Background Although asthma does not appear to be a risk factor for severe coronavirus disease 2019 (COVID-19), outcomes could vary for patients with different asthma subtypes. The objective of this analysis was to compare COVID-19 outcomes in real-world cohorts in the United States among patients with asthma, with or without evidence of allergy. Methods In a retrospective analysis of the COVID-19 Optum electronic health record dataset (February 20, 2020–January 28, 2021), patients diagnosed with COVID-19 with a history of moderate-to-severe asthma were divided into 2 cohorts: those with evidence of allergic asthma and those without (nonallergic asthma). After 1:1 propensity score matching, in which covariates were balanced and potential bias was removed, COVID-19 outcomes were compared between cohorts. Results From a COVID-19 population of 591,198 patients, 1595 patients with allergic asthma and 8204 patients with nonallergic asthma were identified. After propensity score matching ( n = 1578 per cohort), risk of death from any cause after COVID-19 diagnosis was significantly lower for patients with allergic vs nonallergic asthma (hazard ratio, 0.48; 95% CI 0.28–0.83; P = 0.0087), and a smaller proportion of patients with allergic vs nonallergic asthma was hospitalized within − 7 to + 30 days of COVID-19 diagnosis (13.8% [ n = 217] vs 18.3% [ n = 289]; P = 0.0005). Among hospitalized patients, there were no significant differences between patients with allergic or nonallergic asthma in need for intensive care unit admission, respiratory support, or COVID-19 treatment. Conclusions Asthma subtype may influence outcomes after COVID-19; patients with allergic asthma are at lower risk for hospitalization/death than those with nonallergic asthma.

Chronic spontaneous urticaria (CSU) is a debilitating disorder that compromises quality of life. American and European treatment guidelines recommend the use of omalizumab in patients unresponsive to H1-antihistamines. Here we describe real-world effectiveness outcomes for patients with CSU treated with omalizumab in clinical practice.

RATIONALE: ACE2, a critical SARS-CoV-2 entry receptor, has reduced expression in those with allergic sensitizations. Consequently, SARS-CoV-2 infections may impact patients with allergic asthma (AA) or no evidence of allergic asthma (NEAA) differently. We explore demographics of SARS-CoV-2-infected AA and NEAA patients. METHODS: Retrospective data were obtained from the US-representative COVID-19 Optum Electronic Health Record dataset through 10/15/2020. Index was the earliest date of presumed diagnosis or laboratory-confirmed SARS-CoV-2 infection (CDC guidelines) from 02/20/2020, defined as (1) diagnosis code of U07.1/U07.2, or (2) positive diagnostic test for SARS-CoV-2, (3) diagnosis code of B97.29 without a negative molecular SARS-CoV-2 test within a 14-day window (+/-7 days). Patients SARS-CoV-2-positive with evidence of moderate-to-severe asthma at any time (ICD-10 J45.4X or J45.5X) were included. AA was defined as positive specific IgE (≥0.35 kU/L) serum test or skin prick test (code 95004) ordered by a specialist (eg, allergist, pulmonologist, dermatologist) or omalizumab use. NEAA was defined as failing to meet the AA definition and patients with allergic comorbidities were excluded. Baseline demographic and clinical characteristics were obtained 6-12 months before COVID-19 diagnosis. RESULTS: The database included 242,280 SARS-CoV-2-positive patients;569 (0.2%) had evidence of comorbid AA and 3137 (1.3%) had asthma and NEAA. For AA patients, mean (SD) age at index was 48.2 (18.2) years;70.3% were female, with 54.3% White, 26.4% Black, and 12.5% Hispanic (Table 1). Most AA patients were from the US Midwest and Northeast (80.5%). NEAA patients had similar demographics: mean (SD) age at index was 50.7 (19.5) years;67.6% female;with 60.0% White, 21.5% Black, and 13.0% Hispanic;and 81.5% were from the US Midwest and Northeast. A greater proportion of patients had severe asthma in AA versus NEAA groups (220/569 [38.7%] versus 457/3137 [14.6%]). More patients with AA versus NEAA used asthma biologic treatment (62/569 [10.9%] vs 27/3137 [0.9%]). Comorbid conditions (hypertension, diabetes, pregnancy, chronic obstructive pulmonary disease, and Charlson Comorbidity Index), body mass index, and smoking history were comparable between groups. A higher proportion of NEAA patients were current smokers. CONCLUSIONS: A smaller proportion of patients with SARS-CoV-2 infection in this retrospective analysis had comorbid AA versus NEAA, whereas patient demographics and comorbidities were generally comparable between groups. Differences included the proportion of patients with severe asthma and biologic treatment use (greater in AA), and current smoking (lower in AA). The observed lower prevalence of AA versus NEAA in SARS-CoV-2-positive patients warrants further investigation.

