Background
Branch retinal vein occlusion (BRVO) is a common retinal vascular disorder which involves one of the branch retinal veins and is generally less visually disabling than central retinal vein occlusion. Abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal haematological factors constitute the primary mechanism of vessel occlusion. The exact pathogenesis of this disease still remain unanswered. Risk factors are systemic hypertension, diabetes, high erythrocyte sedimentation rate, smoking, glaucoma, coagulopathies, hyperviscocity states, abnormal lipid profile and increase alcohol consumption. BRVO can occur at almost any age but typically in middle to later years, mostly in these aged above 65 years due to more conventional risk factors and their severity ranges from asymptomatic to painfulblind eye. More severe forms manifest as unremitting macular edema, vitreous haemorrhage, neovascular glaucoma or even tractional retinal detachment which can be decreases by early diagnosis and appropriate therapy. Laber was first person to report a case of BRVO.1 Hayreh in 1994 categorised BRVO into two distinct entities : ‘Major BRVO’, when one of the major branch retinal vein is occluded, and ‘macular BRVO’, when one of the macular venules is occluded. Each carries its own prognosis.2
The mainstay of treatment of BRVO is by intravitreal vascular endothelial growth factor inhibitors (anti - VEGF), intravitreal triamcinolone or laser photocoagulation to prevent or treat neovascularization and macular edema and improved vitrectomy technique for advanced cases. Arteriovenous sheathotomy, hemodilution are being tried out.
Materials and Methods
This is a prospective study including 222 patients seen consecutively at the Department of Ophthalmology, in a tertiary Eye care center in state of Odisha. The study period was from October 2018 to September 2020. Ethical committee clearance was taken.
Case Definition of BRVO
Initially either flame shaped, dot or blot haemorrhages and dilation and tortuosity of retinal veins in the distribution of occluded branch retinal vein with the apex of the obstructed tributary system located at an arterio - venous crossing.
Exclusion criteria
Old BRVO with PRP.
Old debilitated patients who cannot undergo Fundus Fluorescein Angiography (FFA) and will not come for follow up.
Young patients with inflammatory retinal disease.
Patients having other occular disease like cataract, corneal opactity, diabetic retinopathy, optic atrophy and any other occular disease affecting visual status or interfering with fundus photography and documentation.
Patient refusal.
Patient lost to follow up.
Clinical evaluation included a detailed history with special emphasis on the presence of systemic hypertension, diabetes millitus, cardio vascular disease, alcohol consumption, smoking, glaucoma. All patients underwent complete ophthalmologic examinations including visual acuity testing with best correction (BCVA), slit lamp biomicroscopy for anterior segment examinations, intraocular pressure (IOP) recording by applanation tonometry, detailed fundus evaluation with indirect ophthalmoscope and fundus photography by fundus camera to locate retinal haemorrhage, venous obstruction, retinal and macular edema, neovascularization. Fundus Fluorescein Angiography (FFA) was done after 3 months of presentation for non responding patients when retinal haemorrhages cleared sufficiently to look for macular edema, neovascularization, macular nonperfusion and capillary nonperfusion> 5 DD and Optical Coherence Tomography (OCT) was carried out whether macular edema is present or not. Goiniscopy was done to know the angle status.
Blood pressure measurement and electrocardiogram (ECG) were done in all cases. Patients with hypertension were defined as those with systolic pressure > 140 mmHg or diastolic pressure > 90 mmHg. ECG were read by cardiologists and reported whether normal or abnormal. Laboratory tests included complete blood count, Erythrocyte Sedimentation Rate (ESR), Fasting Blood Sugar (FBS), Serum lipid profile (total plasma cholesterol, triglyceride, LDL).
Treatment given varied among patients basing on visual acuity of patients, complications of disease and patients’ socioeconomic status. Some patients were kept under observation and followed up. Others were given intravitreal Ranibizumab or intravitreal triamcinolone or laser photocoagulation.
