Bevacizumab is a full-length, humanized monoclonal antibody directed against all the biologically active isoforms of vascular endothelial growth factor (VEGF-A). The antibody was initially designed and studied as an anti-angiogenic strategy to treat a variety of solid tumors. After approval by the US Food and Drug Administration, bevacizumab gained access into ophthalmology to treat various types of neovascular diseases. Since the first report in 2005 more than 100 publications share the experience with bevacizumab in ophthalmology. Two authors independently assessed the research results from Pubmed to April 2007. The reference list is a selection of key publications related to the issue. Currently, there is no well-designed randomized controlled trial yet to establish the efficacy and safety of intraocular bevacizumab for any ocular disease in spite of its assumed characteristics representing the most cost-effective VEGF inhibitor.

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Recent developments may provide an opportunity to improve outcome in individuals who develop neovascular age-related macular degeneration (ARMD). Several therapies have been introduced that show promise for halting the progression of this disorder. However, data from controlled clinical trials to test the relative efficacy of different management strategies across the subtypes of disease remain limited. New treatment modalities that target the neovascularization process, including leakage from choroidal neovascularization (CNV), are currently being developed. Vascular endothelial growth factor (VEGF) has been implicated as a key mediator in the pathogenesis of ARMD-related CNV. Anti-VEGF strategies show promise as potential therapeutic agents for the treatment of CNV and are currently undergoing active clinical investigation. Such strategies include anti-VEGF antibodies, anti-VEGF aptamer, gene therapy and protein kinase C inhibition. This article reviews the mechanism of action and rationale for anti-VEGF drugs in ARMD.

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Background: To report the anatomic and visual acuity response after intravitreal bevacizumab (Avastin) in patients with diffuse diabetic macular edema. Design: Prospective, interventional case series study. Materials and Methods: This study included 20 eyes of metabolically stable diabetes mellitus with diffuse diabetic macular edema with a mean age of 59 years who were treated with two intravitreal injections of bevacizumab 1.25 mg in 0.05 ml six weeks apart. Main outcome measures were 1) early treatment diabetic retinopathy study visual acuity, 2) central macular thickness by optical coherence tomography imaging. Each was evaluated at baseline and follow-up visits. Results: All the eyes had received some form of laser photocoagulation before (not less than six months ago), but all of these patients had persistent diffuse macular edema with no improvement in visual acuity. All the patients received two injections of bevacizumab at an interval of six weeks per eye. No adverse events were observed, including endophthalmitis, inflammation and increased intraocular pressure or thromboembolic events in any patient. The mean baseline acuity was 20/494 (log Mar=1.338±0.455) and the mean acuity at three months following the second intravitreal injection was 20/295 (log Mar=1.094±0.254), a difference that was highly significant ( P =0.008). The mean central macular thickness at baseline was 492 µm which decreased to 369 µm ( P =0.001) at the end of six months. Conclusions: Initial treatment results of patients with diffuse diabetic macular edema not responding to previous photocoagulation did not reveal any short-term safety concerns. Intravitreal bevacizumab resulted in a significant decrease in macular thickness and improvement in visual acuity at three months but the effect was somewhat blunted, though still statistically significant at the end of six months.

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Wet age-related macular degeneration and diabetic retinopathy are pathological consequences of vascular endothelial growth factor (VEGF) release as a reaction to deficiency of oxygen and nutrients in the macular cells. Conventional treatment modalities have been constrained by limited success. Convincing evidence exists that targeting VEGF signaling is a significant approach for the therapy of these ocular angiogenesis-dependent disorders. We have come a long way since the approval of the first angiogenesis inhibitors in medicine. The clinical use of these drugs has provided enormous tempo to clinical and pharmacological research. It has also significantly altered patient outcome and expectations. In the following brief, we will discuss the development and emergence of these drugs as well as the anticipated future course based on evidence.

