Photodynamic Therapy in Central Serous Chorioretinopathy: Treatment Timing, Anatomical Response, and Recurrence in a Large Real-World Cohort

Abstract

Introduction

Central serous chorioretinopathy (CSC) is characterized by pathological accumulation of subretinal fluid (SRF), leading to visual impairment. Photodynamic therapy (PDT) is an established treatment for chronic or persistent CSC. This study aimed to identify predictors of treatment response in a large cohort of patients with CSC treated with PDT.

Methods

In this retrospective, single-center study, clinical characteristics and treatment outcomes of patients with CSC undergoing PDT were systematically analyzed. Central retinal thickness (CRT) and visual acuity were assessed before and after treatment. The interval between initial diagnosis and PDT was evaluated for its impact on therapeutic response.

Results

A total of 115 patients (90 males, 25 females; mean age 49.95 ± 10.15 years) were included. The mean interval from diagnosis to PDT was 3.79 ± 3.53 years. CRT decreased significantly following PDT (p < 0.001), with complete SRF resolution in 51.3% of eyes. Mean visual acuity improved by −0.02 ± 0.22 logMAR (p = 0.0047). Recurrence occurred in 30% of eyes after a mean of 1.1 ± 1.1 years. A significant negative correlation was observed between time to PDT and CRT reduction (r = −0.286, p = 0.001) but not with visual acuity (p = 0.76). Repeat PDT, performed in 16 eyes, resulted in further significant CRT reduction (p = 0.008).

Conclusions

PDT is effective in reducing SRF in CSC. Delayed treatment was associated with diminished anatomical response. Repeat PDT may provide additional benefit in recurrent disease.

Key Summary Points

Why carry out this study?

Central serous chorioretinopathy (CSC) can cause persistent subretinal fluid and visual impairment, but factors predicting response to photodynamic therapy (PDT), including the impact of treatment timing, remain incompletely understood.

Identifying predictors of anatomical and functional treatment response may help optimize patient selection and timing of PDT.

What was learned from the study?

This study evaluated clinical predictors of anatomical and functional response to PDT in CSC, with a particular focus on whether earlier treatment is associated with improved outcomes.

PDT significantly reduced central retinal thickness, achieved complete subretinal fluid resolution in 51.3% of eyes, and resulted in a modest but significant improvement in visual acuity.

Earlier PDT was associated with greater anatomical improvement, whereas delayed treatment was associated with a smaller reduction in central retinal thickness, supporting timely intervention in CSC.

Although recurrence occurred in approximately 30% of eyes, repeat PDT provided additional anatomical benefit, supporting its role as an effective retreatment strategy for recurrent CSC.

Introduction

Central serous chorioretinopathy (CSC) describes a pathological accumulation of subretinal fluid and is one of the four most common diseases of the macula [1]. It is often self-limiting with spontaneous remission after a few months, but in chronic cases it can lead to irreversible vision loss due to atrophic changes in the outer retinal layers and the retinal pigment epithelium.

Despite numerous discussions, the exact pathogenesis remains unclear to this day. Important risk factors for the development of the disease include male sex, high stress and workload [2], and the use of corticosteroids [3]. However, other factors such as arterial hypertension, smoking, parasympathetic hyperactivity, gastroesophageal reflux, sleep apnea, and genetic factors are also being discussed [4].

As one of the diseases of the “pachychoroidal disease spectrum” [5], CSC is characterized by a thickening of the Haller layer of the choroid and, in turn, a thinning of the Sattler layer above it [6]. Physiologically, there is a balance between the fluid flows in the choroid: the hydrostatic pressure in the capillaries is balanced by the colloid osmotic pressure in the extravascular space [7]. Colloids such as albumin move out of the fenestrated capillaries of the choroid through a transscleral fluid flow.

Current evidence suggests that scleral thickening may impair transscleral outflow, leading to choroidal fluid accumulation, vortex vein compression, and secondary leakage [8–10].

This results in retinal pigment epithelium decompensation and subretinal fluid accumulation with subsequent visual impairment [2]. Similar mechanisms have been described in uveal effusion syndrome (UES), supporting the concept of a pachychoroid disease continuum with UES representing a more severe manifestation [6, 11].

Current treatment strategies include mineralocorticoid receptor antagonists, subthreshold micropulse laser therapy, and photodynamic therapy (PDT).

