Early versus deferred treatment with Pascal short-pulse duration plus subthreshold endpoint management laser techniques for central serous chorioretinopathy

Early versus deferred treatment with Pascal short-pulse duration plus subthreshold endpoint management laser techniques for central serous chorioretinopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Early versus deferred treatment with Pascal short-pulse duration plus subthreshold endpoint management laser techniques for central serous chorioretinopathy Murilo Wendeborn Rodrigues, João Pedro Braga, José Augusto Cardillo, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8554824/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To compare anatomical and functional outcomes of combined Pascal focal short-pulse duration laser plus subthreshold diffuse laser (SDL) with Endpoint Management algorithm (SPD plus SDL-EpM) applied promptly or deferred in acute central serous chorioretinopathy (CSC). Design: Retrospective comparative study. Participants: Seventy-nine eyes with acute macular subretinal fluid (SRF) due to CSC treated between July 2022 and January 2024. Methods Group I (n = 55) received prompt SPD plus SDL-EpM laser; Group II (n = 24) received oral spironolactone (50 mg twice daily) with deferred laser after 3 months if SRF persisted. Multimodal evaluation was performed at baseline and at 1, 3, 6, and 12 months. Outcomes included subretinal fluid height (SRFH), best-corrected visual acuity (BCVA), central macular thickness (CMT) and choroid thickness measurement (CTM). Results Sixty-eight eyes (86%) completed 12-month follow-up data analysis. In the intergroup comparison, Group I demonstrated significant SRFH, CMT and BCVA better and faster results (p < 0.05) through initial 3 months. At 12 months, a tendency BCVA (p < 0.1) improvement was sustained. The CTM was not significant different between the groups I and II at all visits study. The SRF resolution was more frequent in Group I than Group II at all visits study with significant percentile from 1º, 3º and 12º months. Conclusions Prompt SPD plus SDL-EpM laser therapy in acute CSC results in faster anatomical and functional recovery compared with deferred laser following oral spironolactone therapy. Long-term outcomes were comparable between groups. central serous chorioretinopathy short-pulse laser subthreshold diffuse laser Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid (SRF) leakage and it is often associated with reduced vision-related quality of life. After neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), CSC is the fourth most common retinopathy that causes macular fluid leakage ( 1 ). In CSC, the leakage through defects in the outer blood-retina barrier of the RPE appears to occur secondary to choroidal abnormalities and dysfunction. Symptoms typically include impaired and/or distorted central vision, often accompanied by altered color perception, and reduced vision-related quality of life ( 2 , 3 ). The treatment of CSC is currently the subject of controversy. Recent evidence suggests benefits from early intervention using either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitizing dye verteporfin in selected cases, which is considered the preferred treatment for chonic CSC. Results from three large randomized controlled trials (RCTs) namely the PLACE, VICI and SPECTRA trials demonstrated: (i) the superiority of half-dose PDT over high-density subthreshold micropulse laser treatment; (ii) the non-superiority of the oral mineralocorticoid receptor antagonist eplerenone treatment compared to placebo, and (iii) the superiority of half-dose PDT over eplerenon ( 4 – 6 ). In acute CSC, treatment has traditionally been deferred for up to 3–4 months after diagnosis, based on earlier studies. However, with advances in imaging devices and refined laser laser tecniques, experts are increasingly encouraged to initiate therapy earlier to achieve safer, faster visual recovery, reduce the likelihood of recurrence, and potentially improve long-term visual outcomes. Since acute CSC often working-age patients, who may experience considerable anxiety about vision loss, early treatment can be a valuable strategy—particularly in low-resource settings where access to costly therapies such as PDT is limited. The dual Pascal ® focal SPD plus SDL-EpM modalities enables effective treatment using only sublethal thermal elevations, thereby avoiding the excessive heat that can cause white burns, tissue necrosis, and other adverse effects (Fig. 1 ). Our group proposed a combined Pascal® laser approach - SPD plus SDL-EpM - first described in the literature for CSC treatment with the aim of providing a flexible repair strategy and promoting rapid visual recovery in CSC management. Methods Study design . This study adheres to the Declaration of Helsinki, and received institutional review board approval from the Ethics and Research Committee of Ribeirão Preto Medical School (Ref. N.: 5.496.883). All data were collected retrospectively. We reviewed the records of all patients in a public vitreoretinal subspecialty practice who received prompt or deferred focal Pascal ® SPD plus SDL-EpM therapy for macular subretinal fluid (SRF) in CSC. The study included 79 eyes treated between July 2022 to January 2024. Patient eligibility and exclusion criteria . The studyinclusion criteria were as follows: 1) age ≥ 18 years; 2) BCVA between 0.3 logMAR (Snellen equivalent: 20/32) and 1.3 logMAR (Snellen equivalent: 20/400); 3) macular center-involving SRF with a minimum height of 100µm on SD-OCT. As for the exclusion criteria it was comprised: 1) Evidence of vitreomacular traction on SD-OCT; 2) no history of vitreoretinal surgery; 3) systemic corticosteroid therapy; 4) any other ocular condition that, in the opinion of the investigator, could affect SRF or alter visual acuity (VA) during the course of the study. Patient Demographics and Evaluations A total of 79 eyes from 79 patients (mean age, 46.8 years ) were retrospectively analyzed (Table 1). No significant differences were observed between Group I (n = 55) and Group II (n = 24) regarding mean age or eye laterality (right vs. left). The overall male-to-female ratio was significantly higher (p < 0.05) in both groups (Group I: 45 males and 10 females; Group II: 16 males and 8 females). Group I received prompt laser therapy , whereas Group II initially underwent oral spironolactone therapy (50 mg twice daily for 3 months) prior to laser treatment. All patients underwent a comprehensive ophthalmic evaluation before laser intervention, including best-corrected visual acuity (BCVA) assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, slit-lamp biomicroscopy , indirect ophthalmoscopy , near-infrared reflectance imaging , fluorescein angiography (FA) , and spectral-domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Germany) . Follow-up examinations were performed at 1, 3, 6, and 12 months , including ETDRS BCVA and SD-OCT imaging for quantification of subretinal fluid height (SRFH) , choroidal thickness measurement (CTM) , and central macular thickness (CMT) . For SRFH and CTM , manual caliper measurements were performed using the SD-OCT software ruler tool. SRFH was defined as the vertical distance between the retinal pigment epithelium (RPE) and the outer photoreceptor layer , while CTM corresponded to the vertical distance from the RPE to the outer boundary of the choroidal Haller layer . CMT values were obtained automatically using the device’s built-in retinal thickness mapping software. If retreatment criteria were met defined as persistent or recurrent subretinal fluid after a minimum 3-month interval, fluorescein angiography was repeated to guide further laser application. Treatment Regimen All treatments were performed using the Pascal® photocoagulation system (Topcon Medical Laser Systems), which delivers a 532-nm frequency-doubled solid-state green laser . An experienced vitreoretinal surgeon administered all procedures within two weeks of OCT-confirmed subretinal fluid (SRF) diagnosis. The combined laser protocol consisted of two consecutive photothermal retinal pigment epithelium (RPE) stimulation techniques : Short-Pulse Duration (SPD) laser , and Subthreshold Endpoint Management (E pM) laser (Figure 1). This dual-modality laser strategy previously described for diabetic macular edema (DME) and dome-shaped maculopathy (DSM) (7, 8) began with titration of the SPD mode (10 ms duration; 100 µm spot size). During titration, 1–3 single test burns were applied near major retinal vessels inside the superior or inferior vascular arcades, adjusting power to produce a barely visible light-gray burn . After titration, focal SPD shots were manually selected on the touchscreen interface at 100% of the titrated power . A small number of barely visible laser spots (typically fewer than 10) were applied precisely to the leakage points identified on fluorescein angiography (FA) . FA-guided “hot spot” patterns were classified as subfoveal , juxtafoveal , or extrafoveal . For subfoveal hot spots, 6–8 barely visible burns were applied circumferentially, 500 µm from the foveal center, forming a 360° ring (Figure 1A, Step 1). Juxtafoveal and extrafoveal hot spots received 3– 5 barely visible shots each (Figure 1B–C, Step 1). Following SPD application (Step 1), SDL- E pM laser titration was performed (15 ms duration; 200 µm spot size) using 1–3 test burns at visible threshold level, again near the optic disc vessels within the superior or inferior arcades. After determining the visible threshold, the E pM power was reduced to 30% and applied in an invisible 16-shot square grid pattern with 0.25 mm spacing , covering the posterior pole in two overlapping passes . The treatment field extended up to 3,000 µm (≈ 2 disc diameters) from the FA-defined leakage point and the SRF area. Each session delivered approximately 800–1,200 invisible subthreshold shots , avoiding the central 300 µm foveal zone and all regions previously treated with SPD (Figure 1A–C, Step 2). Rescue Therapy Rescue or additional laser treatment using the combined Pascal® SPD plus SDL-E pM protocol was offered to Group II (initially treated with oral spironolactone) at the 3-month follow-up , and subsequently to either group whenever persistence or worsening of subretinal fluid (SRF) was observed compared with the previous visit. Retreatment criteria included either: Persistence of SRF on SD-OCT with less than 10% reduction in subretinal fluid height (SRFH) relative to baseline, or Recurrence of SRF after prior resolution. When these criteria were met, fluorescein angiography was repeated to identify new or residual leakage points, guiding subsequent laser application. All retreatment sessions followed the same two-step SPD plus E pM protocol and safety parameters described above. Statistical analysis The variables central macular thickness (CMT) , best-corrected visual acuity (BCVA) , subretinal fluid height (SRFH) , and choroidal thickness measurement (CTM) were analyzed using a linear mixed-effects model (LMM) . The model included TIME , GROUP , and their interaction ( TIME × GROUP ) as