Release Of Vitreomacular Adhesion Research Articles

Vitreomacular interface after anti-VEGF injections in diabetic macular edema

BackgroundThe purpose of this study was to evaluate the incidence of vitreomacular adhesion (VMA) release after anti-VEGF therapy for the treatment of diabetic macular edema (DME) and to evaluate further changes in outcome.Methods This was a retrospective study that enrolled 66 eyes of 66 patients with DME who presented with VMA diagnosed by spectral-domain optical coherence tomography (OCT) at baseline. VMA was classified as focal (attachment: ≤ 1500 μm) or broad (attachment: > 1500 μm). All patients received at least three monthly intravitreal injections of an anti-VEGF agent. Follow-up visits were performed 1 month after each injection to evaluate the incidence of VMA release.ResultsThe mean patient age was 61.4 years (range: 29 to 78 years), and 72.7 % were male. The mean best-corrected visual acuity was 0.62 logMAR, and the mean central retinal thickness (CRT) was 473 μm at baseline. The mean length of follow-up was 18.5 months, and the mean number of injections was 5.8. The intravitreal drugs used were aflibercept (40.9 %), ranibizumab (37.9 %) and bevacizumab (21.2 %). Forty-seven eyes had broad VMA, and 19 had focal VMA. Twenty-two eyes (33.3 %) developed VMA release following a mean of 5.7 injections (range: 3–13). Sixteen eyes (72.7 %) with focal VMA and 6 eyes (27.3 %) with broad VMA at baseline developed VMA release. Twenty-one eyes that developed VMA release showed an improvement in CRT following VMA release (mean: -106 μm; range: 22 to 289 μm).ConclusionsVMA release occurs in approximately 1/3 of patients with DME following anti-VEGF therapy. Most of them show a short-term decrease in CRT.

Prognostic Factors Associated with Ocriplasmin Efficacy for the Treatment of Symptomatic Vitreomacular Adhesion and Full-thickness Macular Hole: Analysis from Four Studies.

PurposeTo assess the effect of patient baseline characteristics on the efficacy of ocriplasmin treatment for symptomatic vitreomacular adhesion (VMA) with full-thickness macular hole (FTMH) from phase 3/4 studies.MethodsPatients with symptomatic VMA and FTMH at baseline and receiving ocriplasmin treatment 125 g were pooled from the MIVI-TRUST, OASIS, and ORBIT studies. Multivariable logistic regression analysis was used to evaluate whether patient baseline characteristics were predictors of having VMA resolution by Day 28 and FTMH closure by Month 6.ResultsTwo hundred and seventy-four patients receiving ocriplasmin treatment were assessed. Overall, 22.6% (62/274) of the patients experienced both VMA resolution by Day 28 and non-surgical FTMH closure by Month 6. Patients with FTMH 250 µm at baseline had a significantly higher success rate compared to those with FTMH 400 µm (29.9% [41/137] vs 2.2% [1/48]; P = 0.009). In patients with VMA resolution by Day 28, both small FTMH size (P = 0.001) and FTMH width at RPE (P = 0.012) were significantly associated with a higher FTMH closure rate. Patients with VMA resolution had higher rates of FTMH closure. Previously identified baseline predictive factors, including age, lens status, or presence of epiretinal membrane (ERM) were not found to be predictive of both VMA release and FTMH closure.ConclusionThe analysis revealed that FMTH 250 µm was the only factor predictive for achieving both pharmacological VMA resolution by Day 28 and nonsurgical FTMH closure by Month 6; neither lens status or presence of ERM, previously identified baseline characteristics favoring VMA resolution, showed statistically significant predictive power for both outcomes.

The prevalence of vitreomacular adhesion in eyes with macular oedema secondary to retinal vein occlusion selected for intravitreal injections.

