Retinale Gefäßverschlüsse: Moderne Therapieansätze

Zusammenfassung

Arterielle Gefäßverschlüsse sollten als Notfall bewertet werden und sind als okuläres Analogon zum zerebralen Apoplex zu sehen. Sie besitzen dieselben arteriosklerotischen Risikofaktoren, die auch bei Herz-, Kreislauf- und zerebrovaskulären Erkrankungen ursächlich sind, weshalb eine intensive interdisziplinäre Abklärung erforderlich ist, um mögliche Komorbiditäten rechtzeitig zu erkennen und gegebenenfalls zu behandeln. Die derzeitigen Therapiemöglichkeiten eines akuten arteriellen Gefäßverschlusses sind in ihrer Effizienz hinsichtlich Visusverbesserung sehr limitiert. Verfahren zur systemischen Lyse können in der Routineversorgung aufgrund ihres deutlich erhöhten Nebenwirkungsprofils nicht empfohlen werden. Hinzu kommt ein begrenztes Zeitfenster von bis zu 6 Stunden nach Symptombeginn (Retinatoleranzzeit), in dem nach Studienlage eine Intervention überhaupt nur sinnvoll zu sein scheint. Dagegen haben die neuen Therapiemöglichkeiten retinaler Venenverschlüsse, insbesondere durch die intravitreale operative Medikamentenapplikation, zu deutlichen Visusverbesserungen geführt. Die Wirksamkeit und Effizienz der einzelnen Anti-VEGF-Medikamente ist nach aktueller Studienlage vergleichbar. Alternativ kann auch der Einsatz von Steroiden erwogen werden, wobei hierbei das Nebenwirkungsprofil sorgfältig abgewogen werden sollte. Des Weiteren kann ergänzend und gerade beim Vorliegen von retinalen Ischämien die periphere Photolaserkoagulation einen visusstabilisierenden Effekt haben und die Ausbildung von Neovaskularisationen verhindern. Es wird angenommen, dass die Kombination aus IVOM- und Lasertherapie einen symbiotischen Effekt haben könnte.

Abstract

Retinal artery occlusion (RAO) should be evaluated as an emergency and can be seen as an ocular analogue to the cerebral apoplex. Both have the same arteriosclerotic risk factors, which are also responsible for cardiac, circulatory and cerebrovascular diseases. That is why an intensive interdisciplinary clarification is necessary to recognize possible comorbidities in time and, if necessary, to treat them. The current therapeutic possibilities of an acute RAO are very limited in their efficiency regarding visual improvement. Methods for systemic lysis cannot be recommended in routine care because of their significantly increased side-effect profile. However, there is a limited window of time of up to 6 hours after the onset of symptoms in which an intervention appears to be useful at all. On the other hand, the new therapeutic possibilities of retinal vein occlusions (RVO) led to marked visual improvements, especially due to the intravitreal application of anti-VEGF. Safety and efficiency of the individual anti-VEGF drugs are comparable according to clinical trials. Alternatively, the use of intravitreal steroids can be considered, whereby the side-effect profile should be carefully weighed. In the presence of retinal ischaemia, peripheral laser coagulation can have a stabilizing effect on visual acuity and prevents neovascularization. It is postulated that the combination of anti-VEGF and laser therapy might have a symbiotic effect.

Schlüsselwörter

retinaler Gefäßverschluss - Zentralarterienverschluss - Arterienastverschluss - Zentralvenenverschluss - Venenastverschluss - Sehverlust

Key words

vascular occlusion - central retinal artery occlusion - branch retinal artery occlusion - central vein occlusion - branch retinal vein occlusion - visual loss

