The efficacy and safety of ocriplasmin for patients with vitreous macular traction.

PURPOSE: To estimate the efficacy and safety of ocriplasmin for patients with vitreous macular traction (VMT). METHODS: The PubMed, EMBASE and Ovid were searched up to May 2020 to identify related studies. Statistical analysis was conducted by R software version 3.6.3. Results in proportion with 95% confidence interval (CI) were calculated by means of Freeman-Tukey variant of arcsine square transformation. RESULTS: The pooling results indicated the overall complete release rate was 50% (95% CI [45%-54%]). For VMT patients younger than 65 years old, with smaller adhesion size of VMT (<1500 µm), phakic eyes, with macular hole (MH) and subretinal fluid (SRF), while without epiretinal membrane (ERM), ocriplasmin could achieve much higher complete release rates than those under opposite conditions. The general nonsurgical closure rate of MH was 34% (95% CI [30%-37%]), and it was positively correlated with the MH size. The visual improvement rate was 45% (95% CI [32%-59%]), and it was higher for patients with VMT resolution (59%, 95% CI [41%-75%]). The secondary pars plana vitrectomy (PPV) rate for patients without MH closure or VMT resolution was about 31% (95% CI [23%-39%]). The incidence of MH progression was 10% (95% CI [4%-18%]), and other severe adverse events such as endophthalmitis, retinal detachment and retinal tear were relatively rare. CONCLUSION: Ocriplasmin is an effective, reliable and relatively safe intervention for the treatment of VMT. The most suitable candidates were patients younger than 65 years old, with smaller adhesion size (<1500 µm), phakic eyes, with MH and SRF, while without ERM.

Plasmin drives burn-induced systemic inflammatory response syndrome.

Severe injuries, such as burns, provoke a systemic inflammatory response syndrome (SIRS) that imposes pathology on all organs. Simultaneously, severe injury also elicits activation of the fibrinolytic protease plasmin. While the principal adverse outcome of plasmin activation in severe injury is compromised hemostasis, plasmin also possesses proinflammatory properties. We hypothesized that, following a severe injury, early activation of plasmin drives SIRS. Plasmin activation was measured and related to injury severity, SIRS, coagulopathy, and outcomes prospectively in burn patients who are not at risk of hemorrhage. Patients exhibited early, significant activation of plasmin that correlated with burn severity, cytokines, coagulopathy, and death. Burn with a concomitant, remote muscle injury was employed in mice to determine the role of plasmin in the cytokine storm and inflammatory cascades in injured tissue distant from the burn injury. Genetic and pharmacologic inhibition of plasmin reduced the burn-induced cytokine storm and inflammatory signaling in injured tissue. These findings demonstrate (a) that severe injury-induced plasmin activation is a key pathologic component of the SIRS-driven cytokine storm and SIRS-activated inflammatory cascades in tissues distant from the inciting injury and (b) that targeted inhibition of plasmin activation may be effective for limiting both hemorrhage and tissue-damaging inflammation following injury.

Engineering of Ocriplasmin Variants by Bioinformatics Methods for the Reduction of Proteolytic and Autolytic Activities.

Background: Ocriplasmin has been developed for the induction of posterior vitreous detachment in patients with vitreomacular adhesion. At physiological pH, ocriplasmin is susceptible to autolytic and proteolytic degradation, limiting its activity duration. These undesirable properties of ocriplasmin can be reduced by site-directed mutagenesis, so that its enzymatic activities can be augmented. This study aimed to design ocriplasmin variants with improved biological/physicochemical characteristics via bioinformatics tools. Methods: This study was performed in Tabriz University of Medical Sciences, Tabriz, Iran, 2019. Through site-directed mutagenesis, three ocriplasmin variants were designed. Structural analysis was performed on the wild-type variant and the mutant variants using the Protein Interactions Calculator (PIC) server. The interactions between the S-2403 substrate and the ocriplasmin variants were studied by molecular docking simulations, and binding capability was evaluated by the calculation of free binding energy. The conformational features of protein-substrate complex systems for all the variants were evaluated using molecular dynamic simulations at 100 nanoseconds. Results: The structural analysis of ocriplasmin revealed that the substitution of threonine for alanine 59 significantly reduced proteolytic activity, while the substitution of glutamic acid for lysine 156 influenced autolytic function. The molecular docking simulation results indicated the appropriate binding of the substrate to the ocriplasmin variants with high-to-low affinities. The binding affinity of the wild-type variant for the substrate was higher than that between the mutant variants and the substrate. Simulation analyses, consisting of the root-mean-square deviation, the root-mean-square fluctuation, and the center-of-mass average distance showed a higher affinity of the substrate for the wild type than for the mutant variants. Conclusion: The mutational analysis of ocriplasmin revealed that A59T and K156E mutagenesis could be used for the development of a new variant with higher therapeutic efficacy.