To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with macular oedema (ME) secondary to retinal vein occlusion (RVO) and to longitudinally evaluate the incidence of vitreomacular interface changes over time and the influence on response to treatment. Retrospective cross-sectional analysis and longitudinal cohort study conducted at two Italian tertiary referral centres. A total of 295 eyes, treated with intravitreal ranibizumab and/or dexamethasone for ME secondary to RVO between June 2008 and May 2018, were enrolled in the study. 280 fellow eyes met the inclusion criteria and were included as control group. The vitreomacular interface status was evaluated by spectral domain optical coherence tomography (OCT) and graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study (IVTS) group. At baseline, VMA was present in 130 (44.07%) RVO eyes and 142 (50.7%) control eyes (no statistically significant difference was found; p=0.455). Mean follow-up (FU) was 35.98months (min 6 - max 112). Throughout the FU, the incidence of spontaneous release of VMA (RVMA) in RVO eyes was significantly higher in comparison with that of the control group [59 (41.84%) RVO eyes versus 18 (12.33%) control eyes; p<0.0001]. The number of injections in VMA+ eyes was significantly higher when compared with VMA- eyes. No significant difference was found between VMA+ and VMA- eyes regarding their mean best-corrected visual acuity (BCVA) at baseline and at each annual time point (p=0.2). Differences in central macular thickness (CMT) were significant only at the baseline evaluation (p=0.0303). Vitreomacular adhesion (VMA) was not found to be more prevalent in eyes with RVO compared to healthy fellow eyes, and RVO, in turn, did not result in a higher persistence of VMA over time. This suggests that VMA and RVO might be two independent retinal phenomena, with no mutual pathogenetic influence. Vitreomacular adhesion (VMA) might have an impact on the response to treatment, since it was found to result in a more intensive treatment regimen; however, it did not affect visual and anatomic outcomes. These results do not support vitrectomy or PVD induction in the prevention, nor the treatment, of RVO.

Vitreomacular interface alterations following peripheral laser retinopexy: Interface changes after laser.

To demonstrate the morphological outcomes of macular hole following prophylactic peripheral laser retinopexy (PPLR). Our retrospective case-control analysis included 92 eyes, 55 in the laser group and 37 in the non-laser group. Fifty-five patients were subjected to prophylactic peripheral laser retinopexy in preparation for pars plana vitrectomy for macular hole, with and without vitreomacular adhesion (laser group). Before and after prophylactic peripheral laser retinopexy, we evaluated any changes in vitreomacular anatomy by optical coherence tomography. Optical coherence tomography changes were also analyzed in the visits preceding pars plana vitrectomy in 37 macular hole eyes not subjected to prophylactic peripheral laser retinopexy (non-laser group). In the laser group, 7 out of 55 eyes (12.7%) showed macular hole closure (6 out of 18 macular hole eyes with vitreomacular adhesion (33.3%) and 1 out of 37 eyes without vitreomacular adhesion (2.7%)), while no patients showed macular hole closure in the non-laser group (p < 0.05). The mean width of the seven closed macular hole was 191.4 µm (range: 59-282 µm). In all except one of the six macular hole eyes with vitreomacular adhesion, the macular hole closed without vitreomacular adhesion release. In our analysis of the patient subgroup with vitreomacular adhesion, we observed a release of vitreomacular adhesion in 3 out of 18 eyes (16.6%) in the laser group and in 1 out of 13 eyes (7.6%) in the non-laser group (p > 0.05). These findings support a possible beneficial role for prophylactic peripheral laser retinopexy in selected individuals with macular hole.

Enzymatic vitreolysis for the treatment of tractional diabetic macular edema

Background:A new approach to address focal vitreomacular adhesion in patients with diabetic macular edema may control and stabilize diabetic macular edema with fewer anti-vascular endothelial growth factor injections.Objectives:The aim of this study was to demonstrate that diabetic macular edema can be improved by inducing the release of a vitreomacular adhesion, with less than 2500 μm, with enzymatic vitreolysis.Methods:From a retrospective analysis of clinical records from patients with diabetic retinopathy, patients with diabetic macular edema and vitreomacular adhesion <2500 μm were selected for a single-arm prospective study. The primary endpoint was to control diabetic macular edema with fewer anti-vascular endothelial growth factor injections after an observed vitreomacular adhesion release. A statistical subanalysis was performed for the following two groups: the group with vitreomacular adhesion release (group 1) and the group without vitreomacular adhesion release (group 2).Results:A total of 23 eyes from 19 patients were included. A reduction of the median number of injections was achieved in group 1 (p = 0.006). Adverse events were mild and transitory.Conclusion:Release of vitreomacular adhesion <2500 μm through enzymatic vitreolysis contributed to the control and stabilization of diabetic macular edema with fewer anti-vascular endothelial growth factor injections, reducing the burden and the risks related to these invasive and frequently chronic treatments.

