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.

ADDITIONAL PNEUMATIC RETINOPEXY IN PATIENTS WITH PERSISTENT RETINAL DETACHMENT AFTER SCLERAL BUCKLING.

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.

MENISCUS MICROPYON: An Ophthalmoscopic Sign Possibly Associated With Epiretinal Proliferation After Retinal Surgery With Gas Tamponade.

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.

[Biomechanics of diabetic vitreopapillary traction syndrome]. / Biomekhanika diabeticheskogo vitreopapillyarnogo traktsionnogo sindroma.

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.

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.

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

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

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

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

Sustained dasatinib treatment prevents early fibrotic changes following ocular trauma.

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

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

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

MeCP2-421-mediated RPE epithelial-mesenchymal transition and its relevance to the pathogenesis of proliferative vitreoretinopathy.

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-ß 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-ß 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-ß. Our results showed that P-MeCP2-421 was highly expressed in PVR membranes and was double labelled with α-SMA, cytokeratin and TGF-ß, knocking down MeCP2 inhibited the activation of Smad2/3 and the expression of collagen I and fibronectin induced by TGF-ß. TGF-ß 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-ß 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.

Surgical outcomes of vitrectomy surgery for proliferative diabetic retinopathy in patients with abnormal renal function.

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 m2), medium (eGFR 30-60 mL/min/1.73 m2), 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 (R2 = 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.

Blockade of MDM2 with inactive Cas9 prevents epithelial to mesenchymal transition in retinal pigment epithelial cells.

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-ß2)-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-ß2-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-ß2-induced responses in RPEs. As a result, we found that MDM2 was expressed obviously in ERMs, and that TGF-ß2-induced expression of MDM2 and EMT biomarkers Fibronectin, N-cadherin and Vimentin in RPEs. Importantly, we discovered that the dCas9/MDM2-sgRNA blocked TGF-ß2-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-ß2-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-ß2-dependent cell proliferation and migration without disturbing the unstimulated basal activity. In conclusion, the CRISPR/dCas9 capability for blocking TGF-ß2-induced expression of MDM2 and EMT biomarkers can be exploited for a therapeutic approach to PVR.

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

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

PREDICTIVE FACTORS FOR PROLIFERATIVE VITREORETINOPATHY FORMATION AFTER UNCOMPLICATED PRIMARY RETINAL DETACHMENT REPAIR.

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.

Intraocular Foreign Body Trauma in Operation Iraqi Freedom and Operation Enduring Freedom: 2001 to 2011.

PURPOSE: We update the incidence of intraocular foreign bodies (IOFB) in soldiers admitted to Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries in Operation Iraqi Freedom and Operation Enduring Freedom. DESIGN: This consecutive retrospective case series included 890 eyes of 652 patients. METHODS: Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were any American soldier or Department of Defense civilian with an IOFB injured in Operation Iraqi Freedom/Operation Enduring Freedom. Closed globe injuries with orbital foreign bodies, injury outside of a combat zone, or non-Department of Defense civilian trauma were the exclusion criteria. MAIN OUTCOME MEASURES: Primary outcome measures were final visual outcome and the number, size, and location of IOFBs. Secondary outcome measures included surgical procedures, use of eye protection, associated complications, source of injury and Ocular Trauma Score. RESULTS: There were 890 eye injuries in 652 patients evacuated to Walter Reed Army Medical Center between 2001 and 2011. IOFBs were found in 166 eyes of 149 patients (18.6%; 95% confidence interval [CI], 16.2%-21.3%). Most patients had a single IOFB (80.7%). An IOFB was positively associated with Ocular Trauma Score grade 1 or 2 (0-65) injuries (odds ratio [OR], 1.58; 95% CI, 1.07-2.38; P = 0.01). There were 130 eyes (78.33%) that had recorded time from initial visual acuity to final visual acuity and it ranged from 8 to 2421 days (mean, 433.24 days). Thirty-eight (25.16%; 95% CI, 18.89%-32.67%) eyes had no change in visual acuity, 98 (64.90%; 95% CI, 57.00%-72.07%) had improved visual acuity, and 15 (9.93%; 95% CI, 6.01%-15.84%) had decreased visual acuity. IOFB was not found to predict final visual acuity of <20/200 in multivariate analysis when other injury features were known (P = 0.1). Pars plana vitrectomy was completed on 124 eyes (74.70%). Removal of IOFB was performed in 118 eyes (71.08%; average of 31.67 days after initial injury) with a delayed procedure occurring after primary closure and antibiotics owing to a lack of surgical capacity in Iraq and Afghanistan. Retinal detachment occurred in 48 eyes (28.92%) and proliferative vitreoretinopathy in 44 eyes (26.5%). CONCLUSIONS: IOFBs occur frequently in combat ocular trauma and are significantly associated with more severe injuries. However, IOFBs were not found to be a significant risk factor for visual acuity of <20/200.

