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Purpose: To evaluate OCT features for vitreomacular traction (VMT) release and change in macular hole (MH) size after treatment with ocriplasmin., Methods: Patients who had undergone treatment with ocriplasmin for VMT with or without MH ≤400 µm were included. The main outcomes were VMT release and changes in minimum linear diameter MH size at 4 weeks in MHs that persisted. OCT features evaluated were central retinal thickness, vitreomacular adhesion length, posterior vitreous cortex (PVC) insertion angles 500 µm from the insertion points, and minimum linear diameter size., Results: Sixty patients were included: 37 had isolated VMT and 23 VMT with a MH. Four weeks after ocriplasmin injection, the overall VMT release rate was 66.7% (40/60); 64.9% (24/37) in eyes with isolated VMT and 69.6% (16/23) in eyes with MH. VMT release was associated with younger age (P = 0.02). Macular hole closure was achieved in 26.1% (6/23) and was associated with a smaller ratio of the temporal to the nasal PVC angle (P < 0.01). Of the 17 persistent MHs, 76.5% (13/17) increased in minimum linear diameter size from baseline 186 (±78) to 358 (±133) µm (P < 0.001). Progression in minimum linear diameter size showed a negative linear association with the size of the nasal PVC angle (R2 = 0.39, P = 0.002) and a positive linear association with the ratio of the temporal to nasal PVC angle (R2 = 0.39, P = 0.002)., Conclusion: In patients with VMT-associated MHs, the risk of MH enlargement following ocriplasmin is negatively correlated with the nasal PVC angle size and is increased if the ratio of the temporal to nasal angle is >1.

Background: Hemophilia A patients are treated with factor (F) VIII prophylactically to prevent bleeding. In general, dosage and frequency are based on pharmacokinetic measurements. Ideally, an alternative dose adjustment can be based on the hemostatic potential, measured with a thrombin generation assay (TGA), like the Nijmegen hemostasis assay., Objective: The objective of this study was to investigate the predicted performance of a previously developed pharmacokinetic-pharmacodynamic model for FVIII replacement therapy, relating FVIII dose and FVIII activity levels with thrombin and plasmin generation parameters., Methods: Pharmacokinetic and pharmacodynamic measurements were obtained from 29 severe hemophilia A patients treated with pdVWF/FVIII concentrate (Haemate P ® ). The predictive performance of the previously developed pharmacokinetic-pharmacodynamic model was evaluated using nonlinear mixed-effects modeling (NONMEM). When predictions of FVIII activity or TGA parameters were inadequate [median prediction error (MPE) > 20%], a new model was developed., Results: The original pharmacokinetic model underestimated clearance and was refined based on a two-compartment model. The pharmacodynamic model displays no bias in the observed normalized thrombin peak height and normalized thrombin potential (MPE of 6.83% and 7.46%). After re-estimating pharmacodynamic parameters, EC 50 and E max values were relatively comparable between the original model and this group. Prediction of normalized plasmin peak height was inaccurate (MPE 58.9%)., Conclusion: Our predictive performance displayed adequate thrombin pharmacodynamic predictions of the original model, but a new pharmacokinetic model was required. The pharmacodynamic model is not factor specific and applicable to multiple factor concentrates. A prospective study is needed to validate the impact of the FVIII dosing pharmacodynamic model on bleeding reduction in patients., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surface and act as a plasminogen receptor to facilitate cell migration via plasmin activation. Our proprietary ENO1 antibody, HL217, was screened for its specific binding to ENO1 and significant inhibition of cell migration and plasmin activation (patent: US9382331B2)., Methods: In this study, effects of HL217 were evaluated in vivo and in vitro for treating lung fibrosis., Results: Elevated ENO1 expression was found in fibrotic lungs in human and in bleomycin-treated mice. In the mouse model, HL217 reduced bleomycin-induced lung fibrosis, inflammation, body weight loss, lung weight gain, TGF-β upregulation in bronchial alveolar lavage fluid (BALF), and collagen deposition in lung. Moreover, HL217 reduced the migration of peripheral blood mononuclear cells (PBMC) and the recruitment of myeloid cells into the lungs. In vitro, HL217 significantly reduced cell-associated plasmin activation and cytokines secretion from primary human PBMC and endothelial cells. In primary human lung fibroblasts, HL217 also reduced cell migration and collagen secretion., Conclusions: These findings suggest multi-faceted roles of cell surface ENO1 and a potential therapeutic approach for pulmonary fibrosis., (© 2023. The Author(s).)

