Macular Degeneration: Zlateva G

Cruess AF, Zlateva G, Pleil AM, Wirostko B. · Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada. · Acta Ophthalmol. · Pubmed #18577193 No free full text.

Abstract: Photodynamic therapy (PDT) with verteporfin has been used less comprehensively in the treatment of exudative age-related macular degeneration (AMD), and specifically of choroidal neovascularization (CNV), since the advent of antiangiogenic therapies. Recently, there has been a renewed interest in PDT as an adjunct to these and other agents in the treatment of neovascular AMD. In light of this new development and the European Medicines Evaluation Agency's (EMEA) recent labelling decision to rescind approval for the use of PDT in occult CNV lesions, the present systematic review was undertaken to revisit the evidence supporting its clinical application. Photodynamic therapy provided the first pharmacological treatment for patients suffering from subfoveal CNV, the major cause of severe vision loss in AMD. Key clinical trials evaluating efficacy and safety have examined patients with all lesion subtypes, with the primary labelled indication (i.e. lesions containing a classic component of > or = 50% ) deriving from the results of the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study. The subsequent TAP Study Group post hoc categorization of lesions as predominantly classic is open to question, however, as it appears that the overall efficacy in this group only may have reflected the especially strong response in 100% classic lesions. Based on a subgroup analysis of the Verteporfin in Photodynamic Therapy Study, the indication for PDT subsequently was expanded in some jurisdictions, including that of the EMEA, to include occult lesions with no classic component. However, the subsequent Visudyne in Occult Study found no benefit in 100% occult lesions, resulting in the EMEA rescinding its approval for this indication.

Wong TY, Wong T, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K, Probst C, Sledge I. · Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia. · Ophthalmology. · Pubmed #17675159 No free full text.

Abstract: PURPOSE: To describe the natural history and progression of visual loss in eyes with untreated neovascular age-related macular degeneration (AMD). DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Four thousand three hundred sixty-two untreated neovascular AMD patients from published interventional studies. METHODS: A systematic review of the literature from 1980 to August 2005 was performed. Studies reporting disease progression outcomes for untreated patients with neovascular AMD were included. Outcome measures were summarized using simple counts and means. Random effects meta-analyses were conducted and tests of heterogeneity were performed where appropriate. MAIN OUTCOME MEASURES: Changes in visual acuity (VA) loss, development of comorbidities, and fellow eye involvement. RESULTS: Fifty-three primary studies were included. Nearly half of the studies (28) were randomized clinical trials. The quality of the studies was high, with over 80% providing level I or II evidence. Mean baseline VA among study patients was 0.64 logarithm of the minimum angle of resolution (logMAR) (approximately 20/87 Snellen). The mean VA change in logMAR progressed from 0.1 (1 line lost) at 3 months to 0.3 (2.7 lines lost) after 12 months and 0.4 (4 lines lost) after 24 months. The proportion of patients who developed severe vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% by 3 years. The proportion of patients with VA worse than logMAR 1.0 (20/200 Snellen) increased from 19.7% at baseline to 75.7% by 3 years. Neovascular AMD developed in the fellow eye in 12.2% of patients by 12 months and in 26.8% by 4 years. Meta-analyses of vision outcome by subtype of neovascular AMD were not possible. CONCLUSIONS: A doubling of the visual angle of presenting VA may be expected to occur in the year after initial presentation in eyes with untreated neovascular AMD. No conclusions can be drawn as to the differences in rates of disease progression by neovascular AMD subtype. The diversity of reporting formats, paucity of long-term natural history data, and heterogeneity among the reported clinical studies impose limits to the clear understanding of long-term prognosis for visual function in neovascular AMD.

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.

Ruiz-Moreno JM, Coco RM, García-Arumí J, Xu X, Zlateva G. · University of Castilla La Mancha, Albacete, Spain. · Curr Med Res Opin. · Pubmed #18547463 No free full text.

