Purpose
To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older.
Design
Population-based observational registry study.
Methods
settings: Membership register of the Danish Association of the Blind, the primary admission criterion of which is best-corrected visual acuity 0.1 (20/200) or lower in a person’s better-seeing eye. study population: A total of 11 848 incident cases of legal blindness from a population of citizens aged ≥50 years numbering 1.71 million in 2000 and 1.87 million in 2010 with free access to a single-payer public health care system. main outcome measures: Incidence rates of legal blindness from AMD from 2000 to 2010.
Results
The incidence rate of legal blindness attributable to AMD in citizens aged ≥50 years decreased from 52.2 cases per year per 100 000 in 2000 to 25.7 cases per year per 100 000 in 2010, corresponding to a reduction of 50% (95% confidence interval [CI 95 ]: 45%-56%, P < .0001, adjusted for age), the bulk of the reduction occurring after 2006. The incidence of legal blindness from causes other than AMD decreased by 33% (CI 95 : 21%-44%, P < .0001), most of the reduction occurring between 2000 and 2006.
Conclusion
From 2000 to 2010 the incidence of legal blindness from AMD fell to half the baseline incidence. The bulk of the reduction occurred after the introduction of intravitreally injected inhibitors of vascular endothelial growth factor in 2006.
Age-related Macular Degeneration (AMD) is the leading cause of legal blindness in people aged 50 years and older in industrialized nations. Two categories of pharmacotherapy are available for neovascular AMD (wet AMD), namely verteporfin photodynamic therapy (PDT), introduced in Denmark in 1999, and intravitreal pharmacotherapy with inhibitors of vascular endothelial growth factor (VEGF), introduced in Denmark in 2006. Both types of treatment are available to all citizens and permanent residents in Denmark under a fully reimbursed single-payer public health care system. In addition to these therapies, the finding that a dietary supplement can reduce the risk of AMD progression, published in 2001, has led to widespread use of a specific nonprescription, nonreimbursed formulation of vitamin C and E, beta carotene, copper, and zinc in people with late-stage AMD.
Intravitreal pharmacotherapy for neovascular AMD is currently one of the most frequently performed intraocular procedures in Denmark, more than 19 500 injections having been administered per million inhabitants aged 50 years and older in the Greater Copenhagen region in 2010. While interventions against AMD may be of value across a wide spectrum of visual performance levels, the potential to prevent legal blindness is of particular interest. In this study, we examined the incidence rates of legal blindness from AMD and from causes other than AMD in the at-risk population for neovascular AMD aged 50 years and older from 2000 to 2010.
Methods
This was a population-based observational registry survey of legal blindness in the background population of persons aged 50 years and older residing in Denmark in the years 2000 to 2010. Incidence rates of legal blindness were assessed on the basis of admission records of the Danish Association of the Blind, a private national organization founded in 1911 that provides free membership, counseling, rehabilitation services, and selected social benefits for blind and visually impaired residents of Denmark and the Faroe Islands. Admission is based on an application containing signed information from an ophthalmologist including refraction, best-corrected visual acuity (BCVA), corrected near vision, visual field outlines, a diagnosis of the cause of visual impairment, and the patient’s signature. Admission requires legal blindness defined as BCVA ≤0.1 (20/200) in both eyes, tunnel vision defined as constriction to 5 degrees eccentricity or less, or homonymous hemianopia. Physicians have no formal obligation to advise patients about the option of joining the Danish Association of the Blind. Admissions where AMD was registered as the only cause or as one of several causes of blindness were included as AMD cases. Data analysis did not subdivide AMD into neovascular and atrophic forms. Demographic information about the background population was obtained from the national bureau of statistics (Danmarks Statistik).
To assess the detection rate of cases of blindness from AMD, we reviewed the charts of all patients, 2325 in total, who had received at least 1 intravitreal injection for neovascular AMD in the Greater Copenhagen region in 2010 (population ≥50 years of age: 559 085 persons in 2010) and determined the fraction of eligible patients that had sought and obtained admission to the Danish Association of the Blind.
Photodynamic therapy using verteporfin (Visudyne; QLT Pharmaceuticals, Vancouver, British Columbia, Canada) for subretinal neovascularization was first given in Denmark on September 16, 1999. Implementation followed gradually and was not subject to centralized planning. The first intravitreal injection in Denmark of a VEGF inhibitor (bevacizumab, Avastin; Genentech, Inc, South San Francisco, California, USA) was given on November 4, 2005. Pegaptanib (Macugen; OSI-Eyetech, New York, New York, USA) was approved on January 31, 2006 but largely neglected in favor of bevacizumab. Ranibizumab (Lucentis; Genentech, Inc) was approved on January 22, 2007 and officially designated by the National Board of Health as the treatment of choice for neovascular AMD in Denmark and made available under uniform treatment guidelines in a universal coverage public health system at 5 designated centers. The officially recommended regimen consists of 3 initial injections of 0.5 mg ranibizumab at 4-week intervals followed by re-treatment as needed based on monthly reexaminations including BCVA assessment, color fundus photography, and optical coherence tomography.
