A DEEP DIVE on CENTRAL SEROUS CHORIORETINOPATHY Management of This Condition Can Be Challenging, Especially in Chronic Cases

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GLOBAL PERSPECTIVES s A DEEP DIVE ON CENTRAL SEROUS CHORIORETINOPATHY Management of this condition can be challenging, especially in chronic cases.

BY JOSÉ A. ROCA, MD, and NATALIA ALPÍZAR-ALVAREZ, MD

another study of 230 patients, Tittl and white subretinal exudation that usually colleagues reported an odds ratio of resolves spontaneously after delivery.6 3.17, supporting this association.3 CSC Another risk factor traditionally is also associated with elevated levels associated with CSC is psychological of endogenous corticosteroids, as in stress and type A personality. Cushing syndrome.4 Yannuzzi’s well-known study of CSC Given the strong association and personality types supports this between CSC and steroids, their use association.7 Other associations PERU should be avoided whenever possible. includes systemic hypertension, gas- Furthermore, patients with CSC should troesophageal reflux disease, and the entral serous chorioretinopathy be questioned about their use of all use of alcohol or sympathomimetic (CSC) is an idiopathic disorder forms of steroids, including products agents, although this last requires characterized by serous retinal that may contain steroids (eg, skin further confirmation.2,8,9 detachment and retinal pigment creams, joint injections, nasal sprays, epithelial detachment (PED). inhalants, and other commonly over- PATHOPHYSIOLOGY CChanges are most often confined to looked forms of glucocorticoid), as The pathophysiology of CSC is the macula and are associated with these could be contributing factors. poorly understood. Some postulate leakage of fluid through the retinal Pregnancy is a recognized risk fac- that a focal increase in permeability pigment epithelium (RPE) into the sub- tor for CSC. Plasma cortisol levels are of the choriocapillaris overwhelms retinal space. Patients with CSC often elevated during pregnancy, particularly the overlying RPE, producing serous experience loss of central vision, central during the third trimester.5 Pregnancy- PEDs and subretinal fluid.10 Guyer scotoma, micropsia, metamorphopsia, associated CSC tends to present as and colleagues suggested that the decreased color vision, and abnormali- ties in contrast sensitivity. Visual acuity may be only moderately reduced, and AT A GLANCE there may be a hyperopic shift.1

This article reviews some of the s basics about this condition, including CSC is an idiopathic condition, the pathophysiology of which is poorly associated risks, pathophysiology, and understood, but several possible vascular causes have been proposed. available treatment options. s RISK FACTORS FOR CSC Focal laser and PDT are current standards of care for chronic CSC, but Numerous risk factors have been micropulse laser is a good alternative in instances in which verteporfin associated with CSC, the most con- is not available. sistent being glucocorticoid use. In a

case-control study of 312 patients with s CSC, Haimovici et al reported an odds Some systemic treatments may benefit patients with chronic CSC. ratio of 10.3 for corticosteroid use.2 In

