IMPLICATIONS OF COMPLETE POSTERIOR VITREOUS DETACHMENT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION.

BACKGROUND/PURPOSE: To evaluate the status of the posterior vitreous hyaloid on presenting optical coherence tomography images of the macula and its relationship to clinical characteristics, treatment patterns, and outcomes in eyes with central retinal vein occlusion. METHODS: This is a retrospective longitudinal cohort study of consecutive patients with acute, treatment-naive central retinal vein occlusion diagnosed between 2009 and 2021 who had at least 12 months of follow-up. Clinical characteristics, treatment patterns, and outcomes were analyzed between eyes stratified based on the presence or absence of a complete posterior vitreous detachment (PVD) on optical coherence tomography at presentation. RESULTS: Of 102 acute, treatment-naive central retinal vein occlusions identified, 52 (51%) had complete PVD at presentation and 50 (49%) did not. Central subfield thickness was significantly lower in those with complete PVD (12 months: 284.9 ± 122.9 µ m vs. 426.8 ± 286.4 µ m, P < 0.001; last follow-up: 278 ± 127.9 vs. 372.8 ± 191.0 µ m, P = 0.022). One-year intravitreal injection burden was significantly less for those with a complete PVD than those without (5.1 ± 3.6 injections vs. 6.7 ± 3.3 injections, P = 0.013). CONCLUSION: Central retinal vein occlusion with complete PVD on presentation had significantly lower central subfield thickness and 1-year injection burden. Assessment of the vitreomacular interface in central retinal vein occlusion may serve as a prognostic imaging biomarker.

Macular dynamics and visual acuity prognosis in retinal vein occlusions - ways to connect.

Background and Objectives: This study aimed to establish possible connections between macular dynamics, various macular features, and visual acuity prognosis among patients with retinal vein occlusions. Materials and Methods: This study included 85 patients with central retinal vein occlusions (CRVO) and 26 with branch retinal vein occlusions (BRVO). We assessed macular features such as central macular thickness (CMT), foveal intraretinal hemorrhage (IRH), the presence and distribution of hyperreflective foci (HF), ellipsoid zone (EZ) disruption, inner retinal layer disorganization (DRIL), and posterior vitreous detachment (PVD), as well as their dynamics over one year of observation and their impact on final visual acuity prognosis, depending on the type of occlusion. Results: Best corrected visual acuity (BCVA) evolution is statistically significant regarding groups of age and type of occlusion and insignificant regarding gender. The best response to intravitreal treatment, quantified as a decrease in CMT, was registered after the first intravitreal injection. Connecting a decrease in CMT with BCVA improvement, we did not register a statistically significant correlation in the CRVO group, only in BRVO cases. The study results showed that complete PVD plays a significant positive role in decreasing CMT and BCVA improvement in cases of CRVO. Our study revealed that no matter the type of occlusion, the presence of foveal IRH will have a negative impact on the BCVA outcome. Statistically significant differences have been noted only for the evolution of visual acuity in non-ischemic CRVO cases, in correlation with the presence of EZ disruption. Outer retinal layer HF has proved to be a predictive factor for poor visual acuity outcomes. Conclusions: The most important non-imaging predicting factors regarding BCVA after retinal vein occlusions are age and baseline BCVA. CMT's dynamics still establish a weak connection with visual acuity fluctuations. The presence of foveal IRH, outer retinal layer HF, and foveal EZ disruption has a negative impact on visual acuity outcomes. Abbreviations: CRVO = central retinal vein occlusions, BRVO = branch retinal vein occlusions, CMT = central macular thickness, IRH = foveal intraretinal hemorrhage, HF = hyperreflective foci, EZ = ellipsoid zone disruption, DRIL = inner retinal layer disorganization, PVD = posterior vitreous detachment, BCVA = best corrected visual acuity, OCT = optical coherence tomography, BCVA Ti = best corrected visual acuity at first, BCVA Tf = best corrected visual acuity after one year, NR of IVI = number of intravitreal injections, SD = standard deviation, M = male, F = female, CMT Ti = central macular thickness at first, CMT T1 = central macular thickness after first injection, CMT T3 = central macular thickness after 3 injections, CMT Tf = central macular thickness after one year.

Choroidal vascularity index changes in different treatments for vitreomacular traction.

