ARCH SOC ESP OFTALMOL 2006; 81: 199-204 ORIGINAL ARTICLE

COST-EFFECTIVENESS OF PHOTODYNAMIC THERAPY

IN AGE-RELATED MACULAR DEGENERATION
COSTE-EFECTIVIDAD DE LA TERAPIA FOTODINÁMICA EN LA
DEGENERACIÓN MACULAR ASOCIADA A LA EDAD
MUSLERA E1, NATAL C2

ABSTRACT
Objective: The aim of this study was to estimate the
public health service cost of visual acuity improve-
ment or maintenance with photodynamic therapy in
patients with age-related macular degeneration
(ARMD). This illness is the most frequent cause of
blindness in elderly patients in western countries.
Methods: A cost-effectiveness analysis was carried
out to compare photodynamic therapy versus no
treatment. The analysis point of view was that of
the health service. The improvement or maintenan-
ce of visual acuity and contrast sensitivity were
considered efficacy results. Direct costs were esti-
mated by means of cost accountancy. Quality adjus-
ted costs per visual acuity life year gained (QAC-
VAG) were calculated through utility values from
other studies.
Results: The cost per year of maintenance of visual
acuity in a two-year period was 36,530 € for
women and 34,804 € for men. If this cost was esti-
mated for life expectancy in Asturias, it would be
reduced to 4,298 € for women and 5,354 € for men.
RESUMEN
Objetivo: Estimar el coste para el servicio público
de salud de la mejora o el mantenimiento de la agu-
deza visual en pacientes con degeneración macular
asociada a la edad mediante la aplicación de la tera-
pia fotodinámica con verteporfina.
Método: Estudio coste efectividad desde la pers-
pectiva de un servicio de salud teniendo en cuenta
la alternativa no tratar. La medida de eficacia es la
ganancia o mantenimiento de la agudeza visual y la
sensibilidad al contraste. Los costes directos liga-
dos al proceso de la intervención son estimados a
partir de la contabilidad analítica. El coste ajustado
por calidad, se estima con valores procedentes de
otros estudios.
Resultados: El coste por año ganado de manteni-
miento de la agudeza visual, en un horizonte de dos
años es de 36.530 € para mujeres y 34.804 € para
hombres. Si el horizonte fuera la esperanza de vida
en Asturias, el coste disminuye a 4.298 € y 5.354 €
respectivamente. El coste por año ganado de mante-
nimiento de agudeza visual ajustado por calidad es,

Received: 23/6/05. Accepted: 19/4/06.

Analysis and Programmes Unit. Health Service of the Principality of Asturias. Spain.
1 Graduate in Economic Sciences.
2 Graduate in Medicine.
Communication partially presented at the 24th Health Economy Meeting (El Escorial 2001) and the 21st Congress of the Spanish Society of
Assistance Quality (Oviedo 2003).

