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Introduction: Rhegmatogenous retinal detachment (RRD) is a vision-threatening complication of viral retinitis, at times compounded by proliferative vitreoretinopathy (PVR) at the junction of the necrotic and unaffected retina., Methods: Retrospective review of eyes with 'junctional PVR' in RRD after viral retinitis. We define junctional PVR as presence of stiffness, transverse traction, epiretinal membrane and/or pucker at the junction of normal and necrotic retina., Results: Five eyes of four patients with a mean age at presentation of 46.5 ± 10.96 years were included. Immunosuppression due to Human immunodeficiency virus (HIV) was the underlying condition in all the cases. Posterior hyaloid removal and epiretinal membrane removal at the junctional PVR was performed in all cases. Favourable outcomes were observed in seven sites where epiretinal membrane (ERM) removal with inner limiting membrane (ILM) peeling was performed; however, one site developed localised RRD requiring re-surgery. The mean logMAR best-corrected visual acuity (BCVA) improved from 1.84 before surgery to 0.64 during the last follow-up. All patients had undergone 23 G vitrectomy and silicone oil tamponade 1500 Centistokes (cSt) was used in all patients for a mean duration of 6.8 months., Conclusion: Management of posterior hyaloid coupled with ERM removal and localised ILM peeling may be used to address junctional PVR in the eyes with RRD after viral retinitis., Competing Interests: Declarations. Conflict of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Rhegmatogenous retinal detachment (RRD) is a sight-threatening condition involving retinal detachment and the accumulation of fluid in the subretinal space. Proliferative vitreoretinopathy (PVR) is a pathologic complication that develops after RRD surgery, and approximately 5-10% of RRD cases develop post-operative PVR. Prolonged inflammation in the wound healing process, epithelial-mesenchymal transition (EMT), retinal pigment epithelial (RPE) cell migration and proliferation, and epiretinal, intraretinal, and subretinal fibrosis are typical in the formation of PVR. RPE cells undergo EMT and become fibroblast-like cells that migrate to the retina and vitreous, promoting PVR formation. Fibroblasts transform into myofibroblasts, which promote fibrosis by overproducing the extracellular matrix (ECM). RPE cells, fibroblasts, glial cells, macrophages, T lymphocytes, and increased ECM production form contractile epiretinal membranes. Cytokine release, complement activation, RPE cells, glial cells, and endothelial cells are all involved in retinal immune responses. Normally, wounds heal within 4 to 6 weeks, including hemostasis, inflammation, proliferation, and remodeling phases. Properly initiated inflammation, complement activation, and the function of neutrophils and glial cells heal the wound in the first stage. In a retinal wound, glial cells proliferate and fill the injured area. Gliosis tries to protect the neurons and prevent damage, but it becomes harmful when it causes scarring. If healing is complicated, prolonged inflammation leads to pathological fibrosis. Currently, there is no preventive treatment for the formation of PVR, and it is worth studying in the future.

