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Rushmia Karim, Benjamin TangUniversity of Sydney School of Public Health, Concord Repatriation General Hospital, Concord, NSW, AustraliaBackground: Diabetic macular edema (DME) is one of the manifestations of diabetic retinopathy leading to loss of central vision and visual acuity. It manifests itself with swelling around the central part of the retina, the area responsible for sharp vision. Current treatment includes laser therapy and intravitreal steroids with preventative measures including diabetes control. No one treatment has guaranteed control of diabetic macular edema which leads to deteriorating visual acuity, function and quality of life in patients. Vascular endothelial growth factor (VEGF) has been shown to be a critical stimulus in the pathogenesis of macular edema secondary to diabetes.1 Antiangiogenic therapy encompassed treatment with anti-VEGF which inhibits VEGF-driven neovascularization hence macular edema leading to decreased visual acuity.Objective: For this review, we evaluated the effectiveness of intravitreal anti-VEGF in treating DME.Data sources: We identified five trials (n = 525) using electronic databases (Cochrane Central Register of Controlled Trials [Central], Medline®, and Excerpta Medica Database [EMBASE®]) in October 2008, supplemented by hand searching of reference lists, review articles, and conference abstracts.Methods: We included all randomized clinical trials (RCTs) evaluating any form of intravitreal anti-VEGF for treating DME. The main outcome factor was change in best-corrected visual acuity and central macular thickness. One author assessed eligibility, methodological quality, and extracted data. Meta analysis was performed when appropriate.Results: We included three trials of adequate methodological quality in our metaanalysis. Patients treated with anti-VEGF showed improvement in visual acuity of -0.17 (95% confidence interval [CI]: -0.23, -0.10) and central macular thickness -84.69 (95% CI: -117.09, -52.30). Patients treated with combined anti-VEGF and intravitreal triamcinolone showed improvement of visual acuity of -0.19 (95% CI: -0.27, -0.11) and central macular thickness mean change being –111.20 (95% CI: -148.13, -74.28).Conclusions: Anti-VEGF has been associated with an improvement in visual acuity and central macular thickness in the analysis, however trial analysis was of a short duration and further research is needed to determine long-term benefits.Keywords: anti-VEGF, diabetic macular edema, ranizubimab, Avastin®, pegaptanib

Yukio Sassa, Yasuaki HataDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, JapanAbstract: Age-related macular degeneration (AMD) complications are the leading cause of severe vision loss among the aging population in the many western countries. The introduction of molecular inhibitors of vascular endothelial growth factor (VEGF), such as pegaptanib, ranibizumab, and bevacizumab, as treatments for wet AMD has provided new hope for affected patients. Now we have these treatment options, which have the possibility to improve or maintain visual acuity for patients suffering from AMD. The treatment needs to be optimized and this is in progress. Based on emerging evidence, adopting a variable VEGF inhibitor-dosing strategy guided by visual acuity assessment and optical coherence tomography are now being tried to reduce the frequency of injections. VEGF inhibitors in combination with photodynamic therapy are another way to optimize treatment. Physicians are waiting for new guidelines for the management of AMD and the results of current and upcoming trials systematically addressing these issues will be expected to provide it.Keywords: age-related macular degeneration, VEGF inhibitor, verteporfin, pegaptanib, ranibizumab, bevacizumab

