Editorial [Hot Topic:Diabetic Retinopathy(Guest Editor: Francisco Gomez-Ulla)]

This issue of CDR contains a range of interesting and up-to-date articles which review the most recent advances in the Treatment of Diabetic Retinopathy and which are written by highly respected groups of investigators. Although laser photocoagulation is considered to be the standard treatment of Diabetic Retinopathy for both macular edema and for retinal neovascularization, there have recently been important advances in this field, in particular with respect to the treatment of both diabetic macular edema (DME) and retinal neovascularization in Proliferative Diabetic Retinopathy (PDR), whether it be with intraocular steroids and new devices of sustained liberation or with anti-angiogenics. The first article, by Rodriguez-Fontal et al., reviews the importance of metabolic control and the long-term benefits of improving glycemic control, which reduces the risk of any type of retinopathy. Intensive therapy is most effective when initiated early in the course of diabetes because it has a beneficial effect on the development and progression of retinopathy. The article which follows, by Crawford et al., examines the role of angiogenic factors and the use of anti-VEGF drugs to block them. Hypoxia is a key regulator of VEGF-induced ocular neovascularization. Following the induction of VEGF by hypoxia, angiogenesis can be controlled by angiogenic inducers and inhibitors. The balance between VEGF and angiogenic inhibitors may well determine the proliferation of angiogenesis in diabetic retinopathy and understanding this is crucial in subsequent therapeutic strategies. Lopez reviews the role of human protein kinases. Several compounds have been developed that are specific inhibitors of protein kinase C beta isoforms. Synthetic inhibitors of protein kinases include small molecules that can be easily administered as oral therapeutic compounds. These inhibitors can rapidly and often specifically alter the activation state of a target kinase. So far two protein kinase C inhibitors, Protein Kinase C 412 and Ruboxistaurin, have been tested in clinical investigations to study the reduction of microvascular complications in patients with diabetes. Ruboxistaurin has appeared as a new alternative in the management of ocular complications of diabetes and it is necessary to determine whether it is sufficiently efficacious to be used alone or whether it has to be used in combination with other treatments in order to prevent visual loss in patients with diabetes. Two papers examine the treatment of DME by the use of intraocular steroids. The first, Abraldes et al., makes a comprenhensive review of the mechanism of action of triamcinolone acetonide, its pharmacology and its intraocular use both as treatment for DME refractary to focal photocoagulation and as adjuvant to panretinal photocoagulation. Special emphasis is placed on safety and efficacy data. The second written by Montero and Ruiz-Moreno, looks at intravitreal inserts, steroids, dexamethasone and fluocinolone. Different multicentric clinical trials and their results are examined. They conclude that the advantages of these systems are that they maintain a stable and sustained concentration of the drug with higher therapeutic efficacy thus reducing the number of injections. However, the complications associated with the use of steroids, such as cataracts and high intraocular pressure, are very common. The use of the different anti-VEGFs which are used in ophthalmology is tackled in three different papers. Each one reviews the main indications, published results and the experiences of the authors with the medicine used, as well as an efficacy and safety profile. The mechanism of action for pegaptanib sodium (Macugen, Pfizer), ranibizumab (Lucentis, Genentech) and bevacizumab (Avastin, Genentech) involves specific neutralization of VEGF. These anti-VEGFs are being evaluated in different studies and partial results, some of which are reviewed in this issue, have already been published. In dealing with Pegaptanib sodium both in the treatment of DME and in the case of PDR, Giuliari et al. conclude that these new pharmacologic therapies will cause a paradigmatic shift in the way we treat patients with ocular diabetic complications.