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Sample records for acetonide intravitreal implant

  1. Mathematical modeling of triamcinolone acetonide drug release from the I-vation intravitreal implant (a controlled release platform).

    PubMed

    Barnett, Peter J

    2009-01-01

    In-vitro drug release of triamcinolone acetonide from the I-vation implant can be controlled and tuned by varying its formulation ingredients. These release characteristics can be modeled using a parabolic partial differential equation to describe one dimensional Fickian drug diffusion in a durable polymer matrix.

  2. Clinical utility of intravitreal fluocinolone acetonide (Iluvien®) implant in the management of patients with chronic diabetic macular edema: a review of the current literature

    PubMed Central

    Saedon, Habiba; Anand, Astha; Yang, Yit C

    2017-01-01

    The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 μg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients. PMID:28392675

  3. Efficacy and safety of sustained-delivery fluocinolone acetonide intravitreal implant in patients with chronic diabetic macular edema insufficiently responsive to available therapies: a real-life study

    PubMed Central

    Massin, Pascale; Erginay, Ali; Dupas, Bénédicte; Couturier, Aude; Tadayoni, Ramin

    2016-01-01

    Purpose To evaluate the efficacy and safety of sustained-delivery fluocinolone acetonide (FAc) intravitreal implant for diabetic macular edema (DME). Patients and methods Prospective study in patients with DME insufficiently responsive to laser and anti-vascular endothelial growth factor (anti-VEGF). Patients with history of rise of intraocular pressure after intravitreal corticosteroids were excluded. Results The macular edema rapidly decreased both in group 1 (prior laser only; n=7 eyes) and group 2 (prior laser and ≥3 monthly anti-VEGF therapy; n=10 eyes) and central subfield thickness was reduced by −299 μm (P=0.008) and −251 μm (P=0.016) at 12 months, respectively. Mean area under the curve from baseline to last value for pseudophakic eyes was +4.2 letters in group 1 and +9.5 letters in group 2. Overall, the FAc implant was well tolerated. Conclusion This prospective study confirms the efficacy of the FAc implant in DME patients insufficiently responsive to laser and anti-VEGF. Moreover, with a careful patient selection, our safety results would support an earlier use of FAc in the DME treatment pathway. PMID:27468222

  4. Long-term outcomes of phakic patients with diabetic macular oedema treated with intravitreal fluocinolone acetonide (FAc) implants

    PubMed Central

    Yang, Y; Bailey, C; Holz, F G; Eter, N; Weber, M; Baker, C; Kiss, S; Menchini, U; Ruiz Moreno, J M; Dugel, P; Lotery, A

    2015-01-01

    Purpose Diabetic macular oedema (DMO) is a leading cause of blindness in working-age adults. Slow-release, nonbioerodible fluocinolone acetonide (FAc) implants have shown efficacy in the treatment of DMO; however, the National Institute for Health and Care Excellence recommends that FAc should be used in patients with chronic DMO considered insufficiently responsive to other available therapies only if the eye to be treated is pseudophakic. The goal of this analysis was to examine treatment outcomes in phakic patients who received 0.2 μg/day FAc implant. Methods This analysis of the phase 3 FAME (Fluocinolone Acetonide in Diabetic Macular Edema) data examines the safety and efficacy of FAc implants in patients who underwent cataract extraction before (cataract before implant (CBI) group) or after (cataract after implant (CAI) group) receiving the implant. The data were further examined by DMO duration. Results Best corrected visual acuity (BCVA) after 36 months was comparable in the CAI and CBI groups. Both the percentage of patients gaining ≥3 lines of vision and mean change in BCVA letter score were numerically greater in the CAI group. In addition, most patients who underwent cataract surgery experienced a net gain in BCVA from presurgery baseline as well as from original study baseline. Conclusions These data support the use of 0.2 μg/day FAc implants in phakic as well as in pseudophakic patients. These findings will serve as a pilot for design of future studies to evaluate the potential protective effect of FAc implants before cataract surgery in patients with DMO and cataract. PMID:26113503

  5. Visualization of residual perfluorocarbon liquid using intravitreal triamcinolone acetonide.

    PubMed

    Hirata, Fumisato; Tamura, Hironori; Ogura, Yuichiro

    2005-01-01

    The visualization of transparent perfluorocarbon liquid (PFCL) using triamcinolone acetonide is described. Intravitreal injection of triamcinolone acetonide enabled visualization of residual PFCL intraoperatively. In addition, it was shown that triamcinolone acetonide could visualize PFCL in an in vitro preparation of balanced salt solution. This in vitro experiment confirmed that triamcinolone acetonide also could be adsorbed by PFCL outside the vitreous. Triamcinolone acetonide was helpful to visualize transparent PFCL both in vivo and in vitro, and may be useful at the end of vitrectomy to completely remove residual PFCL from the eye.

  6. Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema

    PubMed Central

    Spandau, U H M; Derse, M; Schmitz-Valckenberg, P; Papoulis, C; Jonas, J B

    2005-01-01

    Aim: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. Methods: The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3–12 months). Main outcome measures were visual acuity and intraocular pressure. Results: Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). Conclusions: In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used. PMID:16024853

  7. Epiretinal deposit of triamcinolone acetonide at the posterior pole after intravitreal injection.

    PubMed

    Jaissle, Gesine B; Szurman, Peter; Völker, Michael; Bartz-Schmidt, Karl Ulrich

    2007-01-01

    The authors investigated possible toxic side effects of epiretinal triamcinolone acetonide deposits at the posterior pole after an intravitreal injection in both a vitrectomized and a non-vitrectomized eye. The vitrectomized eye developed massive epiretinal triamcinolone acetonide deposits at the posterior pole that were less pronounced in the non-vitrectomized eye. After resolution of the deposits, no morphologic signs of retinal toxicity were apparent. Mild scattered visual field defects did not correlate with the localization of the triamcinolone acetonide deposits. However, because recent in vitro studies indicate potential cytotoxicity, patients should be instructed to keep their heads in an upright position after intravitreal triamcinolone acetonide injection to avoid deposits at the posterior pole.

  8. Efficacy of reduced dose of intravitreal triamcinolone acetonide in a case of active serpiginous choroiditis

    PubMed Central

    Ghose, Avirupa; Bhende, Promod S; Biswas, Jyotirmoy

    2016-01-01

    Active serpiginous choroiditis (SC) is a vision-threatening condition which requires intensive treatment using corticosteroids and/or immunosuppressives, especially if the lesions are involving or encroaching on the macula. Use of oral and intravenous high-dose steroids are contraindicated in uncontrolled diabetics. Intravitreal steroid delivers a localized dose in such situations. This case report highlights the efficacy of reduced dose of intravitreal triamcinolone acetonide (2 mg) in the treatment of active SC. PMID:27853021

  9. Fluocinolone acetonide intravitreal sustained release device – a new addition to the armamentarium of uveitic management

    PubMed Central

    Brumm, Matthew V; Nguyen, Quan Dong

    2007-01-01

    Uveitis is a potentially sight-threatening inflammatory eye disease caused by multiple infectious and non-infectious etiologies for which the standard of care involves corticosteroids or various immunomodulary therapy (IMT) drugs. These available treatments, although effective, may cause significant morbidity and sometimes mortality in uveitis patients due to their toxic side-effects and the necessity of long-term therapy to prevent recurrences. In order to avoid the systemic toxicity of corticosteroids and IMT or the repeated injections of local steroids necessary to control ocular inflammation, and to prevent development of cumulative damage resulting from recurrent episodes of inflammation, researchers have developed a number of local corticosteroid sustained-release devices that can be implanted directly into the vitreous of the eye, at the site of the inflammatory disease. Preliminary studies of such a device, the fluocinolone acetonide (Retisert™) implant, have shown significant reductions in the number of inflammatory episodes and decreased reliance on systemic corticosteroids or other IMT. This review explores the current research evaluating the fluocinolone sustained-release intravitreal implant in the treatment of posterior uveitis and the implications for its future use on a wider scale. PMID:17722513

  10. Pharmacokinetics and retinal toxicity of various doses of intravitreal triamcinolone acetonide in rabbits

    PubMed Central

    Ye, You-Fan; Gao, Yong-Feng; Xie, Hua-Tao

    2014-01-01

    Purpose To compare the pharmacokinetics and retinal toxicity of various doses of intravitreal triamcinolone acetonide (TA) in rabbits. Methods The rabbits received intravitreal injections of 4 mg and 8 mg TA. The drug concentrations were determined with high-performance liquid chromatography after extraction from the vitreous at various time points. The main pharmacokinetics parameters were calculated with 3p97 pharmacokinetics software. The intraocular pressure, electroretinography, and pathological examinations were evaluated before and after intravitreal injection of different doses of TA. Results The half-life of intravitreal injection of 4 mg and 8 mg TA was 24 days and 34 days, respectively. No significant differences were found in intraocular pressure (p>0.05) and the electroretinography b-wave amplitudes (p>0.05) among the rabbits before and after intravitreal injection of 4 mg and 8 mg TA. Light and electron microscopy did not show any retinal damage in any group. Conclusions Intravitreal injection of 4 mg and 8 mg TA are safe for the rabbit retina. The injection of 8 mg TA produced a longer vitreous half-life and had a prolonged effect on the retina. This conclusion may be referenced in the clinical application of TA in retinal diseases. PMID:24868137

  11. Intravitreal Dexamethasone Implant (Ozurdex) in Coats’ Disease

    PubMed Central

    Saatci, Ali Osman; Doruk, Hasan Can; Yaman, Aylin

    2013-01-01

    We injected an intravitreal dexamethasone implant in two eyes of 2 pediatric patients with Coats’ disease in addition to other treatment modalities, such as intravitreal ranibizumab injection and indirect laser photocoagulation. In both eyes, intraocular pressure moderately rose in a temporary fashion. The dexamethasone implant seems to be a valuable addition to the armamentarium of treatment options for Coats’ disease as it necessitates fewer injections than anti-VEGF injections and thereby fewer sessions of general anesthesia in the pediatric population. PMID:24163679

  12. Removal of benzyl alcohol from a commercially available triamcinolone acetonide suspension for intravitreal use.

    PubMed

    Hernaez-Ortega, Maria C; Soto-Pedre, Enrique

    2006-01-01

    Purification of commercially available formulations of triamcinolone acetonide is important to avoid potential toxic effects of the vehicle for intravitreal use. In 2004, a simple and rapid method to remove most of the vehicle with a centrifuge was reported. The aim of this article is to study the degree to which benzyl alcohol can be eliminated with this method. By means of a gas chromatographic procedure, it has been proven that centrifugation is suitable for removing most benzyl alcohol (ie, up to 95.5% at 10,000 rpm, 5 minutes), and it is better at modifying the concentration of the drug than other proposed methods (ie, decantation, filtering methods, or both).

  13. Intravitreal Dexamethasone Implant (Ozurdex) for Refractory Macular Edema Secondary to Retinitis Pigmentosa

    PubMed Central

    Örnek, Nurgül; Örnek, Kemal; Erbahçeci, İnci Elif

    2016-01-01

    Macular edema (ME) in retinitis pigmentosa (RP) often impairs central vision dramatically. A 41-year-old woman diagnosed with RP was referred to our outpatient clinic due to severe visual deterioration in both eyes. The patient was treated with topical carbonic anhydrase inhibitors, topical corticosteroids and intravitreal triamcinolone acetonide injections, but her ME recurred. Intravitreal 0.7 mg dexamethasone implant (Ozurdex, Allergan) was administered into both eyes without complications. On the fourth day after both injections, visual acuity improved and ME almost totally resolved. No recurrence was observed at follow-up six months later. PMID:28058154

  14. Determination of triamcinolone acetonide in silicone oil and aqueous humor of vitrectomized rabbits' eyes: Application for a pharmacokinetic study with intravitreal triamcinolone acetonide injections (Kenalog® 40).

    PubMed

    Fernandes-Cunha, Gabriella M; Saliba, Juliana B; Siqueira, Rubens C; Jorge, Rodrigo; Silva-Cunha, Armando

    2014-02-01

    A simple and accurate method including liquid-liquid extraction and protein precipitation procedures from silicone oil and aqueous humor samples followed by high-performance liquid chromatography (HPLC-UV) was developed and validated to determine the pharmacokinetic profile of triamcinolone acetonide in silicone oil and aqueous humor of rabbits' eyes submitted to the pars plana vitrectomy surgery. The method was successfully applied to quantify the drug remaining in silicone oil and aqueous humor (LOQ range of 1μg/mL). The triamcinolone acetonide remained in silicone oil and aqueous humor of vitrectomized rabbits' eyes for four weeks after the intravitreal injections.

  15. Evaluation of triamcinolone acetonide following intravitreal injection in New Zealand white rabbits.

    PubMed

    McGee, David H; Dembinska, Olga; Gruebbel, Margarita M

    2005-01-01

    The safety of intravitreally injected triamcinolone acetonide suspension (TA) was evaluated in rabbits. Each animal received 0.1 ml (1) balanced salt solution (BSS) vehicle, (2) formulation vehicle, (3) 4% TA (4-mg dose), (4) 16% TrAc (16-mg dose) or (5) 25% TA (25-mg dose) as a single intravitreal injection into the right eye. The left eyes served as untreated controls. All animals were observed for 1 month following treatment. In-life evaluations included clinical signs, body weights, slit-lamp biomicroscopic and indirect ophthalmoscopic examinations, intraocular pressure and corneal thickness measurements, and electroretinograms (ERGs). Ocular tissues were harvested following a 1-month post-treatment observation period, fixed, processed, and evaluated by light microscopy. No significant or treatment-related clinical signs were observed for any animals during the study. The opaque white test article was clearly visible in the eye for all TrAc-treated groups, and remained so throughout the study. No statistically significant differences in mean body weights were present between the control and treatment groups, though changes in body weight varied. Corneal thickness was slightly reduced for some treated groups. Intraocular pressures were not statistically significantly different from controls for any treatment group. No significant changes in ERG were evident between treatment groups or from baseline readings. Microscopically, basophilic material (presumed to be drug) was seen in the vitreous of all or most treated eyes, with accumulations in the vitreous or in clumps adjacent to the retinal surface. No pathological changes were observed in the retina or other ocular structures. Triamcinolone acetonide suspension was safe and well tolerated following intravitreal injection in New Zealand white rabbits.

  16. In vitro benzyl alcohol cytotoxicity: implications for intravitreal use of triamcinolone acetonide.

    PubMed

    Chang, Yi-Sheng; Wu, Chao-Liang; Tseng, Sung-Huei; Kuo, Pao-Ying; Tseng, Shih-Ya

    2008-06-01

    The aim of the study was to investigate the toxicity of benzyl alcohol (BA), the preservative in commercial triamcinolone acetonide (TA) suspensions, on retinal pigment epithelial (RPE) cells. Cultured RPE cells from a human cell line (ARPE-19) and from rabbits were exposed to the balanced salt solution (control) or BA (0.0225, 0.225, 0.9, 3 or 9mg/mL) for 5, 30, 60, or 120min. Morphological changes of RPE cells were evaluated by the trypan blue in situ staining. The proportions of dead cells were quantitatively measured by the trypan blue exclusion assay, and those of functional cells were assessed by a mitochondrial dehydrogenase assay. The mechanism of cytotoxicity was determined by the acridine orange/ethidium bromide staining and DNA laddering technique. Furthermore, ultrastructural changes were observed by transmission electron microscopy. The results showed that RPE cell damage was dose- and time-dependent. BA 0.225mg/mL, the clinically relevant concentration in TA following intravitreal injection, caused ultrastructural damage and impaired human RPE cell function at 2h; but BA 0.0225mg/mL did not. BA 9.0mg/mL, the concentration in commercial TA suspensions, was toxic within 5min on each assay for both human and rabbit RPE cells. The major mechanism of cell death was necrosis. In conclusion, BA in commercial TA suspensions injected intravitreally (0.225-9mg/mL) can damage RPE cells. Our in vitro study on benzyl alcohol cytotoxicity has significant clinical implications for intravitreal use of TA. We suggest that, before a commercial TA solution is used intravitreally, the vehicle should be removed to prevent damaging the RPE layer, particularly during macular hole surgery. Commercial development of a preservative-free TA suspension for intraocular use is urged.

  17. Ocular Pharmacokinetics of Fluocinolone Acetonide Following Iluvien Implantation in the Vitreous Humor of Rabbits

    PubMed Central

    Kane, Frances E.

    2015-01-01

    Abstract Purpose: The purpose of this study was to evaluate the systemic and ocular pharmacokinetics (PK) of fluocinolone acetonide (FAc) following administration of Iluvien® intravitreal implants. Methods: The FAc intravitreal implant was administered to rabbits in 3 doses (0.2, 0.5, and 1.0 μg/day). The concentration of FAc was measured by a validated liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method in plasma and ocular tissues at various time points through month 24. Results: Following administration of the 0.2 μg/day implant, FAc levels peaked in most tissues at day 2 or 8, reached approximate steady state levels by month 3 and very gradually decreased over the duration of the study. The FAc level in the aqueous humor was not measurable at most time points in the rabbit. FAc was still present in most ocular tissues at 2 years. The 0.5 and 1.0 μg/day dose groups followed the same pattern through month 9. The elimination half lives in the tissues for which it was measurable were greater than 83 days. Exposure to FAc was highest in the choroid/retinal pigment epithelium for all doses, followed by lens and retina. Conclusions: The results of this study demonstrate sustained delivery of FAc from the Iluvien intravitreal implant in the ocular tissue of rabbits. Retina and lens FAc levels with the Iluvien implant were approximately 1/10 those reported with the Retisert® implant. FAc levels in the aqueous were not measureable with Iluvien where they were measured for 12 months with Retisert. PMID:25562126

  18. Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

    PubMed

    Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

    2011-02-01

    Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution

  19. Report of 12-months efficacy and safety of intravitreal fluocinolone acetonide implant for the treatment of chronic diabetic macular oedema: a real-world result in the United Kingdom.

    PubMed

    Alfaqawi, F; Lip, P L; Elsherbiny, S; Chavan, R; Mitra, A; Mushtaq, B

    2017-04-01

    PurposeTo report the 12-months visual and anatomical outcomes of chronic diabetic macular oedema (DMO) treated with ILUVIEN in a real-world clinical practice in a single tertiary referral centre.MethodRetrospective data collection and analysis of consecutive 28 eyes of 23 diabetic patients received ILUVIEN implant for refractory DMO. Standard assessment included visual acuity (VA), central retinal thickness (CRT), slit-lamp biomicroscopy, and Goldmann tonometry for intraocular pressure (IOP) at 1, 6, and 12 months.ResultsBaseline mean VA was 47 (SD 18) letters improved to 55 (SD 17) letters (P=0.004) at 12 months. VA was improved in 16 eyes (57%), stabilised in 9 eyes (32%), and decreased in 3 eyes (11%). Seven eyes (25%) gained ≥15 letters, and 10 eyes (36%) gained >10 letters from baseline. The percentage of eyes achieved driving vision (≥70 Early Treatment Diabetic Retinopathy Study letters) was doubled from baseline 18 to 36% at 6 months and 32% at 12 months. Mean CRT decreased by 198 μm from baseline 494 μm (SD 191) to 296 μm (SD 121) at 12 months (P<0.001). Two eyes received additional anti-vascular endothelial growth factor injections after 10 months.

  20. Comparison of In Vivo Gene Expression Profiling of RPE/Choroid following Intravitreal Injection of Dexamethasone and Triamcinolone Acetonide

    PubMed Central

    Smit-McBride, Zeljka; Moisseiev, Elad; Modjtahedi, Sara P.; Telander, David G.; Hjelmeland, Leonard M.; Morse, Lawrence S.

    2016-01-01

    Purpose. To identify retinal pigment epithelium (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. Methods. Differential gene expression of over 34,000 well-characterized mouse genes in the RPE/choroid of 6-week-old C57BL/6J mice was analyzed after intravitreal steroid injections at 1 week and 1 month postinjection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpring GX 12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. Results. Both triamcinolone and dexamethasone caused differential activation of genes involved in “Circadian Rhythm Signaling” pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in “Calcium Signaling” (1 week) and “Glutamate Receptor Signaling” pathways (1 month). In contrast, dexamethasone (Dex) affected the “GABA Receptor Signaling” (1 week) and “Serotonin Receptor Signaling” (1 month) pathways. Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. Conclusions. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. PMID:27429799

  1. A simple and rapid method for purification of triamcinolone acetonide suspension for intravitreal injection.

    PubMed

    Hernaez-Ortega, Maria C; Soto-Pedre, Enrique

    2004-01-01

    Purification of triamcinolone acetonide suspension is important to avoid the potential toxic effects of the vehicle. The aim of this article is to describe a simple and rapid technique to remove the vehicle, instead of the long procedure described in the literature. Triamcinolone acetonide suspension was sedimented by density gradient centrifugation. In a few minutes, this new technique yielded a clear supernatant that was easily replaced by a nontoxic sterile solution. More prolonged procedures may not be convenient for unplanned treatments and may also contribute to a greater chance for contamination of the triamcinolone acetonide suspension.

  2. Dexamethasone intravitreal implant in the treatment of diabetic macular edema

    PubMed Central

    Dugel, Pravin U; Bandello, Francesco; Loewenstein, Anat

    2015-01-01

    Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reaction, and is characterized by blood–retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for ≤6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intravitreal implant (0.35 mg and 0.7 mg) administered at ≥6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a ≥15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effective in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation ≥25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (<2

  3. Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant

    PubMed Central

    Myung, Jane S; Aaker, Grant D; Kiss, Szilárd

    2010-01-01

    Purpose To report our experience with dexamethasone 0.7 mg sustained-release intravitreal implant (Ozurdex®; Allergan, Inc, Irvine, CA) in noninfectious posterior uveitis. Methods A retrospective chart review of patients with noninfectious uveitis treated with sustained-release dexamethasone 0.7 mg intravitreal implant was performed. Complete ophthalmic examination including signs of inflammatory activity, visual acuity, fundus photography, fluorescein angiography, optical coherence tomography, and tolerability of the implant were assessed. Results Six eyes of 4 consecutive patients treated with a total of 8 dexamethasone 0.7 mg sustained-release intravitreal implants for posterior noninfectious uveitis were included. Two patients presented with unilateral idiopathic posterior uveitis; 2 patients had bilateral posterior uveitis, one secondary to sarcoidosis and the other to Vogt-Koyanagi-Harada syndrome. All eyes showed clinical and angiographic evidence of decreased inflammation following implant placement. Mean follow-up time post-injection was 5.25 months. Four eyes received 1 and 2 eyes received 2 Ozurdex implants during the follow-up period. The duration of effect of the implant was 3 to 4 months. No serious ocular or systemic adverse events were noted during the follow-up period. Conclusions In patients with noninfectious posterior uveitis, sustained-release dexamethasone 0.7 mg intravitreal implant may be an effective treatment option for controlling intraocular inflammation. PMID:21188153

  4. Bilateral Severe Sterile Inflammation with Hypopyon after Simultaneous Intravitreal Triamcinolone Acetonide and Aflibercept Injection in a Patient with Bilateral Marked Rubeosis Associated with Ocular Ischemic Syndrome

    PubMed Central

    Durmaz Engin, Ceren; Ayhan, Ziya; Men, Süleyman

    2017-01-01

    We report the clinical course of a diabetic patient with bilateral cataract and rubeosis in association with ocular ischemic syndrome and initially treated him with simultaneous intravitreal 2 mg aflibercept and 2 mg triamcinolone acetonide injection at the same setting prior to planned cataract surgery and further photocoagulation. However, sterile anterior segment inflammation characterized by hypopyon occurred four days apart in OU. Right eye developed the sterile inflammation at the third postinjection day and the left eye developed the sterile inflammation at the seventh postinjection day (two days after the uneventful cataract surgery with intraocular lens implantation) without any pain or significant redness. Vitreous biopsy taken during the right phacovitrectomy was negative for any microbial contamination. Both eyes were treated successfully with intensive topical prednisolone acetate with a relatively good visual outcome. It is likely that underlying ocular ischemic syndrome might have facilitated the formation of sterile inflammation as blood-aqueous barrier disruption and flare have already been present. PMID:28386497

  5. Surgical management of fibrotic encapsulation of the fluocinolone acetonide implant in CAPN5-associated proliferative vitreoretinopathy

    PubMed Central

    Tlucek, Paul S; Folk, James C; Sobol, Warren M; Mahajan, Vinit B

    2013-01-01

    Objective To review fibrosis of fluocinolone acetonide (FA) implants in subjects with CAPN5 autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV). Methods A retrospective case series was assembled from ADNIV patients in which there was fibrotic encapsulation of a fluocinolone acetonide implant. CAPN5 genotypes and surgical repair techniques were reviewed. Results Two eyes of two ADNIV patients developed a fibrotic capsule over the fluocinolone acetonide implant. Both patients had Stage IV disease. Patient A had a c.731T > C mutation in the CAPN5 gene and patient B had a c.728G > T mutation. The fibrotic membrane was surgically excised and the implant function was restored. Conclusion The exuberant fibrotic response in later stages of ADNIV may be resistant to local immunosuppression with steroids. Surgical excision of fibrotic membranes over FA implants can reestablish local steroid delivery in cases of severe proliferative vitreoretinopathy. PMID:23785231

  6. Role of implants in the treatment of diabetic macular edema: focus on the dexamethasone intravitreal implant

    PubMed Central

    Cebeci, Zafer; Kir, Nur

    2015-01-01

    Diabetic macular edema (DME) is the leading cause of sight-threatening complication in diabetic patients, and several treatment modalities have been developed and evaluated to treat this pathology. Intravitreal agents, such as anti-vascular endothelial growth factors (anti-VEGF) or corticosteroids, have become more popular in recent years and are widely used for treating DME. Sustained release drugs appear to be mentioned more often nowadays for extending the period of intravitreal activity, and corticosteroids play a key role in inhibiting the inflammatory process in DME. A potent corticosteroid, dexamethasone (Ozurdex®), in the form of an intravitreal implant, has been approved for various ocular etiologies among which DME is also one. This review evaluates the role of implants in the treatment of DME, mainly focusing on the dexamethasone intravitreal implant. PMID:26604809

  7. Distribution of Triamcinolone Acetonide after Intravitreal Injection into Silicone Oil-Filled Eye.

    PubMed

    Da, Ma; Li, Kenneth K W; Chan, Kevin C; Wu, Ed X; Wong, David S H

    2016-01-01

    There is increasing use of the vitreous cavity as a reservoir for drug delivery. We study the intraocular migration and distribution of triamcinolone acetonide (TA) after injection into silicone oil tamponade agent during and after vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo assessment, intraocular migration of TA was imaged using real-time FLASH MRI scans and high-resolution T2W imaging and the in vitro model was monitored continuously with a video camera. Results of the ex vivo experiment showed that the TA droplet sank to the interface of silicone oil and aqueous almost immediately after injection and remained inside the silicone oil bubble for as long as 16 minutes. The in vitro results showed that, after the shrinkage of the droplet, TA gradually precipitated leaving only a lump of whitish crystalline residue inside the droplet for about 100 minutes. TA then quickly broke the interface and dispersed into the underlying aqueous within 15 seconds, which may result in a momentary increase of local TA concentration in the aqueous portion and potentially toxic to the retina. Our study suggests that silicone oil may not be a good candidate as a drug reservoir for drugs like TA.

  8. Distribution of Triamcinolone Acetonide after Intravitreal Injection into Silicone Oil-Filled Eye

    PubMed Central

    Wu, Ed X.; Wong, David S. H.

    2016-01-01

    There is increasing use of the vitreous cavity as a reservoir for drug delivery. We study the intraocular migration and distribution of triamcinolone acetonide (TA) after injection into silicone oil tamponade agent during and after vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo assessment, intraocular migration of TA was imaged using real-time FLASH MRI scans and high-resolution T2W imaging and the in vitro model was monitored continuously with a video camera. Results of the ex vivo experiment showed that the TA droplet sank to the interface of silicone oil and aqueous almost immediately after injection and remained inside the silicone oil bubble for as long as 16 minutes. The in vitro results showed that, after the shrinkage of the droplet, TA gradually precipitated leaving only a lump of whitish crystalline residue inside the droplet for about 100 minutes. TA then quickly broke the interface and dispersed into the underlying aqueous within 15 seconds, which may result in a momentary increase of local TA concentration in the aqueous portion and potentially toxic to the retina. Our study suggests that silicone oil may not be a good candidate as a drug reservoir for drugs like TA. PMID:27493959

  9. Evaluation of different preparation methods for a preservative free triamcinolone acetonide preparation for intravitreal administration: a validated stability indicating HPLC-method.

    PubMed

    Korodi, T; Lachmann, B; Kopelent-Frank, H

    2010-12-01

    Intravitreally applied triamcinolone acetonide (TA) is used to treat a variety of macular diseases. Commercially available products of TA are mainly intended for intramuscular application and contain benzyl alcohol (BA) as a bacteriostatic preservative. Since this agent damages ocular tissues, different methods such as filtration techniques and centrifugation are usually used to eliminate BA from commercial products (40 mg/mL TA, 9.9 mg/mL BA). In this study, we evaluated these methods in regard to their ability to eliminate benzyl alcohol and to guarantee standard doses of triamcinolone acetonide. A new formulation without BA (TA 40 mg/mL) was developped according to the following criteria: autoclavability, stability, and suitability for intravitreal use. For QA/QC evaluation a new rapid and simple HPLC procedure (C18 RP column, mobile phase consisting of methanol-water, 48:52, v/v) to quantify the respective compounds was developed and validated according to ICH guidelines. The HPLC method was proven to be selective, linear, precise and accurate. Analysis of preparations based on commercial products undergoing different filtration techniques showed variable results: TA concentrations of 22-80% of the declared amount were found, and BA content was not reduced to safe levels (up to 39% of initial content remained). Centrifugation methods decreased the concentration of the preservative adequately, however agglomerated TA crystals were observed, leading to irreproducible and deviating particle sizes that are potentially harmful with ocular use. The newly developed preservative free formulation (TA 40 mg/mL) delivered uniform doses of TA, revealed no drug loss during forced light exposure and was proven to be stable, sterile and bacterial endotoxin free after autoclaving and after storage for three months,. The new formulation may offer an alternative for the in-house production of intravitreally applicable TA preparations in hospital pharmacies and should enhance

  10. Controlled release of triamcinolone acetonide from polyurethane implantable devices: application for inhibition of inflammatory-angiogenesis.

    PubMed

    Pinto, Flávia Carmo Horta; Da Silva-Cunha Junior, Armando; Oréfice, Rodrigo Lambert; Ayres, Eliane; Andrade, Silvia Passos; Lima, Luiza Dias C; Moura, Sandra A Lima; Da Silva, Gisele Rodrigues

    2012-06-01

    The purpose of this study was to develop triamcinolone acetonide-loaded polyurethane implants (TA PU implants) for the local treatment of different pathologies including arthritis, ocular and neuroinflammatory disorders. The TA PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo release of TA from the PU implants was evaluated. The efficacy of TA PU implants in suppressing inflammatory-angiogenesis in a murine sponge model was demonstrated. FTIR results revealed no chemical interactions between polymer and drug. SAXS results indicated that the incorporation of the drug did not disturb the polymer morphology. WAXS showed that the crystalline nature of the TA was preserved after incorporation into the PU. The TA released from the PU implants efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an experimental animal model. Finally, TA PU implants could be used as local drug delivery systems because of their controlled delivery of TA.

  11. Perspective on the role of Ozurdex (dexamethasone intravitreal implant) in the management of diabetic macular oedema

    PubMed Central

    Mehta, Hemal; Gillies, Mark

    2015-01-01

    Diabetic macular oedema (DMO) is the most common cause of visual loss in the working age population. Intravitreal therapy has superseded macular laser as the first-line treatment for the management of centre-involving DMO in most patients. As well as the proven efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, phase II and III clinical trials of Ozurdex intravitreal dexamethasone implants for DMO have also demonstrated a mean increase in visual acuity and corresponding mean reduction in central macular thickness, particularly in pseudophakic eyes. Because of the risk of visual loss from cataract, glaucoma and intraocular infection with the use of intravitreal steroids, Ozurdex tends to be reserved for use in patients unresponsive to anti-VEGF therapy for centre-involving DMO. Situations where Ozurdex may be considered a first-line treatment option for eyes with centre-involving DMO include pseudophakia, impending cataract surgery, or in the context of a recent arterial thromboembolic event. Because of their stable pharmacokinetics, Ozurdex slow-release implants may also be considered in vitrectomized eyes. PMID:26336592

  12. A novel design of one-side coated biodegradable intrascleral implant for the sustained release of triamcinolone acetonide.

    PubMed

    Kim, Yu-Mi; Lim, Jeong-Ok; Kim, Hong-Kyun; Kim, Si-Yeol; Shin, Jae-Pil

    2008-09-01

    The purpose of this study was to evaluate the efficacy and safety of biodegradable intrascleral implants for the slow release of triamcinolone acetonide (TA). Intrascleral implant (1 mm thick; 3 mm diameter) was made of PLA (poly(D,L-lactide)) containing 6.4 mg of TA with one-side coating of high molecular weight PLA to render unidirectional drug absorption through the sclera. In vitro TA release was evaluated by liquid chromatography-mass spectroscopy for 90 days. In vivo release of TA was measured in aqueous humor, vitreous, and retina-choroid at 1, 2, 4, 8, and 12 weeks after intrascleral implantation in 20 rabbit eyes. Implant toxicity and biocompatibility were evaluated by slit lamp examinations, indirect ophthalmoscopy, intraocular pressure measurements, electroretinography, and histological examinations. In vitro studies demonstrated that the implants released TA in a controlled manner over 90 days. In vivo, TA was detected in aqueous humor until 4 weeks and in retina-choroid until 8 weeks after implantation, but was detected constantly over 12 weeks in vitreous. No significant retinal toxicity was observed. These results suggest that the devised intrascleral implant offers a promising controlled release system for the delivery of TA to the posterior segment of the eye.

  13. Simultaneous Therapy with Intravitreal Dexamethasone Implant and Bevacizumab for the Treatment of Macular Edema

    PubMed Central

    de ANDRADE, Felipe L.; LOPES, Flavio S.; de ANDRADE, Gabriel C.; PRATA, Tiago S.; MAIA, André

    2016-01-01

    To investigate the safety profile and benefits of a short-term simultaneous treatment regimen combining two drugs—an intravitreal implant of dexamethasone with an intravitreal injection of bevacizumab—in patients with macular edema. This was a retrospective, non-randomized, open-label case series study. Patients were treated between April 2014 and July 2015 and were diagnosed with recurrent macular edema secondary to diabetic retinopathy and retinal vein occlusion. They underwent simultaneous treatment with an intravitreal injection of bevacizumab (1.25 mg) and an intravitreal implant of dexamethasone (0.7 mg). Patients were evaluated at baseline and at each subsequent visit with a complete ophthalmological examination and spectral-domain optical coherence tomography (OCT) scans. They were examined 24 hours after the treatment, and then followed up after 30 days and 60 days. Twenty patients (representing 20 eyes) were included in the study. At the time of injection (i.e., baseline), the best-corrected visual acuity (BCVA) was 0.758 ± 0.42 logarithm of the minimum angle of resolution (logMAR). It improved significantly to 0.51 ± 0.33 logMAR at 1 month and to 0.5 ± 0.34 logMAR at 2 months (P ≤ 0.03). The median baseline central macular thickness (CMT) was 542 µm (interquartile range, 466 – 751 µm). The median CMT decreased significantly to 321 µm (interquartile range, 288–381 µm) at 1 month and 310 µm (interquartile range, 286 – 354 µm) at 2 months (P ≤ 0.0002). The mean intraocular pressure (IOP) increased from 14.9 ± 2.29 mmHg (at baseline) to 16.5 ± 2.99 mmHg (P = 0.04) after 2 months. Two (10%) eyes showed cataract progression. There were no other ocular or systemic complications for the duration of this study. Simultaneous therapy combining a dexamethasone implant plus bevacizumab for macular edema may be an attractive treatment regimen with an acceptable safety profile. PMID:28289686

  14. Dexamethasone Intravitreal Implant Rescue Treatment for Bevacizumab Refractory Macular Edema Secondary to Branch Retinal Vein Occlusion

    PubMed Central

    Lee, Kyou Ho; Kang, Eui Chun

    2017-01-01

    Purpose To evaluate the prognostic factors and outcomes of dexamethasone intravitreal implant (DEX implant) for intravitreal bevacizumab refractory macular edema secondary to branch retinal vein occlusion (BRVO). Methods This was a retrospective, interventional case series. Medical records were reviewed, and a total of 38 eyes that were treated with DEX implant for macular edema secondary to BRVO that did not respond to at least two consecutive intravitreal bevacizumab injections (IBIs) were included. Best-corrected visual acuity (BCVA), central subfield macular thickness, and central subfoveal choroidal thickness were evaluated at baseline, 2 months, and 6 months after DEX implantation. Results Patients had undergone an average of 6.32 ± 4.66 prior IBI treatments. The average BCVA improved from 0.53 ± 0.26 to 0.41 ± 0.25 and 0.44 ± 0.23 logarithm of the minimal angle of resolution (logMAR) at 2 and 6 months, respectively (p < 0.001). The average central subfield macular thickness was 504.00 ± 121.54 µm at baseline and changed to 293.21 ± 74.17 µm and 427.28 ± 119.57 µm at 2 and 6 months, respectively (p < 0.001 and p = 0.002). Average central subfoveal choroidal thickness was 237.46 ± 92.21 µm at baseline and changed to 204.75 ± 74.74 µm and 226.86 ± 90.77 µm at 2 and 6 months, respectively (p < 0.001 and p = 0.455). Twenty-two eyes (58%) gained ≥0.1 logMAR at 2 months, while 16 eyes showed no improvement. Low BCVA at symptom presentation, low baseline BCVA, and shorter duration of macular edema were correlated with increased BCVA after treatment. Conclusions The DEX implant improves functional and anatomical outcomes for up to 6 months in about half of the patients treated with IBI refractory macular edema secondary to BRVO, particularly in patients with low initial and baseline BCVA. PMID:28367038

  15. Thermoanalytical characterization of clindamycin-loaded intravitreal implants prepared by hot melt extrusion

    PubMed Central

    Tamaddon, Lana; Mostafavi, Seyed Abolfazl; Karkhane, Reza; Riazi-Esfahani, Mohammad; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza

    2015-01-01

    Background: The aim of the present study was to evaluate a non-destructive fabrication method in for the development of sustained-release poly (L, D-lactic acid)-based biodegradable clindamycin phosphate implants for the treatment of ocular toxoplasmosis. Materials and Methods: The rod-shaped intravitreal implants with an average length of 5 mm and a diameter of 0.4 mm were evaluated for their physicochemical parameters. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR), and nuclear magnetic resonance (1H NMR) studies were employed in order to study the characteristics of these formulations. Results: Drug content uniformity test confirmed the uniformity in different implant batches. Furthermore, the DSC, FTIR, and 1H NMR studies proved that the fabrication process did not have any destructive effects either on the drug or on the polymer structures. Conclusion: These studies showed that the developed sustained-release implants could be of interest for long-term sustained intraocular delivery of clindamycin, which can provide better patient compliance and also have good potential in terms of industrial feasibility. PMID:26322295

  16. Sustained-release dexamethasone intravitreal implant in juvenile idiopathic arthritis-related uveitis.

    PubMed

    Pichi, Francesco; Nucci, Paolo; Baynes, Kimberly; Lowder, Careen Y; Srivastava, Sunil K

    2017-02-01

    The purpose of this study is to review the results of treatment of juvenile idiopathic arthritis-related uveitis with the use of intravitreal dexamethasone implant. Sixteen eyes with Juvenile idiopathic arthritis (JIA)-associated uveitis received intravitreal dexamethasone implant to treat recalcitrant anterior segment inflammation (43.7 %), chronic macular edema (6.2 %), or a combination of both (50 %). One month after injection, mean visual acuity had improvement to 39.6 ± 11 ETDRS letters (p < 0.001). Mean AC cells measure at 1 month was 0.79 and 0.75 at 3 months. One month after injection, there was a significant reduction of central retinal thickness (CRT) to 342.4 ± 79.3 µm (p < 0.01). One month after the second implant, 11 eyes (91.6 %) achieved improved activity of the anterior uveitis, and mean best-corrected visual acuity improved to 44.6 ± 8.1 ETDRS letters (p < 0.01). At 1 month after the second injection, 4/5 eyes had resolution of macular edema with CRT of 250.4 ± 13.7 µm (p < 0.01). Of the 16 eyes, 12 eyes received a second injection at mean of 7.5 ± 3.1 months after the first treatment, and 5 eyes received a third Ozurdex injection on average 7 ± 4.6 months after the second injection. Of the 16 eyes, five eyes were pseudophakic prior to injection. Of the remaining 11 eyes, 8 (73 %) developed worsening posterior subcapsular cataract at a mean of 7.3 ± 1.2 months after the first injection. After the first injection, only one eye required topical antiglaucoma therapy with maximum pressure of 25 mmHg. In patients with recalcitrant JIA-associated active uveitis, injection of sustained-release dexamethasone can achieve control of anterior inflammation and resolution of macular edema.

  17. Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema

    PubMed Central

    Thomas, Benjamin J; Yonekawa, Yoshihiro; Wolfe, Jeremy D; Hassan, Tarek S

    2016-01-01

    Objective To compare the effects of intravitreal ranibizumab (RZB) or dexamethasone (DEX) intravitreal implant in cases of recalcitrant diabetic macular edema (DME). Methods Retrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months. Results Eleven patients (22 eyes) were included: mean logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16) to 0.261 (SD ±0.18) at final evaluation, and mean central macular thickness (CMT) improved from 461 µm (SD ±156) to 356 µm (SD ±110; net decrease: 105 µm, P=0.01). Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31) to 0.269 (SD ±0.19) at final evaluation. Mean CMT improved from 421 µm (SD ±147) to 373 µm (SD ±129; net decrease: 48 µm, P=0.26). Conclusion A subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection. PMID:27621587

  18. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    PubMed

    Li, Wenchang; He, Bing; Dai, Wenbing; Zhang, Qiang; Liu, Yuling

    2014-06-01

    Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

  19. Efficacy and Safety of Intravitreal Dexamethasone Implants for Treatment of Refractory Diabetic Macular Edema

    PubMed Central

    Eltutar, Kadir; Sultan, Pınar; Erkul, Sezin Ozdogan; Osmanbasoglu, Ozen Ayranci

    2017-01-01

    Purpose To evaluate the safety and efficacy of intravitreal dexamethasone (IVD) implants in eyes with diabetic macular edema that did not respond to previous treatment. Methods We included 46 eyes of 46 patients in this retrospective study. Each month, we recorded patient visual acuity with logarithm of the minimum angle of resolution using the Early Treatment Diabetic Retinopathy Study chart, central macular thickness measurements with optical coherence tomography, intraocular pressure (IOP), and posttreatment complication occurrence. Results The mean follow-up time was 8.95 ± 1.33 months (range, 6 to 12). Best-corrected visual acuity improved significantly in the first 4 months after IVD, but no statistically significant change was observed over the following 2 months. Although a statistically significant decrease in central macular thickness was observed in the first 3 months, the change was not statistically significant in the following 3 months. There was a statistically significant increase in IOP in the first 2 months, but no statistically significant change was observed in the following months. IOP was controlled with medication in all patients with elevated IOP. Of the 26 phakic patients, two had cataracts requiring surgery. Conclusions Cases of refractory diabetic macular edema that did not respond to previous treatment, such as anti-vascular endothelial growth factor injections and laser photocoagulation, exhibited improvements in visual acuity and decreases in retinal thickness after IVD implantation. Both functional and anatomical effects were observed in the first 3 months after injection. Repeat injections and frequent examination might be required for continued improvement. Side effects, such as cataracts and elevation of IOP, may require medical or surgical treatment. PMID:28367039

  20. Drug delivery implants in the treatment of vitreous inflammation.

    PubMed

    Wang, Jillian; Jiang, Angela; Joshi, Malav; Christoforidis, John

    2013-01-01

    The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article.

  1. Drug Delivery Implants in the Treatment of Vitreous Inflammation

    PubMed Central

    Wang, Jillian; Jiang, Angela; Joshi, Malav; Christoforidis, John

    2013-01-01

    The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article. PMID:24191132

  2. Twelve-Month Results of a Single or Multiple Dexamethasone Intravitreal Implant for Macular Edema following Uncomplicated Phacoemulsification

    PubMed Central

    Abdolrahimzadeh, Solmaz; Fenicia, Vito; Maurizi Enrici, Maurizio; Plateroti, Pasquale; Cianfrone, Dora; Recupero, Santi Maria

    2015-01-01

    The clinical efficacy of one or two intravitreal injections of a continued deliverance dexamethasone 700 μg implant in ten patients with persistent macular edema following uncomplicated phacoemulsification was evaluated. Complete ophthalmological examination and spectral domain optical coherence tomography were carried out. Follow-up was at day 7 and months 1, 2, 4, 6, 8, and 12. At baseline mean best corrected visual acuity was 62 Early Treatment Diabetic Retinopathy Study Chart letters, which showed statistically significant improvement at each follow-up, except at month 6, to reach 79 letters at month 12 (P = 0.018). Prior to treatment mean central foveal thickness was 622 μm, which showed statistically significant improvement at each follow-up to reach a mean value of 282 μm (P = 0.012) at month 12. Five patients received a second dexamethasone implant at month 7. Two patients were excluded from the study at months 4 and 8. Intraocular pressure remained stable during the study period with the exception of mild increase in two patients requiring topical therapy. In conclusion there was statistically significant improvement of best corrected visual acuity and mean central foveal thickness with one or two intravitreal dexamethasone implants over 12 months. PMID:26509151

  3. Health-related quality of life, visual function and treatment satisfaction following intravitreal dexamethasone implant for diabetic macular edema

    PubMed Central

    Ramu, Jayashree; Chatziralli, Irini; Yang, Yit; Menon, Geeta; Bailey, Clare; Eckstein, Michael; Hykin, Phil; Sivaprasad, Sobha

    2017-01-01

    Purpose The aim of this study was to explore and describe quantitatively patient-reported outcome measures (PROMs), ie, health-related quality of life (QoL), visual function and treatment satisfaction, in patients with diabetic macular edema (DME) receiving two different regimens of Ozurdex (intravitreal dexamethasone implant). Methods In this multicenter, prospective study, 100 patients with center-involving refractory DME were randomized 1:1 to either five monthly fixed dosing or optical coherence tomography (OCT)-guided pro re nata (PRN) regimen of dexamethasone intravitreal implant therapy. The primary outcome was the difference between arms in change in PROMs and health-related QoL from baseline to 12 months, as measured by the Retinopathy-Dependent Quality of Life (RetDQoL) questionnaire, Visual Function Questionnaire-25 (VFQ-25) and Retinopathy Treatment Satisfaction Questionnaire (RetTSQ). Results There was no statistically significant difference in the RetDQoL score and VFQ-25 score at month 12 compared to those at baseline, whereas the total mean RetTSQ score increased significantly at the exit visit. The two treatment arms did not differ significantly regarding the change in PROMs and health-related QoL questionnaires. Logistic regression analysis showed that visual acuity (VA) of ≥55 letters, central foveal thickness <300 μm and macular volume <9.2 mm3 at the exit visit (month 12) predicted a higher change in RetTSQ. Conclusion This study showed that there is a statistically significant improvement in treatment satisfaction, as measured by RetTSQ, in patients with DME treated with dexamethasone intravitreal implant, independent of the dose regimen, namely, fixed or PRN. However, it should be noted that the clinically meaningful change could not be assessed accurately, since no thresholds for clinically meaningful change currently exist for the RetTSQ. On the other hand, there was no significant change in health-related QoL, as measured using VFQ-25

  4. Effects of triamcinolone acetonide on microglial morphology and quantitative expression of MHC-II in exudative age-related macular degeneration.

    PubMed

    Penfold, P L; Wong, J G; Gyory, J; Billson, F A

    2001-06-01

    Animal models, in vitro assays and pilot clinical studies suggest that intravitreal triamcinolone acetonide may be useful in the treatment of age-related macular degeneration. The present case study reports the effect of intravitreal triamcinolone acetonide injection on a subretinal neovascular lesion, microglial morphology and quantitative expression of MHC-II antigens. Triamcinolone acetonide significantly decreased MHC-II expression consistent with immunocytochemical observations which revealed condensed microglial morphology. The modulation of subretinal oedema and microglial morphology correlates with in vitro observations suggesting that downregulation of inflammatory markers and endothelial cell permeability are significant features of the mode of action of triamcinolone acetonide.

  5. Randomized Comparison of Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Implant for Intermediate, Posterior and Panuveitis: The Multicenter Uveitis Steroid Treatment Trial

    PubMed Central

    Kempen, John H.; Altaweel, Michael M.; Holbrook, Janet T.; Jabs, Douglas A.; Louis, Thomas A.; Sugar, Elizabeth A.; Thorne, Jennifer E.

    2011-01-01

    Objective To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for non-infectious intermediate, posterior or panuveitis (uveitis). Design Randomized controlled parallel superiority trial. Participants Patients with active/recently active uveitis. Methods Participants were randomized (allocation ratio 1:1) to systemic or implant therapy at 23 centers (three countries). Implant-assigned participants with bilateral uveitis were assigned to have each eye that warranted study treatment implanted. Treatment-outcome associations were analyzed by assigned treatment for all eyes with uveitis. Main Outcome Measures Masked examiners measured the primary outcome: change in best-corrected visual acuity from baseline. Secondary outcomes included patient-reported quality of life (QoL), ophthalmologist-graded uveitis activity, and local and systemic complications of uveitis or therapy. Reading Center graders and glaucoma specialists assessing ocular complications were masked. Participants, ophthalmologists, and coordinators were unmasked. Results Among 255 patients randomized to implant and systemic therapy (479 eyes with uveitis), evaluating changes from baseline to 24 months, the implant and systemic therapy groups respectively had +6.0 vs. +3.2 letters' improvement in visual acuity (p=0.16, 95% confidence interval on difference in improvement between groups: −1.2 to +6.7 letters, positive values favoring implant), +11.4 vs. +6.8 units' vision-related QoL improvement (p=0.043), +0.02 vs. −0.02 change in EuroQol-EQ5D health utility (p=0.060), and 12% vs. 29% had active uveitis (p=0.001). Over 24 months, implant-assigned eyes had a higher risk of cataract surgery (80%, hazard ratio (HR) = 3.3, p<0.0001), treatment for elevated intraocular pressure (61%, HR=4.2, p<0.0001), and glaucoma (17%, HR = 4.2, p=0.0008). Systemic-assigned patients had more

  6. INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA

    PubMed Central

    Bailey, Clare; Loewenstein, Anat; Massin, Pascale

    2015-01-01

    Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans. PMID:26352555

  7. Preliminary results of an intravitreal dexamethasone implant (Ozurdex®) in patients with persistent diabetic macular edema

    PubMed Central

    Pacella, Elena; Vestri, Anna Rita; Muscella, Roberto; Carbotti, Maria Rosaria; Castellucci, Massimo; Coi, Luigi; Turchetti, Paolo; Pacella, Fernanda

    2013-01-01

    Background To evaluate the efficacy and safety of an intravitreal dexamethasone implant (Ozurdex®; Allergan Inc, Irvine, CA, USA) in patients with persistent diabetic macular edema (DME) over a 6-month follow-up period. Methods Seventeen patients (20 eyes) affected by DME were selected. The mean age was 67 + 8 years, and the mean duration of DME was 46.3 + 18.6 months. The eligibility criteria were: age ≥ 18, a best-corrected visual acuity between 5 and 40 letters, and macular edema with a thickness of ≥275 μm. Thirteen patients had also previously been treated with anti-vascular endothelial growth factor medication. Results The mean ETDRS (Early Treatment Diabetic Retinopathy Study) value went from 18.80 + 11.06 (T0) to 26.15 + 11.03 (P = 0.04), 28.15 + 10.29 (P = 0.0087), 25.95 + 10.74 (P = 0.045), 21.25 + 11.46 (P = 0.5) in month 1, 3, 4, and 6, respectively. The mean logMAR (logarithm of the minimum angle of resolution) value went from 0.67 + 0.23 (at T0) to 0.525 + 0.190 (P = 0.03), 0.53 + 0.20 (P = 0.034), and 0.56 + 0.22 (P = 0.12) in month 1, 3, and 4, respectively, to finally reach 0.67 + 0.23 in month 6. The mean central macular thickness value improved from 518.80 + 224.75 μm (at T0) to 412.75 + 176.23 μm, 292.0 + 140.8 μm (P < 0.0001), and 346.95 + 135.70 (P = 0.0018) on day 3 and in month 1 and 3, respectively, to then increase to 476.55 + 163.14 μm (P = 0.45) and 494.25 + 182.70 μm (P = 0.67) in month 4 and 6. Conclusion The slow-release intravitreal dexamethasone implant, Ozurdex, produced significant improvements in best-corrected visual acuity and central macular thickness from the third day of implant in DME sufferers, and this improvement was sustained until the third month. PMID:23901252

  8. Long-term evaluation of dexamethasone intravitreal implant in vitrectomized and non-vitrectomized eyes with macular edema secondary to non-infectious uveitis

    PubMed Central

    Pelegrín, L; de la Maza, M S; Molins, B; Ríos, J; Adán, A

    2015-01-01

    Purpose To compare dexamethasone (DEX) intravitreal implant effect in non-vitrectomized (non-PPV) vs vitrectomized (PPV) eyes with macular edema (ME) secondary to non-infectious uveitis. Methods Medical records of patients with uveitic ME treated with DEX-intravitreal implant were reviewed. Main outcome measures were changes in central retinal thickness (CRT), best corrected visual acuity (BCVA), intraocular pressure (IOP), vitreous haze and adverse events. Statistical analysis was performed by Longitudinal Linear model using the General Estimating Equation methodology. Results Forty-two eyes of 32 patients were included. Median follow-up time was 18 months (interquartile range (IQR): 12–24). Median CRT showed its maximum decrease at the first month in non-PPV and PPV eyes without statistically significant differences between both groups (P=NS). Median Snellen BCVA, converted to logarithm (LogMAR), showed its maximum improvement at third month in both groups without statistically significant differences between them (P=NS). Median IOP was higher in non-PPV eyes than in PPV eyes from third (P=0.025) to 12th month (P=0.013). Vitreous haze score improved in both groups since first month and showed no differences (P=0.706). Reinjection was performed in 45.2% of eyes at a median time of 5 months IQR: (5–6). Ocular hypertension (47.6%) was the most common adverse event. Conclusions DEX-intravitreal implant for uveitic ME has similar long-term safety profile and good response measured in terms of CRT decrease, BCVA, and vitreous haze improvement in both groups. Non-PPV eyes following DEX-intravitreal implant showed higher IOP increase than PPV eyes, showing the need for close IOP monitoring. PMID:25998942

  9. Rhegmatogenous Retinal Detachment with a High Risk of Proliferative Vitreoretinopathy Treated with Episcleral Surgery and an Intravitreal Dexamethasone 0.7-mg Implant

    PubMed Central

    Reibaldi, Michele; Russo, Andrea; Longo, Antonio; Bonfiglio, Vincenza; Uva, Maurizio G.; Gagliano, Caterina; Toro, Mario D.; Avitabile, Teresio

    2013-01-01

    Purpose To report a case of rhegmatogenous retinal detachment with a high risk of proliferative vitreoretinopathy (PVR) effectively treated with episcleral surgery and an intravitreal dexamethasone 0.7-mg implant. Methods A 35-year-old Caucasian man with a macula-off rhegmatogenous subtotal retinal detachment that had persisted for 1 month in his myopic left eye presented several risk factors that could have led to the development of PVR after retinal detachment surgery. His best corrected visual acuity was hand motion. He received an intravitreal dexamethasone 0.7-mg implant (Ozurdex®) after episcleral surgery to prevent this complication. Results At least 9 months after surgery, no sign of PVR or pucker has developed in the treated eye. Visual acuity improved to 0.2, the retina was attached and no complications were observed. Conclusion Intravitreal dexamethasone 0.7-mg implant (Ozurdex) could be considered as off-label treatment following episcleral surgery to prevent PVR. PMID:23687501

  10. Retinal pseudoangiitis after intravitreal triamcinolone

    PubMed Central

    García-Campos, Jose Manuel; García-Basterra, Ignacio; Kamal-Salah, Radua; Baquero-Aranda, Isabel

    2015-01-01

    We present a case of a 40-year-old woman with a fundus image similar to frosted retinal angiitis after undergoing pars plana vitrectomy and intravitreal triamcinolone injection. The patient with diabetic retinopathy was referred to our hospital with vision loss in her right eye secondary to vitreous haemorrhage. After pars plana vitrectomy and injection of triamcinolone acetonide a funduscopy examination revealed deposits of triamcinolone along the retinal vessels simulating a frosted retinal angiitis. Triamcinolone deposits along blood vessels could be the result of the reabsorption process of these crystals by the perivascular macrophages. Further studies are needed. PMID:25678611

  11. Management of macular epiretinal membrane by vitrectomy and intravitreal triamcinolone.

    PubMed

    Shukla, Dhananjay

    2014-04-01

    A patient underwent successful vitrectomy for macular epiretinal membrane with anatomical and functional improvement. 10 weeks later, there was a recurrence of macular edema with corresponding visual decline. An intravitreal injection of triamcinolone acetonide not only restored the macular anatomy but also improved the visual outcome beyond that achieved after surgery.

  12. Efficacy of intravitreal dexamethasone implant for prostaglandin-induced refractory pseudophakic cystoid macular edema: case report and review of the literature

    PubMed Central

    Sacchi, Matteo; Villani, Edoardo; Gilardoni, Francesca; Nucci, Paolo

    2014-01-01

    Background Macular edema is a known complication even after uneventful cataract surgery. The chronic use of prostaglandin analogs is a risk factor for the development of pseudophakic cystoid macular edema (CME). Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered first-line therapy but refractory postsurgical CME represents a therapeutic challenge, as there is not an evidence-based treatment. Objective To report the use of a single implant of intravitreal dexamethasone for tafluprost-associated pseudophakic CME refractory to NSAIDs and to sub-Tenon’s corticosteroid injections. Case report A 64-year-old female with ocular hypertension treated with tafluprost experienced decreased vision (visual acuity 20/60) and metamorphopsia 2 months after uneventful cataract extraction. Spectral domain optical coherence tomography (SD-OCT) revealed CME. After 1 month of topical and oral NSAIDs, CME was still evident on SD-OCT (visual acuity 20/50). Two sub-Tenon’s betamethasone injections were performed at a 2-week interval. As CME was still present, 2 months after the diagnosis of CME (visual acuity 20/40), the patient underwent a single dexamethasone intravitreal implant. One month later, macular appearance was normal, and visual acuity increased to 20/30. This result was maintained throughout the 6 months of follow-up. Conclusion In this report, a single implant of intravitreal dexamethasone successfully treated pseudophakic CME associated with the use of prostaglandin analogs unresponsive to NSAIDs and sub-Tenon’s betamethasone. The results of this report need to be corroborated by powered, prospective, randomized trials. The need for repeated treatments as well as the retreatment interval in patients requiring more than a single injection are issues still needing further investigations. PMID:25061272

  13. Intravitreal Injection of Ozurdex® Implant in Patients with Persistent Diabetic Macular Edema, with Six-Month Follow-Up

    PubMed Central

    Pacella, Fernanda; Ferraresi, Adriana Francesca; Turchetti, Paolo; Lenzi, Tommaso; Giustolisi, Rosalia; Bottone, Andrea; Fameli, Valeria; Romano, Maria Rosaria; Pacella, Elena

    2016-01-01

    AIM To evaluate the efficacy of intravitreal dexamethasone injections in diabetic macular edema (DME). METHODS A 700 μg slow-release intravitreal dexamethasone implant (Ozurdex®) was placed in the vitreal cavity of 17 patients (19 eyes) affected with persistent DME. Best corrected visual acuity (BCVA) was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS). Central macular thickness (CMT) was measured by spectral-domain optical coherence tomography. BCVA and CMT examinations were carried out at baseline (T0) and repeated after three days, one month (T1), three months (T3), four months (T4), and six months (T6) post injection. RESULTS Dexamethasone implant induced an improvement in ETDRS at T1, T3, T4, and T6 post injection. CMT was reduced at T1, T3, and T4, while at T6, CMT values were not statistically different from baseline. No complications were observed during the follow-up. CONCLUSION Our data suggest that dexamethasone implant is effective in reducing DME symptoms within a six-month frame. PMID:27147895

  14. Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Intraocular Implant for Intermediate, Posterior or Panuveitis: 54 month results of The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study

    PubMed Central

    Kempen, John H.; Altaweel, Michael M.; Drye, Lea T.; Holbrook, Janet T.; Jabs, Douglas A.; Sugar, Elizabeth A.; Thorne, Jennifer E.

    2015-01-01

    Purpose To evaluate the risks and quality of life (QoL) outcomes of fluocinolone acetonide implant versus systemic therapy with corticosteroid and immunosuppression when indicated for intermediate, posterior, and panuveitis. Design Additional follow-up of a randomized trial cohort Participants 255 patients with intermediate, posterior or panuveitis, randomized to implant or systemic therapy. Methods Randomized subjects with intermediate, posterior, or panuveitis (479 eyes) were followed over 54 months, with 79.2% completing the 54 month visit. Main Outcome Measures Local and systemic potential complications of the therapies and self-reported health utility, vision-related and generic health-related QoL were studied prospectively. Results Among initially phakic eyes, cataract and cataract surgery, occurred significantly more often in the implant group (hazard ratio (HR)=3.0, p=0.0001 and HR=3.8, p<0.0001 respectively). In the implant group, most cataract surgery occurred within the first two years. IOP elevation measures occurred more frequently in the implant group (range of HR's=3.7-5.6, all p<0.0001), and glaucoma (assessed annually) also occurred more frequently (26.3% vs. 10.2% by 48 months, HR=3.0, p=0.0002). In contrast, potential complications of systemic therapy including measures of hypertension, hyperlipidemia, diabetes, bone disease, and hematological and serum chemistry indicators of immunosuppression toxicity did not differ between groups through 54 months. Indices of QoL initially favored implant therapy by a modest margin. However, all summary measures of health utility and vision-related or generic health-related QoL were minimally and non-significantly different by 54 months with the exception of the SF-36 physical component summary score which favored implant by a small margin at 54 months (3.17 on a scale of 100, p=0.01, not adjusted for multiple comparisons). Mean QoL results were favorable in both groups. Conclusions These results suggest that

  15. An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

    PubMed Central

    Pacella, Fernanda; Romano, Maria Rosaria; Turchetti, Paolo; Tarquini, Giovanna; Carnovale, Anna; Mollicone, Antonella; Mastromatteo, Alessandra; Pacella, Elena

    2016-01-01

    AIM To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema (DME) resistant to anti-vascular endothelial growth factor (VEGF) therapy. METHODS Thirty-two DME patients were enrolled. A 700 microgram slow release Intravitreal Dexamethasone Implant (Ozurdex®) was placed in the vitreous cavity. All patients were followed for 18mo. Best-corrected visual acuity (BCVA) measured with Early Treatment Diabetic Retinopathy Study (ETDRS) and central macular thickness (CMT) exams were carried out at baseline (T0) and after 1 (T1), 3 (T3), 4 (T4), 6 (T6), 9 (T9), 12 (T12), 15 (T15), and 18mo (T18) post injection. RESULTS Repeated measures ANOVA showed an effect of treatment on ETDRS (P<0.0001). Post hoc analyses revealed that ETDRS values were significantly increased at T1, T3, T4, T9, and T15 (P<0.001) as compared to baseline value (T0). At T6, T12, and T18, ETDRS values were still statistically higher than baseline (P<0.001 vs T0). However, at these time points, we observed a trend to return to baseline conditions. ANOVA also showed an effect of treatment (P<0.0001). CMT decreased significantly at T1, T3, T4, T9, and T15 (P<0.001). At T6 (P<0.01), T12 and T18 (P<0.001) CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed. CONCLUSION Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improve BCVA and CMT in DME patients resistant to anti-VEGF therapy. Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects. PMID:27803859

  16. Benefits of Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Intraocular Implant for Intermediate, Posterior and Panuveitis: 54 month results of The Multicenter Uveitis Steroid Treatment Trial (MUST) and Follow-up Study

    PubMed Central

    2015-01-01

    Objective To compare the benefits of fluocinolone acetonide implant therapy versus systemic corticosteroid therapy supplemented (when indicated) with immunosuppression for intermediate, posterior, and panuveitis. Design Additional follow-up of a randomized comparative effectiveness trial cohort Participants 255 patients with intermediate, posterior or panuveitis who had been randomized to implant or systemic therapy. Main Outcome Measures Best-corrected visual acuity (BCVA), visual field mean deviation, activity of uveitis, and presence of macular edema (per Reading Center grading) were ascertained prospectively. Methods Trial participants were followed through 54 months from original randomization. Results The trajectory of visual function in uveitic eyes demonstrated a similar (p = 0.73) degree of modest (not statistically significant) improvement from baseline to 54 months in both groups (mean improvement in BCVA at 54 months: 2.4 and 3.1 letters in the implant and systemic group respectively). Many had excellent initial visual acuity, limiting the potential for improvement. The mean automated perimetry mean deviation score remained similar to baseline throughout 48 months’ follow-up in both groups. Overall control of inflammation was superior in the implant group at every time point assessed (p<0.016), although most eyes in the systemic therapy arm also had substantial inflammatory improvement, achieving complete control or low levels of inflammation. While macular edema improved significantly more often with implant treatment within the first six months, the systemic group gradually improved over time thereafter such that the proportions with macular edema converged in the two groups by 36 months and were overlapping thereafter (p=0.41 at 48 months). Conclusions Visual outcomes of fluocinolone acetonide implant and systemic treatment for intermediate, posterior, and panuveitis were similarly favorable through 54 months. The implant maintains a clear

  17. Long-term follow-up of anatomical and functional macular changes after a single intravitreal implant of dexamethasone 0.7 mg for radiation macular edema secondary to proton beam therapy for choroidal melanoma

    PubMed Central

    Stringa, Francesco; Marzi, Federico; Giannì, Laura; Imparato, Manuela; Bianchi, Alessandro; Bianchi, Paolo Emilio

    2016-01-01

    Purpose To describe the efficacy and safety of a single intravitreal implant of dexamethasone in a patient affected by radiation maculopathy due to proton beam radiotherapy for choroidal melanoma. Patient and methods Retrospective data of a 46-year-old woman treated with a single intravitreal injection of dexamethasone for radiation maculopathy due to proton beam radiotherapy were collected. The main outcome measures were best-corrected visual acuity and central retinal thickness. Intraocular pressure, anterior segment evaluation with slit lamp, macular changes depicted with spectral domain optical coherence tomography, retinal perfusion studied with fundus fluorescein angiography, and grade of macular edema using the Horgan classification were also evaluated during a 16-month follow-up. Results Macular edema occurred 25 months after radiation treatment in the left eye. The patient underwent a single intravitreal implant of dexamethasone. Preinjection visual acuity and central retinal thickness were 6/12 and 502 µm, respectively. After 8 months, visual acuity was 6/6 and remained stable until 16 months. Central retinal thickness was 269 µm at 16 months. Conclusion A single intravitreal implant of dexamethasone could effectively and stably improve visual acuity and central retinal thickness in some patients with radiation macular edema for 16 months after injection. PMID:27942234

  18. Short-term Efficacy of Intravitreal Dexamethasone Implant in Vitrectomized Eyes with Recalcitrant Diabetic Macular Edema and Prior Anti-VEGF Therapy

    PubMed Central

    Shah, Ankoor R.; Xi, Mengqiao; Abbey, Ashkan M.; Yonekawa, Yoshihiro; Faia, Lisa J.; Hassan, Tarek S.; Ruby, Alan J.; Wolfe, Jeremy D.

