D Pauleikhoff

Publications (92)131.58 Total impact

• Article: [In Process Citation].

  D Pauleikhoff, B Bertram, F G Holz, B Kirchhof, U Bartz-Schmidt, N Bornfeld, M Bresgen, N Eter, W Friedrichs, H Heimann, H Helbig, H Hörauf, A Kampik, K D Lemmen, J Roider, F Ziemssen
  Klinische Monatsblätter für Augenheilkunde 02/2013; 230(2):170-7. · 0.51 Impact Factor
• Article: Anti-VEGF-Therapie der exsudativen AMD

  B. Heimes, A. Lommatzsch, M. Zeimer, M. Gutfleisch, G. Spital, D. Pauleikhoff
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  ABSTRACT: HintergrundDas Ziel war es, eventuelle prognostische und prädiktive funktionelle oder morphologische Charakteristika für individuelle Visusergebnisse unter Anti-VEGF-Therapie bei exsudativer AMD zu definieren. Patienten/MethodeBei 128Patienten dieser Gruppe wurden das bestkorrigierte Sehvermögen, die makuläre Netzhautsensitivität, die Netzhautdicke im OCT und Autofluoreszenzmuster (AF) erhoben. ErgebnisseAugen mit einem schlechten Ausgangsvisus und klassische CNV erzielten den größten Visusgewinn, während Augen mit einem initial guten Visus diesen primär stabilisierten. Es bestand keine Korrelation zur initialen Netzhautdicke, jedoch war eine veränderte AF mit einem ausbleibenden Visusgewinn assoziiert. SchlussfolgerungBei geringer Aussagekraft der übrigen Parameter kam der foveolären AF eine größere Bedeutung als prädiktiver Faktor zu. Initiale Schäden im Bereich des retinalen Pigmentepithels und der Netzhaut können für einen ausbleibenden Visusgewinn ursächlich sein. BackgroundThe aim of the study was to evaluate possible prognostic and predictive factors (morphologic and functional) of the individual visual gain/decline after anti-VEGF therapy of exudative AMD. Patients/methodsBest corrected visual acuity (VA), microperimetric sensitivity (RS), retinal thickness (RT) and autofluorescence pattern (AF) were documented in128 patients with exudative AMD. ResultsEyes with classic choroidal neovascularization (CNV) had the best visual gain but still remained at a lower level. Eyes which initially had the lowest VA had the largest gain and those with good initial VA could maintain this level. There was no correlation between RT and visual outcome. Eyes with initially normal AF had a significantly greater visual gain. ConclusionsThe type of CNV, initial VA, RS and the initial RT were only of limited usefulness, while the initial foveal AF was most important predictive factor. This may indicate that preexisting changes and irreversible damage in the outer retina and/or retinal pigment epithelium are responsible for the resulting VA after therapy. SchlüsselwörterAnti-VEGF-Therapie–Exsudative AMD–Prognostische Faktoren–Autofluoreszenz–Mikroperimetrie KeywordsAnti-VEGF therapy–Exudative AMD–Prognostic factors–Autofluorescence–Microperimetry
  Der Ophthalmologe 05/2012; 108(2):124-131. · 0.62 Impact Factor
• Article: Unterschiede in der Therapie der exsudativen altersabhängigen Makuladegeneration in Deutschland und Großbritannien

  H. Heimann, Y. Yang, J. Wachtlin, D. Pauleikhoff
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  ABSTRACT: Die Therapie mit Anti-VEGF-Medikamenten bei altersabhängiger Makuladegeneration hat in den vergangenen Jahren zu deutlichen Verbesserungen, aber auch steigenden Kosten der ophthalmologischen Behandlung geführt. Sowohl in Deutschland mit einem Sozialversicherungssystem als auch in Großbritannien mit einer staatlichen Gesundheitsversorgung wurde diese Therapie erstaunlich schnell in die Praxis umgesetzt. In beiden Ländern wird derzeit überwiegend eine Therapie mit Ranibizumab nach dem Schema von 3Basisinjektionen mit zusätzlichen Injektionen bei persistierender Aktivität durchgeführt. The treatment of age-related macular degeneration with anti-VEGF medications has resulted not only in significant improvements in eye treatment but also in rising costs of ophthalmological therapy. This new treatment has been rapidly introduced into daily practice in Germany with its social security healthcare system and also in Great Britain with its National Health Service. In both countries the most prevalent treatment scheme currently includes three baseline injections of ranibizumab followed by additional injections depending on persisting disease activity. SchlüsselwörterAltersabhängige Makuladegeneration–Ranibizumab–Bevacizumab–Deutschland–Großbritannien KeywordsAge-related macular degeneration–Ranibizumab–Bevacizumab–Germany–Great Britain
  Der Ophthalmologe 05/2012; 108(6):575-584. · 0.62 Impact Factor
• Article: Retinale angiomatöse Proliferationen mit assoziierter Pigmentepithelabhebung

