Central serous chorioretinopathy (CSCR) is a chorioretinal disorder characterized by serous detachment of the neurosensory retina with or without a pigment epithelial detachment (PED). Although the natural history of the disease is favorable, with most eyes resolving spontaneously, some patients tend to develop a chronic disease, which results in a recurrent or persistent course that can lead to permanent vision loss. ^, Even though risk factors for CSCR including male gender, corticosteroid use, psychological stress, and pregnancy have been described ^, , its associations with gender have not been fully investigated. Quantitative measurements of the choroid and retina are known to differ by gender in healthy eyes. Several hypotheses have been proposed to explain these divergences. A leading theory implicates dysregulation of the mineralocorticoid pathway in the pathogenesis of CSCR. From this perspective, hormonal differences may contribute to gender-specific disease behavior; in particular, progesterone, a natural antagonist of the mineralocorticoid receptor, may confer a degree of protection in women by delaying onset or mitigating disease severity. In contrast, genetic predisposition appears to play a lesser role in explaining gender differences. Studies evaluating risk variants such as complement factor H (CFH) have not demonstrated meaningful disparities in allele frequencies between male and female patients. While these observations provide valuable insights, they remain largely fragmented, focusing on isolated imaging characteristics rather than offering a comprehensive assessment of gender-related differences in disease severity, progression, and prognosis. The recent multimodal imaging–based classification of CSCR offers a structured framework to categorize some gender-specific differences in CSCR. However, this work did not include long-term longitudinal follow-up, limiting insights into progression and long-term sequelae. In this study, we aim to address this gap by evaluating the functional outcomes and morphological changes, comparing men vs women during long-term follow-up. Such information may ultimately support the development of patient-specific treatment strategies for CSCR.

This was designed as a retrospective, multicenter center study that was part of the Macula Society CSCR project- Macula Society International CSCR Research Network (MICRoN). The patients recruited were affected by acute or chronic CSCR. The study adhered to the tenets of the Declaration of Helsinki and was approved by the local institutional review boards or Ethics Committee of each participating center. Data sharing agreements among collaborators and the procedures for demographic, clinical, and imaging data collection and analysis have been detailed in prior publications of the project. Inclusion criteria consisted of: (1) women older than 18 years, (2) a confirmed diagnosis of CSCR, and (3) presence of follow-up imaging (in patients with bilateral disease meeting this criterion, only the right eye was analyzed).

Exclusion criteria were: (1) eyes with inadequate or incomplete records, or (2) coexisting retinal diseases, such as high myopia, diabetic retinopathy, glaucomatous optic neuropathy or retinal vasculopathies. Men were selected from the multicentric cohort and were age-matched using a nearest-neighbor matching algorithm.

Baseline demographic and systemic information was obtained, including age, gender, medical comorbidities, smoking status, symptom duration, and prior treatment for CSCR. Gender was recorded as gender assigned at birth (male or female) based on medical records. Baseline and follow-up best recorded visual acuity (BRVA) was documented and was expressed in logMAR. The groups were further stratified into those ≥ 50 years and < 50 years, for sub-group analysis. CSCR was categorized as either acute or chronic based on the duration of serous retinal detachment (SRD); eyes with SRD persisting for more than 3 to 6 months are described as having chronic CSCR. Disease course was classified into three categories based on longitudinal OCT findings: resolution was defined as complete disappearance of subretinal fluid (SRF) with no evidence of recurrence at the final follow-up visit; recurrence was defined as complete SRF resolution followed by reappearance of SRF at any time during the follow-up period; and persistence was defined as continuous presence of SRF from baseline through the final follow-up visit.

