# Diabetic Retinopathy and Ocular Melanoma: How Far We Are?
## 3 Diabetic Retinopathy, Angiogenesis and Anti-Angiogenic Therapy
In the presence of high glucose levels, cell lysis and ATP release occurs, stimulating the function of these receptors and inflammasome (a multimeric complex that activates IL1\(\beta\)-activating caspase), thereby stimulating IL1\(\beta\) generation in human retinal pericytes. Thus, the role of P2X7 receptors in DR was elucidated, translating into a possibility for the therapy of this disease [114]. Inflammation is the main player in retinal dysfunction associated with diabetes. Clinical studies have shown that in DR there is obstruction and increased capillary permeability; taking into account the VEGF function, it is clear that this is one of the major factors for vascular lesions of DR [115; 116]. Thus, anti-VEGF therapy was shown to be successful but has limitations as repeated intraocular injections are required, maximum efficacy is in the late stages of the disease and only 50% of patients in studies respond positively to treatment [117]. It has also been shown that diabetics soon present neuroretinal changes before manifestations of microvascular lesions are visible [118]. DR is clearly proven to be closely related to inflammation, and its inhibition has already been proven to have an impact on the retinas/vitreous humour of animals and diabetic patients [5; 119]. Studies in patients with DR have shown that the use of anti-inflammatory agents (e.g., salicates and minocycline) moderates the inflammatory response, thus preventing vascular and neuronal disorders [120; 121]. Currently, in order to prevent vision loss, DR is treated by laser surgery, pharmacotherapy and vitrectomy, intraocular pharmacotherapy being the most used, together with anti-inflammatory (corticosteroids) and anti-angiogenic agents (VEGF inhibitors) [122; 123]. In some patients, intraocular pharmacotherapy requires only a few injections to make the treatment effective, but in patients with chronic musculoskeletal disorders, more intensive therapy is required. Intravitreal and anti-VEGF corticosteroids were shown to be effective in proliferative DR and in diabetic macular edema, but their use is still limited due to the short-term effect and adverse side effects [124]. Panretinal photocoagulation prevents vision loss in DR, but pharmacotherapy is still needed as an adjuvant treatment. To improve existing forms of therapy, anti-VEGF (afilbercept) and corticosteroids (dexamethasone and fluocinolone insertions) have been approved [125; 126]. The available therapy consists of oral danazol and topical minocycline and loteprednol, which require daily administration, but these drugs have the advantage of a long-term effect. Intravitreal therapy (monotherapy or combined) is currently under development; however, its duration and efficacy have not been fully defined [123]. Thus, these new alternatives, such as long-term drugs, sustained corticosteroid and anti-VEGF delivery systems, and also nanoencapsulation approaches, reduce the treatment burden, but may not obtain regulatory authorization for at least 5 years [59]. Inflammation is instrumental in the pathogenesis of DR and is intimately linked to angiogenesis.