Br J Ophthalmol 96:444-447 doi:10.1136/bjophthalmol-2011-300304
  • Clinical science
  • Original article

Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load

  1. Haraldur Sigurdsson1,2
  1. 1Department of Ophthalmology, Landspitali—The National University Hospital of Iceland, Reykjavik, Iceland
  2. 2Department of Ophthalmology, University of Iceland, Faculty of Medicine, Reykjavik, Iceland
  1. Correspondence to Dr Haraldur Sigurdsson, Department of Ophthalmology, Landspitali—The National University Hospital of Iceland, 101 Reykjavik, Iceland; haraldsi{at}
  1. Contributors All authors contributed equally to the design of the study and interpretation of the data. AG analysed the data and drafted the article, but all co-authors participated in the critical revision of the article as well as approving the final version to be published. HS is responsible for the research for the publishers and the Icelandic government.

  • Accepted 18 July 2011
  • Published Online First 19 August 2011


Background/aims The use of intravitreal vascular endothelial growth factor antibodies for exudative age-related macular degeneration (AMD) has stressed ophthalmology services and drug budgets throughout the world. The authors study the population-based incidence of exudative AMD in Iceland and the use of intravitreal ranibizumab in a defined population.

Methods This is a prospective study of 439 consecutive patients aged 60 years and older with exudative AMD starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to December 2009. All patients initially received three consecutive ranibizumab injections, with regular follow-up visits and re-treatment as needed.

Results In total, 517 eyes from 439 patients received treatment for exudative AMD (mean age 79 years). The annual incidence of exudative AMD in the population 60 years and older is 0.29%. The incidence increased with advancing age, double for patients 85 years and older compared with those 75–79 years. Approximately 2400 ranibizumab injections per 100 000 persons aged 60 years and older were given each year for exudative AMD.

Conclusions These data allow an estimation of the incidence of exudative AMD in a Caucasian population and the treatment load with ranibizumab, which may help plan anti-vascular endothelial growth factor treatment programmes and estimate costs.


Advanced age-related macular degeneration (AMD) is a leading cause of severe visual impairment and irreversible blindness among people 50 years of age or older in industrialised countries.1–3 In recent years, a number of large population-based studies have provided reliable data on the incidence of AMD and shown that the annual incidence of advanced AMD increases with age.4–9 Exudative AMD has been found to be 50–83% of all advanced AMD cases depending on population.10–12 The 10-year cumulative incidence of exudative AMD in the Blue Mountains Eye Study was 2.2% for the whole study population aged 49 years and older at baseline, increasing from 2.0% for persons aged 60–69 years at baseline to 12.4% for those aged 80 years and older.6 Moreover, population projections estimate a substantial increase in the older populations resulting in a further increase in the morbidity of the disease.13 14

Ranibizumab (Lucentis, Genentech, South San Francisco, California), a recombinant humanised monoclonal antibody, is an inhibitor of human vascular endothelial growth factor (VEGF) approved by the US Food and Drug Administration for the treatment of exudative AMD in June 2006. In March 2007, ranibizumab treatment started in Iceland, and it is centralised in one hospital for the entire population of Iceland of 320 000 persons. There is about one ophthalmologist per 10 000 inhabitants in Iceland, mostly practising in and around Reykjavik area where two-thirds of the population resides. More sparsely populated areas are served by satellite eye clinics every few weeks. Between their visits, the respective general practitioner can refer the patient either to the regional ophthalmologist's practice or directly to the University Hospital Eye clinic. The clinic offers prompt service, as all patients with newly diagnosed exudative AMD or an acute worsening of their disease are given an appointment with a consultant ophthalmologist at the clinic and receive anti-VEGF treatment within 1 week from referral.

Ranibizumab treatment requires frequent intravitreal injections and follow-up visits, which increases ophthalmology service load and drug costs. Limited quantitative information is available on the anti-VEGF treatment load in an unselected population. The centralised eye service in Iceland and the contained population provide an opportunity to gauge the service load and costs involved in offering anti-VEGF drugs to patients with exudative AMD on a nationwide scale. The present study describes the population-based incidence of exudative AMD in Iceland and estimates the need for anti-VEGF treatment in a defined population.

Materials and methods


This is a prospective study of 439 consecutive patients with exudative AMD who started intravitreal ranibizumab treatment from March 2007 to December 2009. The study was approved by the Landspitali Ethics Committee and the Icelandic Data Protection Commission, and adhered to the guidelines of the Helsinki Declaration.