Treatment protocol
Macular edema (ME) - IV Ranibizumab, IV Triamcinolone, Grid laser photocoagulation.
Neo vascularization disc (NVD) / Neo vascularization Elsewhere (NVE): Sectoral laser photocoagulation.
Vitreous haemorrhage - Parsplanavitrectomy and endo laser (PPV and EL).
Treatment of underlying systemic condition, if found, was routinely done.
Follow up visits were performed after 1st month, 2nd month, 3rd month and at 6th month. After each follow up visit appropriate treatment was given.
Observation
Table 1
Disease distribution
|
Type of BRVO |
Total No. of Patients |
|
Major BRVO |
207(94.1%) |
|
Macular BRVO |
15(5.9%) |
|
Total |
222(100%) |
The study group included total 222 patients out of which 207 (94.1%) where major BRVO and 15(5.9%) patients were macular BRVO.Table 1
Table 2
Age distribution
Out of total 222 patients, between 41-50yr age group the number of total BRVO patients were 15(6.7%),from 51-60yr age group the number of patients were 72(32.4%), from 61-70yr age group the number of patients were 108(48.6%) and from 71-80yr age group the number of patients were 27(12.1%). From 61-70yr age group there were maximum number of patients i.e. 108(48.6%) and the overall age range was 41-80 years.Table 2
Table 3
|
Statistics |
|||
|
|
Type |
Age_group |
|
|
N |
Valid |
222 |
222 |
|
Missing |
0 |
0 |
|
|
Mean |
|
62.89 |
|
|
Std. Deviation |
|
7.963 |
|
|
Skewness |
|
.108 |
|
|
Std. Error of Skewness |
|
.163 |
|
|
Kurtosis |
|
-.579 |
|
|
Std. Error of Kurtosis |
|
.325 |
|
|
Minimum |
|
47 |
|
|
Maximum |
|
80 |
|
Table 4
Output
Table 5
Sex distribution
|
Sex |
Major BRVO |
Macular BRVO |
Total No. of patients |
|
Male |
117(56.5%) |
9(60%) |
126(56.7%) |
|
Female |
90(43.5%) |
6(40%) |
96(43.3%) |
|
Total |
207 |
15 |
222 |
7% patients were male and 96(43 3% were female. Table 5
Table 6
Laterality
|
Sex |
Major BRVO |
Macular BRVO |
Total No. of patients |
|
Right eye |
114(55.1%) |
3(20%) |
117(52.7%) |
|
Left eye |
90(43.5%) |
12(80%) |
102(45.9%) |
|
Both eye |
3(1.4%) |
0 |
3(1.4%) |
|
Total |
207 |
15 |
222 |
In major BRVO out of total 222 patients, patients, right eye was involved in 114(55.1%) cases and left eye was involved in 90(43.5%) cases and both eye was involved in 3(1.4%) case. Out of 15 Macul.ar BRVO right eye was involved in 3(20%), left eye in 12(80%) and in no case both eye was involved.Table 6
Table 7
Presenting symptoms
Maximum number of patients, 162(72.9%) presented with blurring of vision.Table 7
Table 8
Sector involved in major BRVO
|
Sector involved |
Total No. of cases |
Percentage |
|
Supero temporal |
129 |
58.1 |
|
Supero nasal |
9 |
4.1 |
|
Infero temporal |
66 |
29.8 |
|
Infero nasal |
3 |
1.3 |
|
Macular |
15 |
6.7 |
|
Total |
222 |
100 |
Out of 207 Major BRVO patients 129(58.1%) were at supero temporal quadrant and 66(29.8%) were at infero temporal quadrant, 9(4.1%) were at superonasal and 3(1.3%) were in inferonasal quadrant.Table 8
Table 9
Risk factors
Out of total 207 patients of major BRVO, 103(49.7%) were hypertensive, 33(15.9%) had cardiovascular disease, 33(15.9%) had Diabetes Mellitus, 9(4.3%) had Glaucoma, 21(10.6%) patients were Alcoholic, 18(8.7%) patients were smoker and 12(5.8%) patients had abnormal lipid profile.Table 9
Out of 15 patient with macular BRVO 10(66.7%) were hypertensive, 3(20%) were diabetic,3(20%) patient was smoker.
