Background
Methods
Search methods for identifying studies
Search number | Search strategy | Number of hits |
---|---|---|
1 | ((“Central Retinal Vein Occlusion”[Title/Abstract]) OR CRVO[Title/Abstract]) OR vein, central retinal[MeSH Terms] Filters: Publication date from 2004/01/01 to 2015/03/01; Humans; English | 1058 |
2 | ((Central Retinal Vein Occlusion[Title/Abstract]) OR CRVO[Title/Abstract]) OR vein, central retinal[MeSH Terms]) AND (ishaemic[Title/Abstract] OR ischemic[Title/Abstract]) Filters: Publication date from 2004/01/01 to 2015/03/01; Humans; English | 127 |
3 | (((“Central Retinal Vein Occlusion”[Title/Abstract]) OR CRVO[Title/Abstract]) OR vein, central retinal[MeSH Terms]) AND (efficacy [Title/Abstract] OR “quality of life” [Title/Abstract] OR effectiv* [Title/Abstract] OR “treatment outcome” [Title/Abstract] OR treatment outcome [MeSH Terms] OR quality of life [MeSH Terms]) Filters: Publication date from 2004/01/01 to 2015/03/01; Humans; English | 273 |
4 | (((Central Retinal Vein Occlusion[Title/Abstract]) OR CRVO[Title/Abstract]) OR vein, central retinal[MeSH Terms]) AND (economic [Title/Abstract] OR cost [Title/Abstract] OR “cost analysis” [Title/Abstract] OR cost-effective* [Title/Abstract] OR “treatment cost” [Title/Abstract] OR “health care cost” [Title/Abstract] OR utility [Title/Abstract] OR reimbursement [Title/Abstract] OR “drug cost” [Title/Abstract] OR “cost saving”[Title/Abstract] OR “unit cost” [Title/Abstract] OR Health Expenditures[MeSH Terms] OR Drug Costs[MeSH Terms] OR Cost Sharing[MeSH Terms] OR Cost of Illness[MeSH Terms] OR Cost Savings[MeSH Terms] OR Technology, High-Cost[MeSH Terms] OR Cost Control[MeSH Terms] OR Cost-Benefit Analysis[MeSH Terms] OR Cost Allocation[MeSH Terms] OR Direct Service Costs[MeSH Terms] OR Hospital Costs[MeSH Terms] OR Employer Health Costs[MeSH Terms]) Filters: Publication date from 2004/00/01 to 2015/03/01; Humans; English | 8 |
Final | 1466 |
Eligibility criteria
Study selection
Data collection and risk-of-bias assessment
Results
Study selection
Study characteristics
Study (country) | Study design | Complication secondary to iCRVO | Follow-up period (months) | Treatment arm (% with ischemia in overall CRVO patient population)l
| Comparator arm (% with ischemia in overall CRVO patient population)l
| Age in years (treatment vs. comparator) | Proportion of females (treatment vs. comparator) |
---|---|---|---|---|---|---|---|
ANTI-VEGF TREATMENTS | |||||||
Korobelnik et al. 2014 [17] (multinational) | Prospective, randomized, double-masked, sham-controlled clinical trial | MEa
| 13 | ▪ Intravitreal aflibercept injection | ▪ Sham injection | ▪ NAk
| ▪ NAk
|
o
n = 7 (6.8 % non-perfused of 103) | o
n = 7 (10.3 % non-perfused of 68) | ||||||
Brown et al. 2013 [19] (multinational) | Prospective, randomized, double-masked, sham-controlled clinical trial | MEa
| 12 | ▪ Intravitreal aflibercept injection | ▪ Sham injection | ▪ NAk
| ▪ NAk
|
o
n = 17 (14.9 % non-perfused of 114) | o
n = 12 (16.4 % non-perfused of 73) | ||||||
Boyer et al. 2012 [18] (multinational) | Prospective, randomized, double-masked, sham-controlled clinical trial | MEb
| 6 | ▪ Intravitreal VEGF Trap-Eye (aflibercept) | ▪ Sham injection | ▪ NAk
| ▪ NAk
|
o
n = 17 (14.9 % non-perfused of 114) | o
n = 12 (16.4 % non-perfused of 73) | ||||||
Wittstrom et al. 2012 [16] (Sweden) | Randomized, clinical pilot study | NVGc
| 6 | ▪ Single intravitreal injection of bevacizumab combined with PRP | ▪ PRP | ▪ 78.4 (7.8) vs. 78.0 (8.7) | ▪ 80 % vs. 44 % |
o
n = 9 (100 % ischemic) | o
n = 9 (100 % ischemic) | ||||||
Campochiaro et al. 2008 [27] (USA) | Prospective, randomized, uncontrolled open-label, double-masked trial | MEd
| 3 | ▪ Ranibizumab 0.3 mg (3-monthly injections) | ▪ Ranibizumab 0.5 mg (3-monthly injections) | ▪ 63 (17) vs. 68 (13) | ▪ NA |
o
n = 10 (100 % ischemic) | o
n = 10 (100 % ischemic) | ||||||
STEROID TREATMENTS | |||||||
Asano et al. 2007 [20](Japan) | Randomized controlled study | Ischemic CME or MEe
| 4 (all eyes underwent laser treatment prior to study) | ▪ Sub-tenon triamcinolone injection | ▪ No sub-tenon triamcinolone injection | ▪ 64.0 (7.1) vs. 65.1 (6.4) | ▪ 47 % vs. 47 % |
o
n = 15 (100 % ischemic) | o
n = 15 (100 % ischemic) | ||||||
Ramezani et al. 2006 [21] (Iran) | Randomized, sham-controlled clinical trial | NV preventive effectf; 52 % were ischemic | 4 | ▪ Intravitreal triamcinolone | ▪ Sham subconjunctival injection | ▪ NAk
