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.

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.

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.

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.

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.

THE OASIS MP-1 SUBSTUDY: Characterization of the Effect of Ocriplasmin on Microperimetry Parameters.

PURPOSE: To evaluate the effects of ocriplasmin and symptomatic vitreomacular adhesion resolution on visual fixation and macular sensitivity using microperimetry. METHODS: MP-1 parameters were analyzed from 3 OASIS sites after the use of standardized instruments and testing procedures over 24 months. RESULTS: A total of 27 patients (19 ocriplasmin, 8 sham) were evaluated. Mean distance of the preferred fixation locus to the anatomical center was farther in the sham group at baseline and farther in the sham versus ocriplasmin group throughout the study. Retinal sensitivity values were consistently higher in the ocriplasmin versus sham group after Month 3. Fewer patients in the ocriplasmin group had predominantly eccentric fixation at study end compared with the sham group, which also had an increased number of patients with unstable fixation. Patients with vitreomacular adhesion resolution had lower bivariate contour area, fewer relative scotomas, and higher retinal sensitivity parameters at baseline than those with unresolved vitreomacular adhesion. CONCLUSION: Substudy results suggest that fixation and sensitivity parameters tended to be better in the ocriplasmin group than in the sham group over time. The substudy identified parameters that were distinct between patients with and without vitreomacular adhesion resolution, suggesting that microperimetry warrants further study as a relevant biomarker for visual function.

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.

[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.

INTRAVITREAL OCRIPLASMIN IN CLINICAL PRACTICE: Predictors of Success, Visual Outcomes, and Complications.

PURPOSE: To investigate predictors of success, visual outcomes, and complications of intravitreal ocriplasmin for the treatment of symptomatic vitreomacular adhesion in a clinical care setting. METHODS: Retrospective chart review of 49 consecutive eyes of 47 patients who received intravitreal ocriplasmin. Spectral domain optical coherence tomography scans were examined for vitreomacular traction (VMT) release, full-thickness macular hole (FTMH) closure, and other changes in retinal anatomy. RESULTS: Pharmacologic VMT release occurred in 41% of eyes; positive predictors included age ≤75 years (P = 0.001), phakic status (P = 0.016), VMT width ≤750 µm (P = 0.001), and absence of retinal comorbidities (P = 0.035). Pharmacologic FTMH closure occurred in 25% of cases; positive predictors included successful VMT release (P = 0.042), better preinjection best-corrected visual acuity (P = 0.036), and smaller FTMH aperture width (P = 0.033). Eyes that achieved VMT release and did not undergo surgery attained significant improvement in best-corrected visual acuity (P = 0.015). Complications included subfoveal lucency (33%), ellipsoid zone disruption (33%), and FTMH base enlargement (75%). Only FTMH base enlargement resulted in worse visual outcomes (P = 0.024). Subgroup analysis of 14 eyes with ideal characteristics (all positive predictors listed above) yielded a 93% VMT release rate. CONCLUSION: Proper case selection may facilitate successful pharmacologic vitreolysis with ocriplasmin, improve visual outcomes, and minimize potential complications.

OCRIPLASMIN FOR VITREOMACULAR TRACTION: LOOKING OUTSIDE THE MACULA: A Wide-Field Optical Coherence Tomography Study.

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.

EVALUATION OF FULL-FIELD ELECTRORETINOGRAM REDUCTIONS AFTER OCRIPLASMIN TREATMENT: Results of the OASIS Trial ERG Substudy.

PURPOSE: To explore a possible association between full-field electroretinograms with vitreomacular adhesion resolution and best-corrected visual acuity as part of the prospective, randomized, double-masked, sham-controlled Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial studying ocriplasmin. METHODS: The ERG substudy enrolled 62 of 220 OASIS subjects (randomized 2:1) and analyzed full-field electroretinograms and their association with both vitreomacular adhesion resolution and best-corrected visual acuity from baseline through Month 24. Electroretinogram reductions were defined as acute full-field electroretinogram reductions in amplitude of ≥40% from baseline occurring at postinjection Day 7 or Day 28. RESULTS: In the ocriplasmin group, 16/40 (40%) subjects developed ERG reductions, compared to 1/21 (4.8%) in the sham group; 13/16 (81.3%) and 1/1 (100%) resolved by study end, respectively. A total of 11/16 (68.8%) ocriplasmin-treated subjects with ERG reductions achieved vitreomacular adhesion resolution, compared to those without (9/24, 37.5%). The ocriplasmin-treated subjects with ERG reductions also gained more letters on average (11.3 vs. 9.3 letters) from baseline and had a difference of 6.7 letters in mean best-corrected visual acuity by study end compared to those without ERG reductions. CONCLUSION: Ocriplasmin-treated subjects with ERG reductions had a higher rate of vitreomacular adhesion resolution and showed better visual improvement than their counterparts without ERG reductions or sham subjects by study end.

