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1.
Ophthalmologica ; 246(5-6): 306-313, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37769629

RESUMO

INTRODUCTION: To evaluate the effect of an intravitreal injection of bevacizumab at the time of rhegmatogenous retinal detachment (RRD) surgery, on postoperative proliferative vitreoretinopathy (PVR) in high-risk patients selected by laser flare photometry. METHODS: This single-center observational retrospective cohort study included 137 consecutive patients who underwent pars plana vitrectomy and gas tamponade for primary RRD with increased aqueous flare between July 2016 and June 2021. From June 2019, an intravitreal injection of bevacizumab was administered as an adjunct to RRD repair. Patients who underwent surgery before this time and who did not receive intravitreal bevacizumab served as controls. The main outcome was the rate of retinal redetachment due to PVR. RESULTS: The median flare value was 22.0 (16.5-36.5) pc/ms in the control group and 28.2 (19.7-41.0) pc/ms in the bevacizumab group (p = 0.063). Eyes treated with bevacizumab were more likely to have macula-off RRD (p = 0.003), grade B PVR (p = 0.038), and worse visual acuity (p = 0.004) than controls. The rate of PVR redetachment was significantly lower in the bevacizumab group (11.1%) than in the control (30.1%) (p = 0.012). This difference was more pronounced after adjusting for potential confounding factors (p = 0.005); the risk of developing PVR was 4.5-fold higher in controls (95% CI, 1.6-12.8). After adjustment, the final median visual acuity was also significantly higher in eyes treated with bevacizumab (p = 0.025). CONCLUSION: This pilot study provides preliminary evidence that bevacizumab may reduce the risk of PVR-related recurrent RRD and improve visual outcomes in high-risk patients selected by laser flare photometry.


Assuntos
Descolamento Retiniano , Vitreorretinopatia Proliferativa , Humanos , Bevacizumab , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/prevenção & controle , Estudos Retrospectivos , Injeções Intravítreas , Projetos Piloto , Descolamento Retiniano/cirurgia , Fotometria , Vitrectomia , Lasers
2.
Ophthalmic Res ; 66(1): 599-610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36754031

RESUMO

INTRODUCTION: The efficacy and influence of steroids for reducing the incidence of proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) surgery remain controversial. Systematic review and meta-analysis were conducted to explore the effect of steroids versus placebo on risk of PVR. METHODS: We searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials (RCTs), assessing the effect of steroid drugs as an adjunct for reducing the incidence of PVR after RRD surgery. This meta-analysis was performed using the random-effect model. Data were extracted by two reviewers independently; the quality of RCTs was assessed by the Cochrane risk-of-bias tool. We calculated risk ratio (RR) and the 95% confidence intervals (CIs) of all outcomes and plotted on forest plots. I2 accessed using the χ2 test was applied to quantify the degree of heterogeneity. RESULTS: Four RCTs involving 478 patients (478 eyes) are included in the meta-analysis. There was no significant difference in the incidence of PVR recurrence between steroid groups and control groups (RR: 0.87, 95% CI: 0.70-1.08, p = 0.19). However, the incidence of recurrent PVR was lower in the steroid group (RR: 0.67, 95% CI: 0.46-0.99, p = 0.04) than in the control group when only PVR grades A and B were taken into consideration. Besides, steroids could significantly reduce the incidence of macular edema after surgery (RR: 0.64, 95% CI: 0.47-0.88, p = 0.007). The steroid group and control group had comparable outcomes of retinal reattachment rate and reoperation rate after primary surgery. Additionally, there was no significant difference of the incidence of epiretinal membrane, and the incidence of surgery required by epiretinal membrane. CONCLUSION: This meta-analysis reveals that RRD surgery combined with steroid drugs administration could significantly reduce the recurrence in PVR grade A and B subgroup, as well as the incidence of macular edema after surgery.


Assuntos
Membrana Epirretiniana , Edema Macular , Descolamento Retiniano , Vitreorretinopatia Proliferativa , Humanos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Vitreorretinopatia Proliferativa/prevenção & controle , Membrana Epirretiniana/cirurgia , Edema Macular/cirurgia , Incidência , Esteroides/uso terapêutico , Retina , Vitrectomia/efeitos adversos
3.
Ophthalmology ; 129(10): 1129-1141, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35680097

RESUMO

PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD. DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis. PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry. METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy. MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon. RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified. CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.


