Dataset Information

Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration.

ABSTRACT: We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (n = 129) and polypoidal choroidal vasculopathy (n = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), SKIV2L-C2-CFB (rs429608), C3 (rs2241394), ADAMTS-9 (rs6795735) and CETP (rs3764261) was performed for all participants. A total of 63 PRSs were quantified. There was a positive association between the PRS involving ARMS2, CFH, C3, and ADAMTS-9 and best-corrected visual acuity at twelve months (p = 0.046, multiple regression analysis). When comparing PRSs of patients requiring retreatment and of patients without retreatment, 35 PRSs were significantly greater in patients requiring retreatment than in patients without requiring retreatment, with the PRS involving ARMS2 and CFH being most significantly associated (p = 1.6 × 10-4). The number of additional injections was significantly associated with 40 PRSs and the PRS involving ARMS2 and CFH showed a most significant p-value (p = 2.42 × 10-6). Constructing a PRS using a combination with high-risk variants might be informative for predicting the response to IAI for exudative AMD.

SUBMITTER: Shijo T

PROVIDER: S-EPMC7559528 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration.

Shijo Taiyo T Sakurada Yoichi Y Yoneyama Seigo S Kikushima Wataru W Sugiyama Atsushi A Matsubara Mio M Fukuda Yoshiko Y Mabuchi Fumihiko F Kashiwagi Kenji K

Pharmaceuticals (Basel, Switzerland) 20200920 9

We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (<i>n</i> = 129) and polypoidal choroidal vasculopathy (<i>n</i> = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotypin ...[more]

PMID: 32962278

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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.

Project description:BackgroundAnti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD.MethodsTwo clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included.ResultsMean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity.ConclusionLong-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy.Trial registrationsVIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

Dataset Information

Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration.

Publications

Association between Polygenic Risk Score and One-Year Outcomes Following As-Needed Aflibercept Therapy for Exudative Age-Related Macular Degeneration.

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