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.

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.

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.

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.

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.

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.

Pars plana vitrectomy with silicone oil tamponade in failed scleral buckle surgery.

OBJECTIVE: This study aimed to evaluate the anatomical and functional outcomes of secondary pars plana vitrectomy (PPV) after failed scleral buckling (SB) surgery and to compare it with primary PPV for rhegmatogenous retinal detachment (RRD), including complicated proliferative vitreoretinopathy cases. DESIGN: Retrospective series in a tertiary care centre. PARTICIPANTS: One hundred and twenty consecutive patients. METHODS: The medical records of patients who underwent PPV with silicone oil tamponade for RRD were reviewed. Forty-four eyes were operated on for primary RRD (primary PPV group), and 76 eyes were operated on for failed SB surgery (secondary PPV group). The single-operation anatomical success rate, final anatomical success rate, and best-corrected visual acuity preoperatively, at 6 months, at 1 year, and at final follow-up were analyzed. RESULTS: The single-operation anatomical success rate was 74.2% in the primary PPV group and 77% in the secondary PPV group (p = 0.48). The final anatomical success rate was 90.3% in the primary PPV group and 91.8% in the secondary PPV group (p = 0.55). The number of cases with visual acuities of 3 visual categories (20/50 or better, 20/200 to 20/50, less than 20/200) was not statistically different at each time point. CONCLUSIONS: Consequent PPV with silicone oil tamponade for failed SB surgery seems not to have inferior anatomical and functional outcomes when compared with primary PPV for RRD.

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan.

BACKGROUND: Open globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report. METHODS/DESIGN: ASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20-25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity). TRIAL REGISTRATION: ISRCTN30012492 . Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September 2014.

Adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): study protocol for a phase III, multi-centre, double-masked randomised controlled trial.

BACKGROUND: Eyes sustaining open globe trauma are at high risk of severe visual impairment. Ocular injuries which result in visual loss invariably affect the posterior segment of the eye, and prevention of visual loss involves posterior segment (vitreoretinal) surgery. Despite improvements in vitreoretinal surgical techniques, outcomes in these patients remain unsatisfactory, and development of the intraocular scarring response proliferative vitreoretinopathy is the leading cause. Proliferative vitreoretinopathy is the most common cause of recurrent retinal detachment in these eyes; it is reported to occur in up to 45 % of cases. METHODS/DESIGN: The Adjunctive Steroid Combination in Ocular Trauma (ASCOT) trial is a multi-centre, double-masked, parallel-arm randomised controlled trial with an internal pilot designed to investigate the effectiveness and cost-effectiveness of using intravitreal and sub-Tenon's triamcinolone acetonide peri-operatively in patients undergoing vitrectomy following open globe trauma. In total, 300 eyes of 300 patients will be recruited and randomly allocated to one of two treatment groups. Both groups will receive standard surgical treatment and routine pre-operative and post-operative treatment and care. The treatment group will receive an adjunctive peri-operative steroid combination (triamcinolone acetonide) consisting of 4 mg/0.1 ml into the vitreous cavity and 40 mg/1 ml into the sub-Tenon's space. The trial incorporates a two-stage internal pilot to examine projected recruitment and retention rates. Progression criteria from the internal pilot study will enable us to determine whether to undertake the main trial. Patients and primary outcome assessors will be masked to treatment allocation. The primary outcome will be an improvement from baseline to 6 months of at least 10 on the corrected visual acuity as measured by ETDRS letter score. Secondary outcomes will be development of scarring, retinal detachment, intraocular pressure abnormalities, quality of life and public sector service use. DISCUSSION: This is the first powered, controlled clinical trial to investigate the use of adjunctive triamcinolone in patients undergoing vitrectomy following open globe trauma. TRIAL REGISTRATION: EudraCT2014-002193-37 . Registered on 5 September 2014. ISRCTN30012492 . Registered on 5 September 2014.

Effect of Serial Intrasilicone Oil Bevacizumab Injections in Eyes With Recurrent Proliferative Vitreoretinopathy Retinal Detachment.

