Macular Degeneration: Pauleikhoff D

Pauleikhoff D. · Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany. · Retina. · Pubmed #16340538 No free full text.

Abstract: BACKGROUND: This review summarizes the data reported in peer-reviewed literature and presents current knowledge on differentiation, natural history, and therapeutic outcomes of neovascular age-related macular degeneration (AMD). METHODS: The MEDLINE database was searched to review natural history of neovascular AMD and therapeutic effects of available treatments. RESULTS: The search produced>7,000 articles. Research suggests that fluorescein angiographic characterization of location, composition, and size of neovascular lesions may be important in prognosis and should be considered for evaluation of treatment benefits in conjunction with evidence of recent disease progression for lesions not composed of predominantly classic choroidal neovascularization (CNV). Laser photocoagulation, photodynamic therapy with verteporfin, and administration of pegaptanib sodium reduce the risk of vision loss in selected cases of neovascular AMD, while submacular surgery can reduce the risk of severe visual acuity loss in selected cases of predominantly hemorrhagic CNV; further approaches are under investigation. CONCLUSION: Visual prognosis of neovascular AMD is variable according to lesion location, composition, and size. Often, lesions have a poor prognosis, resulting in rapid and progressive loss of visual acuity and contrast sensitivity. Such losses have a profound effect on patients' quality of life and ability to perform everyday tasks. Reducing the risk of further loss of visual acuity and contrast sensitivity might enable patients with neovascular AMD to maintain better functional abilities.

Pauleikhoff D, Bornfeld N, Gabel VP, Holz F, Roider H, Anonymous00032, Anonymous00033, Anonymous00034. · Augenabteilung des St. Franziskus Krankenhauses, Münster. · Klin Monatsbl Augenheilkd. · Pubmed #15912454 No free full text.

Abstract: BACKGROUND: Until recently, only two options were available for the treatment of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD): laser photocoagulation and photodynamic therapy (PDT) with verteporfin. However, potential new treatments for CNV are under development, and data from phase III clinical trials are now available. Referring to these data, expert guidance is required to supply ophthalmologists with expertise in the management of AMD to select and use the most appropriate therapies in the treatment of neovascular AMD. METHODS: The therapeutic modalities discussed include thermal laser photocoagulation, PDT with verteporfin, triamcinolone acetonide and the possible combination with PDT, anecortave acetate, pegaptanib sodium and ranibizumab. After a short description of the treatment principles, a summary of the discussion of all relevant study results of the different treatment options with respect to the different subtypes of neovascular AMD is presented. These discussions resulted in an "up-to-date" recommendation of therapeutical strategies in neovascular AMD. RESULTS: For subfoveal lesions with predominantly classic CNV, or with occult with non-classic CNV and a lesion size < or = 4 macular photocoagulation study (MPS) disc areas (DA), PDT with verteporfin is recommended; for subfoveal lesions with minimally classic CNV, treatment with PDT or pegaptanib sodium is possible, even if there are some problems with the statistics in the studies with both treatment modalities. PDT with verteporfin should be considered for juxtafoveal lesions that are so close to the fovea that laser photocoagulation would almost certainly extend under the center of the foveal avascular zone, and for all other juxtafoveal lesions and for extrafoveal lesions laser photocoagulation is suggested. Therapy should be performed not later than one week after the initial fluorescein angiogram upon which the clinical decision for treatment is based. At each follow-up best-corrected visual acuity and a fundus examination should be performed as well as a fluorescein angiography every three months. CONCLUSIONS: These recommendations provide good clinical guidance for the choice and use of laser and pharmacotherapies for the management of CNV due to AMD. Revisions of the recommendations will be required as new data become available.

Pauleikhoff D, Spital G. · Augenabteilung, St. Franziskus Hospital, Münster. · Ophthalmologe. · Pubmed #15480699 No free full text.

Abstract: In recent years several prospective studies have dealt with the therapeutic possibilities of PDT. In consideration of lesion size and its composition, a subtly differentiated scheme of therapy has been developed. Based on essential studies, recommendations on the indication for photodynamic therapy are summarized. They are complemented by references to safety and efficacy of photodynamic therapy. Users of PDT are given a short summary of relevant studies with current recommendations, which might ease the daily procedure of indicating photodynamic therapy.

Holz FG, Pauleikhoff D, Klein R, Bird AC. · Department of Ophthalmology (F.G.H.), University of Heidelberg, Heidelberg, Germany. · Am J Ophthalmol. · Pubmed #15013875 No free full text.

