Proliferative Vitreoretinopathy In Eyes Research Articles

Comparison of vitreous/retinal pigment epithelium relative intensity in proliferative vitreoretinopathy and uveitis

Background: Quantitative measurements of vitreous inflammation using vitreous/retinal pigment epithelium-relative intensity (VIT/RPE-Relative Intensity) have been described recently. In proliferative vitreoretinopathy (PVR), inflammation plays a central role in the pathogenesis, inducing retinal fibrosis and contraction. However, no attempts have yet to be made to analyze the severity of inflammation in PVR progression. Methods: A cross-sectional study was conducted by reviewing OCT image sets obtained from patients divided into four groups: (1) proliferative vitreoretinopathy, (2) intermediate and posterior uveitis, (3) panuveitis, (4) normal healthy eyes in Cipto Mangunkusumo Kirana Eye Hospital between April 2021 – December 2021. OCT images were then analyzed in the ImageJ software for VIT/RPE-relative intensity. Results: A total of 19 PVR eyes, 12 intermediate-posterior uveitis eyes, 16 panuveitis eyes, and 28 normal healthy eyes were recruited for this study. The VIT/RPE-Relative Intensity was significantly higher in PVR eyes (0.415±0.178) than in intermediate-posterior uveitis (0.236±0.043, p=0.002) and panuveitis eyes (0.30±0.07, p=0.023). Compared to the normal eyes, PVR and both uveitis groups have significantly higher VIT/RPE relative intensity (p = <0.001 in each group). Conclusions: VIT/RPE-relative intensity may offer quantitative measurements of vitreous inflammation in the role of the pathogenesis of PVR. Comparison with cellular inflammation in the vitreous is required to validate this finding.

Comparison of vitreous/retinal pigment epithelium relative intensity in proliferative vitreoretinopathy and uveitis

Background: Quantitative measurements of vitreous inflammation using vitreous/retinal pigment epithelium-relative intensity (VIT/RPE-Relative Intensity) have been described recently. In proliferative vitreoretinopathy (PVR), inflammation plays a central role in the pathogenesis, inducing retinal fibrosis and contraction. However, no attempts have yet to be made to analyze the severity of inflammation in PVR progression. Methods: A cross-sectional study was conducted by reviewing OCT image sets obtained from patients divided into four groups: (1) proliferative vitreoretinopathy, (2) intermediate and posterior uveitis, (3) panuveitis, (4) normal healthy eyes in Cipto Mangunkusumo Kirana Eye Hospital between April 2021 – December 2021. OCT images were then analyzed in the ImageJ software for VIT/RPE-relative intensity. Results: A total of 19 PVR eyes, 12 intermediate-posterior uveitis eyes, 16 panuveitis eyes, and 28 normal healthy eyes were recruited for this study. The VIT/RPE-Relative Intensity was significantly higher in PVR eyes (0.415±0.178) than in intermediate-posterior uveitis (0.236±0.043, p=0.002) and panuveitis eyes (0.30±0.07, p=0.023). Compared to the normal eyes, PVR and both uveitis groups have significantly higher VIT/RPE relative intensity (p = <0.001 in each group). Conclusions: VIT/RPE-relative intensity may offer quantitative measurements of vitreous inflammation in the role of the pathogenesis of PVR. Comparison with cellular inflammation in the vitreous is required to validate this finding.

A Mouse Model of Proliferative Vitreoretinopathy Induced by Intravitreal Injection of Gas and RPE Cells.