Ocriplasmin for symptomatic vitreomacular adhesion.

Ocriplasmin for symptomatic vitreomacular adhesion.

Macula Society Collaborative Retrospective Study of Ocriplasmin for Symptomatic Vitreomacular Adhesion

To assess anatomic and visual outcomes of ocriplasmin use for symptomatic vitreomacular adhesion (VMA). Retrospective chart review. Macula Society members were surveyed online to collect data on ocriplasmin for symptomatic VMA. Clinical and optical coherence tomography data were collected using standardized data entry forms. There were 208 patients (208 eyes) with symptomatic VMA followed at least 3 weeks after receiving ocriplasmin. At baseline, VMA was focal (<1500 μm) in 179 eyes (86%), broad in 9 eyes (4%), and not reported in 20 eyes (10%). A full-thickness macular hole (MH) was present in 75 eyes (36%); size was <400 μm in 62 eyes (82%). Baseline mean visual acuity was approximately 20/63. Of the 204 eyes with ≥12 weeks follow-up, pars plana vitrectomy (PPVx) was performed in 12 (6%) by 4 weeks, 31 (15%) by 12 weeks, and 64 (31%) by the last visit. VMA had resolved by 12 weeks with ocriplasmin alone in 83 of 191 eyes (43%) by week 12 and in 148 of 200 eyes (74%) by the last visit, including eyes undergoing PPVx. Among eyes with a baseline MH, closure was achieved with ocriplasmin alone in 10 of 65 (15%) by 1 week, 26 of 74 (35%) by 4 weeks, and 30 of 75 (40%) at the last visit. Mean change in visual acuity at the last visit compared with baseline was-0.06±0.40 logarithm of the minimum angle of resolution (logMAR) (modest vision improvement) (P= 0.03). At the last visit, visual acuity improved by ≥2 lines in 69 eyes (35%) and by ≥3 lines in 54 eyes (27%). Visual acuity decreased ≥2 lines in 35 eyes (18%) and by 3 lines in 27 eyes (14%) at the final visit. Complications included photopsias (15%), dimness of vision (14%), decreased color vision (10%), MH development (5%), macular retinal pigment epithelium atrophy (2.7%), retinal detachment (1.9%), and retinal tear (1.4%). No endophthalmitis cases were reported. Physician-reported outcomes on ocriplasmin use confirmed VMA release in 45% and closure of MH in 40% of eyes without PPVx. Visual acuity decreased in approximately 20% of eyes. Adverse events were not infrequent and suggest caution when considering ocriplasmin use.

Vitreomacular Adhesion and the Risk of Neovascular Age-Related Macular Degeneration

To assess the prevalence of vitreomacular adhesion (VMA) in consecutive naïve eyes diagnosed with exudative age-related macular degeneration (AMD) in comparison with eyes with nonexudative AMD and age-matched controls, and to evaluate prospectively the incidence of vitreomacular interface changes over time and their influence on choroidal neovascularization (CNV) development. Retrospective cross-sectional analysis and longitudinal cohort study conducted at Sacrocuore Hospital, Negrar, Verona, Italy. A total of 1067 eyes examined at Sacrocuore Hospital between August 2008 and June 2015 met the inclusion criteria and were evaluated in this study. Eyes were classified into 3 groups: 403 eyes of 364 patients (mean [standard deviation; SD] age 77.8 [8.0] years) affected by exudative AMD; 350 eyes of 298 subjects (mean [SD] age 78.1 [8.2] years) with nonexudative AMD; and 314 eyes of 214 subjects (mean [SD] age 74.2 [8.2] years) with no signs of AMD enrolled as the control group. The vitreomacular interface status was evaluated by spectral-domain optical coherence tomography (OCT) and was graded according to the OCT-based International Classification System developed by the International Vitreomacular Traction Study Group by 2 independent masked observers. VMA was present in 101 (25.1%) eyes with exudative AMD, 84 (24.0%) eyes with nonexudative AMD, and 84 (26.8%) eyes with no signs of AMD (no statistical difference was found; P= 0.3384). Spontaneous release of VMA (RVMA) was found in 15 (15.3%) eyes with exudative AMD, 21 (28.0%) eyes with nonexudative AMD, and 10 (24.4%) eyes with no signs of AMD over a mean follow-up of 25.5, 25.9, and 24.1 months, respectively. The incidence of RVMA in exudative AMD eyes was significantly lower compared with nonexudative (P= 0.0207) and lower, but not statistically significant, with respect to eyes with no signs of AMD (P= 0.1013). In eyes with nonexudative AMD, de novo development of CNV occurred in 91 eyes (30.6%). There was no significant difference regarding the rate of CNV development in the presence or absence of VMA (P= 0.0966). The present study found no significant difference in the prevalence of VMA in eyes affected by AMD compared with age-matched controls and no difference in the rate of de novo CNV development in eyes with or without VMA. Conversely, a lower incidence of RVMA over time was found in eyes affected by exudative AMD. The results of this study suggest that VMA might be a consequence rather than a causative factor in the development of CNV.

