Bone morphogenetic protein 6 (BMP6) antagonises experimental proliferative vitreoretinopathy established by TGF-ß2 stimulation in retinal pigment epithelial cells through modulation of the p38 and JNK MAPK pathways.

The formation of the epiretinal fibrotic membrane by retinal pigment epithelial (RPE) cells is a primary pathological change for proliferative vitreoretinopathy (PVR). Bone morphogenetic protein 6 (BMP6) is an antifibrogenic factor in various cells. To date, it is still unknown whether BMP6 can interfere with the fibrogenesis of RPE cells during the progression of PVR. This work aimed to address the relationship between BMP6 and transforming growth factor-ß2 (TGF-ß2)-elicited fibrogenesis of RPE cells, an experimental model for studying PVR in vitro. The BMP6 level was down-regulated, while the TGF-ß2 level was up-regulated in the vitreous humor of PVR patients. The BMP6 level was down-regulated in human RPE cells challenged with TGF-ß2. The treatment of RPE cells with TGF-ß2 resulted in significant increases in proliferation, migration, epithelial-to-mesenchymal transition (EMT), and extracellular matrix (ECM) remodelling. These effects were found to be inhibited by the overexpression of BMP6 or exacerbated by the knockdown of BMP6. BMP6 overexpression reduced the phosphorylation of p38 and JNK in TGF-ß2-stimulated RPE cells, while BMP6 knockdown showed the opposite effects. The inhibition of p38 or JNK partially reversed the BMP6-silencing-induced promoting effects on TGF-ß2-elicited fibrogenesis in RPE cells. Taken together, BMP6 demonstrates the ability to counteract the proliferation, migration, EMT, and ECM remodelling of RPE cells induced by TGF-ß2. This is achieved through the regulation of the p38 and JNK MAPK pathways. These findings imply a potential connection between BMP6 and PVR, and highlight the potential application of BMP6 in therapeutic interventions for PVR.

Association of Cutaneous Keloids, Hypertrophic Scarring, and Fibrosis with Risk of Postoperative Proliferative Vitreoretinopathy.

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, 10th 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.

Tenascin-C induces transdifferentiation of retinal pigment epithelial cells in proliferative vitreoretinopathy.

Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-ß2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-ß2-induced transdifferentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or α-smooth muscle actin(α-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin αV and ß-catenin in the PVR membranes. ICG-001, a ß-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and ß-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.

Proliferative vitreoretinopathy: an update on the current and emerging treatment options.

Proliferative vitreoretinopathy (PVR) remains the main cause of failure in retinal detachment (RD) surgery and a demanding challenge for vitreoretinal surgeons. Despite the large improvements in surgical techniques and a better understanding of PVR pathogenesis in the last years, satisfactory anatomical and visual outcomes have not been provided yet. For this reason, several different adjunctive pharmacological agents have been investigated in combination with surgery. In this review, we analyze the current and emerging adjunctive treatment options for the management of PVR and we discuss their possible clinical application and beneficial role in this subgroup of patients.

Intravitreal methotrexate as an adjuvant in vitrectomy in cases of retinal detachment with proliferative vitreoretinopathy.

PURPOSE: To compare the rate of re-detachment in patients with rhegmatogenous retinal detachment and Grade-C PVR following vitreoretinal surgery, with and without serial intravitreal injections of methotrexate. METHODS: It was a randomized control trial. Patients aged more than 18 years undergoing pars plana vitrectomy for rhegmatogenous retinal detachment with PVR grade C or more were included in the study. Patients treated with intravitreal injection of methotrexate were grouped as cases and those not injected served as controls. The cases received 3 intravitreal injections of methotrexate at monthly intervals. Patients were evaluated on Day 1, 1st month, 2nd month, 3rd month and 6th month in terms of BCVA, rate of re-attachment and grade of PVR. RESULTS: The case group had 23 patients and the control group had 20 patients. 2 patients in the case group were lost to follow-up after the first follow-up, so they were excluded. So 21 patients in case group and 20 patients in control group were followed up. Six months after surgery, 15 'cases' had completely attached retina whereas 6 patients had partial detachment with macula on. There was no patient amongst the cases with macula-off retinal re-detachment. Out of 20 patients in the control group, 9 had a complete retinal attachment, 4 had partial detachment with macula-on and 7 had partial detachment with macula-off. There was statistically significant difference in macula off retinal detachment rates (p-value- 0.003). CONCLUSION: Serial intravitreal methotrexate injections reduce the incidence of re-detachment in patients undergoing PPV for RRD with PVR-C. Further investigation into this promising therapeutic approach is warranted. KEY MESSAGES: What is known Methotrexate is an anti-inflammatory agent which is safe for intravitreal use There are case series retrospective and prospective studies suggesting potential benefit of intravitreal methotrexate in preventing re-detachment due to PVR What is new First randomized control trial studying the efficacy of intravitreal methotrexate in preventing re-detachment due to PVR Our study showed statistically significant difference in macula off retinal detachment between the 2 groups at 6 months of follow up.

