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Acute Severe Visual Decrease
After Photodynamic Therapy
With Verteporfin: SpectralDomain OCT Features
Pearse A. Keane, MRCOphth, MSc
Elda Aghaian, MD
Yanling Ouyang, MD
Lawrence P. Chong, MD
Srinivas R. Sadda, MD
ABSTRACT
In this report, spectral-domain optical coherence tomography (OCT) was used to characterize the acute
morphologic alterations that occur when photodynamic therapy with verteporfin results in an acute severe
visual decrease. The clinical and imaging records of a
patient with neovascular age-related macular degeneration who suffered this complication were reviewed. Using spectral-domain OCT, two relatively distinct subretinal fluid compartments were visualized: a sparsely
hyperreflective pocket of subretinal fluid overlying the
fibrovascular pigment epithelial detachment, consistent with fibrinous exudation, and a more homogenously hyporeflective compartment at the periphery of
the choroidal neovascular lesion, consistent with serous
exudation. The higher axial resolution, and greater
sensitivity, of spectral-domain OCT allows improved
visualization of the subretinal space. As experience
with spectral-domain OCT grows, new parameters will
emerge—such as those related to subretinal fluid—that
will facilitate improvements in both the qualitative and
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quantitative evaluation of macular disease. [Ophthalmic Surg Lasers Imaging 2010;41:S85-S88.]
INTRODUCTION
Photodynamic therapy (PDT) with verteporfin
(Visudyne; Novartis AG, Basel, Switzerland) is known
to reduce the risk of moderate and severe visual acuity
loss in selected patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).1,2 Only a small percentage
of patients who receive PDT show an improvement
in visual acuity and, as a result, the use of PDT has
been largely supplanted by the use of intravitreal antiangiogenic therapies such as ranibizumab (Lucentis;
Genentech, Inc., South San Francisco, CA) or bevacizumab (Avastin; Genentech).3 More recently, however, efforts have been made to maximize the clinical
benefits of anti-angiogenic therapies. In particular,
the potentially synergistic activity of verteporfin and
anti-angiogenic therapy has offered a rationale for
combination therapy, leading to a revival of interest
in the use of PDT.4
The ocular and systemic safety of verteporfin monotherapy was confirmed in the Treatment of Age-Related
Macular Degeneration With Photodynamic Therapy
(TAP) Investigation1 and the Verteporfin in Photodynamic Therapy (VIP) Trial.2 However, these trials also
reported that “acute severe visual decrease,” defined as
the loss of more than 4 lines (or 20 letters) of visual acuity within 1 week after verteporfin therapy, occurs in approximately 2% of cases and is commonly due to serous
detachment of the macula overlying the CNV lesion.5
In this report, we describe the spectral-domain optical coherence tomography (OCT) features of a pa-
From the Doheny Retina Institute, Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los
Angeles, California.
Originally submitted May 22, 2009. Accepted for publication February 5, 2010.
The authors have no proprietary or financial interest in the materials presented herein.
Address correspondence to Srinivas R. Sadda, MD, Doheny Eye Institute, DEI 3623, 1450 San Pablo Street, Los Angeles, CA 90033. E-mail: [email protected]
doi: 10.3928/15428877-20101031-10
Ophthalmic Surgery, Lasers & Imaging · Vol. 41, No. 6 (Suppl), 2010
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Figure 1. (A) Fluorescein angiographic images obtained prior
to photodynamic therapy with
verteporfin revealed persistent
but sparse choroidal neovascularization leakage. (B) Spectral-domain optical coherence
tomography (Cirrus HD-OCT;
Carl Zeiss Meditec, Dublin, CA)
images obtained prior to photodynamic therapy with verteporfin
revealed evidence of persistent
intraretinal fluid, accompanied
by fibrovascular pigment epithelium detachment.
Figure 2. (A) Fluorescein angiography, performed 5 days following treatment, demonstrated
increased choroidal neovascularization (CNV) leakage in the late
phases. (B) Horizontal and (C)
vertical spectral-domain optical
coherence tomography (Cirrus
HD-OCT; Carl Zeiss Meditec, Dublin, CA) images passing through
the foveal center revealed massive subretinal fluid accumulation.
The fluid under the foveal center
is more hyperreflective (asterisk),
consistent with protein-rich, fibrinous exudation from the CNV lesion compared with the adjacent,
more hyporeflective (arrowhead)
serous exudation from the surrounding choroid.
CASE REPORT
Figure 3. Nine days following photodynamic therapy with verteporfin, spectral-domain optical coherence tomography (3D OCT1000; Topcon, Tokyo, Japan) demonstrated partial resolution of
the exudative response.
tient with neovascular AMD who presented with an
acute severe visual decrease after PDT.
