Indian Journal of Clinical and Experimental Ophthalmology

Print ISSN: 2395-1443

Online ISSN: 2395-1451


Indian Journal of Clinical and Experimental Ophthalmology (IJCEO) is open access, a peer-reviewed medical journal, published quarterly, online, and in print, by the  Innovative Education and Scientific Research Foundation (IESRF) since 2015. To fulfill our aim of rapid dissemination of knowledge, we publish articles ‘Ahead of Print’ on acceptance. In addition, the journal allows free more...

  • Article highlights
  • Article tables
  • Article images

Article statistics

Viewed: 73

PDF Downloaded: 67

Yadav, Kumar, Kumar, Kumar Singh, and Rai: To study early and late effect of intravitreal injection Ranibizumab on Cystoid Macular Edema(CME) due to Branch Retinal Vein Occlusion (BRVO)


  1. Retinal vein occlusion (RVO), is the second most common cause of retinal vascular disease after diabetic retinopathy, and a significant cause of unilateral and painless loss of vision.1, 2, 3 Based on the localization of venous occlusion, the most frequent types are branch RVO (BRVO), defined as occlusion of a branch of the retinal vein system, and central RVO (CRVO), defined as occlusion located in the central retinal vein. 4, 5 RVO is a significant cause of vision loss with overall incidence of 0.21% among patients of age ≥40 years.6

  2. The prevalence of RVO ranges from 0.7 to 1.6%.7 An estimated 16 million people globally develop RVO, of which BRVO comprises 80% of cases.8 BRVO is more common than CRVO, 9 and affects approximately 1% of the population. The estimated prevalence of BRVO ranges from 0.6 to 1.1%.10 It can cause severe vision loss due to macular edema, retinal neovascularization, and retinal detachment.11 Arterial stiffness is main pathogenic mechanism for the development of BRVO, that can cause venous compression in the common adventitial sheath.4, 7 aging, cardiovascular diseases, smoking, and hypertension are the main risk factors for BRVO.12

  3. Treatment for managing macular edema with BRVO include macular grid laser photocoagulation and anti-vascular endothelial growth factor (VEGF) inhibitors. The treatment of retinal vascular diseases, including BRVO, has been improved with the introduction of intravitreal pharmacotherapy. Anti-VEGF therapy has now become the treatment of choice for macular edema due to BRVO. Many multicenter studies have shown that anti-VEGF treatment to be effective in reducing intra retinal fluid (IRF) and retinal hemorrhages, associated with a statistically significant improvement in visual acuity.13, 14, 15 Ranibizumab, dexamethasone implants, off-label bevacizumab, and triamcinolone have demonstrated efficacy in the therapy of macular edema due to RVO and significantly expanded treatment options, becoming the standard of care.14, 15, 16, 17

  4. In the pathogenesis of BRVO, VEGF plays an important role, with upregulated expression by hypoxia and a number of other stimuli. In BRVO patients, the VEGF concentration in the ocular fluid is increased, that correlates with the severity of macular edema.5, 18

  5. Many anti-VEGF agents have been widely used for treating macular edema due to BRVO, including ranibizumab. Ranibizumab binds and inhibits VEGF, an important driver of macular edema in BRVO. The efficacy of intravitreal ranibizumab for treating macular edema in patients with BRVO has been established in many studies.15 The pivotal phase III BRVO.19 study helped the approval of ranibizumab for the treatment of visual impairment due to macular edema secondary to BRVO. Ranibizumab has been approved in the USA (2010) and the European Union (2011) for the treatment of visual impairment due to macular edema due to RVO. Razumab® (the world’s first biosimilar of ranibizumab by Intas Pharmaceuticals Ltd.) was approved by the Drug Controller General of India in February 2015 for the treatment of wet age-related macular degeneration, diabetic macular edema, macular edema following RVO, and visual impairment because of choroidal neovascularization secondary to pathological myopia. The efficacy and safety of ranibizumab in the treatment of BRVO has been established in many prospective, randomized, double-masked clinical trials. The efficacy and safety of Razumab® has been demonstrated in a prospective study in Indian patients with chorioretinal vascular diseases including BRVO.20 Hence, present study was planned “To Study Early And Late Effect Of Intravitreal Injection Ranibizumab on Cystoid Macular Edema Due To Branch Retinal Vein Occlusion ” with following objectives in our setting.

