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Danial Mohabati,1,2 Elon HC van Dijk,1 Thomas J van Rijssen,1 Eiko K de Jong,3 Myrte B Breukink,3 Jose P Martinez-Ciriano,4 Greet Dijkman,1 Carel B Hoyng,3 Sascha Fauser,5 Suzanne Yzer,4 Camiel JF Boon1,6 1Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; 2Department of Ophthalmology, Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands; 3Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; 4Department of Ophthalmology, The Rotterdam Eye Hospital, Rotterdam, the Netherlands; 5Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany; 6Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands Purpose: To describe a spectrum of severe chronic central serous chorioretinopathy (cCSC) cases and their response to photodynamic therapy (PDT).Patients and methods: A total of 66 patients (81 eyes) with active severe cCSC were studied, and their response to PDT was compared with a control group consisting of 35 active cCSCs (37 eyes) that did not display characteristics of severity. Best-corrected visual acuity (BCVA) and complete resolution of subretinal fluid (SRF) were considered as main outcome measures.Results: In severe cCSC cases, we found cumulative areas of diffuse atrophic retinal pigment epithelium alterations in 48 eyes (59%), multiple “hot spots” of leakage in 36 eyes (44%), posterior cystoid retinal degeneration in 25 eyes (31%), and 13 eyes (16%) had a diffuse leakage on fluorescein angiography. After PDT treatment, BCVA increased in both groups, from 66 to 72 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the case group (P

Danial Mohabati,1,2 Thomas J van Rijssen,1 Elon HC van Dijk,1 Gregorius PM Luyten,1 Tom O Missotten,3 Carel B Hoyng,4 Suzanne Yzer,3 Camiel JF Boon1,5 1Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; 2Department of Ophthalmology, Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands; 3Department of Ophthalmology, The Rotterdam Eye Hospital, Rotterdam, the Netherlands; 4Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; 5Department of Ophthalmology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands Purpose: The aim of this study was to investigate disease onset and disease progression in patients with severe chronic central serous chorioretinopathy (cCSC). Patients and methods: The medical records of 143 cCSC patients (199 eyes) were reviewed. All cases had visual complaints for >6 months and showed signs of a severe disease phenotype on optical coherence tomography (OCT) and fluorescein angiography (FA). Clinical presentation at onset was evaluated, together with disease progression on multimodal imaging and final treatment outcome. Results: Twenty-eight cases (14%) had a documented history of an acute episode of CSC, whereas 145 cases (73%) showed pre-existing features of chronicity already at first presentation. The first clinical presentation could not be evaluated in 13% of cases. Best-corrected visual acuity (BCVA) was 70 ± 18 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at onset and 70 ± 22 ETDRS letters at final visit (p = 0.770). Among all studied cases, 173 eyes (87%) were treated, which resulted in complete resolution of subretinal fluid (SRF) in 76% of eyes at final visit. In eyes with fluorescein angiographic follow-up, the area of diffuse atrophic retinal pigment epithelium (RPE) abnormalities (diffuse atrophic RPE alterations [DARA]) had increased significantly in 43 eyes (68%) at final visit. Conclusion: CSC encompasses a clinical spectrum that includes a range of severe phenotypes, in which retinal abnormalities tend to be progressive. Nevertheless, the long-term visual acuity may remain fairly stable with treatment. Few patients with severe chronic CSC have a history of acute CSC, which could indicate that there may be pathogenetic differences between these 2 CSC variants. Keywords: chronic central serous chorioretinopathy, long-term outcome, severity, treatment, photodynamic therapy, posterior cystoid retinal degeneration

Wing H Chung,1 Elon H C van Dijk,1 Danial Mohabati,1 Greet Dijkman,1 Suzanne Yzer,2 Eiko K de Jong,3 Sascha Fauser,4 Reinier O Schlingemann,5–7 Carel B Hoyng,3 Camiel J F Boon1,5 1Department of Ophthalmology, Leiden University Medical Center, Leiden, 2Rotterdam Eye Hospital, Rotterdam, 3Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; 4Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany; 5Department of Ophthalmology, 6Ocular Angiogenesis Group, Departments of Ophthalmology and Cell Biology and Histology, Academic Medical Center, 7Netherlands Institute for Neuroscience, Amsterdam, the Netherlands Purpose: To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. Patients and methods: Medical records of 381 patients were analyzed to identify the cases. The main outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and change in central retinal thickness (CRT). These parameters were reviewed at baseline, first follow-up visit, and after 6, 12, and 24 months. Results: Out of 381 patients, 29 cases (8%) were included (of whom 3 had polypoidal choroidal vasculopathy [PCV]) who were treated with anti-vascular endothelial growth factor (anti-VEGF) therapy which was supplemented by photodynamic therapy (PDT) in the PCV patients. Overall, no statistically significant change in mean BCVA was observed during follow-up. BCVA improved or remained stable (defined as a gain in BCVA, a stable BCVA, or a loss of

