Failure Of Retinal Detachment Surgery Research Articles

Epiretinal Amniotic Membrane Influences the Cellular Behavior of Profibrotic Dedifferentiated Cells of Proliferative Vitreoretinopathy In Vitro

Proliferative vitreoretinopathy (PVR) as a rare fibrotic ocular disease is the main reason for failure of retinal detachment surgery and a reduced prognosis following surgery. Amniotic membrane (AM) is a versatile surgical tool for tissue stabilization, antifibrotic properties, and regeneration. Initial clinical case studies now demonstrated intravitreal tolerance as well as good anatomical and functional results for degenerative retinal diseases. Due to its diverse wound healing properties, AM could have promoting, suppressive, or no effects on PVR. To illuminate the potential of epiretinal AM transplantation in complex retinal detachment cases, we investigated its influence on human primary PVR (hPVR) cells in vitro. In our cell culture study, hPVR cells were isolated from surgically removed PVR membranes. Following incubation with AM for 48 h, AM-incubated hPVR showed significantly reduced proliferation (BrdU-ELISA; p < 0.001 ), migration (Boyden chamber, scratch assay; p = 0.003 and p < 0.001 ), and cell adhesion ( p = 0.005). Collagen contraction was nearly unaffected ( p = 0.04), and toxicity (histone-complexed DNA ELISA, WST-1 assay, and life/dead staining) was excluded. Next, immunofluorescence showed a myofibroblastic phenotype with reduced expression of fibrosis markers in AM-incubated cells, which was confirmed by Western blot analysis. In the proteomics assay, AM significantly regulated proteins by a more than 2-fold increase in expression which were related to the cytoskeleton, lipid metabolism, cell-matrix contraction, and protein folding. In conclusion, this in vitro work suggests no induction of fibrosis and other key steps in the pathogenesis of PVR through AM but rather inhibiting properties of profibrotic cell behavior, making it a possible candidate for suppression of PVR. Further clinical studies are necessary to evaluate the therapeutic relevance.

Artesunate inhibits the development of PVR by suppressing the TGF-β/Smad signaling pathway

Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment surgery failure. The epithelial-mesenchymal transition (EMT) induced by transforming growth factor (TGF-β2) plays an important role in the development of PVR. Artesunate has been widely studied as a treatment for ophthalmic diseases because of its antioxidant, anti-inflammatory, antiapoptotic and antiproliferative properties. The purpose of this study was to investigate the effects of artesunate on the TGF-β2-induced EMT in ARPE-19 cells and PVR development. We found that artesunate inhibited the proliferation and contraction of ARPE-19 cells after the EMT and the autocrine effects of TGF-β2 on ARPE-19 cells. Additionally, the levels of Smad3 and p-Smad3 were increased in clinical samples, and artesunate decreased the levels of Smad3 and p-Smad3 in ARPE-19 cells treated with TGF-β2. Artesunate also inhibited the occurrence and development of PVR in vivo. In summary, artesunate inhibits the occurrence and development of PVR by inhibiting the EMT in ARPE-19 cells.

Topical delivery of a small molecule RUNX1 transcription factor inhibitor for the treatment of proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is the leading cause of retinal detachment surgery failure. Despite significant advances in vitreoretinal surgery, it still remains without an effective prophylactic or therapeutic medical treatment. After ocular injury or retinal detachment, misplaced retinal cells undergo epithelial to mesenchymal transition (EMT) to form contractile membranes within the eye. We identified Runt-related transcription factor 1 (RUNX1) as a gene highly expressed in surgically-removed human PVR specimens. RUNX1 upregulation was a hallmark of EMT in primary cultures derived from human PVR membranes (C-PVR). The inhibition of RUNX1 reduced proliferation of human C-PVR cells in vitro, and curbed growth of freshly isolated human PVR membranes in an explant assay. We formulated Ro5-3335, a lipophilic small molecule RUNX1 inhibitor, into a nanoemulsion that when administered topically curbed the progression of disease in a novel rabbit model of mild PVR developed using C-PVR cells. Mass spectrometry analysis detected 2.67 ng/mL of Ro5-3335 within the vitreous cavity after treatment. This work shows a critical role for RUNX1 in PVR and supports the feasibility of targeting RUNX1 within the eye for the treatment of an EMT-mediated condition using a topical ophthalmic agent.

