No flow through the vitreous humor: how strong is the evidence?

When analyzing vitreal drug delivery, or the pharmacological effects of drugs on intraocular pressure, or when interpreting outflow facility measurements, it is generally accepted that the fluid in the vitreous humor is stagnant. It is accepted that for all practical purposes, the aqueous fluid exits the eye via anterior pathways only, and so there is negligible if any posteriorly directed flow of aqueous through the vitreous humor. This assumption is largely based on the interpretation of experimental data from key sources including Maurice (1957), Moseley (1984), Gaul and Brubaker (1986), Maurice (1987) and Araie et al. (1991). However, there is strong independent evidence suggesting there is a substantial fluid flow across the retinal pigment epithelium from key sources including Cantrill and Pederson (1984), Chihara and Nao-i, Tsuboi (1985), Dahrouj (2014), Smith and Gardiner (2017) and Smith et al. (2019). The conflicting evidence creates a conundrum-how can both interpretations be true? This leads us to re-evaluate the evidence. We demonstrate that the data believed to be supporting no aqueous flow through the vitreous are in fact compatible with a significant normal aqueous flow. We identify strong and independent lines of evidence supporting fluid flow across the RPE, including our new outflow model for the eye. On balance it appears the current evidence favors the view that there is normally a significant aqueous flow across the RPE in vivo. This finding suggests that past and future analyses of outflow facility, interpretations of some drug distributions and the interpretation of some drug effects on eye tissues, may need to be revised.