Retinal redetachment after silicone oil removal: a risk factor analysis.

PURPOSE: To report the rate of retinal redetachment after silicone oil removal following rhegmatogenous retinal detachment surgery and to determine potential risk factors. METHODS: Retrospective observational case series of 161 eyes who underwent rhegmatogenous retinal detachment surgery and subsequent silicone oil removal. Pre- and intraoperative risk factors were evaluated using univariate and multivariate logistic regression. We also evaluated the effect of tamponade duration on anatomical outcomes. RESULTS: The median tamponade duration was 5.9 [4.3;7.6] months. Seventeen (10.6%) eyes underwent silicone oil removal within 3 months of surgery, with a median delay of 2.3 [2.0;2.8] months. The rate of retinal detachment after silicone oil removal was 14.9%. A history of previous unsuccessful surgery was the only significant risk factor for retinal redetachment after silicone oil removal (OR 4.8, 95%CI [1.5;19.0], p = 0.02). The use of 360° laser retinopexy and concomitant air or gas tamponade during silicone oil removal were not found to affect the redetachment rate. Eyes with silicone oil tamponade ≤ 3 months showed an increased, albeit not significant, risk of developing recurrent rhegmatogenous retinal detachment after silicone oil removal (35.3% versus 12.5%, p = 0.06). CONCLUSION: A retinal redetachment occurred in 14.9% of eyes undergoing silicone oil removal following rhegmatogenous retinal detachment surgery. Previous failed surgery was associated with a 4.8-fold increased risk of developing recurrent rhegmatogenous retinal detachment after silicone oil removal. Eyes with silicone oil tamponade ≤ 3 months tended to have a higher redetachment rate. TRIAL REGISTRATION NUMBER: ID NCT05647928 (12th April 2022).

Efficacy of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) in high-risk pediatric retinal detachment; randomized clinical trial.

BACKGROUND: Pediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous. METHODS: After informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks. RESULTS: The study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042). CONCLUSION: This study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA. TRIAL REGISTRATION NUMBER: Registry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered.

Traumatic terson syndrome with a peculiar mass lesion and tractional retinal detachment: a case report.

BACKGROUND: To report a case with bilateral Terson syndrome presented with a unique mushroom-like mass lesion on the optic disc along with proliferative vitreoretinopathy and tractional retinal detachment. CASE PRESENTATION: A 33-year-old man was injured during a traffic accident and had diffuse brain swelling and intraocular hemorrhage. Poor vision in both eyes was noted after the patient regained consciousness. B-scan ultrasonography showed extensive vitreous opacity with a posterior vitreous detachment and without obvious retinal detachment. Vitrectomy was performed in both eyes five months after the accident. After clearing up the vitreous opacity, a peculiar pigmented mushroom-like mass lesion was noted in the posterior pole and had severe adhesion to the underneath optic disc. Extensive multilayered peripapillary epiretinal membrane was found covering the posterior pole and led to tractional retinal detachment around the macula. The mass was presumed to be an organized vitreous hemorrhage originated from the optic disc. The extensive and adherent epiretinal membrane together with the mass lesion were removed as much as possible and silicon oil was injected for tamponade. However, in the right eye, the retina redetached under silicon oil, whereas in the left eye, his vision improved to 20/100. CONCLUSIONS: Terson syndrome usually has a favorable prognosis but may be complicated by proliferative vitreoretinopathy and tractional retinal detachment. Careful monitoring is warranted and early vitrectomy should be considered in cases suspecting additional pathologies.

Examining the etiological factors resulting in retinal detachment following prophylactic vitrectomy in the context of acute retinal necrosis syndrome.