Proliferative vitreoretinopathy (PVR) significantly impacts the prognosis of rhegmatogenous retinal detachment (RRD), one of the most critical and increasing causes of vision loss in the Western world. Despite advancements in surgical instruments and techniques, the failure rate due to PVR remains substantial, necessitating additional surgeries and often leading to unsatisfactory visual outcomes. This comprehensive review explores the role of vitreoschisis-induced vitreous cortex remnants (VCR) as a critical, previously under-recognised factor contributing to PVR. Vitreoschisis, a phenomenon where the inner lamellae of the posterior vitreous cortex detach while the outermost layers remain attached to the retina, creates VCR that may contain hyalocytes and serve as scaffolds for fibrocellular proliferation. These remnants are difficult to visualise without triamcinolone acetonide (TA) staining, leading to their frequent lack of recognition in clinical practice. Moreover, removing VCR can be challenging and time-consuming, often requiring meticulous surgical techniques to avoid retinal damage and ensure complete elimination. This review consolidates insights from basic research and clinical practice, emphasising the importance of complete vitreous removal and effective VCR detection and removal to mitigate PVR risks. It highlights the histopathological and clinical evidence supporting the hypothesis that VCR, containing hyalocytes, play a pivotal role in preretinal membrane formation. The review also discusses epidemiological data, surgical management strategies and potential future directions, including improved visualisation techniques and the development of new surgical tools and methods. This review aims to improve surgical outcomes and reduce the frequency and burden of RRD-related complications by addressing VCR as a critical factor in PVR., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To examine the incidence and risk factors of proliferative vitreoretinopathy (PVR) in the patients who develop rhegmatogenous retinal detachment (RRD) in their fellow eye after having a prior RRD complicated by PVR., Design: Multicenter, retrospective observational study., Subjects: Eyes with retinal detachment and PVR between 2015 and 2023 were identified through the Vestrum Health Database., Methods: Risk factors for PVR development, specifically documented PVR in the fellow eye, gender, age, lens status, and presenting and final visual acuity (VA), were evaluated., Main Outcome Measures: Odds ratio (OR) for PVR development during 6 months postoperative period., Results: Of 57 264 patients, 11% had PVR in ≥1 eye. Of the 50 989 patients who did not develop PVR after the initial RRD, 4834 developed RRD in the fellow eye. One hundred sixty-six of these patients developed PVR in their second eye for a PVR rate of 3% in the fellow eye. Of the 6275 patients who developed PVR after primary RRD repair, 406 of these patients went on to develop RRD in their fellow eye. Forty-two of these patients developed PVR in their second eye for a PVR rate of 10%. A regression model that also included age, gender, and VA led to an OR of 3.42 (P < 0.001). The OR of PVR development generally decreased with age. Pseudophakic patients had a higher OR for PVR development, 1.48 (P = 0.017). Initial patients with VA 20/40 to 20/80 had an OR of 2.15 (P = 0.003). Patients with VA worse than 20/200 had an OR of 2.89 for PVR development (P < 0.001)., Conclusions: Patients with a history RRD with PVR in 1 eye have approximately 3.5 times higher rate of PVR in their second eye after RRD compared with patients without a history of PVR. This finding potential impacts surgical decisions and use of prophylactic anti-PVR therapy if the patient's second eye has RRD. The final VA in the second eye of patients with a history of PVR is better than for the second eye of patients with no history of PVR, which may indicate surgeons are already taking steps to prevent PVR in the patient's second eye., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Background: Autosomal dominant neovascular inflammatory vitreoretinopathy (NIV), formerly called "ADNIV," is a rare autoinflammatory condition mainly of adulthood caused by mutations in calcium-activated calpain-5 protease (CAPN5). Our aim is to report the treatment and visual outcomes of children newly diagnosed with NIV after systemic treatment., Methods: We reviewed charts of patients ≤18 years old with CAPN5 gene mutation, ocular findings consistent with NIV, and treated with systemic immunosuppression for a minimum of 6 months. Treatment response was based on ophthalmic examination, ultra-widefield fluorescein-angiography (UWFFA), and optical coherence tomography (OCT)., Results: Eight children (16 eyes) were diagnosed with NIV at a median age of 14 (Range [R] 9-16) years, with a median follow-up of 18 months (R6-20). At diagnosis, one patient had impaired visual acuity (VA > 0.4), eight had vascular leakage, two had neovascularization, and three had macular edema. All responded to oral or local glucocorticoids but was not sustained. Systemic immunosuppression was started in seven patients with methotrexate and infliximab after a median time from diagnosis of 1.5 months (R0.5-2) and 3.2 months (R2.5-3.1), respectively. Infliximab was discontinued in all after a median time of 7 months (R3.5-10) for ineffectiveness, and 5/7 switched to tocilizumab and 1 to adalimumab. Five failed to respond (4 tocilizumab, 1 adalimumab) and one had a minimal response to tocilizumab., Conclusions: We report on the systemic treatment response of seven children with ADNIV treated with methotrexate, infliximab, and tocilizumab. None were able to control disease. Further studies are needed to understand long-term outcomes and the utility of systemic immunosuppression.

Previous concepts for the pathogenesis of proliferative vitreoretinopathy (PVR) have focused on the central role of retinal pigment epithelium cells only, potentially contributing to the lack of clinical advances. More recent studies have demonstrated the essential role of retinal glial cells in the PVR healing response but failed to identify a consistent triggering mechanism.We propose a revised concept for the pathogenesis of PVR based on retinal injury and response. A posterior vitreous detachment (PVD) is invariably present in patients with rhegmatogenous retinal detachment and PVR. There is evidence to suggest that the shearing forces of acute PVD can cause mechanical injury to the inner retina and trigger a subsequent intraretinal glial healing response. That response is characterised by subclinical glial cell activation and proliferation that may then be amplified into full-blown PVR by coexisting pathology such as retinal breaks and detachment.Whether a PVD causes interface pathology depends on the plane of separation of the posterior vitreous and areas of increased vitreoretinal adhesions. If the vitreous separates in a plane or location that damages the inner retina then glial cell activation and proliferation are likely to develop. The severity of the subclinical inner retinal damage may then represent one of the missing links in our understanding of the pathogenesis of PVR and would explain many of the findings we encounter in clinical practice. Controlling the process of acute PVD and subsequent intraretinal response may be essential in the prevention and management of PVR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Open globe injuries are a significant global cause of visual loss, including unilateral and bilateral blindness. Prognosis is predicted by injury severity, with lower presenting visual acuity and more posterior injuries associated with poor visual outcomes, although even the most severely injured eyes with no perception of light vision may regain some visual function. In addition to severity of the primary injury, the secondary injuries and complications causing poor outcomes include proliferative vitreoretinopathy (PVR) and endophthalmitis. Endophthalmitis is common after open globe injury, affecting up to 16.5% of patients. Systemic antibiotic prophylaxis is commonly used, with a limited evidence base, while intraocular antibiotics are less commonly used but have stronger supporting evidence of efficacy. Endophthalmitis rates are also reduced by prompt primary repair, which may also support recovery of visual acuity. PVR is not prevented or treated by any pharmacologic interventions in current clinical practice, but the incidence of post-traumatic PVR may be reduced by early vitrectomy within the first 4-7 days after injury. Ocular trauma training is often limited in Western ophthalmic surgical training programmes, and patients with ocular trauma often require the input of multiple subspecialists. In this context, it is important that patients have an overview and coordination of the different aspects of their care, with ownership by one lead clinician., (© 2024. Crown.)