fixed effects, with patient ID specified as a random effect to account for intra-subject correlations due to repeated measurements. To adjust for multiple comparisons, p-values were corrected using the False Discovery Rate (FDR) method according to Benjamini–Hochberg . Model adequacy was assessed by examining residual diagnostics, including visual inspection of residual distributions and residuals versus fitted values plots , to verify the assumptions of normality and homoscedasticity . All data are presented as means with 95% confidence intervals (CIs) . Statistical significance was set at a two-tailed alpha level of 0.05 . Analyses were performed using R software (version 4.0.2; R Foundation for Statistical Computing , Vienna, Austria). Results Between July 2022 and January 2024, a total of 79 patients (79 eyes; mean age, 46.8 years; 79% male) were included in the study — 55 in Group I and 24 in Group II. Data for subretinal fluid height (SRFH), best-corrected visual acuity (BCVA), central macular thickness (CMT), and choroidal thickness measurement (CTM) were collected and analyzed over a 12-month follow-up period. Table 1 Demographic population data and additional baseline measurements. Demographic Characteristics GI (n = 55) GII (n = 24) Total (n = 79) P value Age (years) (mean) 47,29 45,75 46,82 P > 0,05 Laterality, right:left 29:26 12:12 41:38 P > 0,05 Gender, male:female 45:10 16:8 61:18 P < 0,05 SRFH (µm) (mean ± SE) 245,80 ± 11,50 179,50 ± 17,40 - P 0,05 CMT (µm) (mean ± SE) 429,00 ± 9,88 390,00 ± 15,00 - P 0,05 Best-Corrected Visual Acuity (BCVA, logMAR) At baseline, there were no significant differences in mean BCVA between the groups ( p > 0.05). During follow-up, Group I exhibited significantly better mean BCVA than Group II at first and third month-visits ( p < 0.05). At the 12-month visit a trend toward superior visual outcomes was maintained (0.121 ± 0.0178 vs. 0.178 ± 0.0263; p = 0.0771). In the intragroup analysis, Group I showed a significant improvement in BCVA at all visits relative to baseline, whereas Group II showed significant improvement only from the 3-month visit onward, which persisted through the final 12-month evaluation (Fig. 3 A). Subretinal Fluid Height (SRFH, µm) At baseline, Group I had a significantly greater mean SRFH than Group II (245.8 ± 11.5 µm vs. 179.5 ± 17.4 µm; * p < 0.05). In the intragroup analysis, both groups showed a significant reduction in mean SRFH at all follow-up visits compared with baseline ( p < 0.05). The intergroup analysis revealed that Group I demonstrated a significantly greater decrease in SRFH at first and third month visits of the study (* p < 0.05). At the 6-month and 12-month visits, no statistically significant intergroup differences were found in mean SRFH reduction (Fig. 3 B). However, SRF resolution was significantly more frequent in Group I than Group II (Fig. 4 ) at 1º, 3º and 12º month visits ( p < 0.05 ). Eyes with any detectable SRF at 12 months were categorized as having persistent SRF (e.g., Fig. 4 , orange asterisk case E, Group II). Central Macular Thickness (CMT, µm) At baseline, Group I presented a significantly higher mean CMT than Group II (429 ± 9.88 µm vs. 390 ± 15.00 µm; * p < 0.05). The intergroup analysis demonstrated a significantly greater decrease in CMT in Group I compared with Group II during the first 3 months (* p < 0.05). Both groups showed a significant intragroup reduction in mean CMT from baseline at all study visits ( p 0.05). Intergroup comparisons revealed no significant differences in mean CTM at any study visit. In the intragroup analysis, Group I showed a significant CTM reduction from baseline starting at month 3, which remained stable through month 12 ( p 0.05) (Fig. 3 D). Rescue Laser Treatment Rescue laser therapy for persistent or recurrent SRF was required at the 3-month visit in 15.7% of Group I patients and 58.3% of Group II patients. At the 6-month follow-up, retreatment was required in 6.4% of Group I and 8.3% of Group II patients. Panels A–D correspond to Group I (prompt laser therapy) and panels E–H to Group II (deferred laser therapy). Each column illustrates the temporal evolution of subretinal fluid height (SRFH) and anatomical recovery following treatment. In the center, a percentile analysis from SRF resolution at all study visits. The SRF resolution was significantly more frequent in Group I than Group II at 1º, 3º and 12º month visits study ( p < 0.05 ). In Group I (*yellow asterisk) is showed an example (case D) of efficient and faster absorption of subretinal hyperreflective material (SHRM) whereas Group II (*yellow asterisk) exhibited an example of delayed SHRM absorption. Also, Group I (*green asterisk) showed early SRF resolution example (case B) with rapid restoration of the ellipsoid/interdigitation (EZ/IZ) zone which was present in 34,5% of cases from 1 month follow-up. Besides, the Group II demonstrate only 8,3% of SRF resolution at 1 month visit study. At 3 and 6 visit study the percentile results from SRF resolution were 64,7% and 68% respectively by the Group I, whereas the Group II showed 33,3% and 50%, respectively. The Group II (*orange asterisk) revealed an example (case E) of persistent SRF forward all study visits which was present in 41% of eyes. In comparison, the Group I revealed only 15,2% of persistent SRF after all study visit. Delayed SRF (*blue asterisk) absorption (case F) example is showed on Group II too. Overall, the OCT sequence highlights the faster anatomical response and sustained resolution achieved with prompt SPD plus SDL-EpM laser treatment compared to deferred laser therapy following oral spironolactone. Adverse Events No cases of acute visual loss due to laser treatment involving the fovea were observed. Additionally, no patients reported new or persistent scotomas during the 12-month follow-up period. Discussion This study proposes a novel laser therapy strategy for the treatment of CSC, combining two macular sublethal laser techniques: Pascal ® SPD and SDL with EpM algorithm, both recently described by Cardillo et al . (2022) and Rodrigues et al . (2023) for DME (diabetic macular edema) and DSM (dome shaped maculopathy), respectively (7,8). Briefly (Fig. 1), for the CSC approach the strategy involves two steps: Step 1 consists of targeted SPD laser application to specific leakage sites identified on FA. In other words, the FA results guide to the selection of “hot spots” hyperfluorescent leaking areas, as targets for SPD application. This initial SPD step requires only a few shots per hot spot (less than ten barely visible marks using 10 ms duration with 100µm spot size) applied to juxtafoveal, extrafoveal and even subfoveal areas. This differs from the SPD approach used in DME and DSM by our group, which typically requires a higher number of shots (150-200) covering thickened macular areas guided by OCT (7,8). Step 2 (Fig. 1) involves the SDL-EpM software technique, which delivers invisible, high-density laser therapy to diffuse areas around 2 disc diameters from the hot spot, including the SRF and adjacent normal areas. In line with the concept of minimal threshold laser effect, Sun et al . (2019) compared the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in CSC (9). After a short study follow-up, at week 12, the changes in BCVA were not statiscally significant between the groups (9, 10). The proportion of patients with complete SRF absorption at week 12 was 63.63% in the SML group, and 81.82% in the TCL group. Similarly, our results showed 64,7% complete SRF absorption at the 12-week follow-up, increasing to 84,78% at the final study visit. Unlike our laser technique, their protocol set the spot duration at 0,05s, compared to our SPD settings of 0,01s with barely visible marks. Thus, the study by Sun et al. demonstrated a similar and safe SRF absorption rate using a minimal threshold laser effect, despite employing longer exposure laser parameters. The advantage of shorter laser exposure in the present study is related to a less extension of heat distribution and horizontal spread of laser effect and consequent larger spots with higher risk of larger areas of retina/RPE atrophy. Lim JW et al. (2011) conducted a prospective small case series and found that laser photocoagulation resulted in slower resolution of visual acuity improvement and SRF resorption compared to half-dose PDT at first month. However, from 3 months onward, anatomical and functional outcomes were similar between the two treatments (11). Their focal laser parameters were approximately 150µm spot and 150 ms exposure duration, producing a light-grey burn at the leaking point. The initial delayed results from laser may be related to the technique parameters used. In contrast, the faster SRF resolution with half-dose PDT is theoretically explained by its direct choriocapillaris targeting, differing from the RPE remodeling mechanism. In comparison, our study showed at one month a total SRF resolution rate of 34,5% in Group I (prompt laser) and 8,3% in Group II (deferred laser). Importantly, our SPD laser parameters (10ms exposure, 100µm spot) were gentler and less damaging, despite the lower early resolution rate, long-term anatomical and functional outcomes were favorable and sustained. Fossataro et al. (2024), published an interesting case series using focal laser to directly target intense FA leakage points (12). They identified, via OCT, a hyporeflective lucency sign co-localized with active inkblot RPE leaks on FA, suggesting RPE pump reversal.To address these lesions, they proposed a focal thermal laser strategy with parameters of 50 ms exposure, 100-µm spot size, and 100mW power. Our SPD technique, in contrast, used shorter exposure and lower power titration, potentially safer near the fovea. In our series, cases with subretinal hyperreflective material (SHRM, Figure 4, cases D and H) demonstrated faster SHRM absorption after early laser (case D) compared to delayed treatment (case H). The rationale for combining SPD and SDL-EpM is supported by Lavinsky et al. (2016) , who demonstrated that Pascal® EpM models the temperature-dependent rate of protein denaturation as an Arrhenius process (13). Accordingly, nondamaging retinal therapy (NRT) acts by heating the chorioretinal complex above the therapeutic threshold but below the damage threshold. Disease chronicity may modulate the response, as chronic cases are associated with RPE atrophy. Given that our cases were acute, the preserved RPE likely contributed to the optimal therapeutic effect observed. Despite Group I presenting significantly higher baseline subretinal fluid height (SRFH) and greater central macular thickness (CMT) than Group II—which theoretically provides a larger “margin for improvement”—the rate of complete SRF resolution was consistently higher in Group I throughout the study (Figure 4). This finding reinforces that the superior anatomical response in Group I cannot be attributed merely to the natural course of observation. Instead, it reflects a true therapeutic effect of early laser treatment, as Group II served as a control during the first three months and demonstrated markedly lower