Vitreous Substitutes Research Articles

Synthesis and characterization of polymethylhydrosiloxane using dichloromethane as a candidate material for vitreous substitution

Synthesis and characterization of polymethylhydrosiloxane using dichloromethane as a candidate material for vitreous substitution

Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes

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.

NMR Characterization of Polymethylhydrosiloxane Synthesized using Dichloromethane and Diethyl Ether as Solvent for Vitreous Substitute

<p class="Abstract">Polymethylhydrosiloxane (PMHS) can be synthesized from dichloromethylsilane (DCHS) by the hydrolysis-condensation method. In this synthesis method, a solvent is needed. Dichloromethane (DCM) or diethyl ether (DE) can be used as a solvent in the synthesis of PMHS. These two solvents greatly affect the physical properties of the resulting PMHS. Therefore, studies are needed to look at the characteristics and chemical content of the PMHS synthesized using these two solvents. In this research, we reported the characteristics and content studies of PMHS synthesized using different solvents, DCM and DE, using <sup>1</sup>H-NMR and <sup>13</sup>C-NMR. It was found that both samples had three peaks (Si-H, Si-CH<sub>3</sub>, and Si-CH<sub>3</sub>) on <sup>1</sup>H-NMR measurement and one peak (Si-CH<sub>3</sub>) on <sup>13</sup>C-NMR measurement. All of the peaks found were by the characteristics of PMHS and no other elements were found from solvents indicating that the PMHS samples had been successfully synthesized with a high degree of purity. In addition, the possibility of structures formed in the PMHS samples was also obtained.</p>

Advances in Polysaccharide- and Synthetic Polymer-Based Vitreous Substitutes.

The vitreous humour is a gel-like structure that composes the majority of each eye. It functions to provide passage of light, be a viscoelastic dampener, and hold the retina in place. Vitreous liquefaction causes retinal detachment and retinal tears requiring pars plana vitrectomy for vitreous substitution. An ideal vitreous substitute should display similar mechanical, chemical, and rheological properties to the natural vitreous. Currently used vitreous substitutes such as silicone oil, perfluorocarbon liquids, and gases cannot be used long-term due to adverse effects such as poor retention time, cytotoxicity, and cataract formation. Long-term, experimental vitreous substitutes composed of natural, modified and synthetic polymers are currently being studied. This review discusses current long- and short-term vitreous substitutes and the disadvantages of these that have highlighted the need for an ideal vitreous substitute. The review subsequently focuses specifically on currently used polysaccharide- and synthetic polymer-based vitreous substitutes, which may be modified or functionalised, or employed as the derivative, and discusses experimental vitreous substitutes in these classes. The advantages and challenges associated with the use of polymeric substitutes are discussed. Innovative approaches to vitreous substitution, namely a novel foldable capsular vitreous body, are presented, as well as future perspectives related to the advancement of this field.

Vitreous Substitutes from Bench to the Operating Room in a Translational Approach: Review and Future Endeavors in Vitreoretinal Surgery.

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.

Vitreous Substitutes as Drug Release Systems.

Vitreous substitutes are traditionally used to stabilize the retina after vitrectomy. In recent years, various approaches have been developed for using the vitreous substitute not only as a tamponade but also as a drug release system to tackle ocular diseases. This review provides an overview of the requirements for vitreous substitutes and discusses the current clinically applied as well as novel polymer-based vitreous substitutes as drug delivery systems, including their release mechanisms, efficiencies, challenges, and future perspectives.

Gas Tamponade for the Prevention of Postoperative Vitreous Hemorrhaging After Diabetic Vitrectomy: A Randomized Clinical Trial

To compare vitreous substitution with sulfur hexafluoride (SF6) gas to balanced salt solution (BSS) for the prevention of postoperative vitreous hemorrhage (VH) in proliferative diabetic retinopathy (PDR) patients undergoing pars plana vitrectomy (PPV) for the indication of non-clearing VH. One hundred forty-four PDR subjects requiring PPV for the indication of non-clearing VH were enrolled into the trial. Subjects were prospectively randomized into 1 of 2 vitreous substitution groups: Group A subjects underwent 20% to 30% SF6 gas tamponade, whereas Group B subjects underwent vitreous substitution with BSS. The primary outcome was the incidence of postoperative VH during the 6-month trial period. Secondary outcomes were unplanned PPV for VH and best corrected visual acuity (BCVA) at 6-months follow-up. Ninety-six subjects underwent randomization and completed 6-months follow-up. Postoperative VH during the trial period occurred in 6 of 54 subjects in Group A (SF6) (11.1%) and 14 of 42 in Group B (BSS) (33.3%) (P=.008). Unplanned PPV during the trial period for postoperative VH occurred in 2 of 54 in Group A (3.7%) and 6 of 42 in Group B (14.2%) (P=.06). The mean BCVA was not significantly different at 6-months follow-up between groups (P=.58). This trial indicates that vitreous substitution with SF6 gas lowers the incidence of postoperative VH compared with BSS in PDR subjects undergoing PPV for the indication of non-clearing VH at 6-months follow-up. Specialists may consider SF6 gas tamponade during PPV as a means of helping reduce postoperative VH in this patient population. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Physical Characterization and In Vitro Toxicity Test of PDMS Synthesized from Low-Grade D4 Monomer as a Vitreous Substitute in the Human Eyes.