Intracerebral haemorrhage is an unmet medical need affecting more than 3 million people worldwide every year and leading to the formation of an intracerebral haematoma. Updated guidelines (2022) for the management of intracerebral haemorrhage patients recognize that minimally invasive approaches for the evacuation of supratentorial intracerebral haemorrhage have demonstrated reductions in mortality compared with medical management alone. However, improvement of functional outcome with a procedure involving thrombolytic therapy was neutral in the last large phase 3 clinical trial and requires a more effective and safer thrombolytic agent than those currently available. Here, we demonstrate that O2L-001 allows for the extended release of W253R/R275S recombinant tissue-type plasminogen activator (rtPA). A new rtPA variant, called optimized tPA (OptPA), offers improved efficacy for haematoma evacuation as well as improved safety. OptPA was produced in a Chinese hamster ovary cell line before purification, nanoprecipitation using the NANOp2Lysis® technological platform followed by suspension in a solution of 17% poloxamer 407 to obtain O2L-001. Plasmin generation assays were performed to demonstrate O2L-001 safety. Ex vivo haematoma models using human blood were used to demonstrate O2L-001 thrombolysis properties and efficacy. For the best translational significance, a clinical sized haematoma was used to ensure catheter placement and to allow administration of the thrombolytic agent into the core of the haematoma via a minimally invasive procedure. The capacity of OptPA to convert plasminogen into plasmin is strongly decreased compared to rtPA, thereby reducing potential bleeding events. However, a clot lysis assay showed that OptPA had the same fibrinolytic activity as rtPA. We demonstrated that long-term exposure to a thrombolytic agent was essential to achieve high thrombolysis efficacy. Indeed, 24 h continuous exposure to 0.1 µg/ml rtPA had similar efficacy than repeated short exposure to 30 µg/ml rtPA. This finding led to the development of O2L-001, allowing the extended release of OptPA in the first 6 h following injection. An ex vivo model using human blood was used to demonstrate O2L-001 efficacy. Interestingly, unlike rtPA, O2L-001 was able to induce the complete lysis of the 5 ml haematoma. In clinical sized haematomas (obtained from 30 ml of human blood), a single injection of O2L-001 at 1 mg/ml into the core of the haematoma led to a 44% increase in thrombolysis compared to rtPA. Taken together, these results demonstrate that O2L-001 provides new hope for haematoma evacuation and the treatment of patients with intracerebral haemorrhage., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background/aims: To describe the clinical impact of external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption and subretinal fluid (SRF) seen on optical coherence tomography (OCT) in eyes with vitreomacular traction (VMT) without macular hole (MH) in the Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole study., Methods: Phase 3b randomised double-blind sham-controlled multicentre study including 144 eyes with VMT without MH. Eyes were randomised to receive a single intravitreal injection of ocriplasmin or sham injection and were followed for 24 months. Eyes were analysed for presence, course and clinical impact of ELM disruption, EZ disruption and SRF on OCT., Results: ELM disruption, EZ disruption and SRF were present in 32.6%, 52.2% and 45.8% of ocriplasmin-treated eyes and 39.6%, 42.6% and 37.5% of sham-treated eyes at baseline. VMT resolution was associated with resolution of ELM and EZ disruption and SRF. A small number of eyes had persistent ELM disruption, EZ disruption and/or SRF at the seventh visit or later (17 months or later) following medical or surgical VMT resolution. Resolution of ELM disruption, EZ disruption and/or SRF was associated with an improvement of visual acuity from baseline. Following VMT resolution, ELM recovery usually preceded EZ recovery and SRF resolution., Conclusions: ELM disruption, EZ disruption and/or SRF are present in a significant percentage of eyes with VMT without MH. Release of VMT is usually associated with outer retinal recovery and an associated improvement in visual acuity. ELM recovery typically precedes EZ recovery and SRF resolution following VMT release., Competing Interests: Competing interests: AST: Alimera Sciences (Consultant), Bausch & Lomb (Consultant), Genentech (Consultant), Knights Templar Foundation (Grant), Zeiss (Consultant). LD: Oxurion NV (Consultant). PK-W: Oxurion NV (Employee). GJ: Neurotech (consultant), Novartis (Consultant), Eyepoint Pharmaceuticals (Consultant), Noveome (Consultant), Iveric (Consultant)., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Salt-sensitive hypertension is associated with poor clinical outcomes. The epithelial sodium channel (ENaC) in the kidney plays pivotal roles in sodium reabsorption and blood pressure regulation, in which its γ subunit is activated by extracellular serine proteases. In proteinuric nephropathies, plasmin filtered through injured glomeruli reportedly activates γENaC in the distal nephron and causes podocyte injury. We previously reported that Dahl salt-sensitive (DS) rats fed a high-salt (HS) diet developed hypertension and proteinuria along with γENaC activation and that a synthetic serine protease inhibitor, camostat mesilate, mitigated these changes. However, the role of plasmin in DS rats remained unclear. In this study, we evaluated the relationship between plasmin and hypertension as well as podocyte injury and the effects of plasmin inhibitors in DS rats. Five-week-old DS rats were divided into normal-salt diet, HS diet, and HS+plasmin inhibitor (either tranexamic acid [TA] or synthetic plasmin inhibitor YO-2) groups. After blood pressure measurement and 24 h urine collection over 5 weeks, rats were sacrificed for biochemical analyses. The HS group displayed severe hypertension and proteinuria together with activation of plasmin in urine and γENaC in the kidney, which was significantly attenuated by YO-2 but not TA. YO-2 inhibited the attachment of plasmin(ogen) to podocytes and alleviated podocyte injury by inhibiting apoptosis and inflammatory/profibrotic cytokines. YO-2 also suppressed upregulation of protease-activated receptor-1 and phosphorylated ERK1/2. These results indicate an important role of plasmin in the development of salt-sensitive hypertension and related podocyte injury, suggesting plasmin inhibition as a potential therapeutic strategy., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Purpose: To evaluate the efficacy of combined pneumatic and enzymatic vitreolysis for treatment of severe cases of vitreomacular traction (VMT)., Methods: We analyzed a retrospective, consecutive series of five patients diagnosed with severe VMT refractory to pneumatic vitreolysis who then received an additional ocriplasmin injection while their gas bubble from pneumatic vitreolysis was still present between February 2015 and February 2019. Vitreomacular traction release was confirmed using spectral-domain optical coherence tomography., Results: Four of the five patients treated with combined pneumatic and enzymatic vitreolysis achieved VMT release by Day 28, and all cases eventually achieved complete VMT release. In addition to having VMT refractory to pneumatic vitreolysis, patient characteristics included broad adhesion diameter (>1,500 µ m, n = 1), presence of epiretinal membrane (n = 2), age >65 years (n = 4), and pseudophakia (n = 1). The visual acuity improved by three or more lines at 6 months in both of the patients with initial vision worse than 20/50 on an Early Treatment Diabetic Retinopathy Study chart but not in those whose vision was already fairly good (i.e., visual acuity >20/60). None of the patients experienced the following complications after receiving this combined treatment: retinal tears or detachments, vitreous floaters, and ellipsoid zone changes., Conclusion: Sequential, combined pneumatic and enzymatic vitreolysis resulted in VMT release in all 5 cases (4 cases by 28 days) and may be a potentially useful alternative to surgical intervention for refractory VMT cases.

Tranexamic acid (TXA) is a popular antifibrinolytic drug widely used in hemorrhagic trauma patients and cardiovascular, orthopedic, and gynecological surgical patients. TXA binds plasminogen and prevents its maturation to the fibrinolytic enzyme plasmin. A number of studies have demonstrated the broad life-saving effects of TXA in trauma, superior to those of other antifibrinolytic agents. Besides preventing fibrinolysis and blood loss, TXA has been reported to suppress posttraumatic inflammation and edema. Although the efficiency of TXA transcends simple inhibition of fibrinolysis, little is known about its mechanisms of action besides the suppression of plasmin maturation. Understanding the broader effects of TXA at the cell, organ, and organism levels are required to elucidate its potential mechanisms of action transcending antifibrinolytic activity. In this article, we provide a brief review of the current clinical use of TXA and then focus on the effects of TXA beyond antifibrinolytics such as its anti-inflammatory activity, protection of the endothelial and epithelial monolayers, stimulation of mitochondrial respiration, and suppression of melanogenesis., (© 2022 AABB.)