On the basis of the currently available evidence, PDT has demonstrated superior efficacy compared with both micropulse laser treatment, as shown in the PLACE trial [12] and mineralocorticoid receptor antagonists, as reported in the SPECTRA study[13]. Therefore, recent treatment recommendations consider PDT the preferred first-line therapy for chronic CSC. Feenstra and colleagues created a flowchart for the treatment strategy of acute and chronic CSC, in which PDT is recommended as first-line therapy [14]. Bousquet et al. similarly proposed photodynamic therapy as the preferred first-line treatment for chronic CSC, while subthreshold micropulse laser therapy may represent a suitable alternative in selected patients [15].

Treatment involves intravenous verteporfin administration followed by laser activation, inducing choroidal vascular remodeling that reduces hyperpermeability and promotes subretinal fluid resolution [14, 16].

Despite compelling evidence supporting PDT, uncertainties persist regarding optimal treatment timing, long-term anatomical and functional outcomes, and recurrence rates, particularly in chronic CSC. Consequently, a standardized evidence-based treatment algorithm has not yet been fully established.

The primary objective of this study was to evaluate the effectiveness of PDT in a large cohort of patients with CSC treated at our institution. Treatment efficacy was defined by a reduction or complete resolution of subretinal fluid on optical coherence tomography. We specifically wanted to assess whether the time interval between disease onset and PDT influences therapeutic response. Secondary objectives included the assessment of recurrence rates and the time to recurrence following treatment.

Methods

For this retrospective study, all patients who underwent photodynamic therapy between 2016 and 2024 at the Department of Ophthalmology, LMU University Hospital, LMU Munich, were collected. All patients were treated with half-dose PDT with a verteporfin dose of 6 mg/m² and light energy of 25 J/cm². Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were used to determine the treatment area (Fig. 1D). The treatment area was defined as the region of fluid leakage corresponding to areas of choroidal hyperpermeability and abnormal choroidal vasculature. Only one eye per patient was included in the analyses. In patients with bilateral involvement, the more severely affected eye was included in the analysis.

Fig. 1.

Representative macular spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography and indocyanine green angiography (FA-ICGA) of a patient with chronic serous chorioretinopathy. A SD-OCT B-scan showing a central serous neurosensory detachment prior to PDT, B OCT scan of the same patient 8 weeks after PDT with completely resolved fluid. C FA with central focal leakage, showing hyperfluorescent area of choroidal vascular hyperpermeability (with arrow), D ICGA imagine with central hyperfluorescent area, showing the planned PDT area areal for laser therapy (yellow circle)

Exclusion criteria were the presence of any ocular diagnosis other than CSC that served as the indication for PDT, as well as patients who did not return for a follow-up visit after treatment. To minimize the risk of diagnostic misclassification, all patients in our cohort underwent fluorescein angiography and indocyanine green angiography (FA-ICGA) prior to PDT treatment planning. These examinations were used to carefully evaluate leakage characteristics and exclude neovascular pathologies as far as possible.

Epidemiological and clinical data were collected for all patients, including age, sex, prior ocular comorbidities or procedures, the time interval from onset to PDT and post-treatment disease recurrence.

Imaging

Imaging included an acquisition of a standard macular volume scan consisting of 49 equally spaced B-scans covering 20° × 20° centered on the fovea (20° × 20° [5.9 × 5.9 mm], 49 horizontal B-scans, resolution: 512 pixels [X] × 496 pixels [Z], 18 ≤ ART ≤ 30, on Spectralis HRA + OCT, Heidelberg Engineering, Heidelberg, Germany). Central retinal thickness (CRT) was calculated in a 3 mm diameter cylinder centered to the fovea derived from a macular volume scan (Fig. 2). The CRT was measured before and after PDT. Central retinal thickness (CRT) was measured from the OCT scans, and the presence of subretinal fluid (SRF) was assessed using the same imaging data. Consequently, both CRT and SRF were evaluated at identical time points, as they were derived from the same OCT examinations. The change in CRT was then calculated. We manually classified the OCT change after therapy into four main groups: a complete resolution of SRF, a reduction of SRF, no response to therapy, with a range of ± 5 µm, and an increase in SRF.

Fig. 2.

