Efficacy and Safety of Ocriplasmin Use for Vitreomacular Adhesion and Its Predictive Factors: A Systematic Review and Meta-Analysis

Symptomatic vitreomacular adhesion (sVMA) impedes visual acuity and quality. Ocriplasmin is a recombinant protease, which may be injected into the vitreous cavity to treat this condition, yet controversy remains with respect to its effectiveness and safety, particularly its patient selection standard. In this systematic review, the PubMed, Embase, and the Cochrane Library were searched to identify studies published prior to August 2020 on the impact of ocriplasmin treatment on VMA release, macular hole (MH) closure, and/or related adverse events (AEs). Data were pooled using a random-effects model. Risk ratios (RRs) with 95% CIs were calculated. Of 1,186 articles reviewed, 5 randomized controlled trials and 50 cohort studies were ultimately included, representing 4,159 patients. Ocriplasmin significantly increased the rate of VMA release (RR, 3.61; 95% CI, 1.99–6.53; 28 days after treatment) and MH closure (RR, 3.84; 95% CI, 1.62–9.08; 28 days after treatment) and was associated with visual function improvement. No increased risk for overall AEs was seen in ocriplasmin treatment. The proportion of VMA release and MH closure in patients was 0.50 and 0.36, respectively. VMA release was more likely in patients with absence of epiretinal membrane (ERM). Patients with smaller MH diameter were more likely to achieve MH closure. Evidence from included studies suggests that ocriplasmin is a suitable and safe approach for treating sVMA. ERM and MH status are important factors when considering ocriplasmin treatment.

Ethical Concerns in Potentially Harmful Procedures in Ophthalmic Clinical Studies

Importance In clinical research, ethical principles and practice must be transparent, clearly defined and monitored. We believe that potentially harmful and non-beneficial interventions in diagnostic and placebo-controlled ophthalmology research should be avoided. We advise on alternative study designs and make recommendations for both researchers and research ethics committees. Observations We discuss the use of potentially harmful diagnostic interventions in clinical investigations, e.g., lumbar puncture in glaucoma patients, and sham saline solution injections in eyes with vitreomacular adhesion. In placebo-controlled research studies, patients in the control group commonly did not receive the standard of care for the condition under consideration, e.g., antiglaucoma therapy in a glaucoma study, anti-vascular endothelial growth factor agents in neovascular age-related macular degeneration or central retinal vein occlusion. Testing new methods and treatments against no intervention control, especially invasive placebo, rather than the usual standard of care, where one exists should not be recommended. Conclusions/Relevance Invasive and potentially harmful procedures in ophthalmology can be replaced by alternative non-invasive techniques or by an analysis of patients undergoing the procedure of interest for other purposes.

The role of intraocular hydrodynamics in inducing posterior hyaloid membrane detachment (preliminary report)

At present, it is believed that the detachment of the vitreous body occurs due to the contraction and liquefaction of the vitreous body, while the exit of the liquid part of the vitreum into the retrovitreal space passes passively through the formed prepapillary opening, after which the vitreous body collapses, however, more precise mechanisms have not been described. Purpose. Substantiate a hypothesis of influence of intravitreal hydrodynamics in inducing detachment of the posterior hyaloid membrane based on the analysis of OCT data. Material and methods. An OCT study was performed in 30 patients with initial detachment of the posterior hyaloid membrane (PHM) with macular adhesion, macular traction, and macular hole. The features of the location of the PHM in the region of the macula, foveola and the place of attachment of the PHM to the optic nerve were studied. Results and discussion. As a result of the analysis of OCT images, it was found that with macular holes, macular adhesion and macular traction, a closed space is formed between the posterior hyaloid membrane and the retina (subbursal space) in the form of a dome, which indirectly indicates an increase in pressure within this space. In 28 patients, the zone of dissection or thinning of the PHM was found parapapillary, through which the intraocular fluid is likely to be injected into the subbursal space. Conclusions: This study suggests the leading role of intravitreal hydrodynamics and the formation of an area of increased pressure in the subbursal space in the induction of the detachment of the PHM, the pathogenesis of vitreomacular adhesion, vitreomacular traction and macular hole. The topic requires more detailed study. Key words: posterior hyaloid membrane, OCT, vitreous body, macular hole.