Assuntos
Descolamento Retiniano , Vitreorretinopatia Proliferativa , Dalteparina/uso terapêutico , Método Duplo-Cego , Fluoruracila , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Descolamento Retiniano/cirurgia , Vitrectomia/efeitos adversos , Vitreorretinopatia Proliferativa/tratamento farmacológico , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/prevenção & controle
4.
Exp Eye Res ; 208: 108622, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022176

RESUMO

Connective tissue growth factor (CTGF) is released by retinal pigment epithelial (RPE) cells and detectable in proliferative membranes (PrMs). This experimental study was performed to investigate the mRNA and protein levels of both CTGF and vascular endothelial growth factor A (VEGF-A) in a rabbit model of proliferative vitreoretinopathy (PVR). In addition, the effects of a single intravitreal injection of the safe dose of anti-CTGF or bevacizumab as monotherapy and in combination were evaluated. PVR was induced in the right eye of albino rabbits by intravitreal injection of cultured adult human RPE cells. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot analysis of CTGF and VEGF-A were performed on whole eye tissue in the PVR model versus controls at different time points. In the next step, the PVR models were assigned to five groups. The monotherapy groups received a single intravitreal injection of 0.1 ml of anti-CTGF 100 µg/ml (final concentration of 6.6 µg/ml in the vitreous) or 0.03 ml of 25 mg/ml bevacizumab. In the combined group, the abovementioned amounts of anti-CTGF and bevacizumab were injected intravitreally from separate sites in one session. No antibody injection was performed in the control group. Intravitreal injection of 0.1 ml of control IgG (1 mg/ml of isotype matched) antibody was performed in the placebo group. After 2 weeks, histologic evaluation including, trichrome staining for collagen, immunostaining by anti-alpha-smooth muscle actin for myofibroblasts, and anti-collagen type-1 antibody on paraffin embedded anterior-posterior sections was done. In addition, fundus photography was performed for clinically equivalent PVR staging. Twenty-four hours following PVR induction, CTGF mRNA and protein levels increased five- and- three-fold compared to controls, respectively (P < 0.001). VEGF-A mRNA and protein levels decreased significantly after 72 h of PVR induction compared to controls (P < 0.05). Means of PrM thickness and myofibroblast cell counts significantly decreased in the anti-CTGF group (P < 0.001 and P < 0.05, respectively). The mean area of collagen type-1 fibers of PrM in the mono- and combination therapy groups that received intravitreal anti-CTGF was significantly reduced (P < 0.001); in addition, mild PVR (stage-1 and 2) formation occurred in comparison with moderate to severe PVR (stage-4 and higher) in other groups. In conclusion, we found that intravitreal injection of CTGF neutralizing antibody resulted in a reduction in PrM thickness, collagen fibers and myofibroblast density in the PVR model. CTGF inhibition may represent a potential therapeutic target for PVR.


Assuntos
Anticorpos Neutralizantes/administração & dosagem , Bevacizumab/administração & dosagem , Fator de Crescimento do Tecido Conjuntivo/administração & dosagem , Epitélio Pigmentado da Retina/efeitos dos fármacos , Vitreorretinopatia Proliferativa/prevenção & controle , Adulto , Inibidores da Angiogênese/administração & dosagem , Animais , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/imunologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Humanos , Imuno-Histoquímica , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Coelhos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/metabolismo
5.
Graefes Arch Clin Exp Ophthalmol ; 259(5): 1103-1111, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33417094

RESUMO

PURPOSE: Posterior ocular trauma and the subsequent fibrotic retinal complication termed proliferative vitreoretinopathy (PVR) are leading causes of blindness in children and young adults. A previous study suggested that changes occurring within the first month post-trauma can lead to development of PVR later. The aim of this study was to examine the effect of dasatinib, a tyrosine kinase inhibitor clinically used to treat chronic myeloid leukemia, on fibrotic changes occurring within the first month following ocular trauma. METHODS: A previously established swine ocular trauma model that mimics both contusion and penetrating injuries was used. Dasatinib was administered on days 4 and 18 post-trauma via intravitreal injection of either bolus solution or suspension of a sustained release system incorporated in biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Animals were followed up to day 32, and the development of traction full-thickness fold in the posterior retina was assessed. RESULTS: A full-thickness retinal fold extending from the wound site developed in 3 out of 4 control eyes injected with PLGA nanoparticles alone at 1 month. Administration of dasatinib solution had little preventative effect with 6 out of 7 eyes developing a fold. In contrast, dasatinib-incorporated PLGA nanoparticle injection significantly reduced the incidence of fold to 1 out of 10 eyes. CONCLUSIONS: Injection of dasatinib-incorporated PLGA significantly reduced early fibrotic retinal changes which eventually lead to PVR following posterior ocular trauma. Thus, our sustained dasatinib release system can potentially be used to both prevent and/or broaden the surgical treatment window for PVR.


Assuntos
Traumatismos Oculares , Vitreorretinopatia Proliferativa , Animais , Dasatinibe/uso terapêutico , Traumatismos Oculares/etiologia , Traumatismos Oculares/prevenção & controle , Injeções Intravítreas , Retina , Suínos , Vitreorretinopatia Proliferativa/tratamento farmacológico , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/prevenção & controle
6.
Ophthalmologe ; 118(1): 3-9, 2021 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-32666172