[Retinal detachment after intravitreal ocriplasmin injection]. / Ablatio retinae nach intravitrealer Ocriplasmin-Injektion.

After an uneventful intravitreal injection (IVI) of Ocriplasmin in a patient with reduced visual acuity due to vitreomacular traction (VMT) and a small macular hole, retinal detachment occurred within a few days after the operation. Although retinal detachment is known as a risk factor of IVI this case is noteworthy: an excessive reaction occurred in the region of the vitreous body, which resulted in the development of severe traction on the retina leading to a posterior vitreous body detachment, retinal holes and complete retinal detachment. This possible complication should be discussed in the preoperative patient informed consent and the reason for this excessive reaction should be the subject of further investigations.

[Efficacy and Safety Profile of Ocriplasmin Treatment - an Update]. / Wirkungen und Nebenwirkungen von Ocriplasmin ­ ein Update.

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.

Retinopatía asociada a ocriplasmina: posible causa de fracaso de cierre de agujero macular / Ocriplasmin retinopathy: Possible cause of macular hole closure failure

CASO CLÍNICO: Mujer de 53 años con agujero macular estadio 2, que recibió como primera opción terapéutica una inyección de ocriplasmina, pero a la que se le tuvo que practicar vitrectomía pars plana por aumento del agujero macular postinyección. La ganancia visual tras la cirugía fue mínima a pesar del cierre del agujero, lo que podría explicarse por la atrofia retiniana externa como consecuencia de los potenciales mecanismos tóxicos asociados a ocriplasmina. Discusión: Son necesarios más estudios para entender el completo impacto de la ocriplasmina en la función visual a largo plazo

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

Ocriplasmin retinopathy: Possible cause of macular hole closure failure. / Retinopatía asociada a ocriplasmina: posible causa de fracaso de cierre de agujero macular.

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.

Ocriplasmin for symptomatic vitreomacular adhesion.