Post hoc analysis of ellipsoid zone changes beyond the central subfield in symptomatic vitreomacular adhesion patients from the OASIS trial

Background/aimsOASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.Methods220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.ResultsA total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.ConclusionsOcriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.Trial registration numberNCT01429441

Epiretinal membrane appearance or progression after intravitreal injection in age-related macular degeneration

Background The purpose of this study is to evaluate the influence of anti-vascular endothelial growth factor (VEGF) in the appearance or progression of epiretinal membranes (ERMs) in age-related macular degeneration (ARMD) and investigate confounding factors causing ERMs. Methods Seventy-six eyes that were treated for more than 36 months from the first anti-VEGF injection were assessed. Binary logistic regression analysis was performed between smoking, lens status, subretinal hemorrhage, posterior vitreous detachment (PVD) status, peripheral retinal degeneration, type of AMD, conditions of contralateral eye, and the number of injections as independent variables and appearance or progression of ERMs during 36 months as dependent variables. Results The presence of vitreomacular adhesion (VMA) or development of PVD during the observation period was significantly associated (Odds ratio [OR]: 5.77; 95% confidence interval [CI], 1.72–19.4; p = 0.005) with the appearance or progression of ERMs. Moreover, peripheral retinal degeneration was significantly associated (OR: 3.87; 95% CI, 1.15–13.0; p = 0.029). Injection number of anti-VEGF was not significantly associated (OR: 1.02; 95% CI, 0.90–1.16; p = 0.72). Conclusion This study suggests possibilities that anti-VEGF injections alone are unable to cause the development of ERMs, that VMA or developing PVD has a prior impact on the developing ERMs in ARMD similar to that of idiopathic ERMs, and that peripheral retinal degenerations and vitreomacular adhesion were both related to ERMs development and pathogenesis of ARMD.

Optical Coherence Tomography Predictors of Favorable Functional Response in Naïve Diabetic Macular Edema Eyes Treated with Dexamethasone Implants as a First-Line Agent

Purpose. To evaluate efficacy and safety of intravitreal dexamethasone 0.7 mg implant in treatment-naïve DME patients and to assess the utility of OCT structural biomarkers as predictors of functional response after treatment. Methods. Thirty-nine eyes of 39 diabetic patients with center involving DME were enrolled. Best-corrected visual acuity (BCVA) and SS-OCT (DRI SS-OCT Triton, Topcon, Japan) to evaluate central retinal thickness (CRT), serous retinal detachment (SRD), intraretinal cysts (IRC), number of hyper-reflective spots (HRS), integrity of the ellipsoid zone (EZ), disorganization of the inner retinal layers (DRIL), vitreomacular adhesion (VMA), vitreomacular traction (VMT), and posterior vitreous detachment (PVD) were evaluated at baseline and at 3, 6, and 12 months after treatment. Multiple logistic analysis was performed to evaluate the possible OCT biomarker as predictive factors for final visual acuity improvement at the end of treatment. Results. At 12 months after treatment, the mean BCVA improved from 51.6 ± 17.5 to 56.9 ± 17.3 ETDRS letters ( p = 0.03 ). Furthermore, there were statistically significant changes in CRT, IRC, HRS, and SRD. Nineteen patients presented a >10-letters improvement in BCVA; the presence of SRD at baseline was a predictor of good functional treatment response at 12 months (OR 2.1; 95% C.I. 1.2–4.9; p = 0.001 ) as well as the presence of EZ integrity preoperatively (OR 1.3; 95% C.I. 0.5–2.4; p = 0.001 ) and the absence of vitreoretinal interface alteration (OR 1.1; 95% C.I. 0.3–2.3; p = 0.02 ). No significant changes in the IOP and lens status were observed throughout the follow-up period. Conclusion. This study empathized the importance of structural biomarkers as predictors of favorable response and confirmed the efficacy and safety of intravitreal dexamethasone implant in treatment-naïve DME patients showing a better functional response in the presence of SRD integrity of EZ and absence of vitreoretinal alterations.

Vitreomacular interface after anti-VEGF injections in diabetic macular edema

Background The 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. Results The 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). Conclusions VMA 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

Purpose: To 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. Methods: Patients with symptomatic VMA and FTMH at baseline and receiving ocriplasmin treatment 125