SRF resolution rates despite having milder baseline disease. Our results showed a markedly faster SRFH resolution rate in prompt laser-treated eyes up to four times higher at one month (33,54% in Group I vs 8,3% in Group II). At the three months, Group I maintained nearly double the resolution rate (64.8% vs. 33.3%). Moreover, persistent significant percentile results was verified by SRF resolution at last endpoint 12 months visit study. No differences related to mean SRFH were observed after the third month, likely due to rescue therapy performed in Group II. BCVA improvement occurred earlier in Group I and later in Group II after rescue therapy, with a final trend toward better vision in Group I. The rapid anatomical recovery may have contributed to better final BCVA, as shorter SRF duration limits photoreceptor and RPE damage. The rapid resolution of subretinal fluid (SRF) and earlier visual recovery observed in Group I may play a protective role against progression to chronic disease. Hata et al. (2013) demonstrated that outer nuclear layer (ONL) thinning begins early in CSC and progresses as long as SRF persists (14), reinforcing the importance of timely intervention. Similarly, Matet et al. (2020) reported that early treatment significantly reduced recurrence rates compared with observation (4% vs. 24%) (15). In other study, Matet et al. (2018) identified steroid exposure, systemic hypertension, increased choroidal thickness (CTM), mild fluorescein angiography (FA) leakage, and shift work as risk factors for CSC chronicity (16). Interestingly, our results partially diverge from these observations. Although Group I presented with higher absolute baseline CTM values—without reaching statistical significance—this group demonstrated superior anatomical and visual outcomes, along with a greater reduction in CTM over time. In contrast, Group II exhibited minimal changes in CTM throughout follow-up. These findings suggest that baseline CTM alone may not fully capture disease severity or treatment responsiveness, and that its interaction with RPE leak location and disease dynamics deserves further investigation. Supporting this hypothesis, Sahoo et al. (2025) showed that CSC cases with subfoveal leakage were associated with higher baseline Haller layer–to–total choroidal thickness ratios and earlier clinical presentation (17). In our cohort, Group II—despite presenting with lower baseline central macular thickness (CMT) and SRF height (SRFH)—demonstrated a delayed and modest CTM reduction, becoming evident only at the 6-month visit based on linear time–response analysis (Figure 3). This pattern suggests that prompt laser intervention may be particularly relevant in acute CSC with subfoveal leakage to optimize choroidal remodeling and functional recovery. However, the absence of a dedicated analysis comparing Haller layer–to–total choroidal thickness ratios and subfoveal leak distribution between Groups I and II represents a limitation that should be addressed in future studies. Yannuzzi et al. were the first to propose ICG-A–guided verteporfin PDT targeting choroidal hyperpermeability in CSC (18). However, adverse events such as transient macular dysfunction, choroidal non-perfusion, RPE atrophy, and CNV have been reported (19, 20). To mitigate these, studies explored reduced fluence, dosage, or activation time, with Erikitola et al. ( 21) concluding that half-dose PDT was the safest and most effective for chronic CSC. In 2018, the PACORES Group compared yellow micropulse (MP) laser to half-dose PDT in chronic CSC over 12 months (22). BCVA improved significantly in the MP group but not in the PDT group. MP laser advantages included lower cost and fewer systemic risks, though it required more retreatments. Compared to PACORES, our study achieved earlier BCVA improvement—already at one month in Group I and later in Group II post-laser—likely due to the acute presentation and healthier RPE, as well as the additive SPD stimulation at FA hot spots. The PLACE trial ( 23) found higher SRF resolution with PDT (67.2%) than with MP laser (28.8%), but no BCVA or quality-of-life differences. Our study achieved even higher SRF resolution (84.7%), emphasizing the effectiveness of the combined SPD plus SDL-EpM approach in acute cases. A recent RCT (24) comparing MP laser and half-dose PDT found both improved retinal sensitivity early, but BCVA gains appeared earlier with PDT. Similarly, the SPECTRA trial (2 5) confirmed the superiority of half-dose PDT over eplerenone for SRF resolution, though BCVA remained comparable. The VICI trial (2 6) also showed eplerenone was safe but not superior to placebo. The AAO 2024 report supports half-dose PDT for anatomical improvement in acute CSC but notes limited long-term visual benefit and potential adverse effects (27). Despite reduced-dose protocols, PDT may still have concern about choroidal ischemia, RPE tears, or systemic complications (28-30). Thus, our combined sublethal laser strategy may represent a safer, cost-effective, and efficient alternative for acute CSC, especially in resource-limited settings. Our recurrence analysis was limited by retrospective design and long intervals between visits. Although persistent SRF occurred in some cases, the lack of monthly OCT prevented detection of transient recurrences. Early treatment may have indirectly promoted choroidal thickness reduction by stimulating RPE activity, enhancing SRF reabsorption and improving outcomes. This supports CTM as a potential biomarker for positive response in acute CSC. This study has limitations, including its retrospective design and absence of functional macular tests such as microperimetry or contrast sensitivity. A prospective, randomized trial would better validate the effectiveness and reproducibility of the proposed combined laser therapy. Technical complexity and required physician expertise remain barriers to broader adoption. Traditionally, CSC management allows deferred intervention, but early treatment may be preferred in patients with occupational visual demands. In developing regions, cost-effective therapies are advantageous. Here, we present an unpublished study comparing early versus deferred combined Pascal® laser treatment (SPD plus SDL-EpM algorithm) for acute CSC, showing promising anatomical and functional outcomes with a safe profile. Declarations Contributors : MWR and JAC are the primary contributors to the research design. MWR is responsible for research execution and JPB for data acquisition. MWR and RJ are primary contributors to data analysis and interpretation. Manuscript preparation by MWR with revisions and interpretation was provided by JAC and RJ. Compliance with ethical standards Conflict of interest: The authors declare that they have no conflict of interest. Human Ethics and Consent to Participate declarations: not applicable. Statement of informed consent Informed consent: Not applicable Ethical approval: This study adheres to the Declaration of Helsinki, and received institutional review board approval from the Ethics and Research Committee of Ribeirão Preto Medical School (Ref. N.: 5.496.883). Clinical Trial number: Not applicable. Funding information: The project had no financial support. References Kido A, Miyake M, Tamura H, Hiragi S, Kimura T, Ohtera S, et al. Incidence of central serous chorioretinopathy (2011–2018): a nationwide population-based cohort study of Japan. Br J Ophthalmol. 2022;106(12):1748–53. 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Retina. 2013;33(2):296–301. Matet A, Jaworski T, Bousquet E, Canonica J, Gobeaux C, Daruich A, et al. Lipocalin 2 as a potential systemic biomarker for central serous chorioretinopathy. Sci Rep. 2020;10(1):20175. Matet A, Daruich A, Zola M, Behar-Cohen F. Risk Factors for Recurrences of Central Serous Chorioretinopathy. Retina. 2018;38(7):1403–14. Sahoo NK, Alagar R, Chang S, et al. Clinical and imaging characteristics of central serous chorioretinopathy with subfoveal leak. European Journal of Ophthalmology. 2025;0(0). Yannuzzi LA, Slakter JS, Gross NE, Spaide RF, Costa DL, Huang SJ, et al. Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study. 2003. Retina. 2012;32 Suppl 1:288–98. Cardillo Piccolino F, Eandi CM, Ventre L, Rigault de la Longrais RC, Grignolo FM. Photodynamic therapy for chronic central serous chorioretinopathy. Retina.2003;23(6):752–63. Chan WM, Lam DS, Lai TY, Tam BS, Liu DT, Chan CK. Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level. Br J Ophthalmol.2003;87(12):1453–8. Erikitola OC, Crosby-Nwaobi R, Lotery AJ, Sivaprasad S. Photodynamic therapy for central serous chorioretinopathy. Eye (Lond).2014;28(8):944–57. Roca JA, Wu L, Fromow-Guerra J, Rodríguez FJ, Berrocal MH, Rojas S, Lima LH,et al. Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group. Br J Ophthalmol. 2018;102(12):1696–1700. 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. doi: 10.1016/j.ophtha.2018.04.021. Brelen ME, Ho M, Li S, Ng DSC, Yip YWY, Lee WS, et al. Comparing Half-Dose Photodynamic Therapy with Subthreshold Micropulse Laser for the Treatment of Central Serous Chorioretinopathy. Ophthalmol Retina. 2024;8(5):490–8. van Rijssen TJ, van Dijk EHC, Tsonaka R, Feenstra HMA, Dijkman G, Peters PJH, et al. Half-Dose Photodynamic Therapy Versus Eplerenone in Chronic Central Serous Chorioretinopathy (SPECTRA): A Randomized Controlled Trial. Am J Ophthalmol. 2022;233:101–10. Lotery A, Sivaprasad S, O’Connell A, Harris RA, Culliford L, Cree A, et al. Eplerenone versus placebo for chronic central serous chorioretinopathy: the VICI RCT. Southampton (UK): NIHR Journals Library; 2021 Jan. PMID: 33471454. Kim LA, Maguire MG, Weng CY, Smith JR, Jain N, Flaxel CJ, et al. Therapies for Central Serous Chorioretinopathy: A Report by the American Academy of Ophthalmology. Ophthalmology. 2025;132(3):343–53. Lee PY, Kim KS, Lee WK. Severe choroidal ischemia following photodynamic therapy for pigment epithelial detachment and chronic central serous chorioretinopathy. Jpn J Ophthalmol. 2009;53(1):52–6. Copete S, Ruiz-Moreno JM, Cava C, Montero JA. Retinal thickness changes following photodynamic therapy in chronic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2012;250(6):803–8. Kim SW, Oh J, Oh IK, Huh K. Retinal pigment epithelial tear after half fluence PDT for serous pigment epithelial detachment in central serous chorioretinopathy. Ophthalmic Surg Lasers Imaging. 2009;40(3):300–3. