Silicone oil (SO) emulsification is a significant concern in vitreoretinal surgery, leading to various complications. Despite the high prevalence of SO emulsification within the eye, there is currently no standardized method for its early detection. The recent introduction of widefield (WF) imaging and ultra-WF (UWF) imaging with navigated central and peripheral optical coherence tomography (OCT) techniques have shown promising results in providing high-resolution images of the peripheral vitreous, vitreoretinal interface, retina, and choroid. This enhanced visualization capability enables the early identification of emulsified SO droplets, facilitating a proactive therapeutic approach, and mitigating associated adverse events. This comprehensive literature review aims to provide an updated overview of the topic, focusing on the role of WFimaging and UWF imaging and navigated central and peripheral swept-source OCT (SS-OCT) in the early detection and management of SO emulsification. The review discusses the current understanding of SO emulsification, its associated complications, and the limitations of existing detection methods. In addition, it highlights the potential of WF and UWF imaging and peripheral OCT as advanced imaging modalities for improved visualization of SO emulsification. This review serves as a valuable resource for clinicians and researchers, providing insights into the latest advancements in the field of vitreoretinal surgery and the promising role of WF imaging and UWF imaging and navigated central and peripheral SS-OCT in the management of SO.

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the physical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for ophthalmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 μM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BDDE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively.

OBJECTIVE: To assess the safety and performance of hyaluronic acid-based vitreous substitutes in phthitic eyes.
METHODS: In this retrospective interventional study a total of 21 eyes from 21 patients with phthisis bulbi were treated at the Eye Clinic Sulzbach between August 2011 and June 2021. Patients who underwent a 23G pars plana vitrectomy received a vitreous substitute composed of (I) a non-crosslinked hyaluronic acid (Healon GV), (II) a crosslinked hyaluronic acid-based hydrogel (UVHA), or (III) silicone oil (SO-5000). Main outcome measures were the intraocular pressure (IOP), the visual acuity and the structural integrity of the retina and choroid assessed by optical coherence tomography.
RESULTS: An increase in IOP ≥ 5 mmHg was achieved with SO-5000 in 5/8 eyes (6/10 interventions, 60.0%) for 36.4 ± 39.5 days, with Healon GV in 4/8 eyes (7/11 interventions, 63.6%) for 82.6 ± 92.5 days and with UVHA in 4/5 eyes (5/6 interventions, 83.3%) for 93.6 ± 92.5 days. Visual acuity increased in 5/21 eyes (23.8%), remained constant in 12/21 eyes (57.1%) and decreased in 4/21 eyes (19.0%). No enucleations were required during the mean follow-up time of 192 ± 182 days. The OCT images indicated the preservation of retinal structures, while choroidal folds were only diminished in UVHA eyes.
CONCLUSIONS: Hyaluronic acid-based hydrogels are biocompatible vitreous substitutes in humans and can increase and stabilize IOP in patients with phthisis bulbi for about 3 months.

Vitreous substitutes are indispensable tools in vitreoretinal surgery. The two crucial functions of these substitutes are their ability to displace intravitreal fluid from the retinal surface and to allow the retina to adhere to the retinal pigment epithelium. Today, vitreoretinal surgeons can choose among a plethora of vitreous tamponades, and the tamponade of choice might be difficult to determine in the ever-expanding range of possibilities for a favorable outcome. The currently available vitreous substitutes have disadvantages that need to be addressed to improve the surgical outcome achievable today. Herein, the fundamental physical and chemical proprieties of all vitreous substitutes are reported, and their use and clinical applications are described alongside some surgical techniques of intra-operative manipulation. The major upcoming developments in vitreous substitutes are extensively discussed, keeping a translational perspective throughout. Conclusions on future perspectives are derived through an in-depth analysis of what is lacking today in terms of desired outcomes and biomaterials technology.

BACKGROUND: Hydrogels show great potential to be used for intraocular applications due to their high-water content and similarity to the native vitreous. Injectable thermosensitive hydrogels through a small-bore needle can be used as a delivery system for drugs or a tamponading substitute to treat posterior eye diseases with clear clinical potential. However, none of the currently available thermosensitive hydrogels can provide intraocular support for up to 3 months or more.
METHODS: In this study, an injectable polytetrahydrofuran (PTHF)-based thermosensitive hydrogel was synthesized by polyurethane reaction. We examined the injectability, rheological properties, microstructure, cytotoxicity, and in vivo compatibility and stability of the hydrogels in rabbit eyes.
RESULTS: We found that the PTHF block type and PTHF component ratio could modulate thermogelation properties of the polyurethane polymers. The PTHF-based hydrogel implants retained normal retinal structure and function. Incorporating bioinert PTHF generated highly biocompatible and more stable thermogels in the vitreous cavity, with gel networks and the presence of polymer still observed after 3 months when other thermogels would have been completely cleared. Moreover, despite lacking hydrolytically cleavable linkages, the polymers could be most naturally removed from the native vitreous by bio-erosion without additional surgical interventions.
CONCLUSIONS: Our findings suggest the potential of incorporating hydrophobic bioinert blocks to enhance the in vivo stability of supramolecularly associated hydrogels for long-term intraocular applications.

