Foldable Capsular Vitreous Body Research Articles

Preliminary study on retinal vascular and oxygen-related changes after long-term silicone oil and foldable capsular vitreous body tamponade.

Silicone oil has been the only long-term vitreous substitute used in the treatment of retinal detachment since 1962 by Cibis. Nevertheless, its effects on retinal vascular morphology and oxygen supply to the retina are ambiguous in current research. We previously invented a foldable capsular vitreous body (FCVB) to use as a new vitreous substitute in the treatment of severe retinal detachment, but its effects on the retinal vessel were unknown. Therefore, in this study, a standard three-port pars plana vitrectomy (PPV) was performed on the right eye of each rabbit and then silicone oil and FCVB were injected into the vitreous cavity as vitreous substitutes. After 180 days of retention, the retinal vascular morphology did not display any distinct abnormalities, and hypoxia-induced factor-1alpha (HIF-1α) and vascular endothelial growth factor (VEGF) did not vary markedly during the observation period in silicone oil tamponade- and FCVB-implanted eyes. This study may suggest that silicone oil and FCVB tamponade in rabbit eyes did not cause retinal vascular pathologic changes or retinal hypoxia for 180 days.

Functional evaluation of a novel vitreous substitute using polyethylene glycol sols injected into a foldable capsular vitreous body

Polyethylene glycol (PEG) is a short-term (41 days) potential vitreous substitute and is too short for an ideal vitreous substitute. Previously, a foldable capsular vitreous body (FCVB) was designed to mimic vitreous function. The aim of this study is to evaluate whether PEG injected into FCVB can serve as a long-term vitreous substitute. In vitro study, a concentration of 5% (w/v) PEG sols showed natural-like mechanical and optical properties in terms of pH, density, light transmittance, refractive index, interfacial tension, viscosity, rheology, and cytotoxicity. Then in vivo tests, 30 rabbits received standard pars plana vitrectomy, of which 12 eyes were implanted with PEG injected into FCVB, nine eyes were injected with PEG sols alone, and nine others were injected with balance salt solution as control. A clinical evaluation of the anterior segment, fundus, and intraocular pressure was measured pre- and postoperatively up to 180 days, which showed that FCVBs had good retina supporting function, except for a higher incidence of cataracts. Gross pathology, hematoxylin and eosin, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining analysis also showed that FCVBs had good biocompatibility, and that all quadrants of the capsular wall fitted well with the retina. This study demonstrated that PEG injected into FCVB can serve as a long-term vitreous substitute and has potential clinical use.

A Novel Vitreous Substitute of Using a Foldable Capsular Vitreous Body Injected with Polyvinylalcohol Hydrogel

Hydrogels may be the ideal vitreous substitutes due to their wonderful physical features and biocompatibility. However, their drawbacks, short residence time, and biodegradation in vivo, have led to the fact that none of them have been approved for clinical use. In this study, we developed a novel approach of using a foldable capsular vitreous body (FCVB) injected with polyvinylalcohol (PVA) hydrogel as a vitreous substitute for long-term tamponade. The 3% PVA hydrogel that was cross-linked by gamma irradiation showed good rheological and physical properties and had no toxicity in vitro. After 180 days retention, the 3% PVA hydrogel inside FCVB remained transparent and showed good viscoelasticity without biodegradation and showed good biocompatibility and retina support. This new approach may develop into a valuable tool to improve the stability performance of PVA hydrogel as a vitreous substitute and to extend the application function of FCVB for long-term implantation in vitreous cavity.

A Preliminary Study to Treat Severe Endophthalmitis via a Foldable Capsular Vitreous Body with Sustained Levofloxacin Release in Rabbits

We investigated whether the foldable capsular vitreous body (FCVB) could release levofloxacin sustainably in vitro and inhibit endophthalmitis in rabbit models. Approximately 1.0 mL levofloxacin (625 μg/mL) was injected into the capsule of nine FCVBS. The levofloxacin release value was determined in the modified franz diffusion cells over time. In the in vivo study, all right eyes of 45 rabbits were infected with Staphylococcus epidermidis AND were divided randomly into three groups at 24 hours after infection: FCVB plus levofloxacin (n = 15), silicone oil plus subconjunctival levofloxacin (n = 15), and an untreated group (n = 15) during a 30-day observation time. Levofloxacin concentrations in the aqueous humor were detected, and therapeutic efficacy was evaluated with clinical evaluation, bacterial counts, cytokine profiles, and histopathology. The FCVB released levofloxacin ranging from 9 to 13.5 ng/mL in vitro and from 42 to 1.6 ng/mL in the aqueous humor during 30 days. In the FCVB and silicone-treated groups, clinical inflammation almost was abolished; no bacteria were detected in the aqueous humor; TNF-α, IL-1β, and IFN-γ expression decreased; and relatively normal corneal and retinal architecture were kept after the 30-day treatment. The FCVB could provide us with dual functions, combining a levofloxacin drug delivery system and a vitreous substitute, to treat endophthalmitis in rabbit eyes.