Fundusphotography (A) with ETDRS Grid and OCT scan (B) and ETDRS Grid measurement (D). Measurement of 3 mm area for calculation of central retinal thickness (CRT), (C, D, red circle) in a representative SD-OCT scan of a patient with central serous chorioretinopathy (CSC) before photodynamic therapy (PDT) was performed

Statistical Analysis

All data were recorded and analyzed in Microsoft Excel spreadsheets (version 16.99 for Mac; Microsoft, Redmond, WA, USA). Statistical analysis was performed with GraphPad Prism (version 10.6.0; GraphPad Software, Boston, MA, USA). A p value of < 0.05 was considered to indicate statistical significance. The Kolmogorov–Smirnov test was applied to assess the normality of the distribution within both groups. Differences in CRT and visual acuity before and after PDT were analyzed using the Wilcoxon signed-rank test. Correlations between the change in CRT and the time interval from initial diagnosis to therapy initiation were calculated by Spearman rank correlation coefficient. Mann–Whitney U test was used for calculation of the difference between the time until therapy was performed in the group with and without a recurrence.

Ethics

This study was conducted in accordance with the tenets of the Declaration of Helsinki and was classified as ethically and legally unobjectionable by the ethics committee of the LMU Munich (identifier: 25-0363). This retrospective study was conducted using anonymized patient data, and therefore, the requirement for informed consent was waived by the local ethics committee in accordance with applicable regulations.

Results

A total of 115 patients were analyzed, including 90 male and 25 female patients (Fig. 3). Sex was recorded as part of the routine demographic data collected at the time of patients’ admission to our clinic, based on patient-reported information documented in the medical record.

Fig. 3.

Demographic patient characteristics of all included patients who undergo photodynamic therapy (PDT). (A) Sex distribution visualized in a pie chart, (B) age distribution visualized as boxplots

Nine patients with a primary diagnosis of polypoidal choroidal vasculopathy (PCV) were excluded, as confirmed by fluorescein angiography and indocyanine green angiography (FA-ICGA), which had been performed in all patients to ensure diagnostic accuracy.

The mean age at initial diagnosis was 49.95 ± 10.15 years (range, 24–79 years). Female patients were significantly older, with a mean age of 56.14 ± 9.50 years (range, 37–78 years), compared with male patients, who had a mean age of 47.83 ± 9.21 years (range, 24–69 years). This difference was statistically significant (Welch’s t test, p = 0.0002; 95% confidence interval, −12.40 to −4.22).

Among the study population, 82 patients (71%) had received prior treatment with a mineralocorticoid receptor antagonist, most commonly spironolactone. Nineteen patients (16.5%) were treated with a carbonic anhydrase inhibitor (acetazolamide), 47 patients (40%) received intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, and 12 patients (10%) were treated with topical nonsteroidal anti-inflammatory drugs. In addition, 23 patients (20%) underwent subthreshold laser therapy with endpoint management (EpM), and 4 patients (3%) received micropulse laser therapy.

The mean interval between initial diagnosis and PDT was 3.79 ± 3.53 years (range, 0.4–18 years). The mean time to the first follow-up visits after PDT was 8.5 ± 3.91 weeks (range 1–20 weeks).

Of the 115 patients, 29 (25%) presented with bilateral disease, including only two female patients. Mean pretreatment visual acuity was 0.29 ± 0.31 logMAR (range −0.1 to 1.3).

Results After Photodynamic Therapy (PDT)

CRT was measured immediately before PDT and at the first follow-up visit after treatment (mean follow-up interval, 8.5 ± 3.91 weeks; range, 1–20 weeks). A significant reduction in CRT was observed following PDT, with a mean decrease of 67.74 μm (IQR, −129.8 to −1.5 μm; n = 115; Wilcoxon signed-rank test, p < 0.001; 95% confidence interval [CI], −85.36 to −50.12, Fig. 4).

Fig. 4.