    2016-01-01

    Purpose: To determine the efficacy of an intravitreal dexamethasone implant (IDI) for diabetic macular edema (DME) in vitrectomized eyes. Methods: This interventional retrospective consecutive case series included vitrectomized eyes undergoing IDI placement for treatment of recalcitrant DME between June 2011 and June 2014. All patients had previously received anti-VEGF therapy (ranibizumab or bevacizumab). Primary endpoints were changes in visual acuity (VA) and central retinal thickness (CRT) from baseline values one month after device implantation. Secondary endpoints were VA and CRT changes at 3 months. Results: A total of 8 eyes of 8 patients met the inclusion criteria. One month after IDI placement, there was a significant (p = 0.01) improvement in VA from 0.79 ± 0.52 logMAR (20/123 Snellen equivalent) to 0.64 ± 0.55 logMAR (20/88), meanwhile CRT improved from 455.75 ± 123.19 to 295.00 ± 90.39 μm (p = 0.02). These findings persisted at 3 months. Conclusion: In vitrectomized eyes previously treated with anti-VEGF agents for recalcitrant DME, implantation of the IDI appears to be efficacious in improving VA and CRT at 1-month with the observed benefits persisting for at least for 3 months. PMID:27413499

  19. Intravitreal controlled release of dexamethasone from engineered microparticles of porous silicon dioxide.

    PubMed

    Wang, Chengyun; Hou, Huiyuan; Nan, Kaihui; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

    2014-12-01

    Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterification Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and

  20. Intravitreal Controlled Release of Dexamethasone from Engineered Microparticles of Porous Silicon Dioxide

    PubMed Central

    Wang, Chengyun; Hou, Huiyuan; Nan, Kaihui; Sailor, Michael J; Freeman, William R.; Cheng, Lingyun

    2014-01-01

    Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterificaion Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and

  1. Efficacy and safety of intravitreal ranibizumab with panretinal photocoagulation followed by trabeculectomy compared with Ahmed glaucoma valve implantation in neovascular glaucoma

    PubMed Central

    Sun, Jin-Tao; Liang, Hai-Jing; An, Meng; Wang, Da-Bo

    2017-01-01

    AIM To evaluate the efficacy and safety of intravitreal ranibizumab (IVR) with panretinal photocoagulation (PRP) followed by trabeculectomy compared with Ahmed glaucoma valve (AGV) implantation in neovascular glaucoma (NVG). METHODS This was a retrospective comparative study. We reviewed the cases of a total of 45 eyes from 45 NVG patients among which 23 eyes underwent AGV implantation and the other 22 underwent trabeculectomy. The causes of neovascular glaucoma included: diabetic retinopathy (25 eyes), and retinal vein occlusion (20 eyes). All patients received preoperative IVR combined with postoperative PRP. The mean best-corrected visual acuities (BCVA) were converted to the logarithms of the minimum angle of resolution (logMAR) for the statisitical analyses. Intraocular pressure (IOP), the logMAR BCVA and surgical complications were evaluated before and after surgery. The follow-up period was 12mo. RESULTS A total of 39 cases showed complete regression of iris neovascularization at 7d after injection, and 6 cases showed a small amount of residual iris neovascularization. The success rates were 81.8% and 82.6% at 12mo after trabeculectomy and AGV implantation, respectively. In the trabeculectomy group, the logMAR BCVA improved at the last follow-up in 14 eyes, remained stable in 6 eyes and decreased in 2 eyes. In 4 cases, slight hyphemas developed after trabeculectomy. A shallow anterior chamber developed in 2 cases and 2 vitreous hemorrhages. In the AGV group, the logMAR BCVA improved in 14 eyes, remained stable in 5 eyes and decreased in 4 eyes. Slight hyphemas developed in 3 cases, and a shallow anterior chamber in 3 cases. The mean postoperative IOP was significantly lower in both groups after surgery (F=545.468, P<0.05), and the mean postoperative logMAR BCVA was also significantly improved (F=10.964, P<0.05) with no significant difference between two groups. CONCLUSION It is safe and effective to treat NVG with this combined procedure, and we found

  2. Location of a Dexamethasone Implant at the Macula after Intravitreal Injection in a Silicone Oil-Filled Eye

    PubMed Central

    Esenulku, Cenap Mahmut

    2016-01-01

    Here, we report a case with cystoid macular edema (CME) due to central retinal vein occlusion (CRVO) presented with a dexamethasone implant (Ozurdex) trapped at the macula in her silicone oil- (SO-) filled eye after injection. No additional complications such as intraocular pressure (IOP) rise or retinal damage were observed. The CME was resolved during the follow-up period. At the last visit, 3 months following the injection, Ozurdex implant was found to be mostly dissolved without any additional ocular complications. PMID:27999699

  3. Intravitreal dexamethasone implant for recurrent cystoid macular edema due to Irvine-Gass syndrome: a prospective case series.

    PubMed

    Sudhalkar, A; Chhablani, J; Vasavada, A; Bhojwani, D; Vasavada, V; Vasavada, S

    2016-12-01

    PurposeTo determine the preliminary efficacy and safety of off-label dexamethasone implant for treatment of recurrent cystoid macular edema (CME) secondary to Irvine-Gass syndrome (IGS).Patients and methodsThis study was set in Raghudeep Eye Clinic, Ahmedabad and LV Prasad Eye Institute, Hyderabad (India). It is a Prospective Case Series. Prospective case series comprising of patients with uncomplicated pseudophakia and CME due to IGS who recurred after one course of topical steroids with NSAIDS and a sub-Tenon corticosteroid injection. A complete ocular and systemic exam, fluorescein angiography, and central subfield thickness (CST) on optical coherence tomography scans were performed. Follow-up visits were on days 1, 15, and 30 and then monthly for a year. Appropriate statistical analysis was done. The primary outcome measure was the change in CDVA at months 1, 6, and 12. Secondary outcome measures were recurrence of CME and complications if any as noted at months 1, 2, 6, and 12.ResultsAbout 27 patients (27 eyes) with 16 males were included. Median age: 63.24±5.62 years. At 1 month, the CDVA improved to 0.04±0.02 (20/25) logMAR from 0.52±0.12 logMAR (20/70) (P=0.001) with a reduction in CST from 454.2±45.3 to 218.32±38.15 microns(P=0.013). The CDVA was 0.04±0.03 logMAR(P<0.001) at month 6 and 0.05±0.02 logMAR(P<0.001) at month 12. The CST was 221±35.2 microns (P=0.013) at month 6 and 214±43.34 microns (P=0.0124) at month 12. All improvements were maintained for a year. Only one patient required a second injection. No complications were noted.ConclusionThe implant is safe and effective for the treatment of recurrent CME due to IGS.

  4. [Viral retinitis following intravitreal triamcinolone injection].

    PubMed

    Zghal, I; Malek, I; Amel, C; Soumaya, O; Bouguila, H; Nacef, L

    2013-09-01

    Necrotizing viral retinitis is associated with infection by the Herpes family of viruses, especially herpes simplex virus (HSV), varicella zoster virus (VZV) and occasionally cytomegalovirus (CMV). When the diagnosis is suspected clinically, antiviral therapy must be instituted immediately. We report the case of a patient presenting with necrotizing viral retinitis 3 months following intravitreal injection of triamcinolone acetonide for diabetic macular edema. Fluorescein angiography demonstrated a superior temporal occlusive vasculitis. A diagnostic anterior chamber paracentesis was performed to obtain deoxyribo-nucleic acid (DNA) for a polymerase chain reaction (PCR) test for viral retinitis. PCR was positive for CMV. The patient was placed on intravenous ganciclovir. CMV retinitis is exceedingly rare in immunocompetent patients; however, it remains the most common cause of posterior uveitis in immunocompromised patients. The incidence of this entity remains unknown. Local immunosuppression, the dose and the frequency of injections may explain the occurrence of this severe retinitis.

  5. Real-Life ILUVIEN (Fluocinolone Acetonide) Case Study: Rapid Drying of the Macula and Improved Vision within 2 Years after Therapy Initiation

    PubMed Central

    Quhill, Hibba; Quhill, Fahd

    2016-01-01

    Importance A case showing sustained structural and functional responses 2 years after a single treatment with ILUVIEN (0.2 µg/day fluocinolone acetonide, FAc) despite suboptimal responses to ranibizumab. Observations A 68-year-old female patient with diabetic macular oedema (DME) from type 2 diabetes mellitus was first diagnosed in October 2010 and had a baseline visual acuity (VA) of 46 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the left eye. Central foveal thickness (CFT) was 712 microns. The patient was treated with 11 intravitreal injections of ranibizumab (5 in combination with a small-interfering RNA agent), and by March 2014, VA and CFT were largely unchanged (55 ETDRS letters and 774 microns). The patient was treated with ILUVIEN as she had a pseudophakic lens and a clearly suboptimal response to the prior therapy with ranibizumab. An implant releasing FAc at a dosage of 0.2 µg/day was administered in March 2014, and the optical coherence tomography indicated that the macula was dry after 7 days (CFT was below 300 microns). This was sustained at 6, 12, and 24 months after the treatment. VA improved by 5 letters within 7 days and by 15 letters within 14 days, and this was maintained after 24 months. Throughout the duration of this study, the intraocular pressure was ≤22 mm Hg, and no glaucoma medication was administered. Conclusions and Relevance In real-life UK practice, this DME patient showed a suboptimal response to multiple intravitreal injections of ranibizumab. When subsequently treated with a single injection of ILUVIEN, there were large and rapid improvements in VA and CFT that were maintained for the following 2 years. PMID:28203186

  6. 21 CFR 524.981a - Fluocinolone acetonide cream.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fluocinolone acetonide cream. 524.981a Section 524.981a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Fluocinolone acetonide cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide....

  7. Delivery of Intraocular Triamcinolone Acetonide in the Treatment of Macular Edema

    PubMed Central

    Pickrell, Aaron; Harris, Alon; Ngo, Sandra; Amireskandari, Annahita; Stewart, Erin; Siesky, Brent

    2012-01-01

    Macular edema (ME) is one of the eventual outcomes of various intraocular and systemic pathologies. The pathogenesis for ME is not yet entirely understood; however, some of the common risk factors for its development have been identified. While this investigation will not discuss the numerous etiologies of ME in detail, it appraises the two most widely studied delivery modalities of intraocular corticosteroids in the treatment of ME—intravitreal injection (IVI) and sub-Tenon’s infusion (STI). A thorough review of the medical literature was conducted to identify the efficacy and safety of IVI and STI, specifically for the administration of triamcinolone acetonide (TA), in the setting of ME in an attempt to elucidate a preferred steroid delivery modality for treatment of ME. PMID:24300190

  8. Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series

    PubMed Central

    Singer, Michael A; Jansen, Michael E; Tyler, Lyndon; Woods, Paul; Ansari, Faisal; Jain, Udit; Singer, Joshua; Bell, Darren; Krambeer, Chelsey

    2017-01-01

    Background One limitation of anti-VEGF therapy is the need for monthly retreatment to maintain efficacy. The purpose of this study was to determine the duration of effect in eyes with macular edema (ME) secondary to branch or central retinal vein occlusion (BRVO or CRVO) treated with anti-VEGF therapy plus sustained-release dexamethasone (DEX implant; Ozurdex). Materials and methods This open-label, interventional case series included 62 eyes with ME due to RVO, central foveal thickness (CFT) >300 μm, and best-corrected visual acuity (BCVA) of 20/40 or worse. Each treatment cycle included an anti-VEGF injection followed 2 weeks later with DEX implant. Patients were eligible for retreatment if CFT increased to >290 μm or increased by >50 μm from the lowest measurement, or if BCVA decreased by six or more Snellen letters. Efficacy and safety were evaluated 2 and 4–6 weeks after the beginning of each treatment cycle and every 4 weeks thereafter until retreatment criteria were met. The primary outcome measure was time to retreatment. Secondary outcome measures included BCVA, CFT, and safety parameters. Results The mean reinjection interval for all patients was 135.5±36.4 days. There was no statistically significant difference in mean intertreatment interval for up to six cycles of treatment or between eyes with BRVO or CRVO (P≥0.058). Mean peak change in BCVA was 13.8 letters, and 47.6% of eyes gained three or more lines of BCVA. The mean peak decrease in CFT across all treatment cycles was 200.9 μm for eyes with BRVO and 219.2 μm for eyes with CRVO. The percentage of patients with CFT ≤300 μm at any time during a given treatment cycle ranged from 78% to 94% among eyes with BRVO and from 85% to 100% among eyes with CRVO. Intraocular pressure increased in 19 of 62 eyes, and 26 of 44 phakic eyes underwent cataract surgery. Conclusion In eyes with ME due to RVO, treatment with an anti-VEGF agent plus DEX implant provided a predictable duration of effect, as

  9. [Sublesional therapy by triamcinolone acetonide (author's transl)].

    PubMed

    Grimmer, H

    1981-04-01

    The application of sublesional injections by using Triamcinolone Acetonide crystal suspension represents a method offering the possibility to achieve a maximum of effectiveness with relatively small doses. Selectively injected in the affected tissue or the immediate neighbourhood respectively the health structures can be preserved largely from undesirable side effects. In diseases chronically relapsing longer symptomless remissions can be reached than with conventional topical methods.

  10. Visual perceptions induced by intravitreous injections of therapeutic agents

    PubMed Central

    Charalampidou, S; Nolan, J; Ormonde, G O; Beatty, S

    2011-01-01

    Purpose The purpose of this study was to conduct a questionnaire-based survey of subjective visual perceptions induced by intravitreous (IVT) injections of therapeutic agents. Patients and methods Patients undergoing an IVT injection of ranibizumab, pegaptanib sodium, or triamcinolone acetonide were administered a questionnaire in the immediate post-injection period and at 2 weeks of follow-up. Results In the immediate post-injection period (75 IVT injections, 75 eyes, 75 patients), lights and floaters were reported after 20 (27%) and 24 (32%) IVT injections, respectively. In comparison, at the 2-week follow-up, the incidence of reported lights (11; 15%) was similar (P>0.05), but the incidence of reported floaters was higher (48; 64% P=0.00). Subgroup analysis for various injection subgroups (no previous injection vsprevious injection(s) in the study eye; injections in study eyes with good VA (logarithm of minimal angle of resolution [logMAR] ≤0.3) vsmoderate VA (0.7 0.3) vspoor VA (logMAR ≥0.7); injections according to pharmacological agent (ranibizumab vspegaptanib vstriamcinolone acetonide); injections in study eyes with choroidal neovascularization (of various causes) vsstudy eyes with macular edema (of various causes); and injections in phakic vspseudophakic eyes) did not reveal any statistically significant associations. Visual perceptions experienced following 15% of IVT injections gave cause for concern to the patient (mean visual analog scale score (±SD): 4.5 (±1.7)), and in 64% of cases, the patients believed that preoperative counseling would have averted the concern. Conclusions Lights and floaters are frequent visual perceptions following IVT injections of therapeutic agents. They can give rise to concern that could be alleviated with preinjection counseling. PMID:21274011

  11. 21 CFR 524.981b - Fluocinolone acetonide solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Fluocinolone acetonide solution. 524.981b Section... § 524.981b Fluocinolone acetonide solution. (a) Specifications. The drug contains 0.01 percent... and certain superficial acute and chronic dermatoses in the cat. (2) A small amount of solution...

  12. 21 CFR 524.981b - Fluocinolone acetonide solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Fluocinolone acetonide solution. 524.981b Section... § 524.981b Fluocinolone acetonide solution. (a) Specifications. The drug contains 0.01 percent... and certain superficial acute and chronic dermatoses in the cat. (2) A small amount of solution...

  13. 21 CFR 524.981b - Fluocinolone acetonide solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Fluocinolone acetonide solution. 524.981b Section... § 524.981b Fluocinolone acetonide solution. (a) Specifications. The drug contains 0.01 percent... and certain superficial acute and chronic dermatoses in the cat. (2) A small amount of solution...

  14. Sterile endophthalmitis rates and particle size analyses of different formulations of triamcinolone acetonide

    PubMed Central

    Dodwell, David G; Krimmel, Darrel A; de Fiebre, Christopher M

    2015-01-01

    Purpose To evaluate the rate of sterile endophthalmitis (SE) following intravitreal injection of three different formulations of triamcinolone acetonide (TA) in a single physician practice and also to assess the mean diameter and concentration of particles of the two TA formulations currently available commercially in the USA. It was hypothesized that TA formulations with smaller particles and/or greater concentrations would have a higher incidence of SE. Methods Single-site, interventional case series in which the medical records of 392 consecutive eyes receiving intravitreal TA as Triesence®, Kenalog®-40, or preservative-free TA between September 2008 and October 2013 were retrospectively reviewed for the incidence of SE. Particle sizing of TA formulations was conducted by an independent commercial laboratory. Results Five cases of SE were identified. The four cases of SE following Triesence® (4.6%) represented a rate significantly higher than the one case of SE following preservative-free TA (0.6%; P=0.049) and the 0% incidence rate of SE following Kenalog®-40 (P=0.0210). Triesence® had significantly smaller particles than Kenalog®-40 (P<0.0001). Conclusion The rate of SE was the highest with the formulation of TA that had the smallest particle size and highest particle load (number of particles injected). The lowest rate of SE was seen with Kenalog®-40, the only TA formulation that contained a benzyl alcohol preservative. The data do not support a principal causative role of benzyl alcohol in the development of TA-induced SE. Instead, the data support the particle theory of TA-induced SE; however, larger-scale, multicenter studies are needed to confirm and expand on these findings. PMID:26089635

  15. Use of triamcinolone acetonide particles to visualize aqueous outflow.

    PubMed

    Devgan, Uday

    2007-01-01

    Using triamcinolone acetonide suspension within the anterior chamber allows visualization of fluid outflow for glaucoma surgeries where aqueous egress from the eye is desired for pressure control. Dilute non-preserved triamcinolone acetonide particles can be injected into the anterior chamber at the end of intraocular surgeries to assess fluid outflow and to provide an anti-inflammatory effect at the end-target tissue.

  16. Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications.

    PubMed

    Araújo, J; Gonzalez-Mira, E; Egea, M A; Garcia, M L; Souto, E B

    2010-06-30

    The purpose of this study was to develop a novel nanostructured lipid carrier (NLC) for the intravitreal-targeting delivery of triamcinolone acetonide (TA) by direct ocular instillation. A five-level central composite rotable design was used to study the influence of four different variables on the physicochemical characteristics of NLCs. The analysis of variance (ANOVA) statistical test was used to assess the optimization of NLC production parameters. The systems were produced by high pressure homogenization using Precirol ATO5 and squalene as solid and liquid lipids respectively, and Lutrol F68 as surfactant. Homogenization at 600 bar for 3 cycles of the optimized formulation resulted in the production of small NLC (mean diameter < 200 nm) with a homogeneous particle size distribution (polydispersity index (PI) approximately 0.1), of negatively charged surface (approximately |45| mV) and high entrapment efficiency (approximately 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and FT-IR analyses confirmed that TA was mostly entrapped into the NLC, characterized by an amorphous matrix. In vivo Draize test showed no signs of ocular toxicity.

  17. Intracellular delivery of dendrimer triamcinolone acetonide conjugates into microglial and human retinal pigment epithelial cells

    PubMed Central

    Kambhampati, Siva P.; Mishra, Manoj K.; Mastorakos, Panagiotis; Oh, Yumin; Lutty, Gerard A.; Kannan, Rangaramanujam M.

    2016-01-01

    Triamcinolone acetonide (TA) is a potent, intermediate-acting, steroid that has anti-inflammatory and anti-angiogenic activity. Intravitreal administration of TA has been used for diabetic macular edema, proliferative diabetic retinopathy and exudative age-related macular degeneration (AMD). However, the hydrophobicity, lack of solubility, and the side effects limit its effectiveness in the treatment of retinal diseases. In this study, we explore a PAMAM dendrimer-TA conjugate (D-TA) as a potential strategy to improve intracellular delivery and efficacy of TA to target cells. The conjugates were prepared with a high drug payload (~21%) and were readily soluble in saline. Compared to free TA, D-TA demonstrated a significantly improved toxicity profile in two important target [microglial and human retinal pigment epithelium (RPE)] cells. The D-TA was ~100-fold more effective than free TA in its anti-inflammatory activity (measured in microglia), and in suppressing VEGF production (in hypoxic RPE cells). Dendrimer-based delivery may improve the efficacy of TA towards both its key targets of inflammation and VEGF production, with significant clinical implications. PMID:25701805

  18. Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration.

    PubMed

    Iezzi, Raymond; Guru, Bharath R; Glybina, Inna V; Mishra, Manoj K; Kennedy, Alexander; Kannan, Rangaramanujam M

    2012-01-01

    Retinal neuroinflammation, mediated by activated microglia, plays a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in age-related macular degeneration and retinitis pigmentosa. Targeted drug therapy for attenuation of neuroinflammation in the retina was explored using hydroxyl-terminated polyamidoamine (PAMAM) dendrimer-drug conjugate nanodevices. We show that, upon intravitreal administration, PAMAM dendrimers selectively localize within activated outer retinal microglia in two rat models of retinal degeneration, but not in the retina of healthy controls. This pathology-dependent biodistribution was exploited for drug delivery, by covalently conjugating fluocinolone acetonide to the dendrimer. The conjugate released the drug in a sustained manner over 90 days. In vivo efficacy was assessed using the Royal College of Surgeons (RCS) rat retinal degeneration model over a four-week period when peak retinal degeneration occurs. One intravitreal injection of 1 μg of FA conjugated to 7 μg of the dendrimer was able to arrest retinal degeneration, preserve photoreceptor outer nuclear cell counts, and attenuate activated microglia, for an entire month. These studies suggest that PAMAM dendrimers (with no targeting ligands) have an intrinsic ability to selectively localize in activated microglia, and can deliver drugs inside these cells for a sustained period for the treatment of retinal neuroinflammation.

  19. Clear, Aqueous Topical Drop of Triamcinolone Acetonide.

    PubMed

    Trinh, Hoang M; Cholkar, Kishore; Joseph, Mary; Yang, Xiaoyan; Mitra, Ashim K

    2017-02-09

    The objective of this study was to develop a clear aqueous mixed nanomicellar formulation (NMF) of triamcinolone acetonide (TA) with a combination of nonionic surfactant hydrogenated castor oil 60 (HCO-60) and octoxynol-40 (Oc-40). In order to delineate the effects of drug-polymer interactions on entrapment efficiency (EE), loading efficiency (LE), and critical micellar concentration (CMC), a design of experiment (DOE) was performed to optimize the formulation. In this study, full-factorial design has been used with HCO-60 and OC-40 as independent variables. All formulations were prepared following solvent evaporation and film rehydration method, characterized with size, polydispersity, shape, morphology, EE, LE, and CMC. A specific blend of HCO-60 and Oc-40 at a particular wt% ratio (5:1.5) produced highest drug EE, LE, and smallest CMC (0.0216 wt%). Solubility of TA in NMF improved 20 times relative to normal aqueous solubility. Qualitative (1)H NMR studies confirmed the absence of free drug in the outer aqueous NMF medium. Moreover, TA-loaded NMF appeared to be highly stable and well tolerated on human corneal epithelial cells (HCEC) and human retinal pigment epithelial cells (D407 cells). Overall, these studies suggest that TA in NMF is safe and suitable for human topical ocular drop application.

  20. Microdialysis of triamcinolone acetonide in rat muscle.

    PubMed

    Rojas, Cioli; Nagaraja, Nelamangala V; Webb, Alistair I; Derendorf, Hartmut

    2003-02-01

    The objective of this study was to compare plasma and muscle concentrations of triamcinolone acetonide (TA) in the rat by microdialysis. Microdialysis experiments were carried out at steady state in rats after an initial I.V. bolus 50 mg/kg of the phosphate ester of TA (TAP) followed by 23 mg/kg/h infusion. In vivo recovery was calculated by retrodialysis. The concentration determined at steady state in microdialysate, corrected for recovery, was 2.73 +/- 0.42 microg/mL compared to 21.9 +/- 2.3 microg/mL in plasma. The pharmacokinetics of TA in plasma was described by an open two-compartment model with a terminal half-life of 2.7 h. The clearance of TA in rats determined by compartmental analysis was 0.94 L/h/kg. The measured microdialysate levels of TA in muscle, corrected for recovery, were comparable to the predicted free drug levels in the peripheral compartment. Protein binding in rat plasma, measured by ultrafiltration, was 90.1%. The microdialysis in vivo recovery in muscle was similar to the in vitro recovery under stirred conditions. The results show the applicability of microdialysis to measure free tissue concentrations of TA in rats.

  1. Ocular toxicity after intravitreal injection of terconazole.

    PubMed

    Schulman, J A; Peyman, G A; Dietlein, J; Fiscella, R; Colantino, B

    1989-09-01

    Terconazole, a new triazole antifungal agent, was injected intravitreally in doses ranging from 10 to 100 micrograms dissolved in dimethyl sulfoxide (DMSO) 60% into the eyes of New Zealand rabbits. Three control eyes received only DMSO. The eyes were evaluated with biomicroscopy, indirect ophthalmoscopy, electroretinography, and histopathologic examination. From these data, it was determined that an intravitreal injection containing a concentration of 10 micrograms/0.1 mL of terconazole is not toxic to the rabbit eye.

  2. Sustained release of triamcinolone acetonide from an episcleral plaque of multilayered poly-ε-caprolactone matrix.

    PubMed

    Meng, Yongchun; Sun, Shumao; Li, Jie; Nan, Kaihui; Lan, Bifei; Jin, Yubin; Chen, Hao; Cheng, Lingyun

    2014-01-01

    A subtenon injection of triamcinolone acetonide (TA) is a widely used treatment modality for various chorio-retinal diseases. Although it is less invasive than intravitreal injection, it can produce dose-associated ocular complications and has the disadvantages associated with systemic TA exposure. In this study we have developed and evaluated an episcleral film consisting of TA and poly-ε-caprolactone (PCL). The films were prepared by spraying a mixture of PCL in dichloromethane and TA in acetone. The films were produced as 6mm wide and 12 mm long episcleral plaques. X-ray diffraction demonstrated an even distribution of TA crystals in PCL, although the TA was less crystalized than a native TA control. Fourier transform infrared spectroscopy revealed effective integration of TA within the PCL matrix. An in vitro study of the release of TA from the episcleral plaques showed that TA release rate was only 40-50% that of the equivalent native TA control. An in vivo study demonstrated that the plaques were well tolerated in rabbit eyes with significantly less systemic TA exposure. The episcleral plaques provided therapeutic vitreous TA levels for 3 months, while TA levels in the vitreous were detectable for only 1 month following an equivalent dose by subtenon TA injection. The PCL-TA 30-60 episcleral plaque may be further developed as a better alternative treatment for many chronic vitreo-retinal diseases, providing longer and controlled release and fewer drug-associated complications than those associated with a conventional subtenon injection of TA.

  3. Triamcinolone acetonide protects the rat retina from STZ-induced acute inflammation and early vascular leakage.

    PubMed

    Kim, Y H; Choi, M Y; Kim, Y S; Park, C H; Lee, J H; Chung, I Y; Yoo, J M; Choi, W S; Cho, G J; Kang, S S

    2007-09-15

    Streptozotocin (STZ) has been commonly used to induce in vivo and in vitro hyperglycemic diabetes and its toxicity leads to inflammation and vascular injury. Triamcinolone acetonide (TA), as an anti-angiogenic/anti-inflammatory drug, is clinically used to improve the visual acuity in neovascular and edematous ocular diseases. The aim of this study was to investigate the effect of TA on early inflammation and vascular leakage in the retina of STZ-induced hyperglycemic rats. Hyperglycemia was induced in 8-week-old male Sprague-Dawley (SD) rats by a single intraperitoneal injection of STZ (65 mg/kg); only rats with blood glucose levels >13.9 mmol/l 1 day after STZ injection were included in STZ-hyperglycemic group. Sex- and age-matched SD rats injected with buffer were used as the control group. One day before STZ and buffer injection, 2 microl TA (4 mg/ml in saline) and 2 microl saline were intravitreal-injected into the right and the left eyes of rats, respectively. Retinal vascular leakage was measured using the Evans-blue method. Changes in pro-inflammatory target genes, such as tumor necrotic factor (TNF)-alpha, intracellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were assessed by immunoblottings, immunostaining, and ELISA analyses. Vascular hyperleakage and up-regulation of most pro-inflammatory genes peaked within a few days after STZ injection and had recovered. However, these changes were blocked by TA pretreatment. Our data suggest that TA controls STZ-induced early vascular leakage and temporary pro-inflammatory signals in the rat retina.

  4. Management of fluocinolone implant dissociation during implant exchange.

    PubMed

    Yeh, Steven; Cebulla, Colleen M; Witherspoon, S Robert; Emerson, Geoffrey G; Emerson, M Vaughn; Suhler, Eric B; Albini, Thomas A; Flaxel, Christina J

    2009-09-01

    Three patients with chronic, noninfectious uveitis requiring immunosuppressive therapy underwent fluocinolone acetonide (FA) implant exchange complicated by dissociation of the medication reservoir from its anchoring strut. In 2 patients, the medication reservoir descended into the vitreous cavity and required pars plana vitrectomy with intraocular foreign body removal techniques for its retrieval. The use of viscoelastic or perfluorocarbon to elevate the device was helpful in the safe removal of the FA implant device. Surgeons performing FA implant exchange should be aware of this potential complication and anticipate the possible need for vitreoretinal instrumentation and personnel. Patients undergoing FA explantation or exchange should be counseled regarding this potential complication prior to surgery.

  5. The effect of triamcinolone acetonide on laser-induced choroidal neovascularization in mice using a hypoxia visualization bio-imaging probe

    PubMed Central

    Takata, Shinsuke; Masuda, Tomomi; Nakamura, Shinsuke; Kuchimaru, Takahiro; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Nagasawa, Hideko; kizaka-Kondoh, Shinae; Hara, Hideaki

    2015-01-01

    Hypoxic stress is a risk factor of ocular neovascularization. Hypoxia visualization may provide clues regarding the underlying cause of angiogenesis. Recently, we developed a hypoxia-specific probe, protein transduction domain-oxygen-dependent degradation domain-HaloTag-Rhodamine (POH-Rhodamine). In this study, we observed the localization of HIF-1α proteins by immunohistochemistry and the fluorescence of POH-Rhodamine on RPE-choroid flat mounts. Moreover, we compared the localization of POH-Rhodamine with pimonidazole which is a standard reagent for detecting hypoxia. Next, we investigated the effects of triamcinolone acetonide (TAAC) against visual function that was evaluated by recording electroretinogram (ERG) and choroidal neovascularization (CNV) development. Mice were given laser-induced CNV using a diode laser and treated with intravitreal injection of TAAC. Finally, we investigated POH-Rhodamine on CNV treated with TAAC. In this study, the fluorescence of POH-Rhodamine and HIF-1α were co-localized in laser-irradiated sites, and both the POH-Rhodamine and pimonidazole fluorescent areas were almost the same. Intravitreal injection of TAAC restored the reduced ERG b-wave but not the a-wave and decreased the mean CNV area. Furthermore, the area of the POH-Rhodamine-positive cells decreased. These findings indicate that POH-Rhodamine is useful for evaluating tissue hypoxia in a laser-induced CNV model, suggesting that TAAC suppressed CNV through tissue hypoxia improvement. PMID:25927172

  6. Assistive Device for Efficient Intravitreal Injections.

    PubMed

    Ullrich, Franziska; Michels, Stephan; Lehmann, Daniel; Pieters, Roel S; Becker, Matthias; Nelson, Bradley J

    2016-08-01

    Intravitreal therapy is the most common treatment for many chronic ophthalmic diseases, such as age-related macular degeneration. Due to the increasing worldwide demand for intravitreal injections, there exists a need to render this medical procedure more time- and cost-efficient while increasing patient safety. The authors propose a medical assistive device that injects medication intravitreally. Compared to the manual intravitreal injection procedure, an automated device has the potential to increase safety for patients, decrease procedure times, allow for integrated data storage and documentation, and reduce costs for medical staff and expensive operating rooms. This work demonstrates the development of an assistive injection system that is coarsely positioned over the patient's head by the human operator, followed by automatic fine positioning and intravitreal injection through the pars plana. Several safety features, such as continuous eye tracking and iris recognition, have been implemented. The functioning system is demonstrated through ex vivo experiments with porcine eyes. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:752-762.].

  7. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate

    PubMed Central

    Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

    2012-01-01

    The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM. PMID:23202396

  8. Polymeric triamcinolone acetonide nanoparticles as a new alternative in the treatment of uveitis: in vitro and in vivo studies.

    PubMed

    Sabzevari, Araz; Adibkia, Khosro; Hashemi, Hassan; Hedayatfar, Alireza; Mohsenzadeh, Navid; Atyabi, Fatemeh; Ghahremani, Mohammad Hossein; Dinarvand, Rassoul

    2013-05-01

    The purpose of this work was to improve the efficacy of triamcinolone acetonide (TA) in the treatment of endotoxin-induced uveitis (EIU) using a polymeric nanoparticulate drug delivery system. Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were prepared using a modified emulsification/solvent diffusion method. Processing factors affecting loading and size were also studied. After physicochemical studies including in vitro release, X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy, in vivo studies were conducted using nanoparticles sized 195 nm with 3.16% drug loading. Inflammatory factors such as flare, cell, and fibrin were studied in rabbit's eye over 96 h period, using laser flare meter and slit lamp examination. Inflammatory mediators such as NO, PGE2, cell, and protein were measured quantitatively 36 h after intravitreal injection of endotoxin in aqueous humor, and the therapeutic effects were compared in different groups. Results indicated statistically significant differences between the effect of nanoparticles in the treatment of EIU compared to microparticles of TA and prednisolone acetate (PA). There were no significant differences between the effects of TA injection and TA nanoparticles. In conclusion, sustain release biodegradable TA nanoparticles are potential new topical treatment options which can provide better patient compliance.

  9. A pharmacokinetic study to evaluate the absolute bioavailability of triamcinolone acetonide following inhalation administration.

    PubMed

    Argenti, D; Shah, B; Heald, D

    1999-07-01

    Triamcinolone acetonide is a glucocorticoid administered by oral inhalation in the management of asthma. With oral inhalation of glucocorticoids, systemic absorption can come from oropharyngeal, gastrointestinal, or airway deposition of the drug. The objectives of this study were to determine the absolute bioavailability of triamcinolone acetonide following inhalation administration and to delineate the airway contribution of triamcinolone acetonide absorption relative to the absolute bioavailability. All subjects received a 5-minute 400 mcg intravenous infusion of triamcinolone acetonide and a single 800 mcg dose of inhaled triamcinolone acetonide with and without oral charcoal administration in a randomized three-way crossover fashion. The oral charcoal allowed for isolating the pulmonary component of absorption by adsorbing the oropharyngeal and gastrointestinal deposited drug. The mean (+/- SD) absolute bioavailability value for inhaled triamcinolone acetonide was 25% (8.75%). Delineation of the airway contribution of triamcinolone acetonide absorption showed that 10.4% of an inhaled dose is absorbed as triamcinolone acetonide from the lungs. Mean (+/- SD) total body clearance was rapid at 0.57 (0.12) L/hr/kg. The mean (+/- SD) apparent volume of distribution following the intravenous dose was a low 1.96 (0.31) L/kg. No significant differences were noted in the apparent terminal elimination half-life of triamcinolone acetonide (approximately 2.4 hr) between treatments.

  10. L-fucose from vitamin C with only acetonide protection.

    PubMed

    Liu, Zilei; Yoshihara, Akihide; Wormald, Mark R; Jenkinson, Sarah F; Gibson, Vicky; Izumori, Ken; Fleet, George W J

    2014-11-07

    Addition of human milk oligosaccharides (HMO) to baby foods may protect infants from disease. As many simple HMOs are fucosylated this is likely to increase the demand for L-fucose as a synthetic building block. Any chemical synthesis must be cheap to compete with a biotechnological process. Acetonide is the only protecting group we have used in this new synthesis of L-fucose from vitamin C in 27% overall yield (purification by recrystallization; no chromatography required in the entire sequence).

  11. Steerable intravitreal inserts for drug delivery: in vitro and ex vivo mobility experiments.

    PubMed

    Bergeles, Christos; Kummer, Michael P; Kratochvil, Bradley E; Framme, Carsten; Nelson, Bradley J

    2011-01-01

    The progress of wet age-related macular degeneration can now be controlled by intravitreal drug injection. This approach requires repeated injections, which could be avoided by delivering the drug to the retina. Intraocular implants are a promising solution for drug delivery near the retina. Currently, their accurate placement is challenging, and they can only be removed after a vitrectomy. In this paper, we introduce an approach for minimally invasive retinal drug delivery using magnetic intraocular inserts. We briefly discuss the electromagnetic-control system for magnetic implants and then focus on evaluating their ability to move in the vitreous humor. The mobility of magnetic intraocular implants is estimated in vitro with synthesized vitreous humors, and ex vivo with experiments on cadaver porcine eyes. Preliminary results show that with such magnetic implants a vitrectomy can be avoided.

  12. Adverse skin reactions following intravitreal bevacizumab injection

    PubMed Central

    Ameen, S; Entabi, M; Lee, N; Stavrakoglou, A

    2011-01-01

    The authors describe two separate cases of skin eruption following intravitreal bevacizumab injection with evidence to suggest that these were adverse drug reactions to bevacizumab. The authors also discuss how each case was treated and report on the final outcome. PMID:22715260

  13. Pharmacokinetics and safety of intravitreal caspofungin.

    PubMed

    Shen, Ying-Cheng; Liang, Chiao-Ying; Wang, Chun-Yuan; Lin, Keng-Hung; Hsu, Min-Yen; Yuen, Hon-Leung; Wei, Li-Chen

    2014-12-01

    Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

  14. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  15. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  16. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  17. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... solution. 524.981e Section 524.981e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent of fluocinolone acetonide in 60...

  18. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... solution. 524.981e Section 524.981e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent of fluocinolone acetonide in 60...

  19. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... solution. 524.981e Section 524.981e Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a) Specifications. Each milliliter of solution contains 0.01 percent of fluocinolone acetonide in 60...

  20. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  1. 21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fluocinolone acetonide, neomycin sulfate cream. 524.981c Section 524.981c Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The...

  2. Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model.

    PubMed

    Chen, Mei; Li, Xiaoli; Liu, Jinkun; Han, Yin; Cheng, Lingyun

    2015-04-10

    Suprachoroidal injection is an emerging technique for drug delivery to the posterior segment, which is hard to reach by non-invasive approaches. However, the injection technique varies and the associated ocular safety is not well understood. In addition, it is not clear if drug formulation is a major factor in optimizing pharmacodynamics using this technique. The current study was designed to compare the suprachoroidal injection of different drug formulations and to characterize the safety and pharmacodynamics of triamcinolone acetonide (TA) delivered by this technique. Both indocyanine green (ICG) solution and TA suspension, at 50μL, 100μL, and 150μL, were suprachoroidally injected and intraocular pressure (IOP) tonometry, fundus photography, and electroretinography were performed over multiple time points up to eight weeks. After 50μL TA (Kenalog-40) suprachoroidal injection, 4-5 animals at 7 time points were sacrificed for aqueous, vitreous, retina, and plasma collections. TA was quantitated using ultra-performance liquid chromatography tandem mass spectrometry. For comparative efficacy study, 50μL (2mg) suprachoroidal TA versus 20mg subtenon TA were performed 4weeks before induction of experimental uveitis with 10ng of intravitreal lipopolysaccharide. After suprachoroidal injection, IOP had an acute elevation, higher volume caused higher IOP (p<0.0001). Equivalent volume of ICG solution led to a significantly smaller IOP elevation than after TA suprachoroidal injection. This finding suggests better distribution of ICG solution than TA suspension in the suprachoroidal space. Following a 50μL suprachoroidal injection, peak TA concentration in the aqueous was below 1ng/mL. In contrast, the posterior vitreous and retina had 1912ng/mL and 400,369ng/mL TA, respectively. Maximum TA in plasma was 11.6ng/mL. Drug exposure to the posterior retina was 523,910 times more than that to the aqueous and 29,516 times more than systemic TA exposure. In the treatment of

  3. Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats.

    PubMed

    Merodio, Marta; Irache, Juan Manuel; Valamanesh, Fatemeh; Mirshahi, Massoud

    2002-04-01

    Cytomegalovirus (CMV) infection mainly affects endothelial cells of ocular vessels, optic nerve and the retina, resulting in direct or autoimmune damages, uveoretinitis and disturbed vision. The use of colloidal carriers for the intravitreal delivery of ganciclovir may prolong its residence in the eye, minimizing the opacification observed for macroscopic implants. The aim of this work was to evaluate the ocular toxicity induced by the prolonged presence of ganciclovir-loaded bovine serum albumin nanoparticles after their intravitreal injection. The intraocular disposition of these carriers was also studied by immunochemistry. Two weeks post-injection, a significant amount of nanoparticles remained in the vitreous cavity, mainly in a thin layer overlying the retina and in the area close to the blood aqueoUs barrier. Their prolonged residence in the eve seemed to be well tolerated and the histological evaluation of the retina, mainly the photoreceptor layer, and adjacent tissues revealed the absence of inflammatory reactions or alterations in the tissue architecture (i.e. cellular infiltrations or vascular inflammation). In addition, nanoparticles neither alter the expression and distribution of arrestin and rhodopsin autoantigens nor the mineralocorticoid receptor. In summary, the vision was not affected by autoimmune phenomena or alterations in the behavior of ophthalmic cells due to the intravitreal injection of these nanoparticles.

  4. Diabetic papillopathy treated with intravitreal ranibizumab

    PubMed Central

    Yildirim, Mine; Kilic, Deniz; Dursun, Mehmet Emin; Dursun, Birgul

    2017-01-01

    In this report, we present a case of diabetic papillopathy that resolved after a single dose of intravitreal ranibizumab injection. A 50-year-old male presented with painless visual loss in his right eye. His visual acuity was 1/10 in the right eye and 10/10 in the left eye. Anterior segment examination of both eyes was unremarkable. Posterior segment of the right eye showed nonproliferative diabetic retinopathy with a swollen optic disc. Fluorescein angiography and optical coherence tomography were performed. There was dye leakage from the right optic disc. Optical coherence tomography revealed a significant increase in retinal nerve fiber layer thickness. Magnetic resonance imaging of the brain and orbit were normal. The patient received a single intravitreal ranibizumab (0.5 mg) injection. Two weeks after the injection, there was a marked regression of the disc swelling. Three months after the injection the optic disc was pallor and visual acuity was 6/10. PMID:28356776

  5. Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy

    NASA Astrophysics Data System (ADS)

    Li, Xingyi; Wang, Yuqin; Yang, Chengbiao; Shi, Shuai; Jin, Ling; Luo, Zichao; Yu, Jing; Zhang, Zhaoliang; Yang, Zhimou; Chen, Hao

    2014-11-01

    Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton®), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases.Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular

  6. Posterior capsule opacification and neovascularization treated with intravitreal bevacizumab and Nd:YAG capsulotomy

    PubMed Central

    Sánchez-Castro, Grimelda Yuriana; Hitos-Fájer, Alejandra; Mendoza-Schuster, Erick; Velez-Montoya, Raul; Velasco-Barona, Cecilio Francisco

    2008-01-01

    We reported a 75-year-old diabetic man, who developed opacification and neovascularization of the posterior capsule after extracapsular cataract extraction and posterior chamber intraocular lens implantation. The patient was treated with two injections of 2.5 mg of intravitreal bevacizumab. The treatment produced an important regression of the posterior capsular new vessels, allowing us to perform a successful Nd:YAG capsulotomy, clearing the visual axis and improving the visualization of the posterior pole. Even though, best corrected visual acuity was 20/200 due to diabetic macular edema. PMID:19668770

  7. Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

    SciTech Connect

    Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.; Hill, D.E.; Hendrickx, A.G.

    1982-11-01

    The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C was cortisol during the 40-min period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the /sup 3/H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6.

  8. Supramolecular nanofibers of triamcinolone acetonide for uveitis therapy.

    PubMed

    Li, Xingyi; Wang, Yuqin; Yang, Chengbiao; Shi, Shuai; Jin, Ling; Luo, Zichao; Yu, Jing; Zhang, Zhaoliang; Yang, Zhimou; Chen, Hao

    2014-11-06

    Supramolecular nanofibers of prodrugs hold advantages for drug release due to their high drug payload, sustained and constant drug release behavior, and stimuli responsiveness. In this study, we report on a supramolecular hydrogel mainly formed by a clinically used drug triamcinolone acetonide (TA). Such a hydrogel could only be prepared via an ester bond hydrolysis process from its prodrug of succinated triamcinolone acetonide (STA). The resulting hydrogel could constantly release TA in the in vitro release experiment. The TA hydrogel possessed an excellent transscleral penetration ability, as evaluated by the in vitro transscleral transport study. The developed TA hydrogel also exhibited a great ocular compatibility in rats, as indicated by the optical coherence tomography (OCT) images, HE observation, and glial fibrillary acidic protein (GFAP) and vimentin immuno-staining assays of the retinas. Our TA hydrogel showed a decreased efficacy to inhibit ocular inflammation in the rat's experiment autoimmune uveitis (EAU) model compared to the commercial TA suspension (Transton), but without causing complications such as high intraocular pressure and cataracts. These promising properties of the hydrogel indicated its great potential for the treatment of eye diseases.

  9. Triamcinolone acetonide modulates permeability and intercellular adhesion molecule-1 (ICAM-1) expression of the ECV304 cell line: implications for macular degeneration.

    PubMed

    Penfold, P L; Wen, L; Madigan, M C; Gillies, M C; King, N J; Provis, J M

    2000-09-01

    Whilst animal studies and a pilot clinical trial suggest that intravitreal triamcinolone acetonide (TA) may be useful in the treatment of age-related macular degeneration (AMD), its mode of action remains to be fully elucidated. The present study has investigated the capacity of TA to modulate the expression of adhesion molecules and permeability using a human epithelial cell line (ECV304) as a model of the outer blood-retinal barrier (BRB). The influence of TA on the expression of ICAM-1 and MHC-I was studied on resting and phorbol myristate acetate (PMA)- or interferon-gamma (IFN-gamma)- and/or tumour necrosis factor-alpha (TNF-alpha)-activated cells using flow cytometry and immunocytochemistry. Additionally, ECV304 cells were grown to confluence in uncoated Transwell chambers; transepithelial resistance (TER) across resting and PMA-activated cells was monitored. TA significantly decreased the paracellular permeability of ECV304 cells and down-regulated ICAM-1 expression, consistent with immunocytochemical observations. PMA-induced permeability changes were dose-dependent and TA decreased permeability of both resting and PMA-activated monolayers. MHC-I expression by ECV304 cells however, was not significantly affected by TA treatment. The modulation of TER and ICAM-1 expression in vitro correlate with clinical observations, suggesting re-establishment of the BRB and down-regulation of inflammatory markers are the principal effects of intravitreal TA in vivo. The results further indicate that TA has the potential to influence cellular permeability, including the barrier function of the retinal pigment epithelium (RPE) in AMD-affected retinae.

  10. Nasal mucosal inflammation has no effect on the absorption of intranasal triamcinolone acetonide.

    PubMed

    Argenti, D; Colligon, I; Heald, D; Ziemniak, J

    1994-08-01

    The potential for enhanced systemic absorption of intranasal triamcinolone acetonide was explored in patients with inflamed nasal mucosa. Twelve allergic rhinitis patients with documented nasal inflammation, and 12 healthy volunteers, each received a single, therapeutic, 400-micrograms dose of triamcinolone acetonide in each nostril. Blood was obtained at fixed time points after the dose, and plasma concentrations of triamcinolone acetonide were determined by radioimmunoassay. There were no statistically significant differences in any of the derived pharmacokinetic parameters (maximum plasma triamcinolone acetonide concentrations [Cmax], time to maximum plasma triamcinolone concentrations [Tmax], elimination half-life [t1/2], and area under the plasma concentration-time curve [AUC0-12] from 0 to 12 hours) between treatment groups. A once-a-day, chronic regimen (6 weeks) of triamcinolone acetonide was also administered to five patients with allergic rhinitis. Pharmacokinetic parameters were similar to the parameters derived from healthy volunteers after acute administration. There was no evidence of drug accumulation. The results of this study indicate that acute and chronic intranasal administration. The results of this study indicate that acute and chronic intranasal administration of therapeutic doses of triamcinolone acetonide to patients with inflamed nasal mucosa does not result in enhanced systemic drug absorption or accumulation.

  11. Intravitreal properties of porous silicon photonic crystals

    PubMed Central

    Cheng, L; Anglin, E; Cunin, F; Kim, D; Sailor, M J; Falkenstein, I; Tammewar, A; Freeman, W R

    2009-01-01

    Aim To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery. Methods A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology. Results No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles). Conclusion The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases. PMID:18441177

  12. The role of intravitreal chemotherapy for retinoblastoma

    PubMed Central

    Manjandavida, Fairooz P; Shields, Carol L

    2015-01-01

    Targeted therapy in retinoblastoma (RB) is widely accepted as the current management tool with an aim of increasing drug availability at the tumor location. Inevitably the effect is several times higher compared to systemic delivery of chemotherapeutic drugs and carries less systemic toxicity. Despite tremendous advancement in saving life, eye salvage in advanced RB especially with active vitreous seeds remains a challenge. The hypoxic environment of the vitreous and reduced vitreous concentration of the drugs delivered makes these tumor seeds resistant to chemotherapy. Direct delivery of chemotherapeutic drugs into the vitreous cavity aids to overcome these challenges and is progressively being accepted worldwide. However, intraocular procedure in RB was abandoned due to high risk of extraocular tumor dissemination. Recently, the forbidden therapeutic technique was re-explored and modified for safe use. Although eye salvage rate has tremendously improved after intravitreal chemotherapy (IVitC), retinal toxicity, and vision salvage are yet to be validated. In our preliminary report of intravitreal melphalan in 11 eyes, we reported 100% eye salvage and 0% recurrence with an extended 15 months mean follow-up. In this review, we analyzed published reports on IVitC in RB via PubMed, Medline, and conference proceedings citation index, electronic database search, without language restriction that included case series and reports of humans and experimental animal eyes with RB receiving IVitC. PMID:25827545

  13. Experience of intravitreal injections in a tertiary Hospital in Oman

    PubMed Central

    Al-Hinai, Ahmed S.

    2015-01-01

    Aim: To find out statistical data regarding intravitreal injections in an outpatient department setup at a tertiary center in Oman. Design: Retrospective chart review. Methods: Data collection of patients who underwent intravitreal injections from November 2009 to May 2013 at Sultan Qaboos University Hospital. Results: Throughout a period of 42 months, a total of 711 intravitreal injections were performed. That included 214 patients (275 eyes). Around one-third of the eyes received two injections or more. The injected agents were bevacizumab (59.8%), ranibizumab (32.3%), triamcinolone (7.5%), and very few patients with endophthalmitis received intravitreal antibiotics and antifungal agents. The three most common indications for the injection therapy were diabetic macular edema (50.9%), choroidal neovascularization (24.3%), and retinal vein occlusive diseases (11.5%). Serious adverse events were rare, and they occurred as ocular (0.9% per patient) and systemic (3.3% per patient). There were 42 eyes received intravitreal triamcinolone, and 24% of them developed intraocular hypertension that required only medical treatment. Conclusion: Different intravitreal agents are currently used to treat many ocular diseases. Currently, therapy with intravitreal agents is very popular, and it carries a promising outcome with more efficiency and safety. PMID:26903722

  14. Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear.

    PubMed

    Engleder, Elisabeth; Honeder, Clemens; Klobasa, Julia; Wirth, Michael; Arnoldner, Christoph; Gabor, Franz

    2014-08-25

    Intratympanic glucocorticoid therapy aims to reduce the side effects associated with systemic long-time therapy of inner ear diseases or traumata after cochlear implantation. For that purpose, thermoreversible hydrogels being fluid at room temperature but solid at body temperature are known to be appropriate drug delivery systems. In this work, the two key parameters sol-gel transition time and temperature of Poloxamer 407 (POX 407) based hydrogels containing oto-compatible micronized triamcinolone acetonide (TAAc) were evaluated by rheological experiments varying the concentrations of the different compounds. A 20% POX 407 hydrogel in PBS containing 30% TAAc emerged as the most appropriate formulation. Oscillation-rotation-oscillation studies at two temperature levels were found to be an useful in-vitro test system for the hydrogel which revealed sufficient storage stability at 4 °C, injectability of the sol, solidification within 20s at body temperature and persistent stiffness indicating prolonged adhesion at the round window membrane. According to the in-vitro release studies using the Transwell™ system, absorption of the poor water soluble TAAc is partly due to the low amount of dissolved drug but predominantly due to micellar transport resulting in a cumulative release of 262.6±13.4 μg TAAc within one week followed by a sustained release of 193.1±8.3 μg TAAc within the next three weeks. Thus, the formation of POX 407 micelles is the basis not only for gel formation but also absorptivity of TAAc. All in all, fine tuned rheological experiments and absorption studies emerged as useful tools for preclinical evaluation of intratympanally administered hydrogels.

  15. Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear

    PubMed Central

    Engleder, Elisabeth; Honeder, Clemens; Klobasa, Julia; Wirth, Michael; Arnoldner, Christoph; Gabor, Franz

    2014-01-01

    Intratympanic glucocorticoid therapy aims to reduce the side effects associated with systemic long-time therapy of inner ear diseases or traumata after cochlear implantation. For that purpose, thermoreversible hydrogels being fluid at room temperature but solid at body temperature are known to be appropriate drug delivery systems. In this work, the two key parameters sol–gel transition time and temperature of Poloxamer 407 (POX 407) based hydrogels containing oto-compatible micronized triamcinolone acetonide (TAAc) were evaluated by rheological experiments varying the concentrations of the different compounds. A 20% POX 407 hydrogel in PBS containing 30% TAAc emerged as the most appropriate formulation. Oscillation–rotation–oscillation studies at two temperature levels were found to be an useful in-vitro test system for the hydrogel which revealed sufficient storage stability at 4 °C, injectability of the sol, solidification within 20 s at body temperature and persistent stiffness indicating prolonged adhesion at the round window membrane. According to the in-vitro release studies using the Transwell™ system, absorption of the poor water soluble TAAc is partly due to the low amount of dissolved drug but predominantly due to micellar transport resulting in a cumulative release of 262.6 ± 13.4 μg TAAc within one week followed by a sustained release of 193.1 ± 8.3 μg TAAc within the next three weeks. Thus, the formation of POX 407 micelles is the basis not only for gel formation but also absorptivity of TAAc. All in all, fine tuned rheological experiments and absorption studies emerged as useful tools for preclinical evaluation of intratympanally administered hydrogels. PMID:24907595

  16. Mechanisms of in vivo release of triamcinolone acetonide from PLGA microspheres.

    PubMed

    Doty, Amy C; Weinstein, David G; Hirota, Keiji; Olsen, Karl F; Ackermann, Rose; Wang, Yan; Choi, Stephanie; Schwendeman, Steven P

    2017-03-22

    Little is known about the underlying effects controlling in vitro-in vivo correlations (IVIVCs) for biodegradable controlled release microspheres. Most reports of IVIVCs that exist are empirical in nature, typically based on a mathematical relationship between in vitro and in vivo drug release, with the latter often estimated by deconvolution of pharmacokinetic data. In order to improve the ability of in vitro release tests to predict microsphere behavior in vivo and develop more meaningful IVIVCs, the in vivo release mechanisms need to be characterized. Here, two poly(lactic-co-glycolic acid) (PLGA) microsphere formulations encapsulating the model steroid triamcinolone acetonide (Tr-A) were implanted subcutaneously in rats by using a validated cage model, allowing for free fluid and cellular exchange and microsphere retrieval during release. Release kinetics, as well as mechanistic indicators of release such as hydrolysis and mass loss, was measured by direct analysis of the recovered microspheres. Release of Tr-A from both formulations was greatly accelerated in vivo compared to in vitro using agitated phosphate buffered saline +0.02% Tween 80 pH7.4, including rate of PLGA hydrolysis, mass loss and water uptake. Both microsphere formulations exhibited erosion-controlled release in vitro, indicated by similar polymer mass loss kinetics, but only one of the formulations (low molecular weight, free acid terminated) exhibited the same mechanism in vivo. The in vivo release of Tr-A from microspheres made of a higher molecular weight, ester end-capped PLGA displayed an osmotically induced/pore diffusion mechanism based on confocal micrographs of percolating pores in the polymer, not previously observed in vitro. This research indicates the need to fully understand the in vivo environment and how it causes drug release from biodegradable microspheres. This understanding can then be applied to develop in vitro release tests which better mimic this environment and cause

  17. A mass balance study to evaluate the biotransformation and excretion of [14C]-triamcinolone acetonide following oral administration.

    PubMed

    Argenti, D; Jensen, B K; Hensel, R; Bordeaux, K; Schleimer, R; Bickel, C; Heald, D

    2000-07-01

    The principle objective of this study was to characterize the absorption, metabolism, and disposition of orally administered [14C]-triamcinolone acetonide. Six healthy male subjects each received a single 100 microCi (approximately 800 micrograms) oral dose of [14C]-triamcinolone acetonide. Plasma, urine, and fecal samples were collected at selected times and analyzed for triamcinolone acetonide and [14C]-derived radioactivity. Plasma protein binding of triamcinolone acetonide was also determined. Metabolite profiling and identification were carried out in plasma and excreta. Principle metabolites were assessed for activity with in vitro anti-inflammatory models. [14C]-triamcinolone acetonide was found to be systemically absorbed following oral administration. The presystemic metabolism and clearance of triamcinolone acetonide were extensive, with only a small fraction of the total plasma radioactivity being made up of triamcinolone acetonide. Little to no parent compound was detected in the plasma 24 hours after administration. Most of the urinary and fecally [14C]-derived radioactivity was also excreted within 24 and 72 hours postdose, respectively. Mean plasma protein binding of triamcinolone acetonide was constant, predictable, and a relatively low 68% over a 24-fold range of plasma concentrations. Three principle metabolites of triamcinolone acetonide were profiled in plasma, urine, and feces. These metabolites were identified as 6 beta-hydroxy triamcinolone, 21-carboxylic acid triamcinolone acetonide, and 6 beta-hydroxy-21-oic triamcinolone acetonide. All three metabolites failed to show any concentration-dependent effects in anti-inflammatory models evaluating IL-5-sustained eosinophil viability and IgE-induced basophil histamine release.

  18. Ex vivo investigation of ocular tissue distribution following intravitreal administration of connexin43 mimetic peptide using the microdialysis technique and LC-MS/MS.

    PubMed

    Bisht, Rohit; Mandal, Abhirup; Rupenthal, Ilva D; Mitra, Ashim K

    2016-12-01

    This study aimed to develop and evaluate an ex vivo eye model for intravitreal drug sampling and tissue distribution of connexin43 mimetic peptide (Cx43MP) following intravitreal injection using the microdialysis technique and LC-MS/MS. An LC-MS/MS method was developed, validated, and applied for quantification of Cx43MP in ocular tissues. Microdialysis probes were calibrated for in vitro recovery studies. Bovine eyes were fixed in a customized eye holder and after intravitreal injection of Cx43MP, microdialysis probes were implanted in the vitreous body. Vitreous samples were collected at particular time intervals over 24 h. Moreover, 24 and 48 h after intravitreal injection ocular tissues were collected, processed, and analyzed for Cx43MP concentrations using LC-MS/MS. The LC-MS/MS method showed good linearity (r (2) = 0.9991). The mean percent recovery for lower (LQC), medium (MQC), and higher quality control (HQC) (0.244, 3.906, and 125 μg/mL) was found to be 83.83, 84.92, and 94.52, respectively, with accuracy ranges between 96 and 99 % and limits of detection (LOD) and quantification (LOQ) of 0.122 and 0.412 μg/mL. The in vitro recovery of the probes was found to be over 80 %. As per microdialysis sample analysis, the Cx43MP concentration was found to increase slowly in the vitreous body up to 16 h and thereafter declined. After 48 h, the Cx43MP concentration was higher in vitreous, cornea, and retina compared to lens, iris, and aqueous humor. This ex vivo model may therefore be a useful tool to investigate intravitreal kinetics and ocular disposition of therapeutic molecules after intravitreal injection.

  19. Successful treatment of pseudophakic cystoid macular edema with intravitreal bevacizumab.

    PubMed

    Barone, Antonio; Prascina, Francesco; Russo, Vincenzo; Iaculli, Cristiana; Primavera, Vito; Querques, Giuseppe; Stella, Andrea; Delle Noci, Nicola

    2008-07-01

    A 67-year-old woman developed refractory pseudophakic cystoid macular edema (CME) after uneventful phacoemulsification. Three months after an intravitreal injection of bevacizumab (1.25 mg), the CME was completely resolved, with resultant improvement in visual acuity.

  20. Corticosteroid implants for chronic non-infectious uveitis

    PubMed Central

    Brady, Christopher J; Villanti, Andrea C; Law, Hua Andrew; Rahimy, Ehsan; Reddy, Rahul; Sieving, Pamela C; Garg, Sunir J; Tang, Johnny

    2016-01-01

    Background Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary body, choroid). Uveitis is the fifth most common cause of vision loss in high-income countries, accounting for 5% to 20% of legal blindness, with the highest incidence of disease in the working-age population. Corticosteroids are the mainstay of acute treatment for all anatomical subtypes of non-infectious uveitis and can be administered orally, topically with drops or ointments, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. Objectives To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com) (last searched 15 April 2013), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform(ICTRP) (www.who.int/ictrp/search/en).We did not use any date or language restrictions in the electronic search for studies. We last searched the electronic databases on 6 November 2015. We also searched reference lists of included study reports, citation databases, and abstracts and clinical study presentations from professional meetings. Selection criteria We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone intravitreal implants with standard

  1. Enhanced bioavailability by buccal administration of triamcinolone acetonide from the bioadhesive gels in rabbits.

    PubMed

    Shin, S C; Bum, J P; Choi, J S

    2000-11-19

    The pharmacokinetics and bioavailability of triamcinolone acetonide were determined to investigate buccal absorption from the mucoadhesive gels in rabbits. The enhancing effect of sodium deoxycholate as an enhancer on the buccal absorption of triamcinolone acetonide from the mucoadhesive gels was evaluated in rabbits. Thus, 2 mg/kg of triamcinolone acetonide was administered from the mucoadhesive gels containing an enhancer (enhancer group) or not (control group) via the buccal routes and compared with intravenous routes (1 mg/kg, i.v. group). AUC of the control, enhancer and i.v group were 2374+/-915, 3778+/-1721 and 3945+/-2085 h ng/ml, respectively, and the absolutive bioavailability of enhancer or i.v to control group were 159.14 or 332.35%, respectively. The average C(max) of control and enhancer group were 263+/-159 and 362+/-201 ng/ml, and the mean T(max) of the control group and enhancer group were 5.00+/-1.67 and 4.33+/-0.82 h, respectively, but there was no significant difference. As the triamcinolone acetonide gels containing sodium deoxycholate as an enhancer was administered to rabbits via the buccal routes, the relative bioavailability showed about 1.59-fold compared with the control group. Buccal administration of triamcinolone acetonide gels containing sodium deoxycholate as an enhancer to rabbits showed a relatively constant, sustained blood concentration with minimal fluctuation.

  2. Diclofenac and triamcinolone acetonide impair tenocytic differentiation and promote adipocytic differentiation of mesenchymal stem cells

    PubMed Central

    2013-01-01

    Background Tendinopathies are often empirically treated with oral/topical nonsteroidal anti-inflammatory medications and corticosteroid injections despite their unclear effects on tendon regeneration. Recent studies indicate that tendon progenitors exhibit stem cell-like properties, i.e., differentiation to osteoblasts, adipocytes, and chondrocytes, in addition to tenocytes. Our present study aims at understanding the effects of triamcinolone acetonide and diclofenac on tenocytic differentiation of mesenchymal stem cells. Methods The murine fibroblast C3H10T1/2 cell line was induced to tenocytic differentiation by growth differentiation factor-7. Cell proliferation and differentiation with the exposure of different concentrations of triamcinolone acetonide and diclofenac were measured by WST-1 assay and real-time polymerase chain reaction analysis, respectively. Results Cell proliferation was decreased in a concentration-dependent manner when exposed to triamcinolone acetonide and diclofenac. In addition to tenocytic differentiation, adipocyte formation was observed, both at gene expression and microscopic level, when the cells were exposed to triamcinolone acetonide or high concentrations of diclofenac. Conclusions Our results indicate that triamcinolone acetonide and diclofenac might alter mesenchymal stem cell differentiation in a nonfavorable way regarding tendon regeneration; therefore, these medications should be used with more caution clinically. PMID:24004657

  3. In vitro permeation studies of triamcinolone acetonide mouthwashes.

    PubMed

    Ungphaiboon, S; Maitani, Y

    2001-06-04

    The effects of vehicle composition, contact time of mouthwash and cosolvent on permeation of triamcinolone acetonide (TA) were investigated in vitro using hamster cheek pouch mucosa and synthetic membranes. Mouthwashes containing 0.1% TA with and without the mucoadhesive carboxyvinyl polymer were formulated. Aqueous suspensions and Orabase were used as control formulations. The contact time of mouthwash was varied from 1 to 5 min. Ethanol was used as a cosolvent in various binary-water mixtures. TA was delivered to a significantly lesser extent to mucosal tissue by the mouthwash than by the aqueous suspension (P < 0.001), but to a higher extent than by the Orabase formulation (P < 0.001). No effects of contact time or the mucoadhesive polymer were observed on amount of TA accumulated in the mucosal membrane. These observations have suggested that the use of carboxyvinyl polymer and a high content of ethanol are not appropriate as vehicles for local drug delivery but are suitable for transmucosal drug carriers.

  4. Uniform suspension of the clustered triamcinolone acetonide particle.

    PubMed

    Sugimoto, Masahiko; Kondo, Mineo; Horiguchi, Masayuki

    2013-01-01

    Purpose. MaQaid (MaQ) is a new triamcinolone acetonide commercialised in Japan to visualize the vitreous. Because MaQ is preservative-free, it has a lower risk of ocular toxicities. However, since MaQ is only available as a powder, it needs suspenssion. Suspension does not always result uniformally, which causes poor visibility. This study reports a new MaQ suspension for better visibility. Methods. After medium addition to a MaQ vial, various methods were used. These included the use of (1) vortex mixer, (2) two syringes and a three-way stopcock, and (3) ultrasonic washer. We calculated suspended MaQ concentration (n = 5). To evaluate the reproducibility, we estimated the coefficient of variance (CV, n = 3). We used this MaQ for pig eyes, and vitreous visualization was simulated. Subsequently, we used this MaQ suspension for humans. Results. MaQ suspensions were sucessfull, and the concentrations of single particles increased significantly (P < 0.01). The CV was 36.1% for the routine method and 9.03% ffor the new method. Administration of a suspended MaQ made it possible to clearly visualize the vitreous in both pig and human eyes. Conclusions. We devised new techniques for uniformal MaQ suspension. These new methods can compensate for the MaQ disadvantages and ensure a safety surgery.

  5. Enhancing the buccal mucosal uptake and retention of triamcinolone acetonide.

    PubMed

    Nicolazzo, Joseph A; Reed, Barry L; Finnin, Barrie C

    2005-07-20

    In this study, the buccal mucosal uptake and retention of triamcinolone acetonide (TAC) were assessed in the presence of the skin penetration enhancer, Azone (AZ). Porcine buccal mucosa was excised, mounted in modified Ussing chambers, and pretreated with ethanolic solutions of AZ. After 2 h, the rate of TAC disappearance from the donor chamber and TAC appearance in the receptor chamber was monitored, and the mucosal retention of TAC was determined at the completion of the experiment. The permeability and mucosal uptake of TAC was also determined using the TAC-containing proprietary product, Kenalog in Orabase (KO), in the presence and absence of AZ. Pretreatment of the buccal mucosa with AZ increased the TAC disappearance permeability coefficient from 4.78+/-0.31x10(-5) cm/s to 7.12+/-0.53x10(-5) cm/s. While the TAC appearance permeability coefficient was also enhanced 3.8-fold, a 4.4-fold increase in the tissue concentration of TAC was observed. Incorporation of AZ into KO did not result in an enhanced tissue concentration of TAC, however, when the tissue was pretreated with AZ, significantly higher amounts of TAC accumulated in the tissue. Pretreatment of the buccal mucosa with AZ results in increased tissue concentrations of TAC, which may be of clinical benefit in the treatment of oral mucosal inflammatory conditions.

