Update On Central Serous Pharmaceuticals, Inc., ThromboGenics, … · 2014-09-18 · 1 Cole Eye Institute Update On Central Serous Chorioretinopathy Rishi P. Singh Assistant Professor

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Cole Eye InstituteCole Eye Institute

Update OnCentral Serous

Chorioretinopathy

Rishi P. Singh

Assistant Professor Of Ophthalmology

Medical Director, Clinical Systems Office

Staff Physician, Cleveland Clinic

Rishi P. Singh

Assistant Professor Of Ophthalmology

Medical Director, Clinical Systems Office

Staff Physician, Cleveland Clinic


Financial Disclosures

• Advisor, consultant, or research support:

• Genentech, Ophthotech Corp, RegeneronPharmaceuticals, Inc., ThromboGenics, Inc., Valean, Alcon

• Will be discussing the off label use of bromfenac, nepafenac, eplerenone, rifampin, and photodynamic therapy

• Advisor, consultant, or research support:

• Genentech, Ophthotech Corp, RegeneronPharmaceuticals, Inc., ThromboGenics, Inc., Valean, Alcon

• Will be discussing the off label use of bromfenac, nepafenac, eplerenone, rifampin, and photodynamic therapy


Update on Central Serous Chorioretinopathy

● Explain the newer diagnostic technologies

● Discuss the most recent data on newer treatments

● Explain the newer diagnostic technologies

● Discuss the most recent data on newer treatments


History

● 1886 - Recurrent Central Retinitis - Von Graefe

● 1955 - Central Serous Retinopathy - Bennet and Maumenee

● 1965 - Central Serous Chorioretinopathy - Gass

● Diffuse retinal pigment epitheliopathy or Chronic CSC.

● 1886 - Recurrent Central Retinitis - Von Graefe

● 1955 - Central Serous Retinopathy - Bennet and Maumenee

● 1965 - Central Serous Chorioretinopathy - Gass

● Diffuse retinal pigment epitheliopathy or Chronic CSC.

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Epidemiology/Demographics

● High percentage of men (72%-88%)

● Males (8-9 to 1)

● No upper age limit

● No cases reported under the age of 20

● Peak prevalence 45 yrs - higher in chronic and female patients.

● Bilateral involvement in 40%

● CSC in older patients more common than you think

● Spaide found 130 patients with neurosensory detachments - 57 were diagnosed with CSC

● High percentage of men (72%-88%)

● Males (8-9 to 1)

● No upper age limit

● No cases reported under the age of 20

● Peak prevalence 45 yrs - higher in chronic and female patients.

● Bilateral involvement in 40%

● CSC in older patients more common than you think

● Spaide found 130 patients with neurosensory detachments - 57 were diagnosed with CSC


Classification

● Two types

● Younger patients

● Bullous focal retinal detachment

● Little fundus change and only mild visual change

● Few areas of hyperfluorescence

● Older patients

● Shallow fluid

● Widespread RPE change

● Diffuse retinal pigment epithelialopathy

● Associated with chronic steroid use

● Two types

● Younger patients

● Bullous focal retinal detachment

● Little fundus change and only mild visual change

● Few areas of hyperfluorescence

● Older patients

● Shallow fluid

● Widespread RPE change

● Diffuse retinal pigment epithelialopathy

● Associated with chronic steroid use


Pathogenesis

Unknown

Theories

Defect in the tight junctions of RPE cells

Polarity of the pump is changed

Choroidal vascular hyperpermeability

Unknown

Theories

Defect in the tight junctions of RPE cells

Polarity of the pump is changed




Initially there is choroidal hyperpermeability with congestion of the choriocapillaris along with exudation of protein and

fluid.

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Retinal pigment epithelium (RPE) pump decompensation occurs over time with the formation of a pigment epithelial detachment.



Eventually, RPE defect develops, leading to leakage into the subretinal space.



This leads to elevation of the neurosensory retina and a neurosensory retinal detachment.