RESUMO

BACKGROUND: Proliferative vitreoretinopathy (PVR) is one of the most important complications following vitreoretinal surgery. So far, surgical strategies have been the gold standard in treatment. Pharmacological approaches for prevention and treatment of PVR are under clinical investigation and intervene in different phases of the PVR cascade. METHODS: The relevant literature as well as own data and experience with PVR are discussed in this review article. The most important aspects of pharmacological approaches for PVR prophylaxis and treatment are explained. RESULTS: A prophylactic use of systemic prednisone administration as an anti-inflammatory substance showed contradictory results, while there was no additional benefit for intravitreal triamcinolone. Orally administered isotretinoin also seems to be able to minimize the formation of PVR after retinal reattachment surgery, whereas there was no improvement in the success rate in established PVR. Cell proliferation inhibitors have already been extensively studied. The combined intravitreal prophylactic approach of 5­fluorouracil and low molecular weight heparin was recently further investigated in a multicenter, placebo-controlled study and showed a positive effect in some studies. New preclinical and experimental approaches include the inhibition of growth factors, modulation of integrin activity and the induction of apoptosis. CONCLUSION: Most clinical studies dealt with an anti-inflammatory or antiproliferative approach. So far, no pharmacological substance has been established for the treatment of PVR but there are promising approaches for prophylaxis.


Assuntos
Descolamento Retiniano , Cirurgia Vitreorretiniana , Vitreorretinopatia Proliferativa , Anti-Inflamatórios/uso terapêutico , Humanos , Descolamento Retiniano/cirurgia , Vitreorretinopatia Proliferativa/prevenção & controle , Vitreorretinopatia Proliferativa/cirurgia , Corpo Vítreo
7.
Eur J Ophthalmol ; 31(6): 3284-3293, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233948

RESUMO

PURPOSE: To evaluate the anatomic and visual outcomes of a new intraocular mitomycin c (MMC) application technique in the treatment of severe traumatic retinal detachment (RD) with advance proliferative vitreoretinopathy (PVR). METHODS: The records of 15 eyes of 14 patients who underwent vitreoretinal surgery and intraoperative MMC application were reviewed retrospectively. SURGICAL TECHNIQUE: After performing complicated vitreoretinal surgical procedures (Pars plana vitrectomy, PVR membrane stripping, large retinotomy/retinectomies and intraocular foreign body removal if found etc. . .) retina was attached with perfluorocarbon liquid (PFCL) and partial fluid-air exchange. Endolaser was performed. PFCL was removed to the posterior borders of retinochoroidal wounds, breaks or retinectomy sites. The remaining PFCL was enough to cover and prevent MMC contact with the posterior vital structures including optic disc, macula and underlying RPE and major vascular arcades. Ciliary epithelium and other anterior segment structures were protected from MMC contact with the use of air in the rest of the eye. Then, a 10 µg/mL concentrated MMC solution was carefully injected above the PFCL bubble until it covered PVR or potential areas of PVR development and removed after 60 s. Finally, the remaining PFCL was removed and all eyes were filled with silicone oil. The patients were followed at least 6 months after silicone oil removal. Visual and anatomic outcomes were determined during follow-up period. RESULTS: The mean follow-up time was 19.6 ± 6 months (range 12-27 months). About 100% retinal attachment was achieved with one vitreoretinal surgery during the follow-up period. PVR was not detected around the retinal breaks or retinotomy sites in any eye. Limited macular epiretinal membrane was detected in two eyes and subsequently peeled during silicone oil removal. Preoperative visual acuities were hand motions in seven eyes and light perception in eight eyes. Nine of 15 eyes had a visual acuity of ⩾0.1 during the follow-up period. The mean preoperative visual acuity was logMAR 2.16 ± 0.15 and postoperative visual acuity was 0.80 ± 0.50 (p = 0.001). There were no additional complications related to intraoperative MMC use during follow-up period. CONCLUSION: Temporary intraocular MMC use in vitreoretinal surgery yielded good anatomic and visual outcomes after the treatment of traumatic RDs with PVR or those with high risk of PVR development. Furthermore, MMC application appeared to prevent further PVR development after vitreoretinal surgery.


Assuntos
Descolamento Retiniano , Vitreorretinopatia Proliferativa , Seguimentos , Humanos , Mitomicina , Retina , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Óleos de Silicone , Vitrectomia , Vitreorretinopatia Proliferativa/tratamento farmacológico , Vitreorretinopatia Proliferativa/prevenção & controle , Vitreorretinopatia Proliferativa/cirurgia
8.
FASEB J ; 33(3): 3212-3224, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30383450

RESUMO

The major pathogenesis of proliferative vitreoretinopathy (PVR) is that retinal pigment epithelial (RPE) cells undergo epithelial-mesenchymal transition (EMT) because of disordered growth factors, such as TGF-ß, in the vitreous humor. Bone morphogenetic proteins (BMPs) are pluripotent growth factors. In this study, we identified the antifibrotic activity of BMP7 in a PVR model both in vivo and in vitro. BMP7 expression was confirmed on the PVR proliferative membranes. BMP7 was down-regulated in the PVR vitreous humor and TGF-ß-induced RPE cell EMT. In the in vivo studies, BMP7 injection attenuated PVR progression in the eyes of the rabbit model. Additionally, BMP7 treatment maintained RPE cell phenotypes and relieved TGF-ß2-induced EMT, migration, and gel contraction in vitro. BMP7 inhibited the TGF-ß2-induced up-regulation of fibronectin and α-smooth muscle actin and the down-regulation of E-cadherin and zona occludens-1 by balancing the TGF-ß2/Smad2/3 and BMP7/Smad1/5/9 pathways. These findings provide direct evidence of the ability of BMP7 in PVR inhibition and the potential of BMP7 for use in PVR therapeutic intervention.-Yao, H., Ge, T., Zhang, Y., Li, M., Yang, S., Li, H., Wang, F. BMP7 antagonizes proliferative vitreoretinopathy through retinal pigment epithelial fibrosis in vivo and in vitro.


