Combination Therapy for Macular Oedema in Retinal Vein Occlusions: 3-Year Results from a Real-World Clinical Practice

Figures & data

Table 1 Discontinuation of Care

Reasons for Discontinuation of Care		Year 1 n = 66	Year 2 n = 61 (92%)	Year 3 n = 48 (72%)
Planned discharge	N (%)	0	0	8 (12%)
	RVO subanalysis		0	3 CRVO 5 BRVO
Transfer of care (to other eye hospitals)	N (%)	0	2 (3%)	3 (4.5%)
	RVO subanalysis		1 CRVO 1 HRVO	1 CRVO 1 NVG 1 BRVO
Persistent non-attendance	N (%)	0	1 (1.5%)	0
	RVO subanalysis		1 CRVO	0
Deceased	N (%)	0	2 (3%)	2 (3%)
	RVO subanalysis		1 CRVO 1 HRVO	1 CRVO 1 BRVO

Notes: The table shows various reasons for discontinuation of care with related subgroup analyses. A total of 92.4% and 72.7% of patients reached a full follow-up period of 2 and 3 years, respectively. Discharge criteria for stable patients in this cohort were “patients received no treatment for at least one year”, the overall planned discharge was 12% recorded only in Year 3. The total number deceased patients over the 3-year follow-up period was 6%. n = total number of patients in the cohort in that year (% = n/66 x100%). N = number of patients left the cohort, Percentage of discontinuation of care was calculated based on original cohort number of 66 patients (% = N/66 x100%).

Abbreviations: RVO, retinal vein occlusion; CRVO, central retinal vein occlusion; HRVO, Hemi retinal vein occlusion; BRVO, branch retinal vein occlusion; NVG, neovascular glaucoma.

Table 2 Treatment Exposure Over 3 Years with Subgroup Analyses

	Year 1 n= 66			Year 2 n= 61			Year 3 n= 48
Total Injections
Mean frequency (SD)	5.5 (1.8)			2.5 (2.3)			2.5 (2.3)
Mode (Range)	5 (2–11)			0 (0–9)			0 (0–10)
Subgroup Analyses	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO
Mean frequency (SD)  Mode (Range)	5.9 (2.0) 5 (0–11)	5.4 (1.5) 7 (0–7)	5.0 (1.6) 4 (0–9)	3.3 (2.4) 4 (0–9)	1.7 (2.2) 0 (0–6)	2.0 (2.1) 0 (0–7)	2.6 (2.2) 0 (0–7)	2.8 (3.5) 0 (0–1)	1.9 (2.6) 0 (0–7)
Ranibizumab Only  Mean frequency (SD)  Mode (Range)	4.3 (1.8) 3 (2–11)			2.2 (2.1) 0 (0–8)			2.1 (2.4) 0 (0–10)
Subgroup Analyses	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO
Mean frequency (SD)  Mode (Range)	4.7 (2.1) 3 (2–11)	4.4 (1.2) 5 (3–6)	4.0 (1.5) 3 (2–8)	2.8 (2.2) 4 (0–8)	1.6 (2.2) 0 (0–6)	1.7 (1.9) 0 (0–6)	2.3 (2.2) 0 (0–7)	2.7 (3.5) 2 (0–10)	1.8 (2.3) 0 (0–7)
Ozurdex Only  Mean frequency (SD)  Mode (Range)	1.1 (0.8) 1 (0–1)			0.4 (0.6) 0 (0–2)			0.2 (0.5) 0 (0–2)
Subgroup Analyses	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO
Mean frequency (SD)  Mode (Range)	1.1 (0.9) 2 (0–3)	1.0 (0.7) 1 (0–2)	1.0 (0.8) 1 (0–2)	0.5 (0.6) 0 (0–2)	0.4 (0.8) 0 (0–2)	0.3 (0.6) 0 (0–2)	0.3 (0.4) 0 (0–1)	0.1 (0.4) 0 (0–1)	0.2 (0.5) 0 (0–2)
Laser Procedures	54 (81.8%)			29 (47.5%)			11 (22.9%)
Subgroup Analyses	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO	CRVO	HRVO	BRVO
	24/29 (82.8%)	7/9 (77.8%)	23/28 (82.1%)	14/27 (51.9%)	5/7 (71.4%)	10/27 (37.0%)	6/21 (28.6%)	3/7 (42.9%)	2/20 (10.0%)

