Photodynamische Therapie bei altersbedingter Makuladegeneration am schlechteren und besseren Auge

Zusammenfassung: Hintergrund: Die PDT ist die Standardbehandlung vieler Formen der exsudativen bzw. neovaskulären Makuladegeneration (AMD). Trotz Therapie fällt die Sehschärfe häufig in den Low-vision-Bereich ab. Die Kosteneffizienz der Therapie am schlechteren Auge wird daher kontrovers diskutiert. Patienten und Methoden: Retrospektive Fallkontrollstudie aller Patienten, welche zwischen September 1999 und November 2004 am Universitätsspital Zürich eine PDT erhalten haben. Die Situation bei Präsentation und der Verlauf unter Therapie wurden bei ersten (schlechteren) und zweiten (besseren) Augen verglichen. Ergebnisse: In 117/228Fällen (51,3%) war der Visus am behandelten Auge bei Präsentation besser (oder gleich) als der Visus am Partnerauge. Der Visus vor Behandlung betrug bei den besseren Augen im Mittel 0,58±0,27logMAR [Snellen: 0,26 (0,14-0,49)] und 0,69±0,4logMAR [Snellen 0,20 (0,08-0,51)] bei den schlechteren Augen (p=0,015). Nach Behandlung bestand zwischen den Gruppen weder bezüglich Visus bzw. Visusveränderung noch bezüglich Membrangröße bzw. Größenveränderung der Membran ein signifikanter Unterschied. Schlussfolgerung: Die Resultate nach PDT sind beim zweiten (bzw. besseren) Auge nicht signifikant besser als beim ersten (bzw. schlechteren) Aug

Coagulation-balance gene predictors influencing visual prognosis in patients treated with photodynamic therapy for classic choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with classic or predominantly classic choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: The clinical records of consecutive AMD patients with classic or predominantly classic CNV, treated with PDTV according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy study criteria, were retrospectively examined. Eighty-six eligible patients were subdivided in responder and non-responder basing on the modifications of best-corrected visual acuity between baseline and 12-month checks. Six gene polymorphisms, i.e. factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in each patient. Binary logistic regression models were used to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS: PDT-V responders were more prevalent among the combined carriers for factor V 1691A and prothrombin 20210A alleles (OR = 5.1 with a 95% CI of 1.0-24.4; P = 0.05), methylenetetrahydrofolate reductase 677 T-allele (OR = 4.3 with a 95% CI of 1.8-10.8; P = 0.002), and methionine synthase reductase 66 G-allele (OR = 2.8 with a 95% CI of 1.1-6.8; P = 0.04). Conversely, PDT-V non-responders were over-represented in patients with factor XIII-A 185 T-allele (OR = 0.22 with a 95% CI of 0.09-0.56; P = 0.001). The other considered predictors did not significantly modify PDT-V effectiveness. CONCLUSIONS: Our study provides evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of visual prognosis at 12 months in AMD patients treated with standardized PDT-V protocol for classic subfoveal CNV

25th RCOphth Congress, President's Session paper:25 years of progress in medical retina

The quarter century since the foundation of the Royal College of Ophthalmologists has coincided with immense change in the subspecialty of medical retina, which has moved from being the province of a few dedicated enthusiasts to being an integral, core part of ophthalmology in every eye department. In age-related macular degeneration, there has been a move away from targeted, destructive laser therapy, dependent on fluorescein angiography to intravitreal injection therapy of anti-growth factor agents, largely guided by optical coherence tomography. As a result of these changes, ophthalmologists have witnessed a marked improvement in visual outcomes for their patients with wet age-related macular degeneration (AMD), while at the same time developing and enacting entirely novel ways of delivering care. In the field of diabetic retinopathy, this period also saw advances in laser technology and a move away from highly destructive laser photocoagulation treatment to gentler retinal laser treatments. The introduction of intravitreal therapies, both steroids and anti-growth factor agents, has further advanced the treatment of diabetic macular oedema. This era has also seen in the United Kingdom the introduction of a coordinated national diabetic retinopathy screening programme, which offers an increasing hope that the burden of blindness from diabetic eye disease can be lessened. Exciting future advances in retinal imaging, genetics, and pharmacology will allow us to further improve outcomes for our patients and for ophthalmologists specialising in medical retina, the future looks very exciting but increasingly busy

Is reduction in the risk of vision loss the only benefit of photodynamic therapy in predominantly classic subfoveal choroidal neovascularization?

