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Table 2 Study characteristics of the included clinical studies

From: Systematic literature review of treatments for management of complications of ischemic central retinal vein occlusion

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

â–ª Intravitreal aflibercept injection

â–ª Sham injection

â–ª NAk

â–ª 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

â–ª Intravitreal aflibercept injection

â–ª Sham injection

â–ª NAk

â–ª 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

â–ª Intravitreal VEGF Trap-Eye (aflibercept)

â–ª Sham injection

â–ª NAk

â–ª 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

â–ª Single intravitreal injection of bevacizumab combined with PRP

â–ª PRP

â–ª 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)

â–ª 63 (17) vs. 68 (13)

â–ª 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)

â–ª Sub-tenon triamcinolone injection

â–ª No sub-tenon triamcinolone injection

â–ª 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

â–ª Intravitreal triamcinolone

â–ª Sham subconjunctival injection

â–ª NAk

â–ª 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)

â–ª No treatment (results were not given by ischemic status)

â–ª NAk

â–ª 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

â–ª Pars plana vitrectomy with radial optic neurotomy

â–ª Pre-operation

â–ª 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

â–ª 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)

â–ª 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

â–ª Retinal endovascular lysis

â–ª Pre-operation

â–ª 67

â–ª NA

o n =13 (100 % ischemic)

Mirshahi et al. 2005 [25] (Iran)

Non-randomized controlled trial

Prevention of NVi

6–18 (mean = 10)

â–ª Surgical induction of chorioretinal venous anastomosis

â–ª No surgery

â–ª 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)

â–ª Aspirin

â–ª No aspirin or anticoagulant

â–ª 70 (12) vs. 68 (16)

▪ 42 % vs. 53 %

o n = 38 (17 % ischemic of 227)

o n = 47 (15 % ischemic of 324)

  1. definitions of ischemia used by study
  2. BCVA best corrected visual acuity, CME cystoid macular edema, CVOS Central Retinal Vein Occlusion Study, iCRVO ischemic central retinal vein occlusion, ME macular edema, NA not available, NV neovascularization, NVG neovascular glaucoma, PRP panretinal photocoagulation, VEGF vascular endothelial growth factor
  3. a≥10 disc areas of non-perfusion (CVOS classification)
  4. bBCVA of 20/40 to 20/320 and ≥10 disc areas of non-perfusion
  5. cNot reported
  6. dBCVA of 20/30 to 20/400
  7. eLarge non-perfusion areas, severe hemorrhages, and severe dye leakage
  8. fCapillary non-perfusion on fluorescein angiography, afferent pupillary defect, visual acuity, severity of intraretinal hemorrhages
  9. gReduced b-wave amplitude on electroretinography and ≥10 disc areas of capillary non-perfusion on fluorescein angiography (CVOS classification)
  10. hCVOS classification
  11. iBCVA <20/200, the presence of a relative afferent pupillary defect of 2+ or more, extensive retinal hemorrhage, ≥10 disc areas of capillary non-perfusion, and the absence of NV
  12. jHayreh’s classification
  13. kData were not reported for ischemic patients separately
  14. lNumber of patients reported refers to the population included in the final analysis sets