Retinal Vein Occlusion: Anti-VEGF Therapy and Ranibizumab
Retinal Vein Occlusion: Anti-VEGF Therapy and Ranibizumab
Purpose To evaluate the efficacy and safety of intravitreal ranibizumab (Lucentis) in patients with treatment-naive retinal vein occlusion.
Design Prospective, consecutive, non-comparative, interventional case series.
Participants Seventeen eyes of 17 consecutive patients with naive retinal vein occlusion.
Methods Consecutive patients were recruited and received, on demand, intravitreal 0.5 mg of ranibizumab; nine had central retinal vein occlusion (CRVO) and eight had branch retinal vein occlusion (BRVO). Pre- and postoperative clinical evaluation included measurement of best corrected visual acuity (BCVA) for distance, and near vision (MNREAD time, reading fluency), contrast sensitivity, colour fundus photography, fluorescein angiography and optical coherence tomography (OCT). All subjects were followed for a minimum of 12 months.
Main outcome measures Change in BCVA, contrast sensitivity, angiographic leakage, OCT central macular thickness (CMT), number of treatments.
Results Patients with CRVO had mean pre-treatment BCVA of 20/240 (1.08±0.25 logarithm of the minimum angle of resolution (logMAR)) and final BCVA of 20/46 (0.36±0.16 logMAR), with significant improvement at 1 year of follow-up (p<0.0001). At 12 months mean BCVA improved to 36.7 letters, with a gain of 6.4 lines, and OCT showed that the mean CMT was 271 μm, with a mean reduction of 360 μm (p<0.0001) from baseline (mean 631 μm). Patients with BRVO had mean pre-treatment BCVA of 20/126 (0.80±0.29 logMAR) and final BCVA of 20/50 (0.41±0.23 logMAR) (p<0.0001). The mean OCT CMT was 278 μm, with a mean reduction of 275 μm (p<0.0001) from baseline (mean 553 μm). Contrast sensitivity, MNREAD time and reading fluency improved significantly in the treated eyes. No ocular or systemic side effects were observed. Eyes with CRVO received an average of 3.0 injections (range 2–4) and those with BRVO 3.6 (range 3–4).
Conclusions Intravitreal ranibizumab for the management of naive CRVO or BRVO can favourably modify the course of the occlusion, indicating that short- and long-term blockade of vascular endothelial growth factor (VEGF)-A may restore the integrity of the inner blood–retinal barrier, reduce CMT and significantly improve visual function, with a good safety profile. Further prospective long-term studies are warranted to confirm the efficacy, safety and optimal treatment regimen for intravitreal ranibizumab.
Branch and central retinal vein occlusions (RVO) are among the most common retinal vascular diseases, and are often associated with moderate to severe vision loss. More than 90% of RVO occur in patients >50 years, but they are reported in all age groups. Central retinal vein occlusion (CRVO) results from thrombosis in the central retinal vein within the optic nerve at variable distances posterior to the lamina cribrosa, with fundus haemorrhage involving the entire retina with oedema, dilated retinal vein and disc swelling. Branch retinal vein occlusion (BRVO) occurs at more distal sites and is caused by focal occlusion of a retinal vein at an arterio-venous crossing-point where compression of the vein by the artery passing anteriorly produces turbulence and thrombosis with haemorrhage and oedema that usually involve the superior or inferior temporal retinal vein.
The exact pathogenesis of the occlusion is poorly understood, but various local and systemic factors appear to play a role in the pathological closure of the retinal veins. The most common risk factors are the same as for cardiovascular disease, including systemic hypertension, atherosclerotic vascular changes, diabetes mellitus and age >65 years. Open-angle glaucoma is also considered a major risk factor and in recent years hyperhomocysteinaemia and hypercoagulable risk factors have been increasingly implicated.
Visual acuity (VA) can be lost due to retinal ischaemia or cystoid macular oedema caused by capillary leakage, with endothelial cell damage combined with increased intracapillary pressure promoting exudation of extracellular proteins, intraretinal fluid and blood, and precipitation of lipids, in the macula. The pathogenesis of macular oedema is generally related to upregulation of vascular endothelial growth factor (VEGF)-A, which may act on capillary hyperpermeability by increasing vesicular transport and/or lowering the abundance of tight-junction proteins among the endothelial cells. Therefore it seems rational to inhibit VEGF-A with the intention of normalising the inner blood–retinal barrier, reducing vascular leakage and macular oedema, and improving visual function.
Short-term clinical trials have shown the effectiveness and safety of intravitreal anti-VEGF-A therapy for treating CRVO. Validation of VEGF-A targeting for therapeutic intervention in CRVO and BRVO comes from clinical studies involving two different intravitreal anti-VEGF-A drugs: bevacizumab (Avastin; Genentech/Roche, Basel, Switzerland) and pegaptanib sodium (Macugen; OSI-Eyetech Pharmaceuticals, New York, USA). Ranibizumab (Lucentis; Genentech Inc., South San Francisco, California, USA) is a Food and Drug Administration (FDA)-approved anti-VEGF-A monoclonal antibody designed specifically to treat exudative age-related macular degeneration (AMD). Two large clinical trials are currently in progress to investigate the efficacy and safety of ranibizumab injections in patients with macular oedema secondary to CRVO (A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion (CRUISE)) and BRVO (Background Regimen of Raltegravir on Virologic Outcome (BRAVO)). The purpose of the present study was to compare VA, reading performance and contrast sensitivity (CS) in patients assigned to receive intravitreal injections of ranibizumab for non-ischaemic CRVO or BRVO with macular oedema.