Abstract: PURPOSE: To review the evidence that exists concerning the pathogenesis of lesions in late age-related macular disease (AMD). DESIGN: Review of the literature. METHODS: A review of both experimental evidence and clinical observations that address these problems. RESULTS: There is good evidence that choroidal neovascularization (CNV) is due to a change in the balance of growth factors derived from the retinal pigment epithelial basolateral plasma membrane domain (retinal pigment epithelium). Retinal angiomatous proliferation may also have a similar pathogenesis involving the apical domain. Detachment of the retinal pigment epithelium is likely to be a consequence of increased resistance of the Bruch membrane to water flow due to deposition of lipids. Geographic atrophy is preceded by accumulation of autofluorescent material in the retinal pigment epithelium and possible causal relationships between the two have been demonstrated. CONCLUSION: There is increasing understanding concerning the sequence of events that lead to those lesions causing loss of central vision in AMD. Therapeutic approaches that address the underlying mechanisms are more likely to succeed than current treatment options. Such an approach has already been initiated in the management of choroidal neovascularization.

Pauleikhoff D, van Kuijk FJ, Bird AC. · Augenabteilung St. Franziskus Hospital Münster. · Ophthalmologe. · Pubmed #11450472 No free full text.

Abstract: The present concepts of the pathogenesis of AMD include cumulative light damage by oxidative processes in the macular photoreceptors as environmental co-factor for the development of AMD. The direct causative connection of this hypothesis has still to be established but wide circumstantial evidence from epidemiological and basic scientific investigations are strongly supportive. Macular pigment consisting of lutein and zeaxanthin through there ability to filter light and by direct antioxidative properties, has been proposed as the most effective protective factor in the central retina ("natural sun glasses") and could be important to reduce light induced oxidative retinal damage. The observation, that with age and especially in eyes with AMD lower concentrations of macular pigment could be found, can be interpreted that low macular pigment concentrations may be associated with higher risk for AMD. Through dietary intake and eventually with supplementation the concentration of macular pigment can be increased, and analysis of the correlation between macular pigment and AMD may be important to characterise a possible influenceable AMD risk factor.

Lommatzsch AP, Heimes B, Gutfleisch M, Spital G, Zeimer M, Pauleikhoff D. · Augenabteilung am St.-Franziskus-Hospital Münster. · Klin Monatsbl Augenheilkd. · Pubmed #18951308 No free full text.

Abstract: INTRODUCTION: 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. METHOD: 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). RESULTS: 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. CONCLUSION: 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.

Dasch B, Fuhs A, Meister A, Behrens T, Krause K, Pauleikhoff D, Hense HW. · Institut für Epidemiologie und Sozialmedizin, Westfälische Wilhelms-Universität Münster. · Ophthalmologe. · Pubmed #15871022 No free full text.

Abstract: BACKGROUND: Epidemiological studies have reported inconsistent associations between cardiovascular risk factors and the occurrence of age-related maculopathy (ARM). METHODS: In the baseline examination of the Muenster Aging and Retina Study (MARS), we assessed this potential relationship in 1060 subjects who underwent clinical and ophthalmologic examinations. The ARM status was graded according to international standardized classifications. RESULTS: There were 974 eye pairs available for analysis. Smoking, hypertension, hypercholesterolemia, and a history of myocardial infarction or stroke were found significantly more often in patients with ARM. There were no statistically significant multivariate associations between overweight, diabetes, or a history of myocardial infarction or stroke. CONCLUSIONS: Our results confirm previous epidemiological studies pointing to a potential role of atherosclerotic processes in the development of ARM.

Wachter A, Sun Y, Dasch B, Krause K, Pauleikhoff D, Hense HW. · Augenärztliche Abteilung, St. Franziskus Hospital Münster. · Ophthalmologe. · Pubmed #14872268 No free full text.

Abstract: BACKGROUND: The association between arteriosclerosis and age-related macular degeneration (AMD) has only been examined in a few studies and the data is still very inconsistent. METHODS: A cross sectional study was initiated with 730 patients from the Münster age and retina study (MARS) which examines patients in the age range 60 to 80 years old who were referred by ophthalmologists from the Muenster area. Patients with narrow angle glaucoma were excluded. All patients underwent a standardized ophthalmoscopic examination und were classified into four groups: group 1 without AMD ( n=190), group 2 with unilateral or bilateral early forms of AMD ( n=340), group 3 with unilateral late forms of AMD ( n=139) and group 4 with bilateral late forms of AMD ( n=50). By means of these groups it was tested if there was a significant difference between the different risk factors for arteriosclerosis. RESULTS: The mean age was 72 years and 58% were women and the sex distribution within the different groups did not differ significantly (all trend tests with p>0.1). General risk factors for arteriosclerosis such as diabetes, body-mass-index and hypertension did not differ significantly (all trend tests with p>0.1). The number of smokers increased significantly with the severity of AMD ( p=0.02). Furthermore, various lipids were examined, adjusted for age and sex and showed significant decrease of HDL ( p=0.087) and significant increases of the HDL/LDL quotient ( p=0.0007) and the non-sober triglyceride values ( p=0.0058) correlated with the severity of AMD. CONCLUSIONS: There was a highly significant, direct association of indicators of dyslipidemia such as increasing HDL/LDL quotient and decreasing HDL with the severity of AMD. These results were underlined by increased triglyceride levels even if they were taken non-sober. The results must be interpreted with caution due to the explorative character of the evaluation.