Experimental proliferative vitreoretinopathy in rabbits by delivery of bioactive proteins with gelatin microspheres

Proliferative vitreoretinopathy (PVR) is a challenging pathological condition, often causing failure of retinal detachment surgery. The purpose of this study was to evaluate the feasibility of a delivery system of bioactive proteins using anionic and cationic gelatin microspheres and to establish a new PVR model in rabbits by intraocular sustained delivery of basic fibroblast growth factor (bFGF) and interferon-beta (IFNβ). Anionic and cationic gelatin microspheres were prepared and immersed in bFGF and IFNβ solution, respectively, to yield a polyion complex between gelatin matrix and a bioactive protein. The bFGF-impregnated microspheres were injected into the subretinal space in rabbit eyes. At week 2, the IFNβ-impregnated microspheres also were injected into the same space. Control eyes received gelatin microspheres without bFGF or IFNß, or both. The eyes then were observed for 8 weeks by ophthalmoscopy, fundus photography, and fluorescein angiography. The eyes also were evaluated histologically. In the group with both bFGF and IFNβ, the number of eyes with more severe PVR increased over time. Histologic examination showed retinal folds. In contrast, no proliferative changes were seen in any control groups. Subretinal implantation of bFGF and IFNβ-impregnated gelatin microspheres induced reproducible PVR in rabbit eyes. This study guaranteed delivery of bioactive proteins with gelatin microspheres.

Evaluation of the Effect of Everolimus on Retinal Pigment Epithelial Cells and Experimental Proliferative Vitreoretinopathy

ABSTRACTPurpose: Failure of retinal detachment surgery is most commonly due to the development of proliferative vitreoretinopathy (PVR). Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), and is available as oral tablets. In this study, we investigated the effect of everolimus on retinal pigment epithelial cells and modification of the severity of experimental PVR.Methods: In our in vitro studies, primary culture of retinal pigment epithelium (RPE) cells was obtained from pigmented Rex rabbits. Cell proliferation was assayed with the tetrazolium dye cytotoxicity test, and cell migration assay was performed in 24-well transwell units with 8-μm filters. In the in vivo study, pigmented Rex rabbits weighing between 2 and 2.5 kg were used. Each rabbit eye underwent gas compression; one week later, 5 × 104 RPE cells were injected into the vitreous cavity to induce PVR, and each eye was graded with indirect ophthalmoscopy on days 1, 3, 7, 14, 21, and 28. The rabbits were administered everolimus (0.5 mg/day orally) from the day of PVR induction. Total proteins extracted from RPE cells and dissected retinal samples were processed for Western blotting analysis of mTOR and ribosomal protein S6 (RPS6).Results: The in vitro studies showed that everolimus significantly inhibited the proliferation of RPE cells at 0.1 μg/ml; additionally, at 10 μg/ml, it suppressed the migration of RPE cells and significantly suppressed the expression of mTOR and RPS6 in RPE cells. The in vivo study did not show any benefit of oral everolimus (0.5 mg/day) in suppressing experimental PVR. Thus, everolimus significantly suppressed the expression of mTOR and RPS6 in PVR.Conclusions: Everolimus suppressed the proliferation and migration of RPE cells in vitro. Oral everolimus (0.5 mg/day) suppressed the expression of mTOR and RPS6 in the retina, but showed no effect in suppressing experimental PVR.

Epithelial-to-Mesenchymal Transition of RPE Cells In Vitro Confers Increased β1,6-N-Glycosylation and Increased Susceptibility to Galectin-3 Binding.