  A. Lommatzsch, B. Heimes, M. Gutfleisch, G. Spital, M. Dietzel, D. Pauleikhoff
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  ABSTRACT: HintergrundIm natürlichen Verlauf und in der Häufigkeit von Komplikationen wie dem Einriss im Pigmentepithel (RIP) stellen vaskularisierte Pigmentepithelabhebungen („pigment epithelial detachment“, PED) auch bei retinalen angiomatösen Proliferationen (RAP) eine morphologische Sonderform der exsudativen altersabhängigen Makuladegeneration (AMD) dar. Die vorgestellte Studie untersucht die Ergebnisse nach „Vascular-endothelial-growth-factor“- (VEGF-)Inhibition bei assoziierter PED bei RAP im Rahmen einer exsudativen AMD. Material und MethodenBei 61 konsekutiven Augen mit RAP im Stadium2 und 3 konnten nach einem mittleren Beobachtungszeitraum von 108Wochen retrospektiv funktionelle und morphologische Daten erhoben werden. Die Patienten wurden mit Bevacizumab (n=15), Ranibizumab (n=29), Pegabtanib (n=17) entsprechend den Empfehlungen der Deutschen Ophthalmologischen Gesellschaft (DOG) und Retinologischen Gesellschaft (RG) behandelt. Nach einem initialen Behandlungszyklus von 3Injektionen alle 4Wochen (6Wochen bei Pegabtanib) wurden in 12-wöchentlichen Abständen neben dem bestkorrigierten Visus („best corrected visual acuity“, BCVA) die Fluoreszenzangiographie (FAG), Indozyaningrünangiographie (ICG-A) und die optische Kohärenztomographie (OCT) ausgewertet. ErgebnisseDie mittlere Sehschärfe betrug vor der Therapie 0,8logMAR und nach der Therapie 0,77logMAR. Die mittlere Visusdifferenz zum Ausgangsvisus betrug somit nach 12Wochen −0,03 und nach 48Wochen 0,00logMAR. Die im OCT gemessene zentrale Netzhautdicke verringerte sich nach dem ersten Injektionszyklus im Mittel um 81,2µm, nach einem Jahr um −68,4µm. Die maximale Höhe der PED konnte im Mittel um 1Einheit und nach einem Jahr um 1,55Einheiten reduziert werden. Funktionell und morphologisch bessere Ergebnisse wurde bei der Therapie mit Ranibizumab und Avastin gegenüber Pegaptanib erhalten (p=0,03). Bei 9,8% der Patienten (n=6) fand sich ein RIP, der im Mittel nach 16Wochen auftrat. SchlussfolgerungenMit dem gegenwärtigen in Deutschland empfohlenen Behandlungsschema können die morphologischen funktionellen Ergebnisse in den ersten Monaten verbessert werden. Im weiteren Verlauf zeigte sich jedoch eine signifikante Verschlechterung der funktionellen Ergebnisse. Somit scheint die Modifikation des Behandlungsschemas hinsichtlich engmaschiger Kontrolluntersuchungen und eventuell frühzeitigerer Wiederbehandlung sinnvoll. BackgroundVascularized pigment epithelial detachment (PED) in retinal angiomatous proliferation (RAP) represents a special morphological form of exudative age-related macular degeneration (ARMD) in the natural course and in the frequency of complications, such as tears in the pigment epithelium. In this study the results of inhibition of vascular endothelial growth factor (VEGF) for exudative ARMD with associated PED and RAP were examined. Materials and methodsFunctional and morphological data were retrospectively collected for 61 consecutive eyes with RAP in stages 2 and 3 over an average observation period of 108 weeks. Patients were treated with bevacizumab (n=15), ranibizumab (n=29) and pegabtanib (n=17) according to the recommendations of the German Society of Ophthalmology (DOG) and the German Retina Society (RG). After an initial treatment cycle of 3 injections every 4 weeks (6 weeks for pegabtanib), best corrected visual acuity (BCVA), fluorescence angiography (FAG), indocyanine green angiography (ICG-A) and optical coherence tomography (OCT) were evaluated every 12 weeks. ResultsThe mean visual acuity was 0.8logMAR before therapy and 0.77logMAR after therapy so that the average difference to the original acuity was −0.03 logMAR after 12 weeks and 0.00logMAR after 48 weeks. The central retinal thickness measured by OCT decreased on average by 81.2µm after the first cycle of injections and by −68.4µm after 1 year. The maximum depth of PED could be reduced on average by 1 unit and after 1 year by 1.55 units. Better functional and morphological results were obtained by therapy with ranibizumab and avastin compared to pegabtanib (p=0.03). An RIP occurred in 9.8% of the patients (n=6) on average after 16 weeks. ConclusionsThe morphological functional results can be improved in the early months using the therapy strategy presently recommended in Germany. However, in later stages there was a significant worsening of the functional results. Modification of the treatment strategy with respect to close surveillance and possibly early stage repeat treatment would seem advisable. SchlüsselwörterExsudative altersabhängige Makuladegeneration–Zentrale Netzhautdicke–„Best corrected visual acuity“–Choroidale Neovaskularisation–Intraretinale Flüssigkeit–Subretinale Flüssigkeit KeywordsExudative age-related macular degeneration–Central retinal thickness–Best corrected visual acuity–Choroidal neovascularization–Intraretinal fluid–Subretinal fluid
  Der Ophthalmologe 04/2012; 108(3):244-251. · 0.62 Impact Factor
• Article: Langzeitergebnisse nach Pars-plana-Vitrektomie mit 25-Gauge-Technik

