Download Persistent Central Serous Chorioretinopathy

PERSISTENT CENTRAL SEROUS CHORIORETINOPATHY SECONDARY TO CHRONIC CORTICOSTEROID
TREATMENT FOR AUTOIMMUNE HEPATITIS
AMANDA S LEGGE
ABSTRACT
CASE REPORT: A sixty one-year-old Hispanic male has been experiencing episodes of blurred vision O.U. for approximately
eleven years. He was diagnosed with chronic central serous chorioretinopathy shortly after beginning steroid treatment for
autoimmune hepatitis twelve years ago. Since that time the posterior pole of both eyes has undergone severe retinal
pigment epithelium atrophy and subsequent permanent deterioration of vision in the right eye. Although subretinal fluid
was still present in both eyes, his vision was stable with minimal active leakage. Treatment options were discussed;
however intervention at this time was deferred. The patient continues to be monitored closely at four month intervals.
DISCUSSION: Central serous chorioretinopathy is an idiopathic disorder in which a serous detachment of the retina or retinal
pigmented epithelium occurs by means of fluid diffusing from the choriocapillaris through Bruch’s membrane. Often the
condition is self-resolving and treatment is unnecessary. However, in the chronic form, laser photocoagulation or medical
intervention is needed to reduce the risk of permanent visual impairment. Several treatment options are available. Each
patient must be evaluated to determine which treatment, if any, will be of maximum benefit with minimal risk.
Central serous chorioretinopathy (CSCR) is a
fairly common, idiopathic, disorder of the
choroid. More specifically it is a disorder of the
choriocapillaris and Bruch’s membrane. Fluid
from the choriocapillaris diffuses through
Bruch’s membrane resulting in a serous
detachment of the sensory retina or retinal
pigment epithelium (RPE). This causes a
blurring or distortion of central vision which
often
resolves
without
intervention.
Chronically, CSCR can result in a dysfunctional
RPE and concomitant visual reduction1.
The following case report illustrates the effects
of persistent CSCR secondary to steroid
treatment for autoimmune hepatitis as well as
treatment considerations.
CASE REPORT
HISTORY
The patient is a 61-year-old Hispanic male. His
medical history is remarkable for Raynaud’s
syndrome, hypothyroidism, hyperlipidemia,
scleroderma, hypertension, and autoimmune
hepatitis. His most current medications
included ranitidine, omneprazole, amlopidine,
levothyroxine, acetaminophen, azathioprine,
and prednisone. He reported allergies to
adhesive tape and rayon.
He was first diagnosed with autoimmune
hepatitis 12 years ago and began a regimen of
long term steroid treatment with prednisone.
The dosage varied based on the patient
symptoms and serum tests including AST, ALT,
alkaline phosphatase, IgG, and bilirubin. The
patient is currently medicated with 20 mg
prednisone per day for the last 8 months. In the
past this ranged from 0 mg to 50 mg per day.
He has also been on a constant dose of
azathioprine 200 mg per day for the last 5 years
to control hepatitis signs and symptoms.
The patient’s ocular history is remarkable for
chronic central serous chorioretinopathy (CSCR)
O.U. which CSCR became relapsing and
remitting approximately 6 months after
beginning steroid treatment. At initiation of
treatment he was given a high dosage of oral
prednisone but was unable to recall the exact
quantity. He reported that he had fluctuating
vision in both eyes for the next few years. The
right eye worsened permanently approximately
9 years ago.
The patient also reported having an episode of
posterior uveitis O.S. more than 15 years ago
that resolved uneventfully without treatment.
The chief complaint upon presentation was
moderate fluctuating vision O.S. and difficulty
adapting from light to dark environments. He
felt that the vision in his left eye improved from
6 months ago when his visual acuity was
measured 20/40.
DIAGNOSTIC DATA
The patient’s aided visual acuity was count
fingers at 3 feet O.D. and 20/25 O.S. without
pinhole improvement O.U. Pupils were round,
equal, and reactive to light with no relative
afferent defect. Extraocular motility testing
found no restrictions of muscle movement.
Confrontation visual fields were full to finger
counting O.D., O.S.
Intraocular pressures measured 14 mmHg O.D.,
O.S. Anterior segment evaluation was
unremarkable O.U.