• Literatur

• 1 Feltgen N, Schmidt D, Hansen L. Arterielle retinale Verschlüsse. Ophthalmologe 2003; 100: 651-665
• 2 Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol 1996; 114: 1243-1247
• 3 Mirshahi A, Feltgen N, Hansen LL. et al. Gefäßverschlüsse der Netzhaut. Dtsch Arztebl 2008; 105: 474-479
• 4 Jonas JB, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonideas treatment of macular edema in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 2002; 240: 782-783
• 5 Stahl A, Agostini H, Hansen LL. et al. Bevacizumab in retinal vein occlusion-results of a prospective case series. Graefes Arch Clin Exp Ophthalmol 2007; 245: 1429-1436
• 6 Hayreh SS, Zimmerman MB. Central retinal artery occlusion: visual outcome. Am J Ophthalmol 2005; 140: 376-391
• 7 Schmidt D, Hetzel A, Geibel-Zehender A. et al. Systemic diseases in non-inflammatory branch and central retinal artery occlusion – an overview of 416 patients. Eur J Med Res 2007; 12: 595-603
• 8 Lorentzen SE. Occlusion of the central retinal artery. A follow-up. Acta Ophthalmol 1969; 47: 690-703
• 9 Eckardt C, Götze O, Utermann D. Life expectancy of patients with circulatory disorders of the posterior eyeball segment. Ophthalmologica 1983; 187: 34-42
• 10 Callizo J, Feltgen N, Pantenburg S. et al. Cardiovascular risk factors in central retinal artery occlusion: results of a prospective and standardized medical examination. Ophthalmology 2015; 122: 1881-1888
• 11 Sharma S, Brown GC, Pater JL. et al. Does a visible retinal embolus increase the likelihood of hemodynamically significant carotid artery stenosis in patients with acute retinal arterial occlusion?. Arch Ophthalmol 1998; 116: 1602-1606
• 12 Sharma S, Naqvi A, Sharma SM. et al. Transthoracic echocardiographic findings in patients with acute retinal arterial obstruction. A retrospective review. Retinal Emboli of Cardiac Origin Group. Arch Ophthalmol 1996; 114: 1189-1192
• 13 Sharma S, Sharma SM, Cruess AF. et al. Transthoracic echocardiography in young patients with acute retinal arterial obstruction. RECO Study Group. Retinal Emboli of Cardiac Origin Group. Can J Ophthalmol 1997; 32: 38-41
• 14 Deutsche Schlaganfall Gesellschaft. Sekundärprophylaxe ischämischer Schlaganfall und transitorische ischämische Attacke. AWMF-Register Nr. 030-133; 2015. http://www.awmf.org/uploads/tx_szleitlinien/030-133m_&%236;S3_Sekun%25C3%25A4rprophylaxe_isch%25C3%25A4mischer_Schlaganfall_2015-02.pdf Stand: 14.12.2016
• 15 Fineman MS, Savino PJ, Federman JL. et al. Branch retinal artery occlusion as the initial sign of giant cell arteritis. Am J Ophthalmol 1996; 122: 428-430
• 16 Schmidt D. Arteriitis temporalis Horton, Vol. 1. St. Gallen: Elephas Medizin; 1997
• 17 Bertram B, Remky A, Arend O. et al. Protein C, protein S, and antithrombin III in acute ocular occlusive diseases. Ger J Ophthalmol 1995; 4: 332-335
• 18 Brown GC, Magargal LE, Shields JA. et al. Retinal arterial obstruction in children and young adults. Ophthalmology 1981; 88: 18-25
• 19 Incandela L, Cesarone M, Belcaro G. et al. Treatment of vascular retinal disease with pentoxifylline: a controlled, randomized trial. Angiology 2002; 53: 31-34
• 20 Fraser SG, Adams W. Interventions for acute non-arteritic central retinal artery occlusion. Cochrane Database Syst Rev 2009; (01) CD001989 DOI: 10.1002/14651858.CD001989.pub2.
• 21 Arend O, Hoberg A, Bertram B. et al. Hemodilution in acute arterial circulatory disorders of the retina. Acta Med Austriaca 1991; 18: 66-68
• 22 Neubauer AS, Mueller AJ, Schriever S. et al. [Minimally invasive therapy for clinically complete central retinal artery occlusion – results and meta-analysis of literature]. Klin Monatsbl Augenheilkd 2000; 217: 30-36
• 23 Rumelt S, Dorenboim Y, Rehany U. Aggressive systematic treatment for central retinal artery occlusion. Am J Ophthalmol 1999; 128: 733-738
• 24 Sandercock P, Gubitz G, Foley P. et al. Antiplatelet therapy for acute ischaemic stroke. Cochrane Database Syst Rev 2003; (02) CD000029