Epithelial-to-mesenchymal transition (EMT) of retinal pigment epithelial cells is a crucial event in the onset of proliferative vitreoretinopathy (PVR), the most common reason for treatment failure in retinal detachment surgery. We studied alterations in the cell surface glycan expression profile upon EMT of RPE cells and focused on its relevance for the interaction with galectin-3 (Gal-3), a carbohydrate binding protein, which can inhibit attachment and spreading of human RPE cells in a dose- and carbohydrate-dependent manner, and thus bares the potential to counteract PVR-associated cellular events. Lectin blot analysis revealed that EMT of RPE cells in vitro confers a glycomic shift towards an abundance of Thomsen-Friedenreich antigen, poly-N-acetyllactosamine chains, and complex-type branched N-glycans. Using inhibitors of glycosylation we found that both, binding of Gal-3 to the RPE cell surface and Gal-3-mediated inhibition of RPE attachment and spreading, strongly depend on the interaction of Gal-3 with tri- or tetra-antennary complex type N-glycans and sialylation of glycans but not on complex-type O-glycans. Importantly, we found that β1,6 N-acetylglucosaminyltransferase V (Mgat5), the key enzyme catalyzing the synthesis of tetra- or tri-antennary complex type N-glycans, is increased upon EMT of RPE cells. Silencing of Mgat5 by siRNA and CRISPR-Cas9 genome editing resulted in reduced Gal-3 binding. We conclude from these data that binding of recombinant Gal-3 to the RPE cell surface and inhibitory effects on RPE attachment and spreading largely dependent on interaction with Mgat5 modified N-glycans, which are more abundant on dedifferentiated than on the healthy, native RPE cells. Based on these findings we hypothesize that EMT of RPE cells in vitro confers glycomic changes, which account for high affinity binding of recombinant Gal-3, particularly to the cell surface of myofibroblastic RPE. From a future perspective recombinant Gal-3 may disclose a therapeutic option allowing for selectively targeting RPE cells with pathogenic relevance for development of PVR.

Defining the Seriousness of Proliferative Vitreoretinopathy by Aspiration of Cytokines from the Anterior Chamber

Proliferative vitreoretinopathy is the major cause of retinal detachment surgery failure. Our prospective cohort study of 27 eyes aimed to determine intraocular levels of growth factors and cytokines in patients with retinal detachment with various degrees of severity of proliferative vitreoretinopathy using multiplex xMAP(®) Technology. The concentrations of 12 proangiogenic, antiangiogenic, inflammatory and neurotrophic factors were measured from 0.05-ml samples of intraocular fluid using multiplex xMAP Technology. The results were compared with levels of various factors, which were measured in samples from the control group of 31 eyes prior to senile cataract surgery. The concentration of the MCP-1 cytokine was found to be higher in eyes with retinal detachment compared with the control group. The concentration of VEGF was found to be higher in eyes with retinal detachment complicated with proliferative vitreoretinopathy compared with the uncomplicated retinal detachment group and the control group. MCP-1 and VEGF may participate in pathogenesis of retinal detachment and proliferative vitreoretinopathy. Biomarkers in disease detection and management have become important tools in modern clinical medicine, and their application to retinal disease should be no exception.

Cytologic analysis in vitreo‐retinal surgery

AbstractPurpose Proliferative vitreoretinopathy (PVR) is the leading cause of failure in retinal detachment surgery. The migration of retinal pigment epithelial cells and the proliferation of the extracellular matrix has been associated with PVR. The purpose of this prospective study was to compare the cellular contents of the vitreous of patients undergoing retinal detachment surgery with patients scheduled for macular surgery.Methods The vitreous samples of patients with epiretinal membrane and rhegmatogenous retinal detachment were obtained at the initial phase of surgery without previous intraocular infusion. A cytological analysis and Papanicolaou staining was performed in all cases. The concentration of vitreous cells in 62 patients with retinal detachment and 62 undergoing macular surgery (52 epiretinal membranes, 6 macular holes and 4 vitreomacular traction syndromes) were analyzed semi‐quantitatively.Results An increased concentration of vitreous cells and free pigment was observed in a higher proportion in retinal detachment specimens compared with patients undergoing macular surgey. In the retinal detachment group, there was a higher amount of hyalocytes (p=0,017) and macrophages (p=0,00865). There was no correlation between any cell concentration and PVR induced recurrence of retinal detachment. Interestingly, in the vitreous of eyes with vitreomacular traction, no cells could be detected.Conclusion Vitreous changes observed in patients with retinal detachment appear to involve vitreous cells particularly hyalocytes and macrophages, whereas in vitreomacular traction, syndromes no cellular reaction could be detected.

Cytopathological findings in the vitreous of patients with retinal detachment

AbstractPurpose Proliferative vitreoretinopathy (PVR) is the leading cause of failure in retinal detachment surgery. The migration of retinal pigment epithelial cells and the occurrence of extracellular matrix changes have been associated with PVR. The purpose of this prospective study was to analyze the cellular contents of the vitreous in patients with retinal detachment.Methods The vitreous samples of patients with epiretinal membrane and rhegmatogenous retinal detachment were obtained at the initial phase of surgery without previous intraocular infusion. A cytopathological analysis and staining of the vitreous was performed in all cases. The vitreous of 40 patients with retinal detachment and 49 patients undergoing epiretinal membrane peeling (control group) were included.Results The preparations displayed a variable cellularity. A higher amount of epithelial cell clumping was observed in retinal detachment specimens compared with controls. Furthermore, in the retinal detachment group, more free pigments were encountered and a higher degree of reticulation of the extracellular matrix was noted. In the vitreous of patients with retinal detachment, there is some cytopathological evidence for a higher concentration and an increased activity of retinal pigment epithelial cells compared with controls.Conclusion The predictive value of cytopathological changes for the occurrence of postoperative proliferative vitreoretinopathy in patients undergoing retinal detachment surgery remains to be demonstrated.