PurposeDevelop a reproducible proliferative vitreoretinopathy (PVR) mouse model that mimics human PVR pathology.MethodsMice received intravitreal injections of SF6 gas, followed by retinal pigment epithelial cells 1 week later. PVR progression was monitored using fundus photography and optical coherence tomography imaging, and histologic analysis of the retina as an endpoint. We developed a PVR grading scheme tailored for this model.ResultsWe report that mice that received gas before retinal pigment epithelial injection developed more severe PVR. In the 1 × 104 retinal pigment epithelial cell group, after 1 week, 0 of 11 mice in the no gas group developed grade 4 or greater PVR compared with 5 of 13 mice in the SF6 gas group (P = 0.02); after 4 weeks, 3 of 11 mice in the no gas group developed grade 5 or greater PVR compared with 11 of 14 mice in the SF6 gas group (P = 0.01). We were able to visualize contractile membranes both on the retinal surface as well as within the vitreous of PVR eyes, and demonstrated through immunohistochemical staining that these membranes expressed fibrotic markers alpha smooth muscle actin, vimentin, and fibronectin, as well as other markers known to be found in human PVR membranes.ConclusionsThis mouse PVR model is reproducible and mimics aspects of PVR pathology reported in the rabbit PVR model and human PVR. The major advantage is the ability to study PVR development in different genetic backgrounds to further elucidate aspects of PVR pathogenesis. Additionally, large-scale experiments for testing pharmacologic agents to treat and prevent PVR progression is more feasible compared with other animal models.Translational RelevanceThis model will provide a platform for screening potential drug therapies to treat and prevent PVR, as well as elucidate different molecular pathways involved in PVR pathogenesis.

Proteomic evidence that ABCA4 is vital for traumatic proliferative vitreoretinopathy formation and development

Proliferative vitreoretinopathy (PVR) is the leading cause of retinal detachment failure. The mechanism of PVR development is complex and still not completely elucidated. There are no proven methods for early prevention or clinical treatment. Retinal proteins are abnormally expressed during the entire PVR disease process. Due to the limitations of research methods and techniques, we do not fully understand the retinal protein changes in PVR. This proteomics study systemically analyzed and identified differential protein expression between retinas of PVR and non-PVR (normal) eyes. Retinal samples were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) coupled with mass spectrometry. Raw data were processed and analyzed by Maxquant software and then searched against the human UniProKB (201510) protein database. Differentially expressed proteins were selected and further validated in a human retinal pigment epithelial (RPE) cell line. The effects of dysregulated proteins on cell proliferation, apoptosis, and migration were studied. Systemic proteomics analysis identified several PVR-enriched proteins. The differentially expressed proteins were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation to find abnormal pathways involved in PVR. Retinal-specific ATP-binding cassette transporter (ABCA4) expression was one of the most increased proteins in PVR tissue. ABCA4 knockdown significantly reduced proliferation and affected the cell cycle in the human RPE cell line. ABCA4 knockdown also induced apoptosis and inhibited retinal cell migration. In conclusion, systemic proteomics analysis identified differentially expressed proteins in traumatic PVR, with ABCA4 being highly expressed. Disruption of ABCA4 expression induced apoptosis and inhibited cell proliferation and migration in a human RPE cell line.

Laser flare photometry for identification of high-risk patients for proliferative vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is acomplication of rhegmatogenous retinal detachment and trauma, which occurs in approximately 10% following vitreoretinal surgery. The visual prognosis for established PVR is poor and so far there is no established conservative treatment for PVR. In the currently recruiting PRIVENT trial the aim is to find a prophylactic treatment possibility for PVR. The PRIVENT study examines the influence of intraoperative adjuvant pharmacotherapy on reducing the incidence of PVR; however, this requires the identification of eyes with increased risk for PVR. Laser flare photometry is asimple method to predict the individual risk for PVR. It is anon-invasive technique that objectifies the Tyndall effect. Various laser flare meter devices are available on the market. In previous studies it could be shown that laser flare photometry can predict the development of PVR in eyes with primary rhegmatogenous retinal detachment with asensitivity of 80%. The identification of these high-risk eyes for PVR could be the first step towards solving the problem of PVR.

Inferior retinotomy and silicone oil tamponade for recurrent inferior retinal detachment and grade C PVR in eyes previously treated with pars plana vitrectomy or scleral buckle.

