Intravitreal Infliximab for the Treatment of Proliferative Vitreoretinopathy (FIXER): A Randomized Controlled Phase 2 Trial.

OBJECTIVE: To study the safety and efficacy of intravitreal infliximab administered at the conclusion of pars plana vitrectomy (PPV) in the treatment of proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD). DESIGN: Randomized controlled phase 2 clinical trial. SUBJECTS: Patients with primary RRD and Grade C PVR, according to the updated Retina Society Classification. METHODS: Sixty-six Patients were randomized in a 1:1 ratio to undergo PPV and silicone oil (SO) injection with or without intravitreal injection of 1 mg/0.05 mL of infliximab in the air-filled globe before SO injection at PPV conclusion. Surgeons were masked to treatment allocation until PPV conclusion. MAIN OUTCOME MEASURES: The primary outcome measure was anatomic success (defined as complete retinal reattachment without a tamponade at 6 months post SO removal). Secondary outcome measures were final best corrected visual acuity (BCVA), single operation success rate (SOSR), rate of recurrent detachment, central macular thickness (CMT) by macular optical coherence tomography (OCT), macular function by multifocal electroretinogram and macular vascular density (VD) by OCT angiography. RESULTS: 60 eyes of 60 patients, 30 eyes in each group, completed the study. At baseline, there were no differences regarding age, gender, history of trauma, lens status, duration of RRD, BCVA, intraocular pressure (IOP), intra-ocular inflammation (IOI), detachment extent in clock hours, number/size of breaks, presence of vitreous hemorrhage, axial length, or grade/extent of PVR between both groups. For the outcome measures, 30 eyes in the infliximab group achieved anatomic success vs 29 eyes in the control group. The SOSR was higher in the infliximab group (26) vs the control (23), but this was not statistically significant (p = 0.317). Final BCVA was better in the infliximab group (mean logMAR (SD) = 0.96 (0.4), Snellen equivalent ≈ 20/180) vs the control (1.14 (0.4), Snellen equivalent ≈ 20/280) (p = 0.044). There were no differences regarding IOP, IOI, time of SO removal, macular function, CMT, or VD. CONCLUSION: PPV with SO tamponade with or without intravitreal infliximab is effective in treating PVR-associated RRD. Infliximab may be associated with modest improvement in final visual outcomes but not anatomical outcomes.

Safety outcomes of SGLT2i in the heart failure trials: A systematic review and Meta-analysis.

AIMS: Sodium-glucose co-transporter inhibitors (SGLT2i) are emerging as a new treatment for heart failure (HF) after demonstrating favorable clinical outcomes in several randomized controlled trials (RCTs). In this meta-analysis, we assessed the safety of SGLT2i in the trials that prespecified heart failure in their inclusion criteria. MATERIALS AND METHODS: We searched the databases for RCTs comparing SGLT2i to placebo in heart failure patients. The primary outcome was the incidence of serious adverse events (SAEs). A sensitivity analysis according to the class of HF was also performed. RESULTS: The incidence of SAEs was significantly lower in the SGLT2i group (OR, 0.85; 95% CI, 0.77-0.92; P, 0.0002) and SAEs remained significantly lower after performing the sensitivity analysis (OR, 0.82; 95% CI, 0.75-0.89; P, <0.00001). Genital infections, urinary tract infections (UTIs), and hypotension were significantly higher in the SGLT2i group. CONCLUSIONS: SGLT2i remain a safe option for patients with HF with a lower incidence of SAEs. However, since they increase the risk of genital infection, UTIs and hypotension, the risks vs benefits in each patient should be weighed when making a prescribing decision.

The benefit of GLP-1RA in different age groups in the cardiovascular outcome trials.

There may be hesitancy in prescribing GLP-1RA in older adults. On pooling results from the CVOTs comparing GLP-1RA to placebo, there was a significantly lower incidence of MACE favoring GLP-1RA in both younger and older adults. GLP-1RA should be considered in high risk patients regardless of age.