Impact of Preinjection Spectral Domain Optical Coherence Tomography Findings in the Use of Intravitreal Ocriplasmin in a Clinical Setting.

PURPOSE: To investigate the impact of spectral domain optical coherence tomography (SD-OCT) morphological predictive markers on visual acuity and outcome using ocriplasmin for macular hole and vitreomacular traction syndrome. METHODS: A series of 40 patients in a retrospective study received intravitreal ocriplasmin. The primary endpoint was defined as morphological resolution of vitreomacular traction or closure of a macular hole. We analyzed the impact of pre- and postinjection SD-OCT findings on the outcome and visual acuity. RESULTS: Thirteen of the 40 patients benefited from treatment. Statistical correlation between baseline characteristics and outcome revealed that higher foveal thickness (p = 0.018) and nontractional epiretinal membranes (p = 0.05) resulted in a worse outcome. In treatment success best corrected visual acuity gained was 9 (SD 12) letters and in failure 1 (SD 9) letter. We could not observe an influence of preinjection SD-OCT findings and other factors on visual outcome. CONCLUSION: We could confirm the therapeutic effect of ocriplasmin injections. SD-OCT morphological factors that influence treatment success and visual acuity were determined.

[Initial Clinical Experiences Using Ocriplasmin for the Treatment of Vitreomacular Traction with or without a Macular Hole]. / Stellenwert von Ocriplasmin bei der Therapie der vitreomakulären Traktion mit und ohne Makulaforamen ­ erste klinische Erfahrungen.

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.

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.

Assessment of intravitreal ocriplasmin treatment for vitreomacular traction in clinical practice.

PURPOSE: To assess treatment effects following intravitreal injection of ocriplasmin for vitreomacular traction (VMT), with or without full-thickness macular hole (FTMH), in real-life setting. METHODS: This is a monocentric, retrospective, consecutive series of 82 eyes from 82 patients who underwent ocriplasmin treatment between July 2013 and December 2016. We included 57 eyes with pure VMT, 17 eyes with small FTMHs, and eight eyes with medium FTMHs. Primary outcome measures were VMT release and MH closure rates. Secondary outcomes were visual acuity (VA), morphological changes, and subjective visual impairment after 1, 3, and 6 months and at last follow-up. RESULTS: After a median follow-up of 10 months, VMT release was achieved by pharmacologic vitreolysis in 57% of all eyes, whereas the macular hole closure rate was 32%. In those presenting with five or more positive prognostic factors (PPF), eyes with pure VMT showed nonsurgical traction release in 88%, and FTMHs were released in 93%, with a closure rate of 20%. Small FTMHs closed in 41% and medium FTMHs in 13%. The mean change in VA (LogMAR) was -0.07 ± 0.24 (median - 0.10) in all eyes. Subretinal fluid accumulation and ellipsoid zone changes were seen in 31% and 37% of all eyes, respectively. They were more frequent in eyes with traction release, but were self-limited. CONCLUSIONS: In a real-life setting, release of VMT by ocriplasmin injection can be achieved in the majority of eyes, relying on a strict patient selection. Closure of FTMHs rather correlates with hole diameter than with presence of PPF, and remains a rare finding in medium FTMHs.

Ocriplasmin treatment for vitreomacular traction in real life: can the indication spectrum be expanded?

