BACKGROUND Method of Literature Search Eligible studies were identified through a comprehensive literature search of electronic databases (Medline, 1966–September 2007 and Science Direct, all years). Additional articles were selected from review of the reference lists of the articles generated from the above search. The following keywords and combinations of these words were used in compiling the search: branch retinal vein occlusion, retinal circulatory disorders, pathogenesis, hematological disorders, risk factors, therapy methods, visual prognosis. In total, 150 of these were used for this mini-review. Epidemiology, Classification 1 , 2 3 4 4 4 5 4 , 6 7 , 8 9 10 4 Pathogenesis The pathogenesis of RVO is multifactorial while BRVO may be due to a combination of three primary mechanisms: compression of the vein at the arteriovenous (A/V) crossing, degenerative changes of the vessel wall, and abnormal hematological factors. In the following sections these factors are discussed. Arteriovenous Crossing 11 12 13 12 12 Degenerative Changes of Vessel Wall 14 , 15 14 15 15 16 1 , 2 , 10 12 , 14 17 Hematological Disorders 18 , 19 18 20 21 Table 1 TABLE 1 Most discussed coagulation and anticoagulation disorders in the etiology of BRVO Resistance to activated protein C (especially factor V Leiden mutation) Protein C or protein S deficiency Deficiency of antithrombin III Genetic mutation in the prothrombin (factor II) gene Anti-phospholipid antibodies Hyperhomocysteinemia Resistance to Activated Protein C and Deficiency of Protein C or Protein S 22 22 23 24 – 26 27 28 29 30 – 34 35 , 36 21 21 Deficiency of Antithrombin and Mutation in the Prothrombin Gene 21 , 26 , 34 , 37 – 40 Anti-Phospholipid Antibodies and Hyperhomocysteinemia 41 42 43 21 , 44 45 46 44 Pathogenesis of Macular Edema in BRVO 47 , 48 49 50 51 , 52 52 53 Clinical Signs and Diagnosis 54 55 Natural Course and Visual Prognosis 56 – 58 56 – 59 59 54 , 58 , 60 57 , 61 60 60 62 63 53 , 56 , 58 , 64 – 66 Table 2 65 58 Table 3 58 Tables 2 3 Table 2 Table 3 p 65 TABLE 2 p  Initial visual acuity 20/50 or better Initial visual acuity 20/200 or worse p Natural course—without laser treatment 56 5% (1/20) 50% (6/12) Significant 58 0% (0/35) 83% (24/29) Significant Had undergone laser treatment 53 25% (2/8) 67% (10/15) No 64 0% (0/9) 33% (3/12) No 58 13% (5/40) 50% (32/64) Significant 66 8% (1/13) 50% (8/16) Significant TABLE 3 p  Initial visual acuity 20/50 or better Initial visual acuity 20/200 or worse p Natural course—without laser treatment 56 90% (18/20) 33% (4/12) Significant 58 89% (31/35) 14% (4/29) Significant Had undergone laser treatment 53 63% (5/8) 20% (3/15) No 64 56% (5/9) 9% (1/12) Significant 58 75% (30/40) 22% (14/64) Significant 66 77% (10/13) 13% (2/16) Significant Treatment Table 4 TABLE 4 Treatment modalities for BRVO Anti-aggregative therapy and firbrinolysis Isovolemic hemodilution Laser treatment Intravitreal and periocular application of steroids Intravitreal injection of VEGF inhibitors Sheathotomy and vitrectomy Anti-Aggregative Therapy and Fibrinolysis 67 68 69 69 Both studies mentioned that investigated the medical treatment of BRVO are limited by a small sample size and short follow-up period (6 and 4 months). Isovolaemic Hemodilution 20 p p 20 70 71 72 n n n 73 p 20 , 73 , 74 The use of hemodilution to treat BRVO is currently not generally accepted. Interpretation of the above-mentioned studies is difficult because most of them incorporated other treatments in combination with the hemodilution. Further prospective randomized trials with adequate controls and sufficient follow-up are required for any definitive conclusions and recommendations. Arteriovenous Crossing Sheathotomy and Vitrectomy 75 Table 5 75 – 96 75 – 96 76 77 , 80 , 96 77 78 78 97 , 98 84 TABLE 5 Summary of studies evaluating the treatment of macular edema in BRVO by sheathotomy (VA = visual acuity, ME = macular edema, ILM = internal limiting membrane) Author Study type Patients Follow-up (mean) Outcomes Comments 75 Case report. 1 eye. 8 months. VA improved from 20/200 to 20/25. First report of sheathotomy. 76 Prospective interventional nonrandomized study. 