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Enhanced Benefit in DME From AKB-9778 Tie2 Activation + VEGF Suppression
August 2016
Campochiaro et al. conducted a phase 2a randomized controlled double-masked clinical trial to assess the effect of AKB-9778 (an investigational Tie-2–activating agent that blocks vascular leakage) alone and in combination with ranibizumab in patients with diabetic macular edema (DME). They found that the combined therapy was more effective than monotherapy with either drug.
Study participants (n = 144) had decreased vision from DME and a central subfield thickness (CST) of ≥325 μm, as measured by spectral-domain optical coherence tomography. They were randomized into 3 groups: 1) AKB-9778 monotherapy—subcutaneous AKB-9778 twice-daily (BID) plus monthly sham intraocular injections; 2) combination therapy—subcutaneous AKB-9778 BID plus monthly intravitreal ranibizumab; or 3) ranibizumab monotherapy—subcutaneous placebo injections BID plus monthly intravitreal ranibizumab. AKB-9778 was administered in 15-mg doses, and ranibizumab in 0.3-mg doses. Best-corrected visual acuity (BCVA) and CST were measured at baseline and every 4 weeks. The primary outcome measure was mean change from baseline CST at week 12. Additional outcomes included BCVA and safety.
At week 12, the mean change from baseline CST was significantly greater in the combination group (–164.4 ± 24.2 μm) than in the ranibizumab monotherapy group (–110.4 ± 17.2 μm; p = .008); in the AKB-9778 monotherapy group, the change was 6.2 ± 13.0 μm. At week 12, mean CST and percentage of eyes with resolved edema were 340.0 ± 11.2 μm and 29.2%, respectively, in the combination group versus 392.1 ± 17.1 μm and 17.0%, respectively, in the ranibizumab monotherapy group.
The mean change from baseline BCVA (in letters) was 6.3 ± 1.3 in the combination group; 5.7 ± 1.2 in the ranibizumab monotherapy group; and 1.5 ± 1.2 in the AKB-9778 monotherapy group. Percentages of eyes that gained ≥10 letters and ≥15 letters were 35.4% and 20.8%, respectively, in the combination therapy group; 29.8% and 17.0%, respectively, in the ranibizumab group; and 8.7% and 4.3%, respectively, in the AKB-9778 group.
AKB-9778 was well tolerated, with no clear differences in adverse events between treatment groups.
Overall, this study demonstrates that activation of Tie2 through subcutaneous injections of AKB-9778 in combination with VEGF suppression is more effective than anti-VEGF therapy alone in treating DME.
Risks for Surgical Treatment of Cataracts in Postmenopausal Women
August 2016
Floud et al. used data on 1,312,051 postmenopausal women in the U.K.’s Million Women Study to identify risk factors associated with cataract surgery in that group. The researchers found that diabetes, smoking, and obesity were significant risk factors for undergoing cataract surgery.
In this population-based cohort study, the average age was 56 years (standard deviation [SD], 4.8), and none of the women had previous cataract surgery, hospital admission with cataracts, or cancer at baseline. The women were followed for an average of 11 (SD, 3) years. The main outcome measure was cataract surgery, identified by linkage to central National Health Service records for inpatient and day-patient admissions. The researchers used Cox regression analysis to calculate adjusted relative risks (RRs) for cataract surgery by lifestyle factors, treatment for diabetes, reproductive history, and use of hormonal therapies.
Over the study period, 89,343 participants (6.8%) underwent cataract surgery. Women with diabetes were at the greatest risk (RR, 2.90; 95% CI, 2.82-2.97). Other factors associated with an increased risk of cataract surgery were smoking 15 or more cigarettes daily (RR, 1.26; 95% CI, 1.23-1.30) and obesity (body mass index [BMI] ≥30 vs. BMI <25 kg/m2: RR, 1.12; 95% CI, 1.10-1.14).
The researchers concluded that diabetes, smoking, and obesity were risk factors for cataract surgery. Among the other factors analyzed, alcohol use, physical activity, reproductive history, and use of hormonal therapies had little, if any, association with cataract surgery risk. Further, the authors commented that because cataracts are a leading cause of visual impairment, and cataract surgery is the most common operation in the U.K., it is important to identify any risk factors that may be modifiable.
Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery
August 2016
Because many infants and young children who require vitreoretinal surgery on both eyes are medically fragile and at risk from general anesthesia, Yonekawa et al. assessed the feasibility and safety of immediate sequential bilateral vitreoretinal surgery (ISBVS) in pediatric patients. They found that ISBVS was a feasible and safe treatment paradigm for these young patients when repeated general anesthesia is undesirable or impractical.
This was a multicenter retrospective interventional case series from 24 centers worldwide. The study included 344 surgeries from 172 ISBVS procedures performed in 167 patients aged 17 years or younger (mean age, 1.3 ± 2.6 years). ISBVS is defined as vitrectomy, scleral buckle, or lensectomy using a vitreous cutter in both eyes sequentially during the same anesthesia session. Nonexclusive indications for ISBVS were rapidly progressive disease, 74.6%; systemic morbidity placing the child at high anesthesia risk, 76.0%; and residence remote from surgery location, 30.2%. The most common diagnoses included retinopathy of prematurity (ROP), 72.7%; familial exudative vitreoretinopathy, 7.0%; abusive head trauma, 4.1%; persistent fetal vasculature, 3.5%; and Norrie disease, 2.3%.
Mean surgical time was 143 ± 59 minutes for both eyes. No intraoperative ocular complications were reported, although 2 eyes (from different patients) experienced unilateral vitreous hemorrhage in the immediate postoperative period. There were no cases of endophthalmitis, choroidal hemorrhage, or hypotony.
Mean total anesthesia time was 203 ± 87 minutes. No cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac events occurred. One patient required reintubation, and 1 had prolonged oxygen desaturation. Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively.
The authors gave a number of guidelines for performing ISBVS safely. Among these were rescrubbing, regowning, and regloving between procedures on the 2 eyes, as well as using new drapes, a new set of instruments, and different medication lots for the second eye. In conclusion, they endorsed ISBVS as a treatment option for patients in whom separate staged bilateral surgeries would unduly increase the risk for vision loss, mortality, or both.
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Ophthalmology summaries are written by Marianne Doran and edited by Susan M. MacDonald, MD.
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