Kathrin Greiner

Retinal vascular occlusion and deficiencies in the protein C pathway

PURPOSE To report abnormalities in the protein C pathway and other vascular occlusion risk factors in patients with retinal vascular occlusion. METHODS In a study, we investigated 76 consecutive patients who had in-patient evaluation of venous or arterial retinal vascular occlusion. All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, and resistance to activated protein C and were screened for vascular disease risk factors. Resistance to activated protein C was confirmed by a polymerase chain reaction method to detect the specific factor V R506Q mutation. For comparative purposes, we also screened 209 consecutive inpatients with deep vein thrombosis from the same geographic region for resistance to activated protein C as well as protein C and protein S deficiencies. RESULTS Ten (29%) of 35 patients with central retinal vein occlusion (CRVO) had factor V R506Q mutation. The factor V R506Q mutation was detected in four (19%) of 21 patients with branch retinal vein occlusion. The higher frequency in factor V R506Q mutation compared with the expected 9% mutation prevalence in a white population was highly significant for the central retinal vein occlusion group but not for the branch retinal vein occlusion group. In all patients with resistance to activated protein C, the factor V R506Q mutation was detected; 16 were heterozygous, one homozygous. No cases of lupus anticoagulants, protein C, or protein S deficiencies were detected. Forty (19%) of 209 patients with deep vein thrombosis were carriers of the factor V R506Q mutation. CONCLUSIONS The prevalence of the factor V R506Q mutation is similar in patients with central retinal vein occlusion and patients with deep vein thrombosis and represents a relevant risk factor. Screening for this mutation is therefore recommended in all patients with central retinal vein occlusion.

Genetic thrombophilia in patients with retinal vascular occlusion

Background: This study was carried out to determine the prevalence of genetic thrombophilia in patients with retinal vascular occlusion.Methods: We investigated 116 consecutive patients with central retinal vein occlusion (CRVO, n = 48), branch retinal vein occlusion (BRVO, n = 33), central retinal artery occlusion (CRAO, n = 21), branch retinal artery occlusion (BRAO, n = 14). All patients underwent comprehensive tests for coagulation disorders including determinations of protein C, protein S, lupus anticoagulants, prothrombin gene mutation (G20210A), resistance to activated protein C (APCR), and were screened for vascular disease risk factors. APC resistance was confirmed by a PCR method to detect the factor V R506Q mutation. A PCR method was also used to detect the G20210A mutation. For comparative purposes, we screened 209 consecutive patients with deep vein thrombosis (DVT) and 581 patients with coronary heart disease (control group) for APC resistance.Results: 13 (27%) of 48 patients with CRVO had the factor V R506Q mutation. The factor V R506Q mutation was detected in six (18%) of 33 patients with BRVO, but in only one patient with CRAO and in two patients with BRAO. Other thrombophilic defects were not detected. The APCR prevalence within the CRVO group was significantly increased when compared to the control group (8%). There was no significant difference in the factor V R506Q mutation prevalence between the CRVO group and the DVT group (19%).Conclusion: The factor V R506Q mutation is the most commoncause of genetic thrombophilia in patients with CRVO and has a similar prevalence as in DVT patients.

Long-term stability of the heparin surface on PMMA-intraocular lenses – results of an in vitro study