PURPOSE: To investigate the effect of serial intrasilicone oil bevacizumab injections (1.25 mg/0.05 mL) on visual acuity (VA) and anatomic outcomes in eyes undergoing proliferative vitreoretinopathy (PVR)-related retinal detachment (RD) repair. DESIGN: Prospective, nonrandomized, historical-control pilot study. METHODS: setting: Tertiary care center. STUDY POPULATION: Nondiabetic eyes undergoing pars plana vitrectomy (PPV) and silicone oil tamponade with or without scleral buckling procedure (SBP) for recurrent RD due to PVR. INTERVENTION: Intrasilicone oil injection of 1.25 mg bevacizumab was performed intraoperatively and at postoperative months 1, 2, and 3. OUTCOMES: Retinal reattachment rate, final VA, and rate of epiretinal membrane (ERM) formation at month 6. RESULTS: Twenty eyes of 20 patients were enrolled and compared to a historical control group composed of 35 age- and sex-matched controls. In the study group, logMAR VA improved from mean 1.78 ± 0.43 (Snellen 20/1205) to 1.43 ± 0.70 (Snellen 20/538, P = .04), retinal reattachment was achieved in 14 of 20 eyes (70%), and ERM formation was observed in 7 of 20 eyes (35%) at 6 months. In the control group, logMAR VA improved from mean 1.50 ± 0.74 (Snellen 20/632) to 1.43 ± 0.58 (Snellen 20/538, P = .64), retinal reattachment was achieved in 25 of 35 eyes (71%), and ERM formation was observed in 7 of 35 eyes (20%) at 6 months. No significant difference in final VA (P = .96), retinal reattachment rate (P = .75), or ERM formation (P = .33) was observed between groups. No intrasilicone oil injection-related adverse events occurred. CONCLUSIONS: Serial intrasilicone oil injections of bevacizumab did not improve retinal reattachment rate, improve final VA, or reduce ERM formation in patients undergoing PVR-related RD surgery.

Inferior retinotomy and silicone oil tamponade for recurrent inferior retinal detachment and grade C PVR in eyes previously treated with pars plana vitrectomy or scleral buckle.

BACKGROUND: One of the most challenging problems in vitro-retinal surgery is the recurrence of retinal detachment in the context of high-grade proliferative vitreoretinopathy (PVR). The aim of our retrospective study was to assess the surgical outcomes of pars plana vitrectomy, 180° inferior retinotomy and silicone oil tamponade combined with phacoemulsification and IOL implantation for recurrent inferior retinal detachment with grade C PVR in phakic eyes. The study was carried out at tertiary referral centre - University Hospital of Rome "Tor Vergata". METHODS: Retrospective analysis of 33 eyes affected by recurrent inferior retinal detachment and grade C PVR after primary encircle scleral buckling (SB group - 12 eyes), or pars plana vitrectomy (PPV group - 21 eyes). All patients subsequently underwent PPV and silicone oil tamponade at our Institution. The first outcome measure was retinal reattachment, and second outcomes were reoperation rates, best-corrected visual acuity (BCVA) and postoperative complications. RESULTS: All patients in the SB group and 19 (90%) patients of the PPV group achieved retinal reattachment. Final BCVA was better in the SB group (p = 0.045). Two eyes in the PPV group required a third vitrectomy with heavy silicone oil tamponade. Postoperative complications included silicone oil in a deep anterior chamber (3 eyes in each group), untreatable hypotony in 1 eye in the PPV group (that led to enucleation due to phthisis bulbi), and elevated intraocular pressure in 3 patients (2 eyes in the PPV group). CONCLUSIONS: Phacoemulsification with IOL implant, PPV with silicone oil tamponade associated with 180° inferior retinotomy may lead to better anatomical success in patients who have previously undergone SB procedure for inferior retinal detachment repair compared with eyes that underwent a primary PPV.

The roles of signaling pathways in epithelial-to-mesenchymal transition of PVR.