Food allergies effect many patients in the US. Limited literature describes the characteristics of patients with single versus multiple food allergies. It is our hypothesis that characteristics differ between these groups and sought to evaluate that from registry data.

The literature shows about 30 million Americans are affected by food allergies (FA), however, the rates of patients seeking care remain unknown. We aim to identify the prevalence of food-allergic individuals seeking care in the US.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease associated with substantial quality of life (QoL) impairment. Omalizumab has demonstrated efficacy in patients with CRSwNP. We summarize the effect of omalizumab on QoL outcomes from two replicate phase 3, randomized, placebo-controlled trials.

PURPOSE:Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered.PATIENTS AND METHODS:This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated.RESULTS:An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%).CONCLUSION:This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

Nasal polyps are associated with substantial quality of life (QoL) impairment. The 22-item sinonasal outcome test (SNOT-22) questionnaire is a widely accepted measure to evaluate the impact of chronic rhinosinusitis with nasal polyps (CRSwNP) on QoL over 4 symptom domains (nasal, otological, sleep, psychological). We examined QoL improvements using SNOT-22 total score (0–110; higher scores=greater impairment) in CRSwNP patients receiving omalizumab vs placebo in two replicate phase III, randomized, placebo-controlled, omalizumab studies, POLYP 1 and POLYP 2. Post-hoc analyses of data from POLYP 1 (n=138) and POLYP 2 (n=127) were performed. The proportion of patients achieving the minimal clinically important difference (MCID) of ≥8.9 point improvement, and adjusted mean change from baseline (95% CI) difference on SNOT-22 total score at Weeks 4, 8, 16 and 24 in omalizumab vs placebo groups are presented for the pooled POLYP 1/2 population. Safety results have been presented previously (Gevaert P, Ann Allergy Asthma Immunol 2019;123[5]:S17). Baseline mean (SD) SNOT-22 total scores were similar for omalizumab- and placebo-treated patients (59.5 [20.0]; N=134 vs 60.1 [16.7]; N=131, respectively). At each study time point, the MCID in SNOT-22 total score was achieved with omalizumab, and SNOT-22 total score improvements were greater vs placebo (adjusted mean differences [95% CI]: -9.38 [-12.78, -5.99], -13.18 [-16.99, -9.38], -15.71 [-19.67, -11.74], and -15.36 [-19.57, -11.16] at Weeks 4, 8, 16, and 24, respectively). Omalizumab-treated patients were more likely than placebo-treated patients to achieve MCID in SNOT-22 at Weeks 4 (66.7% vs 45.7%; OR=2.42; [95% CI: 1.46, 4.01]), 8 (78.2% vs 48.8%; OR=3.91; [2.27, 6.76]), 16 (79.2% vs 45.0%; OR=4.91 [2.81, 8.60]), and 24 (73.4% vs 43.8%; OR=3.66 [2.15, 6.23]). Omalizumab treatment resulted in placebo-corrected mean SNOT-22 clinically meaningful differences, with a substantially higher proportion of omalizumab-treated patients achieving a clinically important improvement in QoL.

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10 years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T. Methods: Costs of aflibercept 2.0 mg or ranibizumab 0.3 mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse. Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10 years. Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment. Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.