BACKGROUND: Symptomatic vitreomacular adhesion (sVMA) is a recognised cause of visual loss and by tradition has been managed by pars plana vitrectomy (PPV). A less invasive alternative to surgery in some people is enzymatic vitreolysis, using an intravitreal injection of ocriplasmin. OBJECTIVES: To assess the efficacy and safety of ocriplasmin compared to no treatment, sham or placebo for the treatment of sVMA. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 1), MEDLINE Ovid (1946 to 24 February 2017), Embase Ovid (1947 to 24 February 2017), PubMed (1946 to 24 February 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 24 February 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 24 February 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 24 February 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people with sVMA. The intervention was intravitreal ocriplasmin 125 µg injection, and this was compared to placebo or sham injection (control). Placebo was defined as a single intravitreal injection of 0.10 mL placebo with identical drug vehicle diluted with saline. A sham injection was defined as the syringe hub or blunt needle touching the conjunctiva to simulate an injection. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant trials, assessed methodological quality and extracted data. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: This review included four RCTs conducted in Europe and the USA with a total of 932 eyes of 932 participants. Participants were 18 to 97 years of age, with evidence of focal vitreomacular adhesion (VMA) on optical coherence tomography (OCT) imaging, with a best corrected visual acuity (BCVA) of 20/25 or worse in the study eye and 20/400 or better in the fellow eye. The interventions compared were intravitreal ocriplasmin versus sham (two RCTs) or placebo (two RCTs) injection. Both sham and placebo injection were classified as the control group. The main outcome measures were assessed at 28 days and six months. Overall, we judged the studies to have a low or unclear risk of bias. All four RCTs were sponsored by the manufacturers of ocriplasmin.Compared with control, ocriplasmin treatment was more likely to result in VMA release within 28 days (risk ratio (RR) 3.46, 95% confidence interval (CI) 2.00 to 6.00; 859 eyes, 4 RCTs, high-certainty evidence). Approximately 97/1000 eyes will have VMA release within 28 days without treatment. An additional 237 eyes will have VMA release within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 96 more to 482 more).Treatment with ocriplasmin was also more likely to result in macular hole closure (RR 2.87, 95% CI 1.50 to 5.51; 229 eyes, 3 RCTs, high-certainty evidence). Approximately 123/1000 eyes with macular holes will have closure with no treatment. An additional 231 eyes will have macular hole closure for every 1000 eyes treated with ocriplasmin (95% CI 62 more to 556 more).Eyes receiving ocriplasmin were also more likely to have complete posterior vitreous detachment (PVD) within 28 days (RR 2.94, 95% CI 1.39 to 6.24; 689 eyes, 3 RCTs, high-certainty evidence). Approximately 40/1000 eyes will have complete PVD within 28 days without treatment. An additional 78 eyes will have complete PVD within 28 days for every 1000 eyes treated with ocriplasmin (95% CI 16 more to 210 more).Eyes receiving ocriplasmin were more likely to achieve 3-line or greater improvement in BCVA at six months (RR 1.95, 95% CI 1.07 to 3.53; 674 eyes, 3 RCTs, moderate-certainty evidence). Approximately 61/1000 eyes will have a 3-line or greater improvement in BCVA at six months without treatment. An additional 58 eyes will have 3-line or greater improvement in BCVA at six months for every 1000 eyes treated with ocriplasmin (95% CI 9 more to 154 more).Receiving ocriplasmin also reduced the requirement for vitrectomy at six months (RR 0.67, 95% CI 0.50 to 0.91; 689 eyes, 3 RCTs, moderate-certainty evidence). Approximately 265/1000 eyes will require vitrectomy at six months without treatment and 87 fewer eyes will require vitrectomy for every 1000 eyes treated with ocriplasmin (95% CI 24 fewer to 132 fewer).Treatment with ocriplasmin resulted in a greater improvement in validated Visual Function Questionnaire form score at six months (mean improvement difference 2.7 points, 95% CI 0.8 to 4.6; 652 eyes, 2 RCTs, moderate-certainty evidence).Eyes receiving ocriplasmin were more likely to have an adverse event (RR 1.22, 95% CI 1.09 to 1.37, 909 eyes, 4 RCTs, moderate-certainty evidence). Approximately 571/1000 eyes will have an adverse event with sham or placebo injection and 106 more eyes will have an adverse event for every 1000 eyes treated with ocriplasmin (95% CI 52 more to 212 more). AUTHORS' CONCLUSIONS: Evidence from a limited number of RCTs suggests that ocriplasmin is useful in the treatment of sVMA. However, up to 20% of eyes treated with ocriplasmin will still require additional treatment with PPV within six months. There were more ocular adverse events in eyes treated with ocriplasmin than control (sham or placebo injection) treatment. Many of these adverse events, particularly vitreous floaters and photopsia, are known to be associated with posterior vitreous detachment. At present however, there is minimal published long-term safety data on eyes treated with ocriplasmin. Further large RCTs comparing ocriplasmin with other management options for sVMA would be beneficial.

Real world outcomes of ocriplasmin use by members of the British and Eire Association of Vitreoretinal Surgeons.

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.

Plasmin (Human) Administration in Acute Middle Cerebral Artery Ischemic Stroke: Phase 1/2a, Open-Label, Dose-Escalation, Safety Study.

