Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives

With the prevalence of eye diseases, such as cataracts, retinal degenerative diseases, and glaucoma, different treatments including lens replacement, vitrectomy, and stem cell transplantation have been developed; however, they are not without their respective shortcomings. For example, current methods to seal corneal incisions induced by cataract surgery, such as suturing and stromal hydration, are less than ideal due to the potential for surgically induced astigmatism or wound leakage. Vitrectomy performed on patients with diabetic retinopathy requires an artificial vitreous substitute, with current offerings having many shortcomings such as retinal toxicity. The use of stem cells has also been investigated in retinal degenerative diseases; however, an optimal delivery system is required for successful transplantation. The incorporation of hydrogels into ocular therapy has been a critical focus in overcoming the limitations of current treatments. Previous reviews have extensively documented the use of hydrogels in drug delivery; thus, the goal of this review is to discuss recent advances in hydrogel technology in surgical applications, including dendrimer and gelatin-based hydrogels for ocular adhesives and a variety of different polymers for vitreous substitutes, as well as recent advances in hydrogel-based retinal pigment epithelium (RPE) and retinal progenitor cell (RPC) delivery to the retina.

Optic coherence tomography features of subretinal vitreous substitutes

Background To draw comparisons between spectral domain optic coherence tomography (SD-OCT) features of subretinal silicon oil (SO), perfluoro-n-octane (PFO) or C3F8 gas. Methods Cases diagnosed with retained subretinal vitreous substitutes (VS) were retrospectively selected. Demographic data were collected and OCT features were analyzed. Results In the 13 cases with subretinal PFO, hyper-reflectivity under the bubble was noted in 8 eyes (61.5%); choroidal shadow at the borders of the bubble in 11 eyes (84.6%); hyper-reflective halo around the bubble in 5 eyes (38.4%) and a hyper-reflective apical dot in 8 eyes (61.5%).The two cases with multiple PFO bubbles had complete septum dividing the bubbles. The one case with subretinal SO had hyper reflectivity under the bubble; no choroidal shadow at the edge of the bubble; hyper-reflective halo was noted around the bubble and the apical hyper-reflective dot was present; there was no complete septum dividing multiple bubbles. The single case with subretinal C3F8 had some bubbles with totally round base, incomplete septum, hyper reflectivity under the bubble, choroidal shadow at the edge of the bubble, a hyper-reflective halo and an apical dot. Conclusion Different subretinal VS share similar SD-OCT characteristics. Round base bubbles are only observed with subretinal C3F8 gas, while incomplete septum are related to retained subretinal SO or gas.

Effect on rabbits’ intraocular structure by cross-linked hyaluronic formations as vitreous substitute

Purpose: To observe the effects of cross-linked hyaluronic hydrogel on retina struct and intraocular biocompatibility in rabbits. Methods: the polymer-derived hyaluronic acid which was formed by UV light cross-linked with N-vinyl-pyrrolidone. Free hyaluronic acid levels were detected by spectrophotometric method. Vitrectomy was then performed in the rabbits, and then cross-linked hyaluronic acid hydrogels of different concentrations were injected. Intraocular pressure measurements, cornea check-up, and B-ultrasound examination were performed during the follow-up period. After six weeks’ follow-up, the rabbits were sacrificed, and both eyes were removed. The eyeballs were fixed for HE staining, and the polymer materials were observed under electron microscopy. Results: The synthetic hydrogel present a transparent substance with a refractive index similar to that of the human vitreous body, which also had sufficient viscosity and elasticity for intraocular usage by rheological measurements. The results of the free hyaluronic acid test showed that the hydrogel had little degrade within one month. The results of the histology, intraocular pressure, B-ultrasound and retinal ultrastructure suggested that cross-linked hyaluronic acid hydrogel had superior tissue biocompatibility intraocular for six weeks. Conclusions: Hyaluronic acid-based cross-linked biopolymers had good biocompatibility in rabbit, which also shown promising potential as vitreous substitutes in clinical practice.

Hydrodynamics of Intravitreal Injections into Liquid Vitreous Substitutes

Intravitreal injections have become the cornerstone of retinal care and one of the most commonly performed procedures across all medical specialties. The impact of hydrodynamic forces of intravitreal solutions when injected into vitreous or vitreous substitutes has not been well described. While computational models do exist, they tend to underestimate the starting surface area of an injected bolus of a drug. Here, we report the dispersion profile of a dye bolus (50 µL) injected into different vitreous substitutes of varying viscosities, surface tensions, and volumetric densities. A novel 3D printed in vitro model of the vitreous cavity of the eye was designed to visualize the dispersion profile of solutions when injected into the following vitreous substitutes—balanced salt solution (BSS), sodium hyaluronate (HA), and silicone oils (SO)—using a 30G needle with a Reynolds number (Re) for injection ranging from approximately 189 to 677. Larger bolus surface areas were associated with faster injection speeds, lower viscosity of vitreous substitutes, and smaller difference in interfacial surface tensions. Boluses exhibited buoyancy when injected into standard S1000. The hydrodynamic properties of liquid vitreous substitutes influence the initial injected bolus dispersion profile and should be taken into account when simulating drug dispersion following intravitreal injection at a preclinical stage of development, to better inform formulations and performance.