Influence of vitreomacular interface score on treatment outcomes of anti-VEGF therapy for neovascular age-related macular degeneration.
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ABSTRACT: Background
To quantitatively evaluate the vitreomacular interface of eyes with neovascular age-related macular degeneration (AMD) and to investigate its association with the 1-year treatment outcome following intravitreal injections of aflibercept (IVA).Methods
This prospective observational case series included 59 eyes of 59 consecutive patients with treatment-naïve neovascular AMD who were treated with three monthly IVA and subsequent four bi-monthly IVA and were followed up for 1 year. We estimated posterior vitreous detachment at 1, 9, and 25 macular points within an area of 6 × 6 mm2 at the center of the fovea using the built-in enhanced vitreous visualization mode of swept-source optical coherence tomography. One year after the initial IVA, we classified the eyes into either wet or dry groups.Results
The wet and dry groups included 12 and 47 eyes, respectively. The resistance rate against IVA was 20.3%. The 25-point interface score was higher in the wet group than in the dry group (23.0 ± 4.3 vs. 18.6 ± 9.8, P = 0.03), whereas there were no significant between-group differences in the 9-point and 1-point scores (P = 0.21, and 0.47, respectively) or in the other studied parameters. Multivariable analysis revealed that the 25-point vitreomacular interface score was strongly correlated with subfoveal choroidal thickness (P = 0.02, β = - 0.31).Conclusions
Our findings suggest that wide-ranged separation of the posterior vitreous membrane from the retina induces poor response to IVA.
SUBMITTER: Miyata M
PROVIDER: S-EPMC8690868 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.
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Project description:The retinal world has been revolutionized by optical coherence tomography (OCT) and anti-vascular endothelial growth factor (VEGF) therapy. The numbers of intravitreal injections are on a constant rise and management in neovascular age-related macular degeneration (nAMD) is mainly driven by the qualitative assessment of macular fluid as detected on OCT scans. The presence of macular fluid, particularly subretinal fluid (SRF) and intraretinal fluid (IRF), has been used to trigger re-treatments in clinical trials and the real world. However, large discrepancies can be found between the evaluations of different readers or experts and especially small amounts of macular fluid might be missed during this process. Pixel-wise detection of macular fluid uses an entire OCT volume to calculate exact volumes of retinal fluid. While manual annotations of such pixel-wise fluid detection are unfeasible in a clinical setting, artificial intelligence (AI) is able to overcome this hurdle by providing real-time results of macular fluid in different retinal compartments. Quantitative fluid assessments have been used for various post hoc analyses of randomized controlled trials, providing novel insights into anti-VEGF treatment regimens. Nonetheless, the application of AI-algorithms in a prospective patient care setting is still limited. In this review, we discuss the use of quantitative fluid assessment in nAMD during anti-VEGF therapy and provide an outlook to novel forms of patient care with the support of AI quantifications.
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Project description:ObjectiveTo 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).DesignProspective cohort study within a multicenter, randomized clinical trial.ParticipantsPatients enrolled in the Comparison of AMD Treatments Trials (CATT).MethodsTreatment 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.Main outcome measuresAnatomic features and VA at baseline and 1 and 2 years and number of treatments.ResultsAt 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).ConclusionsIn 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.
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Project description:We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = -0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P < 0.001) and IL-10 (β coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.
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Project description:PurposeNo established biomarkers currently exist for therapeutic efficacy and durability of anti-VEGF therapy in neovascular age-related macular degeneration (nAMD). This study evaluated radiomic-based quantitative OCT biomarkers that may be predictive of anti-VEGF treatment response and durability.DesignAssessment of baseline biomarkers using machine learning (ML) classifiers to predict tolerance to anti-VEGF therapy.ParticipantsEighty-one participants with treatment-naïve nAMD from the OSPREY study, including 15 super responders (patients who achieved and maintained retinal fluid resolution) and 66 non-super responders (patients who did not achieve or maintain retinal fluid resolution).MethodsA total of 962 texture-based radiomic features were extracted from fluid, subretinal hyperreflective material (SHRM), and different retinal tissue compartments of OCT scans. The top 8 features, chosen by the minimum redundancy maximum relevance feature selection method, were evaluated using 4 ML classifiers in a cross-validated approach to distinguish between the 2 patient groups. Longitudinal assessment of changes in different texture-based radiomic descriptors (delta-texture features) between baseline and month 3 also was performed to evaluate their association with treatment response. Additionally, 8 baseline clinical parameters and a combination of baseline OCT, delta-texture features, and the clinical parameters were evaluated in a cross-validated approach in terms of association with therapeutic response.Main outcome measuresThe cross-validated area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were calculated to validate the classifier performance.ResultsThe cross-validated AUC by the quadratic discriminant analysis classifier was 0.75 ± 0.09 using texture-based baseline OCT features. The delta-texture features within different OCT compartments between baseline and month 3 yielded an AUC of 0.78 ± 0.08. The baseline clinical parameters sub-retinal pigment epithelium volume and intraretinal fluid volume yielded an AUC of 0.62 ± 0.07. When all the baseline, delta, and clinical features were combined, a statistically significant improvement in the classifier performance (AUC, 0.81 ± 0.07) was obtained.ConclusionsRadiomic-based quantitative assessment of OCT images was shown to distinguish between super responders and non-super responders to anti-VEGF therapy in nAMD. The baseline fluid and SHRM delta-texture features were found to be most discriminating across groups.
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Project description:PurposeTo assess the influence of time interval since last injection and time from baseline on central retinal thickness (CRT) in neovascular age-related macular degeneration (nAMD) with fluid refractory to monthly anti-VEGF treatment.MethodsThis retrospective study included nAMD eyes with incomplete response to anti-VEGF defined by the presence of intra- or subretinal fluid on optical coherence tomography despite maximal (monthly) anti-VEGF dosing. The outcome measure was CRT, and two time variables (time from last injection ant time from baseline) were the independent factors included in the individual correlation analyses. In addition, an association analysis was performed.ResultsSixty eyes of 56 patients (67.9% females, mean age: 78.7 ± 6.8 years) were included with a mean included time period of 35.6 months. A significant positive correlation between CRT and the time from last injection occurred in 24 (40%) and 25 (42%) eyes by univariate and multivariate analysis, respectively. Time from baseline was significantly correlated with CRT in 29 (48.3%) and 30 (50%) eyes by univariate and multivariate analysis, respectively. This correlation was positive in 12 (20%) and negative in 18 eyes (30%). No association with such correlation was found.ConclusionSo-called refractory nAMD frequently shows a correlation of CRT with the interval in days from the preceding anti-VEGF injection, revealing that there is a subgroup of short-term responsiveness of the residual fluid. Moreover, slower CRT changes may occur over the years, either decrease or increase. In case of a slow CRT increase, this might require a diagnostic workup and therapeutic change.
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