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Slit-lamp biomicroscopy photograph showing a retinal detachment behind the crystalline lens associated with a superotemporal horseshoe tear.
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Proliferative vitreoretinopathy is a disease process that follows the proliferation of ectopic cell sheets in the vitreous and/or periretinal area, causing periretinal membrane formation and traction, in patients with rhegmatogenous retinal detachments. Currently, vitreous surgery is the standard treatment; however, the results aren't satisfactory...
Context in source publication
Context 1
... is characterized by migration and proliferation of cells following a break in the retina or trauma (Figure 1), leading to formation of membranes in the periretinal area, followed by contraction of the cellular membranes and traction on the retina that causes RD ( Figure 2). It is analogous to a dynamic wound-healing process following tissue injury (the retinal break and/or ocular trauma being the insult in this case) that includes inflammation, proliferation, and modulation of scar that can either go through normal ocular wound healing with tissue remodeling and repair or can take an abnormal path with protracted wound healing, for which the mechanism is not yet fully understood. ...
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Citations
... The formation of fibrotic membranes in PVR leads to retina wrinkle and tractive retinal detachment, which results in a loss of visual acuity and even blindness (Idrees et al. 2019). Vitreoretinal surgery remains the primary therapeutic approach for PVR; however, the recurrence rate following surgical repair is high, resulting in a poor prognosis (Sadaka and Giuliari 2012). Currently, the exploration of effective drug adjuvant therapy has emerged as a prominent research topic for PVR. ...
The formation of the epiretinal fibrotic membrane by retinal pigment epithelial (RPE) cells is a primary pathological change for proliferative vitreoretinopathy (PVR). Bone morphogenetic protein 6 (BMP6) is an antifibrogenic factor in various cells. To date, it is still unknown whether BMP6 can interfere with the fibrogenesis of RPE cells during the progression of PVR. This work aimed to address the relationship between BMP6 and transforming growth factor-β2 (TGF-β2)-elicited fibrogenesis of RPE cells, an experimental model for studying PVR in vitro. The BMP6 level was down-regulated, while the TGF-β2 level was up-regulated in the vitreous humor of PVR patients. The BMP6 level was down-regulated in human RPE cells challenged with TGF-β2. The treatment of RPE cells with TGF-β2 resulted in significant increases in proliferation, migration, epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodelling. These effects were found to be inhibited by the overexpression of BMP6 or exacerbated by the knockdown of BMP6. BMP6 overexpression reduced the phosphorylation of p38 and JNK in TGF-β2-stimulated RPE cells, while BMP6 knockdown showed the opposite effects. The inhibition of p38 or JNK partially reversed the BMP6-silencing-induced promoting effects on TGF-β2-elicited fibrogenesis in RPE cells. Taken together, BMP6 demonstrates the ability to counteract the proliferation, migration, EMT, and ECM remodelling of RPE cells induced by TGF-β2. This is achieved through the regulation of the p38 and JNK MAPK pathways. These findings imply a potential connection between BMP6 and PVR, and highlight the potential application of BMP6 in therapeutic interventions for PVR.
... The incidence of PVR progression after vitrectomy for rhegmatogenous retinal detachment is estimated to be approximately 10% [1][2][3]. In addition, the success rate of treatment for PVR is far lower than that for noncomplicated rhegmatogenous retinal detachment [2,[4][5][6]. Therefore, novel strategies are required to prevent PVR following vitrectomy. ...
This study investigated the effect of anti-autotaxin (ATX) aptamers on the development of proliferative vitreoretinopathy (PVR) in both in vivo and in vitro PVR swine models. For the in vitro study, primary retinal pigment epithelial (RPE) cells were obtained from porcine eyes and cultured for cell proliferation and migration assays. For the in vivo study, a swine PVR model was established by inducing retinal detachment and injecting cultured RPE cells (2.0 × 106). Concurrently, 1 week after RPE cell injection, the anti-ATX aptamer, RBM-006 (10 mg/mL, 0.1 mL), was injected twice into the vitreous cavity. Post-injection effects of the anti-ATX aptamer on PVR development in the in vivo swine PVR model were investigated. For the in vitro evaluation, the cultured RPE cell proliferation and migration were significantly reduced at anti-ATX aptamer concentrations of 0.5–0.05 mg and at only 0.5 mg, respectively. Intravitreal administration of the anti-ATX aptamer also prevented tractional retinal detachment caused by PVR in the in vivo PVR model. We observed that the anti-ATX aptamer, RBM-006, inhibited PVR-related RPE cell proliferation and migration in vitro and inhibited the progression of PVR in the in vivo model, suggesting that the anti-ATX aptamer may be effective in preventing PVR.