Correspondence:
Elvira Muslera Canclini
Unidad de Análisis y Programas
Servicio de Salud del Principado de Asturias
Plaza del Carbayón, 1 y 2, 3.ª planta
33001 Oviedo
Spain
E-mail: elvira.muslera@sespa.princast.es
MUSLERA E, et al.
If costs of the QACVAG, in a two-year period, were
considered, photodynamic therapy would cost
66,931 € for women and 70,249 € for men.
Conclusion: This cost-effectiveness analysis
allows decisions to be made about public financing.
Some research in our country suggests that public
health financing should be provided for interven-
tions whose cost-effectiveness is less than 30,000 €
of CVAQA. The treatment evaluated here far exce-
eds this value. It is recommended that the use of
more restrictive patient selection, incorporating
diagnostic criteria and patient autonomy indicators,
could improve the results of this intervention (Arch
Soc Esp Oftalmol 2006; 81: 199-204).
Key words: Cost-effectiveness, photodynamic the-
rapy, age-related macular degeneration.
INTRODUCTION
Age-related macular degeneration (ARMD) is
one of the main causes of blindness in people over
50, representing between 50 percent and 17 percent
according to different information sources (1-3).
The prevalence of this disease varies according to
the diagnostic criteria and methods. The study
carried out by the Eye Diseases Prevalence Rese-
arch Group estimated are prevalence of ARMD for
all ages of 1,47% (4). Prevalence increases with
age, reaching 2.3% for the age group over 70 (5).
The exudative form has a prevalence of 0.88%. By
age group, prevalence is of 0.17% for the 55-64 age
group, 0.54% for the 65-74 group, 2.52% between
75 and 84 and 5.76% for the over 85 age group.
Thirty-six percent of these appear as subfoveal cho-
roidal neovascularization lesions (NVC) (6), classic
lesions potentially treatable with photodynamic the-
rapy (PT) with verteporfin. Extrapolating these data
to the region of Asturias, it is estimated that at pre-
sent there are 1282 individuals affected by the RMT
and which could be treated with PT. In a number of
these patients both eyes will be involved. By age
group, the highest frequency is found between 75
and 84 years of age, accounting for 45 percent of
cases. Patients over 84 account for 33 percent. In
addition to PT, different treatments for ARMD have
been attempted such as laser photocoagulation,
low-dose radiotherapy, surgery and the use of
200 ARCH SOC ESP OFTALMOL 2006; 81: 199-204
en horizonte de dos años, de 66.931 € para mujeres
y 70.249 € para los hombres.
Conclusión: Los estudios coste-efectividad facili-
tan decidir sobre la pertinencia de la financiación
pública. Algunos autores sugieren incluir sólo
aquellas intervenciones que no superen los 30.000
€ por año ganado de mantenimiento de agudeza
visual ajustado por calidad y en este estudio se
sobrepasa holgadamente este valor. Es recomenda-
ble una selección más rigurosa de los pacientes, tan-
to por criterios diagnósticos como por característi-
cas individuales en relación con su autonomía, lo
que permitiría mejorar los resultados de esta inter-
vención.
Palabras claves: Coste-efectividad, terapia fotodi-
námica, degeneración macular asociada a la edad.
angiogenic and angiostatic agents, as well as trans-
pupillar thermal therapy.
Laser photocoagulation gives good results as
regards the conservation of visual acuity and pre-
servation of contrast sensitivity in patients with
NVC secondary to exudative ARMD. However, as
it does not act selectively on the pathological tissue,
it is indicated only in extrafoveal and juxtafoveal
lesions (7). The low-dose radiotherapy has been
studied without obtaining conclusive results as yet
(8,9).
At present there are high expectations as regards
the results of transpupillar thermal therapy which
could be an option to PT (10).
The Medical Research and Technology Evalua-
tion Agency (Agència d’Avaluació de Tecnologia i
Recerca Mèdiques) established the following
recommendations for PT in treating ARMD: treated
only patients with a classic NVC subfoveal pattern
equal or above 50 percent of the entire surface of the
lesion; focusing treatment and limiting the offer to
hospital centers with a broad experience in macular
pathology; maintaining this centralization for two or
three years at least, carrying out an annual assess-
ment closely linked to the financing thereof (11).
The purpose of this study is to estimate the cost
of the improving on maintaining visual acuity in
patients with predominantly classic subfoveal NVC
due to ARMD by means of the application of PT
with verteporfine.

SUBJECTS, MATERIAL AND
METHODS
A cost-effectiveness study is made from the pers-
pective of a health service, taking into account the
no-treatment alternative.
Measure of efficiency
The efficiency of PT has been measured in two
clinical essays: Verteporfin in Photodynamic The-
rapy (VIP) and Treatment of Age-Related Macular
Degeneration with Photodynamic Therapy (TAP)
(12,13), both performed in centers of Europe and
the United States. The main difference between
both is in the patient selection criteria, with the
most restrictive being those for the TAP study (13).
Whereas the latter includes only patients over 50,
with visual acuity values between 20/40 and 20/200
and classic or predominantly classic choroidal neo-
vascularization caused by ARMD, the VIP study
includes patients with better visual acuity, younger
and with choroidal neovascularization arising from
different causes (13).
The above studies utilized three results measures:
the visual acuity (the main variable of which is the
response rate, defined as the proportion of patients
who lost under three lines of visual acuity vis-à-vis
the baseline), sensitivity to contrast and semi quan-
titative angiographic classification of retina lesions.
Visual acuity was assessed utilizing the Snellen
equivalent in a remote visual acuity test with a
Lighthouse type following standardized refraction.
The classification scale is: a) improvement of
vision, increase of one or more visual acuity lines;
b) stable vision, loss of under three lines, or no
changes: c) moderate loss, between three and five
lines, and d) serious loss of six or more lines.
Sensitivity to contrast is assessed in the TAP
study with the result that the patients in treatments
maintained six letters after two years (p<0,001) (14).
Table I. Usefulness measure according to visual acuity (15)
Status Visual acuity
Normality 20/20 – 20/25
Intermediate 1 20/30 – 20/50
Intermediate 2 20/60 – 20/100
Legal blindness 20/200 – 20/400
Blindness Count fingers up to perception of light
ARCH SOC ESP OFTALMOL 2006; 81: 199-204
Cost effectiveness of Photodynamic Therapy
This study utilizes the efficiency data of the TAP
clinical essay (13) because the selection of patients
was similar to our group of patients (advanced age,
classic or predominantly classic choroidal neovas-
cularization secondary to ARMD). From the essay
it can be concluded that after two years of treat-
ment, 15,3% (p<0,001) of patients lost under three
lines, i.e., they maintained stable vision in compari-
son to those who were given placebo.
PT does not at present healing results and for this
reason its benefits consist in preventing a worsening
of eyesight or delaying blindness. The expected
benefits is expressed as the higher proportion of
patients who maintained or improved their visual
acuity (15.3% in the TAP study) in comparison to
those who did not received treatment.
The intermediate result of measure is fibrosis,
which constitutes reason for dismissal. However, it
can be stated that these two results are supplemen-
tary because, even though an improvement is detec-
ted, treatment cannot be suspended until fibrosis is
verified by means of angiography. Even so, it is also
possible to detect fibrosis with worsening eyesight.
As an additional result of measurement, quality
adjusted visual acuity gain has been considered. For cal-
culating it, the usefulness measures estimated by Brown
et al are utilized (15). The results are shown in table I.
For this study the first 50 patients who fulfilled a
complete treatment cycle were selected. In some
cases, both eyes are treated. The patient selection
criteria are assessed regularly by means of audits,
fulfilling the proposed criteria (11) in all cases (16).
Measure of use of resources
The itinerary followed by the patients began at
the ophthalmology service of the regional reference
hospital to confirm the diagnosis. If positive, the
patient was referred to the area hospital where the
patient of the entire autonomous community are
Usefulness CI 95%
0.89 0.82-0.96
0.81 0.73-0.89
0.57 0.47-0.67
0.52 0.38-0.66
0.40 0.29-0.50
201
MUSLERA E, et al.

