Practical Retina
Incorporating current trials and technology into clinical practice
Current concepts in managing central serous chorioretinopathy by Howard F. Fine, MD, MHSc, and Michael D. Ober, MD
Seenu M. Hariprasad Practical Retina Editor
Despite the extensive advances we have made in the treatment of various macular disorders, we are still without an FDAapproved treatment for central serous chorioreti-
nopathy (CSC). CSC is a very difficult disease to investigate. It typically resolves on its own, leaving one to wonder whether therapy or time caused disease resolution. Also, CSC is not frequently seen in clinic, which leads to fewer patients recruited into trials. Finally, the lack of understanding about its etiology makes it unclear what the treatment target should be. A wide array of treatment strategies have been explored, including PDT, macular laser, H. pylori eradication, intravitreal anti-VEGF, antioxidants, surgery, and systemic pharmacologics. Our community lacks consensus regarding a systematic treatment approach for this condition. In this column, Dr. Howard Fine and Dr. Michael Ober provide an up-to-date summary of treatment options for CSC. I am certain that their insights and review of current treatment approaches will be educational for the retina community.
Central serous c h o r i o r e t i n o p athy (CSC) affects roughly 10 men and two women per 100,000 people, and they are often younger, working-aged individuals with Howard F. Fine Michael D. Ober high visual demands. Randomized clinical trials in CSC are scarce and typically evaluate dozens of patients1-12 (Table, page 11) rather than the hundreds or even thousands of patients evaluated in trials for age-related macular degeneration (AMD), retinal vein occlusion, and diabetic retinopathy. Unfortunately, to date there are no FDAapproved medications for CSC, leaving ophthalmologists without a large treatment armamentarium. Confirming the diagnosis
The first step in approaching CSC is confirming the diagnosis. There are a number of pitfalls to exclude on the differential diagnosis list. In any patient older than 50 years, differentiation must be made from exudative AMD, which can typically be achieved with fluorescein angiography (FA).13 Polypoidal choroidal vasculopathy is well known to masquerade as CSC14 and can be differentiated with indocyanine green (ICG) angiography. Pachychoroid pigment epitheliopathy15 is a recently described entity seen on enhanced depth imaging optical coherence tomography (EDI-OCT) in eyes with a thickened choroid but without subretinal fluid and may lie on a spectrum with CSC. Additionally, posterior uveitis may coexist with CSC due to concomitant steroid use. Uveitis can also mimic CSC, such as in the case of exudative serous detachment in Vogt-KoyanagiHarada syndrome.16
doi: 10.3928/23258160-20131220-01
January/February 2014 · Vol. 45, No. 1
9
Practical Retina
Multimodal imaging
Multimodal imaging is indispensable for both diagnosis and management of CSC. Nearly pathognomonic signs for CSC include the smokestack sign, gravitating tracts, and the acute focal retinal pigment epithelium (RPE) leak or “blow-out” (Figure). While FA and ICG angiography have been the mainstay for diagnostic testing and the guide for treatment, noninvasive imaging with EDI-OCT and fundus autofluorescence (FAF) imaging has gained increasing importance to evaluate the extent of subretinal fluid and pigment epithelial detachment as well as the health of the RPE. Work-up in CSC
A work-up is usually not necessary for patients in the typical demographic: young men, those with a “Type A” personality, and pregnant women. Patients should be asked about sleep apnea,17 phosphodiesterase inhibitors for erectile dysfunction,18 and use of illicit drugs, such as the sympathomimetic “ecstasy.”19 In atypical or severe cases, however, a work-up for Cushing’s syndrome is warranted. A 24-hour urinary free cortisol can be an initial screening test, and other methods include lowdose dexamethasone suppression test, dexamethasone-corticotropin-releasing hormone test, or evening serum and salivary cortisol level. Ophthalmologists might opt to consult an endocrinologist, especially if there is a concern for pituitary adenoma or adrenal tumor.20 Treatment modalities Risk factor reduction Figure. Selected findings in CSC. (A) Classic “smokestack sign” seen in a left eye on fluorescein angiography (FA) and (B) indocyanine green (ICG) angiography. Choroidal hyperpermeability in another left eye less prominent with FA than midphase ICG (D) angiogram. “Blow-out” of the retinal pigment epithelium in a right eye seen as a focal leak on FA (E) and hypo-autofluorescent spot (F) on fundus autofluorescence imaging, with disruption in the retinal pigment epithelium visible on oblique OCT scan (G) through the defect.