Purpose: To evaluate a multivariable model predicting the individual probability of successful intravitreal ocriplasmin (IVO) treatment in eyes with vitreomacular traction (VMT)., Methods: Data from three prospective, multicenter IVO studies (OASIS, ORBIT, and INJECT) were pooled. Patients were included if they were treated for a symptomatic VMT without a full-thickness macular hole. A prediction model for VMT resolution using the factors 'age' and 'horizontal VMT diameter' was validated by receiver operating characteristic analysis and according to grouped prediction after calibration. Multivariable regression analysis was performed to check robustness and explore further improvements., Results: Data from 591 eyes was included. In the univariate analysis all key factors (age, gender, VMT diameter, lens status, ERM) significantly correlated to treatment success. The prediction model was robust and clinically applicable to estimate the success rate of IVO treatment (AUC of ROC: 0.70). A refinement of the model was achieved through a calibration process., Conclusion: The developed multivariable model using 'horizontal VMT diameter' and 'age' is a valid tool for prediction of VMT resolution upon IVO treatment., Competing Interests: CP has nothing to disclose. HM also has nothing to disclose. TR is employed by Oxurion NV, Leuven, Belgium. TB is an employee of Novartis Pharma GmbH, Nuremberg, Germany and a scientific staff member of the Department of Ophthalmology, University Medical Centre Goettingen, Germany. He reports speaker honoraria from Alcon, speaker honoraria, travel and research grants from Novartis, speaker honoraria from Alimera, speaker honoraria and travel grants from Bayer, speaker honoraria from Heidelberg, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Significance: We report 13 patients who received ocriplasmin for symptomatic vitreomacular adhesion. Farnsworth-Munsell 100 (FM 100) hue test total error score (TES) increased from baseline to month 1, before recovering at year 1. Ocriplasmin may alter hue discrimination., Purpose: This study aimed to determine whether intravitreal ocriplasmin affects hue discrimination., Methods: Thirteen patients with symptomatic vitreomacular adhesion received intravitreal ocriplasmin 125 μg. Patients underwent full ocular examination, optical coherence tomography, and FM 100 hue test at baseline, 1 week, 1 month, and 1 year., Results: Mean age was 74.8 years. The median baseline FM 100 TES was similar in the injected and fellow eyes (272 vs. 252, respectively). Median TES in the injected eye increased from 272 to 348 at 1 week (median difference compared with baseline, +52.0; 98.8% confidence interval of difference, -64.0 to 184.0; P = .29), decreased to 324 at 1 month (median difference compared with baseline, -4.0; 98.8% confidence interval of difference, -44.0 to 256.0; P = .40), and decreased to 268 at 1 year (median difference compared with baseline, -108.0; 93.8% confidence interval of difference, -200.0 to 52.0; P = .19). Two patients (15.4%) had anatomic release of vitreomacular adhesion, occurring within 1 month of injection., Conclusions: Ocriplasmin may alter hue discrimination, but larger studies are required to provide sufficient power to detect or exclude a statistically significant effect. Longer follow-up is needed to determine the duration of any effect., Competing Interests: Conflict of Interest Disclosure: JEN has previously received conference support from Thrombogenics and VisionCare Inc., and speaker fees from Novartis. TLJ has previously served as a consultant to Thrombogenics; his employer received site payments for patients enrolled in clinical trials of ocriplasmin from Alcon/Oxurion. VK and CS have no disclosures to declare., (Copyright © 2021 American Academy of Optometry.)

Purpose: To determine a statistically optimal limit of adhesion size in vitreomacular traction (VMT) syndrome for ocriplasmin treatment., Methods: In this retrospective, consecutive, interventional study, we included 106 patients treated with ocriplasmin injection because of VMT between July 2013 and January 2018. A univariate and multivariate risk analysis was performed with grouped factors and continuous factors. We used a receiver operating characteristic curve to measure the prognostic relevance of each continuous factor for therapy success and determined the statistically optimal cutoff value at which specificity and sensitivity are simultaneously maximized., Results: Among the grouped factors, only a phakic lens status showed a highly significant positive influence on the resolution of the VMT. For the continuous factors, only the adhesion diameter before injection was a good predictor of anatomical success. The statistically optimal threshold value for the adhesion size was calculated to be 480 µm. Eyes below this limit had a 6.84-fold better chance of VMT resolution compared with eyes with a larger adhesion diameter., Conclusion: The threshold value of the VMT diameter for ocriplasmin therapy could be statistically defined as 480 µm and may thus be a new quantitative biomarker to predict treatment success.

Objective: To conduct a systematic review looking at the effects of ocriplasmin compared to pars plana vitrectomy on macular holes to assess the effectiveness of the treatment options., Methods: Literature was searched through MEDLINE, EMBASE, CINAHL, Clinical Trials.gov, and ProQuest Dissertations and Theses until June 12, 2018. Conferences held through Association for Research in Vision and Ophthalmology, Canadian Society of Ophthalmology, and American Academy of Ophthalmology were searched until June 18, 2018. A total of 208 records were screened leaving 26. One author independently reviewed them for quality and extracted data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. The adverse events, MH closure rate, change in MH size, and the extent to which the patients' visual acuity is restored by each treatment option; ocriplasmin and vitrectomy., Results: Twenty-six articles were included for qualitative and quantitative analysis. Meta-analysis results showed a 34% closure of macular holes after ocriplasmin treatment compared to 92% after vitrectomy. A significant improvement in visual acuity was seen after vitrectomy (SMD = -1.42; CI: [-1.98, -0.86]) as well as the ocriplasmin treatment (SMD = -0.73; CI: [-0.98, -0.48])., Conclusions: Results suggested 92% macular hole closure after vitrectomy compared to 34% after ocriplasmin. A significant improvement in visual acuity of patients was seen after both treatments. More good quality randomized controlled trials are required to make strong conclusions.

Purpose: To assess the efficacy of ocriplasmin in patients with vitreomacular traction (VMT) syndrome <1,500 μm with or without a full-thickness macular holes of <400 μm., Methods: In this study, a retrospective analysis of 10 eyes of 10 patients with VMT who were treated with ocriplasmin between December 2014 and January 2016 was performed. Ocriplasmin 0.125 mg was injected only once in all cases. Outcome measures included the detachment of VMT, best-corrected visual acuity, the evaluation of optical coherence tomography, including the closure of full-thickness macular holes, and the reduction of macular edema (if present) and the decrease of metamorphopsia if present., Results: Ten patients (7 women and 3 men) with an average age of 75.1 years (range, 63-84 years) were treated with ocriplasmin with a follow-up period of 8 weeks. All patients were treated for VMT syndrome, and 5 patients (50.0%) showed an additional macular hole. An absolute detachment of VMT was seen in 3 patients (30.0%) and partially in 4 patients (40.0%). In three of the five patients, a complete closure of the full-thickness macular holes was seen. The two other patients needed an additional pars plana vitrectomy as a result of the persistent macular hole. An improvement of visual acuity was seen in 6 out of 10 patients (60.0%), a reduction of macular edema in 8 out of 9 patients (88.9%), and a decrease of metamorphopsia in 6 out of 7 patients (85.7%)., Conclusion: In this retrospective analysis, the treatment with ocriplasmin showed a resolution of VMT in 7 of 10 patients (70.0%) after a follow-up period of 8 weeks.

Purpose: To identify characteristics associated with progression from vitreomacular traction (VMT) to a full-thickness macular hole (FTMH) or lamellar hole (LH)., Methods: Post-hoc analysis of the Phase III clinical trial comparing ocriplasmin with placebo for treatment of vitreomacular adhesion (MIVI-TRUST). Exact logistic regression analyses were used to identify baseline characteristics significantly associated with progression from vitreomacular traction to FTMH or LH over the 6-month study period., Results: Twenty eyes (4.5%) developed an FTMH and 38 (9.7%) developed an LH during the study period. The rate of progression to FTMH or LH did not differ significantly between ocriplasmin- and saline-treated eyes (P = 0.090 for FTMH, P = 0.369 for LH). On univariate analysis, the presence of subretinal fluid (adjusted odds ratio 5.64, 95% confidence interval 2.02-17.17, P < 0.001) and mean subretinal fluid thickness (adjusted odds ratio 1.10, 95% confidence interval 1.04-1.16, P = 0.003) were associated with FTMH development. Both remained significantly associated with FTMH development on multivariate testing. On univariate analysis, the presence of macular schisis (adjusted odds ratio 2.26, 95% confidence interval 1.30-3.82, P = 0.004) and mean retinal thickness (adjusted odds ratio 1.06, 95% confidence interval 1.01-1.10, P = 0.010) were associated with LH development. Schisis remained a significant predictor of LH formation on multivariate testing., Conclusion: Vitreomacular traction is more likely to progress to FTMH when associated with subretinal fluid, but when associated with intraretinal changes (such as schisis), vitreomacular traction appears more likely to progress to a LH after a single intravitreal injection of ocriplasmin or saline.