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8554824","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":573855509,"identity":"6f8e0213-58a2-48e7-b31e-3f3518f60d38","order_by":0,"name":"Murilo Wendeborn Rodrigues","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYJCCAw+ABGN7AwMzTIQZt2KolgSQlp4DJGhhAGlhkEggUovujNyHBxIqDuczz3xj+LmgwoaBv707gblwD24tZjfSDQ4knDls2Tg7x1h6xpk0BokzZzcwz3iGT0saw4HEttsGjLNzDKR52w4zGEjkbmDmOUCMlplnjH+TqGUGjxmRtpx5BgzkM/8NGHvSyqx5zqTxgPxyeAY+LcfTmD98qEgzMGw/vPk2T4WNHH9778bHBXi0wIFhA4cBiOYBEcRoYGCQZ2B/QJTCUTAKRsEoGHkAANIBVKQymfVUAAAAAElFTkSuQmCC","orcid":"","institution":"University of São Paulo","correspondingAuthor":true,"prefix":"","firstName":"Murilo","middleName":"Wendeborn","lastName":"Rodrigues","suffix":""},{"id":573855510,"identity":"a99c88ea-dc4c-4f63-986a-b880becab023","order_by":1,"name":"João Pedro Braga","email":"","orcid":"","institution":"University of São Paulo","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"Pedro","lastName":"Braga","suffix":""},{"id":573855511,"identity":"0ebb90d7-757b-46db-a84f-019518fef606","order_by":2,"name":"José Augusto Cardillo","email":"","orcid":"","institution":"University of São Paulo","correspondingAuthor":false,"prefix":"","firstName":"José","middleName":"Augusto","lastName":"Cardillo","suffix":""},{"id":573855512,"identity":"53f761de-7cd4-4706-89ee-9e4f5cc7328f","order_by":3,"name":"Rodrigo Jorge","email":"","orcid":"","institution":"University of São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Rodrigo","middleName":"","lastName":"Jorge","suffix":""}],"badges":[],"createdAt":"2026-01-08 20:08:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8554824/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8554824/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101752367,"identity":"9742e2b1-a27f-48a8-9fb8-20453ab4805c","added_by":"auto","created_at":"2026-02-03 10:27:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":191520,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eIllustration of the combined laser treatment algorithm.\u003c/em\u003e(A–C) Examples of fluorescein angiography (FA) images showing\u003cstrong\u003e subfoveal, juxtafoveal\u003c/strong\u003e, and \u003cstrong\u003eextrafoveal\u003c/strong\u003e active inkblot retinal pigment epithelium (RPE) leakage (“hot-spot” leaks). The FA-identified hot spot is indicated by a \u003cstrong\u003eyellow star\u003c/strong\u003e on the ETDRS grid. Sequential \u003cstrong\u003eSteps 1 and 2\u003c/strong\u003e represent the two laser modalities: Pascal® \u003cstrong\u003eSPD\u003c/strong\u003e and SDL-\u003cstrong\u003eEpM\u003c/strong\u003e, respectively. \u003cstrong\u003eStep 1 (green):\u003c/strong\u003e focal SPD laser application targeted precisely to the FA-guided hot spot (yellow star). \u003cstrong\u003eStep 2 (purple):\u003c/strong\u003e Subthreshold diffuse -EpM laser treatment extending approximately \u003cstrong\u003edouble disc diameter\u003c/strong\u003e from the hot spot, encompassing the leakage area, surrounding subretinal fluid, and adjacent normal retinal tissue.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8554824/v1/19c35d602e09e311675be191.png"},{"id":101498538,"identity":"748db413-3b3f-44bf-baa8-55e7ab2fd6ca","added_by":"auto","created_at":"2026-01-30 13:06:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":370219,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eRepresentative cases of subfoveal (C), juxtafoveal (R), and extrafoveal (J)leakage patterns.\u003c/em\u003e Baseline (yellow dashed line) color fundus photography (A,H,P), autofluorescence (B,I,Q), near-infrared reflectance (D,L,S), fluorescein angiography (C,J,R), and spectral-domain optical coherence tomography images (E,M,T) and at the 12-month follow-up (green dashed line) near-infrared reflectance (F,N,U) and spectral-domain optical coherence tomography (G,O,V). After 12 months, spectral-domain optical coherence tomography demonstrates complete SRF resolution and restoration of normal retinal architecture, confirming stable anatomical outcomes across the different leakage subtypes.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8554824/v1/62ec7073d0955701e72f8a5e.png"},{"id":101498535,"identity":"1c7179b9-ceda-4660-946e-a3035bd0beda","added_by":"auto","created_at":"2026-01-30 13:06:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":140608,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eMean changes and 95% confidence intervals for best-corrected visual acuity (BCVA), subretinal fluid height (SRFH), central macular thickness (CMT), and choroidal thickness (CTM) throughout 12 months of follow-up.\u003c/em\u003e Graphs compare Group I (blue; prompt laser therapy) and Group II (red; deferred laser therapy) at each study visit. (A) BCVA:A significant intergroup difference was observed through 3-month follow-up (*p\u0026lt;0.05), with Group I showing faster visual improvement. At 12 months, Group I maintained a trend toward greater BCVA gain compared with Group II (*p\u0026lt;0.1). (B) SRFH:A significant intergroup difference was observed through 3-month follow-up (*p \u0026lt; 0.05), with Group I showing faster subretinal fluid height decrease. (C) CMT: A significant intergroup difference was observed through 3-month follow-up (*p\u0026lt;0.05), with a greater reduction in Group I during the initial 3 months (p\u0026lt;0.05). (D) CTM: No significant intergroup differences were found at any visit (p \u0026gt; 0.05).\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8554824/v1/87a4b47e6b0c47b7a69d77ac.png"},{"id":101751792,"identity":"0ba840fa-735a-4e10-9f8b-c660505acea5","added_by":"auto","created_at":"2026-02-03 10:23:31","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":340866,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eRepresentative spectral-domain optical coherence tomography (SD-OCT) images from four cases in each treatment group throughout all study visits (baseline, 1, 3, 6, and 12 months).\u003c/em\u003e\u003cbr\u003e\nPanels \u003cstrong\u003eA–D\u003c/strong\u003e correspond to \u003cstrong\u003eGroup I (prompt laser therapy)\u003c/strong\u003e and panels \u003cstrong\u003eE–H\u003c/strong\u003e to \u003cstrong\u003eGroup II (deferred laser therapy)\u003c/strong\u003e. Each column illustrates the temporal evolution of \u003cstrong\u003esubretinal fluid height (SRFH)\u003c/strong\u003e and anatomical recovery following treatment. In the center, a percentile analysis from SRF resolution at all study visits. The SRF resolution was significantly more frequent in Group I than Group II at 1º, 3º and 12º month visits study (\u003cem\u003ep \u0026lt; 0.05\u003c/em\u003e). In Group I (*yellow asterisk) is showed an example (case D) of efficient and faster absorption of subretinal hyperreflective material (SHRM) whereas Group II (*yellow asterisk) exhibited an example of delayed SHRM absorption. Also, Group I (*green asterisk) showed early SRF resolution example (case B) with rapid restoration of the ellipsoid/interdigitation (EZ/IZ) zone which was present in 34,5% of cases from 1 month follow-up. Besides, the Group II demonstrate only 8,3% of SRF resolution at 1 month visit study. At 3 and 6 visit study the percentile results from SRF resolution were 64,7% and 68% respectively by the Group I, whereas the Group II showed 33,3% and 50%, respectively. The Group II (*orange asterisk) revealed an example (case E) of persistent SRF forward all study visits which was present in 41% of eyes. In comparison, the Group I revealed only 15,2% of persistent SRF after all study visit. Delayed SRF (*blue asterisk) absorption (case F) example is showed on Group II too. Overall, the OCT sequence highlights the \u003cstrong\u003efaster anatomical response and sustained resolution\u003c/strong\u003e achieved with \u003cstrong\u003eprompt SPD \u003c/strong\u003e\u003cem\u003e\u003cstrong\u003eplus \u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003eSDL-EpM laser treatment\u003c/strong\u003e compared to deferred laser therapy following oral spironolactone.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8554824/v1/923093c46883f5ba21b64f6c.png"},{"id":101755308,"identity":"6272a26e-799e-4e77-9113-c39351a50fcc","added_by":"auto","created_at":"2026-02-03 10:50:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2982896,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8554824/v1/7e0a5567-c491-496e-abeb-82d60026e132.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Early versus deferred treatment with Pascal short-pulse duration plus subthreshold endpoint management laser techniques for central serous chorioretinopathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCentral serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid (SRF) leakage and it is often associated with reduced vision-related quality of life. After neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO), CSC is the fourth most common retinopathy that causes macular fluid leakage (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn CSC, the leakage through defects in the outer blood-retina barrier of the RPE appears to occur secondary to choroidal abnormalities and dysfunction. Symptoms typically include impaired and/or distorted central vision, often accompanied by altered color perception, and reduced vision-related quality of life (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe treatment of CSC is currently the subject of controversy. Recent evidence suggests benefits from early intervention using either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitizing dye verteporfin in selected cases, which is considered the preferred treatment for chonic CSC. Results from three large randomized controlled trials (RCTs) namely the PLACE, VICI and SPECTRA trials demonstrated: (i) the superiority of half-dose PDT over high-density subthreshold micropulse laser treatment; (ii) the non-superiority of the oral mineralocorticoid receptor antagonist eplerenone treatment compared to placebo, and (iii) the superiority of half-dose PDT over eplerenon (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn acute CSC, treatment has traditionally been deferred for up to 3\u0026ndash;4 months after diagnosis, based on earlier studies. However, with advances in imaging devices and refined laser laser tecniques, experts are increasingly encouraged to initiate therapy earlier to achieve safer, faster visual recovery, reduce the likelihood of recurrence, and potentially improve long-term visual outcomes. Since acute CSC often working-age patients, who may experience considerable anxiety about vision loss, early treatment can be a valuable strategy\u0026mdash;particularly in low-resource settings where access to costly therapies such as PDT is limited.\u003c/p\u003e \u003cp\u003eThe dual Pascal\u003csup\u003e\u0026reg;\u003c/sup\u003e focal SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM modalities enables effective treatment using only sublethal thermal elevations, thereby avoiding the excessive heat that can cause white burns, tissue necrosis, and other adverse effects (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Our group proposed a combined Pascal\u0026reg; laser approach - SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM - first described in the literature for CSC treatment with the aim of providing a flexible repair strategy and promoting rapid visual recovery in CSC management.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study adheres to the Declaration of Helsinki, and received institutional review board approval from the Ethics and Research Committee of Ribeir\u0026atilde;o Preto Medical School (Ref. N.: 5.496.883).\u0026nbsp;All data were collected retrospectively.