[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.

Improved Outcomes with Heavy Silicone Oil in Complex Primary Retinal Detachment: A Large Multicenter Matched Cohort Study.

PURPOSE: To establish whether Densiron 68, a heavier-than-water endotamponade agent, is an effective alternative to conventional light silicone oil in primary rhegmatogenous retinal detachment (RD) surgery for eyes with inferior breaks in the detached retina and severe proliferative vitreoretinopathy (PVR). DESIGN: Cohort study of routinely collected data from the European Society of Retina Specialists and British and Eire Association of Vitreoretinal Surgeons vitreoretinal database between 2015 and 2022. PARTICIPANTS: All consecutive eyes that underwent primary rhegmatogenous RD surgery using Densiron 68 or light silicone oil as an internal tamponade agent. METHODS: To minimize confounding bias, we undertook 2:1 nearest-neighbor matching on inferior breaks, large inferior rhegmatogenous RDs, PVR, and, for visual analyses, baseline visual acuity (VA) between treatment groups. We fit regression models including prognostically relevant covariates, treatment-covariate interactions, and matching weights. We used g-computation with cluster-robust methods to estimate marginal effects. For nonlinear models, we calculated confidence intervals (CIs) using bias-corrected cluster bootstrapping with 9999 replications. MAIN OUTCOME MEASURES: Presence of a fully attached retina and VA at least 2 months after oil removal. RESULTS: Of 1061 eyes enrolled, 426 and 239 were included in our matched samples for anatomic and visual outcome analyses, respectively. The primary success rate was higher in the Densiron 68 group (113 of 142; 80%) compared with the light silicone oil group (180 of 284; 63%), with an adjusted odds ratio of 1.90 (95% CI, 1.63-2.23, P < 0.001). We also observed a significant improvement favoring Densiron 68 of -0.26 logarithm of the minimum angle of resolution (logMAR) in postoperative VA between the 2 groups (95% CI, -0.43 to -0.10, P = 0.002). The anatomic benefit of using Densiron 68 in eyes with inferior retinal breaks and large detachments was more pronounced among eyes with PVR grade C. We found no evidence of visual effect moderation by anatomic outcome or foveal attachment. CONCLUSIONS: Densiron achieved higher anatomic success rates and improved visual outcomes compared with conventional light silicone oil in eyes with inferior retinal pathology and severe PVR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

STRUCTURAL AND FUNCTIONAL MACULAR CHANGES AFTER RETINECTOMY FOR RETINAL DETACHMENT COMPLICATED BY PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: To report anatomical and functional outcomes of nonprimary retinectomy for rhegmatogenous retinal detachment with Grade C proliferative vitreoretinopathy, to assess the structural and functional macular changes in successful eyes. METHODS: Retrospective single-center cohort study: one hundred-one consecutive retinectomies of 101 eyes affected by rhegmatogenous retinal detachment with C proliferative vitreoretinopathy between January 2014 and February 2020 were included. RESULTS: The mean preoperative best-corrected visual acuity (BCVA) was 1.48 ± 0.71 logarithm of the minimal angle of resolution (20/604 Snellen equivalent). The anatomical success rate was 78.2% after one retinectomy and 83.1% after two retinectomies. The final BCVA ≥ 20/200 was achieved in 29% of cases, 8% gained ≥ 20/80. The final mean postoperative BCVA of successes with oil in situ was 1.68 ± 0.59 (20/957 Snellen equivalent) compared with 1.07 ± 0.63 logarithm of the minimal angle of resolution (20/235 Snellen equivalent) of successes after oil removal (P = 0.00005). Postoperative macular optical coherence tomography was obtained from 60/84 successes (71%). The normal macular profile was found in 3%, whereas majority demonstrated exudative maculopathy (51.5%), macular atrophy (22%), tractional maculopathy (21.5%), and macular disciform scar (2%). Bivariate linear relationship between final central foveal thickness and BCVA was statistically significant (P = 0.000013). CONCLUSION: Satisfactory anatomical and functional outcome is possible after retinectomy for C proliferative vitreoretinopathy. Positive prognostic factors include the removal of oil without redetachment, normal macular status, and lower central foveal thickness. The functional outcome was influenced by macular changes, as final BCVA and central foveal thickness correlated.

