|Year : 2017 | Volume
| Issue : 1 | Page : 44-47
Safety and efficacy of single intravitreal injection of ranibizumab in macular edema secondary to recent nonischemic retinal vein occlusion
Department of Ophthalmology, Assiut University Hospital, Assiut; Private Practice, Tiba Center, Tiba Hospital for Eye Surgery, Assiut; Private Practice, Tiba Hospital for Eye Surgery, Assiut, Egypt
|Date of Submission||30-Jul-2016|
|Date of Acceptance||19-Dec-2016|
|Date of Web Publication||6-Mar-2017|
Department of Ophthalmology, Assiut University Hospital, Assiut, 71515
Source of Support: None, Conflict of Interest: None
Objectives This study was designed to evaluate the safety and efficacy of a single large dose (0.7 mg) of ranibizumab for treatment of macular edema secondary to nonischemic central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO).
Setting and design A prospective interventional case series study was conducted at Tiba Hospital for Eye Surgery (private practice) in collaboration with the Ophthalmology Department, Assiut University, Egypt, from March 2013 till March 2014.
Patients and methods A total of 10 eyes of patients having macular edema caused by nonischemic CRVO or BRVO were treated by intravitreal injection of a single large dose (0.7 mg) of ranibizumab. Fluorescein angiography and spectral-domain optical coherence tomography were done for every patient before treatment, and follow-up was done with spectral-domain optical coherence tomography after injection of ranibizumab at 1, 3, and 6 months.
Results There was significant resolution of macular edema after intravitreal injection of a single large dose (0.7 mg) of ranibizumab (macular thickness was 535.5±214.7 µm at baseline compared with 281.3±145 μm at 6 months on follow-up; P=0.045) There was also significant improvement in best-corrected visual acuity (0.15±0.07 at baseline compared with 0.71±0.3 at 6 months on follow-up; P=0.007). There were no ocular or systemic adverse events documented during the 6-month follow-up period.
Conclusion A single intravitreal injection of large dose (0.7 mg) of ranibizumab is a new promising regimen for managing macular edema secondary to nonischemic CRVO or BRVO.
Keywords: antivascular endothelial growth factor, optical coherence tomography, retinal thickness
|How to cite this article:|
Ibrahim W. Safety and efficacy of single intravitreal injection of ranibizumab in macular edema secondary to recent nonischemic retinal vein occlusion. Delta J Ophthalmol 2017;18:44-7
|How to cite this URL:|
Ibrahim W. Safety and efficacy of single intravitreal injection of ranibizumab in macular edema secondary to recent nonischemic retinal vein occlusion. Delta J Ophthalmol [serial online] 2017 [cited 2017 Oct 18];18:44-7. Available from: http://www.djo.eg.net/text.asp?2017/18/1/44/201621
| Introduction|| |
Retinal vascular occlusion (RVO) is considered as the second most common retinal vascular disorder after diabetic retinopathy ,. The incidence of RVOs is estimated at 180 000 eyes per year in the USA, and branch retinal vein occlusions (BRVOs) account for nearly 80% of those .
Several risk factors have been associated with both central retinal vein occlusion (CRVO) and BRVO, including old age, systemic hypertension, atherosclerosis, diabetes mellitus, hyperhomocysteinemia, open-angle glaucoma, and optic disc drusen ,,.
RVO (both CRVO and BRVO) could be classified into ischemic and nonischemic types according to the extent of retinal ischemia. Ischemic RVO could be suspected in patients with poor vision at presentation, relative afferent pupillary defect, extensive retinal hemorrhages, and cotton wool spots. Retinal ischemia could be confirmed by fundus fluorescein angiography (FFA) by the presence of areas of capillary dropout. Reduction in b-wave amplitude could be detected in patients with ischemic RVO evaluated by full-field electroretinogram ,.
Elevated intraocular levels of vascular endothelial growth factor (VEGF) in response to retinal ischemia secondary to retinal vein occlusion have been demonstrated ,. Sustained release of VEGF in primate eyes causes vascular leakage, macular edema, and induction of retinal and anterior segment neovascularization . Those studies made the rationale for the development of ranibizumab (Patient and methods section), a humanized, affinity-matured anti-VEGF antibody fragment that binds to and neutralizes all isoforms of VEGF-A and their biologically active degradation products .