Imaging data were also collected at both baseline and final visits, including fundus autofluorescence (FAF), optical coherence tomography (OCT), and fluorescein angiography (FFA). FAF assessment included: (1) identifying gravitational tracts; (2) assessing peripapillary changes in the retinal pigment epithelium (RPE); (3) measuring the extent of RPE alterations, quantified in disc areas (DA) including both hypo and hyperautofluorescent lesions; and (d) distinguishing between focal and multifocal RPE changes. CSCR cases were further categorized based on the degree of RPE involvement and whether multifocal lesions were present. Simple CSCR referred to cases where the disease was unifocal and confined to two or fewer DA of RPE alteration, while complex CSCR included cases with multifocal changes or lesions extending beyond 2 DA. OCT parameters assessed included central macular thickness (CMT) as well as the height and width of the neurosensory retinal detachment (NSRD). CMT was measured automatically from the macular cube scan produced by the OCT device. The height of the NSRD was measured from the innermost surface of the elevated neurosensory retina at its highest point to the inner border of the RPE at the fovea. Pigment epithelial detachments (PEDs) were detected on OCT as dome-shaped elevations of the RPE. The tallest PED within the scanned volume was selected for height measurement, defined as the vertical distance from Bruch’s membrane to the apex of the RPE elevation. PED width was measured horizontally between the points where the RPE contour returned to normal, using Bruch’s membrane as a reference. The double-layer sign (DLS) was noted when shallow, irregular PEDs with internal hyperreflective, hypo-reflective, or mixed signals were observed. The presence of hyperreflective dots (HRDs) in the choroidal stroma and irregularities in the photoreceptor outer segment (PROS) layer were also recorded. Choroidal measurements included SFCT, Haller vessel diameter, and the thickness of the inner choroid. Subfoveal choroidal thickness (SFCT) was measured within a 500 µm radius of the fovea using the OCT caliper, extending from the outer surface of the RPE to the choroid–sclera junction. Haller vessel thickness was determined by identifying the largest choroidal vessel lumen within 500 µm of the foveal center. The inner choroid, which includes the choriocapillaris and Sattler’s layer, was measured from the inner margin of the largest Haller vessel to the outer surface of the Bruch’s membrane. Detection of choroidal neovascularization (CNV) was based on findings from OCT angiography, FFA or indocyanine green angiography (ICG-A), when available. All images were meticulously analyzed by an experienced retina specialist (NH) and 10% of the sample images were independently reviewed and validated by another masked grader (AZ) to ensure accuracy and consistency. In case of disagreements, the measurements and segmentations were adjudicated by the senior author (JC).

A total of 426 patients [213 women and 213 age-matched men] with CSCR were analyzed. The mean age of the cohort was 50.2 ± 10.8 years and the median duration of symptoms was 2 months for women (IQR 1 to 6 months) and 2 months for men (IQR 0.52 to 7 months). A history of previous treatment was present in 59 (27.7%) women and 51(23.9%) men. Baseline characteristics of the two groups has been summarized in Table 1 .

The overall male cohort consisted of 348 CSCR patients derived from a multicenter dataset. The mean age was 46.8 ± 11.8 years, with a baseline mean BRVA of 0.29 ± 0.32 logMAR. Overall, 42% of patients presented with a simple CSCR phenotype. At presentation, the mean central macular thickness (CMT) was 348.9 ± 156.7 µm, and the mean neurosensory detachment (NSD) was 191.1 ± 141.0 µm. Regarding initial management, 210 patients (60.3%) were observed, 30 (8.6%) underwent photodynamic therapy (PDT), 47 (13.5%) received subthreshold micropulse laser (SMPL), 38 (11%) were treated with anti-VEGF injections, and 23 (6.6%) underwent combination therapy. During follow-up, 85 patients (24.4%) experienced recurrence and 80 (23.0%) demonstrated persistent subretinal fluid, while the remaining cases achieved complete resolution. For the 10% of volumes that were analyzed by a masked second grader (AZ) the ICC was 0.97 (95% CI: 0.95-0.98, P <.001).

