Serous business: delineating the broad spectrum of diseases with subretinal fluid in the macula

A wide range of ocular diseases can present with serous subretinal fluid in the macula and therefore clinically mimic central serous chorioretinopathy (CSC). In this manuscript, we categorise the diseases and conditions that are part of the differential diagnosis into 12 main pathogenic subgroups: neovascular diseases, vitelliform lesions, inflammatory diseases, ocular tumours, haematological malignancies, paraneoplastic syndromes, genetic dis-eases, ocular developmental anomalies, medication-related conditions and toxicity-related diseases, rhegma-togenous retinal detachment and tractional retinal detachment, retinal vascular diseases, and miscellaneous diseases. In addition, we describe 2 new clinical pictures associated with macular subretinal fluid accumulation, namely serous maculopathy with absence of retinal pigment epithelium (SMARPE) and serous maculopathy due to aspecific choroidopathy (SMACH). Differentiating between these various diseases and CSC can be challenging, and obtaining the correct diagnosis can have immediate therapeutic and prognostic consequences. Here, we describe the key differential diagnostic features of each disease within this clinical spectrum, including repre-sentative case examples. Moreover, we discuss the pathogenesis of each disease in order to facilitate the dif-ferentiation from typical CSC.Ophthalmic researc

Subretinal fluid morphology in chronic central serous chorioretinopathy and its relationship to treatment: a retrospective analysis on PLACE trial data

Purpose To explore subretinal fluid (SRF) morphology in chronic central serous chorioretinopathy (cCSC) after one session of either high-density subthreshold micropulse laser (HSML) treatment or half-dose photodynamic therapy (PDT).Methods We retrospectively obtained optical coherence tomography (OCT) scans from a subset of patients from a randomized controlled trial on treatment-naive eyes with cCSC allocated to either HSML treatment or half-dose PDT. OCT scans were evaluated prior to treatment and 6-8 weeks post-treatment, where we measured maximum SRF height and width, calculated the maximum height-to-maximum width-ratio (maxHWR) and calculated the total SRF volume.Results Forty-one eyes of 39 cCSC patients were included. SRF morphology ranged from flat to dome-shaped, quantified as maxHWR ranging between 0.02 and 0.12. SRF volume was median 0.373 mu l (range: 0.010-4.425 mu l) and did not correlate to maxHWR (rho = -0.004, p = 0.982). Half-dose PDT was superior to HSML treatment in complete SRF resolution (RR = 3.28, p = 0.003) and in morphological changes of SRF (Delta(maximum height), p = 0.001; Delta(maximum width), p < 0.001; Delta(volume), p = 0.025). SRF resolved completely in 19/22 PDT-treated eyes (86%) and 5/19 HSML-treated eyes (26%). SRF volume increased in five eyes (26%) after HSML treatment, and in none of the eyes after half-dose PDT. SRF morphology at baseline did not predict treatment outcomes.Conclusion SRF morphology changed after both HSML treatment and half-dose PDT in cCSC, with SRF disappearing in most PDT-treated patients, whereas SRF volume increased in a sizeable proportion of HSML-treated patients. Baseline SRF characteristics measured in this study were unable to predict outcomes after either HSML treatment or half-dose PDT

Estimation of current and post-treatment retinal function in chronic central serous chorioretinopathy using artificial intelligence