Assuntos
Proteína Morfogenética Óssea 7/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Animais , Proteína Morfogenética Óssea 7/genética , Proteína Morfogenética Óssea 7/farmacologia , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Transição Epitelial-Mesenquimal , Fibrose , Técnicas de Silenciamento de Genes , Humanos , RNA Interferente Pequeno/genética , Coelhos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta2/metabolismo , Vitreorretinopatia Proliferativa/patologia , Vitreorretinopatia Proliferativa/prevenção & controle , Corpo Vítreo/metabolismo
9.
Br J Ophthalmol ; 103(9): 1306-1313, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30381390

RESUMO

PURPOSE: To examine the effect of low-dose, oral isotretinoin in lowering the risk of proliferative vitreoretinopathy (PVR) following rhegmatogenous retinal detachment (RRD) repair. METHODS: Prospective, open label, dual-cohort study with pathology-matched historical controls. The prospective experimental arms included two cohorts, composed of 51 eyes with recurrent PVR-related RRD and 58 eyes with primary RRD associated with high-risk features for developing PVR. Eyes in the experimental arms received 20 mg of isotretinoin by mouth once daily for 12 weeks starting the day after surgical repair. The primary outcome measure was single surgery anatomical success rate at 3 months following the study surgery. RESULTS: The single surgery anatomic success rate was 78.4% versus 70.0% (p=0.358) in eyes with recurrent PVR-related retinal detachment exposed to isotretinoin versus historical controls, respectively. In eyes with RRD at high risk for developing PVR, the single surgery success rate was 84.5% versus 61.1% (p=0.005) for eyes exposed to isotretinoin versus historical controls, respectively. For eyes enrolled in the experimental arms, the most common isotretinoin-related side effects were dry skin/mucus membranes in 106 patients (97.2%), abnormal sleep/dreams in 4 patients (3.7%) and fatigue in 3 patients (2.8%). CONCLUSION: The management and prevention of PVR is challenging and complex. At the dose and duration given in this study, oral istotretinoin may reduce the risk of PVR-associated recurrent retinal detachment in eyes with primary RRD at high risk of developing PVR.


Assuntos
Isotretinoína/administração & dosagem , Descolamento Retiniano/complicações , Vitreorretinopatia Proliferativa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Projetos Piloto , Estudos Prospectivos , Vitreorretinopatia Proliferativa/prevenção & controle
10.
Trials ; 19(1): 384, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012187

RESUMO

BACKGROUND: Proliferative vitreoretinopathy (PVR) is the major cause for postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). Adjunct pharmaceutical therapy was found to be ineffective once PVR is established. Preliminary data suggest that prevention of PVR yields better functional outcome. So far, there is no standard therapy to prevent PVR. METHODS/DESIGN: This is a randomized, double-blind, controlled, multicenter, interventional trial with one interim analysis. High-risk patients for PVR with primary RRD will be allocated equally to the following treatment arms: (a) verum: intraoperative adjuvant application of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH) via intraocular infusion during routine pars plana vitrectomy (PPV) and (b) placebo: routinely used intraocular infusion with balanced salt solution during routine PPV. PVR risk is assessed by non-invasive aqueous flare measurement by using laser flare photometry. The primary endpoint of the trial is the occurrence of PVR grade CP (C: full-thickness retinal folds or subretinal strands in clock hours; P: located posterior to equator) 1 or higher within 12 weeks after treatment. Secondary endpoints include PVR grade CA (A: located anterior to equator), best corrected visual acuity, number and extent of surgical procedures to achieve retinal re-attachment, and occurrence of drug-related adverse events within 12 weeks. It is assumed, on the basis of previously published results, that the incidence of PVR grade CP 1 is 35% in the control group and that a reduction by one third would be clinically relevant. Given the sequential design and adjustment for a dropout rate of 5%, a total sample size of 560 patients (280 per group) was calculated to ensure a power of 80% for the confirmatory analysis. DISCUSSION: The present trial uses intraoperative intravitreal 5-FU and LMWH as a prophylactic therapy in high-risk patients with primary RRD, aiming to reduce the incidence of PVR in the group that receives the trial drug. Using laser flare photometry to identify high-risk patients for PVR, this trial will test the effectiveness of a simple treatment to prevent PVR. TRIAL REGISTRATION: EudraCT no.: 2015-004731-12, registered October 21, 2015; ClinicalTrials.gov Identifier: NCT02834559 , registered July 12, 2016. Protocol version: Version 02. Date: September 18, 2016.