  A. Lommatzsch, B. Heimes, M. Trieschmann, G. Spital, D. Pauleikhoff
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  ABSTRACT: ZielBesonders bei epiretinalen pathologischen Veränderungen der Makula bietet die nahtlose Technik bei der chirurgischen Intervention gute Möglichkeiten eines schonenden Verfahrens. Kritisiert wurden zunächst eine unzureichende Dichtigkeit mit einem erhöhten Endophthalmitisrisiko und eine zu hohe Flexibilität der Instrumente. Diese retrospektive Analyse soll das Verfahren der 25-Gauge-Technik der Pars-plana-Vitrektomie bewerten. MethodeEs wurden 625Augen von 620Patienten im Zeitraum von 2002–2006 mit der 25-Gauge-Technik operiert. Die Indikation zur Operation war in allen Fällen eine epiretinale Gliose unterschiedlicher Ausprägung. Alle Operationen wurden nur von 1Operateur durchgeführt. Sämtliche Operationen erfolgten in Vollnarkose, Verwendung fand in allen Fällen das TSV-System. Als optisches System wurde das Biom benutzt. Langzeitergebnisse von 329 operierten Augen wurden hinsichtlich Visus, intraokularem Druck und Komplikationen ausgewertet. ErgebnisseWir konnten eine mittlere Nachbeobachtungszeit von 3,1Jahren zugrunde legen. Die mittlere Visusverbesserung betrug in den ersten 3 postoperativen Monaten –0,41 in LogMAR. Ein postoperativ verminderter Augeninnendruck von durchschnittlich 8mmHg normalisierte sich nach 1Woche auf Werte von 15mmHg. In 9Fällen musste am 1. postoperativen Tag ein Wundverschluss vorgenommen werden; dabei war klinisch eine Amotio chorioideae sichtbar. Eine Ablatio retinae entwickelte sich bei 7Patienten innerhalb des Beobachtungszeitraumes. Bei keinem Patienten beobachteten wir eine Endophthalmitis oder einen erhöhten intraokularen Reizzustand. SchlussfolgerungDie chirurgische Behandlung der epiretinalen Gliose mit nahtloser transkonjunktivaler 25-Gauge-Technik ist ein schonendes und wenig traumatisierendes Verfahren. Durch wenige Instrumentenwechsel und fehlende periphere Pathologie treten bei der Behandlung der epiretinalen Gliose intraoperativ weniger Komplikationen auf. Postoperative Komplikationen wie Endophthalmitis oder Ablatio retinae wurden im Vergleich zur konventionellen Technik nicht vermehrt beobachtet. Durch stabilere Instrumente und bessere Beleuchtungen wurde das Verfahren in den letzten Monaten noch weiter verbessert. BackgroundThe 25-gauge technique of pars plana vitrectomy appears to be a very suitable method, especially for patients with pathological epiretinal alterations of the macula. However, the procedure has been criticized for insufficient impermeability with an increased risk of endophthalmitis and that the flexibility of instruments is too high. MethodBetween 2002 and 2006, 625 eyes from 620 patients were operated on using the 25-gauge technique. Epiretinal membranes in different stages had been diagnosed in all patients. The operations were performed by only one surgeon. ResultsThe epiretinal membranes were successfully removed in all patients and 329 eyes were analyzed with long-term follow up over 3.1 years. The mean improvement in visual acuity before and after surgery was –0.41 in LogMAR. One week postoperatively normal IOP was observed in all cases. The mean preoperative IOP was 17 mmHg and 8 mmHg 1 day after surgery. In nine patients with postoperative hypotony and choroidal detachment an additional suture was required and seven patients developed a retinal detachment. Endophthalmitis was not observed in any of the patients during the follow-up period. ConclusionsThe 25-gauge PPV technique appears to be effective and safe for the treatment of epiretinal membranes. The operation has low complication rates with respect to endophthalmitis or retinal detachment. The procedure has recently been further improved by using more stable instruments and better lighting.
  Der Ophthalmologe 04/2012; 105(5):445-451. · 0.62 Impact Factor
• Article: Kurz- und mittelfristige Änderungen der makulären Pigmentdichte infolge der Supplementation mit Lutein und Zeaxanthin sowie Koantioxidanzien

  M. Zeimer, H.W. Hense, B. Heimes, U. Austermann, M. Fobker, D. Pauleikhoff
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  ABSTRACT: HintergrundDie Supplementation von Lutein (L) und Zeaxanthin(Z) führt zu einem Anstieg in der Konzentration des makulären Pigments (MP). Wie lange bleiben nach Absetzen der Supplementation von L und Z die okulären Konzentrationen des MP erhöht? Methode108 Probanden mit und ohne AMD (51–87Jahre) wurden 6Monate mit 12mg L und 1mg Z täglich (Ocuvite Lutein) supplementiert. Anschließend erfolgten über weitere 9Monate in 3-monatigen Abständen Bestimmungen der optischen Dichte des MP (MPOD). Eine nichtsupplementierte Kontrollgruppe bestand aus 16 Männern und 12 Frauen (57–83Jahre). ErgebnisseUnter der Supplementierung stiegen die Werte des MPOD bei 0,5° (ausgehend von 0,50 ODU) im Mittel um 0,1 ODU (p<0,001). Drei Monate nach Absetzen der Supplementierung wurde die höchste MPOD gemessen (0,59 ODU), dem 3Monate darauf folgenden leichten Abfall (auf 0,54 ODU) folgte ein erneuter Anstieg der MPOD 9Monate nach Absetzen der Supplementierung (auf 0,57 ODU). Es zeigten sich keine signifikanten Anstiege in der Kontrollgruppe (0,03 ODU, p=0,15). SchlussfolgerungSupplementierung von L und Z führt zur Zunahme der MPOD0.5. Noch 9Monate nach Absetzen zeigten sich die mittleren MPOD0.5-Werte deutlich erhöht gegenüber den Ausgangswerten. Längere Beobachtungsphasen im Anschluss an eine Supplementierungsphase könnten klären, ob es im weiteren Verlauf zu deutlicherem Absinken der Werte kommt oder ob ein Plateau auf höherem Niveau erreicht wird. Hohe Dosen an L und Z mögen erforderlich sein, um die Konzentration des makulären Pigments in der Retina zu steigern, anschließend scheint dann aber die Erhaltungsdosis zum Aufrechterhalten der erhöhten Werte über die tägliche Nahrungsaufnahme bereits gedeckt zu werden. BackgroundHow long do the elevated concentrations of macular pigment persist after stopping supplementation with lutein and zeaxanthin? MethodsOne hundred eight (108) probands with and without age-related macular degeneration (68 female, 40 male, age 51–87 years) received a supplement containing 12mg lutein and 1mg zeaxanthin once per day (Ocuvite lutein) for 6 months. Analysis of macular pigment optical density (MPOD) was performed during the period of supplementation and again 3, 6, and 9months following discontinuation of the supplement. A control group of 28subjects received no dietary supplement. ResultsAt baseline, the mean MPOD at 0.5° was 0.50 in the supplemented group. Following supplementation, values rose, and 3 months after discontinuation of supplementation the highest levels of MPOD0.5°(0.59 ODU) were detected (increase of +0.1ODU, (p<0.001). Six months after supplement discontinuation, a slight decrease of mean MPOD0.5° appeared (to 0.54 ODU), followed again by a slight increase 3 months later (to 0.57 ODU). An increment of MPOD0.5° in the control group was not significant (0.03 ODU, p=0.15). DiscussionSupplementation of lutein and zeaxanthin leads to an increase of MPOD0.5°. This effect outlasts the duration of intake, and 9months after supplementation was stopped, the mean MPOD0.5° was still elevated compared with baseline levels. A longer follow-up subsequent to stopping supplementation might clarify whether the values decrease over time or whether a plateau of elevated MPOD levels is reached. High doses of lutein and zeaxanthin seem to be necessary to increase macular pigment density in the retina; afterwards, the amount of carotenoids needed to maintain high concentrations seems to be covered by daily food.
  Der Ophthalmologe 04/2012; 106(1):29-36. · 0.62 Impact Factor
• Article: Neovaskuläre altersabhängige Makuladegeneration in Deutschland