Abstract: BACKGROUND: The burden of illness, including health resource utilization and costs associated with bilateral neovascular age-related macular degeneration (Nv-AMD), was assessed in Spain. PATIENTS AND METHODS: As part of an international prospective, case-controlled study, 89 Spanish patients with bilateral Nv-AMD were recruited by retina specialists and 96 Spanish control subjects were recruited by general practitioners and ophthalmologists. Physicians recorded clinical data and visual acuity (VA). In a subsequent telephone interview, Nv-AMD patients and controls completed the National Eye Institute Visual Function Questionnaire (NEI VFQ)-25, the EuroQol (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS) questionnaire. Annual vision-related and non-vision-related medical costs and non-medical-related costs were calculated from study-specific questions. RESULTS: The mean age was 76.2 years for Nv-AMD patients and 61.9 years for control subjects. The adjusted mean (95% CI) NEI VFQ-25 summary score was 51.9 (48.5; 55.4) for Nv-AMD patients and 87.7 (85.5; 89.9) for control subjects (p<0.05). The summary score of Nv-AMD patients decreased significantly with VA declination. Mean direct vision-related medical and non-medical-related costs were significantly greater for Nv-AMD patients than the control subjects, whereas non-vision-related medical costs were similar between groups. The total mean annual resource utilization cost was euro5733 for Nv-AMD patients compared to euro1070 for control subjects (p<0.0001). CONCLUSIONS: Although the study design is subject to a number of limitations, patients with Nv-AMD in Spain have worse quality of life outcomes, greater depression, and higher healthcare costs as compared with similarly-aged individuals who are not affected by this disease.

Soubrane G, Zlateva G, Xu X, Buggage R, Kosa M. · Département d'Ophtalmologie, Université Paris XII Créteil, Centre Hospitalier Intercommunal de Créteil, France. · J Fr Ophtalmol. · Pubmed #18401314 links to  free full text

Abstract: OBJECTIVE: To assess the impact of bilateral neovascular age-related macula degeneration (NV-AMD) on function and health resource utilization (HRU) in France. PATIENTS AND METHODS: Cross-sectional study including 401 NV-AMD patients and 471 controls conducted in five countries in 2006. In both groups, demographic and clinical data were collected and the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQoL (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), and questionnaires on HRU were administered. RESULTS: Eighty-seven NV-AMD patients and 92 controls were recruited in France. The mean age of the NV-AMD patients was 79 (range, 65-95), and 64% were female. After adjusting for age, gender, and co-morbidities, compared to controls, NV-AMD patients reported substantially worse vision-related quality of life on the NEI-VFQ (adjusted mean, 44.4 [36.2-52.7] versus 91.8 [86.2-97.5], p<0.0001). HADS anxiety and depression scores were significantly worse in NV-AMD patients (anxiety score, 8.5 [6.3-10.8] versus 5.1 [3.5-6.7] p=0.0005; depression score: 7.1 [5.1-9.1] versus 2.9 [1.5-4.4] p<0.0001). Per patient yearly cost analysis showed significantly higher direct medical costs: 3396 euro versus 85 euro (p<0.0001), and indirect nonmedical-related costs (mainly for assistance with activities of daily living): 2985 euro versus 494 euro (p=0.014). CONCLUSIONS: NV-AMD patients in France reported substantially worse QoL and more anxiety and depression symptoms. The functional impact of blindness led to significantly higher health resource utilization in the AMD patients, resulting in higher total health costs compared to a similarly aged control group.

Arias L, Armadá F, Donate J, García-Arumí J, Giralt J, Pazos B, Piñero A, Martínez F, Mondéjar JJ, Ortega I, Zlateva G, Buggage R. · Department of Ophthalmology, Bellvitge University Hospital, Barcelona, Spain. · Eye. · Pubmed #18202712 No free full text.

Abstract: Purpose: To assess the impact on visual acuity of delays between diagnosis and treatment in patients with subfoveal neovascular age-related macular degeneration (NV-AMD) and to evaluate NV-AMD patients' emotional status before therapy initiation. METHODS: This retrospective, multicenter, epidemiological study included newly diagnosed NV-AMD patients registered in the Spanish national health system and referred to regional health centers for evaluation/treatment by a retinal specialist from 09/2005 to 03/2006. Records were reviewed and data abstracted at referring physicians' offices (diagnosis visit) and regional health centers (treatment visit). Treatment was at physicians' discretion. The Hospital Anxiety and Depression Scale was administered at the treatment visit (before therapy). RESULTS: Median time from the diagnosis to treatment visit was 2.3 months (95% confidence interval: 0.2-10.8 months). Vision loss had progressed at the treatment visit with a doubling in the percentage of patients with a visual acuity of 20/400 or worse (from 12.4 to 24.7%). The decrease in visual acuity from the diagnosis to the treatment visit was highly statistically significant (P<0.0001) as was the correlation between months to treatment and visual acuity change (r=0.5234, P<0.0001). Time from the diagnosis to the treatment visit remained a significant predictor of progressive vision loss when visual acuity at diagnosis and change in lesion size between diagnosis and treatment were controlled (P<0.0001). Patients with more severe vision loss prior to treatment tended to report more depression. CONCLUSIONS: Delayed treatment of patients newly diagnosed with NV-AMD is associated with substantial visual acuity loss.