The inclusion criteria were: patients' consent to treatment; age ≥60 years; exudative AMD lesions on macula; signs of presumed recent disease progression, as defined by recent loss of vision, new haemorrhage, signs of exudative AMD on optical coherence tomography (OCT) and/or an increase in lesion size on fluorescein angiography. In patients where the second eye became eligible for ranibizumab treatment during the study period, both eyes were included and handled separately for follow-up visits and re-treatment decision.


The diagnosis of exudative AMD was based on fundus biomicroscopy, OCT and, in selected cases, fluorescein angiography. Best-corrected visual acuity (BCVA) was assessed at baseline and at every postoperative visit on a Snellen visual acuity chart. OCT scans generated by the macular thickness map protocol of the Stratus OCT (Carl Zeiss Meditec, International, Germany) were also evaluated at every visit for the presence or absence of intraretinal and subretinal fluid. Data were collected on the number of intravitreal injections.

All patients were initially treated with three monthly intravitreal 0.5 mg injections of ranibizumab. Thereafter, patients had a follow-up visit a month after the third injection and re-treatment as judged by the consultant ophthalmologist. Re-treatment was considered if there was any deterioration in the signs and symptoms including a drop in BCVA, no improvement or worsening of intraretinal or subretinal fluid, fresh haemorrhage or extension of the lesion. It was proposed that re-treatment would be avoided if there was no improvement in BCVA, persistent unresolving intraretinal and subretinal fluid, evidence of structural damage on OCT or a serious adverse event. Patients with clinical evidence of irreversible damage with no potential benefit from continuing treatment were generally suspended from further ranibizumab treatment. Generally, a modified treat-and-extend regimen was followed with a set of three monthly injections if re-treatment was chosen.

Data analysis

Annual incidence was based on the number of patients diagnosed as having exudative AMD and starting ranibizumab treatment in 2008 and 2009. The numbers from 2007 were not included in the incidence calculations for two reasons. First, not all ophthalmologists around the country had started referring patients for this new treatment in 2007, and second, there may have been some accumulated demand leading to ‘inflated incidence’ in 2007.

For the 12-month follow-up analysis on the number of injections, only eyes (first and second eye where appropriate) from patients who started treatment in 2007 and 2008 were considered. The data from patients initiating treatment in 2009 were not used for the analysis on number of injections, as in early 2010, ranibizumab was abruptly replaced by bevacizumab in our clinic owing to economic reasons, and therefore ranibizumab data for full 12 months were not available for patients starting treatments in 2009.


In total, 517 eyes from 439 patients were enrolled in the study, from 164 males (37%). The mean age of patients at baseline was 79±7 years (median 80, range 61–97); in males 79±7, in females 80±7. In 78 patients (18%), both eyes were treated, and the median interval between symptoms in the right and left eye was 3 months. Right eyes were 246 (48%). All 439 patients diagnosed as having exudative AMD consented to treatment and received the initial three consecutive monthly intravitreal 0.5 mg ranibizumab injections, except four patients (four eyes) who died during the first 3 months of the study period and five patients (five eyes) who decided to discontinue treatment after the first injection. These patients were included in the incidence figures but excluded from the analysis of number of injections.

Incidence of exudative AMD

The annual incidence of exudative AMD is based on a number of first eyes affected from patients enrolling in the study in 2008 and 2009. In total, 293 patients were diagnosed as having exudative AMD over this 2-year period. In Iceland, a mean of 50 000 persons were aged 60 years and older at that time reflecting an annual incidence of 0.29% in that age group. The incidence of exudative AMD increases with advancing age, as can be seen in figure 1.

Figure 1

Annual incidence of exudative age-related macular degeneration in Iceland by age groups (n=293).

Number of injections

The average number of ranibizumab injections was 1213 per year. This amounts to approximately 2400 injections per 100 000 persons aged 60 years and older each year.

Over the course of 12 months, a mean of 5.0±2.3 (median 4, range 3–12) ranibizumab injections were administered per affected eye. Figure 2 shows the total number of ranibizumab injections administered per eye through 12 months.

Figure 2

Number of ranibizumab injections in 1 year for each eye with exudative age-related macular degeneration (n=361).


The population-based data on intravitreal ranibizumab injections in treatment-naïve patients with exudative AMD allow the reader to predict the annual incidence of exudative AMD and the treatment load in a Caucasian population. This may be used to plan anti-VEGF treatment programmes in comparable populations and estimate the costs.

