Spectrum of morphological and visual changes due to vitreomacular interface disorders encountered in a large consecutive cohort of patients.
ABSTRACT: Identify the incidence of vitreomacular traction (VMT) and frequency of reduced vision in the absence of other coexisting macular pathology using a pragmatic classification system for VMT in a population of patients referred to the hospital eye service.A detailed survey of consecutive optical coherence tomography (OCT) scans was done in a high-throughput ocular imaging service to ascertain cases of vitreomacular adhesion (VMA) and VMT using a departmental classification system. Analysis was done on the stages of traction, visual acuity, and association with other macular conditions.In total, 4384 OCT scan episodes of 2223 patients were performed. Two hundred and fourteen eyes had VMA/VMT, with 112 eyes having coexisting macular pathology. Of 102 patients without coexisting pathology, 57 patients had VMT grade between 2 and 8, with a negative correlation between VMT grade and number of Snellen lines (r=-0.61717). There was a distinct cutoff in visual function when VMT grade was higher than 4 with the presence of cysts and sub retinal separation and breaks in the retinal layers.VMT is a common encounter often associated with other coexisting macular pathology. We estimated an incidence rate of 0.01% of VMT cases with reduced vision and without coexisting macular pathology that may potentially benefit from intervention. Grading of VMT to select eyes with cyst formation as well as hole formation may be useful for targeting patients who are at higher risk of visual loss from VMT.
Project description:BACKGROUND:SD-OCT is becoming commonplace in everyday practice. Vitreomacular adhesions (VMAs) are being more routinely diagnosed. Predictive studies to the natural course of VMA are thus clinically significant. Spectral domain-optical coherence tomography (SD-OCT) was presently utilized to analyze the incidence of floaters, the complete vitreomacular separation or VMA, the VMA complication, the vitreomacular angle (VMAng), and the complication mechanism. METHODS:Monthly SD-OCT was performed on patients with/without symptomatic floaters. OCT allowed VMA and vitreomacular separation to be compared. The incidence was assessed applying one-tailed Fisher's exact tests. The VMAngs between the inner retina and posterior hyaloid were measured, and the complication mechanism was studied using OCT image. For macular hole (MH), pre- and/or post-operative best corrected visual acuities (BCVAs; LogMAR), refractions and photoreceptor conditions were also evaluated. RESULTS:Totally, 124 eyes were included; there were 116 eyes with VMA and 8 eyes with vitreomacular separation. Considering the percentages over 124 eyes, floaters were present in 14.5% of enrolled eyes (=18/124), consisting of 12.9% of eyes with VMA (16/124) and 1.6% of eyes with vitreomacular separation (2/124). Moreover, there were twelve eyes (9.7%) with VMA-associated vision-threatening complications, including MH (n?=?8; 6.5%), retinal detachment (RD; n?=?2; 1.6%), vitreomacular traction (VMT; n?=?1; 0.8%) and macular pucker (MP; n?=?1; 0.8%). Eyes with initial VMA had a significantly greater possibility of complications than eyes with initial vitreomacular separation (p?=?0.03). Among these eyes with MH (n?=?8), the pre-operative BCVA (LogMAR) was 1.1?±?0.5, which was insignificantly (p?=?0.35) improved to 0.8?±?0.7 post-operatively. The VMAng of VMA eyes with MHs was 24.2?±?24.9° (n?=?8). The critical VMAng was 13.3°. CONCLUSIONS:A minority of eyes with VMA or vitreomacular separation had floaters. Moreover, the use of SD-OCT could identify vision-threatening sequelae, namely MH, RD, MP and VMT, and this was significantly more frequent in eyes with VMA than in eyes with complete vitreomacular separation. Therefore, SD-OCT might be a useful way of identifying either identity, and evaluating VMA-associated complications. Whether VMA eyes with MH (n?=?8) that have a VMAng greater than critical VMAng have a greater likelihood of tangential traction and subsequent MH needs further investigation.