Polypoidal choroidal vasculopathy (PCV) is an aneurismal type of macular neovascularization that show similarities with age-related macular degeneration and diseases that are part of the pachychoroid disease spectrum. Exudative changes in PCV can be treated with intravitreal anti-vascular endothelial growth factor monotherapy; however, a combination therapy with photodynamic therapy may be required. In this systematic review and meta-analysis, we evaluated the efficacy of faricimab for PCV. We searched 12 literature databases for eligible studies. All study evaluation and data extraction were made by two authors in duplicate. Studies eligible for analysis were included for a qualitative and quantitative review. We identified seven studies with data from 150 eyes with PCV, five studies were of treatment-naïve eyes who were commenced in faricimab monotherapy, and two studies were of switch-over to faricimab from other anti-VEGF drugs. After faricimab loading dose in treatment-naïve eyes, the best-corrected visual acuity (BCVA) remained stable at -0.09 (95% CI: -0.20-0.03) logMAR, central retinal thickness (CRT) decreased -169 (95% CI: -311--27) μm, and 48.7 (95% CI: 32.5-65.0) % of eyes obtained polyp closure. In switch-over eyes, 57%-67% experienced fluid reduction and 21% were able to extend their treatment interval. In conclusion, faricimab monotherapy for PCV leads to acceptable clinical outcomes in terms of stable BCVA, reduction of CRT, and high incidence of polyp closure. Some cases may benefit from a switch to faricimab. However, long-term efficacy studies and controlled comparative studies are warranted., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A variety of daily activities can intentionally or unintentionally cause the Valsalva manoeuvre, which induces a physiological response of elevated peripheral venous pressure. Studies have speculated that it may ultimately affect the choroidal anatomy. This is particularly important from a clinical point-of-view since patients occasionally hold their breath while undergoing macular optical coherence tomography (OCT). In this study, we systematically reviewed the literature to understand the impact of the Valsalva manoeuvre on the choroid and conducted meta-analyses on the changes induced in the subfoveal choroidal thickness (SFCT) and the choroidal vascularity index (CVI). We searched 12 literature databases for studies in healthy participants undergoing Valsalva manoeuvre with choroidal OCT scans before and during the manoeuvre. Seven studies with a total of 444 eyes of 279 individuals were eligible for the review. The Valsalva manoeuvre led to a statistically significant but numerically small increase in the SFCT of 6.5 μm (95% CI: 1.6-11.4 μm; p = 0.01) and a statistically significant increase in the CVI of 1.48 (95% CI: 1.23-1.73; p = 0.0002). Thus, the Valsalva manoeuvre has a measurable impact on the choroid, and we recommend careful observation of how the patient sits and behaves behind the OCT scanner while scanning in order to allow accurate measurements of the choroid for diagnosis and monitoring., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Identifying macular neovascularization (MNV) in eyes with central serous chorioretinopathy (CSC) has important implications for its management. Optical coherence tomography angiography (OCTA) is increasingly used for this purpose. Here, we systematically reviewed the literature and conducted meta-analysis to determine the diagnostic accuracy of OCTA for detecting MNV in eyes with CSC. We systematically searched the literature in 12 databases for relevant studies from database inception until 18 November 2023. Eligible studies had eyes with CSC with MNV and CSC without MNV. Index test was OCTA. Reference test was retinal dye angiography. Study selection and data extraction were performed in duplicate, and study was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2. Our main outcome of interest was the sensitivity and specificity of OCTA for detecting MNV in CSC. Pooled diagnostic test accuracy estimates were computed using MetaDTA. Of 177 records screened, seven fulfilled the eligibility criteria for our study. These studies summarized data from a total of 1061 eyes. Summary estimate sensitivity and specificity to diagnose MNV in eyes with CSC using OCTA was 92.9% (95% CI: 81.7%-97.5%) and 99.4% (95% CI: 84.1%-100.0%), respectively. The main source of bias across studies was the reference standard, as four studies used multimodal imaging including OCTA for the reference standard. OCTA alone is excellent for detecting MNV in CSC compared to retinal dye angiography or multimodal imaging. Using OCTA first before considering retinal dye angiography could potentially save an important number of retinal dye angiographies., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Central serous chorioretinopathy (CSC) is a frequently occurring chorioretinal disease, that is commonly associated with subretinal fluid accumulation in a generally young population. Even though choroidal abnormalities have been found to be of importance, the exact pathogenesis of CSC is still being learned. The origin of pigment epithelial detachments, seen in many CSC patients, is also unclear. Based on the follow-up of a CSC patient for more than 5 years, we hypothesize that intraocular pressure and, by extension, the pressure gradient across the Bruch's membrane, may be one factor in the pathogenesis of pigment epithelial detachments in CSC, which might very well have implications for the occurrence of and possible ways to prevent subretinal fluid in CSC., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy. Understanding risk factors for CSC is important for disease prevention and to provide evidence-based advice to patients. In this study, we systematically reviewed the literature and performed meta-analysis on the association between tobacco consumption and CSC. We searched 12 literature databases on May 5, 2024, and identified 11 eligible studies of 27 595 patients with CSC and 105 354 control individuals. Studies were predominantly clinic-based case-control studies. We calculated a summary estimate of tobacco consumption as a risk factor for CSC at an odds ratio of 2.99 (95% CI: 1.82-4.93, p = 0.000017), which remained statistically significant in the sensitivity analyses. The exact mechanism by which tobacco consumption contribute to the pathophysiology of CSC remains unclear, although several potential hypotheses exist. However, tobacco consumption is a modifiable behaviour and tobacco cessation is an actionable advice with which patients with CSC themselves can play a large role in disease management. Further studies are warranted to understand the impact of tobacco cessation for risk modification and for the prognosis of patients who already have CSC., (© 2024 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objectives: To assess the mismatch between the clinical observation of vitreous alterations and self-reported symptoms in young patients complaining of symptomatic vitreous opacities (SVO). Methods: The ophthalmic medical records of young patients presenting primarily with SVO were retrospectively evaluated. Symptoms severity was assessed using a questionnaire. The status of the vitreous body was examined with indirect ophthalmoscopy at the slit-lamp and classified according to an ad hoc severity scale. Results: Sixty eyes of thirty otherwise healthy patients (median age: 32.5 (IQR: 29.0-37.0) years old) complaining of SVO (median duration: 38 months; interquartile range: 18-84 months) were enrolled. SVO was rated as severe by 50% of participants, affecting all the activities explored in the questionnaire. Twenty-three patients (76.6%) reported SVO-related depression and/or anxiety, for which eleven patients (36.6%) were or had been using medication. Fifty-eight eyes (96.6%) showed no evidence of (or minimal) vitreous opacity, while two eyes (3.3%) were found to have significant vitreous opacity. No significant inter-gender differences ( p > 0.05) and no significant differences ( p > 0.05) were found between the severity of vitreous opacity and patients' reported symptoms nor with their psychological status and medication use. Conclusions: Severe discomfort related to the perception of vitreous floaters exists in young patients whose vitreous gel examination is unremarkable or shows only minor alterations. We believe this discrepancy can be explained by optical anisotropy; significant forward-scattering of light, which results in floater symptoms; and reduced back reflection, which limits the clinical observation.