| ▪ NAk
|
o
n = 9 (69 % non-perfused of 13 eyes) | o
n = 4 (29 % non-perfused of 14 eyes) | ||||||
Jonas et al. 2005 [26] (Germany) | Prospective, non-randomized, clinical interventional study | CMEc
| Treatment: 10.1 (mean); comparator: 6.0 (mean) | ▪ Triamcinolone acetonide intravitreal injection (about 20 mg) | ▪ No treatment (results were not given by ischemic status) | ▪ NAk
| ▪ NAk
|
o
n = 4 (31 % ischemic eyes of 13 eyes) | o
n = 5 (25 % ischemic eyes of 20 eyes) | ||||||
PROCEDURAL TREATMENTS | |||||||
Tabatabaii et al. 2008 [23] (Iran) | Interventional case series study | Not mentionedc
| 3.6 | ▪ Pars plana vitrectomy with radial optic neurotomy | ▪ Pre-operation | ▪ 56 | ▪ 44 % |
o
n = 18 eyes of 16 patients (100 % ischemic) | |||||||
Parodi et al. 2007 [22] (Italy and USA) | Prospective, randomized clinical trial | Anterior-segment NVg
| 12 | ▪ Conventional PRP (performed promptly when two clock hours of iris NV, any angle NV, or both were identified) | ▪ Arm 1—Selective PRP (performed only in selected cases showing progression of iris NV, angle NV, or both during weekly follow-up) | ▪ 69.4 (4.1) vs. 69.5 (5.6) [Arm 1] vs. 67.7 (4.9) [Arm 2] | ▪ 42 % vs. 30 % [Arm 1] vs. 39 % [Arm 2] |
o
n = 19 eyes (100 % ischemic) | o
n = 20 eyes (100 % ischemic) | ||||||
▪ Arm 2—Photodynamic therapy with verteporfin (directed at the iris NV and angle NV) | |||||||
o
n = 18 eyes (100 % ischemic) | |||||||
Feltgen et al. 2007 [24] (Germany) | Prospective, non-randomized, interventional case series | Not mentionedh
| 12 | ▪ Retinal endovascular lysis | ▪ Pre-operation | ▪ 67 | ▪ NA |
o n =13 (100 % ischemic) | |||||||
Mirshahi et al. 2005 [25] (Iran) | Non-randomized controlled trial | Prevention of NVi
| 6–18 (mean = 10) | ▪ Surgical induction of chorioretinal venous anastomosis | ▪ No surgery | ▪ NA | ▪ 60 % vs. 39 % |
o
n = 10 (100 % ischemic) | o
n = 18 (100 % ischemic) | ||||||
MISCELLANEOUS TREATMENTS | |||||||
Hayreh et al. 2011 [28] (USA) | Prospective study | Not mentionedj
| Treatment: 22.8 (median); comparator: 34.8 (median) | ▪ Aspirin | ▪ No aspirin or anticoagulant | ▪ 70 (12) vs. 68 (16) | ▪ 42 % vs. 53 % |
o
n = 38 (17 % ischemic of 227) | o
n = 47 (15 % ischemic of 324) |
Study, country | Form of economic analysis | Treatment | Comparator | Patient population | Model horizon |
---|---|---|---|---|---|
Taylor et al., 2014 [33] UK | Cost-effectiveness | Ranibizumab | Observation | Patients with ME secondary to CRVO | Lifetime |
Eriksson et al., 2014 [29] Sweden | Cost-effectiveness | Aflibercept | Ranibizumab | Patients with ME secondary to CRVO; average starting age 64 years | 15 years |
Duff et al., 2012 [31] USA | Cost-utility | 1) Ranibizumab | 1) Dexamethasone intravitreal implant | Patients with ME secondary to CRVO | 2 years |
2) Dexamethasone intravitreal implant | 2) Steroids | ||||
Haig et al., 2012 [32] Canada | Cost-utility | Ranibizumab | Observation | Patients (66–68 years) with ME secondary to CRVO | Lifetime |
Vincente et al., 2013 [30] Canada | Cost-effectiveness | Dexamethasone intravitreal implant | Observation | Patients with ME and vision loss secondary to CRVO | Lifetime |
Hayward et al., 2011 [34] UK | Cost-utility | Dexamethasone intravitreal implant | Observation | Patients with ME secondary to CRVO from GENEVA 008 and 009 clinical trial studies | Lifetime |
Kowalski et al., 2011 [35] USA | Cost-utility | Dexamethasone intravitreal implant | Observation | Individual patient-level data were pooled from phase 3 studies of patients with ME following CRVO; mean age 65 years and study-eye visual acuity of 20/80 | Lifetime |
Definitions of ischemia
Clinical outcomes
Study (country) | Complication secondary to iCRVO | Study characteristics | BCVA (SD) converted to LogMAR units (Treatment vs. comparator) | CRT (SD) in μm and/or NV (treatment vs. comparator) | Post-treatment complications (treatment vs. comparator) | Quality of evidence (GRADE)* |
---|---|---|---|---|---|---|
ANTI-VEGF TREATMENTS | ||||||
Korobelnik et al. 2014 [17] (multinational) | ME | ▪ T: Intravitreal aflibercept injection | ▪ Mean change in BCVA at: a
| ▪ Mean reduction in CRT: a
| ▪ During the 13-month study, NV development: 43 % vs. 43 % | NA |
o 13 months: +17.4 (16.1) vs. −8.0 (15.8) | o 494.6 (318.4) vs. 294.3 (258.6) | |||||