Purpose: To describe an ophthalmoscopic sign, termed a meniscus micropyon, and its possible association with proliferative vitreoretinopathy/epiretinal membrane (ERM) formation after retinal surgery with gas tamponade., Methods: Patients with intravitreal gas were examined postoperatively by one of six vitreoretinal surgeons from four institutions. A micropyon was defined as a white-yellow, solid-appearing consolidation along the meniscus (i.e., the fluid-gas interface)., Results: A micropyon was visualized and photographed in 49 patients who received intravitreal gas. Preoperatively, retinal breaks were present in all 49 eyes and rhegmatogenous retinal detachment in 45 (92%). Postoperatively, 39 eyes (80%) developed epiretinal proliferation: 16 eyes (33%) developed recurrent rhegmatogenous retinal detachment from proliferative vitreoretinopathy, 6 eyes (12%) re-detached without frank proliferative vitreoretinopathy, 9 eyes (18%) developed postoperative ERM/worsening, and 8 eyes (16%) had postoperative ERM but no preoperative optical coherence tomography to determine if the postoperative ERM was new or worsening. The single-operation anatomical success in eyes with a micropyon was 51%, which was lower than that of a contemporaneous rhegmatogenous retinal detachment control group (91%) in which no micropyon was detected. In two patients, micropyons were biopsied during pars plana vitrectomy and examined histopathologically; they consist predominantly of white blood cells., Conclusion: The meniscus micropyon is an ophthalmoscopic sign that can occur after retinal surgery with gas tamponade. Features that distinguish a micropyon from postvitrectomy fibrin/fibrinoid syndrome include delayed appearance, hyperautofluorescence, absence of translucent strands or sheets in the anterior chamber or vitreous cavity, and the histopathologic identification of white blood cells. A clinically detectable micropyon may be a biomarker of proliferative vitreoretinopathy/ERM formation.

Purpose: To evaluate the predictive value of initial intraocular pressure difference of the detached and fellow eyes of patients with complex rhegmatogenous retinal detachment on postoperative persistent ocular hypotony., Methods: This retrospective observational study included 538 eyes of 538 unilateral complex rhegmatogenous retinal detachment patients with a proliferative vitreoretinopathy grade of C-1 or higher, treated with silicone oil endotamponade following pars plana vitrectomy. The patients were divided into Group A (patients having silicone oil removal without ocular hypotony; n=504) and Group B (patients with persistent ocular hypotony following silicone oil removal [n=8, 23.5%] and with retained silicone oil [n=26, 76.5%] due to the risk of persistent ocular hypotony; total n=34). Ocular hypotony was defined as an intraocular pressure of <6 mmHg on two or more occasions. Patients' demographics, including age, sex, and follow-up time, and ocular characteristics, including ocular surgical and trauma history, initial and final best-corrected visual acuity, intraocular pressure and initial intraocular pressure difference of the detached and fellow eyes, and anatomical success rates and postoperative complications, were retrospectively collected from the electronic patient files., Results: The initial intraocular pressure was significantly lower in the detached eyes of Group B than in Group A (8.3 ± 3.5 vs. 12.9 ± 3.3, p<0.001). Also, the initial intraocular pressure difference was significantly higher in Group B than in Group A (8.9 ± 3.2 vs. 2.2 ± 2.7mmHg, p<0.001). The receiver operating characteristic curve analysis showed that the cutoff value of the initial intraocular pressure difference was 7.5mmHg for the risk of persistent ocular hypotony. The most influential factors on postoperative persistent ocular hypotony in the binary logistic regression analysis were the initial intraocular pressure difference and the need for a retinectomy., Conclusion: In eyes with complex rhegmatogenous retinal detachment treated with pars plana vitrectomy and silicone oil tamponade, the initial intraocular pressure difference could be of value in predicting postoperative persistent ocular hypotony and could guide surgeons on the decision of silicone oil removal.

Purpose: To assess an association between cutaneous keloids, hypertrophic scarring, and fibrosis (KHF) and risk of postoperative proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) repair., Design: Retrospective, population-based cohort study., Participants: Patients aged ≥ 18 years who underwent initial retinal detachment (RD) repair with pars plana vitrectomy with or without scleral buckle (SB) (Current Procedural Terminology [CPT] 67108), pneumatic retinopexy (67110), and primary SB (67107) from January 1, 2003, to March 1, 2023., Methods: A de-identified electronic health record database through TriNetX, a global health research network, was used to analyze patients. Patients were queried for International Classification of Diseases, 10 th Revision (ICD-10) codes L91.0 (hypertrophic scar) and L90.5 (scar conditions and fibrosis of skin). Frequency of subsequent diagnosis of PVR (H35.2) and CPT codes for secondary surgery including complex RD repair (67113) were determined. Patients with proliferative diabetic retinopathy (PDR) (ICD-10 H10.35/H11.35) were excluded. Descriptive statistics (Z-test) and propensity score matching (PSM) were used to match for age, sex, and race., Main Outcome Measures: Prevalence of H35.2 and CPT 67113 within 180 days after RRD repair in the KHF cohort versus the non-KHF cohort., Results: Among patients with CPT 67108, 1061 in each cohort (KHF and non-KHF) were analyzed after PSM. The mean (standard deviation) age was 60.7 (15.2) years. Within 180 days, 10.1% of patients in the KHF cohort and 3.4% in the non-KHF cohort had a diagnosis of PVR (H35.2) (P < 0.001, odds ratio [OR], 3.2; 95% confidence interval [CI], 2.13-4.71). A total of 8.3% of patients in the KHF cohort and 5.4% of patients in the non-KHF cohort underwent complex RD repair (CPT 67113) (P = 0.008; OR, 3.2; 95% CI, 1.13-2.25). When including all RD repair types (CPT 67108, 67110, 67107), the rate of PVR diagnosis was still significantly greater in the KHF cohort than in the non-KHF cohort (9.0% vs 4.2%, P < 0.01; OR, 2.28; 95% CI, 1.64-3.16)., Conclusions: A dermatologic history of KHF may be a risk factor for PVR after RD repair., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