Refined understanding of the association of retinal microstructure with current and future (post-treatment) function in chronic central serous chorioretinopathy (cCSC) may help to identify patients that would benefit most from treatment. In this post-hoc analysis of data from the prospective, randomized PLACE trial (NCT01797861), we aimed to determine the accuracy of AI-based inference of retinal function from retinal morphology in cCSC. Longitudinal spectral-domain optical coherence tomography (SD-OCT) data from 57 eyes of 57 patients from baseline, week 6-8 and month 7-8 post-treatment were segmented using deep-learning software. Fundus-controlled perimetry data were aligned to the SD-OCT data to extract layer thickness and reflectivity values for each test point. Point-wise retinal sensitivity could be inferred with a (leave-one-out) cross-validated mean absolute error (MAE) [95% CI] of 2.93 dB [2.40-3.46] (scenario 1) using random forest regression. With addition of patient-specific baseline data (scenario 2), retinal sensitivity at remaining follow-up visits was estimated even more accurately with a MAE of 1.07 dB [1.06-1.08]. In scenario 3, month 7-8 post-treatment retinal sensitivity was predicted from baseline SD-OCT data with a MAE of 3.38 dB [2.82-3.94]. Our study shows that localized retinal sensitivity can be inferred from retinal structure in cCSC using machine-learning. Especially, prediction of month 7-8 post-treatment sensitivity with consideration of the treatment as explanatory variable constitutes an important step toward personalized treatment decisions in cCSC.Ophthalmic researc

Long-term follow-up of chronic central serous chorioretinopathy after successful treatment with photodynamic therapy or micropulse laser

Purpose To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either primary half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) in the PLACE trial.Methods This multicentre prospective follow-up study evaluated cCSC patients at 1 year after completion of the PLACE trial. Outcomes included: complete resolution of SRF on OCT, best-corrected visual acuity (BCVA) in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, retinal sensitivity on microperimetry and a visual function questionnaire (NEI-VFQ25).Results Twenty-nine out of 37 patients who received half-dose PDT and 15 out of 17 patients who received HSML could be evaluated at final visit. At final visit, 93% of the patients treated with half-dose PDT had complete resolution of SRF, compared with 53% of HSML-treated patients (p = 0.006). At final visit, the mean estimate increase in the PDT group compared with the HSML group was + 2.1 ETDRS letters, +0.15 dB for the retinal sensitivity and + 5.1 NEI-VFQ25 points (p = 0.103, p = 0.784 and p = 0.071, respectively). The mean estimated central retinal thickness in the half-dose PDT group was -7.0 mu m compared with the HSML group (p = 0.566). The mean estimated subfoveal choroidal thickness in the half-dose PDT group was -16.6 mu m compared with the HSML group (p = 0.359).Conclusion At 20 months after treatment, cCSC patients successfully treated with half-dose PDT are less likely to have recurrences of SRF compared with those successfully treated with HSML. However, functional outcomes did not differ.Development and application of statistical models for medical scientific researc

Overlap of genetic loci for central serous chorioretinopathy with age-related macular degeneration

IMPORTANCE Central serous chorioretinopathy (CSC) is a serous maculopathy of unknown etiology. Two of 3 previously reported CSC genetic risk loci are also associated with AMD. Improved understanding of CSC genetics may broaden our understanding of this genetic overlap and unveil mechanisms in both diseases.OBJECTIVE To identify novel genetic risk factors for CSC and compare genetic risk factors for CSC and AMD.DESIGN, SETTING, AND PARTICIPANTS Using International Classification of Diseases, Ninth (ICD-9) and Tenth (ICD-10) Revision code-based inclusion and exclusion criteria, patients with CSC and controls were identified in both the FinnGen study and the Estonian Biobank (EstBB). Also included in ameta-analysis were previously reported patients with chronic CSC and controls. Data were analyzed from March 1 to September 31, 2022.MAIN OUTCOMES AND MEASURES Genome-wide association studies (GWASs) were performed in the biobank-based cohorts followed by ameta-analysis of all cohorts. The expression of genes prioritized by the polygenic priority score and nearest-gene methods were assessed in cultured choroidal endothelial cells and public ocular single-cell RNA sequencing data sets. The predictive utility of polygenic scores (PGSs) for CSC and AMD were evaluated in the FinnGen study.RESULTS A total of 1176 patients with CSC and 526 787 controls (312 162 female [59.3%]) were included in this analysis: 552 patients with CSC and 343 461 controls were identified in the FinnGen study, 103 patients with CSC and 178 573 controls were identified in the EstBB, and 521 patients with chronic CSC and 3577 controls were included in ameta-analysis. Two previously reported CSC risk loci were replicated (near CFH and GATA5) and 3 novel loci were identified (near CD34/46, NOTCH4, and PREX1). The CFH and NOTCH4 loci were associated with AMD but in the opposite direction. Prioritized genes showed increased expression in cultured choroidal endothelial cells compared with other genes in the loci (median [IQR] of log 2 [counts per million], 7.3 [0.6] vs 4.7 [3.7]; P =.004) and were differentially expressed in choroidal vascular endothelial cells in single-cell RNA sequencing data (mean [SD] fold change, 2.05 [0.38] compared with other cell types; P < 7.1 x 10(-20)). A PGS for AMD was predictive of reduced CSC risk (odds ratio, 0.76; 95% CI, 0.70-0.83 per +1 SD in AMD-PGS; P = 7.4 x 10(-10)). This association may have been mediated by loci containing complement genes.CONCLUSIONS AND RELEVANCE In this 3-cohort genetic association study, 5 genetic risk loci for CSC were identified, highlighting a likely role for genes involved in choroidal vascular function and complement regulation. Results suggest that polygenic AMD risk was associated with reduced risk of CSC and that this genetic overlap was largely due to loci containing complement genes.Ophthalmic researc