Hirudo (Leech) for proliferative vitreous retinopathy: A protocol for systemic review and meta-analysis.

INTRODUCTION: Proliferative vitreous retinopathy (PVR) is characterized by proliferation of cells and contraction of membranes on either the retinal surface or in the vitreous cavity, which leads to retinal detachment and visual impairment. PVR is commonly seen in patients with rhegmatogenous retinal detachment and diabetic retinopathy, which seriously affects the patient's work and life. Previous studies indicated that Hirudo (Leech) or compound prescription containing Hirudo (Leech) for treatment of PVR would be effective. However, due to the lack of evidence, there are no specific methods or suggestions, so it is necessary to carry out systematic evaluations on Hirudo (Leech) for PVR and provide effective evidence for further research. METHODS AND ANALYSIS: The following 8 databases will be searched: Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database, and Wanfang Database. All randomized controlled trials in English or Chinese related to Hirudo (Leech) for PVR will be included. Outcomes will include change in Vitreous opacity, Vision changes, production of the anterior macular membrane, and retinal detachment again. The incidence of adverse events will be assessed for safety evaluation. Study inclusion, data extraction and quality assessment will be performed independently by 2 reviewers. Assessment of risk of bias and data synthesis will be performed using Review Manager V.5.3. RESULTS: In this systematic review and meta-analysis, we will synthesize the studies to assess the safety and efficacy of Hirudo (Leech) for PVR. CONCLUSION: The summary of our study will clarify whether Hirudo (Leech) therapy could be an efficient and safe method for PVR, which can further guide the promotion and application of it. OPEN SCIENCE FRAMEWORK OSF REGISTRATION NUMBER: 10.17605/OSF.IO/FP7VG (https://osf.io/fp7vg).

PHACOVITRECTOMY FOR PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: A Retrospective Review.

PURPOSE: To analyze the single surgery success rate and anterior segment complications related to phacoemulsification and intraocular lens implantation in a series of patients undergoing phacovitrectomy for all types of primary rhegmatogenous retinal detachment. METHODS: We performed a retrospective interventional case series on 302 eyes undergoing phacovitrectomy for primary rhegmatogenous retinal detachment repair between November 1, 2016, and February 2, 2019, in Edmonton, Canada. Primary outcomes included single surgery retinal reattachment rate and anterior segment complications. Secondary outcomes included the effects of proliferative vitreoretinopathy and macula and/or peripheral internal limiting membrane peeling on the rate of surgical success. RESULTS: The single surgery success rate of phacovitrectomy for all types of primary rhegmatogenous retinal detachment was 85.1%. The presence of proliferative vitreoretinopathy was associated with lower surgical success (odds ratio, 0.33; P = 0.01). Macular internal limiting membrane peeling was associated with higher surgical success (odds ratio, 2.4; P = 0.05). Anterior segment complications included posterior capsular opacification (28.8%), posterior synechiae (10.9%), and posterior capsular rupture (2.3%). CONCLUSION: Phacovitrectomy is a safe and effective treatment option for the primary repair of rhegmatogenous retinal detachments. This study provides evidence to support the safe incorporation of phacoemulsification and intraocular lens implantation with retinal surgery.

COMPARISON BETWEEN RELEASABLE SCLERAL BUCKLING AND VITRECTOMY IN PATIENTS WITH PHAKIC PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To compare the efficiency of releasable scleral buckling (RSB) and pars plana vitrectomy (PPV) in the treatment of phakic patients with primary rhegmatogenous retinal detachment. METHODS: The current study was a prospective randomized clinical trial. One hundred and ten eyes from 110 patients with primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of Grade B or less were included in this study. The patients were randomly allocated into an RSB group and a PPV group. The functional and anatomical success was compared between groups. RESULTS: The primary anatomical success rate (PPV 41/43 [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB 100%) showed a nonsignificant difference. The best-corrected visual acuity, intraocular pressure, and complications were not different between the groups. However, the incidence of cataract progression was higher in the PPV group (26 of 43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up. The subfoveal choroidal thickness increased significantly in the RSB group 3 months after surgery, but no longer differed at the postoperative 6-month and 12-month follow-ups. The axial length had increased significantly 1 month after surgery, but the difference was no longer significant at 3 months, 6 months, and 12 months. CONCLUSION: The RSB and PPV procedures have the same effects on the functional and anatomical success for patients with phakic primary rhegmatogenous retinal detachment. Nevertheless, based on the few cases of intraocular complications and cataract progression, we believe that the RSB technique should be preferentially recommended.

