For Central Serous Chorioretinopathy, Wait-and-See No More

Acute central serous chorioretinopathy
Acute central serous chorioretinopathy
CSCR experts advise clinicians to use multimodal imaging fully, scrutinize retinal periphery, inspect the contralateral eye, and quantify prior damage.

A new paradigm in the treatment of central serous chorioretinopathy (CSCR) is emerging — it is less about waiting and observing for specifically 3 months before treating this disorder, and more about considering the presenting structural characteristics along a continuum.

“I think that the biggest hurdle with this disease is that we have been calling it acute and chronic,” said Dr Jay Chhablani, vitreoretinal surgery specialist at the University of Pittsburgh Eye Center, associate professor of ophthalmology, and editorial board member at American Journal of Ophthalmology. Patients may seek care only after CSCR has already been causing damage outside of the fovea, so Dr Chhablani treats based on the status of the damage rather than time from presentation.

A “wait and see” approach when caring for patients with CSCR may well apply to a smaller set of those with the disorder than previously thought, according to recent research and observations of clinical experts. Undoubtedly, CSCR often spontaneously resolves in 3 months or less. However, pathology may be originating at the retinal periphery unnoticed.

“I would say that these patients (sometimes) get undertreated significantly,” Dr Chhablani said. He added that a small amount of fluid may not raise caution because vision is still 20/20. “Just because it is 20/20 and we have so-called natural history of the disease, which says that it will resolve on its own, but what it will leave behind, nobody understands.” To start, he and his research team make wide use of multimodal imaging.1 

First, Make More Use of Multimodal Imaging 

Hideki Koizumi, MD, PhD, clinical researcher, professor and chairman at University of the Ryukyus, Okinawa, Japan, uses multimodal imaging to discern subtypes of the disorder. In contrast to steroid-induced CSCR (sCSCR), idiopathic subtypes (iCSCR) may exhibit greater large choroidal vessel layer thickness vs subfoveal choroidal thickness (SCT) ratio and greater luminal vs whole choroidal area ratio.

“In other words, the eyes with idiopathic CSCR demonstrate characteristic pachychoroid features induced by outflow disturbances through the sclera,” Dr Koizumi said.  “Many disorders represent similar manifestations such as serous retinal detachment, and the intrachoroidal structures are useful markers to make the correct diagnosis of idiopathic CSCR.” Considering the intrachoroidal structures of eyes with iCSCR are easier to spot than those with sCSCR, it may be advantageous to employ more than optical coherence tomography (OCT) alone to discriminate sCSCR from normal eyes or other macular pathologies, he added.

Dr Koizumi and colleagues’ most recent work examines medical records for 110 eyes of 110 patients with CSCR who visited a university-based eye center in Japan.2 Participants included 96 eyes with iCSCR, and 14 with sCSCR, as reported in February by Ophthalmology Science. CSCR diagnoses were based on imaging with OCT, fluorescein angiography, as well as indocyanine green angiography (ICGA) which illustrated changed choroidal circulatory patterns such as early filling delay, and middle or later vessel dilation and vascular hyperpermeability. Researchers compared structures in iCSCR vs sCSCR, finding mean scleral thickness was significantly thinner in the sCSCR cohort than in the iCSCR group. This factor suggests there is less scleral involvement in disease pathogenesis for those with steroid-induced disorder.2 

OCT angiography (OCT-A) can also be useful. A comprehensive review published in May 2021 by Survey of Ophthalmology explored the use of OCT-A in detecting structural changes from CSCR and characterizing choroidal neovascular (CNV) lesions, as reported in 59 studies.3 In several investigations, mixed perfusion at disease onset and hyperperfusion after resolution was found, with “mixed flow patterns” at different stages of CSCR. “Therefore, even in presence of confounders, the OCT-A did clearly image the delicate capillary changes better than traditional tools,” according to the literature review.

A number of the studies examined changes in the choriocapillaris (CC) — including findings categorizing flow patterns into concentric areas of low and high flow signals, or “a mosaic pattern of random” low and high flow signals. Overall, OCT-A was found reliable to uncover changes in superficial and deep choroidal vessels. Additionally, OCT-A revealed disrupted CC signals and other important changes in contralateral fellow eyes.3

Second, Look at Retinal Periphery and the Other Eye

Dr Chhablani always studies both eyes. “Don’t read this as a 1-eye disease — there definitely, probably is something going on in the other eye,” he explained. “And a very important thing, which I speak on in many meetings, and always say, ‘don’t ignore a longstanding shallow fluid, even with 20/20.’”