PRELIMINARY EFFICACY AND SAFETY OF A SILICONE OIL–FILLED FOLDABLE CAPSULAR VITREOUS BODY IN THE TREATMENT OF SEVERE RETINAL DETACHMENT

We previously invented a novel foldable capsular vitreous body (FCVB) in the treatment of severe retinal detachment. The purpose of this study was to determine its hydrolytic stability in vitro and further evaluate its efficacy and safety in human eyes. The hydrolytic stability test proceeded according to State Food and Drug Administration guidelines about intraocular lenses of the ophthalmic implants. A standard three-port pars plana vitrectomy was performed, and FCVB was triple folded and sent into the vitreous cavity of three eyes; then silicone oil was injected into the capsule to support the retina. The treated eyes were examined using Goldmann applanation tonometry, fundus photography, optical coherence tomography, noncontact specular microscopy, and ultrasound biomicroscopy during a 12-month follow-up appointment. The mass of FCVB with silicone oil after 60-day accelerating aging temperature was equal to that at baseline. The FCVB can easily be implanted into the vitreous cavity through a 3-mm incision. The visual acuity and intraocular pressure after FCVB implantation show a slight elevation compared with those of preoperative eyes. The fundus and optical coherence tomography showed that the FCVB was well distributed in the vitreous cavity and evenly supported the retina. Retinal reattachment was found in 3 eyes at the 12-month examination. There was no statistically significant decrease in the density of corneal endothelial cells from baseline to 12 months after FCVB implantation. Ultrasound biomicroscopy showed that the FCVB smoothly contacted but not crushed the ciliary body. Silicone oil-filled FCVB was shown to be effective and safe in 3 eyes as a vitreous substitute over a 12-month observation time.

Evaluation of the levofloxacin release characters from a rabbit foldable capsular vitreous body

The authors have manufactured a novel rabbit foldable capsular vitreous body (FCVB). The aim of this study was to determine whether this rabbit FCVB can release levofloxacin in vitro and in vivo, and to evaluate the release characteristics. In vitro, the rabbit FCVB with levofloxacin 500 μg/mL was immersed in cups of modified Franz diffusion cells. Following this, 200 μL of liquid was aspirated at intervals from 10 minutes to 24 hours. In vivo, the FCVB with levofloxacin was implanted into the right eyes of five rabbits. After implantation, the aqueous humor was aspirated on days 1, 7, 14, 28, and 56. The levofloxacin concentrations in the cups and aqueous humor samples were detected by high-performance liquid chromatography–tandem mass spectrometry. The FCVB was observed under a scanning electron microscope. The results showed that the released levofloxacin was stabilized at 20 ng/mL at time points from 10 minutes to 24 hours in vitro. In vivo, levofloxacin concentrations in the aqueous humor were 132, 50, 39, 11, and 15 ng/mL on days 1, 7, 14, 28, and 56, respectively. In the FCVB capsules, 300 nm apertures were observed. These results suggest the rabbit FCVB released levofloxacin stably in vitro and sustainably in vivo. This study provides a novel combined approach, with the FCVB as a vitreous substitute and drug delivery system for the treatment of bacterial endophthalmitis.

Evaluation of 5-fluorouracil released from a foldable capsular vitreous body in vitro and in vivo