SummaryThe surface modification of PMMA-intraocular lenses (IOLs) demonstrated a blood-aqueous-barrier protective effect and reduced the incidence of IOL depositions and postoperative fibrin exudation, especially in risk patients (e. g. pediatric cataract, diabetes mellitus, recurrent uveitis). The long-term stability of the surface modification via phenylimines, which permit a covalent surface linkage of heparin to synthetic polymeric materials by reductive amination, is still unknown. Material and methods: Four heparin surface-modified (HSM) monofocal and two unmodified monofocal sterile PMMA-IOLs were stored in an aqueous-serum mixture at 37 °C over a period of 4 years and 1 months with daily rotation. After 4 years the concentration of surface-bound heparin on two HSM-IOLs of this mixture and two brand-new HSM-IOLs were determined using an orcin-assay after initial heparinase treatment. Four years after incubation, the modified toluidine blue staining method was used to examine the surface-bound heparin on synthetic polymers. This staining technique with toluidine blue, a non-protein basic substance, enables examination and analysis of the homogeneity of the mono-molecular heparin layer even under critical conditions because of its homogeneous staining. Light and scanning electron microscopic examination of the IOL surfaces were subsequently performed. Results: The concentration of heparin (μg/cm2) on the IOL surface after 4 years of incubation and treatment with heparinase was valued at 0.51 ± 0.05 and 0.53 ± 0.04 in the two brand-new HSM-IOLs. A slightly coarse-grained complex agglutination on the IOL surface was detected by the toluidine blue staining method. Light and spectral microscopy of the surface of the stained IOLs as well as scanning electron microscopy of all HSM-IOLs showed a homogeneous heparin structure and coating after 4 years of in vitro storage. No signs of desorption or reduced reactivity of the heparin were observed in comparison with new HSM-IOLs. The unmodified PMMA-IOLs did not stain, as expected. Conclusion: The heparin-modified surface of the examined PMMA-IOLs was intact even after 4 years of storage in an aqueous serum solution. A long-term benefit, in addition to the advantages of the hydrophilisation in the immediate postoperative period, especially for risk patients, is therefore suggested.Hintergrund: Die Beschichtung von PMMA-Intraokularlinsen mit Heparin erwies sich als Blut-Kammerwasser-Schranken-protektiv und reduzierte die Häufigkeit von Ablagerungen auf der IOL oder einer postoperativen Fibrinreaktion besonders bei Risikopatienten (z. B. kindliche Katarakt, Diabetes mellitus, rezidivierende Uveitis). Die Dauer der Stabilität der kovalenten Bindung von Heparin mit dem PMMA über ein Phenylimin ist noch ungeklärt. Material und Methode: Vier heparinbeschichtete (HSM) und 2 unbeschichtete sterile PMMA-Intraokularlinsen wurden über einen Zeitraum von 4 Jahren und 1 Monat in einem Vorderkammerwasser-Serum-Gemisch bei 37 °C unter täglicher Rotation gelagert. Nach 4 Jahren wurde an 2 HSM-IOL und 2 fabrikneuen HSM-IOL die Konzentration des oberflächengebundenen Heparins mittels Orcinassay nach vorheriger Heparinasebehandlung bestimmt. Daraufhin erfolgte an den restlichen IOL die Färbung der IOL mittels der nach Jaques speziell für diesen Anwendungsbereich modifizierten Toluidinblaufärbung, die eine detaillierte Beurteilung der monomolekularen Heparinschicht auch unter kritischen Bedingungen erlaubt. Anschließend wurde die IOL-Oberfläche mittels Licht- und Rasterelektronenmikroskopie untersucht. Ergebnisse: Die Heparinkonzentration (μg/cm2) auf der IOL-Oberfläche nach Heparinasebehandlung betrug nach 4 Jahren Lagerung im Mittel 0,51 ± 0,05 SD und bei den fabrikneuen HSM-IOL 0,53 ± 0,04. Mittels der Toluidinblaufärbemethode konnte die Heparinschicht in Form eines feinen Agglutinatkomplexes auf den HSM-IOL mittels Licht- und Rasterelektronenmikroskopie nachgewiesen werden. Die Heparinschicht zeigte sich nach 4 Jahren unbeeinträchtigt intakt. Anzeichen von Ablösung oder verminderter Reaktionsfähigkeit des Heparins im Vergleich zu nicht eingelagerten HSM-IOL waren nicht nachweisbar. Die unbeschichteten PMMA-IOL färbten sich erwartungsgemäß nicht an. Schlußfolgerung: Die Heparinbeschichtung auf den untersuchten PMMA-Intraokularlinsen war auch nach 4 Jahren in kaum verminderter Konzentration nachweisbar und steht somit zur Protektion zur Verfügung. Möglicherweise profitieren Patienten auch über den frühpostoperativen Zeitraum hinaus von den Vorteilen der Hydrophilisierung der PMMA-IOL-Oberfläche durch die Heparinbeschichtung.

Risk adapted management of central retinal vein occlusion

SummaryThere is no generally accepted therapy for patients with central retinal vein occlusion. Only few of the therapeutic strategies in use demonstrated their effectiveness in studies with large patient populations, others have the disadvantage of unacceptable side effects. The aim of the immediate therapy is the improvement of blood perfusion. Prognostically relevant factors like the activity of components of the blood coagulation system, rheology characteristics and predisposing vascular disease risk factors have to be considered. A risk adapted management includes the immediate anticoagulation with heparin. Haemodilution, fibrinolytic therapy and hyperbaric oxygen therapy represent other therapeutic strategies. The efficacy of new promising therapies has to be thoroughly evaluated in studies with large stratified patient populations.ZusammenfassungFür das Management von Patienten mit Zentralvenenthrombosen existiert keine Standardtherapie. Nur für wenige der bisher angewandten therapeutischen Strategien wurde eine Wirksamkeit in großen Patientenkollektiven nachgewiesen, z. T. wird über ein ungünstiges Nebenwirkungsprofil berichtet. Ziel der Akuttherapie muß die Verbesserung der Restperfusion sein, wobei prognostisch relevante Faktoren wie die Aktivität von Komponenten des Gerinnungssystems, Blutflußparameter und prädisponierende Systemerkrankungen berücksichtigt werden sollten. Ein risikoadaptiertes Management schließt eine frühzeitige Heparinisierung ein. Weitere therapeutische Möglichkeiten sind die Hämodilution, Fibrinolyse und die hyperbare Sauerstofftherapie. In prospektiven Studien muß die Wirksamkeit neuer effizient erscheinender Therapieoptionen an stratifizierten Patientenkollektiven untersucht werden.