Diagnostic Testing

● Angiography – Fluorescein and Indocyanine

● Fundus Autofluorescence (FAF)

● Spectral Domain OCT (SDOCT)

● Angiography – Fluorescein and Indocyanine

● Fundus Autofluorescence (FAF)

● Spectral Domain OCT (SDOCT)

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Fluorescein Angiography

● Most common - pinpoint hyperfluorescence areas

● Fills sensory detachment, but slow

● Areas of leakage usually hypopigmented

● Smokestack 7-25%

● Most common area of leakage is superonasalmacula 0.5 - 1.5 mm from the foveola

● Most common - pinpoint hyperfluorescence areas

● Fills sensory detachment, but slow

● Areas of leakage usually hypopigmented

● Smokestack 7-25%

● Most common area of leakage is superonasalmacula 0.5 - 1.5 mm from the foveola


ICG

● Hot spots● Hot spots


Autofluorescence

Autofluorescence is a rapid non-contact, non-invasive way to evaluate RPE function.

AF can evaluate the amount of lipofuscin that is accumulated in retinal pigment epithelium.

By evaluating fundus autofluorescence images and thus lipofuscin accumulation, disturbances within the RPE can be readily detected.

Helps explain to the patient why their vision isn’t good

Autofluorescence is a rapid non-contact, non-invasive way to evaluate RPE function.

AF can evaluate the amount of lipofuscin that is accumulated in retinal pigment epithelium.

By evaluating fundus autofluorescence images and thus lipofuscin accumulation, disturbances within the RPE can be readily detected.

Helps explain to the patient why their vision isn’t good


AF and CSR

Acute CSC -hypofluorescence at leakage site

Middle to late CSC -granular or semi-confluent hyperfluorescence

Chronic CSC - irregular patterns of mixed hyper and hypofluorescence can be seen.




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FAF and CSR








FAF and CSR








Wide Field FAF in CSR

● Are there abnormalities in FAF in the mid and far periphery?

● Sadda et al 2012

● Yes – 53% have abnormalities

● Are there abnormalities in FAF in the mid and far periphery?

● Sadda et al 2012

● Yes – 53% have abnormalities


OCT

Shallow serous detachments

Subretinal and sub RPE fluid are both possible - rule out CNV

Late chronic disease can show cystoid edema

Shallow serous detachments

Subretinal and sub RPE fluid are both possible - rule out CNV

Late chronic disease can show cystoid edema

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Choroidal OCT Imaging

● Association between choroidal thickness and CSR

● Study by Duker and colleagues identified 23 patients with atypical CSR versus age matched control patients

● Association between choroidal thickness and CSR

● Study by Duker and colleagues identified 23 patients with atypical CSR versus age matched control patients


What is the best way to measure choroidal thickness?

● Currently not automated and no controls to show whether the reading is abnormal

● Obtain an EDI protocol scan

● Manual caliper measurements from the fovea

● Currently not automated and no controls to show whether the reading is abnormal

● Obtain an EDI protocol scan

● Manual caliper measurements from the fovea


What is the best way to measure choroidal thickness?

• Good rule of thumb: Subfoveal retina should be as thick as the subfoveal choroid

• Minor fluctuations of 20-30 microns considered normal

• Make sure to take into account myopic status• >6D myopia = CT avg is

98 microns• Every 1 D of myopia – 8.7

microns of decreased thickness

Cirrus EDI

Spectralis EDI


Treatments

● Acute

● Chronic – defined as the presence of subretinal fluid for greater than 4 months without improvement

● Acute

● Chronic – defined as the presence of subretinal fluid for greater than 4 months without improvement

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Acute: Natural History

● Most resolve within 3 months

● 1/3-1/2 reoccur

● Less than 10% greater than 3 times

● Can consider laser/PDT with need for acute vision

● NSAIDs may hasten recovery

● Most resolve within 3 months

● 1/3-1/2 reoccur

● Less than 10% greater than 3 times

● Can consider laser/PDT with need for acute vision

● NSAIDs may hasten recovery


Non Steroidal Anti-Inflammatory Drugs

● Work well in Cystoid Macular Edema

● Studies also done in AMD and DME

● Different mechanism of action than Corticosteroids

● Block Cox 1 and Cox 2 cycles

● Studies have shown that NSAID decrease cortisol levels during stress vs controls in both and animals

Gravel A, Wilson JM, Pedro DF, Vijayan MM. Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout. Comp Biochem Physiol C Toxicol Pharmacol. 2009 May;149(4):481-90. doi: 10.1016/j.cbpc.2008.11.002. Epub 2008 Nov 19