40 eyes—all underwent vitrectomy, sheathotomy and injection of 25 mg of tissue plasminogen activator into occluded vein. 13 months. Thrombus release in 11 eyes (27.5%)—correlated with early surgery. VA increased from 20/100 to 20/40 (p = 0.016).  77 Retrospective interventional comparative case series. 20 eyes—sheathotomy 16 control eyes (posterior vitreous detachment via vitrectomy). 12 months. VA: significantly better in both groups (p = 0.008 and p = 0.001, respectively). VA and foveal thickness were not significantly different between the groups.  78 Prospective nonrandomized, interventional case series. 13 eyes—sheathotomy. 7 months. Improvement in VA ≥ 2 ETDRS lines in 9 eyes (69%). Absence of previous posterior vitreous detachment correlated with improvement in VA. 79 Retrospective interventional case series. 22 eyes—sheathotomy + ILM peeling in all eyes. 3 months. Improvement in VA (log MAR) from 0.79 ± 0.29 to 0.57 ± 0.33 (p < 0.01). All eyes pretreated with grid laser or triamcinolone. 80 Prospective, randomized, comparative, interventional study. Group 1: 18 eyes—sheathotomy. Group 2: 18 controls (vitrectomy without sheathotomy). 31 months. VA (log MAR) in group 1: 0.52 → 0.08. In group 2: 0.53 → 0.014. Differences between group 1 and 2 was not significant.  81 Retrospective interventional comparative case series. 11 eyes—sheathotomy. 10 control eyes—grid laser photocoagulation. 9 months. VA (log MAR): sheathotomy: 0.84 → 0.36. Grid laser: 1.06 → 0.82. Difference was significant.  82 Interventional case series. 7 eyes. 6 months. Significant improvement in retinal blood flow (p < 0.01) and reduced macular thickness (p = 0.03).  83 Retrospective interventional case series. 12 eyes. 49.9 weeks. VA (logMAR) improved from 1.00 ± 0.32 to 0.56 ± 0.28 (p = 0.0003). 25-gauge transvitreal limited arteriovenous crossing manipulation without vitrectomy. 84 Prospective interventional nonrandomized case-control study. 43 eyes—sheathotomy. 16 eyes additionally + ILM peeling. 25 control eyes. 6 weeks. 26 patients (60%) gained ≥ 2 lines of VA. Better result in patients with ILM peeling. ME and intraretinal hemorrhage resorbed in all patients. All patients had isovolaemic hemodilution for 10 days. 85 Prospective interventional case series. 15 eyes. 6.5 years. Snellen VA improved in 10 patients (67%) by an average of 4 lines vision (range 1–9 lines). In 3 patients resolution of ME but no improvement of VA. Retinal vascular bleeding in 2 patients. 86 Prospective interventional nonrandomized study. 13 eyes—sheathotomy, 5 eyes underwent additionally ILM peeling. 12 months. VA improved in 12 patients (92%). Better results in patients with ILM peeling.  87 Prospective nonrandomized intervention case series. 12 eyes – sheathotomy. 3 months. VA (logMAR) improved from 0.74 to 0.56.  88 Prospective, nonrandomized, comparative interventional study with concurrent control group. 20 eyes—sheathotomy. 20 control eyes (10 of them without intervention and another 10 underwent grid laser). 14 months (sheathotomy). 19 months (controls). VA improvement: Sheathotomy: from 20/250 to 20/63. Controls: from 20/180 to 20/125 (p = 0.02). 45% of the surgical group had final VA ≥ 20/40 compared with 15% of the controls. Data only for whole control group together. 89 Retrospective non-controlled case series. 27 eyes—sheathotomy. 12 months. Resolution of ME in 8 (29.6%) patients, reduction in 14 (51.8%) and persistence in 5 (18.5.%).  90 Prospective nonrandomized interventional case series. 6 eyes (sheathotomy + ILM peeling. 6 controls (ILM peeling only). 6 months. Significant improvement of VA in both groups. No difference in VA or foveolar thickness between the groups (p = 0.5; p = 0.6 respectively).  91 Retrospective interventional case series. 17 eyes—sheathotomy. 6 months. Improvement in VA from 0.26 to 0.4. 53% patients improved ≥ 4 lines (Snellen).  92 Retrospective interventional case series. 3 eyes—sheathotomy. 10 months. No improvement in VA observed. All patients with initial VA < 20/40. 93 Retrospective interventional case series. 3 eyes—sheathotomy. 12 months. VA improved in 2 patients to 20/40, in 1 patient stabilized (20/180).  94 Retrospective interventional case series. 5 eyes—sheathotomy. 