Prevalence of geographic atrophy in Nordic countries and number of patients potentially eligible for intravitreal complement inhibitor treatment: A systematic review with meta‐analyses and forecasting study

We systematically reviewed the literature on the prevalence of geographic atrophy (GA) in Nordic populations, conducted meta‐analyses on age‐stratified estimates, and calculated current and future number of patients and those potentially eligible for intravitreal complement inhibitor treatment. We followed the PRISMA guidelines, and our protocol was registered in PROSPERO. Ten databases were searched on 22 April 2023 for population‐based studies of GA prevalence. Based on clinical descriptive analyses of GA and eligibility criteria of the phase III studies for intravitreal pegcetacoplan (complement C3 and C3b inhibitor), we were able to calculate the proportion of patients with GA potentially eligible for therapy. Finally, we extracted population data for Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, applied prevalence statistics to the extracted census and forecasting data to estimate the number of patients with GA, and then applied the proportion eligible for intravitreal pegcetacoplan therapy. We identified six studies with a total of 10 159 individuals. Prevalence of GA was estimated to 0.4% (95% confidence intervals [CI]: 0.2%–0.8%), 1.5% (95% CI: 0.7%–2.6%), and 7.6% (95% CI: 4.6%–11.3%) for individuals aged 60–69, 70–79, and 80+ years, respectively. In Nordic countries, we estimate a total of 166 307 individuals with GA in 2023, increasing to 277 893 in 2050. Of these, 90 803 individuals in 2023, increasing to 151 730 in 2050, are potentially eligible for intravitreal complement inhibitor treatment. Considering these large numbers, our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing.


| I N T RODUC T ION
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly of the developed world (Flaxman et al., 2017).Early features of AMD include the presence of drusen and changes in the retinal pigment epithelium (RPE) (Fleckenstein et al., 2021).Clinically, a distinction is made between early AMD, which is defined by the presence of moderate-sized drusen (63-125 μm) and no RPE changes, and intermediate AMD, which is defined by the presence of large drusen (>125 μm) or RPE changes (Fleckenstein et al., 2021).These early features of AMD only provide subtle if any visual symptoms (Bjerager et al., 2023;Fleckenstein et al., 2021).In contrast, progression of disease to late AMD often leads to significant visual symptoms (Bjerager et al., 2023;Fleckenstein et al., 2021).In neovascular AMD, the development of macular neovascularization leads to exudative changes and subretinal fibrosis (Fleckenstein et al., 2021).Fortunately, neovascular AMD can be treated with intravitreal administration of vascular endothelial growth factor inhibitors (anti-VEGF), which lead to stabilization of the vision in the majority of cases (Brynskov et al., 2020;Ferløv Baselius et al., 2021;Haji et al., 2023;Subhi & Sørensen, 2017).Another subtype of late AMD is geographic atrophy (GA).In GA, a slow and progressive development of geographically demarcated areas of atrophy in the outer retina and the RPE leads to significant loss of visual acuity and visual function (Fleckenstein et al., 2021).Unfortunately, GA has so far been a disease without any treatment, and a condition in which the ophthalmologist often becomes a bystander of a progressive decline in their patients' visual function and quality of life (Ahluwalia et al., 2023;Holm et al., 2023;Künzel et al., 2021).
The pathogenesis of AMD remains incompletely understood, but studies so far suggest a complex interplay between ageing, dysregulated immune system, and ocular and systemic risk factors (Feng et al., 2020;Forshaw et al., 2019;Heloterä & Kaarniranta, 2022;Holtz et al., 2023;Kaarniranta et al., 2023;Krogh Nielsen et al., 2019, 2020;Nahavandipour et al., 2020;Nielsen et al., 2020;Rozing et al., 2020;Subhi, Krogh Nielsen, et al., 2019;Subhi, Nielsen, et al., 2019).For AMD in general and GA in particular, the complement system has been a hot topic of investigation (Rozing et al., 2020).Genetic variants of complement component 3 (C3), such as CFH, CFI, and CFB, are shown to increase the risk of the development of both neovascular AMD and GA (de Breuk et al., 2021;Nielsen et al., 2020).Evidence of a pathophysiological impact of C3 on GA from observational and experimental studies has led to investigation of C3 targeting as a potential treatment strategy (Desai & Dugel, 2022).Pegcetacoplan is a pharmaceutical compound that binds to C3 and its activation fragment C3b and thus functions as a complement inhibitor.Pegcetacoplan has been subject to recent randomized clinical trials as a potential treatment for GA.In the phase II FILLY trial and the following phase III trials OAKS and DERBY, pegcetacoplan decreased the progression rate of GA (Eye-Wire, 2023; Goldberg et al., 2022;Steinle et al., 2021).Pegcetacoplan has gained approval from the United States Food and Drug Administration (FDA) for treatment of GA and is currently under review by the European Medicines Agency with a decision expected in 2024 (EyeWire, 2023).
In this study, our aim was to better understand the burden of GA and the potential scope of intravitreal complement inhibitor treatment on population level.For this ambition, we systematically reviewed the literature on the prevalence of GA, conducted meta-analyses on age-stratified estimates, calculated current and future number of patients with GA, and calculated number of patients potentially eligible for treatment with intravitreal pegcetacoplan.