  6. In vitro recovery of triamcinolone acetonide in microdialysis.

    PubMed

    Rojas, C; Nagaraja, N V; Derendorf, H

    2000-09-01

    The purpose of this study was to assess the factors affecting the calibration of the microdialysis probe for the in vitro recovery of triamcinolone acetonide (TA). Recoveries of TA were determined in microdialysis, retrodialysis, and no-net flux methods. Experiments were performed at room temperature or 37 degrees C while the reservoir medium was either stirred or unstirred. The effect of the viscosity of the medium on the recovery was studied using methylcellulose gel spiked with TA. Recovery was also calculated by the no-net-flux method in Ringer's solution and in plasma. Stirring the medium increased the recovery of TA by 30%. The recovery was higher at 37 degrees C under stirred or unstirred conditions and was same in either direction of dialysis. Increasing viscosity of the reservoir medium decreased the recovery (55% in Ringer's solution to 14% in 20% methylcellulose gel). Recovery from spiked plasma under stirred conditions was only 15% and this shift which was also seen in no-net-flux method was accounted for by the protein binding. Binding of TA, determined by ultrafiltration, was 20% in 5% gel and 81% in plasma. The recovery determined by the no-net-flux method was similar to the retrodialysis result. Stirring, temperature, viscosity and protein binding in the reservoir medium affected the in vitro recovery of TA.

  7. Multilamellar liposomes of triamcinolone acetonide: preparation, stability, and characterization.

    PubMed

    Clares, B; Gallardo, V; Medina, M M; Ruiz, Ma A

    2009-01-01

    The aim of this study was to assess and characterize the stability of multilamellar liposomes as a delivery vehicle for triamcinolone acetonide. A standardized preparation method for a liposomal delivery vehicle was developed, after varying composition and storage conditions, and assessing encapsulation efficiency and loss of active principle. The assessment of temperature as a factor in formula stability during storage showed that stability improved under refrigeration (4-6 degrees C) (less early diffusion of active principle through the liposomal wall), in comparison with samples stored at room temperature. To improve stability, cholesterol was added to some formulae, which although resulting in a decrease in average encapsulation efficiency, mitigated subsequent losses of retained active principle (formulae 4, 5, and 6), in comparison with those without cholesterol (formulae 1, 2, and 3). This was evident both under refrigerated and room-temperature conditions. Finally, after testing the effects of adding an antioxidant and/or preservative to the formulae, a liposomal design was achieved with acceptable stability, vesicle dimensions, and encapsulation efficiency.

  8. Comparison of intracameral dexamethasone and intracameral triamcinolone acetonide injection at the end of phacoemulsification surgery

    PubMed Central

    Güngör, Sirel Gür; Bulam, Begüm; Akman, Ahmet; Çolak, Meriç

    2014-01-01

    Purpose: To compare the results of intracameral dexamethasone and intracameral triamcinolone acetonide injection in patients that underwent cataract surgery with phacoemulsification. Materials and Methods: Sixty eyes of 60 patients that underwent cataract surgery with phacoemulsification were randomized into two groups. Preoperative visual acuity of all patients was 0.5 or lower and intraocular pressures were under 21mmHg. After surgery, eyes in group 1 (30 eyes) were injected with 0.4 mg/0.1 ml dexamethasone into the anterior chamber, and eyes in group 2 (30 eyes) were injected with 2 mg/0.05 ml triamcinolone acetonide into the anterior chamber. All eyes received standard postoperative prednisolone acetate and moxifloxacin eye drops. The biomicroscopic evaluation, visual acuity, and intraocular pressure measurements were done at baseline (preoperatively) and on postoperative days 1, 7 and 30. Results: There were no statistically significant differences in mean visual acuity, the amount of anterior cells and flare between the two groups (P ≥ 0.05). Mean intraocular pressure values at postoperative first day were significantly higher in group 2 than in group 1 (P = 0.009). The mean intraocular pressures on days 7 and 30 after surgery were not statistically different between the two groups (P ≥ 0.05). Conclusions: Intracameral dexamethasone and intracameral triamcinolone acetonide were similarly effective in controlling postoperative inflammation following phacoemulsification. However, the intraocular pressures on postoperative first day were higher in patients receiving intracameral triamcinolone acetonide. The highest intraocular pressure in triamcinolone acetonide group was 24 mmHg, and stabilized in a few days, therefore using triamcinolone acetonide may impose a minimal risk to patients. Nevertheless, intracameral dexamethasone seems to be a better alternative to apply at the end of surgery to suppress the inflammation during the first 24 hours. PMID

  9. Air entry into the anterior chamber post intravitreal injection of Eylea.

    PubMed

    Lim, Wei Sing; Sikandar, Munir; Jackson, Heather

    2016-07-20

    An 84-year-old man had air entry into the anterior chamber following intravitreal injection. The air bubble was reabsorbed over time without any complications. No further problems occurred with subsequent intravitreal injections.

  10. Intravitreal Melphalan for Vitreous Seeds: Initial Experience in China

    PubMed Central

    Ji, Xunda; Hua, Peiyan; Li, Jing; Li, Jiakai; Zhao, Junyang; Zhao, Peiquan

    2016-01-01

    Purpose. To evaluate the efficacy of intravitreal melphalan for vitreous seeds from retinoblastoma in Chinese patients. Methods. This is a retrospective review of 17 consecutive Chinese patients (19 eyes) with viable vitreous seeds from retinoblastoma. The patients received multiple intravitreal injections of 20 ug melphalan. Results. The International Classification of Retinoblastoma groups were B in 1 eye, C in 5 eyes, D in 11 eyes, and E in 2 eyes. On average, 6 injections (range: 1–15) were given to each eye at the interval of 2–4 weeks. Successful control of vitreous seeds was achieved in 16 of 19 eyes (84.21%). Globe retention was achieved in 73.68% (14/19) eyes. The patients were followed up for 27 months on average (median: 26; range: 17–42 months). There is a significant difference in response to intravitreal melphalan for cloud, spheres, and dust seeds with a median number of injections of 9, 6, and 3, respectively (P = 0.003). Complications related to intravitreal melphalan included vitreous hemorrhage, cataract, salt-and-pepper retinopathy, and pupil posterior synechia. There was no case of epibulbar extension or systemic metastasis within the period of follow-up. Conclusion. Intravitreal melphalan achieved a high local control rate for vitreous seeds without extraocular extension and with acceptable toxicity in Chinese retinoblastoma patients. PMID:26977313

  11. Intravitreal methotrexate infusion for proliferative vitreoretinopathy

    PubMed Central

    Sadaka, Ama; Sisk, Robert A; Osher, James M; Toygar, Okan; Duncan, Melinda K; Riemann, Christopher D

    2016-01-01

    Purpose The purpose of this study was to evaluate intravitreal methotrexate infusion (IMI) during pars plana vitrectomy (PPV) for retinal detachment in patients with high risk for the development of proliferative vitreoretinopathy (PVR). Methods Patients presenting with severe recurrent PVR with tractional retinal detachment and/or a history of severe ocular inflammation were treated with IMI. Clinical outcomes were determined from a retrospective medical chart review. Results Twenty-nine eyes presenting with either tractional retinal detachment and recurrent PVR (n=22) or a history of severe inflammation associated with high PVR risk (n=7) received IMI during PPV. Best-corrected visual acuity at 6 months was ≥20/200 in 19 of 29 eyes (66%) and remained stable or improved compared with initial presentation in 24 of 29 eyes (83%). At the last follow-up examination, the retinas of 26 of 29 eyes (90%) remained attached after IMI while three eyes required another reattachment procedure. Three additional eyes (10%) developed recurrent limited PVR without recurrent RD and were observed. No complications attributable to IMI occurred during a mean follow-up of 27 months. Conclusion Eyes at high risk for PVR development due to a history of prior PVR or intraocular inflammation had a low incidence of PVR following IMI at the time of PPV for RD repair. No significant safety issues from IMI were observed in this series. PMID:27698550

  12. Management of noninfectious posterior uveitis with intravitreal drug therapy

    PubMed Central

    Tan, Hui Yi; Agarwal, Aniruddha; Lee, Cecilia S; Chhablani, Jay; Gupta, Vishali; Khatri, Manoj; Nirmal, Jayabalan; Pavesio, Carlos; Agrawal, Rupesh

    2016-01-01

    Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis). PMID:27789936

  13. Intravitreal infusion: A novel approach for intraocular drug delivery

    PubMed Central

    Tian, Jiao; Liu, Jia; Liu, Xiao; Xiao, Yangyan; Tang, Luosheng

    2016-01-01

    Intraocular injection has become an increasingly important intervention in the treatment of posterior segment diseases. However, an acute intraocular pressure (IOP) elevation after intravitreal injection is a common concern. This study aimed to evaluate the efficacy of intravitreal infusion in maintaining stable IOP in a rabbit model. Trypan blue (TB) 0.06% with an external pump was used to evaluate intravitreal infusion in rabbit eyes. Groups A (50 μL), B (100 μL), C (150 μL), and D (200 μL) were slowly infused over 30 minutes with TB. As a control, Group E underwent conventional intravitreal injection of 100 μL of TB. Group F received a bolus infusion of 100 μL of TB within 1 minute. The mean increases in IOP during infusion for each group were: Group A (7.93 ± 3.80 mmHg), B (13.97 ± 3.17 mmHg), C (19.91 ± 6.06 mmHg) and D (29.38 ± 8.97 mmHg). Immediately post-injection in group E the mean increase in IOP amounted to 34.33 ± 6.57 mmHg. The mean increase in IOP of group F after bolus infusion was 49.89 ± 1.71 mmHg. Intravitreal infusion maintains a stable IOP and provides a controlled infusion speed compared with intravitreal injection. PMID:27886224

  14. Acute sterile endophthalmitis following intravitreal bevacizumab: case series

    PubMed Central

    Orozco-Hernández, Axel; Ortega-Larrocea, Ximena; Sánchez-Bermúdez, Gustavo; García-Aguirre, Gerardo; Cantón, Virgilio Morales; Velez-Montoya, Raul

    2014-01-01

    Background Since the ophthalmological community adopted the use of intravitreal bevacizumab as an accepted off-label treatment for neovascular diseases, the amount of knowledge regarding its effects and properties has been increasing continually. In the last few years, there have been an increasing number of reports about sterile intraocular inflammation and intraocular pressure elevations after intravitreal bevacizumab. In the following case series, we describe the clinical presentation and outcomes of ten consecutive cases of patients developing mild-to-severe sterile intraocular inflammation after intravitreal bevacizumab and their management. Methods This report presents a retrospective case series. We reviewed the medical records of ten consecutive patients from a group of 46, in whom repackaged bevacizumab in individual aliquots from two vials from the same batch were used. All surgical procedures were performed using standard sterile techniques in the operating room. At each follow-up visit, patients underwent a complete ophthalmological examination including visual acuity assessment, intraocular pressure, biomicroscopy, and posterior fundus examination. Results Ten patients presented sterile endophthalmitis with an onset time of 3.5±1.95 days. The clinical characteristics were mild pain, slight visual loss, conjunctival hyperemia, and various degrees of intraocular inflammation with microhypopyon. All cultures were negative. All patients were managed with topical steroids and antibiotics, except two, in whom, due to severe vitreous cells, intravitreal antibiotics were used. Three patients showed a transient elevation of intraocular pressure. Only 50% of the patients regained a visual acuity equal or better to the baseline visual acuity on file. Conclusion The increasing number of intravitreal injections of bevacizumab applied every day, due to its widespread acceptance, might be one reason why the number of cases of sterile endophthalmitis is rising. Fast

  15. 21 CFR 524.981e - Fluocinolone acetonide, dimethyl sulfoxide otic solution.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.981e Fluocinolone acetonide, dimethyl sulfoxide otic solution. (a...-responsive lesions may be due to the presence of an infection which requires identification or...

  16. Short-term efficacy of intravitreal dobesilate in central serous chorioretinopathy

    PubMed Central

    2012-01-01

    Purpose To report the anatomic and functional outcome of intravitreal dobesilate to treat recurrent central serous chorioretinopathy (CSC). Methods This is an interventional case report in which dobesilate was intravitreally injected in a case of recurrent CSC. Main measures included fundoscopy, Snellen visual acuity (VA) testing, fluorescein angiography and optical coherence tomography (OCT). Results We present anatomical and functional evidences, obtained as early as eleven days after the treatment, of the efficacy of intravitreal dobesilate, in the treatment of chronic CSC condition. The effect after intravitreal dobesilate injection for CSC might be related to the normalization of retinal architecture. Conclusions Intravitreal dobesilate may be an effective treatment option for recurrent CSC. PMID:22788836

  17. Intravitreal Bevacizumab with or without Triamcinolone for Refractory Diabetic Macular Edema: Long-term Results of a Clinical Trial

    PubMed Central

    Shoeibi, Nasser; Ahmadieh, Hamid; Entezari, Morteza; Yaseri, Mehdi

    2013-01-01

    Purpose To report the long-term results of intravitreal bevacizumab (IVB) injection alone or combined, at the time of first IVB injection, with intravitreal triamcinolone acetonide (IVT) for treatment of refractory diabetic macular edema (DME). Methods In this randomized clinical trial, 115 eyes of 101 patients with refractory DME were enrolled and randomly assigned to one of the three study arms: the IVB group (41 eyes) received three consecutive injections of 1.25 mg IVB at 6-week intervals; the IVB/IVT group (37 eyes) additionally received 2 mg of IVT at the time of first IVB injection; and the control (sham injection) group. Patients in the IVB and IVB/IVT groups were followed for a mean of 13.3 months and received retreatment with IVB alone whenever indicated. Main outcome measures were best corrected visual acuity (BCVA) and central macular thickness (CMT). Results At the last follow up, CMT decreased significantly in the IVB group (p=0.013) but it was not significant (p=0.13) in the IVB/IVT group. Mean CMT improvement was 91 (95% CI, 20 to 161) microns and 57 (95% CI, -18 to 133) microns in the IVB and IVB/IVT groups, respectively. Mean BCVA improvement from baseline was 0.28 (95% CI, 0.18 to 0.38) logMAR (P=0.017) in the IVB group and 0.19 (95% CI, 0.08 to 0.30) logMAR (P=0.001) in the IVB/IVT group. There was no difference between the two groups in terms of visual improvment (p=0.42). In generalized linear mixed model, only the time interval between the last injection and CMT measurement was statistically significant (P=0.04). The same results were repeated for visual acuity (P=0.03). Conclusion Three loading doses of IVB (added doses if required) have long-term beneficial effects for treatment of refractory DME. Adding triamcinolone to this regimen provides no additional long-term benefit. PMID:23943683

  18. Intravitreal aflibercept versus intravitreal ranibizumab for the treatment of diabetic macular edema

    PubMed Central

    Fouda, Sameh Mosaad; Bahgat, Ahmed M

    2017-01-01

    Purpose The purpose of this study was to compare the efficacy of intravitreal aflibercept and ranibizumab in the treatment of diabetic macular edema (DME) in eyes with moderate visual loss. Patients and methods This study is a randomized prospective study. Seventy eyes with DME were divided into two groups (each containing 35 eyes). Eyes in group I were treated with intravitreal injection of 2 mg/0.05 mL aflibercept and eyes in group II were treated with intravitreal injection of 0.5 mg/0.1 mL ranibizumab. All the eyes had three successive injections as a loading dose (with 1 month interval), and then the patients were followed up monthly for 12 months. The outcomes of the study were visual acuity, central macular thickness (CMT), and the number of re-injections of the drug. Results Mean age of the patients in group I was 55.05±4.7 years and in group II was 56.64±5.8 years (P=0.17). The mean baseline best corrected visual acuity (BCVA) of eyes treated with aflibercept was 0.17±0.05 and with ranibizumab was 0.18±0.04 (P=0.9). BCVA was improved in both the groups at the end of the follow-up period and was found to be 0.42±0.28 and 0.37±0.23, respectively (P=0.27). The mean baseline CMT of eyes in group I was 465.29±33.7 µm and in group II was 471.5±34.4 µm (P=0.65). CMT decreased in both the groups to 360.8±85.7 µm and 387.3±87.8 µm, respectively (P=0.2). The mean number of drug re-injection was 2.62±0.68 and 3.03±0.95 in both the groups, respectively (P=0.02). Conclusion Aflibercept and ranibizumab have the same efficacy in the treatment of DME in eyes with moderate visual loss but with less number of drug re-injection and less treatment burden with aflibercept (2.62±0.68 versus 3.03±0.95). PMID:28356711

  19. Intravitreal Phacoemulsification Using Torsional Handpiece for Retained Lens Fragments

    PubMed Central

    Kumar, Vinod; Takkar, Brijesh

    2016-01-01

    Purpose: To evaluate the results of intravitreal phacoemulsification with torsional hand piece in eyes with posteriorly dislocated lens fragments. Methods: In this prospective, interventional case series, 15 eyes with retained lens fragments following phacoemulsification were included. All patients underwent standard three-port pars plana vitrectomy and intravitreal phacoemulsification using sleeveless, torsional hand piece (OZiL™, Alcon's Infiniti Vision System). Patients were followed up for a minimum of six months to evaluate the visual outcomes and complications. Results: The preoperative best-corrected visual acuity (BCVA) ranged from light perception to 0.3. No complications such as thermal burns of the scleral wound, retinal damage due to flying lens fragments, or difficult lens aspiration occurred during intravitreal phacoemulsification. Mean post-operative BCVA at the final follow-up was 0.5. Two eyes developed cystoid macular edema, which was managed medically. No retinal detachment was noted. Conclusion: Intravitreal phacoemulsification using torsional hand piece is a safe and effective alternative to conventional longitudinal phacofragmentation. PMID:27621783

  20. Tower microneedle minimizes vitreal reflux in intravitreal injection.

    PubMed

    Lee, Chang Yeol; You, Yong Sung; Lee, Sung Ho; Jung, Hyungil

    2013-10-01

    Intravitreal injection is widely used for easy control of drug levels in posterior segment of the eye by injecting the drug directly with hypodermic needles. Patients, however, often experience complications from intravitreal injection due to repeated injections, increased intraocular pressure, and infection. In addition, injected drug reflux after intravitreal injection makes it challenging to maintain predetermined drug dose due to the drug loss through backward effusions. Here, we described that the Tower Microneedle can reduce initial reflux and bleb formation due to its smaller outer diameter compared to a traditional hypodermic needle. Furthermore, we use phenylephrine hydrochloride for pupil expansion and demonstrated that Tower Microneedle induced similar pupil expansions using only half the drug volume, in the same period of time, compared to the 31 Gauge hypodermic needle. Consequently, Tower Microneedle achieves the same therapeutic effect in the vitreous body using fewer drugs than a traditional hypodermic needle due to the decreased backward drug effusion. Tower Microneedle described herein holds great promise for intravitreal injection with less reflux and lower drug dosage.

  1. Successful Resolution of Preretinal Haemorrhage with Intravitreal Ranibizumab

    PubMed Central

    Noorlaila, Baharuddin; Raja-Azmi, Mohd-Noor

    2016-01-01

    We would like to report two cases of preretinal haemorrhage from two different aetiology courses of bleeding being treated with intravitreal ranibizumab and its outcome. Our first case was a 39-year-old man with a diagnosis of severe aplastic anaemia that presented with bilateral premacular haemorrhages in both eyes. His right eye vision was 6/45 and it was counting finger in the left eye. He was treated with intravitreal ranibizumab once to the right eye and twice to the left eye. Right eye showed complete resolution of premacular haemorrhage and minimal residual premacular haemorrhage in the left eye at 3 months after initial presentation. Our second case was a 32-year-old healthy teacher that presented with preretinal haemorrhage at superotemporal region extending to macular area in left eye secondary to valsalva retinopathy. Her left vision was counting finger. She was treated with single intravitreal ranibizumab to the left eye. There was significant reduction of premacular haemorrhage and her left eye vision improved to 6/6 at 10 weeks after injection. Both cases had favourable outcome with intravitreal ranibizumab and can be considered as nonsurgical treatment option in treating premacular haemorrhage. PMID:27800200

  2. Intravitreal injection of Bevacizumab in diabetic macular edema

    PubMed Central

    Ateeq, Asim; Tahir, Muhammad Ali; Cheema, Alyscia; Dahri, Arif; Tareen, Saifullah

    2014-01-01

    Objective: To assess the effectiveness of intravitreal injection of Bevacizumab in the treatment of diabetic macular edema. Methods: This case series was conducted at Department of Ophthalmology, Jinnah Post Graduate Medical Centre (JPMC), Karachi. The duration of study was six months from May 26, 2011 to November 25, 2011. The study group comprised of 54 patients of the Diabetic Macular Edema (DME). Intravitreal injection of 1.25 mg of bevacizumab (Avastin) was injected 3.5 mm from the limbus under topical anaesthetic drops. Post procedure follow up was scheduled on 1st post procedure day and after one month. Post procedure Optical Coherence tomography (OCT) was performed in all patients 1 week before and 1st month after 1st injection. The results were statistically analyzed through SPSS 17. Results: Out of the 54 Eyes of 54 Patients who were given the Intravitreal injection of Avastin (Bevacizumab), 43 Eyes (79.6%) showed more than ten percent decrease in macular thickness from pre-injection thickness, 10 Eyes (18.5%) showed less than ten percent decrease and 1 Eye (1.9%) showed increase in macular thickness post operatively after one month. Conclusions: Intravitreal injection of Bevacizumab (Avastin) is effective in the treatment of diabetic macular edema. PMID:25674143

  3. Intravitreal aflibercept treatment in eyes with exudative age-related macular degeneration following prior treatment with intravitreal ranibizumab

    PubMed Central

    Narayan, Daniel Sanju; Muecke, James

    2015-01-01

    Background: To investigate visual and anatomical outcomes in eyes with exudative age-related macular degeneration treated with intravitreal aflibercept following prior treatment with intravitreal ranibizumab. Materials and Methods: Retrospective, single-center study of 192 eyes treated with 0.5 mg intravitreal ranibizumab every 4 weeks for three consecutive doses followed by a variable dose schedule. After more than 12 months of ranibizumab treatment, eyes that required ranibizumab injections at 4-week or 6-week intervals were switched to aflibercept therapy. Results: After 12–69 months (42 months ± 18 months, mean ± standard deviation [SD]) of treatment with intravitreal ranibizumab, 80 eyes were changed to 2 mg intravitreal aflibercept treatment with follow-up after 12–18 months (16 months ± 1 month, mean ± SD). Thirty-nine eyes had persistent macular fluid after treatment with ranibizumab. Mean logMAR visual acuity (VA) in eyes treated with ranibizumab changed by − 0.089 ± 0.310 (mean ± SD; P = 0.0003), which correlates to an approximate gain of 4.5 letters. The number of eyes with macular fluid decreased from 39 to 23 after aflibercept treatment. Mean logMAR VA in eyes with intraretinal macular fluid treated with aflibercept changed by −0.079 ± 0.134 (mean ± SD; P = 0.006), which correlates to an approximate gain of 4 letters. Mean logMAR VA in eyes with submacular fluid was not significantly different after aflibercept treatment. Conclusion: Eyes with persistent intraretinal macular fluid had visual and anatomic response after changing from ranibizumab to aflibercept treatment. PMID:26669334

  4. In vitro phototoxic properties of triamcinolone 16,17-acetonide and its main photoproducts.

    PubMed

    Miolo, Giorgia; Ricci, Andrea; Caffieri, Sergio; Levorato, Laura; Fasani, Elisa; Albini, Angelo

    2003-11-01

    The phototoxicity of triamcinolone 16,17-acetonide has been estimated through a panel of in vitro tests. The main target involved in phototoxicity induced by triamcinolone appeared to be the cell membrane. Oxygen-independent photohemolysis was observed. A photochemical study in water and buffered solutions supported the conclusion that this is related to the action of radicals formed upon UV irradiation (in particular UV-B) by Norrish Type-I fragmentation of the C-20 ketone group. Peroxy radicals were formed in the presence of oxygen and were the active species in that case. Three photoproducts, isolated from the photodegradation of the drug, were submitted to the same toxicity tests. Two of them were proved to possess toxic or phototoxic properties on erythrocytes, primarily induced by UV-B light, and may participate in the photosensitizing activity of triamcinolone 16,17-acetonide. Our in vitro results suggest that the drug can elicit weak photosensitizing properties in vivo.

  5. Self-assembled phenylalanine-α,β-dehydrophenylalanine nanotubes for sustained intravitreal delivery of a multi-targeted tyrosine kinase inhibitor.

    PubMed

    Panda, Jiban J; Yandrapu, Sarath; Kadam, Rajendra S; Chauhan, Virander S; Kompella, Uday B

    2013-12-28

    Current standard of care for sustained back of the eye drug delivery is surgical placement or injection of large, slow release implants using a relatively large 22 gauge needle. We designed novel dipeptide (phenylalanine-α,β-dehydrophenylalanine; Phe-∆Phe) based nanotubes with a diameter of ~15-30 nm and a length of ~1500 nm that could be injected with a 33 gauge needle for sustained intravitreal delivery of pazopanib, a multi-targeted tyrosine kinase inhibitor. The drug could be loaded during nanotube assembly or post-loaded after nanotube formation, with the former being more efficient at 25% w/w pazopanib loading and ~55% loading efficiency. Plain and peptide loaded nanotube were non-cytotoxic to retinal pigment epithelial cells even at a concentration of 200 μg/ml. Following intravitreal injection of fluorescently labeled nanotubes using a 33 gauge needle in a rat model, the nanotube persistence and drug delivery were monitored using noninvasive fluorophotometry, electron microscopy and mass spectrometry analysis. Nanotubes persisted in the vitreous humor during the 15 days study and pazopanib levels in the vitreous humor, retina, and choroid-RPE at the end of the study were 4.5, 5, and 2.5-folds higher, respectively, compared to the plain drug. Thus, Phe-∆Phe nanotubes allow intravitreal injections with a small gauge needle and sustain drug delivery.

  6. Macular ischemia after intravitreal amikacin on patient with intraocular foreign body.

    PubMed

    Kartasasmita, Arief; Mona, Susi; Iskandar, Erwin; Sovani, Iwan; Panggabean, Djonggi

    2017-01-01

    Background: Although still used in third world countries, amikacin has a harmful effect to be used intravitreally. Purpose: To report macular ischemia after an intravitreal injection of amikacin Methods: A case report regarding a traumatized eye of a 26-year-old man that was injected intravitreally with amikacin due to intraocular foreign body endophthalmitis Results: Angiography and OCT show macular ischemia due to amikacin toxicity. Conclusion: The case reported here is to alert about the potential harmful effect of intravitreally injected amikacin despite its role as an accepted regimen for endohthalmitis cases.

  7. Macular ischemia after intravitreal amikacin on patient with intraocular foreign body

    PubMed Central

    Kartasasmita, Arief; Mona, Susi; Iskandar, Erwin; Sovani, Iwan; Panggabean, Djonggi

    2017-01-01

    Background: Although still used in third world countries, amikacin has a harmful effect to be used intravitreally. Purpose: To report macular ischemia after an intravitreal injection of amikacin Methods: A case report regarding a traumatized eye of a 26-year-old man that was injected intravitreally with amikacin due to intraocular foreign body endophthalmitis Results: Angiography and OCT show macular ischemia due to amikacin toxicity. Conclusion: The case reported here is to alert about the potential harmful effect of intravitreally injected amikacin despite its role as an accepted regimen for endohthalmitis cases.

  8. Safety of intravitreal quinupristin/dalfopristin in an animal model

    PubMed Central

    Giordano, Veronica E.; Hernandez-Da Mota, Sergio E.; Adabache-Guel, Tania N.; Castillejos-Chevez, Armando; Corredor-Casas, Sonia; Salinas-Longoria, Samantha M.; Romero-Vera, Rafael; Jimenez-Sierra, Juan M.; Guerrero-Naranjo, Jose L.; Morales-Canton, Virgilio

    2016-01-01

    AIM To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. METHODS Eighteen New Zealand white rabbits were divided into three treatment groups (groups 1 to 3) and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection (baseline) and after 7, 14, 21 and 28d, followed by enucleation for histological examination. RESULTS Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 (Kruskall-Wallis test, P=0.000). By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealed no significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. CONCLUSION Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/0.1 mL in this rabbit model. PMID:27158605

  9. Intravitreal injections: a review of the evidence for best practice.

    PubMed

    Fagan, Xavier J; Al-Qureshi, Salmaan

    2013-07-01

    Intravitreal injection is a common procedure performed by ophthalmologists. It is a quick and targeted treatment for a number of ophthalmic conditions. Despite this, the potential to cause serious complications and patient discomfort cannot be ignored. This article presents the level of evidence in the scientific literature supporting common practices such as location of the procedure, anaesthetic choice, sterile procedure techniques, comparison of some common pharmaceutical agents and the use of antibiotics.

  10. Intravitreal Bevacizumab (Avastin) for Diabetic Retinopathy: The 2010 GLADAOF Lecture

    PubMed Central

    Arevalo, J. Fernando; Sanchez, Juan G.; Lasave, Andres F.; Wu, Lihteh; Maia, Mauricio; Bonafonte, Sergio; Brito, Miguel; Alezzandrini, Arturo A.; Restrepo, Natalia; Berrocal, Maria H.; Saravia, Mario; Farah, Michel Eid; Fromow-Guerra, Jans; Morales-Canton, Virgilio

    2011-01-01

    This paper demonstrates multiple benefits of intravitreal bevacizumab (IVB) on diabetic retinopathy (DR) including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) at 24 months of followup. This is a retrospective multicenter interventional comparative case series of intravitreal injections of 1.25 or 2.5 mg of bevacizumab for DME, PDR without tractional retinal detachment (TRD), and patients who experienced the development or progression of TRD after an intravitreal injection of 1.25 or 2.5 mg of bevacizumab before vitrectomy for the management of PDR. The results indicate that IVB injections may have a beneficial effect on macular thickness and visual acuity (VA) in diffuse DME. Therefore, in the future this new therapy could complement focal/grid laser photocoagulation in DME. In PDR, this new option could be an adjuvant agent to panretina photocoagulation so that more selective therapy may be applied. Finally, TRD in PDR may occur or progress after IVB used as an adjuvant to vitrectomy. Surgery should be performed 4 days after IVB. Most patients had poorly controlled diabetes mellitus associated with elevated HbA1c, insulin administration, PDR refractory to panretinal photocoagulation, and longer time between IVB and vitrectomy. PMID:21584260

  11. Topical treatment of the buccal mucosa and wounded skin in rats with a triamcinolone acetonide-loaded hydrogel prepared using an electron beam.

    PubMed

    Choi, Soon Gil; Baek, Eun Jung; Davaa, Enkhzaya; Nho, Young-Chang; Lim, Youn-Mook; Park, Jong-Seok; Gwon, Hui-Jeong; Huh, Kang Moo; Park, Jeong-Sook

    2013-04-15

    In this study, a triamcinolone acetonide-loaded hydrogel was prepared by electron beam irradiation and evaluated for use as a buccal mucoadhesive drug delivery system. A poloxamer was modified to have vinyl end groups for preparation of the hydrogel via an irradiation cross-linking reaction. Carbopol was introduced to improve the mucoadhesive properties of the hydrogel. The in vitro release of triamcinolone acetonide from the hydrogel was examined at 37 °C. To investigate the topical therapeutic effect of triamcinolone acetonide on wounded rat skin and buccal mucosa, the appearance and histological changes were evaluated for 15 days after treatment with saline, triamcinolone acetonide solution, triamcinolone acetonide hydrogel, and blank hydrogel, respectively. Triamcinolone acetonide was released constantly from the gel formulation at 37 °C and reach 100% at about 48 h. After 15 days, in the skin of the group treated with the triamcinolone acetonide-loaded hydrogel, the wound was almost completely free of crust and a number of skin appendages, including hair follicles, had formed at the margins of the tissue. Moreover, the inflammatory response in the buccal mucosa was milder than that in the other groups, and the wound surface was completely covered with regenerating, hyperkeratotic, thickened epithelial cells. Our results indicate that the triamcinolone-acetonide hydrogel showed sustained drug release behavior, while causing no significant histopathological changes in buccal and skin tissues. Therefore, this hydrogel system may be a powerful means of drug delivery for buccal administration with controlled release and no tissue irritation.

  12. Intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial.

    PubMed

    Soheilian, Masoud; Karimi, Saeed; Ramezani, Alireza; Montahai, Talieh; Yaseri, Mehdi; Soheilian, Roham; Peyman, Gholam A

    2015-06-01

    The purpose of the study is to compare single injection of intravitreal diclofenac (IVD) with intravitreal bevacizumab (IVB) in the treatment of eyes with naïve diabetic macular edema (DME). In this randomized clinical trial, 57 eyes of 57 patients were randomly assigned to IVD group (30 eyes), cases who received a single intravitreal injection of diclofenac (500 μg/0.1 ml), and IVB group (27 eyes), cases who received a single intravitreal injection of bevacizumab (1.25 mg). Change in best-corrected visual acuity in logMAR at week 12 was the primary outcome measure. Secondary outcomes included changes in central macular thickness, macular leakage, and potential injection-related complications. Best-corrected visual acuity improved significantly more in the IVD group than in the IVB group (P = 0.033), from 0.57 ± 0.25 to 0.49 ± 0.31 versus 0.55 ± 0.24-0.59 ± 0.27 logMAR at 12 weeks, respectively. However, the difference of macular thickness changes was in favor of IVB, but not to a significant level. The amount of change in leakage was not significantly different between the groups either. None of the eyes, in either group, developed ocular hypertension (≥23 mmHg) or cataract progression. No important injection-related complication was observed during the study period. This study demonstrated the superiority of IVD over IVB in the treatment of naïve DME regarding functional, but not anatomical outcomes. Therefore, using IVD as an adjunct or even alternative to other treatments might enhance the functional outcomes in such cases. Further studies are warranted to confirm potential benefit of IVD observed in this study.

  13. Simultaneous determination of triamcinolone acetonide palmitate and triamcinolone acetonide in beagle dog plasma by UPLC-MS/MS and its application to a long-term pharmacokinetic study of triamcinolone acetonide palmitate lipid emulsion injection.

    PubMed

    Liu, Hui; Yang, Mingjing; Wu, Panpan; Guan, Jiao; Men, Lei; Lin, Hongli; Tang, Xing; Zhao, Yunli; Yu, Zhiguo

    2015-02-01

    In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid-liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C18 column (50 mm × 2.1mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5→397.3, 435.3→415.3 and 393.3→355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1-1,000 ng/ml for TAP and 0.5-500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of -8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7-104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs.

  14. Tower microneedle via reverse drawing lithography for innocuous intravitreal drug delivery.

    PubMed

    Lee, Chang Yeol; Lee, Kwang; You, Yong Sung; Lee, Sung Ho; Jung, Hyungil

    2013-06-01

    The "tower microneedle" (TM) via reverse drawing lithography for intravitreal injection by fabricating a long hollow microneedle on the blunt hypodermic needle: The hollow hole between the microneedle and hypodermic needle is aligned concentrically, and fifteen degree bevel angle is introduced to TM by laser cutting to achieve intravitreal injection with minimal damage to eye tissue.

  15. Lowered intraocular pressure in a glaucoma patient after intravitreal injection of ocriplasmin

    PubMed Central

    McClintock, Michael; MacCumber, Mathew W

    2015-01-01

    We report the case of a glaucoma patient who received a single intravitreal injection of 125 µg ocriplasmin for vitreomacular traction in the right eye. The patient had bilateral advanced glaucoma and had previously undergone an implantation of an Ahmed glaucoma valve in the right eye and trabeculectomy in both eyes. The patient was using three topical ophthalmic intraocular pressure (IOP)-lowering medications on the day of injection. Baseline uncorrected Snellen visual acuity was 20/80-1 and IOP was 19 mmHg. Resolution of vitreomacular traction was achieved 1 week after injection. IOP was transiently decreased, reaching a maximum reduction of 12 mmHg below baseline at 1 month after injection, when serous choroidal effusion was also present. IOP returned to baseline levels and choroidal effusion resolved at 2 months after injection of IOP-lowering medication. Vitrectomy with epiretinal membrane and internal limiting membrane peeling, endolaser photocoagulation, and fluid–gas exchange were performed in the right eye ~3.5 months after injection to treat persistent epiretinal membrane, and presumed tractional retinal detachment. Final visual acuity was 20/50+ and IOP was 18 mmHg at 16 weeks after surgery. To our knowledge, this is the first report of IOP reduction and serous choroidal effusion after ocriplasmin injection. PMID:26604668

  16. Expression Profile of Intravitreous Cytokines, Chemokines and Growth Factors in Patients with Fuchs Heterochromic Iridocyclitis

    PubMed Central

    Suzuki, Kaori; Suzuki, Yukihiko; Matsumoto, Mitsuo; Nakazawa, Mitsuru

    2010-01-01

    Purpose To report the postoperative courses of 2 patients with Fuchs heterochromic iridocyclitis (FHI) and the concentrations of various cytokines, chemokines and growth factors in vitreous fluid samples to obtain insights into pathobiochemical aspects. Subjects: The patients were a 27- and a 47-year-old woman. Phacoemulsification and aspiration, intraocular lens (IOL) implantation, and pars plana vitrectomy were performed to treat their cataracts and vitreous opacities. During their early postoperative periods, inflammatory cells precipitated on the IOL and intraocular pressure was increased in both patients. Methods At the time of surgery, undiluted vitreous fluid specimens were collected. The concentrations of multiple cytokines, chemokines and growth factors were measured by a bead array immunodetection system. Results The levels of interleukin-1ra, −5, −6, −8, −10 and −13, interferon-inducible 10-kDa protein, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and regulated upon activation, normal T-cell expressed and secreted (RANTES) were significantly elevated in vitreous fluid in both patients. Conclusion Although the postoperative course was generally favorable in patients with FHI, steroid instillation was necessary for a few months postoperatively, as precipitates easily formed on the IOL surface and elevated intraocular pressure. The profiles of intravitreal concentrations of cytokines, chemokines and growth factors may characterize postoperative inflammatory reactions. PMID:20737053

  17. Pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits

    PubMed Central

    Sinapis, Christos I; Routsias, John G; Sinapis, Angelos I; Sinapis, Dimitrios I; Agrogiannis, George D; Pantopoulou, Alkistis; Theocharis, Stamatis E; Baltatzis, Stefanos; Patsouris, Efstratios; Perrea, Despoina

    2011-01-01

    Purpose: To describe the pharmacokinetics of intravitreal bevacizumab (Avastin®) in rabbits. Methods: The right eye of 20 rabbits was injected intravitreally with 1.25 mg/0.05 mL bevacizumab. Both eyes of four rabbits each time were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in serum, aqueous humor, and vitreous. Results: Maximum vitreous (406.25 μg/mL) and aqueous humor (5.83 μg/mL) concentrations of bevacizumab in the right eye were measured at day 1. Serum bevacizumab concentration peaked at day 8 (0.413 μg/mL) and declined to 0.032 μg/mL at 4 weeks. Half-life values in right vitreous, right aqueous humor, and serum were 6.61, 6.51, and 5.87 days, respectively. Concentration of bevacizumab in the vitreous of the noninjected eye peaked at day 8 (0.335 ng/mL) and declined to 0.218 ng/mL at 4 weeks. In the aqueous humor of the noninjected eye, maximum concentration of bevacizumab was achieved at day 8 (1.6125 ng/mL) and declined (to 0.11 ng/mL) at 4 weeks. Conclusion: The vitreous half-life of 1.25 mg/0.05 mL intravitreal bevacizumab was 6.61 days in this rabbit model. Maximum concentrations of bevacizumab were reached at day 1 in both vitreous and aqueous humor of the right eye and at day 8 in the serum. Very low concentrations of bevacizumab were measured in the fellow noninjected eye. PMID:21629577

  18. Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection

    PubMed Central

    Romero-Aroca, Pedro; Sararols, Laura; Arias, Lluis; Casaroli-Marano, Ricardo P; Bassaganyas, Francisca

    2012-01-01

    Background The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops. Methods The study was conducted in five hospitals in Spain and included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). Results In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049%) in the azithromycin group and five (0.12%) in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32–3.72, P < 0.001). There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049%) and two (0.048%) in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622–1.407, P = 0.407). Conjunctival hyperemia was observed in 12 cases in the azithromycin group and none in the ofloxacin group. Conclusion The risk of endophthalmitis was significantly greater with ofloxacin than with azithromycin. These findings provide a valuable addition to the ever-increasing pool of information on endophthalmitis prophylaxis after intravitreal injection, although further large-scale studies are required to provide definitive conclusions. PMID:23109798

  19. Fundus spectroscopy and studies in retinal oximetry using intravitreal illumination

    NASA Astrophysics Data System (ADS)

    Salyer, David Alan

    This dissertation documents the development of a new illumination technique for use in the studies of retinal oximetry and fundus spectroscopy. Intravitreal illumination is a technique where the back of the eye is illuminated trans-sclerally using a scanning monochromator coupled into a fiber optic illuminator. Retinal oximetry is the process of measuring the oxygen saturation of blood contained in retinal vessels by quantitative measurement of the characteristic color shift seen as blood oxygen saturation changes from oxygenated blood (reddish) to deoxygenated blood (bluish). Retinal oximetry was first attempted in 1963 but due to a variety of problems with accuracy and difficulty of measurement, has not matured to the point of clinical acceptability or commercial viability. Accurate retinal oximetry relies in part on an adequate understanding of the spectral reflectance characteristics of the fundus. The use of intravitreal illumination allows new investigations into the spectral reflectance properties of the fundus. The results of much research in fundus reflectance and retinal oximetry is detailed in this document, providing new insight into both of these related fields of study. Intravitreal illumination has been used to study retinal vessel oximetry and fundus reflectometry resulting in several important findings that are presented in this document. Studies on enucleated swine eyes have provided new insight into the bidirectional reflectance distribution function of the fundus. Research on live swine has shown accurate measurement of retinal vessel oxygen saturation and provided the first in vivo spectral transmittance measurement of the sensory retina. A secondary discovery during this research suggests that vitrectomy alters the retinal vasculature, an finding that should spawn new research in its own right.

  20. Macular laser photocoagulation with or without intravitreal triamcinolone pretreatment for diabetic macular edema: a result from five randomized controlled trials

    PubMed Central

    Liu, Xiang-Dong; Zhou, Xiao-Dong; Wang, Zhi; Shen, Yong-Ming

    2016-01-01

    AIM To assess possible benefits of intravitreal triamcinolone acetonide (IVTA) injection as pretreatment for macular laser photocoagulation (MLP) in patients with diabetic macular edema (DME). METHODS Published randomized controlled trials (RCTs) concerning MLP with or without IVTA pretreatment for DME were retrieved from databases CNKI, Medline, EMbase, Web of Science, and the Cochrane Library. A Meta-analysis on eligible studies was conducted using RevMan 5.0 software. Two investigators independently assessed the quality of the trials and extracted data. Main outcome measures included the change in best corrected visual acuity (BCVA), difference in central macular thickness (CMT) and adverse events reporting in particular elevated intraocular pressure within the follow-up period. The results were pooled using weight mean difference (WMD) or odds risk (OR) with their corresponding 95% confidence intervals (CI). A fixed- or random-effect model was employed depending on the heterogeneity of the inclusion trials. RESULTS Finally, five independent RCTs were identified and used for comparing MLP with IVTA pretreatment (131 eyes) with MLP alone (133 eyes, control group). The overall study quality was relatively higher according to the modified Jadad scale. The Meta-analysis showed that MLP with IVTA pretreatment significantly reduced CMT at one, three and six months (P=0.002, 0.0003 and 0.04, respectively), compared with MLP alone. The IVTA pretreatment group showed statistically significant improvements in BCVA at the one-month follow up as compared with the control group (P=0.03). At three- and six-month follow up, there was a beneficial trend towards improving visual acuity in the IVTA pretreatment group without statistical significance between groups (P=0.06 and 0.20, respectively). The incidence of elevation of intraocular pressure was significantly higher in the IVTA pretreatment group than in the control group (P<0.0001). No evidence of publication bias was

  1. Pharmacokinetics of Intravitreally Injected Bevacizumab in Vitrectomized Eyes

    PubMed Central

    Ahn, Jeeyun; Kim, Hyuncheol; Park, Ji Hyun; Park, Sunyoung; Hwang, Duck Jin; Park, Kyu Hyung

    2013-01-01

    Abstract Purpose To compare the pharmacokinetics (PKs) of intravitreally injected bevacizumab in vitrectomized versus nonvitrectomized control rabbit eyes. Methods Twenty-five-gauge pars plana vitrectomy without lensectomy was performed in 17 right rabbit eyes (V) and 18 nonvitrectomized right rabbit eyes served as controls (C). After 1.25 mg/0.05 mL intravitreal bevacizumab (IVB) injections, eyes were enucleated at 1 h, 1, 2, 5, 14, and 30 days after the injection and immediately frozen at −80°C. Bevacizumab concentrations were determined after separation of frozen vitreous and aqueous humor (AH) compartments using indirect enzyme-linked immunosorbent assay. Bevacizumab concentration–time data were analyzed to obtain PK data. Results Vitreous clearance of IVB consisted of 2 phases, the first fast distribution and second slow elimination phase. Clearance of IVB was accelerated in V eyes only during the first phase and not in the second phase. The vitreous concentration percent ratios between V and C eyes were 94.7% (1 h), 70.5% (1 day), 89.2% (2 days), 94.2% (5 days), 99.2% (14 days), and 79.1% (30 days). Overall vitreous half-lives were 6.99 and 7.06 days for V and C eyes, respectively (1.6-h difference). Conclusion Overall IVB PKs in rabbit eyes after vitrectomy without lensectomy are not substantially different from nonvitrectomized control eyes. PMID:23735192

  2. Retinal toxicity of intravitreal tenecteplase in the rabbit

    PubMed Central

    Rowley, S A; Vijayasekaran, S; Yu, P K; McAllister, I L; Yu, D-Yi

    2004-01-01

    Aim: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes. Methods: Tenecteplase (25–350 μg in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination. Results: No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 μg. At a dose of 150 μg ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 μg and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses. Conclusion: A dose of 50 μg tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion. PMID:15031179

  3. An intravitreal biodegradable sustained release naproxen and 5-fluorouracil system for the treatment of experimental post-traumatic proliferative vitreoretinopathy

    PubMed Central

    Cardillo, J A; Farah, M E; Mitre, J; Morales, P H; Costa, R A; Melo, L A S; Kuppermann, B; Jorge, R; Ashton, P

    2004-01-01

    Background/aims: To determine the potential of an intravitreal sustained release naproxen and 5-fluorouracil (NA/5-FU) codrug for the treatment of experimental proliferative vitreoretinopathy (PVR) in a model for trauma associated tractional retinal detachment (TRD). Methods: Sustained release pellets were prepared by covalently linking naproxen to 5-fluorouracil. Drug release was tested in vitro and toxic effects were evaluated by electroretinography and light microscopy. Traumatic PVR was induced in pigmented rabbits by performing a scleral laceration, followed by repair and intravitreal injection of 0.4 ml of autologous blood. Thirty six eyes were treated with a sustained release implant containing 1.5 mg NA/5-FU as a codrug and 36 control eyes were submitted to surgery alone. Eyes were evaluated for TRD by serial indirect ophthalmoscope examination at different time points followed by postmortem fundus evaluation of the enucleated eye Results: The NA/5-FU pellets were found to provide linear release of 5-FU and naproxen over the 30 day duration of the in vitro release test. Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly lower in eyes treated with the codrug pellet. There were no drug related toxic effects evident on histopathological or electroretinograph examination of eyes containing the NA/5-FU pellet. Conclusions: The results suggest that this NA/5-FU codrug device effectively inhibits the progression of PVR in a rabbit trauma model that closely resembles PVR in humans. Additional studies to add knowledge to these initial findings and to clarify the potential of the codrug device for the treatment of human PVR are warranted. PMID:15317716

  4. Cochlear Implants.

    ERIC Educational Resources Information Center

    Clark, Catherine; Scott, Larry

    This brochure explains what a cochlear implant is, lists the types of individuals with deafness who may be helped by a cochlear implant, describes the process of evaluating people for cochlear implants, discusses the surgical process for implanting the aid, traces the path of sound through the cochlear implant to the brain, notes the costs of…

  5. Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

    PubMed

    Del Amo, Eva M; Urtti, Arto

    2015-08-01

    Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

  6. The remote effects of intravitreal anti-VEGF therapy

    PubMed Central

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the “Prof. Dr. Theodor Burghele” Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life PMID:27928444

  7. The remote effects of intravitreal anti-VEGF therapy.

    PubMed

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.

  8. Intravitreal bevacizumab for persistent macular edema with proliferative diabetic retinopathy.

    PubMed

    Gulkilik, Gokhan; Taskapili, Muhittin; Kocabora, Selim; Muftuoglu, Gulipek; Demirci, Goktug

    2010-12-01

    To evaluate the effectiveness of an intravitreal bevacizumab injection on retinal neovascularization and diabetic macular edema (DME) refractory to laser photocoagulation therapy. Thirty-four eyes of 22 patients with proliferative diabetic retinopathy and DME refractory to laser photocoagulation therapy received an intravitreal injection of 1.25 mg/0.05 ml of bevazicumab. Changes in mean best-corrected visual acuity (BCVA), central macular thickness (CMT), regression of neovascularization over time, and correlation between BCVA and CMT were evaluated. Follow-up visits were at weeks 1, 2 and 4 and months 3 and 6. Mean BCVA was significantly better than baseline only at week 2 (P = 0.036). Mean CMT decreased significantly from baseline at weeks 1, 2, and 4 (P = 0.001). At months 3 and 6, mean CMT increased, albeit insignificantly (P = 0.804 and P = 1.0). The decrease in fluorescein leakage was moderate in all eyes at the end of week 1. At week 2, there was total resolution of fluorescein leakage in 24 (70.5%) eyes and moderate resolution in 10 (29.5%) eyes. At the end of month 3, the fluorescein leakage was fully resolved in 5 (14.7%) eyes, moderately resolved in 24 (70.5%) eyes, and was similar to baseline in 5 (14.7%) eyes. At month 6, the fluorescein leakage was fully resolved in 3 (8.8%) eyes, moderately resolved in 20 (58.8%) eyes, and was similar to baseline in 11 (32.4%) eyes. A moderate but insignificant negative correlation was found between visual acuity and CMT (P > 0.05). Persistence or recurrence of neovascular tissue after panretinal photocoagulation may be attributed to the production of vascular endothelial growth factor by the residual ischemic retina, which also results in persistent or recurrent DME despite macular grid photocoagulation.

  9. Transdermal delivery system of triamcinolone acetonide from a gel using phonophoresis.

    PubMed

    Yang, Jae-Heon; Kim, Dae-Keun; Yun, Mi-Young; Kim, Tae-Youl; Shin, Sang-Chul

    2006-05-01

    Triamcinolone acetonide (TA) is a corticosteroid that is used in the systemic and topical treatment of many inflammatory diseases. In this study, a phonophoretic drug delivery system was designed to enhance the TA permeability and the influence of ultrasound was examined. In order to establish the transdermal delivery system for TA, a hydrophilic carbopol gel containing TA was prepared after adopting phonophoresis. A permeation study through mouse skin was performed at 37 degrees C using a Franz diffusion cell, and the ultrasound treatment was carried out for 10 h. The level of TA permeation through the skin was evaluated under various ultrasound conditions including the frequency (1.0, 3.0 MHz), intensity (1.0, 2.5 W/cm2), and duty cycle (continuous, pulse mode) using a 0.5% TA gel. The highest permeation was observed under the ultrasound treatment conditions of low frequency, high intensity, and in continuous mode.

  10. [Infralesional injections with triamcinolone-acetonide in the treatment of lichen rubber of the mouth mucosa].

    PubMed

    Capusan, I; Lazar, V; Weingart, F

    1983-09-15

    Lichen planus of the buccal mucosa with its various clinical manifestations has proved to be much more resistant to general therapeutical means than the cutaneous lesions. Repeated infralesional (sub-mucosal) injections of triamcinolon-acetonid (Kenalon Volon in a 10 per cent suspension applied to 12 patients, 4 of them with erosive lesions, have revealed particular efficiency if given at 7 oder 14 day's intervals. After 2 to 6 injections, we could already observe positive results occurring faster with papular of reticular than with erosive forms of the disease. Slight relapses may occur after 4 to 6 months disappearing, however, after 1 to 2 injections. Provided that antiseptic measures are maintained, tamponade of the salivary orifices is applied and intravascular injection by aspiration control avoided, unexpected local and general sequelae will not occur. Most of the patients have been in ambulatory care.

  11. Some biochemical effects of triamcinolone acetonide on rat liver and muscle.

    PubMed

    Peters, R F; Richardson, M C; Small, M; White, A M

    1970-02-01

    1. The powerful anti-inflammatory glucocorticoid triamcinolone acetonide, administered to rats at 20 and 2.5mg/kg, leads to a decrease in the incorporation in vivo of [(3)H]uridine and [(32)P]orthophosphate into hind-limb skeletal muscle. 2. At the higher dose, this decrease in the rate of incorporation of precursors into RNA precedes a decrease in the incorporating ability of muscle ribosomes, which commences about 4-5h after drug administration, but is unaccompanied by any changes in the concentration of tissue ATP or free amino acids. 3. The ribosomal dysfunction extends to polyribosomes, which can only be successfully isolated from the muscle of triamcinolone-treated animals after the addition of alpha-amylase to the tissue homogenate to remove glycogen. 4. The specific radioactivity of muscle protein labelled in vivo with (14)C-labelled amino acids does not decrease progressively after triamcinolone administration. After 2h there is an apparent stimulation of incorporation which leads to an overall discrepancy between measurements of protein-synthetic activity made in vivo and in vitro. 5. There is a significant increase in muscle-glycogen concentration between 8 and 12h after the administration of triamcinolone acetonide (20mg/kg), although a significant decrease occurs after 4h. The fall in glycogen concentration may be due to a decrease in the rate of synthesis of protein essential for glucose uptake into the tissues. 6. As judged by (a) incorporation of (14)C-labelled amino acids into protein, (b) [(3)H]uridine and [(32)P]-orthophosphate incorporation into RNA, (c) the rate of induction of tryptophan pyrrolase and (d) changes in the pool sizes of taurine and tryptophan, the responses in liver followed the same time-course as those in muscle after administration of the drug.

  12. Mapping PET-measured triamcinolone acetonide (TAA) aerosol distribution into deposition by airway generation.

    PubMed

    Lee, Z; Berridge, M S; Finlay, W H; Heald, D L

    2000-04-10

    The three dimensional (3D) distribution of inhaled drugs was measured using Positron Emission Tomography (PET) (Berridge, M.S, Muswick, G.J., Lee, Z., Leisure, G.L., Nelson, A.D., Muzic, R.F. Jr., Miraldi, F., Heald, D.L., 1997. PET evaluation of Azmacort(R) ([C-11]triamcinolone acetonide) dose administration. J. Nucl. Med. 38 (5) Suppl., 4-5). Data analysis was based upon regional ratios or penetration indices. To improve the analytical usefulness and objectivity, labeled drug from dynamic PET images was mapped into 23 airway generations following a general framework from a SPECT-based methodology (Fleming, J.S., Nassim, M.A., Hashish, A.H., Bailey, A.G. , Conway, J., Holgate, S., Halson, P., Moore, E., Martonen, T.B., 1995. Description of pulmonary deposition of radiolabeled aerosol by airway generation using a conceptual three dimensional model of lung morphology. J. Aerosol Med. 8, 341-356). A recently developed airway network model was used in this study. Quantitative PET scans of [C-11]triamcinolone acetonide distribution in the lung were determined following administration of Azmacort(R), a commercial metered dose inhaler with an integrated spacer device. Distributions at varying time periods after drug administration were investigated to explore the dynamics and kinetics of the aerosolized drug. Initially, deposition of labeled drug on conducting airways (generations 1-14) was found to be higher than those on acinar airways (generation 15-23), 64% versus 36%. The distribution pattern changed slowly with time. By 47 min, 51% of the dose remaining in the lung was found on conducting airways while 49% was on acinar airways. This study illustrates the value of PET imaging for the evaluation and design of drug formulations.

  13. Relative efficacy of pimecrolimus cream and triamcinolone acetonide paste in the treatment of symptomatic oral lichen planus

    PubMed Central

    Arunkumar, Shantala; Kalappanavar, Anupama N; Annigeri, Rajeshwari G; Kalappa, Shakuntala G

    2015-01-01

    Background and Objectives: Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition that frequently presents with symptoms of pain and burning sensation. It is generally a very unrelenting disorder despite several kinds of treatment. Only symptomatic OLP requires treatment, and it remains a challenging predicament. Efforts are made in a sustained manner for searching for novel therapies for symptomatic OLP. Therefore, this study was aimed to compare the efficacy of treatment with topical pimecrolimus cream 1% with that of triamcinolone acetonide oral paste 0.1% in subjects with symptomatic OLP. Materials and Methods: A prospective, parallel-group, randomized, active control clinical study was conducted among 30 symptomatic OLP subjects (20 females and 10 males, with 15 patients in each treatment group) treated with topical pimecrolimus 1% cream and triamcinolone acetonide 0.1% oral paste four times daily for two consecutive months and treatment-free follow-up was performed for 2 months. Pain or burning sensation, mean clinical score and presence of erythematous areas were assessed. The data obtained were statistically analyzed using Wilcoxon's Rank test and the Mann Whitney test. Results: Subjects in both the groups showed significant improvement in symptom scores; however, the overall treatment response was higher in the pimecrolimus group compared with the triamcinolone acetonide group. On intergroup comparison, there was no statistically significant difference between the groups in the reduction in burning sensation (P = 0.18) and erythematous area (P = 0.07), but there was a statistically highly significant improvement in reduction of clinical scoring (P < 0.01%). Following the termination of the treatment, sustained remission of symptoms and long-lasting therapeutic effects was detected in 93.3% of the patients treated with pimecrolimus. Interpretation and Conclusion: Topical pimecrolimus 1% cream showed better therapeutic response

  14. One-Year Feasibility Study of Replenish MicroPump for Intravitreal Drug Delivery: A Pilot Study

    PubMed Central

    Gutiérrez-Hernández, Juan-Carlos; Caffey, Sean; Abdallah, Walid; Calvillo, Phillip; González, Roberto; Shih, Jason; Brennan, Jeff; Zimmerman, Jenna; Martínez-Camarillo, Juan-Carlos; Rodriguez, Anthony R.; Varma, Rohit; Santos, Arturo; Sánchez, Gisela; Humayun, Mark

    2014-01-01

    Purpose To determine the feasibility of the surgical procedure and to collect some safety data regarding the bioelectronics of a novel micro drug pump for intravitreal drug delivery in a Beagle dog model for up to 1 year. Methods Thirteen Beagle dogs were assigned to two groups. The experimental group (n = 11) underwent pars plana implantation of MicroPump; the body of which was sutured episclerally, while its catheter was secured at a pars plana sclerotomy. The control group (n = 2) underwent sham surgeries in the form of a temporary suturing of the MicroPump, including placement of the pars plana tube. Baseline and follow-up exams included ophthalmic examination and imaging. The experimental animals were euthanized and explanted at predetermined time points after surgery (1, 3, and 12 months), while the control animals were euthanized at 3 months. All operated eyes were submitted for histopathology. Results Eyes were scored according to a modified McDonald-Shadduck system and ophthalmic imaging. Neither the implanted eyes nor the control eyes showed clinically significant pathological changes beyond the expected surgical changes. The operated eyes showed neither significant inflammatory reaction nor tissue ingrowth through the sclerotomy site compared with the fellow eyes. Conclusion This study shows that the Replenish Posterior MicroPump could be successfully implanted with good safety profile in this animal model. Translational Relevance The results of this study in a Beagle dog model are supportive of the biocompatibility of Replenish MicroPump and pave the way to the use of these devices for ocular automated drug delivery after further testing in larger animal models. PMID:25774328

  15. Steroid Differentiation: The Safety Profile of Various Steroids on Retinal Cells in Vitro and their Implications for Clinical Use (An American Ophthalmological Society Thesis)

    PubMed Central

    Kuppermann, Baruch D.; Zacharias, Leandro Cabral; Kenney, M. Cristina

    2014-01-01

    Purpose: To determine if potentially viable alternatives to the clinical use of intravitreal triamcinolone acetonide should be considered based on a comparative assessment of the in vitro effects of five commercially available corticosteroids. We hypothesized that dexamethasone, betamethasone, methylprednisolone, loteprednol etabonate, and fluocinolone acetonide, at clinically relevant doses, may show different levels of in vitro cytotoxicity to retinal cells. Methods: Cultures of human retinal pigment epithelial cells (ARPE-19) and rat embryonal neurosensory precursor retinal cells (R28) were treated with dexamethasone, betamethasone, methylprednisolone, loteprednol, or fluocinolone acetonide. Cell viability as a measure of cell death was determined by trypan blue dye exclusion assay. The mechanical effect of drug crystals was evaluated by solubilizing the steroid formulations. Mitochondrial dehydrogenase and membrane potential were assessed to measure cell damage. Results: Betamethasone, loteprednol, and methylprednisolone, in commercially available forms, caused significant cytotoxic changes to retinal cells in vitro at clinically relevant doses. This effect was less pronounced with solubilized betamethasone. Dexamethasone at concentrations up to 5 times the clinical dose of free drug injections and 1000 times greater than a drug implant did not cause decreased cell viability. Fluocinolone acetonide at doses 1000 times higher than observed with drug delivery systems showed no cytotoxic effect. Conclusions: Betamethasone, loteprednol, and methylprednisolone exhibited cytotoxicity at clinically relevant doses and do not appear to be good therapeutic options for intravitreal use. In comparison, dexamethasone and fluocinolone acetonide, which exhibited fewer cytotoxic effects than other steroids, may be potentially viable alternatives to triamcinolone acetonide for clinical use. PMID:25646032

  16. [Foveolar effects of dexamethasone intravitreal implant in central retinal vein occlusion].

    PubMed

    Bikbov, M M; Faizrakhmanov, R R; Gil'manshin, T R; Gilyazova, I I

    2016-01-01

    Цель — исследовать функциональные и морфометрические характеристики центральной области сетчатки с посттромботическим макулярным отеком (МО) на фоне интравитреального введения имплантата с дексаметазоном. Материал и методы. Обследованы 5 пациентов (5 глаз) с впервые выявленным тромбозом центральной вены сетчатки, осложненным МО, из них 4 мужчины и 1 женщина, средний возраст которых составил 55,8±3,65 года (исследуемая группа). Всем указанным пациентам проведено однократное интравитреальное введение препарата-имплантата с дексаметазоном. Максимальный срок наблюдения составил 12 мес. В группу контроля включены 5 человек (10 глаз) с пресбиопией, средний возраст 59,14±3,14 года. Результаты. Через 1 мес после введения имплантата с дексаметазоном отмечали улучшение максимально корригированной остроты зрения (МКОЗ) с 0,09±0,03 до 0,19±0,05, суммарной световой чувствительности центральной области сетчатки — в среднем с 3,18±0,19 до 11,07±0,97 дБ, уменьшение толщины сетчатки в фовеоле с 425,36±57,87 до 273,75±36,65 мкм. Через 1 год после лечения МКОЗ составила в среднем 0,21±0,14, суммарная световая чувствительность хотя и снизилась до 4,8±0,76 дБ, но осталась выше, чем до лечения. Оптическая когерентная томография показала сглаженность фовеолярного углубления. Толщина сетчатки в фовеоле стала больше относительно показателей контрольной группы в 1,5 раза, а в сравнении с результатами, полученными через 1 мес после введения имплантата, — в 1,2 раза. В течение всего периода исследования не было выявлено значительного повышения уровня внутриглазного давления (ВГД) относительно исходных данных, сохранялась прозрачность оптических сред хрусталика. Выводы. 1. Интравитреальное введение имплантата с дексаметазоном обеспечивает уменьшение посттромботического МО, улучшение зрительных функций и повышение светочувствительности центральной области сетчатки уже через 1 мес после применения. 2. Положительные морфометрические изменения центральной области сетчатки, связанные с действием имплантата с дексаметазоном при посттромботическом МО, касаются внутренних сегментов фоторецепторов, наружного ядерного, наружного сетчатого и внутреннего ядерного слоев. При этом длительность морфофункционального эффекта сохраняется не менее 12 мес после лечения. 3. Не выявлено отрицательного действия имплантата с дексаметазоном на уровень ВГД и прозрачность хрусталика при наблюдении за больными в течение года.

  17. Sterile Inflammation after Intravitreal Injection of Aflibercept in a Korean Population

    PubMed Central

    Kim, Ju Young; You, Yong Sung; Kwon, Oh Woong

    2015-01-01

    Purpose To report the frequency and clinical features of sterile inflammation after intravitreal aflibercept injection in a Korean population. Methods A single-center, retrospective study was performed in patients who received intravitreal aflibercept from July 2013 through January 2015. Results A total of four cases of post-injection sterile inflammation were identified from 723 aflibercept injections in 233 patients. Patients presented 1 to 13 days after intravitreal aflibercept injection (mean, 5 days). The mean baseline visual acuity was 20 / 60, which decreased to 20 / 112 at diagnosis but ultimately recovered to 20 / 60. Three cases had inflammatory cells in the anterior chamber (mean, 2.25+; range, 0 to 4+), and all cases had vitritis (mean, 3+; range, 2+ to 4+). No patients had pain. Only one patient underwent anterior chamber sampling (culture negative) and injection of antibiotics. Three of four patients were treated with a topical steroid, and all experienced improvement in their symptoms and signs of inflammation. Conclusions The overall incidence of sterile inflammation after intravitreal aflibercept injection in a Korean population was 4 of 723 injections (0.55%), or 4 of 233 patients (1.79%). Sterile inflammation after intravitreal aflibercept injection typically presents without pain, and the visual outcomes are generally favorable. PMID:26457038

  18. Influence of Choroidal Neovascularization and Biodegradable Polymeric Particle Size on Transscleral Sustained Delivery of Triamcinolone Acetonide

    PubMed Central

    Kadam, Rajendra S.; Tyagi, Puneet; Edelhauser, Henry F.; Kompella, Uday B.

    2012-01-01

    Purpose One objective of this study was to determine whether polymeric nanoparticles and/or microparticles sustain transscleral choroidal and retinal delivery of triamcinolone acetonide (TA) for two months in therapeutically effective concentrations after single periocular administration. Another objective of this study was to assess the influence of choroidal neovascularization on transscleral delivery of TA. Methods Polymeric nano- and micro-particles of TA were prepared by o/w emulsion- solvent evaporation method using poly-L-lactide (PLA). Particles were characterized for drug loading, size, surface morphology, and the in vitro drug release profile. Choroidal neovascularization (CNV) was induced in brown Norway (BN) rats using a 532 nm diode argon laser and the CNV induction was assessed using fluorescein angiography. In vivo delivery was assessed in control and CNV induced rats at 2 months after periocular injection of TA loaded nano- or micro-particle suspension, or plain TA suspension in PBS (pH7.4). Ocular tissue levels of TA were estimated using LC-MS/MS following liquid-liquid extraction of drug from tissue samples. Nile red loaded microparticles entrapped in periocular tissue at the end of the study were visualized using scanning electron microscopy and confocal microscopy. Inhibitory effect of TA on VEGF secretion was evaluated in ARPE-19 cells. Results Triamcinolone acetonide-PLA nano- (551 nm) and micro-particles (2090 nm), with 14.7 and 29.5 % drug loading, respectively, sustained in vitro TA release for about 45 and 120 days. After subconjunctival injection, microparticles were able to sustain the delivery in all intraocular tissues for 2 months; whereas no drug levels were detected for TA loaded nanoparticles and plain suspension of TA. Intraocular delivery of TA from microparticles was higher in CNV induced rats when compared to control rats. Significant amount of microparticles remained in periocular tissue at 2 months after injection, and

  19. [The results of wet AMD treatment by intravitreal injections--preliminary report].

    PubMed

    Okruszko, Anna; Borucka, Anna I; Ulińska, Magdalena; Szaflik, Jerzy

    2007-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible, severe loss of vision in the developed countries. One of the modern methods of treatment in neovascular form of AMD are repeated intravitreal injections of ranibizumab (Lucentis). Ranibizumab is a recombinant, humanized, monoclonal antibody that neutralizes all biologically active forms of vascular endothelial growth factor A (VEGF-A). The aim of the study was to analyze the results of intravitreal ranibizumab injections in wet AMD patients. There were 57 patients enrolled in the study. 87% of them avoided any loss of visual acuity and 47.3% gained at least one line at visual acuity chart. Authors conclude that treatment with repeated intravitreal injections of ranibizumab is effective in neovascular form of AMD.

  20. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature.

    PubMed

    Polizzi, Silvio; Mahajan, Vinit B

    2015-12-01

    The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.