BackgroundOne of the most challenging problems in vitro-retinal surgery is the recurrence of retinal detachment in the context of high-grade proliferative vitreoretinopathy (PVR). The aim of our retrospective study was to assess the surgical outcomes of pars plana vitrectomy, 180° inferior retinotomy and silicone oil tamponade combined with phacoemulsification and IOL implantation for recurrent inferior retinal detachment with grade C PVR in phakic eyes. The study was carried out at tertiary referral centre - University Hospital of Rome “Tor Vergata”.MethodsRetrospective analysis of 33 eyes affected by recurrent inferior retinal detachment and grade C PVR after primary encircle scleral buckling (SB group – 12 eyes), or pars plana vitrectomy (PPV group – 21 eyes). All patients subsequently underwent PPV and silicone oil tamponade at our Institution. The first outcome measure was retinal reattachment, and second outcomes were reoperation rates, best-corrected visual acuity (BCVA) and postoperative complications.ResultsAll patients in the SB group and 19 (90 %) patients of the PPV group achieved retinal reattachment. Final BCVA was better in the SB group (p = 0.045). Two eyes in the PPV group required a third vitrectomy with heavy silicone oil tamponade. Postoperative complications included silicone oil in a deep anterior chamber (3 eyes in each group), untreatable hypotony in 1 eye in the PPV group (that led to enucleation due to phthisis bulbi), and elevated intraocular pressure in 3 patients (2 eyes in the PPV group).ConclusionsPhacoemulsification with IOL implant, PPV with silicone oil tamponade associated with 180° inferior retinotomy may lead to better anatomical success in patients who have previously undergone SB procedure for inferior retinal detachment repair compared with eyes that underwent a primary PPV.

The upregulation of zinc finger protein 670 and prostaglandin D2 synthase in proliferative vitreoretinopathy

Proteins in the vitreous play an important role on the induction of proliferative vitreoretinopathy (PVR) after retinal detachment. The aim of this study was to investigate the variation of protein patterns in the vitreous of PVR eyes and examine whether differentially expressed protein levels were expressed in experimental PVR retina. Vitreous samples from PVR and macular hole patients were selected for proteomic analysis. The vitreous protein samples were separated by two-dimensional electrophoresis (2-DE). The differentially expressed protein spots in the two groups were excised and subjected to in-gel digestion and identification by electrospray ionization mass spectrometry (ESI-MS) analysis. Two differentially expressed proteins, zinc finger protein 670 (ZFP 670) and prostaglandin D2 synthase (PGD2S), were further validated by immunohistochemical staining and western blotting analysis in the retina of the experimental rabbit PVR model. In proteome analysis of human vitreous samples, five proteins had increased expression in PVR, including zinc finger protein 670 (ZFP 670), prostaglandin D2 synthase (PGD2S), IgG (Immunoglobulin G) light chain, transthyretin precursor, and haptoglobin precursor. ZFP 670 and PGD2S levels were expressed significantly higher in the experimental PVR retinas than in the control group. Levels of ZFP 670 and PGD2S were elevated in the vitreous fluid of patients with PVR. In addition, there were higher expressions of ZFP 670 and PGD2S in the experimental PVR retina. This result will expand our knowledge of pathophysiologic characteristics of PVR, and might be helpful for further developing possible treatment on this disorder.

The Effects of Ozurdex® (Dexamethasone Intravitreal Implant) on Experimental Proliferative Vitreoretinopathy

Purpose: To investigate a new sustained-release formulation of dexamethasone (Ozurdex®) for inhibiting proliferative vitreoretinopathy (PVR) and its effect on the expression of retinal glial reaction and inflammation in experimental PVR eyes. Methods: We used 30 pigmented rabbits for this study. One week after gas compression, the eyes were injected with 5 × 10⁴ retinal pigment epithelial cells into the vitreous cavity to induce PVR. Concurrently, one eye also received an intravitreal injection of Ozurdex; the other eye was used as a control. PVR was graded by indirect ophthalmoscopy on days 1, 3, 7, 14, 21, and 28. The expression of the retinal glial reaction and inflammation in experimental PVR eyes were evaluated by Western blot analysis. Results: PVR severity increased gradually and peaked after 14 days, and no differences in PVR severity between the study and control groups were observed at any time point. The expression of glial fibrillary acid protein (GFAP) increased on days 7 and 14 in both the PVR control and study groups. While the use of Ozurdex in the study group showed less GFAP expression, this difference was not significant. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 significantly increased on days 7 and 14 in PVR control eyes. There was a significant difference in TNF-α between PVR control eyes and Ozurdex-treated eyes on days 7 (p < 0.001) and 14 (p = 0.019). Ozurdex in the study group showed lower IL-6 expression; however, this difference was not significant on days 7 (p = 0.063) and 14 (p = 0.052). Conclusions: The intravitreal injection of Ozurdex suppressed the expression of inflammatory markers; however, it did not mitigate the severity of experimental PVR in this animal model.

Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy?

Proliferative vitreoretinopathy (PVR) is a blinding disorder that occurs in eyes with rhegmatogenous retinal detachment and in eyes that have recently undergone retinal detachment surgery. There are presently no treatment strategies to reduce the risk of developing PVR in eyes with retinal detachment, and surgical intervention is the only option for eyes with retinal detachment and established PVR. Given the poor visual outcome associated with the surgical treatment of PVR, considerable work has been done to identify pharmacologic agents that could antagonize the PVR process. Intensive efforts to identify molecular determinants of PVR implicate vitreal growth factors. A surprise that emerged in the course of testing the 'growth factor hypothesis' of PVR was the existence of a functional relationship amongst growth factors that engage platelet-derived growth factor (PDGF) receptor α (PDGFRα), a receptor tyrosine kinase that is key to pathogenesis of experimental PVR. Vascular endothelial cell growth factor A (VEGF), which is best known for its ability to activate VEGF receptors (VEGFRs) and induce permeability and/or angiogenesis, enables activation of PDGFRα by a wide spectrum of vitreal growth factors outside of the PDGF family (non-PDGFs) in a way that triggers signaling events that potently enhance the viability of cells displaced into vitreous. Targeting these growth factors or signaling events effectively neutralizes the bioactivity of PVR vitreous and prevents PVR in a number of preclinical models. In this review, we discuss recent conceptual advances in understanding the role of growth factors in PVR, and consider the tangible treatment strategies for clinical application.

A pilot study of intraocular use of intensive anti-inflammatory; triamcinolone acetonide to prevent proliferative vitreoretinopathy in eyes undergoing vitreoretinal surgery for open globe trauma; the adjuncts in ocular trauma (AOT) trial: study protocol for a randomised controlled trial

BackgroundEyes sustaining open globe trauma (OGT) is a group at high risk of severe visual impairment. Proliferative vitreoretinopathy (PVR) is the commonest cause of retinal redetachment in these eyes and is reported to occur in up to 45% of cases. Intensive anti-inflammatory agents have been shown to be effective at modifying experimental PVR and to be well tolerated clinically.The Adjuncts in Ocular Trauma (AOT) Trial was designed to investigate the benefits of using intensive anti-inflammatory agents (intravitreal and sub-Tenon’s triamcinolone, oral flurbiprofen and guttae prednisolone 1.0%) perioperatively in patients undergoing vitrectomy surgery following open globe trauma.Methods/designPatients requiring posterior vitrectomy surgery following open globe trauma will be randomised to receive either standard treatment or study treatment. Both groups will receive the standard surgical treatment appropriate for their eye condition and routine perioperative treatment and care, differing only in the addition of supplementary adjunctive agents in the treatment group. The investigated primary outcome measure is anatomical success at 6 months in the absence of internal tamponade.DiscussionThis is the first randomised controlled clinical trial to investigate the use of adjunctive intensive antiinflammatory agents in patients undergoing vitrectomy following open globe trauma. It will provide evidence for the role of these adjuncts in this group of patients, as well as provide data to power a definitive study.EudraCT No2007/005138/35

Activation of neural progenitor cells in human eyes with proliferative vitreoretinopathy

In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial – and NSC-associated markers both after direct fixation and repetitive passages. In conclusion, the adult human eye may harbor two different populations of neuroepithelial stem/progenitor cells; a non-glial population located in the proximal pars plana around peripheral cysts in addition to a population with Müller glia characteristics. Yet, we only found that the glial population was able to respond to retinal injury by targeted migration into the vitreous.

