Vitreous Olink proteomics reveals inflammatory biomarkers for diagnosis and prognosis of traumatic proliferative vitreoretinopathy.

Background: The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model. Methods: The Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7-14 days after open globe injury (OGI) (N = 19) and macular hole patients (N = 22), followed by correlation analysis between DEPs and clinical signs, protein-protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI. Results: Forty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity (R = 0.467-0.699, p < 0.05), and all with optimal AUC values (0.7344-1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669-0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway (N = 14, p < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI. Conclusion: IL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers.

Transition to Chronic Fibrosis in an Animal Model of Retinal Detachment With Features of Proliferative Vitreoretinopathy.

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 was induced in adult Dutch Belted rabbits. Posterior segments were fixed or processed for RNA sequencing at 6 hours and 2, 7, 14, and 35 days after induction. Histochemical staining and immunolabeling for glial fibrillary acidic protein, alpha smooth muscle actin, vascular endothelial growth factor receptor 2, CD68, and RPE 65 kDa protein were performed, and labeling intensity was scored. Single cell RNA sequencing was performed. Results: Acute histopathological 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 was upregulated in chronic lesions. Conclusions: Histological and transcriptional features of this rabbit model simulate important features of human RRD-PVR, including the transition to chronic intraretinal and periretinal fibrosis. This animal model of RRD with features of PVR will enable further research on targeted treatment interventions.

A randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery for open globe trauma - the ASCOT study.

Background: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Proliferative vitreoretinopathy is the most common cause of retinal detachment and visual loss in eyes with open globe trauma. There is evidence from experimental studies and pilot clinical trials that the use of adjunctive steroid medication triamcinolone acetonide can reduce the incidence of proliferative vitreoretinopathy and improve outcomes of surgery for open globe trauma. Objective: The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study aimed to investigate the clinical effectiveness of adjunctive triamcinolone acetonide given at the time of vitreoretinal surgery for open globe trauma. Design: A phase 3 multicentre double-masked randomised controlled trial randomising patients undergoing vitrectomy following open globe trauma to either adjunctive triamcinolone acetonide or standard care. Setting: Hospital vitreoretinal surgical services dealing with open globe trauma. Participants: Patients undergoing vitrectomy surgery who had sustained open globe trauma. Interventions: Triamcinolone acetonide 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml sub-Tenon's or standard vitreoretinal surgery and postoperative care. Main outcome measures: The primary outcome was the proportion of patients with at least 10 letters of improvement in corrected visual acuity at six months. Secondary outcomes included retinal detachment secondary to proliferative vitreoretinopathy, retinal reattachment, macula reattachment, tractional retinal detachment, number of operations, hypotony, elevated intraocular pressure and quality of life. Health-related quality of life was assessed using the EuroQol Five Domain and Visual Function Questionnaire 25 questionnaires. Results: A total of 280 patients were randomised; 129 were analysed from the control group and 130 from the treatment group. The treatment group appeared, by chance, to have more severe pathology on presentation. The primary outcome (improvement in visual acuity) and principal secondary outcome (change in visual acuity) did not demonstrate any treatment benefit for triamcinolone acetonide. The proportion of patients with improvement in visual acuity was 47% for triamcinolone acetonide and 43% for standard care (odds ratio 1.03, 95% confidence interval 0.61 to 1.75, p = 0.908); the baseline adjusted mean difference in the six-month change in visual acuity was -2.65 (95% confidence interval -9.22 to 3.92, p = 0.430) for triamcinolone acetonide relative to control. Similarly, the secondary outcome measures failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal reattachment and stable macular retinal reattachment, outcomes for the treatment group were significantly worse for triamcinolone acetonide at the 5% level (respectively, odds ratio 0.59, 95% confidence interval 0.36 to 0.99, p = 0.044 and odds ratio 0.59, 95% confidence interval 0.35 to 0.98, p = 0.041) compared with control in favour of control. The cost of the intervention was £132 per patient. Health economics outcome measures (Early Treatment Diabetic Retinopathy Study, Visual Function Questionnaire 25 and EuroQol Five Dimensions) did not demonstrate any significant difference in quality-adjusted life-years. Conclusions: The use of combined intraocular and sub-Tenon's capsule triamcinolone acetonide is not recommended as an adjunct to vitrectomy surgery for intraocular trauma. Secondary outcome measures are suggestive of a negative effect of the adjunct, although the treatment group appeared to have more severe pathology on presentation. Future work: The use of alternative adjunctive medications in cases undergoing surgery for open globe trauma should be investigated. Refinement of clinical grading and case selection will enable better trail design for future studies. Trial registration: This trial is registered as ISRCTN 30012492, EudraCT number 2014-002193-37, REC 14/LNO/1428, IRAS 156358, Local R&D registration CHAD 1031. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (12/35/64) and will be published in full in Health Technology Assessment; Vol. 27, No. 12. See the NIHR Journals Library website for further project information.

