A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema

Rajendram, Ranjan; Fraser‐Bell, Samantha; Kaines, Andrew; Michaelides, Michel; Hamilton, Robin; Esposti, Simona Degli; Pető, Tünde; Egan, Catherine; Bunce, Catey; Leslie, Richard; Hykin, Philip

doi:10.1001/archophthalmol.2012.393

Cited by 376 publications

(253 citation statements)

References 22 publications

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“…These medications bind VEGF, thereby decreasing angiogenesis and vascular permeability, causing regression of diabetic neovascularization and reduction in DME respectively [1,5]. Several recent clinical trials suggest that these therapies are more effective for DME than laser therapy [6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

Hussain

Ciulla

2016

Expert Opinion on Biological Therapy

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Section: Introductionmentioning

confidence: 99%

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

Hussain

Ciulla

2016

Expert Opinion on Biological Therapy

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“…It is currently used 'off label' for DMO. The randomised controlled Bevacizumab Or Laser Therapy (BOLT) study (eudract.ema.europa.eu: 2007-000847-89) of 80 eyes showed bevacizumab to be more effective at improving visual and anatomical outcomes than macular focal/grid laser therapy [86]. The improvements in BCVA and reduction of CMT were maintained after 2 years of follow-up.…”

Section: Anti-vegf Therapymentioning

confidence: 99%

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance

Bahrami

Zhu

Hong³

et al. 2016

Diabetologia

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Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood-retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes.

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“…Several pharmacologic agents are now available for the treatment of DMO including anti-VEGF agents [36][37][38][39][40][41] and corticosteroids. 36,[42][43][44][45][46][47][48] These treatments are summarised in Table 1.…”

Section: Pharmacologic Treatmentsmentioning

confidence: 99%

“…Targeting VEGF has resulted in the use of anti-VEGFs, including pegaptanib, ranibizumab, aflibercept, and bevacizumab, in the treatment of DMO. [36][37][38][39][40][41]43 Several clinical studies have investigated the efficacy of steroids, such as triamcinolone, fluocinolone, and dexamethasone, in the treatment of DMO. 13,42,[46][47][48][49][50][51] Corticosteroids may reduce DMO by targeting the non-VEGF-dependent inflammatory pathways including blockage of the arachidonic acid pathway (reduction of prostaglandin synthesis), and inhibition of the release of proinflammatory mediators, including VEGF.…”

Section: Pharmacologic Treatmentsmentioning

confidence: 99%

A review of therapies for diabetic macular oedema and rationale for combination therapy

Amoaku

Saker

Stewart

2015

Eye

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Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5-9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO.

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A 2-Year Prospective Randomized Controlled Trial of Intravitreal Bevacizumab or Laser Therapy (BOLT) in the Management of Diabetic Macular Edema

Abstract: eudract.ema.europa.eu Identifier: 2007-000847-89

Cited by 376 publications

References 22 publications

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

Diabetic macular oedema: pathophysiology, management challenges and treatment resistance

A review of therapies for diabetic macular oedema and rationale for combination therapy

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