| Study design
We first systematically searched the literature for population-based studies of the prevalence of GA secondary to AMD in a Nordic population.Based on extracted data from these studies, we conducted prevalence meta-analyses of the prevalence of GA in different age-strata.Based on large clinical descriptive analyses of consecutive cases of GA, we extracted the proportion of patients with GA secondary to AMD who would be eligible for treatment according to the eligibility criteria as defined in the phase III studies DERBY and OAKS of the efficacy of intravitreal pegcetacoplan therapy (Clin-icalTrials.gov NCT03525600, 2022;ClinicalTrials.gov NCT03525613, 2022).Finally, we extracted age-stratified population census data and forecasts for Nordic countries (defined as Denmark, Finland, Iceland, Norway, and Sweden) from Eurostat, which is a transnational European statistical bureau that collects standardized data from national statistics bureaus.We applied prevalence statistics to the extracted population census and forecasting data to estimate the number of patients with GA in Nordic countries.We then applied the proportion eligible for intravitreal pegcetacoplan therapy to estimate the number of potential patients in Nordic countries.Study aspects dealing with the systematic review and meta-analyses were designed according to the items and considerations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (Moher et al., 2009) and registered in the PROSPERO database (CRD42023422435).We followed the recommendations of the Cochrane Handbook (Cochrane, 2022).According to Danish law, systematic reviews, meta-analyses, and forecasting studies using publicly available data do not require institutional review board approval.

| Eligibility criteria
Eligible studies were defined as those that investigated a population-based sample in a cross-sectional fashion using a minimum of fundus photography and reported the prevalence of GA secondary to AMD.We did not enforce any restrictions on the diagnostic definition or criteria for GA or AMD.However, we only considered cases of GA-only, i.e., prevalence of cases with both GA and macular neovascularization were not considered relevant for our study.We did not consider studies without any original data, conference abstracts, or non-peer reviewed literature.Since AMD is a disease with heterogeneous origin with important impact of genetics and environmental factors, we restricted eligibility to studies of populations in Nordic countries.We only considered studies reported in English language.

| Information sources, search strategy, and study selection
We searched the literature databases PubMed, EM-BASE, Cochrane Central, Web of Science Core Collection, BIOSIS Previews, Current Contents Connect, Data Citation Index, Derwent Innovations Index, KCI-Korean Journal Database, and SciELO Citation Index.Searches were made on 22 April 2023 by one trained author (Y.S.) using phrases tailored the individual databases (File S1).
Records from the literature search were imported to EndNote X9.3.1.for Mac (Clarivate Analytics, Philadelphia, PA, USA) for screening.One author (Y.S.) screened all titles and abstracts to remove obviously irrelevant studies and to remove duplicates.Remaining records were retrieved in full-text.Full-text records were evaluated for eligibility by two authors (A.V. and A.H.K.N.) in an independent fashion.All reference lists were evaluated for potential eligible studies.Eligibility evaluation was compared and discussed, and any discrepancies were consulted with a third author (Y.S.) for final consensus.