Assuntos
Fluoruracila/administração & dosagem , Heparina de Baixo Peso Molecular/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Descolamento Retiniano/cirurgia , Vitreorretinopatia Proliferativa/prevenção & controle , Interpretação Estatística de Dados , Método Duplo-Cego , Determinação de Ponto Final , Humanos , Injeções Intravítreas , Estudos Multicêntricos como Assunto , Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Tamanho da Amostra
11.
Clin Anat ; 31(1): 28-38, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28635048

RESUMO

With its incidence exceeding 60%, proliferative vitreoretinopathy (PVR) remains the most important pathology responsible for loss of vision, even the eyeball, after certain types of severe trauma. In this article, we present results obtained using our novel surgical technique, prophylactic chorioretinectomy (PCR), to prevent the development of PVR. Data on severely injured eyes at high risk for PVR [rupture, posterior laceration, deep-impact intraocular foreign body (IOFB) trauma, perforating injury] were collected prospectively. All eyes underwent vitrectomy (PPV) by PCR within 100 hr of the trauma. Eyes were excluded if they presented with endophthalmitis or if the reconstructive surgery was performed outside this time frame. Forty eyes of 40 consecutive patients were analyzed; full follow-up information was obtained for all of them. The injury was rupture in 27%, penetrating in 15%, (deep-impact) IOFB in 35%, and perforating in 23%. PPV-PCR was performed during primary (wound closure) surgery in 59% of cases. All eyes had at least minimal vitreous hemorrhage, and none had a true posterior vitreous detachment. At the time of PPV, 30% of the eyes had a retinal detachment. Sixteen percent developed PVR, but none from the site of the PCR procedure. In 20%, silicone oil remained in the eye at the last follow-up. The visual acuity improved in 93% of eyes and worsened in none; the improvement was mostly due to surgical clearing of the media opacity. In this subgroup of eyes with severe open-globe trauma, over 60% are expected to develop PVR. PPV/PCR performed within 100 hr reduced the PVR risk significantly, so currently it remains the best option for the surgeon. Clin. Anat. 31:28-38, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Corioide/cirurgia , Traumatismos Oculares/cirurgia , Procedimentos Cirúrgicos Profiláticos , Retina/cirurgia , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/prevenção & controle , Adolescente , Adulto , Idoso , Criança , Corpos Estranhos no Olho/cirurgia , Traumatismos Oculares/complicações , Ferimentos Oculares Penetrantes/cirurgia , Feminino , Humanos , Lacerações/cirurgia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos/métodos , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Risco , Ruptura/cirurgia , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
12.
Vestn Oftalmol ; 133(3): 51-57, 2017.
Artigo em Russo | MEDLINE | ID: mdl-28745657

RESUMO

AIM: to analyze the effect of internal limiting membrane (ILM) peeling in patients undergoing 23-gauge pars plana vitrectomy for the treatment of rhegmatogenous retinal detachment (RRD) with a high risk of proliferative vitreoretinopathy (PVR). MATERIAL AND METHODS: This was a prospective consecutive study of 231 eyes of 227 patients. All eyes underwent vitrectomy with silicone oil/gas tamponade for RRD with a high risk of PVR: in 42 eyes the ILM was peeled (group 1) and in the remaining 189 eyes - was not (group 2). The follow-up period was at least 3 months. RESULTS: In group 1, single-surgery anatomic success was achieved in 85.4% and definitive reattachment - in 95.2% of patients. In group 2, single-surgery anatomic success was achieved in 67.2% and definitive reattachment - in 89.4% of patients. None of the patients from group 1, who had their ILM peeled, developed epiretinal membrane. Final BCVA in groups 1 and 2 was 1.2±0.5 logMAR and 1.34±0.82 logMAR respectively (p=0.297). CONCLUSION: ILM peeling during vitrectomy in RRD patients at high risk of PVR provides high primary anatomic success rate.


Assuntos
Membrana Epirretiniana , Complicações Pós-Operatórias , Descolamento Retiniano/cirurgia , Vitrectomia/efeitos adversos , Vitreorretinopatia Proliferativa , Adulto , Membrana Epirretiniana/patologia , Membrana Epirretiniana/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Medição de Risco , Vitrectomia/métodos , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/prevenção & controle
13.
J Diabetes Complications ; 31(2): 456-461, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27469296