10
The first treatment that should be applied is risk factor reduction. Patients on steroids of any form (oral, inhaled, topical, intra-articular, epidural, or intravenous) should be counseled to reduce or ideally eliminate exogenous steroids if possible. The majority of CSC cases secondary to exogenous steroids will resolve if the steroids are withdrawn.21 Lifestyle modification
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
Practical Retina
TABLE
Randomized Trials in Central Serous Chorioretinopathy Since 1990 Ref. Year
N
Finding
1
2013 Bae SH
Author
32
Low-fluence PDT superior to ranibizumab for chronic CSC at 12 months.
2
2013 Roisman L
15
Subthreshold diode micropulse laser superior to sham for chronic CSC at 3 months.
3
2013 Dang Y
53
H. pylori eradication did not improve acuity or subretinal fluid.
4
2013 Behnia M
37
Macular subthreshold laser therapy improved acuity at 6 months.
5
2013 Semeraro F
22
No significant difference between bevacizumab and low-fluence PDT.
6
2013 Ratanasukon M
51
High-dose antioxidants for acute CSC showed no benefit for acuity or thickness.
7
2011 Wu ZH
34
Half-dose PDT superior to placebo for acuity at 1 year.
8
2011 Bae SH
16
Reduced-fluence PDT superior to ranibizumab at 3 months.
9
2011 Klatt C
30
Selective retina therapy with (Nd:YLF) laser superior to control at 3 months.
10
2010 Lim JW
24
Bevacizumab similar to observation at 6 months.
11
2008 Chan WM
63
Half-dose PDT superior to observation for acuity and thickness at 12 months.
12
2004 Verma L
30
Diode laser superior to argon green laser at 1 month for acuity.
CSC = central serous chorioretinopathy; N = sample size; PDT = photodynamic therapy; Ref. = reference number.
with stress reduction is crucial in those with a type A personality but often difficult to achieve. Limiting work hours, increasing vacation time, encouraging exercise and adequate sleep, changing attitudes about work-life balance, and even professional counseling are all elements that can reduce endogenous cortisol levels.
The Table summarizes 12 randomized trials in CSC performed since 1990. A 2013 search of the PubMed terms “central serous AND randomized trial” resulted in 59 citations, 12 of which were randomized trials of CSC published since 1990.
complete resolution of fluid in 60% by 6 months.22 PDT was administered to hypercyanescent plaques (observed on the mid-phase ICG) at full fluence as in the TAP study: After a 10-minute infusion of verteporfin at a dose of 6 mg/m2 and a wait time of 5 minutes, laser treatment was performed for 83 seconds at 689 nm. Other trials supported these findings. However, PDT is not entirely benign and can be associated with pigmentary change, RPE atrophy, choroidal ischemia, and secondary choroidal neovascularization (CNV). In an effort to reduce collateral damage, less intensive strategies have been employed with reduced-fluence PDT (half the exposure or half the duration of laser treatment) or reduced-dose PDT (half the dose of verteporfin). Chan et al performed a randomized, controlled trial of half-dose PDT versus placebo and demonstrated that 95% of treated patients versus 58% of controls had complete absence of fluid at 1 year; visual acuity was also significantly improved.12 Re-treatment is reasonable to consider when there remains persistent fluid at least 3 months since the previous PDT, especially if there has been a positive response.
Photodynamic therapy
Laser
Photodynamic therapy (PDT) is considered by most as the first-line therapy for treatment of CSC, despite its off-label status. Yannuzzi et al first described ICG-guided PDT treatment in 20 eyes, with
Thermal laser has been the historic treatment of choice for CSC and remains an option for focal leakage outside the perifoveal area. Typical parameters include a spot size of 100 to 200 µm for 100 ms at
Observation
Observation is advisable following the initial diagnosis of acute CSC in the majority of patients because the disease is often self-limited. After 2 to 6 months of risk factor reduction, if the disease fails to improve and is encroaching on or involving the fovea, consideration of treatment is reasonable. Factors that might prompt early treatment include recurrent CSC, vocational demands, and a history of poor response in the fellow eye to initial observation. Clinical trials
January/February 2014 · Vol. 45, No. 1
11
Practical Retina
a low power of 100 to 200 mw. However, thermal laser can induce a scotoma, may increase the risk of late CNV, and is not effective in cases with diffuse RPE decompensation.23 Therefore, it is used only in select extrafoveal cases with focal leakage. Micropulse sub-threshold diode laser shows increasing promise2,4 but requires further study before widespread use for CSC.