Previously, we have confirmed that the foldable capsular vitreous body (FCVB) can serve as a drug delivery system (DDS) as well as a vitreous substitute. Here, we evaluated the characteristics of the release of 5-fluorouracil (5-Fu) from FCVB in vitro and in vivo. For the in-vitro study, various concentrations of 5-FU (50-200μg/ml) were injected into FCVB capsules and immersed in cups of modified Franz diffusion cells, and liquid was aspirated at specific time intervals. In the in-vivo study, FCVB was folded and implanted into the vitreous cavity in the right eyes of five rabbits, and then 1.0ml 5-Fu (200μg/ml) was injected into the capsule. Another five rabbits that were used as the controls received intravitreal injections Aqueous humor was aspirated postoperatively at specific time intervals up to 56days. The 5-Fu contents in vitro were detected by UV spectrophotometry and ultra performance liquid chromatography (UPLC), and the in-vivo 5-FU levels in the aqueous humour were detected by UPLC. The stock solution in the FCVB before-release study and the FCVB residue were collected for UPLC analysis. UV spectrophotometry revealed that 5-FU was released from FCVB in vitro in a time-dependent manner from 20-360min in vitro. UPLC analysis revealed that 5-FU was released sustainably from FCVB. The 5-FU concentration in the aqueous humour was detected until postoperative day 56 (D56), with sustained release from postoperative days 3-56. However, the 5-FU concentration in the control samples was detected until only D7, and could not be detected on D14. Finally, 48.8% of the 5-FU was released on D56 in the in-vivo experiment. FCVB can release 5-Fu sustainably and mechanically, indicating that FCVB can be used as a common vehicle for the sustainable release of different drugs. FCVB is a potentially valuable pharmaceutical adjunct to conventional vitreous surgery for managing or preventing proliferative vitreoretinopathy.

Evaluation of Levofloxacin Release Characteristics from a Human Foldable Capsular Vitreous BodyIn Vitro

We have manufactured a novel human foldable capsular vitreous body (FCVB). In this article, we determine whether the human FCVB releases levofloxacin in vitro and evaluate the release characteristics. Levofloxacin at dosages of 100, 250, and 500 μg/mL in 4.0 mL H2O was injected into the novel human FCVB; then, the capsules were immersed in cups of modified Franz diffusion cells. Two hundred microliters of liquid was aspirated at intervals of 10, 20, 40, 60, 120, 180, 240, 300, and 360 min. The levofloxacin concentrations in the cups were detected using the liquid chromatographic-tandem mass spectrometry (HPLC-MS/MS) method. Five hundred μg/mL levofloxacin liquor at volumes of 4.0, 5.0, and 6.0 mL was injected into the novel human FCVB, and the release characteristics were detected for each. The capsules of the FCVB were observed under scanning electron microscopy before and after the release study. The novel human FCVB released levofloxacin in a time-dependent manner under 100, 250, and 500 μg/mL dosages from 10 to 360 min. Particularly in the 250 μg/mL levofloxacin group, the concentration (Q) had a good linear relationship with time (t(1/2)), Q=1.3381t(1/2)+10.2818 (r=0.9954, Higuchi equation). The human FCVB released levofloxacin in a dose-dependent manner under 100, 250, and 500 μg/mL dosages from 10 to 360 min in the total tendency, but the 500 μg/mL group released less levofloxacin than the 250 group at 300 and 360 min. The human FCVB did not release levofloxacin in a volume-dependent manner with 4.0, 5.0, and 6.0 mL volume. The 4.0-mL volume group released more levofloxacin than the other 2 volume groups. Numerous 300-nm-mili apertures were observed in the capsule of the FCVB at the beginning and end of this observation. A human FCVB can sustainably, in vitro, mechanically release levofloxacin in both a time-dependent and dose-dependent manner, but not in a volume-dependent manner. This study sets forth a novel combined research and therapeutic strategy as a vitreous substitute and intravitreal drug delivery system for the treatment of bacterial endophthalmitis.

Biocompatibility and retinal support of a foldable capsular vitreous body injected with saline or silicone oil implanted in rabbit eyes

The aim of this study was to evaluate over a 180-day period the biocompatibility and retinal support of a foldable capsular vitreous body injected with either saline or silicone oil implanted in rabbit eyes. A standard three-port pars plana vitrectomy was performed, and foldable capsular vitreous bodies were implanted into the vitreous cavity of rabbit eyes (n = 18). Silicone oil tamponade was used as the control group (n = 5). Of the foldable capsular vitreous body-implanted eyes, either saline (n = 9) or silicone oil (n = 9) was injected into the foldable capsular vitreous body to support the retina. The treated eyes were examined using a slit lamp with a non-contact slit-lamp lens, a tonopen, a non-contact specular microscope and a B-scan ultrasound during the 180-day implantation period. A histological examination was performed at 90 and 180 days. During the 180-day implantation period, no significant corneal keratopathy or intraocular inflammation was noted, and the intraocular pressure (IOP) and corneal endothelial numbers remained steady among the three groups. B-scan ultrasonography showed a smoothly increased echogenicity in front of the retina in group of foldable capsular vitreous bodies injected with saline. Gross examination showed that the foldable capsular vitreous bodies injected with saline or silicone oil smoothly supported the retina. The saline or silicone oil inside the foldable capsular vitreous body was homogeneous, transparent and filled the foldable capsular vitreous body. Histological examination showed no obvious abnormality of the cornea, ciliary body or retina in the foldable capsular vitreous body-implanted eyes. These results suggest that foldable capsular vitreous bodies injected with either saline or silicone oil showed good biocompatibility and retinal support in rabbit eyes over a 180-day implantation time.