BCVA could not be converted to LogMAR units as the baseline BCVA was not available
| ||||||
▪ C: Sham injection | ||||||
Brown et al. 2013 [19] (multinational) | ME | ▪ T: Intravitreal aflibercept injection | ▪ Proportion of eyes gaining ≥ 15 letters at: | Not given by ischemic status | ▪ Not given by ischemic status | NA |
o 6 months: 51.4 % vs. 4.3 % | ||||||
o 13 months: 48.6 % vs. 30.4 % | ||||||
▪ C: Sham injection | ||||||
Boyer et al. 2012 [18] (multinational) | ME | ▪ T: Intravitreal VEGF Trap-Eye (aflibercept) | ▪ Mean change in BCVA at: a
| ▪ Mean reduction in CRT from baseline to: b
| ▪ Not given by ischemic status | NA |
o 6 months: +17.8 vs. −2.3 | ||||||
BCVA could not be converted to LogMAR units as the baseline was BCVA was not available
| o 6 months: 473.0 vs.309.4 | |||||
▪ C: Sham injection | ||||||
▪ Proportion of eyes gaining ≥ 15 letters at: | ||||||
o 6 months: 51.4 % vs. 4.3 % | ||||||
Wittstrom et al. 2012 [16] (Sweden) | NVG | ▪ T: Single intravitreal injection of bevacizumab combined with PRP | ▪ Mean baseline BCVA: | ▪ Median iris NV grade (range): | NA | ⊕ ⊕ ⊝⊝ low |
o 1.8 (0.61) vs. 2.0 (0.43) | o At baseline: 2 (0–4) vs. 1 (0–4) | |||||
▪ Mean BCVA at: | ||||||
o 1 week: 1.8 (0.59) vs. 2.2 (0.45) [p = 0.079] | o 1 week: 0 (0–1) vs. 0 (0–3) | |||||
o 2 months: 0 (0–1) vs. 0 (0–2) | ||||||
o 2 months: 1.8 (0.65) vs. 2.3 (0.46) [p = 0.136] | o 6 months: 0 (0–0) vs.0 (0–1) [for T: p = 0.001, for C: p = 0.005] | |||||
▪ C: PRP | o 6 months: 1.7 (0.71) vs. 2.3 (0.55) [p = 0.114] | |||||
▪ Median angle NV grade (range): | ||||||
o At baseline: 1.5 (0–4) vs. 1 (0–4) | ||||||
o At 1 week: 1 (0–3) vs. 0 (0–3) | ||||||
o At 2 months: 0 (0–3) vs. 0 (0–3) | ||||||
o At 6 months: 0 (0–3) vs.0 (0–3) [for T: p = 0.001, for C: p = 0.014] | ||||||
Campochiaro et al. 2008 [27] (USA) | ME | ▪ T: Ranibizumab 0.3 mg (3-monthly injections) | ▪ Mean baseline BCVA: | ▪ Mean baseline CRT: | NA | ⊕ ⊕ ⊕⊝ moderate |
o 0.78 (1.04–0.07) vs. 0.64 (0.96–0.34) | o 346 (88) vs. 297 (126) | |||||
▪ Mean BCVA at: | ▪ Mean CRT at: | |||||
o 3 months: 0.44 vs. 0.56 | o 3 months: 25 vs. 35 (eliminating 93 % vs. 89 % of the edema, respectively) | |||||
▪ C: Ranibizumab 0.5 mg (3 monthly injections) | ||||||
STEROID TREATMENTS | ||||||
Asano et al. 2007 [20] (Japan) | Ischemic CME or ME | ▪ T: Sub-tenon triamcinolone injection | ▪ Mean baseline BCVA: | ▪ Mean baseline CRT: | NA | ⊕ ⊕ ⊝⊝ low |
o 2 weeks before injection: 0.501 (0.229) vs. 0.510 (0.141) | ||||||
▪ C: No sub-tenon triamcinolone injection | ▪ Mean BCVA at: | o At 2 weeks before injection: 439 (148) vs. 436 (133) | ||||
o 1 month: 0.463 (0.359) vs. 0.510 (0.169) | ▪ Mean CRT at: | |||||
o 2 months: 0.488 (0.262) vs. 0.501 (0.330) | o 1 month: 315 (142) vs. 443 (150) | |||||
o 3 months: 0.499 (0.296) vs. 0.501 (0.212) | ||||||
o 4 months: 0.510 (0.203) vs. 0.511 (0.289) | o 2 months: 442 (143) vs. 467 (152) | |||||
o 3 months: 457 (123) vs. 466 (139) | ||||||
o 4 months: 449 (150) vs. 459 (128) | ||||||
Ramezani et al. 2006 [21] (Iran) | NV preventive effect | ▪ T: Intravitreal triamcinolone | ▪ Mean change in BCVA from baseline to: | ▪ Mean change in CRT from baseline to: | Not given by ischemic status | ⊕⊝⊝⊝ very low |
o 1 month: −0.40 (0.17) vs. −0.00 (0.12) | ||||||
o 2 months: −273 (108) vs. −115 (71) | ||||||
▪ C: Sham subconjunctival injection | ||||||
Jonas et al. 2005 [26] (Germany) | CME | ▪ T: Triamcinolone acetonide intravitreal injection (about 20 mg) | ▪ Mean baseline BCVA of ischemic patients in treatment arm: | NA | NA | NA |
o 1.79 (0.51) | ||||||
▪ Mean change in BCVA of ischemic patients in treatment arm: | ||||||
▪ C: No treatment (results were not given by ischemic status) | o From baseline to best post-operative VA: 1.57 (0.64) [p = 0.10] | |||||
PROCEDURAL TREATMENTS | ||||||
Tabatabaii et al. 2008 [23] (Iran) | ME, none of the eyes had NV | ▪ T: Pars plana vitrectomy with RON | ▪ Mean BCVA: | NA | Post-operation | NA |
▪ Iris NV, VH, and increased intraocular pressure in the early post-operative period: 11 % | ||||||
o Post-operation at 3.6 months vs. pre-operation: 1.32 (0.4–1.9) vs. 1.75 (1.5–1.9) [p < 0.01] | ||||||
▪ C: Pre-operation | ||||||
▪ Complicated by retinal detachment requiring pars plana vitrectomy and silicone injection: 5.5 % | ||||||
▪ Development of NV and VH that needed reoperation: 11 % | ||||||