1. Bae SH, Heo J, Kim C, Kim TW, Shin JY, Lee JY, Song SJ, Park TK, Moon SW, Chung H. Low-fluence photodynamic therapy versus ranibizumab for chronic central serous chorioretinopathy: One-year results of a randomized trial [published online ahead of print Nov. 20, 2013]. Ophthalmology. doi: 10.1016/j.ophtha.2013.09.024. 2. Roisman L, Magalhães FP, Lavinsky D, Moraes N, Hirai FE, Cardillo JA, Farah ME. Micropulse diode laser treatment for chronic central serous chorioretinopathy: a randomized pilot trial. Ophthalmic Surg Lasers Imaging Retina. 2013;44(5):465-470. 3. Dang Y, Mu Y, Zhao M, Li L, Guo Y, Zhu Y. The effect of eradicating Helicobacter pylori on idiopathic central serous chorioretinopathy patients. Ther Clin Risk Manag. 2013;9:355-360.
4. Behnia M, Khabazkhoob M, Aliakbari S, Abadi AE, Hashemi H, Pourvahidi P. Improvement in visual acuity and contrast sensitivity in patients with central serous chorioretinopathy after macular subthreshold laser therapy. Retina. 2013;33(2):324-328. 5. Semeraro F, Romano MR, Danzi P, Morescalchi F, Costagliola C. Intravitreal bevacizumab versus low-fluence photodynamic therapy for treatment of chronic central serous chorioretinopathy. Jpn J Ophthalmol. 2012;56(6):608-612. 6. Ratanasukon M, Bhurayanontachai P, Jirarattanasopa P. High-dose antioxidants for central serous chorioretinopathy; the randomized placebo-controlled study. BMC Ophthalmol. 2012;12:20. 7. Wu ZH, Lai RY, Yip YW, Chan WM, Lam DS, Lai TY. Improvement in multifocal electroretinography after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy: a randomized placebo-controlled trial. Retina. 2011;31(7):1378-1386. 8. Bae SH, Heo JW, Kim C, et al. A randomized pilot study of lowfluence photodynamic therapy versus intravitreal ranibizumab for chronic central serous chorioretinopathy. Am J Ophthalmol. 2011;152(5):784-792. 9. Klatt C, Saeger M, Oppermann T, Pörksen E, Treumer F, Hillenkamp J, Fritzer E, Brinkmann R, Birngruber R, Roider J. Selective retina therapy for acute central serous chorioretinopathy. Br J Ophthalmol. 2011;95(1):83-88. 10. Lim JW, Ryu SJ, Shin MC. The effect of intravitreal bevacizumab in patients with acute central serous chorioretinopathy. Korean J Ophthalmol. 2010;24(3):155-158. 11. Chan WM, Lai TY, Lai RY, Liu DT, Lam DS. Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial. Ophthalmology. 2008;115(10):1756-1765. 12. Verma L, Sinha R, Venkatesh P, Tewari HK. Comparative evaluation of diode laser versus argon laser photocoagulation in patients with central serous retinopathy: a pilot, randomized controlled trial. BMC Ophthalmol. 2004;4:15. 13. Eandi CM, Ober M, Iranmanesh R, Peiretti E, Yannuzzi LA. Acute central serous chorioretinopathy and fundus autofluorescence. Retina. 2005;25(8):989-993. 14. Yannuzzi LA, Freund KB, Goldbaum M, Scassellati-Sforzolini B, Guyer DR, Spaide RF, Maberley D, Wong DW, Slakter JS, Sorenson JA, Fisher YL, Orlock DA. Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology. 2000;107(4):767-777. 15. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina. 2013;33(8):1659-1672. 16. Khairallah M, Kahloun R, Tugal-Tutkun I. Central serous chorioretinopathy, corticosteroids, and uveitis. Ocul Immunol Inflamm. 2012;20(2):76-85. 17. Kloos P, Laube I, Thoelen A. Obstructive sleep apnea in patients with central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2008;246(9):1225-1228. 18. Aliferis K, Petropoulos IK, Farpour B, Matter MA, Safran AB. Should central serous chorioretinopathy be added to the list of ocular side effects of phosphodiesterase 5 inhibitors? Ophthalmologica. 2012;227(2):85-89. 19. Hassan L, Carvalho C, Yannuzzi LA, et al. Central serous chorioretinopathy in a patient using methylenedioxymethamphetamine (MDMA) or “ecstasy.” Retina. 2001;21:559-561.