Aim of The Study

Aim of this study "To study early and late effect of intravitreal injection Ranibizumab on Cystoid Macular Edema(CME) due to branch retinal vein occlusion ".

Material and Methods

This is an observational study included 25 eyes in 25 patients(≥ 18years) with cystoid macular edema because of Branch retial vein occlusion in our tertiary care hospital. The treatment procedure was intravitreal ranibizumab at the dose of 0.50 mg in 0.05 ml. An observational study including has been concluded in which improve in visual acuity and reduction in central macular thickness has been compared in patients with cystoid macular edema presented within and after 4 weeks of onset of BRVO.

Inclusion criteria

  1. Age ≥18 years

  2. Macular edema secondary to BRVO

  3. BCVA between 20/400 to 20/40

Exclusion criteria

  1. Presence of any ocular disease that might cause interpretation of study results, compromise VA, affect macular oedema or require medical or surgical intervention in the study eye during study period;

  2. Any active ocular infection or inflammation in either eye at the time of screening or baseline visit;

  3. Uncontrolled glaucoma (intraocular pressure (IOP) =30 mmHg on medication) at the screening or within 6 months before the baseline visit, or neovascularization of the iris or neovascular glaucoma in either eye;

  4. Past episode of BRVO in the study eye;

  5. Past treatment with any anti-angiogenic drug including any anti-VEGF drug in either eye, within 3 months before the baseline visit;

  6. Intra-/periocular corticosteroids within 3 months before the screening visit, past pan-retinal laser photocoagulation,˂3months before visit or scheduled within the next 3 months following baseline visit, past focal/grid laser photocoagulation, ˂4 months before the baseline visit or any intraocular corticosteroid implants in the study eye;

  7. Treatment with any systemic anti-VEGF drug, ˂6 months before the baseline visit;

  8. History of stroke; or

  9. Uncontrolled blood pressure (systolic value of >160 mmHg or diastolic value of >100 mmHg) at the screening.


  1. An informed consent was taken from all patients included in the study and underwent the following pre-operative evaluation

  2. Visual acuity assessment,

  3. Intra-ocular pressure (IOP

  4. Slit lamp examination for anterior Segment

  5. Fundus examination-Direct and Indirect ophthalmoscopy

  6. Optical coherence tomography (OCT

Technique of injecting intravitreal Ranibizumab

The eye was topically anesthetized and a povidone iodine (10%) cleaning was performed on the lids and lashes. A Sterile speculum was placed between the eyelids. Povidone iodine (5%) drops were then instilled on the ocular surface three times. Additional topical anesthetisia was achieved by instilling 4% lidocaine. Ranibizumab (0.05 ml; 0.50mg) in an insulin syringe with a 30-gauge needle was then injected through the pars plana into the vitreous cavity through the sclera 3 to 4 mm posterior to the limbus at infero-temporal quadrant. Post injection light perception was assessed and intraocular pressure(IOP) was monitored. After the injection, the patient was advised to apply topical antibiotics to the injected eye 4 times a day for 3 days.

Follow-up was done at 1st day , 1 week , 2 week, and 4 week post-injection

Figure 1

Pre-injection OCT showing central macular thickness of BRVO patient

Figure 2

Post-injection OCT showing central macular thickness of BRVO patient


Table 1

Number of patients presented within 4 week and after 4 week of onset of BRVO


Within 4 weeks

After 4 weeks







Table 2

Change in BCVA at 4 week followingintravitreal Ranibizumab in patients presented within 4 week and after 4 week of onset of BRVO.

Improved BCVA

No. of pts within 4 weeks


No. of pts after 4 weeks


1 Line





2 Lines





3 Lines





4 Lines





5 Lines





Table 3

Change in CMT

Presentation of pts relative to onset of BRV0

Mean pre-inj CMT

Mean CMT at 4 weeks

Mean decrease in CMT

Within 4 week




After 4 week





Baseline characteristics

  1. A total of 25 eyes from 25 consecutively consented patients received an intravitreal injection of Ranibizumab. All 25 patients completed follow-up visit.