| Data extraction and risk of bias within studies
Data were extracted systematically from all eligible studies using pre-designed extraction forms.Specifically, we extracted data on study design, sample population, diagnostic approach, diagnostic definitions, and prevalence of GA in different age-strata.Since we expected crosssectional study design, the risk of bias within study evaluation was made using the relevant items of the Agency for Healthcare Research and Quality (AHRQ) checklist for Cross-Sectional Studies (items 1-4 and 6), which is the recommended tool for evaluated cross-sectional studies (Zeng et al., 2015).Data extraction and risk of bias within study evaluation were made by two authors (A.V. and B.S.T) in an independent fashion.Any discrepancies were consulted with a third author (Y.S.) for final consensus.

| Outcome measures, data synthesis, and risk of bias across studies
Eligible studies were reviewed qualitatively and summarized in tables.For the meta-analyses, we considered the primary outcome measure as the prevalence of GA in three different age-strata: 60-69 years, 70-79 years, 80+ years.The unit of analysis was per person (not per eye).All meta-analyses were conducted using MetaXL v.5.3.(EpiGear International, Sunrise Beach, QLD, Australia) for Microsoft Excel v.2205 (Microsoft, Redmont, WA, USA).We used the random-effects model to account for heterogeneity across studies.In prevalence meta-analyses, caution must be shown when numbers reach 0% or 100%, as the calculations can lead to variance instability and wrong study weighting (Barendregt et al., 2013).Since we expect the prevalence of GA in the general population to be <5%, this is a potentially important methodological issue.One of the most reliable solutions is to transform all prevalence numbers for analysis using the double arcsine method and then back transform for interpretation (Barendregt et al., 2013), which was employed for this study.Heterogeneity was evaluated using the Cochran's Q and I 2 .Risk of bias across studies was evaluated using Funnel plots.Sensitivity analyses were made by removing each study in turn, recalculating summary measures, and evaluating if the overall findings change significantly depending on the excluded study.For all summary estimates, 95% confidence intervals (95% CI) were reported.

| Geographic atrophy eligible for intravitreal complement inhibitor treatment
For patient eligibility, we followed the criteria as stated in the phase III studies DERBY and OAKS (Clini-calTrials.gov NCT03525600, 2022;ClinicalTrials.gov NCT03525613, 2022) of the efficacy of intravitreal pegcetacoplan therapy.For this study, we decided that most of these criteria were possible to accommodate.These were age ≥60 years, BCVA ≥24 ETDRS letters (≥20/320 Snellen), total GA area between 2.5-17.5 mm 2 (or 1-7 DA), no history of macular neovascularization, no history of central laser therapy, or intraocular surgery apart from cataract surgery.Our assessment was that the details of multifocality were not possible to extract from other studies.Similarly, we assessed that it would not be possible to obtain data on the proportion of those with high myopia (large spherical error/axial length) or the presence of any other active ocular co-morbidity such as glaucoma.
To evaluate the proportion of potentially eligible patients, we used the results from the large, prospective, multicentre, Fundus Autofluorescence in Age-related Macular Degeneration (FAM) study (Holz et al., 2007).Based on a consecutive sample of 195 patients with GA only, the authors reported that 91.3% had presence of any pattern of hyper-autofluorescence (Holz et al., 2007).Median visual acuity of eyes with GA was 0.32 Snellen with an interquartile range of 0.13-0.50Snellen (Holz et al., 2007).Distribution of atrophy size was reported in categories of <1 disc area (DA), 1-3 DA, 3-5 DA, 5-10 DA, and >10 DA (Holz et al., 2007).The percentage of patients with GA with an atrophy size of 1-5 DA and 1-10 DA was 71.4% and 88.1%, respectively (Holz et al., 2007).Based on these numbers, we calculated the proportion of patients eligible for treatment to be the following: 91.3% (any hyper-autofluorescence pattern) × 75% (75% of eyes had a BCVA of 0.13 or better) × 79.8% (midpoint of 71.4% and 88.1%) = 54.6%.