  D. Pauleikhoff, A. Scheider, P. Wiedmann, F. Gelisken, H.P.N. Scholl, I. Roider, A. Mohr, G. Zlateva, X. Xu
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  ABSTRACT: HintergrundJährlich treten in Deutschland etwa 35.000 Neuerkrankungen von neovaskulärer altersabhängiger Makuladegeneration (AMD) auf. Die neovaskuläre Form der AMD (NV-AMD) ist für etwa 90% der Fälle einer schweren Beeinträchtigung des Sehvermögens im Zusammenhang mit der Erkrankung verantwortlich. Diese Studie sollte die humane und wirtschaftliche Belastung von NV-AMD-Patienten in Deutschland untersuchen. MethodeEs wurde eine Querschnittsbeobachtungsstudie auf der Basis einer Befragung der Patienten zu funktioneller Gesundheit, Wohlbefinden und Belastung durch die Erkrankung bei älteren Personen mit (n=83) und ohne (n=93) NV-AMD in Deutschland durchgeführt. Die Patienten beantworteten telefonisch den „National Eye Institute Visual Function Questionnaire“ (NEI-VFQ-25), den EuroQol (EQ-5D) und die „Hospital Anxiety and Depression Skala“ (HADS). Darüber hinaus wurden sie zu aufgetretenen Stürzen, Frakturen und der Inanspruchnahme von Ressourcen des Gesundheitswesens befragt. Die Kosten für die Inanspruchnahme des Gesundheitswesens und die Einheitskosten je NV-AMD-Patient wurden berechnet. ErgebnisseDas Durchschnittsalter der Patienten mit NV-AMD betrug 77,2Jahre und 64% der Patienten waren Frauen. Die Patienten mit NV-AMD berichteten im Vergleich zu den Kontrollpersonen über eine signifikant schlechtere sehbezogene Funktion und ein signifikant schlechteres allgemeines Wohlbefinden (adjustierter Mittelwert NEI-VFQ-25-Gesamtscore: 51,3 vs. 96,3; p<0,0001) und über signifikant mehr depressive Symptome (HADS-Depressions-Skala: 6,2 vs. 2,7; p<0,0001). Patienten mit NV-AMD benötigten darüber hinaus zehnmal häufiger Hilfe bei den Aktivitäten des täglichen Lebens als die Kontrollpersonen (26,5% vs. 2,2%; p<0,0001) und stürzten dreimal häufiger als die Kontrollpersonen (13,3% vs. 4,3%; p=0,031). Die jährlichen Kosten betrugen bei Patienten mit NV-AMD 9871Euro pro Patient und waren damit sechsmal so hoch wie bei älteren Menschen ohne NV-AMD (1559Euro). Die Hälfte der bei den Patienten mit NV-AMD auftretenden Kosten waren direkte nichtmedizinische Kosten (Hilfe bei den Alltagsaktivitäten oder soziale Leistungen), ein Drittel direkte medizinische Kosten. SchlussfolgerungenDie NV-AMD ist mit einer Einschränkung der funktionellen Fähigkeiten und einer Beeinträchtigung der Lebensqualität verbunden, die eine vermehrte Inanspruchnahme der Ressourcen des Gesundheitswesens zur Folge haben. Entsprechend waren die Kosten bei den Patienten mit NV-AMD höher als bei den Kontrollpersonen. Diese Ergebnisse unterstreichen den Bedarf für neue Behandlungsalternativen für die NV-AMD, die einem Verlust des Sehvermögens und einem Fortschreiten der Erkrankung hin zur Erblindung vorbeugen und die sich daraus ergebende wirtschaftliche Belastung reduzieren. Gefördert durch Pfizer Inc. New York, US. BackgroundApproximately 35,000 cases of neovascular age-related macular degeneration (AMD) occur annually in Germany. The neovascular form of AMD (NV-AMD) is responsible for severe vision loss associated with the disease in 90% of the cases. This study was conducted to assess the humanistic and economic burden of NV-AMD in the German population. MethodsA cross-sectional, observational study of subject self-reported functional health, well-being, and disease burden among elderly subjects with (n=83) and without (n=93) NV-AMD in Germany was conducted. Patients participated in telephone surveys involving the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and also reported history of falls, fractures, and healthcare resource utilization. Furthermore, the healthcare utilization and unit costs for the NV-AMD patients were calculated. ResultsThe mean age of NV-AMD patients was 77.2 years and 64% were female. NV-AMD patients reported significantly worse vision-related function and overall well-being than controls (adjusted mean scores: NEI-VFQ-25 overall scale: 51.3 vs 96.3; p<0.0001) and significantly more depression symptoms than controls (HADS depression: 6.2 vs. 2.7; p<0.0001). NV-AMD patients also reported that the need for assistance with daily activities was more than 10 times greater compared to controls (26.5% vs. 2.2%; p<0.0001) and the prevalence of falls was 3 times that of the control group (13.3% vs 4.3%; p=0.031). Annual NV-AMD costs per patient were € 9871, 6 times that of elderly patients without NV-AMD (€ 1559). Of the NV-AMD costs one-half were direct non-medical-related costs (assistance of ADL or social benefit) and one-third were direct medical costs. ConclusionsNV-AMD is associated with decreased functional abilities and quality of life, which result in an increase in healthcare resource utilization. Consequently, costs were higher for NV-AMD patients compared to controls. These findings emphasize the need for new NV-AMD treatments that will prevent vision loss and progression to blindness, and lessen the ensuing economic burden. Sponsored by Pfizer Inc. New York, US
  Der Ophthalmologe 04/2012; 106(3):242-251. · 0.62 Impact Factor
• Article: Are low inflammatory reactions involved in exudative age-related macular degeneration?