The Vitrectomy Timing Individualization System for Ocular Trauma (VTISOT).

Ocular trauma is a major cause of monocular blindness worldwide. Vitrectomy at correct timing can significantly improve the efficacy and prognosis, but the timing of vitrectomy has remained highly controversial for decades. Trauma cases are different from each other, thus, a flexible timing system based on the details of each individual case is recommended. Unfortunately, no such a timing system is available for clinical application up to now. To establish the vitrectomy timing individualization system for ocular trauma (VTISOT), we first identified 6 independent tPVR risk factors (including Zone 3 Injury, Zone 3 retinal Laceration, Massive Vitreous Hemorrhage, Retinal Disorder, Timing of Vitrectomy and Type of Injury) by retrospective study. Then, the tPVR score was established by binary logistic regression analysis. Most importantly and critically, the vitrectomy timing individualization system for ocular trauma was established based on the identified tPVR risk factors and the tPVR score. The following evaluation of the VTISOT showed that the patients consistent with the VTISOT principles exhibited reduced tPVR incidence and better surgical results. In short, the VTISOT principles were established, which may provide a new approach to individualize the timing of vitrectomy and improve the prognosis after trauma.

Inactive Cas9 blocks vitreous-induced expression of Mdm2 and proliferation and survival of retinal pigment epithelial cells.

Mouse double minute (MDM)2 single nucleotide polymorphism (SNP) 309G allele in the second promoter of MDM2 enhances vitreous-induced expression of Mdm2 and degradation of the tumor suppressor protein p53. This MDM2SNP309G contributes to certain cancer development and experimental proliferative vitreoretinopathy. The goal of this study is to discover a novel strategy to only block vitreous-induced expression of Mdm2 for preventing vitreous-induced cell proliferation and survival and thus find a potential novel strategy to treat proliferation-related diseases. We created two mutations (D10A and H840A) in Streptococcus pyogenes (Sp)Cas9 within the nuclease domains (RuvC1 and HNH, respectively) to render this SpCas9 nuclease dead named as dCas9 in a lentiCRISPR v2 vector. Then an MDM2-sgRNA targeting the second promoter of human MDM2 gene was cloned into this vector for producing lentivirus to infect human retinal pigment epithelial (RPE) cells with, which carry a heterozygous genotype of MDM2SNP309 T/G. lacZ-sgRNA was used as a control. As a result, we discovered that vitreous from experimental rabbits induced a 1.9 ±â€¯0.2 fold increase in Mdm2 and a 2.0 ±â€¯0.2 fold decrease in p53 in the RPE cells with dCas9/lacZ-sgRNA compared to those with dCas9/MDM2-sgRNA, suggesting that dCas9 under the guidance of the MDM2-sgRNA prevented RV-stimulated increase in Mdm2. In addition, we found that the rabbit vitreous significantly enhanced cell proliferation (1.5 ±â€¯0.2 fold), survival against apoptosis (2.2 ±â€¯0.2 fold), migration (10 ±â€¯1.5%) and contraction (112.7 ±â€¯14.1 mm2) of the cells with dCas9/lacZ-sgRNA compared with those with dCas9/MDM2-sgRNA. These results indicated that application of the dCas9 targeted to the P2 of MDM2 is a potential therapeutic approach to diseases due to the P2-driven aberrant expression of Mdm2 - such as proliferative vitreoretinopathy.

Update of inflammatory proliferative retinopathy: Ischemia, hypoxia and angiogenesis.

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?

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.

Outcomes of Retinectomy in Rhegmatogenous Retinal Detachment with Proliferative Vitreoretinopathy.