INTRODUCTION: The aim of this study was to examine if choroidal vascularity index (CVI) is different in eyes with unilateral vitreomacular traction (VMT) from their healthy fellow eyes; and whether different treatments affect the CVI. METHODS: The baseline and 8-week post treatment CVIs of 56 unilateral VMT patients that underwent spontaneous resolution (n = 30), vitreoretinal surgery (n = 16) or pneumatic vitreolysis (n = 10) were compared with fellow eyes using paired samples t-test. Partial correlation analyses correcting age and gender was used for calculations between treatment groups. P values < 0.05 were considered statistically significant. RESULTS: The mean baseline CVI for VMT and control eyes had no statistically significant difference (p = 0.81, r= -0.38). The post traction release follow-up CVI of VMT eyes and contralateral eyes had no significant difference (p = 0.12, r = 0.49). In spontaneous resolution group, vitreoretinal surgery group and pneumatic vitreolysis group the baseline and follow up CVIs of VMT eyes were statistically similar (p = 0.72, p = 0.32 and p = 0.79 respectively).Spontaneous detachment patients' CVIs showed a 0.57±5.81% increase, vitreoretinal surgery group had a reduction of 1.098±4.76%, and the pneumatic vitreolysis patients showed a CVI reduction of 0.307±4.24%. However, none of these changes was found to be statistically significant when compared between the groups (p = 0.21, r = 0.02). DISCUSSION: Previous studies have argued that vitreomacular traction might have a role on the choroidal changes seen in the vitreoretinal interface disorders. This study has shown that VMT alone does not cause any significant changes in choroidal vascular index pre or post traction release.

A novel recombinant human microplasminogen induced complete posterior vitreous detachment without morphological change of retina in juvenile rabbits.

Vitreomacular traction syndrome results from persistent vitreoretinal adhesions in the setting of partial posterior vitreous detachment (PVD). Vitrectomy and reattachment of retina is an effective therapeutic approach. The adhesion between vitreous cortex and internal limiting membrane (ILM) of the retina is stronger in youth, which brings difficulties to induce PVD in vitrectomy. Several clinical investigations demonstrated that intravitreous injection of plasmin before vitrectomy could reduce the risk of detachment. In our study, a novel recombinant human microplasminogen (rhµPlg) was expressed by Pichia pastoris. Molecular docking showed that the binding of rhµPlg with tissue plasminogen activator (t-PA) was similar to plasminogen, suggesting rh µPlg could be activated by t-PA to generate microplasmin (µPlm). Moreover, rhµPlg had higher catalytic activity than plasminogen in amidolytic assays. Complete PVD was found at vitreous posterior pole of 125 µg rhµPlg-treated eyes without morphological change of retina in juvenile rabbits via intraocular injection. Our results demonstrate that rhµPlg has a potential value in the treatment of vitreoretinopathy.

THE IMPACT OF THE VITREOMACULAR INTERFACE ON FUNCTIONAL AND ANATOMICAL OUTCOMES IN DIABETIC MACULAR EDEMA TREATED WITH THREE DIFFERENT ANTI-VEGF AGENTS: Post Hoc Analysis of The Protocol T Study.

PURPOSE: To investigate the impact of baseline vitreomacular interface status on treatment outcomes in patients treated with three different anti-vascular endothelial growth factors for diabetic macular edema. METHODS: Post hoc analysis from patients enrolled in the DRCR.net Protocol T study. Optical coherence tomography images were analyzed at baseline and at the end of follow-up to identify the presence of complete vitreomacular adhesion, partial vitreomacular adhesion, vitreomacular traction syndrome, and complete posterior vitreous detachment. RESULTS: Six hundred and twenty-nine eyes were eligible for the study based on the study criteria. Complete adhesion eyes gained on average +3.7 more ETDRS letters compared with the complete posterior vitreous detachment group at the end of the 12 months follow-up ( P < 0.001). Baseline vitreomacular interface status had no significant influence on central subfield thickness at 12 months ( P = 0.144). There was no difference between the treatment arms based on effect of baseline vitreomacular interface status on best-corrected visual acuity gain. CONCLUSION: This study provides evidence that vitreomacular interface status affects functional outcomes in diabetic macular edema patients treated with anti-vascular endothelial growth factor injections. The presence of complete or partial vitreomacular adhesion at baseline may be associated with a larger treatment benefit than those with complete posterior vitreous detachment.