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25 chronic and Recurrences areRecurrences 24 acute 23 In a prospective observationalprospective a In 22 Some authors have proposed thatproposed have authors Some Observation is the standard initialstandard the is Observation Acute CSC is typically a self-limiteda typically is CSC Acute pachychoroid could be an inheritedan be could pachychoroid dominant potentially with condition col and Weenink mode. transmission in pathology CSC-like found leagues withpatients of families (52%) 27 of 14 percentagesmall a Only CSC. chronic symp reported relatives affected of toms. 50%that found al et Lehmann study, second-degreeor first from eyes of hadCSC with patients five of relatives choroids. thick Other Hypotheses and neurosensory retinal changes thatchanges retinal neurosensory and functionalof loss permanent in result terms The vision. bewill months) 3 > persisting (fluid discussion. this in used acutewith patients in management wheninstances are there but CSC, Thesedesirable. be may treatment TREATMENT TALK TREATMENT TALK acuityvisual of process.Recovery months,4 to 1 within occurs typically theof reattachment with coinciding recog few with retina, neurosensory sequelae. visual nized approximatelyin happening common, year. 1 by patients of 50% to 30% recurrencesfrequent with Patients retinalneurosensory chronic with or atrophyRPE develop may detachment ------21 Gal- 20 18,19 ), and, where tissue manifes tissue where and, ), These changes formed the basis for basis the formed changes These En face OCT imaging in a cohort ofcohort a in imaging OCT face En THAT RESULT IN PERMANENT LOSS OF OF IN PERMANENT LOSS THAT RESULT FUNCTIONAL VISION. PATIENTS WITH FREQUENT RECURRENCES RECURRENCES FREQUENT WITH PATIENTS RETINAL NEUROSENSORY OR WITH CHRONIC ATROPHY MAY DEVELOP RPE DETACHMENT CHANGES RETINAL AND NEUROSENSORY emia could be related to the patho the to related be could emia diseases. pachychoroid of genesis milieu that is causative or contributoryor causative is that milieu neovascularization. 1 type to ofzones studied colleagues and Or signal,flow choroidal inner reduced thick choroidal inner reduced of foci Hallerdilated pathologically and ness, pachycho with eyes in vessels layer angiography OCT using disease roid prevalencehigh a found They (OCTA). zonesattenuation signal flow large of thatdisease pachychoroid with eyes in theyand pachyvessels, with correlate isch choroidal inner that proposed revealed that focal choroidal thickeningchoroidal focal that revealed pathologicallyto attributed be could asto (referred veins layer Haller dilated pachyvessels RPE,the of level the at occurred tations cho inner the of thinning paradoxical layer)Sattler and (choriocapillaris roid ante in resulting appreciated, be could into pachyvessels of displacement rior membrane. Bruch to proximity close choriocapillaristhat hypothesis the ischemican produce may attenuation of disease, including CSC, pachychoroidCSC, including disease, of polypoidal(PNV), neovasculopathy focaland (PCV), vasculopathy choroidal excavation. choroidal Proposed Role of Inner Choroidal Ischemia diseasepachychoroid with patients

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The authors demonstrated that thethat demonstrated authors The In 2013, Warrow et al reported a reported al et Warrow 2013, In Recent progress in retinal imagingretinal in progress Recent also showed that some changes hadchanges some that showed also dilatedlarge, over directly developed theto external vesselsdirectly choroidal Shortlycomplex. membrane RPE/Bruch werefeatures pachychoroid thereafter, spectrumwider a with eyes in described to be a forme fruste of CSC. of fruste forme a be to attributedbe could PPE in changes RPE seenas thickening, choroidal of foci to hyper choriocapillarisand OCT, on They ICGA. on seen as permeability, changes occurred in the absence ofabsence the in occurred changes torelated were but detachment serous abnormalitieschoroidal of spectrum a termThe eyes. CSC in typically seen epitheliopathy pigment pachychoroid thisdescribe to introduced was (PPE) consideredauthors these which entity, series of patients with RPE changesRPE with patients of series resembledthat eyes both or one in fellowthe in seen frequently those CSC. unilateral with patients of eyes RPEthese that suggested authors The inner choroidal staining also havealso staining choroidal inner suggestingfilling, choroidal delayed associ with ischemia lobular choroidal dilatation. venous of areas ated Pachychoroid Disease dilated choroidal vessels on EDI-OCTon vessels choroidal dilated on hyperpermeability choroidal and (ICGA)angiography green indocyanine thisin choroid the of role the supports choroidalfor evidence Further disease. stud from comes CSC in vasculopathy midphasewith areas that indicating ies with enhanced depth imaging OCT (EDI- with enhanced depth (SS-OCT)OCT swept-source and OCT) insightsnew provided has technologies andstructural precise enabled and choroid. the of analysis functional andthickness choroidal Increased without associated active pigmentactive associated without PED. or leaks epithelial results CSC that suggests theory tive RPE,the in dysfunctionpump ion from inmovement fluid reverse in resulting direction. chorioretinal a pathogenesis of CSC may be choroidal be may CSC of pathogenesis orwith hyperpermeability vascular RETINA TODAY