Nicola G Ghazi, rian P Conway, James S Tiedeman, Steven J YoonUniversity of Virginia Health System, Department of Ophthalmology, Charlottesville, VA, USAPurpose: To emphasize the effect of photodynamic therapy (PDT) on the size and progression of the neovascular lesion (NL) and evolution of the disciform scar (DS) in predominantly classic subfoveal choroidal neovascularization (SFCNV).Methods: A retrospective study of 62 eyes treated with PDT for SFCNV was performed. The greatest linear dimension (GLD) before and at last follow-up after treatment and the size of the DS post-PDT were analyzed. A subgroup of patients with DS in their fellow eye at presentation without prior PDT was also studied. The size of the scar in these eyes was compared to that following PDT.Results: After an average follow-up at 9 months, the size of the NL was stabilized or reduced in 64% of the study eyes with absence of fluorescein leakage in 45%. Only 3 eyes (5%) developed DS. At presentation, 14 patients already had DS in their fellow eye, the size of which was significantly larger than that post-PDT (p = 0.044). It was also significantly larger than that of the potential scar in the study eyes of the same subgroup of patients (p = 0.002) and of the rest of the patients (p = 0.0001).Conclusion: This study demonstrates a beneficial effect for PDT on the size of the NL and DS in SFCNV, which might be of great significance, particularly when PDT fails to prevent severe vision loss.Keywords: age-related macular degeneration, choroidal neovascularization, classic choroidal neovascularization, disciform scarring, fluorescein angiography, photodynamic therap

Quality of Life in Macular Degeneration Between Photodynamic Therapy and Pegaptanib Treatment Groups

The purpose of this study was to examine quality of life (QOL) in age-related macular degeneration (AMD), particularly across photodynamic therapy (PDT) and pegaptanib sodium injection treatment groups. Patients with AMD were either mailed or were administered in person a modified version of the Visual Function Questionnaire (VFQ-25). Subgroup analysis of the VFQ-25 was performed per NEI prescribed algorithms and additional analyses regarding questions on treatment side effects were also performed. A two-tailed student t-test and mean were calculated for each treatment group and correlations between visual acuity and subgroup outcomes were calculated. Correlations between the subgroup and treatment-related subgroup outcomes were also calculated to determine which QOL deficits might occur together. Multiple linear regression models were used to estimate the association between the overall QOL score and scaled visual acuity, age, gender, and treatment history. 30 patients were interviewed in person and an additional 41 patients returned the questionnaire by mail. Of these, 37 had been treated with PDT (ten had also received intravitreal triamcinolone acetate (IVTA) injections); 16 had been treated with pegaptanib; seven had been treated with both pegaptanib and PDT (two had also received IVTA); and 25 had not been treated with any of these treatments. The mean age was 79 years. Patients lowest subgroup scores were in perception of general vision (43.2) and in driving (50.8). The ocular pain subgroup yielded a mean score of 82.9 for the PDT group and 87.5 for the pegaptanib group (p = 0.59). The average vision worsening score for the first two weeks following treatment was 87.5 for the PDT group and 77.8 for the pegaptanib group (p = 0.29). The average mental health score for concerns related to treatments was 78.2 for the PDT group and 73.6 for the pegaptanib group (p = 0.61), while the average independence score related to treatment appointments was 86.1 for the PDT group and 87.5 for the pegaptanib group (p = 0.92). Strong positive correlations (\u3e 0.45) were seen between general health and ocular pain; between treatment-related mental health and both overall QOL score and treatment-related vision worsening; and between numerous measures of visual function. The best predictor of overall QOL score was the near activities score. Age was moderately or weakly negatively correlated with multiple measures. Stepwise multiple linear regression analysis demonstrated that the square of SVA provided the most explanatory power for the overall QOL score, implying a non-linear relationship between visual acuity and QOL. None of the treatment modalities added explanatory power to the model when added to the square of SVA. In conclusion, QOL, stress regarding treatment, and ocular pain did not differ between PDT and pegaptanib treatment groups. Decreasing visual acuity was associated most strongly with decreases in ability to perform near and distance activities, overall QOL, driving, and independence. Scales denoting worry and frustration about treatment did not demonstrate a strong relationship to visual function, implying patient concern about treatment across the visual acuity spectrum. A nonlinear relationship was seen between QOL and visual acuity