Despite advances in surgical techniques, eye trauma remains a leading cause of blindness and visual impairment. The main cause of trauma is a scarring process within the eye ­ proliferative vitreoretinopathy. There is good evidence from laboratory work and small-scale clinical studies that the addition of a steroid medication, triamcinolone acetonide, given in and around the eye at the time of surgery for eye trauma, can reduce the incidence of proliferative vitreoretinopathy scarring and improve the outcomes of surgery. The Adjunctive Steroid Combination in Ocular Trauma or ASCOT study was a multicentre clinical trial designed to test the use of triamcinolone acetonide as an addition to surgery to improve outcomes in eyes with 'open globe' penetrating injuries. A total of 280 patients were recruited and randomised to receive standard surgery or surgery with the additional steroid (triamcinolone acetonide). No benefit was found from the addition of the steroid medication. The addition of steroid medication was not good value for money. Secondary outcome measures suggested that triamcinolone acetonide may have had a negative effect on outcomes, although this may have been due to the presence of more severe cases amongst the patients allocated to receive the additional steroid (triamcinolone acetonide). The use of adjunctive triamcinolone acetonide in eye trauma cases undergoing surgery is therefore not recommended. Future studies with different additional medications and/or more targeted case selection are indicated to improve outcomes for eyes experiencing penetrating trauma.

Intravitreal Injection of Bevacizumab for the Prevention of Postoperative Proliferative Vitreoretinopathy in High-Risk Patients Selected by Laser Flare Photometry.

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

[Severe contusion of the eyeball as a risk factor for the development of proliferative vitreoretinopathy]. / Kontuziya glaznogo yabloka tyazheloi stepeni kak faktor riska razvitiya proliferativnoi vitreoretinopatii.

The article is devoted to the problem of proliferative vitreoretinopathy (PVR) developing after severe contusions of the eyeball. Some experts doubt the possibility of developing such a severe complication after a closed eye injury, however, the accumulated literature data and research by scientists demonstrate a high probability of developing PVR in such cases, which could lead to adverse outcomes. The article presents the views of different authors and systematizes information about the frequency and the risk factors of developing PVR after different types of closed eye injury. The main purpose of this review is to demonstrate a high probability of developing PVR after a closed eye injury, which should alert specialists at the first stages of treatment in such patients and stimulate timely prevention and treatment of this complication.

Primary Retinal Detachment Repair in Eyes Deemed High Risk for Proliferative Vitreoretinopathy: Surgical Outcomes in 389 Eyes.

PURPOSE: To evaluate surgical outcomes in eyes with primary rhegmatogenous retinal detachment (RRD) deemed at high risk for postoperative proliferative vitreoretinopathy (PVR). DESIGN: Retrospective, consecutive case cohort study. PARTICIPANTS: Eyes undergoing primary RRD repair with pars plana vitrectomy (PPV) or combined PPV with scleral buckling (PPV/SB) between January 1, 2016, and December 30, 2017, at Wills Eye Hospital. METHODS: Eyes were defined as "high risk" if ≥ 1 of the following risk factors for PVR was present on preoperative examination: preoperative PVR grade A or B, vitreous hemorrhage, RRD involving ≥ 50% of retinal area, presence of ≥ 3 retinal breaks, history of prior cryotherapy, presence of choroidal detachment, or duration of RRD > 2 weeks. Surgical failure was defined as an additional intervention required for the retinal reattachment. MAIN OUTCOMES MEASURES: Single surgery attachment success (SSAS) rate 3 months after first surgical intervention for primary RRD. RESULTS: Of 2053 reviewed charts, a total of 389 eyes (18.9%) met the definition of high risk and were included in the analysis. Mean patient age was 63.5 years. PPV/SB was performed in 125 (32.1%) eyes and PPV alone in 264 (67.9%) eyes. SSAS rate of the overall cohort was 71.5% at 3 months. SSAS rate was significantly higher in eyes treated with PPV/SB compared with PPV (80.8% vs. 67%, respectively, P = 0.006). On multivariate analysis, use of PPV/SB was the only feature associated with SSAS (odds ratio, 2.04; 95% confidence interval, 1.12-3.69, P = 0.019). CONCLUSION: In eyes with primary RRD and risk factors for PVR, overall SSAS was 71.5% after primary repair. In this cohort, use of PPV/SB was associated with a significantly higher SSAS compared with PPV alone. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Proliferative Vitreoretinopathy Following Transscleral Diode Cyclophotocoagulation.