12
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Anti-VEGF
There is mounting evidence that anti-VEGF agents are not effective for CSC.24 A recent prospective, randomized trial demonstrated superiority of reduced-fluence PDT over ranibizumab.1 Care must be taken in interpreting positive study results regarding CSC because the natural history is quite favorable. Systemic agents
Systemic anti-glucocorticoids seem a logical approach for refractory cases, but conclusive randomized clinical trial data are lacking to date. Small series exist to support a number of agents, including mifepristone,25 ketoconazole,26 rifampin,27 finesteride,28 and eplerenone.29 Patients with chronic severe CSC that is recalcitrant to local therapy may consider these agents. Unfortunately, the data as of yet remain unconvincing to recommend detection and eradication of H. pylori, nor do they support high-dose anti-oxidant supplementation.6 Lastly, for the most severe cases with exudative detachment, surgical drainage is an option.30
REFERENCES
20. Thoelen AM, Bernasconi PP, Schmid C, Messmer EP. Central serous chorioretinopathy associated with a carcinoma of the adrenal cortex. Retina. 2000;20:98-99. 21. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology. 2002;109:18341837. 22. Yannuzzi LA, Slakter JS, Gross NE, Spaide RF, Costa D, Huang SJ, Klancnik JM Jr, Aizman A. Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study. Retina. 2003;23(3):288-298. 23. Burumcek E, Mudun A, Karacorlu S, Arslan MO. Laser photocoagulation for persistent central serous retinopathy: results of long-term follow-up. Ophthalmology. 1997;104(4):616-622. 24. Chung YR, Seo EJ, Lew HM, Lee KH. Lack of positive effect of intravitreal bevacizumab in central serous chorioretinopathy: meta-analysis and review [published online ahead of print Nov. 8 2013]. Eye (Lond). doi: 10.1038/eye.2013.236. 25. Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina. 2011;31(9):1928-1936. 26. Meyerle CB, Freund KB, Bhatnagar P, Shah V, Yannuzzi LA. Ketoconazole in the treatment of chronic idiopathic central serous chorioretinopathy. Retina. 2007;27(7):943-946. 27. Steinle NC, Gupta N, Yuan A, Singh RP. Oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy. Br J Ophthalmol. 2012;96(1):10-13. 28. Forooghian F, Meleth AD, Cukras C, Chew EY, Wong WT, Meyerle CB. Finasteride for chronic central serous chorioretinopathy. Retina. 2011;31(4):766-771. 29. Bousquet E, Beydoun T, Zhao M, Hassan L, Offret O, BeharCohen F. Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: A Pilot Study. Retina. 2013;33(10):2096-2102. 30. John VJ, Mandelcorn ED, Albini TA. Internal drainage for chronic macula-involving serous retinal detachment in idiopathic central serous chorioretinopathy [published online ahead of print Feb. 14, 2013]. Int Ophthalmol. 2013. doi: 10.1007/s10792-013-9731-9.
Howard F. Fine, MD, MHSc, can be reached at the Department of Ophthalmology, Rutgers – University of Medicine and Dentistry of New Jersey, NJ Retina, 10 Plum St., Suite 600, New Brunswick, NJ 08901; 732-220-1600 ; fax: 732-220-1603; email: [email protected] email. Michael D. Ober, MD, can be reached at Retina Consultants of Michigan, 29201 Telegraph Rd., Suite 606, Southfield, MI 48034; 248-356-8610; fax: 248-356-6473; email: [email protected] email. Seenu M. Hariprasad, MD, can be reached at the Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL 60637; 773-795-1326; email: [email protected]. Disclosures: Dr. Fine is a consultant and/or speaker for Allergan, Genentech, and Regeneron and has equity or patent interests in Auris Surgical Robotics. Dr. Ober is a consultant or speaker for OD-OS, Bayer, and Allergan. Dr. Hariprasad is a consultant or on the speakers’ bureau for Regeneron, Takeda, Alcon, Allergan, Bayer, Optos, Ocular Therapeutix, and OD-OS.