• 25 Cugati S, Varma DD, Chen CS. et al. Treatment options for central retinal artery occlusion. Curr Treat Options Neurol 2013; 15: 63-77
• 26 Hayreh SS, Zimmerman MB, Kimura A. et al. Central retinal artery occlusion: retinal survival time. Exp Eye Res 2004; 78: 723-736
• 27 Chen CS, Lee AW, Campbell B. et al. Efficacy of intravenous tissue-type plasminogen activator in central retinal artery occlusion. Stroke 2011; 42: 2229-2234
• 28 Hattenbach LO, Kuhli-Hattenbach C, Scharrer I. et al. Intravenous thrombolysis with low-dose recombinant tissue plasminogen activator in central retinal artery occlusion. Am J Ophthalmol 2008; 146: 700-706
• 29 Rumelt S, Brown GC. Update on treatment of retinal arterial occlusions. Curr Opin Ophthalmol 2003; 14: 139-141
• 30 Schmidt DP, Schulte-Mönting J, Schumacher M. Prognosis of central retinal artery occlusion: local intraarterial fibrinolysis versus conservative treatment. AJNR Am J Neuroradiol 2002; 23: 1301-1307
• 31 Beatty S, Eong KGA. Local intra-arterial fibrinolysis for acute occlusion of the central retinal artery: a meta-analysis of the published data. Br J Ophthalmol 2000; 84: 914-916
• 32 Landa E, Rehany U, Rumelt S. Visual functions following recovery from non-arteritic central retinal artery occlusion. Ophthalmic Surg Lasers Imaging 2004; 35: 103-108
• 33 Cope A, Eggert JV, OʼBrien E. Retinal artery occlusion: visual outcome after treatment with hyperbaric oxygen. Diving Hyperb Med 2011; 41: 135-138
• 34 Menzel-Severing J, Siekmann U, Weinberger A. et al. Early hyperbaric oxygen treatment for nonarteritic central retinal artery obstruction. Am J Ophthalmol 2012; 153: 454-459
• 35 Gaydar V, Ezrachi D, Dratviman-Storobinsky O. et al. Reduction of apoptosis in ischemic retinas of two mouse models using hyperbaric oxygen treatment. Invest Ophthalmol Vis Sci 2011; 52: 7514-7522
• 36 Aisenbrey S, Krott R, Heller R. et al. Hyperbaric oxygen therapy in retinal artery occlusion. Ophthalmologe 2000; 97: 461-467
• 37 Kiesewetter H, Blume J, Jung F. et al. Haemodilution with medium molecular weight hydroxyethyl starch in patients with peripheral arterial occlusive disease stage II b. J Intern Med 1990; 227: 107-114
• 38 Roth S. The effects of isovolumic hemodilution on ocular blood flow. Exp Eye Res 1992; 55: 59-63
• 39 Neely KA, Ernest JT, Goldstick TK. et al. Isovolemic hemodilution increases retinal tissue oxygen tension. Graefes Arch Clin Exp Ophthalmol 1996; 234: 688-694
• 40 Atebara NH, Brown GC, Cater J. Efficacy of anterior chamber paracentesis and carbogen in treating acute nonarteritic central retinal artery occlusion. Ophthalmology 1995; 102: 2029-2035
• 41 Ffytche T. A rationalization of treatment of central retinal artery occlusion. Trans Ophthalmol Soc U K 1974; 94: 468-479
• 42 Augsburger J, Magargal L. Visual prognosis following treatment of acute central retinal artery obstruction. Br J Ophthalmol 1980; 64: 913-917
• 43 Beatty S, Eong KGA. Acute occlusion of the retinal arteries: current concepts and recent advances in diagnosis and management. Emerg Med J 2000; 17: 324-329
• 44 Boljka M, Peternel P, Kolar G. et al. Die thrombolytische Therapie bei Zentralgefäßverschlüssen. Klin Monatsbl Augenheilkd 1984; 185: 395-396
• 45 Schmidt D, Schumacher M. Zur Therapie des Zentralerterienverschlusses. Klin Monatsbl Augenheilkd 1991; 199: 380
• 46 Schmidt D, Schumacher M, Wakhloo AK. Microcatheter urokinase infusion in central retinal artery occlusion. Am J Ophthalmol 1992; 113: 429-434
• 47 Bertram B, Wolf S, Fisches H. et al. [Thrombolytic treatment of retinal arterial occlusions with plasminogen activator]. Klin Monatsbl Augenheilkd 1991; 198: 295-300
• 48 Richard G, Lerche RC, Knospe V. et al. Treatmet of retinal arterial occlusion with local fibrinolysis using recombinant tissue plasminogen activator. Ophthalmology 1999; 106: 768-773
• 49 Sharma S, Brown M, Brown G. Retinal artery occlusions. Ophthalmol Clin North Am 1998; 11: 591-600