PREDICTIVE FACTORS OF SPONTANEOUS RELEASE OF VITREOMACULAR TRACTION: A Systematic Review and Meta-Analysis.

PURPOSE: To review predictive factors of spontaneous vitreomacular traction (VMT) release. METHODS: A systematic literature search was performed on Ovid MEDLINE, Embase, and Cochrane Library. Studies comparing spontaneously released VMT to persistent VMT were included. A meta-analysis was performed using a random effects model, and weighted mean difference, risk ratio (RR), and 95% confidence intervals (95% CI) were reported as appropriate. RESULTS: Of a search of 258 studies, 12 studies were included, from which 272 of 934 eyes (29%) underwent spontaneous release. Mean age was 70.0 years, 37.2% of patients were men, and mean follow-up was 22.0 months. Significant predictive factors for spontaneous release were smaller VMT diameter (n = 177; weighted mean difference = -212.48 µm, 95% CI = [-417.36, -7.60], P = 0.04), epiretinal membrane absence (n = 162; RR = 2.17, 95% CI = [1.18, 3.97], P = 0.01), and right eye involvement (n = 76; RR = 2.10, 95% CI = [1.14, 3.88], P = 0.02). Nonsignificant factors were age, initial best-corrected visual acuity, sex, ocular comorbidity, fellow-eye posterior vitreous detachment, previous intravitreal injection, and VMT classification with focal defined as ≤400 µm. Mean release time was 15.3 months (n = 212). Mean best-corrected visual acuity improved from 0.34 ± 0.21 (Snellen 20/44) to 0.20 ± 0.58 logMAR (Snellen 20/32) postrelease (n = 121). CONCLUSION: Smaller VMT diameter, epiretinal membrane absence, and right eye involvement may support spontaneous VMT release. If patients have tolerable symptoms, clinicians may consider observation in patients with these predictive factors.

COMBINED PNEUMATIC AND ENZYMATIC VITREOLYSIS FOR SEVERE CASES OF VITREOMACULAR TRACTION.

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.

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.

Ocriplasmin for treatment of vitreomacular traction and macular hole: A systematic literature review and individual participant data meta-analysis of randomized, controlled, double-masked trials.

Ocriplasmin is used to treat vitreomacular traction (VMT), with or without full-thickness macular hole (MH). We systematically reviewed the evidence on ocriplasmin's effect on vitreomacular adhesion resolution (VMAR), MH closure, vitrectomy, and best-corrected visual acuity (BCVA) and investigated the effect of baseline covariates on outcome. We applied individual participant data meta-analyses to the entire population and to subgroups defined by MH or epiretinal membrane (ERM) presence. Safety data were pooled and tabulated. Five randomized controlled trials (1,067 participants) were included. Six months after treatment, ocriplasmin achieved higher rates of VMAR and MH closure versus control, lowered vitrectomy odds, and increased the likelihood of a ≥10-letter BCVA increase. VMAR rates were lower when ERM, broad VMA (> 1500 µm), diabetic retinopathy, or pseudophakia were present and higher in younger participants, women, and eyes with MHs. Ocriplasmin-treated participants experienced more short-term visual impairment that was not predictive of final BCVA, as well as vitreous floaters, photopsia, photophobia, eye pain, blurred vision, and dyschromatopsia. The most common serious adverse events for ocriplasmin and control, respectively, were MH progression (22.5%, 17.3%), new MH (1.5%, 3.4%) and retinal detachment (0.8%, 1.2%). Ocriplasmin promotes VMAR and MH closure. Transient visual phenomena are not uncommon.

Predicting the individual probability of macular hole closure following intravitreal ocriplasmin injections for vitreomacular traction release using baseline characteristics.

