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Francisco R Stefanini,1–3 Maurício Maia,1 Paulo Falabella,1–3 Marcel Pfister,2,3 Moritz Niemeyer,2 Amir H Kashani,3 Mark S Humayun,3 Michael J Koss2,3,41Retina Division, Department of Ophthalmology and Visual Sciences, Federal University of Sao Paulo, Sao Paulo, Brazil; 2Doheny Eye Institute, Los Angeles, CA, USA; 3Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA; 4Department of Ophthalmology, Goethe University, Frankfurt/Main, GermanyAbstract: The recent approval by the US Food and Drug Administration of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA), often associated with vitreomacular traction (VMT) and macular hole (MH), has brought new attention to the field of pharmacologic vitreolysis. The need for an enzyme to split the vitreomacular interface, which is formed by a strong adhesive interaction between the posterior vitreous cortex and the internal limiting membrane, historically stems from pediatric eye surgery. This review summarizes the different anatomic classifications of posterior vitreous detachment or anomalous posterior vitreous detachment and puts these in the context of clinical pathologies commonly observed in clinical practice of the vitreoretinal specialist, such as MH, VMT, age-related macular degeneration, and diabetic macular edema. We revisit the outcome of the Phase II studies that indicated ocriplasmin was a safe and effective treatment for selected cases of symptomatic VMA and MH. Release of VMA at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1% in the placebo group (P