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Introduction: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME and PDR have ushered the development of effective targeted therapy that given intravitreally improves vision and prevents blindness. While effective, these therapies require frequent administration and are not universally effective., Areas Covered: This purpose of this paper is to review the current pathophysiologic understanding and treatments for DME and PDR as well as the novel treatments currently being developed. The treatments will be juxtaposed to the factor in the disease cascade being targeted. The potential role of these novel treatment in the clinical armamentarium are postulated., Expert Opinion: Mono-therapy, single category targeting is the current strategy being utilized clinically. However, diabetic retinopathy needs combination therapy. Therapies that will prove successful will address multiple factors involved in the pathogenesis of diabetic retinopathy.

Purpose: To evaluate the decibel loss on the Macular threshold protocol of the Humphrey visual field as a reliable functional outcome of the intravitreal bevacizumab treatment., Methods: Thirteen patients were evaluated at baseline and on the week 6 for best corrected visual acuity, optical coherence tomography central macular thickness and decibel loss on Macular threshold protocol of the Humphrey visual field after 1.25 mg intravitreal injection of bevacizumab. The outcomes were analyzed separately and in correlation using the Wilcoxon signed ranks test., Results: The improvement of the optical coherence tomography and the Macular threshold protocol of the Humphrey visual field from baseline to week 6 were significant with p=0.032 and p=0.003, respectively. The visual acuity did not show a significant improvement. The correlation of the visual acuity and Macular threshold protocol of the Humphrey visual field was significant at baseline (p=0.041) and on week 6 (p=0.019)., Conclusion: The Macular threshold protocol of the Humphrey visual field significantly improved despite the fact that the best corrected visual acuity did not. The Macular threshold protocol of the Humphrey visual field correlated with the visual acuities significantly. The optical coherence tomography was significant to demonstrate improvement but did not correlate with best corrected visual acuity and Macular threshold protocol of the Humphrey visual field. These findings suggest that the Macular threshold protocol of the visual field may be a more reliable tool for evaluation of global macular function after intravitreal bevacizumab treatment.

The leading cause of blindness in the developed world results from several disorders that have pathologic ocular neovascularization as the common pathway leading to vision loss. These disorders include exudative age related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), retinal vein occlusions (RVO) and ocular tumors. Because neovascularization is the common pathway to blindness in these highly prevalent conditions, the recent understanding of the cascade of angiogenesis has led to clinically available molecular therapeutics that have been proven to restore and preserve vision in patients that suffer from these blinding conditions. This article will summarize the emergence of vascular endothelial growth factor (VEGF) as a validated treatment target for and current understanding of the pathophysiology of ocular neovascularization. The article will then cover promising future strategies and therapeutic targets that are aimed at enhancing the efficacy and/or duration of effect of these clinically available anti-VEGF strategies. In particular molecules that target, VEGF, PDGF, Complement, Inflammation and Integrins that are entering or are currently in clinical trials will be reviewed.

Purpose: To assess outcomes for patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) treated with verteporfin photodynamic therapy (PDT) and bevacizumab., Design: Retrospective, case series database study (registry)., Participants: We included 1196 patients with CNV due to AMD who received > or =1 combination treatment of 1.25 mg intravitreal bevacizumab within 14 days of verteporfin PDT., Methods: Retrospective analysis of baseline data with ongoing follow-up. Physicians from 45 clinical centers entered patient data at baseline and follow-up examinations, including subsequent treatments, into a secure, Web-accessed database. Snellen visual acuity (VA) was converted to logarithm of the minimum angle of resolution (logMAR) for statistical analyses., Main Outcome Measures: Change from baseline in VA and retreatment rates of any therapy after the initial combination treatment., Results: Of 1196 patients, 1073 patients had > or =6 months of follow-up. For these 1073 patients, mean baseline VA was 0.967 logMAR (approximate Snellen 20/185) and 56.3% of patients (604/1073) were treatment naïve. After their baseline combination treatment, patients received a mean of 0.6 additional verteporfin PDT retreatments and 2.0 bevacizumab retreatments over a mean follow-up period of 15.0 months. By 12 months, 82% of patients (578/701) had stable or improved vision (loss of <3 lines or a gain in VA), 36% (255/701) improved by > or =3 lines, and 17% (121/701) improved by > or =6 lines. By 12 months, patients gained approximately 1.2 lines (6 letters) of VA from baseline. Patients who were treatment naïve gained significantly more VA by month 12 (+8.4 letters) compared with those who had been previously treated (+2.4 letters; P<0.01). Most serious adverse events (26/30) were judged by investigators as not related to any study treatment, although 3 ocular events were judged related to bevacizumab alone, and 1 ocular event was judged related to both bevacizumab and PDT., Conclusions: Combination therapy with PDT and bevacizumab led to vision benefit for most patients, particularly those who were treatment naïve at baseline. The number of retreatments was lower than published reports with either treatment delivered as monotherapy. Randomized clinical trials are underway to confirm these findings.

To assess the potential visual benefit of intravitreal bevacizumab in a patient with idiopathic juxtafoveal retinal telangiectasis refractory to focal laser treatment, an intravitreal injection of bevacizumab (1.25 mg) was given. Within 1 week, visual acuity improved from 20/50 to 20/25 and optical coherence tomography demonstrated complete resolution of macular edema. There was no adverse effect. The macular edema recurred after 3 months, requiring a repeat injection of bevacizumab with subsequent resolution of macular edema. An intravitreal injection of bevacizumab may provide potential short-term visual benefit in patients with macular edema from idiopathic juxtafoveal retinal telangiectasis.

Neovascularization characterizes diabetic retinopathy and choroidal neovascularization associated with age-related macular degeneration, the most common causes of severe visual loss in the developed world. Gene transfer to the eye using adeno-associated viral (AAV) vectors is a promising new treatment for inherited and acquired ocular diseases. We used an AAV vector with rapid onset and high levels of gene expression in the retina to deliver three anti-angiogenic factors (pigment epithelium-derived factor, tissue inhibitor of metalloproteinase-3, and endostatin) to the eyes of mice in a mouse model of retinopathy of prematurity. All three vectors inhibited ischemia-induced neovascularization.