Project description:To assess the association of the vitreomacular interface with outcomes of eyes treated with anti-vascular endothelial growth factor drugs for neovascular age-related macular degeneration (AMD).Prospective cohort study within a multicenter, randomized clinical trial.Patients enrolled in the Comparison of AMD Treatments Trials (CATT).Treatment was assigned randomly as either ranibizumab or bevacizumab and as 3 different regimens for dosing over a 2-year period. Masked readers at a reading center assessed optical coherence tomography (OCT) scans at baseline and follow-up for vitreomacular traction (VMT) and vitreomacular adhesion (VMA), fluid, and central thickness. Visual acuity (VA) was measured by masked, certified examiners.Anatomic features and VA at baseline and 1 and 2 years and number of treatments.At baseline, 143 patient eyes (12.8%) had VMT or VMA. Compared with those with neither (n = 972), patients with VMT or VMA were younger (mean ± standard error, 75.5 ± 0.6 vs. 79.7 ± 0.24 years; P < 0.0001) and more likely to be male (52.4% vs. 36.2%; P = 0.0003), to be cigarette smokers (68.5% vs. 55.3%; P = 0.003), and to have subretinal fluid on OCT (86.7% vs. 81.0%; P = 0.047). Vitreomacular interface status was not associated with VA at baseline or follow-up. Among eyes treated as needed (n = 598) and followed up for 2 years (n = 516), the mean number of injections was 15.4 ± 0.9 for eyes having VMT at baseline or during follow-up (n = 60), 13.8 ± 0.7 for eyes with VMA at baseline or follow-up (n = 79), and 12.9 ± 0.4 (P = 0.02) for eyes without VMT or VMA (n = 377). In addition, the mean number of injections in eyes treated as needed increased from 13.0 ± 0.3 when VMT was not observed to 13.6 ± 1.3 when observed once and to 17 ± 1.2 when observed more than once during follow-up. At 2 years, geographic atrophy developed in a lower percentage of eyes with VMT or VMA at baseline (11.7%) than with neither condition (22.5%; P = 0.005).In eyes in the CATT, VMT and VMA were infrequent. At baseline and follow-up, VMT or VMA were not associated with VA. Eyes with VMT or VMA treated as needed required on average 2 more injections over 2 years.
Project description: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 ?m) and MH (smaller than 250 ?m). 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.
Project description:PURPOSE:To evaluate the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with non-infectious uveitis. DESIGN:Phase 2 clinical trial PARTICIPANTS: Data from the Safety, Tolerability, and Efficacy of Tocilizumab in Patients with Non-infectious Uveitis (STOP-Uveitis) study was analyzed. METHODS:In the STOP-Uveitis study, patients with non-infectious uveitis (NIU) received monthly intravenous infusions of either 4 or 8?mg/kg tocilizumab until month 6 (M6). Spectral domain optical coherence tomography (SD-OCT) images of patients that completed M6 of the study were analyzed at baseline to stratify the patients by the presence (VMA+) or absence (VMA-) of VMA. Patients with vitreomacular traction (VMT) or epiretinal membrane causing structural abnormalities within center 1?mm were excluded. All images were graded by two independent graders. MAIN OUTCOME MEASURES:Mean change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and vitreous haze (VH) at M6. RESULTS:Out of 37 patients randomized in the STOP-Uveitis study, 48 eyes (27 patients) were eligible based on the study criteria. At baseline, 19 eyes were classified as VMA+, and 32 eyes were classified as VMA-. The distribution of two doses of TCZ (4?mg/kg and 8?mg/kg) were similar between the two groups. At M6, the mean improvement in BCVA was 2.00?±?5.3 and 6.50?±?7.98 letters in the VMA+ and VMA- groups, respectively (p?=?0.02). The mean improvement in CRT was 34.85?±?72.36 and 80.37?±?157.21??m in the VMA+ and VMA- groups, respectively (p?=?0.18). Similarly, the mean change in VH was -?0.65?±?0.47 and -?0.76?±?0.71 in the VMA+ and VMA- groups, respectively (p?=?0.32). Out of 16 eyes with VMA at baseline, 3 eyes developed posterior vitreous detachment (PVD) at M6. The mean change in BCVA was significantly higher (p =?0.02), while CRT and VH score were similar (p?>?0.05) in eyes with PVD compared to eyes with persistent VMA. CONCLUSIONS:The absence of VMA or development of PVD in eyes with VMA seems to have a beneficial effect on the vision of subjects receiving treatment for uveitis. Therefore, patients with uveitis should be assessed using SD-OCT for the presence of vitreomacular interface abnormalities.