Photodynamische Therapie mit Verteporfin und intravitrealem Triamcinolonacetonid zur Behandlung der subfovealen neovaskulären altersabhängigen Makuladegeneration

Die altersäbhängige Makuladegeneration ist die häufigste Ursache für eine Blindheit im Sinne des Gesetzes in den westlichen Industrienationen und steht an dritter Stelle für eine Blindheit in der Welt. Ein visueller Schaden wird ungefähr zweimal häufiger durch die neovaskuläre altersabhängige Makuladegeneration im Vergleich zu der geographischen Atrophie verursacht. Ranibizumab stellt für die verschiedenen untersuchten Typen der exsudativen AMD die Therapie der ersten Wahl dar. Das fehlende Ansprechen einer Therapie mit Ranibizumab kann den Einsatz der PDT oder die intraokulare Therapie mit Pegaptanib sinnvoll erscheinen lassen (zweiter Wahl Therapie). Die photodynamische Therapie mit dem Ziel die chorioidale Neovaskularisation zu okkludieren, erhöht die Expression von Wachstumsfaktoren, daneben kommt es zur Zunahme ödematöser und entzündlicher Reaktionen. Kortikosteroide haben antiproliferative, antiinflammatorische, angiostatische und antiödematöse Wirkung. Triamcinolonacetonid ist ein synthetisches Glukokortikoid, das in Form einer kristallinen Suspension nach intravitrealer Applikation eine Depotwirkung gewährleistet. Ziel dieser retrospektiven Arbeit ist die Effektivität der photodynamischen Therapie in Kombination mit intravitrealem Triamcinolonacetonid bei der Therapie der subfovealen neovaskulären altersabhängigen Makuladegeneration zu evaluieren. Die Daten von 101 Augen von 101 Patienten (63 Frauen, 38 Männer) mit einer subfovealen neovaskulären altersabhängigen Makuladegeneration, durch- schnittlichem Alter von 76,9±5,6 Jahren und einem Ausgangsvisus von 0,77±0,22 logMAR wurden ausgewertet. Die intravitreale Injektion von ca. 20 mg Triamcinolon-acetonid erfolgte 5 Tage vor der photodynamischen Therapie. Nach 12 Monaten zeigte sich ein mittlerer Visusverlust von 1,9 Visusstufen. Der mittlere Endvisus betrug 0,96±0,32 logMAR und es wurden 1,8 PDT-Behandlungen im Mittel durchgeführt. Die Kombinationsbehandlung zeigte eine ähnliche und sogar etwas bessere Wirksamkeit unabhängig von der Läsionsart und dem Läsionstyp der choroidalen Neovaskularisation bei einer deutlich geringeren Anzahl von PDT-Behandlungen im Vergleich zu der PDT-Monotherapie. Die bekannten Nebenwirkungen des intraokularen Triamcinolonacetonids wie Steigerung des Augeninnendruckes, Endophthalmitisrisiko und Kataraktprogedienz, die in dieser Arbeit nicht untersucht wurden, müssen berücksichtigt werden. Die Dosierung und die zeitliche Abfolge (PDT vor oder nach Triamcinolonacetonid) sind noch unklar. Die Ergebnisse zur Wirksamkeit und Sicherheit der photodynamischen Therapie mit Verteporfin und intravitrealem Triamcinolonacetonid zur Behandlung der subfovealen neovaskulären altersabhängigen Makuladegeneration werden von den begonnenen prospektiven, randomisierten Vergleichsstudien erwartet

Kombinirano liječenje senilne neovaskularne makularne degeneracije primjenom bevacizumaba i fotodinamske terapije : doktorski rad