PURPOSE: To evaluate the efficacy of intravitreal ocriplasmin for the resolution of vitreomacular traction (VMT) with or without a full thickness macular hole (FTMH) in the clinical setting and to assess whether the indication spectrum of this treatment modality can be expanded beyond that of the MIVI-TRUST trials. METHODS: The records of patients with VMT with or without FTMH, who were treated with intravitreal ocriplasmin were reviewed. Patients were divided in two groups. In the first group, VMT with or without FTMH was present without any other macular pathology. In the second group, VMT with or without FTMH occurred alongside of other macular disease including age-related macular degeneration, diabetic maculopathy and post-operative pseudophakic cystoid macular edema. RESULTS: Release of the VMT was achieved in 12/20 patients (12/20 eyes) of the first group. 16 eyes in this group met 3 or more criteria known to be associated with favorable prognosis after intravitreal ocriplasmin treatment. No cases of release of the VMT were observed in the second group, which included 15 patients (15 eyes). Significant improvement of visual acuity and reduction of the central macular thickness was observed only in the subgroup of eyes which responded to treatment. CONCLUSIONS: Concomitant macular pathology was a significant factor for treatment failure and we suggest that ocriplasmin should be regarded with caution in these cases. Careful patient selection for treatment with ocriplasmin using specific criteria in the clinical setting can provide superior results to those reported in the MIVI-TRUST trials.

TREATMENT OF VITREOMACULAR TRACTION WITH INTRAVITREAL PERFLUOROPROPANE (C3F8) INJECTION.

PURPOSE: To assess the posterior vitreous release rates following a single, office-based intravitreal injection of expansile gas in treating vitreomacular traction. METHODS: Thirty eyes of 29 consecutive patients with symptomatic vitreomacular traction received a single, office-based intravitreal injection of up to 0.3 mL of 100% perfluoropropane (C3F8). RESULTS: Overall, vitreomacular traction release occurred in 25 of 30 eyes by the final follow-up visit (83% final release rate); furthermore, 90% (9 of 10 eyes) with diabetes mellitus released, 83% (5 of 6 eyes) with concurrent epiretinal membrane released, and 83% (5 of 6 eyes) previously treated with ocriplasmin released. Vitreomacular traction release occurred overnight in some patients and was documented on spectral domain optical coherence tomography at an average of 13 days (range, 1-62 days). The phakic release rate was 89% (16 of 18 eyes) versus a 75% pseudophakic release rate (9 of 12 eyes) (P = 0.3173). Ellipsoid zone changes on spectral domain optical coherence tomography occurred in 1 of 30 gas-treated eyes. One patient developed pupillary block. CONCLUSION: Office-based intravitreal injection of C3F8 offers an inexpensive and effective treatment for vitreomacular traction, including for patients who underwent previous ocriplasmin administration and in patients with diabetes mellitus or epiretinal membrane.

LONGITUDINAL MICROPERIMETRY EVALUATION AFTER INTRAVITREAL OCRIPLASMIN INJECTION FOR VITREOMACULAR TRACTION.

PURPOSE: To determine whether improvements in microperimetry testing are associated with anatomic resolution after ocriplasmin treatment in patients with symptomatic vitreomacular adhesion (VMA)/vitreomacular traction and relatively preserved baseline best-corrected visual acuity (BCVA). METHODS: Patients with vitreomacular traction received a single 125-µg intravitreal ocriplasmin injection and were followed longitudinally for 6 months with optical coherence tomography, BCVA testing, and microperimetry. Visual function changes were compared between eyes with and without VMA resolution on optical coherence tomography. RESULTS: Eleven of 16 eyes (68.8%) achieved VMA resolution after treatment. Mean baseline BCVA was relatively good (79 ± 3 Early Treatment Diabetic Retinopathy Study letters; 20/52); no patients had a ≥2-line improvement in BCVA over the 6-month follow-up period. In the group with VMA resolution, mean retinal sensitivity significantly increased in the central 4° (15.2 ± 1.9 dB vs. 18.9 ± 0.7 dB, P < 0.001) when comparing baseline and final follow-up microperimetry testing. No change in mean retinal sensitivity was found in the group without VMA resolution. CONCLUSION: Microperimetry demonstrates a significant gain in retinal sensitivity, particularly in the central 4° area, in eyes with anatomic resolution after treatment of vitreomacular traction with intravitreal ocriplasmin injection, even when no significant gain in BCVA is seen.

Experiment of vitreous liquefaction induced by C3F8.