| Estimated and forecasted number of patients in Nordic countries
We extracted population census and forecasting data from Eurostat.The national statistical bureaus continuously compile data on population number, livebirths, deaths, and immigration/emigration trends (Eurostat, 2023).These data are then submitted to Eurostat, which forecasts trends in European countries (Eurostat, 2023).By multiplying the calculated summary estimate of the prevalence of GA in different age-strata with the estimated proportion of eligible patients for treatment, we obtained the prevalence of patients with GA eligible for intravitreal pegcetacoplan treatment.These prevalence estimates were then multiplied with the age-stratified population forecasts to calculate the expected number of patients in all of Nordics, in individual countries, and in geographical strata based on the European geographical standard of Nomenclature of Territorial Units for Statistics (NUTS) at level 3 (Figure 1).We estimated the current prevalence of GA (year 2023) and future prevalence of GA (year 2050).Growth in the number of patients with GA was estimated as percentage increase from year 2023 and the average annual growth in the number of patients was estimated using the exponential growth formula.

| Study selection
The literature search identified 2212 records, of which 602 were duplicates and 1600 obviously irrelevant.Remaining 10 records were read in full text for evaluation of eligibility and all reference lists were reviewed for any additional eligible studies.Of these, six studies were deemed eligible for the qualitative review, and all six studies were also eligible for the quantitative review (Figure 2).

| Study characteristics
The six eligible studies for review included a total of 10 159 individuals.All were population-based and provided relevant cross-sectional data regardless of study design otherwise.Studies originated from Iceland (n = 2), Norway (n = 2), Denmark (n = 1), and Finland (n = 1).Studies focused their demographics to individuals aged at least 50 years and had a balanced distribution of gender.All studies used fundus photography for diagnosis.Buch et al. (2005) also used hand-held fundus photography for participants examined at home or otherwise difficulties in obtaining routine photography.Laatikainen and Hirvelä (1995) used fundoscopy when fundus photography did not provide relevant data.Definition of GA was specified in detail in four studies, but all studies defined that a diagnosis of GA did not include a concurrent diagnosis of neovascular/exudative AMD.Further study characteristics are summarized in detail in Table 1.

| Results of individual studies
From Denmark, Buch et al. (2005) reported results from the Copenhagen City Eye Study, which was a randomly sampled population-based study of urban elderly population residing in the Copenhagen metropolitan area.This study reported baseline and 14-year follow-up findings of the maculae of 297 individuals aged 60-80 at baseline, and we extracted baseline data from this study.None of these individuals had GA at baseline (Buch et al., 2005).From Finland, Laatikainen and Hirvelä (1995) sent an invitation to all inhabitants aged ≥70 years (range 70-95 years) in three communities in Oulu County in 1991.Of 560 eligible inhabitants, 478 participated in the study and provided a gradable fundus photography or sufficient fundoscopy (Laatikainen & Hirvelä, 1995).This study found any GA in 5% of the population and that the prevalence rose from 1.9% of those aged 70-84 to 36% of those aged ≥90 years (Laatikainen & Hirvelä, 1995).From Norway, Erke et al. (2012) reported the results of the Tromsø Eye Study conducted in 2007-2009 in the municipality of Tromsø.These individuals were aged 65-87 years, and 2631 individuals had gradable fundus photographs (Erke et al., 2012).Prevalence of GA increased with age, from 0.3% among those aged 65-69 years to 3.7% among those aged 80-87 years (Erke et al., 2012).Also from Norway, Björnsson et al. (2006) obtained a list of 800 individuals aged ≥51 years living in Oslo city and its surroundings, through a randomly sampled protocol from the Office of the National Registrar in Norway, and invited these individuals for participating in the Oslo Macular Study in 2002.This study included 459 participants aged 51-90 years.Of these, seven individuals had GA: two (1.2%) were aged 61-70 years, one (1.1%) was aged 71-80 years, and four (8.5%) were aged 81-90 years (Björnsson et al., 2006).From Iceland, Jonasson et al. (2003) randomly sampled citizens of Reykjavik aged ≥50 years for participation in the Reykjavik Eye Study in 1996.Gradable fundus photography was obtained from 1022 participants (Jonasson et al., 2003).This study found an increasing prevalence of GA with age, from 0.3% among those aged 50-59 years to 25% among those aged ≥80 years (Jonasson et al., 2003).Jonasson et al. (2011) reported the results of another population-based Age, Gene/Environment Susceptibility Reykjavik Study, in which 5272 Icelandic individuals underwent fundus photography in 2002-2006.Participants were aged 66-91 years (Jonasson et al., 2011).The prevalence of GA rose from 0.2% among those aged 66-69 years to 7.6% among those aged ≥85 years (Jonasson et al., 2011).