A. M. Mahdy1,2, H. F. Galley*,1, M. A. Abdel‐Wahed2, K. F. El‐Korny2, S.Differential modulation of interleukin‐6 and interleukin ‐10 by diclofenac in patients undergoing major surgery , British Journal of Anasthesia Volume 77 Pp 797-802

● Work well in Cystoid Macular Edema

● Studies also done in AMD and DME

● Different mechanism of action than Corticosteroids

● Block Cox 1 and Cox 2 cycles

● Studies have shown that NSAID decrease cortisol levels during stress vs controls in both and animals

Gravel A, Wilson JM, Pedro DF, Vijayan MM. Non-steroidal anti-inflammatory drugs disturb the osmoregulatory, metabolic and cortisol responses associated with seawater exposure in rainbow trout. Comp Biochem Physiol C Toxicol Pharmacol. 2009 May;149(4):481-90. doi: 10.1016/j.cbpc.2008.11.002. Epub 2008 Nov 19

A. M. Mahdy1,2, H. F. Galley*,1, M. A. Abdel‐Wahed2, K. F. El‐Korny2, S.Differential modulation of interleukin‐6 and interleukin ‐10 by diclofenac in patients undergoing major surgery , British Journal of Anasthesia Volume 77 Pp 797-802


Purpose

● To determine if the addition of topical NSAID medication (Bromfenac or Nepafenac) can decrease the time to resolution of edema and restoration of vision in patients with acute central serous , Choroidopathy if dosed at high doses (QID) over an extended period of time.

● To determine if the addition of topical NSAID medication (Bromfenac or Nepafenac) can decrease the time to resolution of edema and restoration of vision in patients with acute central serous , Choroidopathy if dosed at high doses (QID) over an extended period of time.


Control Data vs Combined Data

● Control Data: Charlotte and Cole

● N= 49 patients

● Mean 129 days combined

● 127 days/Charlotte alone Cole alone 140

● Range 12-362 days

● Treated Group : MCOA (define)

● N = 38 patients

● Mean 42 days


● Difference is significant ( p< 0.0002)

● Control Data: Charlotte and Cole

● N= 49 patients

● Mean 129 days combined

● 127 days/Charlotte alone Cole alone 140


● Treated Group : MCOA (define)

● N = 38 patients

● Mean 42 days


● Difference is significant ( p< 0.0002)

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Mean time to resolution of OCT

● Mean time to resolution of OCT

● 80 days in Control

● 44 days Bromfenac

● 44 days Nepafenac

● Control vs treated (p=0.002)

● There was no statistical significance between Bromfenacand Nepafanac, but each of them were statistically superior to control.

● Mean time to resolution of OCT

● 80 days in Control

● 44 days Bromfenac

● 44 days Nepafenac

● Control vs treated (p=0.002)

● There was no statistical significance between Bromfenacand Nepafanac, but each of them were statistically superior to control.

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ASRS PAT Survey 2013 Chronic Treatment of CSR


Chronic CSR Treatment modalities

● Anti-VEGF treatment (Bevacizumab)

● Case reports have shown variable results, some beneficial8,9

and some showed no beneficial effect10

● Finasteride – an inhibitor of dihydrotestosterone synthesis

● Positive response in small case series of chronic CSC patients, but with recurrent exudation after discontinuation11

● Acetylsalicylic acid (aspirin) – anti-inflammatory and antiplatelet effects that may counteract choroidal vascular congestion, ischemia, and inflammation in CSC

● Benefits shown in one study, optimal dose of 75-100 mg12

● Anti-VEGF treatment (Bevacizumab)

● Case reports have shown variable results, some beneficial8,9

and some showed no beneficial effect10

● Finasteride – an inhibitor of dihydrotestosterone synthesis

● Positive response in small case series of chronic CSC patients, but with recurrent exudation after discontinuation11

● Acetylsalicylic acid (aspirin) – anti-inflammatory and antiplatelet effects that may counteract choroidal vascular congestion, ischemia, and inflammation in CSC