Hassenstein A, Spital G, Scholz F, Henschel A, Richard G, Pauleikhoff D. · Universitäts-Augenklinik Hamburg Eppendorf, Martinistrasse 52, 20251 Hamburg, Deutschland. · Ophthalmologe. · Pubmed #19156426 No free full text.

Abstract: BACKGROUND: 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. MATERIALS AND METHODS: 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. CONCLUSION: 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.

Pauleikhoff D, Scheider A, Wiedmann P, Gelisken F, Scholl HP, Roider I, Mohr A, Zlateva G, Xu X. · Augenabteilung am St. Franziskus-Hospital, Münster, Deutschland. · Ophthalmologe. · Pubmed #18709375 No free full text.

Abstract: BACKGROUND: Approximately 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. METHODS: A 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. RESULTS: The 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 <euro> 9871, 6 times that of elderly patients without NV-AMD (<euro> 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. CONCLUSIONS: NV-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.

Neuner B, Wellmann J, Dasch B, Dietzel M, Farwick A, Stoll M, Pauleikhoff D, Hense HW. · Institute of Epidemiology and Social Medicine, Clinical Epidemiology Section, University of Muenster, Muenster, Germany. · Ophthalmic Epidemiol. · Pubmed #18569809 No free full text.

Abstract: PURPOSE: To prospectively evaluate the impact of homozygosity in the A69S-SNP of the LOC387715-gene, smoking history, and their interaction on visual functional status (v-FS) in age-related macular degeneration (AMD). METHODS: The Muenster Aging and Retina Study (MARS) cohort (n = 656; 58.8% women, mean age 70.2 years) was followed over a mean of 2.5 years. AMD-status, genotype and smoking history were assessed at baseline. V-FS [from 0 (low) to 100 (unimpaired) points in general-, near- and far-vision], were AMD-status assessed at baseline and at follow-up. Linear models with stepwise adjustments for covariates were used to analyze decline of v-FS over time. RESULTS: In initial models, homozygosity for the A69S-variant was negatively associated with all three dimensions of the v-FS. After including smoking history, ever smoking was negatively associated with declines in near and far vision (-4.82 and -5.12 points, respectively; each p < 0.05). In smokers homozygous for the A69S-variant the number of cigarettes smoked per day (smoking intensity) was negatively associated with all three dimensions of the v-FS (interaction term each p < 0.05). Time since smoking cessation in former smokers protected against declines in near and far vision. These effects were independent of the AMD-status at baseline. CONCLUSIONS: The interaction of homozygosity for the A69S-variant and smoking intensity had a negative impact on general-, near-, and far visual functional status independent of AMD-status. Quitting smoking seemed to have a time-dependent protective effect on near and far vision.

Zeimer M, Hense HW, Heimes B, Austermann U, Fobker M, Pauleikhoff D. · St. Franziskus Hospital, Münster, Deutschland. · Ophthalmologe. · Pubmed #18551295 No free full text.

Abstract: BACKGROUND: How long do the elevated concentrations of macular pigment persist after stopping supplementation with lutein and zeaxanthin? METHODS: One hundred eight (108) probands with and without age-related macular degeneration (68 female, 40 male, age 51-87 years) received a supplement containing 12 mg lutein and 1 mg 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 9 months following discontinuation of the supplement. A control group of 28 subjects received no dietary supplement. RESULTS: At baseline, the mean MPOD at 0.5 degrees was 0.50 in the supplemented group. Following supplementation, values rose, and 3 months after discontinuation of supplementation the highest levels of MPOD0.5 degrees (0.59 ODU) were detected (increase of +0.1 ODU, (p<0.001). Six months after supplement discontinuation, a slight decrease of mean MPOD0.5 degrees appeared (to 0.54 ODU), followed again by a slight increase 3 months later (to 0.57 ODU). An increment of MPOD0.5 degrees in the control group was not significant (0.03 ODU, p=0.15). DISCUSSION: Supplementation of lutein and zeaxanthin leads to an increase of MPOD0.5 degrees . This effect outlasts the duration of intake, and 9 months after supplementation was stopped, the mean MPOD0.5 degrees 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.