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Age-related macular degeneration (AMD) is one of the most common causes of severe vision loss in the western world. Both animal and human studies have established that vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of this process. Ranibizumab (Lucentis™, Genentech, South San Francisco, CA) is a monoclonal antibody fragment (Fab) directed toward all isoforms of VEGF-A that was specifically designed to target wet AMD. The human antibody fragment is produced by an E. coli expression system and has a molecular weight of 48kD allowing for excellent retinal penetration. The most common ocular complaints of patients receiving ranibizumab injections in randomized clinical trials were transient conjunctival hemorrhage, vitreous floaters, intraocular inflammation, increased intraocular pressure and eye pain. The rates of serious adverse events such as retinal detachment, cataract and endophthalmitis were similar to those that have been reported with other intravitreal injections and patients should always be treated under strict aseptic conditions to reduce this risk. There were no significant non-ocular events found during any study so far and the risk of thromboembolic events was less than 4% and not different than sham. The MARINA, ANCHOR and PIER studies validated the safety and efficacy of ranibizumab amongst a large population with different choroidal neovascular membrane lesion types against sham or standard of care treatment. These studies recommended monthly intravitreal ranibizumab for patients. However, the PIER study reported that an alternative dosing of every three months is acceptable but less effective than monthly injections.

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In the last few years anti-vascular endothelial growth factor (VEGF) therapy has changed the paradigm in the treatment of neovascular age-related macular degeneration (ARMD). Besides, its potential use in the treatment of diabetic retinopathy and other possible proliferative vascular disorders has also shown promise. Clinical trial results have shown tremendous beneficial effect of ranibizumab in ARMD. Off-label use of bevacizumab has also shown similar benefit but long-term and clinical trial results do not exist. Some of the potential questions in the use of anti-VEGF are recurring cost, possible long-term effect on physiological function of VEGF and determination of endpoint of treatment. Overall, the use of anti-VEGF therapy in ocular angiogenesis has proven to be beneficial at least now.

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Age-related macular degeneration (AMD) is now considered an important and leading cause of blindness among elderly patients in developed and developing countries. AMD has two forms, dry and wet; both can lead to visual loss. However, occurrence of subfoveal choroidal neovascular (CNV) membrane in the wet form results in severe visual impairment. Treatment options for choroidal neovascularization are available in order to maintain and in some cases improve vision. Photodynamic therapy (PDT) has been used to treat both classic and occult membranes. It has known to cause choroidal hypoperfusion and production of vascular endothelial growth factor. Intravitreal steroid can possibly reduce the damage caused due to these undesirable effects. In the recent past, intravitreal injection of triamcinolone acetonide (IVTA) has been used extensively as an adjunct to PDT in AMD in order to reduce the number of PDT sessions and evaluate possible beneficial effects on vision. This article reviews the pharmacological attributes of triamcinolone, available evidence of its use as monotherapy or combination therapy to treat AMD, ocular side-effects thereof and ongoing clinical trials on IVTA.

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Age-related macular degeneration (ARMD) is the most common cause for visual impairment in the elderly in western countries. Recently several anti-vascular endothelial growth factor (VEGF) drugs like pegaptanib sodium (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin) are available for use in the management of wet ARMD. A major limitation of these drugs is that they require multiple intravitreal injections, every 4 to 6 weeks interval for a period of 2 years. Moreover, most of these drugs are too expensive for the general masses to afford in developing nations. Avastin, though used "off-label", offers a comparable result at affordable cost, however, long term results are awaited. The drug industry should review the entire pricing policy of these drugs in developing countries like India, and develop affordable alternative compounds. The article reviews the economic burden and affordability issues of these Anti-VEGF drugs in ARMD.

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Angioid streaks are crack-like dehiscences in the Bruch's membrane, which predispose to the development of a choroidal neovascular membrane (CNVM) that carries a poor visual outcome. We report successful treatment in a 25-year-old woman with bilateral angioid streaks and subfoveal CNVM in the left eye who received two doses of intravitreal bevacizumab (1.25 mg) injections six weeks apart, resulting in rapid regression of the CNVM.

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Pegaptanib sodium (Macugen™) is a selective RNA aptamer that inhibits vascular endothelial growth factor (VEGF) ₁₆₅ , the VEGF isoform primarily responsible for pathologic ocular neovascularization and vascular permeability, while sparing the physiological isoform VEGF ₁₂₁ . After more than 10 years in development and preclinical study, pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration. Its excellent ocular and systemic safety profile has also been confirmed in patients receiving up to three years of therapy. Early, well-controlled studies further suggest that pegaptanib may provide therapeutic benefit for patients with diabetic macular edema, proliferative diabetic retinopathy and retinal vein occlusion. Notably, pegaptanib was the first available aptamer approved for therapeutic use in humans and the first VEGF inhibitor available for the treatment of ocular vascular diseases.

