How do macromolecules (large drugs) in the eye reach the bloodstream and what are the relative significances of these pathways?

Question

I am considering the elimination pathways for antibodies (50-150 kDa) from the vitreous humour to the blood stream. My overarching question is what is the most significant route such antibodies could take to get there?

Elimination from the vitreous humour to the aqueous humour is known to be quite a substantial route of clearance, but does drug eliminated through passage into the aqueous humour travel to the blood stream? Notably there are two routes of exit from the aqueous humour, one is directly into the bloodstream and the other is through Schlemm's canal, but where does that lead?

Also for example is the choroid directly in contact with the hyaloid membrane of the vitreous play a significant role in elimination? We also also such drugs penetrate into (and through) the retina, at that point they reach vasculature, however they have to work quite hard to get there.

Answer 1

Antibodies are a unique case. I recommend reading PubMedID: 26726925 regarding the pharmacokinetics of ranibizumab (Lucentis), a Fab fragment, after intravitreal administration.

"We assume that the principal pathway for the ocular clearance of large molecules is by a first-order transfer process from the vitreous to the aqueous chambers, from which the molecule is absorbed into the circulation via Schlemm’s canal by the physiological process of aqueous humor turnover."

A comprehensive analysis of the pharmacokinetic processes are included in the mechanistic model that they have developed. I will not copy and paste them here.