Contamination of anti-vegf drugs for intravitreal injection. How Do Repackaging and Newly Developed Syringes Affect the Amount of Silicone Oil Droplets and Protein Aggregates?

Purpose: The particle counts and the nature of particles of three different antivascular endothelial growth factor agents (VEGF) in different containers in a laboratory setting were compared. Methods: Original prefilled ranibizumab glass syringes, original vials with aflibercept, and repacked ready-to-use plastic syringes with bevacizumab from a compounding pharmacy and a compounding company (CC) were analyzed. Particle counts and size distributions were quantified by different particle characterization methods (nephelometry, light obscuration, Micro-Flow Imaging, nanotracking analysis, resonant mass measurement). Using high-performance size-exclusion chromatography (HP-SEC), levels of protein drug monomer and soluble aggregates were determined. Results: Nearly all samples showed similar product quality. Light obscuration and Micro-Flow Imaging showed a 4-fold to 9-fold higher total particle count in compounding company bevacizumab (other samples up to 42,000 particles/mL). Nanotracking analysis revealed highest values for compounding company bevacizumab (6,375 million particles/mL). All containers showed similar amounts of silicone oil microdroplets. Ranibizumab showed lowest particle count of all tested agents with only one monomer peak in HP-SEC. Repackaged bevacizumab from different suppliers showed varying product quality. Conclusion: All three tested agents are available in similar quality regarding particulate purity and silicone oil microdroplet count. Repackaging can have a major impact on the quality

Changes in intraocular pressure in study and fellow eyes in the IVAN trial

PURPOSE: To describe changes in intraocular pressure (IOP) in the 'alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN)' trial (registered as ISRCTN92166560). DESIGN: Randomised controlled clinical trial with factorial design. PARTICIPANTS: Patients (n=610) with treatment naïve neovascular age-related macular degeneration were enrolled and randomly assigned to receive either ranibizumab or bevacizumab and to two regimens, namely monthly (continuous) or as needed (discontinuous) treatment. METHODS: At monthly visits, IOP was measured preinjection in both eyes, and postinjection in the study eye. OUTCOME MEASURES: The effects of 10 prespecified covariates on preinjection IOP, change in IOP (postinjection minus preinjection) and the difference in preinjection IOP between the two eyes were examined. RESULTS: For every month in trial, there was a statistically significant rise in both the preinjection IOP and the change in IOP postinjection during the time in the trial (estimate 0.02 mm Hg, 95% CI 0.01 to 0.03, p<0.001 and 0.03 mm Hg, 95% CI 0.01 to 0.04, p=0.002, respectively). There was also a small but significant increase during the time in trial in the difference in IOP between the two eyes (estimate 0.01 mm Hg, 95% CI 0.005 to 0.02, p<0.001). There were no differences between bevacizumab and ranibizumab for any of the three outcomes (p=0.93, p=0.22 and p=0.87, respectively). CONCLUSIONS: Anti-vascular endothelial growth factor agents induce increases in IOP of small and uncertain clinical significance

Toxic effects of phenothiazines on the eye

Publications about the retinotoxic action of phenothiazine derivatives led the author to undertake an ophthalmological investigation in two psychiatric hospitals in The Netherlands. The pharmacological actions of phenothiazine preparations are listed and a survey of the phenothiazine derivatives which are at present in use is given. Some retinotoxic substances are discussed and a survey is given of the literature on the ocular complications of phenothiazine therapy. The eyes of 561 patients were examined. of whom 541 are included in this study. 343 of these patients(63.4 %) were found to have retinopathy. The correlation between the retinopathy and the total dose of phenothiazine preparations taken. and between the retinopathy and the duration of treatment. was highly significant. The correlation between the retinopathy and the average daily dose taken was significant. The retinopathy was associated with a reduced standing potential of the eye. as determined by electro-oculography. It was possibly responsible for diminished visual acuity in some cases, and for an abnormally large proportion of protans in the group of patients with colour defects. It was not possible to ascribe a more severe retinotoxic action to one or more specific phenothiazine derivatives than to others. In the author's opinion regular examination of the eyes of patients who are being treated with phenothiazine preparations in high dosage and for for a long period of time is indicated