Efficacy of Treatments for Macular Edema Secondary to RVO
Efficacy of Treatments for Macular Edema Secondary to RVO
Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy and is an important cause of vision loss. It is caused by occlusion of veins at the back of the eye, which become occluded by vascular clot, external compression or vessel wall pathology. Occlusion can occur either in the central retinal vein (central RVO, CRVO) or branches of the retinal veins (branch RVO, BRVO) that combine to form the central vein; prognoses and outcomes vary depending on which is occluded. RVO can lead to fluid leakage from capillaries draining into the obstructed vein, caused in part by secretion of vascular endothelial growth factor (VEGF) and interleukin-6, and resulting in thickening of the retina (oedema). Macular oedema is the most common cause of vision loss from RVO. If left untreated, patients with BRVO will gain on average only 0.23 lines on the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale after 3 years, to an average level of 20/70, but full recovery of vision is generally not achieved owing to persistent oedema and resulting structural damage. Prognosis is worse for patients with macular oedema secondary to CRVO, with visual acuity (VA) declining over time if left untreated. Both BRVO and CRVO are associated with significant impairments in vision-related quality of life (as measured by the National Eye Institute visual function questionnaire, NEI-VFQ).
A number of therapies are currently available for the treatment of RVO. Laser photocoagulation has been the standard of care for treatment of BRVO in the UK based on the results of the BVOS study performed 30 years ago. However, poor vision persists despite photocoagulation treatment in many patients, and its use is not recommended until 3 months after development of BRVO. Laser therapy was also investigated in patients with CRVO, but was found to produce no improvement in VA over no treatment; hence, observation was the standard of care for CRVO in the UK for several decades. Two new treatments – ranibizumab (Lucentis®, Novartis AG, Basel, Switzerland) and dexamethasone intravitreal (IVT) implant (Ozurdex®, Allergan, Irvine, CA, USA) – have recently been approved for treatment of macular oedema secondary to RVO in the UK, Europe and USA. Ranibizumab is a recombinant, humanized, monoclonal antibody fragment developed specifically for IVT use, which binds with high affinity to multiple VEGF isoforms and prevents binding of VEGF to VEGF receptors 1 and 2; it is prescribed at a dose of 0.5 mg. Dexamethasone IVT is a sustained-biodegradable implant containing the corticosteroid dexamethasone. Corticosteroids including dexamethasone are known to have anti-inflammatory, anti-angiogenic properties and may inhibit the expression of VEGF and other proinflammatory cytokines such as IL-6, ICAM-1 and MCP-1; it is prescribed at a dose of 0.7 mg. Two further therapies are also used to treat RVO. Bevacizumab, a full-length anti-VEGF antibody developed for treatment of cancer, has not been developed or licensed for IVT use; however, it is sometimes used to treat RVO. IVT triamcinolone (IVTA), a corticosteroid injection, with a similar mechanism of action to dexamethasone, is used off-label for the treatment of RVO. Since this review was undertaken, a third anti-VEGF treatment – aflibercept (Eylea®, Bayer AG, Berlin, Germany) – has been approved for treatment of macular oedema secondary to RVO.
It is important to consider the relative efficacy of the available therapies for RVO with published data. This systematic review was therefore performed to assess the efficacy and safety of available treatments for RVO as reported in randomized controlled trials (RCTs), and to assess the feasibility of conducting indirect comparisons between ranibizumab and other therapies available in the UK.
Background
Retinal vein occlusion (RVO) is the second most common retinal vascular disease after diabetic retinopathy and is an important cause of vision loss. It is caused by occlusion of veins at the back of the eye, which become occluded by vascular clot, external compression or vessel wall pathology. Occlusion can occur either in the central retinal vein (central RVO, CRVO) or branches of the retinal veins (branch RVO, BRVO) that combine to form the central vein; prognoses and outcomes vary depending on which is occluded. RVO can lead to fluid leakage from capillaries draining into the obstructed vein, caused in part by secretion of vascular endothelial growth factor (VEGF) and interleukin-6, and resulting in thickening of the retina (oedema). Macular oedema is the most common cause of vision loss from RVO. If left untreated, patients with BRVO will gain on average only 0.23 lines on the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale after 3 years, to an average level of 20/70, but full recovery of vision is generally not achieved owing to persistent oedema and resulting structural damage. Prognosis is worse for patients with macular oedema secondary to CRVO, with visual acuity (VA) declining over time if left untreated. Both BRVO and CRVO are associated with significant impairments in vision-related quality of life (as measured by the National Eye Institute visual function questionnaire, NEI-VFQ).
A number of therapies are currently available for the treatment of RVO. Laser photocoagulation has been the standard of care for treatment of BRVO in the UK based on the results of the BVOS study performed 30 years ago. However, poor vision persists despite photocoagulation treatment in many patients, and its use is not recommended until 3 months after development of BRVO. Laser therapy was also investigated in patients with CRVO, but was found to produce no improvement in VA over no treatment; hence, observation was the standard of care for CRVO in the UK for several decades. Two new treatments – ranibizumab (Lucentis®, Novartis AG, Basel, Switzerland) and dexamethasone intravitreal (IVT) implant (Ozurdex®, Allergan, Irvine, CA, USA) – have recently been approved for treatment of macular oedema secondary to RVO in the UK, Europe and USA. Ranibizumab is a recombinant, humanized, monoclonal antibody fragment developed specifically for IVT use, which binds with high affinity to multiple VEGF isoforms and prevents binding of VEGF to VEGF receptors 1 and 2; it is prescribed at a dose of 0.5 mg. Dexamethasone IVT is a sustained-biodegradable implant containing the corticosteroid dexamethasone. Corticosteroids including dexamethasone are known to have anti-inflammatory, anti-angiogenic properties and may inhibit the expression of VEGF and other proinflammatory cytokines such as IL-6, ICAM-1 and MCP-1; it is prescribed at a dose of 0.7 mg. Two further therapies are also used to treat RVO. Bevacizumab, a full-length anti-VEGF antibody developed for treatment of cancer, has not been developed or licensed for IVT use; however, it is sometimes used to treat RVO. IVT triamcinolone (IVTA), a corticosteroid injection, with a similar mechanism of action to dexamethasone, is used off-label for the treatment of RVO. Since this review was undertaken, a third anti-VEGF treatment – aflibercept (Eylea®, Bayer AG, Berlin, Germany) – has been approved for treatment of macular oedema secondary to RVO.
It is important to consider the relative efficacy of the available therapies for RVO with published data. This systematic review was therefore performed to assess the efficacy and safety of available treatments for RVO as reported in randomized controlled trials (RCTs), and to assess the feasibility of conducting indirect comparisons between ranibizumab and other therapies available in the UK.