January/February 2014 · Vol. 45, No. 1
13
Incorporating current trials and technology into clinical practice
Current concepts in managing central serous chorioretinopathy by Howard F. Fine, MD, MHSc, and Michael D. Ober, MD
Seenu M. Hariprasad Practical Retina Editor
Despite the extensive advances we have made in the treatment of various macular disorders, we are still without an FDAapproved treatment for central serous chorioreti-
nopathy (CSC). CSC is a very difficult disease to investigate. It typically resolves on its own, leaving one to wonder whether therapy or time caused disease resolution. Also, CSC is not frequently seen in clinic, which leads to fewer patients recruited into trials. Finally, the lack of understanding about its etiology makes it unclear what the treatment target should be. A wide array of treatment strategies have been explored, including PDT, macular laser, H. pylori eradication, intravitreal anti-VEGF, antioxidants, surgery, and systemic pharmacologics. Our community lacks consensus regarding a systematic treatment approach for this condition. In this column, Dr. Howard Fine and Dr. Michael Ober provide an up-to-date summary of treatment options for CSC. I am certain that their insights and review of current treatment approaches will be educational for the retina community.
Central serous c h o r i o r e t i n o p athy (CSC) affects roughly 10 men and two women per 100,000 people, and they are often younger, working-aged individuals with Howard F. Fine Michael D. Ober high visual demands. Randomized clinical trials in CSC are scarce and typically evaluate dozens of patients1-12 (Table, page 11) rather than the hundreds or even thousands of patients evaluated in trials for age-related macular degeneration (AMD), retinal vein occlusion, and diabetic retinopathy. Unfortunately, to date there are no FDAapproved medications for CSC, leaving ophthalmologists without a large treatment armamentarium. Confirming the diagnosis
The first step in approaching CSC is confirming the diagnosis. There are a number of pitfalls to exclude on the differential diagnosis list. In any patient older than 50 years, differentiation must be made from exudative AMD, which can typically be achieved with fluorescein angiography (FA).13 Polypoidal choroidal vasculopathy is well known to masquerade as CSC14 and can be differentiated with indocyanine green (ICG) angiography. Pachychoroid pigment epitheliopathy15 is a recently described entity seen on enhanced depth imaging optical coherence tomography (EDI-OCT) in eyes with a thickened choroid but without subretinal fluid and may lie on a spectrum with CSC. Additionally, posterior uveitis may coexist with CSC due to concomitant steroid use. Uveitis can also mimic CSC, such as in the case of exudative serous detachment in Vogt-KoyanagiHarada syndrome.16
doi: 10.3928/23258160-20131220-01
January/February 2014 · Vol. 45, No. 1
9
Practical Retina
Multimodal imaging
Multimodal imaging is indispensable for both diagnosis and management of CSC. Nearly pathognomonic signs for CSC include the smokestack sign, gravitating tracts, and the acute focal retinal pigment epithelium (RPE) leak or “blow-out” (Figure). While FA and ICG angiography have been the mainstay for diagnostic testing and the guide for treatment, noninvasive imaging with EDI-OCT and fundus autofluorescence (FAF) imaging has gained increasing importance to evaluate the extent of subretinal fluid and pigment epithelial detachment as well as the health of the RPE. Work-up in CSC
A work-up is usually not necessary for patients in the typical demographic: young men, those with a “Type A” personality, and pregnant women. Patients should be asked about sleep apnea,17 phosphodiesterase inhibitors for erectile dysfunction,18 and use of illicit drugs, such as the sympathomimetic “ecstasy.”19 In atypical or severe cases, however, a work-up for Cushing’s syndrome is warranted. A 24-hour urinary free cortisol can be an initial screening test, and other methods include lowdose dexamethasone suppression test, dexamethasone-corticotropin-releasing hormone test, or evening serum and salivary cortisol level. Ophthalmologists might opt to consult an endocrinologist, especially if there is a concern for pituitary adenoma or adrenal tumor.20 Treatment modalities Risk factor reduction Figure. Selected findings in CSC. (A) Classic “smokestack sign” seen in a left eye on fluorescein angiography (FA) and (B) indocyanine green (ICG) angiography. Choroidal hyperpermeability in another left eye less prominent with FA than midphase ICG (D) angiogram. “Blow-out” of the retinal pigment epithelium in a right eye seen as a focal leak on FA (E) and hypo-autofluorescent spot (F) on fundus autofluorescence imaging, with disruption in the retinal pigment epithelium visible on oblique OCT scan (G) through the defect.