Vitreoretinal interface abnormalities in patients treatedwith ranibizumab for diabetic macular oedema

PurposeIntravitreal anti-vascular endothelial growth factor (VEGF) agents are effective in the treatment of central involving diabetic macular oedema (DMO). Vitreoretinal interface abnormalities (VRIA) are common in patients with DMO, and the effect of these on the response to anti-VEGF treatment is unclear. Furthermore the effect of anti-VEGF agents on the VRIA itself is uncertain.MethodProspective study of consecutive patients treated with ranibizumab (RZB) for DMO as part of routine clinical care in one eye unit over a 1-year period. Visual acuity (Va), central retinal thickness (CRT) and injection frequency data was recorded on an electronic database. Treatment was initiated with four monthly RZB injections and then a monthly PRN regime. All patients underwent high-density spectral-domain optical coherence tomography (SDOCT) at baseline and 12 months. The SDOCTs were graded by two observers masked to the outcome.ResultsOne hundred and four eyes (77 patients) were included in the analysis. The mean age was 62 years, and 62% were male. The mean presenting vision was 62 letters and CRT 472 μm. Eighty eyes retained stable Va, and 17 had an improvement in Va. At baseline, 39 eyes had associated focal vitreomacular adhesion (VMA) and by 12 months this reduced to 30 (p = 0.04), with 12 releasing VMA and three developing it. Patients with VMA had significantly better final Va than those without VMA. Improvement in CRT was greatest in those where VMA released during the study. Forty-five eyes had some degree of foveal involving epiretinal membrane (ERM) at baseline, and 28 were considered to have clinically significant ERM. There was no clinically relevant change in ERM during the study. Patients with significant ERM at baseline had a lower final vision. Multivariate analysis showed that ERM and more severe retinopathy at baseline were predictive of less visual improvement (p < 0.01). Shorter intraretinal cyst length, ERM and the absence of VMA at baseline were predictive of a worsened anatomical response (p < 0.001).ConclusionVRIA are related to outcome in patients treated with RZB. ERM was associated with a worsened visual and anatomic response, and VMA with an improved anatomical response particularly when spontaneous VMA release occurred during treatment. The presence and severity of ERM was not affected by RZB treatment.

Baseline Predictors of Vitreomacular Adhesion/Traction Resolution Following an Intravitreal Injection of Ocriplasmin.

To determine factors predicting response to ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) response in patients with symptomatic vitreomacular adhesion (VMA). Combined analysis of two multicenter, prospective, randomized, double-masked trials of intravitreal ocriplasmin 125 µg injection versus placebo. Patients had vitreomacular traction with or without a full-thickness macular hole (FTMH). Multivariate logistic regression was used to determine factors influencing treatment response (complete VMA release [day 28] and non-surgical FTMH closure [month 6]). Younger age, presence of FTMH (odds ratio [OR] = 2.1; 95% confidence interval [CI], 1.1-3.7), VMA diameter of 1,500 µm or less (OR = 4.9; 95% CI, 2.0-12.4), phakic lens status (OR = 2.8; 95% CI, 1.5-5.2), and absence of epiretinal membrane (OR = 4.1; 95% CI, 2.2-7.9) predicted VMA resolution. FTMHs with apical diameter of 250 µm or less were more likely to close than larger holes (58.3% vs. 24.6%; P = .013). Both FTMH size groups had significantly greater chance of VMA resolution and FTMH closure versus controls. Ocriplasmin is most effective in younger patients with focal VMA and without an epiretinal membrane. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:716-723.].