Table 10
BCVA at presentation
|
Presenting VA |
Major BRVO |
Macular BRVO |
Total No. of patients |
|
6/6-6/18 |
27(13.1%) |
3(20%) |
30(13.5%) |
|
6/24-6/60 |
152(73.4%) |
6(60%) |
158(71.2%) |
|
<6/60 |
28(13.5%) |
6(60%) |
34(15.3%) |
|
Total |
207 |
15 |
222 |
Majority of cases i.e. 158(71.2%) had BCVA between 6/24-6/60, 30(13.5%) cases had BCVA 6/6-6/18 and rest 34(15.3%) cases had BCVA < 6/60.Table 10
Table 11
Ophthalmoscopic findings at presentations
Retinal haemorrhage was present universally in all cases, macular edema was present in 111(50%) cases, Cotton wool spots were present in 102(45.9%) cases, retinal edema in 93(41.8%) cases, and neovascularization in only 9 (4.05%) cases,Vitreous haemorrhages in 5(2.2%) cases, TRD+FVP in 6(2.7%) cases.Table 11
Table 12
OCT findings
|
OCT findings |
Major BRVA |
Macular BRVA |
Total |
|
Macular Edema present |
180(87%) |
15(100%) |
195(87.8%) |
|
Macular Edema absent |
27(13%) |
0 |
27(12.2%) |
8% cases had macular edema and rest 27(12.2% did not have macular edema.Table 12
Table 13
Treatment modalities at presentation
Out of 207 patient of major BRVO at the time of presentation, 12 (5.8%) were kept under observation, 9 (4.3%) patients were given intravitreal triamcinolone and 177 (85.5%) patients were given intravitreal ranibizumab.
Out of 15 patient of macular BRVO, 3 (20%) patients were kept under observation and 12(80%) patients were given intravitreal ranibizumab.Table 13
Out of 222 patient of BRVO at the time of presentation, 15 (16.8%), were kept under observation, 9 (4.1%) patients were given intravitreal triamcinolone and 189 (85.1%) patients were given intravitreal ranibizumab.
Table 14
Relationship between SBP, DBP, ESR, FBS and Cholestrol
|
Mean |
Major BRVO |
Macular BRVO |
|
SBP |
141.78 |
153.6 |
|
DBP |
85.15 |
86.4 |
|
ESR |
14.34 |
15.8 |
|
FBS |
101.27 |
106.6 |
|
Cholestrol |
159.9 |
153.3 |
Table 15
From study, it is clear that Mean SBP, DBP, ESR & FBS are higher in Macular BRVO than Major BRVO, where only cholesterol level is higher in Major BRVO.Table 15
Table 16
Value much less than 0 05 (95% C I shows significance of the test.Table 16
Table 17
Correlation is significant at the 0.01 level (2-tailed).