10
The first treatment that should be applied is risk factor reduction. Patients on steroids of any form (oral, inhaled, topical, intra-articular, epidural, or intravenous) should be counseled to reduce or ideally eliminate exogenous steroids if possible. The majority of CSC cases secondary to exogenous steroids will resolve if the steroids are withdrawn.21 Lifestyle modification
Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
Practical Retina
TABLE
Randomized Trials in Central Serous Chorioretinopathy Since 1990 Ref. Year
N
Finding
1
2013 Bae SH
Author
32
Low-fluence PDT superior to ranibizumab for chronic CSC at 12 months.
2
2013 Roisman L
15
Subthreshold diode micropulse laser superior to sham for chronic CSC at 3 months.
3
2013 Dang Y
53
H. pylori eradication did not improve acuity or subretinal fluid.
4
2013 Behnia M
37
Macular subthreshold laser therapy improved acuity at 6 months.
5
2013 Semeraro F
22
No significant difference between bevacizumab and low-fluence PDT.
6
2013 Ratanasukon M
51
High-dose antioxidants for acute CSC showed no benefit for acuity or thickness.
7
2011 Wu ZH
34
Half-dose PDT superior to placebo for acuity at 1 year.
8
2011 Bae SH
16
Reduced-fluence PDT superior to ranibizumab at 3 months.
9
2011 Klatt C
30
Selective retina therapy with (Nd:YLF) laser superior to control at 3 months.
10
2010 Lim JW
24
Bevacizumab similar to observation at 6 months.
11
2008 Chan WM
63
Half-dose PDT superior to observation for acuity and thickness at 12 months.
12
2004 Verma L
30
Diode laser superior to argon green laser at 1 month for acuity.
CSC = central serous chorioretinopathy; N = sample size; PDT = photodynamic therapy; Ref. = reference number.
with stress reduction is crucial in those with a type A personality but often difficult to achieve. Limiting work hours, increasing vacation time, encouraging exercise and adequate sleep, changing attitudes about work-life balance, and even professional counseling are all elements that can reduce endogenous cortisol levels.
The Table summarizes 12 randomized trials in CSC performed since 1990. A 2013 search of the PubMed terms “central serous AND randomized trial” resulted in 59 citations, 12 of which were randomized trials of CSC published since 1990.
complete resolution of fluid in 60% by 6 months.22 PDT was administered to hypercyanescent plaques (observed on the mid-phase ICG) at full fluence as in the TAP study: After a 10-minute infusion of verteporfin at a dose of 6 mg/m2 and a wait time of 5 minutes, laser treatment was performed for 83 seconds at 689 nm. Other trials supported these findings. However, PDT is not entirely benign and can be associated with pigmentary change, RPE atrophy, choroidal ischemia, and secondary choroidal neovascularization (CNV). In an effort to reduce collateral damage, less intensive strategies have been employed with reduced-fluence PDT (half the exposure or half the duration of laser treatment) or reduced-dose PDT (half the dose of verteporfin). Chan et al performed a randomized, controlled trial of half-dose PDT versus placebo and demonstrated that 95% of treated patients versus 58% of controls had complete absence of fluid at 1 year; visual acuity was also significantly improved.12 Re-treatment is reasonable to consider when there remains persistent fluid at least 3 months since the previous PDT, especially if there has been a positive response.
Photodynamic therapy
Laser
Photodynamic therapy (PDT) is considered by most as the first-line therapy for treatment of CSC, despite its off-label status. Yannuzzi et al first described ICG-guided PDT treatment in 20 eyes, with
Thermal laser has been the historic treatment of choice for CSC and remains an option for focal leakage outside the perifoveal area. Typical parameters include a spot size of 100 to 200 µm for 100 ms at
Observation
Observation is advisable following the initial diagnosis of acute CSC in the majority of patients because the disease is often self-limited. After 2 to 6 months of risk factor reduction, if the disease fails to improve and is encroaching on or involving the fovea, consideration of treatment is reasonable. Factors that might prompt early treatment include recurrent CSC, vocational demands, and a history of poor response in the fellow eye to initial observation. Clinical trials
January/February 2014 · Vol. 45, No. 1
11
Practical Retina
a low power of 100 to 200 mw. However, thermal laser can induce a scotoma, may increase the risk of late CNV, and is not effective in cases with diffuse RPE decompensation.23 Therefore, it is used only in select extrafoveal cases with focal leakage. Micropulse sub-threshold diode laser shows increasing promise2,4 but requires further study before widespread use for CSC.
1. Bae SH, Heo J, Kim C, Kim TW, Shin JY, Lee JY, Song SJ, Park TK, Moon SW, Chung H. Low-fluence photodynamic therapy versus ranibizumab for chronic central serous chorioretinopathy: One-year results of a randomized trial [published online ahead of print Nov. 20, 2013]. Ophthalmology. doi: 10.1016/j.ophtha.2013.09.024. 2. Roisman L, Magalhães FP, Lavinsky D, Moraes N, Hirai FE, Cardillo JA, Farah ME. Micropulse diode laser treatment for chronic central serous chorioretinopathy: a randomized pilot trial. Ophthalmic Surg Lasers Imaging Retina. 2013;44(5):465-470. 3. Dang Y, Mu Y, Zhao M, Li L, Guo Y, Zhu Y. The effect of eradicating Helicobacter pylori on idiopathic central serous chorioretinopathy patients. Ther Clin Risk Manag. 2013;9:355-360.
4. Behnia M, Khabazkhoob M, Aliakbari S, Abadi AE, Hashemi H, Pourvahidi P. Improvement in visual acuity and contrast sensitivity in patients with central serous chorioretinopathy after macular subthreshold laser therapy. Retina. 2013;33(2):324-328. 5. Semeraro F, Romano MR, Danzi P, Morescalchi F, Costagliola C. Intravitreal bevacizumab versus low-fluence photodynamic therapy for treatment of chronic central serous chorioretinopathy. Jpn J Ophthalmol. 2012;56(6):608-612. 6. Ratanasukon M, Bhurayanontachai P, Jirarattanasopa P. High-dose antioxidants for central serous chorioretinopathy; the randomized placebo-controlled study. BMC Ophthalmol. 2012;12:20. 7. Wu ZH, Lai RY, Yip YW, Chan WM, Lam DS, Lai TY. Improvement in multifocal electroretinography after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy: a randomized placebo-controlled trial. Retina. 2011;31(7):1378-1386. 8. Bae SH, Heo JW, Kim C, et al. A randomized pilot study of lowfluence photodynamic therapy versus intravitreal ranibizumab for chronic central serous chorioretinopathy. Am J Ophthalmol. 2011;152(5):784-792. 9. Klatt C, Saeger M, Oppermann T, Pörksen E, Treumer F, Hillenkamp J, Fritzer E, Brinkmann R, Birngruber R, Roider J. Selective retina therapy for acute central serous chorioretinopathy. Br J Ophthalmol. 2011;95(1):83-88. 10. Lim JW, Ryu SJ, Shin MC. The effect of intravitreal bevacizumab in patients with acute central serous chorioretinopathy. Korean J Ophthalmol. 2010;24(3):155-158. 11. Chan WM, Lai TY, Lai RY, Liu DT, Lam DS. Half-dose verteporfin photodynamic therapy for acute central serous chorioretinopathy: one-year results of a randomized controlled trial. Ophthalmology. 2008;115(10):1756-1765. 12. Verma L, Sinha R, Venkatesh P, Tewari HK. Comparative evaluation of diode laser versus argon laser photocoagulation in patients with central serous retinopathy: a pilot, randomized controlled trial. BMC Ophthalmol. 2004;4:15. 13. Eandi CM, Ober M, Iranmanesh R, Peiretti E, Yannuzzi LA. Acute central serous chorioretinopathy and fundus autofluorescence. Retina. 2005;25(8):989-993. 14. Yannuzzi LA, Freund KB, Goldbaum M, Scassellati-Sforzolini B, Guyer DR, Spaide RF, Maberley D, Wong DW, Slakter JS, Sorenson JA, Fisher YL, Orlock DA. Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology. 2000;107(4):767-777. 15. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina. 2013;33(8):1659-1672. 16. Khairallah M, Kahloun R, Tugal-Tutkun I. Central serous chorioretinopathy, corticosteroids, and uveitis. Ocul Immunol Inflamm. 2012;20(2):76-85. 17. Kloos P, Laube I, Thoelen A. Obstructive sleep apnea in patients with central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2008;246(9):1225-1228. 18. Aliferis K, Petropoulos IK, Farpour B, Matter MA, Safran AB. Should central serous chorioretinopathy be added to the list of ocular side effects of phosphodiesterase 5 inhibitors? Ophthalmologica. 2012;227(2):85-89. 19. Hassan L, Carvalho C, Yannuzzi LA, et al. Central serous chorioretinopathy in a patient using methylenedioxymethamphetamine (MDMA) or “ecstasy.” Retina. 2001;21:559-561.