Results after photodynamic therapy (PDT). A Bar chart showing central retinal thickness (CRT) values in μm before and after the photodynamic therapy was performed. Comparison showing a significant reduction of CRT after the therapy (****p < 0.0001; p values and 95% confidence intervals (CI95%) are given for Wilcoxon test). B Bar charts showing the different response groups after the therapy; No response = 11 eyes, reduction n = 36, dry = 59; increase = 9. C Bar chart showing CRT values in in μm before and after the second PDT was performed (*p = 0.0081; p values and 95% confidence intervals (CI95%) are given for Wilcoxon test). Bar chart showing visual acuity before and after PDT was performed (***p = 0.0002, p values and 95% confidence intervals (CI95%) are given for Wilcoxon test)

Optical coherence tomography (OCT) evaluation revealed a complete resolution of SRF in 59 eyes, a reduction of subretinal fluid (SRF) in 36 eyes, no treatment response in 11 eyes, and an increase in SRF in 9 eyes (Fig. 4). After therapy, recurrence was observed in 34 eyes of all 115 treated eyes (30.0%). Of these, 15 eyes had shown a favorable initial response with complete SRF resolution. The mean time to SRF recurrence was 1.10 ± 1.1 years (range, 0.25–4.5 years). The mean interval until a second PDT in patients with recurrence was 3.22 years.

A significant negative correlation was identified between the time from initial diagnosis to PDT and the change in CRT before and after treatment (Spearman rank correlation coefficient r = −0.26, p = 0.001; 95% CI, −0.42 to −0.11), indicating reduced CRT response with longer disease duration prior to PDT. To exclude the possibility that patients with longer disease duration exhibited lower baseline CRT values, thereby limiting the magnitude of CRT reduction and potentially confounding our findings, we investigated the association between baseline CRT and symptom duration. This analysis revealed no significant correlation between baseline CRT and symptom duration (Spearman rank correlation coefficient r = −0.15, p = 0.14; 95% CI, −0.34 to 0.054). The study population was stratified according to symptom duration prior to PDT into patients with a symptom duration of less than 3 years (n = 68) and those with a symptom duration of more than 3 years (n = 45). Analysis revealed a significant difference in CRT reduction between the two groups. Patients with a symptom duration of less than 3 years exhibited a mean CRT decrease of 83.71 ± 76.03 μm, compared with 40.42 ± 102.8 μm in patients with a symptom duration exceeding 3 years (Wilcoxon signed-rank test, p = 0.025; 95% CI, 12–72 μm).

No significant difference was observed in the timing of PDT between eyes with recurrence and those without recurrence (Mann–Whitney U test, p = 0.305).

Mean pretreatment visual acuity was 0.31 ± 0.29 logMAR (range −0.1 to 1.3), post-treatment visual acuity was 0.25 ± 0.31 logMAR (range, −0.1 to 2.0). The mean change in visual acuity from pre- to post-treatment was −0.05 ± 0.16 logMAR, which was statistically significant (Wilcoxon signed-rank test, p = 0.0002; 95% CI, −0.08 to – 0.02, Fig. 4). In the subgroup of eyes with complete SRF resolution, visual improvement was more pronounced, with a mean change of −0.08 ± 0.15 logMAR, reaching statistical significance (Wilcoxon signed-rank test, p = 0.0002; 95% CI, −0.11 to −0.04). The time to treatment initiation showed no significant correlation with pretreatment visual acuity (Spearman’s rank correlation coefficient, r = 0.02, p = 0.75). Furthermore, treatment delay was not associated with visual change or improvement following therapy (Spearman’s rank correlation coefficient, r = 0.017, p = 0.79).

Polypoidal choroidal vasculopathy (PCV) was identified in 24 eyes during follow-up after PDT, necessitating subsequent intravitreal injection therapy.

A second PDT was performed in 16 eyes of all 115 treated eyes: 11 due to recurrence after partial or complete SRF resolution, four as a second attempt following no response to the initial PDT, and one owing to secondary PCV with undulating SRF. Three patients were lost to follow-up after the second PDT. In the remaining 13 patients, CRT was significantly reduced after the second treatment, with a mean reduction of 85.64 ± 117.5 μm (Wilcoxon signed-rank test, p = 0.0081; 95% CI, −153.5 to −17.81).

Discussion

In this retrospective real-world analysis of a large cohort of patients with CSC, PDT proved to be an effective treatment option, leading to a significant reduction in subretinal fluid in the majority of treated eyes. A key finding of our study is the association between earlier initiation of PDT and a more pronounced anatomical response, whereas the timing of treatment did not significantly affect recurrence rates. In addition, our results suggest that repeat PDT may represent a viable therapeutic option in selected cases of disease recurrence.

CSC is the fourth most common retinal disease [17] and is characterized by serous detachment of the neurosensory retina caused by retinal pigment epithelium dysfunction and increased choroidal vascular permeability [14, 18].

