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Based on the success of intravitreal therapies targeting vascular endothelial growth factor,1–3 some of which suggested efficacy independent of lesion subtype,3 we investigated the benefit and safety of pegaptanib sodium in patients with early neovascular age-related macular degeneration (NV-AMD) versus those with established lesions.4 PERSPECTIVES (NCT00327470) was a 102-week, open-label trial. Participants aged ≥50 years with evidence of NV-AMD in at least one eye, clear ocular media and a visual acuity >25 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, and a lesion

The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

Aim To assess the efficacy of pegaptanib as maintenance therapy in neovascular age-related macular degeneration (NV-AMD) patients after induction therapy. Methods A phase IV, prospective, open-label, uncontrolled exploratory study including subjects with subfoveal NV-AMD who had had one to three induction treatments 30–120 days before entry and showed investigator-determined clinical/anatomical NV-AMD improvement. Lesions in the study eye were: any subtype, 12 or fewer disc areas; postinduction centre point thickness (CPT) 275 μm or less or thinning of 100 μm or more (optical coherence tomography); visual acuity (VA) 20/20–20/400. Intravitreal pegaptanib 0.3 mg was administered as maintenance every 6 weeks for 48 weeks with follow-up to week 54. Booster treatment additional unscheduled treatment for wet age-related macular degeneration, was allowed in the study eye at the investigators9 discretion for clinical deterioration. Results Of 568 enrolled subjects, 86% completed 1 year of pegaptanib. Mean VA improvement during induction (49.6 to 65.5 letters) was well preserved (54-week mean 61.8 letters). Mean CPT was relatively stable during maintenance (20 μm increase during the study). Fifty per cent did not receive unscheduled booster treatment to week 54; 46% did have one such booster (mean 147 days after maintenance initiation). Conclusions An induction-maintenance strategy, using non-selective then selective vascular endothelial growth factor (VEGF) inhibitors, could be considered for NV-AMD. This approach may have particular relevance for patients with systemic comorbidities who require long-term anti-VEGF therapy for NV-AMD.

Background: To compare the efficacy of intravitreal pegaptanib (IVP) versus panretinal laser photocoagulation (PRP) in the treatment of active proliferative diabetic retinopathy (PDR). Methods: A prospective, randomized, controlled, open-label, exploratory study. Twenty subjects with active PDR were randomly assigned at a 1:1 ratio to receive treatment in one eye either with IVP (0.3 mg) every 6 weeks for 30 weeks, or with PRP laser. Efficacy endpoints included regression of retinal neovascularisation (NV), and changes from baseline in best-corrected visual acuity (BCVA), and foveal thickness. Safety outcomes included observed and reported adverse events. Results: In 90% of randomized eyes to IVP, retinal NV showed regression by week 3. By week 12, all IVP-eyes were completely regressed, and was maintained through week 36. In the PRP-treated group, at week 36, two eyes demonstrated complete regression, two showed partial regression, and four showed persistent active PDR. Mean change in BCVA at 36 weeks was +5.8 letters in pegaptanib-treated eyes and -6.0 letters in PRP-treated eyes. Only mild to moderate transient ocular adverse events were reported with pegaptanib. Conclusions: IVP produces short-term marked and rapid regression of diabetic retinal NV. Regression of NV was maintained throughout the study and at the final visit.

Background Many authors have hypothesised that cardiovascular disorders and age-related macular degeneration (AMD) share common antecedents and suggested that novel biomarkers associated with CVD be evaluated for their potential relationship with AMD. Purpose To analyse the effect of anti-VEGF treatment on homocysteine levels and CRP (C-Reactive Protein) levels in patients with AMD. Materials and methods A total of 43 patients with exudative AMD and with no previous anti-VEGF treatment were treated with two anti-VEGF treatments: ranibizumab and pegaptanib sodium. The follow up was 6 months. The homocysteine (HCY) and CRP levels were determined before and after treatment. HCY levels were measured quantitatively using an intensifying immunonephelometric particle test in a BN ProSpec analyzer (Tiez, 1995) and CRP analysis was performed by an immunoturbidimetric test (Eda et al . 1998). Results Mean plasma homocysteine level at baseline was 13.1 ± 4.2 mmol/L in patients treated with pegaptanib and at 6 months these values had not changed. In the same way the patients treated with ranibizumab showed no changes in mean baseline plasma homocysteine (12.8 ± 2.5 mmol/L) after intravitreal treatment with ranibizumab. The mean homocysteine values were within the normal range, between 5–20 mmol/L. Of all patients analysed, only 3 of them initially had CRP levels above normal (5–10 mg /L). After antiangiogenic treatment with both ranibizumab and pegaptanib there was a significant increase in CRP. In patients with normal values, anti-angiogenic treatment produced no significant changes. Conclusions We did not find any results in our study to suggest that anti-VEGF treatment in patients with AMD increases cardiovascular risk predictors. No conflict of interest.

Aims: This prospective, open label, non-comparative, observational case series evaluates 6-month results of Pegaptanib Sodium (Macugen®) and Photodynamic Therapy (PDT) in predominantly classic juxtafoveal choroidal neovascularisation (CNV) in age-related macular degeneration (AMD) in seven eyes of seven patients. Results: Best corrected visual acuity (BCVA) diminished with a mean of five letters. Initial area of CNV increased significantly from 1.4 mm2 to 2.7 mm2. There was a significant increase in the greatest linear dimension (GLD) from 1280.3 μm to 2065.7 μm at the 24-week follow-up. Conclusion: Predominantly classic juxtafoveal CNVs are highly aggressive lesions that demonstrate poor response despite combined therapy using PDT and Macugen.

Bevacizumab is better than no treatment, photodynamic treatment, or six weekly intravitreal pegaptanib sodium in neovascular age related macular degeneration (AMD).1 Its long term safety and whether it is as effective as ranibizumab are unknown,2 but available data should be sufficient for the European Medicine Agency (EMA) to …