IMPORTANCE Ocriplasmin cleaves fibronectin and laminin, components of the vitreous gel, and is used as a pharmacologic treatment for vitreomacular traction. Laminin is also found throughout multiple retinal layers. Ocriplasmin injection may lead to acute panretinal dysfunction in some eyes, but the mechanism of this toxic reaction has not been described. OBSERVATIONS We evaluated a 63-year-old woman demonstrating acute panretinal dysfunction after intravitreous ocriplasmin injection for a small macular hole with vitreomacular adhesion. Findings included visual acuity loss, visual field constriction, pupillary abnormalities, attenuated retinal arteries, loss of outer retinal signals on spectral-domain optical coherence tomography, and severely reduced electroretinography responses. B-waves were reduced more than A-waves were, suggesting postreceptoral dysfunction and decreased photoreceptor activity. CONCLUSIONS AND RELEVANCE Retinal dysfunction associated with intravitreous ocriplasmin injection is not limited to the macular region and seems to involve the entire retina. Enzymatic cleavage of intraretinal laminin is a biologically plausible mechanism for acute ocriplasmin retinal toxic effects.