Humanistic and Economic Burden of Geographic Atrophy: A Systematic Literature Review

Figures & data

Table 1 Clinical Trial and Observational Studies Describing the Patient Burden of Geographic Atrophy

Study, Country	Study Type and Objective	Patient Numbers and Characteristics	Instrument	Key Results	Conclusions
Ahluwalia et al (2021)^Citation23 and Ahluwalia et al. (2020)^Citation24 US	Longitudinal study (subset of patients in AREDS) of natural progression of VRQOL in GA	n=206 and n=259 patients with central GA	NEI VFQ-25	Median time to clinically meaningful decline in VRQOL (loss of 5 points) was 4.2 years	After developing advanced AMD, patients continue to experience a decline in VRQOL
Borkenstein and Borkenstein (2020)^Citation28 Austria	Observational study of patients with GA undergoing magnifying cataract surgery	N=11 patients with GA	Questionnaire listing 10 routine activities	10 of 11 patients reported limitations in their ability to complete routine activities (from the list of reading, recognizing photos, eating and cooking, operating a telephone, daily hygiene rituals, brushing teeth, cutting nails, operating household appliances, manual work, and use of low-vision aids)	Patients with GA are limited in their activities of daily living
Carlton et al. (2019)^Citation27 UK	Focus group study to determine impact of GA on daily activities	N=9 patients with GA	Focus group discussion	The overarching themes identified were experience of symptoms and understanding of GA, impact on activities, feelings and emotions, relationships and informal support, accessing formal support, and information needs	GA impacts many activities of daily living, and patients also experience emotions such as fear, frustration, and worry about loss of independence
Higgins et al. (2020)^Citation30 UK	Study to investigate performance in novel computer-based tasks in individuals with non-neovascular AMD	n=11 individuals with no macular disease n=16 individuals with nAMD n=22 individuals with GA	N/A	Participants with GA recorded slower response times for performing visual searches for everyday objects and had fewer correct responses; >50% performed outside the normal limit for task performance	Increasing severity of disease was associated with longer response time and fewer correct responses
Rohart et al. (2008)^Citation29 France	Prospective study investigating the effects of cataract surgery of visual functioning	Subgroup (n=12) with GA and neovascularization (advanced AMD)	VF-14	The mean preoperative VF-14 score was 44/100 in postoperative patients (Note lower score indicated worse visual functioning)	Patients with GA and neovascularization had impaired visual functioning even after removal of the cataract
Sunness et al. (2008)^Citation31 US	Natural history study of GA conducted 1992–2000 Objective was to investigate reading difficulties and progression of reading rates and VA	156 patients with GA who had VA of 20/50 or better (logMAR VA <0.46) in one or both eyes with GA Patients had scotomas with central sparing	NA	Reading speed was affected by the type of GA in patients with scotomas in the central field, but with central sparing that was partially or completely surrounded by scotomas	Reading speed is affected by GA
Sunness et al. (2008)^Citation32 US	Natural history study of GA conducted 1992–2000 Objective was to show that low-luminance visual dysfunction is predictive of subsequent VA	Subset of 91 patients with GA who completed a 2-year study examination	NA	LLVA deficit at baseline and reading rate were found to be a significant risk factor for subsequent loss of VA (relative risk, 2.43 [95% CI, 1.11–5.31])	Patients with GA can experience LLVA and low reading rate
Burguera-Giménez et al. (2020)^Citation21 Spain	Observational study to evaluate visual function in GA versus healthy eyes	Total 63 eyes GA: 32 Healthy: 31 Age, mean (SD), y GA: 78.53 (8.11) Control: 65.42 (7.86)	NEI VFQ-25	In the GA group, there were moderate and strong correlations between the following and the VFQ-25 composite score: Maximum reading speed (r=0.787; P<0.01) Contrast sensitivity spatial frequency 3 cpd (r=0.0441; P<0.05) Macular sensitivity (r=0.484; P<0.05) Atrophic area (r=−0.689; P<0.01) Reading speed, contrast sensitivity, fixation, and macular sensitivity were strongly associated with VRQOL	There was a decrease in composite score and significant reduction in all subscales tested in the GA group versus the control group (P ˂ 0.01) The decreased visual function was reflected in poor QOL in patients with GA
Künzel et al. (2020)^Citation38 Germany	Longitudinal study of VRQOL in GA secondary to AMD and in relation to visual function and structural biomarkers (Directional Spread in Geographic Atrophy Study, NCT02051998)	Cross-sectional: 87 patients with GA secondary to AMD Age, mean (SD), y: 77.07 (7.49) Longitudinal: 66 patients with GA Median (IQR) 2 (2) visits followed-up for 1.08 (0.78) y	NEI VFQ-25	In the multivariate cross-sectional analysis, predictors of VRQOL composite score were BCVA, GA lesion size, and LLVA for the better eye and BCVA, foveal sparing status, and LLVA for the worse eye The multivariate longitudinal analysis showed that the LLVA of both eyes, the reading acuity of both eyes, and the BCVA, GA lesion size, and foveal sparing status of the better eye were important predictors of the VRQOL composite score. Similar results were obtained for the near and distant vision subscales	For clinical trials designed to prove benefits in VRQOL, treatment should be allocated to the better eye. The cross-sectional and longitudinal association of VRQOL with visual functional and structural biomarkers supported the validity of the NEI VFQ-25 VRQOL.
Orr et al. (2016)^Citation39 US	To assess the effects of impaired visual acuity associated with GA (baseline scores in a Phase 1/2 study)	N=32 patients with moderate to severe GA secondary to AMD: 53% female Age, mean (SD), y: 81 (7) Maximum reading speed in treated eye, mean (SD): 32 (35) words per minute GA area 16 (SD 9) mm	NEI VFQ-25	At baseline, there were decrements in many subscales. The lowest scores were these: General vision (eyesight) Near activities (difficulty with close-up activities) Role difficulties (impact in ability to accomplish tasks and activity limitations) Driving (for those patients still driving)	GA negatively affects HRQOL, with decrements in many areas