Purpose: To assess the long-term anatomical and functional findings in patients with symptomatic vitreomacular traction (VMT), with or without full thickness macular hole (FTMH), after eye treatment with intravitreal ocriplasmin injection (IOI). Methods: This longitudinal case series includes 51 eyes from 51 symptomatic patients with VMT (<800 μm) who received a single IOI (Jetrea ® 0.125 mg); 21 cases with an FTMH (<400 μm) were included. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were recorded before IOI, and 1 day to 24 months thereafter. Data are presented as mean ± standard deviation. Results: Mean adhesion size before injection was 345 ± 146 μm. In 34 eyes (67%), complete release of VMT was observed; whereas VMT persisted in 17 eyes (33%). The latter included 15 of the 21 eyes (71%) with FTMH, 15 of which underwent pars plana vitrectomy and inner limiting membrane peeling. BCVA improved from (logarithm of the minimal angle of resolution [logMAR]) 0.41 ± 0.03 before injection to 0.32 ± 0.03 after 1 month and 0.23 ± 0.05 after 6 months and remained stable thereafter (0.24 ± 0.06 after 24 months of follow-up). Forty-five percent of the eyes presented submacular deposits soon after IOI that were not functionally relevant; 61% completely resolved by 12 months. Except floaters that disappeared within 48 h, no other adverse events were reported during follow-up. Conclusions: Treatment with ocriplasmin in a real-life setting showed an overall efficacy of 67% in patients with symptomatic VMT, with better results evident in the absence of an FTMH (70% vs. 62% VMT release) and a visual gain for over 2 years.

Aim: Evaluate the cost-effectiveness of ocriplasmin in symptomatic vitreomacular adhesion (VMA) with or without full-thickness macular hole ≤400 μm versus standard of care. Methods: A state-transition model simulated a cohort through disease health states; assignment of utilities to health states reflected the distribution of visual acuity. Efficacy of ocriplasmin was derived from logistic regression models using Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole trial data. Model inputs were extracted from Phase III trials and published literature. The analysis was conducted from a US Medicare perspective. Results: Lifetime incremental cost-effectiveness ratio was US$4887 per quality-adjusted life year gained in the total population, US$4255 and US$10,167 in VMA subgroups without and with full-thickness macular hole, respectively. Conclusion: Ocriplasmin was cost effective compared with standard of care in symptomatic VMA.

Purpose: To evaluate the anatomical and functional outcomes with ocriplasmin in patients with vitreomacular traction (VMT) with or without macular hole (MH)., Methods: In a Phase 4, multicenter, single-arm, open-label study, eligible patients (VMT with focal adhesion, without epiretinal membrane, and with MH ≤400 µm [if present]) received a single intravitreal injection of ocriplasmin. Nonsurgical resolution of VMT (Day 28 [primary endpoint]), best-corrected visual acuity, MH closure, vitrectomy rate, and safety were assessed through Day 180., Results: Overall, 466 patients were included in the full analysis set, of whom 47.4% had VMT resolution by Day 28; resolution rates in patients with VMT without MH, VMT with MH ≤250 µm, and VMT with MH >250 to ≤400 µm were 43.4%, 68.6%, and 62.7%, respectively. Macular hole closure was higher in eyes with VMT and MH ≤250 µm (57.1%) than in eyes with VMT and MH >250 to ≤400 µm (27.5%) at Day 28. Overall, 30.8% of patients with VMT resolution gained ≥10 letters in best-corrected visual acuity at Day 180. Adverse events were consistent with the known safety profile of ocriplasmin., Conclusion: Ocriplasmin is effective for resolution of VMT without or with MH (≤400 μm); treatment outcomes can be optimized with patient selection.

Pharmacological vitreolysis with ocriplasmin is an effective treatment option for eyes with vitreomacular traction. Pre-marketing and post-marketing clinical studies revealed an improvement of visual function in ocriplasmin treated eyes and showed a release of traction in up to 78% of cases. Treatment success is related to patient selection based on positive predictive factors. Adverse events, such as visual acuity loss, dyschromatopsia or photopsia are known to be self-limited in the majority of eyes. Structural outer retinal layer changes, such as ellipsoid zone disturbances or subretinal fluid accumulation on SD-OCT analysis, as well as ERG abnormalities, are transient and correlated to VMT release. Surgical outcomes in patients with a prior history of ocriplasmin injection have been shown to be comparable with patients who proceeded directly to surgery without ocriplasmin treatment., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Vitreomacular traction (VMT) treatment options include watchful waiting, vitrectomy and intravitreal ocriplasmin injection (Jetrea ® ). This analysis used results from the recently completed OASIS randomized clinical trial to evaluate the 2-year budget impact of ocriplasmin injection availability for treatment of Stage I or II VMT without epiretinal membrane formation in a modeled US health plan., Materials & Methods: VMT prevalence, treatment patterns and disease resolution rates were from literature, a US retinal-specialist survey and the OASIS trial. Medicare payment rates were applied and a national scenario analysis was conducted., Results: With ocriplasmin available, vitrectomy use and complications-related costs decreased. Budget impact of ocriplasmin to the health plan was US$143,599 over 2 years or US$0.0060 per-member per-month., Conclusion: Ocriplasmin was projected to be minimally cost-additive at US$0.0060 per-member per-month over 2 years.

Purpose: To evaluate baseline features and morphologic changes of vitreoretinal adhesion and outer retinal layers outside the macula after intravitreal ocriplasmin injection. To study the relation between vitreous detachment and attenuation of retinal outer segments signal., Methods: Retrospective cases series of 15 eyes. Each eye was scanned with the 55° wide-field optical coherence tomography lens in 6 different locations, three horizontal B-scan (central, temporal, and nasal) and three vertical B-scan (central, superior, and inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection., Results: After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12 patients (80%), 3 of them presenting a complete posterior vitreous detachment. Eight patients (53%) showed a panretinal attenuation of photoreceptors outer segment signal, 7 with VMT resolution and 1 with non-posterior vitreous detachment and no VMT resolution. In three patients after VMT resolution the attenuation involved also areas with no posterior vitreous detachment. The attenuation resolved during follow-up in 7/8 eyes (87.5%)., Conclusion: Intravitreal ocriplasmin injection induced resolution of VMT in most cases and more rarely a release of vitreopapillary adhesion and a complete posterior vitreous detachment. An acute panretinopathy was visible in more than half of the patients and was not related to vitreous detachment.

