The role of vitreous cortex remnants in proliferative vitreoretinopathy formation demonstrated by histopathology: A case report (original) (raw)
Related papers
Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences
Progress in Retinal and Eye Research, 2016
During the last four decades, proliferative vitreoretinopathy (PVR) has defied the efforts of many researchers to prevent its occurrence or development. Thus, PVR is still the major complication following retinal detachment (RD) surgery and a bottleneck for advances in cell therapy that require intraocular surgery. In this review we tried to combine basic and clinical knowledge, as an example of translational research, providing new and practical information for clinicians. PVR was defined as the proliferation of cells after RD. This idea was used for classifying PVR and also for designing experimental models used for testing many drugs, none of which were successful in humans. We summarize current information regarding the pathogenic events that follow any RD because this information may be the key for understanding and treating the earliest stages of PVR. A major focus is made on the intraretinal changes derived mainly from retinal glial cell reactivity. These responses can lead to intraretinal PVR, an entity that has not been clearly recognized. Inflammation is one of the major components of PVR, and we describe new genetic biomarkers that have the potential to predict its development. New treatment approaches are analyzed, especially those directed towards neuroprotection, which can also be useful for preventing visual loss after any RD. We also summarize the results of different surgical techniques and clinical information that is oriented toward the identification of high risk patients. Finally, we provide some recommendations for future classification of PVR and for designing comparable protocols for testing new drugs or techniques.
Proliferative vitreoretinopathy: risk factors and pathobiology
Progress in Retinal and Eye Research, 2002
Proliferative vitreoretinopathy (PVR) is still a major cause of failure of retinal detachment surgery. Despite a dramatic increase in our pathobiologic knowledge of PVR during the last 10 years, little of this information has been used to modify the surgical management of the disease, and, thus, the anatomic and functional results are still unsatisfactory. Collaborative research involving clinicians and basic researchers must be encouraged. PVR must be considered a multifactorial disease caused by interaction of several cells and intra-and extraocular factors. Therefore, therapeutic options based on the inhibition of one factor or phenomenon may be regarded with scepticism. To prevent PVR, it is necessary to determine the factors involved in its development, and because of its relatively small prevalence, large, prospective, multicenter studies seem necessary. In addition, clinical research must not be underestimated. PVR affects both sides of the retina and the retina itself, a point to which little attention has been paid and that is critical for surgical results. Therefore, a new classification that provides information about clinical relevance, such as the evolutionary stages of the disease (biologic activity) and the degree of surgical difficulty (location of the fibrotic process), seems necessary.
BMC Ophthalmology, 2020
Background: The purpose of the study was to explore the immunological components that are responsible for the proliferative alterations in the different forms of retinal detachment (RD). Methods: Vitreous fluids were collected during 23G pars plana vitrectomy from 54 eyes of 54 patients with different RD types, such as rhegmatogenous RD (RRD) without proliferative vitreoretinopathy (PVR) (n = 30), PVR (n = 16) and proliferative diabetic retinopathy (PDR) with tractional RD (n = 8). Vitreous fluids were obtained from 19 eyes with epiretinal membrane (ERM), which were used as control samples. A multiplex chemiluminescent immunoassay was performed to evaluate the concentrations of 48 cytokines, chemokines and growth factors. Results: The expression levels of eotaxin, IFN-gamma, IL-6, IL-8, IL-16, MCP-1, MIF and MIP-1 beta were significantly higher in all RD groups than in the ERM group. The levels of CTACK, IP-10, SCGF-beta, and SDF-1 alpha were significantly higher in patients with diabetic tractional RD and PVR than in other patients. The upregulation of VEGF and IL-18 was detected in PDR. Conclusions: Our results indicate that complex and significant immunological mechanisms are associated with the pathogenesis of different forms of RD: selected cytokines, chemokines and growth factors are upregulated in the vitreous of eyes with RD. The detected proteins are present in different concentrations both in RRD and PVR. In the presence of PVR and PDR, the majority of cytokines are upregulated; thus, they may serve as biomarkers to estimate the progression or severity level of proliferation and later to develop personalized therapeutic strategies to slow down or prevent pathological changes.