Quantitative proteomics analysis of vitreous body from type 2 diabetic patients with proliferative diabetic retinopathy.

BACKGROUND: To compare the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH). METHODS: In this study, we performed mass spectrometry-based label-free quantitative proteomics analysis of vitreous samples from type 2 diabetic patients with PDR (n = 9) and IMH subjects (n = 9) and identified the abundance of 610 proteins. RESULTS: Out of 610 proteins, 64 proteins (Group A) were unique to PDR patients, while 212 proteins (Group B) could be identified in IMH vitreous only. Among the other 334 proteins that could be detected in both PDR and IMH eyes, 62 proteins differed significantly (p < 0.05, fold change > 2), which included 52 proteins (Group C) and 10 proteins (Group D) over- and under-expressed in PDR vitreous compared with the control. All proteins in these four groups were counted as significant proteins in our study. CONCLUSIONS: We identified and quantified 610 proteins in total, which included 338 significant proteins in our study. Protein distribution analysis demonstrated a clear separation of protein expression in PDR and IMH. The protein function analysis illustrated that immunity and transport related proteins might be associated with PDR.

CHOROIDAL THICKNESS CHANGES AFTER VITRECTOMY WITH SILICONE OIL TAMPONADE FOR PROLIFERATIVE VITREORETINOPATHY RETINAL DETACHMENT.

PURPOSE: To access the potential effect of vitrectomy and silicone oil tamponade on the choroid. METHODS: Eighteen patients (18 eyes) who had undergone pars plana vitrectomy with 1,000-cSt silicone oil tamponade for proliferative vitreoretinopathy retinal detachment were included in this retrospective study. All patients underwent ophthalmologic examinations before treatment and 1 week and 1, 3, and 6 months after vitrectomy with silicone oil tamponade. Choroidal thickness was measured using enhanced depth imaging optical coherence tomography (Spectralis; Heidelberg Engineering) in a horizontal and vertical section beneath the fovea. RESULTS: Choroidal thickness statistically significantly decreased till 3 months after pars plana vitrectomy with silicone oil tamponade: under the center of the fovea (P = 0.014) and in the temporal (P = 0.029), superior (P = 0.046), and inferior areas, determined at 1,500 µm from the center of the fovea (P = 0.030). After 6 months, the desired effect in the form of a decrease in the choroidal thickness was even more prominent, both under the center of the fovea (P < 0.001) and in the nasal (P < 0.001), temporal (P < 0.001), superior (P < 0.001), and inferior areas at 1,500 µm from the center of the fovea (P < 0.001). CONCLUSION: Choroidal thickness is reduced in eyes receiving silicone oil intraocular tamponade. Silicone oil tamponade may have an impact on the structure and proper functioning of the choroid. The measurements of the choroidal thickness by optical coherence tomography might be a very good tool to detect early changes in choroidal thickness and impact the decision when to remove silicone oil.

TRAUMATIC PROLIFERATIVE VITREORETINOPATHY: Clinical and Histopathological Observations.