Uvod:Degeneracija makule u svezi s dobi (AMD) je najčešći uzrok gubitka vida u ljudi starijih od 50 godina u zemljama razvijenog svijeta, od čega najveći udio morbiditeta pripada neovaskularnom obliku bolesti. Aktualne metode liječenja, inhibitori djelovanje čimbenika rasta vaskularnog endotela (antiVEGF) te fotodinamska terapija verteporfinom (PDT), ograničenog su funkcionalnog učinka te zahtijevaju dugotrajnu primjenu. Cilj:Utvrditi bi li kombinacija liječenja intravitrealno primjenjenog bevacizumaba (antiVEGF) i PDT-a povećala učinkovitost liječenja u odnosu na monoterapiju bevacizumabom uz poboljšanje najbolje korigirane vidne oštrine (BCVA) i/ili manji broj intravitrealnih reaplikacija uz produženje perioda remisije. Ispitanici i metode: U studiju je uključeno 210 pacijenata sa neovaskularnom AMD praćenih tijekom 2006-2009.g. Početna BCVA mjerena je u logMAR (logaritam minimalne kutne rezolucije) jedinicama, a središnja fovealna debljina (CFT) mjerena je optičkom koherentnom tomografijom (OCT). Pacijenti su uzorkovani u 2 jednake skupine:105 pacijenata u skupinu (KOMB) liječenu inicijalnom kombinacijom PDT-a i intravitrealno primjenjenog bevacizumaba (1,25mg/0,05ml), te 105 pacijenata (BEV) inicijalno liječenih samo intravitrealno primjenjenim bevacizumabom (1,25mg/0,05ml). Tijekom perioda praćenja svakih 6 tjedana u ukupnom trajanju od 3 godine, određivani su BCVA i CFT te je dodatno intravitrealno primjenjivan bevacizumab u obje skupine počevši od 12. tjedna nakon inicijalne terapije i to u slučaju aktivnosti bolesti ili recidiva. Dobiveni BCVA i CFT nakon 1., 2. i 3. godine praćenja uspoređivani su sa početnim vrijednostima unutar svoje skupine pojedinačno te između skupina KOMB i BEV. Uspoređen je također broj primjenjenih intravitrealnih aplikacija bevacizumaba na navedenim kontrolnim periodima praćenja između obje skupine. Rezultati:101 pacijent u KOMB skupini i 100 pacijenata u BEV skupini kompletiralo je period praćenja od 1 godine, 91 pacijent (KOMB i BEV) tijekom 2 godine i 82 pacijenta (KOMB) i 80 pacijenata (BEV) tijekom 3 godine. Početne vrijednosti BCVA i CFT između skupina nisu se statistički razlikovale. Nakon 3 godine praćenja u obje skupine pacijenata došlo je do značajnog poboljšanja (p<0,01) BCVA u odnosu na početnu vrijednost: za 0,132 logMAR (KOMB) i 0,116 logMAR (BEV) tijekom 1. godine; za 0,092 logMAR (KOMB) i 0,096 logMAR (BEV) tijekom 2. godine; za 0,091 logMAR (KOMB) i 0,106 logMAR (BEV) tijekom 3.godine. Također je došlo do značajnog smanjenja CFT (<0,01) za 55 mikrona (KOMB) i 50 mikrona (BEV) tijekom 1. godine; za 57 mikrona (KOMB) i 53 mikrona (BEV) tijekom 2. godine; za 52 mikrona (KOMB) i 60 mikrona (BEV) tijekom 3.godine. U međusobnoj usporedbi tijekom korespondentnih intervala praćenja tijekom1.,2. i 3. godine ovo poboljšanje nije dovelo do značajne razlike u BCVA niti u CFT između KOMB i BEV skupina. Tijekom 1. godine u KOMB skupini primjenjeno je prosječno 3,36 injekcija, a u BEV skupini 4,26 injekcija što je statistički značajno manje (p<0,0001). Tijekom prve dvije godine broj primjenjenih injekcija u KOMB skupini bio je 6,68, a u BEV skupini 7,19 (p=0,035). Tijekom tri godine praćenja u KOMB skupini primjenjeno je 9,95 injekcija, a u BEV skupini 10,4 što nije bilo statističko značajno manje (p=0,143). Tijekom perioda praćenja zabilježeno je 5 puknuća retinalnog pigmentnog epitela u BEV skupini, 10 odvajanja stražnje staklovine (PVD) u KOMB, a 12 PVD-a u BEV skupini. Zaključak: Kombinirano liječenje neovaskularne AMD postiglo je jednako učinkovite rezultate u poboljšanju BCVA i CFT, uz značajno manji broj intravitrealnih aplikacija bevacizumaba tijekom