Notes: The average number of total intravitreal injections required per patient in Year 1 was 5.5, reduced to 2.5 in Years 2 and 3, there was no difference for total injections (or Ranibizumab only injections) for each subgroup in Year 1 but CRVO patients did still require more injections in Year 2. All RVO subgroups shared similar Ozurdex frequency pattern and mode. Laser requirement declined in subsequent years but top-up laser request was common in ischaemic eyes due to inadequate laser (confirmed by repeat fluorescein angiography).

Abbreviations: n, number of eyes; SD, standard deviation; CRVO, central retinal vein occlusion; HRVO, hemi-retinal vein occlusion; BRVO, branch retinal vein occlusion.

Table 3 Number of Patients Received Injections with Varied Combination Modes in Each Year

	R=0	R=1	R=2	R=3	R=4	R=5	R=6	R=7	R=8
Year 1 Received Combined Therapy, n= 46/66 (69.7%)
Oz =1				9	2	3	5	3	1
Oz =2				13	7	1		2
Year 2 Received Combined Therapy, n= 21/61 (34.4%)
Oz =1	3	4	1	4	3			1	1
Oz =2	1	1			1	1
Year 3 Received Combined Therapy, n = 9/48 (18.7%)
Oz =1		2	2	4
Oz =2						1

Notes: This table shows detailed breakdown of different combined therapy modes received by number of patients in that year. For example, in Year 1, all patients who received Ozurdex injection(s) had already received a minimal of 3 Ranibizumab injections – in particular, 9 patients received one Ozurdex injection after 3 Ranibizumab injections, 2 patients received 3 initial Ranibizumab and later had additional one Ozurdex and one Ranibizumab for the rest of Year 1. On average, effectiveness of Ozurdex lasted for 3–4 months, continuation with Ranibizumab injections was common after Ozurdex effect had worn off. Re-injection of Ozurdex was decided by any post-injection intraocular pressure spike and other factors.

Abbreviations: R, ranibizumab injection frequency; Oz, Ozurdex injection frequency.

Figure 1 Number of intravitreal injections received by the whole cohort and by different RVO subgroups in each year.

(A) Percentage of patients (of the whole cohort) received X number of injections each year. (B) Year 1 RVO subgroup analyses: all subgroups shared similar frequency distribution, one CRVO patient (of neovascular glaucoma) needed 11 injections in Year 1. (C) Year 2 RVO subgroup analyses: BRVO and HRVO had the most numbers of patients not needing re-injections this year; and CRVO patients accounted for higher injection frequency. (D) Year 3 RVO subgroup analyses: 55% of BRVO needed no injections in Year 3, one HRVO patient had a severe recurrence and needed 10 injections.

Abbreviations: RVO, retinal vein occlusion; CRVO, central retinal vein occlusion; HRVO, hemi-retinal vein occlusion; BRVO, branch retinal vein occlusion.

Figure 2 Trend of combined modalities received by the whole cohort of each year. All patients received injections in Year 1: 30% required only the initial loading dose of three Ranibizumab for disease stability and 69.7% needed combination therapy for disease stability. In Year 2, 41% received Ranibizumab alone, 6.6% needed just Ozurdex for the whole Year 2. Combination therapy was less frequent in subsequent years; 25% and 40% of patients received no injections in Year 2 and Year 3 respectively.