Overall, two large, multicenter trials − Ranibizumab for the Treatment of Macular Edema after Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) and the Ranibizumab for the Treatment of Macular Edema after Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) Study − were designed to determine the efficacy and safety of ranibizumab in patients with macular edema following retinal vein occlusion. Both BRAVO and CRUISE studies concluded that intravitreal injection of ranibizumab provided statistically significant improvement in visual acuity than sham injection ,.
| Patients and methods|| |
A prospective interventional pilot study was conducted in Tiba Hospital for Eye Surgery (private practice) in collaboration with the Ophthalmology Department, Assiut University, Egypt, from March 2013 till March 2014. Approval of the Ethical Committee of the Faculty of Medicine in Assiut University was obtained. In this study, patients having macular edema owing to recent (past 3 months) nonischemic RVO were included. Patients with a baseline central macular thickness (CMT) of at least 250 μm and without any neovascularization were included. In patients with BRVO, only patients with macular edema persisting longer than 3 months were recruited. Exclusion criteria were RVO presenting after more than 3 months, concomitant retinal pathology (e.g. diabetic retinopathy), previous laser treatment, previous intravitreal injection of anti-VEGF in the past 3 months, and RVO secondary to systemic vasculitis.
All patients underwent thorough systemic evaluation including cardiovascular assessment and blood pressure measurement. Baseline laboratory investigations were tailored according to physician discernment. All patients underwent a complete ophthalmologic evaluation at baseline, day 1, day 7, 1 month, 3 months, and 6 months. During follow-up, examinations included best-corrected visual acuity (BCVA) testing using E-letter chart, slit-lamp and fundus examination including tonometry, spectral-domain optical coherence tomography (SD-OCT) imaging (SPECTRALIS OCT, Heidelberg Engineering GmbH, Heidelberg, Germany), and color fundus photography. FFA was performed at 3 or 6 months according to physician decision to identify the presence of macular edema, the extent of retinal nonperfusion, and the development of retinal neovascularization After 1, 3, and 6 months, patients were examined by optical coherence tomography for evidence of intraretinal or subretinal fluid. For macular thickness evaluation, a 30×30° rectangle encompassing the macula was obtained, averaged to 40 frames and included 31 horizontal line scans to measure the CMT at 1 mm circle.
All patients received a single 0.7 mg dose injection of intravitreal Lucentis (ranibizumab; Genentech Inc., South San Francisco, California, USA). All intravitreal injections were performed in the operating room under sterile conditions after an initial paracentesis under topical anesthesia by benoxinate 0.4% eye drops. Ranibizumab was injected intravitreally via the pars plana using a 30 G needle.
Clinical information, including systemic evaluation, ophthalmic examination, BCVA, and SD-OCT findings, was entered into the database sheets in Microsoft Excel. The statistical analysis employed SPSS software, version 16.0 (SPSS Inc., Chicago, Illinois, USA). Student’s t-test was used to compare means among groups. P value less than 0.05 was considered significant.
| Results|| |
A total of 10 eyes of 10 consecutive patients (six women and four men) were included in the study. The mean age of the study population was 66±13.2 (range: 43–81) years. By systemic evaluation, 80% of the patients had hypertension, 70% had diabetes mellitus, and 20% had ischemic heart diseases. In total, six eyes had cystoid macular edema in association with BRVO, whereas four eyes had cystoid macular edema secondary to CRVO. All 10 patients continued follow-up for at least 6 months after injection. Baseline mean BCVA was 0.15±0.07 (range: 0.05–0.25). Baseline mean 1 mm CMT was 535.5±214.7 μm (range: 340–924 μm) as measured by SD-OCT. FFA was done at 3 or 6 months and revealed macular ischemia in three (30%) eyes.
Visual acuity improved and CMT decreased slightly but not significantly after 1 month to 0.28±0.13 and 337.3±170.6 μm, respectively. However, 3 months after injection, visual acuity improved and CMT decreased but not significantly to 0.4±0.21 and 309.8±150.9 μm, respectively. After 6 months of follow-up, the mean BCVA had significantly increased to 0.71±0.3 (P=0.007) and retinal thickness had significantly decreased to 281.3±145 μm (P=0.045) [Figure 1] and [Figure 2] illustrate the mean changes in BCVA and CMT from baseline up to month 6 after injection. [Table 1] summarizes the changes in BCVA and CMT from baseline up until the 6-month follow-up visit.
|Figure 1 Mean change in best-corrected visual acuity from baseline to month 6.|
Click here to view
|Figure 2 Mean change in central macular thickness from baseline to month 6.|
Click here to view
|Table 1 Baseline and postinjection mean best-corrected visual acuity and mean central macular thickness|
Click here to view
A total of nine (90%) patients showed improvement in both BCVA and CMT in the 6-month follow-up after injection ([Figure 3] and [Figure 4]). A single patient with macular edema secondary to CRVO showed persistent macular edema (CMT at baseline 640 μm compared with 576 μm after 6 months of follow-up) and small improvement in visual acuity (BCVA at baseline 0.1 compared with 0.2 after 6 months of follow-up). On reviewing FFA of this patient, macular ischemia was detected at 6 months and could be attributed to the treatment failure.