| Risk of bias within studies
Our risk of bias evaluation of individual studies found that all studies clearly defined source, eligibility criteria, time period, population-based recruitment, and explained exclusions.For quality assurance, we defined this as at least two different examiners of the fundus photographs, and this was present in all studies.Thus, our evaluation based on the AHRQ checklist for  Grayscale fundus photography (45°) centred on the macula in cycloplegia.Fundoscopy in cases where fundus photography was not possible.Grading was made by two investigators.
Areas with clear-cut atrophy of the RPE of at least 1/3 disc diameter in size without signs of exudative maculopathy.
Cross-Sectional of individual studies found low risk of bias of individual studies (Table 2).

| Meta-analyses of the prevalence of geographic atrophy in Nordic countries
Of 10 159 individuals across studies in total, 9655 individuals were aged 60+ years and eligible for the quantitative analyses.Results of the meta-analyses are summarized in Table 3.

| Estimated number of patients with geographic atrophy in Nordic countries
The estimated number of patients with GA was calculated for all Nordic countries, on individual country level, and according to detailed NUTS level 3 defined areas in Nordic countries (Table 4).
We estimate that 166 307 individuals currently suffer from GA in Nordic countries and expect this number to increase to 277 893 individuals in year 2050, corresponding to an increase of 1.9% per year or 67.1% in total.We estimate that 90.803 individuals are currently potentially eligible for intravitreal pegcetacoplan treatment and that this number is expected to increase to 151 730 in year 2050.
We observed interesting differences when comparing the Nordic countries.Denmark, Finland, and Sweden can expect an annual increase of 1.5%-1.9%,whereas Iceland and Norway can expect a much higher increase of 3.2% and 2.5%, respectively.These differences are expected because of differences in the forecasted demographic developments.
At NUTS level 3, it could be observed that the number of patients with GA is higher in rural areas, which reflect a relatively higher burden in these areas which typically have a larger proportion of elderly inhabitants.Interestingly, we also observed that the growth of the number of patients with GA was highest in the urban areas, which may reflect a general continuous trend of urbanization.

