Novel heavy dyes for retinal membrane staining during macular surgery: multicentre clinical assessment

Purpose: To evaluate the feasibility of two novel ‘heavy’ dye solutions for staining the internal limiting membrane (ILM) and epiretinal membranes (ERMs), without the need for a prior fluid-air exchange, during macular surgery. Methods: In this prospective nonrandomized multicenter cohort study, the high molecular weight dyes ILM-Blue™ [0.025% brilliant blue G, 4% polyethylene glycol (PEG)] and MembraneBlue-Dual™ (0.15% trypan blue, 0.025% brilliant blue G, 4% PEG) were randomly used in vitrectomy surgeries for macular disease in 127 eyes of 127 patients. Dye enhanced membrane visualization of the ILM and ERMs, ‘ease of membrane peeling’, visually detectable perioperative retinal damage, postoperative best-corrected visual acuity (BCVA), dye remnants and other unexpected clinical events were documented by 21 surgeons. Results: All surgeries were uneventful, and a clear bluish staining, facilitating the identification, delineation and removal of the ILM and ERMs, was reported in all but five cases. None of the surgeries required a fluid-air exchange to assist the dye application. BCVA at 1 month after surgery improved in 83% of the eyes in the MembraneBlue-Dual™ group and in 88% in the ILM-Blue™ group. No dye remnants were detected by ophthalmoscopy, and no retinal adverse effects related to the surgery or use of the dyes were observed. Conclusion: The ‘heavy’ dye solutions ILM-Blue™ and MembraneBlue-Dual™ can be injected into a fluid-filled vitreous cavity and may facilitate staining and removal of the ILM and/or ERMs in macular surgery without an additional fluid-air exchange

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions

Purpose The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. Methods ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. Results The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48–2.43, and 10.62, 6.62–17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14– 2.10 and 1.73, 1.18–2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12–3.5, p=0.02), nausea (3.29, 1.57– 6.86, p<0.001), vomiting (2.91, 1.2–7.07, p=0.01) and drug hypersensitivity (8.75, 3.1–24.66, p<0.001). Conclusions Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost