New Concepts in Central Serous Chorioretinopathy

New Concepts in Central
Serous Chorioretinopathy
Daniel D. Esmaili, MD
Research Study Club of Los Angeles
83rd Midwinter Annual Conference
Retina Vitreous Associates
Medical Group
Which patient has CSC ?
Therapy for CSC
1. Destructive Therapy to RPE Leak
–
Thermal laser photocoagulation
–
Ocular Photodynamic Therapy (PDT)
2. Intraocular Medication
–
Bevacizumab
3. Systemic Medication
– Ketoconazole
– Mifepristone (RU 486)
– Beta Blockers
– Methotrexate
– Eplerenone
– Spironolactoce
– Rifampin
Thermal laser case
LASER
20/50 Pre-Laser
Large NSD with
Subretinal Fibrin
Superotemporal to Fovea
Moderately hot laser burn
To area of leakage
Courtesy: K. Packo
Thermal laser case
Area of initial NSD
Pre-Laser
20/40 Post-Laser
20/25 Post-Laser
1 Week After Laser
50% Reduction in NSD Size
Subretinal Fibrin More Intense
1 Month After Laser
All SRF Resorbed
Precipitates remain in area of fibrin
Thermal laser case
20/25 Post-Laser
1 Month After Laser
Hypofluorescence in laser spot
with surrounding window defect
Role for thermal laser
• In the right patient, laser continues to play a
useful role
• Laser is destructive and risks scotoma,
choroidal neovascularization
• Can only be used in cases with focal,
extrafoveal leakage
Photodynamic Therapy
PDT for CSC
Typical Case
36 y/o white male, bond trader, taking prednisone for fibromyalgia
Vision 20/80 OD
Courtesy: K. Packo
Area of PDT
early
late
Fluorescein Angiogram
Shows multiple window defects with one hot spot leak temporal to
fovea
3 months Post PDT
SRF Resolved ~ Va improved to 20/40
PDT for CSC
• First Report of PDT for central serous
• 20 eyes of 15 patients treated
• The area of hyperpermeability on ICG was treated
• Complete resolution: 12 (60%) ~ incomplete resolution: 8 (40%)
PDT for CSC
PDT has not been studied prospectively for CSC, and is an offlabel use of verteporfin. There are issues with its use for CSC:
• Parameters of Therapy ?
•
•
•
Full or half dose verteporfin
Standard or reduced fluence with full time
Standard fluence with full or reduced time
• Area to Treat ?
•
•
Leakage area seen on fluorescein angiogram
Hyperpermeability area seen on ICG angiogram
Half Dose Verteporfin
*85% complete fluid
resolution
Decreased Exposure
Time
Decreased Fluence
*Improved sensitivity in low
fluence group
Macular Society
Review
265 eyes of 237 patients
Full fluence vs half-fluence
SRF resolved in 81% by last visit
VA improved most notably in those <20/100
There were 4 eyes that had acute severe visual decrease
No difference in response by fluence setting, age, race, fluid location
PDT for CSC
How does it work?
• 12 eyes with CSC treated with Laser – 8 eyes treated with PDT
• SRF reduced in both
• The mean choroidal thickness (CT) (assessed by OCT-EDI) doesn’t change with laser,
however with PDT the CT temporarily increases at 2 days, then decreases significantly by
1 week and 4 weeks
•
Choroidal hyperpermeability, (as assessed by ICG angiography) decreases with PDT, and
not with laser
PDT for CSC
How does it work?
Maruko, I. et al. Ophthalmology 2010;117:1792–1799
371 μm
PDT causes
decreased
choroidal
thickness
Decreased
to
315 μm
Decreased
to
289 μm
Increased
to
434 μm
Decreased
to
299 μm
Complications of PDT
PDT for CSC
Potential complications
Complications from PDT for CSC, especially when
modified, are RARE. Complications rarely may include:
• Decreased mfERG
• Decreased contrast sensitivity
• Decreased retinal sensitivity
• Decreased fixation stability
• Decreased vision
• Stimulation of CNV
• Increased subretinal fluid
• The most serious adverse outcome, acute
(within 7 days of treatment) severe visual
acuity decrease, occurs in about one in 50
patients. (Cochrane Review. 2005)
PDT for CSC
PDT is currently the top therapy
for CSC but there are still
problems:
•
Even with modifications (reduced dose, time or fluence), it
may still cause decreased sensitivity, fixation loss, increased
SRF
•
•
•
Leakage points may be too diffuse to allow treatment
Insurance may not cover it, and patient can’t afford the drug
Thus, systemic therapy may be desirable
Pharmacologic
Therapy of
Central Serous
Intraocular
Pharmacologic
Therapy of
Central Serous
Bevacizumab Treatment of CSC
Current Eye Research 35(2), 91–98, 2010
•
•
15 eyes with CSC treated with bevacizumab vs. 15 control eyes who refused injection
•
Treatment showed benefit in resolution of fluid and improvement of vision over
control
Treatment in 15 patients with single intravitreal injection of bevacizumab 2.5 mg/0.1
mL ~ 15 patients control
Bevacizumab Treatment of CSC
Artunay,
et al Current
Eye Research
35(2), 2010
Artunay,
O et alOCurrent
Eye Research
35(2), 91–98,
91–98, 2010
Comparison of Treatment Effect at 6 Months
Resolution of
Subretinal Fluid
Vision Stable or
Improved
Mean + SD OCT
Foveal Thickness
80 %
100 %
174 ± 68 μm
Control
53.3 %
66 %
297 ± 172 μm
P Value
< 0.01
< 0.01
< 0.001
Group
Bevacizumab
Positive treatment effect seen for all parameters
Bevacizumab Treatment of CSC
Korean J Ophthalmol 24(3):155-158, 2010
•
•
24 eyes with CSC randomized to bevacizumab or observation
•
•
All patients showed improvement in vision, FA leakage, and SRF
Treatment in 12 patients with single intravitreal injection of bevacizumab 1.25 mg/0.05
mL ~ 12 patients control
No significant differences in acuity, OCT, or remission duration
Bevacizumab Treatment of CSR
Lim, JW et al Korean J Ophthalmol 24(3):155-158, 2010
No statistical
difference
Bevacizumab Treatment of CSR
Lim, JW et al Korean J Ophthalmol 24(3):155-158, 2010
No statistical
difference
Bevacizumab Treatment of CSC
Eye. 2013 Dec;27(12):1339-46
Bevacizumab Treatment of CSC
• Conflicting studies in
literature, but probably not
effective
• Improvements seen may
still represent the natural
history of the condition
Systemic
Pharmacologic
Therapy of
Central Serous
Medical approaches to CSC
The following drugs and supplements have all been reported in medical or
lay press as potentially beneficial in CSR. None are proven
•
Amino acids: afginine, lysine,
ornithine
•
•
•
•
•
•
Acetazolamide
•
Corticotropin-Releasing Factor
(CRF) Reducers:
• Alpha helical CRF
• Diazepam
• Imipramine
•
Presumed Cortisol Reducers:
• Procaine HCL (“AntiCort”)
• Phosphatidylserine
•
Tranquillizers & Stress Reducers:
• Diazepam
• Prozac
• Tricyclic antidepressants
• Cannabis (Marijuana)
Acycloguanosin (antiviral)
Indomethacin
Picogenol (Pine bark antioxidant)
Acetyl-L-carnitine
Nutritional Supplements:
• Bilberry
• Bayberry bark
• Cayenne (capsicum)
• Red raspberry leaves
Drugs that modulate endogenous
steroids
Ketoconazole (Nystatin) – antifungal, corticosteroid
antagonist
Metyrapone (Metopirone) – blocks cortisol synthesis
Mifepristone RU486 (Mifeprex) – antagonist of
progesterone and glucocorticoid receptors
Mitotane (Lysodren) – directly affects adrenal tissue
Amino-glutethimide (Cytadren) – blocks cortisol creation
Rifampin - induction of cytochrome p450 with increased
hepatic metabolism of endogenous corticosteroids
Eplerenone –(Inspra)
mineralocorticoid antagonist
Spironolactone (Aldactone) - mineralocorticoid
antagonist
Rifampin – Index
case
• Central serous choroidopathy
•
versus
Tuberculous related maculopathy
Index case
+PPD, +CXR, +Quantiferon gold
Started on Quadruple therapy
OD
20/70
Pre-Therapy
OD
20/80
1 mo Later
Fluid Resolved !
Index Case – Rifampin
Abx stopped after 9 mos
OD
20/80
At end of
TB therapy
OD
20/80
2 mo after
stopping
TB meds
Fluid Returned !
Index Case – Rifampin
Meds restarted
OD
20/80
Before restarting
TB therapy
OD
20/80
1 mo after
restarting
TB meds
Fluid Resolved Again
Index Case – Rifampin
1. Is it possible that the retinal findings are
related to tuberculosis, or is this CSC?
2. If this is CSC, why are the TB medications
causing an apparent effect?
Rifampin
• Potent inducer of
cytochrome P-450 in
the liver
• Increases hepatic
metabolism of many
proteins and drugs
• Lowers the effectiveness
of exogenous
corticosteroids
Rifampin
• Possible Mechanism of
Action in CSC:

