New Approaches for the Treatment of Diabetic Macular Edema
New Approaches for the Treatment of Diabetic Macular Edema
The current standard therapy for patients with diabetic macular oedema (DME)—focal/grid laser photocoagulation—usually does not improve impaired vision, and many patients lose vision despite laser therapy. Recent approval of ranibizumab by the European Medicines Agency to treat visual impairment due to DME fulfils the previously unmet medical need for a treatment that can improve visual acuity (VA) in these patients. We reviewed 1- and 2-year clinical trial findings for ranibizumab used as treatment for DME to formulate evidence-based treatment recommendations in the context of this new therapy. DME with or without visual impairment should be considered for treatment when it fulfils the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria for clinically significant oedema. For DME with centre involvement and associated vision loss due to DME, monthly ranibizumab monotherapy with treatment interruption and re-initiation based on VA stability is recommended. Laser therapy based on ETDRS guidelines is recommended for other forms of clinically significant DME without centre involvement or when no vision loss has occurred, despite centre involvement. Because these recommendations are based on randomised controlled trials of 1–2 years duration, guidance may need updating as long-term ranibizumab data become available and as additional therapeutic agents are assessed in clinical trials.
Diabetic macular oedema (DME) is a leading cause of visual impairment in people with diabetes mellitus, and, if left untreated, >50% of patients lose >2 lines of visual acuity (VA) within 2 years. DME mostly affects the working-age population, imposing a significant burden both on society and on individual patients—a burden that is expected to increase with the rising prevalence of diabetes.
The standard therapy for visual impairment due to DME—focal and/or grid laser photocoagulation—is mostly only able to stabilise vision. In the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria in patients with visual impairment due to DME, laser therapy reduced the relative risk of losing 15 letters of VA by 50% compared with deferring treatment. More recent trials reported gains of only 0.9 letters and three letters for patients receiving laser monotherapy according to ETDRS guidelines. Nevertheless, a small group of laser-treated patients (21%) in the DRCR.net protocol I study did achieve a 15-letter improvement in VA at 2 years, suggesting a delayed benefit. Notwithstanding the importance of preventing further vision loss, there was until recently an unmet medical need for therapies that could restore VA in patients with DME who had visual impairment.
Although not fully elucidated, advances in understanding DME pathophysiology have launched the investigation of various pharmacological therapies, including those targeting vascular endothelial growth factor (VEGF), which is upregulated in eyes with DME, and is a major mediator of increased retinal permeability. Investigational anti-VEGF therapies include aflibercept, pegaptanib, and bevacizumab (although bevacizumab is unlicensed for intraocular use). Although some improvements in best-corrected VA (BCVA) has been observed with these agents, robust clinical trial evidence is currently limited.
Ranibizumab (Lucentis Novartis Pharma AG, Basel, Switzerland and Genentech Inc., South San Francisco, CA, USA), a fully humanised monoclonal antibody fragment that binds to multiple variants of VEGF-A, was recently approved by the European Medicines Agency for the treatment of visual impairment due to DME, based on evidence from two pivotal trials, RESOLVE and RESTORE.
New guidance that considers the availability of this agent and how it fits into the overall treatment algorithm for DME is therefore required. A panel of experts was convened, with sponsorship from Novartis Pharma AG, to review available treatment options for DME, including clinical trial evidence for ranibizumab in treating visual impairment due to this disease. The objective was to formulate treatment recommendations that provide the best possible VA outcomes while maintaining treatment regimens that are manageable and practical for both physicians and patients. This guidance is mostly based on 1-year data with ranibizumab, with the inclusion of 2-year data where available.
Abstract and Introduction
Abstract
The current standard therapy for patients with diabetic macular oedema (DME)—focal/grid laser photocoagulation—usually does not improve impaired vision, and many patients lose vision despite laser therapy. Recent approval of ranibizumab by the European Medicines Agency to treat visual impairment due to DME fulfils the previously unmet medical need for a treatment that can improve visual acuity (VA) in these patients. We reviewed 1- and 2-year clinical trial findings for ranibizumab used as treatment for DME to formulate evidence-based treatment recommendations in the context of this new therapy. DME with or without visual impairment should be considered for treatment when it fulfils the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria for clinically significant oedema. For DME with centre involvement and associated vision loss due to DME, monthly ranibizumab monotherapy with treatment interruption and re-initiation based on VA stability is recommended. Laser therapy based on ETDRS guidelines is recommended for other forms of clinically significant DME without centre involvement or when no vision loss has occurred, despite centre involvement. Because these recommendations are based on randomised controlled trials of 1–2 years duration, guidance may need updating as long-term ranibizumab data become available and as additional therapeutic agents are assessed in clinical trials.
Introduction
Diabetic macular oedema (DME) is a leading cause of visual impairment in people with diabetes mellitus, and, if left untreated, >50% of patients lose >2 lines of visual acuity (VA) within 2 years. DME mostly affects the working-age population, imposing a significant burden both on society and on individual patients—a burden that is expected to increase with the rising prevalence of diabetes.
The standard therapy for visual impairment due to DME—focal and/or grid laser photocoagulation—is mostly only able to stabilise vision. In the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria in patients with visual impairment due to DME, laser therapy reduced the relative risk of losing 15 letters of VA by 50% compared with deferring treatment. More recent trials reported gains of only 0.9 letters and three letters for patients receiving laser monotherapy according to ETDRS guidelines. Nevertheless, a small group of laser-treated patients (21%) in the DRCR.net protocol I study did achieve a 15-letter improvement in VA at 2 years, suggesting a delayed benefit. Notwithstanding the importance of preventing further vision loss, there was until recently an unmet medical need for therapies that could restore VA in patients with DME who had visual impairment.
Although not fully elucidated, advances in understanding DME pathophysiology have launched the investigation of various pharmacological therapies, including those targeting vascular endothelial growth factor (VEGF), which is upregulated in eyes with DME, and is a major mediator of increased retinal permeability. Investigational anti-VEGF therapies include aflibercept, pegaptanib, and bevacizumab (although bevacizumab is unlicensed for intraocular use). Although some improvements in best-corrected VA (BCVA) has been observed with these agents, robust clinical trial evidence is currently limited.
Ranibizumab (Lucentis Novartis Pharma AG, Basel, Switzerland and Genentech Inc., South San Francisco, CA, USA), a fully humanised monoclonal antibody fragment that binds to multiple variants of VEGF-A, was recently approved by the European Medicines Agency for the treatment of visual impairment due to DME, based on evidence from two pivotal trials, RESOLVE and RESTORE.
New guidance that considers the availability of this agent and how it fits into the overall treatment algorithm for DME is therefore required. A panel of experts was convened, with sponsorship from Novartis Pharma AG, to review available treatment options for DME, including clinical trial evidence for ranibizumab in treating visual impairment due to this disease. The objective was to formulate treatment recommendations that provide the best possible VA outcomes while maintaining treatment regimens that are manageable and practical for both physicians and patients. This guidance is mostly based on 1-year data with ranibizumab, with the inclusion of 2-year data where available.