Central serous retinopathy (CSR) is a retinal disorder characterized by the accumulation of fluid beneath the neurosensory retina, most commonly in the macula. CSR may present acutely or chronically.
Acute CSR typically manifests as a single episode of painless central vision loss due to subretinal fluid (SRF), often accompanied by a single “hot spot” visible on fluorescein angiography (FA) and/or indocyanine green angiography (ICG) imaging.
Most acute cases resolve spontaneously within 3 to 6 months, and the visual prognosis is generally favorable.1 Patients often report symptoms such as blurred vision, micropsia, metamorphopsia, and/or a central scotoma.
Chronic CSR, however, represents a spectrum of disease in which fluid persists, recurs, or leads to progressive damage to the photoreceptor and retinal pigment epithelium (RPE), often resulting in irreversible visual decline.
The overall prevalence of CSR is estimated at 14 per 100,000 individuals, with a higher risk in men, particularly between the ages of 30 to 60 years.2 Various imaging modalities listed below are often used to confirm and follow the disease process.
Diagnostic imaging techniques for CSR
| Imaging | Findings/Utility |
|---|---|
| Spectral-domain optical coherence tomography (SD-OCT) | Gold standard for visualizing SRF and assessing retinal morphology |
| Enhanced depth imaging OCT (EDI-OCT) | Enables evaluation of choroidal thickness and morphology |
| OCT angiography (OCTA) | Provides non-invasive imaging of potentially abnormal choroidal and retinal vasculature |
| Fundus fluorescein angiography (FFA/FA) | Identifies leakage sites, typically showing the “smokestack” or “inkblot” pattern |
| Indocyanine green angiography (ICGA) | Highlights choroidal hyperpermeability and guides targeted therapies |
| Multicolor imaging (MCI) and fundus autofluorescence (FAF) | Assess RPE alterations and chronic disease changes |
Figure 1: Color fundus photography (CFP) of a CSR patient with localized serous retinal detachment; sheen from the internal limiting membrane can be visualized, there is no evidence of hemorrhage, lipid, or pigmentary changes, and the retinal vasculature appears healthy.
Figure 1: Courtesy of Jay M. Haynie, OD, FAAO, FORS.
Figure 2: OCT imaging of a CSR patient showing an area of subretinal fluid defining the focal neurosensory retinal detachment, and the choroid appears thickened.
Figure 2: Courtesy of Jay M. Haynie, OD, FAAO, FORS.
Figure 3: FA imaging of a patient with chronic CSR demonstrating a focal lesion just outside of the central macula.
Figure 3: Courtesy of Jay M. Haynie, OD, FAAO, FORS.
Figure 4: ICGA imaging in a patient with chronic CSR; a focal extrafoveal leakage in the central macula can be visualized, there is no presence of choroidal neovascularization, but there is hypercyanesence, which is leaking in the choroid.
Figure 4: Courtesy of Jay M. Haynie, OD, FAAO, FORS.
Current standard treatments for chronic CSR
While the natural history of central serous chorioretinopathy is often self-limiting, a subset of patients progress to chronic or recurrent disease, prompting the need for evidence-based interventional strategies.
Photodynamic therapy (PDT)
Photodynamic therapy with verteporfin remains the first-line treatment for chronic CSR, particularly in patients with persistent (chronic and/or recurrent) SRF and visual impairment. PDT induces selective choroidal vascular remodeling through free radical production following laser activation of verteporfin.3
Several protocol modifications have been studied to balance efficacy with reduced risk of choroidal hypoperfusion. A trial comparing standard versus half-fluence PDT found that half-fluence treatment resulted in greater improvement in retinal sensitivity, along with gains in visual acuity (VA) and central retinal thickness (CRT) at 12 months.4 Another study comparing half-dose verteporfin PDT with half-fluence PDT found no significant differences, though both groups improved.5
Alternative approaches have also been compared. Subthreshold diode micropulse therapy, half-dose PDT, and observation showed improvement in all groups at 16 weeks, but without significant differences between treatments.6 A head-to-head trial comparing half-dose PDT with 689nm laser treatment performed without verteporfin found the two approaches to be equally effective.7
Another study comparing half-dose PDT with subthreshold micropulse laser therapy found that both treatments improved BCVA, macular thickness, and SRF. However, SRF resolution rates were higher in the PDT group.8
A 2023 network meta-analysis further confirmed that among available therapies, half-dose or half-fluence PDT remains the most effective and durable treatment, outperforming both conventional laser and SRT.9
Laser photocoagulation
Laser photocoagulation targets focal RPE leakage on angiography to accelerate SRF resolution and reduce recurrences.