Characterization of neuroepithelial progenitor cells in patients with proliferative vitreoretinopathy

AbstractPurpose Proliferative vitreoretinopathy (PVR) is an important cause of retinal diseases such as retinal detachment (RD). In lower vertebrates, retinal damage is known to activate neuroepithelial stem cells (NSCs) in the ciliary margin in an attempt to regenerate the neuroretina. Cells expressing some markers of NSCs are also present in the retina and the ciliary body epithelium (CB) of the adult human eye. We hypothesized that if NSCs exist in the adult human eye, they should be activated by PVR formation.Methods Cells isolated from vitreous samples (n=25) obtained during vitrectomies for RD were directly fixed or cultured in a stem cell‐promoting medium, and compared to cells isolated from post mortem CB and peripheral retina (PR) using sphere‐forming assay, immunohistochemistry, molecular biology and electron microscopy. Markers of NSCs were also studied in whole retinal control/PVR sections obtained from enucleations.Results Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR. These spheres stained for markers of NSCs both in vivo and after repetitive passages. Their mRNA and immunohistochemical profile resembled sphere‐forming cells from the PR with only a few characteristics of CB cells. In situ characterization of the CB revealed that although there were higher numbers of dividing cells in PVR eyes than in controls, we did not detect markers of NSCs. Interestingly, markers of NSCs were evident around PR cysts with some evidence of activation following PVR formation.Conclusion A population of NSC‐like cells are found in the vitreous of patients with PVR. These cells seem to be originated from the retina itself and not the CB.

Primary Retinectomy in Proliferative Vitreoretinopathy

To describe the functional and anatomic results of retinectomy without scleral buckling for anterior proliferative vitreoretinopathy in eyes that did not undergo previous buckling surgery. Retrospective, nonrandomized, interventional case series. We reviewed the results of 123 consecutive cases of retinectomy for rhegmatogenous retinal detachment complicated by anterior proliferative vitreoretinopathy. The primary outcome measure was anatomic success, defined as complete retinal reattachment. Secondary outcome measures were final anatomic success, final visual acuity outcome, number of operations required for retinal reattachment, baseline extent of proliferative vitreoretinopathy, ocular pressure at final follow-up, extent of retinectomy, and occurrence of complications. The anatomic success rate was 77.2%. Final attachment rate was 95.9%, reached after 1 rhegmatogenous retinal detachment reoperation in 21 cases and after 2 rhegmatogenous retinal detachment reoperations in 4 cases. We had a low rate of postoperative hypotony (4.1%). Visual acuity was significantly improved from 2.10 to 1.44 logarithm of the minimal angle of resolution units (P < .001). Improvement was related significantly to retinectomy extent and primary anatomic success. Our results show that primary retinectomy without scleral buckling has good anatomic and functional results.

Levels of pentosidine in the vitreous of eyes with proliferative diabetic retinopathy, proliferative vitreoretinopathy and retinal detachment

Advanced glycosylation end products (AGEs) are thought to play an important role in the pathophysiology of diabetes. Particularly, these products have been implicated in the pathogenesis of proliferative diabetic retinopathy. The majority of these products are formed from a vast range of precursor molecules, the variable chemical nature of which contributes to AGE heterogeneity. There is a growing population of structurally defined AGE adducts such as pyrraline, pentosidine, CML and crossline that have been found to be elevated in diabetic tissues. In the present study, the levels of the glycoxidation product pentosidine were determined in vitreous samples obtained during vitrectomy from eyes with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and retinal detachment (RD). Samples from cadaveric control eyes were also included in the study. The levels of pentosidine were compared among the groups. Seventy-three vitreous samples were collected from eyes undergoing vitrectomy for PDR (n=33), PVR (n=28) and RD (n=12). Eighteen samples from cadaveric control eyes were also included in the study. A modified Bradford's method was used to assay protein content, and vitreous levels of pentosidine were determined by high-performance liquid chromatography after acid hydrolysis and pretreatment with SP-Sephadex. Statistical analyses were performed using a two-sided Mann-Whitney U test. The levels of pentosidine [median (interquartile range)] were 0.92 (0.55-1.26) pmol/mg of protein in the PDR cases, 1.12 (0.46-1.80) pmol/mg of protein in PVR, and 1.02 (0.24-1.44) pmol/mg of protein in RD. In the cadaveric control eyes pentosidine levels were 0.97 (0.68-1.30) pmol/mg of protein. The pentosidine levels of the four groups did not differ significantly. The levels of the glycoxidation product pentosidine (expressed as pmol/mg of protein) in the vitreous of eyes with PDR do not differ significantly from those in the vitreous of eyes with PVR, RD or cadaveric control eyes. Although these results do not refute the findings of previous studies that evaluated globally total AGE levels and the existence of diabetic vitreopathy, further investigation is needed to fully understand their relevance in this multifactorial disorder.