Patel et al. (2020)^Citation22 UK, Canada, Germany, Ireland	Cross-sectional study to compare vision-related functioning and QOL in patients with GA due to AMD versus control group	GA group (n=137): patients aged ≥70 y with physician-confirmed bilateral symptomatic GA Non-GA group (n=52): patients of similar age with no ophthalmic condition that in the opinion of the investigator affected visual function	NEI VFQ-25	Vision-related functioning and QOL were worse in patients with GA vs patients without GA: significantly lower composite score (mean, 53.1 vs 84.5 points; P<0.001) and lower subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision General health was similar between groups GA group vs non-GA group: more patients reported worsening in vision over the past year (82% vs 25%; odds ratio, 13.55; P<0.001) Driving: 55% of patients with GA had a driver’s license, but 52% of these patients did not drive during the day and most (88%) did not drive at night. Eyesight was reported as the most common reason for giving up driving in the GA group (81%)	Patients with GA experience a poorer level of vision-related function and QOL than controls (their peers), especially in relation to driving
Patnaik et al. (2019)^Citation40 US	Cross-sectional study to measure VRQOL in patients with AMD (including GA)	n=594 patients Patient categories: Early/intermediate AMD (n=207) Advanced nAMD (n=113) GA (n=95) Advanced nAMD in one eye and any-stage dry AMD in the other (both) (n=179) Controls (n=306)	NEI VFQ-25	Composite scores were highest in patients with early/intermediate dry AMD (90.2), followed by controls (83.1), patients with both (81.7), GA (77.0), and advanced nAMD (72.1) had the lowest overall mean scores Typically, patients with early/intermediate AMD and controls had higher scores compared with the three advanced AMD groups, particularly nAMD and GA The greatest differences between groups were seen in subscales of mental health, role limitations, dependency, and driving. Lower discrepancies were observed in subscales of general health, general vision, social functioning, color vision, and peripheral vision	Composite scores for patients with GA and advanced nAMD were much lower (worse) than for patients with earlier disease
Patnaik et al. (2020)^Citation20 US	Cross-sectional study to measure visual function and VRQOL in patients with AMD (including GA)	N=739 Patient categories: Early/intermediate AMD (n=294) Advanced nAMD (n=168) nAMD with GA (n=162) GA (n=115) Patients were stratified into unilateral and bilateral disease	NEI VFQ-25	Composite scores were highest in patients with early/intermediate AMD and lowest in patients with bilateral disease that included GA In general, this pattern of scores persisted across subscales The lowest score was for driving in the group of patients with bilateral advanced disease that included GA	Large differences in visual function were seen across different AMD groups and number of eyes affected with AMD Patients with bilateral disease that included GA had the lowest scores for visual functioning and VRQOL
Singh et al. (2019)^Citation5 US	Cross-sectional qualitative study to understand the burden of illness of GA from patient, caregiver, and eye care professional perspectives	Patients with symptomatic GA (n=8), their caregivers (n=6), and eye care professionals (n=5)	Semi-structured interview	The following areas were affected: Patients: Social and psychological factors, helplessness, impact on sports/hobbies, meals or food preparation, religious activities, and long-distance travel. Stopping driving or changing driving patterns was a major concern. 38% of patients modified work schedules due to vision impairment. Caregivers: Modification of schedules, frustration at inability to improve patient’s condition Clinicians: Emotional and mental impact of vision loss, accidents, and injuries	GA has a major negative effect on patients’ and caregivers’ social functioning and HRQOL
Sivaprasad et al. (2019)^Citation25 US, UK, Germany	Cross-sectional ethnographic observational study conducted to understand the impact of bilateral GA on daily functioning	Trained ethnographers visited the patients in their home environment to contextualize their lived experience through discussion (interviews) and observation N=16 Age, mean (SD), y: 80 (7.3) Female, n=10 (62.5%); male, n=6 (37.5%)	NEI VFQ-25 and semi-structured interview guide with questions on daily routine and challenges faced due to visual function deterioration	Interview: Functional impact domains affecting 2 or more patients: Activities of daily living: difficulty reading (n=16); driving (n=12); and watching movies, television, or theatre (n=11) Emotional: frustration (n=7) and fear of blindness (n=7) Social/leisure: interference with hobbies such as playing cards, sewing, playing golf, birdwatching, taking photographs, and woodworking (n=8) and diminished social activities (n=4) Physical: walking into things, tripping or falling (n=4) Financial (n=10) Patients also reported loss of independence (n=9), difficulty recognizing faces (n=10), and difficulty performing household activities such as chores and cooking (n=10). The mean (SD) NEI VFQ-25 composite score was 67 (17) on a scale of 0 (worst) to 100 (best); a mean score of <60 was obtained for general vision and both near and distance activities; mean (SD) driving score was the lowest at 22 (32).	All patients reported that GA affected activities of daily living, particularly reading; driving; watching television, movies, or theatre; recognizing faces; and performing household activities. Most patients also reported financial and social impacts
Wang et al. (2015)^Citation41 Country not reported	A randomized, double-masked, placebo-controlled trial to assess baseline patient-reported visual function for patients with GA entering a clinical study and association between BCVA and GA lesion size	N=191 Age, average (SD), y: 77.2 (8.6) Lesion area, average (SD), mm: 7.7 (4.6) BCVA, average (SD), letters: 62.7 (14.8)	NEI VFQ-25	Mean scores at screening showed a relationship with worsening BCVA and larger GA area The most significant decrements in composite and 6 subscale scores occurred between the >20/40 and 20/40–20/80 subgroups	Patients with GA have significant impairment in many aspects of visual function. The decrement in function is greater during early vision loss and as GA lesion size crosses a median value of 6.6 mm^2.