RESOLUTION OF SUBRETINAL FLUID AND OUTER RETINAL CHANGES IN PATIENTS TREATED WITH OCRIPLASMIN.

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

Predicting macular hole closure with ocriplasmin based on spectral domain optical coherence tomography.

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

Gas-mediated vitreomacular adhesion release with intravitral ranibizumab injections for exudative age-related macular degeneration.

To evaluate the efficiency of gas-assisted vitreomacular adhesion (VMA) release combined with intravitreal ranibizumab injections for exudative age-related macular degeneration (AMD) patients. This prospective, interventional case series included a total of 23 eyes of 22 patients. The eyes were treated with intravitreal injection of 0.3mL of perfluoropropane (C3F8) gas and concomitant intravitreal ranibizumab injection to stimulate VMA release. After three initial loading injections, additional intravitreal ranibizumab injections were performed pro re nata. Over a 12-month period, monthly examinations were performed for best-corrected visual acuity (BCVA, logMAR; logarithm of the minimum angle resolution), optical coherence tomography, and dilated fundus examinations. After gas injection, 22 eyes (95.7%) showed complete VMA release at 1week. Complete VMA was achieved in all eyes at 2months after VMA release, without serious ocular adverse events except one patient who developed a retinal tear. Mean BCVA was 0.61 ± 0.37 logMAR (20/81 Snellen equivalents) at baseline and 0.46 ± 0.30 logMAR (20/57 Snellen equivalents) at 12months (P = 0.135). Mean central macular thickness was 357.9 ± 128.6μm at baseline and 245.6 ± 60.0μm at 12months (P = 0.188). Mean numbers of intravitreal ranibizumab injections were 4.8 ± 2.4 times during 12months (4 to 8 injections). Gas-assisted VMA release can be used as an efficient alternative for exudative AMD patients with obvious VMA.

The Plane of Vitreoretinal Separation and Results of Vitrectomy Surgery in Patients Given Ocriplasmin for Idiopathic Macular Hole.

We assessed whether ocriplasmin (OCP) given to patients with idiopathic macular hole (IMH) results in an altered plane of vitreoretinal (VR) separation compared to patients without OCP exposure. A prospective study was done of 12 patients with IMH and vitreomacular adhesion (VMA) given OCP. Patients in whom the IMH failed to close underwent vitrectomy with peeling of the internal limiting membrane (ILM). The intraoperative staining pattern of the ILM using Brilliant Blue G (BBG) and examination of the excised ILM with transmission electron microscopy (TEM) were compared to results of a matched cohort of 31 patients with IMH who had not received OCP. Among 12 patients treated with OCP, VMA release occurred in 7 (58%) and hole closure was achieved in 3 (25%). Vitrectomy was done on the nine patients without hole closure. In seven of these nine (78%) the ILM had less than 5% of its vitreous surface covered in residual material on TEM, which was significantly less than in the control group (5/31, 16%, P = 0.001). In two OCP patients, large amounts of vitreous side material were present, but the rim of the hole stained evenly with BBG, suggesting that epiretinal material had avulsed with VR separation, a pattern not seen in any of the control patients. All patients had IMH closure after vitrectomy and visual results were not significantly different from the control group. Ocriplasmin facilitates more complete VR separation in patients undergoing surgery for IMH, although it does not result in more eccentric epiretinal tissue release.

Transient vision loss after ocriplasmin injection.

Transient vision loss is a poorly understood complication of ocriplasmin injection. The authors performed a retrospective medical records review of consecutive patients who received ocriplasmin for the treatment of vitreomacular adhesion at The George Washington University Department of Ophthalmology and the Virginia Retinal Center from January 1, 2013, to March 1, 2014, and who had at least 28 days of follow-up. Ellipsoid zone loss on optical coherence tomography was analyzed using the National Institutes of Health's Medical Imaging, Processing, Analysis, and Visualization (MIPAV) software. Ten patients received ocriplasmin injection. Three of the 10 patients (30%) had release of vitreomacular adhesion, and 8 of the 10 (80%) experienced vision loss within the first month. Average baseline visual acuity was 66 Early Treatment Diabetic Retinopathy Study letters. Average visual acuity at Weeks 1, 2, 3, and 4 was 62, 43, 57, and 56 Early Treatment Diabetic Retinopathy Study letters, respectively. Average final visual acuity was 58 Early Treatment Diabetic Retinopathy Study letters. Ellipsoid loss occurred in 5 patients and reached a nadir (-36.9% decrease from baseline) 2 weeks later. Vision loss after ocriplasmin occurred in the majority of patients and was correlated with loss of the ellipsoid layer on optical coherence tomography. More data are needed to analyze this side effect.