  A. Lommatzsch, P. Hermans, K. D. Müller, N. Bornfeld, A. C. Bird, D. Pauleikhoff
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  ABSTRACT: PurposeBasal laminar and linear deposits (BLD) are associated with the development of choroidal neovascularization (CNV). Therefore, analysis of BLD composition may provide further information concerning the pathogenesis of BLD and CNV in age-related macular degeneration (AMD). MethodsBLD in 25 specimens of surgically removed CNV were examined, using histochemical and immunohistochemical methods, for extracellular matrix proteins and their modulating enzymes, and for cell markers and proteins involved in inflammatory processes. In addition, ultrastructural electron microscopic analysis (EM) was performed. ResultsThe chemical and structural composition of all the BLD was similar. Only the inner aspect of the BLD contained laminin and collagen IV, which corresponded to a new RPE basal lamina upon EM analysis. The extracellular matrix protein predominantly found in all layers of BLD was vitronectin, which was seen as a homogeneous material within the BLD upon EM analysis. The metalloproteinases MMP-2 and MMP-9 could only be detected in the inner aspect, while MMP-7 and TIMP-3 were observed predominantly in the outer aspect of BLD. In this area, staining for phospholipids and less intensely for neutral lipids was also visible. The labelling of complement complexes C3 and C5b-9 was intensely positive, and vascular endothelial growth factor (VEGF) was detected in all BLDs. ConclusionsDiffuse deposits such as BLD appear consistently with the development of CNV in AMD. They consist of extracellular matrix components and predominantly vitronectin. However, activated complement and VEGF could also be detected. The results of the current study may support the hypothesis that inflammatory processes are involved in the pathogenesis of BLD and CNV in AMD.
  Albrecht von Graæes Archiv für Ophthalmologie 04/2012; 246(6):803-810. · 2.17 Impact Factor
• Article: Long-term visual outcome of pigment epithelial tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD.

  M Gutfleisch, B Heimes, M Schumacher, M Dietzel, A Lommatzsch, A Bird, D Pauleikhoff
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  ABSTRACT: Retinal pigment epithelium (RPE) tears may develop as a complication after anti-VEGF (vascular endothelial growth factor) treatment for pigment epithelial detachments (PEDs) in exudative age-related macular degeneration (AMD). This retrospective study analyses best-corrected visual acuity (BCVA) and foveal involvement after RPE tears that are associated with anti-VEGF therapy due to PED in exudative AMD. A total of 37 patients with RPE tears during anti-VEGF therapy (bevacizumab 12, ranibizumab 21 and pegaptanib 4 eyes) for progressive PED in AMD (PED with occult choroidal neovascularization 25 eyes and PED with retinal angiomatous proliferation 12 eyes) were included in this study. We analyzed BCVA and different morphologic aspects by means of appearance on fluorescein angiography and optical coherence tomography. Mean follow-up was 88 weeks. RPE tears were diagnosed a mean of 56 days after the first injection. BCVA deteriorated after RPE tear and during follow-up significantly (P<0.001), with 53.2% of eyes being legally blind (WHO, world health organization) at 12 months. RPE-free foveal area, foveal wrinkling of the RPE, and fibrotic scar development were significantly associated with worse visual acuity. RPE tears can be observed in 12-15% of treated eyes during anti-VEGF therapy for PED in exudative AMD. Owing to the close time relationship with the therapy, this complication must be taken into consideration. Visual prognosis is associated with a decrease in vision in the long term, often resulting in a severe visual disability. Relevant factors for a negative visual prognosis were the potential foveal involvement of the central RPE and morphologic fibrovascular transformation of the RPE tear.
  Eye (London, England) 06/2011; 25(9):1181-6. · 1.97 Impact Factor
• Article: [Differences in the treatment of exudative age-related macular degeneration in Germany and Great Britain].

  H Heimann, Y Yang, J Wachtlin, D Pauleikhoff
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  ABSTRACT: The treatment of age-related macular degeneration with anti-VEGF medications has resulted not only in significant improvements in eye treatment but also in rising costs of ophthalmological therapy. This new treatment has been rapidly introduced into daily practice in Germany with its social security healthcare system and also in Great Britain with its National Health Service. In both countries the most prevalent treatment scheme currently includes three baseline injections of ranibizumab followed by additional injections depending on persisting disease activity.
  Der Ophthalmologe 06/2011; 108(6):575-84. · 0.62 Impact Factor
• Source

  Available from: John Greenwood

  Article: Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration.