OBJECTIVE: To evaluate the anatomical and functional outcomes of retinectomy in the management of primary rhegmatogenous retinal detachments with inferior retinal breaks and advanced proliferative vitreoretinopathy (PVR C). STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: LRBT, Free Base Eye Hospital, Karachi, from July 2015 to June 2017. METHODOLOGY: Forty eyes of 40 patients with primary inferior retinal breaks macula off detachments and advanced proliferative vitreoretinopathy (grade C) in which retinectomy was performed were included. Primary outcome measured was anatomic success, defined as complete retinal reattachment between neurosensory retina and retinal pigment epithelium at six months follow-up. Secondary outcomes included changes in best corrected visual acuity and postoperative complications. The follow-up period was up to six months after the last surgery. Association was determined between the retinectomy extension and the best corrected visual acuity postoperatively. RESULTS: Retina was reattached after single operation in 29 eyes (72.5%), after the second operation in eight eyes (20%), and after the third operation in two eyes (5%). Final retinal reattachment was achieved in 39 out of 40 eyes (97.5%). The preoperative visual acuity was counting fingers CF in eight eyes (20%), hand motion HM in 28 eyes (70%), and light perception PL in four eyes (10%). The postoperative visual acuity improved in 27 eyes (67.5%), remained stable in 11 eyes (27.5%), and worsened in 2 eyes (5%). There was no statistically significant association between the retinectomy extension and maximum postoperative best corrected visual acuity (p=0.098). The significant postoperative complications were retinal redetachment and hypotony. CONCLUSION: Retinectomies are effective in managing primary rhegmatogenous retinal detachment with severe PVR (PVR C), and Increase the final retinal reattachment rate.

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.

Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy.

Degeneration of retinal astrocytes precedes hypoxia-driven pathologic neovascularization and vascular leakage in ischemic retinopathies. However, the molecular events that underlie astrocyte loss remain unclear. Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. Cx channels can transfer toxic signals from dying cells to healthy neighbors under pathologic conditions. Here we show that Cx43 plays a critical role in astrocyte apoptosis and the resulting preretinal neovascularization in a mouse model of oxygen-induced retinopathy. Opening of Cx43 hemichannels was not observed following hypoxia. In contrast, GJ coupling between astrocytes increased, which could lead to amplification of injury. Accordingly, conditional deletion of Cx43 maintained a higher density of astrocytes in the hypoxic retina. We also identify a role for Cx43 phosphorylation in mediating these processes. Increased coupling in response to hypoxia is due to phosphorylation of Cx43 by casein kinase 1δ (CK1δ). Suppression of this phosphorylation using an inhibitor of CK1δ or in site-specific phosphorylation-deficient mice similarly protected astrocytes from hypoxic damage. Rescue of astrocytes led to restoration of a functional retinal vasculature and lowered the hypoxic burden, thereby curtailing neovascularization and neuroretinal dysfunction. We also find that absence of astrocytic Cx43 does not affect developmental angiogenesis or neuronal function in normoxic retinas. Our in vivo work directly links phosphorylation of Cx43 to astrocytic coupling and apoptosis and ultimately to vascular regeneration in retinal ischemia. This study reveals that targeting Cx43 phosphorylation in astrocytes is a potential direction for the treatment of proliferative retinopathies.

Phacomorphic Angle-closure Following Silicone Oil Tamponade in a Pediatric Patient.

PURPOSE: The purpose of this study was to report a case of phacomorphic glaucoma following retinal detachment repair with silicone oil (SO) in a pediatric patient. STUDY DESIGN: Case report. METHODS: A chart review was conducted at St. Michael's Hospital and The Hospital for Sick Children (Toronto, Canada), where the patient received ophthalmic care from July 28, 2015 onwards. RESULTS: A 14-year-old boy with a history of traumatic retinal detachment and proliferative vitreoretinopathy in the left eye, requiring 2 pars plana vitrectomies, membrane peel, and SO tamponade, presented with 1-day history of decreased vision in the left eye, severe headache, nausea, and vomiting. Visual acuity was hand motions; intraocular pressure (IOP) was 54 mm Hg; the pupil was middilated and minimally reactive with a reverse relative afferent pupillary defect. Slit-lamp examination revealed an injected eye with diffuse microcystic corneal edema, a shallow anterior chamber (AC), and an intumescent cataract. Gonioscopy demonstrated closed angles in 3 quadrants. Compared with his last examination 6 weeks prior, where only a mild posterior subcapsular cataract was noted, the patient's presentation was suggestive of rapid lens intumescence causing acute angle-closure glaucoma. He was given topical and systemic treatment, including intravenous mannitol, and his IOP reduced to 22 mm Hg after 7 hours. Urgent lensectomy was performed the following day. Preoperative ultrasound biomicroscopy revealed a greatly increased lens thickness of 5.12 mm and an AC depth of 1.12 mm. The integrity of both anterior and posterior lens capsules was confirmed intraoperatively, and SO remained confined to the posterior segment. Postoperatively, the iris returned to a normal configuration with open angles, and IOP was 16 mm Hg with no antiglaucoma medications at the last follow-up. CONCLUSIONS: Acute angle-closure in children is a rare event. To our knowledge, this is the first reported case of phacomorphic glaucoma secondary to vitreoretinal surgery in the pediatric population. Although uncommon, ophthalmologists should be aware of this potential complication with the intraocular use of SO and administer urgent treatment accordingly.