Parodi et al. 2007 [22] (Italy and USA) | Anterior-segment NV | ▪ T: Conventional PRP (performed promptly when two clock hours of iris NV, any angle NV, or both were identified) | ▪ Mean baseline BCVA: | ▪ Iris NV (clock hours): | ▪ At follow-up, rate of NVG development: 5 % in T and C1 groups, and 11 % in C2 [p = 0.713] | ⊕ ⊕ ⊕ ⊕ high |
o 1.18 (0.16) vs. 1.19 (0.18) vs. 1.18 (0.15) | o At baseline:3.26 (1.96) [T] vs. 2.95(1.90)[C1] vs. 3.50 (1.97) [C2] | |||||
▪ Mean BCVA at: | ||||||
o 12 months: 1.23 (0.15) [T] vs. 1.20 (0.18) [C1] vs. 1.15 (0.16) [C2] [p = 0.28] | ||||||
o 1 month: 1.05 (1.12) vs. 3.15 (2.08) vs. 0.27 (0.46) | ||||||
▪ C1: Selective PRP (performed only in selected cases showing progression of iris NV, angle NV, or both during weekly follow-up) | o 6 months: 0.47 (1.07) vs. 3.05 (2.21) vs. 1.77 (1.11) | |||||
o 12 months: 0.52 (2.29) vs. 2.55 (3.05) vs. 2.27 (2.37) | ||||||
▪ C2: Photodynamic therapy with verteporfin (directed at the iris NV and angle NV) | ||||||
▪ Angle NV (clock hours): | ||||||
o At baseline:1.94 (1.12) [T] vs. 1.85 (1.34) [C1] vs. 2.38 (1.88) [C2] | ||||||
o 1 month: 0.68 (0.88) vs. 2.15 (1.81) vs. 0.00 (0.00) | ||||||
o 6 months: 0.52 (1.64) vs. 2.15 (1.89) vs. 0.83 (1.24) | ||||||
o 12 months: 0.57 (2.52) vs. 1.50 (2.64) vs. 1.27 (2.49) | ||||||
Feltgen et al. 2007 [24] (Germany) | Not mentioned | ▪ T: Retinal endovascular lysis | ▪ Mean pre-operative BCVA immediately before surgery: | NA | ▪ Rate of post-operative complication development: | NA |
▪ C: Pre-operation | o +1.2 (SEM +1.6/ minus +1.745) (range, +2.6 to +0.70) (N.B: +2.6 = light perception) | |||||
o NV: 46 % | ||||||
o Retinal detachment: 23 % | ||||||
▪ Mean post-operative BCVA at: | ||||||
o Cataract: 31 % | ||||||
▪ Rate of intra-operative complications: | ||||||
o 6 weeks: +1.31 (SEM plus +1.62/ minus +1.80) (range, +2.6 to +0.4) | ||||||
o Serious retinal detachment: 8 % | ||||||
o 3 months: +1.37 (SEM plus +1.72/ minus +1.85) (range, +2.6 to +0.52) | o VH: 31 % | |||||
▪ To treat these complications, 13 eyes required 22 additional procedures | ||||||
o 6 months: +1.46 (SEM plus +1.66/ minus +1.89) (range, +2.9 to +0.4) (N.B: +2.9 = Blindness) | ||||||
o 12 months: +1.40 (SEM plus 1.58/ minus +1.80) (range, +2.9 to +0.4) | ||||||
[None of these differences were significant] | ||||||
Mirshahi et al. 2005 [25] (Iran) | Prevention of NV | ▪ T: Surgical induction of chorioretinal venous anastomosis | ▪ Mean BCVA at time period from the onset of occlusion to the time of referral: | NA | ▪ Three (30 %) of 10 patients in the treatment arm needed further operations for: | NA |
o 2.5 vs. 1.5 [p < 0.001] | ||||||
▪ C: No surgery | ▪ Change in BCVA after the occurrence of occlusion: | o Cataract: 33.3 % | ||||
o Vitreous cavity hemorrhage: 33.3 % | ||||||
o 8 months: gained 0.94 vs. lost 0.57 [p < 0.001] | ||||||
o Retinal detachment: 33.3 % | ||||||
o NV: 0 % | ||||||
▪ In the control group, 7 (39 %) of 18 patients developed NV: | ||||||
o NVG: 57 % | ||||||
o Disc NV: 29 % | ||||||
o Iris NV: 14 % | ||||||
MISCELLANEOUS TREATMENTS | ||||||
Hayreh et al. 2011 [28] (USA) | Not mentioned | ▪ T: Aspirin | ▪ Baseline BCVA (n = 38 vs. 45 eyes) (p = 0.905) | NA | NA | NA |
▪ C: No aspirin or anticoagulant | ||||||
o Better than 0.5: 0 (0 %) vs. 0 (0 %) | ||||||
o 0.5–0.7: 1 (3 %) vs. 0 (0 %) | ||||||
o 1.0–1.3: 7 (18 %) vs. 11 (24 %) | ||||||
o CF or worse: 30 (79 %) vs. 34 (76 %) | ||||||
▪ Improved BCVA −0.5 or worse at: | ||||||
o 3 months (n = 26 vs. 32): 2 (8 %) vs. 4 (12 %) | ||||||
o 6 months (n = 22 vs. 29): 3 (14 %) vs. 5 (17 %) | ||||||
o 9 months (n = 18 vs. 32): 3 (17 %) vs. 5 (16 %) | ||||||
o 15 months (n = 16 vs. 21): 5 (31 %) vs. 5 (24 %) | ||||||
o 2–5 years (n = 9 vs. 17): 2 (22 %) vs. 4 (24 %) | ||||||
▪ Worsened BCVA −0.5 or worse at: | ||||||
o 3 months (n = 26 vs. 32): 5 (19 %) vs. 4 (12 %) | ||||||
o 6 months (n = 22 vs. 29):4 (18 %) vs. 6 (21 %) | ||||||
o 9 months (n = 18 vs. 32): 2 (11 %) vs. 8 (25 %) | ||||||
o 15 months (n = 16 vs. 21): 4 (25 %) vs. 5 (24 %) | ||||||
o 2–5 years (n = 9 vs. 17): 3 (33 %) vs. 5 (29 %) |
Study (country) | Inclusion criteria, exclusion criteria, baseline co-morbidities | BCVA as reported in the study | Miscellaneous outcomes (treatment vs. comparator) |
---|---|---|---|
ANTI-VEGF TREATMENTS | |||
Korobelnik et al. 2014 [17] (multinational) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | None |