Prevalence and risk factors for proliferative vitreoretinopathy in eyes with rhegmatogenous retinal detachment but no previous vitreoretinal surgery

PurposeTo determine the prevalence of and risk factors for proliferatative vitreoretinopathy (PVR) in eyes with rhegmatogenous retinal detachment but no previous vitreoretinal surgery. DesignObservational case series. MethodsProspective study. SettingA private vitreoretinal clinic in Caracas, Venezuela. Study population119 eyes of 119 patients who presented with rhegmatogenous retinal detachment but no previous vitreoretinal surgery between 1995 and 1998. Observation proceduresData from detailed preoperative and postoperative examinations of each eye were recorded prospectively and entered into an electronic database. Main outcome measuresPrevalence of PVR of any type and severe PVR, preoperative risk factors for PVR of any type and severe PVR, effect of PVR and retinal detachment duration on initial and final visual acuity, and surgical complexity. ResultsThe prevalence of PVR of any type was 52.9% and of severe PVR was 26.9%. The mean retinal detachment duration (±SD) was 58.4 (±129.1) days, and the mean time from initial examination to surgical treatment (±SD) was 24.3 (81.2) days. By univariable analysis, long retinal detachment duration, poor initial visual acuity, and large retinal detachment extent were significantly associated with PVR prevalence and severity. The presence of vitreous hemorrhage was significantly associated with PVR prevalence, and cataract was significantly associated with PVR severity. By multivariable analysis, long retinal detachment duration and large retinal detachment extent were simultaneous risk factors for PVR prevalence, while long retinal detachment, large retinal detachment extent, and poor initial visual acuity were simultaneous risk factors for PVR severity. Eyes with longer retinal detachment duration, PVR of any type, and severe PVR had worse initial and final visual acuities than eyes with shorter retinal detachment duration or those without PVR, respectively. Eyes with PVR had more complex surgery than those without PVR. ConclusionsPVR occurred very frequently in this population and was associated with more complex surgery and worse visual outcomes than among eyes without PVR. We have identified preventable risk factors associated with PVR that suggest a specific and significant need for better access to ophthalmologic care and patient education in this group of patients.

PII: S0886-3350(04)00446-8

In addition to the ability for self-renewal and functional differentiation, neural stem/progenitor cells (NSCs) can respond to CNS injuries by targeted migration. In lower vertebrates, retinal injury is known to activate NSCs in the ciliary marginal zone (CMZ). Cells expressing markers of NSCs are also present in the ciliary body epithelium (CE) and in Müller glia in the peripheral retina (PR) of the adult human eye. However, these cells seem to be quiescent in the adult human eye and recent reports have shown that CE cells have limited properties of NSCs. In order to further clarify whether NSCs exist in the adult human eye, we tested whether NSC-like cells could be activated in eyes with proliferative vitreoretinopathy (PVR). The PR and CE were studied for NSC-associated markers in human enucleated control eyes and eyes with confirmed PVR, as well as in a mouse model of PVR. Furthermore, cells isolated from vitreous samples obtained during vitrectomies for retinal detachment were directly fixed or cultured in a stem cell-promoting medium and compared to cells cultured from the post-mortem retina and CE. In situ characterization of the normal eyes revealed robust expression of markers present in NSCs (Nestin, Sox2, Pax6) only around peripheral cysts of the proximal pars plana region and the PR, the latter population also staining for the glial marker GFAP. Although there were higher numbers of dividing cells in the CE of PVR eyes than in controls, we did not detect NSC-associated markers in the CE except around the proximal pars plana cysts. In the mice PVR eyes, Nestin activation was also found in the CE. In human PVR eyes, proliferation of both non-glial and glial cells co-staining NSC-associated markers was evident around the ora serrata region. Spheres formed in 7/10 vitreous samples from patients with PVR compared to 2/15 samples from patients with no known PVR, and expressed glial – and NSC-associated markers both after direct fixation and repetitive passages. In conclusion, the adult human eye may harbor two different populations of neuroepithelial stem/progenitor cells; a non-glial population located in the proximal pars plana around peripheral cysts in addition to a population with Müller glia characteristics. Yet, we only found that the glial population was able to respond to retinal injury by targeted migration into the vitreous.