PRCIS: Transscleral diode laser cyclophotocoagulation may trigger the development of proliferative vitreoretinopathy. Our article demonstrates one such case leading to tractional macula-off retinal detachment in a child with aphakic glaucoma. PURPOSE: The purpose of this article is to describe a case of proliferative vitreoretinopathy (PVR) developing subsequent to transscleral diode laser cyclophotocoagulation (cyclodiode) in a pediatric patient with aphakic glaucoma. PVR most commonly occurs following rhegmatogenous retinal detachment repair; however, to the best of our knowledge, it has never been reported to appear after cyclodiode. METHODS: Retrospective evaluation of case presentation and intraoperative findings. RESULTS: A 13-year-old girl with aphakic glaucoma presented 4 months after cyclodiode of the right eye with a retrolental fibrovascular membrane and anterior PVR. The PVR extended posteriorly over the next month, after which the patient developed a tractional macula-off retinal detachment. Pars Plana vitrectomy was performed, confirming dense anterior and posterior PVR. A review of the literature suggests that an inflammatory cascade, similar to that seen in PVR development following rhegmatogenous retinal detachment, may occur from the destruction of the ciliary body by cyclodiode. As a result, fibrous transformation may occur, likely accounting for the cause of PVR development in this case. CONCLUSION: The pathophysiology of PVR development remains unclear. This case demonstrates that PVR may occur following cyclodiode and should be considered during postoperative monitoring after this procedure.

Predictive values of systemic inflammation biomarkers in proliferative vitreoretinopathy associated with primary rhegmatogenous retinal detachment.

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.

Novel insights into the pathophysiology of proliferative vitreoretinopathy: The role of vitreoschisis-induced vitreous cortex remnants.

PURPOSE: We previously hypothesized a causal relationship between vitreoschisis-induced vitreous cortex remnants (VCR) and the development of proliferative vitreoretinopathy (PVR). This study aims to substantiate this association through histopathological analysis of surgical specimens in support of strategies to improve therapeutic outcomes. METHODS: A descriptive, prospective, non-consecutive case series. Histopathological and immunohistochemical analyses were performed on membranes removed from the peripheral retinal surface during initial vitrectomy for primary rhegmatogenous retinal detachment (RRD) (n = 11) or recurrent retinal detachment (n = 12). The clinical aspect of the membranes ranged from loose-meshed membranes visualized with triamcinolone to more fibrotic membranes stained with trypan blue. RESULTS: Consistent with the clinical presentation, histopathological analysis revealed membranes with different area characteristics. Paucicellular lamellar collagen-rich areas, suggestive of VCR, appeared to transition to areas of increased cellularity and eventually more fibrotic areas of low cellularity. Five different area characteristics could be identified that seemed to correspond to five histopathological stages in PVR formation, with lamellar VCR collagen acting as an essential precondition: 1. Lamellar collagen, low cellularity (hyalocytes). 2. Lamellar collagen, increased cellularity (hyalocytes, glial cells). 3. Lamellar collagen, high cellularity (macrophages, glial cells, RPE-cells). 4. Early fibrosis, decreased cellularity (myofibroblasts). 5. Fibrosis, low cellularity (myofibroblasts). CONCLUSION: These findings confirm the role of VCR in preretinal PVR formation posterior to the vitreous base. We propose that the presence of VCR over the retinal surface should be qualified as a risk factor for PVR formation. Detection and adequate removal of VCR may improve the success rate of vitreoretinal surgeries.

Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial.

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

Pars Plana Vitrectomy with and without Supplemental Scleral Buckle for the Repair of Rhegmatogenous Retinal Detachment: A Meta-analysis.