Abstract and Introduction
Abstract
Purpose To evaluate the efficacy and safety of intravitreal ranibizumab (Lucentis) in patients with treatment-naive retinal vein occlusion.
Design Prospective, consecutive, non-comparative, interventional case series.
Participants Seventeen eyes of 17 consecutive patients with naive retinal vein occlusion.
Methods Consecutive patients were recruited and received, on demand, intravitreal 0.5 mg of ranibizumab; nine had central retinal vein occlusion (CRVO) and eight had branch retinal vein occlusion (BRVO). Pre- and postoperative clinical evaluation included measurement of best corrected visual acuity (BCVA) for distance, and near vision (MNREAD time, reading fluency), contrast sensitivity, colour fundus photography, fluorescein angiography and optical coherence tomography (OCT). All subjects were followed for a minimum of 12 months.
Main outcome measures Change in BCVA, contrast sensitivity, angiographic leakage, OCT central macular thickness (CMT), number of treatments.
Results Patients with CRVO had mean pre-treatment BCVA of 20/240 (1.08±0.25 logarithm of the minimum angle of resolution (logMAR)) and final BCVA of 20/46 (0.36±0.16 logMAR), with significant improvement at 1 year of follow-up (p<0.0001). At 12 months mean BCVA improved to 36.7 letters, with a gain of 6.4 lines, and OCT showed that the mean CMT was 271 μm, with a mean reduction of 360 μm (p<0.0001) from baseline (mean 631 μm). Patients with BRVO had mean pre-treatment BCVA of 20/126 (0.80±0.29 logMAR) and final BCVA of 20/50 (0.41±0.23 logMAR) (p<0.0001). The mean OCT CMT was 278 μm, with a mean reduction of 275 μm (p<0.0001) from baseline (mean 553 μm). Contrast sensitivity, MNREAD time and reading fluency improved significantly in the treated eyes. No ocular or systemic side effects were observed. Eyes with CRVO received an average of 3.0 injections (range 2–4) and those with BRVO 3.6 (range 3–4).
Conclusions Intravitreal ranibizumab for the management of naive CRVO or BRVO can favourably modify the course of the occlusion, indicating that short- and long-term blockade of vascular endothelial growth factor (VEGF)-A may restore the integrity of the inner blood–retinal barrier, reduce CMT and significantly improve visual function, with a good safety profile. Further prospective long-term studies are warranted to confirm the efficacy, safety and optimal treatment regimen for intravitreal ranibizumab.
Introduction
Branch and central retinal vein occlusions (RVO) are among the most common retinal vascular diseases, and are often associated with moderate to severe vision loss. More than 90% of RVO occur in patients >50 years, but they are reported in all age groups. Central retinal vein occlusion (CRVO) results from thrombosis in the central retinal vein within the optic nerve at variable distances posterior to the lamina cribrosa, with fundus haemorrhage involving the entire retina with oedema, dilated retinal vein and disc swelling. Branch retinal vein occlusion (BRVO) occurs at more distal sites and is caused by focal occlusion of a retinal vein at an arterio-venous crossing-point where compression of the vein by the artery passing anteriorly produces turbulence and thrombosis with haemorrhage and oedema that usually involve the superior or inferior temporal retinal vein.
The exact pathogenesis of the occlusion is poorly understood, but various local and systemic factors appear to play a role in the pathological closure of the retinal veins. The most common risk factors are the same as for cardiovascular disease, including systemic hypertension, atherosclerotic vascular changes, diabetes mellitus and age >65 years. Open-angle glaucoma is also considered a major risk factor and in recent years hyperhomocysteinaemia and hypercoagulable risk factors have been increasingly implicated.
Visual acuity (VA) can be lost due to retinal ischaemia or cystoid macular oedema caused by capillary leakage, with endothelial cell damage combined with increased intracapillary pressure promoting exudation of extracellular proteins, intraretinal fluid and blood, and precipitation of lipids, in the macula. The pathogenesis of macular oedema is generally related to upregulation of vascular endothelial growth factor (VEGF)-A, which may act on capillary hyperpermeability by increasing vesicular transport and/or lowering the abundance of tight-junction proteins among the endothelial cells. Therefore it seems rational to inhibit VEGF-A with the intention of normalising the inner blood–retinal barrier, reducing vascular leakage and macular oedema, and improving visual function.
Short-term clinical trials have shown the effectiveness and safety of intravitreal anti-VEGF-A therapy for treating CRVO. Validation of VEGF-A targeting for therapeutic intervention in CRVO and BRVO comes from clinical studies involving two different intravitreal anti-VEGF-A drugs: bevacizumab (Avastin; Genentech/Roche, Basel, Switzerland) and pegaptanib sodium (Macugen; OSI-Eyetech Pharmaceuticals, New York, USA). Ranibizumab (Lucentis; Genentech Inc., South San Francisco, California, USA) is a Food and Drug Administration (FDA)-approved anti-VEGF-A monoclonal antibody designed specifically to treat exudative age-related macular degeneration (AMD). Two large clinical trials are currently in progress to investigate the efficacy and safety of ranibizumab injections in patients with macular oedema secondary to CRVO (A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion (CRUISE)) and BRVO (Background Regimen of Raltegravir on Virologic Outcome (BRAVO)). The purpose of the present study was to compare VA, reading performance and contrast sensitivity (CS) in patients assigned to receive intravitreal injections of ranibizumab for non-ischaemic CRVO or BRVO with macular oedema.