Heimes B, Lommatzsch A, Zeimer M, Gutfleisch M, Spital G, Bird AC, Pauleikhoff D. · Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 Münster, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18509668 No free full text.

Abstract: BACKGROUND: Autofluorescence (AF) of the retinal pigment epithelium (RPE) are thought to reflect metabolic activity of the RPE cells, which in turn is largely driven by photoreceptor outer segment renewal. In exudative AMD, choroidal new vessels (CNV) may be confined to Bruch's membrane, or transgress the RPE, with consequence loss of photoreceptor cells. It has been suggested that they may be distinguished with autofluorescence imaging. The aim of our study was to analyze the prognostic value of RPE autofluorescence in relationship to the therapeutic outcome of anti-VEGF (vascular endothelial growth factor) therapy in exudative AMD. PATIENTS AND METHODS: AF images (Heidelberg Retina Angiograph) were obtained from 95 eyes (95 patients, mean age 77.64 years, 39 male and 56 female) with exudative macular lesions and associated drusen before therapy with intravitreal Bevacizumab (Avastin). Increased, normal, or decreased AF of a central area with diameters of 500 and 1,000 microm around the foveola were distinguished, and compared with the outcome of central vision. As a measure of data reproducibility (inter- and intraobserver variability), the kappa statistics (K > 0.6 "good", K > 0.8 "excellent") and exact agreement in % were calculated. RESULTS: Analysis of AF showed a significant difference in outcome of visual acuity in eyes with changes in AF of the central 500 and 1000 microm (Mann-Whitney test, p500 mum < 0.001, p1,000 microm = 0.02). Comparison of eyes with increased AF to the other eyes also resulted a significant difference in visual acuity at follow-up (p (incr) < 0.001); those with decreased AF had no significant difference to the eyes with normal or increased AF (p (decr) = 0.1733). CONCLUSIONS: The RPE-AF of exudative AMD lesions varies greatly. The AF differences probably represent different kinds of metabolism disorders in the RPE. Furthermore, they apparently have a great influence on the chances of anti- vascular endothelial growth factor (VEGF) therapy success; in particular the development of visual acuity is less favorable in eyes with initially increased central AF.

Lommatzsch A, Hermans P, Müller KD, Bornfeld N, Bird AC, Pauleikhoff D. · Department of Ophthalmology and Ophtha-Lab, St. Franziskus Hospital Münster, Münster, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #18414889 No free full text.

Abstract: PURPOSE: Basal 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). METHODS: BLD 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. RESULTS: The 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. CONCLUSIONS: Diffuse 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.

Cruess AF, Zlateva G, Xu X, Soubrane G, Pauleikhoff D, Lotery A, Mones J, Buggage R, Schaefer C, Knight T, Goss TF. · Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada. <> · Pharmacoeconomics. · Pubmed #18088159 No free full text.

Abstract: BACKGROUND: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. OBJECTIVE: To document the economic burden of bilateral NV-AMD, the late stage of AMD, in elderly patients, from a societal perspective. STUDY DESIGN, SETTING AND PARTICIPANTS: A cross-sectional, observational study surveyed 401 patients with bilateral NV-AMD and 471 non-AMD subjects in Canada, France, Germany, Spain and the UK. Physicians' records and subjects' standardized telephone interviews were used to record medical resource utilization, assistance with daily living and social benefits. Annual bilateral NV-AMD-related socioeconomic costs were calculated in euro, year 2005 values. MAIN OUTCOME MEASURES: Societal costs including direct vision-related medical costs (e.g. treatment of AMD and vision-related equipment), direct non-vision-related medical costs (e.g. medications) and direct non-medical-related costs (e.g. home healthcare and social services) were the main outcome measures. RESULTS: The demographic profile of NV-AMD patients was similar across countries; however, co-morbid condition profiles varied. NV-AMD patients reported substantial health-related problems and associated health resource utilization (HRU). In the previous 12 months, 12-22% of patients fell, and half of these patients required medical treatments. More than 20% (range 21-59%) of patients were prescribed vision-enhancing equipment. More than half of the patients (54-81%) were living with a spouse or family member and 19-41% reported receiving assistance for activities of daily living.The average annual societal cost per bilateral NV-AMD patient treated was estimated to be euro 7879 in Canada, euro 7349 in France, euro 12 445 in Germany, euro 5732 in Spain and euro 5300 in the UK, and direct vision-related medical costs accounted for 23-63% of the total cost. Half of the patients were diagnosed with bilateral NV-AMD for <1 year, with an average length of 5 months; there were no statistically significant differences in total annual costs per patient between these patients and those who were diagnosed with bilateral disease for > or =1 year. Estimated annual societal costs of bilateral NV-AMD patients in these countries ranged from euro 268 to euro 1311 million. Estimated annual societal costs of all NV-AMD patients in these countries ranged from euro 671 to euro 3278 million. CONCLUSIONS: Bilateral NV-AMD imposes significant functional impairment on patients, leading to increased HRU and a high societal cost burden. Differences in national healthcare systems and NV-AMD treatment patterns were reflected in the wide variation of NV-AMD costs across the five surveyed countries. Even though the prevalence rates and per-patient costs varied by country, the societal costs of NV-AMD patients were substantial in each country. Earlier intervention with effective therapies is expected to reduce disease burden and disability associated with NV-AMD and, thus, decrease the overall societal cost.