RESUMO

PURPOSE: The lack of physical activity, along with obesity, smoking, hypertension and hyperglycaemia are considered as risk factors for the occurrence of diseases such as diabetes. Primary objective of the study was to investigate potential correlation between physical activity and diabetic retinopathy. PATIENTS AND METHODS: Three hundred and twenty patients were included in the study: 240 patients with diabetes type 2 (80 patients with mild to moderate non-proliferative diabetic retinopathy, 80 patients with severe to very severe non-proliferative diabetic retinopathy and 80 ones with proliferative diabetic retinopathy) were compared with 80 non-diabetic patients (control group). Physical activity of patients was assessed by the international physical activity questionnaire (IPAQ, 2002). HbA1c and BMI were also measured in diabetic patients. Group comparisons were attempted for levels of physical activity and sedentary behavior. RESULTS: Total physical activity was decreased in patients with severe to very severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy as compared to patients with mild to moderate non-proliferative diabetic retinopathy and to the control group (p<0.05). Significant negative correlation was detected between HbA1c levels, BMI and physical activity (both p<0.05). Moreover, significant negative correlation between the severity of diabetic retinopathy and physical activity has been demonstrated (p<0.05). CONCLUSIONS: Increased physical activity is associated with less severe levels of diabetic retinopathy, independent of the effects of HbA1c and BMI.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Retinopatia Diabética/prevenção & controle , Exercício Físico , Cooperação do Paciente , Idoso , Terapia Combinada , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Inglaterra/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sedentário , Autorrelato , Índice de Gravidade de Doença , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/epidemiologia , Vitreorretinopatia Proliferativa/fisiopatologia , Vitreorretinopatia Proliferativa/prevenção & controle
14.
Mol Vis ; 23: 933-943, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29296073

RESUMO

Purpose: Proliferative vitreoretinopathy (PVR) is an inflammatory fibrotic disease resulting from the inflammatory milieu after retinal detachment, which can prevent retinal healing. This study aimed to elucidate the effect of substance P (SP) on retinal degeneration caused by retinal detachment in vivo and to examine the role of SP in the tumor necrosis factor-alpha (TNF-α)-induced epithelial-mesenchymal transition (EMT) of human RPE cells in vitro. Methods: PVR-like retinal damage was induced by intravitreally injecting dispase into mice, and SP was systemically injected twice a week for 3 weeks. Histological analysis and cytokine profile with enzyme-linked immunosorbent assay (ELISA) were performed. The direct effect of SP on induction of EMT in vitro was studied by adding SP to TNF-α-treated ARPE-19 cells and then evaluating the change in the characteristics of the epithelial and mesenchymal cells. Results: Dispase injection led to a PVR-like retinal condition, demonstrating an inflammatory response with disruption of RPE interaction within 1 week and severe destruction with enfolding within 3 weeks after the dispase injection. The inflammatory environment promoted apoptosis and migration of fibroblast-like cells in the retinal layer, which can cause fibrotic disease, such as PVR. However, SP treatment suppressed early inflammatory responses by reducing TNF-α and elevating interleukin-10 (IL-10), with cell death and the appearance of fibroblastic cells inhibited and the progression of retinal degeneration obviously delayed. Moreover, SP ameliorated TNF-α-induced EMT of the RPE and directly prevented fibrotic change in the RPE. Conclusions: This study revealed that SP can block apoptosis and EMT due to retinal inflammation and inhibit the development of PVR. This effect most likely occurred by modulating the secretion and action of TNF-α..


Assuntos
Neurotransmissores/uso terapêutico , Substância P/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Vitreorretinopatia Proliferativa/prevenção & controle , Actinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Movimento Celular , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia
15.
Trials ; 17(1): 339, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27449500

RESUMO

BACKGROUND: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Ocular injuries which result in visual loss invariably affect the posterior segment of the eye, and prevention of visual loss involves posterior segment (vitreoretinal) surgery. Despite improvements in vitreoretinal surgical techniques, outcomes in these patients remain unsatisfactory, and development of the intraocular scarring response proliferative vitreoretinopathy is the leading cause. Proliferative vitreoretinopathy is the most common cause of recurrent retinal detachment in these eyes; it is reported to occur in up to 45 % of cases. METHODS/DESIGN: The Adjunctive Steroid Combination in Ocular Trauma (ASCOT) trial is a multi-centre, double-masked, parallel-arm randomised controlled trial with an internal pilot designed to investigate the effectiveness and cost-effectiveness of using intravitreal and sub-Tenon's triamcinolone acetonide peri-operatively in patients undergoing vitrectomy following open globe trauma. In total, 300 eyes of 300 patients will be recruited and randomly allocated to one of two treatment groups. Both groups will receive standard surgical treatment and routine pre-operative and post-operative treatment and care. The treatment group will receive an adjunctive peri-operative steroid combination (triamcinolone acetonide) consisting of 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml into the sub-Tenon's space. The trial incorporates a two-stage internal pilot to examine projected recruitment and retention rates. Progression criteria from the internal pilot study will enable us to determine whether to undertake the main trial. Patients and primary outcome assessors will be masked to treatment allocation. The primary outcome will be an improvement from baseline to 6 months of at least 10 on the corrected visual acuity as measured by ETDRS letter score. Secondary outcomes will be development of scarring, retinal detachment, intraocular pressure abnormalities, quality of life and public sector service use. DISCUSSION: This is the first powered, controlled clinical trial to investigate the use of adjunctive triamcinolone in patients undergoing vitrectomy following open globe trauma. TRIAL REGISTRATION: EudraCT2014-002193-37 . Registered on 5 September 2014. ISRCTN30012492 . Registered on 5 September 2014.


