Abstract
Vitreoretinal surgery involves the removal of the natural vitreous, which is essential for retinal adhesion, intraocular pressure (IOP) homeostasis, and optical transparency. Clinically utilized tamponades, including expansile gases, silicone oil (SO), and semi-fluorinated alkanes, necessitate face-down positioning. These tamponades frequently result in cataracts, glaucoma, or keratopathy, and invariably require a subsequent intervention for removal. As a major component of the vitreous humor, hyaluronic acid (HA) can be fabricated into injectable hydrogels with the characteristics of optical transparency, viscoelasticity, and enzyme-mediated biodegradability. These features render HA hydrogels one of the most promising candidates for vitreous substitutes. This commentary synthesizes recent polymer chemistry advances and emerging preclinical data, while critically examining early human experiences, to outline the current status and realistic trajectory of HA-based vitreous substitutes toward future clinical evaluation.