\u0026nbsp;We reviewed\u0026nbsp;the records of all patients in a public vitreoretinal subspecialty practice who received prompt or deferred focal Pascal\u003csup\u003e\u0026reg;\u003c/sup\u003e SPD\u0026nbsp;\u003cem\u003eplus\u003c/em\u003e SDL-EpM therapy\u0026nbsp;for\u0026nbsp;macular subretinal fluid (SRF)\u0026nbsp;in CSC. The study\u0026nbsp;included\u0026nbsp;79\u0026nbsp;eyes\u0026nbsp;treated between July\u0026nbsp;2022\u0026nbsp;to January 2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient eligibility and exclusion criteria\u003c/strong\u003e\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studyinclusion criteria were as follows: 1) age \u0026ge; 18 years; 2) BCVA between 0.3 logMAR (Snellen equivalent: 20/32) and 1.3 logMAR (Snellen equivalent: 20/400); 3) macular center-involving\u0026nbsp;SRF\u0026nbsp;with\u0026nbsp;a minimum height of 100\u0026micro;m on\u0026nbsp;SD-OCT.\u0026nbsp;As for the exclusion criteria\u0026nbsp;it was comprised: \u0026nbsp;1) Evidence of vitreomacular traction on SD-OCT; 2)\u0026nbsp;no history of vitreoretinal surgery; 3) systemic corticosteroid therapy; 4)\u0026nbsp;any other ocular condition that, in the opinion of the investigator,\u0026nbsp;could\u0026nbsp;affect SRF or alter\u0026nbsp;visual acuity (VA)\u0026nbsp;during the course of the study.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003ePatient Demographics and Evaluations\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eA total of \u003cstrong\u003e79 eyes from 79 patients\u003c/strong\u003e (mean age, \u003cstrong\u003e46.8 years\u003c/strong\u003e) were retrospectively analyzed (Table 1). No significant differences were observed between Group I (n = 55) and Group II (n = 24) regarding mean age or eye laterality (right vs. left). The overall \u003cstrong\u003emale-to-female ratio\u003c/strong\u003e was significantly higher (p \u0026lt; 0.05) in both groups (Group I: 45 males and 10 females; Group II: 16 males and 8 females).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGroup I\u003c/strong\u003e received \u003cstrong\u003eprompt laser therapy\u003c/strong\u003e, whereas \u003cstrong\u003eGroup II\u003c/strong\u003e initially underwent \u003cstrong\u003eoral spironolactone therapy\u003c/strong\u003e (50 mg twice daily for 3 months) prior to laser treatment. All patients underwent a comprehensive ophthalmic evaluation before laser intervention, including \u003cstrong\u003ebest-corrected visual acuity (BCVA)\u003c/strong\u003e assessed with the \u003cstrong\u003eEarly Treatment Diabetic Retinopathy Study (ETDRS)\u003c/strong\u003e chart, \u003cstrong\u003eslit-lamp biomicroscopy\u003c/strong\u003e, \u003cstrong\u003eindirect ophthalmoscopy\u003c/strong\u003e, \u003cstrong\u003enear-infrared reflectance imaging\u003c/strong\u003e, \u003cstrong\u003efluorescein angiography (FA)\u003c/strong\u003e, and \u003cstrong\u003espectral-domain optical coherence tomography (SD-OCT; Spectralis, Heidelberg Engineering, Germany)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eFollow-up examinations were performed at \u003cstrong\u003e1, 3, 6, and 12 months\u003c/strong\u003e, including ETDRS BCVA and SD-OCT imaging for quantification of \u003cstrong\u003esubretinal fluid height (SRFH)\u003c/strong\u003e, \u003cstrong\u003echoroidal thickness\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003emeasurement (CTM)\u003c/strong\u003e, and \u003cstrong\u003ecentral macular thickness (CMT)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eFor \u003cstrong\u003eSRFH\u003c/strong\u003e and \u003cstrong\u003eCTM\u003c/strong\u003e, manual caliper measurements were performed using the SD-OCT software ruler tool. SRFH was defined as the \u003cstrong\u003evertical distance between the retinal pigment epithelium (RPE) and the outer photoreceptor layer\u003c/strong\u003e, while CTM corresponded to the \u003cstrong\u003evertical distance from the RPE to the outer boundary of the choroidal Haller layer\u003c/strong\u003e. \u003cstrong\u003eCMT\u003c/strong\u003e values were obtained automatically using the device\u0026rsquo;s built-in retinal thickness mapping software.\u003c/p\u003e\n\u003cp\u003eIf \u003cstrong\u003eretreatment criteria\u003c/strong\u003e were met defined as persistent or recurrent subretinal fluid after a minimum 3-month interval,\u0026nbsp;\u003cstrong\u003efluorescein angiography\u003c/strong\u003e was repeated to guide further laser application.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eTreatment Regimen\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eAll treatments were performed using the \u003cstrong\u003ePascal\u0026reg; photocoagulation system\u003c/strong\u003e (Topcon Medical Laser Systems), which delivers a \u003cstrong\u003e532-nm frequency-doubled solid-state green laser\u003c/strong\u003e. An experienced vitreoretinal surgeon administered all procedures within \u003cstrong\u003etwo weeks\u003c/strong\u003e of OCT-confirmed subretinal fluid (SRF) diagnosis. The \u003cstrong\u003ecombined laser protocol\u003c/strong\u003e consisted of two consecutive \u003cstrong\u003ephotothermal retinal pigment epithelium (RPE) stimulation techniques\u003c/strong\u003e:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eShort-Pulse Duration (SPD) laser\u003c/strong\u003e, and\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSubthreshold Endpoint Management (E\u003c/strong\u003e\u003cstrong\u003epM) laser\u003c/strong\u003e (Figure 1).\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThis dual-modality laser strategy previously described for diabetic macular edema (DME) and dome-shaped maculopathy (DSM) (7, 8) began with \u003cstrong\u003etitration of the SPD mode\u003c/strong\u003e (10 ms duration; 100 \u0026micro;m spot size). During titration, 1\u0026ndash;3 single test burns were applied near major retinal vessels inside the superior or inferior vascular arcades, adjusting power to produce a \u003cstrong\u003ebarely visible light-gray burn\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eAfter titration, \u003cstrong\u003efocal SPD shots\u003c/strong\u003e were manually selected on the touchscreen interface at \u003cstrong\u003e100% of the titrated power\u003c/strong\u003e. A small number of barely visible laser spots (typically fewer than 10) were applied precisely to the \u003cstrong\u003eleakage points\u003c/strong\u003e identified on\u0026nbsp;\u003cstrong\u003efluorescein angiography (FA)\u003c/strong\u003e.\u003cbr\u003eFA-guided \u0026ldquo;hot spot\u0026rdquo; patterns were classified as \u003cstrong\u003esubfoveal\u003c/strong\u003e, \u003cstrong\u003ejuxtafoveal\u003c/strong\u003e, or \u003cstrong\u003eextrafoveal\u003c/strong\u003e. For subfoveal hot spots, \u003cstrong\u003e6\u0026ndash;8 barely visible burns\u003c/strong\u003e were applied circumferentially, 500 \u0026micro;m from the foveal center, forming a \u003cstrong\u003e360\u0026deg; ring\u003c/strong\u003e (Figure 1A, Step 1). Juxtafoveal and extrafoveal hot spots received \u003cstrong\u003e3\u0026ndash;\u003c/strong\u003e\u003cstrong\u003e5 barely visible shots\u003c/strong\u003e each (Figure 1B\u0026ndash;C, Step 1).\u003c/p\u003e\n\u003cp\u003eFollowing SPD application (Step 1), SDL-\u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003epM laser titration\u003c/strong\u003e was performed (15 ms duration; 200 \u0026micro;m spot size) using 1\u0026ndash;3 test burns at visible threshold level, again near the optic disc vessels within the superior or inferior arcades. After determining the visible threshold, the \u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003epM power was reduced to 30%\u003c/strong\u003e and applied in an \u003cstrong\u003einvisible 16-shot square grid pattern\u003c/strong\u003e with \u003cstrong\u003e0.25 mm spacing\u003c/strong\u003e, covering the posterior pole in \u003cstrong\u003etwo overlapping passes\u003c/strong\u003e. The treatment field extended up to \u003cstrong\u003e3,000 \u0026micro;m (\u0026asymp; 2 disc diameters)\u003c/strong\u003e from the FA-defined leakage point and the SRF area. Each session delivered approximately \u003cstrong\u003e800\u0026ndash;1,200 invisible subthreshold shots\u003c/strong\u003e, avoiding the central \u003cstrong\u003e300 \u0026micro;m foveal zone\u003c/strong\u003e and all regions previously treated with SPD (Figure 1A\u0026ndash;C, Step 2).\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eRescue Therapy\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eRescue or additional laser treatment using the \u003cstrong\u003ecombined Pascal\u0026reg; SPD\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eplus\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;SDL-E\u003c/strong\u003e\u003cstrong\u003epM protocol\u003c/strong\u003e was offered to \u003cstrong\u003eGroup II\u003c/strong\u003e (initially treated with oral spironolactone) at the \u003cstrong\u003e3-month follow-up\u003c/strong\u003e, and subsequently to either group whenever persistence or worsening of subretinal fluid (SRF) was observed compared with the previous visit.\u003c/p\u003e\n\u003cp\u003eRetreatment criteria included either:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003ePersistence of SRF\u003c/strong\u003e on SD-OCT with less than \u003cstrong\u003e10% reduction\u003c/strong\u003e in subretinal fluid height (SRFH) relative to baseline, or\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRecurrence of SRF\u003c/strong\u003e after prior resolution.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eWhen these criteria were met, \u003cstrong\u003efluorescein angiography\u003c/strong\u003e was repeated to identify new or residual leakage points, guiding subsequent laser application. All retreatment sessions followed the same \u003cstrong\u003etwo-step SPD\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eplus\u003c/em\u003e E\u003c/strong\u003e\u003cstrong\u003epM protocol\u003c/strong\u003e and safety parameters described above.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe variables \u003cstrong\u003ecentral macular thickness (CMT)\u003c/strong\u003e\u003cstrong\u003e, \u003cstrong\u003ebest-corrected visual acuity (BCVA)\u003c/strong\u003e,\u003c/strong\u003e \u003cstrong\u003esubretinal fluid height (SRFH)\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e and \u003cstrong\u003echoroidal thickness\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;measurement (CTM)\u003c/strong\u003e were analyzed using a \u003cstrong\u003elinear mixed-effects model (LMM)\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e The model included \u003cstrong\u003eTIME\u003c/strong\u003e\u003cstrong\u003e, \u003cstrong\u003eGROUP\u003c/strong\u003e\u003c/strong\u003e, and their interaction (\u003cstrong\u003eTIME \u0026times; GROUP\u003c/strong\u003e) as fixed effects, with \u003cstrong\u003epatient ID\u003c/strong\u003e specified as a random effect to account for intra-subject correlations due to repeated measurements. To adjust for multiple comparisons, \u003cstrong\u003ep-values were corrected using the False Discovery Rate (FDR) method\u003c/strong\u003e according to \u003cstrong\u003eBenjamini\u0026ndash;Hochberg\u003c/strong\u003e. Model adequacy was assessed by examining residual diagnostics, including \u003cstrong\u003evisual inspection of residual distributions\u003c/strong\u003e and \u003cstrong\u003eresiduals versus fitted values plots\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e to verify the assumptions of \u003cstrong\u003enormality\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003ehomoscedasticity\u003c/strong\u003e. All data are presented as \u003cstrong\u003emeans with 95% confidence intervals (CIs)\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e Statistical significance was set at a \u003cstrong\u003etwo-tailed alpha level of 0.05\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e Analyses were performed using \u003cstrong\u003eR software\u003c/strong\u003e (version 4.0.2; \u003cem\u003eR Foundation for Statistical Computing\u003c/em\u003e, Vienna, Austria).