High intraocular pressure (IOP) is one of the early complications after pars plana vitrectomy (PPV), which may cause glaucoma and poor visual prognosis secondary to surgery. Proliferative vitreoretinopathy (PVR) is one of the complications of retinal detachment (RD) and is the main reason for the poor prognosis, which is related to different kinds of cytokines. It's essential for the basic mechanism to analyze the relative aqueous humor cytokine profiles with IOP after PPV for RD. In this study, we have collected the aqueous humor of 16 patients and qualified 27 cytokines using Luminex and compared biomarkers with the high IOP group and the normal group. As a result, the concentrations of VEGF, IL-6, FGF2, and G-CSF upregulated significantly (P < 0.05), while VEGFR2 downregulated significantly (P < 0.05) in the high IOP group. IL-6 was positively correlated with high IOP (r = 0.561, P = 0.041). Meanwhile, the concentrations of IL-6 (r = 0.543, P = 0.03), IL-5 (r = 0.576, P = 0.019), IL-15 (r = 0.614, P = 0.011), IL-4 (r = 0.517, P = 0.04), ICAM-1 (r = 0.611, P = 0.012), and G-CSF (r = 0.636, P = 0.008) were significantly associated with preoperative PVR classification, and the aqueous humor levels of IL-4 (r = 0.567, P = 0.022), HGF (r = 0.701, P = 0.005), and MCP-1 (r = 0.565, P = 0.035) are significant relative to laser points. Hence, cytokines might potentially be the therapeutic target of high IOP after PPV., (© 2024. The Author(s).)

Purpose: To investigate the efficacy, safety, and indications for additional pneumatic retinopexy (PR) in patients with persistent retinal detachment after scleral buckling., Methods: This retrospective study included patients who underwent additional PR after scleral buckling for primary rhegmatogenous retinal detachment (n = 78). We defined "inadequate buckle" as retinal detachment persistence because of low buckle height despite accurate buckle placement and "buckle misplacement" as an uncovered tear because of incorrect buckle placement., Results: The anatomical success rate after additional PR was 52.6%. Development of proliferative vitreoretinopathy Grade B (hazard ratio, 5.73; P < 0.001) and inferior retinal tears (hazard ratio, 2.12; P = 0.040) were significant risk factors for anatomical failure. The most common cause of anatomical failure was proliferative vitreoretinopathy (19 of 37; 51.4%), and epiretinal membrane formation was a common complication after additional PR (22 of 78; 28.2%). The anatomical success rate with additional PR was significantly higher in the inadequate buckle group than in the misplacement group (8 of 9 [88.9%] vs. 1228 [42.9%]; P = 0.023)., Conclusion: Development of proliferative vitreoretinopathy Grade B and inferior retinal tears were significantly associated with anatomical failure after additional PR. Additional PR may benefit patients with superior retinal tears or low buckle height and those without 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Wang, Yu, Shi, Liang, Chen, He and Yan.)

Diabetic vitreopapillary traction syndrome (VPT) is a variant of diabetic retinopathy (DR) that can lead to vision loss in advanced stages. This review reports on the biomechanics of the vitreous in the pathogenesis of proliferative DR, in particular diabetic VPT. The article analyzes and summarizes literature data, presents the views of different authors on this problem, and provides the results of Russian and foreign scientific research on this pathology. It is concluded that further research in this area can lead to a significant improvement in the results of therapy, timely diagnosis, and preservation of vision in patients with DR.

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.

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., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

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.

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., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023 S. Karger AG, Basel.)

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., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (© 2021. The Author(s).)

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-β2(TGF-β2), the expressions of fibrogenic molecules, YAP activation and the TGF-β2-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-β2-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-β2-induced migration, gel contraction and EMT in vitro. YAP knockdown inhibited the TGF-β2-induced upregulation of connective tissue growth factor (CTGF), smooth muscle actin (SMA-α) and fibronectin. YAP was essential for the TGF-β2-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., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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., Competing Interests: The authors report no conflicts of interest

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-βR inhibitor also significantly alleviated FXa-induced intraocular fibrosis in mice., Conclusions: FXa promotes intraocular fibrosis in mice via mechanisms involving RPE activation.

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.

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.

Background: Proliferative vitreoretinopathy (PVR) is one of the most important complications following vitreoretinal surgery. So far, surgical strategies have been the gold standard in treatment. Pharmacological approaches for prevention and treatment of PVR are under clinical investigation and intervene in different phases of the PVR cascade., Methods: The relevant literature as well as own data and experience with PVR are discussed in this review article. The most important aspects of pharmacological approaches for PVR prophylaxis and treatment are explained., Results: A prophylactic use of systemic prednisone administration as an anti-inflammatory substance showed contradictory results, while there was no additional benefit for intravitreal triamcinolone. Orally administered isotretinoin also seems to be able to minimize the formation of PVR after retinal reattachment surgery, whereas there was no improvement in the success rate in established PVR. Cell proliferation inhibitors have already been extensively studied. The combined intravitreal prophylactic approach of 5‑fluorouracil and low molecular weight heparin was recently further investigated in a multicenter, placebo-controlled study and showed a positive effect in some studies. New preclinical and experimental approaches include the inhibition of growth factors, modulation of integrin activity and the induction of apoptosis., Conclusion: Most clinical studies dealt with an anti-inflammatory or antiproliferative approach. So far, no pharmacological substance has been established for the treatment of PVR but there are promising approaches for prophylaxis.