Purpose: Choroidal vascular hyperpermeability (CVH) on indocyanine green angiography (ICGA) is a hallmark feature of central serous chorioretinopathy (CSC). We identified three distinct CVH phenotypes in CSC: uni-focal indistinct signs of choroidal hyperpermeability (uni-FISH) with one focal area of CVH, multiple areas of focal CVH (multi-FISH), and diffuse hyperpermeability covering most of the posterior pole (DISH). This report investigates the distribution of these phenotypes and their association with signs of disease chronicity., Methods: The CERTAIN study is a monocentric, retrospective study on consecutive CSC patients referred to a large tertiary referral centre that underwent ultra-widefield (UWF) and 55° ICGA. Two independent graders assessed CVH patterns based on mid- to late-phase UWF and 55° ICGA with a third grader acting as referee., Results: Of the 167 eyes of 91 patients included in this study, 43 (26%) showed uni-FISH, 87 (52%) multi-FISH, and 34 (20%) showed DISH based on UWF ICGA. Median age (40 vs. 45 vs. 57; p < 0.001) and logMAR visual acuity (0 vs. 0 vs. 0.1, p < 0.001) differed significantly in-between groups, as did the occurrence of cystoid retinal degeneration (PCRD; 0% vs. 1% vs. 18%, p < 0.001) or diffuse atrophic RPE alterations (DARA; 0% vs. 17% vs. 29%, p < 0.001). The same was true when grading was based on 55° ICGA., Conclusions: The CVH patterns of uni-FISH, multi-FISH, and DISH are typical of CSC. These patterns correlate with established signs of CSC chronicity. Their predictive role in treatment response and prognosis remains to be evaluated., (© 2024 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

The pachychoroid disease spectrum is a phenotype characterized by alterations in choroidal vasculature which result in outer retinal and choriocapillaris damage and visual loss. The presence of pachyvessels is one of the key features of the pachychoroid phenotype. Recent imaging studies suggest that pachyvessels may form because of choroidal venous congestion in one or more quadrants. The formation of intervortex anastomosis may function as a compensatory mechanism to dissipate the increased venous pressure, while outflow obstruction has been hypothesized to occur at the site of the vortex vein exiting the sclera. This review aims to summarize recent imaging findings and discuss evolution in the understanding of pathogenesis of the pachychoroid disease spectrum. We have summarized notable treatment trials in central serous chorioretinopathy and polypoidal choroidal vasculopathy and included an update of the current diagnostic and management strategies of the entities that are part of the pachychoroid disease spectrum., (© 2024. The Author(s).)

Purpose: The purpose of this study was to investigate the presence of sex-steroid receptors in human choroidal tissue across different ages and sex, aiming to better understand the pronounced sex difference in central serous chorioretinopathy (CSC) occurrence., Methods: Paraffin-embedded enucleated eyes of 14 premenopausal women, 15 postmenopausal women, 10 young men (<45 years), and 10 older men (>60 years) were used. A clinically certified immunostaining was performed to detect the presence of the androgen receptor (AR), progesterone receptor (PR; isoform A and B), and estrogen receptor (ERα). The stained slides were scored in a blinded manner for positive endothelial cells and stromal cells in consecutive sections of the same choroidal region., Results: Our analysis revealed the presence of AR, PR, and ERα in endothelial cells and stromal cells of choroidal tissue. The mean proportion of AR-positive endothelial cells was higher in young men (46% ± 0.15) compared to aged-matched women (29% ± 0.12; P < 0.05, 95% confidence interval [CI]). Premenopausal women showed markedly lower mean proportion of ERα (5% ± 0.02) and PR-positive endothelial cells (2% ± 0.01) compared to postmenopausal women (15% ± 0.07 and 19% ± 0.13; both P < 0.05, 95% CI), young men (13% ± 0.04 and 21% ± 0.10; both P < 0.05, 95% CI), and older men (18% ± 0.09 and 27% ± 0.14; both P < 0.05, 95% CI). Mean PR-positive stromal cells were also less present in premenopausal women (12% ± 0.07) than in other groups., Conclusions: The number of sex-steroid receptors in the choroidal tissue differs between men and women across different ages, which aligns with the prevalence patterns of CSC in men and postmenopausal women.