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Figure. The left eye of a patient with CSC before (top images) and after (bottom images) micropulse laser treatment. The subretinal fluid disappeared quickly after treatment, and the external retinal layers normalized within a few weeks. instances include CSC with persistent the foveal avascular zone. PDT.29 The main outcome measures macular subretinal fluid (SRF) or Other types of laser delivery may were BCVA and central macular reduced visual acuity, cases in which also be efficacious in treatment of thickness (CMT) at 12 months. A rapid recovery of vision is required for CSC. Micropulse laser delivery mode probability value of less than .05 was vocational reasons, and those in which (Figure) diminishes the risk of iatro- considered statistically significant. untreated CSC has resulted in a poor genic thermal damage because it does At 12-month follow-up, mean BCVA visual outcome in the fellow eye. not induce visible laser burns and can improved in the micropulse group therefore be used to treat subfoveal from logMAR 0.41 ± 0.27 at baseline to Laser Therapy and Photodynamic Therapy or juxtafoveal focal and diffuse leaks.27 0.21 ± 0.26 (P < .0001). In that group, Focal laser photocoagulation is Photodynamic therapy (PDT) with 48.9% (45/92) of eyes had improve- commonly used to expedite SRF the light-activated drug verteporfin ment of 3 or more lines of BCVA, absorption in acute and chronic CSC. (Visudyne, Bausch + Lomb) has been 48.9% (45/92) of eyes remained within Typically, laser burns are applied to effectively used to treat chronic CSC.28 2 lines of baseline, and 2.2% (2/92) of areas of focal leakage identified by Potential advantages of micropulse eyes lost 3 or more lines from baseline. fluorescein angiography (FA) as the laser over PDT include lower cost and At 12-month follow-up in the PDT principal sources of SRF.26 Treatment no adverse events associated with PDT group, mean BCVA changed from of these leaks usually leads to SRF reso- infusion (eg, transient reduction in logMAR 0.50 ± 0.34 at baseline to 0.47 lution; however, in rare instances, laser macular function, choroidal nonperfu- ± 0.34 (P = .89); 19% (13/67) of eyes photocoagulation may be associated sion, RPE atrophy, and CNV). had improvement of 3 or more lines, with persistent scotoma at the site of Roca et al conducted a multicenter 73% (49/67) of eyes remained within photocoagulation and choroidal neo- retrospective comparative study of 2 lines of baseline, and 7% (5/67) of vascularization (CNV). Thus, laser pho- 159 consecutive eyes with chronic eyes lost 3 or more lines of BCVA from tocoagulation is not recommended if CSC treated with either yellow micro- baseline. There were no adverse events the point of leakage is within or near pulse laser or half-dose verteporfin attributable to yellow micropulse laser

