Early Effects of Intravitreal Triamcinolone Acetonide on Inflammation and Proliferation in Human Choroidal Neovascularization

Tatar, Olcay; Adam, Annemarie; Shinoda, Kei; Kaiserling, E.; Claes, C; Eckardt, Claus; Eckert, Tillmann; Pertile, Grazia; Scharioth, Gábor B.; Yoeruek, Efdal; Szurman, Peter; Bartz‐Schmidt, Karl Ulrich; Grisanti, Salvatore

doi:10.1001/archophthalmol.2008.602

Cited by 9 publications

(11 citation statements)

References 58 publications

(117 reference statements)

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“…Most CNV occurs in macular lesions at the center of the retina and directly causes a severe loss of visual acuity [1,2,3,4]. Inflammation-induced VEGF-A production is essential for development of CNV [5,6,7,8,9,10,11,12]. However, although anti-VEGF-A treatments have proven therapeutic effects, the outcome remains unsatisfactory.…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory processes are thought to be critical in generating CNV [5,6,7]. Many experimental and clinical studies have indicated that the vascular endothelial growth factor A (VEGF-A) family, especially VEGF-A, is essential for promoting CNV [8,9,10,11,12].…”

Section: Introductionmentioning

confidence: 99%

“…This growth factor also influences the production of various pro-inflammatory cytokines. However, although anti-angiogenic treatments have proven therapeutic effects with antagonist against VEGF-A, the therapeutic outcome in patients is not always satisfactory [1,2,3,4,5,6,7,8,9,10,11,12]. …”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

Huo

Li²,

Jiang³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Age-related macular degeneration (AMD) appears to be a disease with increasing incidence in Western countries and may develop into acquired blindness. Choroidal neovascularization (CNV) is the most frequent cause for AMD, and is commonly induced by regional inflammation. Past studies have highlighted vascular endothelial growth factor A (VEGF-A) as a major trigger for CNV. However, studies on the associated angiogenic factors other than VEGF-A are lacking. Methods: Here, we used a well-established laser burn (LB)-induced experimental CNV mouse model to study the molecular mechanisms underlying the development of CNV after ocular injury. We analyzed vessel density by lectin labeling. We isolated macrophages, endothelial cells and other cell types by flow cytometry, and analyzed levels of different angiogenic factors in these populations. We used antisera against VEGF-A (aVEGF) and/or antisera against placental growth factor (PLGF; aPLGF) to antagonize CNV. We used an antibody-driven toxin to selectively eliminate macrophages to evaluate the role of macrophages in CNV. We also examined expression of PLGF in macrophage subtypes. Results: The choroidal vessel density increased significantly 7 days after LB. LB increased significantly the levels of VEGF-A and PLGF in mouse eyes. Treatment with aVEGF significantly blunted increases in vessel density by LB. Treatment with aPLGF alone did not significantly reduce increases in vessel density. However, aPLGF significantly increased the inhibitory effects of aVEGF on vessel density increases. While VEGF-A was produced by endothelial cells, macrophages and other types at similar levels, PLGF seemed to be predominantly produced by macrophages. Selective macrophage depletion significantly reduced CNV. M2, but M1 macrophages produced high levels of PLGF. Conclusions: Together, our data suggest a previously unappreciated role of PLGF in coordination with VEGF-A to regulate CNV during ocular injury. Our study highlights macrophages and their production of PLGF as novel targets for CNV therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

Huo

Li²,

Jiang³

et al. 2015

Cell Physiol Biochem

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“…Intravitreal application of triamcinolone acetonide as adjuvant to PDT or monotherapy does not suppress VEGF but enhances endostatin expression in CNV. Therefore, in CNV treated with triamcinolone acetonide monotherapy or PDT–triamcinolone acetonide combination therapy, the VEGF predominance score over endostatin is reduced to its level in control CNV 47. However, bevacizumab seems to have a dual effect in angiogenesis inhibition by reducing intensity of VEGF expression besides enhancing endostatin.…”

Section: Discussionmentioning

confidence: 99%

Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation

Tatar

Shinoda²,

Kaiserling³

et al. 2008

Br J Ophthalmol

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“…However, in vivo studies demonstrated that TA strongly inhibits VEGF and stromal-derived factor-1 levels inside the vitreous as well [126]. Other recent studies on immunohystochemical staining reported that TA seems to exert its angiogenesis inhibitory effects on CNV by enhancing endostatin expression rather than by suppressing VEGF expression [127].…”

Section: Mechanism Of Action Of Triamcinolone Acetonidementioning

confidence: 97%

Clinical Evidence of Intravitreal Triamcinolone Acetonide in the Management of Age-Related Macular Degeneration

Becerra

Morescalchi

Gandolfo

et al. 2011

CDT

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Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution of cataract. Nevertheless, cataract surgery may stimulate the development of CNV (result in stimulating CNV). However, in large, randomized, clinical trials on combination therapy of TA and PDT, visual acuity failed to show an improvement, even though the lesion size and subretinal fluid had decreased, compared to controls treated with PDT alone. Some authors reported an increased risk of developing macular atrophy after the combination therapy with IVTA and PDT. Reduction of the PDT fluence rate in association with the use of steroids resulted in reducing the risk of macular atrophy and in a better visual acuity outcome. The introduction of anti-VEGF-based drugs has revolutionized the treatment of AMD and has replaced all the previous therapies used for CNV. Visual improvement becomes an expectation in a higher proportion of patients, previously limited to minimizing vision loss. Anti-VEGF therapy also resulted in superior visual improvement compared to all types of combination therapy with IVT and PDT. Nevertheless, anti-VEGF monotherapy also has many...

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Early Effects of Intravitreal Triamcinolone Acetonide on Inflammation and Proliferation in Human Choroidal Neovascularization

Cited by 9 publications

References 58 publications

Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

Inhibition of Ocular Neovascularization by Co-Inhibition of VEGF-A and PLGF

Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation

Clinical Evidence of Intravitreal Triamcinolone Acetonide in the Management of Age-Related Macular Degeneration

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