It has an incidence of approximately 10 newly diagnosed cases per 100,000 individuals per year [19], with a rising trend observed in recent years and projected to continue in the future [20]. This highlights the importance of improving our understanding of the disease. Although the exact pathogenesis remains incompletely understood, established risk factors include exogenous as well as endogenous steroids [21], male sex [22], sleep apnea [23], genetic association [24], pregnancy [25], hyperopia, and Helicobacter pylori infection [26].

While acute CSC often resolves spontaneously, treatment is generally advisable in chronic cases to mitigate persistent subretinal fluid accumulation, reduce the risk of permanent retinal damage, and enhance visual prognosis [23].

In recent years, increasing evidence has supported the efficacy of PDT [14, 27, 28]. Previous studies demonstrated superior efficacy and lower recurrence rates of PDT compared with subthreshold micropulse laser treatment, independent of the leakage pattern [29, 30]. A meta-analysis search of Kim et al. has shown that PDT treatment is superior for acute CSC in comparison with untreated patients and alternative treatment options as intravitreal Anti-VEGF treatment and oral beta blocker usage only show inconsistent treatment results [27].

The PLACE trial demonstrated superior anatomical outcomes of half-dose PDT compared with high-density subthreshold micropulse laser treatment [12], with complete subretinal fluid resolution achieved in 51.2% of eyes after 6–8 weeks. Our findings closely mirror these results, with complete fluid resolution observed in 51.3% of eyes after PDT (59 of 115 eyes). Previous meta-analyses reported comparable, although slightly higher, rates of complete subretinal fluid resolution after PDT, ranging from 51.9 to 72.2% [31]. By contrast, Chang-Wolf et al. found persistent SRF after the first PDT session in 62.5% of eyes, with complete resolution achieved in 37.5% [32].

The PLACE trial demonstrated superior anatomical outcomes of half-dose PDT compared with HSML, with greater reduction of subretinal fluid and lower retreatment rates [12]. Similarly, Latalska et al. reported a mean of 2.8 treatment sessions in chronic and recurrent CSC [33].

The lower recurrence rate observed after PDT may be related to its stronger and more sustained effects on choriocapillaris perfusion compared with micropulse laser therapy [34].

We identified not only a significant decrease in subretinal fluid but also a corresponding improvement in visual acuity. The PLACE trial demonstrated a slightly greater improvement in visual acuity at the first follow-up visit, with a mean gain of 4.6 ETDRS letters (approx. 0.09 logMAR), compared with a change of −0.05 logMAR observed in our cohort. It should be noted that our cohort presented with a lower baseline visual acuity (0.29 logMAR) compared with 76.9 ETDRS letters (0,16 logMAR) letters prior to treatment [12].

The relatively low increase could be explained by chronic changes, where alterations in the retinal pigment epithelium and photoreceptor damage may lead to a decrease in best-corrected visual acuity (BCVA) and a loss of contrast sensitivity [14].

In our study, 20 of 115 treated eyes (17%) showed a poor result, with either no response (11 eyes) or an increase in subretinal fluid (9 eyes). The mechanisms contributing to non-response or suboptimal treatment outcomes remain poorly understood. Further studies with an evaluation of a larger group of non or poor responders should be done for a better prognosis of treatment outcome.

Timing of therapy remains challenging owing to fluctuating subretinal fluid. The “Evidence based treatment guideline” by Feenstra et al. recommends early initiation of treatment in highly symptomatic patients also in cases of acute CSC. However, observation for 4–6 months after onset of the first episode remains a recommendation as well. In chronic CSC, treatment half- dose PDT is recommended as soon as possible. In our cohort, the mean interval from onset to PDT was very long compared with these recommendations and other published studies. Reasons for this are the difficulties that publicly insured patients in Germany face in claiming reimbursement for off-label therapies. The process of reimbursement claim needs to be completed before therapy which leads to significant delays. It should additionally be considered that part of the observation period laid in the COVID-19 pandemic, a time marked by a supply shortage of the required photosensitizer verteporfin which led to delays of PDT in many European countries [35].