  K Lueck, S Wasmuth, J Williams, T R Hughes, B P Morgan, A Lommatzsch, J Greenwood, S E Moss, D Pauleikhoff
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  ABSTRACT: There is evidence for complement dysfunction in age-related macular degeneration (AMD). Complement activation leads to formation of the membrane attack complex (MAC), known to assemble on retinal pigment epithelial (RPE) cells. Therefore, the effect of sub-lytic MAC on RPE cells was examined with regard to pro-inflammatory or pro-angiogenic mediators relevant in AMD. For sub-lytic MAC induction, RPE cells were incubated with an antiserum to complement regulatory protein CD59, followed by normal human serum (NHS) to induce 5% cell death, measured by a viability assay. MAC formation was evaluated by immunofluorescence and FACS analysis. Interleukin (IL)-6, -8, monocytic chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Intracellular MCP-1 was analysed by immunofluorescence, vitronectin by western blotting, and gelatinolytic matrix metalloproteinases (MMPs) by zymography. Incubation of RPE cells with the CD59 antiserum followed by 5% NHS induced sub-lytic amounts of MAC, verified by FACS and immunofluorescence. This treatment stimulated the cells to release IL-6, -8, MCP-1, and VEGF. MCP-1 staining, production of vitronectin, and gelatinolytic MMPs were also elevated in response to sub-lytic MAC. MAC assembly on RPE cells increases the IL-6, -8, and MCP-1 production. Therefore, sub-lytic MAC might have a significant role in generating a pro-inflammatory microenvironment, contributing to the development of AMD. Enhanced vitronectin might be a protective mechanism against MAC deposition. In addition, the increased expression of gelatinolytic MMPs and pro-angiogenic VEGF may be associated with neovascular processes and late AMD.
  Eye (London, England) 05/2011; 25(8):1074-82. · 1.97 Impact Factor
• Article: [Retinal angiomatous proliferation with associated pigment epithelium detachment: anti-VEGF therapy].

  A Lommatzsch, B Heimes, M Gutfleisch, G Spital, M Dietzel, D Pauleikhoff
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  ABSTRACT: Vascularized pigment epithelial detachment (PED) in retinal angiomatous proliferation (RAP) represents a special morphological form of exudative age-related macular degeneration (ARMD) in the natural course and in the frequency of complications, such as tears in the pigment epithelium. In this study the results of inhibition of vascular endothelial growth factor (VEGF) for exudative ARMD with associated PED and RAP were examined. Functional and morphological data were retrospectively collected for 61 consecutive eyes with RAP in stages 2 and 3 over an average observation period of 108 weeks. Patients were treated with bevacizumab (n=15), ranibizumab (n=29) and pegabtanib (n=17) according to the recommendations of the German Society of Ophthalmology (DOG) and the German Retina Society (RG). After an initial treatment cycle of 3 injections every 4 weeks (6 weeks for pegabtanib), best corrected visual acuity (BCVA), fluorescence angiography (FAG), indocyanine green angiography (ICG-A) and optical coherence tomography (OCT) were evaluated every 12 weeks. The mean visual acuity was 0.8 logMAR before therapy and 0.77 logMAR after therapy so that the average difference to the original acuity was -0.03 logMAR after 12 weeks and 0.00 logMAR after 48 weeks. The central retinal thickness measured by OCT decreased on average by 81.2 µm after the first cycle of injections and by -68.4 µm after 1 year. The maximum depth of PED could be reduced on average by 1 unit and after 1 year by 1.55 units. Better functional and morphological results were obtained by therapy with ranibizumab and avastin compared to pegabtanib (p=0.03). An RIP occurred in 9.8% of the patients (n=6) on average after 16 weeks. The morphological functional results can be improved in the early months using the therapy strategy presently recommended in Germany. However, in later stages there was a significant worsening of the functional results. Modification of the treatment strategy with respect to close surveillance and possibly early stage repeat treatment would seem advisable.
  Der Ophthalmologe 03/2011; 108(3):244-51. · 0.62 Impact Factor
• Article: [Anti-VEGF therapy of exudative AMD: Prognostic factors for therapy success].

  B Heimes, A Lommatzsch, M Zeimer, M Gutfleisch, G Spital, D Pauleikhoff
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  ABSTRACT: The aim of the study was to evaluate possible prognostic and predictive factors (morphologic and functional) of the individual visual gain/decline after anti-VEGF therapy of exudative AMD. Best corrected visual acuity (VA), microperimetric sensitivity (RS), retinal thickness (RT) and autofluorescence pattern (AF) were documented in 128 patients with exudative AMD. Eyes with classic choroidal neovascularization (CNV) had the best visual gain but still remained at a lower level. Eyes which initially had the lowest VA had the largest gain and those with good initial VA could maintain this level. There was no correlation between RT and visual outcome. Eyes with initially normal AF had a significantly greater visual gain. The type of CNV, initial VA, RS and the initial RT were only of limited usefulness, while the initial foveal AF was most important predictive factor. This may indicate that preexisting changes and irreversible damage in the outer retina and/or retinal pigment epithelium are responsible for the resulting VA after therapy.
  Der Ophthalmologe 02/2011; 108(2):124-31. · 0.62 Impact Factor
• Article: [New aspects in the treatment of neovascular age-related macular degeneration: the criteria of re-treatment with the anti-VEGF therapy.].

  D Pauleikhoff, B Kirchhof, B Bertram, F G Holz, U B Bartz-Schmidt, N Bornfeld, M Bresgen, H Heimann, H Helbig, H Hörauf, A Kampik, K D Lemmen, J Roider
  Der Ophthalmologe 01/2011; 108(1):85-90. · 0.62 Impact Factor
• Article: Ultrasound biomicroscopic findings of conventional and sutureless sclerotomy sites after 20-, 23-, and 25-G pars plana vitrectomy.

