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NR 4-6/2007
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Macular
microcirculation blood flow in patients with age related macular
degeneration treated with photodynamic therapy and
transpupillary thermotherapy
Mikrokrążenie plamkowe u
pacjentów z AMD leczonych terapią fotodynamiczną i termoterapią
przezźreniczną
Agnieszka Kubicka-Trząska
Department of Ophthalmology, Medical College, Jagiellonian
University, Kraków
Head: Ass. Prof. Bożena Romanowska-Dixon, MD, PhD |
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| Summary: |
Purpose: To assess the
macular retinal and choroidal microcirculation blood
flow in patients with exudative age related macular
degeneration before and after photodynamic therapy (PDT)
or transpupillary thermotherapy (TTT) with Doppler laser
scanning (HRF – Heidelberg retinal flowmeter).
Material and methods: Thirty patients with exudative
age-related macular degeneration were included in a
prospective study. The diagnosis was established based
on ophthalmic examination and fluorescein angiography
results. In all cases the subfoveal choroidal
neovascularization (CNV) was present. Control group
consists of the fellow eyes with early stage of AMD (19
eyes) or with disciform scar (11 eyes). In 15 eyes with
active CNV PDT was performed and in remaining 15 – TTT.
In all cases the macular blood flow was measured with
Heidelberg retina flowmeter (HRF) before therapy and
then 1 week, 4 weeks and 10-12 weeks after treatment.
Results: At the baseline examination in a group of eyes
with active CNV the mean values of macular blood flow
were significantly higher comparing to the fellow eyes
and reached respectively: 678.6 ± 125.0 AU and 298.4 ±
79.2 AU (p=0.001).
Four weeks after treatment all eyes showed the reduction
of macular blood flow comparing to the baseline values
(p=0.001). Ten to twelve weeks after laser therapy in
all cases the increased macular blood flow was detected
comparing to the previous examination (p=0.01). During
the follow-up period the macular blood flow in the
fellow eyes were significantly lower than in treated
eyes.
Conclsions: The measurement of macular blood flow using
Doppler scanning laser (HRF – Heidelberg retinal
flowmeter) may act as a non-invasive and useful
diagnostic tool in assessment of CNV activity in
patients with exudative age-related degeneration before
and after PDT or TTT. |
| Słowa kluczowe: |
AMD, HRF, mikrokrążenie
plamkowe. |
| Key words: |
Age related macular
degeneration, Doppler laser scanning, macular
microcirculation blood flow. |
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Age related macular degeneration (AMD)
is a disease characterized by the presence of functional and
morphological alterations in the retina, Bruch’s membrane, the
retinal pigment epithelium, the choriocapillaris and larger
choroidal vessels in addition to changes in ocular perfusion
(1). In patients with the early stage of AMD, with age-related
maculopathy (ARM) many various vascular alterations have been
reported: a raised number of ischemic retinal capillaries,
reduction of choroidal blood flow, an increase in pulsatility
and decreased velocity of the short posterior ciliary arteries,
increased submacular choriocapillaris density with reduced
density of large choroidal vessels (2,3,4).
There are many methods of non-invasive measurement of the tissue
blood flow in the retina or choroid: color Doppler
ultrasonography, Doppler velocimetry, the laser speckle method,
pulsatile ocular blood flow technique (4). However, the
evaluation of the macular microcirculation by these techniques
has been difficult. Heidelberg retina flowmeter (HRF), which
combines the technique of laser Doppler flowmetry with laser
scanning technology, can measure the blood flow within the
macular region. HRF allows to measure the tissue at the depth of
300 µm, so measurements may have included the choroidal blood
flow in the foveola, where the retina is very thin,
approximately 135 µm (1). It has been known, that perfusion
alterations in retinal and choroidal capillaries within the
macular region may play an important role in pathogenesis of AMD,
and the dynamics of their changes may reflect the clinical
course of the disease (2,5,6,7).
There is a scant number of publications about the evaluation of
macular microcirculation blood flow in patients with exudative
AMD and also there are only a few papers on ocular blood flow in
patients with choroidal neovascularization (CNV) due to AMD
after laser therapy.