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10. Gemenetzi M, De Salvo G, Lotery AJ. Central serous chorioretinopathy: an treatment. One eye in the PDT group benefit of melatonin treatment for update on pathogenesis and treatment. Eye (Lond). 2010;24(12):1743-1756. developed CNV, which was treated chronic CSC. These authors compared 11. Guyer DR, Yannuzzi LA, Slakter JS, Sorenson AJ, Ho A, Orlock D. Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch with anti-VEGF injections. It was melatonin 3 mg three times per day Ophthalmol. 1994;112(8):1057-1062. concluded that both PDT and micro- (9 mg/day) in 13 patients versus place- 12. Spitznas M. Pathogenesis of central serous chorioretinopathy: a new work- ing hypothesis. Graefes Arch Clin Exp Ophthalmol. 1986;224(4):321-324. pulse are effective in restoring macular bo in five patients. At 1-month follow- 13. Potsaid B, Baumann B, Huang D, et al. Ultrahigh speed 1050nm swept anatomy and that, in areas where PDT up, BCVA significantly improved in source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second. Opt Express. 2010;18(19):20029-20048. is not available, yellow micropulse 87.5% of treated patients (seven of eight 14. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain laser may be an adequate treatment patients) (P < .05). All patients showed optical coherence tomography. Am J Ophthalmol. 2008;146(4):496-500. 29 15. Spaide RF, Hall L, Haas A, et al. Indocyanine green videoangiography alternative. significant reduction in CMT (P < .01), of older patients with central serous chorioretinopathy. Retina. and three patients (37.5%) exhibited 1996;16(3):203-213. 16. Imamura Y, Fujiwara T, Margolis R, et al. Enhanced depth imaging optical Systemic Treatment Options complete resolution of SRF. No signifi- coherence tomography of the choroid in central serous chorioretinopathy. Myriad systemic medications have cant side effects were observed, and no Retina. 2009;29(10):1469-1473. 17. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. been investigated as treatments for changes in BCVA or CMT were noted Retina. 2013;33(8):1659-1672. CSC, including rifampin (Rifadin, Sanofi in the placebo group.33 18. Chung H, Byeon SH, Freund KB. Focal choroidal excavation and its association with pachychoroid spectrum disorders: a review of the literature and Aventis), helicobacter pylori triple treat- multimodal imaging findings. Retina. 2017;37(2):199-221. 19. Pang CE, Freund KB. Pachychoroid neovasculopathy. Retina. 2015;35(1):1-9. ment, carbonic anhydrase inhibitors, Anti-VEGF Therapy 20. Dansingani KK, Balaratnasingam C, Naysan J, Freund KB. En face imaging finasteride, beta blockers, antioxidants, Anti-VEGF agents are not consid- of pachychoroid spectrum disorders with swept-source optical coherence tomography. Retina. 2016;36(3):499-516. and aspirin. As a whole, these have had ered first-line treatments for either 21. Gal-Or O, Dansingani KK, Sebrow D, Dolz-Marco R, Freund KB. Inner poor results.30 acute or chronic CSC because aque- choroidal flow signal attenuation in pachychoroid disease: optical coherence tomography angiography [published online ahead of print January 30, Mineralocorticoid receptor ous VEGF levels are not elevated in 2018]. Retina. antagonists appear to be effective in these patients. Anti-VEGF therapy is, 22. Weenink AC, Borsje RA, Oosterhuis JA. Familial chronic central serous chorioretinopathy. Ophthalmologica. 2001;215(3):183-187. patients with chronic or recurrent however, useful in patients in whom 23. Lehmann M, Bousquet E, Beydoun T, et al. Pachychoroid: an inherited CSC, demonstrating anatomic and secondary CNV develops.26 condition? Retina. 2015;35(1):10-16. 24. Klein ML, Van Buskirk EM, Friedman E, et al. Experience with nontreatment functional improvement. Bousquet of central serous choroidopathy. Arch Ophthalmol. 1974;91(4):247-250. et al compared spironolactone CONCLUSION 25. Loo RH, Scott IU, Flynn HW Jr, et al. Factors associated with reduced visual acuity during long-term follow-up of patients with idiopathic central serous 50 mg every day for 30 days versus Advances in imaging techniques chorioretinopathy. Retina. 2002;22:19-24. placebo in patients with persistent have improved our understanding of 26. Nicholson B, Noble J, Forooghian F, et al. Central serous chorioretinopathy: up- 31 date on pathophysiology and treatment. Surv Ophthalmol. 