Novel vitreous substitutes: the next frontier in vitreoretinal surgery

Abstract

Purpose of reviewAfter removing the native vitreous during vitreoretinal surgery, an adequate substitute is required to ensure homeostasis of the eye. Current clinically used endotamponades (silicone oil, gases, semifluorinated alkanes) are effective in promoting retinal reattachment, but lead to complications such as emulsification, prolonged inflammation, blurred vision, raised intraocular pressure, cataract formation or the need for revision surgery. The aim of this review is to provide an update on novel vitreous substitutes with a focus on polymer-based systems. Recent findingsPolymeric hydrogels provide favourable properties such as high water content, optical transparency, suitable refractive indices and densities, adjustable rheological properties, injectability, biocompatibility and their ability to tamponade the retina via viscosity and swelling pressure, comparable to the native human vitreous body. Here, vitreous replacement strategies can be divided into chemically or physically crosslinked hydrogel systems that are applied as preformed or in-situ gelling matrices. SummarySeveral hydrogel-based vitreous substitutes have already been positively evaluated in preclinical tests and have the potential to enter the clinical phase soon.

Long-Term Biocompatibility of a Highly Viscously Thiol-Modified Cross-Linked Hyaluronate as a Novel Vitreous Body Substitute

“…Here we presented the result of a long-term in vivo study (1, 3, and 6 months) of a highly viscous hydrophilic hydrogel based on The GFAP staining was graded as mild (Schulz et al, 2021), moderate (Lin et al, 2021), strong (Kim et al, 2008), or very strong (Duan et al, 2011). Although the GFAP expression was significantly upregulated in all operated eyes throughout the entire study, the total amount of GFAP expression decreased over time.…”

“…In the treatment of pathologies affecting the posterior pole, the vitreous body needs to be removed by vitrectomy following stabilization of the retina with an endotamponade, like silicone oils or gases. Current clinically used endotamponades are effective, especially in promoting retinal reattachment, but are disadvantageous due to their hydrophobic nature, refractive index, and density compared to the human vitreous, resulting in immediate blurred vision after surgery and complications such as raised intraocular pressure (IOP), prolonged inflammation, emulsification, or cataract formation ( Kim et al, 2008 ; Duan et al, 2011 ; Lin et al, 2021 ; Schulz et al, 2021 ). The basic reason for the limitation of endotamponades is their hydrophobic character in a hydrophilic environment of the vitreous cavity and acting via the two physical functions “buoyancy vector” and “surface/interfacial tension.” The tamponade vector can only act in one direction, so complete filling of the vitreous cavity is not possible ( Schnichels et al, 2017 ; Szurman, 2017 ).…”

“…Therefore, there is great demand to develop an ideal vitreous endotamponade that mimics the physiological properties of a natural vitreous body to improve therapeutic efficacy and safety. Recent tamponade strategies aim at hydrophilic, polymeric hydrogel-based systems due to their favorable physical and mechanical properties such as high water content, high optical transparency, suitable refractive indices, viscosity, swelling pressure, adjustable rheological properties, and adaptable biocompatibility ( Schulz et al, 2020 ; Lin et al, 2021 ; Schulz et al, 2021 ; Wang et al, 2021 ). The tamponade effect of a hydrogel is exerted by the viscosity and swelling pressure, the latter via the high water-binding property; therefore, it seems logical to develop hydrogels based on hyaluronic acid, as this is one of the main components of the natural vitreous body ( Nakagawa et al, 1997 ; Schramm et al, 2012 ).…”

Determining vitreous viscosity using fluorescence recovery after photobleaching

“…Previous studies relied on microrheometry such as those carried out by Lee et al [11,12,19]. Although, since the early 1990s when these experiments were performed, microrheometry has advanced significantly, direct diffusion experiments employing small macromolecules similar in MW to drugs may provide a more accurate and sensitive approach to viscosity measurements, for both real vitreous and vitreous substitutes [25].…”

“…Drugs such as ranibizumab (48 kDa) are similar in molecular weight (MW), and bevacizumab (150 kDa] and aflibercept (115 kDa) are less than double the MW [20][21][22][23][24] of the fluorescently labelled macromolecules studied in this work, and their diffusion properties are important for treating age-related macular degeneration. Moreover, polymeric hydrogels have been investigated as vitreous substitutes [4,25]. In addition to biocompatibility and functionality, the optical and rheological properties of these substitute materials, e.g., refractive index, density, water content, stiffness, viscoelasticity and also viscosity, should be as close as possible to the original vitreous humor.…”