● Benefits shown in one study, optimal dose of 75-100 mg12

8. Lee ST, Adelman RA. The treatment of recurrent central serous chorioretinopathy with intravitreal bevacizumab. J Ocul Pharmacol Ther. 2011;27:611-614.9. Inouea M, Kadonosonoa K, Watanabea Y, et al. Results of one-year follow-up examinations after intravitreal bevacizumab administration for chronic central serous chorioretinopathy. Ophthalmologica. 2011;225:37-40.10. Lim JW, Ryu SJ, Shin MC. The effect of intravitreal bevacizumab in patients with acute central serous chorioretinopathy. Kor J Ophthalmol. 2010;24: 155-158.11. Forooghian F, Meleth AD, Cukras C, et al. Finasteride for chronic central serous chorioretinopathy. Retina. 2011;31:766-771.12. Caccavale A, Romanazzi F, Imparato M, et al. Low-dose aspirin as treatment for central serous chorioretinopathy. Clin Ophthalmol. 2010;4:899-903. Cole Eye InstituteCole Eye Institute

Treatment modalities

● Rifampin – increases the metabolism of endogenous steroids

● Successful treatment in small case series of patients treated with 300 mg 2x daily13

● Mifepristone – an antagonist of glucocorticoids and progesterone receptors, inhibits cortisol-induced peripheral vasoconstriction

● Treatment response seen in 16 patients with chronic CSC treated with 200 mg daily for 12 weeks14

● Ketoconazole – inhibits steps of steroid synthesis

● Treatment response seen at 8 weeks when patients were given 600 mg daily for 4 weeks15

● Rifampin – increases the metabolism of endogenous steroids

● Successful treatment in small case series of patients treated with 300 mg 2x daily13

● Mifepristone – an antagonist of glucocorticoids and progesterone receptors, inhibits cortisol-induced peripheral vasoconstriction

● Treatment response seen in 16 patients with chronic CSC treated with 200 mg daily for 12 weeks14

● Ketoconazole – inhibits steps of steroid synthesis

● Treatment response seen at 8 weeks when patients were given 600 mg daily for 4 weeks15

13. Steinle NC, Gupta N, Yuan A, et al. Oral rifampin utilisation for the treatment of chronic multifocal central serous retinopathy. Br J Ophthalmol. 2012;96: 10-13.14. Nielsen JS, Jampol LM.. Oral mifepristone for chronic central serous chorioretinopathy. Retina. 2011;31:1928-1936.15. Meyerle CB, Freund KB, Bhatnagar P, et al. Ketoconazole in the treatment of chronic idiopathic central serous chorioretinopathy. Retina. 2007;27:943-946.

Slide 46

a4 what was statistical methodaantoszyk, 7/17/2013

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Treatment modalities

● Obstructive sleep apnea treatment – hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system overactivation seen with poor sleep quality may contribute to development of CSC.

● Case report indicates Identifying/treating obstructive sleep apnea may allow for resolution of CSC16

● H. pylori treatment

● Small case series used metronidazole and amoxicillin 500 mg 3x daily for 2 weeks and omeprazole 1x daily for 6 weeks in CSC patients – treated patients experienced enhanced absorption of SRF compared to control group17

● Obstructive sleep apnea treatment – hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system overactivation seen with poor sleep quality may contribute to development of CSC.

● Case report indicates Identifying/treating obstructive sleep apnea may allow for resolution of CSC16

● H. pylori treatment

● Small case series used metronidazole and amoxicillin 500 mg 3x daily for 2 weeks and omeprazole 1x daily for 6 weeks in CSC patients – treated patients experienced enhanced absorption of SRF compared to control group17

16. Kim, JT, Eichling, PS, Wang, M. Central serous chorioretinopathy associated with narcolepsy. Retin Cases Brief Rep 2011;5:302-305.17. Bagher M, Rahbani-Nobar R, Alireza Javadzadeh A, et al. The effect of Helicobacter pylori treatment on remission of idiopathic central serous chorioretinopathy. Mol Vis. 2011;17:99-103.


Verteporfin PDT

● Probable mechanism:

● Light-activation of verteporfin (visudyne), a drug used in PDT, selectively occludes choroidal neovascularization and superficial choroidal vessels 5

● Short-term choriocapillaris hypoperfusion 2,5

● Long-term choroidal vascular remodeling – leading to reduction in choroidal congestion, vascular hyperpermeability, and extravascular leakage

● Has minimal effects on overlying retina and deeper choroidal layers 5

● Probable mechanism:

● Light-activation of verteporfin (visudyne), a drug used in PDT, selectively occludes choroidal neovascularization and superficial choroidal vessels 5

● Short-term choriocapillaris hypoperfusion 2,5

● Long-term choroidal vascular remodeling – leading to reduction in choroidal congestion, vascular hyperpermeability, and extravascular leakage