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Ophthalmic Surgery, Lasers & Imaging Retina | Healio.com/OSLIRetina
Anti-VEGF
There is mounting evidence that anti-VEGF agents are not effective for CSC.24 A recent prospective, randomized trial demonstrated superiority of reduced-fluence PDT over ranibizumab.1 Care must be taken in interpreting positive study results regarding CSC because the natural history is quite favorable. Systemic agents
Systemic anti-glucocorticoids seem a logical approach for refractory cases, but conclusive randomized clinical trial data are lacking to date. Small series exist to support a number of agents, including mifepristone,25 ketoconazole,26 rifampin,27 finesteride,28 and eplerenone.29 Patients with chronic severe CSC that is recalcitrant to local therapy may consider these agents. Unfortunately, the data as of yet remain unconvincing to recommend detection and eradication of H. pylori, nor do they support high-dose anti-oxidant supplementation.6 Lastly, for the most severe cases with exudative detachment, surgical drainage is an option.30
REFERENCES
20. Thoelen AM, Bernasconi PP, Schmid C, Messmer EP. Central serous chorioretinopathy associated with a carcinoma of the adrenal cortex. Retina. 2000;20:98-99. 21. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology. 2002;109:18341837. 22. Yannuzzi LA, Slakter JS, Gross NE, Spaide RF, Costa D, Huang SJ, Klancnik JM Jr, Aizman A. Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study. Retina. 2003;23(3):288-298. 23. Burumcek E, Mudun A, Karacorlu S, Arslan MO. Laser photocoagulation for persistent central serous retinopathy: results of long-term follow-up. Ophthalmology. 1997;104(4):616-622. 24. Chung YR, Seo EJ, Lew HM, Lee KH. Lack of positive effect of intravitreal bevacizumab in central serous chorioretinopathy: meta-analysis and review [published online ahead of print Nov. 8 2013]. Eye (Lond). doi: 10.1038/eye.2013.236. 25. Nielsen JS, Jampol LM. Oral mifepristone for chronic central serous chorioretinopathy. Retina. 2011;31(9):1928-1936. 26. Meyerle CB, Freund KB, Bhatnagar P, Shah V, Yannuzzi LA. Ketoconazole in the treatment of chronic idiopathic central serous chorioretinopathy. Retina. 2007;27(7):943-946. 27. Steinle NC, Gupta N, Yuan A, Singh RP. Oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy. Br J Ophthalmol. 2012;96(1):10-13. 28. Forooghian F, Meleth AD, Cukras C, Chew EY, Wong WT, Meyerle CB. Finasteride for chronic central serous chorioretinopathy. Retina. 2011;31(4):766-771. 29. Bousquet E, Beydoun T, Zhao M, Hassan L, Offret O, BeharCohen F. Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: A Pilot Study. Retina. 2013;33(10):2096-2102. 30. John VJ, Mandelcorn ED, Albini TA. Internal drainage for chronic macula-involving serous retinal detachment in idiopathic central serous chorioretinopathy [published online ahead of print Feb. 14, 2013]. Int Ophthalmol. 2013. doi: 10.1007/s10792-013-9731-9.
Howard F. Fine, MD, MHSc, can be reached at the Department of Ophthalmology, Rutgers – University of Medicine and Dentistry of New Jersey, NJ Retina, 10 Plum St., Suite 600, New Brunswick, NJ 08901; 732-220-1600 ; fax: 732-220-1603; email: [email protected] email. Michael D. Ober, MD, can be reached at Retina Consultants of Michigan, 29201 Telegraph Rd., Suite 606, Southfield, MI 48034; 248-356-8610; fax: 248-356-6473; email: [email protected] email. Seenu M. Hariprasad, MD, can be reached at the Department of Ophthalmology and Visual Science, University of Chicago, 5841 S. Maryland Avenue, MC2114, Chicago, IL 60637; 773-795-1326; email: [email protected]. Disclosures: Dr. Fine is a consultant and/or speaker for Allergan, Genentech, and Regeneron and has equity or patent interests in Auris Surgical Robotics. Dr. Ober is a consultant or speaker for OD-OS, Bayer, and Allergan. Dr. Hariprasad is a consultant or on the speakers’ bureau for Regeneron, Takeda, Alcon, Allergan, Bayer, Optos, Ocular Therapeutix, and OD-OS.
January/February 2014 · Vol. 45, No. 1
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