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween July 2022 and January 2024, a total of 79 patients (79 eyes; mean age, 46.8 years; 79% male) were included in the study \u0026mdash; 55 in Group I and 24 in Group II. Data for subretinal fluid height (SRFH), best-corrected visual acuity (BCVA), central macular thickness (CMT), and choroidal thickness measurement (CTM) were collected and analyzed over a 12-month follow-up period.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic population data and additional baseline measurements.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographic Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGI (n\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGII (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years) (mean)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47,29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45,75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46,82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;\u0026gt;\u0026thinsp;0,05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaterality, right:left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29:26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12:12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41:38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;\u0026gt;\u0026thinsp;0,05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, male:female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45:10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16:8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61:18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0,05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSRFH (\u0026micro;m) (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e245,80\u0026thinsp;\u0026plusmn;\u0026thinsp;11,50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e179,50\u0026thinsp;\u0026plusmn;\u0026thinsp;17,40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0,05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA (logMAR) (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,5470\u0026thinsp;\u0026plusmn;\u0026thinsp;0,064\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,3830\u0026thinsp;\u0026plusmn;\u0026thinsp;0,097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u0026thinsp;\u0026gt;\u0026thinsp;0,05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCMT (\u0026micro;m) (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e429,00\u0026thinsp;\u0026plusmn;\u0026thinsp;9,88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e390,00\u0026thinsp;\u0026plusmn;\u0026thinsp;15,00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eP\u0026thinsp;\u0026lt;\u0026thinsp;0,05\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCTM (\u0026micro;m) (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SE)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e394,00\u0026thinsp;\u0026plusmn;\u0026thinsp;15,00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e352,00\u0026thinsp;\u0026plusmn;\u0026thinsp;23,40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u0026thinsp;\u0026gt;\u0026thinsp;0,05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBest-Corrected Visual Acuity (BCVA, logMAR)\u003c/h2\u003e \u003cp\u003eAt baseline, there were no significant differences in mean BCVA between the groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). During follow-up, Group I exhibited significantly better mean BCVA than Group II at first and third month-visits (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). At the 12-month visit a trend toward superior visual outcomes was maintained (0.121\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0178 vs. 0.178\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0263; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0771). In the intragroup analysis, Group I showed a significant improvement in BCVA at all visits relative to baseline, whereas Group II showed significant improvement only from the 3-month visit onward, which persisted through the final 12-month evaluation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSubretinal Fluid Height (SRFH, µm)\u003c/h3\u003e\n\u003cp\u003eAt baseline, Group I had a significantly greater mean SRFH than Group II (245.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.5 \u0026micro;m vs. 179.5\u0026thinsp;\u0026plusmn;\u0026thinsp;17.4 \u0026micro;m; *\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the intragroup analysis, both groups showed a significant reduction in mean SRFH at all follow-up visits compared with baseline (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The intergroup analysis revealed that Group I demonstrated a significantly greater decrease in SRFH at first and third month visits of the study (*\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). At the 6-month and 12-month visits, no statistically significant intergroup differences were found in mean SRFH reduction (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). However, SRF resolution was significantly more frequent in Group I than Group II (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) at 1\u0026ordm;, 3\u0026ordm; and 12\u0026ordm; month visits (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e). Eyes with any detectable SRF at 12 months were categorized as having persistent SRF (e.g., Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, orange asterisk case E, Group II).\u003c/p\u003e\n\u003ch3\u003eCentral Macular Thickness (CMT, µm)\u003c/h3\u003e\n\u003cp\u003eAt baseline, Group I presented a significantly higher mean CMT than Group II (429\u0026thinsp;\u0026plusmn;\u0026thinsp;9.88 \u0026micro;m vs. 390\u0026thinsp;\u0026plusmn;\u0026thinsp;15.00 \u0026micro;m; *\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The intergroup analysis demonstrated a significantly greater decrease in CMT in Group I compared with Group II during the first 3 months (*\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eBoth groups showed a significant intragroup reduction in mean CMT from baseline at all study visits (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eChoroidal Thickness Measurement (CTM, \u0026micro;m)\u003c/h2\u003e \u003cp\u003eAt baseline, no significant difference in mean CTM was observed between Group I and Group II (394\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5 \u0026micro;m vs. 352\u0026thinsp;\u0026plusmn;\u0026thinsp;23.4 \u0026micro;m; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Intergroup comparisons revealed no significant differences in mean CTM at any study visit. In the intragroup analysis, Group I showed a significant CTM reduction from baseline starting at month 3, which remained stable through month 12 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, Group II exhibited no significant CTM change at any time point (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eRescue Laser Treatment\u003c/h2\u003e \u003cp\u003eRescue laser therapy for persistent or recurrent SRF was required at the 3-month visit in 15.7% of Group I patients and 58.3% of Group II patients. At the 6-month follow-up, retreatment was required in 6.4% of Group I and 8.3% of Group II patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePanels A\u0026ndash;D correspond to Group I (prompt laser therapy) and panels E\u0026ndash;H to Group II (deferred laser therapy). Each column illustrates the temporal evolution of subretinal fluid height (SRFH) and anatomical recovery following treatment. In the center, a percentile analysis from SRF resolution at all study visits. The SRF resolution was significantly more frequent in Group I than Group II at 1\u0026ordm;, 3\u0026ordm; and 12\u0026ordm; month visits study (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e). In Group I (*yellow asterisk) is showed an example (case D) of efficient and faster absorption of subretinal hyperreflective material (SHRM) whereas Group II (*yellow asterisk) exhibited an example of delayed SHRM absorption. Also, Group I (*green asterisk) showed early SRF resolution example (case B) with rapid restoration of the ellipsoid/interdigitation (EZ/IZ) zone which was present in 34,5% of cases from 1 month follow-up. Besides, the Group II demonstrate only 8,3% of SRF resolution at 1 month visit study. At 3 and 6 visit study the percentile results from SRF resolution were 64,7% and 68% respectively by the Group I, whereas the Group II showed 33,3% and 50%, respectively. The Group II (*orange asterisk) revealed an example (case E) of persistent SRF forward all study visits which was present in 41% of eyes. In comparison, the Group I revealed only 15,2% of persistent SRF after all study visit. Delayed SRF (*blue asterisk) absorption (case F) example is showed on Group II too. Overall, the OCT sequence highlights the faster anatomical response and sustained resolution achieved with prompt SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM laser treatment compared to deferred laser therapy following oral spironolactone.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eAdverse Events\u003c/h2\u003e \u003cp\u003eNo cases of acute visual loss due to laser treatment involving the fovea were observed. Additionally, no patients reported new or persistent scotomas during the 12-month follow-up period.