PURPOSE: To provide immunohistochemical characterization of sub retinal bands removed during retinal surgery in eyes with proliferative vitreoretinopathy (PVR). METHODS: This study included all eyes with the clinical diagnosis of PVR that underwent pars plana vitrectomy surgery during which the sub retinal tissue causing retinal detachment was obtained. The sub retinal bands were removed "en bloc" through retinotomy using sub retinal intraocular forceps. The excised tissue was sent for histopathologic analysis. Immunohistochemistry (IHC) was performed to confirm the cellular nature and components of these subretinal membranes. The IHC stains included, glial fibrillary acidic protein (GFAP), Pancytokeratin, CD3, CD20, CD68 and CD34. RESULTS: Sub retinal membranes (SRMs) from 7 eyes were included in the analysis. All cases had successful surgical outcome with reattachment six months after surgery. The microscopic examination of the excised tissue nicely demonstrated the constituents of the SRM as follows: retinal pigmented epithelial (RPE) cells that stained positively with cytokeratin (7/7), avascular plaques of RPE cells showing metaplasia in the form of spindle cells (7/7). Fragments of gliotic GFAP-positive neural retina was adherent to the fibrous plaque (6 /7). Bruch's membrane was identified in one specimen. CD 68 positive macrophages were seen in (5/7) being silicon oil- laden macrophages in 2/5. Rare CD3 positive cells were also noted in 1 specimen. CONCLUSIONS: Sub retinal bands in PVR are mainly composed of reactive avascular plaques of RPE metaplasia and macrophage infiltration. The overlying gliotic retina or Bruch's membrane are likely to be adherent to such plaques and might be inadvertently excised during removal of such membranes. Removal of SRMs is essential for successful reattachment of the retina.
bioRxiv (Cold Spring Harbor Laboratory), 2022
Purpose: Proliferative vitreoretinopathy (PVR) is the most common cause of failure of surgically repaired rhegmatogenous retinal detachment (RRD). Chemically-induced and cell-injection PVR models do not fully simulate the clinical characteristics of PVR in the post-RRD context. There is an unmet need for translational models in which to study mechanisms and treatments specific to RRD-PVR. Methods: RRD-PVR was induced in adult Dutch Belted rabbits. Posterior segments of enucleated globes were fixed or processed for RNA-Seq at 6 hours and 2, 7, 14, and 35 days post-induction. Histochemical staining and immunolabeling for glial fibrillary acidic protein (GFAP), alpha smooth muscle actin (αSMA), vascular endothelial growth factor receptor 2 (VEGFR2), CD68, and retinal pigment epithelium 65 kDa protein (RPE65) were performed, and labeling intensity was scored. Single cell RNA sequencing was performed. Results: Acute histopathologic changes included intravitreal and intraretinal hemorrhage, leukocytic vitritis, chorioretinitis, and retinal rarefaction. Chronic lesions showed retinal atrophy, gliosis, fibrotic subretinal membranes, and epiretinal fibrovascular proliferation. Fibrillar collagen was present in the fibrocellular and fibrovascular membranes in chronic lesions. Moderate to strong labeling of glia and vasculature was detected in chronic lesions. At day 14, most cells profiled by single cell sequencing were identified as Mϋller glia and microglia, consistent with immunolabeling. Expression of several fibrillar collagen genes were upregulated in chronic lesions. Conclusions: Histologic and transcriptional features of this rabbit model simulate important features of human RRD-PVR, including the transition to chronic intra and periretinal fibrosis. This high-fidelity in vivo model of RRD-PVR will enable further research on targeted treatment interventions.
Proliferative Vitreoretinopathy Membranes
Ophthalmology, 1989
Proliferative vitreoretinopathy (PVR) is the leading cause of failure after retinal detachment surgery. Therefore, both the extracellular matrix and cellular components of preretinal membranes from 23 eyes with PVR were characterized immunohistochemically. The membrane stroma was composed primarily of types I, II, and III collagen. Laminin and both heparan sulfate proteoglycans and collagens types IV and V were co-distributed in discrete regions within the stroma. Glial and retinal pigment epithelial (RPE) cell populations were identified in these membranes using specific immunohistochemical markers as was a small but significant macrophage population. Double-labeling experiments indicated that RPE cells in these membranes expressed the class II histocompatibility antigen HLA-DR, although neither the RPE monolayer in situ nor cultured RPE cells was HLA-DR positive unless induced by gamma interferon. Only rare isolated vascular endothelial cells were detected in 5 of the 23 membranes.
