Five-Year Outcome of Aflibercept Monotherapy for Exudative Age-Related Macular Degeneration with Good Baseline Visual Acuity.
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SUBMITTER: Kikushima W
PROVIDER: S-EPMC7961756 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Purpose:We report the 2-year outcomes of intravitreal aflibercept (IVA) for exudative age-related macular degeneration (AMD) with good visual acuity (VA) and examine the baseline factors associated with good visual outcome. Materials and methods:This multicenter, prospective study evaluated 39 eyes (39 AMD patients) enrolled from August 2013 to August 2014 at 12 and 24 months. Only patients with initial best-corrected VA (BCVA) >0.3 logarithm of the minimum angle of resolution (20/40 Snellen) were eligible. Three consecutive monthly IVA injections were followed by 2 monthly injections for 12 months. Thereafter, patients received injections on a treat- and-extend regimen for up to 24 months. Outcome measures included BCVA and central macular thickness (CMT) at 12 and 24 months. Post hoc analysis, BCVA, and CMT were evaluated by AMD types (typical AMD [tAMD], type 1, and type 2 polypoidal choroidal vasculopathy [PCV]). Baseline characteristics and BCVA associations were evaluated with linear regression analysis and Student's t-test. Results:Mean age was 69 years and 26 of 39 eyes were male. tAMD, type 1 and type 2 PCV occurred in 18, 12, and 9 eyes, respectively. Baseline mean BCVA was 0.097 logarithm of the minimum angle of resolution (20/25 Snellen) and showed significant improvement to 0.058 (20/22 Snellen, P=0.03) at 12 months and 0.066 (20/23) at 24 months. CMT improved significantly from 320 (99) µm (mean [SD]) to 250 (93) µm (P=0.002) at 12 months and 240 (93) µm (P=0.0005) at 24 months. BCVA and CMT were not significantly different among the three groups. Only subretinal hemorrhage (SRH) was significantly associated with improved BCVA. BCVA change from baseline was -0.12 with SRH and -0.011 without SRH (P=0.017) at 12 months. Conclusion:IVA showed good efficacy for exudative AMD with good VA at 24 months. tAMD and type 1 and 2 PCV showed similar prognosis. Baseline SRH predicted favorable long-term vision in AMD with good VA.
| S-EPMC6022819 | biostudies-literature
Project description:BackgroundTo determine the safety and efficacy of intravitreal sirolimus and adjunct aflibercept in subjects with persistent, exudative age-related macular degeneration despite previous intravitreal anti-vascular endothelial growth factor (VEGF) treatment.MethodsThis institutional review board approved, registered (NCT02732899), prospective, subject-masked, single center, randomized controlled trial in subjects with persistent, exudative age-related macular degeneration compared alternating monthly intravitreal sirolimus and aflibercept (combination) versus aflibercept monotherapy (control) every 2 months over the course of 36 weeks. The primary measure of efficacy in the study was the mean change in central subfield thickness.Results20 subjects were enrolled in the study, with 10 subjects assigned to each treatment group. Subjects had an average of 38 previous anti-VEGF injections. Mean central subfield thickness decreased in the combination group by 54.0 μm compared to 0.1 μm in the control group (p = 0.28). Mean visual acuity improved in the combination group by 2.5 ETDRS letters versus 0.8 ETDRS letters in the control group (p = 0.42). There were no serious ocular adverse events in either group; however, there were three serious systemic events in the combination group, including hospitalizations due to pancreatitis, pneumonia, and worsening hypertension.ConclusionThere was no statistically significant difference in the mean central subfield thickness change between the combination and control groups. However, intravitreal sirolimus with adjunct aflibercept did appear to have potential anatomical benefits as a treatment for persistent, exudative age-related macular degeneration and requires further investigation with a larger cohort to better understand the potential risks and benefits.Trial registrationClinicalTrials.gov, NCT02732899. Registered 11 March 2016, https://clinicaltrials.gov/ct2/show/NCT02732899 . This trial was approved by the institutional review board at Advarra. Funding was provided by an investigator-initiated grant from Santen. Santen played no role in the design or implementation of this study.
| S-EPMC9814330 | biostudies-literature
Project description:Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD) causes more severe visual acuity (VA) loss compared with the dry form due to formation of choroidal neovascularization (CNV). Antivascular endothelial growth factor (anti-VEGF) agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders. This article aims to discuss the baseline factors associated with VA outcome such as age, initial VA, lesion types, disease duration, optical coherence tomography (OCT) features, fundus autofluorescence findings, and the presence of particular genotype risk alleles in patients with wAMD. Recommendations are provided regarding when to consider discontinuation of therapy because of either success or futility. Understanding the predictive factors associated with VA outcome and treatment frequency response to anti-VEGF therapy may help retina specialists to manage patients' expectations and guide treatment decisions from the beginning of treatment on the basis of "personalized medicine."