Intravitreal (IVT) injection is a frequently used method for the therapeutic management of many intraocular diseases, particularly those affecting the posterior segment of the eye. Already over the past 5 years, the frequency of IVT injections has increased tremendously for both seasoned and newly trained ophthalmologists. In fact, IVT injection has become one of the most common medical procedures performed in the United States.1 Approximately 1.75 million Americans aged over 50 years are living with advanced vision-threatening age-related macular degeneration (AMD), and this number is expected to increase 50% to 2.95 million by 2020.2 Although the complication rate and learning curve of other retinal and ophthalmologic procedures have been investigated, 3–7 those associated with IVT injections has not. Because of the recent precipitous increase in the frequency of these injections by many surgeons it is important to know how safe these are to our patients. Even experienced surgeons who may have not performed large numbers of these procedures in the past now are doing so. It is normal for the newly diagnosed patient with exudative AMD to be anxious about having a needle repeatedly placed in their eye to deliver medication, and it is helpful for them to understand how safe these treatments are. The Eyetech Phase II study had a 4.8% incidence of retinal detachment (RD) and the VISION (VEGF Inhibition Study in Ocular Neovascularization) Study Year 1 had a 1.3% incidence of endophthalmitis.8,9 Later the PIER (Phase IIIb, Multicenter, Randomized, Double-Masked, Sham Injection- Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization [CNV] with or without Classic CNV Secondary to AMD) study had no cases of endophthalmitis or RDs.10 Other serious IVT complications can also include iritis/uveitis, intraocular hemorrhage, ocular hypertension, retinal vascular occlusions, cataract, and hypotony. Prevention of retinal complications is important enough that a vitreoretinal surgical simulator has been developed for novice, inexperienced, and trained surgeons in order to minimize the incidence of these.11 This begs the question as to whether a surgeon’s initial IVT injections are safe. Although complication rates have been reported in clinical trials, these do not shed light on the initial complication rates of individual surgeons nor of their learning curves. Since most patients who receive these injections have neovascular exudative AMD, and the larger published studies are for this disease, we believed it was important to examine complication rates in this patient group. A highly effective treatment for exudative AMD involves the direct injection of anti vascular endothelial growth factor (anti-VEGF) into the vitreous, which inhibits intraocular angiogenesis. Administering anti-VEGF directly into the vitreous not only maximizes intraocular drug levels, but also minimizes the risk of toxicity associated with systemic administration.12 Specifically, the anti-VEGF agents pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, New York, NY) and ranibizumab (Lucentis; Genentech, South San Francisco, CA) have been used successfully in the treatment of exudative AMD.8,13 Bevacizumab (Avastin; Genentech), another anti-VEGF derived from the same parent molecule as ranibizumab, has also been used successfully as an IVT injection for the treatment of exudative AMD.14 The purpose of this study was to analyze the safety of initial consecutive IVT injections and to review the complications that may be attributed to the injection procedure when utilizing a specific protocol. Given the variation in complication rates that have been published for IVT in different time periods, we also wanted to attempt to understand whether complication rates are related to the learning curve of an individual surgeon or whether they are due to modifications of various methodologies associated with the techniques that have evolved.

Luis AriasDepartment of Ophthalmology, Bellvitge University Hospital, Barcelona, SpainPurpose: Evaluate the efficacy of pegaptanib, a selective anti-vascular endothelial growth factor (VEGF) agent, and bevacizumab, a nonselective anti-VEGF agent, for retinal pigment epithelial detachment (PED) associated with occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).Methods: Prospective, comparative, nonrandomized pilot study included patients with PED comprising >50% of total lesion in subfoveal location with visual acuity (VA) 20/40–20/400 and lesions either previously untreated or treated only with photodynamic therapy/verteporfin. Seven patients received pegaptanib 0.3 mg intravitreally (IVT); eight received IVT bevacizumab 1.25 mg. Follow-up occurred every 4–6 weeks for 6 months. Reinjection of initial medication occurred if there was intra- or subretinal fluid observed by optical coherence tomography (OCT) or increased PED. Endpoints were mean changes from baseline to month 6 in VA (ETDRS) and foveal thickness.Results: At baseline, mean VA was lower, and mean foveal thickness was greater in pegaptanib versus bevacizumab-treated patients (36.1 vs 49.5 letters; 470.4 vs 321.1 μm). Mean improvements to month 6 in VA and foveal thickness were greater for pegaptanib (VA: +9.1 vs +7.2 letters; foveal thickness: −88.2 vs −52.9 μm). On average, pegaptanib-treated patients had slower but more sustained improvement in VA and foveal thickness; bevacizumab-treated patients showed rapid improvement with a slow return towards baseline. Both agents were well tolerated. Conclusion: Intravitreal injections of pegaptanib or bevacizumab are both efficacious and safe treatments for PED associated with occult CNV secondary to AMD.Keywords: bevacizumab, pegaptanib, retinal pigment epithelial detachment

The first antivascular endothelial growth factor (anti-VEGF) was developed as an anticancer drug for colonic carcinomas. Since then, anti-VEGFs have developed in scope and indications. They have revolutionized the treatment of exudative macular degeneration and have had a major impact on treatment of several other conditions. This has resulted in an increased number of patients seeking treatment with new treatment options and has had a considerable financial impact on health care resources. Anti-VEGFs have been used in the treatment of all age groups of the population ranging from infants where it is used for treatment of retinopathy of prematurity to the elderly where it is used in exudative macular eegeneration.