Zhaoxin Jiang

Refractive shifts in four selected artificial vitreous substitutes based on Gullstrand-Emsley and Liou-Brennan schematic eyes.

PURPOSE To determine and compare the refractive shifts based on Gullstrand-Emsley and Liou-Brennan schematic eyes after filling them with four selected artificial vitreous substitutes: silicone oil, heavy silicone oil, hydrogels, and encapsuled balanced salt solution. METHODS The optical constants of artificial vitreous body-filled eyes were calculated based on Gullstrand-Emsley and Liou-Brennan schematic eyes with accommodation relaxed. The theoretical refractive shifts in these two models were compared in pars plana vitrectomy (PPV), PPV plus lensectomized and PPV plus intraocular lens (IOL) eyes after four artificial vitreous tamponades. RESULTS The Gullstrand-Emsley schematic eye shows refractive shifts of +8.710, -4.544, +1.136, and -0.338 D in PPV eyes; +11.044, +20.332, +16.351, and +17.413 D in PPV plus lensectomized eyes; and the need for IOL powers of +22.195, +22.366, +22.292, and +22.312 D in PPV plus IOL eyes in silicone oil, heavy silicone oil, hydrogels, and encapsuled balanced salt solution tamponade eyes, respectively. Similarly, the Liou-Brennan schematic eye induced shifts of +6.260, -3.266, +0.817, and -0.272 D in PPV eyes; +13.181, +20.654, +17.451, and +18.305 D in PPV plus lensectomized eyes; and the need IOL powers of +13.522, +23.767, +19.389, and +20.558 D in PPV plus IOL eyes, respectively. CONCLUSIONS The Gullstrand-Emsley schematic eye is a convenient and accurate model for predicting refractive shifts for hydrogels and encapsuled balanced salt solution substitutes in PPV eyes. The Liou-Brennan schematic eye is recommended for silicone oil and heavy silicone oil in PPV eyes and for all four substitutes in PPV plus lensectomized eyes and PPV plus IOL eyes. In addition, the encapsuled balanced salt solution changes the refraction little in either schematic eye.

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

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS The FCVB was shown to be flexible, effective, and safe as a vitreous substitute over a 3-month implantation time. (ClinicalTrials.gov number, NCT00910702.).

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

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Preliminary efficacy and safety of a silicone oil-filled foldable capsular vitreous body in the treatment of severe retinal detachment.

Purpose: 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. Methods: 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. Results: 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. Conclusion: Silicone oil–filled FCVB was shown to be effective and safe in 3 eyes as a vitreous substitute over a 12-month observation time.

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.

A preliminary study to treat severe endophthalmitis via a foldable capsular vitreous body with sustained levofloxacin release in rabbits.

PURPOSE We investigated whether the foldable capsular vitreous body (FCVB) could release levofloxacin sustainably in vitro and inhibit endophthalmitis in rabbit models. METHODS 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. RESULTS 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. CONCLUSIONS The FCVB could provide us with dual functions, combining a levofloxacin drug delivery system and a vitreous substitute, to treat endophthalmitis in rabbit eyes.

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

Introduction:  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.

Migration of Retinal Pigment Epithelium Cells Is Regulated by Protein Kinase Cα In Vitro

PURPOSE Retinal pigment epithelium (RPE) cell migration and proliferation are considered key elements in proliferative vitreoretinopathy (PVR). Downregulation of protein kinase Cα (PKCα) can inhibit RPE cell proliferation. Here, we sought to analyze whether PKCα affects the migration of RPE cells. METHODS Human RPE (hRPE) cells were cultured, confirmed by immunofluorescence staining, and divided into four groups: control, thymeleatoxin, non-small interfering RNA (siRNA), and siRNA-PKCα. Thymeleatoxin was used to activate PKCα, and siRNA-PKCα was used to knock it down. Expression of PKCα was confirmed by quantitative RT-PCR (qRT-PCR). Cell migration ability was analyzed by wound healing assay and transwell chamber assay. Expression of zonula occludens (ZO)-1 and occludin was determined by immunofluorescence. RESULTS Pure populations of hRPE cell cultures were observed using light and fluorescence microscopy. The mRNA levels of PKCα were not significantly increased by thymeleatoxin, but were reduced by siRNA-PKCα as determined by qRT-PCR assay. The wound healed faster in the thymeleatoxin group than in the control group at time points 12, 15, and 20 hours. The wound healed more slowly in the siRNA-PKCα group than in the non-siRNA group at the three time points. A similar tendency among the four groups was consistently observed in regard to cell numbers counted in the transwell chamber assay. The expression of ZO-1 was highest in the siRNA-PKCα group, similar in the control and non-siRNA groups, and lowest in the thymeleatoxin group. After migration, the fluorescence intensity of ZO-1 was reduced to similarly weak levels among the four groups. CONCLUSIONS Retinal pigment epithelium cell migration is enhanced by a PKCα agonist and suppressed by a PKCα antagonist. The results suggest that a PKCα-mediated signal transduction pathway plays a crucial role in hRPE cell migration and may be a potential therapeutic target against hRPE cell migration and PVR disease.

Three-Year Efficacy and Safety of a Silicone Oil-Filled Foldable-Capsular-Vitreous-Body in Three Cases of Severe Retinal Detachment

Purpose We previously designed a novel foldable capsular vitreous body (FCVB) to treat severe retinal detachment and evaluated its performance in a 1-year follow up study. The purpose of this study was to determine the efficacy and safety of a silicone oil (SO)-filled FCVB in a 3-year follow-up. Methods Standard three-port pars plana vitrectomy was performed, and the FCVB was triple folded and implanted in the vitreous cavity of three eyes. The SO then was injected into the capsule to support the retina. The eyes were examined using Goldmann applanation tonometry, fundus photography, optical coherence tomography (OCT), noncontact specular microscopy, and ultrasound biomicroscopy over a 3-year implantation period. Results At the 3-year follow-up, retinal reattachment was achieved in all three cases, with steady intraocular pressure. The visual acuity showed slight fluctuations, and it was slightly increased compared to baseline. Optical coherence tomography revealed decreased retinal thickness and an altered retinal structure in the implanted eyes compared to the control eyes. No keratopathy, glaucoma, SO leakage, SO emulsification, or other apparent complications occurred during the observation period. Conclusion The SO-filled FCVB was effective and safe as a vitreous substitute in three eyes over a 3-year observation period. Translational Relevance Silicone oil emulsification is a severe complication after retinal detachment surgery. On the basis of animal experiments, we investigated a new strategy and product, the FCVB, to overcome this complication. In this pilot study, FCVB limited SO emulsification and migration. This study could lay the foundation for a further multicenter clinical trial.