- Patients had a >50 μm increase in CRT compared with the lowest previous measurement, new or persistent cystic changes within the neurosensory retina or subretinal fluid | |||
- Persistent diffuse edema ≥250 μm in the central subfield | |||
- Loss of ≥5 letters from the best prior measurement in conjunction with any increase in CRT, or an increase of ≥5 letters in BCVA from the most recent visit, suggesting potentially further improvements upon a subsequent injection | |||
Brown et al. 2013 [19] (multinational) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | None |
- Patients aged >18 years | |||
- Center-involved ME secondary to CRVO diagnosed within 9 months of study initiation | |||
- All study eyes had mean central subfield retinal thickness >250 mm using OCT from Zeiss Stratus OCT (Version 4.0 or later; Carl Zeiss Meditec, Jena, Germany) | |||
- Protocol refracted ETDRS12 BCVA of 20/40 to 20/320 (73 to 24 letters) | |||
▪ Exclusion criteria: | |||
- Any previous treatment with anti-angiogenic drugs; prior panretinal or macular laser photocoagulation; and any ocular disorders that could confound interpretation of study results | |||
- Previous use of intraocular corticosteroids or use of periocular corticosteroids within the 3 months prior to day 1 | |||
- Iris NV, VH, traction retinal detachment, or preretinal fibrosis involving the macula; history or presence of AMD (dry or wet form) that significantly affected central vision; diabetic ME or diabetic retinopathy, defined as eyes of diabetic subjects with more than 1 microaneurysm outside the area of the vein occlusion; and infectious blepharitis, keratitis, scleritis, or conjunctivitis | |||
Boyer et al. 2012 [18] (multinational) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | None |
- Patients with eyes whose mean central subfield retinal thickness was 250 μm or more on OCT from Zeiss Stratus OCT | |||
- ETDRS BCVA of 20/40 to 20/320 (73 to 24 letters) | |||
▪ Exclusion criteria: | |||
- Patients with a history of vitreoretinal surgery in the study eye, including RON or sheathotomy, current bilateral retinal vein occlusion, previous panretinal or macular laser photocoagulation | |||
- Other causes for decreased VA, ocular conditions with poorer prognosis in the fellow eye | |||
- History or presence of AMD, diabetic ME, or diabetic retinopathy, any use of intraocular or periocular corticosteroids, or anti-angiogenic treatment in the study eye at any time or in the fellow eye in the preceding 3 months | |||
- Iris NV, VH, traction retinal detachment, or preretinal fibrosis involving the macula, vitreomacular traction or epiretinal membrane that significantly affected central vision, ocular inflammation, uveitis, any intraocular surgery in the preceding 3 months | |||
- Aphakia, uncontrolled glaucoma, hypertension, or diabetes, spherical equivalent of a refractive error of more than 8 diopters, myopia, infectious blepharitis, keratitis, scleritis, or conjunctivitis, cerebral vascular accident, or myocardial infarction in the preceding 6 months | |||
- Other conditions that may interfere with interpretation of the results or increase the risk of complications | |||
Wittstrom et al. 2012 [16] (Sweden) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | ▪ Intraocular pressure (mmHg): |
- Patients with iris or anterior chamber angle NV and IOP greater than 22 mmHg were defined as having NVG | ○ At baseline: 38.1 (11.1) vs. 38.1 (11.1) | ||
○ At 1 week: 30.3 (6.6) vs. 24 (11) | |||
- Open angle was defined as normal angle structures being visible for more than 90° | |||
○ At 2 months: 25.2 (8.3) vs. 25.7 (12.4) | |||
○ At 6 months: 24.8 (12.3) vs. 18.4 (6.8) | |||
- A closed angle was defined as the presence of peripheral anterior synechiae for more than 270° | |||
▪ Rod response (b-wave amplitude): | |||
○ At baseline: 24.1 (23.0) vs. 22.8 (43.9) | |||
▪ Exclusion criteria: | |||
○ At 6 months: 24.3 (20.5) vs. 17.2 (25.1) | |||
- Patients with a VA less than light perception, diabetes mellitus, ocular inflammation, or cloudy media due to cataract, keratopathy, VH, a history of thromboembolic disorders including myocardial infarction or cerebrovascular accident and uncontrolled systemic hypertension | |||
▪ Rod response (b-wave implicit time): | |||
○ At baseline: 82.4 (33.0) vs. 56.6 (42.2) | |||