An ongoing global shortage of verteporfin (Visudyne ® ) limits the treatment possibilities for several chorioretinal diseases, including central serous chorioretinopathy, choroidal hemangioma, and polypoidal choroidal vasculopathy. Verteporfin is required to perform photodynamic therapy in these ocular diseases. Therefore, the current situation has a substantial impact on eye care worldwide. The worldwide supply of verteporfin appears to be manufactured by a single factory, which is situated in the United States. The distribution of verteporfin is done by different companies for different regions of the world. Official communication on the shortage by the responsible companies has been scarce and over the past years several promises with regards to resolution of the shortage have not been fulfilled. The delivery of new batches of verteporfin is at irregular intervals, unpredictable, and may not be fairly balanced between different regions or countries in the world. To ensure a fair distribution of available verteporfin within a country, several measures can be taken. In the Netherlands, a national committee, consisting of ophthalmologists, is in place to arrange this. On the European level, the European Union and European Medicine Agency have plans to monitor medicine shortages more closely and to intervene if necessary. With a more intensified monitoring and regulation of medicine supplies, future impending shortages may be prevented. Remarkably, the amount of medicine shortages is increasing, having a significant and sometimes irreversible impact on patient care. Thus, efforts should be undertaken to minimize the consequences and, whenever possible, to prevent future medicine shortages., (© 2024. The Author(s).)

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC., Competing Interests: Declaration of competing interest Bailey Freund is an consultant for Bayer, Genentech, Heidelberg Engineering, Nidek, Novartis, Regeneron, and Zeiss. The author authors declare not to have conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To compare intra- and postoperative results of sutureless scleral fixated Carlevale intraocular lens (IOL) with iris fixated Artisan IOL., Methods: Monocentre, retrospective analysis of refractive outcomes and intra- and postoperative complications of patients who received a Carlevale or Artisan IOL between January 2019 and March 2022., Results: 178 eyes of 169 patients were included (101 Carlevale and 77 Artisan IOLs). The standard follow-up time was 1 month. Two statistically significant differences were found: in the deviation of the postoperative spherical equivalent of the refraction from the preoperative chosen IOL target (p = 0.019; mean deviation was -0.46 in the Carlevale and 0.08 in the Artisan group), and the number of eyes with complications between the Carlevale and Artisan groups (p = 0.003; 33 in the Carlevale and 42 in the Artisan group)., Conclusion: The current study is the largest so far comparing both refractive outcomes and complications after implantation of Carlevale and Artisan IOL. The Carlevale IOL does not carry a greater complication risk on the short-term follow-up. This provides additional evidence that the Carlevale IOL has to be added to the armamentarium of the ophthalmic surgeon., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Aim: To adopt a novel artificial intelligence (AI) optical coherence tomography (OCT)-based program to identify the presence of biomarkers associated with central serous chorioretinopathy (CSC) and whether these can differentiate between acute and chronic central serous chorioretinopathy (aCSC and cCSC)., Methods: Multicenter, observational study with a retrospective design enrolling treatment-naïve patients with aCSC and cCSC. The diagnosis of aCSC and cCSC was established with multimodal imaging and for the current study subsequent follow-up visits were also considered. Baseline OCTs were analyzed by an AI-based platform (Discovery® OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). This software allows to detect several different biomarkers in each single OCT scan, including subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HF) and flat irregular pigment epithelium detachment (FIPED). The presence of SRF was considered as a necessary inclusion criterion for performing biomarker analysis and OCT slabs without SRF presence were excluded from the analysis., Results: Overall, 160 eyes of 144 patients with CSC were enrolled, out of which 100 (62.5%) eyes were diagnosed with cCSC and 60 eyes (34.5%) with aCSC. In the OCT slabs showing presence of SRF the presence of biomarkers was found to be clinically relevant (> 50%) for HF and FIPED in aCSC and cCSC. HF had an average percentage of 81% (± 20) in the cCSC group and 81% (± 15) in the aCSC group (p = 0.4295) and FIPED had a mean percentage of 88% (± 18) in cCSC vs. 89% (± 15) in the aCSC (p = 0.3197)., Conclusion: We demonstrate that HF and FIPED are OCT biomarkers positively associated with CSC when present at baseline. While both HF and FIPED biomarkers could aid in CSC diagnosis, they could not distinguish between aCSC and cCSC at the first visit. AI-assisted biomarker detection shows promise for reducing invasive imaging needs, but further validation through longitudinal studies is needed., (© 2024. The Author(s).)

Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: Choroidal venous overload was recently suggested to be a pathogenetic factor in central serous chorioretinopathy (CSC). Manifestations of venous overload on ultrawidefield indocyanine green angiography (UWF ICGA) include asymmetric arterial choroidal filling (AACF), enlarged choroidal vessels ("pachyvessels"), and asymmetric venous drainage (AVD) leading to choroidal intervortex venous anastomoses (CVAs) accompanied by choroidal vascular hyperpermeability (CVH). The purpose of the current study is to assess the presence of these signs of venous overload in a large cohort of CSC patients., Design: Monocentric retrospective cohort study., Participants: Consecutive CSC patients seen at a large tertiary referral center., Methods: For the CERTAIN study, patients underwent a standardized imaging protocol including UWF ICGA. Features of choroidal venous overload were graded for each eye individually by 2 independent graders and, in case of disagreement, by a third grader., Main Outcome Measures: Presence of AAFC, pachyvessels, AVD, CVA, and CVH., Results: In total, 178 eyes of 91 patients were included in this study. Mean patient age was 47.6 (± 12.0) years and 75 patients (82%) were male. The 116 eyes (65%) that showed subretinal fluid were considered affected (bilateral disease in 29 patients). In affected eyes, AACF was present in 62 eyes (85% of gradable eyes), pachyvessels in 102 eyes (88%), AVD in 81 eyes (74%), CVA in 107 eyes (94%), and CVH in 100% of affected eyes. For fellow eyes, prevalence of pachyvessels (94%), AVD (67%), and CVA (90%) was similar to affected eyes, whereas CVH was present in 85% of fellow eyes. Intergrader agreement was excellent for CVH (94%), and 74%-82% for all other criteria. Patients with pachyvessels and AVD in 1 eye were more likely to also show the same characteristic in the fellow eye (odds ratios 22.2 and 9.9, P < 0.01)., Conclusions: Signs of venous overload are seen in the vast majority of CSC patients, both in affected and unaffected eyes. Although pachyvessels, AVD, and CVA are observed frequently, CVH was observed in all affected eyes, showed excellent intergrader reliability, and is diagnostic for CSC. This supports the concept of choroidal venous overload as a major factor in CSC pathogenesis., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To identify optical coherence tomography (OCT) features to predict the course of central serous chorioretinopathy (CSC) with an artificial intelligence-based program., Methods: Multicenter, observational study with a retrospective design. Treatment-naïve patients with acute CSC and chronic CSC were enrolled. Baseline OCTs were examined by an artificial intelligence-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). Through this platform, automated retinal layer thicknesses and volumes, including intaretinal and subretinal fluid, and pigment epithelium detachment were measured. Baseline OCT features were compared between acute CSC and chronic CSC patients., Results: One hundred and sixty eyes of 144 patients with CSC were enrolled, of which 100 had chronic CSC and 60 acute CSC. Retinal layer analysis of baseline OCT scans showed that the inner nuclear layer, the outer nuclear layer, and the photoreceptor-retinal pigmented epithelium complex were significantly thicker at baseline in eyes with acute CSC in comparison with those with chronic CSC ( P < 0.001). Similarly, choriocapillaris and choroidal stroma and retinal thickness (RT) were thicker in acute CSC than chronic CSC eyes ( P = 0.001). Volume analysis revealed average greater subretinal fluid volumes in the acute CSC group in comparison with chronic CSC ( P = 0.041)., Conclusion: Optical coherence tomography features may be helpful to predict the clinical course of CSC. The baseline presence of an increased thickness in the outer retinal layers, choriocapillaris and choroidal stroma, and subretinal fluid volume seems to be associated with acute course of the disease.

Purpose: To systematically review and report the rate of exudative progression over time in patients with nonexudative macular neovascularization (MNV) in age-related macular degeneration (AMD)., Design: Systematic review with prevalence meta-analyses and individual participant meta-analysis., Methods: We searched 10 literature databases on March 26, 2023, for studies of consecutive patients with treatment-naïve nonexudative MNV in AMD. The primary outcome of interest was time from diagnosis to exudative progression. We conducted meta-analyses on the prevalence of exudative progression at 1 and 2 years. Where possible, we extracted individual participant data from studies and conducted an individual participant meta-analysis and explored the exudative progression using a time-to-event curve., Results: We identified 16 eligible studies with a total of 384 eyes with nonexudative MNV. Exudative progression had occurred in 20.9% (95% CI 13.1%-29.8%) of eyes at 1 year and in 30.7% (95% CI 21.8%-40.4%) at 2 years. Similar results were observed in the individual participant meta-analysis, showing exudative progression in 18.9% (95% CI 13.5%-26.3%) of eyes at 1 year and 31.3% (95% CI 24.2%-40.0%) at 2 years. Risk factors for a fast exudative progression were the presence of subretinal lipid globules, large MNV areas, rapid MNV growth, growth in pigment epithelium detachment height and width, appearance of a branching pattern, and development of a hyporeflective halo around the MNV., Conclusions: Nonexudative MNVs in AMD are at high risk of exudative progression. Recognition of these lesions may allow for better individualized follow-up regimens in which closer monitoring may facilitate earlier diagnosis of exudative progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The presence of peripapillary intraretinal fluid (IRF) has a broad differential diagnosis, including several types of neovascular and pachychoroid-related diseases. However, the clinician may encounter cases without signs of neovascular or pachychoroid disease, or any other previously described diagnosis. For these patients, we propose the term NOn-Pachychoroid PEripapillary Schisis (NOPPES) of the retina, and we discuss the differential diagnosis., Design: A retrospective chart study set in a tertiary referral center for retinal diseases in Amsterdam, the Netherlands., Methods: Using multimodal imaging, cases suspected of peripapillary pachychoroid syndrome were reviewed. Cases without signs of neovascular or pachychoroid disease were included in this study. These cases were discussed in a group of senior retinal specialists to establish a diagnosis, and if there was no evidence for any previously described diagnostic entity, these cases were categorized as NOPPES., Results: Four cases of NOPPES were identified, 3 female patients and 1 male patient, aged between 58 and 75 years. Two patients were myopic, and 1 patient had a mild hyperopia. Three out of 4 cases showed unilateral peripapillary IRF, and 1 case had bilateral IRF. No improvement was seen after intravitreal bevacizumab or aflibercept, nepafenac eye drops, oral acetazolamide, vitrectomy with internal limiting membrane peeling, or surgery for carotid stenosis. One case showed a reduction in IRF after starting prednisolone eye drops., Conclusions: We describe NOPPES, a new form of peripapillary schisis-like IRF. NOPPES seems relatively therapy-resistant. More research is needed to delineate the clinical spectrum of NOPPES and its pathogenesis and treatment., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Competing Interests: The authors have no funding or conflicts of interest to declare.