He added that, although a patient may be presenting to the ophthalmologist for the first time, upon examination it could become clear that the damage is not recent. In that scenario, he would offer treatment sooner rather than later. Conversely, if the patient has a recent onset and there are only limited changes in limited areas, he typically waits and carefully observes for about 2 months. If the fluid does not resolve in this time, then he would offer a treatment option.

Dr Koizumi observes a similar timeline. He wants to prevent damage from retinal detachment. “In idiopathic central serous chorioretinopathy, I usually wait for 3 months unless the patient wishes early treatment, since previous experimental studies suggested that the photoreceptors might start to show apoptosis in the presence of retinal detachment after 4 months,” he said. In steroid-induced CSCR, both eyes of a patient may be affected and he consults with their physician whether the steroid may be safely discontinued. 

Third, Check for Common Masqueraders of CSCR

Dr Chhablani is a senior author of the systematic review “Masqueraders of Central Serous Chorioretinopathy,” published in Survey of Ophthalmology.1 CSCR is often misdiagnosed due to structural characteristics that overlap with those of other disorders, or patients presenting with atypical signs. 

Investigators analyzed close to 100 English-language papers based on an extensive literature search. They discovered disorders imitating CSCR could be placed into 5 general categories: 

  1. Choroidal vascular diseases 
  2. Inflammatory conditions 
  3. Retinal vascular diseases
  4. Anatomic abnormalities
  5. “Other” — including bilateral diffuse uveal melanocytic proliferation, bestrophinopathies, and uveal effusion syndrome.1

“I think that one of the most common masqueraders is age related macular degeneration (AMD), honestly,” Dr Chhablani explained. He added that another common masquerader is polypoidal choroidal vasculopathy. Also, he has observed that vitelliform deposits are at times confused with CSCR.

Bestrophinopathies, the set of diseases caused by BEST1 gene mutation, can also result in central vision loss. In best vitelliform macular dystrophy, egg-yolk-like lesions may appear at the maculae. Subretinal deposits imaged with OCT can be seen as hyperreflective, but deposits may be “replaced by a clear fluid,” and mimic a subretinal deposit typical with CSCR.1

“All I would say is the knowledge of multimodal imaging findings — that is actually the very key component in differentiating these diseases,” he added. “If you have some more doubts, then you can always push from a non-invasive test to an invasive test.”

Double Layer Sign Helps Detect Macular Neovascularization

Regarding noninvasive testing, more clinics have access to OCT than to OCT-A, and a structural parameter, double layer sign (DLS) is thought to help identify patients at risk for macular neovascularization (MNV) secondary to CSCR. The DLS was defined as a region of elevated retinal pigment epithelium (RPE) with a minimum length of 1000 μm and maximum height of 150 μm, and examined as a diagnostic aid, including core characteristics under raised RPE, according to a new retrospective study published in American Journal of Ophthalmology.4

Using OCT-A as the reference standard, investigators in the UK looked at the medical records of 163 eyes of 132 patients with a clinical diagnosis of CSCR. Mean age of participants was 55.2±12.2 years at time of scans, taken between November 2016 and March 2020.

Investigators calculated the sensitivity for DLS to detect MNV was 87.0% and specificity 56.0%. Notably, features of the sub-RPE space were found to be independently connected to MNV: hyper-reflectivity (P <.001) and non-homogeneity (P =.02). Upon incorporating hyper-reflectivity and non-homogeneity with DLS in all CSCR-diagnosed eyes, sensitivity to discern MNV was slightly lower at 85.2%, but specificity reached 82.6%. 

“Non-homogeneous and hyper-reflective space under an elevated RPE of any length or height indicates an eye with higher risk of MNV than DLS,” according to the analysis. “OCT-A should at least be performed for these eyes to confirm the presence of MNV and treat accordingly.”4  

A prospective, interventional study monitored 96 eyes of 96 patients with new-onset CSCR, and 210 eyes of 210 control individuals for 2 years in an analysis of multimodal imaging to distinguish 2 subtypes: retinal pigment epithelium-related CSCR (RPE-CSCR), and choroid-related CSCR, according to the paper published in Translational Vision Science & Technology.5 

Researchers found the RPE-CSCR phenotype displayed a normal choroidal thickness, along with “irregular hypofluorescence in the late ICGA phases with corresponding outer retinal band signal attenuations on structural OCT.” The choroidal-CSCR type exhibited pachychoroid, including dilation of choroidal vessels in early ICGA — in late ICGA, isofluorescent background was observed, without deficiencies in the outer retinal band.