Uncontrolled allergic asthma is responsible for increased asthma-related health care resource utilization (HCRU). The effect of omalizumab treatment on asthma exacerbations and asthma-related HCRU was examined using data from the real-world Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) study. PROSPERO was a US-based, 48-week, multicenter, prospective, observational study. Patients aged ≥12 years with allergic asthma initiated omalizumab based on physician-assessed need. Asthma exacerbations (worsening of asthma symptoms requiring oral corticosteroids, emergency department [ED] visit or hospitalization), asthma-related hospital admissions, ED visits, and unscheduled physician's office visits at baseline and study end were compared. Of 806 enrolled patients, 801 were treated with omalizumab for a mean [SD] of 9.7 [3.4] months (median: 11.2 months). Patients were primarily female (63.5%), and white (70.3%). Asthma exacerbation data for 796 patients were available at baseline and end of study. After initiation of omalizumab, patients experienced a 74% reduction in asthma exacerbations during the study compared to the 12 months prior to study entry. The mean (SD) number of asthma-related hospital admissions, ED visits, and unscheduled physician's office visits decreased from 0.1 (0.45), 0.3 (0.77), and 0.6 (1.13) within 90 days prior to baseline to 0.06 (0.35), 0.14 (0.56) and 0.39 (0.86) after 12 months of omalizumab treatment, respectively. No new safety issues were identified. Patients in the real-world treated with omalizumab experienced meaningful improvements in asthma control (measured by mean number of asthma exacerbations) and reductions in asthma-related HCRU providing important data supporting omalizumab use.

Objective: Uncontrolled asthma is associated with considerable clinical burden and costs to payers and patients. US economic models evaluating biologics using data from clinical trials demonstrate high incremental cost-effectiveness ratios (ICERs), but the cost-effectiveness based on real-world treatment patterns is unknown. This analysis used real-world evidence to assess the cost-effectiveness of adding omalizumab to standard of care (SOC). Methods: A Markov model was applied to track patients' health states in 2-week cycles, comparing costs and treatment effects of SOC alone versus SOC + omalizumab over a lifetime (US payer perspective). Outcomes included exacerbation events, life years, quality-adjusted life years (QALYs), total costs, and an ICER. Patient characteristics, exacerbations, patient-reported outcomes, and work productivity were derived from the real-world PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab) study. Published literature informed mortality, exacerbation-related disutility, and unit costs. Sensitivity analyses assessed model robustness. Results: Over a lifetime horizon, omalizumab was associated with an increase of 2.0 QALYs at a cost of $US 148,319 in patients with uncontrolled asthma (ICER of $75,319/QALY gained) and a reduction in exacerbations of 6.0 events/patient. Accounting for responder status improved the ICER ($70,505/QALY); incorporating indirect costs further reduced the ICER. One-way and multivariate sensitivity analyses confirmed that the base case outcome was robust to variation in inputs. Conclusions: Based on real-world outcomes, omalizumab may be cost-effective for uncontrolled asthma from the US payer perspective. Including broader evidence on treatment discontinuation, caregiver burden, and oral corticosteroid reduction from real-world studies may better reflect the effects and value of omalizumab for all healthcare stakeholders.

Chronic idiopathic urticaria (CIU) is reported to have a major impact on quality of life (QOL) comparable to that experienced by patients with coronary artery disease awaiting bypass surgery. Patients with CIU often experience sleep deprivation, psychiatric comorbidity, and work-activity impairment. In the double-blind phase of the XTEND-CIU study, we explored the effects of CIU on QOL and the potential of omalizumab to improve these measures. XTEND-CIU enrolled 206 patients ≥12 years of age with CIU who were symptomatic despite standard H1 antihistamine treatment. Following a 24-week open-label period, patients were randomized to either placebo or omalizumab for an additional 24 weeks. Patients completed the following patient-reported outcome measurements: Insomnia Severity Index (ISI), Work Productivity and Activity Impairment Questionnaire (WPAI), and Generalized Anxiety Disorder 7 item (GAD-7) Scale. At baseline, patients reported severe negative effects on QOL due to CIU. During the double-blind phase (week 24 to 48), patients randomized to receive omalizumab exhibited significantly better ISI scores (mean (SD) change of 1.4 (6.0) vs. 8.8 (11.2), p<0.0001) and overall WPAI activity impairment (mean (SD) change of 6.6 (22.3) vs. 33.0 (38.0), p<0.0001) compared to placebo. Anxiety scores decreased in all patients throughout the 48-week study, and the change in mean (SD) GAD-7 was not statistically significant between groups during the double-blind period (1.19 (3.7) vs 1.65 (4.6), p=0.5360). This long-term study demonstrates that patients continuing omalizumab treatment to 48 weeks exhibited significantly better patient-reported outcomes, other than anxiety, when compared to patients withdrawing treatment after 24 weeks.