  1. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature

    PubMed Central

    Mahajan, Vinit B.

    2015-01-01

    Abstract The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms “pegaptanib,” “bevacizumab,” “ranibizumab,” “aflibercept,” “anti-VEGF,” “intravitreal injection,” “pregnant,” “pregnancy,” “abortion,” “miscarriage,” “preeclampsia,” “embryo–fetal toxicity,” “fetal malformations,” “teratogenesis,” “adverse events,” and “maternofetal complications” in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients. PMID:26302032

  2. The Efficacy of Triamcinolone Acetonide in Keloid Treatment: A Systematic Review and Meta-analysis

    PubMed Central

    Wong, Thian-Sze; Li, John Zeng-Hong; Chen, Siqi; Chan, Jimmy Yu-Wai; Gao, Wei

    2016-01-01

    Keloid is a cutaneous dermal outgrowth resulting from uncontrolled deposition of collagen and glycosaminoglycan around the wound. The uncontrolled and persistent growth of keloids scar will result in cosmetic disfigurement, functional impairment, and affect the quality of life. Triamcinolone acetonide (TAC) is traditionally employed in treating keloid scars. In this study, we aim to evaluate the effectiveness of TAC and compare it with other common therapy employed in keloid treatment. Only randomized controlled trial (RCT) and controlled trial were included. Inverse variance risk ratio, weighted mean difference, and corresponding 95% confidence intervals were calculated to evaluate the effect of intervention. Meta-analysis indicated that TAC treatment significantly reduced the size of keloid compared to untreated control. Reduction in size was statistically different in favor of TAC compared to silicone gel sheet. Significant difference in favor of TAC was observed compared with verapamil in term of vascularity and scar pliability. TAC treatment was more effective in reducing scar thickness in comparison with cryotherapy. However, the current meta-analysis has several limitations. Only a limited number of trials with the same comparison are available. Most trials recruited a small number of patients and used inconsistent outcome assessment. Most trials did not provide detail information on allocation concealment and blinding. Therefore, further evaluation in multi-center RCTs with consistent comparisons and outcome measurements are warrant to reach a consensus on the selection between TAC and different treatment modalities. PMID:28083534

  3. Effect of thermodynamic activity on skin permeation and skin concentration of triamcinolone acetonide.

    PubMed

    Ishii, Hiroshi; Todo, Hiroaki; Sugibayashi, Kenji

    2010-04-01

    Effects of thermodynamic activity and the state (solution/suspension) of triamcinolone acetonide (TA) on skin permeation and concentration were physicochemically and kinetically analyzed. Permeation of TA through a silicone membrane, hairless rat skin (full-thickness skin or stripped skin) or a three-dimensional cultured human skin model (LSE-high) was determined and a permeability coefficient (P), partition coefficient (K) , diffusion coefficient (D) and steady-state flux (J) were calculated. The resulting J values proportionally increased with an increase in the TA activity in the drug solution and similar P, K and D values were obtained independent of the TA state (solution/suspension) in all membranes except for full-thickness hairless rat skin. On the other hand, the TA permeation through full-thickness hairless rat skin with the 1000 microg/ml suspension was higher than that expected judging by the thermodynamic acidity of TA. Higher D and P values were also obtained in the skin permeation of TA from the 1000 microg/ml suspension. Morphological observation of the skin surface by scanning electron microscope (SEM) showed the presence of TA solids in the hair follicles after application of the TA suspension. These results suggest that dissolved TA may be permeated predominantly through the stratum corneum, but that solid TA may be passed through the hair follicles to enter the dermis. The present physicochemical and kinetic analysis provides useful information to develop topical steroid formulations.

  4. The influence of hydrocolloid patch composition on the bioavailability of triamcinolone acetonide in humans.

    PubMed

    Martin, G P; Ladenheim, D; Marriott, C; Hollingsbee, D A; Brown, M B

    2000-01-01

    Triamcinolone acetonide (TACA) is a corticosteroid; it is used in the systemic and topical treatment of a variety of inflammatory conditions, including eczema and psoriasis. Conventionally, for topical use, the drug is formulated in a cream or ointment. However, it has been observed in vitro that percutaneous penetration of corticosteroids can be influenced by hydrocolloid patches. Corticosteroids produce a pallor or blanching when applied to the skin that correlates with anti-inflammatory activity; this property has been used extensively as a bioassay. The aim of this study therefore was to evaluate the occlusive properties of a range of hydrocolloid patches containing TACA on the drug's penetration in vivo using visual assessment and a graded multiple measurement. The in vivo hydration of these dermatological patches was also investigated. Statistical analysis of the weight gains of patches containing either NaCMC 39% or pectin 39% showed that there was a significant difference in the rates of hydration of the two types of patch (p < .005). An increase in application time of the hydrocolloid patches allowed more TACA to be released, which was illustrated by an increase in both the maximum percentage total possible score (%TPS) values and AUC, although changes in the hydrocolloid composition did not significantly alter the blanching response. All of the patches adhered well, were unobtrusive to the normal activity of the wearers, and showed great potential for the convenient, localized, prolonged delivery of drugs to the skin.

  5. Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform.

    PubMed

    Rudnik-Jansen, Imke; Colen, Sascha; Berard, Julien; Plomp, Saskia; Que, Ivo; van Rijen, Mattie; Woike, Nina; Egas, Annelies; van Osch, Gerjo; van Maarseveen, Erik; Messier, Ken; Chan, Alan; Thies, Jens; Creemers, Laura

    2017-03-09

    Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA loaded microspheres were shown to release TAA for over 60days in PBS. Furthermore, the bioactivity lasted at least 28days, demonstrated by a 80-95% inhibition of PGE2 production using TNFα-stimulated chondrocyte culture, indicating inhibition of inflammation. Microspheres loaded with the near infrared marker NIR780-iodide injected in healthy rat joints or joints with mild collagenase-induced OA showed retention of the microspheres up till 70days after injection. After intra-articular injection of TAA-loaded microspheres, TAA was detectable in the serum until day seven. Synovial inflammation was significantly lower in OA joints injected with TAA-loaded microspheres based on histological Krenn scores. Injection of TAA-loaded nor empty microspheres had no effect on cartilage integrity as determined by Mankin scoring. In conclusion, the PEA platform shows safety and efficacy upon intra-articular injection, and its extended degradation and release profiles compared to the currently used PLGA platforms may render it a good alternative. Even though further in vivo studies may need to address dosing and readout parameters such as pain, no effect on cartilage pathology was found and inflammation was effectively lowered in OA joints.

  6. Development of a novel triamcinolone acetonide-loaded spray solution for the treatment of stomatitis.

    PubMed

    Kim, Dong Wuk; Kim, Yong-Il; Ud Din, Fakhar; Cho, Kwan Hyung; Kim, Jong Oh; Choi, Han-Gon

    2014-07-01

    To develop a novel triamcinolone acetonide (TAA)-loaded spray for the treatment of stomatitis, several spray solutions were prepared using various amounts of TAA, Eudragit L100 (Eudragit L) and PEG 400, and 100 ml ethanol. Their viscosity and spraying potential were investigated, with the result that the spraying threshold was 9.5 cP. The effect of PEG 400 on the properties of films formed after spraying was assessed. Its anti-inflammatory effect in mice was evaluated and compared to a commercial product. As the PEG 400 concentration increased, the film elongation and washability by the saliva solution increased, and tensile strength decreased. PEG 400 had little effect on mucoadhesive force and drug release. The TAA-loaded spray solution containing TAA, Eudragit L, PEG 400 and ethanol at the ratio of 1:6:3:100 (w/w/w/v) was easy to spray onto stomatitis lesions in the mouth via a spraying vessel incorporating a long straw. After spraying, the TAA-loaded spray formed a film with suitable elongation, tensile strength and washability that attached onto the mucosal membrane and released the drug. Moreover, it had excellent anti-inflammatory properties, similar to those of the commercial product. Thus, this novel TAA-loaded spray solution was easy to administer, had good film properties and excellent anti-inflammatory efficacy, and is therefore a potential candidate for the treatment of stomatitis.

  7. A Comparison of Intralesional Triamcinolone Acetonide Injection for Primary Chalazion in Children and Adults

    PubMed Central

    Lee, Jacky W. Y.; Yau, Gordon S. K.; Wong, Michelle Y. Y.; Yuen, Can Y. F.

    2014-01-01

    Purpose. To investigate outcome differences of intralesional triamcinolone acetonide (TA) injection for primary chalazia in children versus adults. Methods. A retrospective review of consecutive subjects with primary chalazion who received intralesional TA injection was conducted. A single investigator injected 0.05–0.15 mL of TA (40 mg/mL) intralesionally. Patients were stratified into the pediatric (<18 years old) and adult (≥18 years old) group. In both groups, the correlation of resolution time with chalazion size and TA dose was performed. Results. 17 children and 24 adults were enrolled, with a mean age of 7.4 ± 5.5 and 39.3 ± 16.7 years, respectively. Both groups had statistically similar baseline characteristics. There was no significant difference between the resolution time in the pediatric (18.2 ± 11.4 days) and adult (16.5 ± 11.0 days) group (P = 0.7). There were no significant complications from the TA injection. There was no significant correlation of resolution time to chalazion size (P = 0.7) nor TA dose (P = 0.3) in both groups. Conclusion. TA for the treatment of primary chalazion was equally effective in children and adults, without any significant complications, and the rate of clinical response did not appear to be dose-dependent. PMID:25386597

  8. Dental Implants.

    PubMed

    Zohrabian, Vahe M; Sonick, Michael; Hwang, Debby; Abrahams, James J

    2015-10-01

    Dental implants restore function to near normal in partially or completely edentulous patients. A root-form implant is the most frequently used type of dental implant today. The basis for dental implants is osseointegration, in which osteoblasts grow and directly integrate with the surface of titanium posts surgically embedded into the jaw. Radiologic assessment is critical in the preoperative evaluation of the dental implant patient, as the exact height, width, and contour of the alveolar ridge must be determined. Moreover, the precise locations of the maxillary sinuses and mandibular canals, as well as their relationships to the site of implant surgery must be ascertained. As such, radiologists must be familiar with implant design and surgical placement, as well as augmentation procedures utilized in those patients with insufficient bone in the maxilla and mandible to support dental implants.

  9. Cochlear Implants

    MedlinePlus

    ... NIDCD A cochlear implant is a small, complex electronic device that can help to provide a sense ... are better able to hear, comprehend sound and music, and speak than their peers who receive implants ...

  10. Cochlear implant

    MedlinePlus

    ... antenna. This part of the implant receives the sound, converts the sound into an electrical signal, and sends it to ... implants allow deaf people to receive and process sounds and speech. However, these devices do not restore ...

  11. Macular Hole Formation After Intravitreal Ranibizumab Injection in Wet Age-Related Macular Degeneration

    PubMed Central

    Mukherjee, Chandoshi; Mitra, Arijit; Kumar, N. Ajith; Elsherbiny, Samer; Lip, Peck Lin

    2015-01-01

    Ranibizumab is a monoclonal antibody fragment that inhibits angiogenesis by inhibiting vascular endothelial growth factor A, used as a treatment for patients with wet aged-related macular degeneration (ARMD). Adverse effects from intravitreal Ranibizumab injections are well recognised. Macular hole formation following Ranibizumab injection is a complication that has been recently reported in few case reports. We present a larger case series of five patients, who developed full thickness macular holes (FTMH) after intravitreal Ranibizumab injections for treatment of wet ARMD that we were aware of between 2009 and 2013. PMID:26962382

  12. An unusual presentation of nonarteritic ischemic optic neuropathy with subretinal fluid treated with intravitreal bevacizumab

    PubMed Central

    Dave, Vivek Pravin; Pappuru, Rajeev R

    2016-01-01

    A 62-year-old hypertensive male presented with acute nonarteritic ischemic optic neuropathy (NAION) with contiguous macular edema and subretinal fluid in the right eye. Presenting vision was 20/1000. The patient was treated with intravitreal bevacizumab 1.25 mg/0.05 ml. At 1 month follow-up, the macular edema and the optic nerve head edema completely resolved with a good visual improvement up to 20/40. The visual improvement was maintained at the last follow-up 6 months postinjection. Intravitreal bevacizumab may be a good option for acute NAION especially in an unusual presentation with macular edema and subretinal fluid. PMID:26953030

  13. Improving treatment provision of Wet AMD with intravitreal ranibizumab.

    PubMed

    Ghazala, Fadi; Hovan, Marta; Mahmood, Sajjad

    2013-01-01

    Wet age-related macular degeneration (AMD) treatment using intravitreal ranibizumab needs to be started as soon as possible and treatment must be administered based on regular review to achieve the best results. In clinical practice this tight schedule is a challenge and methods of carrying out such timely treatment is the objective of this quality improvement work. A departmental audit was carried out on the service providing treatment for patients with wet AMD in 2009. This audit identified that the appointment system did not meet the ideal standards and subsequently wet AMD patients' visual outcome were poorer than the standard set in trials where the patients were seen and treated at predetermined intervals. In order to enhance the visual benefit of the administered therapy for our patients we thought it necessary to find ways to see and treat patients sooner as well as reduce time intervals between follow-up appointments. The quality improvement was carried out through redesigning the service in the macular treatment centre of Manchester Royal Eye Hospital. Three main strategies were implemented including: changes to the appointment system, expansion of the treatment facility and employment of additional staff. Following changes made, regular re-audits were used to analyse the effectiveness of the new strategies. The changes introduced have brought appointment standards to the level of Royal College of Ophthalmologists' recommendations. Consequently visual outcomes were approaching the standards set by landmark studies. The visual improvement of treated patients seen in the 2011 audit are comparable to other reports outside clinical trials in the UK. In order to enhance the efficacy of ranibizumab for wet AMD it is essential for treatment to be initiated as soon as possible and administered to patients at the recommended time intervals. The actions we have taken were effective in helping develop a service performing to higher standards.

  14. Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635

    PubMed Central

    Agurto-Rivera, Ricardo; Diaz-Rubio, Jose; Torres-Bernal, Luis; Macky, Tamer A; Colina-Luquez, Juner; Papa-Oliva, Gabriela; Jager, Rama D; Martinez-Jardon, Susana; Fromow-Guerra, Jans; Quiroz-Mercado, Hugo

    2005-01-01

    Background To assess the effect of intravitreal triamcinolone acetonide (iTA) as an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD). Methods This prospective randomized controlled pilot study comprised 26 patients scheduled to receive TTT, due to either absent indications for photodynamic therapy or financial issues. Patients were assigned into; Group A (n = 14) received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for; best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by optical coherence tomography (OCT). Results All 26 patients completed 6 months of follow ups. The average age for both groups was 74 years. Occult CNV formed 64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic 15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045 for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and 2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six months the proportion of patients gained ≥ 1 lines was 14% and 25% (P = 0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P = 0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P = 0.341), for group A and B respectively. Conclusion The use of iTA as an adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better functional results. However due to the small sample size of the study a statistically significant results could not be reached. PMID:16309554

  15. Association of ranibizumab (Lucentis®) or bevacizumab (Avastin®) with dexamethasone and triamcinolone acetonide: an in vitro stability assessment.

    PubMed

    Veurink, Marieke; Stella, Cinzia; Tabatabay, Cyrus; Pournaras, Constantin J; Gurny, Robert

    2011-06-01

    The in vitro stability of monoclonal antibodies used for age-related macular degeneration, ranibizumab and bevacizumab, was investigated. The aggregation profile of the antibodies was compared, alone and after association with dexamethasone sodium phosphate or triamcinolone acetonide. Commercial formulations of ranibizumab and bevacizumab were dialysed into three different buffers. After dialysis, samples were stored at 4°C, 25°C and 40°C during 35 days, alone and in combination with dexamethasone sodium phosphate, triamcinolone acetonide phosphate solution or triamcinolone acetonide suspension. Combined formulations based on both commercial formulations were investigated as well. The aggregation state of the antibodies was measured by multi-angle light scattering (MALS) after separation by asymmetrical flow field-flow fractionation (AFFF) or size-exclusion chromatography (SEC). Ranibizumab results to be more stable than bevacizumab, alone and in combination with dexamethasone sodium phosphate or triamcinolone acetonide. Elevation in concentration, pH and temperature causes a decrease in stability of both antibodies. The association of triamcinolone acetonide phosphate solution with either ranibizumab or bevacizumab is observed to be the least stable combination of all samples tested. Dexamethasone sodium phosphate was shown to have a stabilizing effect on bevacizumab, although this is not the case for its combination with the commercial formulation Avastin®. The results demonstrate that the in vitro association of either ranibizumab or bevacizumab with dexamethasone sodium phosphate or triamcinolone acetonide suspension does not decrease the stability of these antibodies. Although ranibizumab is more stable than bevacizumab in vitro, further research has to point out how this affects their mechanism of action in vivo.

  16. The action of prostaglandin E2 and triamcinolone acetonide on the firing activity of lumbar nerve roots.

    PubMed

    Muramoto, T; Atsuta, Y; Iwahara, T; Sato, M; Takemitsu, Y

    1997-01-01

    Sciatica, due to lumbar disc herniation, is understood electrophysiogically to be an ectopic firing originating from a nerve root. The recent concept of chemical radiculitis implies the involvement, not only of mechanical compression, but also of chemical mediators which contribute to the generation of ectopic firing. The present study demonstrates that prostaglandin E2, a chemical mediator of inflammation, provoked the ectopic firing of nerve roots in a canine in vitro model which indicates that it may play a part in the irritation of nerve roots. In contrast, triamcinolone acetonide suppressed the firing induced by prostaglandin suggesting that steroids may be effective in the treatment of root symptoms.

  17. Influence of selected variables on fabrication of Triamcinolone acetonide loaded solid lipid nanoparticles for topical treatment of dermal disorders.

    PubMed

    Pradhan, Madhulika; Singh, Deependra; Singh, Manju Rawat

    2016-01-01

    Aim of the study was to develop solid lipid nanoparticles (SLN) of triamcinolone acetonide (TA) and to study the effect of various process variables in order to optimize the formulation for effective delivery. Drug loaded SLNs were successfully prepared and characterized by TEM, XRD and DSC study. Process variables like surfactant concentration, drug concentration, lipid concentration etc. showed significant effect on the particle size and entrapment efficiency. SLNs exhibited prolonged drug release following Higuchi release kinetics (R(2) = 0.9909). In vitro skin distribution study demonstrated systemic escape of drug from TA loaded SLNs which might eliminate side effects associated with systemic exposure.

  18. Successful use of intravitreal bevacizumab and pascal laser photocoagulation in the management of adult Coats' disease.

    PubMed

    Raoof, Naz; Quhill, Fahd

    2013-01-01

    Traditional methods of managing exudative retinal detachment secondary to Coats' disease have been associated with varying degrees of success. We describe a case of a 34 year-old male who presented with a sub-total exudative retinal detachment of the right eye that encroached upon the macula, associated with a vasoproliferative tumor secondary to Coats' disease. The patient under-went successful treatment with two intravitreal injections of bevacizumab (Avastin, Genetech Inc., San Francisco, CA, USA) combined with targeted laser photocoagulation with a 532 nm Pascal laser (Topcon Corp., Tokyo, Japan). The visual acuity improved 5 days after the second intravitreal injection from 6/18 to 6/5, with no residual macular edema and complete regression of the vasoproliferative tumor. The improvement in visual acuity was maintained at 12 months post-treatment. We believe this is the first case report describing the successful use of Pascal laser photocoagulation with intravitreal bevacizumab in the treatment of Coats' disease. Our aim was to defer laser treatment until 'near total' retinal reattachment and regression of the vasoproliferative tumor was achieved. There are, however, reports of vitreous fibrosis in patients with Coats' disease treated with intravitreal bevacizumab. This suggests further long-term follow-up studies are required in patients treated with this approach.

  19. Intravitreal Ampicillin Sodium for Antibiotic-Resistant Endophthalmitis: Streptococcus uberis First Human Intraocular Infection Report

    PubMed Central

    Velez-Montoya, Raul; Rascón-Vargas, Dulce; Mieler, William F.; Fromow-Guerra, Jans; Morales-Cantón, Virgilio

    2010-01-01

    Purpose. To describe the clinical characteristics, diagnosis, and treatment with intravitreal ampicillin sodium of a postoperative endophthalmitis case due to Streptococcus uberis; an environmental pathogen commonly seen in mastitis cases of lactating cows. Methods. Case Report. A 52-year-old, Hispanic diabetic patient who suddenly developed severe pain and severe loss of vision, following vitrectomy. Results. The patient was diagnosed with postoperative endophthalmitis secondary to a highly resistant strain of Streptococcus uberis that did not respond to intravitreal antibiotics. He was treated with an air-fluid interchange, anterior chamber washout, intravitreal ampicillin sodium (5 mg/0.1 mL), and silicon oil tamponade (5000 ck). The eye was anatomically stabilized, though there was no functional recovery. Conclusion. Streptococcus uberis is an uncommon pathogen to the human eye, which has unique features that help the strain in developing resistance to antibiotics. While treatment with intravitreal ampicillin is feasible, there are still concerns about its possible toxicity. PMID:20706679

  20. Dramatic resolution of vitreous hemorrhage after an intravitreal injection of dobesilate.

    PubMed

    Cuevas, Pedro; Outeiriño, Luis Antonio; Azanza, Carlos; Angulo, Javier; Giménez-Gallego, Guillermo

    2015-01-01

    Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.

  1. Anterior segment changes following intravitreal bevacizumab injection for treatment of neovascular glaucoma

    PubMed Central

    Canut, MI; Alvarez, A; Nadal, J; Abreu, R; Abreu, JA; Pulido, JS

    2011-01-01

    Background: The purpose of this study was to describe anterior segment changes in a prospective, interventional, noncomparative case series of patients with neovascular glaucoma secondary to proliferative diabetic retinopathy treated with intravitreal bevacizumab. Methods: Five consecutive patients with neovascular glaucoma and a refractory, symptomatic elevation of intraocular pressure and pronounced anterior segment congestion received intravitreal bevacizumab 1.25 mg/0.05 mL. Follow-up examinations were performed at 4–16 weeks by the same specialists, with testing performed at hour 48, week 1, and months 1, 3, and 6 after intravitreal bevacizumab. Results: We observed a significant difference (P = 0.021) between initial and mean neovascularization at three months in all the quadrants. At three months, median intraocular pressure was 19 ± 5.38 (range 12–26) mmHg. In three of the five cases, diode laser cyclophotocoagulation was required, and in one case a trabeculectomy was performed. One patient showed complete synechial angle closure 48 hours after treatment which required cyclodestructive procedures to normalize intraocular pressure. Conclusion: Intravitreal bevacizumab achieves complete regression of neovascularization in neovascular glaucoma secondary to proliferative diabetic retinopathy, and this regression is stable when associated with treatment of the underlying disease and should be investigated more thoroughly as an adjunct in the management of neovascular glaucoma. PMID:21629579

  2. Evaluation of the reporting level to detect triamcinolone acetonide misuse in sports.

    PubMed

    Matabosch, Xavier; Pozo, Oscar J; Pérez-Mañá, Clara; Papaseit, Esther; Marcos, Josep; Segura, Jordi; Ventura, Rosa

    2015-01-01

    Triamcinolone acetonide (TA) is prohibited in sport competitions using systemic administrations (e.g., intramuscular, IM), and it is allowed by other routes (e.g., intranasal, IN, or topical, TOP). A reporting level of 30 ng/mL is used to discriminate between forbidden and allowed administrations. We examined urinary profiles of TA metabolites after TOP, IN and IM administrations to evaluate the suitability of the current reporting level and to define the best criteria to discriminate between these administrations. TA was administered to healthy volunteers by different routes: a single IM dose (n=2), IN doses for three days (n=6), and TOP doses for five days followed by a single IM dose (n=8). Urine samples were collected at different time intervals and they were analyzed by liquid chromatography-tandem mass spectrometry to measure TA and eight metabolites. After TOP and IN administrations, concentrations of the metabolites were significantly lower (p<0.05) than after IM administrations. Concentrations of TA after IM administration were lower than 30 ng/mL for all volunteers (range 0.7-29.7 ng/mL), and they were lower than 5 ng/mL after multiple IN or TOP doses (0.1-3.6 ng/mL and 0-1.7 ng/mL, respectively). For 6β-hydroxy-TA, the main TA metabolite, greater concentrations were obtained: 10.7-469.1 ng/mL, 2.2-90.6 ng/mL and 0-57.2 ng/mL after IM, IN and TOP administrations, respectively. These results suggest that the current reporting level is not suitable to detect forbidden IM administration of TA. A lower concentration of the parent drug or the use of specific metabolites could discriminate IM from TOP or IN administrations.

  3. Effects of triamcinolone acetonide on an in vivo equine osteochondral fragment exercise model.

    PubMed

    Frisbie, D D; Kawcak, C E; Trotter, G W; Powers, B E; Walton, R M; McIlwraith, C W

    1997-09-01

    The objective of this study was to determine the effects of intra-articularly administered triamcinolone acetonide (TA) in exercised equine athletes with carpal osteochondral fragmentation. Eighteen horses were randomly assigned to each of 3 groups. An osteochondral chip fragment was created in one randomly chosen intercarpal joint of each horse. Both intercarpal joints in the placebo control group (CNT) horses were injected with intra-articular administration (IA) of polyionic fluid. Both joints in the TA control group (TA CNT) horses were treated with 12 mg of TA in the intercarpal joint without an osteochondral fragment, and the opposite intercarpal joint was injected with a similar volume of polyionic fluid. The TA treated group (TA TX) horses were treated with 12 mg of TA in the joint that contained the osteochondral fragment and the opposite intercarpal joint was injected with a similar volume of polyionic fluid. All horses were treated IA on days 13 and 27 after surgery and exercised on a high speed treadmill for 6 weeks starting on Day 14. Horses in the TA TX group were significantly less lame than horses in the CNT and TA CNT groups. Horses in either TA CNT or TA TX groups had lower total protein, and higher hyaluronan, and glycosaminoglycan concentrations in synovial fluid than did those in the CNT group. Synovial membrane collected from subjects in TA CNT and TA TX groups had significantly less inflammatory cell infiltration, subintimal hyperplasia and subintimal fibrosis compared to the CNT group. Articular cartilage histomorphological parameters were significantly better from the TA CNT and TA TX groups compared to the CNT group. In conclusions, results from this study support favourable effects of TA on degree of clinically detectable lameness, and on synovial fluid, synovial membrane, and articular cartilage morphological parameters, both with direct intra-articular administration and remote site administration as compared to placebo treatment. The

  4. [Clinical effectiveness of salvianolic acid B and triamcinolone acetonide in treatment of oral submucous fibrosis].

    PubMed

    Jian, X C; Zheng, L; Zhu, R; Wang, B P; Zhou, T; Du, Y X

    2017-01-09

    Objective: To evaluate the clinical effectiveness of salvianolic acid B (SA-B) and triamcinolone acetonide (TA) by means of combined intralesional injection in the treatment of oral submucous fibrosis (OSF). Methods: According to clinical findings and symptoms, TA combined with SA-B were consecutively applied intralesionally 1 time weekly for 30 times. Mouth opening degree, color change of the buccal mucosae and numeral increase of the capillary vessels were determined by degree Ⅰ-Ⅳ visual analog scale were evaluated at 12, 24, and 36 months, respectively. Results: One hundred and fourteen subjects fulfilled the study without obvious adverse reactions. After treatment for 1 year, the net gain in mouth opening of the early stage group was (5.5 ± 1.5) mm at 12 months, (8.8 ± 1.6) mm at 24 months and (12.0±1.2) mm at 36 months. The net gain in mouth opening of the middle stage group were (5.3±1.7) mm at 12 months, (10.5±1.5) mm at 24 months and (14.5±2.4) mm at 36 months. The net gain in mouth opening of the advanced stage group were (5.7±1.3) mm at 12 months, (13.7±1.3) mm at 24 months and (15.5±1.5) mm at 36 months. The effective rates of color change of the buccal mucosae and numeral increase of the capillary vessels after treatment for 36 months were 100% in early stage group, 93% (51/55) in middle stage group and 90% (36/40) in advanced stage group. Conclusions: TA and SA-B combined intralesional injection in the treatment of oral submucous fibrosis is effective.

  5. Simultaneous determination of triamcinolone acetonide and oxymetazoline hydrochloride in nasal spray formulations by HPLC.

    PubMed

    Sudsakorn, Sirimas; Kaplan, Leonard; Williams, David A

    2006-03-18

    A high-performance liquid chromatography (HPLC) method with UV detection at 232 nm was developed and validated for the simultaneous determination of triamcinolone acetonide (TAA) and oxymetazoline hydrochloride (OXY) in nasal spray formulations. The chromatographic system consisted of a micro Bondapak CN column (150 mm x 3.9 mm), 5 microm particle size with a mobile phase composition of acetonitrile:ammonium acetate (pH 5.0, 20mM) (10:90, v/v) at a flow rate of 1.0 mL/min. Calibration curves were linear for both TAA and OXY in the concentration range of 2.5-25.0 microg/mL. The limit of detection and quantitation were 0.29 and 0.88 microg/mL for OXY and 0.24 and 0.73 microg/mL for TAA. The described method was further applied to the analysis and stability studies of two nasal spray formulations I and II prepared from TAA and OXY commercial nasal spray products. The stability of OXY and TAA in the commercial products and the nasal formulations I and II were analyzed after 30 days at room temperature and 30 days at 40 degrees C/60% relative humidity. The results of the stability study showed that OXY and TAA in the commercial nasal spray products and the nasal formulations I and II were stable at 20-25 degrees C (room temperature) but TAA was unstable at 40 degrees C/60% relative humidity. TAA exhibited more than 10% loss at 14 days in both the nasal formulations and in the commercial products. OXY showed increased degradation at 40 degrees C/60% relative humidity but <10%.

  6. The Biomechanics and Optimization of the Needle-Syringe System for Injecting Triamcinolone Acetonide into Keloids

    PubMed Central

    2016-01-01

    Purpose. Injecting triamcinolone acetonide (TA) into a keloid is physically challenging due to the density of keloids. The purpose was to investigate the effects of various syringe and needle combinations on the injection force to determine the most ergonomic combination. Materials and Methods. A load cell was used to generate and measure the injection force. Phase 1: the injection force of 5 common syringes was measured by injecting water into air. The syringe that required the lowest injection force was evaluated with various needle gauges (25, 27, and 30 G) and lengths (16, 25, and 38 mm) by injecting TA (40 mg/mL) into air. The needle-syringe combination with the lowest injection force (CLIF) was deemed the most ergonomic combination. Phase 2: comparisons between the CLIF and a standard combination (SC) were performed by injecting TA into air and tap water into a keloid specimen. Intraclass Correlation Coefficient (ICC) and independent t-test were used. Results. Increasing the syringe caliber, injection speed, and needle gauge and length significantly increased the injection force (p value < 0.001). The SC required a maximum force of 40.0 N to inject water into keloid, compared to 25.0 N for the CLIF. Injecting TA into keloid using the SC would require an injection force that was 103.5% of the maximum force female thumbs could exert compared to 64.8% for the CLIF. ICC values were greater than 0.4. Conclusions. The 1 mL polycarbonate syringe with a 25 G, 16 mm needle (CLIF) was the most ergonomic combination. The SC required a substantial injection force, which may represent a physical challenge for female thumbs. PMID:27843936

  7. Repeated intraarticular injections of triamcinolone acetonide alter cartilage matrix metabolism measured by biomarkers in synovial fluid.

    PubMed

    Céleste, Christophe; Ionescu, Mirela; Robin Poole, A; Laverty, Sheila

    2005-05-01

    Although intraarticular (IA) corticosteroids are frequently used to treat joint disease, the effects of their repeated use on articular cartilage remains controversial. The aim of our study was to determine the effects of a clinically recommended dose of IA triamcinolone acetonide (TA), on synovial fluid (SF) biomarkers of cartilage metabolism. Ten adult horses, free of osteoarthritis (OA) in their radiocarpal joints, were studied. One radiocarpal joint of each horse was randomly chosen for treatment and the contralateral anatomically paired joint acted as the control. Aseptic arthrocentesis was performed weekly on both joints for 13 weeks. The initial results from the first 3 weeks of the experimental period established baseline untreated control marker levels for each joint, each being its own control. On weeks 3, 5, and 7, a sterile suspension of 12 mg of TA was injected into the treated joint and an equivalent volume of sterile saline solution (0.9%) was injected into the control joint. SF was immunoassayed for biomarkers of aggrecan turnover (CS 846 & KS), types I and II collagen cleavage (C1,2C) and type II collagen synthesis (CPII). In treated joints, there was a significant increase in CS 846, KS, C1,2C and CPII epitope concentrations following IA TA injections when compared to baseline levels. There was also a significant increase in C1,2C and CPII epitope concentrations in the contralateral control joints following IA TA injections in the treated joint. Significant differences were observed between treated and control joints for all markers except CPII. These findings indicate that TA alters articular cartilage and collagen metabolism in treated and, interestingly, also in control joints, suggesting a systemic effect of the drug. Though intuitively the observed findings would favor the hypothesis that long-term IA TA treatment changes joint metabolism and this may have detrimental effects; further studies would be necessary to confirm this.

  8. Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis.

    PubMed

    Benoist d'Azy, Cédric; Pereira, Bruno; Naughton, Geraldine; Chiambaretta, Frédéric; Dutheil, Frédéric

    2016-01-01

    Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and "intravitreal injection*". To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384-1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics.

  9. Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis

    PubMed Central

    Benoist d’Azy, Cédric; Pereira, Bruno; Naughton, Geraldine; Chiambaretta, Frédéric; Dutheil, Frédéric

    2016-01-01

    Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and “intravitreal injection*”. To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384–1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta-analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics. PMID

  10. Implantable Microimagers

    PubMed Central

    Ng, David C.; Tokuda, Takashi; Shiosaka, Sadao; Tano, Yasuo; Ohta, Jun

    2008-01-01

    Implantable devices such as cardiac pacemakers, drug-delivery systems, and defibrillators have had a tremendous impact on the quality of live for many disabled people. To date, many devices have been developed for implantation into various parts of the human body. In this paper, we focus on devices implanted in the head. In particular, we describe the technologies necessary to create implantable microimagers. Design, fabrication, and implementation issues are discussed vis-à-vis two examples of implantable microimagers; the retinal prosthesis and in vivo neuro-microimager. Testing of these devices in animals verify the use of the microimagers in the implanted state. We believe that further advancement of these devices will lead to the development of a new method for medical and scientific applications. PMID:27879873

  11. Application of electrospraying as a one-step method for the fabrication of triamcinolone acetonide-PLGA nanofibers and nanobeads.

    PubMed

    Jahangiri, Azin; Davaran, Soodabeh; Fayyazi, Behnam; Tanhaei, Ali; Payab, Shahriar; Adibkia, Khosro

    2014-11-01

    The aim of the present project was to prepare triamcinolone acetonide nanofibers and nanobeads with prolonged anti-inflammatory activity. Triamcinolone acetonide-loaded PLGA nanoformulations were prepared by electrospraying method. The physicochemical and morphological properties of the fabricated nanoparticles were characterized as well. In vitro drug release of the prepared formulations was also studied. Differential scanning calorimetry and X-ray powder diffractometery showed that drug crystallinity was notably decreased during the electrospraying process. In vitro dissolution tests verified that the pure drug and physical mixtures had faster drug release pattern compared to the nanoformulations. Electrosprayed samples with the drug:polymer ratio of 1:10 revealed slower release profiles compared to those with a 1:5 ratio. Results obtained from SEM images of the prepared formulations indicated that polymer solution concentration was the critical parameter in the formation of fibers or beads; so that, fiber formation was increased proportionally with increasing polymer concentration. Moreover, the size of obtained nanostructures was also increased in order of polymer concentrations. As a final point, electrosprayed triamcinolone-loaded biodegradable micro/nanofibers and nanobeads with modified physicochemical characteristics and sustained drug release profiles were successfully prepared via simple, one-step and cost effective electrospraying technique.

  12. Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate.

    PubMed

    Liu, Wei; Hu, Meiling; Liu, Wenshuang; Xue, Chengbin; Xu, Huibi; Yang, XiangLiang

    2008-11-19

    The purpose of this study was to investigate solid lipid nanoparticles (SLN) hydrogel for transdermal iontophoretic drug delivery. Triamcinolone acetonide acetate (TAA), a glucocorticoids compound, was employed as the model drug. SLN containing the drug triamcinolone acetonide acetate (TAA-SLN) and their carbopol gel with stable physicochemical properties were prepared. The use of TAA-SLN carbopol gel as a vehicle for the transdermal iontophoretic delivery of TAA was evaluated in vitro using horizontal diffusion cells fitted with porcine ear skin. We found that the TAA-SLN gel possessed good stability, rheological properties, and high electric conductance. Transdermal penetration of TAA from TAA-SLN gel cross the skin tissue was significantly enhanced by iontophoresis. The enhancement of the cumulative penetration amount and the steady-state penetration flux of the penetrated drug were related to the particle size of TAA-SLN and the characteristics of the applied pulse electric current, such as density, frequency, and on/off interval ratio. These results indicated that SLN carbopol gel could be used as a vehicle for transdermal iontophoretic drug delivery under suitable electric conditions.

  13. Endodontic implants

    PubMed Central

    Yadav, Rakesh K.; Tikku, A. P.; Chandra, Anil; Wadhwani, K. K.; Ashutosh kr; Singh, Mayank

    2014-01-01

    Endodontic implants were introduced back in 1960. Endodontic implants enjoyed few successes and many failures. Various reasons for failures include improper case selection, improper use of materials and sealers and poor preparation for implants. Proper case selection had given remarkable long-term success. Two different cases are being presented here, which have been treated successfully with endodontic implants and mineral trioxide aggregate Fillapex (Andreaus, Brazil), an MTA based sealer. We suggest that carefully selected cases can give a higher success rate and this method should be considered as one of the treatment modalities. PMID:25298723

  14. Comparison of skin stripping, in vitro release, and skin blanching response methods to measure dose response and similarity of triamcinolone acetonide cream strengths from two manufactured sources.

    PubMed

    Pershing, Lynn K; Bakhtian, Shahrzad; Poncelet, Craig E; Corlett, Judy L; Shah, Vinod P

    2002-05-01

    The collective studies compare in vitro drug release, in vivo skin stripping, and skin blanching response methods for dose responsiveness and bioequivalence assessment of triamcinolone acetonide cream products, as a function of application duration, drug concentration, and manufacturer source. Commercially available triamcinolone acetonide creams (0.025%, 0.1%, and 0.5%) from two manufacturers were evaluated in vitro for rate and extent of drug release across synthetic membranes and in vivo for rate, extent, and variability of drug uptake into human stratum corneum and skin blanching response in human forearm skin. Data demonstrate that increasing triamcinolone acetonide cream concentration applied increased the rate and extent of drug released in vitro as well as the extent of drug uptake and skin blanching response in human skin in vivo. No difference (p < 0.05) between the two sources of 0.1% or 0.5% creams was measured by the skin stripping or skin blanching response methods. Dermatopharmacokinetic analysis of triamcinonide acetonide in vivo is therefore dose responsive to drug concentration applied and application duration and agrees with in vivo skin blanching results. Data support the use of dermatopharmacokinetic methods for bioequivalence and bioavailability assessment of topical drug products.

  15. Ocular and systemic toxicity of intravitreal topotecan in rabbits for potential treatment of retinoblastoma.

    PubMed

    Buitrago, Emiliano; Del Sole, María José; Torbidoni, Ana; Fandino, Adriana; Asprea, Marcelo; Croxatto, J O; Chantada, Guillermo L; Bramuglia, Guillermo F; Schaiquevich, Paula

    2013-03-01

    Treatment of intraocular retinoblastoma with vitreous seeding is a challenge. Different routes of chemotherapy administration have been explored in order to attaining pharmacological concentrations into the posterior chamber. Intravitreal drug injection is a promissing route for maximum bioavailability to the vitreous but it requires a well defined dose for achieving tumor control while limited toxicity to the retina. Topotecan proved to be a promising agent for retinoblastoma treatment due to its pharmacological activity and limited toxicity. High and prolonged concentrations were achieved in the rabbit vitreous after 5 μg of intravitreal topotecan. However, whether a lower dose could achieve potentially therapeutic levels remained to be determined. Thus, we here study the pharmacokinetics of topotecan after 0.5 μg and the toxicity profile of intravitreal topotecan in the rabbit eye as a potential treatment of retinoblastoma. A cohort of rabbits was used to study topotecan disposition in the vitreous after a single dose of 0.5 μg of intravitreal topotecan. In addition, an independent cohort of non-tumor bearing rabbits was employed to evaluate the clinical and retinal toxicity after four weekly injections of two different doses of intravitreal topotecan (Group A, 5 μg/dose; Group B, 0.5 μg/dose) to the right eye of each animal. The same volume (0.1 ml) of normal saline was administered to the left eye as control. A third group of rabbits (Group C) served as double control (both eyes injected with normal saline). Animals were weekly evaluated for clinical and hematologic values and ocular evaluations were performed with an inverse ophthalmoscope to establish potential topotecan toxicity. Weekly controls included topotecan quantitation in plasma of all rabbits. Electroretinograms (ERGs) were recorded before and after topotecan doses. One week after the last injection, topotecan concentrations were measured in vitreous of all eyes and samples for retinal

  16. Breast Implants

    MedlinePlus

    ... sale in the United States: saline-filled and silicone gel-filled. Both types have a silicone outer shell. They vary in size, shell thickness, ... implant them. Provide information on saline-filled and silicone gel-filled breast implants, including data supporting a ...

  17. A Phase 2 Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Objective To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). Design Randomized phase 2 clinical trial. Participants 121 eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32-20/320. Interventions Random assignment to one of five groups: focal photocoagulation at baseline (N=19, Group A), intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks (N=22, Group B), intravitreal injection of 2.5mg bevacizumab at baseline and 6 weeks (N=24, Group C), intravitreal injection of 1.25mg bevacizumab at baseline and sham injection at 6 weeks (N=22, Group D), or intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (N=22, Group E). Main Outcome Measures Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. Results At baseline, median CST was 411 microns and median Snellen VA equivalent was 20/50. Compared with Group A, Groups B and C had a greater reduction in CST at 3 weeks and about one line better median visual acuity over 12 weeks. There were no meaningful differences between Groups B and C in CST reduction or VA improvement. A CST reduction >11% (the reliability limit) was present at 3 weeks in 36/84 (43%) bevacizumab-treated eyes and in 5/18 (28%) eyes treated with laser alone, and at 6 weeks in 31/84 (37%) and 9/18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in one eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (N=2), congestive heart failure (N=1), elevated blood pressure (N=3), and worsened renal function (N=3). Conclusion These results demonstrate that

  18. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles.

    PubMed

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

    2013-11-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals.

  19. Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

    PubMed Central

    Ye, Zhuo; Ji, Yan-Li; Ma, Xiang; Wen, Jian-Guo; Wei, Wei; Huang, Shu-Man

    2015-01-01

    AIM To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid) (PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form. METHODS Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection. RESULTS The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form. CONCLUSION The result of this study

  20. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles

    PubMed Central

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2013-01-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. PMID:24036388

  1. The Effect of Adjuvant Intracameral Triamcinolone Acetonide on the Surgical Results of Trabeculectomy with Mitomycin C

    PubMed Central

    Alagöz, Neşe; Alagöz, Cengiz; Yıldırım, Yusuf; Yeşilkaya, Ceren; Altan, Çiğdem; Bozkurt, Ercüment; Şatana, Banu; Başarır, Berna; Taşkapılı, Muhittin

    2016-01-01

    Objectives: To evaluate the effect of adjuvant intracameral triamcinolone acetonide (TA) on the surgical results of trabeculectomy with mitomycin C. Materials and Methods: All consecutive trabeculectomy cases performed in the glaucoma clinic between July 2012 and December 2013 were retrospectively reviewed from the patient charts. Only those with follow-up of 12 months or longer were included. Patients with intraoperative intracameral TA (study group, n=19) were compared to those without TA (control group, n=21) in terms of surgical success, intraocular pressure (IOP) change, medication use and complications. Results: Forty eyes of 31 patients (21 male/10 female, mean age 64.2±13.8 years) were included in the study. The mean follow-up period was 20.9±5.1 months and 20.7±6.7 months in the study and control groups, respectively (p=0.830). Baseline IOP was 26.4±9.9 and 25.2±7.6 mmHg (p=0.979), and final IOP was 12.7±2.6 and 13.6±3 mmHg in both groups respectively (p=0.226). At the final follow-up, complete success was observed in 68.4% and 52.4% of the study and control groups (p=0.349) and anti-glaucoma medication was used by 31.6% (mean number of medications: 0.79±1.2) and 47.6% (mean number of medications: 1.33±1.7), respectively (p>0.05). Bleb encapsulation, leakage, suture-lysis and hypotony rates were similar in both groups (for all, p>0.05). Cataract progression was noted in six (35.3%) and in five (26.3%) of the phakic eyes in the study and control groups, respectively (p=0.720). Conclusion: When used intracamerally, TA did not increase the complication rate in trabeculectomy surgery. Although the group that received TA showed lower IOP levels, use of fewer medications and fewer eyes requiring medication, the differences did not reach significance. PMID:28058152

  2. Effects of Low-dose Triamcinolone Acetonide on Rat Retinal Progenitor Cells under Hypoxia Condition

    PubMed Central

    Xing, Yao; Cui, Li-Jun; Kang, Qian-Yan

    2016-01-01

    Background: Retinal degenerative diseases are the leading causes of blindness in developed world. Retinal progenitor cells (RPCs) play a key role in retina restoration. Triamcinolone acetonide (TA) is widely used for the treatment of retinal degenerative diseases. In this study, we investigated the role of TA on RPCs in hypoxia condition. Methods: RPCs were primary cultured and identified by immunofluorescence staining. Cells were cultured under normoxia, hypoxia 6 h, and hypoxia 6 h with TA treatment conditions. For the TA treatment groups, after being cultured under hypoxia condition for 6 h, RPCs were treated with different concentrations of TA for 48–72 h. Cell viability was measured by cell counting kit-8 (CCK-8) assay. Cell cycle was detected by flow cytometry. Western blotting was employed to examine the expression of cyclin D1, Akt, p-Akt, nuclear factor (NF)-κB p65, and caspase-3. Results: CCK-8 assays indicated that the viability of RPCs treated with 0.01 mg/ml TA in hypoxia group was improved after 48 h, comparing with control group (P < 0.05). After 72 h, the cell viability was enhanced in both 0.01 mg/ml and 0.02 mg/ml TA groups compared with control group (all P < 0.05). Flow cytometry revealed that there were more cells in S-phase in hypoxia 6 h group than in normoxia control group (P < 0.05). RPCs in S and G2/M phases decreased in groups given TA, comparing with other groups (all P < 0.05). There was no significant difference in the total Akt protein expression among different groups, whereas upregulation of p-Akt and NF-κB p65 protein expression and downregulation of caspase-3 and cyclin D1 protein expression were observed in 0.01 mg/ml TA group, comparing with hypoxia 6 h group and control group (all P < 0.05). Conclusion: Low-dose TA has anti-apoptosis effect on RPCs while it has no stimulatory effect on cell proliferation. PMID:27364798

  3. Effects of triamcinolone acetonide on human trabecular meshwork cells in vitro

    PubMed Central

    Sharma, Ashish; Patil, A Jayaprakash; Gupta, Navin; Estrago-Franco, MF; Mansoor, Saffar; Raymond, Vincent; Kenney, M Cristina; Kuppermann, Baruch D

    2014-01-01

    Aim: To study the effects of triamcinolone acetonide (TA) on cultured human trabecular meshwork (HTM) cells. Materials and Methods: HTM cells were cultured and treated with 125, 250, 500 and 1000 μg/mL concentration of TA for 24 h. The cells were treated with both crystalline TA (TA-C) (commercial preparation) and solubilized TA (TA-S). Cell viability was measured by a trypan blue dye exclusion test. The activity of caspse-3/7 was measured by a fluorescence caspase kit and DNA laddering was evaluated by electrophoresis on 3% agarose gel. Levels of lactate dehydrogenase (LDH) were assessed with LDH cytotoxicity assay kit-II. Results: Mean cell viabilities of HTM cells after 24 h exposure to TA-C 125, 250, 500, and 1000 μg/mL were 75.4 ±2.45% (P < 0.0001), 49.43 ± 1.85% (P < 0.0001), 17.07 ± 2.39% (P < 0.0001), and 3.7 ± 0.9% (P < 0.0001), respectively, compared with the untreated HTM cells 92.49 ± 1.21%. The mean cell viabilities with 125, 250, 500, and 1000 μg/mL of TA-S were 94.47 ± 1.60% (P > 0.05), 90.13 ± 0.40% (P < 0.01), 85.57 ± 0.47% (P < 0.001), and 71.67 ± 3.30% (P < 0.0001), respectively, compared to DMSO-equivalent cultures. Untreated HTM control had a cell viability of 96.57 ± 1.98%. DMSO-treated controls of 125, 250, 500, and 1000 μg/mL had a cell viability of 94.73 ± 0.57%, 96.97 ± 1.08%, 93.97 ± 1.85%, and 97.27 ± 1.15%, respectively. There was no increase of caspase-3/7 activity in cultures treated with either TA-C or TA-S. DNA laddering showed no bands in the TA-C or TA-S treated cultures. There were significantly higher LDH release rates at all concentrations of TA-C compared to TA-S. Conclusions: Results show that the effect of TA-C and TA-S on HTM cells is due to cell death by necrosis at all concentrations except 125 μg/mL of TA-S. Elevated levels of LDH confirmed necrotic cell death. Our study also infers the relative safety of TA-S over TA-C. PMID:24817746

  4. Randomized Comparison of Topical Betamethasone Valerate Foam, Intralesional Triamcinolone Acetonide and Tacrolimus Ointment in Management of Localized Alopecia Areata

    PubMed Central

    Kuldeep, CM; Singhal, Himanshu; Khare, Ashok Kumar; Mittal, Asit; Gupta, Lalit K; Garg, Anubhav

    2011-01-01

    Background: Alopecia areata (AA) is a common, non-scarring, patchy loss of hair at scalp and elsewhere. Its pathogenesis is uncertain; however, auto-immunity has been exemplified in various studies. Familial incidence of AA is 10-42%, but in monozygotic twins is 50%. Local steroids (topical / intra-lesional) are very effective in treatment of localized AA. Aim: To compare hair regrowth and side effects of topical betamethasone valerate foam, intralesional triamcinolone acetonide and tacrolimus ointment in management of localized AA. Materials and Methods: 105 patients of localized AA were initially registered but 27 were drop out. So, 78 patients allocated at random in group A (28), B (25) and C (25) were prescribed topical betamethasone valerate foam (0.1%) twice daily, intralesional triamcinolone acetonide (10mg/ml) every 3 weeks and tacrolimus ointment (0.1%) twice daily, respectively, for 12 weeks. They were followed for next12 weeks. Hair re-growth was calculated using “HRG Scale”; scale I- (0-25%), S II-(26-50%), S III - (51-75%) and S IV- (75-100%). Results: Hair re-growth started by 3 weeks in group B (Scale I: P<0.03), turned satisfactory at 6 weeks in group A and B (Scale I: P<0.005, Scale IV: P<0.001)), good at 9 weeks (Scale I: P<0.0005, Scale IV: P<0.00015), and better by 12 weeks of treatment (Scale I: P<0.000021, Scale IV: P<0.000009) in both A and B groups. At the end of 12 weeks follow-up hair re-growth (>75%, HRG IV) was the best in group B (15 of 25, 60%), followed by A (15 of 28, 53.6%) and lastly group-C (Nil of 25, 0%) patients. Few patients reported mild pain and atrophy at injection sites, pruritus and burning with betamethasone valerate foam and tacrolimus. Conclusion: Intralesional triamcinolone acetonide is the best, betamethasone valerate foam is better than tacrolimus in management of localized AA. PMID:21769231

  5. Spectral Domain OCT Documented Resolution of Pseudophakic Cystoid Macular Edema after Intravitreal Triamcinolone

    PubMed Central

    Murthy, Ravi K; Chalam, Kakarla V.

    2010-01-01

    Cystoid macular edema (CME) is an important cause of visual loss after cataract surgery. Treatment is usually with topical anti-inflammatory agents, with anti-vascular endothelial growth factor agents and steroids used intravitreally in resistant cases. Even though time-domain Stratus OCT can quantify the macular thickness, it cannot prognosticate visual outcomes due to the poor resolution of images, especially the outer segment-inner segment junction. Spectral-domain OCT (SD-OCT) by its ability to acquire large number of images in a short span of time provides high resolution cross-sectional images of the retina, which not only highlights the underlying pathological changes, but in addition can prognosticate visual recovery. We describe pre and post SD-OCT features of a case of refractory CME who was treated with intravitreal triamcinolone actetonide. PMID:23861610

  6. Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study

    PubMed Central

    Glacet-Bernard, A.; Kuhn, D.; Vine, A.; Oubraham, H.; Coscas, G.; Soubrane, G.

    2000-01-01

    AIMS—To study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO).
METHODS—15 patients with recent onset CRVO (from 1-21 days' duration, mean 8 days) were given 75-100 µg of tPA intravitreally associate with low dose low molecular weight heparin. CRVO was perfused in nine patients and with mild ischaemia not exceeding 100 disc diameters in six patients. Follow up ranged from 5 to 21 months for 14 patients (mean 8 months). Visual acuity measurement, macular threshold (Humphrey perimeter), fluorescein angiography with the scanning laser ophthalmoscope with special emphasis on retinal circulation times, and retinal perfusion were performed at days 0, 1, and 8 and months 1, 3, and 6.
RESULTS—Visual acuity was significantly improved on the first day after treatment in only one eye, and decreased transiently in six eyes (40%). Retinal blood velocity was not significantly modified by tPA injection. Retinal ischaemia developed in six eyes (43%), leading to panretinal photocoagulation in five eyes including one with rubeosis iridis. At the end of follow up, visual acuity had improved to 20/30 or better in five eyes (36%), including two with complete recovery; visual acuity was worse than 20/200 in three eyes (28%). No complication of tPA injection was observed.
CONCLUSION—Intravitreal tPA treatment for CRVO appears to be simple and safe, but did not significantly modify the course of the occlusion in our patients immediately after treatment. Final visual outcome did not differ significantly from that observed in the natural course of the disease, but final visual acuity seemed to be slightly better. A randomised study is required to determine if intravitreal tPA actually improves visual outcome in CRVO.

 PMID:10837386

  7. Neuroprotective effect of systemic and/or intravitreal rosuvastatin administration in rat glaucoma model

    PubMed Central

    Unlu, Metin; Aktas, Zeynep; Gocun, Pinar Uyar; Ilhan, Sevil Ozger; Hasanreisoglu, Murat; Hasanreisoglu, Berati

    2016-01-01

    AIM To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS Ocular hypertension was induced in right eyes of Long-Evans rats (n=30) by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups: oral rosuvastatin, intravitreal rosuvastatin, oral+intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell (RGC) number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling (TUNEL) staining and the expression of glial fibrillary acidic protein (GFAP) in RGC layer was also examined. RESULTS A significant intraocular pressure (IOP) elevation was seen (P=0.002). Elevated IOP resulted in a significant decrease in number of RGCs in group 5 (70.33±8.2 cells/mm2) when compared with controls (92.50±13.72 cells/mm2; P=0.03). The RGC number in group 1 (92.4±7.3 cells/mm2) was significantly higher than group 5 (P=0.03). The numbers of RGC in groups 2, 3 (57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2) were comparable with that of group 5 (P=0.18 and P=0.31). The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreactivity. CONCLUSION Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. However intravitreal rosuvastatin showed a contrary effect and further studies are required. PMID:27158600

  8. Pharmacokinetic analysis of topotecan after intra-vitreal injection. Implications for retinoblastoma treatment.

    PubMed

    Buitrago, Emiliano; Höcht, Christian; Chantada, Guillermo; Fandiño, Adriana; Navo, Elliot; Abramson, David H; Schaiquevich, Paula; Bramuglia, Guillermo F

    2010-07-01

    Topotecan is a promising drug with activity against retinoblastoma, however, attaining therapeutic concentrations in the vitreous humor is still a challenge for the treatment of vitreous seeds in retinoblastoma. Our aim was to characterize topotecan pharmacokinetics in vitreous and aqueous humor, and to assess the systemic exposure after intra-vitreal injection in rabbits as an alternative route for maximizing local drug exposure. Anesthetized rabbits were administered intra-vitreal injections of 5 microg of topotecan. Vitreous, aqueous, and blood samples were collected at pre-defined time points. A validated high-performance liquid chromatography assay was used to quantitate topotecan (lactone and carboxylate) concentrations. Topotecan pharmacokinetic parameters were determined in vitreous, aqueous and plasma using a compartmental analysis. Topotecan lactone concentrations in the vitreous of the injected eye were about 8 ng/mL 48 h after drug administration. The median maximum vitreous, aqueous and plasma total topotecan concentrations (C(max)) were 5.3, 0.68 and 0.21 microg/mL, respectively. The C(max) vitreous/aqueous of treated eyes and the C(max) vitreous/plasma were approximately 8 and 254, respectively. Total topotecan exposure (AUC) in the vitreous of the injected eye was 50 times greater than the total systemic exposure. These findings suggest that intra-vitreal administration of only 5 microg of topotecan reaches significant local levels over an extended period of time while minimizing systemic exposure in the rabbit. Intra-vitreal topotecan administration offers a promising alternative route for enhanced drug exposure in the vitreous humor with potential application for treatment of vitreal seeds in retinoblastoma while avoiding systemic toxicities.

  9. Intravitreal Topotecan Inhibits Laser-induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Gholipour, Mohammad Ali; Kanavi, Mozhgan Rezaei; Ahmadieh, Hamid; Aldavood, Seyed Javid; Nourinia, Ramin; Hosseini, Seyed Bagher; Daftarian, Narsis; Nashtaei, Ebrahim Mohammad; Tousi, Adib; Safi, Sare

    2015-01-01

    Purpose: A two-phase preclinical study was designed to determine the safe dose of intravitreal topotecan and its inhibitory effect on experimental choroidal neovascularization (CNV) in a rat model. Methods: In phase I, 42 rats were categorized into 6 groups, 5 of which received intravitreal topotecan injections of 0.125 μg, 0.25 μg, 0.5 μg, 0.75 μg, and 1.0 μg/5 μl, respectively; the control group received an injection of normal saline. Ophthalmic examination and electroretinography (ERG) were performed on days 7 and 28, and enucleated globes were processed for histopathology and immunostaining for glial fibrillary acidic protein. In phase II, CNV was induced via laser burns in 20 rats and the animals were divided into 2 groups. One group received topotecan and the other received normal saline intravitreally. Four weeks later, mean scores of fluorescein leakage on fluorescein angiography as well as mean CNV areas on histology sections were compared. Results: In phase I, clinical, ERG and histopathologic results were unremarkable in terms of retinal toxicity in all groups. Based on the results of phase I, a dose of 1 μg/5 μl topotecan was chosen for phase II. Leakage scores obtained from late-phase fluorescein angiography were significantly lower in topotecan-treated than control eyes (P < 0.01) four weeks after induction of CNV. Compared to control eyes, topotecan-treated eyes showed a significantly lower incidence of fibrovascular proliferation (8.7% vs. 96.2%) and significantly smaller areas of CNV (P < 0.01). Conclusion: Intravitreal injection of topotecan at a dose of 1 μg/5 μl is safe and may be a promising treatment for CNV. PMID:26730316

  10. Intravitreal aflibercept for the treatment of choroidal neovascularization associated with pathologic myopia: a pilot study

    PubMed Central

    Korol, Andrii R; Zadorozhnyy, Oleg S; Naumenko, Volodymyr O; Kustryn, Taras B; Pasyechnikova, Nataliya V

    2016-01-01

    Purpose To determine the efficacy of intravitreal aflibercept injections for the treatment of patients with choroidal neovascularization (CNV) associated with pathologic myopia. Methods In this uncontrolled, prospective cohort study, 31 eyes of 30 consecutive patients affected by CNV associated with pathologic myopia were treated with intravitreal aflibercept (2 mg) as needed following two initial monthly doses and observed over a 12-month follow-up period. The primary endpoint was change in best-corrected visual acuity (BCVA) at month 12, while central retinal thickness (CRT) on optical coherence tomography (OCT), neovascularization activity on fluorescein angiography, the number of aflibercept injections administered, and safety were examined as secondary endpoints. Results Patients received a mean of 2.6 intravitreal aflibercept injections over the 12-month study period. Compared with baseline, BCVA improved significantly at all time points (P<0.05). Mean (standard deviation [SD]) decimal BCVA was 0.2 (0.1) at baseline and 0.35 (0.16) at month 12. The greatest improvement in BCVA was seen within the first 2 months (P=0.01). Mean (SD) CRT on OCT decreased from 285 (62) µm at baseline to 227 (42) µm (P=0.01) at month 12. There was a continuous decrease in mean CRT on OCT over time. No cases of endophthalmitis, uveitis, stroke, or retinal detachment were noted. No patient demonstrated an intraocular pressure >20 mmHg during any study visit. Conclusion The 12-month results of intravitreal aflibercept for myopic CNV using an as-needed regimen were positive, showing benefits in visual and anatomic outcomes and an acceptable tolerability profile. PMID:27853350

  11. Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats

    PubMed Central

    Akkoç, Tolga; Eraslan, Muhsin; Şahin, Özlem; Özkara, Selvinaz; Vardar Aker, Fugen; Subaşı, Cansu; Karaöz, Erdal; Akkoç, Tunç

    2016-01-01

    Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function. PMID:27300133

  12. Visual performance in patients with neovascular age-related macular degeneration undergoing treatment with intravitreal ranibizumab.

    PubMed

    Sabour-Pickett, Sarah; Loughman, James; Nolan, John M; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  13. Patients’ tolerance of bimanual lid retraction versus a metal speculum for intravitreal injections

    PubMed Central

    Alattas, Khadijah

    2016-01-01

    Objective To compare patients’ acceptance of and correlate their pain level for bimanual versus metal speculum fixation in intravitreal injections. Design Prospective analysis. Participants Seventy-three eyes of 56 patients. Methods A questionnaire indicating patients’ discomfort and pain grading immediately after intravitreal injections using either bimanual fixation or metal speculum fixation (Barraquer Wire Speculum). Results Fifty-six patients who underwent intravitreal injections were enrolled in this study for various conditions. Patients’ overall pain and discomfort were as follows, right eye – bimanual was 0.3 on our grading scale with a standard deviation of 0.54, right eye – metal was 1.6 on our grading scale with a standard deviation of 1.5, left eye – bimanual was 0.41 on our grading scale with a standard deviation of 0.87, and left eye – metal was 1.91 on our grading scale with a standard deviation of 1.14 (P=0.003). Conclusion Patients who underwent bimanual fixation had a much more comfortable experience with less pain in comparison to patients who underwent metal speculum fixation. PMID:27660408

  14. Intravitreal Injection of Splice-switching Oligonucleotides to Manipulate Splicing in Retinal Cells.

    PubMed

    Gérard, Xavier; Perrault, Isabelle; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel

    2015-09-01

    Leber congenital amaurosis is a severe hereditary retinal dystrophy responsible for neonatal blindness. The most common disease-causing mutation (c.2991+1655A>G; 10-15%) creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. Recently, we reported that splice-switching oligonucleotides (SSO) allow skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients, supporting the feasibility of a SSO-mediated exon skipping strategy to correct the aberrant splicing. Here, we present data in the wild-type mouse, which demonstrate that intravitreal administration of 2'-OMePS-SSO allows selective alteration of Cep290 splicing in retinal cells, including photoreceptors as shown by successful alteration of Abca4 splicing using the same approach. We show that both SSOs and Cep290 skipped mRNA were detectable for at least 1 month and that intravitreal administration of oligonucleotides did not provoke any serious adverse event. These data suggest that intravitreal injections of SSO should be considered to bypass protein truncation resulting from the c.2991+1655A>G mutation as well as other truncating mutations in genes which like CEP290 or ABCA4 have a mRNA size that exceed cargo capacities of US Food and Drug Administration (FDA)-approved adeno-associated virus (AAV)-vectors, thus hampering gene augmentation therapy.

  15. Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

    PubMed Central

    Loughman, James; Nolan, John M.; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A.; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition. PMID:23533703

  16. Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration

    PubMed Central

    Reis, Gustavo MSM; Grigg, John; Chua, Brian; Lee, Anne; Lim, Ridia; Higgins, Ralph; Martins, Alessandra; Goldberg, Ivan

    2017-01-01

    ABSTRACT Aim The aim of this article is to evaluate the rate of patients developing sustained elevated intraocular pressure (IOP) after ranibizumab (Lucentis) intravitreal (IVT) injections. Design This is a retrospective study. Participants Charts of 192 consecutive patients receiving Lucentis for age-related macular degeneration (AMD) were retrospectively reviewed. Materials and methods We enrolled patients with at least two IOP measurements between injections. Elevated IOP was defined as >21 mm Hg with an increase of at least 20% from baseline. Noninjected contralateral eyes of the same patient cohort were used as control. Main outcome measures Primary outcome was defined as elevated IOP. Secondary outcomes were presence and type of glaucoma, number of injections, and time to IOP elevation. Results Elevated IOP occurred at a significantly higher rate in eyes receiving IVT ranibizumab (7.47%; n = 9) compared with control (0.93%; n = 1). Patients with preexisting glaucoma or ocular hypertension (OHT) were more likely to develop elevated IOP after IVT ranibizumab injection. Conclusion Intravitreal ranibizumab injections are associated with sustained IOP elevation in some eyes. How to cite this article Reis GMSM, Grigg J, Chua B, Lee A, Lim R, Higgins R, Martins A, Goldberg I, Clement CI. The Incidence of Intraocular Pressure Elevation following Intravitreal Ranibizumab (Lucentis) for Age-related Macular Degeneration. J Curr Glaucoma Pract 2017;11(1):3-7. PMID:28138211

  17. Pharmacokinetics, Electrophysiological, and Morphological Effects of the Intravitreal Injection of Mycophenolic Acid in Rabbits

    PubMed Central

    Gasparin, Fabio; Aguiar, Renata Genaro; Ioshimoto, Gabriela Lourençon; Silva-Cunha, Armando; Fialho, Silvia Ligório; Liber, André Mauricio; Nagy, Balázs Vince; Oiwa, Nestor Norio; Costa, Marcelo Fernandes; Joselevitch, Christina; Ventura, Dora Fix

    2014-01-01

    Abstract Purpose: To determine the half-life of mycophenolic acid (MPA) in the vitreous of New Zealand albino rabbits after intravitreal injection and the retinal toxicity of different doses of MPA. Methods: Ten micrograms of MPA (Roche Bioscience, Palo Alto, CA) was injected in the vitreous of 16 rabbits, animals were sacrificed at different time-points, and vitreous samples underwent high-performance liquid chromatography. For functional and morphological studies, 5 doses of MPA (0.05, 0.5, 2, 10, and 100 μg) were injected in the vitreous of 20 rabbits. As control, contralateral eyes were injected with aqueous vehicle. Electroretinograms (ERGs) were recorded before injection and at days 7, 15, and 30. Animals were sacrificed on day 30 and retinas were analyzed under light microscopy. Results: MPA half-life in the vitreous was 5.0±0.3 days. ERG revealed photoreceptor functional impairment in eyes injected with 0.5 μg and higher on day 30, while eyes injected with 100 μg presented the same changes already from day 15. No morphological change was found. Conclusions: MPA vitreous half-life is 5.0 days. Intravitreal injection of 0.5 μg MPA and higher causes dose- and time-related photoreceptor sensitivity decrease in rabbits. The MPA dose of 0.05 μg may be safe for intravitreal use in rabbits. PMID:24828287

  18. Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro.

    PubMed

    Ahn, Jae-Soon; Choi, Hoo-Kyun; Chun, Myong-Kwan; Ryu, Jei-Man; Jung, Jae-Hee; Kim, Yue-Un; Cho, Chong-Su

    2002-03-01

    Transmucosal drug delivery (TMD) system using mucoadhesive polymer has been recently interested due to the rapid onset of action, high blood level, avoidance of the first-pass effect and the exposure of the drug to the gastrointestinal tract. A novel mucoadhesive polymer complex composed of chitosan and poly(acrylic acid) (PAA) was prepared by template polymerization of acrylic acid in the presence of chitosan for the TMD system. Triamcinolone acetonide (TAA) was loaded into the chitosan/PAA polymer complex film. TAA was evenly dispersed in chitosan, PAA polymer complex film without interaction with polymer complex. Release behavior of TAA from the mucoadhesive polymer film was dependent on time, pH, loading content of drug, and chitosan PAA ratio. The analysis of the drug release from the mucoadhesive film showed that TAA might be released from the chitosan/PAA polymer complex film through non-Fickian diffusion mechanism.

