Clinical science
Sequential therapy with ranibizumab and dexamethasone intravitreal implant is better than dexamethasone monotherapy for macular oedema due to retinal vein occlusion Lawrence P Iu,1 Paul Zhao,2 Ian Y Yeung,1 Nicholas S Fung,1 Jacky W Lee,1 Raymond L Wong,1 Victor Chong,3 Ian Y Wong1 1
Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 2 Department of Ophthalmology, National University Hospital, Singapore, Singapore 3 Department of Ophthalmology, University of Oxford, Oxford, UK Correspondence to Dr Ian Y Wong, Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Room 301, Level 3, Block B, Cyberport 4, Pokfulam, Hong Kong; [email protected] Received 10 June 2014 Revised 12 July 2014 Accepted 19 July 2014 Published Online First 19 August 2014
ABSTRACT Purpose To evaluate the efficacy and safety of sequential therapy with ranibizumab followed by dexamethasone intravitreal implant compared with dexamethasone monotherapy for macular oedema (MO) secondary to retinal vein occlusion (RVO). Methods In this retrospective interventional study, the medical records of subjects with MO due to RVO who received either ranibizumab followed by dexamethasone intravitreal implant (Group 1) or dexamethasone-implant monotherapy (Group 2) were included. Primary outcome was the proportion of subjects who exhibited bestcorrected visual acuity (VA) gain and resolution of MO within 6 months. Results Thirty-three eyes were included (17 in Group 1, 16 in Group 2). More subjects in Group 1 exhibited a VA gain of at least 0.5 (LogMAR units hereafter) than Group 2 (29% vs 0%, p=0.044). The speed of VA gain was greater in Group 1 (1.4±0.8 months vs 2.7±1.4 months, p=0.020). MO was controlled in more subjects in Group 1 at all measured time intervals, and this difference was statistically significant at 3 months and 4 months. Subjects with branch RVO experienced VA gain more rapidly if they were from Group 1 (p=0.023). Conclusions Sequential therapy was found to be more effective than dexamethasone monotherapy in treating MO due to RVO.
INTRODUCTION
To cite: Iu LP, Zhao P, Yeung IY, et al. Br J Ophthalmol 2015;99: 210–214. 210
Retinal vein occlusion (RVO) is the second most common retinal vascular disease in developed countries, after diabetic retinopathy.1 2 Macular oedema (MO) is a complication common to central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), and is the main cause of visual loss in RVO sufferers.2 3 The exact mechanism by which RVO gives rise to MO is not fully understood,4 but MO is thought to be secondary to the following factors: the build-up of venous pressure due to blocked veins; the enhanced expression of inflammatory markers such as prostaglandins and interleukin 6; the breakdown of the bloodretinal barrier; and the increased expression of vascular endothelial growth factor (VEGF).5 6 Laser photocoagulation is the standard treatment for MO secondary to BRVO,7 but not for MO secondary to CRVO.8 Intravitreal triamcinolone (IVTA) has been proposed for the latter purpose, but its use is limited by potential complications such as cataracts and glaucoma.9 The introduction
of intravitreal anti-VEGF agents has revolutionised the management of MO secondary to RVO. Intravitreal injections of ranibizumab have been found to be beneficial in terms of visual gain among subjects with MO secondary to both BRVO and CRVO.1 6 10 11 Recently, a newer intravitreal agent, dexamethasone implant, has also been found to be effective in reducing oedema and improving vision; in addition, it has relatively fewer side effects and a longer intraocular half-life.12 13 To date, the use of combination therapy with bevacizumab and dexamethasone implant to treat MO secondary to RVO has been reported in two studies,14 15 but the current study is the first to investigate the combination of ranibizumab and dexamethasone implant. The aim of this study was to compare the efficacy and safety profiles of sequential therapy with ranibizumab followed by dexamethasone intravitreal implant and dexamethasone intravitreal implant monotherapy as treatments for MO secondary to RVO.