Purpose: To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy)., Methods: Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed., Results: Eighteen eyes from 18 patients (mean age: 28 ± 19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10 of 18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth., Conclusion: SMACH seems to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, the authors propose renaming this entity "stellate multiform amelanotic choroidopathy," a name that retains its previous abbreviation "SMACH."

Purpose: This study is to assess the possible correlation between findings on fundus autofluorescence (FAF) and fluorescein angiography (FA) in patients with chronic central serous chorioretinopathy (cCSC)., Methods: This multicentre retrospective cohort study included 71 cCSC patients (92 eyes) with at least 6 months of follow-up, who had a FAF-FA imaging discrepancy larger than 0.5 optic disc diameters in size in the corresponding areas of hyperfluorescent abnormalities. A comparison was performed between progression in size of areas of hyperautofluorescent retinal pigment epithelium (RPE) abnormalities on FAF (HF-FAF) and the hyperfluorescent areas on FA (HF-FA) at first visit and last visit. The possible correlations were estimated between FAF-FA discrepancy and disease characteristics., Results: The median area of HF-FAF at first visit was 7.48 mm 2 (1.41-27.9). The median area of HF-FA at first visit and last visit was 2.40 mm 2 (0.02-17.27) and 5.22 mm 2 (0.53-25.62), respectively. FAF-FA discrepancy was associated with follow-up duration and the area of HF-FAF at first visit. A mathematical algorithm for grading FAF-FA discrepancy in time was suggested, which predicted the enlargement of hyperfluorescent RPE abnormalities on FA in 82.6% of cases., Conclusion: There is a statistically significant relationship between the areas of HF-FAF and HF-FA in cCSC patients with FAF-FA imaging discrepancy at first presentation. Long-term changes in RPE alterations in cCSC on FA can be predicted based on baseline HF-FAF and follow-up duration., (© 2023. The Author(s).)

Purpose: We performed a multicenter, retrospective study on patients with bilateral chronic central serous chorioretinopathy (cCSC) who received single-session bilateral reduced-settings photodynamic therapy (ssbPDT) and assessed anatomical (resolution of subretinal fluid [SRF]) and functional (best-corrected visual acuity [BCVA]) outcomes and safety., Methods: Patients who underwent ssbPDT between 01/01/2011 and 30/09/2022 were included. The resolution of SRF at first, second, and final follow-up was assessed on optical coherence tomography (OCT), and BCVA measurements were collected at these visits. When fovea-involving ssbPDT was performed, ellipsoid zone (EZ) and external limiting membrane (ELM) integrity was graded before and after treatment., Results: Fifty-five patients were included in this study. Sixty-two of hundred and eight eyes (56%) showed a complete resolution of SRF at the first follow-up, which increased to 73/110 (66%) at the final follow-up. The mean logMAR BCVA improved by -0.047 ( P = 0.02) over follow-up. EZ integrity increased from 14/21 (67%) to 24/30 (80%) while ELM integrity increased from 22/30 (73%) to 29/30 (97%)., Conclusion: Patients with cCSC with bilateral SRF at baseline showed significant anatomical and functional improvements after ssbPDT, both at short-term and long-term follow-up. No relevant adverse events were noted., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Background: Systematic literature searches are the cornerstone of systematic reviews. In this study, we evaluated database coverage of randomized clinical trials for central serous chorioretinopathy (CSC)., Methods: We searched 12 databases (BIOSIS Previews, CINAHL, the Cochrane Central, Current Contents Connect, Data Citation Index, Derwent Innovations Index, EMBASE, KCI-Korean Journal Database, MEDLINE, PubMed, SciELO Citation Index, and Web of Science Core Collection) on 10 April 2023 for randomized clinical trials for CSC. After identifying all eligible studies across all databases, we investigated the coverage of these studies within each database, including the coverage of any combination of two databases., Results: The 12 databases yielded 848 records for screening, of which 76 were randomized clinical trials for CSC. No single database provided full coverage. The most comprehensive coverage was provided by EMBASE (88%), the Cochrane Central (87%), and PubMed (75%). A combined search in the Cochrane Central and PubMed led to complete coverage (100%) while reducing the number of records for screening from 848 to 279., Conclusions: Systematic review search design should include multiple databases. For randomized clinical trials for CSC, the combination of the Cochrane Central and PubMed provides an excellent balance between coverage and workload.