The aim of this study is the evaluation of macular retinal and
choroidal microcirculation blood flow with Doppler laser
scanning (HRF – Heidelberg retinal flowmeter) in patients with
exudative AMD treated with photodynamic therapy (PDT) or
transpupillary thermotherapy (TTT).
Material and methods
Thirty patients with exudative age related macular
degeneration were included in a prospective study. There were 13
males and 17 females, in age from 64 to 81 years, mean age: 73±
6.2 years. The diagnosis was established based on ophthalmic
examination and fluorescein angiography results. In each patient
the exudative AMD was present in one eye; the subfoveal CNV was
present, which in 17 cases was classic and in 13 – occult. The
distance visual acuity in this group of eyes ranged from
counting fingers at the distance of 3 meters to 0.4. Control
group consists of the fellow eyes with disciform scar (11 eyes)
or with an early stage of AMD (age related maculopathy – ARM)
that is characterized by the presence of drusen ≥ 63 µm and/or
RPE atrophy and/or RPE proliferation (19 eyes). The distance
visual acuity in this group of eyes ranged from hand movements
to 0.9.
Based on qualification criteria in 15 eyes with active CNV PDT
was performed; this group includes 11 eyes with classic CNV and
4 with occult CNV. In the remaining 15 eyes with classic CNV in
6 eyes and occult CNV in 9 eyes, not qualified for PDT because
of a very large lesion size and visual acuity worse than 0.1 –
TTT was performed.
Photodynamic therapy was performed using a diode laser with an
emission wavelength at 689 nm (laser Opal, Coherent) and an
intravenous injection of 6 mg/m2 BSA verteporfin (Novartis AG,
Switzerland). The therapy was started 5 minutes after the
infusion of verteporfin was completed.
Transpupillary thermotherapy was performed with a diode laser
with an emission wavelength at 810 nm (IRIS Medical Instruments,
Mountain View, California, USA). In every case the diameter of a
laser spot was established based on a largest linear diameter of
CNV measured on fluorescein angiography to which 1000 µm was
added. The laser power for PDT was stable: 50J/cm2, but for TTT
depended on laser spot size and ranged from 520 mW do 680 mW.
The tissue blood flow in the macular area was measured using a
scanning laser flowmeter (Heidelberg retina flowmeter,
Heidelberg, Germany). The measurement area included a zone of 10
x 2.5o, that equals to 2.8 x 0.7 mm. During each measurement the
foveola was located in the central part of the scanned area
(Fig. 1). The macular blood flow was measured before therapy and
then 1 week, 4 weeks and 10-12 weeks after treatment. During
each follow-up the measurements were performed in each eye at
least 3 times.
The results of microcirculation blood flow were presented in
arbitrary units – AU. The calculation of macular area capillary
blood flow was performed with AFFPIA program (automatic
full-field perfusion image analyzer). The results were
statistically analysed using a t-Student test for independent
trials. Level of significance was p≤0.01.
Results
At the baseline examination in eyes with CNV qualified for
PDT or TTT the mean values of macular blood flows were: 678.6 ±
125.0 AU and 702 ± 168.0 AU, respectively. In the fellow eyes
the mean values of microcirculation blood flow in macu lar area
were statistically significantly lower: 298.4 ± 79.2 AU
(p=0.001).
In all treated eyes 1 week after therapy significantly decreased
mean values of blood flow in macular region were recorded. In
eyes after PDT the mean values of blood flow were: 390.3 ± 101.8
AU and in eyes treated with TTT: 360.71 ± 121.2 AU.
Four weeks after treatment all eyes showed the reduction of
macular blood flow comparing to the baseline values (p=0.001)
and they reached: 359± 108.7 AU in eyes treated with PDT and
371.45± 111.9 AU in eyes treated with TTT. In the third
follow-up examination performed 10-12 weeks after laser therapy
significantly increased values of macular blood flow were
detected in treated eyes as compared to the previous results.
These values were as follows: 608.7 ± 124.6 AU in eyes after PDT
and 512.4 ± 101.3 AU in eyes after TTT (p=0.01).
During the whole follow-up period the mean values of macular
blood flow in the fellow eyes were significantly lower comparing
to the treated eyes.