The primary objective was to create and establish a new formula that predicts the individual probability of macular hole closure for eyes with full thickness macular holes (FTMH) accompanied by vitreomacular traction (VMT) which received enzymatic vitreolysis using intravitreally administered ocriplasmin. The secondary objective was to evaluate the forecast reliability of a previously published formula for VMT resolution in VMT-only eyes (OddsIVO-Success = eIntercept × ORyears × ORln(µm); ProbabilityIVO-Success = OddsIVO-Success/(OddsIVO-Success + 1)) on VMT resolution using the current dataset of eyes with FTMH accompanied by VMT. Retrospective analysis of the OASIS, ORBIT, and INJECT-studies. Patients with FTMH and VMT with complete information (n = 213) were included. The effect of gender, age, FTMH diameter, lens status and the presence of epiretinal membranes (ERM) on FTMH closure was assessed using separate univariate logistic regression analyses. With regard to VMT release separate univariate regression analyses were carried out and results were compared with formerly published data of VMT resolution in eyes with VMT only. Overall, 126 eyes (63%) experienced VMT resolution within 28 days. Younger age (p < 0.0001) and VMT diameter (p = 0.041) had a significant impact on VMT release. Overall, 81 eyes (38%) treated with ocriplasmin showed FTMH closure within 28 days. Univariate analysis of the different predictors analyzed revealed that FTMH diameter < 250 µm had a significant impact on treatment success (p = 0.0495). It was not possible to calculate and establish a new multivariate formula that can predict the individual FTMH closure probability for eyes with FTMHs and VMT. However, the results of VMT release prediction in eyes with FTMHs accompanied by VMT matched the prediction of VMT release in eyes with VMT only when using the previously published formula. All in all, predictors for calculating the individual probability of VMT resolution on the one hand and FTMH closure on the other hand are different suggesting diverse pathophysiological mechanisms.

Indications and outcomes for intravitreal injection of C3F8 gas for symptomatic vitreomacular traction.

To evaluate the indications and outcomes of perfluoropropane (C3F8) gas injection for symptomatic vitreomacular traction (VMT). A retrospective analysis of eyes with VMT treated with 0.3 mL of C3F8 gas was performed. Patients were not asked to posture after gas injection. In phakic patients, cataract surgery was performed simultaneously. Patients were examined after one week and one month postoperatively. Twenty-nine consecutive eyes of 26 patients with symptomatic VMT who underwent pneumatic vitreolysis were included. A complete posterior vitreous detachment was achieved in 18 eyes (62.1%) after a single gas injection at the final visit. The rate of posterior vitreous detachment was reduced significantly with the presence of epiretinal membrane (ERM) (p = 0.003). Three eyes formed a macular hole (MH) postoperatively and another eye developed a retinal detachment. Mean visual acuity increased significantly after one month (p < 0.008). Pneumatic vitreolysis is a viable option for treating VMT with few adverse events. Patient with concomitant ERM had a significantly lower success rate.

The effect of posterior vitreous detachment on aflibercept response in diabetic macular oedema.

PURPOSE: To investigate the effect of posterior vitreous detachment (PVD) on aflibercept response in treatment-naïve diabetic macular oedema (DME). DESIGN: A retrospective cohort study. METHODS: One hundred and fifty eyes of 150 treatment-naïve patients with DME were enrolled. The patients were divided into three groups according to their PVD status: group 1 (no PVD during injections), group 2 (PVD during injections) and group 3 (PVD already present initially). Three consecutive aflibercept injections at intervals of 1 month were applied to all patients. The efficacy of the aflibercept treatment on DME was assessed by comparing changes in central retinal thickness (CRT) and best-corrected visual acuity (BCVA) values after three loading dose injections. RESULTS: After three consecutive injections, the mean reduction of CRT in groups 1, 2 and 3 were -199.6±106.9, -224.9±124.1 and -210.7±126.3, respectively. The decrease in CRT was significant in all groups (p<0.001 in all groups, paired-samples t-test); however, mean changes in CRT were similar among groups (all p>0.05, one-way analysis of variance (ANOVA)). The mean improvement in BCVA in groups 1, 2 and 3 was 6.6±0.9, 6.5±0.8 and 6.1±0.4 ETDRS letters, respectively. The improvement of BCVA was significant in all groups (p<0.001 in all groups, paired-samples t-test) and mean changes were similar between groups (p>0.05, one-way ANOVA). There was no significant relationship between the presence or development of PVD and the mean decrease of CRT and improvement of BCVA (for CRT r=-0.052, p=0.531 and for BCVA r=-0.078, p=0.342). CONCLUSION: In the present study, it was observed that the efficacy of aflibercept treatment in patients with DME did not depend on PVD status.