Perfluorohexyloctane endotamponade for treatment of subfoveal hemorrhage.

To report on the use of perfluorohexyloctane as a heavy liquid to temporarily tamponade the fovea for the prevention of recurrent massive subfoveal hemorrhage in patients with exudative age-related macular degeneration (ARMD). The case series comprised seven patients with acute massive subfoveal hemorrhage due to exudative ARMD. The patients underwent pars plana vitrectomy, drainage of the subretinal blood, and foveal endotamponade with perfluorohexyloctane. The perfluorohexyloctane was removed 80.4 +/- 38.1 days (median 98 days; range 22-118 days) after the primary surgery in a second pars plana intervention. In six patients (85.7%) the subretinal hemorrhage removed during the first pars plana vitrectomy did not recur after removal of perfluorohexyloctane. In the seventh, however, a subretinal hemorrhage re-developed five days after release of perfluorohexyloctane. No large epiretinal membranes were observed. In six eyes (85.7%), the retina remained attached after removal of perfluorohexyloctane but in one eye proliferative vitreoretinopathy developed, with central retinal detachment. After the first pars plana vitrectomy, visual acuity increased slightly but not significantly (p = 0.25), from 0.03 +/- 0.03 to 0.05 +/- 0.07. Intraocular pressure rose from 15.0 +/- 1.9 mm Hg to 24.9 +/- 16.9 mm Hg. After a follow-up of 69.7 +/- 121.0 days after removal of the perfluorohexyloctane, final visual acuity was 0.02 +/- 0.04. Perfluorohexyloctane may be a useful additional tool for preventing the recurrence of subfoveal re-bleeding in exudative ARMD.

Triamcinolone-assisted pars plana vitrectomy improves the surgical procedures and decreases the postoperative blood-ocular barrier breakdown.

To determine the effect of a triamcinolone-assisted pars plana vitrectomy (PPV) on the visibility of hyaloid during surgery and the postoperative clinical outcome. Thirty-one patients with proliferative retinal disease [8 with diabetic macular edema (DME), 10 with proliferative diabetic retinopathy (PDR), 13 with proliferative vitreoretinopathy (PVR)] underwent PPV, where the vitreous body was visualized by the intravitreal injection of triamcinolone solution during the operation. The visual acuity, intraocular pressure (IOP), tamponade, corneal pathology, after-cataract, vitreous hemorrhage, and necessity of reoperation, were thereafter examined for at least 3 months after surgery. The anterior chamber laser flare cell meter was used on postoperative day 8 in DME eyes with triamcinolone-assisted PPV and with routine PPV to evaluate the breakdown of the blood-ocular barrier. The vitreous body was clearly seen by means of triamcinolone during surgery, which greatly helped us to perform a posterior hyaloid resection safely and thoroughly. Six of 8 DME eyes, 8 of 10 PDR eyes, and 5 of 13 PVR eyes showed an improvement in their vision postoperatively. No eye except one experienced IOP elevation above 21 mmHg for 7 days. Six eyes had vitreous hemorrhage. The DME eyes which received triamcinolone-assisted PPV showed significantly less breakdown of the blood-ocular barrier than those with routine PPV (Mann-Whitney U-test, P<0.01). Triamcinolone improved the visibility of the hyaloid and the safety of the surgical procedures during PPV and also inhibited the postoperative breakdown of the blood-ocular barrier. Although the long-term effects are still unknown, this method appears potentially useful as an improved treatment for proliferative retinal diseases.