Soubrane G, Cruess A, Lotery A, Pauleikhoff D, Monès J, Xu X, Zlateva G, Buggage R, Conlon J, Goss TF. · Department of Ophthalmology, University Paris XII, Centre Hospitalier Intercommunal de Créteil, 40 Avenue de Verdun, Créteil, France. · Arch Ophthalmol. · Pubmed #17846366 links to  free full text

Abstract: OBJECTIVE: To describe the burden of bilateral neovascular age-related macular degeneration (NV-AMD) on patient-reported functioning and health resource utilization. METHODS: A cross-sectional study of 401 patients with bilateral NV-AMD and 471 elderly control subjects without AMD was conducted in 5 countries. Subjects completed a telephone survey, including the National Eye Institute 25-Item Visual Function Questionnaire, the EuroQol instrument, the Hospital Anxiety and Depression Scale, and history of falls, fractures, and health care resource utilization. RESULTS: The mean age for patients with NV-AMD was 78.1 years, and 65% were women. The patients reported 45% worse vision-related functioning, 13% worse overall well-being, and 30% more anxiety and 42% more depression symptoms than controls after adjusting for covariates (all, P < .001). The effect of NV-AMD was also observed as a doubled fall rate (16% vs 8% [P < .001]) and a quadrupled need for assistance with daily activities (29% vs 7% [P < .001]) in the patients compared with controls. CONCLUSIONS: The evidence of extensive decline in quality of life and increased need of daily living assistance for patients with NV-AMD compared with a control population substantiates the need for new treatments that prevent vision loss and progression to blindness.

Lommatzsch A, Hermans P, Weber B, Pauleikhoff D. · Department of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48145 Münster, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #17704937 No free full text.

Abstract: BACKGROUND: Complement factor H (CFH) polymorphism Y402H has been shown to be significantly associated with age-related macular degeneration (AMD). Furthermore, histopathological studies in AMD have implicated basal laminar deposits (BLD) in the development of choroidal neovascularization (CNV) membranes. The purpose of this study was to correlate CFH staining in BLD with the CFH genotype at the tyrosine 402 histidine (Y402H) polymorphism. PATIENTS AND METHODS: During macular translocation, 21 angiographically confirmed CNV membranes were extracted in 21 patients. The specimens were analysed histologically for BLD. The presence of CFH, complement proteins, and vitronectin was determined by immunohistochemistry. Finally, the CFH Y402H genotype was established by direct sequencing analysis. RESULTS: Histological examination demonstrated BLD in all of the excised CNV membranes. By immunostaining CFH was detected in the peripheral aspect at the inner and outer surface of BLD, which colocalized with other proteins of the complement cascade (C3, C5b-9). Similarly, vitronectin was detected in all of the BLD investigated. Four patients were noncarriers of CFH Y402H polymorphism, nine patients were heterozygous and eight patients homozygous for the CFH Y402H polymorphism. CONCLUSIONS: BLD are composed of different complement factors (factor H, C3, C5b-9) and extracellular matrix proteins such as vitronectin. The prevalence of homozygous carriers in regard to CFH Y402H polymorphism, which is suspicious for AMD, might be associated with increased secretion of vitronectin in response to dysregulation of the complement cascade.

Neuner B, Wellmann J, Dasch B, Behrens T, Claes B, Dietzel M, Pauleikhoff D, Hense HW. · Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany. · Ann Epidemiol. · Pubmed #17531503 No free full text.