[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.

A time-dependent study of nano-mechanical and ultrastructural properties of internal limiting membrane under ocriplasmin treatment.

Vitreomacular traction (VMT) syndrome has only been surgically treated for a long time. Recently, enzymatic vitreolysis with ocriplasmin has emerged as a possible option to release VMT and, in some cases, close full thickness macular holes (FTMHs). Despite its clinical relevance, gathering information about the ocriplasmin-induced alterations of the Inner Limiting Membrane (ILM) of the retina in a clinical study is a complex task, mainly because of the inter-individual variability among patients. To obtain more insights into the mechanism underlying the drug action, we studied in-vitro the mechanical and morphological changes of the ILM using Atomic Force Microscopy (AFM). To this aim, we measured the ILM average Young's modulus (YM), hysteresis (H) and adhesion work (A) over time under ocriplasmin treatment. Our data unveil a time-dependent increase in the membrane YM of 19% of its initial value, along with changes in its adhesive and dissipative behavior. Such modifications well correlate with the morphological alterations detected in the AFM imaging mode. Taken all together, the results here presented provide more insights into the mechanism underlying the ocriplasmin action in-vivo, suggesting that it is only able to alter the top-most layer of the vitreal side of the membrane, not compromising the inner ILM structure.

Induction of posterior vitreous detachment (PVD) by non-enzymatic reagents targeting vitreous collagen liquefaction as well as vitreoretinal adhesion.

Induction of posterior vitreous detachment (PVD) by pharmacologic vitreolysis has been largely attempted through the use of enzymatic reagents. Ocriplasmin has been the only FDA-approved clinical reagent so far. Several adverse effects of ocriplasmin have emerged, however, and the search for alternative PVD-inducing reagents continues. Since i) collagen forms an important structural component of the vitreous, and ii) strong vitreo-retinal adhesions exist between the cortical vitreous and the internal limiting membrane (ILM) of the retina, an effective PVD-inducing reagent would require both, vitreous liquefaction, and concurrent dehiscence of vitreoretinal adhesion, without being toxic to retinal cells. We designed a combination of two reagents to achieve these two objectives; a triple helix-destabilizing collagen binding domain (CBD), and a fusion of RGD (integrin-binding) tripeptide with CBD (RCBD) to facilitate separation of posterior cortical vitreous from retinal surface. Based on in vitro, ex-vivo, and in vivo experiments, we show that a combination of CBD and RCBD displays potential for safe pharmacologic vitreolysis. Our findings assume significance in light of the fact that synthetic RGD-containing peptides have already been used for inhibition of tumor cell invasion. Proteins such as variants of collagen binding domains could have extended therapeutic uses in the future.

Short-term changes in posterior vitreous cortex following intravitreal ocriplasmin for symptomatic vitreomacular traction syndrome: a prospective study.

PURPOSE: To describe and analyze short-term posterior vitreous abnormalities following intravitreal ocriplasmin in eyes with symptomatic vitreomacular traction syndrome (VMT). METHODS: In this institutional, prospective and interventional study enrolled patients with symptomatic focal VMT syndrome treated with intravitreal ocriplasmin. In all cases, spectral-domain optical coherence tomography scans were quantitatively and qualitatively analyzed preoperatively and at 1 and 4 weeks postoperatively. RESULTS: Twenty-three patients, of which 5 were males and 18 females, with a mean age of 69.5 ± 8.2 years were included in this study. Postoperatively, VMT resolved in 11 of 23 eyes (47.8%). In 9 out of 11 cases (81.8%), VMT resolved by postoperative week 1, whether in the remaining 2 (18.2%) anatomical restoration, was diagnosed at postoperative week 4. At postoperative week 1, a foveolar detachment was detected in 9 out of 23 eyes (39.1%). The foveolar detachment resolved all but one eye by the end of postoperative week 4. At the end of the follow-up period, the presence of subretinal fluid was detected in 7 out of 9 eyes (77.8%), and it was significantly associated with a shrinkage of the posterior vitreous cortex (p < 0.006). At the end of the follow-up period, visual acuity was significantly higher in those eyes with VMT resolution (p < 0.001). CONCLUSION: Intravitreal ocriplasmin is effective for the treatment of patients with VMT. The postoperative presence of posterior hyaloid shrinkage may be associated with higher traction over the foveal area and the appearance of foveolar detachment.

