Safety and efficacy of intracapsular tranilast microspheres in experimental posterior capsule opacification

Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, Peoples Republic of China.
Journal of Cataract and Refractive Surgery (Impact Factor: 2.72). 01/2008; 33(12):2122-8. DOI: 10.1016/j.jcrs.2007.07.041
Source: PubMed


To evaluate the safety and efficacy of a sustained-release agent designed to reduce posterior capsule opacification (PCO).
Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, Peoples Republic of China.
Free tranilast (TFree) was incorporated into polylactic acid microspheres and then tested using a rabbit model of PCO. Twenty-nine rabbits were randomized into 5 groups treated with balanced saline solution (BSS control); TFree; or 0.5, 1.0, or 2.0 mg tranilast microspheres (TMicro). Standard phacoemulsification cataract surgery, including manual aspiration of all visible soft lens matter, was performed in all groups. The selected test agent was then injected into the lens capsule. Postoperative clinical examinations were performed at 1, 3, 7, 14, 30, 60, and 90 days. Posterior capsule opacification was quantified using high-resolution computer image analysis at 1, 2, and 3 months. Histological examination was performed at 3 months.
Eyes treated with TMicro had significantly less PCO than the eyes in the BSS and TFree groups. While the BSS control eyes had increased PCO over 3 months, eyes in the TMicro group had reduced PCO over time in a dose-dependent fashion. Histological examination showed reduced lens epithelial cell proliferation in the TMicro groups, with no manifest damage to the cornea, iris, or retina compared with the BSS controls. There was a transient increase in postoperative inflammation in all tranilast-treated groups compared with the BSS controls.
Sustained-release intracapsular tranilast reduced PCO in an experimental model of PCO, suggesting further investigation of its therapeutic potential is justified.

