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BackgroundData comparing systemic exposure and systemic vascular endothelial growth factor (VEGF) suppression of ranibizumab, bevacizumab and aflibercept following intravitreal injection are lacking.MethodsFifty-six patients with wet age-related macular degeneration received intravitreal ranibizumab (0.5 mg), bevacizumab (1.25 mg), or aflibercept (2.0 mg). Serum pharmacokinetics and plasma free VEGF were evaluated after the first and third injections.ResultsFollowing the first dose, systemic exposure to aflibercept was 5-, 37-, and 9-fold higher than ranibizumab, whereas, bevacizumab was 9-, 310-, and 35-fold higher than ranibizumab, based on geometric mean ratio of peak and trough concentrations and area under the curve, respectively. The third dose showed accumulation of bevacizumab and aflibercept but not ranibizumab. Aflibercept substantially suppressed plasma free VEGF, with mean levels below lower limit of quantitation (10 pg/mL) as early as 3 h postdose until ≥7 days postdose. Mean free (unbound) VEGF levels with ranibizumab were largely unchanged, with mean trough level of 14.4 pg/mL compared with baseline of 17 pg/mL.ConclusionsThere are notable differences in systemic pharmacokinetics and pharmacodynamics among anti-VEGF treatments after intravitreal administration. All three agents rapidly moved into the bloodstream, but ranibizumab very quickly cleared, whereas bevacizumab and aflibercept demonstrated greater systemic exposure and produced a marked reduction in plasma free VEGF.Trial registration numberNCT02118831.

After monthly intravitreal injections, the systemic exposures of aflibercept, bevacizumab, and ranibizumab were distinct and correlated with different reductions in plasma free–vascular endothelial growth factor, which could provide biologic plausibility for potential differences in systemic adverse events.

Endophthalmitis is an inflammatory reaction of intraocular fluids or tissues. Infectious endophthalmitis is one of the most serious complications of ophthalmic surgery. Occasionally, infectious endophthalmitis is the presenting feature of an underlying systemic infection. Successful management of infectious endophthalmitis depends on timely diagnosis and institution of appropriate therapy. Recognition of the different clinical settings in which endophthalmitis occurs and awareness of the highly variable presentation it may have facilitate timely diagnosis. Biopsy of intraocular fluid/tissue is the only method that permits reliable diagnosis and treatment. The different presenting clinical settings, a rational approach to diagnosis (i.e., when, what, and how to biopsy), and the treatment of infectious endophthalmitis are reviewed.