Asthma is increasingly recognized as a highly heterogeneous disease, with various asthma subtypes proposed, such as allergic or eosinophilic. It is unclear what proportion of asthma patients have overlapping allergic and eosinophilic subtypes. Our study aimed to characterize this proportion in the moderate-to-severe asthma population. Two post-hoc analyses of adult (≥18 years) asthma populations were conducted. The first analysis was conducted in a study population not selected for any subtype (non-subtype, N=1044), and the second analysis was conducted in a population selected for allergic asthma (N=1546). The percentage of overlapping/non-overlapping asthma subtypes in each study population was assessed using the following definitions: allergic asthma - a positive skin test or in vitro reactivity to an aeroallergen; and eosinophilic asthma - a blood eosinophil count ≥300 cells/μL. Baseline characteristics for the subtypes were also summarized. In the non-subtype selected population, 78.0% had allergic asthma and 39.3% had eosinophilic asthma. Among patients with allergic asthma, only 39.5% also had eosinophilic asthma, while 76.0% of patients with eosinophilic asthma also had allergic asthma. In the population selected for allergic asthma, 40.2% had eosinophilic asthma. Baseline demographics were similar between allergic and eosinophilic subtypes with respect to age, sex, smoking status, body mass index, and exacerbation history. Total IgE levels were similar between allergic and eosinophilic asthma. Predictably, eosinophil levels were higher in the eosinophilic asthma subtype compared with the allergic asthma subtype. In these large post-hoc analyses, allergic asthma was more prevalent than eosinophilic asthma. Although an overlap was observed between subtypes, a minority of patients with allergic asthma had concomitant eosinophilic asthma. The consistency of findings across populations provided robustness to the overlaps identified. This study quantified the degree of overlap between subtypes and may help payors to better understand patient populations and assist in formulary development.

Objective Geographic atrophy (GA) is a progressive, irreversible advanced form of age-related macular degeneration. There is limited information on the burden of illness of GA from patient, caregiver, and eye care professional perspectives. This study identifies key factors that should be included for assessment in future studies of patients with GA. Methods In this cross-sectional qualitative study, patients with symptomatic GA (n = 8), their caregivers (n = 6), and eye care professionals who treat patients with GA (n = 5) were interviewed at US sites. Interview guides were designed to evaluate the understanding of the disease, costs and burden of illness, use of vision aids or services, and impact on emotional or psychological well-being and on daily activities. Results Half of the patients mentioned social, psychological, or helplessness issues. Patients reported the impact of GA on sports and outdoor hobbies, meals or food preparation, religious activities, and long-distance travel. Patients reported having stopped driving or changing driving patterns as a major concern. 38% of all patients reported previously modifying their work schedules due to vision impairment. All patients reported the use of at least one vision aid, with 88% of patients purchasing the aids out of pocket. Caregivers reported modifying their schedules to provide assistance as needed and expressed frustration over their inability to improve patients’ health. Eye care professionals noted the emotional impact of vision loss, accidents, and injuries, and identified mental health as a key topic for patients with GA. Conclusions Although limited by size, this study indicates that GA has a major negative impact on patients’ and caregivers’ social functioning and health-related quality of life. This study has identified indirect resource use, including caregiving needs, and direct patient out-of-pocket costs as factors relevant to patients with GA. Future larger studies are needed to further characterize the burden of illness of GA for patients and caregivers.

Purpose: (1) To assess long-term adherence to American Diabetes Association guideline-recommended retinal screening among population with diabetes in the United States. (2) To determine factors associated with long-term adherence to routine eye screening exams.Methods: A retrospective cohort study was conducted in adult patients with diabetes identified from January 2009 to December 2010. Patients were followed until disenrollment, death, or study end date (December 2013). A patient was defined as adherent when having at least one exam in each 12-month period if there was evidence of retinopathy, or at least one exam in each 24-month period if there was no evidence of retinopathy. Multivariate logistic regressions were used to investigate patient demographics and other baseline characteristics associated with adherence to guidelines.Results: A total of 204,073 patients were identified; the mean age (SD) was 61 (13)years and 48% were female. Overall, 71.1% were adherent to the retinal screening guidelines during a median of 4.8years of follow-up including 27.7% who received an eye exam every year. Patient socioeconomic status (younger age, black race, lower income/education), less comorbidity, insulin use, higher specialist copayment plans, and proxies for poor patient behavior (lower adherence to the oral hypoglycemic agents, less diabetes education, hemoglobin A1C >9%) were associated with nonadherence to routine eye screening exams.Conclusion: During nearly 5years of follow-up, 28.9% of patients with diabetes were nonadherent to the retinal screening guidelines. Future research should focus on the development of interventions to address modifiable factors associated with nonadherence.