Clinical device‐related article evaluation of morphology and functions of a foldable capsular vitreous body in the rabbit eye

We previously proposed a new strategy to replace a vitreous body with a novel foldable capsular vitreous body (FCVB). In this study, the FCVB was designed to mimic natural vitreous morphology, and evaluate its physiological functions compared with traditional silicone oil substitutes, in an established rabbit model of proliferative vitreoretinopathy. We found that FCVB was a very good replacement for closely mimicking the morphology and restoring the physiological functions, such as the support, refraction, and cellular barriers, of the rabbit vitreous body. The study has provided us with a novel research and therapy strategy that could effectively mimic the morphology and physiological function of the rabbit vitreous body.

Evaluation of supporting role of a foldable capsular vitreous body with magnetic resonance imaging in the treatment of severe retinal detachment in human eyes

To determine the supporting role of a novel foldable capsular vitreous body (FCVB) with magnetic resonance imaging (MRI) in the treatment of severe retinal detachment in human eyes. The study examined nine eyes of nine patients. Among the nine eyes, five had suffered penetrating injuries while four had suffered contusions of the eyeball involving large defects of the retina or choroids. A standard three-port pars plana vitrectomy was performed, FCVB was triple-folded and sent into the vitreous cavity; balanced salt solution (BSS) was injected into the capsule to support the retina. Three cardinal axes of nine eyes were examined using MRI at baseline and at the 3-month follow up. MRI revealed that the signal intensity of the FCVB was similar to the normal vitreous body, with low-signal intensity on T1-weighted image and high-signal intensity on T2-weighted image. In three pre-operative silicone oil- or heavy silicone oil-filled eyes, FCVBs were not fully inflated, and eyeball deformation was observed in one eye. Shifts of three cardinal axes of three eyes (horizontal, anteroposterior, and vertical) according to MRI, were -4.33, -4.67, and -2.67 mm. In the remaining six eyes, FCVBs were well distributed in the vitreous cavity and evenly supported the retina; the cardinal axes of the eyes were similar to pre-operation. Shifts of three cardinal axes of six eyes were -0.34, -0.34, and -0.34 mm. In a total of nine eyes, shifts of three cardinal axes were -1.67, -1.77, and -1.11 mm. Statistically significant difference showed only between the horizontal axis of nine eyes pre-operatively and post-operatively (P1=0.041, P2=0.058, P3=0.123). This study demonstrated the effectiveness of MRI to monitor the supporting role of an FCVB in the treatment of severe retinal detachment in human eyes.

Evaluation of the Flexibility, Efficacy, and Safety of a Foldable Capsular Vitreous Body in the Treatment of Severe Retinal Detachment

To determine the flexibility, efficacy, and safety of a novel foldable capsular vitreous body (FCVB) in the treatment of severe retinal detachment in human eyes. The study involved 11 patients with 11 severe retinal detachments. A standard three-port pars plana vitrectomy was performed, and the FCVB was triple-folded and implanted into the vitreous cavity. Balanced salt solution was then injected into the capsule of the FCVB to support the retina. The treated eyes were examined by ophthalmoscopy, fundus photography, and tonometry during a 3-month implantation period. B-scan ultrasonography, optical coherence tomography (OCT), ultrasound biomicroscopy (UBM), and electroretinogram (ERG) were also performed. The FCVB was removed and examined in the laboratory at the end of the 3-month treatment time. The FCVB was easily implanted into the vitreous cavity through a 3-mm incision and was easily removed through a 2-mm scleral incision. Retinal reattachment was found in 8 (73%) of 11 eyes at the end of the 3-month treatment time. The fundus, B-scan, and OCT showed that the FCVB was well distributed in the vitreous cavity and evenly supported the retina. IOP and visual acuity in the FCVB-treated eyes did not show a significant difference when compared with the preoperative measurements. UBM showed that the FCVB smoothly contacted but did not crush the ciliary body. Laboratory examinations showed no significant inflammatory cells in the balanced salt solution, no decrease in spectral transmittance, and no blocking of tiny apertures from the FCVB after a 3-month implantation period. The FCVB was shown to be flexible, effective, and safe as a vitreous substitute over a 3-month implantation time. (ClinicalTrials.gov number, NCT00910702.).