Assuntos
Traumatismos Oculares/cirurgia , Glucocorticoides/administração & dosagem , Descolamento Retiniano/prevenção & controle , Triancinolona Acetonida/administração & dosagem , Cirurgia Vitreorretiniana/efeitos adversos , Vitreorretinopatia Proliferativa/prevenção & controle , Administração Oftálmica , Quimioterapia Adjuvante , Protocolos Clínicos , Análise Custo-Benefício , Método Duplo-Cego , Custos de Medicamentos , Traumatismos Oculares/economia , Traumatismos Oculares/fisiopatologia , Glucocorticoides/efeitos adversos , Glucocorticoides/economia , Custos Hospitalares , Humanos , Projetos Piloto , Projetos de Pesquisa , Descolamento Retiniano/economia , Descolamento Retiniano/etiologia , Descolamento Retiniano/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos , Triancinolona Acetonida/economia , Reino Unido , Visão Ocular , Cirurgia Vitreorretiniana/economia , Vitreorretinopatia Proliferativa/economia , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/fisiopatologia
16.
Invest Ophthalmol Vis Sci ; 57(8): 3935-43, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27472081

RESUMO

PURPOSE: Previous studies have shown that vitreous stimulates degradation of the tumor suppressor protein p53 and that knockdown of phosphatidylinositol 5-phosphate 4-kinases (PI5P4Kα and -ß) abrogates proliferation of p53-deficient cells. The purpose of this study was to determine whether vitreous stimulated expression of PI5P4Kα and -ß and whether suppression of PI5P4Kα and -ß would inhibit vitreous-induced cellular responses and experimental proliferative vitreoretinopathy (PVR). METHODS: PI5P4Kα and -ß encoded by PIP4K2A and 2B, respectively, in human ARPE-19 cells were knocked down by stably expressing short hairpin (sh)RNA directed at human PIP4K2A and -2B. In addition, we rescued expression of PI5P4Kα and -ß by re-expressing mouse PIP4K2A and -2B in the PI5P4Kα and -ß knocked-down ARPE-19 cells. Expression of PI5P4Kα and -ß was determined by Western blot and immunofluorescence. The following cellular responses were monitored: cell proliferation, survival, migration, and contraction. Moreover, the cell potential of inducing PVR was examined in a rabbit model of PVR effected by intravitreal cell injection. RESULTS: We found that vitreous enhanced expression of PI5P4Kα and -ß in RPE cells and that knocking down PI5P4Kα and -ß abrogated vitreous-stimulated cell proliferation, survival, migration, and contraction. Re-expression of mouse PIP4Kα and -ß in the human PI5P4Kα and -ß knocked-down cells recovered the loss of vitreous-induced cell contraction. Importantly, suppression of PI5P4Kα and -ß abrogated the pathogenesis of PVR induced by intravitreal cell injection in rabbits. Moreover, we revealed that expression of PI5P4Kα and -ß was abundant in epiretinal membranes from PVR grade C patients. CONCLUSIONS: The findings from this study indicate that PI5P4Kα and -ß could be novel therapeutic targets for the treatment of PVR.


Assuntos
Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Vitreorretinopatia Proliferativa/prevenção & controle , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Knockout , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/deficiência , Coelhos , Descolamento Retiniano/prevenção & controle , Vitreorretinopatia Proliferativa/etiologia , Corpo Vítreo/metabolismo
17.
Curr Pharm Des ; 21(32): 4698-702, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26350528

RESUMO

Proliferative vitreoretinopathy (PVR) can occur in eyes with rhegmatogenous retinal detachment (RRD) or after RRD surgery, and it is the most common cause of failure of this surgery, accounting for about 75% of all primary failures. Complex biological pathways induce PVR development, with growth factors and cytokines from the vitreous and from the serum (as a result of the breakdown of the blood-retinal barrier) stimulating RPE and Muller cells transformation and proliferation, and membrane formation and contraction. Identification of pre-operative risk factors, recognition of the early signs of PVR, use of adequate surgical techniques and of pharmacological therapy can reduce the PRV incidence. Steroids can influence the inflammatory and proliferative components of PVR, by reducing the breakdown of the blood-retinal barrier, and the proliferation of Müller cell and of RPE cells. Some new formulation of intravitreal steroids are promising tool for the prevention of the PVR formation in eyes treated by vitreoretinal surgery.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Descolamento Retiniano/cirurgia , Triancinolona Acetonida/uso terapêutico , Vitreorretinopatia Proliferativa/prevenção & controle , Anti-Inflamatórios/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Dexametasona/administração & dosagem , Humanos , Injeções Intravítreas , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Fatores de Risco , Triancinolona Acetonida/administração & dosagem , Vitreorretinopatia Proliferativa/etiologia , Vitreorretinopatia Proliferativa/patologia
18.
Drug Des Devel Ther ; 9: 1393-400, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25834397