Plumbagin induces RPE cell cycle arrest and apoptosis via p38 MARK and PI3K/AKT/mTOR signaling pathways in PVR.

BACKGROUND: This study aimed to explore the effects of plumbagin (PLB) on ARPE-19 cells and underlying mechanism. METHODS: Cultured ARPE-19 cells were treated with various concentrations (0, 5, 15, and 25 µM) of PLB for 24 h or with 15 µM PLB for 12, 24 and 48 h. Then cell viability was evaluated by MTT assay and DAPI staining, while apoptosis and cell cycle progression of ARPE cells were assessed by flow cytometric analysis. Furthermore, the level of main regulatory proteins was examinated by Western boltting and the expression of relative mRNA was tested by Real-Time PCR. RESULTS: PLB exhibited potent inducing effects on cell cycle arrest at G2/M phase and apoptosis of ARPE cells via the modulation of Bcl-2 family regulators in a concentration- and time-dependent manner. PLB induced inhibition of phosphatidylinositol 3-kinase (PI3K) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways contributing to the anti-proliferative activities in ARPE cells. CONCLUSIONS: This is the first report to show that PLB could inhibit the proliferation of RPE cells through down-regulation of modulatory signaling pathways. The results open new avenues for the use of PLB in prevention and treatment of proliferative vitreoretinopathy.

A clinical analysis of vitrectomy for severe vitreoretinopathy in patients with chronic renal.

BACKGROUND: The recent advancement in the management of chronic renal failure (CRF) has significantly increased the longevity of the patients, which increase the incidence of severe vitreoretinopathy. The vitrectomy is highly risky in this particular group of patients due to their systemic comorbidity. The timing surgical intervention is usually delayed because of the systemic conditions. This study is to evaluate the safety and effectiveness of 25-guage vitrectomy for severe vitreoretinopathy in the CRF patients. METHODS: In this retrospective study, 16 eyes of 16 CRF patients with severe vitreoretinopathy were undergone 25-guage vitrectomy in the department of Ophthalmology of the Second Hospital of Tianjin Medical University from February 2015 to April 2017. The visual outcome, complications and perioperative medical management were documented and analyzed. RESULTS: The best-corrected visual acuity(BCVA)of fourteen eyes were lower than 20/200 preoperatively. Surgery duration ranged from 28 to 72 min, with a mean of 48.4 ± 13.6 min. During the surgery, 12 eyes were diagnosed with DR, while two them were complicated with tractional retinal detachment and one with branch retinal vein occlusion. Three eyes were diagnosed with branch retinal vein occlusion, and one eye was diagnosed with hypertensive retinopathy. Postoperative BCVA of six eyes ≥20/40, seven eyes ≥20/200, and three eyes < 20/200. BCVA of eight eyes improved more than three lines, three eyes improved two lines, and four eyes improved one line. BCVA decreased from hand movement to light perception in one patient who developed neovascular glaucoma two weeks after surgery. CONCLUSION: In chronic renal failure patients with severe vitreoretinopathy, the well-planned minimally invasive vitrectomy is effective and safe. Additionally, careful management of the perioperative systemic conditions is important to improve the visual acuity and quality of life as well.

Association of functional SNP-1562C>T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients.