Longitudinal ellipsoid zone and subretinal fluid mapping following ocriplasmin injection in the prospective observational ORBIT trial.

BACKGROUND: Ocriplasmin is approved for the treatment of symptomatic vitreomacular traction (VMT). However, several retrospective reports have identified ellipsoid zone (EZ) alterations on spectral domain optical coherence tomography (SDOCT) after ocriplasmin injection. This report quantitatively analysed outer retinal changes after intravitreal ocriplasmin. METHODS: Ocriplasmin Research to Better Inform Treatment is a prospective, observational phase IV clinical study where subjects received a single intravitreal injection of ocriplasmin for symptomatic VMT. Macular cube scans were imported into a semiautomated EZ mapping and fluid feature extraction software for SDOCT analysis. Change in visual acuity, VMT release, macular hole (MH) closure, EZ integrity/volume and subretinal fluid (SRF) volume on SDOCT macular cube scans were recorded and analysed. RESULTS: This analysis included 55 participants with 6 months of follow-up. Intravitreal ocriplasmin injection caused VMT release in 67% and MH closure in 82% of participants. Visual acuity improved by 4.5 letters (p<0.05) in the whole cohort and by 6.0 letters (p<0.05) in participants with VMT release. EZ volume was reduced by 23.4% at week 1 (p<0.001) and recovered to baseline by between months 3 and 6. EZ volume loss at week 1 did not correlate with ETDRS acuity at final visit. CONCLUSION: Ocriplasmin treatment resulted in VMT release, MH closure and visual acuity gains in a significant portion of eyes. EZ volume was significantly reduced at week 1, but recovered to baseline levels by final follow-up and was not associated with final visual acuity.

Reduced perfusion density of superficial retinal capillary plexus after intravitreal ocriplasmin injection for idiopathic vitreomacular traction.

BACKGROUND: To investigate, using optical coherence tomography angiography (OCT-A), changes in perfusion density and in the foveal avascular zone (FAZ) in eyes with idiopathic vitreomacular traction (VMT) after ocriplasmin injection. METHODS: In this pilot study, we enrolled sixteen VMT eyes treated with intravitreal ocriplasmin injection. Sixteen healthy eyes were considered as controls. Macular perfusion density in 3 plexuses [superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC)] was calculated at baseline and at 1 month after injection. RESULTS: After injection, VMT anatomically resolved in 9 eyes (56.2%), whereas 7 eyes (43.8%) achieved an incomplete VMT separation. Superficial capillary plexus perfusion density was reduced significantly after injection (from 0.427 ± 0.027 to 0.413 ± 0.028; p = 0.0146), while no differences were noted in the DCP (p = 0.2717) nor in the CC (p = 0.6848). Study-eye perfusion density was statistically similar to control eyes in all three plexuses, both at baseline and at follow-up. The FAZ in the SCP area remained unchanged after injection (p = 0.168) but was significantly inferior to controls both at baseline and at 1 month (0.198 ± 0.074 vs. 0.196 ± 0.070; p = 0.007). CONCLUSIONS: Eyes with VMT have a perfusion density comparable to healthy controls, but a smaller FAZ. After ocriplasmin injection the perfusion density in the SCP is reduced, regardless the anatomical success. Limited by the small sample size and the pilot nature of the study, we found microvascular changes after ocriplasmin injection, which may be due to retinal traction release.

Ocriplasmin Treatment Leads to Symptomatic Vitreomacular Adhesion/Vitreomacular Traction Resolution in the Real-World Setting: The Phase IV ORBIT Study.

