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Central Serous Chorioretinopathy

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Last updated: February 21st, 2022

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Summary of Evidence

Mineral receptor antagonist

Eplerenone did not significantly improve BCVA in chronic CSCR after 12 months of treatment.(VICI, 2020). {Lotery A, Sivaprasad S, O’Connell A, Harris RA, Culliford L, Ellis L, Cree A, Madhusudhan S, Behar-Cohen F, Chakravarthy U, Peto T, Rogers CA, Reeves BC; VICI trial investigators. Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial. Lancet. 2020 Jan 25;395(10220):294-303.}

Photodynamic therapy

PDT vs subthreshold micropulse laser

 

Half-dose PDT is superior to high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy.(PLACE, 2018). {van Dijk EHC, Fauser S, Breukink MB, Blanco-Garavito R, Groenewoud JMM, Keunen JEE, Peters PJH, Dijkman G, Souied EH, MacLaren RE, Querques G, Downes SM, Hoyng CB, Boon CJF. Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy: The PLACE Trial. Ophthalmology. 2018 Oct;125(10):1547-1555.}

 

Crossover to half-dose PDT after previous unsuccessful HSML treatment for CSCR may lead to improved anatomic and functional endpoints, but not vice versa.(PLACE, 2020). {van Rijssen TJ, van Dijk EHC, Scholz P, Breukink MB, Dijkman G, Peters PJH, Tsonaka R, MacLaren RE, Downes SM, Fauser S, Boon CJF, Hoyng CB. Crossover to Photodynamic Therapy or Micropulse Laser After Failure of Primary Treatment of Chronic Central Serous Chorioretinopathy: The REPLACE Trial. Am J Ophthalmol. 2020 Aug;216:80-89.}

 

 

 

Evidence

1. Background

Review

2020 Kaye et.al.

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2020
Review

Review of the current pathophysiology hypotheses surrounding CSC in addition to future directions in cellular work from human induced pluripotent stem cell derived choroidal endothelial cells from CSC patients. Update on the clinical aspects of CSC including risk factors, diagnostic challenges and findings from multimodal imaging. {Kaye R, Chandra S, Sheth J, Boon CJF, Sivaprasad S, Lotery A. Central serous chorioretinopathy: An update on risk factors, pathophysiology and imaging modalities. Prog Retin Eye Res. 2020 Nov;79:100865.}

Kaye et.al.
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Review

2019 Cheung et.al.

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2019
Review

Review of Pachychoroid disease:

  • Several clinical manifestations have been described to reside within the pachychoroid disease spectrum, including central serous chorioretinopathy, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, focal choroidal excavation, peripapillary pachychoroid syndrome.
  • Review of clinical and imaging features, management considerations, as well as current understanding of pathogenesis of these disorders. {Cheung CMG, Lee WK, Koizumi H, Dansingani K, Lai TYY, Freund KB. Pachychoroid disease. Eye (Lond). 2019 Jan;33(1):14-33.}

Cheung et.al.
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Review

2015 Daruich et.al.

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2015
Review

Review of the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. {Daruich A, Matet A, Dirani A, Bousquet E, Zhao M, Farman N, Jaisser F, Behar-Cohen F. Central serous chorioretinopathy: Recent findings and new physiopathology hypothesis. Prog Retin Eye Res. 2015 Sep;48:82-118.}

Daruich et.al.
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1.1 Principles of management

Review

2019 van Rijssen et.al.

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2019
Review

Review of the current rationale and evidence with respect to the variety of interventions available for treating CSC, including pharmacology, laser treatment, and photodynamic therapy. {van Rijssen TJ, van Dijk EHC, Yzer S, Ohno-Matsui K, Keunen JEE, Schlingemann RO, Sivaprasad S, Querques G, Downes SM, Fauser S, Hoyng CB, Piccolino FC, Chhablani JK, Lai TYY, Lotery AJ, Larsen M, Holz FG, Freund KB, Yannuzzi LA, Boon CJF. Central serous chorioretinopathy: Towards an evidence-based treatment guideline. Prog Retin Eye Res. 2019 Nov;73:100770.}

van Rijssen et.al.
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Meta-analysis

2015 Salehi et.al. (Cochrane review)

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2015
Meta-analysis

Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. {Salehi M, Wenick AS, Law HA, Evans JR, Gehlbach P. Interventions for central serous chorioretinopathy: a network meta-analysis. Cochrane Database Syst Rev. 2015 Dec 22;(12):CD011841.}

Salehi et.al. (Cochrane review)
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Review

2013 van Rijssen et.al.