Correlation is significant at the 0.05 level (2-tailed).Table 17
Table 18
At one month follow up, out of 222 patients, 144 (64.9%) patients were kept under observation, 3 (1.4%) patients were given IV triamcinolone and 75 (33.7%) were given IV Rranibizumab to those whose visual acuity get worsened or did not improve.Table 18
Table 19
At 2nd month of follow up the result is quiet better.196 (88.3%) patients improved their VA.But 23(11.1%) major BRVO cases and 3(20%) macular BRVO cases were given 3rd dose of intravitreal Ranibizumab.Table 19
Table 20
FFA findings
|
FFA findings |
Major BRVO |
Macular BRVO |
Total |
|
Neovascularization |
6 |
0 |
6 |
|
Macular edema |
12 |
3 |
15 |
|
Macular Non perfusion |
3 |
0 |
3 |
|
Capillary Non perfusion >5DD |
3 |
0 |
3 |
Despite 2nd dose of intravitreal Ranibizumab and Triamcinolone, some patients did not show improvement.so FFA was done. It was found that 6 patients had neovascularisation, 15 patients had persistant macular edema, 3 patients had Macular non perfusion and 3 macular BRVO patients had capillary non perfusion >5DD.Table 20
So at 3rd month follow up,Grid laser photocoagulation done in 6 (2.9%) major BRVO cases, sector photocoagulation done in 3 (1.4%) major BRVO cases and 3rd dose of intravitreal Ranibizumab given in 6(2.9%) in major BRVO cases and 3(20%) cases in macular BRVO.
Table 21
Treatment modality at 3rd month follow up
At 3 month follow up, out of 207 patients of major BRVO, 192 (92.7%) patients were kept under observation, 6(2.9.%) patients were given grid laser photocoagulation, 3(1.4%) patients were given sector laser photocoagulation and 6(2.9%) patients were given IV Ranibizumab.Table 21
Out of 15 patients of macular BRVO, 12 (80%) patients were kept under observation and 3(20%) patients were given IV Ranibizumab.
Table 22
Treatment modality at 6th month follow up
All patients were kept under observation at 6 month follow up.Table 22
Table 23
Final BCVA at 6th month follow up:
|
BCVA at 6th month follow up |
Major BRVO |
Macular BRVO |
Total No. of patients |
|
6/6 – 6/18 |
180(86.95%) |
9(60%) |
189(85.1%) |
|
6/24 – 6/60 |
21(10.15%) |
6(40%) |
27(12.2%) |
|
<6/60 |
6(2.9%) |
0 |
6(2.7%) |
|
Total |
207 |
15 |
222 |
Out of total 207 patients of major BRVO, 180 (86.95%) had BCVA between 6/6 to 6/18, 21 (30.4%) patients had BCVA of 6/24 to 6/60 and 6 (2.9%) had BCVA of <6/60 after 6 months of follow up. Out of 15 cases of macular BRVO, 9(60%) had BCVA of 6/6 to 6/18 and 6(40%) had BCVA of 6/24 to 6/60.Table 23
Compiling it was found that in BRVO majority of patients i.e. 189 (85.1%) patients had BCVA between 6/6-6/18, 27 (12.2%) cases had BCVA of 6/24 to 6/60 and only 6(2.7%) patients had BCVA <6/60.
In our study, out of 222 sample size, we have given intravitreal injection in 177 patients at presentation, 66 patients were givern 2nd dose of iv Ranibizumab, 23 patients were given 3rd dose of Ranibizumab. At the end of 3 month 9 patients received intravitreal Ranibizumab.6 patients had grid laser photocoagulation after 3 months (p value 0.076), 3 patients got sector laser photocoagulation (p value 0.09.
Hence our study showed that there is dramatical improvement of vision after receiving intravitreal Ranibizumab (p value0.041) which are statistically significant.
Table 24
Complications observed after 6 months
Out of total 207 patients of Major BRVO, 23 (11.1%) patients had persistent macular edema, 4(5.7%) had NVE, 8(3.8%) vitreous haemorrhage, 6(2.8%) had retinal detachment as complication. Out of 15 patients with macular BRVO, only 1(6.6%) patient had recurrent macular edema.Table 24
Out the data, out of total 222 patients of BRVO, 24 (10.8%) patients had recurrent macular edema and 4 (5.4%) had NVE as complication.