Clinical evaluation of ocriplasmin as a vitreolytic agent

Incomplete perifoveal posterior vitreous detachment (PVD) associated with abnormal vitreomacular adhesion (VMA) can cause vitreomacular traction (VMT) and macular hole (MH) formation, which require vitrectomy treatment. Pharmacologic vitreolysis, which is intravitreal injection with vitreolytic enzymes to resolve VMA, may be used as an alternative therapy.Ocriplasmin, formerly known as microplasmin, is a recombinant truncated form of plasmin with proteolytic activity against fibronectin and laminin.It was recently approved for VMA treatment in the European Union and USA. Phase III studies indicated that ocriplasmin injection was a safe and effective treatment for selected cases of symptomatic VMA and MH. VMA release was achieved in 26.5% of ocriplasmin-injected eyes versus 10.1% of the placebo group. MH closure was achieved in 40.6% as compared with 10.6% of the placebo group.In comparison with the outcome after vitrectomy, the success rate of ocriplasmin was still far below expectation. Ocular adverse events included vitreous floaters, photopsia and profound visual decline. Its efficacy and safety need to be further evaluated in more clinical trials.

Early evolution of the vitreomacular interface and clinical efficacy after ocriplasmin injection for symptomatic vitreomacular adhesion.

To determine early evolution of the vitreomacular interface and clinical efficacy and safety profile after ocriplasmin treatment. Retrospective, multicenter, observational case series. Patients with vitreomacular adhesion (VMA) confirmed on optical coherence tomography (OCT) received a single intravitreal ocriplasmin injection. Changes in the vitreomacular interface were evaluated by spectral-domain OCT. Adverse events were monitored at all visits. Of 22 patients treated with ocriplasmin, 14 (64%) had VMA resolution, with six (43%) achieving VMA release within the first week. Eight patients (36%) showed improvement in visual acuity (VA) of at least two Snellen lines. Rate of VMA resolution was 79% for VA less than 20/40 and 38% for VA of 20/40 or greater. Safety findings include changes in the ellipsoid layer (n = 3) and transient increases in subretinal fluid (n = 6). Ocriplasmin was effective for VMA resolution, with a rapid onset of action. Patients with worse baseline VA showed a higher VMA resolution rate.

Safety of Intravitreal Ocriplasmin for Focal Vitreomacular Adhesion in Patients with Exudative Age-Related Macular Degeneration

The evaluation of the safety and preliminary efficacy of 125 μg ocriplasmin intravitreal injection in patients with focal vitreomacular adhesion (VMA) and exudative age-related macular degeneration (AMD). Randomized, sham-injection controlled, double-masked, multicenter, phase II trial. A total of 100 patients with VMA and wet AMD were randomized 3:1 to receive 125 μg ocriplasmin intravitreal injection or sham injection. Study treatment was administered in the mid-vitreous cavity by injection. Post-treatment safety and efficacy assessments were made at baseline and on days 7, 14, and 28 and months 3, 6, and 12 after injection. Secondary efficacy end points were exploratory in nature. The safety and tolerability of ocriplasmin were evaluated. The primary efficacy end point was the proportion of patients with VMA release at day 28 after injection. Secondary end points reported included VMA release over time, total posterior vitreous detachment (PVD), change in visual acuity from baseline, and number of anti-vascular endothelial growth factor (VEGF) injections. The safety of ocriplasmin in patients with VMA and wet AMD was shown to be comparable to the known safety profile, with the majority of adverse events in the study eye occurring in the first 7 days after study treatment. A greater proportion of patients achieved VMA resolution and total PVD at month 12 with ocriplasmin compared with sham treatment. There was a decrease in the number of anti-VEGF injections with ocriplasmin at month 12 compared with the sham group, although no differences in visual acuity were observed. Ocriplasmin treatment in this population seems to be generally safe and well tolerated and resulted in more patients achieving VMA resolution and PVD with less anti-VEGF use compared with sham treatment.