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2013
Review

Review of pathophysiology and treatment of Central serous chorioretinopathy. Although focal laser and photodynamic therapy are the current standard of care for persistent subretinal fluid in CSC, they are not appropriate in all cases, and the optimal timing of intervention remains unclear. {Nicholson B, Noble J, Forooghian F, Meyerle C. Central serous chorioretinopathy: update on pathophysiology and treatment. Surv Ophthalmol. 2013 Mar-Apr;58(2):103-26.}

van Rijssen et.al.
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1.1.1 Oral medications

Review

2020 Fusi-Rubiano et.al.

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2020
Review

Review of the current evidence for oral agents that have been used for treatment of CSCR, including eplerenone, spironolactone, beta blockers, H. pylori agents, omeprazole, rifampicin, methotrexate, aspirin, acetazolamide, mifepristone, melatonin, finasteride, ketoconazole, antioxidants and curcumin phospholipid. {Fusi-Rubiano W, Saedon H, Patel V, Yang YC. Oral medications for central serous chorioretinopathy: a literature review. Eye (Lond). 2020 May;34(5):809-824.}

Fusi-Rubiano et.al.
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1.2 Association with glucocorticoids

Review

2018 Nicholson et.al.

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2018
Review

Review of the evidence of the association between exogenous glucocorticoid use and central serous chorioretinopathy. {Nicholson BP, Atchison E, Idris AA, Bakri SJ. Central serous chorioretinopathy and glucocorticoids: an update on evidence for association. Surv Ophthalmol. 2018 Jan-Feb;63(1):1-8.}

Nicholson et.al.
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2. Mineralocorticoid receptor antagonist

2.1 Eplerenone

Clinical Trial

2020 Lotery et.al. (VICI)

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2020
Clinical Trial

Eplerenone did not significantly improve BCVA in chronic CSCR after 12 months of treatment. {title=”Lotery A, Sivaprasad S, O’Connell A, Harris RA, Culliford L, Ellis L, Cree A, Madhusudhan S, Behar-Cohen F, Chakravarthy U, Peto T, Rogers CA, Reeves BC; VICI trial investigators. Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial. Lancet. 2020 Jan 25;395(10220):294-303.”}

  • Randomized controlled trial of Eplerenone vs placebo in CSCR (114 patients)
  • Findings (1-year):
    • Mean BCVA was 79.5 letters in the placebo group and 80.4 letters in the eplerenone group – adjusted estimated mean difference of 1.73 letters.

Lotery et.al. (VICI)
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3. Photodynamic therapy

Meta-analysis

2015 Salehi et.al. (Cochrane review)

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2015
Meta-analysis

Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials. {Salehi M, Wenick AS, Law HA, Evans JR, Gehlbach P. Interventions for central serous chorioretinopathy: a network meta-analysis. Cochrane Database Syst Rev. 2015 Dec 22;(12):CD011841.}

Salehi et.al. (Cochrane review)
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3.1 PDT vs subthreshold micropulse laser

Clinical Trial

2020 van Rijssen et.al. (REPLACE)

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2020
Clinical Trial

Crossover to half-dose PDT after previous unsuccessful HSML treatment for CSCR may lead to improved anatomic and functional endpoints, but not vice versa. {van Rijssen TJ, van Dijk EHC, Scholz P, Breukink MB, Dijkman G, Peters PJH, Tsonaka R, MacLaren RE, Downes SM, Fauser S, Boon CJF, Hoyng CB. Crossover to Photodynamic Therapy or Micropulse Laser After Failure of Primary Treatment of Chronic Central Serous Chorioretinopathy: The REPLACE Trial. Am J Ophthalmol. 2020 Aug;216:80-89.}

  • Patients from the PLACE trial without complete resolution of SRF received crossover treatment (42 patients)
  • Findings (1-year):
    • At 1-year from baseline (in PLACE), 78% of the PDT group and 67% of the HSML group had complete resolution of SRF.
    • The mean VA and QOL score did not change significantly in both groups.

van Rijssen et.al. (REPLACE)
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Clinical Trial

2018 van Dijk et.al. (PLACE)

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2018
Clinical Trial

Half-dose PDT is superior to high-density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy. {title=”van Dijk EHC, Fauser S, Breukink MB, Blanco-Garavito R, Groenewoud JMM, Keunen JEE, Peters PJH, Dijkman G, Souied EH, MacLaren RE, Querques G, Downes SM, Hoyng CB, Boon CJF. Half-Dose Photodynamic Therapy versus High-Density Subthreshold Micropulse Laser Treatment in Patients with Chronic Central Serous Chorioretinopathy: The PLACE Trial. Ophthalmology. 2018 Oct;125(10):1547-1555.”}

  • Randomized controlled trial of half-dose verteporfin photodynamic therapy vs high-density subthreshold micropulse laser in CSCR (179 patients).
  • Findings (8-months):
    • At 6-8 weeks, subretinal fluid had resolved in 51.2% of the PDT group and 13.8% of the HSML group. The PDT group also had significantly higher increase in BCVA and retinal sensitivity, although the vision-related quality of life was similar.
    • At 7-8 months, there was no subretinal fluid in 67.2% of the PDT group vs 28.8% of the HSML group.
Outcome Time point PDT HSML
Subretinal fluid resolution 6-8 weeks 51.2% 13.8%
No subretinal fluid 7-8 months 67.2% 28.8%
Increase in BCVA (letters) 6-8 weeks +4.6 +1.39
Increase in retinal sensitivity 6-8 weeks +2.01 +0.92

van Dijk et.al. (PLACE)
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