  19. Histrelin Implant

    MedlinePlus

    ... implant (Supprelin LA) is used to treat central precocious puberty (CPP; a condition causing children to enter puberty too soon, resulting in faster than normal bone growth and development of sexual characteristics) in girls ...

  20. Penile Implants

    MedlinePlus

    ... placed inside the penis to allow men with erectile dysfunction (ED) to get an erection. Penile implants are ... complications and follow-up care. For most men, erectile dysfunction can be successfully treated with medications or use ...

  1. Cochlear implants.

    PubMed

    Connell, Sarah S; Balkany, Thomas J

    2006-08-01

    Cochlear implants are cost-effective auditory prostheses that safely provide a high-quality sensation of hearing to adults who are severely or profoundly deaf. In the past 5 years, progress has been made in hardware and software design, candidate selection, surgical techniques, device programming, education and rehabilitation,and, most importantly, outcomes. Cochlear implantation in the elderly is well tolerated and provides marked improvement in auditory performance and psychosocial functioning.

  2. An application of second-order UV-derivative spectrophotometry for study of solvolysis of a novel fluocinolone acetonide ester

    NASA Astrophysics Data System (ADS)

    Markovic, Bojan; Vladimirov, Sote; Cudina, Olivera; Savic, Vladimir; Karljikovic-Rajic, Katarina

    2010-02-01

    A novel topical corticosteroid FA-21-PhP, 2-phenoxypropionate ester of fluocinolone acetonide, has been synthesized in order to investigate the possibility of decreasing systemic side effects. In this study model system for in vitro solvolytic reaction of FA-21-PhP has been analyzed in ethanol/water (90:10, v/v) with excess of sodium hydrogen carbonate. The selected conditions have been used as in vitro model for activation of corticosteroid C-21 ester prodrug. The second-order derivative spectrophotometric method (DS) using zero-crossing technique was developed for monitoring ternary mixture of solvolysis. Fluocinolone acetonide (FA) as a solvolyte was determined in the mixture in the concentration range 0.062-0.312 mM using amplitude 2D 274.96. Experimentally determined LOD value was 0.0295 mM. The accuracy of proposed DS method was confirmed with HPLC referent method. Peak area of parent ester FA-21-PhP was used for solvolysis monitoring to ensure the initial stage of changes. Linear relationship in HPLC assay for parent ester was obtained in the concentration range 0.054-0.54 mM, with experimentally determined LOD value of 0.0041 mM. Investigated solvolytic reaction in the presence of excess of NaHCO 3 proceeded via a pseudo-first-order kinetic with significant correlation coefficients 0.9891 and 0.9997 for DS and HPLC, respectively. The values of solvolysis rate constant calculated according to DS and HPLC methods are in good accordance 0.038 and 0.043 h -1, respectively.

  3. Contraceptive implants.

    PubMed

    McDonald-Mosley, Raegan; Burke, Anne E

    2010-03-01

    Implantable contraception has been extensively used worldwide. Implants are one of the most effective and reversible methods of contraception available. These devices may be particularly appropriate for certain populations of women, including women who cannot use estrogen-containing contraception. Implants are safe for use by women with many chronic medical problems. The newest implant, Implanon (Organon International, Oss, The Netherlands), is the only device currently available in the United States and was approved in 2006. It is registered for 3 years of pregnancy prevention. Contraceptive implants have failure rates similar to tubal ligation, and yet they are readily reversible with a return to fertility within days of removal. Moreover, these contraceptive devices can be safely placed in the immediate postpartum period, ensuring good contraceptive coverage for women who may be at risk for an unintended pregnancy. Irregular bleeding is a common side effect for all progestin-only contraceptive implants. Preinsertion counseling should address possible side effects, and treatment may be offered to women who experience prolonged or frequent bleeding.

  4. Combined therapy (intravitreal bevacizumab plus verteporfin photodynamic therapy) versus intravitreal bevacizumab monotherapy for choroidal neovascularization due to age-related macular degeneration: a 1-year follow-up study

    PubMed Central

    Saviano, Sandro; Leon, Pia Easter; Mangogna, Alessandro; Tognetto, Daniele

    2016-01-01

    Purpose To assess the efficacy and safety of combined intravitreal bevacizumab and low-fluency-rate photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) and to compare it with intravitreal bevacizumab monotherapy. Methods A total of 62 eyes of 62 patients with angiographic evidence of CNV were divided into 2 groups: the eyes of one group were treated with a combined therapy of 1 intravitreal bevacizumab injection (1.25 mg) and PDT within 7 days; the eyes of the other group received intravitreal bevacizumab monotherapy. Clinical evidence of complications, best-corrected visual acuity (BVCA) and fluorescein leakage were evaluated. Best-corrected visual acuity and optical coherence tomography (OCT) were tested monthly and followed for 12 months. Results In the combined group the mean BCVA increased from 0.61 logMAR before the treatment to 0.54 logMAR at 12 months’ follow-up. In the monotherapy group the mean BCVA increased from 0.65 logMAR to 0.60 logMAR at 12 months’ follow-up. There was no significant difference in visual acuity outcomes between groups (P > 0.05). In the combined group the mean number of treatments was 1.19 per patient; in the monotherapy group, 5.31 per patient (P < 0.01). Conclusions Combined therapy appears to be an effective option for CNV associated with AMD treatment allowing a significant reduction of intravitreal injections. PMID:27582675

  5. In vitro and in vivo evaluation of a bondable compact for the prolonged delivery of triamcinolone acetonide to the oral cavity in patients with lichen planus.

    PubMed

    Deasy, P B; Collins, A E; Burke, F M; Shanley, D B

    1989-01-01

    Compacts weighing 40 mg and containing triamcinolone acetonide 70-90% and polyhydroxybutyric acid (PHB) 30-10% or poly (DL-lactic acid) 20% with a diameter of 5 mm were bonded onto the side-wall of molar teeth. In vitro dissolution studies showed the compacts to release 12% of drug in 30 days with an initial burst effect. Drug loading or polymer matrix type had little effect. In vivo studies in dogs showed that compacts containing 80% drug in PHB produced salivary levels of triamcinolone acetonide for 30 days. When evaluated in five patients with lichen planus resistant to conventional therapy, these compacts produce a slight clinical improvement in three subjects. Differential scanning calorimetry studies confirmed that the drug and polymer were present as a physical mix in these compacts.

  6. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study

    PubMed Central

    Satarian, Leila; Nourinia, Ramin; Safi, Sare; Kanavi, Mozhgan Rezaei; Jarughi, Neda; Daftarian, Narsis; Arab, Leila; Aghdami, Nasser; Ahmadieh, Hamid; Baharvand, Hossein

    2017-01-01

    Purpose: To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). Methods: A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs. The patients were followed for one year. Further evaluation of MSCs was performed by injection of these cells into the mouse vitreous cavity. Results: No, adverse events were observed in eyes of 2 out of 3 patients after transplantation of MSCs. These patients reported improvements in perception of the light after two weeks, which lasted for 3 months. However, severe fibrous tissue proliferation was observed in the vitreous cavity and retrolental space of the third patient's eye, which led to tractional retinal detachment (TRD), iris neovascularization and formation of mature cataract. Injection of this patient's MSCs into the vitreous cavity of mice also resulted in fibrosis; however, intravitreal injections of the two other patients' cells into the mouse vitreous did not generate any fibrous tissue. Conclusion: Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\ PMID:28299008

  7. High-dose methotrexate following intravitreal methotrexate administration in preventing central nervous system involvement of primary intraocular lymphoma.

    PubMed

    Akiyama, Hiroki; Takase, Hiroshi; Kubo, Fumito; Miki, Tohru; Yamamoto, Masahide; Tomita, Makoto; Mochizuki, Manabu; Miura, Osamu; Arai, Ayako

    2016-10-01

    In order to prevent central nervous system (CNS) involvement and improve the prognosis of primary intraocular lymphoma (PIOL), we prospectively evaluated the efficacy of combined therapy using intravitreal methotrexate (MTX) and systemic high-dose MTX on treatment-naïve PIOL. Patients with newly diagnosed PIOL whose lymphoma was limited to the eyes were enrolled. The patients were treated with weekly intravitreal MTX until the ocular lesions were resolved, followed by five cycles of systemic high-dose MTX (3.5 g/m(2) ) every other week. Ten patients were enrolled in this study and completed the treatment. All patients achieved complete response for their ocular lesions with rapid decrease of intravitreal interleukin-10 concentration. Adverse events of intravitreal and systemic high-dose MTX were mild and tolerable. With a median follow-up of 29.5 months, four patients (40%) experienced the CNS disease development and the mean CNS lymphoma-free survival (CLFS) time was 51.1 months. Two-year CLFS, which was the primary end-point of the study, was 58.3% (95% confidence interval, 23.0-82.1%). In contrast, eight patients were treated with intravitreal MTX alone in our institute, and their 2-year CLFS was 37.5% (95% confidence interval, 8.7-67.4%). In conclusion, systemic high-dose MTX following intravitreal MTX is feasible and might be effective in preventing CNS involvement of PIOL. Further arrangements are worth considering in order to improve the effects. This study was registered with UMIN Clinical Trials Registry (UMIN000003921).

  8. Cochlear Implants

    MedlinePlus

    ... outside of the body, behind the ear. A second part is surgically placed under the skin. An implant does not restore normal hearing. It can help a person understand speech. Children and adults can benefit from them. National Institute on Deafness and Other Communication Disorders

  9. Vitreous pharmacokinetics and electroretinographic findings after intravitreal injection of acyclovir in rabbits

    PubMed Central

    Damico, Francisco Max; Scolari, Mariana Ramos; Ioshimoto, Gabriela Lourençon; Takahashi, Beatriz Sayuri; da Silva Cunha, Armando; Fialho, Sílvia Ligório; Bonci, Daniela Maria; Gasparin, Fabio; Ventura, Dora Fix

    2012-01-01

    OBJECTIVES: Acute retinal necrosis is a rapidly progressive and devastating viral retinitis caused by the herpesvirus family. Systemic acyclovir is the treatment of choice; however, the progression of retinal lesions ceases approximately 2 days after treatment initiation. An intravitreal injection of acyclovir may be used an adjuvant therapy during the first 2 days of treatment when systemically administered acyclovir has not reached therapeutic levels in the retina. The aims of this study were to determine the pharmacokinetic profile of acyclovir in the rabbit vitreous after intravitreal injection and the functional effects of acyclovir in the rabbit retina. METHODS: Acyclovir (Acyclovir; Bedford Laboratories, Bedford, OH, USA) 1 mg in 0.1 mL was injected into the right eye vitreous of 32 New Zealand white rabbits, and 0.1 mL sterile saline solution was injected into the left eye as a control. The animals were sacrificed after 2, 9, 14, or 28 days. The eyes were enucleated, and the vitreous was removed. The half-life of acyclovir was determined using high-performance liquid chromatography. Electroretinograms were recorded on days 2, 9, 14, and 28 in the eight animals that were sacrificed 28 days after injection according to a modified protocol of the International Society for Clinical Electrophysiology of Vision. RESULTS: Acyclovir rapidly decayed in the vitreous within the first two days after treatment and remained at low levels from day 9 onward. The eyes that were injected with acyclovir did not present any electroretinographic changes compared with the control eyes. CONCLUSIONS: The vitreous half-life of acyclovir is short, and the electrophysiological findings suggest that the intravitreal delivery of 1 mg acyclovir is safe and well tolerated by the rabbit retina. PMID:22948462

  10. Streptococcus Endophthalmitis Outbreak after Intravitreal Injection of Bevacizumab: One-year Outcomes and Investigative Results

    PubMed Central

    Goldberg, Roger A.; Flynn, Harry W.; Miller, Darlene; Gonzalez, Serafin; Isom, Ryan F.

    2013-01-01

    Purpose To report the one-year clinical outcomes of an outbreak of Streptococcus endophthalmitis after intravitreal injection of bevacizumab, including visual acuity outcomes, microbiological testing and compound pharmacy investigations by the Food and Drug Administration (FDA). Design Retrospective consecutive case series. Participants 12 eyes of 12 patients who developed endophthalmitis after receiving intravitreal bevacizumab prepared by a single compounding pharmacy. Methods Medical records of patients were reviewed; phenotypic and DNA analyses were performed on microbes cultured from patients and from unused syringes. An inspection report by the FDA based on site-visits to the pharmacy that prepared the bevacizumab syringes was summarized. Main Outcome Measures Visual acuity, interventions received, time-to-intervention; microbiological consistency; FDA inspection findings. Results Between July 5 and July 8, 2011, 12 patients developed endophthalmitis after intravitreal bevacizumab from syringes prepared by a single compounding pharmacy. All patients received initial vitreous tap and injection, and eight (67%) subsequently underwent pars plana vitrectomy (PPV). After twelve months follow-up, outcomes have been poor: 7 patients (58%) required evisceration or enucleation, and only one patient regained pre-injection visual acuity. Molecular testing using real time polymerase chain reaction, partial sequencing of the groEL gene, and multilocus sequencing of 7 housekeeping genes confirmed the presence of a common strain of Streptococcus mitis/oralis in vitreous specimens and seven unused syringes prepared by the compounding pharmacy at the same time. An FDA investigation of the compounding pharmacy noted deviations from standard sterile technique, inconsistent documentation, and inadequate testing of equipment required for safe preparation of medications. Conclusions In this outbreak of endophthalmitis, outcomes have been generally poor and PPV did not improve

  11. Randomized Clinical Trial Evaluating Intravitreal Ranibizumab or Saline for Vitreous Hemorrhage from Proliferative Diabetic Retinopathy

    PubMed Central

    Bhavsar, Abdhish R.; Torres, Karisse; Beck, Roy W.; Bressler, Neil M.; Ferris, Frederick L.; Friedman, Scott M.; Glassman, Adam R.; Maturi, Raj K.; Melia, Michele; Singer, Michael A.; Stockdale, Cynthia R.

    2014-01-01

    Objective To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage (VH) from proliferative diabetic retinopathy (PDR). Main Outcome Cumulative probability of vitrectomy within 16 weeks. Methods Study eyes had VH from PDR precluding panretinal photocoagulation (PRP) completion. Eyes were randomly assigned to 0.5-mg ranibizumab (N = 125) or saline (N = 136) at baseline, 4, and 8 weeks. Results Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab versus 17% with saline (difference 4%, 95% confidence interval −4%–13%) and of complete PRP without vitrectomy by 16-weeks was 44% and 31% respectively (P = 0.05). The mean (±SD) visual acuity improvement from baseline to 12 weeks was 22±23 letters and 16±31 letters respectively (P = 0.04). Recurrent VH occurred within 16 weeks in 6% and 17% respectively (P = 0.01). One eye developed endophthalmitis after saline. Conclusions Overall the 16 week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with VH from PDR. Short term secondary outcomes including visual acuity improvement, increased PRP completion rates, and reduced recurrent VH rates suggest biologic activity of ranibizumab. Long term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab are different than observation alone cannot be determined from this study. Application to Clinical Practice Intravitreal ranibizumab does not appear to reduce vitrectomy rates compared with saline for VH from PDR. PMID:23370902

  12. Intravitreal ziv-aflibercept for macular edema following retinal vein occlusion

    PubMed Central

    Paulose, Remya; Chhablani, Jay; Dedhia, Chintan J; Stewart, Michael W; Mansour, Ahmad M

    2016-01-01

    Aim To report the efficacy of intravitreal ziv-aflibercept injections in eyes with macular edema due to retinal vein occlusions (RVOs). Methods Consecutive patients with persistent or recurrent macular edema (central macula thickness >250 μm) due to RVO were enrolled in this prospective study. Study eyes received intravitreal injections of ziv-aflibercept (1.25 mg/0.05 mL) at baseline. Patients were reassessed monthly for 4 months and given additional injections pro re nata for worsening best-corrected visual acuity (BCVA), intraretinal edema or subretinal fluid seen on spectral domain optical coherence tomography, or central macular thickness (CMT) measurements >250 μm. The primary endpoint was improvement in mean CMT at 4 months. Secondary endpoints included improvement in mean BCVA, and ocular and systemic safety signals. Results Nine eyes (five central and four branch RVOs) of nine patients were enrolled. The mean ± standard deviation CMT decreased from 604±199 μm at baseline to 319±115 μm (P=0.001) at 1 month and to 351±205 μm (P=0.026) at 4 months. The mean BCVA did not improve significantly from baseline (1.00 LogMAR) to the 1-month (0.74 LogMAR; P=0.2) and 4-month (0.71 LogMAR; P=0.13) visits. No safety signals were noted. Conclusion In this small prospective study, intravitreal ziv-aflibercept significantly improved mean CMT in eyes with persistent or recurrent macular edema due to RVOs. Prospective, randomized trials comparing ziv-aflibercept with standard pharmacotherapy are needed to better define efficacy and safety. PMID:27703326

  13. Comparison of in vivo activation of triamcinolone acetonide- and RU 38486-receptor complexes in the CEM-C7 and IM-9 human leukemic cell lines.

    PubMed

    Schmidt, T J

    1989-08-15

    RU 38486 functions as a pure antiglucocorticoid in the human leukemic cell lines CEM-C7 and IM-9. Despite the fact that RU 38486 has been reported to promote considerable in vitro receptor activation to a DNA-binding form, this steroid may be relatively incapable of promoting this physiologically relevant conformational change in vivo. In the experiments reported here the potential ability of RU 38486 to promote in vivo activation has been compared with that of a potent agonist, triamcinolone acetonide. In vivo activation was evaluated by DEAE-cellulose chromatographic analyses of cytosolic extracts prepared from lysed cells which had previously been labeled with either 30 nM [3H]triamcinolone acetonide or [3H]RU 38486 and subsequently incubated at 37 degrees C. Using this anion-exchange procedure, in vivo activation of the agonist-receptor complexes was shown to occur in both a time- and temperature-dependent fashion in both cell lines. This in vivo activation was reflected by progressive decreases in the bound [3H]triamcinolone acetonide associated with the unactivated (high salt-eluting) peaks eluted from DEAE-cellulose, small yet detectable increases in the bound radioactivity eluted in the activated (low-salt eluting) peaks, and a significant increase in the ability of the cytoplasmic [3H]triamcinolone acetonide-receptor complexes to bind to DNA-cellulose. Additional experiments employing DEAE-cellulose chromatography demonstrated that after incubation at 37 degrees C for 1 h, at least some in vivo activation of cytosolic [3H]RU 38486-receptor complexes could be detected in CEM-C7 cells, although the antagonist was less effective than the agonist in facilitating this conformational change. In IM-9 lymphocytes essentially no in vivo activation could be detected using this same protocol. Nuclear translocation assays were also independently performed to evaluate in vivo receptor activation. Incubation of intact cells with 30 nM [3H]triamcinolone acetonide or [3H

  14. Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy.

    PubMed

    Zlotcavitch, Leonid; Flynn, Harry W; Avery, Robert L; Rachitskaya, Aleksandra

    2015-01-01

    We report a patient with progression to a macula-off tractional retinal detachment in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection. A 32-year-old diabetic man noted decreased vision in his left eye 1 week following 25 gauge pars plana vitrectomy, gas tamponade, and intraoperative injection of bevacizumab in his right eye. Left eye visual acuity decreased from 20/80 to 20/200, and macula-off tractional retinal detachment was seen on clinical exam and imaging. Progression of tractional retinal detachment associated with proliferative diabetic retinopathy in a fellow eye after a contralateral intraoperative intravitreal bevacizumab injection may occur.

  15. Incidence of endophthalmitis following intravitreal Bevacizumab injection at a tertiary care hospital in Eastern Province of Saudi Arabia

    PubMed Central

    Cheema, Rizwan A.; Alshihry, Ahmad M.; Cheema, Haider R.

    2014-01-01

    The aim of this communication is to report the incidence of endophthalmitis following the use of intravitreal Bevacizumab (IVB) at a tertiary care hospital in the Eastern province of Saudi Arabia. A total of 2769 intravitreal Bevacizumab injections were carried out between January 2009 and April 2014. During this period, one case of endophthalmitis following IVB injection occurred. The overall incidence of clinical endophthalmitis was 0.036% (1/2769; 95% confidence interval: 0.0001–0.002%). This compares favorably with studies reported from other parts of the world. PMID:25892933

  16. Panretinal photocoagulation versus panretinal photocoagulation plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy

    PubMed Central

    Zhou, Ai-Yi; Zhou, Chen-Jing; Yao, Jing; Quan, Yan-Long; Ren, Bai-Chao; Wang, Jian-Ming

    2016-01-01

    AIM To evaluate the effects of panretinal photocoagulation (PRP) compared with PRP plus intravitreal bevacizumab (IVB) in patients with high-risk proliferative diabetic retinopathy (PDR) according to the Early Treatment Diabetic Retinopathy Study criteria. METHODS The data were collected retrospectively from the eyes of high-risk PDR patients, which were divided into two groups. After treated with standard PRP, the eyes were randomly assigned to receive only PRP (PRP group) or PRP plus intravitreal injection of 1.25 mg of bevacizumab (PRP-Plus group). Patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), intraocular pressure (IOP), and new vessel size in fluorescein angiography (FA) and optical coherence tomography for the assessment of central subfield macular thickness (CSMT) at baseline and at weeks 12 (±2), 16 (±2), 24 (±2) and 48 (±2). Main outcome measures also included vitreous clear-up time and neovascularization on the disc (NVD) regression time. Adverse events associated with intravitreal injection were investigated. RESULTS Thirty consecutive patients (n=36 eyes) completed the 48-week follow-up. There was no significant difference between the PRP and PRP-Plus groups with respect to age, gender, type or duration of diabetes, area of fluorescein leakage from active neovascularizations (NVs), BCVA or CSMT at baseline. The mean vitreous clear-up time was 12.1±3.4wk after PRP and 8.4±3.5wk after PRP combined with IVB. The mean time interval from treatment to complete NVD regression on FA examination was 15.2±3.5wk in PRP group and 12.5±3.1wk in PRP-Plus group. No significant difference in CSMT was observed between the groups throughout the study period. However, the total area of actively leaking NVs was significantly reduced in the PRP-Plus group compared with the PRP group (P<0.05). Patients received an average of 1.3 injections (range: 1-2). Ten eyes (27.8%) underwent 2 injections. Two eyes had ocular

  17. Ocular penetration of grepafloxacin after intravitreal administration in albino and pigmented rabbits.

    PubMed

    Solans, C; Bregante, M A; Garcia, M A; Perez, S

    2004-06-01

    Ocular penetration of grepafloxacin into several ocular tissues was determined in albino and pigmented rabbits following a single intravitreal administration. After administration, grepafloxacin was detected in all ocular tissues studied in both breeds of rabbits. The superior mean penetration ratios were found in the chorioretina and lens of albino rabbits, and in the chorioretina, iris and lens of pigmented rabbits. A significantly greater penetration of grepafloxacin was found in the chorioretina and iris of the pigmented rabbits than in those of the albino rabbits. As a final conclusion, grepafloxacin detected in different ocular structures could attain therapeutic concentrations against a variety of ocular conditions.

  18. [A technique of rhesus monkey neural progenitor cells intravitreal transplant to rats].

    PubMed

    Bian, Hui; Fan, Yao-Dong; Guo, Li-Yun; Yu, Hua-Lin

    2012-02-01

    To investigate a simple and effective intraocular xenotransplant technique of rhesus monkey neural progenitor cells to rats, mechanical injury was induced in the rat's right retina. And the GFP-labeled rhesus monkey neural progenitor cells suspension was slowly injected into the vitreous space of the right injured and left control eye. Confocal image suggested that the xenografted cells survived in both the injured and control eye, meanwhile the cells integrated in the injured right retina. The results demonstrated that intravitreal xenotransplant could be adopted as a simple and reliable method.

  19. Evaluation of Intravitreal Ranibizumab on the Surgical Outcome for Diabetic Retinopathy With Tractional Retinal Detachment

    PubMed Central

    Dong, Feng; Yu, Chenying; Ding, Haiyuan; Shen, Liping; Lou, Dinghua

    2016-01-01

    Abstract This study aims to investigate intravitreal injection of Ranibizumab on the surgical outcome for diabetic patients who had tractional retinal detachment but did not receive any preoperative retinal photocoagulation. Ninety-seven patients (97 eyes) who had diabetic retinopathy with tractional retinal detachment were enrolled to receive 23-G pars plana vitrectomy (PPV). They were assigned to an experimental group (Group I, n = 47 eyes) and a control group (Group II, n = 50 eyes). The patients in Group I were given 1 injection of intravitreal Ranibizumab (Lucentis 0.5 mg/0.05 mL) 1 week before surgery, whereas those in Group II went down to surgery directly. Follow-ups were performed for 6 months to 3 years (16 ± 6 months), and indicators observed included postoperative best-corrected visual acuity, complications, and retinal thickness in the macula measured by optical coherence tomography. In Group I, BCVA improved from logMAR 1.92 ± 0.49 to logMAR 0.81 ± 0.39 following surgery, whereas in Group II, BCVA improved from logMAR 1.91 ± 0.49 to logMAR 0.85 ± 0.41. There was significant postoperative gain in vision, but there was no significant difference between the 2 groups at postoperative follow-up visits. The mean duration of vitrectomy in Group I and Group II was (40 ± 7) minutes and (53 ± 9) minutes, respectively, with significant difference. Iatrogenic breaks were noted in 5 eyes (11%) in the experimental group and 17 eyes (34%) in the control group; the difference was significant. The retinal thickness in the macula measured by OCT was (256 ± 44) μm and (299 ± 84) μm in Group I and Group II respectively with significant difference. Besides, there were significantly more eyes in Group II that required silicone oil tamponade and postoperative retinal photocoagulation. 23-G PPV combined with intravitreal tamponade and panretinal photocoagulation still remains an effective regimen for the

  20. Peristence of triamcinolone crystals after intra-vitreal injection: Benign crystalline hyaloidopathy

    PubMed Central

    Zarifa, Rafik; Shaikh, Saad; Kester, Elizabeth

    2013-01-01

    We report a case of unusually long persistence of triamcinolone crystals after intra-vitreal injection. Crystals were noted on fundus examination predominantly confined to the posterior pole. Optical coherence tomography localized the crystals to the posterior hyaloidal surface. Over 6 years of follow-up the patient has retained good visual acuity and no observable changes in the retina. As the condition clinically resembles both crystalline maculopathy and asteroid hyalosis, we suggest the term ‘drug-induced benign crystalline hyaloidopathy’. PMID:23685493

  1. [Time course of changes in aqueous flare following intravitreous gas injection in rabbits].

    PubMed

    Yamamoto, K

    1991-06-01

    The quantitative changes of the aqueous flare following intravitreous gas injection were determined by laser flare-cell metry in rabbits. A volume of 0.4 ml of air, 100% sulfur hexafluoride (SF6), or 100% perfluoropropane (C3F8), was injected separately into the vitreous of pigmented rabbits. The normal range of the aqueous flare was 7.8 +/- 3.0 (photon counts/msec). Each model showed an increase of aqueous flare on the first day (air: 18.9 +/- 9.1, SF6: 19.5 +/- 11.5, C3F8: 40.8 +/- 22.8). Subsequently, the aqueous flare of air-injected eyes gradually decreased, while that of SF6-injected eyes increased on the 4th day, and then gradually decreased. Also that of C3F8-injected eyes increased on the 4th day, and the 7th day, then decreased on the 14th day, but it was still higher than normal. Cataracts developed in two of the five eyes injected with SF6 and all of the four eyes injected with C3F8. These findings revealed that following intravitreous gas injection, disruption of the blood-ocular barrier depended on the expansibility of the gas and the length of time it remained in the vitreous cavity.

  2. Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model.

    PubMed

    Aly, Eman; Ebrahim, Amal

    2016-04-01

    The aim of this study was to explore the changes in electroretinogram of rabbit retina and apoptosis in methotrexate-induced toxicity. Rabbits were divided into 5 groups. Group I served as control in which saline solutions was injected intravitreally. Methotrexate (800 μg, 1.76 μmol) was injected into the vitreous of both eyes of rabbits groups II, III, IV and V by an insulin injector with a 26 gauge needle under general anesthesia. Retinal function was assessed by electroretinogram (ERG) after 2, 4, 10 days and one month then animals were decapitated. The eyes were enucleated and processed for DNA fragmentation studies by gel electrophoresis to retinae and measurement of caspase-3 activities. The results indicated a significant reduction (p ˂ 0.05) in a- and b-wave, a time-dependent appearance of the typical ladder pattern of internucleosomal fragmentation, a characteristic of apoptosis and increase of relative caspase-3 activity after methotrexate intravitreal injection. Methotrexate lead to apoptosis, increase of caspase-3 and affect retinal function.

  3. Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections

    PubMed Central

    Levin, Ariana M; Rusu, Irene; Orlin, Anton; Gupta, Mrinali P; Coombs, Peter; D’Amico, Donald J; Kiss, Szilárd

    2017-01-01

    Purpose The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. Methods This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Results Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. Conclusion In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA. PMID:28176934

  4. Intravitreal Kinetics of Hesperidin, Hesperetin and Hesperidin G: Effect of Dose and Physicochemical Properties

    PubMed Central

    Srirangam, Ramesh; Hippalgaonkar, Ketan; Majumdar, Soumyajit

    2014-01-01

    Hesperidin, a flavanone glycoside, and its aglycone hesperetin, are potential candidates for the treatment of diabetic retinopathy and macular edema. The objective of this study was to delineate the vitreal pharmacokinetics of hesperidin and hesperetin and the hydrophilic derivative hesperidin G (glucosyl hesperedin), following intravitreal administration in anaesthetized rabbits. Concentration changes in the vitreous humor were monitored using microdialysis sampling procedure. All three molecules were administered intravitreally at three dose levels (50 μl injection volume containing 1.5, 4.5 and 15 µg of the drug, resulting in a final vitreal concentration of 1, 3 and 10 μg/mL). Vitreal microdialysis samples were collected every 20 minutes over a period of 10 h. All three molecules exhibited linear pharmacokinetics, within the dose range tested, since AUC and Cmax increased linearly with increasing dose and a significant difference in the elimination parameters, like clearance or half-life, was not observed. The vitreal elimination half-life of these three compounds was observed to correlate with the molecular weight and lipophilicity of the molecules. The findings from this study provide practical information that will be useful in the future design of ocular drug delivery strategies for the bioflavonoids. PMID:22228207

  5. Intravitreal bevacizumab injections for diabetic macular edema – predictors of response: a retrospective study

    PubMed Central

    Joshi, Lavnish; Bar, Asaf; Tomkins-Netzer, Oren; Yaganti, Satish; Morarji, Jiten; Vouzounis, Panayiotis; Seguin-Greenstein, Sophie; Taylor, Simon R; Lightman, Sue

    2016-01-01

    Background Outcomes of intravitreal antivascular endothelial growth factor injections are variable among patients with diabetic macular edema (DME). The aim of this study was to determine the ocular and systemic predictors of DME response to intravitreal bevacizumab (IVB). Methods Retrospective review over 2 years of 78 eyes from 54 patients. An anatomical response to IVB was defined as a 20% reduction in central macula thickness after the first course (three injections) of IVB. Results Twenty-eight percent of patients had an anatomical response after the first course of IVB. Systemic hypertension (odds ratio, 95% confidence interval: 12.1, 0.7–21) was a statistically significant predictor (P=0.025) of a good response to IVB, whereas previous macular laser was a statistically significant (P=0.0005) predictor of a poor response (0.07, 0.01–0.32). Sixty-eight percent of eyes underwent subsequent treatment for DME after the first course of IVB. The visual acuity gain at 24 months in hypertensive (0.7±3.6 letters) and nonhypertensive (5.2±3.7 letters) patients was not significantly different (P=0.41). Conclusion Hypertension and previous macular laser were positive and negative predictors of response to IVB, respectively. However, long-term visual acuity changes were not significantly different between eyes with and without systemic hypertension. PMID:27799737

  6. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma

    PubMed Central

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A.; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J.; Pulido, Jose S.; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S.; Gentile, Ronald C.; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y. Y.; Massoud, Vicky; Ghazi, Nicola G.

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma. PMID:25147732

  7. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma.

    PubMed

    Mansour, Ahmad M; Arevalo, J Fernando; Al Kahtani, Eman; Zegarra, Hernando; Abboud, Emad; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J; Pulido, Jose S; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S; Gentile, Ronald C; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y Y; Massoud, Vicky; Ghazi, Nicola G

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  8. Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide.

    PubMed

    Koocheki, Saeid; Madaeni, Sayed Siavash; Niroomandi, Parisa

    2011-01-01

    We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly(D,L-lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement.

  9. Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

    PubMed Central

    Koocheki, Saeid; Madaeni, Sayed Siavash; Niroomandi, Parisa

    2011-01-01

    We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly(d,l-lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement. PMID:21589650

  10. Physicochemical characterization and in vivo evaluation of triamcinolone acetonide-loaded hydroxyapatite nanocomposites for treatment of rheumatoid arthritis.

    PubMed

    Jafari, Samira; Maleki-Dizaji, Nasrin; Barar, Jaleh; Barzegar-Jalali, Mohammad; Rameshrad, Maryam; Adibkia, Khosro

    2016-04-01

    The current study was aimed to investigate the anti-inflammatory effect of triamcinolone acetonide-loaded hydroxyapatite (TA-loaded HAp) nanocomposites in the arthritic rat model. The HAp nanocomposites were synthesized through a chemical precipitation method and the drug was subsequently incorporated into the nanocomposites using an impregnation method. The physicochemical properties as well as cytotoxicity of the prepared nanoformulation were examined as well. To evaluate the therapeutic efficacy of the prepared nanoformulation, the various parameters such as paw volume, haematological parameters and histological studies were assessed in the arthritic rats. The nanocomposites with the particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 41.94% were obtained in this study. The specific surface area (aBET) as well as the volume of nitrogen adsorbed on one gram of HAp to complete the monolayer adsorption (Vm) were decreased after the drug loading process. The prepared nanoformulation revealed the slower drug release profile compared to the pure drug. Furthermore, the obtained data from MTT assay showed that the TA-loaded nanocomposites had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines as compared to the pure drug. Furthermore, TA-loaded HAp nanocomposites demonstrated favorable effects on the paw volume as well as the haematological and histopathological abnormalities in the adjuvant-induced arthritic rats. Therefore, TA-loaded HAp nanocomposites are potentially suggested for treatment of rheumatoid arthritis after further required evaluations.

  11. Influence of micronization method on the performance of a suspension triamcinolone acetonide pressurized metered-dose inhaler formulation.

    PubMed

    Williams, R O; Brown, J; Liu, J

    1999-05-01

    The purpose of this study was to investigate the influence of micronization technique on performance and stability of the model drug formulated in a suspension-based pressurized metered-dose inhaler (pMDI). The model drug, triamcinolone acetonide (TAA), was subjected to ball milling or air-jet milling prior to formulation of the pMDI. The dose delivery characteristics of the emitted aerosol cloud were monitored for the ball-milled, air-jet-milled, and unmicronized TAA pMDI formulations prior to and after storage at 25 and 40 degrees C. Cascade impaction was used to determine the aerodynamic particle size distribution of the emitted dose. Both micronization techniques reduced the drug particle size distribution and the polydispersity of the drug particles to a similar extent, but the ball-milling technique reduced the crystallinity of the drug to a greater degree compared to the air-jet-milling technique. The air-jet-milled and unmicronized TAA pMDI displayed similar aerodynamic particle size distributions of the emitted aerosol and respirable fractions over the storage period. The ball-milled TAA resulted in a pMDI formulation with the smallest aerodynamically sized particles and the highest respirable fraction compared to the air-jet-milled or unmicronized TAA pMDI formulations. The micronization techniques significantly influenced the dose delivery characteristics as a result of different initial particle size distributions, amorphous contents, and surface energies.

  12. Fractional Laser Ablation for the Cutaneous Delivery of Triamcinolone Acetonide from Cryomilled Polymeric Microparticles: Creating Intraepidermal Drug Depots.

    PubMed

    Singhal, Mayank; Del Río-Sancho, Sergio; Sonaje, Kiran; Kalia, Yogeshvar N

    2016-02-01

    The efficacy of some dermatological therapies might be improved by the use of "high dose" intraepidermal drug reservoir systems that enable sustained and targeted local drug delivery, e.g., in the treatment of keloids and hypertrophic scars. Here, a fractionally ablative erbium:YAG laser was used to enable "needle-less" cutaneous deposition of polymeric microparticles containing triamcinolone acetonide (TA). The microparticles were prepared using a freeze-fracture technique employing cryomilling that resulted in drug loading efficiencies of ∼100%. They were characterized by several different techniques, including scanning electron microscopy, powder X-ray diffraction and differential scanning calorimetry. TA was quantified by validated HPLC-UV and UHPLC-MS/MS analytical methods. In vitro release studies demonstrated the effect of polymer properties on TA release kinetics. Confocal laser scanning microscopy enabled visualization of cryomilled microparticles containing fluorescein and Nile Red in the cutaneous micropores and the subsequent release of fluorescein into the micropores and its diffusion throughout the epidermis and upper dermis. The biodistribution of TA, i.e. the amount of drug as a function of depth in skin, following microparticle application was much more uniform than with a TA suspension and delivery was selective for deposition with less transdermal permeation. These findings suggest that this approach may provide an effective, targeted and minimally invasive alternative to painful intralesional injections for the treatment of keloid scars.

  13. Short Implants: New Horizon in Implant Dentistry.

    PubMed

    Jain, Neha; Gulati, Manisha; Garg, Meenu; Pathak, Chetan

    2016-09-01

    The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration.

  14. Short Implants: New Horizon in Implant Dentistry

    PubMed Central

    Gulati, Manisha; Garg, Meenu; Pathak, Chetan

    2016-01-01

    The choice of implant length is an essential factor in deciding the survival rates of these implants and the overall success of the prosthesis. Placing an implant in the posterior part of the maxilla and mandible has always been very critical due to poor bone quality and quantity. Long implants can be placed in association with complex surgical procedures such as sinus lift and bone augmentation. These techniques are associated with higher cost, increased treatment time and greater morbidity. Hence, there is need for a less invasive treatment option in areas of poor bone quantity and quality. Data related to survival rates of short implants, their design and prosthetic considerations has been compiled and structured in this manuscript with emphasis on the indications, advantages of short implants and critical biomechanical factors to be taken into consideration when choosing to place them. Studies have shown that comparable success rates can be achieved with short implants as those with long implants by decreasing the lateral forces to the prosthesis, eliminating cantilevers, increasing implant surface area and improving implant to abutment connection. Short implants can be considered as an effective treatment alternative in resorbed ridges. Short implants can be considered as a viable treatment option in atrophic ridge cases in order to avoid complex surgical procedures required to place long implants. With improvement in the implant surface geometry and surface texture, there is an increase in the bone implant contact area which provides a good primary stability during osseo-integration. PMID:27790598

  15. Retinal safety of intravitreal rtPA in healthy rats and under excitotoxic conditions

    PubMed Central

    Daruich, Alejandra; Parcq, Jérôme; Delaunay, Kimberley; Naud, Marie-Christine; Le Rouzic, Quentin; Picard, Emilie; Crisanti, Patricia; Vivien, Denis; Berdugo, Marianne

    2016-01-01

    Purpose Intravitreal recombinant tissue plasminogen activator (rtPA) is used off-label for the surgical management of submacular hemorrhage, a severe complication of neovascular age-related macular degeneration. rtPA is approved for coronary and cerebral thrombolysis. However, in ischemic stroke rtPA is known to increase excitotoxic neural cell death by interacting with the N-methyl-D-aspartate (NMDA) receptor. We therefore investigated the retinal toxicity of rtPA in healthy rats and in a model of NMDA-induced retinal excitotoxicity. Methods First, rtPA at three different doses (2.16 µg/5 µl, 0.54 µg/5 µl, and 0.27 µg/5 µl) or vehicle (NaCl 0.9%) was injected intravitreally in healthy rat eyes. Electroretinograms (ERGs) were performed at 24 h or 7 days. Annexin V-fluorescein isothiocyanate (FITC)-labeled apoptotic retinal ganglion cells (RGCs) were counted on flatmounted retinas at 24 h or 7 days. Next, NMDA + vehicle or NMDA + rtPA (0.27 µg/5 µl) was injected intravitreally to generate excitotoxic conditions. Apoptotic annexin V-FITC-labeled RGCs and surviving Brn3a-labeled RGCs were quantified on flatmounted retinas and radial sections, 18 h after treatment. Results In healthy rat eyes, the number of apoptotic RGCs was statistically significantly increased 24 h after the administration of rtPA at the highest dose (2.16 µg/5 µl; p = 0.0250) but not at the lower doses of 0.54 and 0.27 µg/5 µl (p = 0.36 and p = 0.20), compared to vehicle. At day 7, there was no difference in the apoptotic RGC count between the rtPA- and vehicle-injected eyes (p = 0.70, p = 0.52, p = 0.11). ERG amplitudes and implicit times were not modified at 24 h or 7 days after injection of any tested rtPA doses, compared to the baseline. Intravitreal administration of NMDA induced RGC death, but under these excitotoxic conditions, coadministration of rtPA did not increase the number of dead RGCs (p = 0.70). Similarly, the number of surviving RGCs on the flatmounted retinas and

  16. Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

    PubMed

    De Francesco, Sonia; Galluzzi, Paolo; Bracco, Sandra; Menicacci, Felice; Motolese, Edoardo; Hadjistilianou, Theodora

    2015-12-01

    To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.

  17. Dramatic regression of persistent tunica vasculosa lentis associated with retinopathy of prematurity following treatment with intravitreal bevacizumab.

    PubMed

    Goldman, Darin R; Baumal, Caroline R

    2013-06-04

    The authors describe a preterm infant who developed advanced retinopathy of prematurity bilaterally with a prominent tunica vasculosa lentis. Treatment with intravitreal bevacizumab resulted in regression of the tunica vasculosa lentis and posterior manifestations of the retinopathy of prematurity. RetCam imaging (Clarity Medical Systems, Pleasanton, CA) of the anterior segment was used to document the dramatic tunica vasculosa lentis resolution.

  18. Poly(ortho ester) nanoparticles targeted for chronic intraocular diseases: ocular safety and localization after intravitreal injection.

    PubMed

    Li, Huiling; Palamoor, Mallika; Jablonski, Monica M

    2016-10-01

    Treatment of posterior eye diseases is more challenging than the anterior segment ailments due to a series of anatomical barriers and physiological constraints confronted by drug delivery to the back of the eye. In recent years, concerted efforts in drug delivery have been made to prolong the residence time of drugs injected in the vitreous humor of the eye. Our previous studies demonstrated that poly(ortho ester) (POE) nanoparticles were biodegradable/biocompatible and were capable of long-term sustained release. The objective of the present study was to investigate the safety and localization of POE nanoparticles in New Zealand white rabbits and C57BL/6 mice after intravitreal administration for the treatment of chronic posterior ocular diseases. Two concentration levels of POE nanoparticles solution were chosen for intravitreal injection: 1.5 mg/ml and 10 mg/ml. Our results demonstrate that POE nanoparticles were distributed throughout the vitreous cavity by optical coherence tomography (OCT) examination 14 days post-intravitreal injection. Intraocular pressure was not changed from baseline. Inflammatory or adverse effects were undetectable by slit lamp biomicroscopy. Furthermore, we demonstrate that POE nanoparticles have negligible toxicity assessed at the cellular level evidenced by a lack of glia activation or apoptosis estimation after intravitreal injection. Collectively, POE nanoparticles are a novel and nontoxic as an ocular drug delivery system for the treatment of posterior ocular diseases.

  19. Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

    PubMed Central

    Molokhia, Sarah A.; Jeong, Eun-Kee; Higuchi, William I.; Li, S. Kevin

    2008-01-01

    The distribution and clearance of macromolecules in ocular delivery are not well understood. It has been hypothesized that iontophoresis can enhance transscleral delivery of macromolecules. The objective of this study was to investigate the ocular distribution of a macromolecule after transscleral iontophoretic delivery and intravitreal injection in vivo using nuclear magnetic resonance imaging (MRI) and to compare these results. Experiments of constant current transscleral iontophoresis of 4 mA or intravitreal injection were performed on New Zealand white rabbits in vivo. Iontophoresis experiments were also performed on rabbits postmortem. Galbumin™ (Gd-labeled albumin) was the model permeant surrogate to clinical therapeutic agents. MRI was used to monitor the distribution of the molecule in the eye after ocular iontophoresis and intravitreal injection. In addition, the conjunctiva, sclera, choroid, and retina were extracted in the transscleral iontophoresis study to determine the amounts of Galbumin™ in these tissues using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The results show that iontophoresis enhanced the ocular delivery of Galbumin™. The macromolecule was mainly delivered into the conjunctiva and sclera in microgram quantities and then diffused towards the posterior section in the upper hemisphere of the eye in vivo. Both in vivo and postmortem studies show that the iontophoretic delivery of Galbumin™ into the vitreous was below the detection limit. In the intravitreal injection study, the diffusion coefficient of Galbumin™ in the vitreous humor was estimated to be close to that of free aqueous diffusion. PMID:19000673

  20. Dual Intravitreal Injections With Foscarnet and Ganciclovir for Ganciclovir-Resistant Recurrent Cytomegalovirus Retinitis in a Congenitally Infected Infant.

    PubMed

    Boss, Joseph D; Rosenberg, Kevin; Shah, Rajiv

    2016-10-22

    Resistant strains of cytomegalovirus can be difficult to treat in cases of congenital cytomegalovirus retinitis. The authors describe a case of recurrent bilateral congenital cytomegalovirus retinitis in an immunocompetent newborn with ganciclovir resistance successfully treated uniquely with dual therapy of intravenous ganciclovir and foscarnet and dual intravitreal injections with ganciclovir and foscarnet. [J Pediatr Ophthalmol Strabismus. 2016;53:e58-e60.].

  1. Use of an Intravitreal Dexamethasone Implant (Ozurdex) in a Case with Accidental Foveal Photocoagulation by Alexandrite Laser

    PubMed Central

    Bulut, Muhammed Nurullah; Çallı, Ümit; Göktaş, Eren; Bulut, Kezban; Kandemir, Baran; Özertürk, Yusuf

    2016-01-01

    Alexandrite laser is one of the most common methods of hair removal. Its utilization is gradually increasing due to easy accessibility and high effectiveness. However, the disuse of protective goggles during the application of this laser is a serious problem. In this case report, we presented a 35-year-old male patient who had foveal injury by alexandrite laser. The inflammatory process secondary to the foveal injury and subsequent macular edema were treated with Ozurdex because of its potent antiedematous effect. PMID:27293415

  2. Use of an Intravitreal Dexamethasone Implant (Ozurdex) in a Case with Accidental Foveal Photocoagulation by Alexandrite Laser.

    PubMed

    Bulut, Muhammed Nurullah; Çallı, Ümit; Göktaş, Eren; Bulut, Kezban; Kandemir, Baran; Özertürk, Yusuf

    2016-01-01

    Alexandrite laser is one of the most common methods of hair removal. Its utilization is gradually increasing due to easy accessibility and high effectiveness. However, the disuse of protective goggles during the application of this laser is a serious problem. In this case report, we presented a 35-year-old male patient who had foveal injury by alexandrite laser. The inflammatory process secondary to the foveal injury and subsequent macular edema were treated with Ozurdex because of its potent antiedematous effect.

  3. Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration.

    PubMed

    Michalska-Małecka, Katarzyna; Kabiesz, Adam; Kimsa, Malgorzata W; Strzałka-Mrozik, Barbara; Formińska-Kapuścik, Maria; Nita, Malgorzata; Mazurek, Urszula

    2016-01-01

    The purpose of this study was to evaluate the systemic effects of intravitreal ranibizumab (Lucentis) treatment in patients with neovascular age-related macular degeneration (AMD). The impact of intravitreal ranibizumab injections on central retinal thickness (CRT) of treated and contralateral untreated eyes, and differences in gene expression patterns in the peripheral blood mononuclear cells were analyzed. The study included 29 patients aged 50 years old and over with diagnosed neovascular AMD. The treatment was defined as 0.5 mg of ranibizumab injected intravitreally in the form of one injection every month during the period of 3 months. CRT was measured by optical coherence tomography. The gene expression profile was assigned using oligonucleotide microarrays of Affymetrix HG-U133A. Studies have shown that there was a change of CRT between treated and untreated eyes, and there were differences in CRT at baseline and after 1, 2, and 3 months of ranibizumab treatment. Three months after intravitreal injection, mean CRT was reduced in the treated eyes from 331.97±123.62 to 254.31±58.75 μm, while mean CRT in the untreated fellow eyes reduced from 251.07±40.29 to 235.45±36.21 μm at the same time. Furthermore, the research has shown that among all transcripts, 3,097 expresses change after the ranibizumab treatment in relation to controls. Among these transcripts, 1,339 were up-regulated, whereas 1,758 were down-regulated. Our results show the potential systemic effects of anti-VEGF therapy for AMD. Moreover, our study indicated different gene expression in peripheral blood mononuclear cells before and after intravitreal ranibizumab treatment.

  4. Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration

    PubMed Central

    Michalska-Małecka, Katarzyna; Kabiesz, Adam; Kimsa, Malgorzata W; Strzałka-Mrozik, Barbara; Formińska-Kapuścik, Maria; Nita, Malgorzata; Mazurek, Urszula

    2016-01-01

    The purpose of this study was to evaluate the systemic effects of intravitreal ranibizumab (Lucentis) treatment in patients with neovascular age-related macular degeneration (AMD). The impact of intravitreal ranibizumab injections on central retinal thickness (CRT) of treated and contralateral untreated eyes, and differences in gene expression patterns in the peripheral blood mononuclear cells were analyzed. The study included 29 patients aged 50 years old and over with diagnosed neovascular AMD. The treatment was defined as 0.5 mg of ranibizumab injected intravitreally in the form of one injection every month during the period of 3 months. CRT was measured by optical coherence tomography. The gene expression profile was assigned using oligonucleotide microarrays of Affymetrix HG-U133A. Studies have shown that there was a change of CRT between treated and untreated eyes, and there were differences in CRT at baseline and after 1, 2, and 3 months of ranibizumab treatment. Three months after intravitreal injection, mean CRT was reduced in the treated eyes from 331.97±123.62 to 254.31±58.75 μm, while mean CRT in the untreated fellow eyes reduced from 251.07±40.29 to 235.45±36.21 μm at the same time. Furthermore, the research has shown that among all transcripts, 3,097 expresses change after the ranibizumab treatment in relation to controls. Among these transcripts, 1,339 were up-regulated, whereas 1,758 were down-regulated. Our results show the potential systemic effects of anti-VEGF therapy for AMD. Moreover, our study indicated different gene expression in peripheral blood mononuclear cells before and after intravitreal ranibizumab treatment. PMID:27069359

  5. Dental Implant Surgery

    MedlinePlus

    Dental implant surgery Overview By Mayo Clinic Staff Dental implant surgery is a procedure that replaces tooth roots with ... look and function much like real ones. Dental implant surgery can offer a welcome alternative to dentures ...

  6. Hip Implant Systems

    MedlinePlus

    ... Devices Products and Medical Procedures Implants and Prosthetics Metal-on-Metal Hip Implants Hip Implants Share Tweet Linkedin Pin ... devices available with different bearing surfaces. These are: Metal-on-Polyethylene: The ball is made of metal ...

  7. Posterior Vitreous Detachment With Microplasmin Alters the Retinal Penetration of Intravitreal Bevacizumab (Avastin) in Rabbit Eyes

    PubMed Central

    Goldenberg, David T.; Giblin, Frank J.; Cheng, Mei; Chintala, Shravan K.; Trese, Michael T.; Drenser, Kimberly A.; Ruby, Alan J.

    2010-01-01

    Purpose Intravitreal bevacizumab (Avastin) is frequently used for the treatment of age-related macular degeneration. Previous studies have demonstrated full thickness retinal penetration. Intravitreal recombinant microplasmin (MP) has been shown to successfully induce a posterior vitreous detachment (PVD) and vitreous liquefaction in animals. It has been suggested that a PVD may alter the retinal penetration of molecules in the vitreous cavity. The aim of this study was to compare bevacizumab (BV) retinal penetration in rabbit eyes with and without a MP-induced PVD. Methods Twelve adult rabbits were injected with 0.1 ml (0.4 mg) of MP into the vitreous cavity of one eye. One week later, the rabbits were injected with 0.05 ml (1.25 mg) of BV into both eyes. Both eyes of three rabbits each were harvested at 6, 12, 24, and 72 hours after the BV injection. Frozen retinal cross sections were prepared, and BV retinal penetration was evaluated with immunohistochemistry using a fluorescence-labeled antibody against BV. Two eyes from one rabbit were not injected with either agent and used as controls to compare the background autofluorescence. Peripapillary retinal sections were recorded with a digital camera, and intra-retinal BV fluorescence-labeled antibody was measured by qualitative photographic interpretation. Two additional rabbits received an intravitreal injection of 0.1 ml of MP in one eye. One week later, both eyes from each rabbit were enucleated and frozen retinal sections were prepared and analyzed with light microscopy to evaluate for histologic damage. Results Full thickness BV retinal penetration was observed throughout the retina in both eyes of each rabbit. All of the MP-injected eyes exhibited increased antibody labeling in retinas evaluated 6, 12, and 24 hours after BV injection when compared with the contralateral non-MP-injected eyes. By three days after BV injection, all eyes demonstrated decreased antibody labeling compared to earlier time periods

  8. Controlled Release of Dexamethasone From an Intravitreal Delivery System Using Porous Silicon Dioxide

    PubMed Central

    Hou, Huiyuan; Wang, Chengyun; Nan, Kaihui; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun

    2016-01-01

    Purpose The current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina. Methods Dexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated for the pharmacological effect of the payload on cultured ARPE19 cells before intravitreal injection. The Dex release profile was investigated in a custom designed dynamic dissolution chamber to mimic the turnover of vitreous fluid in rabbit eyes. Ocular safety, in vivo release, and pharmacodynamics were evaluated in rabbit eyes, and the human VEGF-induced rabbit retinal vascular permeability model. Results Loading efficiency of Dex was 69 ± 9 μg per 1 mg of the pSiO2-COO-Dex particles. Dynamic in vitro release demonstrated a sustained mode when compared to free Dex, with the drug half-life extended by 5 times. The released Dex was unaltered and biologically active. In vivo drug release in rabbit eyes revealed a mode similar to the release seen in vitro, with a vitreous half-life of 11 days. At 2 and 4 weeks after a single intravitreal injection of pSiO2-COO-Dex particles (mean 2.71 ± 0.47 mg), intravitreal 500 ng of VEGF did not induce significant retinal vessel dilation or fluorescein leakage, while these events were observed in the eyes injected with empty pSiO2 particles or with free Dex. The retinal vessel score from fluorescein angiography for the control eyes was double the score for the eyes injected with pSiO2-COO-Dex. No adverse reaction was observed for the eyes injected with drug-loaded pSi particles during the course of the study. Conclusions The porous silicon-based Dex delivery system (pSiO2-COO-Dex) can be administered safely into vitreous without toxicity. Dex release from the porous silicon particles was sustained for 2 months and was effective against VEGF-induced retinal vessel reaction. PMID:26882530

  9. Fast and controlled release of triamcinolone acetonide from extrusion-spheronization pellets based on mixtures of native starch with dextrin or waxy maize starch.

    PubMed

    Sergio, Almeida-Prieto; Isabel, de Sá Ferreira da Rocha Cristiana; José, Blanco-Méndez; Otero-Espinar, Francisco J

    2007-09-01

    Pellets composed chiefly of inexpensive starches allow modulation of the rate of release of the poorly soluble drug triamcinolone acetonide in media of pH 1.2-6.8. Wheat- or maize-starch-based pellets with 20% of white dextrin release the drug in vitro almost completely within 20 min, while maize-starch-based pellets with 5-35% of waxy maize starch sustain gradual release over periods of 9-12 hr or longer when prepared using appropriate amounts of granulation fluid.

  10. “Magic Bullet”: Eccentric Macular Hole as a Complication from Dexamethasone Implant Insertion

    PubMed Central

    Sanders, Riley; Olson, Jeffrey

    2016-01-01

    Introduction. Intravitreal drug injections and implants are generally safe but do carry some risk, from both the procedure itself and adverse effects of the medications. We report a case of an eccentric macular hole after dexamethasone implant (Ozurdex®) administration. Ex vitro force testing was performed to evaluate dexamethasone implant injection force. Methods. Five dexamethasone implant (Ozurdex) applicators were placed 16 mm from a force plate and the force of the injected dexamethasone pellet was recorded in Newtons. Four dexamethasone implant applicators were placed 16 mm from a force plate in a basic saline solution and the force of the pellet was recorded. Results. Average maximum force in air was 0.77 N and 0.024 N in a basic saline solution (BSS). Conclusion. We present a case report of an eccentric macular hole after dexamethasone implant administration. We hypothesize a mechanical injury to the retina during insertion caused the macular hole. Force testing done in air demonstrated sufficient force from the pellet injection to cause retinal damage though injections done in BSS showed reduced forces. PMID:27800199

  11. Triamcinolone Acetonide Selectively Inhibits Angiogenesis in Small Blood Vessels and Decreases Vessel Diameter within the Vascular Tree

    NASA Technical Reports Server (NTRS)

    McKay, Terri L.; Gredeon, Dan J.; Vickerman, Mary B.; Hylton, alan G.; Ribita, Daniela; Olar, Harry H.; Kaiser, Peter K.; Parsons-Wingerter, Patricia

    2007-01-01

    The steroid triamcinolone acetonide (TA) is a potent anti-angiogenesis drug used to treat retinal vascular diseases that include diabetic retinopathy, vascular occlusions and choroidal neovascularization. To quantify the effects of TA on branching morphology within the angiogenic microvascular tree of the chorioallantoic membrane (CAM) of quail embryos. Increasing concentrations of TA (0-16 ng/ml) were applied topically on embryonic day 7 (E7) to the chorioallantoic membrane (CAM) of quail embryos cultured in Petri dishes, and incubated for an additional 24 or 48 hours until fixation. Binary (black/white) microscopic images of arterial end points were quantified by VESGEN software (for Generational Analysis of Vessel Branching) to obtain major vascular parameters that include vessel diameter (Dv), fractal dimension (Df), tortuosity (Tv) and densities of vessel area, length, number and branch point (Av, Lv, Nv and Brv). For assessment of specific changes in vascular morphology induced by TA, the VESGEN software automatically segmented the vascular tree into branching generations (G1...G10) according to changes in vessel diameter and branching. Vessel density decreased significantly up to 34% as the function of increasing concentration of TA according to Av, Lv, Brv, Nv and Df. TA selectively inhibited the growth of new, small vessels, because Lv decreased from 13.14plus or minus 0.61 cm/cm2 for controls to 8.012 plus or minus 0.82 cm/cm2 at 16 ng TA/ml in smaller branching generations (G7-G10), and for Nv from 473.83 plus or minus 29.85 cm(-)2 to 302.32 plus or minus 33.09 cm-()2. In contrast, vessel diameter (Dv) decreased throughout the vascular tree (G1-G10).

  12. In vitro effects of triamcinolone acetonide and in combination with hyaluronan on canine normal and spontaneous osteoarthritis articular cartilage.

    PubMed

    Euppayo, Thippaporn; Siengdee, Puntita; Buddhachat, Kittisak; Pradit, Waranee; Chomdej, Siriwadee; Ongchai, Siriwan; Nganvongpanit, Korakot

    2016-08-01

    The purposes of this study were to examine the cartilage degradation effects of triamcinolone acetonide (TA) on normal and osteoarthritic (OA) primary canine chondrocytes and cartilage explants and to examine the cartilage degradation effects of TA in combination with low-molecular-weight hyaluronan (LMWHA). To assess the effects of these drugs on cell culture, 3,[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and real-time PCR were used to measure chondrotoxicity and determine gene expression, respectively. Uronic acid and hydroxyproline remaining in cartilage and histopathology were used to estimate the effects of these drugs on cartilage explants. In chondrocyte cultures, TA reduced chondrocyte viability in a concentration-dependent manner. LMWHA 2.5 mg/ml combined with TA at IC20 (0.09 mg/ml) could increase the viability of normal chondrocytes when compared with TA-treated alone. TA at IC20 induced down-regulation of ACAN and induced up-regulation of ADAMTS5 in canine normal chondrocytes. TA at IC20 (0.11 mg/ml) up-regulated ADAMTS5, MMP2, MMP3, MMP13, and ACAN expression in canine OA chondrocytes. In explant culture, TA at 1.25, 2.5, and 5 mg/ml increased the severity of structural damage, chondrocyte loss and cluster formation, and proteoglycan loss in OA cartilage. LMWHA could decrease the chondrotoxicity of TA at IC20 only in normal chondrocytes, as observed by chondrocyte viability. The combination of LMWHA and TA did not show clearly beneficial effects in all other normal and OA samples. Consequently, using TA alone or in combination with LMWHA in OA cartilage should be of concern because it may lead to cartilage destruction.

  13. Viral Retinitis Following Intravitreal Triamcinolone Injection in Patients with Predisposing Medical Comorbidities

    PubMed Central

    Shah, Ankur M.; Oster, Stephen F.; Freeman, William R.

    2009-01-01

    Purpose To review the cases of viral retinitis following intravitreal steroid administration at a single center, to estimate the incidence, and to propose risk factors for its occurrence. Design Retrospective, observational case series Methods 736 intravitreal triamcinolone (IVTA) injections were given in the clinic and operating room by three retina specialists at a single academic medical center, between September 2002 to November 2008. Inclusion criteria were simply a history of one or more IVTA injections during the period. The overall incidence of viral retinitis following IVTA was calculated. Subsequently, a chart audit was performed to estimate the number of patients with immune-altering conditions who had received IVTA during the time period, and the incidence within this subgroup was calculated. Results Viral retinitis developed following IVTA injection in three patients, yielding an overall incidence of 3/736 or 0.41%. An estimated 334 injections were given to patients with an immune-altering condition, including diabetes. All three of the patients who developed viral retinitis following IVTA possessed abnormal immune systems, yielding an incidence rate of 3/334 or 0.90% within this subgroup. Conclusions Our high reported incidence for this potentially devastating complication can be attributed to multiple factors, including coexisting medical immunocompromising comorbidities, a higher dose with a longer duration of local immunosuppression in the vitreous, multiple injections, as well as previous viral retinitis. Caution with a high index of clinical suspicion and frequent follow-up is advised in patients receiving IVTA with potentially immune-altering conditions, even after apparent immune recovery. PMID:20172069

  14. Ocular Decompression with Cotton Swabs Lowers Intraocular Pressure Elevation Following Intravitreal Injection

    PubMed Central

    Gregori, Ninel Z.; Weiss, Matthew J.; Goldhardt, Raquel; Schiffman, Joyce C.; Vega, Edgardo; Mattis, Cherrie-Ann; Shi, Wei; Kelley, Linda; Hernandez, Vilma; Feuer, William J.

    2013-01-01

    Objective To determine the effect of pre-injection ocular decompression by cotton swabs on the immediate rise in intraocular pressure (IOP) after intravitreal injections. Methods Forty-eight patients receiving 0.05-ml ranibizumab injections in a retina clinic were randomized to two anesthetic methods in each eye on the same day (if bilateral disease) or on consecutive visits (if unilateral disease). One method utilized cotton swabs soaked in 4% lidocaine applied to the globe with moderate pressure and the other 3.5% lidocaine gel applied without pressure. IOPs were recorded at baseline (before injection) and at 0, 5, 10, and 15 minutes after the injection until the IOP was ≤30 mmHg. The IOP elevations from baseline were compared after the two anesthetic methods. Results The pre-injection mean IOP (SD, mmHg) was 15.5 (3.3) before the cotton swabs and 15.9 (3.0) before the gel (p=0.28). Mean IOP (SD, mmHg) change immediately after injection was 25.7 (9.2) after the cotton swabs and 30.9 (9.9) after the gel (P=0.001). Thirty-five percent of gel eyes had IOP ≥50 mmHg compared to only 10% of cotton swab eyes immediately after the injection (P<0.001). Conclusion Decompressing the eye with cotton swabs during anesthetic preparation prior to an intravitreal injection produces a significantly lower IOP spike after the injection. PMID:23632408

  15. Characteristics of Macular Edema in Behcet Disease after Intravitreal Bevacizumab Injection

    PubMed Central

    Ghassemi, Fariba; Mirak, Sohrab Afshari; Chams, Hormoz; Sabour, Siamak; Ahmadabadi, Mehdi Nilli; Davatchi, Fereidoun; Shahram, Farhad

    2017-01-01

    Purpose: To investigate the effect of intravitreal bevacizumab (IVB) injection on macular edema (ME) secondary to Behcet's disease. Methods: This prospective case series included 15 patients with bilateral ME due to Behcet's disease. Intravitreal bevacizumab was injected into the more severely involved eye; the contralateral eye was evaluated as the control. Patients were followed up with comprehensive ocular examination, optical coherence tomography, and fluorescein angiography (FA) for a minimum of 6 months by a single ophthalmologist. Results: Patients with a mean age of 30.6 ± 7.4 years received a mean number of 3.3 IVB injections during the 6 months. The mean preinjection vision was 0.6 ± 0.3 and 0.4 ± 0.4 LogMAR in the case and control groups, respectively, with no significant improvement at 6 months. Mean central foveal thickness was 375.3 ± 132.1 and 307.2 ± 84.5 μm in the case and control groups, respectively, and these changed to 401 ± 199.9 (P = 0.65) and 307.7 ± 82.8 μm (P = 0.73) at month 6, respectively. A statistically nonsignificant improvement in ME was observed during the first 3 months in the case group. However, it did not persist up to month 6 on an as-needed basis. IVB injections caused a disproportionate decrease in the thickness of macular subfields. A reduction in disc leakage was observed on FA (P = 0.058). Logistic regression analysis revealed no statistically significant predictive factor for an improvement in visual acuity (VA) and a reduction in foveal thickness. Conclusion: During a 6-month period, IVB injections based on an as-needed protocol provided no statistically significant improvement in VA and ME. PMID:28299006

  16. Intravitreal aflibercept in neovascular age-related macular degeneration previously treated with ranibizumab

    PubMed Central

    Lim, Rachel Hui Fen; Gupta, Bhaskar; Simcock, Peter

    2017-01-01

    AIM To report the change in visual acuity and central macular thickness (CMT) following treatment with intravitreal aflibercept injections in patients with neovascular age-related macular degeneration (nAMD) with suboptimum response to ranibizumab. METHODS This was a retrospective study. The inclusion criteria were patients with nAMD who responded poorly to ranibizumab. Patients then received either 3 consecutive aflibercept injections followed by pro re nata (PRN) treatment or PRN alone. Primary endpoints were mean change in best-corrected visual acuity (BCVA) and CMT at 12mo. Secondary endpoints were number of injections and adverse events. RESULTS Forty-nine eyes from 49 patients met the inclusion criteria and completed 12-month follow up on aflibercept. Thirty-eight eyes received 3 consecutive aflibercept injections followed by PRN treatment and 11 eyes received PRN injections alone. At 12mo, mean BCVA improved by one letters (logMAR 0.56±0.31 to 0.54±0.34) and mean CMT decreased from 303.9±82.1 to 259.2±108.3 µm. Four percent of eyes gained 15 letters or more, 6% lost more than 15 letters and the remaining 90% had stable BCVA. The mean number of aflibercept injections was 6. There was one case of infectious endophthalmitis. CONCLUSION Intravitreal aflibercept in patients with nAMD with a previous suboptimal response to ranibizumab resulted in an anatomical improvement in macular appearance at 12mo without a corresponding improvement in visual acuity. PMID:28393034

  17. Glioprotection of Retinal Astrocytes After Intravitreal Administration of Memantine in the Mouse Optic Nerve Crush Model

    PubMed Central

    Maciulaitiene, Ruta; Pakuliene, Giedre; Kaja, Simon; Pauza, Dainius Haroldas; Kalesnykas, Giedrius; Januleviciene, Ingrida

    2017-01-01

    Background In glaucoma, non-intraocular pressure (IOP)-related risk factors can result in increased levels of extracellular glutamate, which triggers a cascade of neurodegeneration characterized by the excessive activation of N-methyl-D-aspartate (NMDA). The purpose of our study was to evaluate the glioprotective effects of memantine as a prototypic uncompetitive NMDA blocker on retinal astrocytes in the optic nerve crush (ONC) mouse model for glaucoma. Material/Methods Optic nerve crush was performed on all of the right eyes (n=8), whereas left eyes served as contralateral healthy controls (n=8) in Balb/c/Sca mice. Four randomly assigned mice received 2-μl intravitreal injections of memantine (1 mg/ml) after ONC in the experimental eye. One week after the experiment, optic nerves were dissected and stained with methylene blue. Retinae were detached from the sclera. The tissue was immunostained. Whole-mount retinae were investigated by fluorescent microscopy. Astrocyte counts for each image were performed manually. Results Histological sections of crushed optic nerves showed consistently moderate tissue damage in experimental groups. The mean number of astrocytes per image in the ONC group was significantly lower than in the healthy control group (7.13±1.5 and 10.47±1.9, respectively). Loss of astrocytes in the memantine-treated group was significantly lower (8.83±2.2) than in the ONC group. Assessment of inter-observer reliability showed excellent agreement among observations in control, ONC, and memantine groups. Conclusions The ONC is an effective method for investigation of astrocytic changes in mouse retina. Intravitreally administered memantine shows a promising glioprotective effect on mouse retinal astrocytes by preserving astrocyte count after ONC. PMID:28265105

  18. Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model

    PubMed Central

    Park, S J; Oh, J; Kim, Y-K; Park, J H; Park, J Y; Hong, H K; Park, K H; Lee, J-E; Kim, H M; Chung, J Y; Woo, S J

    2015-01-01

    Purpose To determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model. Methods VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately frozen at −80 °C. Concentration of VEGF-Trap in vitreous, aqueous humor, and retina/choroid was determined using an indirect enzyme-linked immunosorbent assay and analyzed to obtain pharmacokinetic properties. Results Maximum concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one-compartment model of distribution was selected as the final model for all tissues studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9% of vitreous exposure, respectively. Conclusion The vitreous half-life of VEGF-Trap is 3.63 days. This is shorter than that of bevacizumab (6.99 days) and longer than that of ranibizumab (2.51 days), as shown in studies using the same experimental settings. The concentration of VEGF-Trap peaked at 1 h after injections in all eye tissues studied. PMID:25592118

  19. Intravitreal injection

    MedlinePlus

    ... disorder that slowly destroys sharp, central vision Macular edema: Swelling or thickening of the macula, the part ... 29, 2013. Mitchell P, Wong TY, Diabetic Macular Edema Treatment Guideline Working Group. Management paradigms for diabetic ...

