Progression from Early/Intermediate to Advanced Forms of Age-Related Macular Degeneration in a Large UK Cohort: Rates and Risk Factors.

PURPOSE: To estimate rates and risk factors for progression to geographic atrophy (GA) or choroidal neovascularization (CNV) among eyes diagnosed with early or intermediate age-related macular degeneration (AMD) in clinical practice. DESIGN: Retrospective cohort analysis of a multicenter electronic medical record (EMR) database from the United Kingdom. PARTICIPANTS: Patients aged 50 years or more with diagnosis of early/intermediate AMD in at least 1 eye (the study eye) and no evidence of CNV or GA in the study eye, from 10 clinical sites using the EMR. METHODS: Anonymized data for 40 543 patients with a diagnosis of early/intermediate AMD were extracted between October 2000 and February 2016 from EMR database records held in the 10 sites. A sample of records randomly selected from each center was used to validate disease definitions. Records were analyzed by subgroup, based on the AMD status of the fellow eye. Multivariate Cox regression models identified other predictors of disease progression. MAIN OUTCOME MEASURES: Progression rate (per 100 person-years) to GA or CNV in study eyes with early/intermediate AMD by fellow eye status and identified risk factors for progression. RESULTS: Study eyes with early/intermediate AMD and a diagnosis of CNV in the fellow eye progressed to CNV fastest (at a rate of 15.2 per 100 person-years), and those with a diagnosis of GA in the fellow eye progressed to GA fastest (11.2 per 100 person-years), compared with the rates per 100 person-years of progression to CNV (3.2-11.9) or GA (2.0-7.8) in the other subgroups. In individuals with bilateral early/intermediate AMD, rates of progression to GA or CNV were 2.0 and 3.2 per 100 person-years, respectively. In the multivariate model, age, female sex, and cardiovascular disease were associated with an increased risk for progression to advanced AMD, whereas diabetes and glaucoma were associated with a decreased rate of progression (hazard ratios, 0.45 and 0.64, respectively). CONCLUSIONS: Progression to GA or CNV was observed frequently in eyes with early/intermediate AMD, with the status of the fellow eye affecting the rate of progression. Novel associations with risk factors were observed and require replication in other cohorts.

Burden of Illness in Geographic Atrophy: A Study of Vision-Related Quality of Life and Health Care Resource Use.

PURPOSE: To gain comprehensive information on the burden of illness due to geographic atrophy (GA). METHODS: This cross-sectional study with a retrospective chart review involved patients aged ≥70 years with physician-confirmed bilateral symptomatic GA due to age-related macular degeneration (GA group), as well as patients of similar age with no ophthalmic condition that in the opinion of the investigator affected visual function (non-GA group). Data relating to patients' current disease status and sociodemographics were self-reported on patient questionnaires at study entry and extracted from patient charts. Historical data on health care resource utilization (HCRU) were also collected via patient questionnaires and retrospective chart review (GA group only). Overall vision-related functioning and quality of life (QoL) were compared between the GA and non-GA groups using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) composite and subscales, and change in vision over the past year was assessed using the Global Rating of Change Scale. RESULTS: Vision-related functioning and QoL were poorer in patients with vs without GA (n=137 vs 52), as demonstrated by significantly lower NEI-VFQ-25 composite score (mean, 53.1 vs 84.5 points, respectively; P<0.001), as well as lower subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision. Substantially more patients with GA than without GA reported worsening in vision over the past year (82% vs 25%, respectively; odds ratio, 13.55; P<0.001). In the GA group, associated mean annual costs for direct ophthalmological resource use per patient amounted to €1772 (mostly for tests/procedures), and for indirect ophthalmological resource use, €410 (mostly for general practitioner visits). CONCLUSION: Patients with GA experience a poorer level of vision-related function and QoL than their peers, especially in relation to driving. GA is also associated with notable HCRU/associated costs, mostly direct costs attributed to diagnostic tests/procedures.

Direct Ophthalmic Healthcare Resource Use among Patients with Geographic Atrophy in a Large Cohort from the United Kingdom.