|Figure 3 A 58-year-old male patient with macular edema secondary to central retinal vein occlusion. Patient received a single dose of 0.7 mg ranibizumab intravitreal injection at baseline. BCVA, best-corrected visual acuity.|
Click here to view
|Figure 4 A 62-year-old male patient with macular odema secondary to branch retinal vein occlusion. Patient received a single dose of 0.7 mg ranibizumab intravitreal injection at baseline. BCVA, best-corrected visual acuity.|
Click here to view
At the end of 6 months of follow-up, no severe ocular (endophthalmitis, retinal detachment, traumatic cataract, uveitis) or systemic (thromboembolic event, systemic hypertension) adverse events were reported. No patient developed neovascularization of the optic disc, iris, or elsewhere in the retina.
| Discussion|| |
A single 0.7 mg dose of intravitreal injection of ranibizumab for treating patients with macular edema secondary to nonischemic CRVO or BRVO was associated with a significant and constant improvement in BCVA (0.15 at baseline compared with 0.71 after 6 months of follow-up) and with a marked reduction of CMT (535.5 μm at baseline compared with 281.3 μm after 6 months of follow-up) in 90% of the patients which is nearly similar to that achieved by repeated injections with lower doses that was demonstrated in the study by Campochiaro et.al. .
During treatment with this high dose, there was neither serious ocular nor systemic drug-related adverse events (apart from paracentesis for lowering the intraocular pressure). These results were equivalent to that observed in multiple intravitreal injections of doses ranging from 0.3–0.5 mg of ranibizumab or even 1.25 mg intravitreal injection of bevacizumab for treating macular edema secondary to nonischemic CRVO or BRVO .
This method of treatment with the high dose of ranibizumab also seems to be a new modality of treatment to avoid the short durability of lower doses. It could provide a more economic regimen for patients not covered by health insurance in our country.
The limitation of this study is the small sample size, and thus, a larger number of participants is recommended to provide a solid data on safety, efficacy, and possibility of recurrence of macular edema.
| Conclusion|| |
A single intravitreal injection of large dose (0.7 mg) of ranibizumab is a new regimen for managing macular edema secondary to nonischemic CRVO or BRVO.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc 2000; 98:133–143.
Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study. Arch Ophthalmol 2006; 124:726–732.
Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol 2008; 126:513–518.
Hayreh SS, Zimmerman B, McCarthy MJ, Podhajsky P. Systemic diseases associated with various types of retinal vein occlusion. Am J Ophthalmol 2001; 131:61–77.
Blondel J, Glacet-Bernard A, Bayani N, Blacher J, Lelong F, Nordmann JP et al.
Retinal vein occlusion and hyperhomocysteinemia. J Fr Ophthalmol 2003; 26:249–253.
Rath EZ, Frank RN, Shin DH, Kim C. Risk factors for retinal vein occlusion. A case-control study. Ophthalmology 1992; 99:509–514.
Hayreh SS. Classification of central retinal vein occlusion. Ophthalmology 1983; 90:458–474.
Sato E, Yamamoto S, Ogata K, Kubota M, Sugawara T, Mizunoya S. Changes of electroretinogram without improvement of retinal circulation after radial optic neurotomy for central retinal vein occlusion. Doc Ophthalmol 2008; 116:153–158.
Aiello LP, Avery RL, Paul G, Arrigg PG, Keyt BA, Jampel HD et al.
Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331:1480–1487.
Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T et al.
Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol 2005; 140:256–261.
Ozaki H, Hayashi H, Vinores SA, Moromizato Y, Campochiaro PA, Oshima K. Intravitreal sustained release of VEGF causes retinal neovascularization in rabbits and breakdown of the blood-retinal barrier in rabbits and primates. Exp Eye Res 1997; 64:505–517.
Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV et al.
Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther 2008; 16:791–799.
Campochiaro PA. Safety and efficacy of intravitreal ranibizumab (Lucentis) in patients with macular edema secondary to branch retinal vein occlusion: The BRAVO Study. In: The American Society of Retina Specialists Retina Congress; 4 October 2009; New York, New York, USA; 2009.
Brown DM. Safety and efficacy of intravitreal ranibizumab (Lucentis) in patients with macular edema secondary to central retinal vein occlusion: The CRUISE Study. In: The American Society of Retina Specialists Retina Congress; 4 October 2009; New York, New York, USA; 2009.
Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC et al.
Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 2010; 117:1102–1112.
Prager F, Michels S, Kriechbaum K, Georgopoulos M, Funk M, Geitzenauer W et al.
Intravitreal bevacizumab (avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial. Br J Ophthalmol 2009; 93:452–456.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]