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 a meta-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 a meta-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 a meta-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 × 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 × 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.

Importance: Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring., Objective: To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses., Data Sources: A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022., Study Selection: Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.)., Data Extraction and Synthesis: Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.)., Main Outcomes and Measures: Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD., Results: Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies., Conclusions and Relevance: Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.

Purpose: A retrospective study was performed with data from the prospective randomized controlled trials, PLACE and SPECTRA, assessing the risk of foveal atrophy and the likelihood of structural and functional improvement on optical coherence tomography, after foveal half-dose photodynamic therapy in chronic central serous chorioretinopathy., Methods: A total of 57 chronic central serous chorioretinopathy patients received a single half-dose photodynamic therapy with a treatment spot that included the fovea. Optical coherence tomography scans and fundus autofluorescence images were analyzed for structural improvement and possible atrophy development, at baseline and at several visits after treatment. Main outcome measures were integrity of the external limiting membrane and ellipsoid zone on optical coherence tomography and hypoautofluorescence on fundus autofluorescence., Results: The subfoveal external limiting membrane was graded as continuous in 21 of 57 of patients (36.8%) at baseline, and the subfoveal ellipsoid zone was graded as continuous in 5 of 57 patients (8.8%) at first visit, which improved to 50 of 51 (98.0%) and 32 out of 51 (62.7%) at the final visit at 2 years, respectively (both P < 0.001). Hypoautofluorescent changes on fundus autofluorescence were present in 25 of 55 patients (45.5%) at baseline and in 23 of 51 patients (45.1%) at the final visit ( P = 0.480)., Conclusion: In patients with chronic central serous chorioretinopathy who received a single, foveal, half-dose photodynamic therapy, a significant improvement in structure and function was seen at the final follow-up. None of the patients developed foveal atrophy., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short-term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta-analyses to compare to non-treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half-dose or half-fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half-dose or half-fluence PDT (OR: 20.6; 95% CI: 6.3-66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0-655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7-6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best-corrected visual acuity was only obtained by half-dose/-fluence PDT (-0.13 logMAR; 95% CI: -0.20 to -0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half-dose/-fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long-term data available for PDT-based treatments finding persisting treatment results, half-dose or half-fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Comparing anatomic and functional efficacy and safety of primary treatment with either half-dose photodynamic therapy (PDT) or oral eplerenone, or crossover treatment in chronic central serous chorioretinopathy patients., Methods: After the SPECTRA trial baseline visit, patients were randomized to either half-dose PDT or eplerenone and received crossover treatment if persistent subretinal fluid (SRF) on optical coherence tomography (OCT) was present at first follow-up (at 3 months). Presence of SRF and best-corrected visual acuity (BCVA) was evaluated at 12 months., Results: Out of the 90 patients evaluated at 12 months, complete SRF resolution was present on OCT in 43/48 (89.6%) of patients who were primarily randomized to half-dose PDT and in 37/42 (88.1%) who were primarily randomized to eplerenone. Out of the 42 patients that were primarily randomized to eplerenone, 35 received crossover treatment with half-dose PDT. The BCVA improved significantly more at 12 months in patients who had received primary half-dose PDT as compared to the primary eplerenone group (p = 0.030)., Conclusions: Twelve months after baseline visit, most patients treated with half-dose PDT (either primary or crossover treatment) still had complete SRF resolution. The long-term BCVA in patients who receive primary half-dose PDT is better than in patients in whom PDT is delayed due to initial eplerenone treatment with persistent SRF., (© 2022. The Author(s).)

Similar to ultrasound adapting soundwaves to depict the inner structures and tissues, optical coherence tomography (OCT) utilizes low coherence light waves to assess characteristics in the eye. Compared to the previous gold standard diagnostic imaging fluorescein angiography, OCT is a noninvasive imaging modality that generates images of ocular tissues at a rapid speed. Two commonly used iterations of OCT include spectral-domain (SD) and swept-source (SS). Each comes with different wavelengths and tissue penetration capacities. OCT angiography (OCTA) is a functional extension of the OCT. It generates a large number of pixels to capture the tissue and underlying blood flow. This allows OCTA to measure ischemia and demarcation of the vasculature in a wide range of conditions. This review focused on the study of four commonly encountered diseases involving the retina including age-related macular degeneration (AMD), diabetic retinopathy (DR), central serous chorioretinopathy (CSC), and macular telangiectasia (MacTel). Modern imaging techniques including SD-OCT, TD-OCT, SS-OCT, and OCTA assist with understanding the disease pathogenesis and natural history of disease progression, in addition to routine diagnosis and management in the clinical setting. Finally, this review compares each imaging technique's limitations and potential refinements.