  20. Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates.

    PubMed

    Kotterman, M A; Yin, L; Strazzeri, J M; Flannery, J G; Merigan, W H; Schaffer, D V

    2015-02-01

    Gene delivery vectors based on adeno-associated viruses (AAV) have exhibited promise in both preclinical disease models and human clinical trials for numerous disease targets, including the retinal degenerative disorders Leber's congenital amaurosis and choroideremia. One general challenge for AAV is that preexisting immunity, as well as subsequent development of immunity following vector administration, can severely inhibit systemic AAV vector gene delivery. However, the role of neutralizing antibodies (NABs) in AAV transduction of tissues considered to be immune privileged, such as the eye, is unclear in large animals. Intravitreal AAV administration allows for broad retinal delivery, but is more susceptible to interactions with the immune system than subretinal administration. To assess the effects of systemic anti-AAV antibody levels on intravitreal gene delivery, we quantified the anti-AAV antibodies present in sera from non-human primates before and after intravitreal injections with various AAV capsids. Analysis showed that intravitreal administration resulted in an increase in anti-AAV antibodies regardless of the capsid serotype, transgene or dosage of virus injected. For monkeys injected with wild-type AAV2 and/or an AAV2 mutant, the variable that most significantly affected the production of anti-AAV2 antibodies was the amount of virus delivered. In addition, post-injection antibody titers were highest against the serotype administered, but the antibodies were also cross-reactive against other AAV serotypes. Furthermore, NAB levels in serum correlated with those in vitreal fluid, demonstrating both that this route of administration exposes AAV capsid epitopes to the adaptive immune system and that serum measurements are predictive of vitreous fluid NAB titers. Moreover, the presence of preexisting NAB titers in the serum of monkeys correlated strongly (R=0.76) with weak, decaying or no transgene expression following intravitreal administration of AAV

  1. Feasibility of binary composition in development of nanoethosomal glycolic vesicles of triamcinolone acetonide using Box-behnken design: in vitro and ex vivo characterization.

    PubMed

    Akhtar, Nida; Verma, Anurag; Pathak, Kamla

    2016-07-01

    Triamcinolone acetonide (TA) employed for the treatment of atopic dermatitis exhibits limited penetration into the epidermis. This investigation aimed to explore the role of binary solvents in topical drug delivery of TA by developing nanoethosomal glycolic lipid vesicles by infusion method. Screening of vesicles (TA1-TA17) formulated by Box Behnken design identified the optimized formulation (TA10) that was developed as carbomer gels. The gels were then evaluated for pharmaceutical properties and compared with control and reference ethosomal gel (RG). Higher in vitro permeation was found in gels containing TA10, prepared with or without using penetration enhancer (EGP 83.76 ± 0.72% and EG 82.42 ± 0.89%, respectively). CLSM studies depicted deeper uniform penetration of fluorescent tracer into the epidermis via EG as compared with RG and control gel. Enhanced penetration was due to combinational solvent effect exerted by ethanol and propylene glycol. Histological analysis confirmed the non-irritant potential of the gel. Thus, it can be concluded that nanoethosomal glycolic vesicles proved to be an effective non irritant carrier for improvised penetration of triamcinolone acetonide for potential topical therapeutics.

  2. [Bilateral cochlear implantation].

    PubMed

    Kronenberg, Jona; Migirov, Lela; Taitelbaum-Swead, Rikey; Hildesheimer, Minka

    2010-06-01

    Cochlear implant surgery became the standard of care in hearing rehabilitation of patients with severe to profound sensorineural hearing loss. This procedure may alter the lives of children and adults enabling them to integrate with the hearing population. In the past, implantation was performed only in one ear, despite the fact that binaural hearing is superior to unilateral, especially in noisy conditions. Cochlear implantation may be performed sequentially or simultaneously. The "sensitive period" of time between hearing loss and implantation and between the two implantations, when performed sequentially, significantly influences the results. Shorter time spans between implantations improve the hearing results after implantation. Hearing success after implantation is highly dependent on the rehabilitation process which includes mapping, implant adjustments and hearing training. Bilateral cochlear implantation in children is recommended as the proposed procedure in spite of the additional financial burden.

  3. Six month delivery of GDNF from PLGA/vitamin E biodegradable microspheres after intravitreal injection in rabbits.

    PubMed

    García-Caballero, Cristina; Prieto-Calvo, Esther; Checa-Casalengua, Patricia; García-Martín, Elena; Polo-Llorens, Vicente; García-Feijoo, Julián; Molina-Martínez, Irene Teresa; Bravo-Osuna, Irene; Herrero-Vanrell, Rocío

    2017-03-01

    Local long-term delivery of glial cell line derived neurotrophic factor (GDNF) from vitamin E/poly-lactic-co-glycolic acid microspheres (MSs) protects retinal ganglion cells in an animal model of glaucoma for up to 11weeks. However, the pharmacokinetics of GDNF after intravitreal injection of MSs is not known. We evaluated the GDNF levels after a single intravitreal injection of GDNF/VitE MSs. Biodegradable MSs were prepared by the solid-oil-in-water emulsion-solvent evaporation technique and characterized. Rabbits received a single intravitreal injection (50μL) of GDNF/VitE MSs (4%w/v; 24 right eyes; 74.85ng GDNF), blank MSs (4%w/v; 24 left eyes), and balanced salt solution (4 eyes). Two controls eyes received no injections. At 24h, 1, 4, 6, 8, 12, 18, and 24weeks after injection, the eyes were enucleated, and the intravitreal GDNF levels were quantified. Pharmacokinetic data were analysed according to non-compartmental model. Intraocular GDNF levels of 717.1±145.1pg/mL were observed at 24h for GDNF-loaded MSs, followed by a plateau (745.3±25.5pg/mL) until day 28. After that, a second plateau (17.4±3.7pg/mL) occurred from 8 to 24weeks post-injection, significantly higher than the basal levels. Eyes injected with GDNF/vitE and Blank-MSs did not show any abnormalities during the six-months follow up after administration. The single injection of GDNF/VitE MSs provided a sustained controlled release of the neurotrophic factor in a controlled fashion for up to six months.

  4. Natural Short-term Course of Recurrent Macular Edema Following Intravitreal Bevacizumab Therapy in Branch Retinal Vein Occlusion

    PubMed Central

    Yoo, Su Jin; Lee, Tae Gon; Kim, Jong Woo; Cho, Sung Won; Han, Jung Il

    2017-01-01

    Purpose To evaluate the 3-month natural course of recurrent macular edema secondary to branch retinal vein occlusion (BRVO) treated with intravitreal bevacizumab. Methods This retrospective, observational study included 36 eyes with macular edema secondary to BRVO. All patients were initially treated with intravitreal bevacizumab for macular edema. Recurrence of macular edema was either not treated (untreated group) or treated with a single intravitreal bevacizumab injection (treated group). Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) were compared at the time of recurrence and 3 months later. Results At the time of recurrence, the mean CFT and logarithm of the minimum angle of resolution BCVA were 484.9 ± 124.1 µm and 0.58 ± 0.26 in the untreated group (n = 19) and 456.3 ± 126.8 µm and 0.51 ± 0.21 in the treated group (n = 17), respectively. Three months later, the mean CFT and BCVA had changed to 493.7 ± 123.9 µm and 0.62 ± 0.29 in the untreated group and 294.7 ± 104.4 µm and 0.40 ± 0.24 in the treated group, respectively. The differences in CFT and BCVA between the two time points were not significant in the untreated group (p = 0.106 and p = 0.687, respectively), whereas statistically significant differences were noted in the treated group (p = 0.002 and p < 0.001, respectively). Conclusions Unlike the first episode of macular edema following BRVO, recurrent macular edema following intravitreal bevacizumab therapy did not spontaneously resolve, suggesting the potential benefit of prompt treatment. PMID:28367036

  5. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases

    PubMed Central

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-01-01

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement. PMID:22948997

  6. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases.

    PubMed

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-09-03

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement.

  7. Statin medication in patients with epiretinal membrane is associated with low intravitreal EPO, TGF-beta-1, and VEGF levels

    PubMed Central

    Tuuminen, Raimo; Loukovaara, Sirpa

    2016-01-01

    Background In eyes with idiopathic epiretinal membrane (iERM), the intravitreal growth factor and cytokine levels may associate with postvitrectomy outcomes. Here, we have analyzed the perioperative intravitreal protein levels of potent vasoactive, proinflammatory, and extracellular matrix-remodeling factors in iERM eyes and evaluated the postvitrectomy outcomes. Methods This was an institutional, observational study. Eyes operated on for iERM (n=26) were analyzed according to the use of statin medication. Vitreous samples were subjected to protein measurements of angiopoietin-1 and -2, erythropoietin, transforming growth factor-β1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay, and of matrix metalloproteinase-2 and -9 by gelatin zymography. One-month visual outcomes and 1-year revitrectomy rates were recorded. Results In iERM eyes of patients taking statins, intravitreal levels of erythropoietin (mean ± standard deviation, 10.8±4.9 vs 82.9±119.5 mIU/mg, P=0.003), transforming growth factor-β1 (2.3±4.7 vs 15.8±16.3 pg/mg, P=0.035), and vascular endothelial growth factor (5.5±9.9 vs 236.6±491.6 pg/mg, P=0.006) were lower than in nonstatin-treated patients. At 1-month, visual gain did not significantly differ between iERM eyes of patients with statins and those without (improvement 0.27±0.20 vs 0.16±0.38 logarithm of the minimum angle of resolution units, P=0.118). Conclusion Systemic statin therapy might have a favorable effect on intravitreal factors involved in vascular permeability, inflammation, and fibroproliferation in aging human iERM eyes. PMID:27284236

  8. Mobile ultra-clean unidirectional airflow screen reduces air contamination in a simulated setting for intra-vitreal injection.

    PubMed

    Lapid-Gortzak, Ruth; Traversari, Roberto; van der Linden, Jan Willem; Lesnik Oberstein, Sarit Y; Lapid, Oren; Schlingemann, Reinier O

    2017-02-01

    The aim of this study is to determine whether the use of a mobile ultra-clean laminar airflow screen reduces the air-borne particle counts in the setting of a simulated procedure of an intra-vitreal injection. A mobile ultra-clean unidirectional airflow (UDF) screen was tested in a simulated procedure for intra-vitreal injections in a treatment room without mechanical ventilation. One UDF was passed over the instrument tray and the surgical area. The concentration of particles was measured in the background, over the instrument table, and next to the ocular area. The degree of protection was calculated at the instrument table and at the surgical site. Use of the UDF mobile screen reduced the mean particle concentration (particles > 0.3 microns) on the instrument table by a factor of at least 100.000 (p < 0.05), and over the patient's eye by at least a factor of 436 (p < 0.05), which in clinical practice translates into significantly reduced air contamination. Mobile UDF screen reduces the mean particle concentration substantially. The mobile UDF screen may therefore allow for a safer procedural environment for ambulatory care procedures such as intra-vitreal injections in treatment rooms.

  9. Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

    PubMed

    Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

    2014-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

  10. Intravitreal tPA Injection and Pneumatic Displacement for Submacular Hemorrhage in a 10-Year-Old Child

    PubMed Central

    Hirose, Hiroshi; Hattori, Tomohiro

    2016-01-01

    Background. Submacular hemorrhage can occur after blunt trauma to the eye. Intravitreal tissue plasminogen activator (tPA) and gas injection are often used for treatment and are effective for submacular hemorrhage caused by age-related macular degeneration. This report describes the clinical outcome in a child with submacular hemorrhage caused by traumatic choroidal rupture who underwent successful intravitreal tPA injection and pneumatic displacement. Case Presentation. A 10-year-old boy developed sudden decrease of vision and a central scotoma in his right eye after trauma. Submacular hemorrhage was found in the eye. Visual acuity was 20/70 OD. Tissue plasminogen activator (12.5 μg in 0.05 mL) and 0.3 mL of pure sulfur hexafluoride were injected into the vitreous cavity under general anesthesia. After surgery, the patient was instructed to maintain a prone position. Displacement of the submacular hemorrhage from the fovea revealed a choroidal rupture, presumed to be the cause of the hemorrhage. After 4 months of follow-up, visual acuity was restored and final visual acuity is 20/16. Conclusion. Intravitreal tPA and gas injection can be an effective treatment for children with submacular hemorrhage. PMID:27722001

  11. Protocol: Effect of intravitreal bevacizumab (avastin) in the treatment of macular edema: A systematic review of randomized controlled trials

    PubMed Central

    Qazi, Hammad A.

    2012-01-01

    Cystoid macular edema (CME) is a relatively common painless condition usually accompanied by blurred vision. The prevalence of CME varied from 5% to 47% depending on cause of pathology. There are several treatments available for ME including intravitreal use of bevacizumab that has been used in different doses in few studies. However, there is still scarcity of data available on the use of bevacizumab for the treatment of ME. A systematic review is needed to provide a foundational base to discuss and synthesize the available information on the effectiveness and safety of intravitreal bevacizumab in macular edema, so that recommendations and policies can be built regarding controversial use of bevacizumab in macular edema. We have planned to perform a systematic review with an objective to compare the effects of a single injection of 1.25 mg intravitreal bevacizumab (avastin) in the improvement of visual acuity, macular edema, and thickness with other interventions/controls for the treatment of macular edema at 3 and 6 months interval using randomized controlled trials. This is only a protocol of the review and we will be conducting a full length review, addressing the issue in future. PMID:23853638

  12. Neuroprotective effects of BDNF and GDNF in intravitreally transplanted mesenchymal stem cells after optic nerve crush in mice

    PubMed Central

    Hu, Zong-Li; Li, Ni; Wei, Xin; Tang, Li; Wang, Ting-Hua; Chen, Xiao-Ming

    2017-01-01

    AIM To assess the neuro-protective effect of bone marrow mesenchymal stem cells (BMSCs) on retinal ganglion cells (RGCs) following optic nerve crush in mice. METHODS C56BL/6J mice were treated with intravitreal injection of PBS, BMSCs, BDNF-interference BMSCs (BIM), and GDNF-interference BMSCs (GIM) following optic nerve crush, respectively. The number of surviving RGCs was determined by whole-mount retinas and frozen sections, while certain mRNA or protein was detected by q-PCR or ELISA, respectively. RESULTS The density (cell number/mm2) of RGCs was 410.77±56.70 in the retina 21d after optic nerve crush without any treatment, compared to 1351.39±195.97 in the normal control (P<0.05). RGCs in BMSCs treated eyes was 625.07±89.64/mm2, significantly higher than that of no or PBS treatment (P<0.05). While RGCs was even less in the retina with intravitreal injection of BIM (354.07+39.77) and GIM (326.67+33.37) than that without treatment (P<0.05). BMSCs injection improved the internal BDNF expression in retinas. CONCLUSION Optic nerve crush caused rust loss of RGCs and intravitreally transplanted BMSCs at some extent protected RGCs from death. The effect of BMSCs and level of BDNF in retinas are both related to BDNF and GDNF expression in BMSCs. PMID:28149774

  13. Mechanistic analysis of triamcinolone acetonide release from PLGA microspheres as a function of varying in vitro release conditions.

    PubMed

    Doty, Amy C; Zhang, Ying; Weinstein, David G; Wang, Yan; Choi, Stephanie; Qu, Wen; Mittal, Sachin; Schwendeman, Steven P

    2017-04-01

    In vitro tests for controlled release PLGA microspheres in their current state often do not accurately predict in vivo performance of these products during formulation development. Here, we introduce a new mechanistic and multi-phase approach to more clearly understand in vitro-in vivo relationships, and describe the first "in vitro phase" with the model drug, triamcinolone acetonide (Tr-A). Two microsphere formulations encapsulating Tr-A were prepared from PLGAs of different molecular weights and end-capping (18kDa acid-capped and 54kDa ester-capped). In vitro release kinetics and the evidence for controlling mechanisms (i.e., erosion, diffusion, and water-mediated processes) were studied in four release media: PBST pH 7.4 (standard condition), PBST pH 6.5, PBS+1.0% triethyl citrate (TC), and HBST pH 7.4. The release mechanism in PBST was primarily polymer erosion-controlled as indicated by the similarity of release and mass loss kinetics. Release from the low MW PLGA was accelerated at low pH due to increased rate of hydrolysis and in the presence of the plasticizer TC due to slightly increased hydrolysis and much higher diffusion in the polymer matrix. TC also increased release from the high MW PLGA due to increased hydrolysis, erosion, and diffusion. This work demonstrates how in vitro conditions can be manipulated to change not only rates of drug release from PLGA microspheres but also the mechanism(s) by which release occurs. Follow-on studies in the next phases of this approach will utilize these results to compare the mechanistic data of the Tr-A/PLGA microsphere formulations developed here after recovery of microspheres in vivo. This new approach based on measuring mechanistic indicators of release in vitro and in vivo has the potential to design better, more predictive in vitro release tests for these formulations and potentially lead to mechanism-based in vitro-in vivo correlations.

  14. Twelve-Month Follow-Up of Dexamethasone Implants for Macular Edema from Various Diseases in Vitrectomized and Nonvitrectomized Eyes.

    PubMed

    Novais, Eduardo A; Maia, Mauricio; Filho, Paulo Augusto de Arruda Mello; Dias, João Rafael de Oliveira; Garcia, José Maurício B B; de Andrade, Gabriel C; Louzada, Ricardo N; Ávila, Marcos; Maia, André; Arevalo, J Fernando; Wu, Lihteh; Berrocal, Maria; Badaró, Emmerson; Farah, Michel

    2016-01-01

    Purpose. To evaluate the best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of dexamethasone implants needed to treat cystoid macular edema (CME) from various etiologies over 12 months in vitrectomized and nonvitrectomized eyes. Methods. This multicenter retrospective cohort study included 112 patients with CME secondary to retinal diseases treated pro re nata (PRN) with a 0.7 mg intravitreal dexamethasone implant for 12 months. The BCVA, CRT, adverse events, safety data, and number of implants were recorded. Results. Vitrectomized and nonvitrectomized eyes received means of three implants and one implant, respectively, over 12 months (P < 0.001). The mean BCVA of all patients improved from 0.13 at baseline to 0.33 (P < 0.001) 12 months after one (P = 0.001), two (P = 0.041), and three (P < 0.001) implants but not four implants (P = 0.068). The mean baseline CRT decreased significantly (P < 0.001) from 463 to 254 microns after 12 months with one (P < 0.001), two (P = 0.002), and three (P = 0.001) implants but not with four implants (P = 0.114). The anatomic and functional outcomes were not significantly different between vitrectomized and nonvitrectomized eyes. Increased IOP was the most common adverse event (23.2%). Conclusions. Dexamethasone implant administered PRN improved VA and decreased CRT in CME, with possible long-term clinically relevant benefits for treating CME from various etiologies. Vitrectomized eyes needed more implants compared with nonvitrectomized eyes.

  15. Twelve-Month Follow-Up of Dexamethasone Implants for Macular Edema from Various Diseases in Vitrectomized and Nonvitrectomized Eyes

    PubMed Central

    Filho, Paulo Augusto de Arruda Mello; Dias, João Rafael de Oliveira; de Andrade, Gabriel C.; Louzada, Ricardo N.; Ávila, Marcos; Berrocal, Maria; Farah, Michel

    2016-01-01

    Purpose. To evaluate the best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of dexamethasone implants needed to treat cystoid macular edema (CME) from various etiologies over 12 months in vitrectomized and nonvitrectomized eyes. Methods. This multicenter retrospective cohort study included 112 patients with CME secondary to retinal diseases treated pro re nata (PRN) with a 0.7 mg intravitreal dexamethasone implant for 12 months. The BCVA, CRT, adverse events, safety data, and number of implants were recorded. Results. Vitrectomized and nonvitrectomized eyes received means of three implants and one implant, respectively, over 12 months (P < 0.001). The mean BCVA of all patients improved from 0.13 at baseline to 0.33 (P < 0.001) 12 months after one (P = 0.001), two (P = 0.041), and three (P < 0.001) implants but not four implants (P = 0.068). The mean baseline CRT decreased significantly (P < 0.001) from 463 to 254 microns after 12 months with one (P < 0.001), two (P = 0.002), and three (P = 0.001) implants but not with four implants (P = 0.114). The anatomic and functional outcomes were not significantly different between vitrectomized and nonvitrectomized eyes. Increased IOP was the most common adverse event (23.2%). Conclusions. Dexamethasone implant administered PRN improved VA and decreased CRT in CME, with possible long-term clinically relevant benefits for treating CME from various etiologies. Vitrectomized eyes needed more implants compared with nonvitrectomized eyes. PMID:27721989

  16. Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick

    PubMed Central

    Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank

    2012-01-01

    Purpose Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Methods Chicks were treated with either +7 D, −7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-AktThr308, and anti-phospho-Erk1/2(Thr202/Tyr204) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Results Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens–treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor

  17. Effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections

    PubMed Central

    Ataş, Mustafa; Başkan, Burhan; Özköse, Ayşe; Mutlu Sarıgüzel, Fatma; Demircan, Süleyman; Pangal, Emine

    2014-01-01

    AIM To evaluate the effects of moxifloxacin exposure on the conjunctival flora and antibiotic resistance profile following repeated intravitreal injections. METHODS Seventy-two eyes of 36 patients [36 eyes in control group, 36 eyes in intravitreal injection (IVI) group] were enrolled in the study. All the eyes had at least one IVI and had diabetic macular edema (DME) or age-related macular degeneration (ARMD). Moxifloxacin was prescribed to all the patients four times a day for five days following injection. Conjunctival cultures were obtained from the lower fornix via standardized technique with every possible effort made to minimize contamination from the lids, lashes, or skin. Before the application of any ophthalmic medication, conjunctival cultures were obtained from both eyes using sterile cotton culture. An automated microbiology system was used to identify the growing bacteria and determine antibiotic sensitivity. RESULTS The bacterial cultures were isolated from 72 eyes of 36 patients, sixteen of whom patients (44.4%) were male and twenty (55.6%) were female. Average age was 68.4±9.0 (range 50-86). The average number of injections before taking cultures was 3.1+1.0. Forty-eight (66.7%) of 72 eyes had at least one significant organism. There was no bacterial growth in 8 (20.5%) of IVI eyes and in 16 (44.4%) of control eyes (P=0.03). Of the bacteria isolated from culture, 53.8% of coagulase negative staphylococci (CoNS) in IVI eyes and 47.2% CoNS in control eyes. This difference between IVI eyes and control eyes about bacteria isolated from culture was not statistically significant (P=0.2). Eleven of 25 bacteria (44.0%) isolated from IVI eyes and 11 (57.9%) of 19 bacteria isolated from control eyes were resistant to oxacillin. The difference in frequency of moxifloxacine resistance between two groups was not statistically significant (12.0% in IVI eyes and 21.1% in control eyes) (P=0.44). There were no cases of resistance to vancomycin, teicoplanin and

  18. Surface Engineering of Porous Silicon Microparticles for Intravitreal Sustained Delivery of Rapamycin

    PubMed Central

    Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2015-01-01

    Purpose. To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Methods. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. Results. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Conclusions. Porous silicon–based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. PMID:25613937

  19. Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats

    PubMed Central

    Lu, Yan; Zhou, Nan; Huang, Xiao; Cheng, Jin-Wei; Li, Feng-Qian; Wei, Rui-Li; Cai, Ji-Ping

    2014-01-01

    AIM To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF) protein and VEGF mRNA in the retina of diabetic rats. METHODS Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3µL of physiological saline, while in groups B and C were injected with 3µL (75µg) of bevacizumab and 3µL of bevacizumab-chitosan nanoparticles (containing 75µg of bevacizumab), respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries. RESULTS Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05), while the VEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05). Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05) in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05) in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05). The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05). No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone. CONCLUSION The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of

  20. Effect of initial retinal thickness on outcome of intravitreal bevacizumab therapy for diabetic macular edema

    PubMed Central

    Mushtaq, Bushra; Crosby, Niall J; Dimopoulos, Antonios T; Lip, Peck Lin; Stavrou, Panagiota; El-Sherbiny, Samer; Yang, Yit

    2014-01-01

    Purpose To investigate whether eyes with diabetic macular edema (DME) and central retinal thickness (CRT) >400 μm had better visual and anatomical outcomes compared to eyes with a CRT <400 μm when treated with intravitreal bevacizumab in a real-world setting. Patients and methods Patients undergoing intravitreal bevacizumab therapy for DME were identified from the departmental database of a tertiary referral unit. Following the initial injection, a retreatment was performed for any persistent macular edema, unless there had been no previous response to repeated doses. Recorded parameters included visual acuity, CRT on optical coherence tomography (spectral domain optical coherence tomography [SD-OCT]), and SD-OCT characteristics. Comparisons were made between data at baseline and 12 months after the first injection, and differences were tested for statistical significance using the Student’s t-test. Results In all, 175 eyes of 142 patients were analyzed. Patients in group 2 (CRT >400 μm) had significantly more injections than group 1 (CRT <400 μm) (4.0 versus 3.3; P=0.003). Both groups had similar numbers of eyes with preexisting epiretinal membrane and/or vitreomacular traction at baseline. The reduction in CRT was significantly greater in group 2 when compared to group 1 (P<0.0001). In terms of visual gain between baseline and month 12, each gained significantly by a mean of 0.12 logarithm of the minimum angle of resolution units (P=0.0001), but there was no difference between groups 1 and 2 (P=0.99). Conclusion These results do not support a 400 μm baseline CRT cut-off for treating DME with bevacizumab, in contrast to published data on ranibizumab. Our results also indicate that patients with a thicker CRT require more bevacizumab injections, making treatment less cost-effective for these patients. Our results could be used by practitioners to support the use of bevacizumab in DME without applying a CRT cut-off. PMID:24812486

  1. [Biomaterials in cochlear implants].

    PubMed

    Stöver, T; Lenarz, T

    2009-05-01

    Cochlear implants (CI) represent the "gold standard" for the treatment of congenitally deaf children and postlingually deafened adults. Thus, cochlear implantation is a success story of new bionic prosthesis development. Owing to routine application of cochlear implants in adults but also in very young children (below the age of one), high demands are placed on the implants. This is especially true for biocompatibility aspects of surface materials of implant parts which are in contact with the human body. In addition, there are various mechanical requirements which certain components of the implants must fulfil, such as flexibility of the electrode array and mechanical resistance of the implant housing. Due to the close contact of the implant to the middle ear mucosa and because the electrode array is positioned in the perilymphatic space via cochleostomy, there is a potential risk of bacterial transferral along the electrode array into the cochlea. Various requirements that have to be fulfilled by cochlear implants, such as biocompatibility, electrode micromechanics, and although a very high level of technical standards has been carried out there is still demand for the improvement of implants as well as of the materials used for manufacturing, ultimately leading to increased implant performance. General considerations of material aspects related to cochlear implants as well as potential future perspectives of implant development will be discussed.

  2. Acute Hemorrhagic Retinopathy following Intravitreal Melphalan Injection for Retinoblastoma: A Report of Two Cases and Technical Modifications to Enhance the Prevention of Retinal Toxicity

    PubMed Central

    Aziz, Hassan A.; Kim, Jonathan W.; Munier, Francis L.; Berry, Jesse L.

    2017-01-01

    Aims To report the occurrence of acute hemorrhagic retinopathy following intravitreal melphalan injection for retinoblastoma. Methods This is a retrospective case series of 2 patients with retinoblastoma treated with intravitreal melphalan for vitreous seeding who developed acute hemorrhagic retinopathy. Results Patient 1 is a 6-month-old female with bilateral retinoblastoma (Group D right eye and Group B left eye) treated with 4 cycles of systemic chemotherapy and 2 intravitreal melphalan injections in each eye. Patient 2 is a 10-month-old male with unilateral Group D retinoblastoma treated with 6 cycles of systemic chemotherapy and 2 injections of intravitreal melphalan. At the 1-week follow-up after the second injection, both patients had an acute hemorrhagic retinopathy that resulted in chorioretinal toxicity with a sharp demarcation line between the normal and abnormal retina. At the last follow-up (22 and 12 months, respectively), there was total tumor control and resolution of vitreous seeding in both patients. Conclusions Although intravitreal melphalan injection is effective for vitreous seeding in eyes with retinoblastoma, acute hemorrhagic retinopathy and diffuse chorioretinal atrophy is a possible complication of this treatment modality. Given the clinical findings observed in these patients, the development of this retinal toxicity most likely results from a retrohyaloid overdose. Consequently we suggest preventive measures aimed at limiting the risk of retrohyaloid injection.

  3. Breast Implants: Saline vs. Silicone

    MedlinePlus

    ... to women of any age for breast reconstruction. Silicone breast implants Silicone implants are pre-filled with ... likely be inserted at the same time. Ruptured silicone implant If a silicone breast implant ruptures, you ...

  4. Electroretinographic evaluations of retinal function before, just after, and after intravitreal injections

    PubMed Central

    Yagura, Kazuma; Shinoda, Kei; Matsumoto, Soiti; Terauchi, Gaku; Kawashima, Makoto; Watanabe, Emiko; Matsumoto, Harue; Iwata, Takeshi; Mizota, Atsushi; Miyake, Yozo

    2016-01-01

    Intravitreal injections (IVI) have become a part of daily practice for a growing number of procedures. We evaluated the retinal function by recording intraoperative photopic electroretinograms (ERGs) before an injection (T1), just after the injection (T2), and after the aspiration of the anterior chamber fluid (T3) of 19 eyes of 19 patients (mean age 70.6 years; men = 11) who received an IVI of an anti-vascular endothelial growth factor. The mean amplitudes of the b-wave, photopic negative responses (PhNR), and oscillatory potentials (OPs) 1 and 2 at T2 were significantly smaller than that at T1, but no significant difference was observed between T3 and T1. The mean implicit times of the a-wave and OP1, 2, and 3 at T2 and the a-wave and the OP2 at T3 were significantly longer than that at T1. The mean intraocular pressure (IOP) at T2 (49.32 mm Hg) was significantly higher and the IOP at T3 (8.74 mm Hg) was significantly lower than that at T1 (21.05 mm Hg). The retinal function was reduced and the IOP elevated just after the IVI. The response of each ERG component was different suggesting a different sensitivity of each type of retinal neuron to IVI. PMID:27492923

  5. Routes for Drug Delivery to the Eye and Retina: Intravitreal Injections.

    PubMed

    Meyer, Carsten H; Krohne, Tim U; Charbel Issa, Peter; Liu, Zengping; Holz, Frank G

    2016-01-01

    The advantage of intravitreal injections is an immediate and increased therapeutic effect in the intended retinal tissue. The accuracy, precision and reproducibility of the delivered volume depend on the size of the syringe and the physician's manual experience. The eyelids and eyelashes are usually disinfected using a povidone-iodine solution (10%); a sterile speculum is placed and drops of povidone-iodine (5%) are applied. The use of adequate anesthetic topical lidocaine 2% is required. The injection site should be located 3.5-4 mm posterior to the limbus. The angle of the incision through the sclera may be directed in an oblique fashion of 30°. The diameter of the needle should be smaller than 25 G, and the injected volume should be limited to 0.15 ml without a routine paracentesis. The incidence of lens injury is 0.006% (2/32,318) and 0.013% (5/35,942) for rhegmatogenous retinal detachments. The rate of suspected endophthalmitis is 0.018% after bevacizumab and 0.027% after ranibizumab injections. Sterile inflammations have been observed after Avastin injections. The concentrations of vascular endothelial growth factor inhibitors decline in a monoexponential fashion. The half-life of unbound bevacizumab is 9.82 days and that of ranibizumab 7.19 days.

  6. Intravitreal Injection of Bevacizumab for Retinopathy of Prematurity in an Infant with Peters Anomaly

    PubMed Central

    Minami, Tsuyoshi; Kuniyoshi, Kazuki; Kusaka, Shunji; Sugioka, Koji; Sakuramoto, Hiroyuki; Sakamoto, Masuo; Izu, Akane; Wada, Norihisa; Shimomura, Yoshikazu

    2014-01-01

    Purpose To report our findings in an infant with Peters anomaly type II whose retinopathy of prematurity (ROP) was treated with an anti-VEGF agent and surgeries. Case Report A male infant weighing 548 g was born prematurely at 23 weeks and 1 day with corneal opacity and shallow anterior chambers in both eyes. At the postmenstrual age of 35 weeks and 3 days, the infant was tentatively diagnosed with stage 3 ROP because of a dilated tunica vasculosa lentis and ultrasonographic findings. The boy was treated with bilateral intravitreal injections of bevacizumab (IVB) because laser photocoagulation of the retina could not be performed due to the corneal opacity. The retina in the right eye detached 3 times, namely 5 days, 16 days, and 7 months after the IVB; encircling the scleral buckle and a vitrectomy with endolaser photocoagulation were therefore required. In his left eye, the retina was reattached after the initial IVB, and no additional treatment was required. ROP was not reactivated in both eyes until the last examination at the age of 2 years and 6 months. Conclusions Our results showed that IVB is a useful treatment for ROP in patients with Peters anomaly. However, a retinal detachment can be a complication after IVB. The optimal timing of IVB for ROP in infants with hazy media needs to be determined. PMID:25408672

  7. Intravitreal ranibizumab as a primary or a combined treatment for severe retinopathy of prematurity

    PubMed Central

    Arámbulo, Odalis; Dib, Gabriel; Iturralde, Juan; Duran, Fahir; Brito, Miguel; Fortes Filho, João B

    2015-01-01

    Purpose The aim of the study was to assess the outcomes of severe retinopathy of prematurity (ROP) in zone I or posterior zone II treated with intravitreal ranibizumab (IVR) as monotherapy or combined treatment with laser photocoagulation. Methods This is a retrospective study analyzing clinical records of the included patients. Patients were divided into two groups: group 1 included patients who received only IVR treatment; and group 2 was subdivided into group 2A – including patients with IVR as initial treatment and complementary laser photocoagulation if retinal neovascularization or plus disease did not regress, and group 2B – including patients with initial laser photocoagulation and IVR as rescue therapy. Favorable outcomes were regression of the retinal neovascularization and plus disease, meaning control of the disease. Unfavorable outcomes were progression to stages 4 and 5 of ROP. Results Fifty-seven eyes were included in the study. Mean birth weight and gestational age were 1,281±254 g and 29.5±2.1 weeks, respectively. Group 1 comprised of 16 eyes, with favorable outcomes in 14 eyes (87.5%). Group 2 comprised of 41 eyes, with favorable outcomes in 29 eyes (70.7%), in a mean follow-up period of 12.8 months. Conclusion IVR was effective to treat severe cases of ROP as a primary or a combined treatment. Forty-three of the 57 treated eyes (75.4%) achieved regression of ROP and favorable outcomes. PMID:26604673

  8. Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab

    PubMed Central

    2013-01-01

    Background To determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory. Methods Eyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss’ kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography. Results Among the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P < .001, Mann–Whitney U test). The inter-rater agreement was high with a Fleiss’ kappa = 0.95, P < .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann–Whitney U test). Conclusions Eyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy. PMID:23962072

  9. Development of a murine ocular posterior segment explant culture for the study of intravitreous vector delivery.

    PubMed

    Denk, Nora; Misra, Vikram; Sandmeyer, Lynne S; Bauer, Bianca B; Singh, Jaswant; Forsyth, George W; Grahn, Bruce H

    2015-01-01

    The objective of this study was to develop a murine retinal/choroidal/scleral explant culture system to facilitate the intravitreous delivery of vectors. Posterior segment explants from adult mice of 2 different age groups (4 wk and 15 wk) were cultured in serum-free medium for variable time periods. Tissue viability was assessed by gross morphology, cell survival quantification, activated caspase-3 expression, and immunohistochemistry. To model ocular gene therapy, explants were exposed to varying transducing units of a lentiviral vector expressing the gene for green fluorescent protein for 48 h. Explant retinal cells remained viable for approximately 1 wk, although the ganglion cell layer developed apoptosis between 4 and 7 d. Following vector infusion into the posterior segment cups, viral transduction was noted in multiple retinal layers in both age groups. An age of donor mouse influence was noted and older mice did not transduce as well as younger mice. This explant offers an easily managed posterior segment ocular culture with minimum disturbance of the tissue, and may be useful for investigating methods of enhancing retinal gene therapy under controlled conditions.

  10. Catalytic Nanoceria Are Preferentially Retained in the Rat Retina and Are Not Cytotoxic after Intravitreal Injection

    PubMed Central

    Wong, Lily L.; Hirst, Suzanne M.; Pye, Quentin N.; Reilly, Christopher M.; Seal, Sudipta; McGinnis, James F.

    2013-01-01

    Cerium oxide nanoparticles (nanoceria) possess catalytic and regenerative radical scavenging activities. The ability of nanoceria to maintain cellular redox balance makes them ideal candidates for treatment of retinal diseases whose development is tightly associated with oxidative damage. We have demonstrated that our stable water-dispersed nanoceria delay photoreceptor cell degeneration in rodent models and prevent pathological retinal neovascularization in vldlr mutant mice. The objectives of the current study were to determine the temporal and spatial distributions of nanoceria after a single intravitreal injection, and to determine if nanoceria had any toxic effects in healthy rat retinas. Using inductively-coupled plasma mass spectrometry (ICP-MS), we discovered that nanoceria were rapidly taken up by the retina and were preferentially retained in this tissue even after 120 days. We also did not observe any acute or long-term negative effects of nanoceria on retinal function or cytoarchitecture even after this long-term exposure. Because nanoceria are effective at low dosages, nontoxic and are retained in the retina for extended periods, we conclude that nanoceria are promising ophthalmic therapeutics for treating retinal diseases known to involve oxidative stress in their pathogeneses. PMID:23536794

  11. Population Pharmacokinetics and Pharmacodynamics of Lampalizumab Administered Intravitreally to Patients With Geographic Atrophy.

    PubMed

    Le, K N; Gibiansky, L; van Lookeren Campagne, M; Good, J; Davancaze, T; Loyet, K M; Morimoto, A; Strauss, E C; Jin, J Y

    2015-10-01

    Intravitreally administered lampalizumab is an investigational complement inhibitor directed against complement factor D (CFD) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration. We sought to develop an integrated ocular and systemic pharmacokinetic/pharmacodynamic model for lampalizumab in patients with GA using the data from the clinical phase I and II studies. The kinetics of lampalizumab and CFD disposition were well described by the combined ocular/serum target-mediated drug disposition model using a quasi-steady-state approximation. This model takes into account the drug, target, and drug-target complex clearance, their transfer rates between ocular and serum compartments, and turnover kinetics of CFD. The constructed model provided a prediction of target occupancy in ocular tissues and supported that the two dosing regimens (10 mg q4w and 10 mg q6w) selected for the phase III studies are expected to be efficacious and able to achieve near-complete target engagement in the vitreous humor.

  12. Photoreceptor-targeted gene delivery using intravitreally administered AAV vectors in dogs

    PubMed Central

    Boyd, RF; Sledge, DG; Boye, SL; Boye, SE; Hauswirth, WW; Komáromy, AM; Petersen-Jones, SM; Bartoe, JT

    2016-01-01

    Delivery of therapeutic transgenes to retinal photoreceptors using adeno-associated virus (AAV) vectors has traditionally required subretinal injection. Recently, photoreceptor transduction efficiency following intravitreal injection (IVT) has improved in rodent models through use of capsid-mutant AAV vectors; but remains limited in large animal models. Thickness of the inner limiting membrane (ILM) in large animals is thought to impair retinal penetration by AAV. Our study compared two newly developed AAV vectors containing multiple capsid amino acid substitutions following IVT in dogs. The ability of two promoter constructs to restrict reporter transgene expression to photoreceptors was also evaluated. AAV vectors containing the interphotoreceptor-binding protein (IRBP) promoter drove expression exclusively in rod and cone photoreceptors, with transduction efficiencies of ~ 4% of cones and 2% of rods. Notably, in the central region containing the cone-rich visual streak, 15.6% of cones were transduced. Significant regional variation existed, with lower transduction efficiencies in the temporal regions of all eyes. This variation did not correlate with ILM thickness. Vectors carrying a cone-specific promoter failed to transduce a quantifiable percentage of cone photoreceptors. The newly developed AAV vectors containing the IRBP promoter were capable of producing photoreceptor-specific transgene expression following IVT in the dog. PMID:26467396

  13. Safety of bilateral same-day intravitreal injections of anti-vascular endothelial growth factor agents

    PubMed Central

    Ruão, Miguel; Andreu-Fenoll, María; Dolz-Marco, Rosa; Gallego-Pinazo, Roberto

    2017-01-01

    Purpose The aim was to evaluate the safety of bilateral same-day injections with intravitreal antiangiogenic drugs for macular diseases. Methods Cross-sectional retrospective review of unilateral and bilateral same-day antiangiogenic injections was conducted between January 2011 and March 2016 in the Unit of Macula, University and Polytechnic Hospital La Fe (Valencia, Spain). A total of 8,172 injections were administered, among which 6,560 were unilateral and 1,612 were bilateral injections. Patients were included in the study regardless of the diagnosis. Ranibizumab and aflibercept were the antiangiogenic drugs used. The presence of endophthalmitis or retinal detachment was evaluated. Results A total of 1 (0.012%) culture-proven endophthalmitis and 19 (0.233%) acute intraocular inflammations were registered. In the unilateral injections group, there were 18 (0.274%) acute intraocular inflammations and 1 (0.015%) culture-proven endophthalmitis. One (0.062%) of the 1,612 bilateral same-day injections had a unilateral acute intraocular inflammation, and there were no culture-proven endophthalmitis in this group. Conclusion Bilateral same-day injections are more convenient for patients and their caregivers than the unilateral injections administered on different days. In our study, the prevalence of culture-proven endophthalmitis and acute intraocular inflammation was lower in the bilateral injections than in the unilateral group. These data support the idea that bilateral same-day injections are a safe and valid treatment to use in our clinical practice. PMID:28203056

  14. Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome

    PubMed Central

    Yılmaz, Turgut; Dikci, Seyhan; Genç, Oğuzhan; Mutlu, Kayhan

    2017-01-01

    Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is characterized by small, round, discrete, macular or mid peripheral atrophic (punched out) chorioretinal lesions (histo spots), peripapillary scarring, choroidal neovascularization (CNV), and the absence of anterior uveitis and vitritis. Diagnosis of this disorder is based upon characteristic clinical findings and a positive histoplasmin skin test or residence in an endemic region for Histoplasma capsulatum. There is no active systemic disease during diagnosis of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known complication which leads to loss of visual acuity or visual disturbance. Without therapy, the visual prognosis in these patients is unfavorable. Submacular surgery, radiation, steroids, photodynamic therapy, and most recently anti-vascular endothelial growth factor therapy are current therapeutic options for this condition. We report a case with persistent CNV secondary to POHS in a middle-aged woman with moderate myopia and the clinical course of treatment with multiple intravitreal ranibizumab (Lucentis®, Novartis) injections.

  15. Waiting time reduction in intravitreal clinics by optimization of appointment scheduling: balancing demand and supply

    PubMed Central

    Ugarte, Marta

    2015-01-01

    This study was designed guided by the Model for Improvement framework to reduce waiting times and visit duration in the intravitreal therapy clinic, while improving patient and staff experience. In our aim to provide good quality, patient-centred care and constantly improve, we optimised the appointment profile and patient flow. We involved a multidisciplinary team (one consultant, junior doctors, staff nurses, technicians, and receptionist), as well as patients and relatives, to try to understand the main delays in the clinic. Process mapping, a fishbone diagram, run charts, together with feedback from patients and staff, provided an insight on the possible roots of the delays experienced by our patients. The results of the inquiry led us to take actions focused on optimising appointment scheduling. After implementing the new scheduling profile (with a gap in the middle of the session), various cycles of plan-do-study-act and a comparative, qualitative study by interviewing 10 patients demonstrated that the waiting times decreased, and patients and staff experience improved. PMID:26734454

  16. Photoreceptor-targeted gene delivery using intravitreally administered AAV vectors in dogs.

    PubMed

    Boyd, R F; Sledge, D G; Boye, S L; Boye, S E; Hauswirth, W W; Komáromy, A M; Petersen-Jones, S M; Bartoe, J T

    2016-02-01

    Delivery of therapeutic transgenes to retinal photoreceptors using adeno-associated virus (AAV) vectors has traditionally required subretinal injection. Recently, photoreceptor transduction efficiency following intravitreal injection (IVT) has improved in rodent models through use of capsid-mutant AAV vectors; but remains limited in large animal models. Thickness of the inner limiting membrane (ILM) in large animals is thought to impair retinal penetration by AAV. Our study compared two newly developed AAV vectors containing multiple capsid amino acid substitutions following IVT in dogs. The ability of two promoter constructs to restrict reporter transgene expression to photoreceptors was also evaluated. AAV vectors containing the interphotoreceptor-binding protein (IRBP) promoter drove expression exclusively in rod and cone photoreceptors, with transduction efficiencies of ~4% of cones and 2% of rods. Notably, in the central region containing the cone-rich visual streak, 15.6% of cones were transduced. Significant regional variation existed, with lower transduction efficiencies in the temporal regions of all eyes. This variation did not correlate with ILM thickness. Vectors carrying a cone-specific promoter failed to transduce a quantifiable percentage of cone photoreceptors. The newly developed AAV vectors containing the IRBP promoter were capable of producing photoreceptor-specific transgene expression following IVT in the dog.

  17. Restoration of foveal photoreceptors after intravitreal ranibizumab injections for diabetic macular edema

    PubMed Central

    Mori, Yuki; Suzuma, Kiyoshi; Uji, Akihito; Ishihara, Kenji; Yoshitake, Shin; Fujimoto, Masahiro; Dodo, Yoko; Yoshitake, Tatsuya; Miwa, Yuko; Murakami, Tomoaki

    2016-01-01

    Anti-vascular endothelial growth factor drugs are the first-line treatment for diabetic macular edema (DME), although the mechanism of the visual acuity (VA) improvement remains largely unknown. The association between photoreceptor damage and visual impairment encouraged us to retrospectively investigate the changes in the foveal photoreceptors in the external limiting membrane (ELM) and ellipsoid zone (EZ) on spectral-domain optical coherence tomography (SD-OCT) images in 62 eyes with DME treated with intravitreal ranibizumab (IVR) injections. The transverse lengths of the disrupted EZ and ELM were shortened significantly (P < 0.001 and P = 0.044, respectively) at 12 months. The qualitative investigation also showed restoration of the EZ and ELM lines on SD-OCT images. The EZ at 12 months lengthened in 34 of 38 eyes with discontinuous EZ and was preserved in 16 of 21 eyes with complete EZ at baseline. VA improvement was positively correlated with shortening of the disrupted EZ at 12 months (ρ = 0.463, P < 0.001), whereas the decrease in central subfield thickness was associated with neither VA improvement nor changes in EZ status (ρ = 0.215, P = 0.093 and (ρ = 0.209, P = 0.103, respectively). These data suggested that photoreceptor restoration contributes to VA improvement after pro re nata treatment with IVR injections for DME independent of resolved retinal thickening. PMID:27966644

  18. Implants for lucky few

    NASA Astrophysics Data System (ADS)

    Brandon, David

    2011-08-01

    In his article "Vision of beauty" (May pp22-27), Richard Taylor points the way to fractal design for retinal implants and makes an enthusiastic case for incorporating such features into the next generation of such implants.

  19. Release profile and transscleral permeation of triamcinolone acetonide loaded nanostructured lipid carriers (TA-NLC): in vitro and ex vivo studies.

    PubMed

    Araújo, Joana; Garcia, Maria L; Mallandrich, Mireia; Souto, Eliana B; Calpena, Ana C

    2012-08-01

    Nanostructured lipid carriers (NLC) have been developed for sustained release of triamcinolone acetonide (TA), a corticosteroid commonly indicated for macular edema, neovascularization, and other ocular inflammatory disorders. TA-NLC were prepared by high-pressure homogenization and characterized for in vitro release by dialysis bag. Ex vivo permeation profile was assessed using rabbit sclera isolated and mounted in Franz diffusion cells. TA-NLC were placed in episcleral donor compartment and choroidal side was perfused with HEPES buffer. Tissue sections underwent drug wash-out, following analysis by validated RP-HPLC of drug content and perfused fractions collected over 24 hours. Drug release followed one-order kinetics and permeability studies confirmed that TA is able to diffuse across rabbit sclera in sustained profile, following zero-order kinetics. Strong tissue binding was observed, providing a drug depot. These findings are of potential use when designing future TA therapy strategies for ocular diseases of posterior segment.

  20. Fluocinolone Acetonide Is a Potent Synergistic Factor of TGF-β3-Associated Chondrogenesis of Bone Marrow-Derived Mesenchymal Stem Cells for Articular Surface Regeneration.

    PubMed

    Hara, Emilio Satoshi; Ono, Mitsuaki; Pham, Hai Thanh; Sonoyama, Wataru; Kubota, Satoshi; Takigawa, Masaharu; Matsumoto, Takuya; Young, Marian F; Olsen, Bjorn R; Kuboki, Takuo

    2015-09-01

    Articular cartilage repair remains a challenging problem. Based on a high-throughput screening and functional analysis, we found that fluocinolone acetonide (FA) in combination with transforming growth factor beta 3 (TGF-β3) strongly potentiated chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). In an in vivo cartilage defect model in knee joints of immunocompromised mice, transplantation of FA/TGF-β3-treated hBMSCs could completely repair the articular surface. Analysis of the intracellular pathways revealed that FA enhanced TGF-β3-induced phosphorylation of Smad2 and Smad3. Additionally, we performed a pathway array and found that FA activates the mTORC1/AKT pathway. Chemical inhibition of mTORC1 with rapamycin substantially suppressed FA effect, and inhibition of AKT completely repressed chondrogenesis of hBMSCs. Inhibition of glucocorticoid receptor with mifepristone also suppressed FA effect, suggesting that FA involves binding to the glucocorticoid receptor. Comparative analysis with other glucocorticoids (triamcinolone acetonide [TA] and dexamethasone [DEX]) revealed the unique ability of FA to repair articular cartilage surgical defects. Analysis of intracellular pathways showed that the mTORC1/AKT pathway and the glucocorticoid receptor was highly activated with FA and TA, but to a lesser extent with DEX. Collectively, these results show a unique ability of FA to enhance TGF-β3-associated chondrogenesis, and suggest that the FA/TGF-β3 combination may be used as major inducer of chondrogenesis in vitro. Additionally, FA/TGF-β3 could be potentially applied in a clinical setting to increase the efficiency of regenerative approaches based on chondrogenic differentiation of stem cells.

  1. A study comparing the clinical pharmacokinetics, pharmacodynamics, and tolerability of triamcinolone acetonide HFA-134a metered-dose inhaler and budesonide dry-powder inhaler following inhalation administration.

    PubMed

    Argenti, D; Shah, B; Heald, D

    2000-05-01

    The impending phaseout of chlorofluorocarbons as propellants in pressurized metered-dose inhalers used in the treatment of asthma has resulted in the development of alternative devices to deliver drug to the pulmonary airways. These alternative devices include metered-dose inhalers using environmentally friendly hydroflurocarbon propellants and breath-actuated dry-powder inhalers. The purpose of this study was to compare the single- and multiple-dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide (Azmacort HFA 225 mcg Inhalation Aerosol) to that of the dry-powder formulation of budesonide (Pulmicort Turbuhaler 200 mcg). This three-way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide, 600 mcg dose of budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic-pituitary-adrenal axis function as measured by 8 a.m. serum cortisol, 24-hour overnight serum cortisol AUC(0-24), and 24-hour urinary-free cortisol after the last evening dose of test drug. Tolerability was assessed through physical examinations, vital signs, 12-lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24-hour serum cortisol AUC(0-24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12-lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.

  2. Implantable Heart Aid

    NASA Technical Reports Server (NTRS)

    1984-01-01

    CPI's human-implantable automatic implantable defibrillator (AID) is a heart assist system, derived from NASA's space circuitry technology, that can prevent erratic heart action known as arrhythmias. Implanted AID, consisting of microcomputer power source and two electrodes for sensing heart activity, recognizes onset of ventricular fibrillation (VF) and delivers corrective electrical countershock to restore rhythmic heartbeat.

  3. Development of a dry powder inhaler, the Ultrahaler, containing triamcinolone acetonide using in vitro-in vivo relationships.

    PubMed

    Lim, Joe G P; Shah, Bharti; Rohatagi, Shashank; Bell, Alex

    2006-01-01

    Triamcinolone acetonide (TAA) is safe and effective corticosteroid that is marketed as an MDI (metered dose inhaler) (Azmacort) for the treatment of asthma. A novel dry powder inhaler (DPI), the Ultrahaler, has been developed to deliver Azmacort as another alternative to provide non-CFC formulation for the asthmatic patients. The Ultrahaler is breath actuated and, unlike MDI, does not require coordination of inhalation with the actuation of the device. However, with the Ultrahaler device, like any dry powder inhalation device, the challenge was the on-target and uniform delivery of the drug at the site of action (lungs) with different dose strengths. Due to the complexities of oral inhaled formulations and the topical nature of drug delivery to the lung for efficacy, the reformulation requires careful consideration and support throughout their development, using a combination of in vitro and in vivo studies. This paper describes in vitro studies and two clinical pharmacokinetic studies conducted in a sequence that helped to establish optimum doses for the Ultrahaler. In vitro data were used to guide the initial selection of doses that were then compared in vivo using a pharmacokinetic study with a charcoal block. The in vitro tests included quantifying the target-delivered dose, dose uniformity throughout the life of the device, and the particle size distribution. Particle size distribution was measured using multistage liquid impinger (MSLI) or the Andersen Cascade Impactor (ACI). For in vitro testing, TAA was measured by HPLC methods. Based on the preliminary in vitro data for the respirable fraction, dose strengths with an MDI and the Ultrahaler for the first study were determined. The in vivo assessment consisted of a four-way crossover study following oral inhalation using both MDI (75 and 225 microg/actuation, reference treatment) and comparable respirable doses in the DPI (130 and 360 microg/actuation) devices in healthy volunteers in the presence (lung

  4. Evaluation of Peripapillary Nerve Fiber Layer after Dexamethasone Implantation (Ozurdex) in Branch Retinal Vein Occlusions

    PubMed Central

    Özertürk, Yusuf; Çallı, Ümit; Akçay, Güzide; Kıvrak, Ulviye; Bulut, Kezban

    2016-01-01

    Purpose. To evaluate the peripapillary retinal nerve fiber layer (RNFL) thicknesses of patients treated with intravitreal Ozurdex implant due to branch retinal vein occlusion (BRVO) related macular edema (ME). Methods. Thirty-three eyes of 33 patients treated with Ozurdex implant due to ME associated with BRVO were included in the study. Ophthalmic examinations including determination of best corrected visual acuity (BCVA), measurement of intraocular pressure (IOP), and central macular thickness (CMT) and peripapillary RNFL assessment with optical coherence tomography (OCT) were performed before the injection of Ozurdex implant and during the 6-month follow-up period after the injection. Results. The mean age was 55.2 ± 7.4 (range: 40–68) years. The BCVAs were significantly increased and CMTs were significantly decreased at month 3 and month 6 visits compared to baseline values. The mean IOP was significantly increased from baseline at day 1, week 1, and month 1 visits (p1 = 0.008, p2 = 0.018, and p3 = 0.022, resp.). The average and inferior quadrant peripapillary RNFL thicknesses were significantly reduced at month 6 control visit compared to baseline values (both p < 0.001). Conclusions. Ozurdex implant improved the BCVA and reduced the CMT in the eyes with RVO related ME. However, IOP elevations occurred within the first month after the injection and the average and inferior quadrant RNFL thinning was found six months after the injection. Further controlled studies are warranted. PMID:27882244

  5. Trends in Cochlear Implants

    PubMed Central

    Zeng, Fan-Gang

    2004-01-01

    More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic aspects of cochlear implants, focusing on their psychophysical, speech, music, and cognitive performance. This report also forecasts clinical and research trends related to presurgical evaluation, fitting protocols, signal processing, and postsurgical rehabilitation in cochlear implants. Finally, a future landscape in amplification is presented that requires a unique, yet complementary, contribution from hearing aids, middle ear implants, and cochlear implants to achieve a total solution to the entire spectrum of hearing loss treatment and management. PMID:15247993

  6. Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections

    PubMed Central

    Belviranli, Selman; Malik, Rayaz A.; Kerimoglu, Hurkan; Satirtav, Gunhal; Zengin, Nazmi

    2017-01-01

    Purpose To evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD). Methods Sixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects. Results The mean number of ranibizumab injections per eye was 8.9±5.0 (range 3–20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P = 0.237), and the eyes of healthy control subjects (P = 0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters. Conclusions Multiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD. PMID:28085965

  7. Post-intravitreal anti-VEGF endophthalmitis in the United Kingdom: incidence, features, risk factors, and outcomes

    PubMed Central

    Lyall, D A M; Tey, A; Foot, B; Roxburgh, S T D; Virdi, M; Robertson, C; MacEwen, C J

    2012-01-01

    Purpose To describe the incidence, features, management, and risk factors of post-intravitreal anti-VEGF endophthalmitis (PIAE) in patients undergoing treatment for exudative age-related macular degeneration in the United Kingdom. Methods Prospective observational case control study. Forty-seven cases of PIAE were identified through the British Ophthalmological Surveillance Unit from January 2009 to March 2010. Data collected at diagnosis and at 6 months follow-up included patient demographics, intravitreal injection details, pre- and post-injection management, visual acuity, clinical features and management of PIAE, causative organisms, and clinical outcomes. Details were compared with 200 control cases from 10 control centres to identify potential risk factors. Results Estimated PIAE was 0.025%. Culture-positive PIAE incidence was 0.015%. Mean age of presentation was 78 years. Mean number of intravitreal injections before PIAE was 5. Mean days to presentation was 5 (range 1–39). Positive microbiology culture was found in 59.6%. The majority of causative organisms were Gram positive (92.8%). Significant risk factors were failure to administer topical antibiotics immediately after the injection (P=0.001), blepharitis (P=0.006), subconjunctival anaesthesia (P=0.021), patient squeezing during the injection (P=0.021), and failure to administer topical antibiotics before anti-VEGF injection (P=0.05). Discussion The incidence of PIAE in the United Kingdom is comparable to other studies at a rate of 0.025%. The most common causative organisms were Gram positive. Measures to minimise the risk of PIAE include treatment of blepharitis before injection, avoidance of subconjunctival anaesthesia, topical antibiotic administration immediately after injection with consideration to administering topical antibiotics before injection. PMID:23060022

  8. Clinical effects and safety of treating diabetic macular edema with intravitreal injection of ranibizumab combined with retinal photocoagulation

    PubMed Central

    Yan, Panshi; Qian, Cheng; Wang, Wenzhan; Dong, Yi; Wan, Guangming; Chen, Yue

    2016-01-01

    Background This study was designed to examine the clinical effects of treating diabetic macular edema with an intravitreal injection of ranibizumab in combination with retinal photocoagulation. Methods Sixty-two cases (75 eyes) with confirmed severe proliferative diabetic retinopathy or proliferative diabetic retinopathy in combination with macular edema were randomly divided into the observation group (37 eyes were given an intravitreal injection of ranibizumab combined with retinal photocoagulation) and the control group (38 eyes received retinal photocoagulation only). Vision, fundus condition, central macular thickness, and the macular leakage area were recorded before and after treatment. Results The best-corrected visual acuity and macular leakage area were similar between the observation and control groups (P>0.05). The best-corrected visual acuity in the observation group was higher than that in the control group 3 and 6 months after treatment (P<0.05) and showed a rising tendency. The macular leakage area in the observation group was significantly lower than that in the control group 1 and 3 months after treatment (P<0.05). However, the macular leakage area was similar 6 months after treatment (P>0.05). The central macular thickness of the observation group was lower than that in the control group 1, 3, and 6 months after treatment (P<0.05). The laser energy used in the observation group was also smaller than that in the control group (P<0.05). The intraocular pressure was not significantly different between the groups (P<0.05). No patients in the two groups developed eye or systemic complications, such as glaucoma, cataract, or vitreous hemorrhage during treatment. Conclusion Intravitreal injection of ranibizumab combined with retinal photocoagulation was proven to be effective in treating diabetic macular edema as it improved vision and resulted in fewer complications. PMID:27103811

  9. Synthesis and the absolute configuration of both enantiomers of 4,5-dihydroxy-3-(formyl)cyclopent-2-enone acetonide as a new chiral building block for prostanoid synthesis.

    PubMed

    Łukasik, Beata; Mikołajczyk, Marian; Bujacz, Grzegorz; Żurawiński, Remigiusz

    2015-01-21

    The synthesis of both enantiomers of 4,5-dihydroxy-3-(formyl)cyclopent-2-enone acetonide (5) was accomplished in five steps starting from meso-tartaric acid (6). The key steps involved are preparation of the isopropylidene protected 3-[(dimethoxyphosphoryl)methyl]-4,5-dihydroxycyclopent-2-enone (9), resolution of the diastereoisomeric products 10 of the Horner reaction of racemic 9 with (R)-glyceraldehyde acetonide and the final regioselective ozonolysis of the exocyclic carbon–carbon double bond of the separated dienones 10 leading to both enantiomeric title compounds 5. The absolute configuration of both enantiomers was initially assigned based on the comparison of the chiroptical properties obtained from the DFT calculations with the experimental data and finally confirmed by X-ray analysis.

  10. Intravitreal invading cells contribute to vitreal cytokine milieu in proliferative vitreoretinopathy

    PubMed Central

    El-Ghrably, I; Dua, H.; Orr, G.; Fischer, D.; Tighe, P.

    2001-01-01

    AIM—To examine the contribution of infiltrating cells in the local production of cytokines within the vitreous of patients with proliferative vitreoretinopathy (PVR).
METHODS—The presence of mRNA coding for IL-6, IL-8, IL-1β, IL-1α, TNFα, IFNγ, IL-12, and HPRT was investigated in 25 vitreous samples from patients with PVR, 11 vitreous samples from patients with retinal detachment (RD) not complicated by PVR, and 10 vitreous samples from patients with macular hole (MH). A quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using an internal competitor was used to investigate these samples. From these samples, 15 PVR, 8 RD, and 8 MH were analysed for the protein levels of the same cytokines using enzyme linked immunosorbent assay (ELISA). Spearman correlation was used to test any association between mRNA and cytokine protein levels, as an indicator of the contribution these cells make to the intravitreal cytokine milieu.
RESULTS—A strong correlation was found between mRNA and their respective cytokine levels (protein products) for IL-6, IL-8, IL-1β, IL-1α, TNFα, IFNγ (Spearman r = 0.83, 0.73, 0.67, 0.91, 0.73, and 0.73 respectively), but not for IL-12. The median levels of IL-6, IL-8, IL-1β, and IFNγ mRNA and their respective cytokines were significantly higher (p <0.05) in patients with PVR than in those with macular hole. There was no statistically significant difference in the median levels of IL-1α mRNA between PVR and MH but the cytokine IL-1α was detected at a significantly higher level in PVR compared with MH patients. Between PVR and RD patients, there was no statistically significant difference in mRNA levels for all the investigated cytokines (p >0.05) except for IL-6 where there was a statistical significance (p= 0.038). In contrast, the median levels of IL-6, IL-8, and IL-1β cytokines were significantly higher (p <0.05) in patients with PVR than in those with RD, whereas for IL-1α and IFNγ no

  11. REDUCTION OF AMYLOID-BETA LEVELS IN MOUSE EYE TISSUES BY INTRA-VITREALLY DELIVERED NEPRILYSIN

    PubMed Central

    Parthasarathy, Rajni; Chow, K. Martin; Derafshi, Zahra; Fautsch, Michael P.; Hetling, John R.; Rodgers, David W.; Hersh, Louis B.; Pepperberg, David R.