Proliferative vitreoretinopathy (PVR) is the major cause of failure in patients undergoing surgery for rhegmatogenous retinal detachment (RRD). Characterized by the formation of an abnormal contractile membrane within the eye, PVR can cause tractional retinal redetachment. Epithelial-to-mesenchymal transition (EMT), in which epithelial cells morphologically and phenotypically transdifferentiate into mesenchymal cells, is the major pathological process implicated in PVR. Among the various cell types involved in the process, retinal pigment epithelium cells are primary contributors although, after decades of research, the mechanisms underlying EMT have remained elusive. Recently, signaling pathways, some involving growth factors, have been demonstrated to contribute to EMT. In this article, we review research to date about the roles of such signaling, including including transforming growth factor-beta-, hepatocyte growth factor-, platelet-derived growth factor-, and Notch-, Wnt/ß-catenin-, and Hippo-signaling pathways, in the EMT of PVR.

The Effects of Ozurdex® (Dexamethasone Intravitreal Implant) on Experimental Proliferative Vitreoretinopathy.

PURPOSE: To investigate a new sustained-release formulation of dexamethasone (Ozurdex®) for inhibiting proliferative vitreoretinopathy (PVR) and its effect on the expression of retinal glial reaction and inflammation in experimental PVR eyes. METHODS: We used 30 pigmented rabbits for this study. One week after gas compression, the eyes were injected with 5 × 10(4) retinal pigment epithelial cells into the vitreous cavity to induce PVR. Concurrently, one eye also received an intravitreal injection of Ozurdex; the other eye was used as a control. PVR was graded by indirect ophthalmoscopy on days 1, 3, 7, 14, 21, and 28. The expression of the retinal glial reaction and inflammation in experimental PVR eyes were evaluated by Western blot analysis. RESULTS: PVR severity increased gradually and peaked after 14 days, and no differences in PVR severity between the study and control groups were observed at any time point. The expression of glial fibrillary acid protein (GFAP) increased on days 7 and 14 in both the PVR control and study groups. While the use of Ozurdex in the study group showed less GFAP expression, this difference was not significant. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 significantly increased on days 7 and 14 in PVR control eyes. There was a significant difference in TNF-α between PVR control eyes and Ozurdex-treated eyes on days 7 (p < 0.001) and 14 (p = 0.019). Ozurdex in the study group showed lower IL-6 expression; however, this difference was not significant on days 7 (p = 0.063) and 14 (p = 0.052). CONCLUSIONS: The intravitreal injection of Ozurdex suppressed the expression of inflammatory markers; however, it did not mitigate the severity of experimental PVR in this animal model. © 2015 S. Karger AG, Basel.

Development of an experimental model of proliferative retinopathy by intravitreal injection of VEGF165.

PURPOSE: To develop an experimental model of proliferative retinopathy by intravitreal injection of vascular endothelial growth factor 165 (VEGF165) in pigmented rabbits. METHODS: A prospective, controlled, comparative intervention study. Six pigmented rabbits (Chinchilla breed) were subjected to intravitreal injection of VEGF165 in their right eye. The left eye was used as control and received an injection of balanced salt solution. In group 1, 3 rabbits received a 10-µg injection, and in group 2, 3 rabbits received a 20-µg injection. At baseline, all subjects were analyzed by anterior biomicroscopy, retinography, fluorescein angiography, and optical coherence tomography (OCT) fundus images. Biomicroscopy and all ancillary examinations were repeated at weeks 1, 2, and 5. In the fifth week after the injection, the rabbits were euthanized and the eyes were enucleated and subjected to histological evaluation. RESULTS: Seven days after the intravitreal VEGF165 injection, all rabbits developed intense neovascularization of the retina and anterior segment. Neovascularization of the posterior pole was similar in both groups, and the anterior segment was more florid in group 2. At weeks 1 and 2, neovascularization persisted with a minor decrease in conjunctival hyperemia in both groups. At week 5, there was a partial regression of neovascularization of the posterior pole, which was more prominent in group 1 than group 2, with persistent anterior neovascularization in both groups. OCT showed a statistically significant increase in retinal thickness, hyaloid detachment, and tractional retinal detachment. After the 5-week period, ocular histopathological evaluation showed an increase in retinal thickness, hyaloid detachment, and intense neovascularization in both groups, especially group 2. CONCLUSION: This pilot study of a neovascularization model using intravitreal injection of VEGF165 in pigmented rabbits showed that both doses of 10 and 20 µg were successful and effective in inducing vascular growth in the retina and anterior segment and can therefore be used for evaluating drug efficacy in future studies.