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    • "Posterior capsule opacification (PCO) still remains a common complication of the modern cataract surgery, and develops from residual lens epithelial cells (LECs) that undergo proliferation, migration, metaplasia, differentiation, and opacification in the capsular bag after cataract surgery.[123] Various mechanical,[4567] physical,[891011] and immunological[12] methods have been described to prevent PCO; however, no method has been reported as practical, effective, and safe in clinical practice. Neodymium-doped yttrium aluminum garnet laser capsulotomy is the treatment of PCO. "
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    ABSTRACT: Purpose: To determine the effect of a capsular tension ring (CTR) implantation in preventing posterior capsular opacification (PCO) after cataract surgery in patients with high myopia. Materials and Methods: In this prospective single-surgeon standardized-surgical-procedure fellow-eye comparison trial, 34 patients with high myopia had phacoemulsification surgery. Although one eye received an acrylic intraocular lens (IOL) and CTR, other eye received only an IOL as control. PCO, within the capsulorhexis overlap, was documented by standardized digital retroillumination images at least 2 years post-operatively, and the percentage area of PCO was scored (scale 0%-100%) using the POCOman software system. The PCO score and the incidence of neodymium-doped yttrium aluminum garnet (Nd: YAG) capsulotomy of groups, and correlations between PCO score and presence of CTR, age, phaco time, refraction, and axial length (AL) were determined. Results: The mean time interval from surgery to PCO measurement was 43.4 ± 11.2 months for the eyes with a CTR and 43.1 ± 11.6 months for the controls (P = 0.91). The PCO score of the eyes with a CTR was significantly lower than in the controls (5.9 ± 4.3 vs. 22.3 ± 12.2, respectively; P < 0.001). There were statistically insignificant correlations between PCO score and pre-operative refraction (r = 0.02; P = 0.90), AL (r = 0.03; P = 0.80), phaco time (r = 0.11; P = 0.53), and patient's age (r = 0.23; P = 0.55). No patient with a CTR had a Nd: YAG laser capsulotomy, but it was six in controls (P = 0.025). Conclusions: CTR implantation seems to be effective in reducing the PCO and Nd: YAG laser capsulotomy rates in high myopic eyes.
    Indian Journal of Ophthalmology 09/2013; 62(3). DOI:10.4103/0301-4738.116469 · 0.90 Impact Factor
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    • "Many methods have previously been developed to prevent the development of such fibrosis. These include topical administration of anti-inflammation medications (e.g., dexamethasone, heparin, diclofenac) [6]–[8] or anti-metabolic agents (e.g., 5-fluorouracil, mitomycin) [9], [10], improved design of intraocular lens (IOL) [11], [12], new IOL materials, and modified surgical procedures (e.g., bag-in-the-lens IOL implantation, optic buttonholing) [13]–[15]. However, none of the pharmacological therapies is effective and safe enough for the prevention of PCO, and some of them are toxic [16], [17]. "
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    ABSTRACT: Posterior capsular opacification (PCO) is a common complication of cataract surgery. Transforming growth factor-β2 (TGF-β2) plays important roles in the development of PCO. The existing pharmacological treatments are not satisfactory and can have toxic side effects. We evaluated the effect of pirfenidone on proliferation, migration and epithlial-mesenchymal transition of human lens epithelial cell line SRA01/04 (HLECs) in vitro. After treatment with 0, 0.25, and 0.5 mg/ml pirfenidone, cell proliferation was measured by MTT assay. Cell viability was determined by trypan blue exclusion assay and measurement of lactate dehydrogenase (LDH) activity released from the damaged cells. And cell migration was measured by scratch assay in the absence or presence of transforming growth factor-β2 (TGF-β2). The expressions of TGF-β2 and SMADs were evaluated with real-time RT-PCR, western blot, and immunofluorescence analyses. The mesenchymal phenotypic marker fibronectin (FN) was demonstrated by Immunocytofluorescence analyses. The cells had high viability, which did not vary across different concentrations of pirfenidone (0 [control] 0.3, 0.5 or 1.0 mg/ml) after 24 hours. Pirfenidone (0∼0.5 mg/ml) had no significant cytotoxicity effect on SRA01/04 by LDH assay. Pirfenidone significantly inhibited the proliferation and TGF-β2-induced cell migration and the effects were dose-dependent, and inhibited TGF-β2-induced fibroblastic phenotypes and TGF-β2-induced expression of FN in SRA01/04 cells. The cells showed dose-dependent decreases in mRNA and protein levels of TGF-β2 and SMADs. Pirfenidone also depressed the TGF-β2-induced expression of SMADs and blocked the nuclear translocation of SMADs in cells. Pirfenidone inhibits TGF-β2-induced proliferation, migration and epithlial-mesenchymal transition of human lens epithelial cells line SRA01/04 at nontoxic concentrations. This effect may be achieved by down regulation of TGF-β/SAMD signaling in SRA01/04 cells.
    PLoS ONE 02/2013; 8(2):e56837. DOI:10.1371/journal.pone.0056837 · 3.23 Impact Factor
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    • "Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer that is used extensively in biomedical applications, including in the eye.13 In addition, growth factor- and/or drug-incorporated PLGA microparticles have also been exploited as drug delivery vehicles to the posterior segment with in vivo rabbit studies demonstrating the biocompatibility of intravitreally administered PLGA microparticles.14–16 Furthermore, PLGA can be extensively modified by various modalities that can render it more hydrophilic and enhance its biocompatibility.17 "
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    ABSTRACT: Aims To demonstrate the potential use of in vitro poly(lactic-co-glycolic acid) (PLGA) microparticles in comparison with triamcinolone suspension to aid visualisation of vitreous during anterior and posterior vitrectomy. Methods PLGA microparticles (diameter 10–60 μm) were fabricated using single and/or double emulsion technique(s) and used untreated or following the surface adsorption of a protein (transglutaminase). Particle size, shape, morphology and surface topography were assessed using scanning electron microscopy (SEM) and compared with a standard triamcinolone suspension. The efficacy of these microparticles to enhance visualisation of vitreous against the triamcinolone suspension was assessed using an in vitro set-up exploiting porcine vitreous. Results Unmodified PLGA microparticles failed to adequately adhere to porcine vitreous and were readily washed out by irrigation. In contrast, modified transglutaminase-coated PLGA microparticles demonstrated a significant improvement in adhesiveness and were comparable to a triamcinolone suspension in their ability to enhance the visualisation of vitreous. This adhesive behaviour also demonstrated selectivity by not binding to the corneal endothelium. Conclusion The use of transglutaminase-modified biodegradable PLGA microparticles represents a novel method of visualising vitreous and aiding vitrectomy. This method may provide a distinct alternative for the visualisation of vitreous whilst eliminating the pharmacological effects of triamcinolone acetonide suspension.
    The British journal of ophthalmology 05/2010; 94(5):648-53. DOI:10.1136/bjo.2009.163642 · 2.98 Impact Factor
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