BACKGROUND: This phase 1/2a, open-label, multicenter, dose-escalation, safety study describes the first evaluation of plasmin as an intracranial thrombolytic treatment for acute ischemic stroke in the middle cerebral artery. The rationale for intrathrombus administration is that plasmin would bind fibrin inside the targeted clot, protecting it from circulating inhibitors. METHODS: Plasmin was given in escalating doses within 9 hours of stroke onset, and treatment efficacy was determined in 5 patient cohorts (N = 40): cohort 1 (20 mg, .5 mL/min), cohort 2a (40 mg, .05 mL/min), cohort 2b (40 mg, .33 mL/min), cohort 3a (80 mg, .67 mL/min), and cohort 3b (80 mg, .33 mL/min). RESULTS: Plasmin was generally safe at doses as high as 80 mg. No symptomatic intracranial hemorrhage was observed, and the rate of asymptomatic intracranial hemorrhage (12.5%) was consistent with that expected under supportive care. No relationship was observed between the plasmin dose and the incidence or severity of bleeding events, any particular serious adverse events, nor death. Changes in clinical chemistry, hematology, and coagulation parameters following plasmin treatment were unremarkable and unrelated to the dose. Plasmin administration resulted in successful reperfusion of the occluded vessel in 25% of patients across all cohorts, with no relationship between successful perfusion and total plasmin dose but a potential increase in reperfusion with slower infusion rates. CONCLUSIONS: Plasmin treatment of the occluded middle cerebral artery within 9 hours of stroke onset was well tolerated and did notincrease adverse outcomes; however, successful recanalization was achieved in only a limited number of patients.

The Efficacy and Safety Profile of Ocriplasmin in Vitreomacular Interface Disorders.

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.

From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety.

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.

Rhegmatogenous retinal detachment following intravitreal ocriplasmin.

PURPOSE: To describe the characteristics and outcomes of patients presenting with rhegmatogenous retinal detachment (RRD) after ocriplasmin (OCP) injection. METHODS: Retrospective, multi-centre, observational case series with case note review. RESULTS: Eight patients with symptomatic vitreomacular traction (six with concomitant macular hole) were diagnosed with RRD after a median of 16 days (range 3-131 days) post-OCP injection. Presentation was within 3 weeks of the OCP injection in six of the cases. Five patients presented with symptoms post-OCP, and three were diagnosed asymptomatically on planned visits. Seven cases were phakic, one had high myopia (>8 dioptres), and two cases had lattice degeneration. Following RRD surgery, hole closure was achieved in 5/6 MH cases. The final median BCVA at 7 months was 20/80 (range 20/40-20/1200) similar to the baseline BCVA 20/80, with four patients gaining ≥1 line of vision compared to baseline but three losing ≥3 lines. CONCLUSIONS: RRD is a non-negligible risk associated with intravitreal OCP, and it should be used with caution in eyes with high myopia and peripheral retinal pathology predisposing to RRD. Detailed peripheral retinal examination is recommended pre- and postoperatively at all visits. Patients should be advised to seek attention if symptoms recur after initial presentation.

Transient Subfoveal Fluid and Visual Loss after Ocriplasmin.

BACKGROUND: Intravitreal injection of ocriplasmin for the enzymatic resolution of vitreomacular traction was approved for the EU in 2013. We wish to report our clinical findings and adverse effects that were not observed in the registration trial. THERAPY AND OUTCOME: In 5 of our first 12 consecutive cases, resolution of the vitreomacular traction occurred after injecting ocriplasmin. 9 of the 12 patients developed subfoveal fluid, manifest at day 3 post-intervention; this was completely re-absorbed by 6 weeks in 8 of 9 eyes. All 9 cases with subretinal fluid exhibited a significant reduction in mean visual acuity at the first visit, of 0.33 LogMAR (p = 0.008, Wilcoxon signed rank test). After regression of the subretinal fluid, visual acuity returned to the baseline value. CONCLUSIONS: In the light of the documented adverse effects of the registration trial, the relatively high rate of subfoveal fluid after injecting ocriplasmin was surprising. Possible causes include enzymatic lysis of the matrix between the outer segments of the photoreceptors and the microvilli of the RPE-cells, or barrier disturbances in the RPE through lysis of the zonulae occludentes.

Post-Marketing Survey of Adverse Events Following Ocriplasmin.