• 50 Schumacher M, Schmidt D, Jurklies B. et al. EAGLE-Study Group. Central retinal artery occlusion: local intra-arterial fibrinolysis versus conservative treatment, a multicenter randomized trial. Ophthalmology 2010; 117: 1367-1375
• 51 Feltgen N, Neubauer A, Jurklies B. et al. EAGLE-Study Group. Multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. EAGLE Study report no. 1: EAGLE Study report no. 1. Graefes Arch Clin Exp Ophthalmol 2006; 244: 950-956
• 52 Reynard M, Hanscom TA. Neodymium: yttrium-aluminum-garnet laser arteriotomy with embolectomy for central retinal artery occlusion. Am J Ophthalmol 2004; 137: 196-198
• 53 Haritoglou C, Wolf A, Ulbig MW. Laser embolectomy for central retinal artery occlusion. Ophthalmologe 2010; 107: 465-467
• 54 Opremcak EM, Benner JD. Translumenal Nd : YAG laser embolysis for branch retinal artery occlusion. Retina 2002; 22: 213-216
• 55 Tang WM, Topping TM. Vitreous surgery for central retinal artery occlusion. Arch Ophthalmol 2000; 118: 1586-1587
• 56 Peyman GA, Gremillion CM. Surgical removal of a branch retinal artery embolus: a case report. Int Ophthalmol 1990; 14: 295-298
• 57 Garcia-Arumi J, Martinez-Castillo V, Boixadera A. et al. Surgical embolus removal in retinal artery occlusion. Br J Ophthalmol 2006; 90: 1252-1255
• 58 Inomata K, Shinoda K, Ohde H. et al. Transcorneal electrical stimulation of retina to treat longstanding retinal artery occlusion. Graefes Arch Clin Exp Ophthalmol 2007; 245: 1773-1780
• 59 Kurimoto T, Oono S, Oku H. et al. Transcorneal electrical stimulation increases chorioretinal blood flow in normal human subjects. Clin Ophthalmol 2010; 4: 41441-41446
• 60 Kuhli-Hattenbach C, Miesbach W, Scharrer I. et al. Thrombophiliediagnostik und Abklärung systemischer Risikofaktoren bei Patienten mit venösen retinalen Gefäßverschlüssen. Ophthalmologe 2011; 108: 104-110
• 61 Feltgen N, Pielen A. Retinaler Venenverschluss. Therapie des retinalen Venenverschlusses. Ophthalmologe 2015; 112: 695-706
• 62 Plunkett O, Lip PL, Lip GYH. Atrial fibrillation and retinal vein or artery occlusion: looking beyond the eye. Br J Ophthalmol 2014; 98: 1141-1143
• 63 Squizzato A, Manfredi E, Bozzato S. et al. Antithrombotic and fibrinolytic drugs for retinal vein occlusion: a systematic review and a call for action. Thromb Haemost 2010; 103: 271-276
• 64 Osterloh MD, Charles S. Surgical decompression of branch retinal vein occlusions. Arch Ophthalmol 1988; 106: 1469-1471
• 65 Mester U, Dillinger P. Behandlung retinaler Venenastverschlüsse. Ophthalmologe 2001; 98: 1104-1109
• 66 Saika S, Tanaka T, Miyamoto T. et al. Surgical posterior vitreous detachment combined with gas/air tamponade for treating macular edema associated with branch retinal vein occlusion: retinal tomography and visual outcome. Graefes Arch Clin Exp Ophthalmol 2001; 239: 729-732
• 67 Opremcak EM, Bruce RA, Lomeo MD. et al. Radial optic neurotomy for central retinal vein occlusion. Retina 2001; 21: 408-415
• 68 Hayreh SS. Radial optic neurotomy for central retinal vein occlusion. Retina 2002; 22: 374-379
• 69 Berger AR, Cruess AF, Altomare F. et al. Optimal treatment of retinal vein occlusion: Canadian expert consensus. Ophthalmologica 2015; 234: 6-25
• 70 Pielen A, Feltgen N, Isserstedt C. et al. Efficacy and safety of intravitreal therapy in macular edema due to branch and central retinal vein occlusion: a systematic review. PLoS One 2013; 8: e78538
• 71 German Ophthalmological Society, Retinological Society, Professional Association of German Ophthalmologists, Hoerauf H, Feltgen N, Bartz-Schmidt KU et al. [Statement of the German Ophthalmological Society, the Retinological Society and the Professional Association of German Ophthalmologists on therapy for macular oedema in cases of retinal vein occlusion]. Klin Monatsbl Augenheilkd 2010; 227: 542-556
• 72 Campochiaro PA, Brown DM, Awh CC. et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: twelve-month outcomes of a phase II study. Ophthalmology 2011; 118: 2041-2049
• 73 Brown DM, Campochiaro PA, Bhisitkul RB. et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology 2011; 118: 1594-1602
