Anti-Vascular Endothelial Growth Factor Strategies for the Treatment of Choroidal Neovascularization From Age-Related Macular Degeneration

Barouch, Fina C.; Miller, Joan W.

doi:10.1097/00004397-200404430-00005

Cited by 31 publications

(17 citation statements)

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“…Although new vessel growth and maturation are complex processes involving multiple stimuli, VEGF appears to be a particularly important signal 10 -13 and was found to be overexpressed in RPE cells of eyes with AMD at autopsy and in RPE cells from CNV membranes obtained at surgery. 11,12 An ideal therapy would eradicate existing CNV, as well as reduce inflammation and VEGF expression to prevent further CNV growth, with one treatment. No single therapy possesses all of these modes of action and the safety and convenience of one treatment cycles, so a combination strategy is warranted.…”

mentioning

confidence: 99%

Triple Therapy for Choroidal Neovascularization Due to Age-Related Macular Degeneration

Augustin

Puls

Offermann

2007

Retina

191

124

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Purpose:To evaluate the efficacy and safety of triple therapy with verteporfin photodynamic therapy (PDT), dexamethasone, and bevacizumab in choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).Methods: This prospective, noncomparative, interventional case series included 104 patients. Verteporfin PDT was administered with a reduced light dose (42 J/cm 2 , accomplished by light delivery time of 70 seconds). Approximately 16 hours after PDT, dexamethasone (800 g) and bevacizumab (1.5 mg) were injected intravitreally. Patients attended follow-up visits every 6 weeks, undergoing visual acuity and intraocular pressure measurement, slit-lamp and ophthalmoscopic examination, and optical coherence tomography (OCT). Fluorescein angiography was performed every 3 months or earlier if OCT showed significant edema.Results: All 104 patients received one triple therapy cycle (5 patients received a second triple treatment due to remaining CNV activity). The triple therapy was complemented in 18 patients (17.3%) by an additional intravitreal injection of bevacizumab. The mean follow-up period was 40 weeks (range, 22-60 weeks). Mean increase in visual acuity was 1.8 lines (P Ͻ 0.01). Mean decrease in retinal thickness was 182 m (P Ͻ 0.01). No serious adverse events have been observed. Conclusion:In most patients with CNV due to AMD, triple therapy results in significant and sustained visual acuity improvement after only one cycle of treatment. In addition, the therapy offers a good safety profile, potentially lower cost compared with therapies that must be administered more frequently, and convenience for patients.RETINA 27:133-140, 2007 A s new therapies have become available to treat patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), it is clear that no single therapy addresses the multifactorial pathogenesis of the disease. CNV progresses from age-related changes in the retina and supporting tissues. With age, the cells of the retinal pigment epithelium (RPE) are less able to detoxify, and cellular debris (drusen) accumulates between Bruch membrane and the RPE. 1,2 As Bruch membrane and the adjacent choriocapillaris age, they become brittle, reducing the size of the choroidal capillaries, and in turn affect metabolic activity and lead to hypoxia. [1][2][3] This choroidal vascular atrophy with the associated inflammatory response is thought to be the principal cause of dry AMD development. 2,3 Immunologic signals associated with acute vascular compromise may lead to

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confidence: 99%

Triple Therapy for Choroidal Neovascularization Due to Age-Related Macular Degeneration

Augustin

Puls

Offermann

2007

Retina

191

124

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“…In particular, VEGF has been identified as one of the most important mediators of physiologic and pathologic angiogenesis. Many strategies for blocking VEGF signaling in neovascular diseases have been developed, including anti-VEGF antibodies, anti-VEGF aptamer, soluble VEGF receptors or chimeric VEGF receptors, protein kinase C inhibition and VEGF receptor kinase inhibitors (Takeda et al, 2003;Barouch and Miller 2004;Liu and Regillo 2004;Kinose, Roscilli et al 2005). Several clinical trials (Gragoudas, Adamis et al 2004;Rosenfeld, Schwartz et al 2005) have demonstrated therapeutic efficacy and recently Macugen (anti-VEGF aptamer) has been approved for treating wet AMD.…”