Impact of Vitreomacular Adhesion on Ranibizumab Mono- and Combination Therapy for Neovascular Age-Related Macular Degeneration

To investigate the influence of vitreomacular adhesion on the efficacy of pro re nata (PRN) ranibizumab monotherapy and verteporfin photodynamic therapy (PDT) combination therapy for neovascular age-related macular degeneration. Post hoc analysis of prospective randomized 12-month multicenter clinical trial data. Total of 255 treatment-naïve patients with subfoveal choroidal neovascularization. Assessment of the vitreomacular interface on monthly optical coherence tomography with division of patients into the following categories according to continuous 1-year grading: posterior vitreous detachment (n=154), dynamic release of vitreomacular adhesion (n=32), stable vitreomacular adhesion (n=51). Mean best-corrected visual acuity (BCVA) letter and central retinal thickness changes at month 12 in the vitreomacular interface groups. Mean BCVA changes at month 12 were +3.5 (posterior vitreous detachment), +4.3 (release of vitreomacular adhesion), and +6.3 (vitreomacular adhesion) in patients receiving monotherapy (P=.767), and +0.1 (posterior vitreous detachment), +6.6 (release of vitreomacular adhesion), and +9.2 (vitreomacular adhesion) in patients receiving combination therapy (P=.009). Mean central retinal thickness changes were -113 μm (posterior vitreous detachment), -89 μm (release of vitreomacular adhesion), and -122 μm (vitreomacular adhesion) in monotherapy (P=.725) and -121 μm (posterior vitreous detachment), -113 μm (release of vitreomacular adhesion), and -113 μm (vitreomacular adhesion) in combination therapy (P=.924). Mean ranibizumab retreatments during 12 months were 4.9 (posterior vitreous detachment), 6.6 (release of vitreomacular adhesion), and 5.3 (vitreomacular adhesion) in monotherapy (P=.018) and 4.7 (posterior vitreous detachment), 5.2 (release of vitreomacular adhesion), and 5.8 (vitreomacular adhesion) in combination therapy (P=.942). This study adds evidence that the vitreomacular interface status impacts functional outcomes and retreatment requirements. Patients with posterior vitreous detachment achieve acceptable results with fewer injections in PRN monotherapy, but lose potential vision gain with PDT. Patients with other vitreomacular interface configurations may potentially achieve optimized vision outcomes by combination of antiangiogenic treatment and vaso-occlusive PDT.

Profile of ocriplasmin and its potential in the treatment of vitreomacular adhesion.

The recent approval by the US Food and Drug Administration of ocriplasmin for the treatment of symptomatic vitreomacular adhesion (VMA), often associated with vitreomacular traction (VMT) and macular hole (MH), has brought new attention to the field of pharmacologic vitreolysis. The need for an enzyme to split the vitreomacular interface, which is formed by a strong adhesive interaction between the posterior vitreous cortex and the internal limiting membrane, historically stems from pediatric eye surgery. This review summarizes the different anatomic classifications of posterior vitreous detachment or anomalous posterior vitreous detachment and puts these in the context of clinical pathologies commonly observed in clinical practice of the vitreoretinal specialist, such as MH, VMT, age-related macular degeneration, and diabetic macular edema. We revisit the outcome of the Phase II studies that indicated ocriplasmin was a safe and effective treatment for selected cases of symptomatic VMA and MH. Release of VMA at day 28 was achieved by 26.5% of patients in the ocriplasmin group versus 10.1% in the placebo group (P<0.001). Interestingly, for MHs, the numbers were more remarkable. Predictive factors for successful ocriplasmin treatment were identified for VMT (VMA diameter smaller than 1,500 μm) and MH (smaller than 250 μm). In comparison with the highly predictable outcome after vitrectomy, the general success rate of ocriplasmin not under clinical trial conditions has not fully met expectations and needs to be proven in real-world clinical settings. The ocriplasmin data will be compared in the future with observational data on spontaneous VMA release, will help retina specialists make more accurate predictions, and will improve outcome rates.