Study population
There was a total of 120 eyes (120 patients) with RVO in the time specified. Of these, 21 eyes that also had concomitant diseases for vision impairment were excluded thus, only 99 eyes were available for the analysis. Three-fifths eyes (60%) had BRVO while two-fifths had CRVO. Participants had a mean (SD) age of 56 (15) years. The mean (SD) duration of vision loss was 70 (86) days. Risk factors were documented in most (81 patients, 82%) of them at baseline. The more frequent individual associated factors were hypertension in 59 (60%), smoking in 27 (27%), diabetes in 22 (22%), hyperlipidemia in 19 (19%) and alcohol consumption in 10 (10%). The proportion of patients with these factors were similar in both CRVO and BRVO groups (Table 1). Eyes with CRVO had worse vision (VA: 1.13 logMAR [6/75 Snellen equivalent] versus 0.75 logMAR [6/30] for BRVO, p = 0.001) and macular thickness (CST: 519 µm versus 423 µm, p = 0.02) at baseline than those with BRVO. Table 1 gives an overview of baseline characteristics of eyes in the two groups.
Table 1. Demographic characteristics
|
CRVO
|
BRVO
|
p value
|
Patients, n
|
39
|
60
|
|
Female, n (%)
|
17 (44)
|
35 (58)
|
|
Right Eye, n (%)
|
26 (67)
|
32 (53)
|
|
Hypertension, %
|
51
|
65
|
0.25
|
Diabetes, %
|
18
|
25
|
0.56
|
Hyperlipidaemia, %
|
15
|
22
|
0.6
|
Smoking, %
|
28
|
27
|
1
|
Alcohol, %
|
10
|
10
|
1
|
Glaucoma, %
|
0.1
|
0
|
0.15
|
Vision loss, days mean (SD)
|
82 (78)
|
114 (144)
|
0.16
|
Age, years mean (SD)
|
53 (17)
|
58 (13)
|
0.09
|
Baseline VA logMAR, mean (SD)
|
1.13 (0.61)
|
0.75 (0.42)
|
0.001
|
VA ≤ 0.3 logMAR, %
|
10
|
20
|
0.31
|
VA ≥ 1 logMAR, %
|
59
|
37
|
0.04
|
Baseline IOP mm Hg, mean (SD)
|
19 (11)
|
16 (3)
|
0.07
|
CST mm, mean (SD)
|
519 (213)
|
423 (151)
|
0.02
|
Presence of Ischaemia
|
|
|
|
Ischaemic, %
|
18
|
20
|
1
|
NonIschaemic, %
|
82
|
80
|
|
n - Number, SD – Standard Deviation, VA – Visual Acuity, CST – Central Subfield Thickness, logMAR – logarithm of minimum angle of resolution
|
Visual outcomes at 12 months
The mean (SD) VA in the RVO cohort 0.6 (0.61) logMAR (6/24 Snellen equivalent) at 12 months improved from the baseline of 0.89 (0.53) logMAR (6/48 Snellen equivalent, p < 0.001). The mean (95% confidence interval) VA change at 12 months was -0.29 (-0.4, -0.18) logMAR. The mean VA in eyes with good initial vision (≤0.3 logMAR, 6/12 Snellen equivalent or better) dropped from the baseline while those presenting with > 0.3 logMAR (6/15 or worse) improved. The proportion of eyes with VA ≤ 0.3 logMAR (6/12 or better) increased to 53% at 12 months from 16% at baseline (p = 0.02) while those with VA ≥ 1 logMAR (6/60 or worse) decreased to 24% from 45% at baseline (p < 0.01).