| DI SC US SION
In this study, our aim was to better understand the burden of GA in the Nordic countries and the scope of intravitreal complement inhibitor treatment.We identified six studies with relevant epidemiological data on GA in Nordic populations.It is important to note that all these studies were at least 10 years old and employed older diagnostic definitions based on fundus photography or fundoscopy.Our prevalence meta-analyses highlighted the strong age-correlation in the prevalence of GA.This condition affects 0.4% of individuals aged 60-69 years, a number that almost quadruples in individuals aged 70-79 years, and increases dramatically to 7.6% T A B L E 2 Risk of bias within individual studies evaluated using the Agency for Healthcare Research and Quality checklist for Cross-Sectional Studies.among those 80+ years.In other words, one in 13 individual aged 80+ the Nordics is expected to suffer from GA. Overall, we estimate the number of patients with GA to be 166 307 across all Nordic countries, corresponding to 0.6% of the entire population.We found a noticeable difference in the prevalence between rural areas compared to urban areas.In Denmark, this is highlighted by the strong difference between the rural area of Bornholm with a GA prevalence of 0.9% and the urban area of Copenhagen City of 0.3%.Considering the ageing demographics across all Nordic countries (England & Azzopardi-Muscat, 2017), the number of patients with GA is expected to increase.Indeed, our population estimates show that in year 2050, we expect the number of patients to increase by 67.1% (1.8% per year).Meanwhile, the overall population of the Nordic countries is expected to increase at a slower pace from 27.8 million in year 2023 to 30.5 million in year 2050, corresponding to 9.5% (0.3% per year).These numbers highlight that the societal burden of GA is expected to increase, at least until year 2050.Interestingly, our analyses also revealed that the increase of patients with GA is expected to be most pronounced in urban capital areas of the Nordic countries: Copenhagen (Byen København) at 2.8% per year, Helsinki (Helsinki-Uusimaa) at 2.3% per year, Reykjavik (Höfudborgarsvaedi) at 3.6%, Oslo (Oslo) at 3.1%, and Stockholm (Stockholms län) at 2.6%.These numbers likely reflect the urbanization trend towards large cities.Three previous studies have explored overlapping topics in regarding to an estimation of the burden of GA in Nordic countries.Lindekleiv and Erke (2013) estimated neovascular AMD and GA in Denmark, Norway, and Sweden from 2012 to 2040 using prevalence estimates from a multicentre European study.This study estimated 104 000 individuals with GA in year 2012 and 183 000 in year 2040; in comparison, our estimate for individuals with GA in year 2023 for only Denmark, Norway, and Sweden summarizes to 127 505 individuals, which are in line with the study by Lindekleiv and Erke (2013).Colijn et al. (2017) estimated early and late AMD in Europe using prevalence estimates from a multicentre European study.This study did not provide numbers specific to Nordic countries but found that both early AMD and late AMD had a higher prevalence in countries defined as Northern Europe (Denmark, Estonia, Finland, Iceland, Ireland, Latvia, Lithuania, Norway, Sweden, United Kingdom) as compared to other European countries (Colijn et al., 2017).Sedeh et al. (2017) estimated neovascular AMD and GA in Denmark using prevalence estimates from Jonasson et al. (2011).This study reported a prevalence estimate of 20.580 individuals with GA in year 2016, expected to increase to ~23 000 in year 2020, ~34 000 in year 2030, ~41 000 in year 2040, ~48 000 in year 2050, and ~50 000 in year 2060 (Sedeh et al., 2017).In comparison, our estimate for Denmark in year 2023 was 34 724 individuals, expected to increase to 58 159 in year 2050.Overall, the findings of these studies are generally in line with those reported in this study; and this study provides for the first time more detailed estimates for the entire Nordic region, and arguably also more accurate estimates based on age-stratified prevalence meta-analyses of studies of only Nordic populations.