| S-EPMC5846359 | biostudies-literature
Project description:PurposeTo evaluate associations of morphologic features with 5-year visual acuity (VA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT).DesignCohort study within a randomized clinical trial.ParticipantsParticipants in CATT.MethodsEyes with age-related macular degeneration-associated choroidal neovascularization (CNV) and VA between 20/25 and 20/320 were eligible. Treatment was assigned randomly to ranibizumab or bevacizumab and to 3 dosing regimens for 2 years and was at the ophthalmologists' discretion thereafter.Main outcome measuresVisual acuity, thickness and morphologic features on OCT, and lesion size and foveal composition on fundus photography (FP) and fluorescein angiography (FA).ResultsVisual acuity and image gradings were available for 523 of 914 participants (57%) alive at 5 years. At 5 years, 60% of eyes had intraretinal fluid (IRF), 38% had subretinal fluid (SRF), 36% had subretinal pigment epithelium (RPE) fluid, and 66% had subretinal hyper-reflective material (SHRM). Mean (standard deviation) foveal center thickness was 148 μm (99) for retina, 5 μm (21) for SRF, 125 μm (107) for subretinal tissue complex, 11 μm (33) for SHRM, and 103 μm (95) for RPE + RPE elevation. The SHRM, thinner retina, greater CNV lesion area, and foveal center pathology (all P < 0.001) and IRF (P < 0.05) were independently associated with worse VA. Adjusted mean VA letters were 62 for no pathology in the foveal center; 61 for CNV, fluid, or hemorrhage; 65 for non-geographic atrophy (GA); 64 for nonfibrotic scar; 53 for GA; and 56 for fibrotic scar. Incidence or worsening of 8 pathologic features (foveal GA, foveal scar, foveal CNV, SHRM, foveal IRF, retinal thinning, CNV lesion area, and GA area) between years 2 and 5 was independently associated with greater loss of VA from years 2 to 5 and VA loss from baseline to year 5.ConclusionsAssociations between VA and morphologic features previously identified through year 1 were maintained or strengthened at year 5. New foveal scar, CNV, intraretinal fluid, SHRM and retinal thinning, development or worsening of foveal GA, and increased lesion size are important contributors to the VA decline from years 2 to 5. A significant need to develop therapies to address these adverse pathologic features remains.
| S-EPMC6462189 | biostudies-literature
Project description:PurposeTo evaluate the 6-month safety and efficacy of ziv-aflibercept intravitreal injections for treating exudative age-related macular degeneration.MethodsFifteen patients with unilateral exudative age-related macular degeneration were enrolled. The best-corrected visual acuity was measured and spectral domain optical coherence tomography was performed at baseline and monthly. Full-field electroretinography and multifocal electroretinography were obtained at baseline and 4, 13, and 26 weeks after the first injection. All patients received three monthly intravitreal injections of ziv-aflibercept (1.25 mg) followed by as-needed treatment.ResultsBetween baseline and 26 weeks, the mean logMAR best-corrected visual acuity improved (P = 0.00408) from 0.93 ± 0.4 (20/200) to 0.82 ± 0.5 (20/160) logarithm of the minimum angle of resolution, respectively; the central retinal thickness decreased significantly (P = 0.0007) from 490.3 ± 155.1 microns to 327.9 ± 101.5 microns; the mean total macular volume decreased significantly (P < 0.0001) from 9.51 ± 1.36 mm to 8.08 ± 1.34 mm, and the a-wave implicit time increased, with no differences in the other full-field electroretinography parameters. The average multifocal electroretinography macular responses within the first central 15° showed significantly (P < 0.05) increased P1 amplitudes at 26 weeks. No systemic or ocular complications developed.ConclusionIntravitreal ziv-aflibercept significantly improved the best-corrected visual acuity, multifocal electroretinography amplitudes, central retinal thickness, and total macular volume from baseline to 26 weeks. No retinal toxicity on full-field electroretinography or adverse events occurred during the follow-up period.
| S-EPMC5549635 | biostudies-literature
Project description:ImportanceComparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment.ObjectiveTo provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography.Design, setting, and participantsPost hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015.InterventionsRepeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol.Main outcomes and measuresOne-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 µm) or thinner (250 to 399 µm) CST.ResultsIn the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17% to 60%) for aflibercept vs bevacizumab, 25% (5% to 46%) for ranibizumab vs bevacizumab, and 13% (-8% to 35%) for aflibercept vs ranibizumab.Conclusions and relevanceThese post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients.Trial registrationclinicaltrials.gov Identifier: NCT01627249.