... Для повышения функциональных и анатомических результатов высокотехнологичного хирургического лечения ТОС, развивающейся в результате пролиферативного посттравматического процесса как исхода двух различных патологических состояний (ПВР и швартообразования), необходимо учитывать комплекс посттравматических повреждений оболочек глаза, которые и определяют активность пролиферации. Персонализированный подход к хирургическому лечению в зависимости от вида травмы и массивности повреждений должен сопровождаться использованием патогенетически ориентированного медикаментозного лечения, использование которого тормозило бы пролиферацию и являлось профилактикой развития репролиферации после операции [11,12]. ...
Purpose . To evaluate the possibility of predicting the anatomical and functional results of surgical treatment of traumatic retinal detachment (RD) in trauma of various geneses, taking into account the clinical picture and the severity of the proliferative syndrome based on large clinical data. Materials and methods . A comprehensive analysis of the clinical picture (using 22 features) and long-term results of surgical treatment of 427 patients with traction traumatic RD (TRD) after open and closed eye injury was carried out. The patients were divided into 7 groups depending on the mechanism of injury. The observation period was 5 years. Results . The most severe proliferative syndrome was observed in TRD after an open injury: OEI A (contusions with scleral rupture), OEI D (double puncture wound) and OEI E (explosive trauma with scleral rupture), when both the process of mooring and PVR are present, as well as with CEI A (contusion) in the event that after the first operation PVR continued to progress. We found a direct dependence of PVR activity in TRD on the area of the detached retina and the presence of a traumatic cataract, and the inverse dependence on the presence of intraocular foreign body (IFB), its size and the ability of IFB to cause metallosis. A direct dependence of long-term functional results of treatment on the PVR stage, the area of detached retina and the diagnosed retinal rupture during the first vitreoretinal surgical intervention was established. Conclusion . In order to make the surgical treatment of TRD more effective, it is worth using antiproliferative drugs intravitreally during vitreoretinal surgery, especially in OEI A, OEI D and OGI E, when the proliferative syndrome is caused both by PVR and mooring, as well as in CEI A in the case of a pronounced PVR stage.
... Only 10 to 40% of retinal detachments with PVR result in anatomic success, despite repeated surgery attempts [6,7]. In addition, only 40 to 80% of patients who achieve anatomic success achieve so-called "ambulatory vision", meaning vision that is good enough to see large objects at close range [6]. ...
... The postoperative risk factors include uveitis, intraocular hemorrhage after surgery, choroidal detachment, multiple surgical procedures, persistent traction on retinal tears, and air tamponade [5,7,8]. ...
Proliferative vitreoretinopathy (PVR) remains the main cause of failure after retinal detachment (RD) surgery. Despite the development of modern technologies and sophisticated techniques for the management of RD, the growth of fibrocellular membranes within the vitreous cavity and on both sides of the retinal surface, as well as intraretinal fibrosis, can compromise surgical outcomes. Since 1983, when the term PVR was coined by the Retina Society, a lot of knowledge has been obtained about the physiopathology and risk factors of PVR, but, despite the proposal of a lot of therapeutic challenges, surgical skills seem to be the only effective way to manage PVR complications.
... Proliferative vitreoretinopathy (PVR) is the abnormal process of vision damage due to scarring that occurs as a complication after treatment for rhegmatogenous retinal detachment [1][2][3]. The incidence of PVR after surgery is approximately 5%-10% and is also the major cause of surgical failure [4]. Retinal pigment epithelial (RPE) cells are highly polarized and terminally differentiated cells that perform various biological functions, including serving as ion channels, absorbing scattered light, and providing barrier activity [5]. ...
Background:
The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is the most crucial step in the etiopathogenesis of proliferative vitreoretinopathy. This study aimed to investigate the role of miR-143-5p in the EMT of RPE cells induced by palmitic acid (PA).
Methods:
ARPE-19 cells were treated with PA to induce EMT, followed by E-cadherin and α-smooth muscle actin (α-SMA) expression and the microRNA expression profile analyses. Subsequently, miR-143-5p mimics/inhibitors, and plasmids expressing its predicted target gene c-JUN-dimerization protein 2 (JDP2), were transfected in ARPE-19 cells using lipofectamine 3000, and followed by PA treatment. Their impacts on EMT were explored using wound healing and Western blot assays. Additionally, miR-143-5p mimics and JDP2-expressing plasmid were co-transfected into ARPE-19 cells and treated with PA to explore whether PA induced EMT of ARPE-19 cells via the miR-143-5p/JDP2 axis.
