Evaluation of cardiac parameters and other safety outcomes of brolucizumab treatment in patients with neovascular age-related macular degeneration.

This was a prospective, single-dose, single-arm, open-label, non-randomized, multicenter clinical study to determine cardiovascular safety after a single brolucizumab 6 mg intravitreal injection in neovascular age-related macular degeneration patients (N = 14). Electrocardiogram (ECG) data were collected at different time points using 12-lead Holter and standard ECG, and patients were followed up to 8 days (end of study) for any signs of ocular and non-ocular adverse events (AEs). No clinically meaningful changes were observed in cardiac parameters. No patient had a ≥30 msec change from baseline in heart rate-corrected QT using Fridericia's formula (QTcF), and no patient had a new QTcF value of ≥450 msec between 20 and 24 h after treatment. No deaths or serious AEs were reported during the study period. These results are in line with the absence of new cardiovascular safety signal based on the ECG recordings collected over the first year of the pivotal studies performed with brolucizumab in DME. Trial Registration: ClinicalTrials.gov identifier: NCT03954626.

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial.

BACKGROUND: Despite increasing worldwide use of anti-vascular endothelial growth factor agents for treatment of retinopathy of prematurity (ROP), there are few data on their ocular efficacy, the appropriate drug and dose, the need for retreatment, and the possibility of long-term systemic effects. We evaluated the efficacy and safety of intravitreal ranibizumab compared with laser therapy in treatment of ROP. METHODS: This randomised, open-label, superiority multicentre, three-arm, parallel group trial was done in 87 neonatal and ophthalmic centres in 26 countries. We screened infants with birthweight less than 1500 g who met criteria for treatment for retinopathy, and randomised patients equally (1:1:1) to receive a single bilateral intravitreal dose of ranibizumab 0·2 mg or ranibizumab 0·1 mg, or laser therapy. Individuals were stratified by disease zone and geographical region using computer interactive response technology. The primary outcome was survival with no active retinopathy, no unfavourable structural outcomes, or need for a different treatment modality at or before 24 weeks (two-sided α=0·05 for superiority of ranibizumab 0·2 mg against laser therapy). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02375971. INTERPRETATION: Between Dec 31, 2015, and June 29, 2017, 225 participants (ranibizumab 0·2 mg n=74, ranibizumab 0·1 mg n=77, laser therapy n=74) were randomly assigned. Seven were withdrawn before treatment (n=1, n=1, n=5, respectively) and 17 did not complete follow-up to 24 weeks, including four deaths in each group. 214 infants were assessed for the primary outcome (n=70, n=76, n=68, respectively). Treatment success occurred in 56 (80%) of 70 infants receiving ranibizumab 0·2 mg compared with 57 (75%) of 76 infants receiving ranibizumab 0·1 mg and 45 (66%) of 68 infants after laser therapy. Using a hierarchical testing strategy, compared with laser therapy the odds ratio (OR) of treatment success following ranibizumab 0·2 mg was 2·19 (95% Cl 0·99-4·82, p=0·051), and following ranibizumab 0·1 mg was 1·57 (95% Cl 0·76-3·26); for ranibizumab 0·2 mg compared with 0·1 mg the OR was 1·35 (95% Cl 0·61-2·98). One infant had an unfavourable structural outcome following ranibizumab 0·2 mg, compared with five following ranibizumab 0·1 mg and seven after laser therapy. Death, serious and non-serious systemic adverse events, and ocular adverse events were evenly distributed between the three groups. FINDINGS: In the treatment of ROP, ranibizumab 0·2 mg might be superior to laser therapy, with fewer unfavourable ocular outcomes than laser therapy and with an acceptable 24-week safety profile. FUNDING: Novartis.

Comparison of optical particle sizing and cascade impaction for measuring the particle size of a suspension metered dose inhaler.

Optical techniques for the particle size characterization of metered dose inhaler (MDI) suspensions have been developed as an alternative to the labor-intensive and time-consuming impaction method. In this study, a laser diffraction (LD) apparatus with a liquid cell ("wet cell" method) and a "time-of-flight" apparatus named aerodynamic particle sizer (APS) were utilized to assess MDI suspensions with varied formulation compositions and storage conditions. The results were compared with the conventional Anderson cascade impaction (ACI) data. The two optical methods were able to detect the changes in particle size distributions between formulations, yet to a lesser extent than those observed using the cascade impaction methodology. The median aerodynamic particle size measured by the APS method and the median geometric particle size obtained from the LD method were linearly correlated with the corresponding ACI results in the range of 2-5 µm. It was also found that the APS measurement was biased towards the finer particle size region and resulted in overestimated fine particle fraction (FPF) values which were 2-3 times folds of the ACI results. In conclusion, the optical particle sizing techniques may, under some circumstances, be viable techniques for the rapid assessment of MDI suspensions. The "wet cell" LD method, in particular, is found to be a valuable means of detecting active pharmaceutical ingredient (API) particle size changes in an MDI suspension. Using both the LD and the APS methods in early formulation screening followed by a final assessment with cascade impaction analysis can improve the efficiency of MDI formulation development.

Prevalence and predictors of Sjogren's syndrome in a prospective cohort of patients with aqueous-deficient dry eye.

AIMS: To assess the prevalence and determine predictors of Sjögren's syndrome (SS) in patients with clinically significant aqueous-deficient dry eye. METHODS: Patients enrolled in an industry-sponsored, multicentre clinical trial (NCT00784719) were assessed prospectively for the presence of SS. Ocular testing included Schirmer test, corneal fluorescein staining, conjunctival lissamine green staining, and tear-film breakup time. Review of systems questionnaire, medical history, dry eye questionnaire and laboratory work-up (Sjögren-specific antibody A (SSA), Sjögren-specific antibody B (SSB), rheumatoid factor (RF) and antinuclear antibody (ANA)) were obtained. RESULTS: Of 327 patients, 38 (11.6%) had SS: 21 (6.4%) with primary SS (pSS), and 17 (5.2%) with secondary SS. Nine patients (3%) were newly diagnosed using the applied diagnostic criteria based on American-European consensus criteria. Patients with SS had significantly worse conjunctival and corneal staining, Schirmer test (with and without anaesthesia), and symptoms compared with patients without SS. pSS Was significantly more likely to occur in patients with positive ANA (OR: 13.9) and RF (OR: 4.8). CONCLUSIONS: Ophthalmologists caring for patients with clinically significant dry eye should have a high index of suspicion for underlying SS and low threshold for serological work-up. RF and ANA are recommended as useful tests in SSA/SSB-negative patients for further diagnostic referral.