● Has minimal effects on overlying retina and deeper choroidal layers 5


Summary Of Randomized Trials Since 1990Year Author N Findings

2013 Bae SH 32 Low fluence PDT superior to ranibizumab for chronic CSR at 12 months

2013 Roisman L 15 Subthreshold diode micropulse laser superior to sham for chronic CSC at 3 months

2013 Dang Y 53 H. Pylori eradication did not improve acuit or subretinal fluid

2013 Behnia M 37 Macular subthreshold laser therapy improved acuity at 6 months

2013 Semeraro F 22 No significant difference between bevacizumab and low fluence PDT

2013 Ratanasukon M 51 High-dose antioxidants for acute CSC showed no benefit for acuity or thickness

2011 Wu ZH 34 Half-dose PDT superior to placebo for acuity at 1 year

2011 Bae SH 16 Reduced-fluence PDT superior to ranibizumab at 3 months

2011 Klatt C 30 Selective retina therapy with Nd:YLF laser superior to control at 3 months

2010 Lim JW 24 Bevacizumab similar to observation at 6 months

2008 Chan WM 63 Half-dose PDT superior to observation for acuity and thickness at 12 months

2004 Verma L 30 Diode laser superior to argon green laser at 1 month for acuity


Verteporfin PDT

● Previous treatments, such as laser photocoagulation, would shorten the duration of symptoms without providing visual benefits or having any impact on the final recurrence rate.2

● Also, only targets RPE leak without specifically treating the underlying hyperpermeability

● May cause RPE damage

● PDT with verteporfin recently has demonstrated beneficial visual outcomes in most patients

● Previous treatments, such as laser photocoagulation, would shorten the duration of symptoms without providing visual benefits or having any impact on the final recurrence rate.2

● Also, only targets RPE leak without specifically treating the underlying hyperpermeability

● May cause RPE damage

● PDT with verteporfin recently has demonstrated beneficial visual outcomes in most patients

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Half-fluence PDT

● “Standard” fluence and dose

● 83 seconds at an exposure of 600 J/cm2 after a 10 min infusion of 6 mg/m2 verteporfin dose

● Low “half” fluence/”half” dose

● 42 seconds after an exposure of 300 J/cm2 after infusion of 3 mg/m2 of verteporfin dose

● Evidence suggests lower PDT fluence and dosage of verteporfin may be as effective as conventional PDT while minimizing adverse effects.2,4,6

● “Standard” fluence and dose

● 83 seconds at an exposure of 600 J/cm2 after a 10 min infusion of 6 mg/m2 verteporfin dose

● Low “half” fluence/”half” dose

● 42 seconds after an exposure of 300 J/cm2 after infusion of 3 mg/m2 of verteporfin dose

● Evidence suggests lower PDT fluence and dosage of verteporfin may be as effective as conventional PDT while minimizing adverse effects.2,4,6


Investigating PDT for CSC

● Previous studies were small in magnitude and may not be reflective of the large-scale impact of verteporfin PDT on chronic CSC patients

● Recent study conducted by Lim et al investigated the outcomes on the largest collection of patient cases with chronic CSC treated with verteporfin PDT.7

● Retrospective case series of 265 eyes

● Observed visual acuities (VA) over time and presence/absence of subretinal fluid (SRF)

● Previous studies were small in magnitude and may not be reflective of the large-scale impact of verteporfin PDT on chronic CSC patients

● Recent study conducted by Lim et al investigated the outcomes on the largest collection of patient cases with chronic CSC treated with verteporfin PDT.7

● Retrospective case series of 265 eyes

● Observed visual acuities (VA) over time and presence/absence of subretinal fluid (SRF)

7. Lim JI, Glassman AR, Aiello LP, et al. Collaborative retrospective macula society study of photodynamic therapy for chronic central serous chorioretinopathy.