Project description:BACKGROUND:If left untreated, vitreomacular traction (VMT) will infrequently improve through spontaneous resolution of vitreomacular adhesion (VMA), and patients remain at risk of further deterioration in vision. The mainstay of treatment for VMT is vitrectomy, an invasive procedure that carries the risk of rare but serious complications and further vision loss. As such, a 'watch and wait' approach is often adopted before this surgical intervention is performed. Ocriplasmin (microplasmin) is a potential alternative treatment for patients with symptomatic VMT that may remove the requirement for vitrectomy. OBJECTIVE:The purpose of this study was to evaluate the cost-effectiveness of ocriplasmin for the treatment of VMT in comparison to standard of care. STUDY DESIGN:A cohort-based computer simulation model was developed, capturing three mutually exclusive subgroups: 1) VMT without epiretinal membrane (ERM) or full thickness macular hole (FTMH), 2) VMT with ERM but no FTMH, and 3) VMT with FTMH. Transition probabilities between health states, utilities, and resource utilisation were estimated based on clinical trial results, the literature, and expert opinion. The cost per quality-adjusted life year (QALY) gained was estimated over a lifetime, using UK unit costs and utilities associated with visual acuity, adverse events, metamorphopsia, and surgical interventions. SETTING:Analyses were conducted from a UK payer perspective. POPULATION:Transition probabilities for the model were primarily estimated from patient-level data from the combined Phase 3 MIVI-TRUST trials in patients with symptomatic VMA/VMT, including when associated with a FTMH ?400 µm. INTERVENTION:Ocriplasmin (microplasmin) is a one-time intravitreal injection designed specifically to release the abnormal traction between the macula and the vitreous and thereby treat VMT, as well as macular hole with persistent vitreous attachment. MAIN OUTCOME MEASURE:The main outcome measure of the economic evaluation was cost per QALY. RESULTS:In all subgroups, ocriplasmin management generated more QALYs: 1) VMT without ERM or FTMH (0.105, (0.036, 0.191)); 2) VMT with ERM but no FTMH (0.041, (0.011, 0.131)); and 3) VMT with FTMH (0.053, (-0.002, 0.113)). The initial treatment costs were partially offset by later savings and net costs were estimated at £1,901 (£1,325, £2,474), £2,491 (£1,067, £2,511), and £1,912 (£1,233, £2,506), respectively. Costs per QALY were estimated at £18,056 (£8,241, £64,874), £61,059 (£8,269, £168,664), and £36,250 (-£144,788, £290,338), respectively. Short-term efficacy parameters were found to be key drivers of results. CONCLUSION:Ocriplasmin is most cost-effective in VMT patients without either ERM or FTMH.
Project description:PURPOSE:To evaluate the anatomical and functional outcomes with ocriplasmin in patients with vitreomacular traction (VMT) with or without macular hole (MH). METHODS:In a Phase 4, multicenter, single-arm, open-label study, eligible patients (VMT with focal adhesion, without epiretinal membrane, and with MH ?400 µm [if present]) received a single intravitreal injection of ocriplasmin. Nonsurgical resolution of VMT (Day 28 [primary endpoint]), best-corrected visual acuity, MH closure, vitrectomy rate, and safety were assessed through Day 180. RESULTS:Overall, 466 patients were included in the full analysis set, of whom 47.4% had VMT resolution by Day 28; resolution rates in patients with VMT without MH, VMT with MH ?250 µm, and VMT with MH >250 to ?400 µm were 43.4%, 68.6%, and 62.7%, respectively. Macular hole closure was higher in eyes with VMT and MH ?250 µm (57.1%) than in eyes with VMT and MH >250 to ?400 µm (27.5%) at Day 28. Overall, 30.8% of patients with VMT resolution gained ?10 letters in best-corrected visual acuity at Day 180. Adverse events were consistent with the known safety profile of ocriplasmin. CONCLUSION:Ocriplasmin is effective for resolution of VMT without or with MH (?400 ?m); treatment outcomes can be optimized with patient selection.
Project description:Vitreomacular traction is a multicategory entity that may cause substantial visual loss due to the formation of a macular hole or traction-induced tissue distortion. The advent of optical coherent tomography (OCT) has demonstrated the anatomic features of persistent vitreomacular attachment (VMA) more definitively, including in many asymptomatic or minimally symptomatic patients. The indications for intervention are unclear, since it is not possible to predict which eyes might be likely to develop progressive visual loss. This has been especially important since for many years, the only treatment option involved surgical intervention (vitrectomy) to release the persistent VMA. Recently, a pharmacolytic agent, ocriplasmin, has become available after many years of development and investigation, and may offer a feasible alternative to surgery, or even a risk/benefit ratio sufficiently favorable to offer intervention at an earlier stage of VMA. Several studies, including a large, prospective clinical trial, have established the foundation of its rationale and efficacy, providing the basis of its approval. The role for ocriplasmin in clinical practice is in the process of being determined. This paper summarizes current knowledge and status of investigations regarding ocriplasmin-induced pharmacologic vitreolysis, and offers some evidence-based considerations for its use.