TOPIC: It is unclear whether there are differences in safety and efficacy between pars plana vitrectomy (PPV) alone and PPV with a supplemental scleral buckle (SB; PPV-SB) for the treatment of rhegmatogenous retinal detachment. CLINICAL RELEVANCE: This meta-analysis aimed to compare the safety and efficacy of these surgical procedures. METHODS: In this meta-analysis, Ovid MEDLINE, Embase, and Cochrane Library were systematically searched (January 2000-June 2021). The primary outcome was the final best corrected visual acuity (BCVA), whereas the secondary outcomes were reattachment rates and complications. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs) and the risk of bias in nonrandomized studies of interventions tool for nonrandomized studies. RESULTS: This study included 15 661 eyes from 38 studies (32 observational studies and 6 RCTs). The median follow-up duration was 6 months. The final BCVA was similar between PPV and PPV-SB (weighted mean difference [WMD], -0.03 logarithm of the minimum angle of resolution [-0.14 to 0.07]; P = 0.55). There was a significant difference in the single-operation success rate (SOSR) (88.2% versus 86.3%; relative risk [RR], 0.97 [0.95-1.00]; P = 0.03), favoring PPV-SB; however, there was no significant difference in the final reattachment rate (RR, 1.00 [0.99-1.01]; P = 0.56). Pars plana vitrectomy required a significantly higher number of operations to achieve final anatomical reattachment (WMD, 0.13 [0.02-0.24]; P = 0.02). In terms of complications, PPV was significantly less likely to be associated with macular edema (RR, 0.47 [0.25-0.88]; P = 0.02) and epiretinal membrane formation (RR, 0.70 [0.52-0.94]; P = 0.02), but these differences were no longer significant in studies published after 2010 or in RCTs. Significant proliferative vitreoretinopathy, lens status, and macular attachment status did not mediate differences in these effects. CONCLUSIONS: There were no significant differences in the final visual acuity outcomes between PPV and PPV-SB. Pars plana vitrectomy with supplemental SB was associated with a greater SOSR than standalone PPV, although the magnitude of the effect was small, with a high number needed to treat. The final reattachment rate was similar. In recent studies and in RCTs, the risk of complications was similar between the procedures.

Vitreoschisis and retinal detachment: New insight in proliferative vitreoretinopathy.

PURPOSE: To assess the occurrence of peripheral vitreoschisis-induced vitreous cortex remnants (p-VCRs) in primary rhegmatogenous retinal detachment (RD) and investigate whether the presence of p-VCRs results in a greater risk of RD recurrence, secondary to Proliferative Vitreoretinopathy (PVR) development after pars plana vitrectomy (PPV). METHODS: Patients who underwent PPV for primary rhegmatogenous RD between January 2016 and December 2018 were included. The presence of residual p-VCRs was confirmed intraoperatively using triamcinolone acetonide (TA). Patients with p-VCRs were divided into two groups: Group A comprised of patients who underwent PPV without p-VCR removal, while Group B included patients who underwent PPV with p-VCR removal. RESULTS: Four hundred-thirteen eyes with evidence of p-VCR were analyzed. Two-hundred-twenty-three eyes underwent PPV without VCR removal (Group A), while 190 eyes underwent PPV with p-VCR removal (Group B). Primary anatomical success was 91.5% in the Group A and 95.4% in the group B. Retinal re-detachment due to PVR occurred in 17 (7.6%) eyes in Group A and in four (2.1%) eyes in Group B within the first 3 months (p = 0.01). Among group A, in 11 eyes, there was a diffuse posterior PVR grade C, while six eyes were focal PVR grade C. In Group B, we observed four retinal re-detachment due to focal PVR grade C. CONCLUSION: The presence of p-VCRs seems to be associated with a higher incidence of PVR development and might also result in more complex RD recurrence, this suggests the need for more aggressive VCRs removal during the first surgery.

Vitrectomy versus Combined Vitrectomy and Scleral Buckle for Repair of Primary Rhegmatogenous Retinal Detachment with Vitreous Hemorrhage.