Explains exclusions
We estimated number of patients potentially eligible for intravitreal complement inhibitor treatment to be 90.803 in all Nordic countries.These numbers should be interpreted with caution.First, we used the eligibility criteria for intravitreal pegcetacoplan treatment as stated in the phase III studies DERBY and OAKS (ClinicalTrials.govNCT03525600, 2022).It is generally well-described that eligibility criteria for industrysponsored randomized clinical trials are very restrictive to ensure clear demonstration of efficacy, whereas patients in real-life clinical practice who would not be considered eligible for such trials receive treatment based on these trials (Kim et al., 2018;van Spall et al., 2007).This would lead to an underestimation of the actual number of patients for intravitreal pegcetacoplan treatment.Second, we used the results from a large clinical study of GA to determine the number of potentially eligible patients (Holz et al., 2007).A certain proportion of patients are considered ineligible because of too poor vision or too large atrophy size, and these represent cases with a longer history with GA and therefore longer time of progression.However, if a treatment option emerges, cases may be identified and  referred at an earlier stage before the development of a too large atrophy.Consequently, this source of uncertainty would also lead to a potentially higher number of patients for intravitreal pegcetacoplan treatment.Regardless, ~90 000-100 000 potential patients for regular intravitreal treatment are a large number considering that the entire population of Nordic countries constituted 27.8 million in year 2023.The economical and organizational aspects alone of such an endeavour are substantial and need to be appropriately analysed, debated, and funded, if pegcetacoplan, or other complement inhibitor treatment, is enrolled widescale for GA in the Nordic countries.Considering the uncertainties around atrophy size and its correlation to visual function and vision-related quality-of-life (Holm et al., 2023), while also considering the burden of repeated intravitreal treatment and risk of adverse events such as endophthalmitis (Petri et al., 2020), a widescale enrollment of such treatment for GA should be an important topic for debate as well as a topic for further studies.Limitations need to be acknowledged when interpreting the results of this systematic review and metaanalysis.Our estimates are only as good as the studies that provide such estimates.Therefore, one strength of this study is that we do not rely on prevalence estimate of single studies for our forecasting analyses, but rather on the meta-analytic summary estimate of multiple studies.Further, another strength is that we only rely on data from Nordic populations to calculate and forecast on Nordic populations.A limitation is that all studies in this review rely on diagnostics based on fundus photography or fundoscopy.This older method is in contrast to the macular optical coherence tomography (OCT), which provides a significant leap in the diagnostic certainty for AMD and GA (Clevenger & Rachitskaya, 2023;Crincoli et al., 2022).In line with this, our review highlights another important aspect, which is that newer epidemiological studies with multimodal imaging or at least using OCT are needed to better understand the epidemiology of the clinical phenomena of our daily practice, which are largely based on routine access to multimodal imaging and at least an OCT (Clevenger & Rachitskaya, 2023;Crincoli et al., 2022).
In conclusion, this study systematically reviews the epidemiology of GA in the Nordic countries, provides the best available age-stratified prevalence of GA in a Nordic population, estimates detailed number of patients for the entire area, its countries, and regional subdivisions, and estimates the first potential burden analysis of employing intravitreal complement inhibitor treatment.Our study highlights the importance of this topic in the coming years and its potential to significantly impact our clinical practice, organization, and staffing.

F U N DI NG I N FOR M AT ION
No funding was obtained for this study.

CON F L IC T OF I N T E R E ST STAT E M E N T
Author J.G. has received speaker fee from and has served as an advisory board member for Bayer, Novartis, Roche, and Allergan, not related to this work.Author Y.S. declares to have received speaker fee for lectures from Bayer and Roche, not related to this work.Remaining authors declare no potential conflicts of interest.

F
I G U R E 1 The Eurostat geographical standard of Nomenclature of Territorial Units for Statistics (NUTS) level 3 for Denmark, Finland, Iceland, Norway, and Sweden.Geographical demarcations within each country indicate NUTS3 defined areas.Definitions for NUTS3 vary across countries, i.e., Denmark: Landsdele; Finland: Maakunnat; Iceland: Höfuðborgarsvaeðið and Landsbyggð; Norway: Fylkeskommune; Sweden: Län.The island territories of Svalbard and Jan Mayen lie outside of the county system of Norway and therefore also from the NUTS3 classification.The autonomous Danish territories of Greenland and the Faroe Islands are not covered by the NUTS3 geographical system.Maps are courtesy of Eurostat (Creative Commons licence CC BY 4.0).

F
Study selection process using the PRISMA flow diagram.T A B L E 1 Characteristics of eligible studies in review and their approach for diagnosis of geographic atrophy (GA).

Patients with GA in 2023, N (%) Patients with GA in 2050, N (%) Growth in % 2023-2050, total (annual) Potentially eligible for IPT in 2023, N Potentially eligible for IPT in 2050, N
current and future prevalence of geographic atrophy (GA) in Nordic countries patients potentially eligible for intravitreal pegcetacoplan treatment (IPT).
T A B L E 4