attended to. Here, the visual acuity test was carried The marginal cost (cost of each additional ses-
out on the same day as the angiography and treat- sion) reaches in the fourth session the minimum
ment with verteporfine. Finally, a checkup appoint- value of 6,993 € and in the fifth session it increases
ment is set for three months. These sessions are to 28,050 €, the highest value. This situation is
repeated not more than eight times. foreseeable because the number of aggregated favo-
It is possible to enhance the study perspective by rable cases increases in a smaller proportion (only
including the assumption that visual acuity is main- one more) between the 7th and 8th session.
tained during the life expectancy and adding infor- In the group of the study, only 12% exhibited
mation about the quality of life of affected patients. slight improvement, 70% maintained visual acuity
For the first assumption we utilized the life and 18% exhibited a reduction thereof. The mean
expectancy estimation for Asturias for the age brac- age of women was 71.2 years and men 71.8.
ket 70-74 for men (during which they commence Taking into account the efficacy date of the TAP
treatment), which is of 13 years, and 17 years for clinical essay, only 15% more of individuals who
women in the same age bracket. underwent PT achieved stable vision (loss of under
In addition, an estimation of the cost was made, 3 lines) vis-à-vis the patients who were given place-
adjusted for quality of maintenance of visual acuity. bo. Applying this effectiveness measure to our data
This was calculated by applying the usefulness we obtained the cost values presented in table II.
indices of the Sharma study to the visual acuity The cost per year gained of visual acuity in a 2-year
years gained in our population (17) because our timeframe — the period for which we have infor-
study is retrospective and it is not possible to apply mation — is of 34,804 € for men and 36,530 € for
any quality of life index. women. The considered discount rate is of 2.5%.
For calculating costs, we utilized the analytical
accountancy of the area hospital. The estimation Table II. Cost per session at the study hospital
considered the direct costs linked to the process of Costs per item Euros %
the intervention from when the patient is diagnosed
to the time of release due to fibrosis or after two 1. Personnel 39.4 2
years from treatment initiation. 2. Materials 1301.6 68
Verteporfin injection 1252.2
Material for angiography 49.4
3. Storeroom management cost 39.4 2
RESULTS 4. Equipment cost 505.0 26
Ophthalmic laser 251.7
Infusion pump 253.3
Of all the treatments applied, 63.15% (36 eyes) 5. General costs 30.2 2
were released due to remission of the lesion (fibro- Maintenance, cleaning, water, 30.2
sis). Only in one case we had release due to treat- electricity, security, documents
ment failure in the 6th session, and 16 patients were Total session cost 1915.7 100%
lost in two years.
The mean number of sessions was 5.08 per
Table III. Cost per patient and visual acuity gained year
patient. Fibrosis occurred in 70% of patients who in Asturias
followed a complete cycle. The abandonments
accumulated in the last sessions. Costs Amount (€)
The most important cost is the medication (verte-
Cost per patient 10,729 €
porfin), which accounts for 65% of each session Cost per patient who maintains or 71,525 €
cost (table II), followed by ROI of the equipment improves eyesight
(photo-coagulating ophthalmic laser), with 26%. Cost per year of maintained
The total cost (cost of all sessions given to patient visual acuity (2 years):
• Men 34,804 €
during the period) reached 549,611 €. The cost per • Women 36,530 €
patient was of 10,729 € and the cost per «success- Cost per year of maintained visual
ful» patient —those who improved or maintained acuity (assuming stability during life
their visual acuity due to the application of PT, dif- expectancy period)
• Men (13 years) 5,354 €
ference between option of not treating and the tre- • Women (17 years) 4,298 €
atment— amounted to 71,525 € (table III).
202 ARCH SOC ESP OFTALMOL 2006; 81: 199-204