Amsler grid revealed a significant superior nasal
scotoma O.D. The patient reported that this has
been stable for many years. The left eye
showed mild central metamorphopsia only.
Humphrey 24-2 visual field showed the same
superior nasal scotoma O.D. and was within
normal limits O.S.
Posterior segment examination of the right eye
revealed a shallow 1.5 disc diameter serous
detachment inferior to the macula along with
several areas of pigmented atrophy. Pigment
changes associated with guttering was found
along the inferior arcade. The left eye showed
minimal foveal fluid, although a small retinal
pigment epithelium (RPE) detachment was seen
in the papillomacular bundle and a small area
of subretinal fluid was seen just temporal to the
foveal avascular zone. (figure 1)
Figure 1. Fundus Photography illustrating tracts of retinal and RPE disturbance and minimal subretinal fluid O.U.
Optical coherence tomography was performed
Inferior, diffuse, intraretinal thickening O.D.
was seen. The left eye showed a small RPE
O.D.
detachment and an area of subretinal fluid in
the papillomacular bundle was noted. This
coincided with the fundus findings. (figure 2)
O.S.
Figure 2. Optical Coherence Tomography illustrating the diffuse
macular thickening O.D. and both subretinal fluid and a small RPE detachment O.S.
Fundus autofluorescence (FAF) photography
showed the extent of the RPE atrophy O.U. The
more recent descending tracts of RPE atrophy
are hypoautofluorescent surrounded by an area
of hyperautofluorescence most obvious
inferiorly O.D. This indicates recent leakage and
subsequent RPE damage that has migrated
inferiorly.
Discrete
hyperautofluorescent
granules were seen temporal to the macula O.S
revealing evidence of a chronic serous
detachment in that area. (figure 3)
Figure 3. Fundus Autofluorescence illustrating the extensive RPE alterations and minimal leakage O.U.
A fluorescein angiography was performed.
Results showed mild, diffuse active leakage
greater O.D. than O.S. Again, as with FAF, no
pinpoint leakage was detected in either eye.
The right macula showed significant RPE
window defects that accounts for his poor
vision in that eye. (figure 4)
Figure 4. Early and late phase fluoroscein angiography illustrating minimal diffuse, active
subretinal leakage and RPE window defects O.D. greater than O.S.
DIAGNOSIS AND FOLLOW-UP
At this presentation the vision and subretinal
fluid was stable in both eyes. Although the FAF
photographs revealed mild subretinal fluid, the
fluorescein angiography did not show any
active leakage O.D., O.S. Because active leakage
was not evident, he is currently not a candidate
for thermal laser treatment.
Treatment options were discussed, including
photodynamic therapy (PDT) and intravitreal
injections.
At this time PDT was not advised because of his
stable visual acuity O.U. and the potential for
PDT to cause choroidal neovascularization or
RPE atrophy.
Intravitreal
injection
of
anti-vascular
endothelial growth factor drugs, such as
Lucentis, was discussed. The patient was also
educated on the lack of a definite positive
correlation of anti-VEGF drugs reducing CSCR in
current studies. The patient decided to defer
treatment at present.
The patient was instructed to maintain careful
4 month follow ups. Any rapid changes in vision
were to be reported so treatment options could
be altered if necessary.
The patient understood that because of his
ongoing steroid regimen his prognosis is
guarded. The patient’s primary care physician
was made aware of his chorioretinopathy and is
cognizant of keeping the prednisone at the
lowest possible therapeutic dosage.
The patient is wearing polycarbonate dress
glasses full time for protection of his left eye.
He is aware of the necessity to guard this eye
because of his monocular status. He wears
safety goggles for yard work and vehicle
maintenance.
DISCUSSION
Central serous chorioretinopathy (CSCR) is an
idiopathic disorder of the choroid and retina.
The acute form is most common and often
resolves spontaneously without intervention
within 4 months2. Typical symptoms include
micropsia, metamorphopsia, and decreased
vision.
Chronic CSCR has the potential to cause diffuse
retinal pigment epitheliopathy or choroidal
neovascularization, either of which can cause a
permanent decrease in vision1. Several
treatment options are then considered to stop
the recurrent leakage and prevent vision loss.
Although most cases are idiopathic, CSCR has a
strong association with increased cortisol
levels, whether endogenous or exogenous.