We aimed to assess the feasibility of machine learning (ML) algorithm design to predict proliferative vitreoretinopathy (PVR) by ophthalmologists without coding experience using automated ML (AutoML). The study was a retrospective cohort study of 506 eyes who underwent pars plana vitrectomy for rhegmatogenous retinal detachment (RRD) by a single surgeon at a tertiary-care hospital between 2012 and 2019. Two ophthalmologists without coding experience used an interactive application in MATLAB to build and evaluate ML algorithms for the prediction of postoperative PVR using clinical data from the electronic health records. The clinical features associated with postoperative PVR were determined by univariate feature selection. The area under the curve (AUC) for predicting postoperative PVR was better for models that included pre-existing PVR as an input. The quadratic support vector machine (SVM) model built using all selected clinical features had an AUC of 0.90, a sensitivity of 63.0%, and a specificity of 97.8%. An optimized Naïve Bayes algorithm that did not include pre-existing PVR as an input feature had an AUC of 0.81, a sensitivity of 54.3%, and a specificity of 92.4%. In conclusion, the development of ML models for the prediction of PVR by ophthalmologists without coding experience is feasible. Input from a data scientist might still be needed to tackle class imbalance-a common challenge in ML classification using real-world clinical data.

Background and Objective: To determine the risk factors associated with developing proliferative vitreoretinopathy (PVR) from combat ocular injuries in U.S. service members., Patients and Methods: Retrospective review of associated risk factors and outcomes of PVR within the Walter Reed Ocular Trauma Database. Ocular injuries in U.S. service members wounded during Operation Enduring Freedom and Operation Iraqi Freedom from 2001 to 2011 were assessed, and of these all cases of PVR were studied. Principal outcome measures were the risk factors associated with PVR development and rate of final visual acuity (VA) less than 20/200., Results: Eight hundred ninety eyes of 651 U.S. service members were evaluated. A total of 76 eyes (8.5%) of 66 patients developed PVR. Five patients had bilateral PVR. Nineteen patients had bilateral eye injuries. Sixty-one eyes (80.2%) had a final VA less than 20/200. PVR was found to be a significant risk factor for a poor final VA (P < .001). Retinal detachment (RD) was found in 52 eyes (68.4%) of patients. In patients with a RD, intraocular foreign bodies (IOFBs) (P < .001), unsuccessful repair (P = .002), and macular hemorrhage (P = .04) were significant risk factors for the development of PVR. Time to initial retina surgery was not found to be a risk factor for PVR development (P = .5). Time to initial retina surgery was available in 41 patients and the time to surgery on average was 22.56 days (range: 3 to 87 days)., Conclusions: PVR occurs frequently in combat trauma and is a significant cause of poor final VA. In patients with PVR and RD, injuries caused by an IOFB, macular hemorrhage, or unsuccessful repair were significant risk factors for the development of PVR. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:556-563.]., (Copyright 2020, SLACK Incorporated.)

Proliferative vitreoretinopathy (PVR) is a blinding eye disease. Epithelial-mesenchymal transition (EMT) of RPE cells plays an important role in the pathogenesis of PVR. In the current study, we sought to investigate the role of the methyl-CpG-binding protein 2 (MeCP2), especially P-MeCP2-421 in the pathogenesis of PVR. The expressions of P-MeCP2-421, P-MeCP2-80, PPAR-γ and the double labelling of P-MeCP2-421 with α-SMA, cytokeratin, TGF-β and PPAR-γ in human PVR membranes were analysed by immunohistochemistry. The effect of knocking down MeCP2 using siRNA on the expressions of α-SMA, phospho-Smad2/3, collagen I, fibronectin and PPAR-γ; the expression of α-SMA stimulated by recombinant MeCP2 in ARPE-19; and the effect of TGF-β and 5-AZA treatment on PPAR-γ expression were analysed by Western blot. Chromatin immunoprecipitation was used to determine the binding of MeCP2 to TGF-β. Our results showed that P-MeCP2-421 was highly expressed in PVR membranes and was double labelled with α-SMA, cytokeratin and TGF-β, knocking down MeCP2 inhibited the activation of Smad2/3 and the expression of collagen I and fibronectin induced by TGF-β. TGF-β inhibited the expression of PPAR-γ, silence of MeCP2 by siRNA or using MeCP2 inhibitor (5-AZA) increased the expression of PPAR-γ. α-SMA was up-regulated by the treatment of recombinant MeCP2. Importantly, we found that MeCP2 bound to TGF-β as demonstrated by Chip assay. The results suggest that MeCP2 especially P-MeCP2-421 may play a significant role in the pathogenesis of PVR and targeting MeCP2 may be a potential therapeutic approach for the treatment of PVR., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