To investigate the effect and safety of vitreous liquefaction induced by C3F8 (an inert gas) injected into vitreous cavit of rabbit eyes. 24 rabbits (48 eyes) were randomly divided into four groups, named group A, group B, group C and group D, with 6 rabbits in each group. The right eye in each rabbit was taken as the experimental eye while the left as the control eye. The experimental eyes in group A were injected with 0.1mL disinfectant air; the experimental eyes in group B, group C and group D were all injected with C3F8 0.1mL, 0.2mL and 0.3mL respectively after receiving anterior chamber penetration; and the controlled eyes in all group were injected with 0.1mL balanced salt solution (BSS). During the first 7 d after injection, all the rabitts' eyes were examined by slit lamp, ophthalmoscope, intraocular pressure (IOP) and dark-adapted retina Electroretinography (ERG) each day. After that, the examination of IOG and ERP were reviewed weekly. Besides, B ultrasound should be examined to observe the situation of posterior vitreous detachment (PVD) in the 4th and 8th weeks. The rabbits were killed in the end of the 8th week, with their specimens examined by the light microscope, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Except group A, all the experimental eyes were produced with vitreous liquefaction. In group C and group D, in addition to the produced vitreous liquefaction, posterior vitreous detachment (PVD), even complete PVD, were induced in different extent. But in group B, the vitreous body was returned to the gel state at 2 weeks after gas absorption. In group C and group D, the vitreous body was not found to recover its original state at 8 weeks. In group D, there was a little increase of intraocular pressure, a mild delay of wave a and wave b after ERG in the 4th day after the gas injection. While there was no such situation in other groups. After the examination of B ultrasound in the 8th week, the complete PVD occurred in group C (with 2 experimental eyes occurred) and group D (with 4 experimental eyes occurred). Light microscope and transmission electron microscope examination showed no obvious abnormality. Smooth inner limiting membrane could be seen in the eye with PVD occurred when scanning electron microscope used. The injection of C3F8 into rabbit eyes can improve the vitreous liquefaction of the vitreous body and a certain volume of C3F8 can successfully and safely induce the PVD, and a larger volume of C3F8 was also effective but with a transient high IOP in rabbit eyes.

Results of the 2-Year Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) Randomized Trial.

PURPOSE: The Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole (OASIS) trial was designed to evaluate the long-term efficacy and safety profile of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA)/vitreomacular traction, including full-thickness macular hole (FTMH). DESIGN: Phase 3b, randomized, sham-controlled, double-masked, multicenter clinical trial. PARTICIPANTS: Sample size was 220 subjects (146 ocriplasmin, 74 sham) randomized in a 2:1 ratio to receive intravitreal ocriplasmin 0.125 mg or sham injection. METHODS: The trial involved 12 visits over 24-months. Inclusion criteria included presence of VMA and best-corrected visual acuity (BCVA) of 20/32 or worse in the study eye. Exclusion criteria included FTMH >400 µm, presence of epiretinal membrane (ERM), and aphakia in the study eye. MAIN OUTCOME MEASURES: The primary efficacy end point was the proportion of subjects with pharmacologic VMA resolution at day 28. Secondary efficacy end points were assessed at month 24 and included proportion of subjects with BCVA gain from baseline, nonsurgical FTMH closure, vitrectomy, and Visual Function Questionnaire 25 (VFQ-25) outcomes. RESULTS: The OASIS trial met its primary end point with pharmacologic VMA resolution at day 28 being significantly higher in the ocriplasmin group (41.7%) compared with the sham group (6.2%). The treatment effect was maintained until study end. In the ocriplasmin group, pharmacologic VMA resolution at day 28 was higher in subgroups with the following baseline characteristics compared with the complementary subgroups without them: presence of focal VMA, presence of FTMH, absence of ERM, and phakic lens status. In the ocriplasmin group, 50.5% of subjects had a ≥2-line improvement in BCVA from baseline compared with 39.1% of subjects in the sham group. The nonsurgical FTMH closure rate was 30.0% for the ocriplasmin group compared with 15.4% for the sham group. All other secondary end points also favored ocriplasmin over sham. Regarding safety, most adverse events were mild to moderate, had a short onset time, and were transient, with no new safety signals identified. CONCLUSIONS: The OASIS trial demonstrates the long-term efficacy and safety of ocriplasmin, providing improved resolution of symptomatic VMA compared with previous phase 3 trials with no additional safety signals identified.