眼底病学术会议

Medical management of age-related macular degeneration

Yasuo Tano

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Medical treatment of age-related macular degeneration (AMD) associated with choroidal neovascularization (CNV) has been dynamically changing, especially since the introduction of pharmacologic intervention. Although macular photocoagulation studies (19791994) have proven the long-term efficacy of macular laser photocoagulation, it has never been widely employed in Asian countries mainly due to the sudden loss of central vision in the treated group. Medical treatment of AMD became popular when photodynamic therapy (PDT) was introduced based on promising results from Treatment of AMD with Photodynamic Therapy (TAP) and Verteporphin in Photodynamic Therapy (VIP) studies. The Japanese AMD Trial (JAT) showed more amenable results among AMD patients in Japan. Meanwhile, higher incidence of polypoidal choroidal vasculopathy (PCV) among Asian AMD population has been realized. Better treatment results with PDT in Asian population are considered partly because of more frequent association of PCV and smaller size of CNV compared to the western population. In order for better visual outcomes with fewer repeated therapies, PDT combined with triamcinolone injection has been attempted for better improvement of vision and possible reduction of PDT fluence. Anecortave acetate (Retaane(r)), a cortisol structural analog devoid of glucocorticoid activity is a novel angiostatic cortisene, which showed potent angiostatic activity in vitro and in vivo. However, clinical trials failed to prove its beneficial superiority over PDT and risk reduction trial for the fellow eyes at high risk was initiated. Concept of anti-VEGF therapy was initiated by anti-VEGF aptamer, Pegaptanib (Macugen(r)) which selectively inhibits VEGF165 isoform. VEGF inhibition Study in Ocular Neovascularization (VISION) has proven pegaptanib provides a significant beneficial efficacy compared to PDT along with favorable safety profile through two years. Ranibizumab (Lucentis(r)) is a fragment of humanized monoclonal antibody which binds to all isoforms of VEGF and penetrates retinal layers effectively. MARINA and ANCHOR studies showed remarkable treatment effect of Ranibizumab with significant improvement of visual acuity in AMD patients for the first time. Ranibizumab is currently considered as the first line of therapy for the wet AMD. Bevacizumab (Avastin(r)) is a full-length humanized monoclonal antibody which also binds to all isoforms of VEGF. Bevacizumab has been approved for treatment of metastatic colorectal cancer. Beneficial effect for AMD compatible to Ranibizumab has been reported with the offlabel use of Bevacizumab by intravitreal injection of 1 to 1.25 mg. More recently various clinical trials are underway including therapies with VEGF trap, SiRNA, tyrosine kinase inhibitors and so forth. Due to ever-increasing numbers of intravitreal injections in out-patient clinics, however, various combination therapies have been designed in an attempt to optimize effect while reducing number of treatment sessions. Either adjuvant therapies or combination therapies will be employed more and more frequently.
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Department of Ophthalmology,Osaka University Medical School.