The mean values of macular microcirculation blood flow in
patients with CNV treated with PDT and TTT and in fellow eyes
during a 3-months follow-up period are presented in table I.
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Discussion
It has been known that alterations of ocular circulation
both retinal and choroidal play an important role in
ethiopathogenesis of AMD. It has been documented that in
patients with an early stage of AMD; with age related
maculopathy which is characterized by the presence of soft
drusen and RPE changes and also in eyes with geographic atrophy
the decreased retinal capillaries blood flow is observed. The
more advanced stage of the disease the more increased values of
tissue ocular blood flow are present, what is suggestive for
ischemia as an important factor in development of AMD (8,9,10).
Chen et al. in eyes with CNV showed increased values of ocular
pulsatile blood flow while in eyes with disciform scar its
reduction was observed (11). In our material in eyes with drusen
and/or RPE changes and in eyes with disciform scar we also found
lower mean values of macular blood flow using the HRF comparing
to the eyes with an active CNV. We have found only one
publication about the assessment of ocular blood flow measured
with the pulsatile ocular blood flow technique in patients with
AMD treated with TTT (11). In our study we evaluated the changes
in macular blood flow in two groups of eyes; treated with PDT or
TTT. We noted decreased values of macular blood flow 1 and 4
weeks after laser therapy. In a follow-up examination performed
10-12 weeks after treatment the mean values of macular
microcirculation blood flow in both group of treated eyes
significantly increased. Our results are similar to those
presented by Chen et al. however it is worth to underline that
in both studies two different methods of assessment of ocular
blood flow were used (11).
Both PDT and TTT lead to obliteration of pathological vessels
within the CNV. In TTT the mechanism is associated with thermal
effect, while in PDT with activation of photochemical reactions,
that lead to damage of endothelial cells and activation of
clotting cascade. It has been known that recanalization of CNV
after PDT is observed in about 94% of cases within 12 weeks
after treatment. This phenomenon is thus indicative that PDT
does not eliminate the vasoactive factors.
The increased values of macular blood flow in eyes with active
CNV was the result of detection by Doppler scanning laser the
increased density of choroidal vessels in submacular region
forming the CNV. The obliteration of pathological vessels within
CNV after PDT or TTT was correlated with the reduction of
macular blood flow.
The measurement of macular retinal and choroidal
microcirculation blood flow in patients with exudative age
related degeneration before and after PDT or TTT with Doppler
scanning laser (HRF – Heidelberg retinal flowmeter) may act as a
non-invasive and useful diagnostic tool in assessment of CNV
activity.
Literature
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Inoue M, Mashina Y., Katsura H., Oguchi Y.: Retinal blood flow
in the macular area before and after scleral buckling procedures
for rhegmatogenous retinal detachment without macular
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the choroid, Bruch’s membrane and retinal pigment epithelium in
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Brucker A, Maguire AM, Ho AC: Foveolar, choroidal blood flow in
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8. Grunwald JE, Metelitsina I, DuPont JC, Ying GS, Maguire MG:
Reduced foveolar choroidal blood flow in eyes with increasing
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Sci 2005, 46(3), 1033-1038.
9. Pilas-Pomykalska M, Nowak I, Czajkowski J, Omulecki W:
Retinal capillary blood flow in nonexudative age-related macular
degeneration. Klin Oczna 2005, 107(1-3), 60-62.
10. Chen SJ, Cheng CY, Lee AF, Lee FL, Chen JC, Hsu WM, Liu JH:
Pulsatile ocular blood flow in asymmetric exudative age-related
macular degeneration. Br J Ophthalmol 2001, 85(12), 1411-1415.
11. Chen SJ, Cheng CY, Lee AF, Lee FL, Hsu WM, Liu H: Pulsatile
ocular flow of choroidal neovascularization in asymmetric
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Praca wpłynęła do Redakcji 21.07.2006 r. (877)
Zakwalifikowana do druku 25.02.2007 r.Adres do
korespondencji (Reprint requests to):
dr n. med. Agnieszka Kubicka-Trząska
Lea Street 244/7
30-133 Kraków
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