Project description:Posterior vitreous detachment (PVD) is a common phenomenon in the aging eye. However, this may be complicated by persistent symptomatic vitreomacular adhesions that exert tractional forces on the macula (vitreomacular traction; VMT). VMT itself may be associated with epiretinal membrane formation and the development of idiopathic macular holes (IMH). Such pathologies may cause visual disturbances, including metamorphopsia, photopsia, blurred vision, and decreased visual acuity, which impact an individual's quality of life. Technologies such as optical coherence tomography allow an increasingly more accurate visualisation of the macular anatomy, including quantification of macular hole characteristics, and this facilitates treatment decision-making. Pars plana vitrectomy remains the primary treatment option for many patients with VMT or IMH; for the latter, peeling of the inner limiting membrane (ILM) of the retina has shown improved outcomes when compared with no ILM peeling. The development of narrow-gauge transconjunctival vitrectomy systems has improved the rate of visual recovery following surgery. Ocriplasmin, by degrading laminin and fibronectin at the vitreoretinal interface, may allow induction of PVD in a non-invasive manner. Indeed, clinical studies have supported its use as an alternative to surgery in certain patient populations. However, further research is still needed with respect to greater understanding of the pathophysiology underlying the development of VMT and IMH.
Project description:To evaluate the real world clinical outcomes of intravitreal ocriplasmin in patients with vitreomacular traction (VMT) with and without full thickness macular holes (FTMH) treated according to NICE guidance.Retrospective observational case series of 25 patients treated with a single intravitreal ocriplasmin injection between December 2013 and December 2015. Best corrected visual acuity and optical coherence tomography exams were performed to determine visual outcomes and anatomical VMT release and FTMH closure over time. Two patient groups were identified: ocular macular co-morbidity (OCM) and no OCM (nOCM), with follow-up at 4, 12, and 24 weeks.Twenty-five patients were identified that included 19 patients with VMT, and 6 patients with VMT plus FTMH. In the nOCM group of 22 patients, the release rate of VMT was 44%, 63%, and 69% at 4, 12 and 24 weeks respectively. In the "real-world" OCM group of 25 patients, the VMT release rate was 37%, 53%, and 58% at the same time-points. In both groups, the FTMH closure rate was 33%, 50%, and 67% at 4, 12, and 24 weeks. At mean follow-up of 30 weeks in the VMT group with nOCM, the mean LogMAR VA improved significantly from 0.44 to 0.28 (p = 0.0068, paired t-test). Three were no serious adverse events.This study reports improved efficacy of intravitreal ocriplasmin for both VMT and FTMH, and is more favourable in patients with no ocular co-morbidity. We highlight the importance of careful patient selection and structured standard of care pathways to identify patients who will benefit from the positive visual and anatomical effects of intravitreal ocriplasmin.
Project description:<h4>Objectives</h4>To report the prevalence and severity of metamorphopsia, estimate its impact on vision-related quality of life (VRQoL) and evaluate predictors of VRQoL in patients with vitreomacular traction (VMT).<h4>Patients and methods</h4>A prospective, cross-sectional multi-centre study in the United Kingdom of 185 patients with VMT, with or without a full thickness macular hole (FTMH). Self-reported metamorphopsia was determined using the metamorphopsia questionnaire. VRQoL was assessed using the Visual Function Questionnaire (VFQ-25). Physicians recorded clinical and ocular characteristics in both eyes including a physician assessment of metamorphopsia. ANOVA and predicted least-squares means were used to estimate the impact of metamorphopsia on VRQoL. Predictors of VRQoL were assessed using ordinary-least-squares regression adjusting for clinically important variables.<h4>Results</h4>The prevalence of self-reported metamorphopsia was 69.7% (95% CI 62.6-76.3%) and was higher in eyes with a concomitant FTMH vs. without FTMH (85.4% vs. 64.2%). Physician assessment of metamorphopsia was 53.0% (95% CI: 45.5-60.3%). Comparing eyes with metamorphopsia vs. without metamorphopsia, the VFQ-25 composite score was lower (82.3 vs. 91.4), and mean VA (LogMAR) was worse (0.44 vs. 0.33). The largest difference in VFQ-25 scores was observed for near activities (metamorphopsia: 75.3, No metamorphopsia: 90.2). The adjusted model showed that metamorphopsia severity and age were significantly associated with lower VFQ-25 scores.<h4>Conclusion</h4>Metamorphopsia was highly prevalent in patients with VMT and associated with significantly lower VRQoL. Physician assessment of symptoms underestimated the self-reported presence of metamorphopsia. Metamorphopsia severity acts as a predictor of impaired VRQoL, over and above decrements due to reduced vision.