PURPOSE: To evaluate clinical outcomes and safety up to 12 months after ocriplasmin injection for the treatment of patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction (VMT) in a real-world setting. DESIGN: The Phase IV Ocriplasmin Research to Better Inform Treatment (ORBIT) trial (NCT02079883) was a Phase IV multicenter, prospective, observational study. PARTICIPANTS: Patients aged ≥18 years with symptomatic VMA/VMT treated with ocriplasmin. METHODS: Patients received a single 0.125 mg intravitreal injection of ocriplasmin. All assessments and treatment decisions were at the discretion of the treating physician. Spectral-domain OCT (SD-OCT) images were analyzed by an independent central reading center (CRC). All enrolled patients were included in demographic, baseline characteristics, and safety analyses. Patients with symptomatic VMA/VMT at baseline determined by CRC were included in baseline ocular characteristics and efficacy analyses. MAIN OUTCOME MEASURES: Clinical outcomes were measured up to 12 months and included resolution of symptomatic VMA, closure of full-thickness macular hole (FTMH), mean change from baseline in best-corrected visual acuity (BCVA), incidence of vitrectomy, and time to first vitrectomy. Safety outcomes included the incidence and timing of onset of adverse drug reactions (ADRs). RESULTS: Of the 539 patients enrolled, 480 were determined to have symptomatic VMA/VMT at baseline post-CRC assessment. After treatment with ocriplasmin, the rate of VMA/VMT resolution was 45.8% (95% confidence interval [CI], 41.3-50.4) at month 1 and 59% (95% CI, 54.4-63.4) at months 10 to 12. The rate of FTMH closure was 30.5% (95% CI, 22.4-39.7) at month 1 and 32.2% (95% CI, 23.9-41.4) at months 10 to 12. Mean (standard deviation) change from baseline in BCVA was 1.5 (11.19) letters at month 1 and 5.2 (13.60) letters at months 10 to 12. Vitrectomy was performed in 28.5% of patients, with a median time to vitrectomy of 63 days. Adverse drug reactions were reported by 30.6% of patients; 5.2% experienced a serious ADR. CONCLUSIONS: Results from the ORBIT study demonstrate that treatment with ocriplasmin is effective and well tolerated in patients with symptomatic VMA/VMT in a real-world setting. The percentage of patients with VMA/VMT resolution at month 1 was higher than previously reported in well-controlled clinical trials. No new safety signals were identified.

Subfoveal Lucency after Treatment of Vitreomacular Traction without Macular Hole in the Phase 3 Trials of Ocriplasmin Vitreolysis.

PURPOSE: To describe the clinical impact of subfoveal lucency (SFL) seen on OCT before and after treatment of vitreomacular traction (VMT) or symptomatic vitreomacular adhesion (VMA) without macular hole (MH) in the prospective phase 3 trials of ocriplasmin vitreolysis. DESIGN: Randomized double-blind placebo-controlled multicenter study. PARTICIPANTS: Four hundred ninety-nine eyes with VMT or VMA without MH. METHODS: Eyes were randomized to either a single intravitreal injection of ocriplasmin or placebo treatment and were followed up for 6 months. MAIN OUTCOME MEASURES: Eyes were analyzed for presence, dimensions, and course of SFL on OCT, release of VMT, and their effect on visual acuity (VA). RESULTS: Among eyes without baseline SFL, new SFL was more frequent after ocriplasmin than placebo at week 1 (23.1% vs. 6.54%; P = 0.0002) and week 2 (19.7% vs. 3.85%; P = 0.0001), but was similar in frequency by week 4 (8.37% vs. 7.69%; P = 0.83). Six-month VA for eyes demonstrating SFL after ocriplasmin during the first 2 weeks was comparable with those without SFL at any point in the study (P = 0.12). In placebo-treated eyes but not ocriplasmin-treated eyes, SFL was associated with worse VA at all visits. The increase in SFL width from baseline to week 2 was significantly greater with ocriplasmin than placebo (P = 0.029). Among ocriplasmin-treated eyes at month 6, those with SFL and VMT release had better VA than those with SFL and persistent adhesion (P = 0.037) and similar VA to those with persistent adhesion without SFL (P = 0.17). In the placebo group, those with baseline SFL showed low rates of spontaneous VMT release at month 6 compared with those without baseline SFL (3/21 eyes vs. 33/99 eyes; P = 0.045). CONCLUSIONS: Compared with placebo, SFL occurred more frequently only in the initial weeks after treatment with ocriplasmin. When SFL developed after ocriplasmin administration, VA was not impacted at the 6-month visit. Persistent SFL in ocriplasmin-treated eyes at month 6 was associated with poorer vision if VMT had not released. Eyes with SFL at baseline had low rates of spontaneous VMT release and may need treatment.