Table 2. One-year outcomes
|
|
CRVO
|
BRVO
|
p value
|
Patients, n
|
39
|
60
|
|
Baseline VA logMAR, mean (SD)
|
1.13 (0.61)
|
0.75 (0.42)
|
0.001
|
Final VA logMAR, mean (SD)
|
0.92 (0.75)
|
0.4 (0.4)
|
<0.001
|
Change VA logMAR,
mean (95% CI)
|
-0.2
(-0.43, 0.02)
|
-0.35
(-0.46, -0.23)
|
0.25
|
VA ≤ 0.3 %, baseline/final
|
10 / 36
|
20 / 63
|
0.01
|
VA ≥ 1 %, baseline/final
|
59 /47
|
37 /12
|
<0.001
|
Improvement ≥ 3 lines, %
|
32
|
60
|
0.37
|
Worsening ≥ 3 lines, %
|
8
|
7
|
0.31
|
Baseline IOP mmHg, mean (SD)
|
19 (11)
|
16 (3)
|
0.07
|
Final IOP mmHg, mean (SD)
|
17 (2)
|
15 (5)
|
0.05
|
Change IOP mmHg,
mean (95% CI)
|
-3
(-6, 0)
|
-2
(-4, -1)
|
0.64
|
Baseline CST mm, mean (SD)
|
519 (213)
|
423 (151)
|
0.02
|
Final CST mm, mean (SD)
|
343 (160)
|
281 (133)
|
0.09
|
Change CST mm,
mean (95% CI)
|
-184
(-276, -91)
|
-114
(-189, -40)
|
0.24
|
Injections α, median (Q1, Q3)
|
2 (1, 3)
|
2 (1, 3)
|
1
|
Additional Macular Laser, n
|
0
|
2
|
0.52
|
Additional Triamcinolone, n
|
2
|
2
|
0.65
|
Additional PRP, n
|
16
|
15
|
0.17
|
n – Number, VA – Visual Acuity, SD – Standard Deviation, CI – Confidence Interval, CST – Central Subfield Thickness, Q1 – First Quantile, Q3 – Third Quantile, PRP – Panretinal photocoagulation, * Last observation carried forward for lost to follow-up, α Number of bevacizumab injections.
|
Figure 1 illustrates the mean VA over 12 months in eyes with CRVO and BRVO that completed 12 months’ observation. The mean (95% CI) VA change at 12 months in BRVO, -0.35 (-0.46, -0.23) logMAR, was significant (p < 0.001) but those of CRVO, -0.2 (-0.43, 0.02) logMAR, was not (p = 0.19, Table 2). The proportion of eyes with VA ≤ 0.3 logMAR increased and those with VA ≥ 1 logMAR decreased in both groups but more in eyes with BRVO (Table 2).
Table 3. Outcomes stratified by Visual Acuity at presetation
|
|
CRVO(n = 39)
|
BRVO(n = 60)
|
p value
|
Eyes with presenting VA ≤0.3 logMAR
|
Eyes, n (%)
|
4 (10)
|
12 (20)
|
0.05
|
Baseline VA logMAR, mean (SD)
|
0.28 (0.05)
|
0.18 (0.13)
|
0.5
|
Final VA logMAR, mean (SD)
|
0.54 (0.83)
|
0.22 (0.25)
|
0.71
|
Change VA logMAR,
mean (95% CI)
|
0.26
(-1.04, 1.57)
|
0.03
(-0.13, 0.2)
|
0.61
|
Baseline CST mm, mean (SD)
|
423 (152)
|
330 (102)
|
0.31
|
Final CST mm, mean (SD)
|
268 (50)
|
230 (110)
|
0.46
|
Change CST mm,
mean (95% CI)
|
-155
(-390, 80)
|
-79
(-206, 48)
|
0.42
|
Injections, median (Q1, Q3)
|
0.5 (0, 1.5)
|
0 (0, 1.2)
|
0.94
|
Additional Macular Laser, n
|
0
|
0
|
1
|
Additional Triamcinolone, n
|
0
|
0
|
1
|
Additional PRP, n
|
1
|
5
|
1
|
Eyes with presenting VA ≤0.3 logMAR
|
Eyes, n (%)
|
35 (90)
|
48 (80)
|
|
Baseline VA logMAR, mean (SD)
|
1.22 (0.57)
|
0.89 (0.34)
|
0.02
|
Final VA logMAR, mean (SD)
|
0.97 (0.74)
|
0.44 (0.42)
|
<0.001
|
Change VA logMAR,
mean (95% CI)
|
-0.26
(-0.49, -0.03)
|
-0.44
(-0.57, -0.32)
|
0.15
|
Baseline CST mm, mean (SD)
|
531(218)
|
449 (153)
|
0.07
|
Final CST mm, mean (SD)
|
355 (168)
|
291(137)
|
0.12
|
Change CST mm,
mean (95% CI)
|
-188
(-294, -82)
|
-120
(-206, -34)
|
0.30
|
Injections, median (Q1, Q3)
|
2 (1, 3)
|
2 (1, 3)
|
0.72
|
Additional Macular Laser, n
|
0
|
2
|
0.5
|
Additional Triamcinolone, n
|
2
|
2
|
1
|
Additional PRP, n
|
15
|
10
|
0.05l
|
n – Number, VA – Visual Acuity, SD – Standard Deviation, CI – Confidence Interval, CST – Central Subfield Thickness, Q1 – First Quantile, Q3 – Third Quantile, PRP – Panretinal photocoagulation, * Last observation carried forward for lost to follow-up, α Number of bevacizumab injections. lOdd’s ratio = 2.8