To describe the 25-year surgical trends, long-term outcomes and risk factors affecting the outcomes of giant retinal tear-related rhegmatogenous retinal detachments (GRT-RRD). Patients' demographics, pre-operative characteristics, risk factors, operative procedures and post-operative outcomes were collected and divided into three groups - Group A: 1991 to 2015 (overall); Group B: 1991 to 2005, and Group C: 2006 to 2015. Functional and anatomical successes were monitored over a 5-year period. Multivariate logistic regression analysis was performed to identify the risk factors related to functional and anatomical success.127 eyes of 127 patients were included in the study. At 5 th year, 69.4% patients had visual acuity (VA) < logMAR 1.0 with 87.5% primary anatomical success rate. While the functional outcome remained the same between group B and C, there was an increase in the anatomical success from 89.7% to 100%, albeit not statistically significant. Patients with worse presenting VA, 150 degrees or more of giant retina tear, macula-detached status and presence of PVR were associated with VA of> logMAR 1.0 (all p < 0.05). The types of surgery (TPPV vs combined SB/TPPV), number of breaks, lens extraction and additional cryotherapy were not associated with the functional or anatomical success. In conclusion, the GRT-RRD functional and structural outcomes were comparable between 1991-2005 and 2006-2015, albeit a statistically insignificant improvement of anatomical outcome over the past 25 years. Worse presenting VA, 150 degrees or more of giant retinal tear, detached macula and presence of PVR were associated with poorer visual outcome.

Proliferative vitreoretinopathy (PVR) remains a significant challenge for vitreoretinal surgeons. Its incidence, as a complication of retinal detachment, does not appear to have altered despite improvement in surgical techniques. Extensive laboratory research has been undertaken to investigate the pathogenesis of PVR and the use of adjunctive mediations to modify the disease process. To date these studies have not resulted in improved clinical management of PVR. Previous concepts of the pathogenesis of PVR, focussing on a central role for RPE cells, may be flawed and could potentially have contributed to the lack of clinical advances. Revised clinical classifications and novel approaches to adjunctive treatment may in the future result in improved surgical outcomes.

Purpose: To determine the indications, findings, and outcomes of patients with open globe injury (OGI) requiring pars plana vitrectomy (PPV)., Design: Retrospective, single-vitreoretinal surgeon case series., Participants: Sixty-one consecutive eyes with OGI that required PPV., Methods: Retrospective chart review of consecutive patients who underwent PPV after OGI between March 1, 2011, and August 1, 2017, at Massachusetts Eye and Ear by 1 surgeon., Main Outcome Measures: Final visual acuity and rates of recurrent retinal detachment (RD) and proliferative vitreoretinopathy (PVR)., Results: Sixty-one eyes of 61 consecutive patients underwent PPV after sustaining OGI. Mean follow-up was 12.8±12.1 months (range, 0.5-65 months). At the time of presentation after OGI, 64% of eyes showed light perception or worse vision. The indications for PPV, which was performed on average of 15 days after injury, included RD without retinal incarceration (39%), RD with retinal incarceration in the scleral or corneal wound or both (13%), media opacity without RD (28%), vitreous traction without RD (11%), intraocular foreign body (5%), and endophthalmitis (3%). At the time of PPV, substantial comorbidities were noted, including corneal trauma (20%), hyphema (41%), iris trauma (62%), lens expulsion (54%), subretinal hemorrhage (51%), and choroidal hemorrhage (30%). Using multivariate analysis, factors associated with RD after initial PPV were preoperative subretinal hemorrhage (odds ratio [OR], 5.73; P = 0.03), PVR found at initial PPV (OR, 11.94; P = 0.021), and retinectomy (OR, 17.88; P = 0.003). No patients were inoperable, because all patients left the operating room with complete retinal reattachment. Of 35 eyes that showed RD, 19 (54%) redetached as a result of PVR. In 80% of eyes with RD at initial presentation (28/35 eyes), the retina remained completely attached at last follow-up, and 5 additional eyes remained partially attached (33/35 [94%]). Of 61 total eyes included in this study, 89% remained completely attached, and 42 (69%) achieved visual acuity of 20/200 or better at last follow-up., Conclusions: Despite substantial ocular comorbidities, PPV can result in retinal reattachment in even the most severe cases. Good visual outcomes can be achieved for most patients who undergo vitreoretinal surgery after open globe trauma., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To investigate the clinical characteristics and visual outcomes of patients with work-related open globe injuries (OGIs) and compare them with patients with non-work-related OGIs., Design: Retrospective, observational, multicentre, case-control study., Methods: A total of 374 patients with work-related OGIs and 170 patients with non-work-related OGIs who presented to hospitals that belong to the Japan-Clinical Research of Study group from 2005 to 2015 were included in this study. Clinical data including age, sex, initial and final visual acuity, type of open globe injury, lens status, zone of injury, wound length, and presence of proliferative vitreoretinopathy, retinal detachment, expulsive haemorrhage, and endophthalmitis were recorded., Main Outcome Measures: Visual acuity. Results Work-related OGIs were associated with younger age, male sex, better initial and final visual acuity, more laceration, smaller wounds, presence of retinal detachment, and expulsive haemorrhage, compared with non-work-related OGIs. Multiple regression analysis revealed that final visual acuity is significantly associated with initial visual acuity, wound length, and the presence of proliferative vitreoretinopathy in work-related OGIs., Conclusions: Work-related OGIs showed better visual outcomes than other OGIs. Initial visual acuity, wound length, and the presence of proliferative vitreoretinopathy are predictors of visual outcomes in patients with work-related OGIs.