OBJECTIVE: The aim of this study is to elucidate the factors contributing to the occurrence of retinal detachment (RD) following prophylactic vitrectomy in cases of acute retinal necrosis (ARN) syndrome. METHODS: A retrospective examination was undertaken, encompassing the medical records of patients diagnosed with ARN who underwent prophylactic vitreous intervention at the Ophthalmology Department of Wuhan University Renmin Hospital East Campus between October 2019 and September 2023. Subsequently, patients who manifested RD in the postoperative period were identified, and a comprehensive analysis was conducted to ascertain the factors underlying the occurrence of RD post-surgery. RESULTS: This study comprised 14 cases (involving 14 eyes) of patients diagnosed with ARN who underwent prophylactic vitreous intervention. The findings revealed that 4 patients experienced postoperative RD, resulting in an incidence rate of 28.57%. Notably, among these cases, 3 cases of RD manifested in the presence of silicone oil, while 1 case occurred subsequent to the removal of silicone oil. All 4 cases of RD exhibited varied degrees of proliferative vitreoretinopathy. Following the occurrence of RD, all patients underwent a secondary vitreous intervention coupled with silicone oil tamponade, leading to successful reattachment of the retina. However, despite these interventions, there was no significant enhancement observed in postoperative visual outcomes when compared to preoperative levels. CONCLUSION: RD following prophylactic vitrectomy in cases of ARN is not an infrequent occurrence and is primarily linked to the postoperative onset of proliferative vitreoretinopathy.

Pirfenidone: A Promising Drug in Ocular Therapeutics.

Pirfenidone, initially indicated for lung fibrosis, has gone beyond its original purpose, and shown promise in eye care. This detailed review tracks its evolution from lung treatment to aiding eye healing as evidenced by published literature. Pirfenidone's multifaceted attributes extend to mitigating corneal fibrosis, inflammation, and trauma. Through rigorous investigations, its efficacy emerges in diabetic retinopathy, macular degeneration, and postoperative glaucoma interventions. As an unheralded protagonist, pirfenidone reshapes ocular care paradigms, inviting renewed research opportunities.

Tricetin suppresses the cell migration and BMP-6 expression through p38 signaling pathways in human retinal pigment epithelium cells.

Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.

Proliferative Vitreoretinopathy in Retinal Detachment: Perspectives on Building a Digital Twin Model Using Nintedanib.

Proliferative vitreoretinopathy (PVR) is a pathological process characterized by the formation of fibrotic membranes that contract and lead to recurrent retinal detachment. Pars plana vitrectomy (PPV) is the primary treatment, but recurrence rates remain high, as surgery does not address the underlying molecular mechanisms driving fibrosis. Despite several proposed pharmacological interventions, no approved therapies exist, partly due to challenges in conducting preclinical and in vivo studies for ethical and safety reasons. This review explores the potential of computational models and Digital Twins, which are increasingly gaining attention in medicine. These tools could enable the development of progressively complex PVR models, from basic simulations to patient-specific Digital Twins. Nintedanib, a tyrosine kinase inhibitor targeting PDGFR, VEGFR, and FGFR, is presented as a prototype for computational models to simulate its effects on fibrotic pathways in virtual patient cohorts. Although still in its early stages, the integration of computational models and Digital Twins offers promising avenues for improving PVR management through more personalized therapeutic strategies.

Anti-inflammatory potential of simvastatin and amfenac in ARPE-19 cells; insights in preventing re-detachment and proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery.

PURPOSE: Rhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina if recovery from surgery fails. Inflammation and changes in retinal pigment epithelial (RPE) cells are important contributors to the disease. Here, we studied the effects of simvastatin and amfenac on ARPE-19 cells under inflammatory conditions. METHODS: ARPE-19 cells were pre-treated with simvastatin and/or amfenac for 24 h after which interleukin (IL)-1α or IL-1ß was added for another 24 h. After treatments, lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) processing, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, prostaglandin E2 (PGE2) level, and extracellular levels of IL-6, IL-8, monocytic chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor, as well as the production of reactive oxygen species (ROS) were determined. RESULTS: Pre-treatment of human ARPE-19 cells with simvastatin reduced the production of IL-6, IL-8, and MCP-1 cytokines, PGE2 levels, as well as NF-κB activity upon inflammation, whereas amfenac reduced IL-8 and MCP-1 release but increased ROS production. Together, simvastatin and amfenac reduced the release of IL-6, IL-8, and MCP-1 cytokines as well as NF-κB activity but increased the VEGF release upon inflammation in ARPE-19 cells. CONCLUSION: Our present study supports the anti-inflammatory capacity of simvastatin as pre-treatment against inflammation in human RPE cells, and the addition of amfenac complements the effect. The early modulation of local conditions in the retina can prevent inflammation induced PVR formation and subsequent retinal re-detachment.