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.

Cruess A, Zlateva G, Xu X, Rochon S. · Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, NS. · Can J Ophthalmol. · Pubmed #18026200 links to  free full text

Abstract: BACKGROUND: Age-related macular degeneration (AMD) is a retinal disease affecting more than 2 million Canadians over the age of 50. The neovascular form of AMD is responsible for 90% of severe vision loss associated with the disease. This study was conducted to assess the burden of neovascular AMD in the Canadian population. METHODS: A cross-sectional, observational study was conducted of self-reported functional health, well-being, and disease burden among elderly subjects in Canada with (n = 67) and without (n = 99) neovascular AMD. Subjects completed telephone surveys of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), the EuroQol questionnaire (EQ-5D), and the Hospital Anxiety and Depression Scale (HADS). Subjects also reported their history of falls and fractures and annual health care resource utilization. RESULTS: Subjects with neovascular AMD reported significantly worse vision-related functioning and overall well-being than controls (adjusted mean scores on the NEI-VFQ-25: 48.0 vs. 87.5; p < 0.0001) and significantly more depression symptoms than controls (HADS depression: 5.8 vs. 4.3; p = 0.037). Subjects with neovascular AMD also reported more than twice the need for assistance with daily activities compared with controls (19.4% vs. 9.1%; p = 0.013) and a nearly 3 times higher fall rate than the control group (22.4% vs. 8.1%; p = 0.014). The annual neovascular AMD cost per patient was Can dollars 11,334, which is over 8 times that of elderly subjects without neovascular AMD (Can dollars 1,412). Over half of the neovascular AMD costs were direct medical costs. INTERPRETATION: Neovascular AMD is associated with significant limitation in functional abilities and quality of life, resulting in increased health care resource utilization and high patient support costs. These findings emphasize the need for new treatments for neovascular AMD that will prevent vision loss and progression to blindness in order to lessen the ensuing economic burden.

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.

Leys A, Zlateva G, Shah SN, Patel M. · Department of Opthalmology, University Hospital Leuven, Leuven, Belgium. · Eye. · Pubmed #17585313 No free full text.

Abstract: PURPOSE: To assess the impact of treatment with pegaptanib sodium vs usual care on vision-related quality of life (VRQoL) in patients with age-related macular degeneration (AMD). METHODS: VRQoL was a secondary end point in the trial, a prospective, randomized, double-masked, multicentre, dose-ranging study. Three doses of pegaptanib (0.3, 1, and 3 mg) were compared with usual care with respect to changes in VRQoL as indicated by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25), administered at baseline and weeks 30 and 54. Four of the NEI-VFQ 25 domains were prospectively designated as primary: near vision, distance vision, role limitations, and dependency. Between-group differences were assessed using an analysis of covariance model with age, gender, and baseline score as covariates. RESULTS: NEI-VFQ 25 data were available for 569 subjects. At week 54, improvements in the distance vision and role limitations domains were greater in pegaptanib than usual care arms. No substantial increase in ocular pain was noted in pegaptanib-treated patients. No clear superiority of any particular dosage strength of pegaptanib was demonstrated, and no significant differences or trends favoured usual care on any domain score or the NEI-VFQ 25 composite score. The greatest VRQoL benefit was seen in responders (lost<3 lines) to treatment. CONCLUSION: The VISION trial provided evidence of trends in quality-of-life benefit associated with effective treatment of AMD using pegaptanib. Treatment with pegaptanib is expected to contribute significantly to VRQoL improvement for responder patients.