The demographic characteristics of our cohort are consistent with the known epidemiology of CSC, which predominantly affects males and typically presents later in women [17, 36]. The relatively high age at first presentation among male patients in our clinic may be attributable to delayed detection, potentially owing to earlier evaluations and treatments conducted by independent community ophthalmologists. Also the lower number of females in the group of bilateral disease has been described previously [37]. Investigating potential sex-related differences in treatment response is an important aspect and needs to be considered as a valuable direction for future research.

A main limitation of this study, besides its retrospective design, is the variability in follow-up intervals owed to the real-world setting of this cohort. Currently, no standardized recommendation for the timing of post-PDT follow-up visits exists. An excessively early follow-up may underestimate the therapeutic effect. Therefore, the establishment of a standardized follow-up protocol would be desirable to enhance the comparability of results, particularly in multicenter or register studies.

Another limitation of this study is that, although all patients underwent FA and ICGA, OCTA was not available in all cases. Therefore, secondary neovascularization may have been missed, particularly occult neovascular networks that can be detected by OCTA but remain undetected on conventional angiography, as reported in PCV. Consequently, the presence of undiagnosed neovascularization cannot be completely excluded.

Conclusions

Overall, this study confirms the effectiveness of PDT in a large real-world cohort treated at our center. Earlier initiation of PDT was associated with a greater reduction in subretinal fluid, underscoring the potential benefit of timely intervention. Notably, the interval between initial diagnosis and treatment did not significantly influence recurrence rates. Furthermore, our results indicate that repeat PDT can be an effective therapeutic option in cases of disease recurrence. Further prospective studies are warranted to better define the optimal timing of PDT and to clarify the efficacy and indications of repeated treatment.

Author Contribution

Caroline M. Stüven, Benedikt Schworm, Julian Klaas, Jakob Siedlecki, Tina Herold, and Paul Foerster contributed to the conceptualization and methodology of the study. Benedikt Schworm, Julian Klaas, Jakob Siedlecki, Tina Herold, Paul Foerster, Leonie F. Keidel, and Siegfried G. Priglinger contributed to validation, data curation, and manuscript review and editing. Benedikt Schworm and Siegfried G. Priglinger additionally provided supervision. Material preparation, data collection, and data analysis were performed by Caroline M. Stüven. The first draft of the manuscript was written by Caroline M. Stüven and Benedikt Schworm. All authors commented on previous versions of the manuscript, read, and approved the final manuscript.

Funding

An intramural funding was granted to Dr Keidel (Munich Medical & Clinician Scientist Program, LMU Munich, Funding number: CS 051; https://www.med.lmu.de/karriere/mcsp/index.html). The funder played no role in study design, data collection, analysis and interpretation of the data or the writing of this manuscript. The journal’s Rapid Service Fee was funded by the authors.

Data Availability

Data available on request owing to privacy restrictions.

Declarations

Conflicts of Interest

None of the authors’ financial interests are directly or indirectly related to this work. Caroline M. Stüven has no financial disclosure to declare. Benedikt Schworm has received previous speaker fees of Novartis Pharma, Bayer Vital, Amgen. Tina Herold received previous Honoraria of Novartis, Bayer Healthcare, Abbvie, Roche, Novonordisk and travel expenses of Roche. Julian Klaas has received previous speaker fees and Advisory Honoraria for Novartis und Roche. Jakob Siedlecki is part of the advisory board and got honoraria of Novaris Pharma, Abbvie/Pharm-Allergan, Roche, Apellis, Sandoz/Hexal and he is part of the advisory board of Bayer. Paul Foerster has no financial disclosure to declare. Siegfried G. Priglinger is part of the advisory board and received previous honoraria of Novartis Pharma, Pharm Allergan, Zeiss, Bayer, Bausch and Lomb, Roche, AbbVie, he is a Consulant of BVI Medical, Bausch and Lomb, Roche and AbbVie. Leonie F. Keidel received previous speaker fees and/or travel expenses from Novartis Pharma, Recordati Rare Diseases Inc., CHIESI, Roche Diagnostics, DORC Holding BV and Santen.

Ethical Approval

This study was conducted in accordance with the tenets of the Declaration of Helsinki and was classified as ethically and legally unobjectionable by the ethics committee of the LMU Munich (identifier: 25-0363). This retrospective study was conducted using anonymized patient data, and therefore, the requirement for informed consent was waived by the local ethics committee in accordance with applicable regulations.

Thanking Patients

We thank the participants of the study.