RESUMO

BACKGROUND: This meta-analysis was performed to determine the effectiveness of steroids as an adjunct following rhegmatogenous retinal detachment (RRD) surgery. METHODS: RRD patients with or without proliferative vitreoretinopathy (PVR) were included. The treatment group included patients in whom steroids were used as an adjunct and a control group in which placebo was used. Only randomized controlled trials were included. We searched the main electronic databases and included studies published until July 2014. PVR odds ratio, visual acuity, retinal reattachment rate, and complications were evaluated in three trials. RESULTS: Three randomized controlled trials were included in the meta-analysis. There was no significant difference in the incidence of postoperative PVR between groups (heterogeneity I (2)=48%, P=0.14). However, the incidence of postoperative PVR was lower in the treatment group (I (2)=0%, P<0.0001) than in the control group when a PVR grade C study was excluded. There was no statistically significant difference in postoperative visual acuity between the treatment and control groups (odds ratio -0.18; 95% confidence interval -0.38, 0.02; P=0.08). The two groups had similar results for primary/final retinal reattachment and reoperation rate. There was no significant difference in postoperative intraocular pressure. CONCLUSION: This systematic review demonstrates that steroids may significantly reduce the incidence of postoperative PVR grade B or lower following RRD surgery.


Assuntos
Descolamento Retiniano/complicações , Descolamento Retiniano/cirurgia , Esteroides/farmacologia , Vitreorretinopatia Proliferativa/complicações , Vitreorretinopatia Proliferativa/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Esteroides/administração & dosagem , Esteroides/uso terapêutico
19.
BMC Ophthalmol ; 14: 144, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25421815

RESUMO

BACKGROUND: P21 is one kind of cyclin-dependent kinase inhibitor that can prevent cells from going through the G1/S phase checkpoint and inhibit cell proliferation. Proliferative vitreoretinopathy (PVR) is a proliferative response in the eye. The aim of this study was to determine whether p21Waf1/Cip1 (p21) suppresses the proliferation and migration of retinal pigment epithelial (RPE) cells in vitro and controls PVR development in vivo. METHODS: Cell cycle analyses and transwell assays were conducted to assess cell proliferation characteristics and the migration ability of RPE cells after transfection with p21. Western blot and reverse-transcription polymerase chain reaction technologies were used to detect the expression of p21, CDK2 and cyclinE in RPE cells and rabbit retinal tissues. The impact of increasing p21 expression on PVR development was conducted by implantation of an adenovirus vector containing rabbit p21 (rAd-p21) in a PVR rabbit model. The prevalence of PVR and retinal detachment was determined by indirect ophthalmoscopy on days 3, 7, 14, and 21 after the injection of rAd-p21 into the vitreous. B scans and hematoxylin-eosin staining were employed to check rabbit retinas on day 21. RESULTS: Cell cycle analyses and transwell assays showed that p21 inhibited the proliferation and migration of RPE cells. Increased expression of p21 was detected in cultured RPE cells and rabbit retinas after transfection with the p21 gene, whereas levels of CDK2 and cyclinE were decreased. The increase in p21 expression effectively suppressed the development of PVR in a rabbit model. CONCLUSIONS: The increase in p21 expression in RPE cells not only inhibits the proliferation and migration of RPE cells in vitro, but also suppresses the development of PVR in vivo, which indicates its therapeutic potential in treating PVR.


Assuntos
Ciclina E/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Inibidor de Quinase Dependente de Ciclina p21/fisiologia , Modelos Animais de Doenças , Epitélio Pigmentado da Retina/patologia , Vitreorretinopatia Proliferativa/prevenção & controle , Adenoviridae/genética , Animais , Western Blotting , Ciclo Celular , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Progressão da Doença , Citometria de Fluxo , Vetores Genéticos , Humanos , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/patologia
20.
Am J Pathol ; 184(11): 3052-68, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25261788

RESUMO

Proliferative vitreoretinopathy (PVR) is a nonneovascular blinding disease and the leading cause for failure in surgical repair of rhegmatogenous retinal detachments. Once formed, PVR is difficult to treat. Hence, there is an acute interest in developing approaches to prevent PVR. Of the many growth factors and cytokines that accumulate in vitreous as PVR develops, neutralizing vascular endothelial growth factor (VEGF) A has recently been found to prevent PVR in at least one animal model. The goal of this study was to test if Food and Drug Administration-approved agents could protect the eye from PVR in multiple animal models and to further investigate the underlying mechanisms. Neutralizing VEGF with aflibercept (VEGF Trap-Eye) safely and effectively protected rabbits from PVR in multiple models of disease. Furthermore, aflibercept reduced the bioactivity of both experimental and clinical PVR vitreous. Finally, although VEGF could promote some PVR-associated cellular responses via VEGF receptors expressed on the retinal pigment epithelial cells that drive this disease, VEGF's major contribution to vitreal bioactivity occurred via platelet-derived growth factor receptor α. Thus, VEGF promotes PVR by a noncanonical ability to engage platelet-derived growth factor receptor α. These findings indicate that VEGF contributes to nonangiogenic diseases and that anti-VEGF-based therapies may be effective on a wider spectrum of diseases than previously appreciated.


Assuntos
Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Vitreorretinopatia Proliferativa/prevenção & controle , Animais , Modelos Animais de Doenças , Coelhos , Transdução de Sinais/fisiologia
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