PURPOSE: To compare pars plana vitrectomy (PPV) with combined PPV and scleral buckle (PPV/SB) for repair of primary rhegmatogenous retinal detachment (RRD) with associated vitreous hemorrhage (VH). DESIGN: Retrospective, observational study. PARTICIPANTS: Patients with RRD and associated VH who underwent PPV or PPV/SB from January 1, 2010, through August 31, 2020, were analyzed. METHOD: We performed a single-institution, retrospective, observational study of 224 eyes with RRD and VH at the time of detachment. We excluded eyes with <6 months of follow-up, a prior history of retinal detachment (RD) repair with vitrectomy or SB, VH that resolved before surgical intervention, and tractional or combined tractional and rhegmatogenous detachments. MAIN OUTCOME MEASURES: Single-surgery anatomic success (SSAS) at 6 months, defined as no recurrent RD requiring surgical intervention. RESULTS: Pars plana vitrectomy and PPV/SB were performed on 138 eyes (62%) and 85 eyes (38%), respectively. The mean age of the PPV and PPV/SB patients was 61.9 and 60.2 years, respectively. Single-surgery anatomic success was achieved in 107 of 138 eyes (77.5%) that underwent PPV and 78 of 85 eyes (91.7%) that underwent PPV/SB. The difference in SSAS between types of treatment was significant (P = 0.006). Mean visual acuity improvement in the PPV/SB group was 0.54 logMAR units greater than that in the PPV group (P = 0.126). The incidence of postoperative proliferative vitreoretinopathy in the PPV/SB group (11.7%) was lower than that in the PPV group (19.5%; P = 0.128). The rate of repeat PPV for non-RD reasons was similar for both the groups (P = 0.437). Final reattachment status was achieved in 137 of the 138 and 84 of the 85 eyes in the PPV and PPV/SB groups, respectively. Final visual acuity improvement was significantly better in eyes with PPV/SB than in eyes with PPV alone (logMAR 2.12 vs. 1.26, respectively; P = 0.011). CONCLUSIONS: In patients with RRD and VH, SSAS was superior in patients treated with PPV/SB compared with those treated with PPV alone. Although not significantly different, the PPV/SB group had better visual outcomes and a lower postoperative proliferative vitreoretinopathy rate.

Postoperative proliferative vitreoretinopathy development is linked to vitreal CXCL5 concentrations.

The specific changes linked to de novo development of postoperative PVR have remained elusive and were the object of the underlying study. Vitreous fluid (VF) was obtained at the beginning of vitrectomy from 65 eyes that underwent vitrectomy for primary rhegmatogenous retinal detachment (RRD) without preoperative PVR. Eyes developing postoperative PVR within 6 months after re-attachment surgery were compared to those which did not regarding the preoperative concentrations of 43 cytokines and chemokines in the VF, using multiplex beads analysis. For all comparisons Holm's correction was applied in order to control for multiple comparisons. Twelve out of 65 eyes (18.5%) developed PVR postoperatively. While 12 of the chemokines and cytokines presented concentration differences on a statistical level of p < 0.05 (CXCL5, CCL11, CCL24, CCL26, GM-CSF, IFN-γ, CCL8, CCL7, MIF, MIG/CXCL9, CCL19, and CCL25), CXCL5 was the only cytokine with sufficiently robust difference in its VF concentrations to achieve significance in eyes developing postoperative PVR compared to eyes without PVR. CXCL5 may represent a potent biomarker for the de novo development of postoperative PVR. In line with its pathophysiological role in the development of PVR, it might serve as a basis for the development of urgently needed preventive options.

Yes-associated protein is essential for proliferative vitreoretinopathy development via the epithelial-mesenchymal transition in retinal pigment epithelial fibrosis.

This study was aim to investigate whether the progression of proliferative vitreoretinopathy (PVR) depended on the activation of Yes-associated protein (YAP) and the subsequent epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cell. The effect of YAP activation on retinal fibrosis in a PVR mouse model and in human ARPE-19 cells in vitro was studied. After treated with transforming growth factor-ß2(TGF-ß2), the expressions of fibrogenic molecules, YAP activation and the TGF-ß2-Smad signalling pathway in ARPE-19 cells were detected by Western blot and immunocytochemical analyses. The effect of YAP on change in fibrosis and EMT was tested by knockdown experiment using verteporfin (YAP inhibitor). YAP was upregulated in the PVR mouse model and during TGF-ß2-induced RPE cell EMT. In an in vivo study, verteporfin attenuated PVR progression in a mouse model. Additionally, YAP knockdown retained phenotype of RPE cells and ameliorated TGF-ß2-induced migration, gel contraction and EMT in vitro. YAP knockdown inhibited the TGF-ß2-induced upregulation of connective tissue growth factor (CTGF), smooth muscle actin (SMA-α) and fibronectin. YAP was essential for the TGF-ß2-induced nuclear translocation and phosphorylation of Smad2/3. Our work provides direct evidence that YAP is an essential regulator of EMT and profibrotic responses in PVR and indicates that YAP inhibition could be a potential target in PVR therapeutic intervention.