Type A personality is a well recognized etiology
of CSCR where increased endogenous cortisol
levels are routinely measured2,3. Similarly
patients treated with exogenous steroids,
administered by any route, for autoimmune or
inflammatory disorders are at risk for
developing CSCR3,4.
The mechanism by which cortisol causes CSCR
is minimally understood. Cortisol may be
responsible for choroidal vascular spasm by
inhibiting the parasympathetic nervous system
and promoting the sympathetic nervous
system. This spasm causes temporary damage
to the choroid and results in leakage of serous
fluid. The pressure created beneath Bruch’s
membrane and the RPE disrupts the outer
blood retinal barrier and allows the
accumulation of fluid under the retina5.
Permanent vision loss is thought to be caused
by the persistent detachment of the
photoreceptors to the RPE and source of
nourishment6.
Studies show that CSCR typically resolves
spontaneously once exogenous steroids are
discontinued4. Unfortunately many patients
cannot discontinue a steroid regimen because
of a systemic inflammatory disease. Therefore
careful
monitoring
and
treatment
considerations must be given to this complex
population.
DIAGNOSTIC TECHNIQUES
Several techniques are used to diagnose and
determine appropriate management of CSCR.
These include biomicroscopy, optical coherence
tomography (OCT), fluorescein angiography,
indocyanine green angiography, and fundus
autofluorescence photography as well as visual
field and Amsler grid testing.
Commonly biomicroscopy is all that is needed
to diagnose CSCR because of its unique
presentation. In active CSCR, a serous
detachment of the retina is seen near the
fovea, although it can rarely be eccentric near
the vascular arcades. Retinal pigment
epithelium (RPE) abnormalities are present
once the fluid resolves. RPE hypopigmentation
rather than atrophy is most common; however
RPE atrophy is the cause of severe, permanent
vision loss from CSCR7. Primary RPE
hyperpigmentation is rare. Rather, the
accumulation of subretinal fibrous deposits is
reflected darkly during biomicroscopy1.
Other techniques are used to monitor the
retinal status quantitatively over time. OCT can
determine the amount of fluid and
consequential thickness of the macula
noninvasively and objectively. It is also used to
monitor progression over time.
Retinal thickness during CSCR is a result of the
buildup of serous fluid under the retina as well
as subclinical edematous cells within retina8.
The symptom of micropsia is thought to be
caused by the intracytoplasmic swelling of the
Müller cells which causes photoreceptor
disruption9. OCT testing shows any serous
retinal detachment as low reflectivity under the
retinal layers or below the RPE in the case of an
RPE detachment. Additionally, the detached
retina itself often shows intraretinal areas of
low reflectivity demonstrating the subclinical
intraretinal swelling8.
Angiographic studies are useful to determine
any active leakage sites and vascular changes.
The two most recognizable fluoroscein
angiography (FA) leaks are the ink blot and
smokestack patterns. A majority of CSCR leaks
are characterized by leakage of fluid within the
serous detachment zone without any typical
pattern. FA typically shows a focal leak as an
enlarging exudation of dye which can guide
photocoagulation laser10.
Alternatively, indocyanine green angiography
(ICGA) typically shows a more widespread
exudation of dye from the choriocapillaris
surrounding a focal leakage. This demonstrates
that CSCR is foremost a choroidal disease11.
Furthermore ICGA shows hypofluorescent areas
not evident in FA in chronic CSCR. These are
areas of RPE damage that are often subclinical
during biomicroscopy or FA which illustrates
the widespread damage that CSCR causes to
subretinal structures12.
A noninvasive imaging technique for CSCR is
fundus
autofluorescence
(FAF).
The
fluorescence is derived from lipofuscin, a
yellow-brown aging pigment commonly found
in the retina. Therefore it indirectly gives
information about the metabolic activity of the
RPE. Loss of photoreceptors results in
decreased autofluorescence because the
metabolic demand on the RPE is diminished.
Focal increase in autofluorescence is due to
increased turnover of the outer photoreceptor
segments or an abnormality in the phagosomal
uptake of lipofuscin from them13.
FAF in acute CSCR is consistent with a focal
increase in autofluorescence over the serous
retinal detachment. This is due to the abnormal
degradation of phagosomal material from the
photoreceptor outer segments because of a
sick RPE13,14.