[Morphological features of vasoproliferative tumor of the retina]. / Morfologicheskie osobennosti vazoproliferativnoi opukholi setchatki.

Vasoproliferative retinal tumor (VPT) is a term proposed by ophthalmologists in relation to the totality of manifestations of an intraocular volumetric process with involvement of the inner lining of the eye, an integral part of which is the active growth of blood vessels. The available literature data on the morphology of this process are very contradictory and ambiguous. The article presents two clinical cases of vasoproliferative retinal tumor with own illustration of morphological studies.

Targeting non-muscle myosin II inhibits proliferative vitreoretinopathy through regulating epithelial-mesenchymal transition.

Proliferative vitreoretinopathy (PVR) is a common complication of rhegmatogenous retinal detachment, eventually leading to vision loss. To date, there are no effective drugs for the treatment of this disease. In this study, we investigated the effect of blebbistatin, a non-muscle myosin II inhibitor, on the ARPE-19 cell line and in a rabbit model of proliferative vitreoretinopathy. In vitro, we found that blebbistatin inhibited the epithelial-mesenchymal transition of retinal pigment epithelial (RPE) cells and inhibited the ability of RPE cells to migrate, proliferate, generate extracellular matrix, and affect contractility. In vivo the PVR model showed that blebbistatin significantly delayed PVR progression. It also partially prevents the loss of retinal function caused by PVR. Our results suggest that blebbistatin is a potential drug with clinical applications for the treatment of PVR.

Vitreous humor proteome: unraveling the molecular mechanisms underlying proliferative and neovascular vitreoretinal diseases.

Proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and neovascular age-related macular degeneration (nAMD) are among the leading causes of blindness. Due to the multifactorial nature of these vitreoretinal diseases, omics approaches are essential for a deeper understanding of the pathophysiologic processes underlying the evolution to a proliferative or neovascular etiology, in which patients suffer from an abrupt loss of vision. For many years, it was thought that the function of the vitreous was merely structural, supporting and protecting the surrounding ocular tissues. Proteomics studies proved that vitreous is more complex and biologically active than initially thought, and its changes reflect the physiological and pathological state of the eye. The vitreous is the scenario of a complex interplay between inflammation, fibrosis, oxidative stress, neurodegeneration, and extracellular matrix remodeling. Vitreous proteome not only reflects the pathological events that occur in the retina, but the changes in the vitreous itself play a central role in the onset and progression of vitreoretinal diseases. Therefore, this review offers an overview of the studies on the vitreous proteome that could help to elucidate some of the pathological mechanisms underlying proliferative and/or neovascular vitreoretinal diseases and to find new potential pharmaceutical targets.

Endoscopy-assisted pars plana vitrectomy in retinal detachments associated with anterior proliferative vitreoretinopathy and epiciliary membranes.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is the leading cause of recurrent retinal detachment. Anterior PVR can contribute to recurrent retinal detachment and is often difficult to remove during conventional pars plana vitrectomy. The purpose of this study is to report surgical outcomes of single endoscopy-assisted pars plana vitrectomy (E-PPV) in patients with tractional retinal detachments associated with anterior proliferative vitreoretinopathy and epiciliary membranes. METHODS: Retrospective review of E-PPV between 2017 and 2021 at a tertiary referral center. Inclusion criteria involved adult patients who underwent E-PPV for tractional retinal detachment with anterior PVR and epiciliary membranes. Data collection included patients' demographics, ophthalmic exam findings, and surgical outcomes. A series of independent sample tests of proportion were conducted using a p-value of 0.05 as the threshold for statistical significance. RESULTS: Eighteen out of 55 patients who underwent E-PPV met the inclusion criteria. There were six females (33%) and 12 males (p-value = 0.096). Age ranged between 27 and 82 years old (mean age 52.1 ± 17.3 years). Nine patients (50%) had a history of ipsilateral retinal detachment repair. Single E-PPV success rate was 100% after three months, and 94.4% at the latest follow up visit. Recurrent retinal detachment with posterior PVR occurred in one patient four months after surgery. Cataract progressed in 57% (8/14) of phakic patients, with 63% (5/8) undergoing cataract extraction surgery within the first postoperative year. CONCLUSION: E-PPV enabled epiciliary membrane and anterior PVR visualization and removal. The single E-PPV success rate remained high at the latest follow up visit. E-PPV enabled the preservation of the phakic lens in all study patients. Larger prospective studies are needed on the role of E-PPV in retina surgeries.