• 74 Campochiaro PA, Sophie R, Pearlman J. et al. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study. Ophthalmology 2014; 121: 209-219
• 75 Brown DM, Heier JS, Clark WL. et al. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol 2013; 155: 429-437
• 76 Korobelnik JF, Holz FG, Roider J. et al. Intravitreal aflibercept injection for macularedema resulting from central retinal vein occlusion: one-year results of the phase 3 GALILEO study. Ophthalmology 2014; 121: 202-208
• 77 Campochiaro PA, Clark WL, Boyer DS. et al. Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study. Ophthalmology 2015; 122: 538-544
• 78 Hoerauf H, Feltgen N, Weiss C. et al. Clinical efficacy and safety of ranibizumab versus dexamethasone for central retinal vein occlusion (COMRADE C): a European label study. Am J Ophthalmol 2016; 169: 258-267
• 79 Hattenbach LO. COMRADE-B study group. Efficacy and safety of 0.5 mg ranibizumab compared with 0.7 mg dexamethasone intravitreal implant in patients with branch retinal vein occlusion over 6 months: The COMRADE-B study. Invest Ophthalmol Vis Sci 2014; 55: 1830
• 80 Haller JA, Bandello F, Belfort jr. R. et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010; 117: 1134-1146
• 81 Ip MS, Scott IU, Van Veldhuisen PC. et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs. Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Arch Ophthalmol 2009; 127: 1101-1114
• 82 Scott IU, Ip MS, Van Veldhuisen PC. et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs. Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol 2009; 127: 1115-1128
• 83 Bezatis A, Spital G, Höhn F. et al. Functional and anatomical results after a single intravitreal ozurdex injection in retinal vein occlusion: a 6-month follow-up – the SOLO study. Acta Ophthalmol 2013; 91: 340-347
• 84 Schmitz K, Maier M, Clemens CR. et al. German Retinal Vein Occlusion Group. Reliability and safety of intravitreal ozurdex injections. The ZERO study. Ophthalmologe 2014; 111: 44-52
• 85 Augustin AJ, Holz FG, Haritoglou C. et al. Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion. Ophthalmologica 2015; 233: 18-26
• 86 Groneberg T, Trattnig JS, Feucht N. et al. [Morphologic patterns on spectral-domain optical coherence tomography (SD-OCT) as a prognostic indicator in treatment of macular edema due to retinal vein occlusion]. Klin Monatsbl Augenheilkd 2016; 233: 1056-1062
• 87 The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol 1984; 98: 271-282
• 88 Lang GE. Ergebnisse der Laserkoagulation beim retinalen Zentralvenenverschluss. Klin Monatsbl Augenheilkd 1993; 203: 247-251
• 89 Pielen A, Mirshahi A, Feltgen N. et al. Ranibizumab for Branch Retinal Vein Occlusion Associated Macular Edema Study (RABAMES): six-month results of a prospective randomized clinical trial. Acta Ophthalmol 2015; 93: 29-37
• 90 Leitritz MA, Gelisken F, Ziemssen F. et al. Grid laser photocoagulation for macular oedema due to branch retinal vein occlusion in the age of bevacizumab? Results of a prospective study with crossover design. Br J Ophthalmol 2013; 97: 215-219
• 91 Brown DM, Wykoff CC, Wong TP. et al. Ranibizumab in preproliferative (ischemic) central retinal vein occlusion: the rubeosis anti-VEGF (RAVE) trial. Retina 2014; 34: 1728-1735
• 92 Central Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion: the Central Vein Occlusion Study Group N report. Ophthalmology 1995; 102: 1434-1444
• 93 Rehak M, Tilgner E, Franke A. et al. Early peripheral laser photocoagulation of nonperfused retina improves vision in patients with central retinal vein occlusion (results of a proof of concept study). Graefes Arch Clin Exp Ophthalmol 2014; 252: 745-752
• 94 Tomomatsu Y, Tomomatsu T, Takamura Y. et al. Comparative study of combined bevacizumab/targeted photocoagulation vs. bevacizumab alone for macular oedema in ischaemic branch retinal vein occlusions. Acta Ophthalmol 2016; 94: 225-230
• 95 Rehak M, Wiedemann P. Retinal vein thrombosis: pathogenesis and management. J Thromb Haemost 2010; 8: 1886-1894