Transferrin and prealbumin: indicators of PVR and risk of recurrence in retinal detachment

AbstractPurpose Proliferative vitreoretinopathy (PVR) is the leading cause of failure in retinal detachment surgery. Increased levels of transferrine have been found in proliferative vitreoretinopathy. A relationship between the level of prealbumin and the functional outcome has been previously reported. The purpose of this prospective study was to look for a link between the vitreous levels and preoperative PVR or post‐operative outcome.Methods The vitreous samples of patients with epiretinal membrane and rhegmatogenous retinal detachment (RD) were obtained at the initial phase of surgery without previous intraocular infusion. The levels of transferrine (TF) and prealbumin (PA) were determined in all cases. The functional (visual acuity) and anatomical outcome (OCT mean foveal thickness, RD recurrence) was assessed.Results The vitreous levels of TF (193 mg/l vs. 44mg/l; p=0.038) and PA(115 mg/l vs. 15mg/l; p=0.0002) were significantly higher in the RD group(n=23) than in the macular surgery group(n=35). In eyes with RD, the intravitreal levels of TF in eyes with PVR A and B were higher than in eyes with PVR C (121 mg/l vs.356 mg/l; p=0,0233). In eyes with PA > 200 mg/l, 2 cases of RD recurrence were observed, when PA < 200 mg, no recurrence was observed (p=0.0296).Conclusion Increased prealbumin levels in the vitreous appear to correlate with an increased recurrence rate of retinal detachment. The predictive value of prealbumin for the occurrence of postoperative proliferative vitreoretinopathy in patients undergoing retinal detachment surgery remains to be demonstrated and requires a prospective multicenter study.

Vitreous proteomic analysis of proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is the most common cause of anatomic failure in retinal detachment surgery. To understand the molecular mechanisms, vitreous proteomes of patients with PVR were investigated by two-dimensional-nano-liquid chromatography coupled with tandem mass spectrometry. Vitreous samples of moderate PVR (grade B), and severe PVR (grade C or D) were aspirated during pars plana vitrectomy before infusion. In the current study, 129, 97 and 137 proteins were identified in vitreous of normal control, moderate and severe PVR, respectively. In PVR vitreous samples, complement components, serine proteinase inhibitors, and extracellular proteins were up-regulated or appeared, while normal cytoskeleton and metabolism proteins were down-regulated or disappeared. It was noteworthy that the proteins involved in transcription and translation regulation increased in vitreous with PVR. Among 102 PVR-specific proteins, kininogen 1 was specifically detected in both vitreous and the corresponding serum. Therefore, it can be concluded that PVR is a complicated pathology process with great amount of proteins involved in metabolism dysfunction, immune reactions, and cytoskeleton remolding. Kininogen 1 may be a candidate biomarker of PVR. Further investigations of these special proteins will provide additional targets for treatment or prevention of ocular proliferative diseases.

The Role of Gremlin, a BMP Antagonist, and Epithelial-to-Mesenchymal Transition in Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy (PVR), a major reason for failure of retinal detachment surgery, is characterized by the formation of scarlike tissue that contains transdifferentiated retinal pigment epithelial (RPE) cells. The scar tissue occurs in response to growth factors such as transforming growth factor (TGF)-beta and epidermal growth factor (EGF). The authors postulate that transdifferentiation of RPE cells may arise via epithelial-to-mesenchymal transition (EMT). Bone morphogenetic proteins (BMPs) are expressed in the retina and have an antiproliferative role. Gremlin is expressed in the outer retina and is a BMP antagonist. The study was conducted to establish a model of PVR by inducing EMT in the human RPE cell line ARPE-19, using TGF-beta and EGF and to establish the contribution of gremlin to EMT. ARPE-19 cells were cultured and stimulated with TGF-beta1, EGF, and gremlin. The expression of alpha-smooth muscle actin (alpha-SMA), vimentin, and zona occludens (ZO)-1 were examined via PCR, Western blot analysis, and immunofluorescence. Zymography was performed for matrix metalloproteinase (MMP) activity. Scratch assays were performed to assess migration. A model of EMT was established in the ARPE-19 cell line. The characteristics of EMT include gain of alpha-SMA, loss of ZO-1, upregulation of MMP activity and enhanced migration. Gremlin plays an important role in this process, contributing to the gain of alpha-SMA, loss of ZO-1, and upregulation of MMP activity. EMT occurs in vitro in the ARPE-19 cell line in response to the growth factors TGF-beta1 and EGF. EMT is also induced by Gremlin.