Polydimethylsiloxane (PDMS) is one of the most superior materials and has been used as a substitute for vitreous humor in the human eye. In previous research, we have succeeded in producing PDMS with low and medium viscosity using octamethylcyclotetrasiloxane (D4) monomer with a low grade of 96%. Both have good physical properties and are comparable to commercial product PDMS and PDMS synthesized using D4 monomer with a high grade of 98%. An improvement of the synthesis process is needed to ensure that PDMS synthesized from a low-grade D4 monomer under specific synthesis conditions can repeatedly produce high-quality PDMS. Apart from good physical properties, the PDMS as a substitute for vitreous humor must also be safe and not cause other disturbances to the eyes. Here, we reported the process of synthesizing and characterizing the physical properties of low- and medium-viscosity PDMS using a low-grade D4 monomer. We also reported for the first time the in vitro toxicity test using the Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) test method. We have succeeded in obtaining PDMS with viscosities of 1.15 Pa.s, 1.17 Pa.s, and 1.81 Pa.s. All samples have good physical properties such as refractive index, surface tension, and functional groups that are similar to commercial PDMS. The HET-CAM test results showed that all samples did not show signs of irritation indicating that samples were non-toxic. From the results of this study, it can be concluded that PDMS synthesized from a low-grade D4 monomer under specific synthesis conditions by the ROP method is very safe and has the potential to be developed as a substitute for vitreous humor in human eyes.

DNA Supramolecular Hydrogel as a Biocompatible Artificial Vitreous Substitute

AbstractPars plana vitrectomy plays an important role in treating serious ophthalmic diseases, which requires subsequent substitution of the natural vitreous. However, the current substitutes are known for the drawbacks in instability, toxicity, and injection‐induced fragmentation, so there is a very urgent need in novel artificial vitreous substitute for clinical practice. In this study, DNA supramolecular hydrogel is evaluated as a potential artificial vitreous substitute. It is observed that DNA supramolecular hydrogel exhibits relatively strong mechanical strength, shear‐thinning behavior, rapid recoverability, and other physical properties similar to the human vitreous body. The in vivo experiments further prove the injectability, excellent biocompatibility, and in vivo stability. With the support of the DNA supramolecular hydrogel, the morphology and basic functions of the operated eyes are well recovered without obvious inflammation, which demonstrate the DNA supramolecular hydrogel shows enormous potential as vitreous substitute.

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.

SILICONE OIL VERSUS PERFLUOROPROPANE GAS TAMPONADE DURING VITRECTOMY FOR TRACTIONAL RETINAL DETACHMENT OR FIBROUS PROLIFERATION: A Randomized Clinical Trial.

To compare vitreous substitution with silicone oil to perfluoropropane gas in proliferative diabetic retinopathy subjects undergoing pars plana vitrectomy (PPV) for the treatment of tractional retinal detachment or extensive fibrous proliferation. Randomized clinical trial. Three hundred and two proliferative diabetic retinopathy subjects with tractional retinal detachment or extensive fibrous proliferation requiring PPV were enrolled into the trial. Subjects were prospectively randomized into one of two vitreous substitution groups during PPV: Group A subjects underwent 1,000 centistoke silicone oil tamponade, whereas Group B subjects underwent 14% to 16% silicone oil to perfluoropropane gas tamponade. The principal outcome was the best-corrected visual acuity at 6-month follow-up. Secondary outcomes were postoperative complications and unplanned PPV during the 6-month trial interval. Two hundred and fifty-eight subjects were randomized to receive a vitreous substitute and completed 6-month follow-up. Group B had better best-corrected visual acuity, more subjects ending up with 0.4 logarithm of the minimum angle of resolution (20/50) or better visual acuity, and more subjects ending up with 1 logarithm of the minimum angle of resolution (20/200) or better visual acuity at 6 months compared with Group A (P < 0.001, P = 0.02, P < 0.001, respectively). There were no significant differences in baseline characteristics, intraoperative or postoperative complications, or incidence of unplanned PPV between groups. This trial demonstrated that vitreous substitution with silicone oil to perfluoropropane gas resulted in better visual acuity at 6 months compared with silicone oil tamponade in proliferative diabetic retinopathy patients undergoing PPV for tractional retinal detachment or extensive fibrous proliferation. Surgeons should consider silicone oil to perfluoropropane gas tamponade as the first-line vitreous substitute in this patient population.