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A 92-year-old woman with a diagnosis of neovascular AMD affecting her left eye presented to the
Doheny Eye Institute for ongoing management of her
condition. Visual acuity in the left eye was 20/70 and
she had received six previous intravitreal injections of
bevacizumab. Despite continued treatment, spectraldomain OCT (Cirrus HD-OCT; Carl Zeiss Meditec,
Dublin, CA) revealed persistent intraretinal fluid, accompanied by fibrovascular pigment epithelium detachment (Fig. 1). In an effort to obtain a more durable
and pronounced treatment effect and, thus, to reduce
the re-treatment frequency, combination therapy was
offered. An intravitreal injection of bevacizumab was
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Figure 4. Proposed mechanism
for subretinal fluid formation following photodynamic therapy
(PDT) with verteporfin (adapted
from Yamaguchi et al.11). Application of PDT leads to an acute
extravasation of protein-rich,
fibrinous fluid that accumulates
in the subretinal space. (A) A
fibrin membrane then forms on
the retinal pigment epithelium
(RPE). Additional serous exudation through the RPE detaches
the fibrin membrane from the
RPE. (B) The detached fibrin
membrane forms septae, which
divide the subretinal space into
multiple compartments.
again performed, followed 7 days later by the application of PDT with verteporfin using reduced fluence
parameters (300 mW/25 J). Visual acuity in the left eye
immediately prior to PDT was 20/60.
Five days following treatment, the patient returned
complaining of severe visual loss in the left eye and with
a visual acuity of 20/400. Fundus examination revealed
a large serous detachment of the neurosensory retina.
Fluorescein angiography demonstrated leakage from
occult CNV in the late phases (Fig. 2A). Spectral-domain OCT revealed massive subretinal fluid accumulation consistent with protein-rich, fibrinous exudation
from the CNV lesion and serous exudation from the
surrounding choroid (Figs. 2B and 2C).
Nine days following treatment, visual acuity had
improved to 20/60 and spectral-domain OCT demonstrated partial resolution of the exudative response (Fig.
3). Continued observation was recommended and, 3
months following verteporfin therapy, spectral-domain
OCT revealed almost complete resorption of subretinal fluid, with a final visual acuity of 20/50.
DISCUSSION
Patients receiving PDT often experience transient
visual disturbances shortly after treatment, although
severe visual decreases are rare.6 In this report, an acute
severe visual decrease was accompanied by serous macular detachment, the features of which were consistent with alterations in choroidal perfusion dynamics
known to occur in the immediate aftermath of PDT.7
Treatment with PDT begins with the intravenous injection of a photosensitive compound, verteporfin; this
compound is then activated by illumination with light
with a wavelength of 689 nm. Verteporfin activation
results in the generation of reactive oxygen species, with
resultant endothelial cell injury, platelet activation, and
thrombus formation—a process that ultimately leads
to vascular occlusion. Verteporfin therapy preferentially affects the proliferating blood vessels of the CNV
lesion, although the surrounding choroidal vasculature
may also be affected. Prior to vessel thrombo-occlusion,
the release of inflammatory mediators and the effects of
endothelial cell injury on the already hyperpermeable
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CNV lesion commonly result in acute fluid extravasation. Transient dysfunction of the outer blood–retinal
barrier formed by the retinal pigment epithelium may
further contribute to accumulation of this fluid in the
subretinal space.
Several clinical studies have employed time-domain
OCT to document the time course and morphology of
the vascular events that occur immediately after PDT.8-10
In this report, we further characterize these changes using
spectral-domain OCT technology. Two relatively distinct
subretinal fluid compartments were visualized: a sparsely
hyperreflective pocket of subretinal fluid overlying the
fibrovascular pigment epithelial detachment, consistent
with fibrinous exudation from the CNV vessels, and a
more homogenously hyporeflective compartment at the
periphery of the CNV lesion, consistent with serous exudation from the more structurally mature choroidal vessels. Although common, transient increases in subretinal
fluid after PDT are not often associated with profound
visual loss. In the current report, the large volume of exudation, combined with its dense fibrinous nature at the
foveal center, may account for the more severe effects on
vision. The formation of distinct subretinal fluid compartments separated by fibrinous membranes has previously
been described in the context of Vogt–Koyanagi–Harada
syndrome, and a similar mechanism may occur in neovascular AMD (Fig. 4).11 Profuse exudation in neovascular AMD, seen after PDT or in particularly active classic
CNV lesions, may thus explain the formation of loculated
fluid compartments that may sometimes be seen on fluorescein angiography in this condition.12
In addition to possessing a higher axial resolution than time-domain OCT, the greater sensitivity of
spectral-domain OCT results in improved signal-tonoise ratios, thus providing improved visualization and
differentiation of retinal structures, such as the demonstration of different types of exudative material in
the subretinal space described in this report. Recently,
Ahlers et al. used custom software to quantify the optical density of subretinal fluid compartments using
spectral-domain OCT and suggested that subretinal
fluid analysis may be used to distinguish between disorders such as chronic central serous chorioretinopathy
and neovascular AMD.13 From this and other studies, it
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is clear that the introduction of spectral-domain OCT
will facilitate the discovery of new OCT parameters for
both qualitative and quantitative evaluation of macular
disease. Use of such parameters may provide insights
on the pathophysiology of macular disorders, aid the
diagnosis of such disorders, and facilitate understanding of adverse treatment effects.
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