Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration

Abstract

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 limitations due to the need of repetitive treatments, increased costs and tachyphylaxis. Treatment regimens involving TA in combination therapy with anti-VEGF and PDT may preserve benefits for substantially longer periods. A question remains open on whether a combination treatment with anti-VEGF, triamcinolone and/or PDT may be a treatment option in patients with exudative AMD, by offering, with one cycle of therapy, functional VA benefits comparable to those observed with continued monthly anti-VEGF therapy. Further trials, of higher scientific significance, are needed to study the potential of these treatment options.