OBJECTIVE: Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C>T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C>T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population. METHODS: This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C>T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results. RESULTS: T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p<0.0001 by T allele; p=0.002 by TT and p<0.0001 by CT genotype). CONCLUSIONS: The present study suggests that the functional SNP-1562C>T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis.

Slow-Release Dexamethasone in Proliferative Vitreoretinopathy: A Prospective, Randomized Controlled Clinical Trial.

PURPOSE: To test the hypothesis that adjunctive slow-release dexamethasone implant (Ozurdex; Allergan Inc, Irvine, CA) can improve the outcomes of vitreoretinal surgery for established proliferative vitreoretinopathy (PVR). DESIGN: A 2-year, single-center, prospective, participant- and surgeon-masked randomized controlled clinical trial (EudraCT No. 2011-004498-96). PARTICIPANTS: A total of 140 patients requiring vitrectomy surgery with silicone oil for retinal detachment with established PVR (Grade C) were randomized to standard (control) or study treatment (adjunct) in a 1:1 allocation ratio. METHODS: Intraoperatively, the adjunct group received an injection of 0.7 mg of slow-release dexamethasone (Ozurdex) at the time of (1) vitrectomy surgery and (2) silicone oil removal. The control group received standard care. MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of patients with a stable retinal reattachment with removal of silicone oil without additional vitreoretinal surgical intervention at 6 months. Secondary outcomes included (1) final visual acuity (VA) (median and Early Treatment Diabetic Retinopathy Study [ETDRS] of 55 letters or better); (2) cystoid macular edema (CMO), foveal thickness, and macular volume; (3) development of overt PVR recurrence; (4) complete and posterior retinal reattachment; (5) tractional retinal detachment; (6) hypotony/increased intraocular pressure (IOP); (7) macula pucker/epiretinal membrane; (8) cataract; and (9) quality of life. RESULTS: All 140 patients were recruited within 25 months of study commencement; 138 patients had primary outcome data. Primary outcome assessment showed similar results in anatomic success between the 2 groups (49.3% vs. 46.3%, adjunct vs. control; odds ratio, 0.89; 95% confidence interval, 0.46-1.74; P = 0.733). Mean VA at 6 months was 38.3 ETDRS letters and 40.2 letters in the adjunct and control groups, respectively. Secondary anatomic outcomes (complete/posterior reattachment rates and PVR recurrence) were comparable between the 2 groups. At 6 months, fewer adjunct patients had CMO (42.7%) or a foveal thickness of >300 µm (47.6%) compared with controls (67.2% and 67.7%, respectively, P = 0.004, P = 0.023). CONCLUSIONS: A slow-release dexamethasone implant did not improve the primary anatomic success rate in eyes undergoing vitrectomy surgery with silicone oil for PVR. Further clinical trials are indicated to improve anatomic and visual outcomes in these eyes, but this study suggests that there is a greater reduction in CMO observed at 6 months in vitrectomized eyes treated with slow-release dexamethasone.

Physical activity and its correlation to diabetic retinopathy.

PURPOSE: The lack of physical activity, along with obesity, smoking, hypertension and hyperglycaemia are considered as risk factors for the occurrence of diseases such as diabetes. Primary objective of the study was to investigate potential correlation between physical activity and diabetic retinopathy. PATIENTS AND METHODS: Three hundred and twenty patients were included in the study: 240 patients with diabetes type 2 (80 patients with mild to moderate non-proliferative diabetic retinopathy, 80 patients with severe to very severe non-proliferative diabetic retinopathy and 80 ones with proliferative diabetic retinopathy) were compared with 80 non-diabetic patients (control group). Physical activity of patients was assessed by the international physical activity questionnaire (IPAQ, 2002). HbA1c and BMI were also measured in diabetic patients. Group comparisons were attempted for levels of physical activity and sedentary behavior. RESULTS: Total physical activity was decreased in patients with severe to very severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy as compared to patients with mild to moderate non-proliferative diabetic retinopathy and to the control group (p<0.05). Significant negative correlation was detected between HbA1c levels, BMI and physical activity (both p<0.05). Moreover, significant negative correlation between the severity of diabetic retinopathy and physical activity has been demonstrated (p<0.05). CONCLUSIONS: Increased physical activity is associated with less severe levels of diabetic retinopathy, independent of the effects of HbA1c and BMI.