Table 4 Comparison of VA and CRT Against Baselines

	Year 1 n = 66			Year 2 n = 61			Year 3 n = 48
Comparison of Vision in LogMAR (Snellen Equivalent)
Baseline median VA	0.71 (6/30)
[IQR]	[0.43–1.16]
Median VA	0.48 (6/18)			0.48 (6/18)			0.48 (6/18)
[IQR]	[0.18–0.78]			[0.18–0.89]			[0.18–1.00]
of cohort year	p<0.001			p<0.001			p=0.006
Subgroup Analyses	CRVO n=29	HRVO n=9	BRVO n=28	CRVO n=27	HRVO n=7	BRVO n=27	CRVO n=21	HRVO n=7	BRVO n=20
Baseline median VA  LogMAR (Snellen)	1.00 (6/60)	0.72 (6/30)	0.61 (6/24)
Median VA each year  (Snellen equivalent)  p value	0.78 (6/36) 0.055	0.44 (6/15) 0.033	0.54 (6/20) <0.001	1.00 (6/60) 0.628	0.30 (6/12) 0.272	0.30 (6/12) <0.001	1.00 (6/60) 0.627	0.33 (6/12) 0.106	0.39 (6/12) <0.001
Visual Changes in Comparison to Baseline per Each Cohort Year
Worse	10 (15%)			12 (21%)			13 (27%)
Stable	5 (8%)			6 (10%)			5 (10%)
Improved	51 (77%)			42 (69%)			30 (63%)
Improved by ≥ 3-lines	34 (52%)			23 (38%)			19 (40%)
Achieved 6/12 or better	30 (46%)			28 (46%)			19 (40%)
Comparison of Central Retinal Thickness (in μm)
Baseline median CRT [IQR]	531 [435–622]
Median CRT [IQR]	245 [221–351] p<0.001			266 [231–369] p<0.001			264 [230–378] p<0.001
Subgroup Analyses	CRVO n=29	HRVO n=9	BRVO n=28	CRVO n=27	HRVO n=7	BRVO n=27	CRVO n=21	HRVO n=7	BRVO n=20
Baseline median CRT	571	513	499
Median CRT each year p value	236 <0.001	285 0.009	252 <0.001	264 <0.001	256 0.022	276 <0.001	280 0.002	271 0.030	258 <0.001

Notes: Visual improvement was statistically significant compared to baseline for the whole cohort in each year and remained so only in BRVO subgroup in each subsequent year. The 3 neovascular glaucoma patients belonged to CRVO subgroup accounting for the poorer visual outcome. Macular oedema improvement, however, remained statistically significant in each subgroup from year 1 to 3. (Statistical analysis using Wilcoxon signed-rank test; statistical significant: p<0.05).

Abbreviations: VA, visual acuity; CRT, central retinal thickness; IQR, Inter-quartile-range; Crvo, central retinal vein occlusion; Hrvo, hemi-retinal vein occlusion; Brvo, branch retinal vein occlusion.

Figure 3 Trend in median visual acuity (VA) and median central retinal thickness (CRT) for each cohort year. Both VA and CRT improved and stabilised after a loading phase of Ranibizumab. In particular, VA stabilisation at LogMAR 0.48 (Snellen 6/18) level in each year was similar as VA first achieved after the loading phase. Hence, it is possible that “vision achieved 4-weeks post-loading phase” could potentially be useful as a prognostic VA predictor in longer term.

Table 5 Adverse Effects and Other Ocular Procedures

	Year 1	Year 2	Year 3
Ozurdex-Related Complications  Raised IOP >21mmHg  Vitreous haemorrhage  Cataract from injection procedure  Cataract from Ozurdex effect	19/46 (41%) 2/46 (4%) 0 Unknown	8/20 (40%) 0 0 Unknown	3/5 (60%) 0 0 Unknown
Concomitant Surgeries / Procedures
Cataract surgeries	12/66 (18%)	10/61 (16%)	1/48 (2%)
Laser iridotomies / trabeculoplasty / SLT	5	2	2
Cyclodiode laser (for NVG only)	3	1	2
Progression to NVG	0	1	0
Endophthalmitis	0	0	0

Notes: number of patients received Ozurdex is different each year. Data recording is unable to determine if a cataract formation is from repetitive Ozurdex injection or natural progression.

Abbreviations: IOP, Intraocular Pressure; SLT, selective laser trabeculoplasty; NVG, neovascular glaucoma.