Abstract: PURPOSE: Smoking is an established risk factor for the development of age-related maculopathy (ARM), and its end stage, age-related macular degeneration (AMD). We evaluated the benefit of various smoking-related variables in modeling the association of smoking with ARM and AMD in a mixed sample of current, former, and never smokers. METHODS: This was a cross-sectional study in participants of the Muensteraner Altern- und Retina-Studie (MARS). Participants were classified according to the Rotterdam classification system as healthy, or having ARM or AMD. Using multinomial logistic regression techniques, the association with number of cigarettes, years of smoking, pack-years and time since cessation in former smokers were evaluated. RESULTS: Mean age of the 982 participants (58.6% females) was 70.9 +/- 5.5 years. ARM was present in 483 (49.2%) and AMD in 285 (29.0%) individuals. The adjusted prevalence odds ratio (OR) in current smokers versus never smokers was 2.61 (95% confidence interval [CI] 1.34-5.09) for ARM and 3.94 (95% CI 1.91-8.14) for AMD. This effect decreased in former smokers with an OR = 0.55 (95% CI 0.33-0.99) per log-transformed time since smoking cessation for ARM and an OR = 0.52 (95% CI 0.30-0.90) for AMD. CONCLUSIONS: By including a variable for time since smoking cessation, we were able to handle current, former, and never smokers in one model that estimates the association of smoking with ARM or AMD. Logarithmical transformation of the time since smoking cessation seemed to increase the model fit and to reflect a non-linear protective effect of smoking cessation on the onset of ARM and AMD in former smokers.

Trieschmann M, van Kuijk FJ, Alexander R, Hermans P, Luthert P, Bird AC, Pauleikhoff D. · Department of Ophthalmology, St Franziskus Hospital, Münster, Germany. · Eye. · Pubmed #17401321 No free full text.

Abstract: PURPOSE: Clinical investigations have demonstrated variation in both the peak optical density and the spatial distribution of macular pigment. To confirm these impressions histologically, the present study examined the distribution of macular pigment in the human retina. MATERIALS AND METHODS: The macular retina of 11 donor eyes of different ages (28-91 years) were examined histologically on 100 microm vibratome sections directly, without further staining. Measurements were made in two dimensions: (1) adding the number of macular sections with visible macular pigment, and (2) direct measurement of the extension of macular pigment in the foveolar section, which visibly contained the most macular pigment. RESULTS: The measurements with two methods demonstrated good correlation. The macula demonstrated a variation in the spatial extension of the visible macular pigment between 200 and 900 microm diameter around the centre of the fovea, which was also found when direct measurements were taken. There was no correlation with the donor age. The main location of macular pigment was in the layer of the fibres of Henle in the fovea and in the inner nuclear layer at the parafoveal site. CONCLUSIONS: Histologically, a wide variation of the spatial distribution of macular pigment was found that confirms clinical observations. The primary localization of human macular pigment is in the inner retinal layers.

Lommatzsch A, Spital G, Trieschmann M, Pauleikhoff D. · Augenabteilung am St. Franziskus Hospital, Münster, Deutschland. · Ophthalmologe. · Pubmed #17334745 No free full text.

Abstract: Angioid streaks are the typical ophthalmological manifestation of the systemic disease pseudoxanthoma elasiticum. Fundoscopy reveals angioid streaks as irregular dark brownish lines radiating from the area around the optic disc. Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with angioid streaks. Argon-laser treatment of CNV secondary to angioid streaks shows poor results. Photodynamic therapy (PDT) with verteporfin does not seem to be an effective treatment for achieving stabilization of visual acuity and lesion size in CNV secondary to angioid streaks. Results after a combination of the intravitreal application of triamcinolone with PDT did not show the expected benefit. In the era of promising new intravitreal treatments for patients suffering from age-related macular degeneration, it is interesting to observe this effect of angiogenesis inhibitors (bevacizumab, ranibizumab, pegaptanib) in patients with neovascilarization secondary to angioid streaks. In our case, we observed a deterioration in visual acuity and leakage of the CNV after treatment with PDT alone. However, after the intravitreal injection of bevacizumab, we observed an improvement in vision, and the area of neovascularization changed into a fibrotic scar. A controlled study with long-term results is needed to definitively evaluate this kind of treatment.

Trieschmann M, Beatty S, Nolan JM, Hense HW, Heimes B, Austermann U, Fobker M, Pauleikhoff D. · Institute of Ophthalmology, St. Franziskus Hospital, and Institute of Epidemiology, University of Münster, Germany. · Exp Eye Res. · Pubmed #17306793 No free full text.

