ABSTRACT
Objective To evaluate the safety and efficacy ofdexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO).Methods This study was a six-month,randomized,double-masked,sham-controlled,multicenter,phase 3 clinical trial with a 2-month open-label study extension.Patients with branch or central RVO received DEX (n=129) or sham procedure (n=130) in the study eye at baseline;all patients who met re-treatment criteria received DEX at month 6.Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS),best-corrected visual acuity (BCVA),and central retinal thickness (CRT) on optical coherence tomography.Results Time to ＞ 15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (P＜ 0.001).At month 2 (peak effect),the percentage of patients with ≥ 15-letter BCVA improvement from baseline was DEX:34.9％,sham:11.5％;mean BCVA change from baseline was DEX:10.6± 10.4 letters,sham:1.7 ± 12.3 letters;and mean CRT change from baseline was DEX:-407 ± 212 μm,sham:-62 ± 224 μm (all P＜0.001).Outcomes were better with DEX than sham in both branch and central RVO.The most common treatment-emergent adverse event was in-creased intraocular pressure (IOP).Increase sin IOP generally were controlled with topical medication.Mean IOP normalized by month 4,and no patient required incisional glaucoma surgery.Conclusions DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO.Visual and anatomic outcomes were improved with DEX relative to sham for 3-4 months after a single implant.
ABSTRACT
Pseudomonas aeruginosa (PA) pneumonia is a refractory,even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process.We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells,i.e.,Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10).Seventy-two BALB/c mice were divided into four groups randomly:control (A),PA pneumonia (B),immunosuppression (C) and immunosuppression with PA pneumonia (D).Mice were sacrificed at 4,8 and 24 h after establishing experimental models.The pathological changes of lung tissue were graded,and the FOXP3 mRNA and serum IL-10 levels were detected.Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C,but significantly pathological changes were found in groups B and D,especially in group D at 8 h (P＜0.05).The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points,which were significantly lower than those in groups B and D (P＜0.05).FOXP3 mRNA levels were lowest at 4 h,and there was significant difference between groups B and D (P＜0.05).The serum levels of IL-10 in groups A and C were almost normal at the three time points,but decreased significantly in groups B and D (P＜0.05).The serum levels ofIL-10 decreased to the lowest at 8 h,especially in group D (P＜0.05).The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly,which may be associated with Treg cells function disturbance.And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.