  2. These 25 patients had a mean age of 58 53 year.

  3. Out of 25 patients with BRVO, 13 were male and 12 female.

  4. Out of 25 patients,10 patients were presented within 4 weeks and 15 patients after 4 weeks of onset of BRVO.

  5. Of the 25 eyes, none had received prior therapy like laser photocoagulation or intravitreal triamcinolone before receiving intravitreal Ranibizumab.

  6. The baseline mean systolic and diastolic BP value were 139 22 and 85 27mmHg respectively.


  1. A total of 25 injection of Ranibizumab was performed in 25 eyes and follow-up was done at 1st day, 1 week, 2 weeks and 1 month post- injection.

  2. The injection was well tolerated in all patients. There were no episode of inflammation or severe vision loss. There were no case of endophthalmitis, uveitis, ocular toxicity, retinal detachment or lens damage.

  3. Blood pressure was monitored before injection and each follow-up and no significant elevation was observed over course of study. Known hypertensive continued their antihypertensive treatment with no new antihypertensive additions.

  4. During follow-up, there were no thromboembolic events like cerebrovascular accidents, transient ischaemic attacks, myocardial infarction or peripheral vascular disease.

  5. During follow-up, IOP was stable. No topical anti-glaucoma therapy was needed. Since injected volume of Ranibizumab was very small (0.05 ml) ,no paracentesis was needed.

Visual acuity outcomes

  1. Within 1 week after Ranibizumab injection improvement in visual acuity were observed and these significant changes continued through 4 weeks.

  2. At week 4, out of 10 patients of BRVO who presented within 4 weeks of onset of BRVO, 2 patients showed 1 lines improvement, 1 patient 2 lines, 2 patients 3 lines, 4 patients 4 lines and 1 patient showed 5 lines improvement in visual acuity.

  3. Out of 15 patients of BRVO who presented after 4 weeks of onset of BRVO , 5 patients showed 1 line improvement, 7 patients 2 lines,1 patient 3 lines and 2 patients showed 4 lines improvement in visual acuity.

Optical coherence tomography outcomes

Mean decrease in central macular thickness in 10 patients of BRVO who presented within 4 weeks of onset of BRVO was 195 µm and in 15 patients who presented after 4 weeks of onset of BRVO was 125 µm.


  1. Intravitreal Ranibizumab treatment was associated, on average, with rapid gain of visual acuity in patients who presented within 4 weeks of onset of Branch Retinal Vein Occlusion (BRVO) compare to presented after 4 weeks of onset of BRVO.

  2. This was paralled by a rapid decrease in central macular thickness in patients who presented within 4 weeks of onset of Branch retinal vein occlusion (BRVO) compare to presented after 4 weeks of onset of BRVO.

Visual acuity

  1. In our study, 25 patients were of BRVO

  2. At the end of 4 weeks, out of 25 patients of BRVO, 10 patients presented within 4 weeks of onset of BRVO and showed improvement in BCVA of 1 line in 2 patients (20%), 2 lines in 1 patients (10%), 3 lines in 2 patients (20%), 4 lines in 4 patients (40%) and 5 lines in 1 patients (10%).

  3. Out of 25 patients of BRVO, 15 patients presented after 4 weeks of onset of BRVO and showed improvement in BCVA of 1 line in 5 patients(33.33%), 2 lines in 7 patients (46.67%),3 lines in 1 patients (6.67%), 4 lines in 2 patients (13.33%) and none showed further improvement.

Central Macular Thickness(CMT)

In BRVO, patients who presented within 4 weeks of onset of BRVO showed mean reduction in CMT was 195 µm and who presented after 4 weeks of onset of BRVO, showed mean reduction in CMT was 125 µm(P=0.040).


  1. In the present prospective, observational study, an intravitreal Ranibizumab injection 0.50 mg in 0.05 ml for cystoid macular edema due to Branch retinal vein occlusion was safe and tolerated with improvement in visual acuity and reduction in central macular thickness on OCT.

  2. Results of my study are comparative to the result of previous studies. The difference between the baseline values and during follow-up and maximum BCVA and decreased CMT was significant.

  3. Gain in VA at 4 weeks was more in patients presented within 4 weeks of onset of BRVO as compare to present after 4 weeks of onset of BRVO.