Owing to the relatively high number of ophthalmologists per capita in Iceland and unrestricted access of patients to ophthalmologists, a high proportion of those with visual loss from exudative AMD are likely to seek medical assistance and to receive rapid anti-VEGF treatment if needed. However, a few patients may be too frail, mentally and/or physically, to seek medical help. Therefore, the incidence numbers shown here may be considered to be the minimum annual incidence of exudative AMD in our population, and we believe it to be very close to the total incidence. All newly diagnosed AMD patients referred to our clinic from March 2007 to December 2009 were included in the study and received the anti-VEGF treatment. However, five patients decided to discontinue the treatment after the first intravitreal injection.

There were on average 147 patients diagnosed as having exudative AMD per year, giving an annual incidence of 0.29% in the population aged 60 years and older. We are not aware of any other studies showing the actual number of exudative AMD in a defined population. In Germany, it is estimated that 50 000 persons are diagnosed as having exudative AMD each year.15 According to German population data, this can be estimated to be 0.24% of the population aged 60 years and older.16 In the UK, comparable assessment estimates that each year 0.20% of the population aged 60 years and older will develop exudative AMD, which is 26 000 new patients per year.17 These estimated incidence figures are slightly lower than our population-based data.

The annual incidence of exudative AMD increased with advancing age, from 0.06% in the age group 60–69 years to 0.81% in all patients aged 80 years and older. This increase is in agreement with the 5-year incidence paper from the Blue Mountain Eye Study, in which the calculated annual incidence of exudative AMD for the same age-groups was 0.1% and 0.72%, respectively.5 Moreover, for our study, the annual incidence was more than twofold for patients 85 years and older compared with those 75–79 years and nearly 20-fold in comparison with the youngest age group of 60–69 years, which is also in agreement with a recent Icelandic population-based study that found persons aged 85 and older to have a 10-fold higher prevalence of advanced AMD than those aged 70–74 years old and fivefold higher for those 75–79 years old.10 Another Icelandic study on advanced AMD in the very old demonstrated a 37% increase in advanced AMD in persons aged 95 years and older compared with those aged 75 years and older.18

The optimal dosing schedule for anti-VEGF therapy in exudative AMD is still debatable. Improvements in BCVA in the therapy for exudative AMD were first demonstrated with a monthly dosing regimen of ranibizumab in the phase III random clinical trials ANCHOR19 and MARINA.20 Some patients may require monthly injections in order to achieve the best possible result in visual acuity and to preserve retinal function over time. However, many patients do not need monthly injections, and therefore other treatment regimens, such as the pro re nata (PRN) variable-dosing treatment regimen and the treat-and-extend regimen, are commonly in practice in ophthalmology departments and aim to decrease the number of unnecessary injections per year. The PrONTO Study was the first prospective study to assess PRN variable-dosing regimen following the initial three monthly injections. It showed that a regimen with the three loading doses followed by PRN re-treatment was as effective as a fixed monthly dosing regimen in improving visual acuity and OCT findings with a far lower number of ranibizumab injections, or a mean 5.6±2.3 (range 3–13) over a period of 12 months,21 which is comparable with our experience.

In our clinic, patients are commonly treated according to a modified treat-and-extend regimen following a loading dose of three initial monthly injections. The modification is based on the re-treatment regimen, where a set of three additional monthly injections is usually ordered if re-treatment is needed. The participants of the present study received a mean number of 5.0±2.3 injections per 12 months, which is comparable with the PrONTO Study with 5.6±2.3 injections.

Approximately 1200 ranibizumab injections for exudative AMD were given in our clinic per year, but if every patient had a monthly injection, the number would have been close to 2900 ranibizumab injections per year.

With the confined Icelandic population and the fact that anti-VEGF therapy is centralised, it is possible to estimate the service load and costs involved in offering anti-VEGF drugs to patients with exudative AMD in a Caucasian population. In our population, about 2400 injections of ranibizumab are required per 100 000 population aged 60 years and older over the course of a year.

In conclusion, our population-based data show a 0.29% incidence of exudative AMD in the age group 60 years and older in a Caucasian population and an annual intravitreal ranibizumab injection rate of about 2400 per 100 000 persons aged over 60 years old. These data may help in planning anti-VEGF treatment programmes in comparable populations and estimate the costs of treatment.


We are very grateful to H Hablaub for the patient data collection.


  • Competing interests None.

  • Ethics approval Ethics approval was provided by the Landspitali Ethics Committee and the Icelandic Data Protection Commission.

  • Provenance and peer review Not commissioned; externally peer reviewed.


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