Purpose: To analyse the influence of renal function on the outcomes of vitrectomy for tractional-related complications in cases of severe proliferative diabetic retinopathy (PDR)., Methods: Retrospective consecutive case series of 109 eyes that underwent vitreoretinal interventions for traction-related complications of severe PDR from 2014 to 2017. Data collected included patient demographics, best-corrected visual acuity (BCVA), surgical complications, and systemic markers including HbA1c and estimated glomerular filtration rate (eGFR). Renal function categories were defined as low (eGFR < 30 mL/min/1.73 m 2 ), medium (eGFR 30-60 mL/min/1.73 m 2 ), and normal (eGFR > 60 mL/min/1.73m  2 )., Results: A total of 109 eyes (56% (n = 61) female) were included in the study. Overall, mean baseline BCVA improved from 1.33 logMAR to 0.91 logMAR (p < 0.001) postoperatively. Patients with low eGFR had significantly worse baseline BCVA (p = 0.039) and demonstrated greater improvement in mean BCVA (p = 0.059). Multivariate regression analysis indicated that seven predictors explained 65.5% of the variance (R 2  = 0.655, F(11,97) = 16.7, p < 0.01)., Conclusions: Reduced renal function does not adversely affect visual outcomes of vitrectomy for traction-related complications of PDR.

Epithelial to mesenchymal transition (EMT) plays an important role in the pathogenesis of proliferative vitreoretinopathy (PVR). We aimed to demonstrate the role of mouse double minute 2 (MDM2) in transforming growth factor-beta 2 (TGF-β2)-induced EMT in human retinal pigment epithelial cells (RPEs). Immunofluorescence was used to assess MDM2 expression in epiretinal membranes (ERMs) from patients with PVR. A single guide (sg)RNA targeting the second promoter of MDM2 was cloned into a mutant lentiviral Clustered Regularly Interspaced Short Palindromic Repeats (lentiCRISPR) v2 (D10A and H840A) vector for expressing nuclease dead Cas9 (dCas9)/MDM2-sgRNA in RPEs. In addition, MDM2-sgRNA was also cloned into a pLV-sgRNA-dCas9-Kruppel associated box (KRAB) vector for expressing dCas9 fused with a transcriptional repressor KRAB/MDM2-sgRNA. TGF-β2-induced expression of MDM2 and EMT biomarkers were assessed by quantitative polymerase chain reaction (q-PCR), western blot, or immunofluorescence. Wound-healing and proliferation assays were used to evaluate the role of MDM2 in TGF-β2-induced responses in RPEs. As a result, we found that MDM2 was expressed obviously in ERMs, and that TGF-β2-induced expression of MDM2 and EMT biomarkers Fibronectin, N-cadherin and Vimentin in RPEs. Importantly, we discovered that the dCas9/MDM2-sgRNA blocked TGF-β2-induced expression of MDM2 and the EMT biomarkers without affecting their basal expression, whereas the dCas9-KRAB/MDM2-sgRNA suppressed basal MDM2 expression in RPEs. These cells could not be maintained continuously because their viability was greatly reduced. Next, we found that Nutlin-3, a small molecule blocking the interaction of MDM2 with p53, inhibited TGF-β2-induced expression of Fibronectin and N-cadherin but not Vimentin in RPEs, indicating that MDM2 functions in both p53-dependent and -independent pathways. Finally, our experimental data demonstrated that dCas9/MDM2-sgRNA suppressed TGF-β2-dependent cell proliferation and migration without disturbing the unstimulated basal activity. In conclusion, the CRISPR/dCas9 capability for blocking TGF-β2-induced expression of MDM2 and EMT biomarkers can be exploited for a therapeutic approach to PVR.

Aim: Main failure of diabetic tractional retinal detachment (TRD) surgery is the development of proliferative vitreoretinopathy (PVR), causing higher re-detachment rates. We investigated whether the use of dexamethasone (DEX) implant at the end of pars plana vitrectomy (PPV) with silicone oil tamponade might have an impact on these outcomes., Design: Comparative, nonrandomized, retrospective study., Participants: A total of 148 eyes from 148 patients that underwent PPV with silicone oil tamponade for diabetic TRD (with DEX implant, n = 52; without DEX implant, n = 96)., Methods: Consecutive patients' records were reviewed for time between TRD diagnosis and surgery; lens status before surgery and after 6, 12, and 24 months; retina attachment rate after primary PPV; change in postoperative PVR severity; rate of re-detachment at 6, 12, and 24 months; use of IOP lowering treatment after 6, 12, and 24 months; surgery details; intra- and postoperative complications. Correlations between outcome measures, postoperative PVR severity, and re-detachment rates were analyzed., Main Outcome Measures: Change in postoperative PVR severity and retinal re-detachment rates with and without the adjuvant use of DEX implant., Results: Retinal re-detachment rates were significantly higher in the group of patients that did not receive DEX implant [11/96 (11.5%) vs. 0/52 (0%), p = 0.049; 11/84 (12.9%) vs. 4/52 (7.7%), p = 0.007; 14/71 (19.7%) vs. 5/52 (10%) p < 0.001 at 6, 12, and 24 months, respectively]. PVR severity correlated with retinal status at 12 and 24 months (p = 0.018 and p = 0.027, respectively). The difference in PVR severity between the two groups was statistically significant at 6, 12, and 24 months (p < 0.001)., Conclusions: DEX implant at the end of PPV in patients with diabetic TRD improves PVR severity and decreases re-detachment rates. This should be considered as an option in the customized treatment of TRD.

