Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes

Heier, Jeffrey S.; Brown, David M.; Shah, Sumit P; Saroj, Namrata; Dang, Sabin; Waheed, Nadia K.; Wykoff, Charles C.; Prenner, Jonathan L.; Boyer, David S.

doi:10.1001/jamaophthalmol.2021.0221

Cited by 24 publications

(16 citation statements)

References 11 publications

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“… 39 , 40 Furthermore, clinical trials of anti-VEGF prophylaxis in eyes with non-exudative AMD did not reduce the subsequent neovascular conversion rate. 41 , 42 Taken together, the current clinical consensus is, therefore, to closely monitor subclinical MNV unless signs of exudation develop. 38 …”

Section: Discussionmentioning

confidence: 99%

The Fovea-Protective Impact of Double-Layer Sign in Eyes With Foveal-Sparing Geographic Atrophy and Age-Related Macular Degeneration

Fukuyama

Huang

BouGhanem

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to investigate the impact of double-layer sign (DLS) on geographic atrophy (GA) progression in eyes with foveal-sparing GA and age-related macular degeneration (AMD). Methods This is a retrospective, consecutive case series of eyes with foveal-sparing GA secondary to AMD with more than 6 months of follow-up. The size of the foveal-sparing area was measured on the fundus autofluorescence images at the first and last visits. Each eye was evaluated for the presence or absence of DLS inside the foveal-sparing area. We graded eyes based on the presence of DLS within the foveal-sparing area and compared the progression of GA between two groups (DLS (+) versus DLS (−)). Results We identified 25 eyes with foveal-sparing GA with at least 2 follow-up visits (average interval = 22.7 ± 11.8 months between visits). The mean foveal sparing area was 1.74 ± 0.87 mm 2 (range = 0.42–4.14 mm 2 ) at baseline and 1.26 ± 0.75 mm 2 (range = 0.25–2.92 mm 2 ) at the last visit. Seventeen eyes (65.3%) were graded as DLS (+) within the foveal-sparing area. Square root progression of GA toward the fovea was significantly faster in the DLS (−) eyes (0.149 ± 0.078 mm/year) compared to the DLS (+) group (0.088 ± 0.052 mm/year; P = 0.04). Conclusions The DLS (−) group showed significantly faster centripetal GA progression than the DLS (+) group. Our data suggest that the presence of DLS in the spared foveal area could be a protective factor against foveal progression of GA in eyes with AMD.

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Section: Discussionmentioning

confidence: 99%

The Fovea-Protective Impact of Double-Layer Sign in Eyes With Foveal-Sparing Geographic Atrophy and Age-Related Macular Degeneration

Fukuyama

Huang

BouGhanem

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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“…Persistent expression of ANGPTL4 in the eyes of patients with nvAMD may help explain why the majority of patients receiving monthly injections with anti-VEGF therapy have intraretinal and/or subretinal fluid despite treatment ( 50 ). The increased expression of ANGPTL4 in nvAMD compared with patients with nnvAMD may further help explain why prophylactic treatment of patients with nnvAMD with anti-VEGF therapy failed to prevent their conversion to nvAMD ( 65 ).…”

Section: Discussionmentioning

confidence: 99%

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization

Yu¹,

Dinabandhu²,

Sanchez³

et al. 2022

JCI Insight

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Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.

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“…Ocular neovascularization contributes to visual impairment in several ocular diseases. Targeting pathological neovessels is an important advancement for treating ocular diseases 25 – 27 . DCZ19931 treatment could reduce the size of CNV lesions compared with the control group in the laser-induced CNV model.…”

Section: Discussionmentioning

confidence: 99%

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

Zhang

Ding

et al. 2022

Sci Rep

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Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.

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Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes

Cited by 24 publications

References 11 publications

The Fovea-Protective Impact of Double-Layer Sign in Eyes With Foveal-Sparing Geographic Atrophy and Age-Related Macular Degeneration

The Fovea-Protective Impact of Double-Layer Sign in Eyes With Foveal-Sparing Geographic Atrophy and Age-Related Macular Degeneration

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

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