OBJECTIVE: Hydrogel-based vitreous substitutes have the potential to overcome the limitations of current clinically used endotamponades. With the goal of entering clinical trials, the present study aimed to (I) transfer the material synthesis of hyaluronic acid-based hydrogels into a routine, pharmaceutical-appropriate production and (II) evaluate the properties of the vitreous substitutes in terms of the current regulations for medical devices (MDR/ISO standards).
METHODS: The multistep manufacturing process of the vitreous substitutes, including the modification of hyaluronic acid with glycidyl methacrylate, photocopolymerization with N-vinylpyrrolidone, and successive hydrogel purification, was developed under laboratory conditions, characterized using 1 H-NMR, FT-IR and UV/Vis spectroscopies and HPLC, and transferred towards a pharmaceutical production environment considering GMP standards. The optical and viscoelastic characteristics of the hyaluronic acid-based hydrogels were compared with those of extracted human vitreous and silicone oil. The effect of the hydrogels on the metabolic activity, proliferation and apoptosis of fibroblast (MRC-5, BJ, L929), retinal pigment epithelial (ARPE-19, hiPSC-derived RPE) and photoreceptor cells (661W) was studied as well as their mucosal tolerance via a HET-CAM assay.
RESULTS: Hyaluronic acid-based hydrogels having a suitable purity, sterility, high transparency (>90%), appropriate refractive index (1.3365) and viscoelasticity (G\' > G″) were prepared in a standardized manner under controlled process conditions. The metabolic activity, proliferation and apoptosis of various cell types as well as egg choroid were unaffected by the hyaluronic acid-based vitreous substitutes, demonstrating their biocompatibility.
CONCLUSIONS: The present study demonstrates the successful transferability of the crucial synthesis steps of hyaluronic acid-based hydrogels into a routine, GMP-compliant production process while achieving the optical and viscoelastic properties, biocompatibility and purity required for their clinical use as vitreous substitutes.

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.

Vitreous or vitreous humor is a complex transparent gel that fills the space between the lens and retina of an eye and acts as a transparent medium that allows light to pass through it to reach the photoreceptor layer (retina) of the eye. The vitreous humor is removed in ocular surgery (vitrectomy) for pathologies like retinal detachment, macular hole, diabetes-related vitreous hemorrhage detachment, and ocular trauma. Since the vitreous is not actively regenerated or replenished, there is a need for a vitreous substitute to fill the vitreous cavity to provide a temporary or permanent tamponade to the retina following some vitreoretinal surgeries. An ideal vitreous substitute could probably be left inside the eye forever. The vitreous humor is transparent, biocompatible, viscoelastic and highly hydrophilic; polymeric hydrogels with these properties can be a potential candidate to be used as vitreous substitutes. To meet the tremendous demand for the vitreous substitute, many scientists all over the world have developed various kinds of vitreous substitutes or tamponade agent. Vitreous substitutes, whatsoever developed till date, are associated with several advantages and disadvantages, and there is no ideal vitreous substitute available till date. This review highlights the polymer-based vitreous substitutes developed so far, along with their advantages and limitations. The gas-based and oil-based substitutes have also been discussed but very briefly.

More and more people worldwide are affected by severe eye diseases eventually leading to visual impairment or blindness. In most cases, the treatment involves the application of ophthalmic dosage forms such as eye drops, suspensions or ointments. Unfortunately, some of the therapeutic approaches have major shortcomings, especially in the treatment of the posterior segment of the eye, where many vision-threatening diseases originate. Therefore, research focuses on the development of new materials (e.g., for vitreous substitution) and more advanced drug delivery systems. Hydrogels are an extremely versatile class of materials with many potential applications in ophthalmology. They found widespread application as soft contact lenses, foldable intraocular lenses, in situ gelling formulations for ophthalmic drug delivery and ocular adhesives for wound repair; their use as vitreous substitutes and intravitreal drug delivery systems is currently under investigation. In this article, we review the different applications of hydrogels in ophthalmology with special emphasis placed on the used polymers and their suitability as ocular drug delivery systems.