6.5 years. VA preoperative in all patients ≤ 20/200. Improved in 4 eyes from 20/30 to 20/70. 1 eye with counting fingers remained unchanged.  95 Retrospective interventional case series. 12 eyes—sheathotomy. 20 months. VA improved in 9 eyes (75%), in 1 eye (8.3%) remained unchanged and deteriored in 2 eyes (16.7%). 2 patients received additionally 25 mg triamcinolone acetonide at the end of the surgery. 96 Retrospective interventional case series. 20 eyes—pars plana vitrectomy and dissection of the arteriovenous crossing without separation of the vessels. 10.5 months. In 16 eyes (80%) improved VA ≥ 2 lines. Mean improvement of VA (logMAR) was = 0.44 ± 0.14 (p = 0.016).  Steroids Intravitreal Corticosteroids 99 – 117 Table 6 99 p p 100 101 p 103 118 119 , 120 120 121 TABLE 6 Summary of studies evaluating the treatment of macular edema in BRVO by intravitreal application of triamcinolone acetonide (TA = triamcinolone acetonide, VA = visual acuity, ME = macular edema, MLG = macular laser grid photocoagulation) Author Study type Patients Follow-up (mean) Outcomes Comments 99 Randomized interventional, parallel, three-arm clinical trial. Intravitreal TA (4mg): 22 eyes. MLG: 21 eyes. TA+MLG: 20 eyes. 9 months. TA group: VA improved from 0.82 to 0.23 log MAR (p = 0.04). MLG-group: VA unchanged. TA+MLG group, VA improved from 0.83 to 0.20. logMAR (p = 0.003). Different etiology of ME, only 6 eyes with BRVO. 100 Retrospective interventional comparative case series. 20 eyes with ME (4 mg TA) Disease duration: 10 eyes ≤ 3 months; 10 eyes > 3 months. 6 months. Group ≤ 3 months: VA (logMAR) improved from 1.07to 0.63 in 1 month (p = 0.012) and to 0.34 in 6 months (p = 0.005).  101 Retrospective, non-controlled case series. 19 treated eyes (8 mg TA). 6.2 months. VA (logMAR) improved from 1.01 ± 0.16 to 0.62 ± 0.22. VA improved in 17 eyes and remained unchanged in 2 eyes.  102 Prospective nonrandomized comparative study. 10 treated eyes (20 mg TA). 20 untreated controls. TA patients: 10.1 months. Controls: 6 months. TA patients: VA increased from 0.27 ± 0.11 to 0.45 ± 0.27 (p = 0.02). Controls: VA decreased significantly (p = 0.007). VA increased higher in non-ischemic group. Significant increase of intraocular pressure in treated group. 103 Retrospective non-controlled case series. 13 eyes (4 mg TA). 13 months. VA: improved in 7 eyes, remained the same in 4 eyes, worsened in 2 eyes. Foveolar thickness decreased in 56% of patients (p < 0.001). VA improvement significantly correlated with patient age (p = 0.026). 104 Retrospective, non-controlled case series. 6 eyes (4 mg TA). 149.5 days. Improvement in VA ≥ 2 lines in 5 eyes (83.3%). VA from 20/166 to final 20/106. 3 eyes treated with re-application of TA. 105 Retrospective interventional comparative case series. 15 eyes (8 mg TA). 19 eyes MLG. 6.3 months. VA (logMAR) improved in TA group from 0.98 to 0.24 and in MLG group from 1.02 to 0.5 (in both groups p < 0.001). Improvement in TA group was significantly higher than in MLG (p < 0.001).  106 Retrospective, non-controlled case series. 12 eyes (4 mg TA). 15.3 months. VA improved >3 lines in 50% of eyes after 1 month and in 42% of eyes at last follow up. 8 eyes developed recurrent ME at an average of 5.5 months after initial TA injection. 107 Prospective nonrandomized interventional comparative study. 16 eyes (4 mg TA). 11 controls (without TA). 103 days in TA-group. 94.5 days in controls. VA (logMAR). In TA-group: improvement from 0.77 ± 0.43 to 0.44 ± 0.43 (p < 0.001). No significant change of VA in controls. Significant reduction of ME in TA-group (P < 0.001). 108 Case report. 1 eye (4 mg TA). 3 months. Improvement in VA from counting fingers to 20/80. Eye with macular ischaemia. 109 Prospective interventional non-controlled case series. 18 eyes (4 mg TA). All patients completed 9 months, 12 eyes completed 12 months. VA (logMAR) improved from 0.81 ± 0.36 to 0.65 ± 0.3 (p = 0.03) after 1 months, no significant difference in VA after 3, 6, 9 and 12 months. Eye with macular ischaemia. All eyes with macular ischaemia. 110 Prospective interventional non-controlled case series. 17 eyes (vitrectomy + 10 mg TA intravitreal), 12 eyes of them with recurrent ME received sub-tenon 20 mg TA. 12.1 months. 