In a two-year scenario, the cost estimate for each
year of quality-adjusted gained visual acuity is of
66.931 € for women and 70.249 € for men. This
estimate is detailed in table IV.
DISCUSSION
Although some questions remain, subject to the
results of the essays still in process (18), at this time
PT is the choice for exudative ARMD. The option
is to do nothing because other therapeutic options
are in experimental stages or have proved to have
negligible efficiency rates.
From the viewpoint of health services it is neces-
sary to determine the cost-effectiveness ratio of PT
and, in the light of the results, to establish whether
allocating public funds to PT is justified. In this study
the yearly cost for the health services for maintaining
visual acuity in ARMD patients by applying PT is in
the area of 36,000 €. The benefits of PT consist in
maintaining or slightly improving visual acuity. For
this reason it is extremely important that treated
patients must exhibit good visual acuity, far from the
current situation (which borders legal blindness).
If it is assumed that the results will be maintained
during the life expectancy period, costs go down
substantially: 5,354 € for men 4,298 € for women
(table III). This scenario is also shown by Sharma et
al, who consider a life expectancy of 11 years wit-
hout gender differentiation (17).
To justify the priority which can be given to PT
within the public services portfolio we have the cri-
terion established by the study of Sacristán et al
who considered as cost-effective (in Spain) the
interventions with a value per year of quality-adjus-
ted gained visual acuity not exceeding 30,000 €
(19). Even though the measure of health results is
somewhat different in this study —year of quality-
Table IV. Cost per year of quality-adjusted gained visual
acuity
Item Amount (€)
Cost per year of maintaining visual
acuity (2 years)
• Men 70,249
• Women 66,931
Cost per year of maintaining visual
acuity (in life expectancy period)
• Men (13 years) 9,743
• Women (17 years) 7,794
ARCH SOC ESP OFTALMOL 2006; 81: 199-204
Cost effectiveness of Photodynamic Therapy
adjusted maintained visual acuity— this reference
must be taken into account in decision-making
because the cost for that results increases to 68,000
€. With a similar analysis, Sharma et al (17) consi-
der that this intervention is moderately cost-effecti-
ve for patients with an initial VA of 20/40 and cost-
ineffective for patients with a VA of 20/200 (this is
the VA for most of our patients, with only 28%
having higher values). The same conclusion was
reached by Hopley et al (20) three years later.
If we estimate that the benefits are maintained up
to the patients’ life expectancy age, the results go
down to 5,354 € for men and 4,298 € for women.
The life expectancy timeframe for PT analysis has
been utilized by other authors (18) but it has impor-
tant limitations because we still don’t have docu-
mented evidence indicating that benefits are sustai-
ned at such a long term. It would be more adequate
for future benefits to be related to more global eva-
luations of patients, such as functional indices
because maintaining eyesight in independent
elderly people is more valuable than for dependent
people. In this way, it would be possible to cons-
truct cost scenarios for different benefits.
The limitations of the study are firstly in its
retrospective nature, which prevents the utilization
of quality-of-life questionnaires and a greater con-
trol of the application of PT in both eyes. Additio-
nal limitations relate to the size of the studied sam-
ple due to the low prevalence of the disease in the
general population with a long-term intervention
which has been introduced in clinical practice only
recently. The number of patients who complete the
treatment is limited and does not allow for further
analyses. However, said limitations do not invalida-
te the shown results, which must be considered as a
decision-making support tool for public health ser-
vices resource managers.
The recommendations which arise of the study
are the need of improving early detection —eyes
with many druses or hyperpigmentation are at gre-
ater risk (21)— and the definition of treatment pro-
tocols allowing for increased effectiveness.
ACKNOWLEDGEMENTS
The authors would like to express their gratitude to
the Hospital del Oriente de Asturias for their help in
data collection and Dr. Patricio Adúriz Alonso reve-
aling to us some of the mysteries of ophthalmology.
203
MUSLERA E, et al.
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