Background/aims: To evaluate predictive factors for the treatment success of ocriplasmin and to use these factors to generate a multivariate model to calculate the individual probability of successful treatment., Methods: Data were collected in a retrospective, multicentre cohort study. Patients with vitreomacular traction (VMT) syndrome without a full-thickness macular hole were included if they received an intravitreal injection (IVI) of ocriplasmin. Five factors (age, gender, lens status, presence of epiretinal membrane (ERM) formation and horizontal diameter of VMT) were assessed on their association with VMT resolution. A multivariable logistic regression model was employed to further analyse these factors and calculate the individual probability of successful treatment., Results: 167 eyes of 167 patients were included. Univariate analysis revealed a significant correlation to VMT resolution for all analysed factors: age (years) (OR 0.9208; 95% CI 0.8845 to 0.9586; p<0.0001), gender (male) (OR 0.480; 95% CI 0.241 to 0.957; p=0.0371), lens status (phakic) (OR 2.042; 95% CI 1.054 to 3.958; p=0.0344), ERM formation (present) (OR 0.384; 95% CI 0.179 to 0.821; p=0.0136) and horizontal VMT diameter (µm) (OR 0.99812; 95% CI 0.99684 to 0.99941, p=0.0042). A significant multivariable logistic regression model was established with age and VMT diameter., Conclusion: Known predictive factors for VMT resolution after ocriplasmin IVI were confirmed in our study. We were able to combine them into a formula, ultimately allowing the calculation of an individual probability of treatment success with ocriplasmin in patients with VMT syndrome without FTHM., Competing Interests: Competing interests: HH reports personal fees from Allergan, personal fees from Alcon, personal fees from Bayer, personal fees from Heidelberg Engineering, personal fees from Novartis, personal fees from Alimera, outside the submitted work; NF reports personal fees and non-financial support from Allergan, personal fees and non-financial support from Bayer, personal fees from Heidelberg Engineering, personal fees and non-financial support from Novartis, personal fees and non-financial support from Alimera, outside the submitted work; JW reports personal fees from Allergan, personal fees from Bayer, personal fees from Novartis, personal fees from Alcon, outside the submitted work; HK reports personal fees from Abbott Medical Optics, personal fees from Alimera Sciences, personal fees from Alcon, personal fees from Allergan, personal fees from Carl Zeiss Meditec AG, personal fees from Dres. Schlegel + Schmidt, personal fees from Ellex, personal fees from Geuder, personal fees from Novartis, personal fees from Oculentis, personal fees from Oertli Instrumente AG, personal fees from Polytech Domilens, personal fees from Topcon Medical, outside the submitted work; SM reports personal fees from Bayer healthcare, personal fees from Novartis, outside the submitted work; MJK reports personal fees from Allergan, personal fees from Allimera, personal fees from Bayer, personal fees from Insight Instruments, personal fees from Novartis, outside the submitted work; SF reports personal fees from Roche, outside the submitted work; MMM reports personal fees from Allergan, personal fees from Bayer, personal fees from Novartis, personal fees from Heidelberg Engineering, personal fees from Alcon, personal fees from Zeiss, outside the submitted work; RGS reports personal fees from Allergan, personal fees from Novartis, outside the submitted work; SM has nothing to disclose. PC reports personal fees from Novartis, outside the submitted work; PS has nothing to disclose. AL reports personal fees from Alcon, personal fees from Bayer, outside the submitted work; TB reports personal fees from Alcon, personal fees from Novartis, personal fees from Alimera, personal fees from Bayer, personal fees from Heidelberg, outside the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Case Report: A 53 year-old woman with a stage 2 macular hole received ocriplasmin injection as a first approach. She subsequently underwent pars plana vitrectomy due to enlargement of the hole post-injection. The visual gain following the surgery was minimal despite closure of the hole. This could be explained by outer retina atrophy as a consequence of potential toxic mechanisms related to ocriplasmin., Discussion: Further studies may be warranted to fully understand the impact of ocriplasmin on long-term visual function., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: In vitreomacular traction (VMT), there is abnormal adhesion between the vitreous cortex and the retina, especially in the fovea. Symptoms of VMT include metamorphopsia and a decrease in visual acuity. Since 2013, ocriplasmin (Jetrea®) has been approved for treatment of symptomatic vitreomacular traction with or without macular holes (≤ 400 µm)., Methods: We retrospectively examined twenty-three eyes of twenty-one patients who underwent intravitreal ocriplasmin treatment for symptomatic vitreomacular traction with or without macular holes. Best corrected visual acuity and central retinal thickness (CRT) were measured in advance and after ocriplasmin treatment. The numbers of resolved vitreomacular traction and closed macular holes were documented., Results: Vitreomacular traction was resolved in eight of twenty-three eyes (34.8 %); in fifteen eyes (65.2 %) it was persistent and two of four macular holes were found closed. The average best corrected visual acuity was 0.39 ± 0.25 logMAR at baseline and 0.41 ± 0.24 logMAR at the first follow-up visit after injection (p = 0.613). The average CRT was 453.3 ± 172.7 µm at baseline, with a slight decrease to 412.0 ± 212 µm (p = 0.124)., Conclusion: Intravitreal injection of ocriplasmin appears is an experimental therapy in patients with symptomatic vitreomacular traction. Patient selection seems to be critically important for the therapeutic outcome, whereas greater age, specific VMT morphology and missing chromatopsia seem to be negative predictors., Competing Interests: Interessenkonflikt: Nein., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To assess the effect of ocriplasmin on visual function response (VFR) measured using visual acuity (VA) and vision-related quality of life, and to quantify the association between release of vitreomacular adhesion (VMA) at day 28 and VFR., Methods: Prespecified analysis of secondary endpoints from a randomized controlled trial. Of 220 participants with symptomatic VMA/vitreomacular traction (VMT), including VMT associated with a macular hole up to 400 μm, 146 received a single intravitreal injection of 125 μg ocriplasmin and 74 a sham injection. Based on principal components analysis results, a VFR was defined as either a VA improvement of ≥2 lines or an improvement exceeding the minimal clinically important difference (MCID) in the composite or the mental health subscale scores of the Visual Function Questionnaire (VFQ-25). The MCID was estimated using the standard error of measurement approach. The main outcome measure was the VFR at month 6, with further assessments at months 12 and 24., Results: The MCID was estimated at 3.71 points for the VFQ-25 composite score and 10.71 for the VFQ-25 mental health subscale score. A VFR occurred in 51.0% of ocriplasmin versus 23.3% of sham participants (P = 0.0001). The VFR was maintained through months 12 and 24: 53.1% and 50.3% in ocriplasmin versus 21.9% and 20.5% in sham participants, respectively (P < 0.0001). Resolution of VMA at day 28 significantly increased the odds of a VFR at each assessment period., Conclusions: Treatment with ocriplasmin compared with sham resulted in a significant improvement in VFR. The 6-month treatment effect was sustained at months 12 and 24.