Current Situation and Challenges in Vitreous Substitutes.

Vitreo-retinal disorders constitute a significant portion of treatable ocular diseases. These pathologies often require vitreo-retinal surgery and, as a consequence, the use of vitreous substitutes. Nowadays, the vitreous substitutes that are used in clinical practice are mainly divided into gases (air, SF6 , C2 F6 , C3 F8 ) and liquids (perfluorocarbon liquids, silicone oils, and heavy silicone oils). There are specific advantages and drawbacks to each of these, which determine their clinical indications. However, developing the ideal biomaterial for vitreous substitution continues to be one of the most important challenges in ophthalmology, and a multidisciplinary approach is required. In this sense, recent research has focused on the development of biocompatible, biodegradable, and injectable hydrogels (natural, synthetic, and smart), which also act as medium and long-term internal tamponade agents. This comprehensive review aims to cover the main characteristics and indications for use of the extensive range of vitreous substitutes that are currently used in clinical practice, before going on to describe the hydrogels that have been developed recently and which have emerged as promising biomaterials for vitreous substitution.

Synthesis of Low Viscosity Polydimethylsiloxane Using Low Grade of Octamethylcyclotetrasiloxane

Polydimethylsiloxane (PDMS) has been widely used as a vitreous humour substitution in vitreoretinal surgery. Due to its limited availability and increasing domestic needs, the price of PDMS in Indonesia became very expensive. Previously, we reported the synthesized of PDMS from a high grade of monomer of 98% of Octamethylcyclotetrasiloxane (D4) and found that all PDMS samples produced high quality samples similar to that of commercial one. However, by considering the ease of obtaining raw materials and also the production costs, the synthesis of PDMS using monomer which easy to be found in Indonesia and low production costs is needed to be developed. Here, we reported the synthesis of PDMS using low grade of 96% of D4 in order to produce high quality of PDMS with low viscosity that can be used for vitreous humous substitution in vitreoretinal surgery. PDMS samples with low viscosity value of 0.94-1.35 Pa.s have been successfully synthesized from low grade of D4 and MM using ring-opening polymerization method. The yields of PDMS resulted in this research were in the range between 67.27% and 76.26%. From FTIR spectroscopy, it is found that all synthesized samples have structure and functional groups similar to PDMS using high grade of monomer of 98% Octamethylcyclotetrasiloxane (D4). From refractometer and surfgauge measurements, all samples have refractive index in the range of 1,4034-1,4040 and the value surface tension was 21 m.N/m.

Substitutes and Colloidal System for Vitreous Replacement and Drug Delivery: Recent Progress and Future Prospective.

Vitreoretinal surgeries for ocular diseases such as complicated retinal detachment, diabetic retinopathy, macular holes and ocular trauma has led to the development of various tamponades over the years in search for an ideal vitreous substitute. Current clinically used tamponade agents such as air, perfluorocarbons, silicone oil and expansile gases serve only as a short-term solution and harbors various disadvantages. However, an ideal long-term substitute is yet to be discovered and recent research emphasizes on the potential of polymeric hydrogels as an ideal vitreous substitute. This review highlights the recent progress in the field of vitreous substitution. Suitability and adverse effects of various tamponade agents in present day clinical use and biomaterials in the experimental phase have been outlined and discussed. In addition, we introduced the anatomy and functions of the native vitreous body and the pathological conditions which require vitreous replacement.

Alginate- and Hyaluronic Acid-Based Hydrogels as Vitreous Substitutes: An In Vitro Evaluation.

PurposeTo study alginate- and hyaluronic acid–based hydrogels in vitro as vitreous substitutes.MethodsBiopolymeric hydrogels based on high-molecular alginate (0.5% and 1.0%) and hyaluronic acid (1.0% and Healaflow) were compared with extracted human vitreous bodies and silicone oil (SIL-5000) regarding their optical properties (refractive index, transmission) and viscoelastic characteristics (storage modulus G′, loss modulus G″). The cytotoxic (metabolic activity, apoptosis) and antiproliferative profiles were determined using cultured human fibroblasts, ARPE-19, and photoreceptor cells. The hydrogel systems were applied to human fetal retinal pigment epithelial cells cultured for two months until maximum transepithelial electrical resistance (TEER) to investigate the effect of the gel matrices on tight junctions using TEER measurements and immunostainings against the tight junction protein ZO-1.ResultsTested alginate- and hyaluronic acid–based hydrogels resembled the natural refractive index of human vitreous bodies (1.3356–1.3360) in contrast to SIL-5000 (1.4034) and showed high optical transparency (>90%) within the visible light region. The biopolymeric hydrogels exhibited viscoelastic properties similar to juvenile vitreous bodies with G′>G″ adjustable via different gelation times, contrary to SIL-5000 (G′<G″). The metabolic activity, apoptosis and tight junctions of all tested ocular cells were unaffected by the alginate- and hyaluronic acid–based vitreous substitutes.ConclusionsThe present in vitro study demonstrates good optical, viscoelastic, and biocompatible properties of alginate- and hyaluronic acid–based hydrogels required for their use as vitreous substitutes.Translational RelevanceBiopolymer-based hydrogels represent a promising vitreous replacement strategy to treat vitreoretinal diseases.