Steroid Drugs as an Adjunct for Reducing the Incidence of Proliferative Vitreoretinopathy after Rhegmatogenous Retinal Detachment Surgery: A Meta-Analysis of Randomized Controlled Studies.

INTRODUCTION: The efficacy and influence of steroids for reducing the incidence of proliferative vitreoretinopathy (PVR) after rhegmatogenous retinal detachment (RRD) surgery remain controversial. Systematic review and meta-analysis were conducted to explore the effect of steroids versus placebo on risk of PVR. METHODS: We searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials (RCTs), assessing the effect of steroid drugs as an adjunct for reducing the incidence of PVR after RRD surgery. This meta-analysis was performed using the random-effect model. Data were extracted by two reviewers independently; the quality of RCTs was assessed by the Cochrane risk-of-bias tool. We calculated risk ratio (RR) and the 95% confidence intervals (CIs) of all outcomes and plotted on forest plots. I2 accessed using the χ2 test was applied to quantify the degree of heterogeneity. RESULTS: Four RCTs involving 478 patients (478 eyes) are included in the meta-analysis. There was no significant difference in the incidence of PVR recurrence between steroid groups and control groups (RR: 0.87, 95% CI: 0.70-1.08, p = 0.19). However, the incidence of recurrent PVR was lower in the steroid group (RR: 0.67, 95% CI: 0.46-0.99, p = 0.04) than in the control group when only PVR grades A and B were taken into consideration. Besides, steroids could significantly reduce the incidence of macular edema after surgery (RR: 0.64, 95% CI: 0.47-0.88, p = 0.007). The steroid group and control group had comparable outcomes of retinal reattachment rate and reoperation rate after primary surgery. Additionally, there was no significant difference of the incidence of epiretinal membrane, and the incidence of surgery required by epiretinal membrane. CONCLUSION: This meta-analysis reveals that RRD surgery combined with steroid drugs administration could significantly reduce the recurrence in PVR grade A and B subgroup, as well as the incidence of macular edema after surgery.

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.

Use of Heavy Silicon Oil as Intraocular Tamponade for Inferior Retinal Detachment Complicated by Proliferative Vitreoretinopathy: A Multicentric Experience.

INTRODUCTION: This is a multicentric study on the use of heavy silicon oil (HSO) as an intraocular tamponade for inferior retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR). METHODS: 139 eyes treated for RD with PVR were included in the study. 10 (7.2%) were affected by primary RD with inferior PVR, while 129 (92.8%) were affected by recurrent RD with inferior PVR. 102 eyes (73.9%) had received a silicon oil (SO) tamponade in a previous intervention prior to receiving HSO. Mean follow-up was 36.5 (standard deviation = 32.3) months. RESULTS: The median interval between HSO injection and removal was 4 months (interquartile range: 3). At the time of HSO removal, the retina was attached in 120 eyes (87.6%), whereas in 17 eyes (12.4%), it had re-detached while the HSO was in situ. 32 eyes (23.2%) showed recurrent RD. A subsequent RD relapse was observed in 14.2% of cases with no RD at the time of HSO removal, and in 88.2% if an RD was present at the time of HSO removal. Advancing age showed a positive association with retinal attachment at the end of follow-up, while the risk of RD relapse at the end of the follow-up showed a significant negative association with HSO tamponade duration and with the use of SO rather than air or gas as post-HSO tamponade materials. Mean best corrected visual acuity was 1.1 logarithm of minimum angle of resolution at all follow-up time points. 56 cases (40.3%) needed treatment for elevated intraocular pressure (IOP), with which no clinically relevant variables were associated during follow-up. CONCLUSION: HSO represents a safe and effective tamponade in cases of inferior RD with PVR. The presence of RD at the time of HSO removal is a negative prognostic factor for the development of a subsequent RD relapse. According to our findings, in cases of RD at the time of HSO removal, a short-term tamponade should definitely be avoided, in favor of SO. Special attention must be paid to the risk of IOP elevation, and patients should be closely monitored.