|
We divided the cohort into two subgroups according to the VA at baseline, eyes with VA ≤ 0.3 logMAR and those with VA > 0.3 logMAR, to study the relationship of the initial VA on VA gains with treatment.Eyes with good initial vision (VA ≤ 0.3 logMAR) had a minimal mean (95% CI) VA change at 12 months, 0.03 (-0.13, 0.2) logMAR from a mean (SD) of 0.22 (0.25) logMAR at baseline (p = 0.68) in BRVO and 0.26 (-1.04, 1.57) logMAR from a mean (SD) of 0.28 (0.05) logMAR at baseline (p = 0.57) in CRVO. The mean (95% CI) VA change in eyes with initial vision > 0.3 logMAR was greater in BRVO, -0.44 (-0.57, -0.32) logMAR from 0.89 (0.34) logMAR at baseline (p<0.001), but was not so for CRVO, -0.26 (-0.49, -0.03) logMAR from 1.22 (0.57) logMAR at baseline (p = 0.1). However, the final vision in the initial VA > 0.3 logMAR subgroup in BRVO, despite the higher gain, was lower than in the good initial vision group (Table 3).
Macular thickness
Bevacizumab significantly reduced the mean CST in eyes with RVO (Figure 1). The mean (95% CI) change in CST at 12 months was -145 (-203, -88) µm from a mean of -460 (183) µm at baseline (p<0.001). The mean (95% CI) change in CST at 12 months in CRVO, -184 (-276, -91) µm (p < 0.001), and in BRVO, -114 (-189, -40) µm (p = 0.003), was similar (0.24, Table 2). Eyes in both VA subgroups had significant reduction in the mean CST after 12 months of treatment that were similar for both CRVO and BRVO (Table 3).
Treatments
The median (Q1, Q3) number of bevacizumab injections in eyes with RVO over 12 months was 2 (1, 3). Less than two-fifths (36%) eyes required additional treatments, including laser (macular and panretinal photocoagulation) and intravitreal steroid (triamcinolone) injections, during the 12 months (Table 2). None of the eyes that received additional steroid continued treatment of RVO with steroid. The median number of bevacizumab injections in CRVO and BRVO were (2 [1, 3]) versus (2 [1, 3], p = 1). There was no difference in the median number of bevacizumab injections when eyes were stratified based on the initial VA, however, more eyes with CRVO in the initial vision > 0.3 logMAR group received panretinal photocoagulation (Odd’s ration = 2, Table 3).
Non-completion rate at 12 months
Thirty-seven eyes (37%, CRVO – 12 and BRVO – 25 eyes, p = 0.37 ) were lost before the 12 month’s visit. The mean (95% CI) VA change from the start of treatment to their last visit was -0.36 (-0.55, -0.2) logMAR for BRVO (p < 0.001) and -0.31 (-0.56, -0.06) logMAR for CRVO (p = 0.01) while the CST change was -98 (-222, 26) µm for BRVO (p = 0.11) and -204 (-384, -25) µm for CRVO (p = 0.03). These eyes received a median (Q1, Q3) of 2 (1, 2) for BRVO and 2 (1, 3) for CRVO bevacizumab injections. Figure 2 illustrates the mean VA and CST trajectory of CRVO and BRVO eyes from baseline to their last observed visit before the dropout.
Adverse Events
Neovascularisation of the retina was observed in one-fifth eyes (CRVO – 11 [28%], BRVO – 10 [17%], p = 0.26). Of these, 3 eyes required a surgical procedure for vitreous haemorrhage. Three-fifths eyes with CRVO (59%) developed iris neovascularisation over 12 months of which, 7 had angle neovascularisation. Glaucoma was controlled with medications in 9 eyes. Glaucoma drainage procedure was required in 2 eyes. Injection related complications, including endophthalmitis, was not observed over 12 months.