| S-EPMC5567793 | biostudies-literature
Project description:PurposeTo explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study.MethodsOutcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study.ResultsThe mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF.ConclusionIVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not.Trial registrationClinicalTrials.gov Identifier: NCT02305238.
| S-EPMC8589769 | biostudies-literature
Project description:IntroductionTo evaluate the effect of a 9-week treatment deferral due to healthcare restrictions caused by Austria's first governmental lockdown associated with the coronavirus disease 2019 (COVID-19) pandemic on visual acuity (VA) in eyes compromised by exudative neovascular age-related macular degeneration (nAMD) after 1 year.MethodsRetrospective data collection of 98 eyes (98 patients) with a treatment discontinuation at a tertiary eye care center (Clinic Landstraße, Vienna Healthcare Group, Austria) between March 16 and May 4, 2020. Prior to the lockdown, patients received multiple intravitreal injections (IVI) of anti-vascular endothelial growth factor with a personalized treatment interval for 3 years on average and at least three IVI after the lockdown.ResultsWhen the treatment interval doubled to 117.6 ± 31.4 days in spring 2020, patients lost 2.2 ± 4.6 ETDRS letters (p = 0.002) on average before reinitiating therapy. In total, 4.1 ± 8.1 letters (p < 0.0001) were lost despite continuous individual re-treatment over the course of the next year. In a univariate analysis, the extended interval time remained statistically significant (p < 0.0001), indicating a larger VA reduction within intervals with increasing interval time in days.ConclusionThe short-term treatment interruption had a persistent negative impact on the VA course of eyes under therapy after 1 year. Continuous therapy independent of the underlying treatment regimen remains of utmost importance in exudative nAMD. Our data should create awareness to regulators regarding future decisions despite the global pandemic.
| S-EPMC8351565 | biostudies-literature
Project description:Though anti-vascular endothelial growth factor therapy has become the standard treatment for exudative age-related macular degeneration (AMD), retreatment after the initial loading injection is inevitable in most eyes with residual or recurrent exudative changes. In the present study, we studied 140 treatment naïve eyes with typical neovascular AMD (n = 71) or polypoidal choroidal vasculopathy (PCV) (n = 69) and investigated the incidence and risk factors of retreatment after 3-monthly intravitreal aflibercept injection for exudative AMD during the 12-month period. At 12 months, best-corrected visual acuity (BCVA) improved significantly from 0.45 ± 0.39 to 0.26 ± 0.33 (P = 4.1 × 10-11). Multiple regression analysis revealed that better baseline BCVA (P = 3.6 × 10-14) and thicker subfoveal choroidal thickness (P = 0.039) were associated with better BCVA at 12-months. Retreatment was required in 94 out of 140 (67.1%) eyes. Multivariate logistic regression analysis revealed that older age (P = 7.2 × 10-3) and T-allele of ARMS2 A69S (rs10490924) variants (P = 1.9 × 10-3) were associated with retreatment. Cox-regression analysis revealed that older age (P = 1.0 × 10-2) and T-allele of the ARMS2 gene (P = 6.0 × 10-3) were associated with retreatment-free period. The number of retreatment episodes was significantly different among the ARMS2 genotypes (P = 8.1 × 10-4). These findings might be helpful for physicians when considering the optimal treatment regimen for exudative AMD.
| S-EPMC5339812 | biostudies-literature
Project description:ObjectiveTo describe the effects of treatment for 1 year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity (VA) in eyes with neovascular age-related macular degeneration (AMD).DesignProspective cohort study within a randomized clinical trial.ParticipantsParticipants in the Comparison of Age-related Macular Degeneration Treatments Trials.MethodsParticipants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as-needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and VA testing were performed periodically throughout 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes.Main outcome measuresFluid type and location and thickness by OCT, size, and lesion composition on FP, FA, and VA.ResultsIntraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and retinal, subretinal, and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks, and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 μm) or thick (>212 μm) retinas had worse VA than those with normal thickness (120-212 μm). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features.ConclusionsAnti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA. Monthly ranibizumab dosing yielded more eyes with no fluid and an abnormally thin retina, although the long-term significance is unknown. These results have important treatment implications in eyes undergoing anti-VEGF therapy for neovascular AMD.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.
| S-EPMC3737287 | biostudies-literature