Vitreoretinal interface pathologies, such as vitreomacular traction syndrome, epiretinal membranes and macular holes are sight-threatening conditions and one of the important causes of vision defects and vision loss. To this date, vigilance with observation of how the vitreomacular traction resolves, or vitreoretinal surgery in more severe cases, were the only treatment options. Recent rapid progress in ophthalmology, especially in diagnostic and visualization techniques, provided better insight into the mechanisms taking place on the vitreoretinal surface, which enabled a more accurate selection of treatment options. Development of ophthalmic pharmacological procedures, such as treatment of vitreomacular traction syndrome with ocriplasmin, constitutes an innovative breakthrough in ophthalmology. The enzyme is a genetically engineered form of human plasmin, a component of blood coagulation cascade that has been envisioned for human therapy since 1950s. It has never been used for vitreolysis in ophthalmology before. The aim of this review is to analyze and compare therapeutic options for symptomatic vitreomacular adhesion and vitreoretinal traction, with particular emphasis on microplasmin. We reviewed the results of recent studies comparing ocriplasmin to other widespread treatment options, such as pars plana vitrectomy.

Purpose: To identify favorable ocriplasmin candidates from a cohort of idiopathic full thickness macular hole surgery patients., Methods: The records of patients with full thickness macular hole who underwent pars plana vitrectomy surgery between 2011 and 2015 were reviewed. Clinical data collected included patient demographics, pre- and post-operative Snellen visual acuity, optical coherence tomography findings, and lens status. The authors defined "favorable" ocriplasmin candidates as patients with focal vitreomacular traction, no epiretinal membrane, and hole size ≤400 μm. The authors further categorized "optimal" candidates as age ≤65, phakic, no epiretinal membrane, with focal vitreomacular traction, and hole size ≤400 μm., Results: The records of 238 patients were assessed; 30.7% were male while mean age was 68.6 ± 8.3 years. The mean logMAR acuity was 1.2 (Snellen 20/317) preoperatively and 0.90 (Snellen 20/159) postoperatively. Optical coherence tomography findings indicated that 46.5% of the macular holes studied were less than ≤400 μm in size, 14.8% had an epiretinal membrane, and 25.3% had vitreomacular traction. A total of 17.7% of study patients were found to be favorable candidates, whereas 3.8% were optimal ocriplasmin candidates., Conclusion: Only a minority of full thickness macular hole surgical candidates in this cohort would be considered favorable ocriplasmin candidates.

PurposeTo describe a survey of the use of ocriplasmin by members of the British and Eire Association of VitreoRetinal Surgeons (BEAVRS) for VitreoMacular Traction (VMT) and Full Thickness Macular Hole (FTMH) and compare it to published MIVI TRUST trial data.MethodsAll 173 BEAVRS members were contacted by email in October 2014 requesting data on all cases treated with ocriplasmin up to that date. The total number of cases, FTMH closure rate, VMT release rate and the frequency of adverse events were recorded. Results were compared with trial data.Results48 members responded reporting results from 241 eyes. The respective BEAVRS and MIVI TRUST trial closure rates for small FTMHs were 42.1 and 58.3% (P=0.09) and for medium FTMH 12.7 and 36.7% (P=0.01). The respective VMT release rates were 34.1 and 37.4% (P=NS). Retinal detachment was observed in 3.3% of the BEAVRS cohort compared with 0.4% in MIVI TRUST. Reduction in visual acuity to <6/60 was observed in 5.8% of the BEAVRS cohort and 0.6% in MIVI TRUST. Other complications not reported in the MIVI TRUST trial included an increase in FTMH basal diameter following unsuccessful ocriplasmin use in 46.9% of BEAVRS cases and zonular instability at the time of subsequent phacoemulsification in 2.4%.ConclusionMacular hole closure rates were lower in the BEAVRS survey than published in the MIVI TRUST trial data. The incidence of adverse events was greater than previously reported. The reasons for these disparities are unknown but could include positive reporting bias inherent to retrospective surveys, treatment and population differences., Competing Interests: RJ Haynes: Alcon ocriplasmin advisory board member. D Steel: Alcon Consultancy, Research funding. DAH Laidlaw: Alcon ocriplasmin advisory board member. This work received no support in the form of grants, equipment or drugs.

Vitreomacular adhesion (VMA) describes the adhesion of the posterior hyaloid face to the inner retina in any part of the macula. This can arise after incomplete separation of the posterior vitreous cortex from the macula during vitreous liquefaction. While the VMA may resolve spontaneously, a strong and persistent adhesion can lead to a variety of anatomical changes, including vitreomacular traction (VMT) and macular hole (MH). Both conditions can present with metamorphopsia and decreased vision. In cases of symptomatic VMT and full-thickness macular hole, pars plana vitrectomy has long been the standard of care. However, due to the possible surgical complications and need for postoperative care, many have searched for non-surgical options via pharmacologic vitreolysis. Ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) is a recombinant protease approved in October 2012 for the treatment of symptomatic vitreomacular adhesion (VMA). There have been conflicting views on the safety of Ocriplasmin with changes in the ellipsoid zone seen on OCT and changes seen on ERG indicating photoreceptor damage. This publication reviews the efficacy and safety of ocriplasmin injection for VMA based on previously published data.

This review article highlights 4 case reports published in 2015 that provided substantive contributions to the field of retina. The first describes postoperative hemorrhagic occlusive retinal vasculitis, a newly described and visually devastating complication of cataract surgery. The second discusses ocriplasmin as a novel treatment for foveal schisis in patients with X-linked retinoschisis. The third describes a case of retinal toxicity from sertraline, a common psychiatric drug often sold as name brand Zoloft (Pfizer Inc, New York, NY). The last article shares 10-year results from a blind patient who received the Argus I retinal prosthesis. The study of vitreoretinal disease is both complex and fascinating. Case reports and case series are a means by which clinicians can share clinical experiences in managing retinal disease. By sharing our clinical experiences from individual patients, we begin the process of describing new diseases, new medications, and new surgical techniques. To obtain a list of published reports, we performed a MEDLINE search for case reports with the keyword retina . In 2015 there were 195 publications meeting these criteria. We selected 4 articles that highlight interesting developments in the field of retina.

Objective: The purpose of this study was to evaluate the safety of intravitreal ocriplasmin prospectively, reporting potential complications in patients with vitreomacular traction (VMT) alone or associated with macular hole (MH)., Materials and Methods: Participants in this prospective, multicenter study, were 24 patients with VMT (17 with VMT alone and seven with MH combined with VMT). All patients were treated with a single ocriplasmin injection and followed-up prospectively at baseline, day 7, 28 and the last examination of the follow-up for each patient (mean ± SD: 64.2 ± 24.4 d, range: 40-145 d). Best-corrected visual acuity (BCVA) was assessed, and spectral-domain optical coherence tomography was performed at each visit while the percentage of resolution of VMT and the association with various potential adverse events were recorded and analyzed., Results: 66.7% of patients presented VMT release at the end of the follow-up, while 28.6% exhibited MH closure. Severe adverse events, such as enlargement of preexisting MH and formation of lamellar MH, were observed in one and four cases, respectively and remained till the end of the follow-up. Moderate adverse events, such as ellipsoid zone disruption and subretinal fluid development, became evident seven days after injection, in four cases. Formation of cystoid macular edema (CME), not evident at baseline, was noticed in three cases at day 28 after injection. Mild adverse events, like vitreous floaters, photopsias, eye pain and foreign body sensation, were noticed at day 7 and resolved till the end of the follow-up., Conclusions: Mild and moderate adverse events occurred mainly during the first week of the follow-up, while severe adverse events, such as the lamellar MH formation and CME at day 28 post injection were seen.