Protein kinase Cα downregulation via siRNA-PKCα released from foldable capsular vitreous body in cultured human retinal pigment epithelium cells

We previously found that downregulation of protein kinase Cα (PKCα) can inhibit retinal pigment epithelium (RPE) cell proliferation involved in the development of proliferative vitreoretinopathy (PVR). In this study, we tested whether PKCα could be downregulated via small interfering RNA (siRNA)-PKCα released from foldable capsular vitreous body (FCVB) in cultured human RPE cells. SiRNA-PKCα content, determined by ultraviolet (UV) spectrophotometer, was released from FCVB containing 200, 300, 400, 500, and 600 nm siRNA-PKCα in a time-dependent manner from 1 to 96 hours and a dose-dependent manner at five concentrations. The content (y) had a good linear relationship with time (x), especially in the 600 nm siRNA-PKCα group (y = 16.214x, R2 = 0.9809). After treatment with siRNA-PKCα released from FCVBs, the PKCα was significantly decreased by RT-PCR, Western blot, and immunofluorescence analysis in RPE cells. These results indicate that PKCα was significantly downregulated by siRNA-PKCα released from FCVB in human RPE cells and provide us with a new avenue to prevent PVR.

Technical Standards of a Foldable Capsular Vitreous Body in Terms of Mechanical, Optical, and Biocompatible Properties

We previously proposed a new strategy to fabricate a novel foldable capsular vitreous body (FCVB) as a vitreous substitute and found that the FCVB was a very good replacement for closely mimicking the morphology and restoring the physiologic function of the rabbit vitreous body. The aim of this article was to assess the mechanical, optical, and biocompatible properties of a FCVB made from liquid silicone rubber. The mechanical properties show that the shore hardness is 37.80 degrees, the tear strength is 47.14 N/mm, the tensile strength is more than 7.28 MPa, and the elongation ratio is more than 1200%; in addition, the FCVB has 300 nm mili apertures in the capsule. The optical properties reveal that transmittances are 92%, hazes are 5.74%, and spectral transmittance is 97%. The transmittance mission is 2.3% and can sustain a 1500 mW, 0.2 s, 532 nm green laser. The biocompatible properties are shown in the stable extracts experiment, no significant fever, good genetic safety, and no structural abnormality or apoptosis in the cornea, ciliary body, and retina over a 6-month observation period. These results indicate that the FCVB has good mechanical, optical, and biocompatible properties, and the assessment results can be recommended as the FCVB technical standards for industrial manufacturing and inspection.

Sustained Mechanical Release of Dexamethasone Sodium Phosphate from a Foldable Capsular Vitreous Body

Since 300-nm-mili apertures were present in the capsule of the foldable capsular vitreous body (FCVB), the authors tested whether the FCVB could mechanically release dexamethasone sodium phosphate (DexP) from its capsule. In the in vitro study, DexP at concentrations of 0.25, 0.5, 1, 2, and 4 mg/mL in a balanced salt solution were injected into the capsules, which were immersed in cups of modified Franz diffusion cells. Two hundred microliters of liquid was aspirated at time intervals of 10, 20, 40, 60, 120, 180, 240, 300, and 360 minutes. In the in vivo study, the capsule was folded and implanted into the vitreous cavities of five rabbits. Approximately 0.6 mL DexP (2 mg/mL) was then injected into the capsule. An intravitreal injection with DexP was performed on another five rabbits as the control group. Aqueous humor was aspirated on days 1, 3, 7, 14, 28, and 42 after implantation. The DexP contents in the cups and aqueous humor were detected by HPLC-MS/MS. FCVB released DexP in a time-dependent and dose-dependent manner in vitro with five dosages from 10 to 360 minutes. Especially in the 0.25 mg/mL DexP group, the content (y) had good linear relationships with time (x), as shown by y = 0.7635x + 10.205. The DexP contents in the aqueous humor were detected until day 28 and were undetectable on day 42. However, the DexP contents were detected only before day 3 in the controls. FCVB can sustainably and mechanically release DexP by capsule apertures in a time-dependent and dose-dependent manner in addition to serving as a vitreous substitute.