MNV was found in 19% of the overall sample. Of these, 72% were members of the RPE-CSCR subgroup, and 28% were in the choroidal-CSCR subgroup.5

Ask About Stress and Steroids

Dr Chhablani noted that another challenge with CSCR is that it affects a younger population, often a working population. “Their vision may be really good in numbers, such as 20/40, 20/60, but still they are very upset and it’s affecting their quality of life,” he explained.

A working set may be more affected by stress, cortisol, and endogenous and exogenous steroids. “Although speculative, long-term steroid use may induce the changes in scleral thickness or quality,” Dr Koizumi said. “Steroids may possibly alter the number and arrangement of collagen fiber bundles and/or the amount and quality of matrix in the sclera.“ However, he added that the effect of steroids on scleral quality and thickness is still unclear.

Interestingly, steroids may hinder norepinephrine uptake by glial cells, and thus raise norepinephrine level at sympathetic nerve endings, prompting dominance of the sympathetic nervous system.2 “Exogenous steroid use may have an additive effect on the choroid in steroid-induced CSCR. Increased sympathetic activity hypothetically causes cardiac output elevation systemically, and arterial vasoconstriction and resultant imbalanced blood flow in the choroid locally,” Dr Koizumi explained.

One notable case report published in Retinal Cases & Brief Reports presents instances of 2 married couples — each spouse was diagnosed with CSCR.6 The analysis speculates that the 2 pairs may have been exposed to shared stressors or secondary steroid exposure. The first couple presented to the clinic on the same day, but neither individual was aware of any contact with steroids. Conversely, the husband in the second couple, (34 years of age), had chronic sinusitis and was taking nasal and oral steroids. He had a one-month history of “blurry vision” in his right eye. VA for this eye was 20/30. His subretinal fluid did not resolve at 3 months and he underwent photodynamic therapy (PDT). Three days after this treatment, his wife (38 years of age), complained of bilateral blurring, although her VA was 20/20. OCT imaged thick choroid in both eyes, a large pigment epithelial detachment (PED) in the right eye, and 3 small PEDs in the left. She reported recent high levels of stress.6

In a 2018 resident lecture at University of South Florida, Dr Steven Cohen, clinical professor of ophthalmology, talked about another unique case of the disorder experienced by a female patient, 12 years of age.7 She visited the clinic with a 2-week history of central vision loss in her right eye, VA of 20/400 — the left eye was at 20/20. The patient had just started menstruating, exhibited history of hypothyroidism, and had been using a steroid nasal spray for sinus infection. 

Examination, OCT, and FA testing revealed slight swelling around the optic nerve and a large serous retinal detachment in the macula of the right eye. With concern for pediatric differentials, such as increased intracranial pressure, Dr Cohen  did not want to wait for long. However, her vision improved to 20/50 in 3 days upon discontinuing the intranasal spray, and the serous retinal detachment approached full resolution. After 1 month, VA returned to 20/20 with normal maculae.7

Subthreshold Laser Therapy is Often Chosen

Current therapies often chosen for CSCR include PDT, continuous wave laser, and subthreshold or micropulse, laser. Dr Chhablani considers where the leakage is occurring. “If the leakage or the laser is going to involve the central area, then I would say that conventional laser is definitely not an option, but the subthreshold laser or photodynamic therapy are options,” he explained. “And if both are available, I would prefer a subthreshold laser, because that does not lead to any structural damage.” He has been employing this therapy for 6 to 7 years with good results and feels confident that if needed, it can be repeated.

Micropulse helps to control temperature rise in the tissue, and “triggers an anti-angiogenic and restorative biological response resulting in the reabsorption of subretinal fluid through the restoration of the RPE cells,” according to a report.8 

Researchers in Poland demonstrated the effectiveness of early transfoveal subthreshold micropulse laser therapy for 32 patients, mean age 48.2±11.0 years who developed CSCR — with mean duration of symptoms 3.4±2.3 months (range 3 weeks to 6 months), according to the investigation published in 2019 by the Journal of Clinical Medicine.9 After micropulse, subretinal fluid was completely resolved for 81.25% of participants. Notably, patients who received treatment within 2 months of symptom onset experienced better mean BCVA at 0.09±0.09 logMAR, than those who obtained micropulse 2 to 6 months after symptoms began, 0.34±0.20 logMAR (P =.00003).