Purpose: To describe the natural history of eyes with symptomatic idiopathic vitreomacular traction (VMT)., Methods: Retrospective multicenter study of 168 eyes with spectral-domain optical coherence tomography (SD-OCT) findings consistent with idiopathic VMT. All eyes were graded according to SD-OCT findings. Grade 1 was defined as incomplete cortical vitreous separation with foveal attachment. Grade 2 was defined as Grade 1 plus intraretinal cysts or clefts. Grade 3 was defined as Grade 2 plus a foveal detachment. All patients were followed for at least 6 months., Results: There were 168 patients (51 men) with a mean age of 68.8 ± 10.7 years. Patients were followed for a mean of 22.7 ± 20.1 months. The mean duration of symptoms before the initial presentation was 3.65 ± 5.42 months. At baseline, 72 eyes had Grade 1, 74 eyes had Grade 2, and 22 eyes had Grade 3 SD-OCT findings. Over the follow-up period, 36 eyes (21.4%) had spontaneous resolution of the VMT with normalization of the foveal anatomy. The mean time to resolution was 12.3 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of the eyes, with 6 eyes developing a lamellar macular hole and 7 eyes developing a full-thickness macular hole. This occurred at a mean of 10.3 ± 10.7 months after the presentation. Subgroup analysis based on baseline SD-OCT grade showed that 4.1% (3 of 73) of Grade 1 eyes compared with 6.8% (5 of 74) of Grade 2 eyes, and 23.8% (5 of 21) of Grade 3 eyes developed a full-thickness macular hole or lamellar macular hole (P = 0.0109, chi-square test). In the remaining 119 eyes, at the last follow-up, 65 eyes had Grade 1, 42 eyes had Grade 2, and 12 eyes had Grade 3 VMT. On average, the best-corrected visual acuity improved from 0.40 ± 0.35 logarithm of the minimum angle of resolution (Snellen, 20/50) at baseline to 0.35 ± 0.36 logarithm of the minimum angle of resolution (Snellen, 20/45; P = 0.0372), and the mean central macular thickness improved from 350 ± 132 μm to 323 ± 121 μm., Conclusion: Spontaneous resolution of VMT occurred in 21.4% (36 of 168) of eyes after a mean follow-up of 11.4 ± 12.6 months. An unfavorable anatomical outcome occurred in 7.7% (13 of 168) of eyes. The baseline SD-OCT grade may predict the progression to full-thickness macular hole.

Introduction: Pharmacologic vitreolysis is a strategy used to treat anomalous posterior vitreous detachment, by weakening vitreoretinal adhesion with an intravitreal drug. Pharmacologic vitreolysis facilitates surgery, and abnormalities of the vitreoretinal interface including vitreomacular traction (VMT) and early stage macular hole (MH) could be resolved. Ocriplasmin is a recombinant protease, active against fibronectin and laminin, which are important components of the vitreoretinal interface. Ocriplasmin has been approved for symptomatic treatment of VMT and MH with visible traction, and it functions by dissolving the proteins that link the vitreous to the macula, thereby creating a complete posterior vitreous detachment (PVD)., Areas Covered: This paper reviews the current knowledge and status of investigations regarding the use of ocriplasmin for pharmacologic vitreolysis and its safety., Expert Opinion: Ocriplasmin is a non-specific enzyme; therefore, it dissolves vitreal proteins as well as possibly proteins associated with visual function in the retina, choroid, and lens. Ocular adverse events (OAEs) of ocriplasmin include transient visual loss, intraocular inflammation, vitreous floaters, lens opacification, zonular instability of the lens, and intraocular hemorrhage. The prevalence of the OAEs is very low; however, on rare occasions, they can result in widespread retinal dysfunction. Research into the acute and long-term safety of ocriplasmin is required.

Purpose: To evaluate the efficacy of an intravitreal ocriplasmin injection using anterior chamber paracentesis to release symptomatic vitreomacular traction (VMT)., Methods: Five patients with symptomatic VMT were enrolled. All patients underwent a complete ophthalmologic examination including acquisition of spectral-domain optical coherence tomography. Before intravitreal injection of ocriplasmin, anterior chamber paracentesis was performed in the study eye to induce mild ocular hypotonia. Control visits were performed the day after the injection, at 1 week, and after 1, 2, and 3 months., Results: In 4 patients, we had complete release of VMT and visual improvement after the intravitreal ocriplasmin injection preceded by anterior chamber paracentesis. No adverse events were observed., Conclusions: In our small case series, anterior chamber paracentesis performed before intravitreal ocriplasmin seemed to increase the efficacy of the drug in the resolution of symptomatic VMT. Our success estimate is imprecise due to small sample size (95% confidence interval 0.28 to 0.99) and no definitive conclusion can be reached. Further research is worth being conducted to assess the potential usefulness of paracentesis before ocriplasmin injection to increase vitreoretinal traction release rate.

Background: To evaluate the functional recovery of patients with symptomatic vitreomacular traction (VMT) after Ocriplasmin treatment., Methods: Prospective, single centre, consecutive case series. Patients were treated with a single intravitreal injection of Ocriplasmin (Jetrea, Thrombogenics Inc, USA, Alcon/Novartis EU). The following outcome measures are considered: resolution of VMT, evaluated through the use of optical coherence tomography (SD-OCT), functional recovery evidenced by multifocal-electroretinogram (mfERG) and microperimetry (MP1) after treatment with Ocriplasmin., Results: Four eyes of four patients were treated with Ocriplasmin injection. We observed a VMT non-surgical resolution in all patients. The longitudinal statistical analysis showed a significant improvement of best corrected visual acuity (BCVA) in the treated eye of about 0.97 letters/week (p = 0.033). No significant difference was observed in mean sensitivity (p > 0.05) assessed by MP1 in both eyes, while improvement in fixation stability was assessed in treated eyes (β = 0.39; p = 0.029). In the four treated eyes mfERG revealed an increased foveal peak response over the follow-up. The longitudinal analysis of mfERG data shows a significant increase of N1 and P1 amplitude in the first rings and a significant decrease of N1 and P1 implicit time in most rings., Conclusions: We report on four cases with resolution of VMT after Ocriplasmin treatment. Our preliminary results demonstrate that Ocriplasmin is safe and effective in the treatment of VMT, because it not only leads to a morphological recovery but mostly to a restoration of macular functionality, evaluated through the use of different objective tests, such as MP1 and mfERG over a six-month follow-up.