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study proposes a novel laser therapy strategy for the treatment of CSC, combining two macular sublethal laser techniques: Pascal\u003csup\u003e®\u003c/sup\u003e SPD and SDL with EpM algorithm, both recently\u0026nbsp;described by Cardillo \u003cem\u003eet al\u003c/em\u003e. (2022) and Rodrigues \u003cem\u003eet al\u003c/em\u003e. (2023) for DME\u0026nbsp;(diabetic macular edema)\u0026nbsp;and DSM\u0026nbsp;(dome shaped maculopathy), respectively (7,8). Briefly\u0026nbsp;(Fig. 1), for the CSC approach the\u0026nbsp;strategy involves\u0026nbsp;two steps:\u0026nbsp;Step 1\u0026nbsp;consists of targeted\u0026nbsp;SPD laser application to\u0026nbsp;specific leakage sites\u0026nbsp;identified on FA. In other words, the FA results guide to the\u0026nbsp;selection of\u0026nbsp;“hot spots” hyperfluorescent leaking areas, as targets for SPD\u0026nbsp;application. This initial SPD step requires only a few shots per hot spot (less than ten barely visible marks using 10 ms duration with 100µm spot size) applied to juxtafoveal, extrafoveal and even subfoveal areas. This differs from the SPD approach used in DME and DSM by our group, which typically requires a higher number of shots (150-200) covering thickened macular areas guided by OCT (7,8). Step 2 (Fig. 1) involves the SDL-EpM software technique, which delivers invisible, high-density laser therapy to diffuse areas around 2 disc diameters from the hot spot, including the SRF and adjacent normal areas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with the concept of minimal threshold laser effect, Sun \u003cem\u003eet al\u003c/em\u003e. (2019) compared the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in CSC (9). After a short study follow-up, at week 12, the changes in BCVA were not statiscally significant between the groups (9, 10). The proportion of patients with complete SRF absorption at week 12 was 63.63% in the SML group, and 81.82% in the TCL group. Similarly, our results showed 64,7% complete SRF absorption at the 12-week follow-up, increasing to 84,78% at the final study visit. Unlike our laser technique, their protocol set the spot duration at 0,05s, compared to our SPD settings of 0,01s with barely visible marks. Thus, the study by Sun \u003cem\u003eet al.\u003c/em\u003e demonstrated a similar and safe SRF absorption rate using a minimal threshold laser effect, despite employing longer exposure laser parameters. The advantage of shorter laser exposure in the present study is related to a less extension of heat distribution and horizontal spread of laser effect and consequent larger spots with higher risk of larger areas of retina/RPE atrophy.\u003c/p\u003e\n\u003cp\u003eLim JW \u003cem\u003eet al.\u003c/em\u003e (2011) conducted a prospective small case series and found that laser photocoagulation resulted in slower resolution of visual acuity improvement and SRF resorption compared to half-dose PDT at first month. However, from 3 months onward, anatomical and functional outcomes were similar between the two treatments (11). Their focal laser parameters were approximately 150µm spot and 150 ms exposure duration, producing a light-grey burn at the leaking point. The initial delayed results from laser may be related to the technique parameters used. In contrast, the faster SRF resolution with half-dose PDT is theoretically explained by its direct choriocapillaris targeting, differing from the RPE remodeling mechanism.\u0026nbsp;In comparison, our study showed at one month a total SRF resolution rate of \u0026nbsp;34,5% in Group I (prompt laser) and 8,3% in Group II (deferred laser). Importantly, our SPD laser parameters (10ms exposure, 100µm spot) were gentler and less damaging, despite the lower early resolution rate, long-term anatomical and functional outcomes were favorable and sustained.\u003c/p\u003e\n\u003cp\u003eFossataro \u003cem\u003eet al.\u003c/em\u003e (2024), published an interesting case series using focal laser to directly target intense FA leakage points (12). They identified, via OCT, a\u0026nbsp;hyporeflective lucency sign\u0026nbsp;co-localized with active inkblot RPE leaks\u0026nbsp;on FA,\u0026nbsp;suggesting\u0026nbsp;RPE pump\u0026nbsp;reversal.To address these lesions,\u0026nbsp;they\u0026nbsp;proposed a focal thermal laser strategy with parameters of\u0026nbsp;50\u0026nbsp;ms\u0026nbsp;exposure,\u0026nbsp;100-µm spot size,\u0026nbsp;and 100mW power.\u0026nbsp;Our SPD technique, in contrast, used shorter\u0026nbsp;exposure\u0026nbsp;and\u0026nbsp;lower\u0026nbsp;power\u0026nbsp;titration,\u0026nbsp;potentially safer near the fovea. In our series, cases with \u003cstrong\u003esubretinal hyperreflective material\u003c/strong\u003e (SHRM,\u0026nbsp;Figure 4, cases D and H) demonstrated faster SHRM absorption after early laser (case D) compared to delayed treatment (case H).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe rationale for combining SPD and SDL-EpM is supported by \u003cstrong\u003eLavinsky et al. (2016)\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e who demonstrated that Pascal® EpM models the temperature-dependent rate of protein denaturation as an Arrhenius process (13). Accordingly, nondamaging retinal therapy (NRT) acts by heating the chorioretinal complex above the therapeutic threshold but below the damage threshold. Disease chronicity may modulate the response, as chronic cases are associated with RPE atrophy. Given that our cases were acute, the preserved RPE likely contributed to the optimal therapeutic effect observed.\u003c/p\u003e\n\u003cp\u003eDespite Group I presenting\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003esignificantly higher baseline subretinal fluid height (SRFH)\u003c/strong\u003e\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;\u003cstrong\u003egreater central macular thickness (CMT)\u003c/strong\u003e\u003c/strong\u003e than Group II—which theoretically provides a larger “margin for improvement”—the \u003cstrong\u003erate of complete SRF resolution was consistently higher in Group I\u003c/strong\u003e throughout the study (Figure 4). This finding reinforces that the superior anatomical response in Group I cannot be attributed merely to the natural course of observation. Instead, it reflects a \u003cstrong\u003etrue therapeutic effect\u003c/strong\u003e of early laser treatment, as Group II served as a control during the first three months and demonstrated markedly lower SRF resolution rates despite having milder baseline disease. Our results showed a markedly faster SRFH resolution rate in prompt laser-treated eyes up to four times higher at one month\u0026nbsp;(33,54% in Group I vs 8,3% in Group II). At the three months, Group I\u0026nbsp;maintained nearly double the resolution rate (64.8% vs. 33.3%).\u0026nbsp;Moreover, persistent significant percentile results was verified by SRF resolution at last endpoint 12 months visit study.\u0026nbsp;No differences\u0026nbsp;related to mean SRFH\u0026nbsp;were observed after the third month, likely due to rescue therapy performed in Group II. BCVA improvement occurred earlier in Group I and later in Group II after rescue therapy, with a final trend toward better vision in Group I. The rapid anatomical recovery may have contributed to better final BCVA, as shorter SRF duration limits photoreceptor and RPE damage.\u003c/p\u003e\n\u003cp\u003eThe rapid resolution of subretinal fluid (SRF) and earlier visual recovery observed in Group I may play a protective role against progression to chronic disease. Hata et al. (2013) demonstrated that outer nuclear layer (ONL) thinning begins early in CSC and progresses as long as SRF persists (14), reinforcing the importance of timely intervention. Similarly, Matet et al. (2020) reported that early treatment significantly reduced recurrence rates compared with observation (4% vs. 24%) (15). In other study, Matet et al. (2018) identified steroid exposure, systemic hypertension, increased choroidal thickness (CTM), mild fluorescein angiography (FA) leakage, and shift work as risk factors for CSC chronicity (16). Interestingly, our results partially diverge from these observations. Although Group I presented with higher absolute baseline CTM values—without reaching statistical significance—this group demonstrated superior anatomical and visual outcomes, along with a greater reduction in CTM over time. In contrast, Group II exhibited minimal changes in CTM throughout follow-up. These findings suggest that baseline CTM alone may not fully capture disease severity or treatment responsiveness, and that its interaction with RPE leak location and disease dynamics deserves further investigation. Supporting this hypothesis, Sahoo et al. (2025) showed that CSC cases with subfoveal leakage were associated with higher baseline Haller layer–to–total choroidal thickness ratios and earlier clinical presentation (17). In our cohort, Group II—despite presenting with lower baseline central macular thickness (CMT) and SRF height (SRFH)—demonstrated a delayed and modest CTM reduction, becoming evident only at the 6-month visit based on linear time–response analysis (Figure 3). This pattern suggests that prompt laser intervention may be particularly relevant in acute CSC with subfoveal leakage to optimize choroidal remodeling and functional recovery. However, the absence of a dedicated analysis comparing Haller layer–to–total choroidal thickness ratios and subfoveal leak distribution between Groups I and II represents a limitation that should be addressed in future studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Yannuzzi et al.\u003c/strong\u003e were the first to propose ICG-A–guided verteporfin PDT targeting choroidal hyperpermeability in CSC (18). However, adverse events such as transient macular dysfunction, choroidal non-perfusion, RPE atrophy, and CNV have been reported (19, 20). To mitigate these, studies explored reduced fluence, dosage, or activation time, with \u003cstrong\u003eErikitola et al. (\u003c/strong\u003e\u003cstrong\u003e21)\u003c/strong\u003e concluding that half-dose PDT was the safest and most effective for chronic CSC.\u003c/p\u003e\n\u003cp\u003eIn 2018, the \u003cstrong\u003ePACORES Group\u003c/strong\u003e compared yellow micropulse (MP) laser to half-dose PDT in chronic CSC over 12 months (22). BCVA improved significantly in the MP group but not in the PDT group. MP laser advantages included lower cost and fewer systemic risks, though it required more retreatments. Compared to PACORES, our study achieved earlier BCVA improvement—already at one month in Group I and later in Group II post-laser—likely due to the acute presentation and healthier RPE, as well as the additive SPD stimulation at FA hot spots.\u003c/p\u003e\n\u003cp\u003eThe \u003cstrong\u003ePLACE trial (\u003c/strong\u003e\u003cstrong\u003e23)\u003c/strong\u003e found higher SRF resolution with PDT (67.2%) than with MP laser (28.8%), but no BCVA or quality-of-life differences. Our study achieved even higher SRF resolution (84.7%), emphasizing the effectiveness of the combined SPD\u0026nbsp;\u003cem\u003eplus\u003c/em\u003e SDL-EpM approach in acute cases. A recent RCT (24) comparing MP laser and half-dose PDT found both improved retinal sensitivity early, but BCVA gains appeared earlier with PDT. Similarly, the \u003cstrong\u003eSPECTRA trial (2\u003c/strong\u003e\u003cstrong\u003e5)\u003c/strong\u003e confirmed the superiority of half-dose PDT over eplerenone for SRF resolution, though BCVA remained comparable. The \u003cstrong\u003eVICI trial (2\u003c/strong\u003e\u003cstrong\u003e6)\u003c/strong\u003e also showed eplerenone was safe but not superior to placebo. The \u003cstrong\u003eAAO 2024\u003c/strong\u003e report supports half-dose PDT for anatomical improvement in acute CSC but notes limited long-term visual benefit and potential adverse effects (27). Despite reduced-dose protocols, PDT may still\u0026nbsp;have concern about\u0026nbsp;choroidal ischemia, RPE tears, or systemic complications (28-30). Thus, our combined sublethal laser strategy may represent a safer, cost-effective, and efficient alternative for acute CSC, especially in resource-limited settings.