PURPOSE: To determine the phases of traumatic proliferative vitreoretinopathy after open globe injury by assessing cellular components, extracellular matrix constituents of proliferative vitreoretinopathy membranes, and intraretinal changes over time. METHODS: Twenty-one epiretinal and/or subretinal membrane specimens were obtained from 21 patients with open globe injuries. The patients were divided into Groups A (≤28 days), B (29-120 days), and C (>120 days) according to the interval between injury and vitrectomy. The staining intensity and percentage of positive cells in membranes were compared among the groups, and proliferative indices for Ki-67 and proliferating cell nuclear antigen were assessed. Intraretinal changes were evaluated through histology and immunohistochemistry. Fundus photography was performed during vitrectomy. RESULTS: The proliferating cell nuclear antigen proliferative index was significantly higher in Group B (P = 0.002) than in Group A, and lower in Group C (P < 0.001) than in Group B. α-smooth muscle actin expression increased from day 29 to 120 after injury. Meanwhile, intraretinal gliosis and fibrosis developed. CONCLUSION: Active proliferation and contraction in proliferative vitreoretinopathy membranes continue until 120 days after injury, and are accompanied by the initiation of intraretinal gliosis and fibrosis. These findings provide further insight into the optimal timing of vitrectomy after trauma.

SMOKING IS A RISK FACTOR FOR PROLIFERATIVE VITREORETINOPATHY AFTER TRAUMATIC RETINAL DETACHMENT.

PURPOSE: To determine the incidence of retinal redetachment due to proliferative vitreoretinopathy after open-globe trauma in smokers and nonsmokers. METHODS: A total of 892 patients comprising 893 open-globe injuries, in whom 255 eyes were diagnosed with a retinal detachment, and 138 underwent surgical repair were analyzed in a retrospective case-control study. Time to redetachment was examined using the Kaplan-Meier method and analysis of risk factors was analyzed using Cox proportional hazards modeling. RESULTS: Within one year after retinal detachment surgery, 47% (95% CI, 39-56%) of all 138 repaired retinas redetached because of proliferative vitreoretinopathy. Being a smoker was associated with a higher rate of detachment (adjusted hazard ratio 1.96, P = 0.01). As shown in previous studies, the presence of proliferative vitreoretinopathy at the time of surgery was also an independent risk factor for failure (adjusted hazard ratio 2.13, P = 0.005). Treatment with vitrectomy-buckle compared favorably to vitrectomy alone (adjusted hazard ratio 0.58, P = 0.04). Only 8% of eyes that redetached achieved a best-corrected visual acuity of 20/200 or better, in comparison to 44% of eyes that did not redetach (P < 0.001). CONCLUSION: Proliferative vitreoretinopathy is a common complication after the repair of retinal detachment associated with open-globe trauma, and being a smoker is a risk factor for redetachment. Further study is needed to understand the pathophysiologic mechanisms underlying this correlation.

[The significance of fibroblasts in experimental modeling of proliferative vitreoretinopathy]. / Rol' fibroblastov v modelirovanii proliferativnoi vitreoretinopatii.

AIM: to investigate the role of heterogeneous fibroblasts in the development of epiretinal membrane in eyes with modeled proliferative vitreoretinopathy. MATERIAL AND METHODS: The material for investigation were 6 eyes of 3 Chinchilla rabbits. Suspended fibroblasts (fibroblasts of the human skin - 200000 cells in 0.1 ml) were injected into the vitreous cavity via the pars plana. The animals were followed up for 1 month and then made out of the experiment. The eyes were enucleated and fixed in 10% neutral buffered formalin for routine histological examination. Microscopy was performed on the Leica system. RESULTS: The main clinical and morphological criteria for a rabbit model of PVR induced by intravitreal injection of heterogenic fibroblasts have been established: epiretinal membrane formation, changes in intraocular structures (the retinal pigment epithelium and retina), and inflammation (due to transplantation immunity). Particularities of the epiretinal membrane development and the role of different intraocular structures have been described. CONCLUSION: The experimental fibroblastic model of PVR reproduces the final, fibrous, stage of PVR, which is significant for efficacy evaluation of antiproliferative drugs.