Objective: 

Hydrogel-based vitreous substitutes have the potential to overcome the limitations of existing clinically used endotamponades (e.g. oils and gases). The aim is to transfer hyaluronic acid-based hydrogels into clinical use as vitreous substitutes.

Methods: 

The glycosaminoglycan hyaluronic acid, as the polymeric and non-immunogenic main component of native vitreous, is a natural candidate for an authentic vitreous substitute. The multi-step manufacturing process, including modification of hyaluronic acid with glycidyl methacrylate, photocopolymerization with N-vinylpyrrolidone by ultraviolet light and successive hydrogel purification, was developed under laboratory conditions, analytically evaluated and transferred to a pharmaceutical production environment following GMP standards. After crosslinked hydrogels based on hyaluronic acid demonstrated suitable optical and mechanical properties as well as biocompatibility and functionality in vitro and in animal models in various long-term trials, individual healing attempts were carried out in patients with advanced phthisis bulbi and the safety and performance of the hyaluronic acid-based vitreous substitutes were evaluated retrospectively.

Results: 

An increase in intraocular pressure ≥ 5 mmHg was achieved with hyaluronic acid-based hydrogels in 4/5 of the patients for a mean duration of 93.6 ± 92.5 days. Visual acuity remained constant in 3/5 eyes and decreased by 0.95 ± 0.6 logMAR in 2/5 eyes. No enucleations were required during the maximum follow-up period of 709 days. OCT images showed preservation of retinal structures while choroidal folds were reduced.

Conclusion: 

Hyaluronic acid-based hydrogels are biocompatible as vitreous substitutes in humans and can increase and stabilize intraocular pressure in patients with phthisis bulbi for about 3 months. Future multicenter studies are needed for the use of hyaluronic acid-based hydrogels as vitreous substitutes in humans.