Optic coherence tomography features of subretinal vitreous substitutes

BackgroundTo draw comparisons between spectral domain optic coherence tomography (SD-OCT) features of subretinal silicon oil (SO), perfluoro-n-octane (PFO) or C3F8 gas.MethodsCases diagnosed with retained subretinal vitreous substitutes (VS) were retrospectively selected. Demographic data were collected and OCT features were analyzed.ResultsIn 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.ConclusionDifferent 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.

Bioinspired Thermosensitive Hydrogel as a Vitreous Substitute: Synthesis, Properties, and Progress of Animal Studies.

In many vitreal diseases, the surgeon removes the natural vitreous and replaces it with silicone oils, gases, or balanced salt solutions to fill the eyeball and hold the retina in position. However, these materials are often associated with complications and have properties that differ from natural vitreous. Herein, we report an extension of our previous work on the synthesis of a biomimetic hydrogel that is composed of thiolated gellan as an analogue of type II collagen and poly(methacrylamide-co-methacrylate-co-bis(methacryloyl)cystamine), a polyelectrolyte, as an analogue of hyaluronic acid. This thermosensitive hydrogel can be injected into the eye as a viscous solution at 45 °C. It then forms a physical gel in situ when it reaches body temperature, and later forms disulfide covalent crosslinks. In this article, we evaluated two different formulations of the biomimetic hydrogels for their physical, mechanical, and optical properties, and we determined their biocompatibility with several cell lines. Finally, we report on the progress of the four-month preclinical evaluation of our bio-inspired vitreous substitute in comparison to silicone oil or a balanced salt solution. We assessed the eyes with a slit-lamp examination, intraocular pressure measurements, electroretinography, and optical coherence tomography. Preliminary results are very encouraging for the continuing evaluation of our bio-inspired hydrogel in clinical trials.

Optimization of Polydimethylsiloxane Synthesized Parameters as Vitreous Humour Substitutes

Polydimethylsiloxane (PDMS) with two type viscosity that commonly used as vitreous humour substitutes in vitreoretinal surgery has been successfully synthesized by ring-opening polymerization. Optimization of synthesized parameters such as ratio of monomer and chain terminator, the amount of initiator, mixing temperature and reaction time was carried out to obtain PDMS materials having similar properties with commercial product. PDMS with viscosity of 1.17 Pas that very close to viscosity of commercial PDMS of 1.08 Pas, was successfully synthesized with a ratio of 26:10 monomer and terminator chain, 0.58 M of initiator KOH, 170 oC of mixing temperature and 35 minutes of reaction time. By changing reaction time to 40 minutes, PDMS was successfully synthesized with viscosity of 3.42 that similar to that of commercial one.

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.

Surgical Repair of a Persistent Full-Thickness Macular Fold With Base-to-Base Photoreceptor Apposition Secondary to Hypotony From Trabeculectomy Surgery and Postoperative Laser Suturelysis

Purpose: To report the successful repair of a persistent full-thickness retinal fold secondary to hypotony from trabeculectomy surgery. Results: Laser suturelysis was performed on a patient to relieve an elevated intraocular pressure posttrabeculectomy surgery. This resulted in chronic hypotony, a full-thickness retinal fold, and a decline in visual acuity to “count fingers.” The patient underwent a pars plana vitrectomy with internal limiting membrane peeling, subretinal injection of balanced saline solution, fluid-air exchange, injection of F-Decalin, peripheral retinotomy, endolaser photocoagulation, and vitreous substitution with 15% C3F8 gas. Anatomic improvement was documented via multimodal imaging. Six months postoperatively best-corrected visual acuity (BCVA) returned to 20/30. Conclusions: We describe a surgical approach to full-thickness retinal folds and review the management options previously reported in the setting of hypotony. We provide support for the active management of appositional full-thickness retinal folds involving the fovea and demonstrate that surgical correction can significantly improve BCVA even after 4 months of hypotony.