MATERIALS AND METHODS The study was retrospective in design, and entailed a review of the medical records of eligible subjects. Individuals with MO secondary to RVO who were treated at the Eye Clinic at the University of Hong Kong between June 2012 and November 2013 were eligible. The approval of the Institutional Review Board at the University of Hong Kong was obtained, and the study adhered to the Declaration of Helsinki. The types of treatment investigated were as follows: (1) sequential therapy with ranibizumab followed by dexamethasone intravitreal implant and (2) dexamethasone intravitreal implant alone. The selected participants (A) had a baseline central foveal thickness (CFT) of ≥300 mm, (B) exhibited a best-corrected visual acuity (VA) between 20/32 and 20/1250 (equivalent to LogMAR values of 0.2 to 1.8) and (C) had followed up for at least 6 months after treatment. Subjects were excluded if they had received macular laser treatment within 3 months or IVTA within 6 months prior to the treatment programmes. Those who experienced panretinal photocoagulation during the period of study were also excluded. The eligible subjects were divided into two groups (based on the treatment they had received) for the main analysis. The subjects in Group 1 (the sequential therapy group) received an
Iu LP, et al. Br J Ophthalmol 2015;99:210–214. doi:10.1136/bjophthalmol-2014-305661
Clinical science injection of ranibizumab followed within 4 weeks by a dexamethasone intravitreal implant injection. The subjects in Group 2 (the dexamethasone monotherapy group) received an injection of dexamethasone intravitreal implant alone. Subgroup analysis was also performed with respect to different types of RVOs. Data were collected on background demographics, changes in VA, changes in CFT and any complications encountered during the course of treatment within the 6-month follow-up period. CFT was measured using spectral-domain optical-coherence tomography (Spectralis, Heidelberg Engineering). A Snellen chart was used to measure best-corrected VA and the results were converted to LogMAR values before the statistical analysis. We defined functional success as a VA gain of at least 0.1 LogMAR units (equivalent to a five-letter score on the Early Treatment Diabetic Retinopathy Study scale). Anatomical success was defined as a reduction of MO to
Sequential therapy with ranibizumab and dexamethasone intravitreal implant is better than dexamethasone monotherapy for macular oedema due to retinal vein occlusion Lawrence P Iu,1 Paul Zhao,2 Ian Y Yeung,1 Nicholas S Fung,1 Jacky W Lee,1 Raymond L Wong,1 Victor Chong,3 Ian Y Wong1 1
Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong 2 Department of Ophthalmology, National University Hospital, Singapore, Singapore 3 Department of Ophthalmology, University of Oxford, Oxford, UK Correspondence to Dr Ian Y Wong, Department of Ophthalmology, LKS Faculty of Medicine, The University of Hong Kong, Room 301, Level 3, Block B, Cyberport 4, Pokfulam, Hong Kong; [email protected] Received 10 June 2014 Revised 12 July 2014 Accepted 19 July 2014 Published Online First 19 August 2014
ABSTRACT Purpose To evaluate the efficacy and safety of sequential therapy with ranibizumab followed by dexamethasone intravitreal implant compared with dexamethasone monotherapy for macular oedema (MO) secondary to retinal vein occlusion (RVO). Methods In this retrospective interventional study, the medical records of subjects with MO due to RVO who received either ranibizumab followed by dexamethasone intravitreal implant (Group 1) or dexamethasone-implant monotherapy (Group 2) were included. Primary outcome was the proportion of subjects who exhibited bestcorrected visual acuity (VA) gain and resolution of MO within 6 months. Results Thirty-three eyes were included (17 in Group 1, 16 in Group 2). More subjects in Group 1 exhibited a VA gain of at least 0.5 (LogMAR units hereafter) than Group 2 (29% vs 0%, p=0.044). The speed of VA gain was greater in Group 1 (1.4±0.8 months vs 2.7±1.4 months, p=0.020). MO was controlled in more subjects in Group 1 at all measured time intervals, and this difference was statistically significant at 3 months and 4 months. Subjects with branch RVO experienced VA gain more rapidly if they were from Group 1 (p=0.023). Conclusions Sequential therapy was found to be more effective than dexamethasone monotherapy in treating MO due to RVO.
