This paper discusses the lack of complete selectivity in the photodynamic closure of choroidal neovasculature (CNV) associated with age-related macular degeneration. The arguments presented are supported by examples of clinical observations and may be useful for the design of the next generation of photosensitizers.

Based on worldwide patient follow-up, it can be concluded that a substantial number of the more than 200000 treatments that have been dispensed so far could have resulted in stabilization of the disease for at least a number of years. Clinical observations also indicate that, in addition to the effective closure of the CNV observed 1 week after PDT, a significant closure (or at least reduced leakage) of normal choriocapillaries is observed in the treated area. Some of the concepts associated with the selectivity of Visudyne photodynamic therapy of choroidal neovascularization in age-related macular degeneration are also discussed.

Novel approaches to improving selectivity could include attaching a photosensitizer to a targeting moiety such as a monoclonal antibody or a peptide. The undesirable closure of normal choriocapillaries in the treated area is one area of possible improvement to be sought for the next generation of drugs.

La photothérapie dynamique (PDT) à la Visudyne® est utilisée pour la fermeture de la néovascularisation choroïdienne associée à la dégénération maculaire de la rétine liée à l’âge. Si la sélectivité de ce traitement, en ce qui concerne la protection de la vascularisation rétinienne est prouvée et effective, nous justifierons et discuterons de l’intérêt d’améliorer la sélectivité de cette thérapie pour la fermeture des néovaisseaux choroïdiens seulement, tout en protégeant la vascularisation choroïdienne normale. Sur la base de cette argumentation, nous aborderons quelques aspects de la conception d’une nouvelle génération de photosensibilisateurs.