Evolution of Outer Retinal Folds Occurring after Vitrectomy for Retinal Detachment Repair
Investigative Ophthalmology & Visual Science, 2012
PURPOSE. To assess the evolution of outer retinal folds (ORFs) occurring after repair of rhegmatogenous retinal detachment (RRD) using spectral domain-optical coherence tomography (sd-OCT) and fundus autofluorescence (FAF), and to discuss their pathogenesis. METHODS. Twenty patients were operated on with 25-gauge pars plana vitrectomy and 20% sulfur hexafluoride gas injection for primary macula-off RRD repair and were followed prospectively. Sd-OCT and FAF images were recorded at 1, 3 and 6 months postoperatively. RESULTS. ORFs appeared on sd-OCT as hyperreflective lesions consisting of folded inner segment/outer segment of photoreceptors band and external limiting membrane band. Corresponding lines of increased or decreased autofluorescence were observed on FAF. Over the follow-up, the thick hypoautofluorescent lines progressively evolved to thick hyperautofluorescent lines and to thin hyperautofluorescent lines and eventually disappeared. Concomitantly, OCT scans revealed that the corresponding hyperreflective lesions decreased in number, height, and size. In six cases FAF assessment at month 6 was precluded by cataract development. CONCLUSIONS. ORFs tend to resolve spontaneously within a few months from operation leaving no or subtle abnormalities at the level of the outer retinal layers. OCT is superior to FAF to follow the evolution of ORFs in phakic eyes. The following factors might be involved in ORFs pathogenesis: structural changes occurring in the detached retina, residual pockets of subretinal fluid after retinal reattachment, intravitreal gas, unintentional retinal translocation, and intraoperative or perioperative hypotony.
Proliferative vitreoretinopathy—developments in adjunctive treatment and retinal pathology
Eye, 2002
Proliferative vitreoretinopathy (PVR) remains a difficult management problem despite advances in vitreoretinal surgery. There is still a significant incidence of PVR in rhegmatogenous retinal detachment and other forms of retinal disease. Surgery for PVR now has a high anatomical success rate although visual results are often disappointing. The use of adjunctive treatments to prevent cellular proliferation holds promise for the prevention of PVR or recurrences after surgery. Control of proliferation and strategies aimed at improving visual outcome are important areas of future research in PVR and other forms of retinal disease. Studies of the intraretinal and peri-retinal pathology of PVR have demonstrated characteristic changes which may have a significant influence on visual outcome and surgical management.
Influence on collagen metabolism of vitreous from eyes with proliferative vitreoretinopathy
Ophthalmology, 1995
Purpose: Proliferative vitreoretinopathy (PVR) is characterized by cell proliferation and membrane formation on the vitreoretinal cavity of the eye. The membranes are composed of extracellular matrix, mainly collagen type I. To explore the possible mechanisms involved in PVR membrane formation, the authors analyzed the role of vitreous humor on collagen turnover.
PLOS ONE, 2020
Our purpose was to evaluate the concentrations of vitreous cytokines in patients with rhegmatogenous retinal detachment (RRD). We hypothesized that patients with macula on RRD have lower levels of cytokines compared to patients with macula off RRD and proliferative vitreoretinopathy (PVR). Vitreous fluids were collected during 23G pars plana vitrectomy from 58 eyes of 58 patients. Indication for vitrectomy included macula off and macula on RRD, PVR, and idiopathic epiretinal membrane (ERM). A multiplex chemiluminescent immunoassay was performed to measure the concentrations of 48 cytokines, chemokines, and growth factors. Levels of HGF, IL-6, IL-8, IL-16, IFN-gamma, MCP-1, and MIF were significantly higher in all groups of retinal detachment compared to ERM. Levels of CTACK, eotaxin, G-CSF, IP-10, MIG, SCF, SCGF-beta, SDF-1alpha were significantly higher in PVR compared to macula on RRD and ERM. Levels of IL-1ra, IL-5, IL-9, M-CSF, MIP-1alpha, and TRIAL were significantly higher in PVR compared to macula on RRD. Our results indicate that the position of macula lutea and the presence of PVR significantly influence vitreous cytokine expression. The detected proteins may serve as biomarkers to estimate the possibility of PVR formation and may help to invent personalized therapeutic strategies to slow down or prevent PVR.