Background: Patients with type 2 diabetes are prone to the asymptomatic obstructive coronary artery disease (AO-CAD). The association of proliferative diabetic retinopathy (PDR) with AO-CAD is unknown. The aim of the study is to explore the specific relationship of PDR with AO-CAD. Methods: We performed coronary angiography and retinal photographs in 1332 participants with unknown CAD status in a retrospective discovery set and 252 patients with non-CAD enrolled in a prospective validation cohort. Main outcome measures are prediction of PDR to AO-CAD. Results: In the case-control retrospective discovery set, investigation included 211 nondiabetic retinopathy (NDR) and 140 PDR. Individuals with PDR had a 2.16 times higher risk of AO-CAD compared with individuals without diabetic retinopathy ( P  < 0.01). Relative risk between individuals with PDR and the risk of AO-CAD varied by different adjusted covariates, 2.53 (1.48-4.32) by age and gender; 2.16 (1.10-4.31) by additionally other covariates. In the prospective validation set, after adjustment for covariates, the cumulative risk of AO-CAD was significantly higher in the PDR group compared with NDR group, followed up for a median of 4.3 years (hazard ratio = 3.07, 95% confidence interval 1.81-5.21, P  < 0.001). Conclusions: PDR showed superior identification performance over traditional risk factors in screening for AO-CAD. PDR may predict persons at high risk of AO-CAD.

Aim: To assess the long-term anatomical and functional outcomes in addition to complications of a new surgical technique of localized intraocular application of mitomycin C (MMC) to prevent proliferative vitreoretinopathy (PVR) in eyes with open globe trauma., Methods: Prospective non-comparative interventional case series of 16 consecutive eyes with perforating and deep choroidal impact foreign body injuries presenting over a 2-year period. Patients underwent vitrectomy with intraocular application of MMC at the site of the chorioretinal injury and were followed-up for 1 year. The primary outcome measure was the rate of postoperative PVR. Secondary outcome measures were number of vitreoretinal surgeries (VRS) required, best corrected visual acuity (BCVA), final anatomical success rate and globe survival rate (GSR)., Results: Patients underwent VRS at a mean time of 8.5 ± 4.6 days after the injury. Postoperative PVR developed in 2 (13 %) eyes and required only one additional VRS each. One other eye underwent further peeling of an epimacular membrane. BCVA improved from mean LogMAR 3.08 ± 0.72 preoperatively to 0.66 ± 0.79 at 1 year. All 10 eyes without a macular injury had a final BCVA of LogMAR 0.40 or better. The final anatomical success rate was 94% and GSR rate was 100%. There were no complications related to the intraocular use of MMC., Conclusions: Vitrectomy and intraocular application of Mitomycin C may have a potential role in reducing the rate of post traumatic PVR and improving anatomical and functional outcomes in eyes with perforating and deep choroidal impact foreign body injuries.

Purpose: To determine predictive factors of proliferative vitreoretinopathy (PVR) formation after uncomplicated primary retinal detachment repair., Methods: Retrospective, single-center, case-control study of 74 consecutive patients with (37 eyes) and without (37 eyes) PVR formation after undergoing uncomplicated primary surgery for retinal detachment repair. Logistic regression was used to assess factors associated with PVR formation., Results: Retinal detachment involving the macula was 4.2 times (adjusted odds ratio; 95% confidence interval, 1.4-12.9; P = 0.0119) more likely to have PVR formation compared with those without. Patients who were current or former smokers were 3.6 times (adjusted odds ratio; 95% confidence interval, 1.1-11.7; P = 0.0352) more likely to have PVR formation compared with nonsmokers. Compared with 25-gauge (g) vitrectomy, larger gauge vitrectomy (20 g or 23 g) was 3.6 times (adjusted odds ratio; 95% confidence interval, 1.2-11.3; P = 0.0276) more likely to have PVR formation. Duration of retinal detachment symptoms, high myopia, lens status, lattice degeneration, location of retinal break, number of retinal breaks, and surgical technique (e.g., scleral buckle with or without vitrectomy versus vitrectomy alone) were not found to be predictive of PVR formation., Conclusion: Cigarette smoking and macular involvement are significant risk factors predictive of PVR formation after uncomplicated primary retinal detachment repair.

Diabetic retinopathy (DR) and retinopathy of prematurity (ROP) present two examples of proliferative retinopathy, characterized by the same stages of progression; ischemia of the retinal vessels, leads to hypoxia and to correct the problem there is the setting up of uncontrolled angiogenesis, which subsequently causes blindness or even detachment of the retina. The difference is the following; that DR initiated by the metabolic complications that are due to hyperglycemia, and ROP is induced by overexposure of the neonatal retina to oxygen. In this review, we will demonstrate the physiopathological mechanism of the two forms of proliferative retinopathy DR and ROP, in particular the role of the CD40/CD40L axis and IL-1 on vascular complications and onset of inflammation of the retina, the implications of their effects on the onset of pathogenic angiogenesis, thus understanding the link between platelets and retinal ischemia. In addition, what are the therapeutic targets that could slow its progression?, (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)