○ At 6 months: 92.6 (29.4) vs. 72.5 (40.0) | |||
▪ Standard combined rod/cone response (a-wave amplitude): | |||
○ At baseline: 45.5 (23.7) vs. 23.8 (20.3) | |||
○ At 6 months: 18.5 (9.0) vs. 29.2 (21.9) | |||
▪ Standard combined rod/cone response (a-wave implicit time): | |||
○ At baseline: 29.7 (5.6) vs. 34.3 (6.9) | |||
○ At 6 months: 28.7 (5.0) vs. 31.6 (4.9) | |||
▪ 30-Hz flicker cone(b-wave amplitude): | |||
○ At baseline: 19.0 (12.4) vs. 14.4 (11.7) | |||
○ At 6 months: 10.0 (5.2) vs. 12.1 (9.7) | |||
▪ 30 Hz flicker cone (b-wave implicit time): | |||
○ At baseline: 42.3 (1.1) vs. 43.6 (2.5) | |||
○ At 6 months: 42.1 (3.1) vs. 43.8 (1.9) | |||
Campochiaro et al. 2008 [27] (USA) | ▪ Inclusion criteria: | ▪ Mean baseline BCVA (ETDRS letters at 4 months): | ▪ Proportion of patients gaining at least 15 letters (%): |
- Patients >18 years with VA between 20/30 and 20/400 from ME due to CRVO and foveal thickness (central subfield) >250 μm | ○ 16 (13) vs. 23 (15) | ○ At 3 months: 70 vs. 40 | |
▪ Mean change in BCVA from baseline to (ETDRS letters at 4 months): | |||
○ 3 months: 17 vs. 14 | |||
▪ Exclusion criteria: | |||
- Patients with VA <20/400 in the fellow eye | |||
- A sign of possible permanent vision loss in the study eye such as atrophy or prominent pigmentary change in the macula | |||
- Laser photocoagulation or intraocular surgery within the previous 3 months | |||
- Intraocular injection of a VEGF antagonist within the previous 3 months | |||
- Intraocular steroids within the previous 4 months | |||
- Vitreomacular traction or an epiretinal membrane | |||
▪ Baseline comorbidities: hypertension (55 %), diabetes mellitus (30 %), hyperlipidemia (55 %), elevated homocysteine (20 %), glaucoma (2 %) | |||
STEROID TREATMENTS | |||
Asano et al. 2007 [20] (Japan) | ▪ Inclusion criteria: not reported | Given in LogMAR (see Table 3) | ▪ Mean affected eye/ fellow eye ratio of aqueous flare: |
○ 2 weeks before injection: 2.82 (0.28) vs. 2.77 (0.36) | |||
▪ Exclusion criteria: | |||
- Patients with bilaterally affected eyes | ○ 1 month: 1.49 (0.32) vs. 2.64 (0.61) [p < 0.05] | ||
- Those younger than 50 years of age | ○ 2 months: 2.38 (0.22) vs. 2.77 (0.28) | ||
- Eye pathologies related to blood–aqueous barrier breakdown or CME such as diabetes mellitus, uveitis, or previous intraocular surgery | ○ 3 months: 2.67 (0.33) vs. 2.75 (0.31) | ||
○ 4 months: 2.76 (0.28) vs. 2.79 (0.33) | |||
- Pathologies that could lead to artifacts in aqueous flaremetry, such as advanced cataract or poor mydriasis or allergy to fluorescein sodium | |||
- Symptoms for more than 3 months and those that had no detectable ME | |||
Ramezani et al. 2006 [21] (Iran) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | None |
- Patients with eyes suffering from iCRVO of less than 2 months’ duration | |||
▪ Exclusion criteria: | |||
- Patients with monocularity, previous intraocular surgery or laser therapy, VA ≥20/40, glaucoma or ocular hypertension, significant media opacity, NV, accompanying arterial occlusion, signs of chronicity (such as cilioretinal and/or retinal shunt vessels) | |||
- Existence of other significant retinal disease | |||
- Noncompliance | |||
Jonas et al. 2005 [26] (Germany) | ▪ Inclusion criteria: Not reported | Given in LogMAR (see Table 3) | None |
▪ Exclusion criteria: Not reported | |||
PROCEDURAL TREATMENTS | |||
Tabatabaii et al. 2008 [23] (Iran) | ▪ Inclusion criteria: | ▪ Mean BCVA: | None |
- Patients with onset of CRVO less than 12 months, severe hemorrhage in funduscopy and initial VA worse than 20/400 | ○ Post-operation at 3.6 months vs. pre-operation: 20/400 (20/1600–20/50) vs. 20/1000 (20/1600–20/630) [p < 0.01] | ||
▪ Exclusion criteria: | |||
- Patients with presence of optic atrophy or macular scar | |||
▪ Baseline comorbidities: systemic hypertension (33 %), diabetes mellitus (39 %), open-angle glaucoma (28 %), afferent pupillary defect (83 %) | |||
Parodi et al. 2007 [22] (Italy and USA) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | None |
- Patients with diagnosis of iCRVO | |||
- presence of two clock hours of iris NV, any angle NV, or both, and availability to undergo both treatment and control examinations | |||
▪ Exclusion criteria: | |||
- Patients with active hepatitis or clinically significant liver disease, porphyria, or other porphyrin sensitivity | |||