Compared with patients who responded to therapy, those who did not respond tended to have worse starting VA, but not necessarily lengthier disease. “In light of these findings, it appears that, even in cases of self-limiting CSCR, potentially visually limiting retinal damage begins with disease onset and worsens as the disease persists,” the analysis suggests.9

Eplerenone and Combination Therapies Work For Some

Dr Chhablani has had mixed results with eplerenone, noting that some patients show no response, and others have responded well. “That’s why I keep eplerenone in my treatment armamentarium, because if the patients don’t respond to anything, sometimes you would like them to try the eplerenone, or sometimes I use this in a combination therapy,” he explains.

A large, double-blind study examines results for 114 participants at 22 hospitals in the UK randomized 1:1 to oral eplerenone plus usual care or placebo plus usual care for a period of 12 months between January 2017 and February 2018.10 Eplerenone dosage was 25 mg per day for 1 week, and increased to 50 mg per day for up to 1 year. The primary outcome measured was BCVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters.

Modeled mean BCVA at 1 year was not significantly different between cohorts: 80.4±4.6 letters for those taking eplerenone compared with 79.5±4.5 for placebo, with an adjusted mean difference of 1.73 letters (P =0.24). The investigation discourages use of eplerenone as a first-line mode of therapy.10

Additional research has focused on anti-VEGF injections for CSCR.

Current State of Funding and Trials

Dr Chhablani notes that AMD is a well-known blinding condition, receiving a lion’s share of funding for new trials — CSCR receives less support from industry and public granting agencies. Therefore, a struggle still exists to understand both the pathogenesis of the disorder and standardization of best treatments. He has been connecting with an international group of concerned ophthalmologists, working on new studies focused on classification systems and looking at the efficacy of therapeutic options.

“It is a very frustrating disease both for the physician as well as for the patient,” he said. “(Lack of funding is an) “unfortunate part, which is what makes me strive to work more on this disease.”


1. Sahoo NK, Singh SR, Rajendran A, Shukla D, Chhablani J. Masqueraders of central serous chorioretinopathy. Survey of Ophthalmology. 2019;64(1):30-44. doi:10.1016/jsurvophthal.2018.09.001

2. Sawaguchi S, Terao N, Imanaga N, et al. Scleral thickness in steroid-induced central serous chorioretinopathy. Ophthalmol Science. Published online on February 7, 2022. doi:10.1016/j.xops.2022.100124

3. Pujari A, Surve A, Azad SV, et al. Optical coherence tomography angiography in central serous chorioretinopathy: The current clinical role and future perspectivesSurv Ophthalmol. 2022;67(1):68-82. doi:10.1016/j.survophthal.2021.05.003

4. Hagag AM, Rasheed R, Chandra S, Jeffery G, Sivaprasad S. The diagnostic accuracy of double-layer sign in detection of macular neovascularization secondary to central serous chorioretinopathy. Am J Ophthalmol. Published online first October 23, 2021. doi:10.1016/j.ajo.2021.10.021

5. Arrigo A, Aragona E, Bordato A, et al. Acute central serous chorioretinopathy subtypes as assessed by multimodal imagingTrans Vis Sci Tech. 2021;10(13):6. doi:10.1167/tvst.10.13.6

6. Kanesa-thasan A, Fawzi AA, Gill MK. Presentation of central serous chorioretinopathy in two husband and wife couples. Retinal Cases & Brief Reports.2018;12(2):100-102. doi:10.1097/ICB.0000000000000452

7. Cohen S. Central serous chorioretinopathy. Resident lecture February 2018. Published February 5, 2018. Accessed February 14, 2022.

8. Munir Escaf, MD. Laser therapy may offer fast-acting option for CSR resolution. Modern Retina. Published November 12, 2018. Accessed February 11, 2022.

9. Gawęcki M, Jaszczuk-Maciejewska A, Jurska-Jaśko A, Kneba M, Grzybowski A. Transfoveal micropulse laser treatment of central serous chorioretinopathy within six months of disease onsetJ Clin Med. 2019;8(9):1398. doi:10.3390/jcm809139810.

10. Lotery A, Sivaprasad S, O’Connell A, Harris RA, Culliford L, et al. Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomized, double-blind, placebo-controlled trial. The Lancet. 2020;395(10220):294-303. doi:10.1016/S0140-6736(19)32981-2