Abbreviations: AMD, age-related macular degeneration; AREDS, Age-Related Eye Disease Study; BCVA, best corrected visual acuity; cpd, cycles per degree; GA, geographic atrophy; HRQOL, health-related quality of life; IQR, interquartile range; LLVA, low-luminance visual acuity; logMAR, logarithm of the minimum angle of resolution; NA, not applicable; nAMD, neovascular age-related macular degeneration; NEI VFQ-25, National Eye Institute Visual Function Questionnaire; QOL, quality of life; SD, standard deviation; UK, United Kingdom; US, United States; VA, visual acuity; VF-14, Visual Function Index 14; VRQOL, vision-related quality of life.

Figure 1 All-cause health care resource use (first year) by patients with GA in the United States.

Notes: Study captured all-cause RU and specific contributing factors to the economic burden of GA, and differentiators between severity levels were not explored. Costs have been adjusted to 2020 US dollars. Data from Kim A³⁴.

Abbreviations: ED, emergency department; GA, geographic atrophy; RU, resource use.

Figure 2 Median monitoring costs over 2 years across GA subgroups.

Notes: Patients with GA in the study eye and GA (GA:GA), choroidal neovascularization (GA:CNV), or early/intermediate AMD (GA:E) in the fellow eye, and patients with bilateral early/intermediate AMD (E:E). Costs applied per visit were $153.63 (relating to Healthcare Resource Group service code 130: Ophthalmology; average unit cost) for a standard monitoring visit and $190.94 (relating to Healthcare Resource Group cost code BZ88A; average unit cost) for a retinal tomography visit. Estimated median costs do not include treatment costs (eg, anti-VEGF plus injection). Patients were identified in the electronic medical record system from 10 clinical sites in the United Kingdom. Analyses were restricted to patients with the year of the index date being on or after January 1, 2011, and who underwent ≥2 years of follow-up. Costs have been adjusted to 2020 US dollars. Data from Chakravarthy et al³.

Abbreviations: GA, geographic atrophy; IQR, interquartile range; NR, not reported; VEGF, vascular endothelial growth factor.

Figure 3 Medical and nonmedical resource utilization in the geographic atrophy group.

Notes: Mean (standard deviation) values are based on nonmissing values. ^aFor each patient, a cost was calculated for each test/procedure or treatment per period. Costs were adjusted if the patient had <24 months of history. Costs have been adjusted to 2020 US dollars. ^bThe unit cost per prescription was defined as the mean cost of all available prescriptions for each treatment, regardless of use. For Canada, a cost per pill was collected for amoxicillin, and because it is generally prescribed for depression with along duration of treatment, costs for its use were calculated for 6 months of treatment with aposology of one pill perday. ^cOnly one piece of equipment per period was considered to calculate the cost of vision-related equipment. Because the cost of reading aids was very different between the United Kingdom and Germany, the cost collected in the United Kingdom was applied to Germany. Data from Patel et al²².

Abbreviation: NR, not reported.

Figure 4 Annual loss to the US gross domestic product due to GA or drusen ≥125 μm in diameter.

Notes: Details on dry AMD not specified in the article. Results are pooled for GA and dry AMD with drusen ≥125 μm and thus should be interpreted with caution. Costs have been adjusted to 2020 US dollars. Data from Brown et al³⁷.

Abbreviations: AMD, age-related macular degeneration; GA, geographic atrophy; US, United States.

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