  M Gutfleisch, M Dietzel, B Heimes, G Spital, D Pauleikhoff, A Lommatzsch
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  ABSTRACT: We examined sclerotomies that were performed using 20-G systems and non-stitch 23-G systems, one-step (23/1) and two-step procedures (23/2), as well as one-step 25-G systems for pars plana vitrectomy (PPV) with ultrasound biomicroscopy (UBM) to assess subconjunctival bleb formation, vitreous incarceration, and wound closure. This study is a prospective, non-randomized, monocentre study comprising 40 patients; we examined sclerotomies using UBM after 20-G, 23/1-G, 23/2-G, and 25-G PPV in 10 patients each on days 1 and 30 postoperatively. Subconjunctival bleb formation was not detected in any of the eyes on the first day after surgery in the 20-G and 23/2-G groups and was observed in 5 (50%, 25 G) and 2 eyes (20%, 23/1 G). By day 30 postoperatively, all blebs had spontaneously resolved. The sclerotomy tunnel could be detected by UBM at day 1 postoperatively in 10 (100%, 20 G), 9 (90%, 25 G), 7 (70%, 23/1 G), and 7 eyes (70%, 23/2 G). Thirty days postoperatively, it was present in 10 (100%, 20 G), 1 (10%, 25 G), 3 (30%, 23/1 G), and 1 (10%, 23/2 G) eye. Vitreous incarceration occurred in 2 (20%, 20 G), 7 (70%, 25 G), 4 (40%, 23/1 G), and 2 (20%, 23/2 G) eyes. Anatomical closure of sclerotomies without subconjunctival bleb formation as seen on UBM was achieved at day 1 after 23/2-G and 20-G PPV and after 30 days postoperatively in all other non-stitch PPV techniques. Vitreous incarceration is common after 25-G PPV. Non-stitch sclerotomies can frequently no longer be detected by UBM 30 days postoperatively.
  Eye (London, England) 12/2009; 24(7):1268-72. · 1.97 Impact Factor
• Article: Serous pigment epithelial detachment in age-related macular degeneration: comparison of different treatments.

  A Lommatzsch, B Heimes, M Gutfleisch, G Spital, M Zeimer, D Pauleikhoff
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  ABSTRACT: To investigate the therapeutic effects of different treatments on serous pigment epithelium detachment (PED) in age-related macular degeneration (AMD). A total of 328 patients suffering from serous PED in AMD were retrospectively analysed. We treated only patients with documented visual deterioration: 86 patients with bevacizumab, 128 with ranibizumab, 60 with pegaptanib, and 54 with photodynamic therapy (PDT) combined with intravitreal triamcinolone acetonide (IVTA). Best-corrected vision was determined in the logarithm of the minimal angle of resolution (logMAR). We also analysed morphological findings such as full foveal thickness by optical coherence tomography (OCT), manually calculated height of PED as measured by OCT, and fluorescence angiography. The mean follow-up was 42.4 weeks. The best-corrected visual acuity of 0.78 logMAR before treatment could be improved by about 0.066 logMAR after treatment. Retinal thickness decreased in all patients with PED, in the mean by about 64.06 microm, and the mean value of the manually calculated height decreased by about 0.98 units. All functional and morphological results proved to be significantly better after injection of ranibizumab and bevacizumab than after pegaptanib and the combined treatment with PDT and IVTA. In all, 41 (12.5%) of our patients developed a tear of the retinal pigment epithelium (RPE). The therapeutic results were significantly better in patients treated with bevacizumab and ranibizumab than in those treated with pegaptanib or with a combination of PDT and IVTA. Even with treatment, tears of the RPE or only a partial flattening of the PED always indicated a worse prognosis in eyes with exudative AMD than in eyes with classic choroidal neovascularization.
  Eye (London, England) 03/2009; 23(12):2163-8. · 1.97 Impact Factor
• Article: [Optical coherence tomography for macula diagnostics. Review of methods and standardized application concentrating on diagnostic and therapy control of age-related macula degeneration].

  A Hassenstein, G Spital, F Scholz, A Henschel, G Richard, D Pauleikhoff
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  ABSTRACT: Optical coherence tomography (OCT) has gained increasing relevance for follow-up after the treatment of macular diseases especially after anti-VEGF therapy. Therefore it seemed reasonable to develop standardized evaluation strategies and OCT examination guidelines for Stratus OCT III. Basic guidelines for the Stratus OCT III examination of macular diseases were developed. The first part contains basic advice for the OCT examination with respect to the examiner, patients, image quality, movement artefacts, algorithms, archiving and interpretation of OCT images. The second part consists of the relevance and indications for OCT examination especially in age-related macular degeneration (AMD), subgroups of AMD and follow-up after treatment. The third part demonstrates a brief outlook on future developments, such as the digital integration method (DIM), which provides identical scan localization in follow-up and eliminates any movement artefacts. The application of standardized routine scanning and analysis protocols in Stratus OCT III for macular diseases and follow-up examinations provides an optimized, time-saving and comparable use of OCT. Therefore, the relevance and quality of OCT is increased for routine use in outpatient departments, hospitals and also for clinical studies.
  Der Ophthalmologe 02/2009; 106(2):116-26. · 0.62 Impact Factor
• Article: Optische Kohärenztomographie in der Makuladiagnostik