Abstract: Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to protect the retina from photo-oxidative damage. The current study investigates, in terms of MP optical density (MPOD) and serum concentrations of its constituent carotenoids, response to supplemental L and Z, and co-antioxidants. An intervention (I) group, consisting of 108 subjects (mean [+/-SD] age: 71.5 [+/-7.1] years), of which 92.6% exhibited features of age-related macular degeneration (AMD), received a daily supplement consisting of 12 mg L and 1 mg Z, both provided as ester 120 mg vitamin C, 17.6 mg vitamin E, 10 mg zinc, 40 microg selenium (Ocuvite Luteintrade mark) for a period of 6 months. MPOD was measured, by 2-wavelength autofluorescence (AF), on five occasions during the period of supplementation, and once again 3 months following discontinuation of the supplement. A control (C) group of 28 subjects (mean [+/-SD] age: 71.0 [+/-8.1] years), who received no dietary supplementation or modification, was examined at baseline and once again after a mean of 29.4 (+/-9.3) weeks. At baseline, mean (+/-SD) MPOD (at 0.5 degrees) was 0.504 (+/-0.197) and 0.525 (+/-0.189) in the I and C groups, respectively. There was a statistically significant increase in MPOD (at 0.5 degrees) for the I group (0.1 [+/-0.009]; p<0.0008), whereas no significant increase was seen in the C group (0.03 [+/-0.02]; p>0.05), over the period of supplementation. In order to classify supplemented subjects into quartiles, in terms of MPOD response, we calculated the difference between MPOD (at 0.5 degrees) at visit 6 and at baseline (visit 1). Quartile 1 (the "non-responder" quartile) displayed no increase in MPOD (at 0.5 degrees), in spite of rises seen in serum concentrations of L and Z. The three "responder" quartiles reached similar final plateaus of MPOD (at 0.5 degrees), reflected in final mean (+/-SEM) values of 0.59 (+/-0.04) optical density unit (ODU), 0.64 (+/-0.03) ODU and 0.64 (+/-0.03) ODU for quartiles 2, 3 and 4, respectively. Subjects with low baseline MPOD were more likely to exhibit a dramatic rise in MPOD, or to exhibit no rise in MPOD, in response to supplements than subjects with medium to high baseline MPOD values. Supplementation with 12 mg L and 1 mg Z, combined with co-antioxidants, resulted in an increase of MPOD at 0.5 degrees eccentricity in a majority of subjects, including those afflicted with AMD. However, there remains a substantial proportion of subjects for whom, in spite of rises in serum concentrations of L and Z in these subjects, MPOD augmentation in response to supplemental L, Z and co-antioxidants could not be detected over the study period, thus indicating that intestinal malabsorption of these carotenoids is not responsible for the lack of a macular response to such supplements. Further, our results suggest that saturable mechanisms play a role in the retinal capture and/or stabilisation of the macular carotenoids.

Gutfleisch M, Spital G, Mingels A, Pauleikhoff D, Lommatzsch A, Heiligenhaus A. · Department of Ophthalmology, St Franziskus Hospital, Hohenzollernring, Muenster, Germany. · Br J Ophthalmol. · Pubmed #17005547 No free full text.

Abstract: OBJECTIVE: To investigate the effect of pars plana vitrectomy (PPV) in combination with intraoperative intravitreal triamcinolone acetonide injection on the course of cystoid macular oedema (CME) in patients with uveitis. METHODS: Patients with uveitis with CME (n = 19) not responding to systemic corticosteroids and/or immunosuppression combined with acetazolamide were retrospectively studied after PPV with additional intravitreal injection of 4 mg triamcinolone acetonide. Patients had chronic anterior uveitis (n = 4), intermediate uveitis (n = 9), posterior uveitis (n = 3) or panuveitis (n = 3). Visual acuity tests, tonometry, fluorescein angiographic appearance and postoperative complications were analysed. Mean follow-up was 14 months (SD 4.6). RESULTS: CME improved in 58% of the patients within the first 6 weeks postoperatively. After 12 months, CME was further improved in 44% and worsened in another 12%. Improvement of visual acuity was noted in 42% after 3 months and in 28% after 12 months. Cataract progressed in 85% of the phacic patients postoperatively. Increased intraocular pressure was detected in 27% at 2 weeks and in 11% at 12 months after surgery. CONCLUSION: Uveitic CME that is unresponsive to systemic immunosuppression and acetazolamide may improve after PPV with additional intravitreal triamcinolone application. The effect seems to be transient in many of the patients. Frequent complications were cataract formation and ocular hypertension.

Chakravarthy U, Soubrane G, Bandello F, Chong V, Creuzot-Garcher C, Dimitrakos SA, Korobelnik JF, Larsen M, Monés J, Pauleikhoff D, Pournaras CJ, Staurenghi G, Virgili G, Wolf S. · Queen's University and Royal Victoria Hospitals, Belfast, UK. · Br J Ophthalmol. · Pubmed #16929063 No free full text.