Lowers serum cortisol
levels via increased
hepatic metabolism

Competes for peripheral
glucocorticoid receptors
(conflicting literature)

Eradicates H. pylori
infection
Index Case – Rifampin
Rifampin monotherapy
• Infectious Disease:
 Gallium scan – no evidence
of active tuberculosis
 CXR looked inactive
 No pulmonary symptoms
• Recommendation:
 Switch patient to
rifampin monotherapy
Index Case – Rifampin
1 mo later
• 20/70+ OD 20/30 OS
• OCT remains dry
• Patient continued on rifampin alone for 6
months, and no subretinal fluid occurs
Rifampin – Side Effects
Orange Urine
• Headache
• Nausea
• Urine/fluids turns orange
• Back pain
• Allergy
• Hepatotoxicity
• Increases metabolism of some
medications (coumadin, Viagra)
Rifampin for Ocular Central
Serous ChoroidopThy And Retinopathy
Principal Investigator: Zac B. Ravage, MD
Eplerenone (Inspra) and
Spironolactone (Aldactone)
Mineralocorticoid receptor
antagonism in the treatment of
chronic central serous
chorioretinopathy: a pilot study
Spironolactone in the treatment of
central serous chorioretinopathy - a
case series.
Bousquet E et al
Retina. 2013 Nov-Dec;33(10):2096-102
Herold TR, Prause K, Wolf A, Mayer WJ, Ulbig
Graefes Arch Clin Exp Ophthalmol
Non-randomized
Non-randomized
N=18, CSC of at least 4 mos
25-50mg/day oral eplerenone
Significant SRF reduction
Uncontrolled, N=18
25mg bid x 12 weeks
Significant SRF reduction
Conclusion
• There are a multitude of treatment options
available for patients with non-resolving CSR
• Ongoing clinical trials will help better
elucidate systemic treatment options
Thank you