Visual function after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy

PURPOSE: To assess functional and anatomical outcomes after foveal translocation with 360-degree retinotomy and simultaneous torsional muscle surgery in patients with myopic neovascular maculopathy. METHODS: Foveal translocation with 360-degree retinotomy was performed in 11 eyes of 11 patients with myopic neovascular maculopathy. Ten eyes had simultaneous torsional muscle surgery with recession of the superior oblique muscle and tucking of the inferior oblique muscle. Silicone oil removal with or without intraocular lens implantation was performed 2 to 8 weeks after the primary procedure. Visual acuity, binocular function, and degree of cyclotorsion were assessed preoperatively and postoperatively. Angles of retinal and globe rotation, distance of foveal shift, and surgical complications were also investigated. RESULTS: With a mean postoperative follow-up of 6.2 months (range, 3 to 13 months), vision improved (greater than 0.2 logarithm of minimal angle of resolution [logMAR] units) in eight eyes, was unchanged in two eyes, and worsened (greater than 0.2 logMAR units) in 1 eye. Seven of 11 eyes (64%) had a final visual acuity of 20/50 or better. Five patients developed or maintained binocular fusion, four patients continued to have suppression, and two patients developed diplopia that was managed by spectacles with Fresnel prisms. Subjective cyclotorsion was less than 8 degrees in 10 eyes. Mean retinal and globe rotations were 23.4 degrees and 19.8 degrees, respectively. Average size of the choroidal neovascular membrane was 0.8 disk diameter, whereas the average distance of foveal shift was 1.5 disk diameter. After the primary procedure, three eyes developed retinal detachment, one eye macular hole, and one eye proliferative vitreoretinopathy. These complications were successfully managed by additional surgery. CONCLUSION: Foveal translocation with 360-degree retinotomy is effective in restoring vision in some patients with myopic neovascular maculopathy. Although the development of torsional diplopia is generally obviated by simultaneous extraocular muscle surgery, a relatively high incidence of surgical complications should be taken into account with this procedure.

Silicone oil in the repair of pediatric complex retinal detachments: A prospective, observational, multicenter study

ObjectiveTo report anatomic and visual acuity outcomes, as well as complications, after using 1000-centistoke silicone oil as a retinal tamponade for the treatment of complex retinal detachments in a pediatric population. DesignA prospective, observational, multicenter study. ParticipantsThe study cohort consisted of 205 patients 16 years of age or younger (211 eyes) treated at community and university-based ophthalmology clinics for complex retinal detachments associated with trauma, proliferative vitreoretinopathy (PVR), giant retinal tear (GRT), or retinopathy of prematurity (ROP). InterventionVitrectomy surgery for complex retinal detachment with 1000-centistoke silicone oil as the retinal tamponade. Main outcome measuresAnatomic outcomes include complete retinal attachment and macular attachment. Visual acuity outcomes include ambulatory vision (≥4/200) and preservation of preoperative visual acuity. Complications include rates of secondary intraocular pressure (IOP) elevation (≥30 mmHg), hypotony (≤5 mmHg), corneal opacification (including band keratopathy, corneal edema, and corneal abrasions), oil emulsification, and cataract. All outcome measures were assessed 6, 12, and 24 months after surgery and at last examination. ResultsAt the 6-month examination, the retina was completely attached in 43 (57%) of 76 eyes in the trauma group, 24 (63%) of 38 PVR eyes, 23 (68%) of 34 GRT eyes, and 6 (33%) of 18 ROP eyes. The macula was attached in 60 (79%), 33 (87%), 26 (76%), and 8 (44%) eyes, respectively. Ambulatory vision was achieved in 19 (25%) eyes in the trauma group, 18 (47%) PVR eyes, 19 (56%) GRT eyes, and 4 (22%) ROP eyes. Visual acuity was preserved in 53 (70%), 26 (68%), 28 (82%), and 9 (50%) eyes, respectively. The corresponding rates of complications for traumatic, PVR, GRT, and ROP eyes were: elevated IOP—3 (4%) of 76, 1 (3%) of 38, 1 (3%) of 34, and 0 (0%) of 18; hypotony—9 (12%), 3 (8%), 2 (6%), and 2 (11%); corneal opacity—25 (33%), 8 (21%), 15 (44%), and 5 (28%); emulsification—4 (5%), 1 (3%), 3 (9%), and 1 (6%); and cataract in phakic eyes—1 (33%) of 3, 2 (67%) of 3, 2 (50%) of 4, and 1 (33%) of 3. ConclusionsRetinal reattachment and preserved visual acuity were achieved in the majority of eyes using vitrectomy and silicone oil retinal tamponade. Complete retinal and macular attachment was achieved less frequently in ROP eyes than in eyes in the other diagnostic groups. Use of 1000-centistoke silicone oil can be considered in the management of pediatric complex retinal detachments associated with multiple etiologies.