    2015-01-01

    Amyloid-beta (Aβ) is a group of aggregation-prone, 38- to 43-amino acid peptides generated in the eye and other organs. Numerous studies suggest that the excessive build-up of low-molecular-weight soluble oligomers of Aβ plays a role in the progression of Alzheimer’s disease and other brain degenerative diseases. Recent studies raise the hypothesis that excessive Aβ levels may contribute also to certain retinal degenerative diseases. These findings, together with evidence that a major portion of Aβ is released as monomer into the extracellular space, raise the possibility that a technology enabling the enzymatic break-down of monomeric Aβ in the living eye under physiological conditions could prove useful for research on ocular Aβ physiology and, perhaps ultimately, for therapeutic applications. Neprilysin (NEP), an endopeptidase known to cleave Aβ monomer into inactive products, is a membrane-associated protein. However, sNEP, a recombinant form of the NEP catalytic domain, is soluble in aqueous medium. With the aim of determining the Aβ-cleaving activity of exogenous sNEP in the microenvironment of the intact eye, we analyzed the effect of intra-vitreally delivered sNEP on ocular Aβ levels in mice that exhibit readily measurable, aqueous buffer-extractable Aβ40 and Aβ42, two principal forms of Aβ. Anesthetized 10-month wild-type (C57BL/6J) and 2–3-month 5XFAD transgenic mice received intra-vitreal injections of sNEP (0.004 – 10 μg) in one eye and were sacrificed at defined post-treatment times (30 min – 12 weeks). Eye tissues (combined lens, vitreous, retina, RPE and choroid) were homogenized in phosphate-buffered saline, and analyzed for Aβ40 and Aβ42 (ELISA) and for total protein (Bradford assay). The fellow, untreated eye of each mouse served as control, and concentrations of Aβ (pmol/g protein) in the treated eye were normalized to that of the untreated control eye. In C57BL/6J mice, as measured at 2 hr after sNEP treatment, increasing

  12. Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

    PubMed Central

    Zhao, Chun; Zhang, Zhen; Chen, Lei; Wang, Fang; Xu, Ding

    2016-01-01

    Background We sought to observe the effectiveness of intravitreal injection of ranibizumab in treating neovascular age-related macular degeneration (nAMD) with serous pigment epithelial detachment (sPED). Material/Methods A retrospective, noncomparative case series was performed. Twenty-3 eyes of 23 patients with sPED secondary to nAMD who had received intravitreal injections of ranibizumab were included in this study. All patients underwent best-corrected visual acuity (BCVA), synchronous fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) examinations. All patients were treated with pro re nata intravitreal injections after 3 loading doses of ranibizumab and were followed up for 12 months. The differences in the BCVAs, maximum PED heights, PED volumes and CFTs of the affected eyes were compared between the baseline and last visit. Results Twelve months after the first injection, improved visual acuity was observed in 16 of the 23 eyes. 4 eyes exhibited stable visual acuity, and 3 eyes exhibited impaired visual acuity. The mean post-injection logMAR BCVA was 0.58±0.05, which was much better than that at baseline (0.76±0.08; t=1.751, P=0.0869). The mean maximum PED height at baseline was 350.17±35.73μm and it was decreased to 238.87±36.87μm (t=2.192, P=0.0337) at the last visit. The mean PED volume after injection was 0.34±0.1 mm3, which was significantly decreased compared with that at baseline (0.81±0.21 mm3; t=2.021, P=0.0494).The mean CFT decreased, but this difference was not statistically significant (t=1.003, P=0.3211). None of the patients exhibited endophthalmitis, uveitis or RPE tears. Conclusions Intravitreal injection of ranibizumab for the treatment of neovascular age-related macular degeneration with serous pigment epithelial detachment safely and effectively improved the patients’ visual acuities and decreased their PED heights volumes. PMID:26972376

  13. Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: Host-microbe interactions in intraocular infection

    PubMed Central

    Sadaka, Ama; Durand, Marlene L; Gilmore, Michael S

    2012-01-01

    Bacterial endophthalmitis is a sight threatening infection of the interior structures of the eye. Incidence in the US has increased in recent years, which appears to be related to procedures being performed on an aging population. The advent of outpatient intravitreal therapy for management of age-related macular degeneration raises yet additional risks. Compounding the problem is the continuing progression of antibiotic resistance. Visual prognosis for endophthalmitis depends on the virulence of the causative organism, the severity of intraocular inflammation, and the timeliness of effective therapy. We review the current understanding of the pathogenesis of bacterial endophthalmitis, highlighting opportunities for the development of improved therapeutics and preventive strategies. PMID:22521570

  14. Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents.

    PubMed

    Gemenetzi, M; Lotery, A J; Patel, P J

    2017-01-01

    Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet age-related macular degeneration (AMD). However, there are emerging signals that anti-VEGF treatment can potentially increase development of geographic atrophy (GA). Histopathologic, animal, and clinical studies support this hypothesis although direct proof of a relationship between GA and use of anti-VEGF agents in neovascular AMD is not yet established. This review presents current evidence supporting an association between anti-VEGF therapy and progression of geographic atrophy. The need of exploring alternative methods of treating AMD is indirectly but clearly emphasized.

  15. Involution patterns of retinopathy of prematurity after treatment with intravitreal bevacizumab: implications for follow-up

    PubMed Central

    Isaac, M; Tehrani, N; Mireskandari, K

    2016-01-01

    Purpose To describe involution patterns following monotherapy with intravitreal bevacizumab injection (IVB) for type 1 retinopathy of prematurity (ROP) in zone I or zone II posterior. Methods A retrospective chart review of infants treated with IVB from January 2010–April 2014. Infants with minimum of 82 weeks postmenstrual age at last follow-up were included. Primary outcome was timing of involution of type 1 ROP for the first 12 weeks post treatment. Secondary outcomes were development of any recurrence and structural outcome at last follow-up. Retinal examination records, fundus, and flourescein angiography images were reviewed. Results Twenty-eight eyes were included. Average follow-up post treatment was 33.9±9.7 months (range 21.4–61.9). Cumulative frequency of regression of plus disease was seen in 73.3, 86.7, and 100% of eyes by days 3, 5, and 8, respectively. Regression of both stage 3 and plus disease was observed in 29, 82, 88, and 100% by weeks 1, 2, 3, and 4, respectively. Within the first 3 months, 17/28 eyes developed recurrence to stage 1 or 2 after regression. None developed recurrence of plus disease. By the end of 3 months 18% of eyes vascularized into zone III. At a mean of 24±17.3 months, 39% of eyes were not vascularized into zone III as seen on flourescein angiography with scleral indentation. Conclusion Our experience suggests regression of plus disease and stage 3 are expected within the first 4 weeks after bevacizumab treatment. Recurrence may occur despite initial regression and requires careful follow-up. PMID:26869159

  16. Practice patterns of ophthalmologists administering intravitreal injections in Europe: a longitudinal survey

    PubMed Central

    Huang, Kui; Sultan, Marla B; Zhou, Duo; Tressler, Charles S; Mo, Jingping

    2016-01-01

    Purpose This study was performed to understand the practice patterns of ophthalmologists administering intravitreal (IVT) injections in Europe after the procedure became routine. Methods As part of a prospective, multinational, non-interventional cohort study in 13 countries in Europe between 2006 and 2012, ophthalmologists completed the Baseline Questionnaire and the Follow-up Questionnaire 1 year after baseline. Results and discussion Of the 125 ophthalmologists who participated in the study, 113 (90.4%) completed the Baseline Questionnaire. Most of these ophthalmologists were medical retina specialists (43.0%). The median number of IVT injections that the ophthalmologists performed per month during the year prior to completing the Baseline Questionnaire was 20.0. The majority of the ophthalmologists had performed their last IVT injection prior to completing the questionnaire in an operating room or theater (68.4%). When performing IVT injections, a majority of the ophthalmologists reported applying povidone–iodine (90.4%) before IVT injections and topical antibiotics right after IVT injections (89.5%). In addition, 81.6% of the ophthalmologists reported using a sterile adhesive eye drape and 80.7% reported using an eyelid speculum. In all, 95 ophthalmologists (76%) completed the Follow-up Questionnaire. The median number of IVT injections performed per month during the year prior to completing the Follow-up Questionnaire by these ophthalmologists was increased to 35. The results of the Follow-up Questionnaire on administering IVT injections were similar to those of the Baseline Questionnaire. A majority of the ophthalmologists reported applying povidone–iodine (87.4%) before IVT injections, topical antibiotics right after IVT injections (89.5%), and an eyelid speculum (85.3%). Conclusion The results of this study indicated a good adherence to all aspects of the guidelines on IVT injections. It seemed that ophthalmologists were more experienced in IVT

  17. A sustained intravitreal drug delivery system with remote real time monitoring capability

    PubMed Central

    Hou, Huiyuan; Nieto, Alejandra; Belghith, Akram; Nan, Kaihui; Li, Yangyang; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun

    2015-01-01

    Many chorioretinal diseases are chronic and need sustained drug delivery systems to keep therapeutic drug level at the disease site. Many intravitreal drug delivery systems under developing do not have mechanism incorporated for a non-invasive monitoring of drug release. Current study prepared rugate porous silicon (pSi) particles by electrochemical etching with the currents frequency (K value) of 2.17 and 2.45. Two model drugs (Rapmycin and Dexamethasone) and two drug-loading strategies were tested for the feasibility to monitor drug release from the pSi particles through a color fundus camera. The pSi particles (k=2.45) with infiltration loading of rapamycin demonstrated progressively more violet color reflection which was negatively associated with the rapamycin released into the vitreous (r=−0.4, p<0.001, pairwise). In contrast, pSi with K value of 2.17 demonstrated progressive color change towards green and a weak association between rapmycin released into vitreous and green color abundance was identified (r=−0.23, p=0.002, pairwise). Dexamethasone was covalently loaded on to the fully oxidized pSi particles that appeared in vitreous as yellow color and fading over time. The yellow color decrease over time was strongly associated with the dexamethasone detected from the vitreous samples (r=0.7, p<0.0001, pairwise). These results suggest that engineered porous silicon particles may be used as a self-reporting drug delivery system for a non-invasive real time remote monitoring. PMID:26087110

  18. Aqueous cytokine levels are associated with reduced macular thickness after intravitreal ranibizumab for diabetic macular edema

    PubMed Central

    Kato, Satoshi; Araki, Fumiyuki; Ueta, Takashi; Miyaji, Tempei; Yamaguchi, Takuhiro

    2017-01-01

    Purpose It is controversial whether the administration of anti-vascular endothelial growth factor drugs for diabetic macular edema (DME) affects intraocular inflammatory cytokines. In this study, we measured cytokine concentration in aqueous humor before and after intravitreal injection of ranibizumab (IVR). The aim was to determine changes in cytokine concentration and their effects on DME reduction. Methods Twelve patients (13 eyes) with DME received two IVR (0.5 mg) with a 1 month interval, and a total of 26 aqueous humor samples were obtained. Macular thickness was measured with an optical coherence tomography (OCT) using thickness-map mode with an Early Treatment Diabetic Retinopathy Study (ETDRS) 9-zone grid that was divided into two zones: a central circle with a diameter of 1 mm (zone1); and an outer circle with a diameter of 6 mm (zone2). Results The concentration of eotaxin-1 in aqueous humor samples decreased significantly after IVR. Baseline cytokine concentration was associated with IVR-induced DME reduction. In zone1, higher baseline concentration of interferon-induced protein (IP)-10, and in zone 2, higher baseline concentration of granulocyte-macrophage colony-stimulating factor, IP-10, and tumor necrosis factor (TNF) α; and lower baseline concentration of eotaxin-1, interleukin (IL)-5, and IL-8 were associated with improved DME. Cytokine changes were associated with IVR-induced DME reduction. In zone1, lower concentration of IP-10 compared to baseline or higher concentration of macrophage inflammatory protein (MIP) -α, and in zone 2, lower concentration of IL-5 compared to baseline, IL-8, and IP-10 or higher concentration of eotaxin-1 and MIP-1β were associated with improved DME. Conclusions These findings suggest that ranibizumab affects the concentration of cytokines in aqueous humor. Various cytokines contribute to a decrease in retinal thickness, both in the center of the macula and in a larger area of the retina. PMID:28346545

  19. The Efficacy of Intravitreal Bevacizumab in Vitreous Hemorrhage of Diabetic Subjects

    PubMed Central

    Alagöz, Cengiz; Yıldırım, Yusuf; Kocamaz, Murat; Baz, Ökkeş; Çiçek, Uğur; Çelik, Burcu; Demirkale, Halil İbrahim; Yazıcı, Ahmet Taylan; Taşkapılı, Muhittin

    2016-01-01

    Objectives: To evaluate the efficacy of intravitreal bevacizumab (IVB) in the resolution of vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR). Materials and Methods: Seventy eyes of 70 patients (43 male, mean age 55.6±12.2 years) diagnosed with VH secondary to PDR were evaluated retrospectively. Demographic characteristics of the patients, baseline and final clinical results, and the interventions the patients were subject to were recorded. The patients who received IVB injections (group 1, n=29) were compared to those who did not receive injections (group 2, n=41) in terms of VH clearance time and surgery rates. Results: The mean follow-up time was 14.5±6.1 months in group 1 and 18.4±9.6 months in group 2 (p=0.185). The mean visual acuity was similar between the groups at baseline and at the last visit (for all p>0.05). Panretinal photocoagulation could be applied in 86% of subjects in group 1 and in 58% in group 2 2 within the first month (p=0.016). VH clearance time was not different between the groups (2.3±2.1 months in group 1 and 3.4±2.6 months in group 2, p=0.146). The number of subjects requiring surgery was 7 (24%) in group 1 and 20 (48.8%) in group 2 (p=0.048). Conclusion: IVB was found effective in cases with VH secondary to PDR in terms of reducing the need for surgery and increasing the rate of subjects to whom panretinal photocoagulation could be applied in the early period, although there was no impact on final visual acuity. PMID:28058164

  20. A new solution-based intranasal triamcinolone acetonide formulation in patients with perennial allergic rhinitis: how does the pharmacokinetic/pharmacodynamic profile for cortisol suppression compare with an aqueous suspension-based formulation?

    PubMed

    Hochhaus, Günther; González, Mario A; Dockhorn, Robert J; Shilstone, Jonathan; Karafilidis, John

    2002-06-01

    The present study was undertaken to describe the pharmacokinetics of a new solution-based intranasal triamcinolone acetonideformulation (Tri-Nasal) in patients with perennial allergic rhinitis and to use a pharmacokinetic/pharmacodynamic (PK/PD) simulation approach to compare the potential effects on plasma cortisol with that of an aqueous suspension-based nasal triamcinolone acetonide formulation (Nasacort AQ). Data from an open-label, randomized, three-way crossover study in patients with perennial allergic rhinitis receiving three doses (100, 200, and 400 microg) of a nasal solution-based triamcinolone acetonide formulation (Tri-Nasal) over 7 days were used to describe the pharmacokinetics of this formulation. Available literature data for a suspension-based aqueous triamcinolone acetonide formulation (Nasacort AQ) were used to describe its pharmacokinetic profile after similar single doses of 110, 220, and 440 microg. A PK/PD simulation approach was used to predict the anticipated cumulative cortisol suppression (CCS) of these two formulations. These simulations suggested a cortisol suppression of 8% to 16% for the single and steady-state doses of the solution-based product. Similar CCS estimates were predicted for equivalent doses of the aqueous suspension-based triamcinolone acetonide formulation with no difference between both formulations. Post hoc power analysis suggested that the predicted cortisol suppression is not likely to be significant for either preparation, including the clinically recommended doses of 200 and 220 microg of the solution-based and suspension-based formulations, respectively. In summary, based on the results of this PK/PD simulation, the plasma levels observed afternasal administration of the solution or the aqueous suspension are unlikely to induce a clinically relevant cortisol suppression, especially for the recommended dosing regimens of 200 and 220 microg/day.

  1. [Cochlear implant in adults].

    PubMed

    Bouccara, D; Mosnier, I; Bernardeschi, D; Ferrary, E; Sterkers, O

    2012-03-01

    Cochlear implant in adults is a procedure, dedicated to rehabilitate severe to profound hearing loss. Because of technological progresses and their applications for signal strategies, new devices can improve hearing, even in noise conditions. Binaural stimulation, cochlear implant and hearing aid or bilateral cochlear implants are the best opportunities to access to better level of comprehension in all conditions and space localisation. By now minimally invasive surgery is possible to preserve residual hearing and use a double stimulation modality for the same ear: electrical for high frequencies and acoustic for low frequencies. In several conditions, cochlear implant is not possible due to cochlear nerve tumour or major malformations of the inner ear. In these cases, a brainstem implantation can be considered. Clinical data demonstrate that improvement in daily communication, for both cochlear and brainstem implants, is correlated with cerebral activation of auditory cortex.

  2. Intravitreal Injection of Bevacizumab in Primary Vitrectomy to Decrease the Rate of Retinal Redetachment: A Randomized Pilot Study

    PubMed Central

    Tousi, Adib; Hasanpour, Hossein; Soheilian, Masoud

    2016-01-01

    Purpose: To evaluate the effect of intravitreal bevacizumab (IVB) as a surgical adjunct in prevention of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. Methods: In this controlled, randomized pilot study, 27 patients with primary retinal detachment undergoing pars plana deep vitrectomy were included. Of these, 12 received IVB at the end of procedure. The anatomic success and best corrected visual acuity (BCVA) were compared to the control group at months 3 and 6 postoperatively. Results: At three month follow-up, 3 of 11 eyes (27.3%) had detached retinas in the IVB group versus 6 of 12 (50.0%) in the control group (P = 0.40). At six-month follow-up, 3 of 10 eyes (30%) had detached retinas in the IVB group versus 3 in 8 (37.5%) in the control group (P > 0.99). Mean logMAR BCVA improved significantly in both groups relative to baseline, but did not show a significant difference at three-and six-month follow-ups between the two groups. Conclusion: Our preliminary results show neither a benefit nor any harm from intervention in both anatomic and visual outcomes. Our results support conducting additional studies to evaluate the effect of intravitreal bevacizumab on postoperative PVR. PMID:27621784

  3. Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys.

    PubMed

    Takahashi, Kazuhisa; Igarashi, Tsutomu; Miyake, Koichi; Kobayashi, Maika; Yaguchi, Chiemi; Iijima, Osamu; Yamazaki, Yoshiyuki; Katakai, Yuko; Miyake, Noriko; Kameya, Shuhei; Shimada, Takashi; Takahashi, Hiroshi; Okada, Takashi

    2017-01-04

    The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 μL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.

  4. Management of Acute Submacular Hemorrhage with Intravitreal Injection of Tenecteplase, Anti-vascular Endothelial Growth Factor and Gas

    PubMed Central

    Lee, Jung Pil; Park, Jun Sang; Kwon, Oh Woong; You, Yong Sung

    2016-01-01

    Purpose To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas. Methods This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed. Results The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied. Conclusions A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration. PMID:27247518

  5. Intravitreal AAV2.COMP-Ang1 Prevents Neurovascular Degeneration in a Murine Model of Diabetic Retinopathy

    PubMed Central

    Cahoon, Judd M.; Rai, Ruju R.; Carroll, Lara S.; Uehara, Hironori; Zhang, Xiaohui; Medina, Reinhold J.; Das, Subtrata K.; Muddana, Santosh K.; Olson, Paul R.; Nielson, Spencer; Walker, Kortnie; Flood, Maggie M.; Messenger, Wyatt B.; Archer, Bonnie J.; Barabas, Peter; Krizaj, David; Gibson, Christopher C.; Li, Dean Y.; Koh, Gou Y.; Gao, Guangping; Stitt, Alan W.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in the U.S. The vision-threatening processes of neuroglial and vascular dysfunction in DR occur in concert, driven by hyperglycemia and propelled by a pathway of inflammation, ischemia, vasodegeneration, and breakdown of the blood retinal barrier. Currently, no therapies exist for normalizing the vasculature in DR. Here, we show that a single intravitreal dose of adeno-associated virus serotype 2 encoding a more stable, soluble, and potent form of angiopoietin 1 (AAV2.COMP-Ang1) can ameliorate the structural and functional hallmarks of DR in Ins2Akita mice, with sustained effects observed through six months. In early DR, AAV2.COMP-Ang1 restored leukocyte-endothelial interaction, retinal oxygenation, vascular density, vascular marker expression, vessel permeability, retinal thickness, inner retinal cellularity, and retinal neurophysiological response to levels comparable with nondiabetic controls. In late DR, AAV2.COMP-Ang1 enhanced the therapeutic benefit of intravitreally delivered endothelial colony-forming cells by promoting their integration into the vasculature and thereby stemming further visual decline. AAV2.COMP-Ang1 single-dose gene therapy can prevent neurovascular pathology, support vascular regeneration, and stabilize vision in DR. PMID:26340930

  6. A cluster of presumed, noninfectious endophthalmitis after intravitreal injection of bevacizumab: long-term follow-up

    PubMed Central

    Ricci, Federico; Calabrese, Antonio; De Felici, Cecilia; Missiroli, Filippo; Pileri, Marco; Regine, Federico

    2016-01-01

    Purpose To report the outcome of 5 consecutive cases of presumed, noninfectious endopththalmitis following intravitreal injection of bevacizumab (IVB). Methods Ten pre-loaded syringes of bevacizumab (1.25 mg/50 µL) furnished by a compounding pharmacy were injected intravitreally. Treatments were performed in the operating room by the same surgeon on 2 consecutive days. Results Of 10 eyes, 5 showed moderate to severe ocular inflammation within a few days of injection. All patients were treated in the same surgical session. Vitreous tap performed in the patient presenting with the most severe grade of inflammation was negative for bacteria and fungi. At the time of the vitreous biopsy, this patient was injected with vancomycin 1 mg/100 µL in the vitreous cavity. Other eyes with moderate inflammation received topical and systemic antibiotics and topical steroid treatment. Visual acuity returned to pre-endophthalmitis or better levels in all eyes within 1 month. The other 5 patients treated with IVB from the same batch in the other surgical session did not develop inflammation. Conclusions IVB can induce noninfectious endophthalmitis. The use of compounded syringes can explain clustering of the inflammation. We were unable to identify the reasons for the variable grade of inflammation we observed in our patients. PMID:27582674

  7. Implant treatment planning considerations.

    PubMed

    Kao, Richard T

    2008-04-01

    As dental implants become a more accepted treatment modality, there is a need for all parties involved with implant dentistry to be familiar with various treatment planning issues. Though the success can be highly rewarding, failure to forecast treatment planning issues can result in an increase of surgical needs, surgical cost, and even case failure. In this issue, the focus is on implant treatment planning considerations.

  8. Osseointegrated implant prosthodontics.

    PubMed

    Rogoff, G S

    1992-06-01

    This review covers recent literature on prosthodontic aspects of osseointegrated implants. Long-term prognosis, diagnosis and treatment planning, and clinical impression techniques and fabrication technology are discussed.

  9. Dexamethasone implant in diabetic macular edema in real-life situations

    PubMed Central

    Chhablani, J; Bansal, P; Veritti, D; Sambhana, S; Sarao, V; Pichi, F; Carrai, P; Massaro, D; Lembo, A; Mansour, A M; Banker, A; Gupta, S R; Hamam, R; Lanzetta, P

    2016-01-01

    Purpose To report outcome of eyes with recalcitrant and naive eyes with diabetic macular edema (DME) treated with intravitreal dexamethasone implants (Ozurdex) injection. Methods Retrospective multicenter data analysis of eyes with DME treated with Ozurdex implant and with minimum follow-up of at least one year after the first implant. Data collected included demographic details, history of presenting illness, past treatment history, clinical examination details including visual acuity at presentation, and follow-up with imaging and treatment details. Paired sample t-test was used to measure mean differences between pre- and post-implant values obtained at baseline and last follow-up. Results A total of 79 eyes (62 subjects) were included. Sixty-four eyes had been previously treated; 15 eyes were naive. Among the previously treated eyes, mean interval between first Ozurdex injection and any previous treatment was 7.69±8.2 months. In naive eyes, the visual acuity improved from baseline 0.58±0.25 to 0.44±0.33 logMAR at last follow-up (P=0.05). In eyes that had been previously treated, the improvement was from 0.65±0.34 at baseline to 0.48±0.35 logMAR (P=0.01). Mean treatment-free interval was 6.5±4.5 months. Nine eyes were steroid responder with controlled intraocular pressure (IOP), none showed any spike in IOP during the follow-up period. Conclusions Ozurdex implant could be a good alternative for recalcitrant as well as naive eyes with DME. The visual gain after initial implant injection was fairly maintained, with additional treatment usually after 6 months in naive eyes. Ozurdex appeared safe even in steroid responders with good control of IOP with antiglaucoma medications. PMID:26611849

  10. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

    PubMed

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-11-13

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate.

  11. Vitrectomy Before Intravitreal Injection of AAV2/2 Vector Promotes Efficient Transduction of Retinal Ganglion Cells in Dogs and Nonhuman Primates.

    PubMed

    Tshilenge, Kizito-Tshitoko; Ameline, Baptiste; Weber, Michel; Mendes-Madeira, Alexandra; Nedellec, Steven; Biget, Marine; Provost, Nathalie; Libeau, Lyse; Blouin, Véronique; Deschamps, Jack-Yves; Le Meur, Guylène; Colle, Marie-Anne; Moullier, Philippe; Pichard, Virginie; Rolling, Fabienne

    2016-06-01

    Recombinant adeno-associated virus (AAV) has emerged as a promising vector for retinal gene delivery to restore visual function in certain forms of inherited retinal dystrophies. Several studies in rodent models have shown that intravitreal injection of the AAV2/2 vector is the optimal route for efficient retinal ganglion cell (RGC) transduction. However, translation of these findings to larger species, including humans, is complicated by anatomical differences in the eye, a key difference being the comparatively smaller volume of the vitreous chamber in rodents. Here, we address the role of the vitreous body as a potential barrier to AAV2/2 diffusion and transduction in the RGCs of dogs and macaques, two of the most relevant preclinical models. We intravitreally administered the AAV2/2 vector carrying the CMV-eGFP reporter cassette in dog and macaque eyes, either directly into the vitreous chamber or after complete vitrectomy, a surgical procedure that removes the vitreous body. Our findings suggest that the vitreous body appears to trap the injected vector, thus impairing the diffusion and transduction of AAV2/2 to inner retinal neurons. We show that vitrectomy before intravitreal vector injection is an effective means of overcoming this physical barrier, improving the transduction of RGCs in dog and macaque retinas. These findings support the use of vitrectomy in clinical trials of intravitreal gene transfer techniques targeting inner retinal neurons.

  12. Durable recovery of the macular architecture and functionality of a diagnosed age-related macular degeneration 1 year after a single intravitreal injection of dobesilate

    PubMed Central

    Cuevas, P; Outeiriño, L A; Azanza, C; Giménez-Gallego, G

    2013-01-01

    Among the age-related diseases that affect vision, age-related macular degeneration is the most frequent cause of blindness in patients older than 60 years. In this communication, we report the full anatomical and functional recovery of a patient diagnosed with wet age-related macular degeneration 1 year after a single intravitreal injection of dobesilate. PMID:24225910

  13. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells

    PubMed Central

    Kokubu, T.; Mifune, Y.; Inui, A.; Sakata, R.; Harada, Y.; Takase, F.; Kurosaka, M.

    2016-01-01

    Objectives Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Methods Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. Results Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. Conclusions The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury. Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint

  14. Gene therapy following subretinal AAV5 vector delivery is not affected by a previous intravitreal AAV5 vector administration in the partner eye

    PubMed Central

    Li, Wensheng; Kong, Fansheng; Li, Xia; Dai, Xufeng; Liu, Xiaoqiang; Zheng, Qinxiang; Wu, Ronghan; Zhou, Xiangtian; Lü, Fan; Chang, Bo; Li, Qiuhong; Hauswirth, William W.; Pang, Ji-jing

    2009-01-01

    Purpose In an earlier study we found normal adeno-associated viral vector type 2 (AAV2)-mediated GFP expression after intravitreal injection to one eye of normal C57BL/6J mice. However, GFP expression was very poor in the partner eye of the same mouse if this eye received an intravitreal injection of the same vector one month after the initial intravitreal injection. We also found both injections worked well if they were subretinal. In this study, we tested whether the efficiency of subretinal AAV vector transduction is altered by a previous intravitreal injection in the partner eye and more importantly whether therapeutic efficiency is altered in the rd12 mouse (with a recessive RPE65 mutation) after the same injection series. Methods One μl of scAAV5-smCBA-GFP (1x1013 genome containing viral particles per ml) was intravitreally injected into the right eyes of four-week-old C57BL/6J mice and 1 μl of scAAV5-smCBA-hRPE65 (1x1013 genome containing viral particles per ml) was intravitreally injected into the right eyes of four-week-old rd12 mice Four weeks later, the same vectors were subretinally injected into the left eyes of the same C57BL/6J and rd12 mice. Left eyes of another cohort of eight-week-old rd12 mice received a single subretinal injection of the same scAAV5-smCBA-hRPE65 vector as the positive control. Dark-adapted electroretinograms (ERGs) were recorded five months after the subretinal injections. AAV-mediated GFP expression in C57BL/6J mice and RPE65 expression and ERG restoration in rd12 mice were evaluated five months after the second subretinal injection. Frozen section analysis was performed for GFP fluorescence in C57BL/6J mice and immunostaining for RPE65 in rd12 eyes. Results In rd12 mice, dark-adapted ERGs were minimal following the first intravitreal injection of scAAV5-smCBA-RPE65. Following subsequent subretinal injection in the partner eye, dramatic ERG restoration was recorded in that eye. In fact, ERG b-wave amplitudes were

  15. Teeth and implants.

    PubMed

    Palmer, R

    1999-08-28

    An osseointegrated implant restoration may closely resemble a natural tooth. However, the absence of a periodontal ligament and connective tissue attachment via cementum, results in fundamental differences in the adaptation of the implant to occlusal forces, and the structure of the gingival cuff.

  16. A no bleed implant.

    PubMed

    Ersek, R A; Navarro, J A; Nemeth, D Z; Sas, G

    1993-01-01

    Breast implants have evolved from the original saline-filled, smooth-surfaced silicone rubber bag to silicone gel-filled smooth-walled sacs to a combination of a silicone gel-filled bag within a saline-filled sac, and, most recently, a reversed, double-lumen implant with a saline bag inside of a gel-filled bag. Texture-surfaced implants were first used in 1970 when the standard silicone gel-filled implant was covered with a polyurethane foam. Because of concerns about the degradation products of this foam, they were removed from the market in 1991. In 1975 double-lumen silicone textured implants were developed, followed by silicone gel-filled textured implants. In 1990 a new radiolucent, biocompatible gel was produced that reduced the problem of radioopacity of silicone implants. Because of the gel's sufficiently low coefficient of friction, leakage caused by fold flaw fracture may also be decreased. We present a case where this new biocompatible gel implant was repositioned after four months. The resulting scar capsule in this soft breast was thin [< 0.002 cm (0.008 in.)] and evenly textured as a mirror image of the textured silicone surface. Scanning electron microscopy and x-ray defraction spectrophotometry revealed no silicone bleed.

  17. Smoking and dental implants

    PubMed Central

    Kasat, V.; Ladda, R.

    2012-01-01

    Smoking is a prevalent behaviour in the population. The aim of this review is to bring to light the effects of smoking on dental implants. These facts will assist dental professionals when implants are planned in tobacco users. A search of “PubMed” was made with the key words “dental implant,” “nicotine,” “smoking,” “tobacco,” and “osseointegration.” Also, publications on tobacco control by the Government of India were considered. For review, only those articles published from 1988 onward in English language were selected. Smoking has its influence on general as well as oral health of an individual. Tobacco negatively affects the outcome of almost all therapeutic procedures performed in the oral cavity. The failure rate of implant osseointegration is considerably higher among smokers, and maintenance of oral hygiene around the implants and the risk of peri-implantitis are adversely affected by smoking. To increase implant survival in smokers, various protocols have been recommended. Although osseointegrated dental implants have become the state of the art for tooth replacement, they are not without limitations or complications. In this litigious era, it is extremely important that the practitioner clearly understands and is able and willing to convey the spectrum of possible complications and their frequency to the patients. PMID:24478965

  18. Batteryless implanted echosonometer

    NASA Technical Reports Server (NTRS)

    Kojima, G. K.

    1977-01-01

    Miniature ultrasonic echosonometer implanted within laboratory animals obtains energy from RF power oscillator that is electronically transduced via induction loop to power receiving loop located just under animal's skin. Method of powering device offers significant advantages over those in which battery is part of implanted package.

  19. Implantable CMOS Biomedical Devices

    PubMed Central

    Ohta, Jun; Tokuda, Takashi; Sasagawa, Kiyotaka; Noda, Toshihiko

    2009-01-01

    The results of recent research on our implantable CMOS biomedical devices are reviewed. Topics include retinal prosthesis devices and deep-brain implantation devices for small animals. Fundamental device structures and characteristics as well as in vivo experiments are presented. PMID:22291554

  20. Implantable, Ingestible Electronic Thermometer

    NASA Technical Reports Server (NTRS)

    Kleinberg, Leonard

    1987-01-01

    Small quartz-crystal-controlled oscillator swallowed or surgically implanted provides continuous monitoring of patient's internal temperature. Receiver placed near patient measures oscillator frequency, and temperature inferred from previously determined variation of frequency with temperature. Frequency of crystal-controlled oscillator varies with temperature. Circuit made very small and implanted or ingested to measure internal body temperature.

  1. Percutaneous and skeletal biocarbon implants

    NASA Technical Reports Server (NTRS)

    Mooney, V.

    1977-01-01

    Review of carbon implants developed by NASA discussed four different types of implants and subsequent improvements. Improvements could be of specific interest to rehabilitation centers and similar organizations.

  2. Graphene for Biomedical Implants

    NASA Astrophysics Data System (ADS)

    Moore, Thomas; Podila, Ramakrishna; Alexis, Frank; Rao, Apparao; Clemson Bioengineering Team; Clemson Physics Team

    2013-03-01

    In this study, we used graphene, a one-atom thick sheet of carbon atoms, to modify the surfaces of existing implant materials to enhance both bio- and hemo-compatibility. This novel effort meets all functional criteria for a biomedical implant coating as it is chemically inert, atomically smooth and highly durable, with the potential for greatly enhancing the effectiveness of such implants. Specifically, graphene coatings on nitinol, a widely used implant and stent material, showed that graphene coated nitinol (Gr-NiTi) supports excellent smooth muscle and endothelial cell growth leading to better cell proliferation. We further determined that the serum albumin adsorption on Gr-NiTi is greater than that of fibrinogen, an important and well understood criterion for promoting a lower thrombosis rate. These hemo-and biocompatible properties and associated charge transfer mechanisms, along with high strength, chemical inertness and durability give graphene an edge over most antithrombogenic coatings for biomedical implants and devices.

  3. Derivatization Strategies for the Detection of Triamcinolone Acetonide in Cartilage by Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

    PubMed

    Barré, Florian P Y; Flinders, Bryn; Garcia, João P; Jansen, Imke; Huizing, Lennart R S; Porta, Tiffany; Creemers, Laura B; Heeren, Ron M A; Cillero-Pastor, Berta

    2016-12-20

    Osteoarthritis (OA), characterized by degeneration of the cartilaginous tissue in articular joints, severely impairs mobility in many people worldwide. The degeneration is thought to be mediated by inflammatory processes occurring in the tissue of the joint, including the cartilage. Intra-articular administered triamcinolone acetonide (TAA) is one of the drug treatments employed to ameliorate the inflammation and pain that characterizes OA. However, the penetration and distribution of TAA into the avascular cartilage is not well understood. We employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which has been previously used to directly monitor the distribution of drugs in biological tissues, to evaluate the distribution of TAA in human cartilage after in vitro incubation. Unfortunately, TAA is not easily ionized by regular electrospray ionization (ESI) or MALDI. To overcome this problem, we developed an on-tissue derivatization method with Girard's reagent T (GirT) in human incubated cartilage being able to study its distribution and quantify the drug abundance (up to 3.3 ng/μL). Our results demonstrate the depth of penetration of a corticosteroid drug in human OA cartilage using MALDI-MSI.

  4. Detection and quantitation of fatty acid acyl conjugates of triamcinolone acetonide via gas chromatography-electron-capture negative-ion mass spectrometry.

    PubMed

    Hubbard, Walter C; Blum, Andrew E; Bickel, Carol A; Heller, Nicola M; Schleimer, Robert P

    2003-11-15

    The inherent electron-capture properties of triamcinolone acetonide (TAA) fatty acid conjugates were exploited for development of a GC-MS technique for quantitation of C21 long-chain fatty esters of TAA synthesized in BEAS-2B cells, an immortalized airway epithelium cell line. TAA esters extracted from BEAS-2B cells were purified and detected via selected ion monitoring of the molecular anions generated from the TAA esters under electron-capture negative-ion mass spectrometric conditions. Standard curves were linear over a range of 0.0 to >4.5 ng/mg protein with r(2) values = 1. Levels of TAA conjugates extracted from BEAS-2B treated with 10(-5)M TAA for 24h ranged from 0.024 to 0.301 ng/mg protein. Further evidence for confirmation of the identity of TAA fatty esters formed in BEAS-2B cells was obtained via selected reaction monitoring. The transition monitored was formation of the carboxy anion generated from each of the respective molecular anions of the TAA esters during collision-induced decomposition. These findings indicate that the GC-MS analysis is suitable for studies of the kinetics of the TAA fatty acid conjugates formation in vitro and may be directly applicable to determination of the kinetics of TAA fatty acid conjugation in vivo.

  5. An in-vitro study of the effect of hydrocolloid patch occlusion on the penetration of triamcinolone acetonide through skin in man.

    PubMed

    Ladenheim, D; Martin, G P; Marriott, C; Hollingsbee, D A; Brown, M B

    1996-08-01

    The aim of this study was to evaluate the effect of occlusion using hydrocolloid-containing patches on in-vitro triamcinolone acetonide (TACA) penetration of the epidermis while monitoring the uptake of water by the patches as a result of transepidermal water loss. The hydrocolloid patches were a laminate of a pressure-sensitive hydrophobic adhesive (containing a dispersion of 39% of either pectin or carmellose sodium) and a polyethylene film. The diffusion of a representative corticosteroid (TACA) through isolated epidermal sheet was shown to depend on the site from which the skin was removed. The two patch-types exhibited markedly different hydration rates when applied to the membranes. For example, after 96 h the carmellose sodium patch showed ten times the weight increase of the pectin patch. Epidermal diffusion rates were, however, similar, both showing a 3-4-fold enhancement over unoccluded conditions. The increase in TACA diffusion with the patches can be explained by the increase in skin hydration that occurs during occlusion. Despite the large differences in transepidermal water transfer through the epidermal membranes with the two types of hydrocolloid patch, however, this level of stratum corneum hydration was apparently similar. As the rate of diffusion was also independent of hydrocolloid patch component, it seems possible that the hydrophobic component of the patch matrix may also influence the level of skin hydration and consequent drug diffusion.

  6. Dissociation of tumor promoter-stimulated ornithine decarboxylase activity and DNA synthesis in mouse epidermis in vivo and in vitro by fluocinolone acetonide, a tumor-promotion inhibitor.

    PubMed Central

    Lichti, U; Slaga, T J; Ben, T; Patterson, E; Hennings, H; Yuspa, S H

    1977-01-01

    12-O-Tetradecanoyl phorbol-13-acetate (TPA), a tumor promoter, stimulates DNA synthesis in mouse epidermal cells in vivo and in vitro. This response appears to be mediated through polyamine metabolism because ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17)activity is markedly increased shortly after promoter exposure and this induction varies in magnitude according to dose and promoter potency of a series of phorbol esters. In vitro, exogenous putrescine (0.01-10 mM) results in a dose-related increase and prolongation of promoter-stimulated DNA DNA synthesis, a phenomenon noted in other systems of polyamine-mediated growth stimulation. The anti-inflammatory steroid fluocinolone acetonide (FA), an inhibitor of tumor promotion, prevents TPA stimulation of epidermal proliferation in vivo and in vitro. In vitro, FA most effectively prevents stimulation of DNA synthesis when applied is not required. Paradoxially, FA potentiates the increase in ornithine decarboxylase activity after TPA administeration both in vivo and in vitro. Furthermore, the inhibition of TPA-stimulated DNA synthesis by FA in vitro can be reversed by exogenous putrescine. These results suggestthat FA exerts its antipromotion effect by reducing the sensitivity of the cell to polyamines or by reducing intracellular polyamine levels. PMID:269443

  7. Long-term safety of a non-chlorofluorocarbon-containing triamcinolone acetonide inhalation aerosol in patients with asthma. Azmacort HFA Study Group.

    PubMed

    Nelson, H S; Kane, R E; Petillo, J; Banerji, D

    2000-04-01

    In response to environmental concerns regarding chlorofluorocarbon (CFC), two new triamcinolone acetonide (TAA) inhalation aerosol (Azmacort Inhalation Aerosol) formulations have been developed using a more environmentally favorable propellant, HFA-134a (1,1,1,2-tetrafluoroethane). This multicenter, open-label study evaluated the safety of switching asthma patients from TAA-CFC to one of two TAA-HFA formulations. After a 2- or 4-week baseline period during which patients received only CFC-containing TAA Inhaler, 552 patients were randomized to receive TAA-HFA 75 or 225 microg for 6 or 12 months. A total of 493 patients completed treatment. Seven patients discontinued because of adverse events and two because of ineffective asthma control. The incidence of adverse events was similar in the two treatment groups, and most events were mild to moderate in severity and were not considered related to study medication. No clinically relevant suppression of the hypophyseal-pituitary-adrenal (HPA) axis was observed. Pulmonary function tests were not adversely affected by use of either study medication, and improvements were noted in forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25%-75%) throughout the course of treatment. This study confirms that TAA-HFA provides effective, long-term asthma control and can safely be substituted for the currently marketed CFC-containing TAA product.

  8. Measurement of low picomolar levels of triamcinolone acetonide in human bronchoalveolar lavage fluid by gas chromatography-electron-capture negative-ion mass spectrometry.

    PubMed

    Hubbard, W C; Liu, M C; Bickel, C; Argenti, D; Heald, D; Schleimer, R P

    2001-03-01

    The intense inherent electron-capture properties of the C21 acetate derivative of triamcinolone acetonide (TAA) under methane chemical ionization mass spectrometric conditions were exploited for the development of a highly sensitive and selective gas chromatography-mass spectrometric (GC-MS) technique for measurement of levels of TAA in human bronchoalveolar lavage (BAL) fluid. After the addition of 3.0 ng of a heptadeuterated analog of TAA and varying concentrations of TAA to 2-ml aliquots of BAL fluid, the deuterium and protium forms of the steroid were extracted with diethyl ether, converted to the C21 acetate derivative, and purified via adsorptive chromatography prior to GC-MS analysis. Standard curves obtained from 2-ml aliquots of BAL fluid were linear over a wide range of concentrations of TAA from 0.0 to 24,600 pg/2-ml aliquots of BAL fluid. Levels as low as 6.0 pg/ml (13.8 pmol x L(-1)) in BAL fluid can be reliably determined in 2-ml aliquots of the biological fluid with <10% error. These findings suggest that the assay method exploiting the intense electron-capture properties of TAA is highly suitable for determination of the deposition pattern and in vivo kinetics of TAA in human airways following inhalation of the steroid.

  9. Comparisons of retinal nerve fiber layer thickness after indocyanine green, brilliant blue g, or triamcinolone acetonide-assisted macular hole surgery.

    PubMed

    Toba, Yoshiharu; Machida, Shigeki; Kurosaka, Daijiro

    2014-01-01

    Purpose. To compare the postoperative changes of the retinal nerve fiber layer (RNFL) thickness in patients with macular holes (MHs) treated with vitrectomy with indocyanine green- (ICG-), brilliant blue G- (BBG-), or triamcinolone acetonide- (TA-)assisted internal limiting membrane (ILM) peeling. Methods. Sixty-one eyes of 61 consecutive patients with MHs were studied. Each eye was randomly selected to undergo either ICG- (n = 18), BBG- (n = 21), or TA-assisted (n = 22) ILM peeling. The circumferential retinal nerve fiber layer (RNFL) thickness was determined by spectral-domain optical coherence tomography (SD-OCT) before and 1, 3, 6, 9, and 12 months postoperatively. The mean overall and the sectoral thicknesses of the RNFL were obtained for each group. Results. A transient increase of the RNFL thickness was seen in the mean overall and sectoral thicknesses except for the nasal/inferior sector at 1 month after surgery for the three groups. Then, the thickness gradually decreased and returned to the baseline level in all sectors except for the nasal/inferior sector. The differences in the RNFL thickness among the groups were not significant for at least 12 months postoperatively. Conclusions. The degree of change of the RNFL thickness was not significantly related to the type of vital stain used during MH surgery.

  10. Single implant tooth replacement.

    PubMed

    Briley, T F

    1998-01-01

    It has been shown that direct bone anchorage of dental implants will provide long-term predictability for single tooth implants and multi-unit implants. The function of implant-supported restoration is now routinely achieved. The real challenge facing the restorative dentist and laboratory technician is to achieve optimal aesthetics. The learning objective of this article is to review the prosthodontic procedures essential to maximizing natural aesthetics in implant supported restorations. It will provide a review of master impression techniques, prepable titanium abutments and designing the cement on restoration. Particular emphasis is directed to the soft tissue model from which a series of sequenced techniques can be followed to achieve optimal aesthetics. Analysis of the implant alignment with regard to the neighboring teeth will result in having to make a choice of which prepable abutment will maximize the aesthetic result. The following case outlines how to replace a single missing tooth using an externally hexed implant system and a prefabricated titanium abutment on a 26-year-old male patient.

  11. Boron implanted strontium titanate

    NASA Astrophysics Data System (ADS)

    Cooper, C. J. M.

    Single crystals of strontium titanate implanted with boron were found to have highly conductive surface layers. The effects of varying dose from 10 to the 16th power to 10 to the 17th power ions/sq cm, implantation voltage from 50 to 175 keV and annealing conditions on the room temperature surface resistance and Hall mobility are presented. Variation of the implantation voltage did not have a major effect on the sheet resistances obtained by boron implantation of strontium titanate, while dose and annealing conditions have major effects. Doses of 5 x 10 to the 16th power ions/sq cm required annealing on the order of one hour at 500 K for maximum reduction of the room temperature resistance in the implanted layer. Samples implanted with a dose of 1 x 10 to the 17th power ions/sq cm required slightly higher temperatures (approximately 575 K) to obtain a minimum resistance at room temperature. Long term (several weeks) room temperature annealing was found to occur in high dose samples. After one to two months at room temperature followed by an anneal to 575 K, the surface resistances were found to be lower than those produced by the annealing of a freshly implanted sample to 575 K.

  12. Dental Implant Systems

    PubMed Central

    Oshida, Yoshiki; Tuna, Elif B.; Aktören, Oya; Gençay, Koray

    2010-01-01

    Among various dental materials and their successful applications, a dental implant is a good example of the integrated system of science and technology involved in multiple disciplines including surface chemistry and physics, biomechanics, from macro-scale to nano-scale manufacturing technologies and surface engineering. As many other dental materials and devices, there are crucial requirements taken upon on dental implants systems, since surface of dental implants is directly in contact with vital hard/soft tissue and is subjected to chemical as well as mechanical bio-environments. Such requirements should, at least, include biological compatibility, mechanical compatibility, and morphological compatibility to surrounding vital tissues. In this review, based on carefully selected about 500 published articles, these requirements plus MRI compatibility are firstly reviewed, followed by surface texturing methods in details. Normally dental implants are placed to lost tooth/teeth location(s) in adult patients whose skeleton and bony growth have already completed. However, there are some controversial issues for placing dental implants in growing patients. This point has been, in most of dental articles, overlooked. This review, therefore, throws a deliberate sight on this point. Concluding this review, we are proposing a novel implant system that integrates materials science and up-dated surface technology to improve dental implant systems exhibiting bio- and mechano-functionalities. PMID:20480036

  13. Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections.

    PubMed

    Xu, Xu; Xu, Zhaokang; Liu, Junyi; Zhang, Zhaoliang; Chen, Hao; Li, Xingyi; Shi, Shuai

    To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone)-polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers.

  14. [The effects of antioxidants on the reflex from an eye-ground and electric activity of retina during intravitreal haemorrhage].

    PubMed

    Guliyeva, U

    2008-10-01

    The object of investigation was to study the reflex from an eye-ground, the character of the disorder of electric activity of retina during the experimental vitreous haemorrhage and the possibility of correction of these alterations by the antioxidants. The research was conducted on 5 month 300 chinchilla rabbits of male sex, weight 2.8-3.2 kg. The phenosan kali, superoxidedismutase (SOD), catalasa, "Hemaza", ditikarbomat natrium (DTKN), mannitol, tocopherol acetate, deferooxamin were used. The rabbits treated with the antioxidants complex and "Hemasa" showed the best dynamic of the restoration of the ophthalmological conditions. It was found that, vitreous haemorrhage considerably damaged the formation of ERG. Separate application of antioxidants: phenosan kali, SOD and mannitol restore the amplitude of ERG retina during intravitreal haemorrhage, not influencing the temporal parameters. The application of antioxidants complex considerably restores the amplitude characteristics, becoming close to the norm, not influencing the time of ERG parameters development.

  15. Nanotechnology for dental implants.

    PubMed

    Tomsia, Antoni P; Lee, Janice S; Wegst, Ulrike G K; Saiz, Eduardo

    2013-01-01

    With the advent of nanotechnology, an opportunity exists for the engineering of new dental implant materials. Metallic dental implants have been successfully used for decades, but they have shortcomings related to osseointegration and mechanical properties that do not match those of bone. Absent the development of an entirely new class of materials, faster osseointegration of currently available dental implants can be accomplished by various surface modifications. To date, there is no consensus regarding the preferred method(s) of implant surface modification, and further development will be required before the ideal implant surface can be created, let alone become available for clinical use. Current approaches can generally be categorized into three areas: ceramic coatings, surface functionalization, and patterning on the micro- to nanoscale. The distinctions among these are imprecise, as some or all of these approaches can be combined to improve in vivo implant performance. These surface improvements have resulted in durable implants with a high percentage of success and long-term function. Nanotechnology has provided another set of opportunities for the manipulation of implant surfaces in its capacity to mimic the surface topography formed by extracellular matrix components of natural tissue. The possibilities introduced by nanotechnology now permit the tailoring of implant chemistry and structure with an unprecedented degree of control. For the first time, tools are available that can be used to manipulate the physicochemical environment and monitor key cellular events at the molecular level. These new tools and capabilities will result in faster bone formation, reduced healing time, and rapid recovery to function.

  16. The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews.

    PubMed

    Ward, Alexander H; Siegwart, John T; Frost, Michael R; Norton, Thomas T

    2016-04-01

    lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye - control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 μL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 μL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (-0.15 ± 0.08 D/day) was significantly less than in the FD group (-0.55 ± 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (-0.09 ± 0.05 D/day) and H2O + ascorbic acid

  17. The effect of intravitreal vascular endothelial growth factor on inner retinal oxygen delivery and metabolism in rats.

    PubMed

    Blair, Norman P; Wanek, Justin; Teng, Pang-yu; Shahidi, Mahnaz

    2016-02-01

    Vascular endothelial growth factor (VEGF) is stimulated by hypoxia and plays an important role in pathologic vascular leakage and neovascularization. Increased VEGF may affect inner retinal oxygen delivery (DO2) and oxygen metabolism (MO2), however, quantitative information is lacking. We tested the hypotheses that VEGF increases DO2, but does not alter MO2. In 10 rats, VEGF was injected intravitreally into one eye, whereas balanced salt solution (BSS) was injected into the fellow eye, 24 h prior to imaging. Vessel diameters and blood velocities were determined by red-free and fluorescent microsphere imaging, respectively. Vascular PO2 values were derived by phosphorescence lifetime imaging of an intravascular oxyphor. Retinal blood flow, vascular oxygen content, DO2 and MO2 were calculated. Retinal arterial and venous diameters were larger in VEGF-injected eyes compared to control eyes (P < 0.03), however no significant difference was observed in blood velocity (P = 0.21). Thus, retinal blood flow was greater in VEGF-injected eyes (P = 0.007). Retinal vascular PO2 and oxygen content were similar between control and VEGF-injected eyes (P > 0.11), while the arteriovenous oxygen content difference was marginally lower in VEGF-injected eyes (P = 0.05). DO2 was 950 ± 340 and 1380 ± 650 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.005). MO2 was 440 ± 150 and 490 ± 190 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.31). Intravitreally administered VEGF did not alter MO2 but increased DO2, suggesting VEGF may play an offsetting role in conditions characterized by retinal hypoxia.

  18. Efficacy of intravitreal bevacizumab combined with pan retinal photocoagulation versus panretinal photocoagulation alone in treatment of proliferative diabetic retinopathy

    PubMed Central

    Sameen, Murtaza; Khan, Muhammad Saim; Mukhtar, Ahsan; Yaqub, Muhammad Amer; Ishaq, Mazhar

    2017-01-01

    Objective: To compare effectiveness of pan-retinal photocoagulation alone versus panretinal photocoagulation combined with intravitreal bevacizumab on visual acuity and central macular thickness in patients presenting with proliferative diabetic retinopathy. Methods: This Randomized controlled trial was carried out at Armed Forces Institute of ophthalmology, Pakistan from Jan 2016 to Aug 2016. Seventy six eyes of 50 patients having proliferative diabetic retinopathy and diabetic macular edema were included in the study. All the patients were subjected to detailed clinical examination that included Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), slit lamp examination of anterior and posterior segments. Optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) were carried out and patients were divided in two groups (GP and GI). Three monthly sessions of Pan retinal photocoagulation (PRP) using Pattern Scan Laser (PASCAL) alone was performed in group GP while PRP along with three monthly intravitreal bevacizumab (IVB) was performed in group GI. BCVA and CMT was recorded 04 weeks after the third PRP session in both the groups. Results: Seventy six eyes of 50 patients (38 in each group) were treated with three sessions of PRP alone and PRP with IVB in Group GP and GI respectively. Mean age of the patient in group GP was 57.47± 6.08 years while that in group GI was 55.69 ±6.58. The magnitude of induced change in BCVA was 0.09 ± 0.15 in GP while 0.22 + 0.04 in GI groups while mean induced change in CMT after treatment was 77.44 ± 92.30 um and 117.50 ± 93.82 um in group GP and GI. Conclusion: Laser PRP combined with IVB has superior visual and anatomical outcome than PRP alone in patients with combined presentation of PDR and DME. PMID:28367188

  19. Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury

    PubMed Central

    Adornetto, Annagrazia; Cavaliere, Federica; Varano, Giuseppe Pasquale; Rusciano, Dario; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2015-01-01

    Purpose Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Methods Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, homotaurine, and L-carnosine were intravitreally injected and RGC survival evaluated following retrograde labeling with FluoroGold. Total and phosphorylated Akt and glycogen synthase kinase-3β (GSK-3β) protein levels, as well as calpain activity, were analyzed with western blot. Protein kinase A (PKA) was inhibited by intravitreal injection of H89. Results A synergic neuroprotective effect on RGC survival was observed following the combined treatment with forskolin, homotaurine, and L-carnosine compared to forskolin alone. The observed neuroprotection was associated with reduced calpain activity, upregulation of phosphoinositide 3-kinase (PI3K)/Akt pathway, and inhibition of GSK-3β but was independent from PKA activation and distinct from the hypotensive effects of forskolin. Conclusions A multidrug/multitarget approach, by interfering with several pathways involved in RGC degeneration, may be promising to achieve glaucoma neuroprotection. PMID:26167113

  20. Photodynamic Therapy and Intravitreal Bevacizumab with Versus without Triamcinolone for Neovascular Age-related Macular Degeneration; a Randomized Clinical Trial

    PubMed Central

    Piri, Niloofar; Ahmadieh, Hamid; Taei, Ramin; Soheilian, Masoud; Karkhaneh, Reza; Lashay, Alireza; Golbafian, Faegheh; Yaseri, Mehdi; Riazi-Esfahani, Mohammad

    2014-01-01

    Purpose: To compare the outcomes of photodynamic therapy (PDT) combined with intravitreal bevacizumab (IVB) with versus without intravitreal triamcinolone (IVT) in neovascular age-related macular degeneration (AMD). Methods: Eighty-four eyes with active CNV secondary to AMD with no prior treatment were enrolled and followed for 1-year. Eligible eyes were randomly assigned to either PDT/IVB or PDT/IVB/IVT. The main outcome measure was change in best-corrected visual acuity (BCVA). Results: Mean patient age was 71 ± 9 years. BCVA changes from baseline were statistically significant in both study arms at all follow-up intervals, however no significant difference was observed between the two groups regarding BCVA changes at week 12 (95% CI:-0.11–0.12 LogMAR) and other time points (all P > 0.6). Mixed model analysis revealed a significant effect from age (P < 0.001), pigment epithelial detachment (P = 0.009) and baseline BCVA (P < 0.001) on visual improvement. Significant central macular thickness (CMT) reduction occurred at all-time points as compared to baseline in both groups which was comparable between the study arms. There was no significant difference between the study arms in terms of retreatment rate (P = 0.1) and survival to the first repeat IVB injection (P = 0.065). Conclusion: Additional low-dose IVT to a PDT/IVB regimen for neovascular AMD provided no beneficial effects in terms BCVA or CMT, yet demonstrated a trend toward extending the injection-free period. PMID:25709773

  1. Experiences of patients undergoing repeated intravitreal anti-vascular endothelial growth factor injections for neovascular age-related macular degeneration.

    PubMed

    Boyle, Jessica; Vukicevic, Meri; Koklanis, Konstandina; Itsiopoulos, Catherine; Rees, Gwyneth

    2017-01-09

    Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) entails regular intravitreal anti-vascular endothelial growth factor (VEGF) injections, often indefinitely. Little is known about the burden imposed on patients by this repetitive treatment schedule and how this can be best managed. The aim of this study was to explore the psychosocial impact of repeated intravitreal injections on patients with neovascular AMD. Forty patients (16 males, 24 females) with neovascular AMD undergoing anti-VEGF treatment were recruited using purposive sampling from a private ophthalmology practice and public hospital in Melbourne. Patients were surveyed using the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ; Bradley, Health Psychology Research Unit, Surrey, England) and underwent semi-structured, one-on-one interviews. Interview topics were: treatment burden and satisfaction; tolerability; barriers to adherence; treatment motivation; and patient education. Interviews were audio recorded and thematic analysis performed using NVivo 10 (QSR International, Doncaster, Australia). Patients recognised the importance of treatment to preserve eyesight, yet experienced significant psychosocial and practical burden from the treatment schedule. Important issues included treatment-related anxiety, financial considerations and transport burden placed on relatives or carers. Many patients were restricted to sedentary activities post-injection owing to treatment side effects. Patients prioritised treatment, often sacrificing family, travel and social commitments owing to a fear of losing eyesight if treatment was not received. Whilst anti-VEGF injections represent the current mainstay of treatment for neovascular AMD, the ongoing treatment protocol imposes significant burden on patients. An understanding of the factors that contribute to the burden of treatment may help inform strategies to lessen its impact and assist

  2. Biomedical implantable microelectronics.

    PubMed

    Meindl, J D

    1980-10-17

    Innovative applications of microelectronics in new biomedical implantable instruments offer a singular opportunity for advances in medical research and practice because of two salient factors: (i) beyond all other types of biomedical instruments, implants exploit fully the inherent technical advantages--complex functional capability, high reliability, lower power drain, small size and weight-of microelectronics, and (ii) implants bring microelectronics into intimate association with biological systems. The combination of these two factors enables otherwise impossible new experiments to be conducted and new paostheses developed that will improve the quality of human life.

  3. Implantable cardioverter-defibrillator

    MedlinePlus

    ... ncbi.nlm.nih.gov/pubmed/23265327 . Swerdlow CD, Wang PJ, Zipes DP. Pacemakers and implantable cardioverter-defibrillators. ... and lifestyle Controlling your high blood pressure Dietary fats explained Fast food tips Heart attack - discharge Heart ...

  4. Biocompatibility of surgical implants

    NASA Technical Reports Server (NTRS)

    Kaelble, D. H.

    1979-01-01

    Method of selecting biocompatible materials for surgical implants uses fracture mechanic relationships and surface energies of candidate materials in presence of blood plasma. Technique has been used to characterize 190 materials by parameters that reflect their biocompatibility.

  5. Risks of Breast Implants

    MedlinePlus

    ... has traveled to other parts of the body. Connective Tissue Disease The FDA has not detected any association between silicone gel-filled breast implants and connective tissue disease, breast cancer, or reproductive problems. In order ...

  6. Breast Reconstruction with Implants

    MedlinePlus

    ... removes your breast to treat or prevent breast cancer. One type of breast reconstruction uses breast implants — silicone devices filled with silicone gel or salt water (saline) — to reshape your breasts. Breast reconstruction ...

  7. Urinary incontinence - injectable implant

    MedlinePlus

    Intrinsic sphincter deficiency repair; ISD repair; Injectable bulking agents for stress urinary incontinence ... Urine leakage that gets worse Pain where the injection was done Allergic reaction to the material Implant ...

  8. Breast reconstruction - implants

    MedlinePlus

    ... cosmetic surgery after breast cancer can improve your sense of well-being and your quality of life. Alternative Names Breast implants surgery References Roehl KR, Wilhelmi BJ, Phillips LG. Breast reconstruction. ...

  9. Superelastic Orthopedic Implant Coatings

    NASA Astrophysics Data System (ADS)

    Fournier, Eric; Devaney, Robert; Palmer, Matthew; Kramer, Joshua; El Khaja, Ragheb; Fonte, Matthew

    2014-07-01

    The demand for hip and knee replacement surgery is substantial and growing. Unfortunately, most joint replacement surgeries will fail within 10-25 years, thereby requiring an arduous, painful, and expensive revision surgery. To address this issue, a novel orthopedic implant coating material ("eXalt") has been developed. eXalt is comprised of super elastic nitinol wire that is knit into a three-dimensional spacer fabric structure. eXalt expands in vivo to conform to the implantation site and is porous to allow for bone ingrowth. The safety and efficacy of eXalt were evaluated through structural analysis, mechanical testing, and a rabbit implantation model. The results demonstrate that eXalt meets or exceeds the performance of current coating technologies with reduced micromotion, improved osseointegration, and stronger implant fixation in vivo.

  10. Simple Implant Augmentation Rhinoplasty

    PubMed Central

    Nguyen, Anh H.; Bartlett, Erica L.; Kania, Katarzyna; Bae, Sang Mo

    2015-01-01

    Augmentation rhinoplasty among Asian patients is often performed to improve the height of the nasal dorsum. As the use of autogenous tissues poses certain limitations, alloplastic materials are a viable alternative with a long history of use in Asia. The superiority of one implant prosthesis over another for augmentation rhinoplasty is a matter of debate, with each material representing varying strengths and weaknesses, indications for use, and precautions to consider in nasal implant placement. An implant prosthesis should be used on a case-by-case basis. Augmentation rhinoplasty requires the consideration of specific anatomical preoperative factors, including the external nose, nasal length, nasofrontal angle, humps, and facial proportions. It is equally important to consider several operative guidelines to appropriately shape implants to minimize the occurrence of adverse effects and postoperative complications. The most common postoperative complications include infection, nasal height change, movement of implant prosthesis, and silicone implant protrusion. In addition, the surgeon should consider the current standards of Asian beauty aesthetics to better understand the patient's desired outcome. PMID:26648804

  11. Biomaterials in cochlear implants

    PubMed Central

    Stöver, Timo; Lenarz, Thomas

    2011-01-01

    The cochlear implant (CI) represents, for almost 25 years now, the gold standard in the treatment of children born deaf and for postlingually deafened adults. These devices thus constitute the greatest success story in the field of ‘neurobionic’ prostheses. Their (now routine) fitting in adults, and especially in young children and even babies, places exacting demands on these implants, particularly with regard to the biocompatibility of a CI’s surface components. Furthermore, certain parts of the implant face considerable mechanical challenges, such as the need for the electrode array to be flexible and resistant to breakage, and for the implant casing to be able to withstand external forces. As these implants are in the immediate vicinity of the middle-ear mucosa and of the junction to the perilymph of the cochlea, the risk exists – at least in principle – that bacteria may spread along the electrode array into the cochlea. The wide-ranging requirements made of the CI in terms of biocompatibility and the electrode mechanism mean that there is still further scope – despite the fact that CIs are already technically highly sophisticated – for ongoing improvements to the properties of these implants and their constituent materials, thus enhancing the effectiveness of these devices. This paper will therefore discuss fundamental material aspects of CIs as well as the potential for their future development. PMID:22073103

  12. Contraceptive implants and lactation.

    PubMed

    Díaz, Soledad

    2002-01-01

    The safety and efficacy of four contraceptive implants, plant, Implanon, Nestorone and Elcometrine, have been evaluated during use in the postpartum period by lactating women. These implants provide highly effective contraceptive protection with no negative effect on breastfeeding or infant growth and development. Breastfeeding women initiating Norplant use in the second postpartum month experience significantly longer periods of amenorrhea than do untreated women or intrauterine device users. After weaning, the bleeding pattern is similar to that observed in non-nursing women. Norplant use does not affect bone turnover and density during lactation. Norplant and Implanon release orally active progestins while Nestorone and Elcometrine implants release an orally inactive progestin, which represents an advantage since the infant should be free of steroidal effects. The infant's daily intake of steroids (estimated from concentrations in maternal milk during the first month of use) range from 90 to 100 ng of levonorgestrel (Norplant), 75-120 ng of etonogestrel (Implanon), and 50 ng and 110 ng of Nestorone (Nestorone and Elcometrine implants, respectively). Nursing women needing contraception may use progestin-only implants when nonhormonal methods are not available or acceptable. Implants that deliver orally active steroids should only be used after 6 weeks postpartum to avoid transferring of steroids to the newborn.

  13. Biocompatible implant surface treatments.

    PubMed

    Pattanaik, Bikash; Pawar, Sudhir; Pattanaik, Seema

    2012-01-01

    Surface plays a crucial role in biological interactions. Surface treatments have been applied to metallic biomaterials in order to improve their wear properties, corrosion resistance, and biocompatibility. A systematic review was performed on studies investigating the effects of implant surface treatments on biocompatibility. We searched the literature using PubMed, electronic databases from 1990 to 2009. Key words such as implant surface topography, surface roughness, surface treatment, surface characteristics, and surface coatings were used. The search was restricted to English language articles published from 1990 to December 2009. Additionally, a manual search in the major dental implant journals was performed. When considering studies, clinical studies were preferred followed by histological human studies, animal studies, and in vitro studies. A total of 115 articles were selected after elimination: clinical studies, 24; human histomorphometric studies, 11; animal histomorphometric studies, 46; in vitro studies, 34. The following observations were made in this review: · The focus has shifted from surface roughness to surface chemistry and a combination of chemical manipulations on the porous structure. More investigations are done regarding surface coatings. · Bone response to almost all the surface treatments was favorable. · Future trend is focused on the development of osteogenic implant surfaces. Limitation of this study is that we tried to give a broader overview related to implant surface treatments. It does not give any conclusion regarding the best biocompatible implant surface treatment investigated till date. Unfortunately, the eventually selected studies were too heterogeneous for inference of data.

  14. [Larynx: implants and stents].

    PubMed

    Sittel, C

    2009-05-01

    There is a wide variety of devices and materials to be implanted into the human larynx. Some are intended to remain only for a period of time, like laryngeal stents. If removal is not intended the device meets the definition for a medical implant. The majority of implants is used for the treatment of unilateral vocal fold immobility. There a 2 types of implants serving this purpose: Implants in a stricter sense are devices of solid material, which are brought into the paraglottic space through a window in the laryngeal framework (medialization thyroplasty). Several different products are presented in this review. In contrast, there are different substances available for endoscopic injection into the paralyzed vocal fold (injection laryngoplasty). Since some of these substances show a corpuscular consistency and a high viscosity they need to be deposited into the lateral paraglottic space. Therefore, the term "injectable implants" has been coined for these materials. The different substances available are discussed in detail in this review. Laryngeal stents are primarily used in the early postoperative phase after open reconstruction of the larynx. The different devices available on the market are described with their specific characteristics and intended use.

  15. Indocyanine green angiography-guided laser photocoagulation combined with sub-Tenon's capsule injection of triamcinolone acetonide for idiopathic macular telangiectasia.

    PubMed

    Hirano, Yoshio; Yasukawa, Tsutomu; Usui, Yoshimi; Nozaki, Miho; Ogura, Yuichiro

    2010-05-01

    AIMS Type 2 (perifoveal) telangiectasia often is refractory to treatment, because focal targets such as aneurysms are not detected by fluorescein angiography (FA) in these eyes. The authors evaluated the efficacy of indocyanine green angiography (IA)-guided laser photocoagulation and sub-Tenon's capsule injection of triamcinolone acetonide (STTA) for idiopathic macular telangiectasia. METHODS Seven eyes (seven patients; mean age, 72 years) were enrolled, five eyes with type 1 and two eyes with type 2. The mean follow-up was 10.6 months (range 7 to 19). FA and IA were performed with the Heidelberg Retina Angiogram 2. Laser photocoagulation was applied to leaky vessels detected by late-phase IA (wavelength, 577 nm; power, 100-200 mW; spot size, 100-200 microm; and duration, 0.2 s). STTA (20 mg) was injected after photocoagulation. The central macular thickness and macular volume were measured periodically by optical coherence tomography. The logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was measured. RESULTS IA identified leaky aneurysms or vessels. The final mean logMAR VA and the central macular thickness improved significantly from baseline (p=0.040, p=0.0002, respectively). The VA improved by 0.3 or more logMAR unit in two eyes (29%) and stabilised in five eyes (71%). No adverse effects were reported throughout follow-up. CONCLUSIONS IA can detect microangiopathy in eyes with idiopathic macular telangiectasia. IA-guided laser photocoagulation combined with STTA might be effective for treating types 1 and 2 idiopathic macular telangiectasia. Further studies are needed to access the efficacy of IA-guided photocoagulation for treating type 2 telangiectasia.

  16. A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations.

    PubMed

    Salama, Alaa H; Mahmoud, Azza A; Kamel, Rabab

    2016-10-01

    Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye.