Inhibition of p38MAP kinase suppresses fibrotic reaction of retinal pigment epithelial cells

Proliferative vitreoretinopathy (PVR) is one of the major causes of the failure of retinal detachment surgery. Its pathogenesis includes a fibrotic reaction by the retinal pigment epithelium and other retina-derived non-neural cells, leading to fixation of the detached retina. We examined the role of p38 mitogen-activated protein kinase (MAPK) in transforming growth factor (TGF)-β2-dependent enhancement of the fibrogenic reaction in a human retinal pigment epithelial cell line, ARPE-19, and also evaluated the therapeutic efficacy of inhibiting p38MAPK by adenoviral gene transfer of dominant-negative (DN) p38MAPK in a mouse model of PVR. Exogenous TGF-β2 activates p38MAPK in ARPE-19 cells. It also suppresses cell proliferation, but this was unaffected by addition of the p38MAPK inhibitor, SB202190. SB202190 interfered with TGF-β2-dependent cell migration and production of collagen type I and fibronectin, but had no effect on basal levels of these activities. While SB202190 did not affect phosphorylation of the C-terminus of Smads2/3, it did suppress the transcriptional activity of Smads3/4 as indicated by a reporter gene, CAGA12-Luc. Gene transfer of DN-p38MAPK attenuated the post-retinal detachment fibrotic reaction of the retinal pigment epithelium in vivo in mice, supporting its effectiveness in preventing/treating PVR.

Adjuvants pharmacologiques du traitement chirurgical de la prolifération vitréorétinienne

Proliferative vitreoretinopathy (PVR) is the major cause of retinal detachment surgery failure. Many adjuvants were studied in vitro and on animals, some were studied on humans. Daunomycin seems to reduce PVR recidivism. 5-FU and steroids are nontoxic but their efficacy is not clear. Heparin reduced postoperative inflammation and seems to reduce PVR recidivism when associated with 5-FU. Associating heparin and steroids seems to reduce PVR in some groups of patients (aphakic, anterior PVR). Colchicine and retinoic acid per os are ineffective, silicone oil is effective as an internal tamponade but not as an adjuvant of PVR. Currently, no molecule has proven efficacy as an adjunctive treatment of PVR.

Proliferative vitreoretinopathy: risk factors and pathobiology

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.

Risk factors for proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is one of the major causes of failure in retinal detachment surgery. To prevent PVR, it is necessary to determine factors predisposing its development. In primary PVR, large retinal tears, long duration of retinal detachment, vitreous hemorrhages, aphakia and choroidal detachment were demonstrated as clinical risk factors for PVR. In postoperative PVR, it was revealed that large breaks, pre- and postoperative choroidal detachment, minor intra- or postoperative hemorrhages, signs of uveitis, extensive retinal detachment, vitrectomy, cryopexy, air injection and preoperative PVR were risk factors for PVR by multivariate analysis. Almost all risk factors for PVR are associated with intravitreal dispersion of retinal pigment epithelial (RPE) cells or breakdown of the blood-ocular barrier which are prerequisite to development of PVR.