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Intracameral injection of bevacizumab (Avastin) helped in the successful regression of an anterior chamber neovascular membrane in a painful blind eye. The effect was persistent even after six months of follow-up. This is the first report on intracameral administration of bevacizumab with six months of follow-up.

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A prospective cohort study of 200 anisometropic amblyopes was conducted. The patients were classified into two groups. Group A: Patients less than 12 years of age. This consisted of 144 (72%) patients, the average age being 7.77 years (±2.34, range 1 to 12). Group B: Patients more than 12 years of age. This comprised 56 (28%) patients, the average age being 19.8 years (±5.47, range 12 to 30). Criterion for success was defined as best corrected visual acuity of 20/40 (0.5 logMAR equivalent) or better. The Chi-square test was used to compare baseline characteristics and success rates. There were no significant differences in the baseline characteristics between the two groups ( P =0.07). The treatment was successful in 108 (75%) in Group A and in 34 (60.7%) in Group B ( P = 0.07). There was no statistically significant change in the success rate of treatment of anisometropic amblyopia, even beyond 12 years of age.

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A case of Lenz microphthalmia syndrome in a seven-month-old male child having features of unilateral anophthalmia, microcephaly, external ear and finger abnormalities, hydrocele and hypospadias is being reported. The unilateral involvement and anophthalmia is rare in Lenz syndrome. The manifestation of hydrocele in association with this syndrome has not been seen in earlier cases. This is the first documented case from India.

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Blunt trauma can result in indirect scleral rupture with subsequent dislocation of the crystalline lens in the subconjunctival or subtenon space. This retrospective review of eight patients with traumatic phacocele highlights the clinical presentation, management and visual outcome. This study provides evidence that timely and effective intervention can ensure good visual recovery.

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We report a case series of endophthalmitis by an organism hitherto not reported in the eye. Nineteen of 63 cataract patients operated in a high-volume setup were urgently referred to us with acute onset of decreased vision one to two days following cataract surgery. All patients had clinical evidence of acute endophthalmitis with severe anterior chamber exudative reaction. Vitreous tap was done in three representative patients and repeated intravitreal injections were given as per established protocol. The vitreous sample from all three patients grew Enterobacter amnigenus Biogroup II, a gram-negative bacillus which, to the best of our knowledge, has never been reported in the eye. With prompt and accurate microbiological support, it was possible to salvage 17 of these eyes without performing vitrectomy. Six eyes regained 6/200 or better vision.

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We report a series of retinal pigment epithelial (RPE) tears after intravitreal bevacizumab therapy for choroidal neovascularization associated with age-related macular degeneration (ARMD). Retinal pigment epithelial tears were estimated to occur at an incidence of 1.6% in this patient population at our institution. Ophthalmologists should be aware of this rare but serious finding associated with exudative macular degeneration therapy.

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A case of spontaneous, painless partial III (pupil-sparing) and IV fascicular nerve paresis as the first presentation of anaplastic astrocytoma is reported. The other ocular, neurological and systemic examination was within normal limits. The literature and possible anatomical location of this atypical presentation is reviewed.

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Foldable acrylic intraocular lenses (IOLs) are known to reduce posterior capsule opacification by preventing migration of lens epithelial cells with its square edge design and its property of tackiness. Studies have reported a mean adhesiveness to posterior capsule more than three times higher for certain acrylic foldable IOLs than polymethyl methacrylate IOLs. The authors would like to report two cases where the force of tackiness was compensated, thereby presenting with delayed accumulation of lens material in the capsular bags behind the IOL with temporary loss of vision.

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We report a case of a 55-year-old male patient with breast carcinoma, who developed choroidal metastasis. The patient had undergone mastectomy for carcinoma of right breast, five years ago. The patient was advised close follow-up for the left eye, as he was already on tamoxifen therapy (started a month ago) for spinal metastasis. On last follow-up, a year later, the choroidal lesion had completely scarred, with no recurrences. Systemic hormonal therapy like tamoxifen given for the breast primary and other systemic metastases may cause regression of the choroidal metastasis, thereby avoiding ocular radiotherapy. Medline search revealed only one published case of regression of choroidal metastasis from a male breast primary, on tamoxifen therapy.

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