Comparison between the age less than 50 and the age equal to or more than 50 years cohorts

Age-stratified analysis showed that baseline BRVA was better in females < 50 years (0.20 ± 0.22 logMAR, Snellen equivalent 20/32), compared to men < 50 years (0.28 ± 0.34 logMAR, Snellen equivalent 20/40) ( P =.031). In terms of imaging parameters, men < 50 years showed a greater extent of RPE alterations ( P =.003), PROS irregularities ( P =.003) and maximum width of PEDs ( P =.05). Among patients ≥ 50 years, females were more likely to present with simple CSCR (73.8% vs 45%, P =.003), while peripapillary RPE alterations ( P =.029) as well as the length of DLS ( P =.005), the maximum width of PED ( P =.04), and the overall amount of RPE alterations ( P =.02) were more common in men ≥ 50 years. ( Table 2 )

Table 2

Baseline Characteristics of the Age-Stratified Groups

Parameter	CSCR Women < 50 [ n = 109] Baseline	CSCR Men < 50 [ n = 113] Baseline	p -Value	CSCR Women ≥ 50 Baseline [ n = 104]	CSCR Men ≥ 50 Baseline [ n = 100]	P -Value
Age, years	41.9 ± 6.6	42.2 ± 6.2	.3	59 ± 6.7	59.3 ± 6.9	.4
Systemic co-morbidities(%)	34 (31,2%)	55 (48.7%)	.009	60 (57.7%)	72 (72%)	.04
Smoking (%)	11 (10.1%)	18 (15.9%)	.09	14 (13.5%)	30 (30%)	.006
Duration of symptoms [Median (IQR)], months	2 [0.86 to 6]	1.45 [0.75 to 6]	.18	3 [1 to 6]	2 [0.7 to 6]	.11
Ocular parameters
BRVA, logMAR	0.20 ± 0.22	0.28 ± 0.34	.031	0.29 ± 0.25	0.33 ± 0.35	.16
Simple CSCR (%)	56 (51.4%)	54 (52%)	.31	71(73.8%)	45 (45%)	.003
Area of RPE alterations, disc areas	1.65 ± 1.69	2.15 ± 1.56	.003	1.5 ± 1.4	2.5 ± 2.3	.027
Gravitational tract (%)	5 (5.4%)	8 (9%)	.21	4 (4.16%)	3 (3%)	.14
Peripapillary RPE alterations (%)	9 (9.8%)	14 (15.8%)	.16	7 (7.2%)	15 (15%)	.029
OCT
CMT, microns	336.7 ± 134.5	351.6 ± 137.9	.21	335.0 ± 115.07	314.8 ± 148.11	.13
NSRD height, microns	190.14 ± 137.2	194.5 ± 168.3	.42	157.2 ± 112.59	156.0 ± 130	.47
Irregular PROS (%)	79 (86.1%)	80(90.4%)	.28	79(82.2%)	71 (71%)	.42
HRF in PROS (%)	27 (29.4%)	34 (38.4%)	.42	25(26%)	20 (20%)	.05
DLS (%)	40 (43.65)	48 (54.2%)	.23	53(55.1%)	45 (45%)	.17
Length of DLS, microns	1096.2 ± 1159.7	1256.5 ± 1052.7	.24	1052.4 ± 614.1	1459.8 ± 876.6	.005
Max height of DLS, micron	46.19 ± 17.0	46.2 ± 19.43	.49	50.0 ± 23.34	46.35 ± 20.05	.20
SFCT, microns	386.9 ± 97.69	403.8 ± 102.84	.10	339.0 ± 86.24	344.2 ± 117.57	.36
Haller vessel thickness, microns	283.4 ± 95.4	301.7 ± 97.5	.07	255.2 ± 85.5	245.9 ± 93.1	.23
Inner choroidal thickness, microns	97.5 ± 44.3	104.3 ± 56.4	.16	93.9 ± 49.9	93.6 ± 47.6	.48
Pachyvessels (present) (%)	78 (85%)	98 (86.7%)	.18	66(63.5%)	66 (66%)	.32
Number of PEDs	1.7 ± 2.51	1.6 ± 0.67	.40	2.1 ± 3.3	1.4 ± 1.3	.21
Maximum height of PEDs, microns	122.8 ± 74.6	135.8 ± 98.8	.28	90.6 ± 56.4	126.7 ± 93.9	.14
Maximum width of PEDs, microns	445.5 ± 299.5	621.7 ± 516.8	.05	435.0 ± 240.9	674.1 ± 592.1	.04
SHRM	2(1.8%)	3(2.7%)	.34	5(4.8%)	2(2%)	.08
CNV after baseline	8 (7.3%)	11 (9.7%)	.29	24(23.1%)	27(27%)	.28

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