Purpose: To evaluate treatment options for vitreomacular traction (VMT)., Methods: A retrospective, consecutive case series and a literature search with Boolean search logic. A random-effects meta-analysis was conducted to combine the rates of VMT resolution per treatment. Patients from studies analyzed were placed into cohorts based on the treatment received., Case Series: Zero of 10 control, 3 of 7 intravitreal ocriplasmin (IVO, P = 0.10), 7 of 8 intravitreal expansile gas (pneumatic vitreolysis, PV, P < 0.01), and 10 of 10 pars plana vitrectomy (P < 0.01)-treated eyes experienced VMT release (VMTr) at Day 28. No patients developed retinal tears or detachment. One PV-treated (12.5%) eye developed a macular hole. Meta-analysis: Twenty-three of 131 prospective or retrospective and consecutive articles were included. Sixty-three eyes were treated with PV, 726 eyes were treated with intravitreal ocriplasmin, and 253 eyes were characterized as the control group (saline injection). The weighted rate of VMT resolution for the control group was 0.09 (95% confidence interval [CI]: 0.06-0.13), PV was 0.84 (95% CI: 0.76-0.92), and intravitreal ocriplasmin was 0.26 (95% CI: 0.23-0.29)., Conclusion: Our analysis found that PV releases VMT in most patients and suggest that PV may be as effective or superior to nonsurgical options for VMTr at Day 28 with a similar risk profile.

Objective: To review the evidence on the cost-effectiveness of ocriplasmin as a treatment for vitreomacular traction (VMT), and to estimate the impact on the Spanish National Health System (NHS)., Material and Methods: 1) Systematic review. The following databases were searched in January 2015: MEDLINE, PREMEDLINE, EMBASE, CRD, the Cochrane Library, and key websites. Selection criteria were: full economic evaluations that compared ocriplasmin with usual care ('watch and wait' and/or vitrectomy) in patients with VMT. The outcomes to extract were costs of the alternatives and the incremental cost-effectiveness ratio. Studies of budget impact analysis were also included. The methodological quality was assessed, and a narrative synthesis of the included studies was carried out. 2) Estimation of budget impact. The impact on the budget as a result of the introduction of ocriplasmin in the NHS was estimated, including data from different sources., Results: Six studies were identified, none of them performed in Spain. The two best studies concluded that ocriplasmin is cost-effective in their respective countries (Canada and United Kingdom), but only in patients with certain conditions (without epiretinal membrane, for example). The results of the budget impact analysis are different between countries. The analysis for Spain showed that the introduction of ocriplasmin would mean a saving over 1 million Euros for the NHS in 5 years., Conclusions: The cost-effectiveness of ocriplasmin has not been demonstrated in Spain. However, good studies performed in other countries found that ocriplasmin is cost-effective in selected patients. Given the current prices in Spain, ocriplasmin could involve a saving for the Spanish NHS., (Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

PurposeTo assess the preoperative features of patients with idiopathic macular hole (IMH) and vitreomacular adhesion (VMA) treated with ocriplasmin (OCP) that can predict successful closure.MethodData were prospectively collected on all patients with IMH treated with OCP in three British ophthalmic centres. Several preoperative variables were recorded including the IMH base diameter (BD), minimum linear diameter (MLD), and VMA width measured on spectral domain optical coherence tomography. Several other IMH indices were derived including a 'width factor', defined as the BD minus the MLD in μm. The occurrence of VMA release and hole closure were used as the main outcome measures.ResultsThirty-three patients in total with IMH were treated with OCP. Two patients developed rhegmatogenous retinal detachment and were excluded. The mean age of the remaining 31 patients was 71 years, and 71% were female. VMA release occurred in 19 of the 31 (61%) patients and macular hole closure in 11 (35%). Width factor was the most predictive feature for closure on multivariate analysis. The deviance R(2) was 67% (P<0.001). An IMH with a width factor of <60 μm had a 95% certainty of closure, whereas if >290 μm then there was less than a 5% chance of closure. Neither VMA width nor MLD alone was associated with VMA release or closure.ConclusionsPatients with macular holes where the BD was close in size to the MLD had an improved probability of closure than holes with wider base configurations.

Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the aftermarket efficacy of ocriplasmin for vitreomacular adhesion (VMA) and identify the frequency and duration of structural changes on optical coherence tomography., Methods: The authors conducted a retrospective case series of 36 eyes treated with ocriplasmin for symptomatic VMA at a single center between February 2013 and September 2013. Eyes were evaluated for release of VMA at 1 month postinjection, preinjection adhesion size, postinjection closure of macular hole, presence of subretinal fluid after release of adhesion, size of subretinal fluid, outer retinal structural change, and visual acuity at 1 month, 6 months, and 1 year., Results: Fifteen eyes (42%) had complete release of VMA at 1 month postinjection, and 78% of eyes had closure of the macular hole. Eyes that did not have an epiretinal membrane that had a smaller initial adhesion size and a smaller macular hole size were more likely to have complete release of VMA. Subretinal fluid was present after release in 73.3% of treated eyes, and ellipsoid zone changes were present in 66.7% of treated eyes. At the end of 1 year, complete resolution of subretinal fluid occurred in 87% of treated eyes with only trace subretinal fluid remaining in 2 eyes. Complete resolution of ellipsoid zone changes was found in all eyes. Best-corrected visual acuity improved throughout the first year after treatment., Conclusion: Ocriplasmin is effective in the treatment of patients with symptomatic VMA. Results can be improved with patient selection based on specific criteria. Subretinal fluid and ellipsoid zone changes are common after treatment but mostly resolve over 1 year.

This study aimed to report the clinical and structural outcomes of intravitreal ocriplasmin in the treatment of vitreomacular interface disorders in two tertiary centers in Brazil. A retrospective study was performed by reviewing medical records and spectral domain optical coherence tomography (SD-OCT) findings of seven patients who were treated with a single ocriplasmin injection. A total of 57.14% of patients achieved resolution of vitreomacular traction as evidenced by SD-OCT. Regarding our functional results, 87.71% maintained or improved visual acuity after follow-up. To the best of our knowledge, this is the first study reporting initial results of ocriplasmin therapy in Brazil.

Objective assessment of retinal layer integrity with optical coherence tomography (OCT) is currently limited. The ellipsoid zone (EZ) has been identified as an important feature on OCT that has critical prognostic value in macular disorders. In this report, we describe a novel assessment tool for EZ integrity that provides visual and quantitative assessment across an OCT data set. Using this algorithm, we describe the findings in multiple clinical examples, including normal controls, age-related macular degeneration, drug effects (eg, ocriplasmin, hydroxychloroquine) and effects of surgical manipulation (eg, following membrane peeling using intraoperative OCT). EZ mapping provides both en face visualisation of EZ integrity and EZ-retinal pigment epithelium height. Additionally, volumetric, area and linear measurements are feasible using this assessment tool., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)