INTRODUCTION
To cite: Iu LP, Zhao P, Yeung IY, et al. Br J Ophthalmol 2015;99: 210–214. 210
Retinal vein occlusion (RVO) is the second most common retinal vascular disease in developed countries, after diabetic retinopathy.1 2 Macular oedema (MO) is a complication common to central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), and is the main cause of visual loss in RVO sufferers.2 3 The exact mechanism by which RVO gives rise to MO is not fully understood,4 but MO is thought to be secondary to the following factors: the build-up of venous pressure due to blocked veins; the enhanced expression of inflammatory markers such as prostaglandins and interleukin 6; the breakdown of the bloodretinal barrier; and the increased expression of vascular endothelial growth factor (VEGF).5 6 Laser photocoagulation is the standard treatment for MO secondary to BRVO,7 but not for MO secondary to CRVO.8 Intravitreal triamcinolone (IVTA) has been proposed for the latter purpose, but its use is limited by potential complications such as cataracts and glaucoma.9 The introduction
of intravitreal anti-VEGF agents has revolutionised the management of MO secondary to RVO. Intravitreal injections of ranibizumab have been found to be beneficial in terms of visual gain among subjects with MO secondary to both BRVO and CRVO.1 6 10 11 Recently, a newer intravitreal agent, dexamethasone implant, has also been found to be effective in reducing oedema and improving vision; in addition, it has relatively fewer side effects and a longer intraocular half-life.12 13 To date, the use of combination therapy with bevacizumab and dexamethasone implant to treat MO secondary to RVO has been reported in two studies,14 15 but the current study is the first to investigate the combination of ranibizumab and dexamethasone implant. The aim of this study was to compare the efficacy and safety profiles of sequential therapy with ranibizumab followed by dexamethasone intravitreal implant and dexamethasone intravitreal implant monotherapy as treatments for MO secondary to RVO.
MATERIALS AND METHODS The study was retrospective in design, and entailed a review of the medical records of eligible subjects. Individuals with MO secondary to RVO who were treated at the Eye Clinic at the University of Hong Kong between June 2012 and November 2013 were eligible. The approval of the Institutional Review Board at the University of Hong Kong was obtained, and the study adhered to the Declaration of Helsinki. The types of treatment investigated were as follows: (1) sequential therapy with ranibizumab followed by dexamethasone intravitreal implant and (2) dexamethasone intravitreal implant alone. The selected participants (A) had a baseline central foveal thickness (CFT) of ≥300 mm, (B) exhibited a best-corrected visual acuity (VA) between 20/32 and 20/1250 (equivalent to LogMAR values of 0.2 to 1.8) and (C) had followed up for at least 6 months after treatment. Subjects were excluded if they had received macular laser treatment within 3 months or IVTA within 6 months prior to the treatment programmes. Those who experienced panretinal photocoagulation during the period of study were also excluded. The eligible subjects were divided into two groups (based on the treatment they had received) for the main analysis. The subjects in Group 1 (the sequential therapy group) received an
Iu LP, et al. Br J Ophthalmol 2015;99:210–214. doi:10.1136/bjophthalmol-2014-305661
Clinical science injection of ranibizumab followed within 4 weeks by a dexamethasone intravitreal implant injection. The subjects in Group 2 (the dexamethasone monotherapy group) received an injection of dexamethasone intravitreal implant alone. Subgroup analysis was also performed with respect to different types of RVOs. Data were collected on background demographics, changes in VA, changes in CFT and any complications encountered during the course of treatment within the 6-month follow-up period. CFT was measured using spectral-domain optical-coherence tomography (Spectralis, Heidelberg Engineering). A Snellen chart was used to measure best-corrected VA and the results were converted to LogMAR values before the statistical analysis. We defined functional success as a VA gain of at least 0.1 LogMAR units (equivalent to a five-letter score on the Early Treatment Diabetic Retinopathy Study scale). Anatomical success was defined as a reduction of MO to
