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Aim: To evaluate the baseline visual and optical coherence tomography (OCT) factors on outcomes after intravitreal bevacizumab treatment of subfoveal neovascular age-related macular degeneration (AMD)., Methods: A retrospective analysis of 73 eyes treated with intravitreal bevacizumab for subfoveal neovascular AMD was performed. Change in best corrected Snellen visual acuity (BCVA) and central retinal thickness (CRT) on OCT were the primary outcomes. Automated and manual measurements were made for all OCT characteristics., Results: Seventy-three (100%) and 58 (79.5%) eyes were followed for 3 and 6 months, respectively. The mean BCVA improved from 20/177 to 20/160 (p = 0.03) at 3 months and to 20/143 (p = 0.04) at 6 months. The mean CRT decreased 93 microm (p<0.0001) and 105 microm (p<0.0001) at 3 and 6 months, respectively. Baseline BCVA worse than 20/100 was associated with greater visual improvement (p< or =0.04). Eyes with baseline CRT greater than 400 microm experienced a greater mean CRT reduction (p<0.05). Treatment-naïve patients had a greater mean CRT reduction than those previously treated with any modality (p<0.05), Conclusions: Baseline BCVA and CRT positively influence mean visual and CRT improvement, respectively, after intravitreal bevacizumab in wet AMD. Any prior treatment predicted less CRT reduction.

Aims: To evaluate the photoreceptor layer status after antivascular endothelial growth factor (VEGF) therapy in choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT)., Design: Prospective, consecutive case series., Methods: Twenty-three eyes of 22 patients with CNV secondary to AMD with foveal thickness less than 250 microm after treatment with anti-VEGF therapy and no obvious leakage on time domain OCT, and eight healthy subjects as controls, were imaged with at least one of four different SD-OCT devices. The inner and outer segment (IS/OS) photoreceptor layers were graded, and correlated with various characteristics including visual acuity., Results: The IS/OS layer was detected in eight eyes (35%) of patients with AMD and all eyes (100%) of the healthy control subjects (p = 0.002). Eyes in patients with AMD with preserved IS/OS had a significantly better BCVA and mean change in BCVA, and were more likely not to have had previous laser treatment compared with eyes with absent IS/OS., Conclusions: SD-OCT is a useful tool to visualise IS/OS status. IS/OS is often absent in patients who have received treatment with anti-VEGF therapy for CNV due to AMD. The IS/OS status after anti-VEFG therapy correlates with BCVA and mean change in vision.

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical activator of angiogenesis in neovascular AMD is VEGF. Several therapies have been and are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, VEGF receptor decoy VEGF Trap, small interfering RNA-based therapies bevasiranib and AGN211745, sirolimus, and tyrosine kinase inhibitors including vatalanib, pazopanib, TG100801, TG101095, AG013958 and AL39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still investigational in nature offer the potential for further advances.

Age-related macular degeneration (AMD) is the leading cause of adult blindness among individuals aged 50 and older in the Western world, with the neovascular form of AMD responsible for the most severe and rapid visual loss. Although monotherapy with currently available treatments can slow the rate of loss of vision in eyes with neovascular AMD, they do not significantly improve vision. Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment that targets all VEGF-A isoforms and their biologically active degradation products. Clinical trials have reported that ranibizumab treatment resulted in greater proportions of patients achieving a < 15 letter loss of visual acuity and improved vision at 12 and 24 months than control groups. The incidence of serious ocular and systemic adverse events was low in all ranibizumab trials to date. Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate significant improvement in vision for many patients and represents a major advance in treating neovascular AMD.

Objective: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches., Scope: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites., Findings: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation., Conclusions: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials.

Purpose: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration., Methods: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold., Results: All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye., Conclusions: Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.