Central serous chorioretinopathy : from pathogenesis to treatment

The aim of this thesis is to increase the understanding of genetic and clinical aspects of central serous chorioretinopathy, a common and mysterious chorioretinal disease. Moreover, more insight into the optimal treatment for central serous chorioretinopathy is provided, since this thesis includes the first randomised controlled trial assessing the outcome of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment. As central serous chorioretinopathy mainly occurs in middle-aged professionally active patients, and can lead to progressive decline in visual acuity and vision-related quality of life, gaining knowledge on the disease and its treatment is of great importance. </table

Central serous chorioretinopathy : from pathogenesis to treatment

The aim of this thesis is to increase the understanding of genetic and clinical aspects of central serous chorioretinopathy, a common and mysterious chorioretinal disease. Moreover, more insight into the optimal treatment for central serous chorioretinopathy is provided, since this thesis includes the first randomised controlled trial assessing the outcome of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment. As central serous chorioretinopathy mainly occurs in middle-aged professionally active patients, and can lead to progressive decline in visual acuity and vision-related quality of life, gaining knowledge on the disease and its treatment is of great importance. </table

Central serous chorioretinopathy : from pathogenesis to treatment

The aim of this thesis is to increase the understanding of genetic and clinical aspects of central serous chorioretinopathy, a common and mysterious chorioretinal disease. Moreover, more insight into the optimal treatment for central serous chorioretinopathy is provided, since this thesis includes the first randomised controlled trial assessing the outcome of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment. As central serous chorioretinopathy mainly occurs in middle-aged professionally active patients, and can lead to progressive decline in visual acuity and vision-related quality of life, gaining knowledge on the disease and its treatment is of great importance. The research described in this thesis was financially supported by Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Landelijke Stichting voor Blinden en Slechtzienden, Retina Nederland Onderzoek Fonds, Stichting Blinden-Penning, and Stichting Macula Fonds (which all contributed through UitZicht), Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting Leids Oogheelkundig Ondersteuningsfonds, and Stichting Ooglijders. Moreover, support was received from a Gisela Thier Fellowship of Leiden University and a VENI grant of the Netherlands Organisation for Scientific Research, which were awarded to prof. dr. C.J.F. Boon to fund this research line.LUMC / Geneeskund

Comment on 'Comparison of subthreshold micropulse laser (577 nm) treatment and half-dose photodynamic therapy in patients with chronic central serous chorioretinopathy'

Ophthalmic researc

Serous maculopathy with absence of retinal pigment epithelium (SMARPE)

Ophthalmic researc