Abstract: BACKGROUND: Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)-thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT-V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. METHODS: Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. RESULTS: PDT-V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size <or=4 Macular Photocoagulation Study (MPS) disc areas (DA). The new classes of anti-angiogenic agents-namely, pegaptanib sodium and ranibizumab (the latter when peer reviewed phase III data become available) are recommended for subfoveal lesions with any proportion of classic CNV or occult with no classic CNV. For juxtafoveal classic CNV, PDT-V or anti-angiogenic therapy should be considered if the new vessels are so close to the fovea that laser photocoagulation would almost certainly extend under the centre of the foveal avascular zone. For all other well demarcated juxtafoveal lesions and for extrafoveal classic lesions, laser photocoagulation remains the standard treatment. Therapy should be undertaken within 1 week of the fluorescein angiogram on which the clinical decision to treat is based. At each follow up, fluorescein angiography should be performed and best corrected visual acuity measured as a minimum requirement. CONCLUSIONS: These recommendations provide evidence based guidance for the choice and use of non-surgical therapies for the management of neovascular AMD. Revisions of the recommendations may be required as new data become available.

Trieschmann M, Heimes B, Hense HW, Pauleikhoff D. · Department of Ophthalmology, St. Franziskus Hospital Münster, Münster, Germany. · Graefes Arch Clin Exp Ophthalmol. · Pubmed #16642363 No free full text.

Abstract: BACKGROUND: Measurement of macular pigment (MP) can be performed by analysis of autofluorescence (AF) images. These can be obtained by standard 488-nm argon-imaging alone (one wavelength, 1-Lambda) or with additional digital subtraction of a second image at 514 nm (two wavelengths, 2-Lambda). The analyses are easy to perform, and we present a comparison of both methods and investigate their reliability and repeatability. METHODS: Inter-individual variability of MP optical density (MPOD) measurements was assessed in single eyes of 120 subjects with a modified Heidelberg retina angiograph (HRA). MPOD values obtained with one (488 nm) Lambda (MPOD(1Lambda)) were compared with those obtained with two (488 nm and 514 nm) Lambda (MPOD(2Lambda)). To test the repeatability of the two methods, 20 subjects were subjected to five repeated measurements. RESULTS: Among 120 individuals, mean MPOD(1Lambda) at 0.5 degrees eccentricity was 0.59 (range 0.06-1.32), mean MPOD(2Lambda) was 0.5 (range 0.01-1.21). Apart from this systematic difference, 1-Lambda and 2-Lambda measurements at 0.5 degrees agreed well across the range of MPOD values (beta=0.964, around the fovea, a systematic difference (0.11) was accompanied by declining agreement at higher MPOD values (beta=0.669, 95% CI 0.519-0.844; R=0.48). Among 20 subjects with five repeated measurements, the reliability ratio was 0.97 for 1-Lambda and 0.94 for 2-Lambda at 0.5 degrees and 0.93 and 0.94, respectively, at a distance of 2 degrees. CONCLUSIONS: Both methods showed a high repeatability with little influence of measurement error. They agree well at the fovea centre in terms of ranking individuals according to their MPOD, but provide increasingly deviating results at a distance of 2 degrees around the fovea, probably because the 1-Lambda method, in contrast to the 2-Lambda method, cannot compensate for disruptive influences and for heterogeneous distributions of the lipofuscin fluorophores. The 1-Lambda method can be performed by standard HRA and could therefore be used for screening in multicentre studies, but only approaches the actual amounts of MP. The 2-Lambda method remains the more precise method for MPOD measurement in autofluorescence imaging.

Dasch B, Fuhs A, Behrens T, Meister A, Wellmann J, Fobker M, Pauleikhoff D, Hense HW. · Institute of Epidemiology and Social Medicine, University of Muenster, Germany. · Arch Ophthalmol. · Pubmed #16286611 No free full text.

Abstract: OBJECTIVE: To evaluate recent reports indicating that plasma levels of fibrinogen and high-sensitivity C-reactive protein (CRP) are associated with age-related maculopathy (ARM). METHODS: From the baseline examinations of the Muenster Aging and Retina Study, a cohort of 1060 subjects aged 59 to 82 years was assembled. Of these, 873 persons (82%) with bilateral gradable fundus photographs and complete data on fibrinogen, CRP, and potential confounders were included in a cross-sectional analysis. The main outcome measure was the association among fibrinogen, CRP, and ARM as assessed by multivariate logistic regression analysis. RESULTS: Fibrinogen and CRP levels were higher among participants with early and late ARM than among those without ARM. The crude odds ratios for ARM between the highest vs the lowest quartile were 1.90 (95% confidence interval [CI], 1.29-2.80) for fibrinogen and 1.43 (95% CI, 0.97-2.10) for CRP. After adjustment for cardiovascular risk factors, these odds ratios were 1.37 for fibrinogen (95% CI, 0.91-2.06) and 1.12 (95% CI, 0.73-1.73) for CRP. CONCLUSIONS: After adjustment for cardiovascular risk factors, we found no statistically significant association between fibrogen, CRP, and ARM. Therefore, our results do not indicate a role of systemic inflammation in ARM beyond what is already present owing to concurrent cardiovascular disease.