PDT treatments

49% 48%

2.5% 1% 0

10

20

30

40

50

60

Full‐flu nce Half‐fluence Very low flue nce Not recorded

Series 1

94% eyes had 83 seconds treatment duration

Full-fluence 600 J/cm2

Half-fluence 300 J/cm2

Number of PDT treatments

% of patients

1 90%

2 7%

3 3%

ICG-guidance 51%


Change in visual acuity from baseline VA

4% 7%

26%

1% 4% 5%

55%

29%

1%

13%

59%

48%

0

10

20

30

40

50

60

70

Loss of 3 or more lines

Loss of 2 or more lines

2 or more lines

3 or more lines

20/32 or be er

20/40 to 20/80

20/100 or worse

Baseline VA:

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Retinal findings


Conclusions

● Verteporfin PDT therapy resulted in improved VA, resolution of SRF, and reduction in FA leakage in the majority of treated eyes

● Adverse side effects were uncommon: post-treatment acute severe VA decreases occurred rarely (1.5%)

● Prospective studies should be done with an untreated comparison group to validate these findings

● More large-scale studies are warranted to investigate optimal fluence and dosing

● Verteporfin PDT therapy resulted in improved VA, resolution of SRF, and reduction in FA leakage in the majority of treated eyes

● Adverse side effects were uncommon: post-treatment acute severe VA decreases occurred rarely (1.5%)

● Prospective studies should be done with an untreated comparison group to validate these findings

● More large-scale studies are warranted to investigate optimal fluence and dosing


Case study

● 55 year old male, previously treated for CSR by referring physician

● CSR both eyes – was on rifampin orally but liver enzymes increased significantly

● Pinpoint leakage on FA would be amenable to PDT both eyes

● 55 year old male, previously treated for CSR by referring physician

● CSR both eyes – was on rifampin orally but liver enzymes increased significantly

● Pinpoint leakage on FA would be amenable to PDT both eyes


First visit (VA OD 20/300)

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First visit (VA OS 20/25 -2)


Case study: 1 week follow-up

● PDT OD:

● 6 mL verteporfin over 10 minutes

● Fluence: 50 J/cm2

● Spot size: 3.9 microns

● Duration: 82 seconds

● PDT OD:

● 6 mL verteporfin over 10 minutes

● Fluence: 50 J/cm2

● Spot size: 3.9 microns

● Duration: 82 seconds

VA OD 20/250

VA OS 20/30


Case study

VA OD 20/300

VA OD 20/200

VA OD 20/300

VA OD 20/400

VA OD 20/25 -2

VA OD 20/30

VA OD 20/25

VA OD 20/20

Baseline

Month 1

Month 2

Month 4

* Received PDT

* Received PDT


Eplerenone

● It has recently been proposed that excessive glucocorticoid-dependent choroidal mineralcorticoid receptor (MR) activation in choroidal vessels may be involved in CSCR’s pathogenesis.1,2,3

● Recent case reports have observed eplerenone, an MR antagonist, significantly improving visual and anatomical outcome of patients with CSCR – further investigation with more patients on eplerenone for CSCR is warranted

● It has recently been proposed that excessive glucocorticoid-dependent choroidal mineralcorticoid receptor (MR) activation in choroidal vessels may be involved in CSCR’s pathogenesis.1,2,3

● Recent case reports have observed eplerenone, an MR antagonist, significantly improving visual and anatomical outcome of patients with CSCR – further investigation with more patients on eplerenone for CSCR is warranted

1. Zhao M, Celerier I, Bousquet E, et al. Mineralcorticoid receptor is involved in rat and human ocular chorioretinopathy. J Clin Invest. 2012;122(7):2672-2679. 2. Gruszka A. Potential involvement of mineralcorticoid receptor activation in the pathogenesis of central serous chorioretinopathy: A case report. European Review for Medical and Pharmacological Sciences. 2013;17:1369-1373.3. Bousquet E, Beydoun T, Zhao M, Hassan L, Offret O, Cohen-Behar F. Mineralcorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: A pilot study. Retina. 2013;33:2096-2102.

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Methods

● Retrospective analysis on 17 patients with a history of CSCR on eplerenone

● Outcome measures include: LogMar visual acuity, central subfield thickness, cube volume, cube average thickness, horizontal subretinal fluid measurement, and vertical subretinal fluid measurement

● Time to first visit was divided into 4 frames:

● baseline (0 day to first visit)

● 0-90 days

● 91-181 days

● 181+ days.

● Retrospective analysis on 17 patients with a history of CSCR on eplerenone

● Outcome measures include: LogMar visual acuity, central subfield thickness, cube volume, cube average thickness, horizontal subretinal fluid measurement, and vertical subretinal fluid measurement

● Time to first visit was divided into 4 frames:

● baseline (0 day to first visit)

● 0-90 days

● 91-181 days

● 181+ days.