82% of eyes rapid resolution of ME within 2 months (p = 0.041). 12 eyes (70.5%) received sub-tenon TA because of recurrent ME. Final VA (logMAR) improved from 0.74 ± 0.40 to 0.40 ± 0.34 (p = 0.010). 14 eyes with vitrectomy underwent additional phacoemulsification with lens implantation. 111 Prospective interventional non-controlled case series. 8 eyes (4 mg TA). All eyes with serous macular detachment. 6 months. After TA regression of ME and serous macular detachment in all eyes. After 6 months recurrence in 2 eyes (25%) re-treatment occurred. Final VA improved in 7 eyes (87.5%).  112 Prospective interventional non-controlled case series. 9 eyes (4 mg TA). 6 months. Significant improvement in reading VA only after 1 month (p = 0.02). No significant improvement in VA for distance. No significant reduction in macular thickness. 5 eyes non-ischaemic BRVO. 4 eyes ischaemic BRVO. 113 Case report. 2 patients: 1 eye BRVO 1 eye CRVO (25 mg TA). 5 weeks. Patient with BRVO improved VA from 0.25 to 0.5. Patient with CRVO from 0.4 to 0.5.  114 Prospective interventional non-controlled case series. 5 eyes with CRVO. 11 eyes with BRVO. All eyes received sub-tenon injection of 20 mg TA. 7 months. 8 eyes (50%) improved VA and 2 eyes (12.5%) had worsening of VA at the time of final examination. Reduction of ME >30% of initial thickness in 13 eyes (81.3%). Because of recurrent ME – in 7 eyes repeated sub-tenon application of TA. 1 eye with BRVO pretreated with laser photocoagulation because of retinal ischemia. 115 Retrospective interventional case series. 5 eyes (4 mg TA). 6 months Improvement of VA in 4 eyes. 1 eye underwent re-injection after 3 months because of recurrent ME.  116 Retrospective interventional comparative case-control study. 8 eyes TA-injected group (simultaneous intravitreal and sub-tenon TA injection). 7 eyes vitrectomy with TA group (treated by vitrectomy and intravitreal or sub-tenon TA). 12 months. VA improved significantly from baseline in both the TA-injected (p = 0.0069) and vitrectomy with TA groups (p = 0.0145). There was no significant difference in VA and macular thickness between the two groups.  117 Randomized interventional clinical trial. 105 (20 with venous occlusion) eyes in each group: I. 700 μg Posurdex II. 350 μg Posurdex III. controls. 3 months. Improvement of VA of ≥10 lines (ETDRS) 35% eyes in group 700 μg Posurdex, 24% in 350 μg Posurdex and 13% in control group (p < 0.001 versus 700 μg group; p = 0.04 versus 350 μg group). Preliminary report 60 eyes with retinal venous occlusion include eyes with CRVO and BRVO. https://web.emmes.com/study/score 117 p p 117 Periocular Application of Triamcinolone Acetonide 122 123 Intravitreal Injection of VEGF Inhibitors 124 – 140 124 125 125 – 134 126 , 127 126 128 129 136 – 139 140 Prospective, controlled studies are mandatory to develop standardized treatment protocols that allow safe and effective application of anti-VEGF drugs. Laser Treatment Laser treatment is an established method for use in patients with BRVO. A large number of publications concerning the role of photocoagulation in the management of BRVO have appeared. Various laser techniques can be used: macula grid photocoagulation and the method of arterial crimping for treatment of ME, and peripheral scatter photocoagulation for treatment of retinal and/or disc neovascularization. Macular Grid Laser Photocoagulation 141 141 142 , 143 61 , 62 , 141 141 65 63 , 141 , 144 Scatter Photocoagulation 54 145 54 Arteriolar Constriction 146 64 147 – 149 149 150 CONCLUSIONS The pathogenesis of BRVO is multifactorial. Its resulting visual loss is due primarily to ME, macular nonperfusion, and retinal neovascularization. A large number of treatments have been advocated in its management. Unfortunately, almost all of these lack sufficient evidence for their effectiveness. Randomized prospective trials are essential. The only one established treatment for ME is macular grid photocoagulation in patients with BRVO longer than 3 months and a VA of 20/40 or worse. Additionally, the initial VA may play a crucial role in the prognosis of BRVO and determinates the final VA.