Results:
PA decreased E-cadherin expression and increased those of α-SMA and miR-143-5p. Inhibiting miR-143-5p suppressed the migration of ARPE-19 cells and altered the expressions of E-cadherin and α-SMA. However, additional PA treatment attenuated these alterations. JDP2 was a target of miR-143-5p. Overexpression of JDP2 inhibited the EMT of ARPE-19 cells, resulting in α-SMA downregulation and E-cadherin upregulation, which were reversed by additional PA treatment via inhibiting JDP2 expression. Overexpression of miR-143-5p reversed the effect of JDP2 on the EMT of ARPE-19 cells and additional PA treatment markedly enhanced the effect of miR-143-5p mimics.
Conclusion:
PA promotes EMT of ARPE-19 cells via regulating the miR-143-5p/JDP2 axis, and these findings provide significant insights into the potential targeting of this axis to treat proliferative vitreoretinopathy.
... Remnant vitreous will always lead to an incomplete tamponade. 44 U. Spandau et al. Is there an association between macula off detachments and visual acuity within the first two weeks? ...
... For instance, because the Retina Society Committee defined PVR as a "proliferative disease," many treatments based on the inhibition of cell proliferation were developed for more than 20 years, none of which appears to have produced a significant clinical advance. Therefore, a review of both the classification and the pathogenesis of PVR appears to be appropriate to aid the development of new treatments [2,43,44]. This use of different and non-normalized classifications creates severe communication problems between clinicians and comparison of different studies became problematic or even impossible. ...
Proliferative vitreoretinopathy (PVR) is a term adopted in 1983 for describing a complication occurring after some retinal detachments (RD). Pathogenesis, in the original description, was focused on the formation of membranes on both surfaces of the retina, but more recently, the existence of intra-retinal changes has been added as the more severe form of PVR. Two problems have persisted ever since. The failure of prophylaxis measures, and the absence of a classification that really reflects the activity and severity of the process and is easily usable in the clinic. Our group has added to the original concept the role of genetics (and therefore the ability to predict its appearance) and the existence of intraretinal PVR, as an original contribution.
... Remnant vitreous will always lead to an incomplete tamponade. 44 U. Spandau et al. Is there an association between macula off detachments and visual acuity within the first two weeks? ...
... For instance, because the Retina Society Committee defined PVR as a "proliferative disease," many treatments based on the inhibition of cell proliferation were developed for more than 20 years, none of which appears to have produced a significant clinical advance. Therefore, a review of both the classification and the pathogenesis of PVR appears to be appropriate to aid the development of new treatments [2,43,44]. This use of different and non-normalized classifications creates severe communication problems between clinicians and comparison of different studies became problematic or even impossible. ...
In this chapter special surgical techniques for PVR detachment are described step-by-step: Staining of peripheral membranes, removal of subretinal membranes and 180° retinotomy.
... Conversely, negatively regulating Smad2/3 activity would inhibit these processes. For example, in RPE, inhibiting Smad2/3 signaling hampered the migration and proliferation of RPE and alleviated PVR progression [46]. Inhibited phospho-Smad2/3 by overexpressing Smad7 suppressed migration, proliferation and fibrogenic responses in RPE after retinal detachment in a mice model. ...
Background
Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration.
Results
Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway.
Conclusion
In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.
... Proliferative vitreoretinopathy (PVR) is characterised by fibrocellular membrane formation and intraocular fibrosis and is the major cause of recurrent retinal detachment in 5-10% of patients with rhegmatogenous retinal detachment (RRD). [1][2][3] With time, the progression of the epiretinal and subretinal fibrocellular membranes leads to converting a RRD to tractional retinal detachment and causes blindness. 4 Patients with penetrating ocular trauma, large and multiple retinal breaks, choroidal detachment, and intensive laser treatment during the first surgery are at a higher risk for developing PVR. ...
Clinical relevance
Proliferative vitreoretinopathy (PVR) is still the leading cause of surgical failure after rhegmatogenous retinal detachment (RRD) repair. The factors that can predict the development of PVR remain to be elucidated.
Background
This study evaluates the predictive values of the systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with primary RRD with and without PVR.