LATE PRESENTATION OF RETINAL DETACHMENT: CLINICAL FEATURES AND SURGICAL OUTCOMES.

PURPOSE: To describe and evaluate demographic, clinical features, prognostic factors, and rate of success of surgery and visual outcomes in patients with late presentation of retinal detachment. METHODS: A retrospective, comparative, observational case series of patients with late presentation retinal detachment, defined as retinal detachment with the loss of central vision for 4 weeks or more, over a period of 12 months. RESULTS: The mean of onset of central visual loss was 12.7 weeks (SD, 21.3). Proliferative vitreoretinopathy at the first operation was identified in 69% of eyes. The overall primary success rate was 69.2%, significantly less than that was found in outcomes for nonselected retinal detachment (primary success rate, 86%; P = 0.006). The initial best-corrected visual acuity was 20/500, and the final was 20/160 (P = 0.0027). There were no identifiable statistically significant socioeconomic factors related to late presentation. CONCLUSION: A high rate of established proliferative vitreoretinopathy on presentation was identified, and although cases can be treated with good anatomical results, visual outcomes are often less favorable. Primary surgical success is lower, and more reoperations are required compared with standard retinal detachments.

Activated Blood Coagulation Factor X (FXa) Contributes to the Development of Traumatic PVR Through Promoting RPE Epithelial-Mesenchymal Transition.

Purpose: Uncontrolled coagulation reactions contribute to pathological fibroproliferation in several organs, and yet their role in proliferative vitreoretinopathy (PVR) remains to be elucidated. In this study, we evaluated the profibrotic effects of FXa in RPE cells and in a mouse model of PVR. Methods: FXa levels in the eyes of traumatic PVR patients and rabbit models of mechanical ocular trauma was measured by ELISA and immunohistochemistry. FXa-induced RPE EMT was assessed by examining cell proliferation, migration, tight junction changes, and expression of fibrotic markers. For in vivo study, FXa was injected into dispase-injured eyes, then intraocular fibrosis was evaluated by histological analysis and Western blotting. The therapeutic effect of FXa inhibitor was also examined in PVR mouse models. Results: Vitreous FXa were higher in patients with traumatic PVR compared to patients with macular hole. Moreover, expressions of FXa and PAR1 were found in the epiretinal membranes from traumatic PVR patients. Vitreous FXa were markedly increased after mechanical ocular trauma in rabbits. In vitro, FXa stimulated RPE EMT characterized as ZO-1 disruption, compromised cell polarity, and increased fibronectin expressions. Co-injection of FXa and dispase in mice induced more severely damaged retinal structures, and increased α-SMA expressions than FXa or dispase treatment alone. Oral FXa or thrombin inhibitors significantly blocked intraocular fibrosis in PVR mouse models. FXa promoted phospho-activation of p38 in ARPE19 cells, which was dependent on PAR1. Moreover, TGF-ßR inhibitor also significantly alleviated FXa-induced intraocular fibrosis in mice. Conclusions: FXa promotes intraocular fibrosis in mice via mechanisms involving RPE activation.

Sustained dasatinib treatment prevents early fibrotic changes following ocular trauma.

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

Comparison of Chemokine CXCL-1 and Interleukin-6 Concentrations in the Subretinal Fluid and Vitreous in Rhegmatogenous Retinal Detachment.

Purpose: Comparison of IL-6 and CXCL-1 concentrations and CXCL-1/IL-6 ratio correlations with clinical parameters (RRD extent, duration, and proliferative vitreoretinopathy - PVR-grade) between subretinal fluid (SRF) and vitreous during rhegmatogenous retinal detachment (RRD) complicated with PVR.Methods: A total of 71 eyes of 71 patients with primary RRD possibly complicated with PVR were included; 36 eyes treated with scleral buckling and 35 eyes with pars-plana vitrectomy. Enzyme-Linked Immuno-sorbent Assay was employed for CXCL-1/IL-6 measurement (ng/ml).Results: Correlation analysis between mean CXCL-1/IL-6 ratio and clinical parameters revealed non-significant results. CXCL-1/IL-6 ratio was significantly elevated in phakic eye vitreous. Optimum circumstances for elevated chemokine levels during RRD were considerable extent (2-3-quadrant) and duration (29-60-day) complicated with PVR C.Conclusions: SRF appears to be characterized by greater chemokine concentrations while vitreous retains several structural characteristics that may assist in investigating inflammation and improving understanding of underlying pathophysiological mechanisms during RRD complicated with PVR.