BACKGROUND AND OBJECTIVE: To study the post-marketing safety profile of ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) as experienced by retinal physicians in the United States. STUDY DESIGN/MATERIALS AND METHODS: Two thousand four hundred sixty-five retinal physicians were surveyed regarding their frequency of use of ocriplasmin and reports of ocular adverse events. RESULTS: There were 270 respondents (11%) who reported treating 1,056 eyes with ocriplasmin. The reports of adverse events (AE) were as follows: acute decline in visual acuity (16.95%), development of submacular fluid or serous retinal detachment (10.23%), dyschromatopsia (9.09%), progression of vitreomacular traction to macular hole (8.71%), development of retinal detachment (2.65%), development of retinal tear (1.99%), development of afferent pupillary defect (1.80%), electroretinography abnormalities (0.57%), crystalline lens instability (0.38%), and vasculitis (0.28%). CONCLUSION: Although the frequency of some ocular AEs reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology and clinical relevance of ocular AEs of ocriplasmin.

Complications of intravitreal ocriplasmin for vitreomacular traction and macular hole: a prospective spectral-domain optical coherence tomography study.

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.

A RANDOMIZED, PLACEBO-CONTROLLED STUDY OF INTRAVITREAL OCRIPLASMIN IN PEDIATRIC PATIENTS SCHEDULED FOR VITRECTOMY.

PURPOSE: To evaluate safety and preliminary efficacy of 175 µg of intravitreal ocriplasmin in pediatric patients scheduled for vitrectomy. METHODS: Based on a single-center, prospective, randomized, placebo-controlled, and double-masked Phase 2 study, 22 pediatric patients scheduled for vitrectomy were randomized 2:1 to 175-µg ocriplasmin injection or placebo. Treatment was administered midvitreous 30 minutes to 60 minutes before vitrectomy. Safety was assessed by reported adverse events (AEs), ophthalmologic examinations, fundus photography, and fluorescein angiography. The primary efficacy endpoint was the proportion of eyes with total macular posterior vitreous detachment before vitrectomy or after application of suction. Secondary endpoints included vitreous liquefaction assessment before vitrectomy and immediate postoperative retinal reattachment. RESULTS: All patients experienced at least 1 AE. Most AEs were ocular and occurred in the study eye. Serious AEs were reported for 2 of 16 eyes (3.4%) in the ocriplasmin group and 2 of 8 eyes (11.1%) in the placebo group. One case of lens subluxation due to zonular disruption was observed in the ocriplasmin group. A clear efficacy signal was not observed. CONCLUSION: Intravitreal injection of 175 µg of ocriplasmin was tolerated in pediatric patients before vitrectomy; however, the small sample size in this study precluded adequate efficacy comparisons. AEs reported were consistent with those anticipated in pediatric patients.

Vitrectomy After ocriplasmin for VitreOmacular adhesion Or Macular hole (VAVOOM) study.

BACKGROUND/AIMS: To describe the results of pars plana vitrectomy (PPV) for persistent symptomatic vitreomacular traction (VMT) with or without macular hole (MH) after intravitreal ocriplasmin injection. METHODS: Multicentre retrospective study of eyes that received intravitreal ocriplasmin between January 2013 and January 2014 for symptomatic VMT with or without MH, and then went on to PPV (ocriplasmin-treated group) for persistent pathology, compared with a control group of patients with symptomatic VMT with or without MH who were offered ocriplasmin injection but proceeded directly to PPV (PPV-only group). Intraoperative characteristics, visual acuity (VA) outcomes and spectral-domain optical coherence tomography images were reviewed for the two groups. Primary outcome measure was VA after PPV. RESULTS: 51 eyes of 51 patients underwent PPV after receiving ocriplasmin, and 22 eyes of 22 patients proceeded directly to PPV. Although VA was significantly better at all time points in the PPV-only compared with the ocriplasmin-treated group, at 3 and 6 months after PPV both groups had similar amount of visual improvement. Both groups had similar rates of pathology resolution; 50/51 (98%) eyes in the ocriplasmin group and 22/22 (100%) eyes in the PPV-only group had release of VMT and/or MH closure after PPV. The two groups had similar PPV-related complication rates. CONCLUSIONS: Eyes with persistent symptomatic VMT and/or MH have similarly high rates of pathology resolution as well as similar VA gains regardless of whether they received ocriplasmin prior to PPV.