\u003c/p\u003e\n\u003cp\u003eOur recurrence analysis was limited by retrospective design and long intervals between visits. Although persistent SRF occurred in some cases, the lack of monthly OCT prevented detection of transient recurrences. Early treatment may have indirectly promoted choroidal thickness reduction by stimulating RPE activity, enhancing SRF reabsorption and improving outcomes. This supports CTM as a potential biomarker for positive response in acute CSC.\u003c/p\u003e\n\u003cp\u003eThis study has limitations, including its retrospective design and absence of functional macular tests such as microperimetry or contrast sensitivity. A prospective, randomized trial would better validate the effectiveness and reproducibility of the proposed combined laser therapy. Technical complexity and required physician expertise remain barriers to broader adoption.\u003c/p\u003e\n\u003cp\u003eTraditionally, CSC management allows deferred intervention, but early treatment may be preferred in patients with occupational visual demands. In developing regions, cost-effective therapies are advantageous. Here, we present an unpublished study comparing early versus deferred combined Pascal® laser treatment (SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM algorithm) for acute CSC, showing promising anatomical and functional outcomes with a safe profile.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eContributors\u003c/strong\u003e: MWR and JAC are the primary contributors to the research design. MWR is responsible for research execution and JPB for data acquisition. MWR and RJ are primary contributors to data analysis and interpretation. Manuscript preparation by MWR with revisions and interpretation was provided by JAC and RJ.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with ethical standards\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of informed consent Informed consent:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003eThis study adheres to the Declaration of Helsinki, and received institutional review board approval from the Ethics and Research Committee of Ribeirão Preto Medical School (Ref. N.: 5.496.883).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial number:\u003c/strong\u003e Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding information:\u003c/strong\u003e The project had no financial support.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKido A, Miyake M, Tamura H, Hiragi S, Kimura T, Ohtera S, et al. Incidence of central serous chorioretinopathy (2011\u0026ndash;2018): a nationwide population-based cohort study of Japan. Br J Ophthalmol. 2022;106(12):1748\u0026ndash;53.\u003c/li\u003e\n\u003cli\u003eBreukink MB, Dingemans AJ, den Hollander AI, Keunen JE, MacLaren RE, Fauser S, et al. Chronic central serous chorioretinopathy: long-term follow-up and vision-related quality of life. Clin Ophthalmol. 2016;11:39\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eSahin A, Bez Y, Kaya MC, T\u0026uuml;rkc\u0026uuml; FM, Sahin M, Yuksel H. 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Eye (Lond). 2020;34(9):1592\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eWu L, Roca JA. Correspondence on: Efficacy and safety of subthreshold micropulse laser compared with threshold conventional laser in central serous chorioretinopathy. Eye (Lond). 2021;35(11):3161\u0026ndash;2.\u003c/li\u003e\n\u003cli\u003eLim JW, Kang SW, Kim YT, Chung SE, Lee SW. Comparative study of patients with central serous chorioretinopathy undergoing focal laser photocoagulation or photodynamic therapy. Br J Ophthalmol. 2011;95(4):514\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eFossataro F, Fossataro C, Abraham N, Fouad Y, Mrejen S, Tan ACS, et al. Pathogenesis of Central Serous Chorioretinopathy and the Link Between Choroidal Hyperpermeability and Retinal Pigment Epithelium Pump Reversal. Am J Ophthalmol. 2024;266:206\u0026ndash;17. \u003c/li\u003e\n\u003cli\u003eLavinsky D, Wang J, Huie P, Dalal R, Lee SJ, Lee DY, et al. Nondamaging Retinal Laser Therapy: Rationale and Applications to the Macula. Invest Ophthalmol Vis Sci. 2016;57(6):2488\u0026ndash;500. \u003c/li\u003e\n\u003cli\u003eHata M, Oishi A, Shimozono M, Mandai M, Nishida A, Kurimoto Y. Early changes in foveal thickness in eyes with central serous chorioretinopathy. Retina. 2013;33(2):296\u0026ndash;301. \u003c/li\u003e\n\u003cli\u003eMatet A, Jaworski T, Bousquet E, Canonica J, Gobeaux C, Daruich A, et al. Lipocalin 2 as a potential systemic biomarker for central serous chorioretinopathy. Sci Rep. 2020;10(1):20175. \u003c/li\u003e\n\u003cli\u003eMatet A, Daruich A, Zola M, Behar-Cohen F. Risk Factors for Recurrences of Central Serous Chorioretinopathy. Retina. 2018;38(7):1403\u0026ndash;14. \u003c/li\u003e\n\u003cli\u003eSahoo NK, Alagar R, Chang S, et al. Clinical and imaging characteristics of central serous chorioretinopathy with subfoveal leak. European Journal of Ophthalmology. 2025;0(0).\u003c/li\u003e\n\u003cli\u003eYannuzzi LA, Slakter JS, Gross NE, Spaide RF, Costa DL, Huang SJ, et al. Indocyanine green angiography-guided photodynamic therapy for treatment of chronic central serous chorioretinopathy: a pilot study. 2003. Retina. 2012;32 Suppl 1:288\u0026ndash;98. \u003c/li\u003e\n\u003cli\u003eCardillo Piccolino F, Eandi CM, Ventre L, Rigault de la Longrais RC, Grignolo FM. Photodynamic therapy for chronic central serous chorioretinopathy. Retina.2003;23(6):752\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eChan WM, Lam DS, Lai TY, Tam BS, Liu DT, Chan CK. Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level. Br J Ophthalmol.2003;87(12):1453\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eErikitola OC, Crosby-Nwaobi R, Lotery AJ, Sivaprasad S. Photodynamic therapy for central serous chorioretinopathy. Eye (Lond).2014;28(8):944\u0026ndash;57.\u003c/li\u003e\n\u003cli\u003eRoca JA, Wu L, Fromow-Guerra J, Rodr\u0026iacute;guez FJ, Berrocal MH, Rojas S, Lima LH,et al. Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group. Br J Ophthalmol. 2018;102(12):1696\u0026ndash;1700. \u003c/li\u003e\n\u003cli\u003eVan 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. doi: 10.1016/j.ophtha.2018.04.021. \u003c/li\u003e\n\u003cli\u003eBrelen ME, Ho M, Li S, Ng DSC, Yip YWY, Lee WS, et al. Comparing Half-Dose Photodynamic Therapy with Subthreshold Micropulse Laser for the Treatment of Central Serous Chorioretinopathy. Ophthalmol Retina. 2024;8(5):490\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003evan Rijssen TJ, van Dijk EHC, Tsonaka R, Feenstra HMA, Dijkman G, Peters PJH, et al. Half-Dose Photodynamic Therapy Versus Eplerenone in Chronic Central Serous Chorioretinopathy (SPECTRA): A Randomized Controlled Trial. Am J Ophthalmol. 2022;233:101\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eLotery A, Sivaprasad S, O\u0026rsquo;Connell A, Harris RA, Culliford L, Cree A, et al. Eplerenone versus placebo for chronic central serous chorioretinopathy: the VICI RCT. Southampton (UK): NIHR Journals Library; 2021 Jan. PMID: 33471454.\u003c/li\u003e\n\u003cli\u003eKim LA, Maguire MG, Weng CY, Smith JR, Jain N, Flaxel CJ, et al. Therapies for Central Serous Chorioretinopathy: A Report by the American Academy of Ophthalmology. Ophthalmology. 2025;132(3):343\u0026ndash;53. \u003c/li\u003e\n\u003cli\u003eLee PY, Kim KS, Lee WK. Severe choroidal ischemia following photodynamic therapy for pigment epithelial detachment and chronic central serous chorioretinopathy. Jpn J Ophthalmol. 2009;53(1):52\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eCopete S, Ruiz-Moreno JM, Cava C, Montero JA. Retinal thickness changes following photodynamic therapy in chronic central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2012;250(6):803\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eKim SW, Oh J, Oh IK, Huh K. Retinal pigment epithelial tear after half fluence PDT for serous pigment epithelial detachment in central serous chorioretinopathy. Ophthalmic Surg Lasers Imaging. 2009;40(3):300\u0026ndash;3.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"central serous chorioretinopathy, short-pulse laser, subthreshold diffuse laser","lastPublishedDoi":"10.21203/rs.3.rs-8554824/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8554824/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eTo compare anatomical and functional outcomes of combined Pascal focal short-pulse duration laser plus subthreshold diffuse laser (SDL) with Endpoint Management algorithm (SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM) applied promptly or deferred in acute central serous chorioretinopathy (CSC).\u003c/p\u003e\u003ch2\u003eDesign:\u003c/h2\u003e \u003cp\u003eRetrospective comparative study.\u003c/p\u003e\u003ch2\u003eParticipants:\u003c/h2\u003e \u003cp\u003eSeventy-nine eyes with acute macular subretinal fluid (SRF) due to CSC treated between July 2022 and January 2024.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eGroup I (n\u0026thinsp;=\u0026thinsp;55) received prompt SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM laser; Group II (n\u0026thinsp;=\u0026thinsp;24) received oral spironolactone (50 mg twice daily) with deferred laser after 3 months if SRF persisted. Multimodal evaluation was performed at baseline and at 1, 3, 6, and 12 months. Outcomes included subretinal fluid height (SRFH), best-corrected visual acuity (BCVA), central macular thickness (CMT) and choroid thickness measurement (CTM).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSixty-eight eyes (86%) completed 12-month follow-up data analysis. In the intergroup comparison, Group I demonstrated significant SRFH, CMT and BCVA better and faster results (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) through initial 3 months. At 12 months, a tendency BCVA (p\u0026thinsp;\u0026lt;\u0026thinsp;0.1) improvement was sustained. The CTM was not significant different between the groups I and II at all visits study. The SRF resolution was more frequent in Group I than Group II at all visits study with significant percentile from 1\u0026ordm;, 3\u0026ordm; and 12\u0026ordm; months.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePrompt SPD \u003cem\u003eplus\u003c/em\u003e SDL-EpM laser therapy in acute CSC results in faster anatomical and functional recovery compared with deferred laser following oral spironolactone therapy. Long-term outcomes were comparable between groups.\u003c/p\u003e","manuscriptTitle":"Early versus deferred treatment with Pascal short-pulse duration plus subthreshold endpoint management laser techniques for central serous chorioretinopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-30 13:06:50","doi":"10.21203/rs.3.rs-8554824/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a718d419-eb2e-4856-847c-9e82ac7b3d82","owner":[],"postedDate":"January 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-30T13:06:50+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-30 13:06:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8554824","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8554824","identity":"rs-8554824","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}