Baseline characteristics

Baseline characteristic Mean ± Standard Deviation

Age 57 ± 15 years, range 29 – 85 years

Time on eplerenone 181 ± 81 days, range 38 – 300 days

Best Corrected Visual Acuity 20/69, range 20/20 – 20/250

LogMar Visual Acuity 0.42 ± 0.08, range 0 – 1.097

Central Subfield Thickness (μm) 364.5 ± 40.0, range 211 – 874

Cube Volume (mm3) 11.2 ± 0.52, range 8.1 – 18.8

Cube Average Thickness (μm) 312.2 ± 14.5, range 226 – 527

Subretinal Fluid (μm)Horizontal diameterVertical height

2174.4 ± 1743.8, range 455 – 5520 131.5 ± 246.8, range 43 – 706


LogMar Visual Acuity

p-value

Time effect Test trend

0.070 0.012 *

n=17n=15

n=10

n=8

* values of significance

p=0.41

p=0.19

p=0.024

*


Central Subfield Thickness

p-value


0.09 0.029 *

n=17

n=15n=10

n=8


p=0.048p=0.08

p=0.023

*

*

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Cube Volume

p-value


0.24 0.16

n=17

n=15n=10

n=8p=0.07

p=0.16p=0.14


Cube Average Thickness

p-value


0.22 0.13

n=17

n=15n=10

n=8p=0.07

p=0.18

p=0.10


Subretinal Fluid – horizontal measurement

n=15

n=13

n=8 n=6

p-value


0.014 * 0.002 *

p=0.002

*


p=0.11

p=0.06


Subretinal Fluid – vertical measurement

n=15

n=13

n=8

n=6

p-value


0.049 * 0.007 *

p=0.007

*


p=0.16

p=0.10

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Conclusions

● Eplerenone treatment on CSCR did not significantly improve LogMar visual acuity, but did improve CST, cube volume, and cube average thickness within this cohort

● Eplerenone treatment on CSCR did not significantly improve LogMar visual acuity, but did improve CST, cube volume, and cube average thickness within this cohort


Eplerenone case

● OS: total of 7 Avastin injections OS, little change with injections

● OD: Worsening SRF, stable vision

● Patient begins eplerenone 25 mg qd on 11/07/2012 (about 8 months since initial visit date)

● OS: total of 7 Avastin injections OS, little change with injections

● OD: Worsening SRF, stable vision

● Patient begins eplerenone 25 mg qd on 11/07/2012 (about 8 months since initial visit date)

VA (OD): 20/50 +1 VA (OS): 20/250


Following Eplerenone

Baseline

Month 1

Month 3*patient begins 50 mg

Month 6

VA (OD): 20/50 +1

VA (OD): 20/40 -1

VA (OD): 20/30 -2

VA (OD): 20/20

VA (OS): 20/250

VA (OS): 20/200

VA (OS): 20/150

VA (OS): 20/150


Following Eplerenone

Month 6

Month 11*patient continues eplerenone 50mg qd

Month 15

VA (OD): 20/20 VA (OS): 20/150

VA (OD): 20/20 VA (OS): 20/160 +1

VA (OD): 20/20 VA (OS): 20/125

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Conclusions

● Advancements in diagnostic tests allow for better detection of disease over previous methods

● For acute phases of the disease, observation alone is sufficient and NSAIDs might hasten anatomic recovery

● For chronic phases, a variety of treatment options exist:

● Discontinue inciting agent

● Consider adding oral therapy – Eplerenone and Rifampin

● Consider PDT – Reduced fluence or Full fluence

● None are approved therapies so a RCT would be helpful in determining efficacy of these agents.

● Advancements in diagnostic tests allow for better detection of disease over previous methods

● For acute phases of the disease, observation alone is sufficient and NSAIDs might hasten anatomic recovery

● For chronic phases, a variety of treatment options exist:

● Discontinue inciting agent

● Consider adding oral therapy – Eplerenone and Rifampin

● Consider PDT – Reduced fluence or Full fluence

● None are approved therapies so a RCT would be helpful in determining efficacy of these agents.

Documents

Update On Central Serous Pharmaceuticals, Inc., ThromboGenics, … · 2014-09-18 · 1 Cole Eye Institute Update On Central Serous Chorioretinopathy Rishi P. Singh Assistant Professor