Statistical analyses were made using SAS software (version 9.1; SAS Institute, Cary, North Carolina, USA). Poisson regression (PROC GENMOD) was used to calculate incidence rates and incidence rate ratios with 2-tailed P values and 95% confidence intervals (CI 95 ) obtained from Wald tests. Incidence rate ratios (RR) were adjusted for age, which was treated categorically in the following groups: 50 to 59, 60 to 69, 70 to 79, 80 to 89, and ≥90 years. The population at risk was defined as the number of persons aged 50 years or older living in Denmark on January 1 in a given year.
Results
The population of Denmark, which is predominantly of Northern European ethnicity, was 5.53 million as of January 1, 2010. For this study we included inhabitants 50 years of age and older, a subpopulation that increased from 1.71 million in 2000 to 1.87 million in 2010. Throughout the decade, the proportions of persons in the oldest age groups (80−89 years and ≥90 years) were stable at 10% and 1.7% to 1.9%, respectively, of the total study population. The age group 50 to 59 years decreased from 41% to 35%, whereas the age group 60 to 69 years increased from 27% to 34%, an effect of large birth cohorts from the 1940s.
From 2000 to 2010 a total of 11 848 incident cases of legal blindness in people aged 50 years and older were admitted to the Danish Association of the Blind. Of these, 8827 (74.5%) had been diagnosed with AMD. The mean age of new cases of legal blindness during the 10-year period varied from a minimum 80.0 years in 2002 to a maximum 81.3 years in 2007 (ANOVA, P = .986; not tabulated).
The incidence rate of legal blindness from AMD in people aged 50 years and older decreased from 52.2 cases per 100 000 person-years in 2000 to 25.7 cases per 100 000 person-years in 2010, an age-adjusted incidence RR of 0.50 compared to 2000 (CI 95 : 0.44−0.55, P < .0001, Table , Figure ). The bulk of the reduction in the incidence rate occurred after 2006, the incidence rate in 2007 being 25% below the rate in 2000 (RR 0.75, CI 95 : 0.68−0.83, P < .0001, adjusted for age) with a continuous decrease in incidence rates occurring during the subsequent years ( Table , Figure ). In 2005 the incidence rate of legal blindness from AMD was 11% lower (RR 0.89, CI 95 : 0.81−0.98, P = .020, adjusted for age) than in 2000, whereas the rate in 2006 was statistically indistinguishable from the reference year ( Table , Figure ). A monotonous decrease in AMD-related blindness was seen from 2006 in all 5 health care regions in Denmark (data not shown).
| Age-Related Macular Degeneration | Other Causes | |||||||
|---|---|---|---|---|---|---|---|---|
| Year | Number of Incident Cases | Incidence Rate, Per 100 000 | Incidence Rate Ratio a (CI 95 ) | Yearly Change, a % | Number of Incident Cases | Incidence Rate, Per 100 000 | Incidence Rate Ratio a (CI 95 ) | Yearly Change, a % |
| 2000 | 896 | 52.2 | ref | — | 301 | 17.6 | ref | — |
| 2001 | 1001 | 57.9 | 1.10 (1.01−1.21) | +10.2 | 340 | 19.7 | 1.12 (0.96−1.31) | +11.8 |
| P = .23 | P = .034 | P = .16 | P = .16 | |||||
| 2002 | 1001 | 57.3 | 1.09 (1.00−1.20) | −0.79 | 376 | 21.6 | 1.23 (1.06−1.43) | +9.8 |
| P = .052 | P = .86 | P = .0079 | P = .21 | |||||
| 2003 | 957 | 54.4 | 1.04 (0.95−1.14) | −4.5 | 290 | 16.5 | 0.94 (0.80−1.11) | −23.2 |
| P = .35 | P = .31 | P = .48 | P = .0007 | |||||
| 2004 | 846 | 47.7 | 0.92 (0.81−1.01) | −12.0 | 236 | 13.3 | 0.76 (0.64−0.90) | −19.2 |
| P = .077 | P = .0068 | P = .0018 | P = .015 | |||||
| 2005 | 831 | 46.4 | 0.89 (0.81−0.98) | −2.7 | 285 | 15.9 | 0.91 (0.78−1.07) | +19.5 |
| P = .020 | P = .57 | P = .26 | P = .043 | |||||
| 2006 | 877 | 48.5 | 0.94 (0.85−1.03) | +4.7 | 232 | 12.8 | 0.73 (0.62−0.87) | −19.4 |
| P = .16 | P = .35 | P = .0004 | P = .014 | |||||
| 2007 | 711 | 39.0 | 0.75 (0.68−0.83) | −19.7 | 232 | 12.7 | 0.73 (0.61−0.86) | −1.1 |
| P <.0001 | P <.0001 | P = .0002 | P = .90 | |||||
| 2008 | 632 | 34.3 | 0.66 (0.60−0.73) | −11.7 | 265 | 14.4 | 0.82 (0.70−0.97) | +13.1 |
| P <.0001 | P = .023 | P = .020 | P = .17 | |||||
| 2009 | 594 | 32.0 | 0.62 (0.56−0.68) | −7.0 | 245 | 13.2 | 0.75 (0.63−0.89) | −8.6 |
| P <.0001 | P = .20 | P = .0009 | P = .31 | |||||
| 2010 | 481 | 25.7 | 0.50 (0.44−0.55) | −19.6 | 219 | 11.7 | 0.67 (0.56−0.79) | −11.4 |
| P <.0001 | P = .0004 | P <.0001 | P = .19 | |||||
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