  A. Hassenstein, G. Spital, F. Scholz, A. Henschel, G. Richard, D. Pauleikhoff
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  ABSTRACT: HintergrundDie zunehmende Bedeutung des OCT (optische Kohärenztomographie) in der Makuladiagnostik bei Verlaufskontrollen nach Makulatherapie und einer hohen Anzahl von Kontrollen nach Anti-VEGF-Therapie lassen standardisierte Auswertungsstrategien und OCT-Untersuchungsrichtlinien sinnvoll erscheinen. Methode und ErgebnisseFür das Status OCT III wurden grundsätzliche Guidelines zur Untersuchung von Makulaerkrankungen erarbeitet. Im ersten Teil des Beitrags geht es um grundsätzliche Tipps für die OCT-Untersuchung bezüglich Untersuchungsdurchführung, Patientencompliance, Bildqualität, Bewegungsartefakte, Algorithmen, Archivierung und Interpretation von OCT-Bildern. Im zweiten Teil werden der Stellenwert und die Einsatzempfehlung des OCT bei der altersbedingen Makuladegeneration (AMD) und deren Therapiekontrollen zusammengefasst sowie entsprechend ihrerer einzelnen Formen unterteilt. Im dritten Teil wird ein kurzer Ausblick auf Weiterentwicklungen wie die digitale Integrationsmethode (DIM) gegeben, die beim Stratus OCT III eine identische Scanlokalisation im Verlauf und Ausschluss von Bewegungsartefakten gewährleistet. SchlussfolgerungDurch den standardisierten Einsatz des Stratus OCT III und geeigneter Auswertungsprogramme zur Makuladiagnostik im Verlauf nach Therapie kann der Einsatz des OCT optimiert, zeitsparend eingesetzt und v.a. vergleichbar gemacht werden. Damit erhöht sich die Aussagequalität sowohl für die Routine in Arztpraxen und Kliniken sowie auch für Studien. BackgroundOptical coherence tomography (OCT) has gained increasing relevance for follow-up after the treatment of macular diseases especially after anti-VEGF therapy. Therefore it seemed reasonable to develop standardized evaluation strategies and OCT examination guidelines for Stratus OCT III. Materials and methodsBasic guidelines for the Stratus OCT III examination of macular diseases were developed. The first part contains basic advice for the OCT examination with respect to the examiner, patients, image quality, movement artefacts, algorithms, archiving and interpretation of OCT images. The second part consists of the relevance and indications for OCT examination especially in age-related macular degeneration (AMD), subgroups of AMD and follow-up after treatment. The third part demonstrates a brief outlook on future developments, such as the digital integration method (DIM), which provides identical scan localization in follow-up and eliminates any movement artefacts. ConclusionThe application of standardized routine scanning and analysis protocols in Stratus OCT III for macular diseases and follow-up examinations provides an optimized, time-saving and comparable use of OCT. Therefore, the relevance and quality of OCT is increased for routine use in outpatient departments, hospitals and also for clinical studies.
  Der Ophthalmologe 01/2009; 106(2):116-126. · 0.62 Impact Factor
• Article: Variations in five genes and the severity of age-related macular degeneration: results from the Muenster aging and retina study.

  A Farwick, B Dasch, B H F Weber, D Pauleikhoff, M Stoll, H-W Hense
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  ABSTRACT: Little is known about the role of genetic variants in the early stages of age-related macular degeneration (AMD). We aimed to investigate how genetic variations within five well-defined genes relate to AMD severity. We analysed SNPs in the genes for complement factor H (CFH), age-related maculopathy susceptibility (ARMS2), HtrA serine peptidase 1 (HtrA1), complement factor B (CFB), and complement component 2 (C2)in 183 controls and 730 patients with increasing severity of AMD from the Muenster aging and retina study (MARS). Severity scoring was based on the Rotterdam classification of fundus photographs. Compared with controls, patients with very early AMD showed a significantly increased minor allele frequency (MAF) only for CFH-rs1061170. With increasing severity of AMD, SNPs in CFH-rs1061170,as well as ARMS2-rs10490924, became consistently more common (P<0.001). Likewise, HtrA1-rs11200638 was less clearly associated with AMD severity, whereas C2-rs9332739 and CFB-rs641153 showed no relation. Multifactorial models confirmed CFH and ARMS2 as major determinants of AMD severity, whereas addition of HtrA1, C2 and CFB did not improve model prediction. In the models, age did not contribute to very early but to all more severe AMD stages, whereas smoking history had a significant impact only for late AMD. Our findings indicate that the CFH gene is involved in the onset of AMD, whereas both, the CFH and ARMS2 genes, and more weakly, the HtrA1 gene, appear to account for the advancement of AMD. The results for SNPs in the C2 and CFB genes were inconclusive. Genetic factors dominated in their impact over age and smoking history.
  Eye (London, England) 01/2009; 23(12):2238-44. · 1.97 Impact Factor
• Article: [Treatment of vascularised serous pigment epithelium detachment in AMD - observations after changing the intravitreal agent due to lack of response].

  A P Lommatzsch, B Heimes, M Gutfleisch, G Spital, M Zeimer, D Pauleikhoff
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  ABSTRACT: Based on data from multicentric studies the treatment of exudative age-related macular degeneration (AMD) with VEGF inhibitors has recently become a more and more standard procedure. Nevertheless, the proper end point of the treatment and also the adequate interval between single injections have not been defined yet. In subtypes of AMD associated with pigment epithelium detachment. (PED) the natural course as well as laser coagulation treatment and photodynamic therapy (PDT) showed unsatisfactory results. The main cause of decreased visual acuity has proven to be recurrence of choroidal neovascularisation and ruptures of the pigment epithelium (RIP). This retrospective study presents the clinical results following a change of the injected VEGF inhibitor after ineffective initial therapy. 15 patients with serous PED, 7 patients with PED associated with retinal angiomatous proliferation (RAP) exhibited insufficient stabilisation after initial treatment with pegaptanib (Macugen). Therefore we continued treatment with ranibizumab (Lucentis). The mean age was 74.67 years. Best corrected visual acuity was evaluated with logMAR. Additional morphological parameters were fovea full thickness (OCT), measurement of the height of pigment epithelium detachment and finally fluorescein and indocyaningreen angiography. In cases of functional and morphological deterioration, we changed the treatment from 1.25 mg pegaptanib (Macugen) to 0.5 mg ranbizumab (Lucentis). During the mean follow-up of 46.5 weeks (95 % CI 35.9 - 57.1) no RIP occurred. After changing the drug, visual acuity showed a stabilisation or improvement in 11 cases. Also the height of PED decreased after beginning with ranbizumab. Regarding the therapeutic outcome, no difference between eyes with serous PED caused by occult CNV or RAP could be observed. Treatment using VEGF inhibitors in patients suffering from AMD with exudative serious PED has proven to be effective regarding both the morphological damage and functional injuries. In cases of therapeutic failure after pegaptanib functional and/or morphological stabilisation of the course of this disease can be achieved by changing to ranbizumab. Nevertheless, prospective clinical studies with a larger number of patients are necessary for confirmation of these findings.
  Klinische Monatsblätter für Augenheilkunde 11/2008; 225(10):874-9. · 0.51 Impact Factor