- Any previous surgical or laser eye treatment within the past 2 years | |||
▪ Baseline comorbidities: hypertension (82 %), cardiovascular disorders (46 %), diabetes mellitus (72 %) | |||
Feltgen et al. 2007 [24] (Germany) | ▪ Inclusion criteria: | ▪ Mean post-operative BCVA at: | None |
- Patients with clinically and angiographically diagnosed iCRVO between 6 and 20 weeks after CRVO onset, optimally corrected VA of 0.7 the minimum angle of resolution (LogMAR) or more (decimal VA ≤ 0.2), over 18 years in age | ○ 6 weeks: 0.049 + 0.024/ 0.016 (range, LP–0.4) | ||
○ 3 months: 0.043 + 0.019/ 0.014 (range, LP–0.3) | |||
○ 6 months: 0.035 + 0.022/ 0.013 (range, blindness– 0.4) | |||
12 months: 0.04 + 0.026/ 0.016 (range, blindness– 0.4) [None of these differences were significant]
| |||
- Ability to give informed consent | |||
▪ Exclusion criteria: | ▪ Mean pre-operative BCVA immediately before surgery: | ||
- Patients with retinal or disc NV needing photocoagulation at first presentation | |||
○ 0.063 + 0.025/ 0.018 (range, LP–0.2) | |||
- Other eye diseases that reduced VA, except cataract, e.g., glaucoma with visual-field loss in the other eye | |||
- Diabetic retinopathy, macular degeneration, uveitis, vitreous opacity, history of retinal detachment with visual impairment, of retinal vein or artery occlusion, and of neuro-ophthalmological diseases with visual-field defects, amblyopia in the affected eye | |||
- Inability to give informed consent | |||
Mirshahi et al. 2005 [25] (Iran) | ▪ Inclusion criteria: | Given in LogMAR (see Table 3) | None |
- Patients with a VA of ≤20/200, the presence of a RAPD pupillary defect of 2+ or more | |||
- Extensive retinal hemorrhage | |||
- 10 or more disc areas of capillary non-perfusion | |||
- Absence of NV | |||
▪ Baseline comorbidities: hypercholesterolemia in treatment vs. comparator arms was 60 % vs. 17 %, respectively | |||
MISCELLANEOUS TREATMENTS | |||
Hayreh et al. 2011 [28] (USA) | ▪ Inclusion criteria: | ▪ Baseline BCVA (n = 38 vs. 45 eyes) (p = 0.905) | None |
- Patients with a definite diagnosis of CRVO | ○ Better than 20/70, n(%): 0 (0 %) vs. 0 (0 %) | ||
▪ Exclusion criteria: | ○ 20/70–20/100, n(%): 1 (3 %) vs. 0 (0 %) | ||
- Patients with all other retinopathies mimicking CRVO or hemi-CRVO | |||
○ 20/200–400, n(%): 7 (18 %) vs. 11 (24 %) | |||
- Inadequate information or doubtful diagnosis, any retinal or optic nerve lesion or any other factor (e.g. cataract), including any treatment for CRVO or hemi-CRVO that could have influenced the visual status | |||
○ CF or worse, n(%): 30 (79 %) vs. 34 (76 %) | |||
▪ Improved BCVA - 20/70 or worse at: | |||
○ 3 months (n = 26 vs. 32): 2 (8 %) vs. 4 (12 %) | |||
- Diagnosis of glaucoma and visual-field loss | ○ 6 months (n = 22 vs. 29): 3 (14 %) vs. 5 (17 %) | ||
○ 9 months (n = 18 vs. 32): 3 (17 %) vs. 5 (16 %) | |||
○ 15 months (n = 16 vs. 21): 5 (31 %) vs. 5 (24 %) | |||
○ 2–5 years (n = 9 vs. 17): 2 (22 %) vs. 4 (24 %) | |||
▪ Worsened BCVA - 20/70 or worse at: | |||
○ 3 months (n = 26 vs. 32): 5 (19 %) vs. 4 (12 %) | |||
○ 6 months (n = 22 vs. 29): 4 (18 %) vs. 6 (21 %) | |||
○ 9 months (n = 18 vs. 32): 2 (11 %) vs. 8 (25 %) | |||
○ 15 months (n = 16 vs. 21): 4 (25 %) vs. 5 (24 %) | |||
○ 2–5 years (n = 9 vs. 17): 3 (33 %) vs. 5 (29 %) | |||
- Included were CRVO and hemi-CRVO patients with only background diabetic retinopathy, but those who had active NV, VH, traction detachment, or other complications influencing the VA or fields were excluded | |||
- Those with elevated IOP with documented normal visual field before the onset of CRVO were included | |||
▪ Baseline comorbidities: arterial hypertension (45 %), ischemic heart disease (29 %), diabetes mellitus (21 %), transient ischemic attack/cerebrovascular accident (3 %) |
Economic outcomes
Study details | Discounting | Economic endpoints measured | Costs reported | Adjusted costs in 2015 GBPa
| Sensitivity analyses results |
---|---|---|---|---|---|
ANTI-VEGF TREATMENTS | |||||
Taylor et al., 2014 [33] | 3.50 % | Ranibizumab | At a willingness-to-pay threshold of £30,000/QALY gained, the probability of ranibizumab being cost-effective is 68.3 % | ||
UK; CEA | Cost per treatment | £742.17 | £798 | ||
T: ranibizumab | Cost of administration | £192.00 | £206 | ||
C: observation | Total costs | £20,646 | £22,189 | ||
Cost year: 2011 | QALYs | 7.383 | NA | ||
Observation | |||||