PURPOSE: To estimate the direct ophthalmic healthcare resource use in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). DESIGN: Retrospective analysis of anonymized data derived from electronic medical records (EMRs) acquired at 10 clinical sites in the United Kingdom. PARTICIPANTS: Patients aged ≥50 years with ≥1 eye with a clinical record of GA or, for comparison, bilateral early/intermediate AMD. Four subgroups were identified: GA in both eyes (GA:GA); GA in 1 eye, choroidal neovascularization (CNV) in the fellow eye (GA:CNV); GA in 1 eye with early or intermediate AMD in the fellow eye (GA:E); and early/intermediate AMD in both eyes (E:E). METHODS: The EMRs were analyzed to derive the median number of visits over the first 2 years after diagnosis of GA or early/intermediate AMD. Clinical tests recorded at visits were used to calculate estimated costs (payer perspective) of monitoring. Analyses were restricted to patients with an initial diagnosis on or after January 1, 2011, to represent present day monitoring and costs associated with AMD. MAIN OUTCOME MEASURES: Median number of visits and estimated monitoring costs per patient (in £) over the first 2 years among patients with ≥2 years of follow-up and in the individual subgroups. Intravitreal treatment costs in the GA:CNV group were excluded. RESULTS: For all 3 GA subgroups (n = 1080), the median number of visits over the first 2 years was 5, and monitoring costs were £460.80 per patient. The GA:CNV subgroup (n = 355) had the highest number of visits (median, 15), with a cost of £1581, compared with the GA:E subgroup (n = 283; median 4 visits; cost ∼£369) and the GA:GA subgroup (n = 442; median 3 visits; cost ∼£277). Ophthalmic tests were conducted most frequently in the GA:CNV subgroup. Visits and costs in the E:E subgroup (n = 6079) were lower. CONCLUSIONS: Resource use in patients with GA varies considerably and is strongly influenced by the concomitant presence of CNV and lack of monitoring strategies for GA.

Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration.

PURPOSE: To understand levels of disease burden and progression in a real-world setting among patients from the United Kingdom with bilateral geographic atrophy (GA) secondary to age-related macular degeneration (AMD). DESIGN: Retrospective cohort analysis of a multicenter electronic medical record (EMR) database. PARTICIPANTS: Patients who were aged ≥50 years with bilateral GA and no history of choroidal neovascularization (CNV) and who attended 1 of 10 clinical sites using the EMR. METHODS: A deidentified data set was constructed from the records held at the 10 sites. An algorithm was used to extract cases with a GA diagnosis, of which 1901 had bilateral GA and form the basis of this report. A sample of records randomly selected from each center was used to validate disease definitions. MAIN OUTCOME MEASURES: Progression to blindness (visual acuity [VA] <20 letters or Snellen 3/60 in the better-seeing eye), driving ineligibility (VA ≤70 letters or Snellen 6/12 in the better-seeing eye), progression to CNV, loss of 10 or more letters, and mean change in VA over time. RESULTS: At first record of GA, 7.1% had a VA in the better-seeing eye equal to or lower than the cutoff for blindness registration and 71.1% had a VA that would have rendered them ineligible to drive. Over time, 16% became legally blind (median time to outcome, 6.2 years) and 66.7% became ineligible to drive (median time to outcome, 1.6 years). In the worse-seeing eye, 40.1% lost ≥10 letters in 2.4 years. Among patients with baseline and 24-month VA measurements, mean VA decline was 6.1 letters in the worse-seeing eye (n = 413) and 12.4 letters in the better-seeing eye (n = 414). The rate of progression to CNV in either eye was 7.4% per patient-year. CONCLUSIONS: At initial diagnosis, based on VA in the better-seeing eye, a high proportion of patients with bilateral GA were ineligible to drive and approximately 7% were eligible for UK blindness registration. The subsequent reduction in VA that occurred in the better-seeing eye would render a further two-thirds ineligible to drive. These findings emphasize the severity of the visual disability associated with GA secondary to AMD.

Effectiveness of a risk-minimization activity involving physician education on metabolic monitoring of patients receiving quetiapine: results from two postauthorization safety studies.