2013;58(2)103-126. SRF for at least 3 months. These the choroid and choroidal disorders. 27. Sivaprasad S, Elagouz M, McHugh D, et al. Micropulsed diode laser therapy: authors found a statistically signifi- Management of CSC is challenging, evolution and clinical applications. Surv Ophthalmol. 2010;55(6):516-530. 28. Yannuzzi LA, Slakter JS, Gross NE, et al. Indocyanine green angiography- cant reduction in SRF and reduction particularly chronic CSC. Although guided photodynamic therapy for treatment of chronic central serous of subfoveal choroidal thickness in focal laser and PDT are current chorioretinopathy: a pilot study. Retina. 2003;23(3):288-298. 29. Roca JA, Wu L, Fromow-Guerra J et al. Yellow (577 nm) micropulse laser spironolactone-treated eyes com- standards of care in chronic CSC, versus half-dose verteporfin photodynamic therapy in eyes with chronic central pared with placebo. No significant micropulse laser is a good alternative serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group [published online ahead of print February 8, 2018]. changes were observed in BCVA, and in instances when verteporfin is not Br J Ophthalmol. no complications related to treat- available. Some systemic treatments 30. Delyani JA. Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Kidney Int. 2000;57(4):1408-1411. 31 ment were reported. may benefit patients with chronic 31. Bousquet E, Beydoun T, Rothschild PR, Bergin C, et al. Spironolactone for nonresolving central serous chorioretinopathy: a randomized controlled Schwartz and colleagues compared CSC by decreasing the rate of thera- crossover study. Retina. 2015;35(12):2505-2515. the efficacy and safety of the aldoste- py-induced complications. n 32. Schwartz R, Habot-Wilner Z, Martinez MR, et al. Eplerenone for chronic rone antagonist eplerenone 50 mg/day central serous chorioretinopathy-a randomized controlled prospective study. 1. Wang M, Munch IC, Hasler PW, et al. Central serous chorioretinopathy. Acta Acta Ophthalmol. 2017;95(7):e610-e618. (Inspra, Pfizer) in patients with chronic Ophthalmol. 2008;86:126-145. 33. Gramajo AL, Marquez GE, Torres VE, Juárez CP, Rosenstein RE, Luna JD. CSC versus placebo.32 The main out- 2. Haimovici R, Koh S, Gagnon DR, et al; Central Serous Chorioretinopathy Therapeutic benefit of melatonin in refractory central serous chorioretinopathy. Case-Control Study Group. Risk factors for central serous chorioretinopathy: a Eye (Lond). 2015;29(8):1036-1045. come measure was change in SRF case-control study. Ophthalmology. 2004;111(2):244-249. at 3 months. Secondary outcomes 3. Tittl MK, Spaide RF, Wong, et al. Systemic findings associated with central serous chorioretinopathy. Am J Ophthalmol. 1999;128(1):63-68. included choroidal thickness and 4. Bouzas EA, Scott MH, Mastorakos G, et al. Central serous chorioretinopathy NATALIA ALPÍZAR-ALVAREZ, MD BCVA changes. In this study, eplere- in endogenous hypercortisolism. Arch Ophthalmol. 1993;111(9):1229-1233. n Retina Fellow, Oftalmologos Contreras, Lima, Peru 5. Cousins L, Rigg L, Hollingsworth D, et al. Qualitative and quantitative assess- 32 n none was not superior to placebo. ment of the circadian rhythm of cortisol in pregnancy. Am J Obstet Gynecol. Financial disclosure: None Spironolactone is known to have a 1983;145(4):411-416. 6. Chumbley LC, Frank RN. Central serous retinopathy and pregnancy. Am J higher mineralocorticoid receptor affin- Ophthalmol. 1974;77(2):158-160. JOSÉ A. ROCA, MD ity than eplerenone, along with a higher 7. Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Trans n Associate Professor, Cayetano Heredia University, Am Ophthalmol Soc. 1986;84:799-845. incidence of side effects, including 8. Michael JC, Pak J, Pulido J, de Venecia G. Central serous chorioretinopathy Lima, Peru hyperkalemia, gynecomastia, reduced associated with administration of sympathomimetic agents. Am J Ophthalmol. n Chief, Retina Division, Ricardo Palma Clinic, Lima, Peru 2003;136(1):182-185. 30 n libido, and menstrual changes. 9. Mansuetta CC, Mason JO 3rd, Swanner J, et al. An association between [email protected] central serous chorioretinopathy and gastroesophageal reflux disease. Am J n Financial disclosure: None Gramajo et al reported a therapeutic Ophthalmol. 2004;137(6):1096-100.

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