prve dvije godine praćenja i jednako dobar sigurnosni profil liječenja.Introduction: Age-Related Macular Degeneration is a leading cause of severe visual loss in population over 50 in Western countries with neovascular subtype accounting for the most of severe cases. Available treatment modalities including Vascular Endothelial Growth Factor inhibitors (antiVEGF) and verteporfin photodynamic therapy (PDT) are of limited efficiency and require prolonged treatment. Aim: To investigate whether PDT combined with intravitreal bevacizumab (antiVEGF) would result in increased treatment efficiency in comparison to bevacizumab monotherapy in terms of better best corrected visual acuity (BCVA) and/or reduced need for intravitreal bevacizumab injections. Participants and methods: 210 patients included in the study were followed-up from 2006- 2009. Baseline BCVA was measured in logMAR units (logarithm of minimal angle resolution), and central foveal thickness (CFT) was determined by optical coherence tomography (OCT). Patients were randomly assigned to 2 equal groups: at baseline 105 patients in combination group (KOMB) received a single session of PDT combined with intravitreal bevacizumab (1,25mg/0,05ml), while 105 patients (BEV) received only intravitreal bevacizumab (1,25mg/0,05ml). During 3 year follow-up period at 6 week intervals BCVA and CFT were checked and patients retreated with intravitreal bevacizumab starting from the week 12 post initial therapy, in case of persistent leakage or leakage reoccurrence. The BCVA and CFT results obtained at 1, 2 and 3 year intervals were compared to baseline values within groups and between groups at the corresponding follow-up intervals. Number of required intravitreal injections was also compared between groups at the corresponding follow-up intervals. Results:101 patients in KOMB group and 100 patients in BEV group completed the 1 year follow-up, 91 patients in (KOMB and BEV) completed 2 year follow-up, and 82 patients (KOMB) and 80 patients (BEV) completed 3 year follow-up. There was no statistical difference in BCVA and CFT at baseline between groups. At 3 year follow-up a significant improvement in BCVA (p<0,01) compared to baseline was observed within both groups: 0,132 logMAR (KOMB) and 0,116 logMAR (BEV) increase at 1 year; 0,092 logMAR (KOMB) and 0,096 logMAR (BEV) increase at 2 years; 0,091 logMAR (KOMB) and 0,106 logMAR (BEV) increase at 3 years. A significant decrease in CFT was also observed within both groups (<0,01): 55 microns (KOMB) and 50 microns (BEV) decrease at 1 year; 57 microns (KOMB) and 53 microns (BEV) at 2 years; 52 microns (KOMB) and 60 microns (BEV) at 3 years. These improvements did not result in statistically significant difference in BCVA and CFT between groups at corresponding follow-up intervals at 1, 2 and 3 years. During first year a total of 3,36 injections was given in KOMB group which was significantly less (p<0,0001) when compared to total number of 4,26 injections given in BEV group. During first 2 years a total number injections given in KOMB group was 6,68 and in BEV group 7,19 (p=0,035). During the 3 year period 9,95 injections were given in KOMB group while 10,4 injections were given in BEV group (p=0,143). 5 retinal pigments epithelium rips were noted in BEV group, 10 posterior vitreous detachments were observed in KOMB and 12 in BEV groups. Conclusion: PDT combined with intravitreal bevacizumab has resulted in non-inferior visual treatment outcome to bevacizumab monotherapy with significantly smaller number of required intravitreal injections during first 2 years of treatment. Safety profile was comparable between groups