Following Good Pharmacovigilance Practices Module XVI, two complementary studies were performed that included process and outcome measurements of the effectiveness of physician education on metabolic monitoring of patients receiving quetiapine. A multinational survey of 800 European Union physicians was utilized to assess the receipt of educational materials and also to assess the degree of monitoring as reported by physicians. Recall of receipt of educational materials ranged from 16.0 to 69.0% across the participating countries; however, physicians reported that 64.5% of patients were being monitored, with the majority reporting performance of three or more of four key metabolic-monitoring activities. Higher rates of monitoring were reported by those who reported receiving materials. Assessment of outcomes in a separate retrospective analysis of electronic medical record data showed lower levels of monitoring performed by specialist physicians. The monitoring activities observed were assessed as acceptable on the basis of the established performance of UK physicians, who are incentivized to deliver preventive screening.

Improvement of the microstructure and mechanical properties of bioceramic scaffolds using electrohydrodynamic spraying with template modification.

Porous scaffolds play a key role in tissue engineering (TE) approaches and new processing methods and materials are constantly being developed to cater for the wide range of specifications and requirements. Electrospraying is a relatively new processing method used for producing open-pore scaffolds. In this work, the electrospraying technique was manipulated to make the process more efficient, and the effect of spraying time on the pore size and strut thickness of zirconia scaffolds was explored. Scaffolds of adequate pore size and interconnectivity, with an average compressive strength of approximately 7.5 MPa, by electrospraying for only 10 min are reported. The effect of modifying the sacrificial template on the microstructure and mechanical properties of the sintered scaffolds was also investigated. A combination of template surface hydroxylation and improved conductivity produced a thicker ceramic coating, leading to enhanced mechanical properties.

Dipping and electrospraying for the preparation of hydroxyapatite foams for bone tissue engineering.

A novel fabrication technique, a combination of slurry dipping and electrospraying, was used to produce hydroxyapatite foams as potential matrices for bone tissue engineering applications. In this study, scaffolds that were slurry dipped and electrosprayed for different time intervals were compared with foams prepared by the individual methods of dipping and electrospraying. Significant differences in the distribution of cracks on the struts, the strut thickness and porosity were observed on the sintered foams prepared under the varied conditions. All the sintered structures had average porosities in the range 84-94% and desirable pore interconnections, while the combined method produced foams of uniform pore distribution, thicker struts and improved mechanical properties. Further improvement of the mechanical properties has also been achieved by altering the sintering conditions.

Novel preparation of graded porous structures for medical engineering.

The gradation of porosity in a biomaterial can be very useful for a variety of medical engineering applications such as filtration, bone replacement and implant development. However, the preparation of such structures is not a technologically trivial task and replication methods do not offer an easy solution. In this work, we elucidate the preparation of structures having a graded porosity by electrohydrodynamic spraying, using zirconia (ZrO2), which is widely used in biomedical and other applications. The processes are generic and can be achieved using other bioactive ceramics with similar particle characteristics. The pores on the sprayed surface, the innermost surface and lengthwise cross sections have been analysed in addition to the change in depth of penetration as a function of spraying time. Control of porosity, pore size and depth of penetration has been obtained by varying parameters such as the spraying time, sintering temperature and the sacrificial template. It has been possible to obtain structures with interconnected pore networks of pore size greater than 100microm as well as scattered pores smaller than 10microm in size.

Novel method of preparing hydroxyapatite foams.

Porous scaffolds are considered a key strategy in the concept of bone tissue engineering. Hydroxyapatite, which is a bioceramic has been used as a popular scaffold material due to its bioactive and osteoconductive properties. A combination of slurry-dipping and electrospraying has been used as a new foam fabrication method to produce porous and interconnected foam structures. The combined method has shown to overcome the shortcomings of the individual methods and it has produced open pores in the desired range of 100-350 microm. The porosity which was determined by calculation and microtomography was between 84% and 88%. Reduced cracks and thicker struts were observed in the microstructure, pointing to improved mechanical properties.