  17. Pneumatic Displacement with Perfluoropropane Gas and Intravitreal Tissue Plasminogen Activator for Subretinal Subfoveal Hemorrhage after Focal Laser Photocoagulation in Central Serous Chorioretinopathy

    PubMed Central

    Espinoza, Juan V.; Lasave, Andres F.; Savino-Zari, Dario; Arevalo, Fernando A.

    2014-01-01

    Objective. To report the visual and anatomic outcomes of pneumatic displacement with perfluoropropane (C3F8) gas and intravitreal tissue plasminogen activator (IVTPA) for subretinal subfoveal hemorrhage after focal laser photocoagulation in central serous chorioretinopathy (CSCR). Method. Interventional, retrospective case report of one eye (one patient). Outcome measures included visual acuity (VA), central macular thickness (CMT), and size of the lesion at two weeks of followup. Fluorescein angiography (FA) and optical coherent tomography (OCT) were used to measure anatomic outcomes. Results. A 35-year-old man with history of chronic CSCR received focal laser photocoagulation in the right eye two days before presentation. At initial examination, VA was 20/200 (ETDRS chart), CMT was 398 μ, and a subretinal subfoveal hemorrhage was seen. Tissue plasminogen activator (tPA) at a dose of 25 µg/0.1 mL was injected intravitreally before intravitreal C3F8 injection, and prone positioning was indicated postoperatively. At 24 hours, the hemorrhage had been displaced inferiorly and VA improved to 20/100. Two weeks later, VA improved to 20/80, CMT decreased to 225 μ, and the hemorrhage decreased without foveal involvement. Conclusions. The technique seems safe and effective in treating visually significant subretinal subfoveal hemorrhage. PMID:25485161

  18. [Intravitreous injection of bevacizumab and C3F8 gas for the treatment of submacular hemorrhage due to age-related macular degeneration: case reports].

    PubMed

    Ferraz, Daniel Araújo; Bressanim, Gláucio Luciano; Morita, Celso; Takahashi, Walter Yukihiko

    2010-01-01

    The purpose of this case series is to describe if the intravitreal use of bevacizumab and perfluoropropane gas (C3F8) would be beneficial to the displacement of subretinal hemorrhage in patients with age-related macular degeneration (AMD). A retrospective study of 5 eyes that received concurrent intravitreal injection of bevacizumab and C3F8 was performed. The results were graded according to blood displacement under the fovea, best final visual acuity and intraoperative complications. At the initial presentation, mean age of patients was 72.6 +/- 8.9 years-old and duration of symptoms was 13 +/- 9.7 days. From the 5 patients, 3 (60%) were male and 2 (40%) female. The success of submacular hemorrhage full displacement was achieved in 4 patients. The mean preoperative visual acuity (VA) was 1.12 +/- 0.34 logMAR and the mean postoperative VA was 0.92 +/- 0.4 logMAR. No cases of retinal detachment, endophthalmitis, vitreous hemorrhage, uveitis, cataracts and increased intraocular pressure were noted during the follow-up period. Intravitreal bevacizumab and C3F8 injection, associated to prone position can be a valuable therapeutic option for eyes with neovascular age-related macular degeneration and subretinal hemorrhage to the blood displacement out of the foveal area.

  19. Pneumatic displacement with perfluoropropane gas and intravitreal tissue plasminogen activator for subretinal subfoveal hemorrhage after focal laser photocoagulation in central serous chorioretinopathy.

    PubMed

    Al Rubaie, Khalid; Espinoza, Juan V; Lasave, Andres F; Savino-Zari, Dario; Arevalo, Fernando A; Arevalo, J Fernando

    2014-01-01

    Objective. To report the visual and anatomic outcomes of pneumatic displacement with perfluoropropane (C3F8) gas and intravitreal tissue plasminogen activator (IVTPA) for subretinal subfoveal hemorrhage after focal laser photocoagulation in central serous chorioretinopathy (CSCR). Method. Interventional, retrospective case report of one eye (one patient). Outcome measures included visual acuity (VA), central macular thickness (CMT), and size of the lesion at two weeks of followup. Fluorescein angiography (FA) and optical coherent tomography (OCT) were used to measure anatomic outcomes. Results. A 35-year-old man with history of chronic CSCR received focal laser photocoagulation in the right eye two days before presentation. At initial examination, VA was 20/200 (ETDRS chart), CMT was 398 μ, and a subretinal subfoveal hemorrhage was seen. Tissue plasminogen activator (tPA) at a dose of 25 µg/0.1 mL was injected intravitreally before intravitreal C3F8 injection, and prone positioning was indicated postoperatively. At 24 hours, the hemorrhage had been displaced inferiorly and VA improved to 20/100. Two weeks later, VA improved to 20/80, CMT decreased to 225 μ, and the hemorrhage decreased without foveal involvement. Conclusions. The technique seems safe and effective in treating visually significant subretinal subfoveal hemorrhage.

  20. A Single Intravitreal Injection of Ranibizumab Provides No Neuroprotection in a Nonhuman Primate Model of Moderate-to-Severe Nonarteritic Anterior Ischemic Optic Neuropathy

    PubMed Central

    Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Steven L.

    2015-01-01

    Purpose Ranibizumab, a vascular endothelial growth factor-antagonist, is said to be neuroprotective when injected intravitreally in patients with nonarteritic anterior ischemic optic neuropathy (NAION). We evaluated the efficacy of a single intravitreal (IVT) injection of ranibizumab in a nonhuman primate model of NAION (pNAION). Methods We induced pNAION in one eye of four adult male rhesus monkeys using a laser-activated rose Bengal induction method. We then immediately injected the eye with either ranibizumab or normal saline (NS) intravitreally. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in three of the animals (one animal developed significant retinal hemorrhages and, therefore, could not be analyzed completely) prior to induction, 1 day and 1, 2, and 4 weeks thereafter. Following the 4-week analysis of the first eye, we induced pNAION in the contralateral eye and then injected either ranibizumab or NS, whichever substance had not been injected in the first eye. We euthanized all animals 5 to 12 weeks after the final assessment of the second eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves of both eyes. Results A single IVT dose of ranibizumab administered immediately after induction of pNAION resulted in no significant reduction of clinical, electrophysiological, or histologic damage compared with vehicle-injected eyes. Conclusions A single IVT dose of ranibizumab is not neuroprotective when administered immediately after induction of pNAION. PMID:26624498

  1. Extraoral prostheses using extraoral implants.

    PubMed

    Pekkan, G; Tuna, S H; Oghan, F

    2011-04-01

    The aim of this study was to evaluate extraoral prostheses and the use of extraoral implants in patients with facial defects. 10 cases were treated utilizing maxillofacial prostheses employing extraoral implants in five cases. 16 extraoral implants were installed. Seven implants were placed in irradiated sites in the orbital regions. Six implants were placed in mastoid regions and three in a zygoma region that was irradiated. Two implants failed before initial integration was achieved in irradiated areas. Using 14 extraoral implants as anchors, five extraoral prostheses were set. The other five cases were treated with extraoral prostheses without using extraoral implants due to cost and patient-related factors. The data included age, sex, primary disease, implant length, implant failure, prosthetic attachment, radiation therapy, and peri-implant skin reactions. The use of extraoral implants for the retention of extraoral prostheses has simplified the placement, removal, and cleaning of the prosthesis by the patient. The stability of the prostheses was improved by anchors. Clinical and technical problems are presented with the techniques used for their resolution. Using extraoral implants resulted in a high rate of success in retaining facial prostheses and gave good stability and aesthetic satisfaction.

  2. Towards biodegradable wireless implants.

    PubMed

    Boutry, Clémentine M; Chandrahalim, Hengky; Streit, Patrick; Schinhammer, Michael; Hänzi, Anja C; Hierold, Christofer

    2012-05-28

    A new generation of partially or even fully biodegradable implants is emerging. The idea of using temporary devices is to avoid a second surgery to remove the implant after its period of use, thereby improving considerably the patient's comfort and safety. This paper provides a state-of-the-art overview and an experimental section that describes the key technological challenges for making biodegradable devices. The general considerations for the design and synthesis of biodegradable components are illustrated with radiofrequency-driven resistor-inductor-capacitor (RLC) resonators made of biodegradable metals (Mg, Mg alloy, Fe, Fe alloys) and biodegradable conductive polymer composites (polycaprolactone-polypyrrole, polylactide-polypyrrole). Two concepts for partially/fully biodegradable wireless implants are discussed, the ultimate goal being to obtain a fully biodegradable sensor for in vivo sensing.

  3. Perforated microelectrode arrays implanted in the regenerating adult central nervous system.

    PubMed

    Heiduschka, P; Romann, I; Stieglitz, T; Thanos, S

    2001-09-01

    Adult mammalian optic nerve axons are able to regenerate, when provided with the permissive environment of an autologous peripheral nerve graft, which is usually the sciatic nerve. This study demonstrates the ability of adult rat optic nerve axons to regenerate through the preformed perforations of a polyimide electrode carrier implanted at the interface between the proximal stump of the cut optic nerve and the stump of the peripheral nerve piece used for grafting. Evidence that retinal ganglion cells regenerated their axons through the perforated electrode carrier was obtained by retrograde labeling with a fluorescent dye deposited into the sciatic nerve graft beyond the nerve-carrier-nerve junction. The number of regenerating cells could be enhanced by injecting neuroprotective drugs like aurintricarboxylic acid and cortisol intravitreally. A second line of evidence was obtained by immunohistochemical staining with antibodies to neurofilament. Third, electrical activity of the regenerating nerves was recorded after stimulating the retina with a flash of light. The results suggest that a regenerating central nerve tract may serve as an experimental model to implant artificial microdevices to monitor the physiological and topographical properties of neurites passing through the device or to stimulate them, thus interfering with their potential to grow. This study reports for the first time that the optic nerve has unique properties, which aids in the realization of these goals.

  4. Implantable Heart Aid

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Medrad utilized NASA's Apollo technology to develop a new device called the AID implantable automatic pulse generator which monitors the heart continuously, recognizes the onset of ventricular fibrillation and delivers a corrective electrical shock. AID pulse generator is, in effect, a miniaturized version of the defibrillator used by emergency squads and hospitals to restore rhythmic heartbeat after fibrillation, but has the unique advantage of being permanently available to the patient at risk. Once implanted, it needs no specially trained personnel or additional equipment. AID system consists of a microcomputer, a power source and two electrodes which sense heart activity.

  5. Hydroxylapatite Otologic Implants

    SciTech Connect

    McMillan, A.D.; Lauf, R.J.; Beale, B.; Johnson, R.

    2000-01-01

    A Cooperative Research and Development Agreement (CRADA) between Lockheed Martin Energy Research Corporation (LMER) and Smith and Nephew Richards Inc. of Bartlett, TN, was initiated in March 1997. The original completion date for the Agreement was March 25, 1998. The purpose of this work is to develop and commercialize net shape forming methods for directly creating dense hydroxylapatite (HA) ceramic otologic implants. The project includes three tasks: (1) modification of existing gelcasting formulations to accommodate HA slurries; (2) demonstration of gelcasting to fabricate green HA ceramic components of a size and shape appropriate to otologic implants: and (3) sintering and evaluation of the HA components.

  6. Current trends in dental implants

    PubMed Central

    Gaviria, Laura; Salcido, John Paul; Guda, Teja

    2014-01-01

    Tooth loss is very a very common problem; therefore, the use of dental implants is also a common practice. Although research on dental implant designs, materials and techniques has increased in the past few years and is expected to expand in the future, there is still a lot of work involved in the use of better biomaterials, implant design, surface modification and functionalization of surfaces to improve the long-term outcomes of the treatment. This paper provides a brief history and evolution of dental implants. It also describes the types of implants that have been developed, and the parameters that are presently used in the design of dental implants. Finally, it describes the trends that are employed to improve dental implant surfaces, and current technologies used for the analysis and design of the implants. PMID:24868501

  7. The silicone breast implant controversy.

    PubMed

    Guerette, P H

    1995-02-01

    Feminists call it objectification. Consumer advocates call it victimization. Medical personnel call it augmentation. Women, implantation. Whatever the term, media hype and the increasing number of lawsuits against U.S. manufacturers of silicone breast implants has caused widespread concern among women and raised serious questions about the long term health risks and safety of breast implant devices.

  8. Semiconductor Ion Implanters

    NASA Astrophysics Data System (ADS)

    MacKinnon, Barry A.; Ruffell, John P.

    2011-06-01

    In 1953 the Raytheon CK722 transistor was priced at 7.60. Based upon this, an Intel Xeon Quad Core processor containing 820,000,000 transistors should list at 6.2 billion! Particle accelerator technology plays an important part in the remarkable story of why that Intel product can be purchased today for a few hundred dollars. Most people of the mid twentieth century would be astonished at the ubiquity of semiconductors in the products we now buy and use every day. Though relatively expensive in the nineteen fifties they now exist in a wide range of items from high-end multicore microprocessors like the Intel product to disposable items containing `only' hundreds or thousands like RFID chips and talking greeting cards. This historical development has been fueled by continuous advancement of the several individual technologies involved in the production of semiconductor devices including Ion Implantation and the charged particle beamlines at the heart of implant machines. In the course of its 40 year development, the worldwide implanter industry has reached annual sales levels around 2B, installed thousands of dedicated machines and directly employs thousands of workers. It represents in all these measures, as much and possibly more than any other industrial application of particle accelerator technology. This presentation discusses the history of implanter development. It touches on some of the people involved and on some of the developmental changes and challenges imposed as the requirements of the semiconductor industry evolved.

  9. Semiconductor Ion Implanters

    SciTech Connect

    MacKinnon, Barry A.; Ruffell, John P.

    2011-06-01

    In 1953 the Raytheon CK722 transistor was priced at $7.60. Based upon this, an Intel Xeon Quad Core processor containing 820,000,000 transistors should list at $6.2 billion. Particle accelerator technology plays an important part in the remarkable story of why that Intel product can be purchased today for a few hundred dollars. Most people of the mid twentieth century would be astonished at the ubiquity of semiconductors in the products we now buy and use every day. Though relatively expensive in the nineteen fifties they now exist in a wide range of items from high-end multicore microprocessors like the Intel product to disposable items containing 'only' hundreds or thousands like RFID chips and talking greeting cards. This historical development has been fueled by continuous advancement of the several individual technologies involved in the production of semiconductor devices including Ion Implantation and the charged particle beamlines at the heart of implant machines. In the course of its 40 year development, the worldwide implanter industry has reached annual sales levels around $2B, installed thousands of dedicated machines and directly employs thousands of workers. It represents in all these measures, as much and possibly more than any other industrial application of particle accelerator technology. This presentation discusses the history of implanter development. It touches on some of the people involved and on some of the developmental changes and challenges imposed as the requirements of the semiconductor industry evolved.

  10. Cochlear Implantation in Neurobrucellosis

    PubMed Central

    Bajin, Münir Demir; Savaş, Özden; Aslan, Filiz; Sennaroğlu, Levent

    2016-01-01

    Background: Neurobrucellosis is a disease consisting of a wide spectrum of complications such as peripheral neuropathy, cranial nerve involvement, ataxia, meningeal irritation, paraplegia, seizures, coma, and even death. The vestibulocochlear nerve seems to be the most commonly affected cranial nerve (10%). We present a patient with neurobrucellosis whose auditory perception and speech intelligibility skill performances improved after cochlear implantation. Case Report: A 35 year-old woman was admitted to another hospital 2 years ago with the symptoms of headache, nausea, and altered consciousness, who was finally diagnosed with neurobrucellosis. She developed bilateral profound sensorineural hearing loss during the following 6 months. There was no benefit of using hearing aids. After successful treatment of her illness, she was found to be suitable for cochlear implantation. After the operation, her auditory perception skills improved significantly with a Categories of Auditory Performance (CAP) score of 5. According to clinical observations and her family members’ statements, her Speech Intelligibility Rating (SIR) score was 3. Her speech intelligibility skills are still improving. Conclusion: Our case report represents the second case of hearing rehabilitation with cochlear implantation after neurobrucellosis. Cochlear implantation is a cost-effective and time-proven successful intervention in post-lingual adult patients with sensorineural hearing loss. Early timing of the surgery after appropriate treatment of meningitis helps the patient to achieve better postoperative results. PMID:26966626

  11. Remote actuated valve implant

    DOEpatents

    McKnight, Timothy E; Johnson, Anthony; Moise, Jr., Kenneth J; Ericson, Milton Nance; Baba, Justin S; Wilgen, John B; Evans, III, Boyd McCutchen

    2014-02-25

    Valve implant systems positionable within a flow passage, the systems having an inlet, an outlet, and a remotely activatable valve between the inlet and outlet, with the valves being operable to provide intermittent occlusion of the flow path. A remote field is applied to provide thermal or magnetic activation of the valves.

  12. Implantable Drug Dispenser

    NASA Technical Reports Server (NTRS)

    Collins, E. R. J.

    1983-01-01

    Drugs such as insulin are injected as needed directly into bloodstream by compact implantable dispensing unit. Two vapor cavities produce opposing forces on drug-chamber diaphragm. Heaters in cavities allow control of direction and rate of motion of bellows. Dispensing capsule fitted with coil so batteries can be recharged by induction.

  13. Practicing implant dentistry profitably.

    PubMed

    Stump, G; Adams, M; Alwan, M

    1997-03-01

    The success of dental implants has opened up countless treatment possibilities for restorative dentists to offer to their patients. Just as our clinical paradigms have had to change because of this new technology, so too must our paradigms concerning the way we communicate with our patients change if we are to get them to say "yes" to treatment that we know that they need. Success in clinical treatment using implants requires a systematic approach. A systematic approach to communicating with your patients will allow you to have the same high degree of success with treatment acceptance that is possible with dental implants. The key to the systems we have discussed is Relationship Centered Care. A relationship is fostered and enhanced through a Comprehensive Examination Process, a structured Consultation Process utilizing the influencing process and Financial Arrangements that allow the patient to receive what they want while the office maintains the profitability that it needs. A system for calculating rational fees can be utilized that allows the practice to have control over an area that traditionally was controlled by anecdotal factors. The Pride Institute has developed this material and is presenting it to the profession so that restorative dentists can truly practice implant dentistry profitably.

  14. Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection.

    PubMed

    Wassmer, Sarah J; Carvalho, Livia S; György, Bence; Vandenberghe, Luk H; Maguire, Casey A

    2017-03-31

    Widespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors. Vectors were IVT injected into the eyes of adult mice. GFP expression was noninvasively monitored by fundus imaging and retinal expression was analyzed 4 weeks post-injection by qRT-PCR and histology. Exo-AAV2 outperformed conventional AAV2 in GFP expression based on fundus image analysis and qRT-PCR. Exo-AAV2 demonstrated deeper penetration in the retina, efficiently reaching the inner nuclear and outer plexiform, and to a lesser extent the outer nuclear layer. Cell targets were ganglion cells, bipolar cells, Müller cells, and photoreceptors. Exo-AAV2 serves as a robust gene delivery tool for murine retina, and the simplicity of production and isolation should make it widely applicable to basic research of the eye.

  15. Combination of Intravitreal Injection of Ranibizumab and Photocoagulation for the Treatment of Aggressive Posterior Retinopathy of Prematurity with Vitreous Hemorrhage

    PubMed Central

    Huang, Qiujing; Lv, Jiao

    2016-01-01

    To investigate the efficacy of intravitreal ranibizumab (IVR) combined with laser photocoagulation for aggressive posterior retinopathy of prematurity (AP-ROP) patients with vitreous hemorrhage, we conducted a retrospective observational case series study. A total of 37 eyes of 20 patients' medical records were reviewed. Patients first received IVR (0.25 mg/0.025 mL) and later photocoagulation. The mean postconceptual age of injection was 34.6 ± 1.4 weeks, and the mean follow-up period was 39.3 ± 8.3 weeks. During the follow-up, 96.6% eyes had various degree of rapid absorption of vitreous hemorrhage after IVR. The mean time of received first photocoagulation after IVR was 4.8 ± 2.9 weeks. Ten (27.0%) eyes received second laser therapy and the mean time of second laser therapy after IVR was 3.2 ± 0.8 weeks. All eyes exhibited adequate regression of ROP and were stable with attached retina. Fibrosis membrane was observed in seven eyes (18.9%) and three of them demonstrated mild ectopic macula. No significant side effects related to IVR were observed. So IVR could be conducted as primary treatment of AP-ROP associated with vitreous hemorrhage, which can improve the fundus visibility, followed by conventional photocoagulation. Further randomized controlled trials are necessary to compare the clinical efficacy and safety with conventional interventions. PMID:28070414

  16. Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection

    PubMed Central

    Wassmer, Sarah J.; Carvalho, Livia S.; György, Bence; Vandenberghe, Luk H.; Maguire, Casey A.

    2017-01-01

    Widespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors. Vectors were IVT injected into the eyes of adult mice. GFP expression was noninvasively monitored by fundus imaging and retinal expression was analyzed 4 weeks post-injection by qRT-PCR and histology. Exo-AAV2 outperformed conventional AAV2 in GFP expression based on fundus image analysis and qRT-PCR. Exo-AAV2 demonstrated deeper penetration in the retina, efficiently reaching the inner nuclear and outer plexiform, and to a lesser extent the outer nuclear layer. Cell targets were ganglion cells, bipolar cells, Müller cells, and photoreceptors. Exo-AAV2 serves as a robust gene delivery tool for murine retina, and the simplicity of production and isolation should make it widely applicable to basic research of the eye. PMID:28361998

  17. Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications.

    PubMed

    Stahl, Andreas; Stumpp, Michael T; Schlegel, Anja; Ekawardhani, Savira; Lehrling, Christina; Martin, Gottfried; Gulotti-Georgieva, Maya; Villemagne, Denis; Forrer, Patrik; Agostini, Hansjürgen T; Binz, H Kaspar

    2013-01-01

    The next-generation ophthalmic anti-VEGF therapeutics must aim at being superior to the currently available agents with regard to potency and improved drug delivery, while still being stable and safe to use at elevated concentrations. We show here the generation of a set of highly potent VEGF-A antagonistic DARPins (designed ankyrin repeat proteins) delivering these properties. DARPins with single-digit picomolar affinity to human VEGF-A were generated using ribosome display selections. Specific and potent human VEGF-A binding was confirmed by ELISA and endothelial cell sprouting assays. Cross-reactivity with VEGF-A of several species was confirmed by ELISA. Intravitreally injected DARPin penetrated into the retina and reduced fluorescein extravasation in a rabbit model of vascular leakage. In addition, topical DARPin application was found to diminish corneal neovascularization in a rabbit suture model, and to suppress laser-induced neovascularization in a rat model. Even at elevated doses, DARPins were safe to use. The fact that several DARPins are highly active in various assays illustrates the favorable class behavior of the selected binders. Anti-VEGF-A DARPins thus represent a novel class of highly potent and specific drug candidates for the treatment of neovascular eye diseases in both the posterior and the anterior eye chamber.

  18. Biochemical changes induced by intravitreally-injected doxorubicin in the iris-ciliary body and lens of the rabbit eye.

    PubMed

    Phylactos, A C; Unger, W G

    1998-01-01

    The aim of this study was to examine the chronic effects and mode of action of doxorubicin in ocular tissues. A dose of 10 microg (17.24 nanomoles) of doxorubicin hydrochloride in 20 microl sterile saline were intravitreally injected, under local anaesthesia, in one eye of 13 rabbits and 50 microg (86.20 nanomoles) were similarly injected in one eye of 3 rabbits. The contralateral eye received 20 microl of saline only. The dose of 50 microg induced initially mild uveal inflammation which became chronic and turned into circular iritis. Both doses of the drug induced cataract of the lens and clouding of the cornea within 2-3 months. The activity of superoxide dismutase, in iris-ciliary bodies and lenses treated with either 10 or 50 microg of the compound, was significantly lower relative to that in respective control tissues. In contrast to superoxide dismutase, catalase showed an increased activity in experimental tissues relative to control. The lysosomal hydrolases acid phosphatase, N-acetyl-B-D-glucosaminidase, aryl sulphatase and acid cathepsin, all showed significantly elevated activities in iris-ciliary body tissues one year after injection with the 50 microg doxorubicin. The reduction in superoxide dismutase activity may render ocular tissues susceptible to peroxidative attack and the increased activities of lysosomal hydrolases may contribute to chronic cell injury and inflammation.

  19. Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

    PubMed Central

    Xu, Xu; Xu, Zhaokang; Liu, Junyi; Zhang, Zhaoliang; Chen, Hao; Li, Xingyi; Shi, Shuai

    2016-01-01

    To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)–poly(ε-caprolactone)–polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers. PMID:27785015

  20. Effective Intravitreal Injections of Bevacizumab in a Case of Serous Macular Detachment from the Superior Border of the Posterior Staphyloma

    PubMed Central

    Tsubota, Yukiko; Takahashi, Hidenori; Sugisaki, Kenji; Tanabe, Tatsuro; Fujino, Yujiro

    2017-01-01

    Purpose We present an atypical case of submacular fluid leading to serous macular detachment. Method/Patient A 69-year-old man was evaluated for metamorphopsia in the left eye. Results Best-corrected visual acuity was 20/25 in both eyes. He had undergone cataract surgeries in both eyes 12 years ago. The axial length was 25.93 mm (OD) and 24.12 mm (OS). Optical coherence tomography showed posterior staphylomas and subretinal fluid on the superior border of the staphylomas in both eyes; in the left eye, submacular fluid was noted extending up to the macula. Fundus fluorescein angiography revealed leakage from the superior border of the staphylomas in both eyes. The fluid persisted for 4 months. Four consecutive, monthly injections of bevacizumab (1.25 mg/0.05 mL) were administered in the left eye; subsequently, the subretinal fluid gradually dissipated from the macula and became localized at the superior border of the staphyloma. This localization persisted for 12 months. Conclusions We have detailed a case of submacular fluid that spread from the superior border of the posterior staphyloma in a patient with macular detachment, in whom intravitreal injections of bevacizumab were highly effective in eliminating the fluid. PMID:28203196

  1. Efficacy of triamcinolone acetate and methylprednisolone acetonide for intrabursal injection after ultrasound-guided percutaneous treatment in painful shoulder calcific tendonitis: a randomized controlled trial.

    PubMed

    Battaglia, Milva; Guaraldi, Federica; Gori, Davide; Castiello, Emanuela; Arvat, Emanuela; Sudanese, Alessandra

    2016-01-01

    Background Ultrasound-guided percutaneous irrigation of calcific tendinopathy (US-PICT) with intrabursal steroid injection is an elective treatment for painful rotator cuff calcific tendinopathy. Purpose To compare the efficacy of post-US-PICT intrabursal 40 mg injection of triamcinolone acetonide (TA) versus methylprednisolone acetate (MA). Material and Methods Forty patients (22 women; mean age 48.7 ± 7.2 years) with painful shoulder calcific tendinopathy, treated with TA or MA injected intrabursally after US-PICT, were included in this randomized controlled trial. At baseline and after 1, 7, 15, 30, 45, and 180 days, patients underwent US and clinical examination, using Constant (CS) and VAS (VS) scores. Complications and analgesic use were also recorded. Results Compared to baseline, at the 45-day follow-up, TA and MA group showed a similar improvement (Δ) in CS (42 ± 10 versus 36 ± 9 points) and VS (-4.4 ± 1.3 versus -3.6 ± 1.3 points). At the 180-day follow-up, the improvement was higher in TA versus MA (ΔCS: 53 ± 7 versus 44 ± 7 points; ΔVS: -4.9 ± 1.1 versus -3.9 ± 1 points). Multivariate analysis showed a mean CS higher ( P = 0.02) in TA versus MA group, while VS was similar. TA had a 5 × higher ( P = 0.007) chance of reaching complete remission (CS = 100 points) than MA group. A progressive decrease in analgesic use, concomitant to a significant and similar reduction of bursitis and calcifications, was observed in both groups. No major complications occurred. Conclusion Two-needle US-PICT with intrabursal steroid injection is safe and effective. The chance of reaching better scores and, even more important for a clinical perspective, of functional recovery, is higher in patients treated with TA than MA.

  2. Effect of implant design on initial stability of tapered implants.

    PubMed

    Chong, Linus; Khocht, Ahmed; Suzuki, Jon B; Gaughan, John

    2009-01-01

    Implant design is one of the parameters for achieving successful primary stability. This study aims to examine the effect of a self-tapping blades implant design on initial stability in tapered implants. Polyurethane blocks of different densities were used to simulate different bone densities. The two different implant designs included one with self-tapping blades and one without self-tapping blades. Implants were placed at 3 different depths: apical third, middle third, and fully inserted at 3 different densities of polyurethane blocks. A resonance frequency (RF) analyzer was then used to measure stability of the implants. Repeated-measures analysis of variance was used to examine the effect of implant design, insertion depth, and block density on RF. Analysis of covariance was used to examine the strength of association between RF and the aforementioned factors. In both medium-density (P = .017) and high-density (P = .002) blocks, fully inserted non-self-tapping implants showed higher initial stability than self-tapping implants. No differences were noted between the 2 implant designs that were not fully inserted. The highest strength of association was with insertion depth (standardized beta [std beta] = -0.60, P = .0001), followed by block density (std beta = -0.15, P = .0002). Implant design showed a weak association (std beta = -0.07, P = .09). In conclusion, fully inserted implants without self-tapping blades have higher initial stability than implants with self-tapping blades. However, the association strength between implant design and initial stability is less relevant than other factors, such as insertion depth and block density. Thus, if bone quality and quantity are optimal, they may compensate for design inadequacy.

  3. [Allergic reactions to implant materials].

    PubMed

    Thomas, P

    2003-01-01

    The extent of the immune response upon implantation of metallic devices depends on the individual reactivity and on material characteristics. If specific T-cellular sensitization occurs or an allergy to metal preexists, hypersensitive reactions to implant components may develop. They include eczema, impaired wound healing, and sterile osteomyelitis. The existence of allergy-induced implant loosening is still an open question. Further improvement of clinical allergological diagnostics, better understanding of peri-implantar immune reactions, and interdisciplinary collection of epidemiological data concerning allergy to implants will contribute to a better knowledge about tolerance of implant material in humans.

  4. Prosthodontic management of implant therapy.

    PubMed

    Thalji, Ghadeer; Bryington, Matthew; De Kok, Ingeborg J; Cooper, Lyndon F

    2014-01-01

    Implant-supported dental restorations can be screw-retained, cement-retained, or a combination of both, whereby a metal superstructure is screwed to the implants and crowns are individually cemented to the metal frame. Each treatment modality has advantages and disadvantages. The use of computer-aided design/computer-assisted manufacture technologies for the manufacture of implant superstructures has proved to be advantageous in the quality of materials, precision of the milled superstructures, and passive fit. Maintenance and recall evaluations are an essential component of implant therapy. The longevity of implant restorations is limited by their biological and prosthetic maintenance requirements.

  5. Impression techniques for implant dentistry.

    PubMed

    Chee, W; Jivraj, S

    2006-10-07

    The object of making an impression in implant dentistry is to accurately relate an analogue of the implant or implant abutment to the other structures in the dental arch. This is affected by use of an impression coping which is attached to the implant or implant abutment. This impression coping is incorporated in an impression - much as a metal framework is 'picked up' in a remount impression for fixed prosthodontics. With implant copings the coping is usually attached to the implant or abutment with screws. The impression material used is usually an elastomeric impression material; the two types most widely used and shown to be the most appropriate are polyether and polyvinyl siloxane impression materials.

  6. Engineered porous metals for implants

    NASA Astrophysics Data System (ADS)

    Vamsi Krishna, B.; Xue, Weichang; Bose, Susmita; Bandyopadhyay, Amit

    2008-05-01

    Interest is significant in patient-specific implants with the possibility of guided tissue regeneration, particularly for load-bearing implants. For such implants to succeed, novel design approaches and fabrication technologies that can achieve balanced mechanical and functional performance in the implants are necessary. This article is focused on porous load-bearing implants with tailored micro-as well as macrostructures using laser-engineered net shaping (LENS™), a solid freeform fabrication or rapid prototyping technique that can be used to manufacture patient-specific implants. This review provides an insight into LENS, some properties of porous metals, and the potential applications of this process to fabricate unitized structures which can eliminate longstanding challenges in load-bearing implants to increase their in-vivo lifetime, such as in a total hip prosthesis.

  7. Piezosurgery in implant dentistry

    PubMed Central

    Stübinger, Stefan; Stricker, Andres; Berg, Britt-Isabelle

    2015-01-01

    Piezosurgery, or the use of piezoelectric devices, is being applied increasingly in oral and maxillofacial surgery. The main advantages of this technique are precise and selective cuttings, the avoidance of thermal damage, and the preservation of soft-tissue structures. Through the application of piezoelectric surgery, implant-site preparation, bone grafting, sinus-floor elevation, edentulous ridge splitting or the lateralization of the inferior alveolar nerve are very technically feasible. This clinical overview gives a short summary of the current literature and outlines the advantages and disadvantages of piezoelectric bone surgery in implant dentistry. Overall, piezoelectric surgery is superior to other methods that utilize mechanical instruments. Handling of delicate or compromised hard- and soft-tissue conditions can be performed with less risk for the patient. With respect to current and future innovative surgical concepts, piezoelectric surgery offers a wide range of new possibilities to perform customized and minimally invasive osteotomies. PMID:26635486

  8. Change in choroidal thickness after intravitreal aflibercept in pretreated and treatment-naive eyes for neovascular age-related macular degeneration

    PubMed Central

    Mazaraki, Kyriaki; Fassnacht-Riederle, Heidi; Blum, Robert; Becker, Matthias; Michels, Stephan

    2015-01-01

    Aim Evaluation of effects of intravitreal aflibercept therapy on choroidal thickness (CT) in neovascular age-related macular degeneration. Methods Retrospective cohort study evaluating the change in CT following a loading dose of three intravitreal aflibercept injections at 4 weeks interval. Pretreated and treatment-naive eyes as well as untreated fellow eyes were evaluated at five retinal locations (subfoveal, 300 and 2500 µm nasal and temporal to the fovea) using spectral domain optical coherence tomography prior to and 4 weeks after a loading dose of three intravitreal aflibercept injections. Results A total of 84 treated eyes (61 pretreated, 23 treatment naive) and 48 fellow eyes were enrolled into the study. Treatment-naive and pretreated eyes showed a significant reduction in CT at all retinal locations. The effect was more pronounced in treatment-naive eyes. In the pretreated group, the mean reduction in CT was greatest at 2500 µm temporal to the fovea at 10.7 µm compared with 22.4 at 300 µm nasal to the fovea in the treatment-naive group. Only the fellow eyes in the treatment-naive group showed a significant CT reduction 12 weeks after initiation of therapy to the partner eye. Conclusions Aflibercept induces a reduction in CT in treatment-naive and pretreated eyes with neovascular age-related macular degeneration. There is some evidence of a systemic effect of aflibercept reflected by CT reduction in untreated fellow eyes. PMID:25877895

  9. A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion

    PubMed Central

    Ip, Michael S.; Scott, Ingrid U.; VanVeldhuisen, Paul C.; Oden, Neal L.; Blodi, Barbara A.; Fisher, Marian; Singerman, Lawrence J.; Tolentino, Michael; Chan, Clement K.; Gonzalez, Victor H.

    2009-01-01

    Objective: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). Methods: Multicenter, randomized, clinical trial of 271 participants. Main Outcome Measure: Gain in visual acuity letter score of 15 or more from baseline to month 12. Results: Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR],5.0; 95% confidence interval [CI], 1.8-14.1; P=.001) and 5.0 times greater in 4-mg group than the observation group (OR,5.0; 95% CI, 1.8-14.4; P=.001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P=.97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. Conclusions: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice: Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. Trial Registration: clinicaltrials.gov Identifier: NCT00105027 PMID:19752419

  10. The breast implant controversy.

    PubMed

    Cook, R R; Harrison, M C; LeVier, R R

    1994-02-01

    The breast implant issue is a "bad news/good news" story. For many women with implants, the controversy has caused a fair degree of anxiety which may or may not be resolved as further information becomes available. It has also taken its toll on Dow Corning. Whole lines of medical products have been eliminated or are being phase out. The development of new medical applications has been terminated. As a consequence, employees have lost their jobs. What the effect will be on the biomedical industry as a whole remains to be seen (11). While silicones have been an important component in various medical devices, it is likely that other materials can be used as replacements. However, suppliers of non-silicone materials are also reevaluating their role in this market. For example, Du Pont, the nation's largest chemical company, has determined that the unpredictable and excessive costs of doing business with manufacturers of implantable medical devices no longer justifies the unrestricted sale of standard raw materials into this industry. Other companies are quietly following suit. On the up side, it is possible that the research being driven by this controversy will result in a greater understanding of the immunologic implications of xenobiotics, of the importance of nonbiased observations, of the need for ready access to valid data sets, and of the opportunity for valid scientific information to guide legal decisions. Only time will tell.

  11. [Neurotology and cochlear implants].

    PubMed

    Merchán, Miguel A

    2015-05-01

    In this review we analyse cochlear implantation in terms of the fundamental aspects of the functioning of the auditory system. Concepts concerning neuronal plasticity applied to electrical stimulation in perinatal and adult deep hypoacusis are reviewed, and the latest scientific bases that justify early implantation following screening for congenital deafness are discussed. Finally, this review aims to serve as an example of the importance of fostering the sub-specialty of neurotology in our milieu, with the aim of bridging some of the gaps between specialties and thus improving both the knowledge in the field of research on auditory pathologies and in the screening of patients. The objectives of this review, targeted above all towards specialists in the field of otorhinolaryngology, are to analyse some significant neurological foundations in order to reach a better understanding of the clinical events that condition the indications and the rehabilitation of patients with cochlear implants, as well as to use this means to foster the growth of the sub-specialty of neurotology.

  12. Electronic retinal implant surgery.

    PubMed

    MacLaren, R E

    2017-02-01

    Blindness due to outer retinal degeneration still remains largely untreatable. Photoreceptor loss removes light sensitivity, but the remaining inner retinal layers, the optic nerve, and indeed the physical structure of the eye itself may be unaffected by the degenerative processes. This provides the opportunity to restore some degree of vision with an electronic device in the subretinal space. In this lecture I will provide an overview of our experiences with the first-generation retinal implant Alpha IMS, developed by Retina Implant AG and based on the technology developed by Eberhart Zrenner as part of a multicentre clinical trial (NCT01024803). We are currently in the process of running a second NIHR-funded clinical trial to assess the next-generation device. The positive results from both studies to date indicate that the retinal implant should be included as a potential treatment for patients who are completely blind from retinitis pigmentosa. Evolution of the technology in future may provide further opportunities for earlier intervention or for other diseases.

  13. Tubo-uterine implantation.

    PubMed

    Green-armytage, V G

    1957-02-01

    After characterizing 2 types of patients presenting with tubal infertility (1 that is "as a rule overweight (the uterus is fixed (and there is easily palpable tubo-uterine pathology," and 1 that is "slim, young, intelligent and often beautiful", 12 1-sentence suggestions are made to increase the success of tubo-uterine implantations in the second type of presenting patient (because the first group has, in the author's mind, disappointing prognosis). Figures are the bulk of the document, with 3 figures demonstrating the type of operation, 3 showing the scheme of the operation, 1 figure showing a posterior view of the implanted tube in utero with a polyethylene prosthesis in situ down to the cervix, and 1 figure showing the instruments used in the operation. A few points of experience the author shares are: 1) operate immediately after a menstrual period; 2) give antibiotics prophylactically and after the procedure; 3) use a Bonney Myomectomy Clamp to elevate the uterus; 4) never use a knife or bistoury at the cornua; 5) use polyethylene rods, when available; and 6) caesarean section is the indicated delivery route after tubo-uterine implantation. Out of 38 patients with the requisite history and findings who have been operated on by this author, 14 have gone to full-term, i.e., 36.1%; 2 have aborted, giving a pregnancy rate of 42.2%, and there was 1 ectopic pregnancy.

  14. Bone Substitutes for Peri-Implant Defects of Postextraction Implants

    PubMed Central

    Santos, Pâmela Letícia; Gulinelli, Jéssica Lemos; Telles, Cristino da Silva; Betoni Júnior, Walter; Chiacchio Buchignani, Vivian; Queiroz, Thallita Pereira

    2013-01-01

    Placement of implants in fresh sockets is an alternative to try to reduce physiological resorption of alveolar ridge after tooth extraction. This surgery can be used to preserve the bone architecture and also accelerate the restorative procedure. However, the diastasis observed between bone and implant may influence osseointegration. So, autogenous bone graft and/or biomaterials have been used to fill this gap. Considering the importance of bone repair for treatment with implants placed immediately after tooth extraction, this study aimed to present a literature review about biomaterials surrounding immediate dental implants. The search included 56 articles published from 1969 to 2012. The results were based on data analysis and discussion. It was observed that implant fixation immediately after extraction is a reliable alternative to reduce the treatment length of prosthetic restoration. In general, the biomaterial should be used to increase bone/implant contact and enhance osseointegration. PMID:24454377

  15. [Choroidal metastasis from a lung adenocarcinoma treated by intravitreal injection of anti-VEGF and external beam radiotherapy: A case report].

    PubMed

    Menoux, I; Guihard, S; Antoni, D; Bijon, J-C; Noël, G

    2017-03-23

    Choroidal metastases of lung cancer are very uncommon. This localization should be suspected on blurred vision and confirmed with an ophthalmological examination. Its treatment is not entirely codified. We report a case of blurred vision secondary to bilateral choroidal metastasis in a patient with choroidal metastases from a lung adenocarcinoma, treated by intravitreal anti-vascular endothelial growth factor (VEGF) injection and external beam radiotherapy. According to a literature review, we analyzed the place of the targeted treatments used alone or combined with the radiotherapy.

  16. Intravitreal Bevacizumab Versus Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration: Findings from a Cochrane Systematic Review

    PubMed Central

    Solomon, Sharon D.; Lindsley, Kristina B.; Krzystolik, Magdalena G.; Vedula, Satyanarayana S.; Hawkins, Barbara S.

    2015-01-01

    Topic To summarize the relative effects of bevacizumab (Avastin®, Genentech, Inc.) and ranibizumab (Lucentis®, Genentech, Inc.), using findings from a Cochrane Eyes and Vision Group systematic review . Clinical relevance Neovascular age-related macular degeneration (NVAMD) is the most common cause of uncorrectable vision loss in the elderly in developed countries. Bevacizumab and ranibizumab are the most frequently-used anti-VEGF agents injected intravitreally to treat NVAMD Methods We included only randomized controlled trials (RCTs) in which the two anti-VEGF agents had been compared directly. The primary outcome was 1-year gain in best-corrected visual acuity (BCVA) of 15 or more logMAR letters. We followed Cochrane methods for trial selection, data extraction, and data analyses. Relative effects of bevacizumab versus ranibizumab are presented as estimated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Results We identified 6 eligible RCTs with 2809 participants. The proportion of eyes that gained 15 or more letters of BCVA by 1 year was similar for the two agents when the same regimens were compared: RR=0.90, 95% CI: 0.73 to 1.11. The mean change in BCVA from baseline also was similar: MD=−0.5 letter; 95% CI: −1.6 to +0.6. Other BCVA and quality-of-life outcomes were similar for the two agents. One-year treatment cost with ranibizumab was 5.1 and 25.5 times the cost for bevacizumab in the two largest trials. Ocular adverse events were uncommon (<1%); rates were similar for the two agents. Conclusions We found no important difference in effectiveness or safety between bevacizumab and ranibizumab for NVAMD treatment but a large cost difference. PMID:26477843

  17. The combination of phacoemulsification surgery and intravitreal triamcinolone injection in patients with cataract and diabetic macular edema

    PubMed Central

    Ozgur, Ozlen Rodop; Ozkurt, Yelda; Kulekci, Zeynep; Evciman, Tufan

    2015-01-01

    Purpose To assess the safety and efficiency of combined phacoemulsification (PHACO) surgery and intravitreal triamcinolone (IVTA) injection with or without macular grid laser photocoagulation in patients with cataract and diabetic macular edema. Material and methods This prospective study included 41 eyes of 36 diabetic patients with cataract and coexisting clinically significant macular edema (CSME). After PHACO and IVTA injection eyes were divided into two groups: the laser and IVTA group (Group 1) and only IVTA group (Group 2). Preoperative and postoperative best corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were recorded. Paired sample t-test was used to compare data in the groups and C square test for qualitative variables. Results Postoperative BCVA was significantly higher than the initial BCVA during the follow-up period in both groups (p < 0.01). The BCVA 6 months after surgery was significantly higher in group 1 than in group 2 (p < 0.01). There was no statistically significant difference in IOP between two groups preoperatively and postoperatively during the follow-up period (p > 0.05). There was no statistically significant difference between both groups in mean CMT preoperatively and 2nd week, 2nd month and 3rd month after surgery (p > 0.05). The mean CMT 6 months after surgery was statistically significantly lower in group 1 than in group 2 (p < 0.01). Conclusions PHACO surgery combined with IVTA injection improves BCVA and provides a decrease in CMT in diabetic patients with CSME. Additional macular grid laser photocoagulation after surgery helps to preserve this improvement in BCVA and decrease in CMT. PMID:26949356

  18. Development of an ultra high performance liquid chromatography method for determining triamcinolone acetonide in hydrogels using the design of experiments/design space strategy in combination with process capability index.

    PubMed

    Oliva, Alexis; Monzón, Cecilia; Santoveña, Ana; Fariña, José B; Llabrés, Matías

    2016-07-01

    An ultra high performance liquid chromatography method was developed and validated for the quantitation of triamcinolone acetonide in an injectable ophthalmic hydrogel to determine the contribution of analytical method error in the content uniformity measurement. During the development phase, the design of experiments/design space strategy was used. For this, the free R-program was used as a commercial software alternative, a fast efficient tool for data analysis. The process capability index was used to find the permitted level of variation for each factor and to define the design space. All these aspects were analyzed and discussed under different experimental conditions by the Monte Carlo simulation method. Second, a pre-study validation procedure was performed in accordance with the International Conference on Harmonization guidelines. The validated method was applied for the determination of uniformity of dosage units and the reasons for variability (inhomogeneity and the analytical method error) were analyzed based on the overall uncertainty.

  19. Comparison of the hypothalamic-pituitary-adrenal axis susceptibility upon single-dose i.m. depot versus long-acting i.v. triamcinolone acetonide therapy: a direct pharmacokinetic correlation.

    PubMed

    Abraham, Getu; Demiraj, Fioralba; Ungemach, Fritz Rupert

    2006-11-01

    The effects of single injections of glucocorticoid (GC) depot suspension and of long-acting GC were studied in conscious dogs. Both the depot suspension GC triamcinolone-16,17-alpha-acetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific time-dependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13-15 and > 120 nmol/l at 1 h respectively). Intravenous TAA-DHP reduced cortisol levels for 12 h, i.m. TAA reduced cortisol levels as of 1.5 h and the effect lasted for at least 4 weeks. Both treatments blunted the peak response to ACTH. ACTH elevated cortisol levels to or above baseline values within 10 days following TAA-DHP treatment, but the TAA treatment suppressed an ACTH response for at least 4 weeks. Kinetic analysis of both the preparations demonstrated rapid absorption (tmax, 0.6-1.5 h) and low maximum plasma concentrations (peak Cmax, 2.99-5.51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13.9 +/- 1.3 h) was very much shorter than that of TAA (125.9 +/- 15.8 h). In addition, the mean residence time differed very much (11 vs 160 h for TAA-DHP and TAA respectively), in line with a delayed elimination of the depot compared with the long-acting formulation. Application of these TAA formulations needs careful evaluation for their surprisingly different effects on endocrine stress axis activity.

  20. Graphene synthesis by ion implantation

    PubMed Central

    Garaj, Slaven; Hubbard, William; Golovchenko, J. A.

    2010-01-01

    We demonstrate an ion implantation method for large-scale synthesis of high quality graphene films with controllable thickness. Thermally annealing polycrystalline nickel substrates that have been ion implanted with carbon atoms results in the surface growth of graphene films whose average thickness is controlled by implantation dose. The graphene film quality, as probed with Raman and electrical measurements, is comparable to previously reported synthesis methods. The implantation synthesis method can be generalized to a variety of metallic substrates and growth temperatures, since it does not require a decomposition of chemical precursors or a solvation of carbon into the substrate. PMID:21124725

  1. Implant biomaterials: A comprehensive review

    PubMed Central

    Saini, Monika; Singh, Yashpal; Arora, Pooja; Arora, Vipin; Jain, Krati

    2015-01-01

    Appropriate selection of the implant biomaterial is a key factor for long term success of implants. The biologic environment does not accept completely any material so to optimize biologic performance, implants should be selected to reduce the negative biologic response while maintaining adequate function. Every clinician should always gain a thorough knowledge about the different biomaterials used for the dental implants. This article makes an effort to summarize various dental bio-materials which were used in the past and as well as the latest material used now. PMID:25610850

  2. Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres.

    PubMed

    Doty, Amy C; Hirota, Keiji; Olsen, Karl F; Sakamoto, Naoya; Ackermann, Rose; Feng, Meihua R; Wang, Yan; Choi, Stephanie; Qu, Wen; Schwendeman, Anna; Schwendeman, Steven P

    2016-12-01

    Here we describe development of a silicone rubber/stainless steel mesh cage implant system, much like that used to assess biocompatibility of biomaterials [1], for easy removal of injectable polymer microspheres in vivo. The sterile cage has a type 316 stainless steel mesh size (38 μm) large enough for cell penetration and free fluid flow in vivo but small enough for microsphere retention, and a silicone rubber shell for injection of the microspheres. Two model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist, leuprolide, were encapsulated in PLGA microspheres large enough (63-90 μm) to be restrained by the cage implant in vivo. The in vitro release from both formulations was followed by ultra-performance liquid chromatography (UPLC) with and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 + 0.05% sodium azide, at 37 °C. Pharmacokinetics (PK) in rats was assessed after SC injection or SC in-cage implantation of microspheres with plasma analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely unaffected after the initial burst irrespective of the cage or test tube incubation vessel and release was much slower than observed in vivo for both drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage were highly similar during the 2-3 week release duration before a significant inflammatory response was caused by the cage implant. Hence, the PK-validated cage implant provides a simple means to recover and evaluate the microsphere drug carriers in vivo during a time window of at least a few weeks in order to characterize the polymer microsphere release and erosion behavior in vivo. This approach may facilitate development of mechanism-based in vitro/in vivo correlations and enable development of more accurate and useful in vitro release tests.

  3. Implantable medical sensor system

    DOEpatents

    Darrow, Christopher B.; Satcher, Jr., Joe H.; Lane, Stephen M.; Lee, Abraham P.; Wang, Amy W.

    2001-01-01

    An implantable chemical sensor system for medical applications is described which permits selective recognition of an analyte using an expandable biocompatible sensor, such as a polymer, that undergoes a dimensional change in the presence of the analyte. The expandable polymer is incorporated into an electronic circuit component that changes its properties (e.g., frequency) when the polymer changes dimension. As the circuit changes its characteristics, an external interrogator transmits a signal transdermally to the transducer, and the concentration of the analyte is determined from the measured changes in the circuit. This invention may be used for minimally invasive monitoring of blood glucose levels in diabetic patients.

  4. Broad beam ion implanter

    DOEpatents

    Leung, K.N.

    1996-10-08

    An ion implantation device for creating a large diameter, homogeneous, ion beam is described, as well as a method for creating same, wherein the device is characterized by extraction of a diverging ion beam and its conversion by ion beam optics to an essentially parallel ion beam. The device comprises a plasma or ion source, an anode and exit aperture, an extraction electrode, a divergence-limiting electrode and an acceleration electrode, as well as the means for connecting a voltage supply to the electrodes. 6 figs.

  5. Broad beam ion implanter

    DOEpatents

    Leung, Ka-Ngo

    1996-01-01

    An ion implantation device for creating a large diameter, homogeneous, ion beam is described, as well as a method for creating same, wherein the device is characterized by extraction of a diverging ion beam and its conversion by ion beam optics to an essentially parallel ion beam. The device comprises a plasma or ion source, an anode and exit aperture, an extraction electrode, a divergence-limiting electrode and an acceleration electrode, as well as the means for connecting a voltage supply to the electrodes.

  6. Age at implantation and auditory memory in cochlear implanted children.

    PubMed

    Mikic, B; Miric, D; Nikolic-Mikic, M; Ostojic, S; Asanovic, M

    2014-05-01

    Early cochlear implantation, before the age of 3 years, provides the best outcome regarding listening, speech, cognition an memory due to maximal central nervous system plasticity. Intensive postoperative training improves not only auditory performance and language, but affects auditory memory as well. The aim of this study was to discover if the age at implantation affects auditory memory function in cochlear implanted children. A total of 50 cochlear implanted children aged 4 to 8 years were enrolled in this study: early implanted (1-3y) n = 27 and late implanted (4-6y) n = 23. Two types of memory tests were used: Immediate Verbal Memory Test and Forward and Backward Digit Span Test. Early implanted children performed better on both verbal and numeric tasks of auditory memory. The difference was statistically significant, especially on the complex tasks. Early cochlear implantation, before the age of 3 years, significantly improve auditory memory and contribute to better cognitive and education outcomes.

  7. Clinical outcomes of primary intraocular lymphoma patients treated with front-line systemic high-dose methotrexate and intravitreal methotrexate injection.

    PubMed

    Ma, Wei-Li; Hou, Hsin-An; Hsu, Ya-Jui; Chen, Yin-Kai; Tang, Jih-Luh; Tsay, Woei; Yeh, Po-Ting; Yang, Chung-May; Lin, Chang-Ping; Tien, Hwei-Fang

    2016-03-01

    A standard treatment for patients with primary intraocular lymphoma (PIOL) remains unclear. This study retrospectively analyzed the clinical features and outcomes of 19 patients with PIOL who were treated with a first-line therapy comprising combined intravenous high-dose methotrexate and intravitreal methotrexate between January 2003 and December 2013. Thirteen (68.4 %) patients were female, and the median age at diagnosis was 57 (39-77 years). Diagnoses were based on the identification of abnormal lymphoid cells in vitreous fluid. Ten (52.6 %) patients had bilateral eye involvement, and six had concurrent central nervous system (CNS) involvement. All 19 patients achieved complete remission (CR) as confirmed by cytological examination of vitreous and cerebrospinal fluid and brain imaging if CNS was involved. Patients with concurrent brain involvement required a longer time to achieve CR. However, the duration of complete remission did not differ between patients with and without CNS involvement. The 5-year overall survival rate was 55.8 % for the total cohort and was higher (68.8 %) in patients with isolated PIOL than in those with concurrent CNS involvement. In all patients, methotrexate treatment was well tolerated, with manageable side effects. We conclude that combined intravitreal methotrexate and systemic high-dose methotrexate treatment is effective in patients with PIOL.

  8. Human umbilical cord blood-derived mesenchymal stem cells do not differentiate into neural cell types or integrate into the retina after intravitreal grafting in neonatal rats.

    PubMed

    Hill, Andrew J; Zwart, Isabel; Tam, Henry H; Chan, Jane; Navarrete, Cristina; Jen, Ling-Sun; Navarrete, Roberto

    2009-04-01

    This study investigated the ability of mesenchymal stem cells (MSCs) derived from full-term human umbilical cord blood to survive, integrate and differentiate after intravitreal grafting to the degenerating neonatal rat retina following intracranial optic tract lesion. MSCs survived for 1 week in the absence of immunosuppression. When host animals were treated with cyclosporin A and dexamethasone to suppress inflammatory and immune responses, donor cells survived for at least 3 weeks, and were able to spread and cover the entire vitreal surface of the host retina. However, MSCs did not significantly integrate into or migrate through the retina. They also maintained their human antigenicity, and no indication of neural differentiation was observed in retinas where retinal ganglion cells either underwent severe degeneration or were lost. These results have provided the first in vivo evidence that MSCs derived from human umbilical cord blood can survive for a significant period of time when the host rat response is suppressed even for a short period. These results, together with the observation of a lack of neuronal differentiation and integration of MSCs after intravitreal grafting, has raised an important question as to the potential use of MSCs for neural repair through the replacement of lost neurons in the mammalian retina and central nervous system.

  9. [Implant rehabilitation of distal mandibular atrophy using a blade implant].

    PubMed

    Veron, C; Chanavaz, M

    1997-11-01

    After a brief revision of the anatomy of the posterior mandible and its natural resorption pattern, the ramus plate-form implant would be the implant of choice for the rehabilitation of this region. This "site specific" implant is inserted on the top of the crest and superficially impacted within the residual alveolar bone at the distal segment of the horizontal branch and guided to climb parallel to the anterior aspect of the ascending ramus. Its form and specific dimensions are perfectly compatible with the frequently limited quantity of available bone above the nerve canal in patients with advanced atrophy of the posterior mandible. It provides a predictable abutment for the implant-supported or dento-implant-supported prostheses of the posterior mandible.

  10. Implant Maintenance: A Clinical Update

    PubMed Central

    Gulati, Minkle; Govila, Vivek; Anand, Vishal; Anand, Bhargavi

    2014-01-01

    Introduction. The differences in the supporting structure of the implant make them more susceptible to inflammation and bone loss when plaque accumulates as compared to the teeth. Therefore, a comprehensive maintenance protocol should be followed to ensure the longevity of the implant. Material and Method. A research to provide scientific evidence supporting the feasibility of various implant care methods was carried out using various online resources to retrieve relevant studies published since 1985. Results. The electronic search yielded 708 titles, out of which a total of 42 articles were considered appropriate and finally included for the preparation of this review article. Discussion. A typical maintenance visit for patients with dental implants should last 1 hour and should be scheduled every 3 months to evaluate any changes in their oral and general history. It is essential to have a proper instrument selection to prevent damage to the implant surface and trauma to the peri-implant tissues. Conclusion. As the number of patients opting for dental implants is increasing, it becomes increasingly essential to know the differences between natural teeth and implant care and accept the challenges of maintaining these restorations. PMID:27437506

  11. Regenerative Surgical Treatment of Peri-implantitis

    ClinicalTrials.gov

    2016-08-31

    Failure of Dental Implant Due to Infection; Infection; Inflammation; Peri-implantitis; Bacterial Infections; Bleeding of Subgingival Space; Molecular Sequence Variation; Periodontal Diseases; Mouth Diseases

  12. Effect of prophylactic timolol 0.1% gel on intraocular pressure after an intravitreal injection of ranibizumab: a randomized study

    PubMed Central

    Pece, Alfredo; Allegrini, Davide; Montesano, Giovanni; Dimastrogiovanni, Andrea Fabio

    2016-01-01

    Purpose The purpose of this study is to make a prospective evaluation of the effect of timolol 0.1% eye gel on short-term intraocular pressure (IOP) after an intravitreal injection (IVI) of ranibizumab. Participants and methods One hundred and fifty eyes of 150 IVI-naïve patients with macular edema caused by various pathological conditions (age-related macular degeneration, central or branch retinal vein occlusion, and diabetic retinopathy) were scheduled to undergo an IVI of ranibizumab (0.5 mg/0.05 cc). The patients were randomly divided into three groups: 50 were not treated with timolol before the IVI (group 1); 50 received an instillation of timolol 0.1% eye gel the evening before the IVI (group 2); and 50 received an instillation of timolol 0.1% eye gel 2 hours before the IVI (group 3). The incidence of clinically significant intraocular hypertensive spikes (>25 mmHg and >40 mmHg) was then assessed. Results Our findings showed that mean IOP at baseline was significantly higher than at both 5 and 60 minutes after IVI (P<0.01). Spikes of >25 mmHg were recorded at either time in 27 patients (54%) in group 1, 23 patients (44%) in group 2, and 24 patients (48%) in group 3. None of the between-group differences were significant. Spikes of >40 mmHg (which were only detected 5 minutes after IVI) were recorded in nine (18%), eight (16%), and one patient (2%) in groups 1, 2, and 3, respectively. The only significant difference was between the control and group 3 (P=0.012). Conclusion An increase in IOP after antivascular endothelial growth factor IVI is a frequent complication. The prophylactic use of timolol 0.1% gel effectively reduced the mean IOP when administered 2 hours before IVI and was also effective in preventing dangerous IOP spikes of >40 mmHg. It is therefore recommended before IVIs as a means of preventing emergency procedures and preserving the health of the optic nerve. PMID:27382246

  13. Progestin implants for female contraception.

    PubMed

    Croxatt, Horacio B

    2002-01-01

    Four different implants, in the form of capsules or covered rods, that release one of the synthetic progestins levonorgestrel, etonogestrel, Nestorone, or Elcometrine and nomegestrol acetate were reviewed. Biocompatible polymers or copolymers of polydimethyl/polymethylvinyl-siloxanes or ethylvinylacetate are used to hold the steroid crystals and to control the rate of release. Once inserted under the skin, these implants release the corresponding steroid continuously over prolonged periods, a process that can be readily interrupted by implant removal. During long-term use of the implant, the released steroid circulates in blood at a fairly stable level. The physical characteristics of the implants, including drug contents and rate of release, serum levels of the progestin during use, and the duration of their effective life are described. Total steroid loads vary in the range of 50 mg to 216 mg; average release rates are in the range of 30-100 ug/day, and effective lives from 6 months to 7 years.

  14. Bimodal fitting or bilateral implantation?

    PubMed

    Ching, Teresa Y C; Massie, Robyn; Van Wanrooy, Emma; Rushbrooke, Emma; Psarros, Colleen

    2009-01-01

    This paper summarises findings from studies that evaluated the benefits of bimodal fitting (combining a hearing aid and a cochlear implant in opposite ears) or bilateral cochlear implantation, relative to unilateral implantation, for children (Ching et al., 2007). On average, the size of binaural speech intelligibility advantages due to redundancy and head shadow was similar for the two bilateral conditions. An added advantage of bimodal fitting was that the low-frequency cues provided by acoustic hearing complemented the high-frequency cues conveyed by electric hearing in perception of voice and music. Some children with bilateral cochlear implants were able to use spatial separation between speech and noise to improve speech perception in noise. This is possibly a combined effect of the directional microphones in their implant systems and their ability to use spatial cues. The evidence to date supports the provision of hearing in two ears as the standard of care.

  15. Cochlear implantation following cerebellar surgery.

    PubMed

    Saeed, Shahad; Mawman, Deborah; Green, Kevin

    2011-08-01

    Cochlear implantation in patients with known central nervous system conditions can result in wide-ranging outcomes. The aim of this study is to report two cases of cochlear implantation outcomes in patients with acquired cerebellar ataxia following cerebellar surgery. The first is a female implanted with the Nucleus 24 implant in September 2000 and the second is a male implanted with a MED-EL Sonata Flexsoft electro-acoustic stimulation in July 2009. Programming these patients resulted in significant non-auditory stimulation which resulted in less than optimum map fittings. The patients did not gain any open set speech perception benefit although both of them gained an awareness of sound with the device. However, patient 2 elected to become a non-user because of the limited benefit.

  16. Hydrogen Implants for Layer Exfoliation

    NASA Astrophysics Data System (ADS)

    Cherekdjian, S.; Couillard, J. G.; Wilcox, C.

    2011-01-01

    Researchers at Corning Incorporated have developed a process whereby single crystal silicon thin films are transferred onto a flat panel display glass substrate using hydrogen ion implantation. The energy of the implant controls the effective exfoliation thickness, agreeing well with SRIM calculations, while the hydrogen ion dose controls the size of the platelets formed. The ion dose was found to influence the final void defect count in exfoliated films. Finally, the ion beam and ion implant end-station cooling characteristics were investigated. These parameters control the effective implant heat load generated during ion beam processing. The temperature at which exfoliation occurs during an exfoliation heat cycle was found to be inversely proportional to the hydrogen ion dose when the temperature during ion implantation is <100 °C. The most sensitive exfoliation temperature to ion dose dependence was observed for cooler implants, i.e. <35 °C. Data indicates that at the minimum exfoliation dose the exfoliation temperature is reduced significantly by increasing the implant heat generated during ion beam processing. Higher hydrogen doses than the minimum required for exfoliation exhibit only a small exfoliation temperature variation with ion dose. By optimizing the implant heat load generated during ion beam processing it is observed that the efficiency of the exfoliation process is also enhanced. Implant temperatures of 150 to 160 °C were found to further reduce the minimum implant dose required for exfoliation by an additional 5%, as verified by calorimetric measurements. These results enable us to further conclude that hydrogen out-diffusion is not significant in this process.

  17. Late-onset Citrobacter koseri endophthalmitis with suture exposure after secondary intraocular lens implantation.

    PubMed

    Kang, Hae Min; Chung, Eun Jee

    2011-08-01

    A 54-year-old male patient was seen in clinic for ocular pain and decreased vision in the right eye with duration of two days. He underwent a cataract operation for his right eye 12 years ago, then a sclera-fixated secondary intraocular implantation and pars plana vitrectomy three years ago due to intraocular lens dislocation. At the initial visit, his visual acuity was restricted to the perception of hand motion. An edematous cornea, cells, flare with hypopyon, and exposed suture material at were observed at the six o'clock direction by slit lamp. Vitreous opacity was noted from B-scan ultrasonography. The patient was diagnosed with late-onset endophthalmitis and an intravitreal cocktail injection was done. On the next day, the hypopyon was aggravated, and therefore a pars plana vitrectomy was performed. A vitreous culture tested positive for Citrobacter koseri. After 12 weeks, the best corrected visual acuity of the right eye improved to 0.7 and a fundus examination revealed a relatively normal optic disc and retinal vasculature. We herein report the first case of endophthalmitis caused by Citrobacter koseri in Korea. Exposed suture material was suspected as the source of infection in this case and prompt surgical intervention resulted in a relatively good visual outcome.

  18. Tribological properties of nitrogen implanted and boron implanted steels

    SciTech Connect

    Kern, K.T.; Walter, K.C.; Griffin, A.J. Jr.; Kung, H.; Lu, Y.; Nastasi, M.; Tesmer, J.R.; Fayeulle, S.

    1996-06-01

    Samples of a steel with high chrome content was implanted separately with 75 keV nitrogen ions and with 75 keV boron ions. Implanted doses of each ion species were 2-, 4-, and 8 {times} 10{sup 17}/cm{sup 2}. Retained doses were measured using resonant non-Rutherford Backscattering Spectrometry. Tribological properties were determined using a pin-on-disk test with a 6-mm diameter ruby pin with a velocity of 0.94 m/min. Testing was done at 10% humidity with a load of 377 g. Wear rate and coefficient of friction were determined from these tests. While reduction in the wear rate for nitrogen implanted materials was observed, greater reduction (more than an order of magnitude) was observed for boron implanted materials. In addition, reduction in the coefficient of friction for high-dose boron implanted materials was observed. Nano-indentation revealed a hardened layer near the surface of the material. Results from grazing incidence x-ray diffraction suggest the formation of Fe{sub 2}N and Fe{sub 3}N in the nitrogen implanted materials and Fe{sub 3}B in the boron implanted materials. Results from transmission electron microscopy will be presented.

  19. Double valve Implantation

    PubMed Central

    Stassano, Paolo; Mannacio, Vito; Musumeci, Antonino; Golino, Alessandro; Maida, Piero; Ferrigno, Vincenzo; Buonocore, Gaetano; Spampinato, Nicola

    1991-01-01

    From January 1976 through December 1987, 194 patients with a mean age of 43.3 ± 13.7 years (range, 11 to 74 years) underwent double (mitral and aortic) replacement of native valves with 8 types of bioprostheses: Carpentier-Edwards, 127 valves; Hancock, 76 valves; Liotta-Bioimplant, 57 valves; Ionescu-Shiley, 53 valves; Vascor, 27 valves; Carpentier-Edwards Pericardial, 22 valves; Angell-Shiley, 20 valves; and Implamedic, 6 valves. Concomitant cardiac procedures were performed in 25 patients (12.8%). There were 18 operative deaths (9.27%). Our retrospective analysis was restricted to 352 bioprostheses implanted in the 176 patients who survived surgery and were considered at risk for valve tissue failure. The overall cumulative duration of follow-up was 1,174.1 patient-years (range, 1 to 13 years). The durations of follow-up for specific valves were: Carpentier-Edwards, 920.2 valve-years; Hancock, 383.8 valve-years; Liotta-Bioimplant, 310.2 valve-years; Ionescu-Shiley, 357.7 valve-years; Vascor, 131.2 valve-years; Carpentier-Edwards Pericardial, 52.0 valve-years; Angell-Shiley, 167.0 valve-years; and Implamedic, 31.0 valve-years. Thirty patients had thromboembolic a