The PLACE trial compared half-dose PDT with a high-density subthreshold micropulse laser and demonstrated superior outcomes with PDT: 51.2% of PDT patients achieved SRF resolution at 6 to 8 weeks, compared with only 13.8% in the micropulse group, along with greater improvements in BCVA and retinal sensitivity.10
Interestingly, another study reported the opposite, finding better outcomes with micropulse laser, including a more significant reduction in CRT.11 Long-term data also support focal laser in select patients. Over nearly 5 years of follow-up, eyes treated with focal laser had shorter detachment duration, better final BCVA, and no recurrences, while untreated controls frequently experienced recurrences.12
Figure 5: Near-infrared reflectance (NIR) imaging in a patient with chronic CSR after laser photocoagulation; the yellow circle highlights where the laser treatment was performed, and mottling of the pigment can be visualized beneath the treated tissue.
Figure 5: Courtesy of Jay M. Haynie, OD, FAAO, FORS.
Anti-VEGF therapy
The role of anti-VEGF agents in CSR remains controversial. Sometimes the clinical manifestations of a concurrent or isolated choroidal neovascularization are challenging to distinguish, especially when there are other risk factors such as advancing age, myopia, past trauma, etc.
Intravitreal bevacizumab (Avastin, Genentech/Roche) has been reported to improve VA and CRT compared with controls.13 In a larger series of 78 eyes, SRF resolution occurred in 60 treated eyes, with associated improvements in VA, CRT, and subfoveal choroidal thickness. Notably, baseline thin choroid and hypertension were predictors of a poorer response.14
Head-to-head comparisons with PDT highlight limitations. A pilot study showed that 89% of patients receiving half-fluence PDT achieved complete SRF resolution at 12 months, compared to only 12.5% in the ranibizumab group.15 Another comparison of PDT versus bevacizumab found no significant differences in VA or CRT at 9 months, though the PDT group started with a better baseline VA.16
A subset of patients with chronic CSR may develop secondary choroidal neovascularization (CNV). In these cases, intravitreal anti-VEGF agents represent the treatment of choice.17
New and investigational treatments for CSR
Beyond established therapies, a range of emerging and investigational treatments for chronic CSR are under study, reflecting ongoing efforts to target alternative pathways and improve outcomes in patients with limited response to standard care.
Mineralocorticoid receptor antagonists
Spironolactone and eplerenone have been widely studied based on the proposed role of corticosteroid pathways in CSR. However, high-level evidence has tempered enthusiasm.
The VICI trial, a large multicenter, placebo-controlled study, found no significant BCVA difference between eplerenone and placebo at 12 months, recommending discontinuation of eplerenone use for CSR.18 Smaller crossover studies exploring spironolactone and eplerenone showed within-group improvements but lacked robust between-group comparisons.19
Aspirin
The role of aspirin in CSR is weakly supported. Some studies have proposed potential benefits, but overall, the evidence is limited and inconsistent, and it is not considered a standard treatment.
Carbonic anhydrase inhibitors
Oral acetazolamide combined with topical nepafenac resulted in faster SRF resolution, but did not improve BCVA.20 A larger retrospective study found that both acetazolamide and mineralocorticoid receptor antagonists led to significant improvements in SRF and retinal prominence, with associated VA gains, while observation alone did not produce significant benefit.21
Helicobacter pylori eradication
CSR has been associated with H. pylori infection, with higher prevalence reported in patients with recurrent disease.22
Treatment studies have shown mixed results. In one series, eradication led to SRF resolution in 14 of 15 eyes, though some required adjunct laser therapy.23 Other investigations reported shorter disease duration, reduced recurrence frequency, and improved VA.24,25 Structural improvements without consistent VA benefit were also reported.25,26
Selective retina therapy (SRT)
SRT employs a Q-switched neodymium: YLF laser to target the RPE while sparing the neurosensory retina selectively.
Early randomized studies demonstrated significant improvements in BCVA and SRF resolution versus controls.27 A more recent study using real-time feedback-controlled dosimetry (RFD) showed a significantly higher rate of SRF resolution, with 70.3% of eyes achieving complete resolution at 12 weeks.28
Image-based titration techniques have been introduced to optimize SRT dosing, with studies reporting favorable functional and anatomical outcomes.29
Key takeaways
- PDT remains the gold standard for chronic CSR, with half-fluence or half-dose protocols balancing efficacy and safety.
- Laser photocoagulation may benefit select patients, with variable evidence for subthreshold micropulse techniques.
- Anti-VEGF therapy has shown limited and inconsistent benefit, especially compared to PDT.
- Mineralocorticoid receptor antagonists, aspirin, and carbonic anhydrase inhibitors remain experimental, with mixed evidence.
- H. pylori eradication may help in select patients but is not universally recommended.
- SRT shows promise as a novel RPE-targeted therapy; however, meta-analytic evidence suggests its benefit is modest compared to PDT.
In conclusion
Central serous retinopathy remains a complex disorder with a variable natural history and diverse therapeutic landscape.
While photodynamic therapy remains the most reliable and effective intervention for chronic cases, ongoing research into pharmacological, antimicrobial, and laser-based strategies reflects the unmet need for alternative options in patients who are poor candidates or non-responders.
Ultimately, individualized treatment guided by multimodal imaging and careful patient selection is essential. As new investigational therapies evolve, continued high-quality clinical trials will be critical to refining management algorithms and improving long-term visual outcomes for patients with CSR.