Risk factors for surgical failures in rhegmatogenous retinal detachment

The evaluation of further risc factors predesposing failure in retinal detachment surgery than those already known to be associated with PVR was the goal of this retrospective study. The data from 130 cases with unilateral rhegmatogenous retinal detachment treated initially with buckling procedures, were retrospectively reviewed to investigate pre-, intra- and postoperative factors which may predispose anatomical failure in retinal detachment surgery. None of the selected consecutively operated eyes had risk factors, which have already been associated with an unfavourable outcome, such as the presence of preoperative macular holes, PVR or assumed PVR-inducing factors, such as ocular trauma, giant retinal tears, vitreous hemorrhage, previous vitrectomy, cryopexy and laser photocoagulation. The anatomic success rate after scleral buckling procedures was 78.5% and the overall success rate after multiple surgery including vitrectomy increased to 94.6%. 102 (78.5%) cases, treated with a maximum of two scleral buclking operations were statistically compared to the 28 cases which needed further vitreoretinal surgery. The statistical analysis revealed as preoperative risk factors for failure in rhegmatogenous retinal detachment surgery 1) retinal detachment exceeding two retinal quadrants (p < 0.05) and 2) size of the retinal tear larger than 60 degrees (p < 0.05), whereas postoperative risk factors were 1) presence of subretinal hemorrhage (p < 0.01) and 2) persistent subretinal fluid at least two days after surgery (p < 0.01). Eyes with preoperative visual acuity less than 0.1, pseudophacic eyes with posterior chamber intraocular lenses and eyes with severe intraoperative hypotony also showed a tendency to unfavourable outcome, but without a statistically significant level. Possible ways of interfering in the retinal reattachment process and the clinical importance of these evaluated factors are discussed. They should be taken in consideration for the prognosis of the postoperative anatomical result and treatment modalities if further surgery is required.

Class II Histocompatibility Antigen Expression by Cellular Components of Vitreous and Subretinal Fluid in Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is the major cause of failure in retinal detachment surgery. It is characterized by the formation of membranes extending along both surfaces of the detached retina and within the vitreous, but the nature of the growing cells has not yet been determined. Using cytologic and immunocytologic procedures with 13 different monoclonal antibodies directed against Class II histocompatibility antigens and various markers of epithelial and immunocompetent cells, 30 specimens were studied of vitreous or subretinal fluid removed from patients with PVR. Five main types of cells could be identified: heavily pigmented cells, poorly pigmented ones, large totally unpigmented macrophage-resembling ones, smaller unpigmented cells, and lymphocytes. Analysis of intravitreal pigment granules, using autofluorescence by epiillumination and cytologic procedures, showed two different populations of pigmented cells: one with autofluorescent lipofuscin granules and the other with exclusively melanin pigment. Immunostaining procedures confirmed the epithelial nonmacrophage lineage of the intravitreal and subretinal cells because most of these cells were positive for cytokeratin but negative for macrophage markers. In addition, 40-100% of these epithelial-derived cells strongly expressed Class II histocompatibility antigens HLA-DR and -DQ. Lymphocytes were found in 13 specimens; B-cells were seen, but no T-lymphocytes could be identified. These results confirm the involvement of retinal pigment epithelial cells and the strong morphologic changes they undergo during the course of PVR. Moreover, the expression of Class II histocompatibility antigens by the growing cells may be related to inflammatory phenomena, but their eventual role in the development and the extension of periretinal proliferation has not been determined.

Management of anterior vitreous traction in proliferative vitreoretinopathy.

The major cause of failure in retinal detachment surgery is proliferative vitreoretinopathy. The surgical treatment of proliferative vitreoretinopathy has improved dramatically over the past ten years. Still failure is too common and the need for reoperation remains high. We believe this is often due to anterior vitreous traction. We report our present "conservative" surgical approach to treating such patients using newly developed fiberoptic instrumentation. Using this approach, we have achieved total retinal reattachment in 42 of 48 patients with C3 or greater proliferative vitreoretinopathy with six months or greater follow up.

Prolieferative Vitreoretinopathy: The Mechanism of Development of Vitreoretinal Traction

Proliferative vitreoretinopathy (PVR) is the leading cause of failure of retinal detachment surgery. In this disorder, contractile cellular membranes form within the vitreous cavity. Retinal pigment epithelial (RPE) cells are an early and important component of these membranes. Contraction is mediated by cellular events and this contraction results in the formation of traction retinal detachments. Using the techniques of time-lapse cinemicrography, the authors studied the interaction of single RPE cells with individual strands of collagen. RPE cells pull the collagen fibers toward them using alternating extension and retraction of their lamellipodia. (The mechanism can be likened to sailors pulling in sheets of a sail in a hand-over-hand manner.) The collagen is not engulfed by the cell, but instead is piled up in a small bundle adjacent to the cell. Using this mechanism, each cell can reel in several times its length of collagen in 1 hour. In this manner, a small number of RPE cells may be able to collapse the vitreous gel and exert tractional forces.