Discussion
In our study we got more number of patients with major BRVO 207(94.1%) than macular BRVO 15(5.9%). Maximum number of patients were between 61-70 years. Mean age is 62.89 years. This could be due to more conventional risk factors at this age. This is in accordance with the study by Duke Elder (average age 60 years)3 and Zhao et al, mean age 63.7 years (range 31-80 years).4 There were 56.7% male and 43.3% female patients. This may be due to males are more concerned for their health and come for regular check up. As per Joffe et al there was equal incidence of male:female.5 The Eye Disease Case Control Study group, men to women was 53%:43%.6 Supero temporal retina involve more frequently than infero temporal in major BRVO patients which is in accordance with studies by Ammann7 and Weinberg DV et al 8. Hypertension 113(50.9%), Diabetes 36(16.2%) and cardiovascular disease 33(14.9%) are major risk factors for BRVO. Appiah AP et al in his case control study with BRVO, hypertension was noted in 58% patients.9 This is same as The Beaver Dam Eye Study. 10 From our study the mean SBP, DBP, ESR and FBS were higher in macular BRVO than major BRVO, where only cholesterol level is higher in major BRVO. Majority (71.2%) of BRVO patients presented with initial BCVA within 6/24 to 6/60 and 13.5% of patients had BCVA worse than 6/60 at presentation. Common ophthalmoscopic findings are retinal haemorrhage (100%), macular edema (47.8%), cotton wool spots (44.9%). By OCT 195(87.8%) patients were detected with macular edema. Out of 222 sample size, we have given intravitreal injection of Ranibizumab in 177 patients at presentation, 66 patients were given 2nd dose of IV Ranibizumab, 23 patients were given 3rd dose of IV Ranibizumab. At the end of 3 months 9 patients received IV Ranibizumab. 6 patients had grid laser photocoagulation after 3 months (P value- 0.076), 3 patients got sector laser photocoagulation (P value 0.988). Hence our study showed there is dramatical improvement of vision after receiving IV Ranibizumab (P value 0.041) which is statistically significant. It is also similar with other studies. BRAVO STUDY suggests the improvements from base line are maintained with IV Ranibizumab in patients with macular edema following retinal vein occlusion. MARVEL study found that Ranibizumab improves VA by 2.53 letters than Bevacizumab. IV Triamcinolone and Grid laser photocoagulation are equally effective in reducing macular edema with few limitations. The Branch Vein Occlusion Study (BVOS) group established the efficacy of Grid pattern laser photo coagulation for treatment of macular edema in BRVO.11 The Score Study found IV Triamcinolone to be effective as macular grid laser photocoagulation treatment which is the current benchmark for BRVO treatment in case of chronic macular edema with VA below 6/12 in absence of macular capillary non-perfusion. Branch Vein Occlusion Study (BVOS) group established peripheral scatter laser photocoagulation significantly reduced the development of retinal neovascularization and vitreous haemorrhage. 12
At the end of six months, in majority of patients that is 85.1% had BCVA between 6/6 to 6/18, only 2.7% of patients had BCVA<6/60. Out of total 222 patients of BRVO, 10.8% patients had recurrent macular edema, 5.4% had NVE, 3.6% had vitreous haemorrhage, 2.7% had retinal detachment as complication at last visit so recurrent macular edema was responsible for non-resolving of BRVO in some patients who responded poorly to the treatment.
Conclusion
Multiple factors are involved in the pathogenesis of BRVO. Conventional risk factors like hypertension diabetes and cardiovascular diseases are highly associated with BRVO. The mean SBP, DBP, ESR, FBS are higher macular BRVO than major BRVO, where only cholesterol level is higher in major BRVO. Macular edema, macular non-perfusion and vitreous haemorrhage resulting from retinal neovascularization are common causes of reduced vision. IV Ranibizumab, Grid laser photocoagulation, IV Triamcinolone and sector laser photocoagulation are effective treatment for BRVO, although these lack sufficient evidences. There is dramatical improvement of vision after receiving IV Ranibizumab (P value 0.041) which is statistical significant. Visual prognosis depends on initial status with careful monitoring for macular ischaemia, macular edema, development of neovascularization and subsequent neovascular glaucoma.