Total costs | £11,430 | £12,284 | |||
QALYs | 6.844 | NA | |||
£17,103 | £18,381 | ||||
ICER, cost/QALY | £423 | £455 | |||
Incremental cost per month free from blindness | |||||
Eriksson et al., 2014 [29] | NR | Aflibercept | PSA showed that aflibercept was dominating over ranibizumab in 70 % of the simulations | ||
Sweden; CEA | Incremental costs | −35,000 SEK | −£2654 | ||
T: aflibercept | Incremental QALYs | 0.061 | NA | ||
C: ranibizumab | Ranibizumab | −8537 SEK | −£647 | ||
Cost year: not reporteda
| Incremental drug cost | −5793 SEK | −£439 | ||
Incremental administration cost | |||||
Duff et al., 2012 [31] | 3 % | Ranibizumab | PSA demonstrated that at a threshold of $50,000/QALY, ranibizumab was cost-effective in 88.3 % of simulations | ||
USA; CUA | Product cost per vial | $1950 | £1419 | ||
T: ranibizumab | Cost of adverse events | $376 | £274 | ||
C: dexamethasone intravitreal implants | Dexamethasone | $1295 | £942 | ||
Cost year: 2011 | Product cost per implant | $180 | £131 | ||
Cost of administration | $63 | £46 | |||
Cost of adverse events | |||||
ICER, cost/QALY | $34,204 | £24,882 | |||
Haig et al., 2012 [32] | 5 % | ICER, cost/QALY | Not reported | ||
Canada; CUA | Healthcare perspective | CAD$28,046 | £16,243 | ||
T: ranibizumab | Societal perspective | CAD$2103 | £1218 | ||
C: observation | |||||
Cost year: not reported | |||||
STEROID TREATMENTS | |||||
Vicente et al., 2013 [30] | 5 % | ICUR, cost/QALY | Throughout the 1000 iterations of the PSA the ICER consistently fell below a willingness-to-pay threshold of CAD$50,000/QALY gained. Although robust, the model was most sensitive to age of entry and the utilities used for both the best-seeing eye and worst-seeing eye | ||
Canada; CUA | Public payer perspective | CAD$21,568 | £12,492 | ||
T: dexamethasone 700 μg intravitreal implant | Societal perspective | CAD$14,103 | £8168 | ||
C: observation | |||||
Cost year: 2012 | |||||
Duff et al., 2012 [31] | 3 % | Dexamethasone | At low cost-effectiveness thresholds (<$19,000/QALY), steroid treatment was most likely to be cost-effective | ||
USA; CUA | Product cost per implant | $1295 | £942 | ||
T: dexamethasone intravitreal implants | Cost of administration | $180 | £131 | ||
C: steroids: triamcinolone acetonide | Cost of adverse events | $63 | £46 | ||
Cost year: 2011 | Steroid | $3 | £2 | ||
Product cost | $123 | £89 | |||
Cost of adverse events | $19,126 | £13,913 | |||
ICER, cost/QALY | |||||
Hayward et al., 2011 [34] | NR | Dexamethsone | PSA showed that at a threshold of £30,000, dexamethasone was a cost-effective option in 85.2 % of simulations | ||
UK; CEA | Total costs | £12,332 | £13,254 | ||
T: dexamethasone intravitreal implants | QALYs | 11.18 | NA | ||
C: observation | Observation | ||||
Cost year: not reporteda
| Total costs | £7600 | £8168 | ||
QALYs | 10.89 | NA | |||
ICER, cost/QALY | £16,522 | £17,757 | |||
Kowalski et al., 2011 [35] | 3 % | ICER, cost/QALY | $20,597 | £14,983 | PSA demonstrated that the ICERs fall below a threshold of $50,000 per QALY in 92 % of simulations. ICER was sensitive to the percentage of patients incurring CRVO in the best-seeing eye, risk of fellow eye occurrence, and cost of vision loss |
USA | |||||
T: dexamethasone 700 μg intravitreal implant | |||||
C: observation | |||||
Cost year: not reporteda
|
Risk of bias
Study | Random sequence generation (selection bias) | Allocation concealment (selection bias) | Blinding of participants and personnel (performance bias) | Blinding of outcome assessment (detection bias) | Incomplete outcome data (attrition bias) | Selective reporting (reporting bias) | Other bias |
---|---|---|---|---|---|---|---|
Korobelnik et al. 2014 [17] | + | ? | + | + | – | – | + |
Brown et al. 2013 [19] | + | ? | + | + | – | – | + |
Boyer et al. 2012 [18] | + | ? | + | ? | – | – | + |
Wittstrom et al. 2012 [16] | ? | ? | ? | ? | + | + | + |
Campochiaro et al. 2008 [27] | – | ? | + | ? | – | – | + |
Asano et al. 2007 [20] | – | – | – | – | – | + | + |
Ramezani et al. 2006 [21] | – | – | – | – | – | – | + |
Jonas et al. 2005 [26] | – | – | – | – | – | – | + |
Tabatabaii et al. 2008 [23] | – | – | – | – | + | + | + |
Parodi et al. 2007 [22] | + | + | ? | ? | + | + | + |
Feltgen et al. 2007 [24] | – | – | – | – | + | + | + |
Mirshahi et al. 2005 [25] | – | – | – | – | + | + | + |
Hayreh et al. 2011 [28] | – | – | – | – | + | + | + |