) on the dysfunction of high glucose (HG)-induced human retinal microvascular endothelial cells (HRMECs) and to elucidate the underlying molecular mechanism.

HRMEC dysfunction model was established by 48h glucose (30 mmol/L) treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activator (Nigericin). Cell viability/apoptosis were assessed by cell counting kit-8 (CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining and flow cytometry assays. Levels of apoptosis- (Bcl-2-associated X protein, Bax/B-cell lymphoma 2, Bcl-2), vascular permeability-(vascular endothelial growth factor, VEGF) and inflammasome activation-related proteins (NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD, ASC), as well as inflammatory factors (interleukin, IL-6/IL-1β/tumor necrosis factor, TNF-α/IL-18) were determined with Western blot/enzyme linked immunosorbent assay (ELISA). Cell permeability/reactive oxygen species (ROS) level/superoxide dismutase (SOD) activity/malondialdehyde (MDA) content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe/SOD kit/MDA kit.

HRMEC dysfunction was successfully induced by HG, evidenced by decreased viability (P<0.001), increased apoptosis (P<0.001), permeability (P<0.001), and inflammatory factor levels (P<0.001). Feno treatment significantly ameliorated HG-induced HRMEC dysfunction (P<0.01). Meanwhile, HG induction increased ROS production (P<0.001) and MDA content (P<0.001) in HRMECs, while reducing SOD activity (P<0.001), indicative of oxidative stress. This was, however, abolished by Feno (P<0.05). Moreover, Feno eliminated activation of NLRP3 inflammasomes (P<0.05) in HG-induced HRMECs. Strikingly, activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction (P<0.05).

Feno represses oxidative stress and NLRP3 inflammasome activation, consequently alleviating HG-induced HRMEC dysfunction.