  4. Similarly, decrease in CMT at 4 weeks was more in patients presented within 4 weeks of onset of BRVO as compare to presented after 4 week of onset of BRVO.

  5. Thus, intravitreal Ranibizumab is more effective in patients presented early than late in improving BCVA and decreasing CMT.

Source of Funding


Conflict of interest




S Sain Y Sharma A Venkataraman K Vivek R Azad P Chandra Ranibizumab as an adjunct to laser for macular edema secondary to branch retinal vein occlusionIndian J Ophthalmol2012604263


R Klein B E Klein S E Moss S M Meuer The epidemiology of retinal vein occlusion: the Beaver Dam Eye StudyTrans Am Ophthalmol Soc2000981413


P Mitchell W Smith A Chang Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye StudyArch Ophthalmol19961141012437


P Kolar Definition and classification of retinal vein occlusionInt J Ophthalm Res201621249


W T Song X B Xia Ranibizumab for macular edema secondary to retinal vein occlusion: a meta-analysis of dose effects and comparison with no anti-VEGF treatmentBMC Ophthalmol201515


R David L Zangwill M Badarna Y Yassur Epidemiology of Retinal Vein Occlusion and Its Association with Glaucoma and Increased Intraocular PressureOphthalmologica198819726974


J Rehak M Rehak Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment ModalitiesCurr Eye Res200833211131


Y Minami T Nagaoka A Ishibazawa A Yoshida Correlation between short- and long-term effects of intravitreal ranibizumab therapy on ji17BMC Ophthalmol201717190


S S Hayreh R Thapa S Bajimaya G Paudyal Khanals S Tan Prevalence, patternand risk factors of retinal vein occlusion In an elderly population in Nepal: the Bhaktapur Retina StudyIndian J Ophthalmol19944210162


I Tsui A Bajwa V Franco-Cardenas C K Pan H Y Kim S D Schwartz Peripheral fluoresce angiographic findings in fellow eyes of patients with branch retinal vein occlusion2013464127


K A Aghdam L Reznicek M S Sanjarim C Framme A Bajor A Klingenstein Peripheral retinal non perfusion and treatment response in branch retinal vein occlusionInt J Ophthalmol20169685862


S Rezar K Eibenberger W Bühl M Georgopoulos U S Erfurth S Sacu Anti-VEGF treatment in branch retinal vein occlusion: a real-world experience over 4 yearsActa Ophthalmol201593871925


P Hahn S Fekrat Best practices for treatment of retinal vein occlusionCurr Opin Ophthalmol201223317581


D M Brown P A Campochiaro R P Singh Z Li S Gray N Saroj Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III studyOphthalmology20101176112433


I U Scott M S Ip P C Van Veldhuisen Odennl B A Blodi M Fisher A randomizedtrial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report6Arch Ophthalmol2009127111528


J A Haller F Bandello R Belfort M S Blumenkranz M Gillies J Heier X Y Li Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusionOphthalmology20101176113446


H Gerding J Monés R Tadayoni F Boscia IPearce S Priglinger Ranibizumab in retinal vein occlusion: treatment recommendations by an expert panelBr J Ophthalmol2015993297304


C Ehlken E S Rennel D Michels B Grundel A Pielen B Junker Levels of VEGF but not VEGF165b are Increased in the Vitreous of Patients With Retinal Vein OcclusionAm J Ophthalmol20111522298303


P A Campochiaro J S Heier L Feiner S Gray N Saroj A C Rundle Ranibizumab for Macular Edema following Branch Retinal Vein OcclusionOphthalmology20101176110212.


V V Sameera A G Apoorva S Joshi A S Guruprasad Safety and efficacy of Razumab – The new biosimilar in India: Our experienceKerala J Ophthalmol20162831805


© This is an open access article distributed under the terms of the Creative Commons Attribution License - Attribution 4.0 International (CC BY 4.0). which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Article type

Original Article

Article page


Authors Details

Ram Yash Singh Yadav, Anil Kumar, Ram Kumar, Ashutosh Kumar Singh, Chiranjee Rai

Article History

Received : 08-01-2021

Accepted : 21-01-2021

Available online : 02-04-2021

Article Metrics

View Article As


Downlaod Files