Chronic spontaneous urticaria (CSU) may impair work performance as it affects a young population and is a visible disease. Omalizumab rapidly improved Work Productivity and Activity Impairment (WPAI) scores during the initial open-label period of XTEND-CIU, a Phase IV randomized study of omalizumab in symptomatic patients with CSU (≥12 years). Here, we compare changes in WPAI scores between omalizumab and placebo during the double-blind period of XTEND-CIU, where placebo patients are taken off omalizumab. Responders from the 24-week open-label period subsequently entered a 24-week randomized, double-blind period (3:2 randomization omalizumab 300 mg subcutaneously every 4 weeks [n=81] or placebo [n=53]), during which patients completed the WPAI (0-100%; high scores indicate high impairment) at Weeks 24, 36, and 48. WPAI is a 6-item patient-reported outcome (PRO) tool that assesses absenteeism and activity/overall work impairment. Among 134 randomized patients (75% female, median age 46 years), the mean change (95%CI) from Week 24 to Week 48 in WPAI Activity Impairment score with omalizumab (6.6 [1.7, 11.6]) was significantly lower than with placebo (33.0 [22.6, 43.5], P<0.0001). Similarly, the mean change (95%CI) in WPAI Overall Work Impairment percent scale was significantly lower with omalizumab (1.2 [-2.6, 4.9]) than placebo (24.4 [11.1, 37.6], P=0.0001). The mean change (95%CI) in Work Time Missed from Week 24 to Week 48 was also lower with omalizumab (-0.2% [-1.5, 1.1]) than placebo (1.6% [-6.2, 9.4]). Overall Work Impairment score and Work Time Missed in the omalizumab group were similar at Week 24 and Week 48. Omalizumab responders randomized to additional 24-week omalizumab treatment sustained improvements in WPAI scores from Weeks 24 to 48. For placebo patients, who stopped omalizumab at Week 24, WPAI scores increased (worsened) by Week 48. These results highlight the long-term positive impact of omalizumab on work productivity and activity impairment.

Introduction The understanding of asthma pathophysiology has evolved over time, impacting investigation of asthma biologics. Differences in eligibility criteria amongst trials for patients with diverse asthma severity and phenotypes have resulted in relevant differences in baseline characteristics. A systematic literature review explored these differences. Methods PubMed, EMBASE, Cochrane, ClinicalTrials.gov, and conferences were searched from 2003 onwards. Randomized controlled trials (RCTs) were included with: ≥24 weeks’ duration; biologic (omalizumab [OMA]/dupilumab [DUPI]/benralizumab [BENRA]/mepolizumab [MEPO]/reslizumab [RESLI]) + daily high-dose ICS + ≥1 controller; adults ≥18 years with moderate/severe uncontrolled asthma and evidence of Type 2 inflammation (eg, blood eosinophils). Results 27 RCTs (9 OMA/3 DUPI/6 BENRA/7 MEPO/2 RESLI) were included. Overall, BENRA/MEPO/RESLI trials enrolled patients with more severe asthma than OMA/DUPI (Table 1). Per inclusion criteria, the number of prior exacerbations was higher in BENRA/MEPO versus OMA/DUPI/RESLI trials. Baseline blood eosinophil levels varied between trials, but were highest in RESLI. There was a trend towards higher baseline FEV1 in OMA/RESLI trials compared with others. Most patients received medium/high dose ICS + LABAs, with more patients in MEPO trials receiving maintenance OCS. Conclusions Transitivity, an important assumption in network meta-analysis (NMA), requires populations and study designs be sufficiently similar or have differences that can be adjusted for by accepted methods. Substantial heterogeneity in baseline characteristics existed between trials of asthma biologics and OMA. These characteristics are potential treatment effect modifiers with limited evidence for adjustment. Therefore, comparison of OMA to other asthma biologics through NMA is not clinically valid and inconsistent with best practices. Table 1. Summary of eligibility criteria and baseline patient characteristics across randomized controlled trials of biologic agents in moderate-to-severe asthma.

To compare a near decade of follow-up, newer control cohort data, use of both the societal and third party insurer cost perspectives, and integration of unilateral/bilateral therapy on the comparative effectiveness and cost-effectiveness of intravitreal ranibizumab therapy for neovascular, age-related macular degeneration (AMD).