Methods
A total of 150 patients with RRD and 51 age- and sex-matched healthy participants were included in the study. Patients who developed PVR within three months after surgery were enrolled as PVR cases (n = 75, Group 1), and those who did not develop PVR were enrolled in RRD without the PVR group (n = 75, Group 2). Ocular examination findings and medical records of all participants were analysed retrospectively. Peripheral blood samples were collected, and systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratios were calculated. The systemic immune-inflammation index calculation formula is: (Neutrophil/lymphocyte) × Platelet.
Results
The median neutrophil-to-lymphocyte ratio and systemic immune-inflammation index levels were significantly higher in Group 1 patients compared to Group 2 and the control groups (p = 0.01, for both). However, the groups were similar regarding median platelet-to-lymphocyte ratio (p = 0.917). The optimal cut-off values of neutrophil-to-lymphocyte ratio and systemic immune-inflammation index were calculated as 1.72 (with 72% sensitivity and 48% specificity) and 407.9 (with 72% sensitivity and 49.3% specificity), respectively, for predicting PVR development in patients with RRD.
Conclusion
Neutrophil-to-lymphocyte ratio and systemic immune-inflammation index may be useful biomarkers for predicting the risk of PVR development in RRD patients.
... Studies have proposed the use of adjuvant pharmacological agents, such as anti-inflammatory and antineoplastic agents, to limit the proliferative disease process, but with limited success or high rates of adverse events [4][5][6]. Methotrexate (MTX) is a widely used antineoplastic agent. It is a potent competitive inhibitor of enzymes important for synthesis of DNA, thereby inhibiting cell proliferation [7]. ...
... Intraocular MTX therapy has been found to be safe in both animal models and clinical practice [6,11,12]. Objective assessment of retinal and optic nerve function through different electrophysiological studies is commonly used to assess drug toxicity [13]. Hence, our study aimed to assess the efficacy of intravitreal MTX infusion (IMI) during pars plana vitrectomy (PPV) in preventing postoperative PVR in eyes with established PVR grade C or a high risk for PVR development, and to evaluate retinal and optic nerve function using full-field electroretinogram (ff-ERG) and flash visual evoked potential (VEP). ...
... Each group was further subdivided into a subgroup with high-risk factors for developing PVR (group IA in the control group and IIA in the intervention group), such as large retinal breaks, aphakia, hypotony, ocular trauma, vitreous hemorrhage, uveitis, and pediatric patients with RRD [3,6,7], and another subgroup with established preoperative PVR grade C (subgroup IB in the control group and IIB in the intervention group). Subgroups IA, IB, and IIB each included 12 eyes, whereas subgroup IIA included 11 eyes. ...
Background:
Proliferative vitreoretinopathy (PVR) is the leading cause of recurrent retinal detachment after surgical repair of rhegmatogenous retinal detachment (RRD). Our study aimed to assess the efficacy and safety of intravitreal methotrexate infusion (IMI) for the prevention of PVR after pars plana vitrectomy (PPV) in eyes with RRD.
Methods:
This prospective comparative interventional study was conducted from September 2020 to November 2021 at Ain Shams University Hospitals, Egypt. We recruited a consecutive, non-randomized sample of 47 eyes of 47 patients with RRD undergoing PPV. Participants were allocated to a control group or an intervention group that received IMI during surgery. Each group was subdivided into subgroups of eyes at high-risk of developing PVR and eyes with established preoperative PVR grade C. Outcome measures at the 3-month postoperative follow-up were the rate of retinal attachment, incidence of PVR, reoperation rate to flatten the retina, and changes in the retina and/or optic nerve function as assessed by full-field electroretinogram and flash visual evoked potential.
Results:
Data from 47 eyes (23 and 24 eyes in the intervention and control groups, respectively) were evaluated. Subgroups IA, IB, and IIB each included 12 eyes, subgroup IIA included 11 eyes, and all subgroups had comparable sex ratios and age distributions. Postoperative PVR at 1 month and between 1 and 3 months was present in 13% and 4% of eyes in the intervention group, respectively. Reoperation to flatten the retina was required in 2 (9%) eyes in the intervention group, while 22 eyes (96%) had complete flattening of the retina at 3 months. No significant differences were found between the study groups and the corresponding subgroups regarding the outcome measures (all P > 0.05). No adverse events attributable to IMI were detected up to 3 months postoperatively.
Conclusions:
Although IMI was safe for intraocular use in eyes with RRD and PVR grade C or a high risk of developing PVR, it did not affect the anatomical success rate or development of PVR up to 3 months after PPV. Further multicenter randomized clinical trials with longer follow-up periods and larger sample sizes are needed to verify these preliminary outcomes.