Section: Discussionmentioning

confidence: 99%

“…Anti-VEGF strategies with promise as potential therapeutic agents for the treatment of CNV are currently undergoing or have completed clinical trials (pegaptanib sodium, Macugen; ranibizumab, Lucentis; VEGF-Trap) (Barouch and Miller 2004). Macugen has been approved by the FDA for use in the treatment of neovascular AMD.…”

Section: Introductionmentioning

confidence: 99%

Receptor tyrosine kinase inhibitors AG013764 and AG013711 reduce choroidal neovascularization in rat eye

Wang

Shi

Niesman

et al. 2007

Experimental Eye Research

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Age-related macular degeneration (AMD) is the major cause of blindness for people over 60. In the "wet" form of AMD compounds targeting growth factor signaling pathways such as VEGF have been a major focus for therapeutic interventions. In a previously developed rat model of CNV, we utilized two receptor tyrosine kinase inhibitors (RTKi) to block VEGFR-1, VEGFR-2 and PDGFR signaling following the establishment of CNV. AAV-VEGF 165 was injected into the subretinal space of rats at postnatal days 15-17. Six weeks later, a suspension of RTK inhibitors, AG013764 or AG013711, was injected intraperitoneally (IP, twice daily) or intravitreally (every five days) over a two week period. FITC-dextran whole-mounts of RPE-choroid-sclera were prepared after the animals were sacrificed. CNV area was quantified using Neurolucida to measure the hyperfluorescence on FITC-dextran whole-mounts. Histology and immunohistochemistry were performed as described previously. VEGF expression in control and treated eyes was confirmed by immunohistochemistry and histological sections indicated recovery of retinal morphology and CNV reduction in treated eyes. In the animals IP injected with AG013764 or AG013711 the mean CNV level was reduced by 25 to 33% compared to control, but this effect did not achieve statistical significance. Intravitreal injections of AG013764 or AG013711 reduced the level of CNV by approximately 60% compared to control (p< 0.005 or p< 0.05, respectively). These data show that two RTK inhibitors, AG013764 or AG013711, delivered intravitreally, significantly reduce blood vessel proliferation in this AAV-VEGF 165 model of CNV.

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“…Most neovascularization is preceded by a hypoxic insult, causing an increase in VEGF (or a decrease in PEDF). If one could avoid the hypoxia or responsive VEGF increase, one may be in a better position to decrease retinal neovascularization [50]. Conversely if one could preserve PEDF, neovascularization could potentially be decreased leading to less ocular neovascularization.…”

Section: Therapeutic Windowmentioning

confidence: 99%

Ocular Neovascularization: Genomic Implications

Higgins¹

2005

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Ocular neovascularization in the form of retinopathy, choroidal neovascularization, and age-related macular degeneration can be sight-threatening. Therapies have been directed at tissue ablation consisting of laser surgery and cryotherapy as well as medical therapies to reduce intraocular pressure. These therapies occur later in the course of many kinds of ocular neovascularization. Advances in the field of angiogenesis biology have been critical to understanding the biology of various forms of ocular neovascularization. Vascular endothelial growth factor (VEGF) is the prime candidate for target of new therapies. Basic cellular experiments, animal studies and studies in genetically altered mice have been extremely helpful in elucidating ocular vascular pathology. Identification of factors involved in neovascularization, such as VEGF, and modification of their expression are vital to moving the field of ocular angiogenesis forward for ultimate clinical benefit. Applications of genomics to neovascularization are being developed both for detection of populations at high risk and for potential therapeutic intervention. Molecular biologic tools such as angiostatic gene transfer may prove to be sight-saving in the near future.

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Anti-Vascular Endothelial Growth Factor Strategies for the Treatment of Choroidal Neovascularization From Age-Related Macular Degeneration

Cited by 31 publications

References 0 publications

Triple Therapy for Choroidal Neovascularization Due to Age-Related Macular Degeneration

Triple Therapy for Choroidal Neovascularization Due to Age-Related Macular Degeneration

Receptor tyrosine kinase inhibitors AG013764 and AG013711 reduce choroidal neovascularization in rat eye

Ocular Neovascularization: Genomic Implications

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