In the chronic form, FAF shows mixed hyperand
hypoautofluorescence.
The
hypoautofluorescence
in
chronic
CSCR
corresponds with loss of photoreceptor outer
segments with secondary reduction in RPE
metabolic activity. The atrophy of this layer
coincides with a reduction of vision, especially
if present centrally15.
THERAPEUTIC CONSIDERATIONS
Treatment is considered if a serous detachment
is persistent for several months, recurrence if
any previous episode caused a sustained visual
deficit, or if the patient requires faster
restoration of vision2.
Thermal photocoagulation and photodynamic
therapy (PDT) are currently the mainstay of
CSCR treatment. Other possibilities are antivascular endothelial growth factor (anti-VEGF)
injections, anti-glucocorticoid agents, oral
acetazolamide, and adrenergic receptor
inhibition1.
Photocoagulation has been used for decades in
the treatment of CSCR. The application of
thermal laser to the site of leakage resolves the
serous fluid at a faster rate than no treatment.
Resolving the detachment may prevent
photoreceptor loss by shortening the length of
time these cells are separated from the RPE,
choriocapillaris, and proper nutrition17.
Thermal photocoagulation carries risks that are
important to consider before proceeding with
treatment. These include inadvertent foveal
burns, pre- and subretinal fibrosis, choroidal
neovascularization, and progressive expansion
of laser burns18.
A pinpoint, extrafoveal, leak must be seen on
FA in order to proceed with this laser therapy.
With candidacy, the goal of photocoagulation in
CSCR is 200µm confluent spots in the area of
leakage at an intensity to bleach without
whitening the outer retina1,19. This limits the
amount of damage to the choroid and reduces
the
risk
of
secondary
choroidal
neovascularization. Minimal laser treatment
with maximal results is the objective.
Visudyne PDT is often utilized when
photocoagulation is inappropriate. This
includes sub- or juxtafoveal leakage sites or
when a pinpoint site of leakage is not defined.
PDT decreases subretinal fluid by selectively
occluding vessels in the choriocapillaris. This
occurs through cytotoxic damage of endothelial
cells and consequential thrombosis20. Minimal
retinal or choroidal damage occurs with this
technique21.
Although overall less damaging to the RPE,
choroid, and retina, PDT also has the potential
to induce choroidal neovascularization. In
addition it requires avoidance of sunlight after
treatment for 24-36 hours because of
photosensitization22. This must be weighed
against the benefits when considering PDT
treatment.
More recent studies are considering anti-VEGF
agents for the treatment of CSCR. VEGF has
profound
effects
on
vascular
hyperpermeability, which is the underlying
reason for CSCR. These agents are thought to
reduce subretinal fluid by decreasing the
concentration of VEGF released by choroidal
ischemia23.
These studies have not shown a highly positive
link to reducing CSCR and improving vision long
term24. Anti-VEGF injections come with low risk
and have shown short term benefit to reducing
leakage in CSCR in some studies. Thus it is a
viable treatment option for CSCR when other
methods are avoided.
Anti-glucocorticoid medications, such as
mifepristone and ketoconazole, are an
alternative currently being investigated for the
treatment of CSCR25,26. Increased cortisol levels
are well documented to cause CSCR. Antiglucocorticoid agents aim to reduce cortisol
levels thereby reducing serous detachments
and improving visual acuity in patients. Both
medications have mixed results according to
recent studies26,27. More studies are warranted
before they become standard treatment
options.
Several other treatment methods have been
proposed for CSCR including acetazolamide,
adrenergic receptor inhibition, and beta
blockers28. Alternative medicines, such as
acupuncture29, have also been studied. None
have been shown to have a direct positive
correlation with the long term reduction or
preservation of vision from CSCR.
Chronic central serous chorioretinopathy is
difficult to manage when caused by persistent
steroid use that cannot be discontinued.
Several options exist for the treatment of CSCR.
The risk and benefit of all treatment strategies
must be considered.
The patient in this case is currently best
managed with observation because of his
stable vision and the potential for tapering his
prednisone dosage in the near future. Close
monitoring along with proper patient education
and primary care physician involvement is an
appropriate treatment option at this time.
Medical interventions will be discussed if the
patient’s vision or retinal status decreases over
time.
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