Central serous chorioretinopathy (CSC) has remained an enigmatic disease since its initial description by Von Graefe. Over the years, multiple risk factors have been recognized: these include psychological stress, behavioral traits, and corticosteroids. The basic pathophysiology of CSC involves choroidal thickening, vascular congestion, altered choroidal blood flow (ChBF), and choroidal hyperpermeability, leading to retinal pigment epithelium decompensation and subsequent neurosensory detachment. Multiple organ systems, mainly the nervous, cardiovascular, endocrinal, and renal systems participate in the control of the vascular tone and the ChBF via hypothalamus-pituitary-adrenal axis and renin-angiotensin-aldosterone system, while others such as the hepatic system regulate the enzymatic degradation of corticosteroids. Many vasoactive and psychotropic drugs also modulate the ocular perfusion. In addition, there are anatomical and genetic predispositions that determine its progression to the chronic or recurrent form, through cellular response and angiogenesis. We herein review the basic pathophysiology and immunogenetics in CSC along with the role of multiple organ systems. With this background, we propose an etiological classification that should provide a framework for customized therapeutic interventions., Competing Interests: The authors declare that there are no conflicts of interests of this paper., (Copyright: © 2022 Taiwan J Ophthalmol.)

The pachychoroid disease spectrum (PDS) includes several chorioretinal diseases that share specific choroidal abnormalities. Although their pathophysiological basis is poorly understood, diseases that are part of the PDS have been hypothesized to be the result of venous congestion. Within the PDS, central serous chorioretinopathy is the most common condition associated with vision loss, due to an accumulation of subretinal fluid in the macula. Central serous chorioretinopathy is characterized by distinct risk factors, most notably a high prevalence in males and exposure to corticosteroids. Interestingly, sex differences and corticosteroids are also strongly associated with specific types of arteriovenous anastomoses in the human body, including dural arteriovenous fistula and surgically created arteriovenous shunts. In this manuscript, we assess the potential of such arteriovenous anastomoses in the choroid as a causal mechanism of the PDS. We propose how this may provide a novel unifying concept on the pathophysiological basis of the PDS, and present cases in which this mechanism may play a role., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option., Materials and Methods: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage., Results: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries., Conclusion: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare the efficacy and safety of crossover treatment to half-dose photodynamic therapy (PDT) and eplerenone treatment after the failure of primary treatment in patients with chronic central serous chorioretinopathy (cCSC)., Design: Multicenter crossover clinical trial., Subjects: At 3 months after the baseline visit of the SPECTRA (Half-Dose Photodynamic Therapy Versus Eplerenone: Treatment Trial for Chronic Central Serous Chorioretinopathy) randomized controlled trial, either half-dose PDT or eplerenone treatment was evaluated for each patient, and patients who still demonstrated subretinal fluid (SRF) were included in the current study, the SPECS (Central Serous Chorioretinopathy Treated with Half-Dose PDT or Eplerenone Crossover Study) trial., Methods: At the baseline visits for the current SPECS trial, crossover treatment was performed for patients who still demonstrated SRF. These patients received either half-dose PDT or oral eplerenone for 12 weeks. Both anatomic and functional parameters were evaluated 3 months after crossover treatment., Main Outcome Measures: Complete resolution of SRF on OCT., Results: Forty-nine patients were included in the SPECS trial (38 received primary eplerenone treatment; 11 received half-dose PDT). At 3 months after crossover treatment, 32 of 37 (86.5%) in the crossover to half-dose PDT group and 2 of 9 (22.2%) in the crossover to eplerenone group had complete SRF resolution (P = 0.030). The mean foveal sensitivity increased significantly more in the crossover to half-dose PDT group (mean, +3.08 dB) compared with the crossover to eplerenone group (mean, -0.27 dB; P = 0.009)., Conclusions: Patients with cCSC with the persistence of SRF after primary eplerenone treatment can benefit from half-dose PDT, which can induce a relatively fast and complete SRF resolution, along with an improvement in foveal sensitivity., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Intravitreal injections and cataract surgery are two common procedures in the elderly. Posterior capsular rupture (PCR) is a rare but important complication of cataract surgery. We systematically reviewed the literature on previous intravitreal injections as a risk factor of PCR and performed meta-analyses to provide pooled summary risk estimates., Methods: We searched 13 literature databases on 1 June 2021 for studies evaluating the risk of PCR in eyes undergoing cataract surgery with data on previous intravitreal injections. Data extraction was made independently by two authors and discussed afterwards until reaching consensus. Random effects meta-analyses on the pooled odds ratio (OR) of PCR in eyes with previous intravitreal injections were made using MetaXL 5.3., Results: Six studies on 1 051 097 eyes undergoing cataract surgery were eligible for the qualitative and quantitative review. Previous history of intravitreal injections was present in 7034 eyes (majority was anti-VEGF). Our meta-analyses revealed that any previous intravitreal injection was a risk factor for PCR with an OR of 2.30 (95% CI 1.39-3.81). For each previous intravitreal injection, the risk of PCR was OR 1.04 (95% CI 1.01-1.08) (equivalent of relative risk ~1.04). In other words, risk of PCR increases by 4% for each previous intravitreal injection., Conclusions: Previous intravitreal injection is a risk factor for PCR and should be taken into account when planning cataract surgery. However, to be regarded as a clinically significant risk of PCR, a substantial number of previous intravitreal injection (e.g. ≥10) should have been administered, considering that the a priori risk of PCR is very low (~1%)., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The purpose of this study was to provide an estimate of the number of current and future patients with polypoidal choroidal vasculopathy (PCV) in Europe. We systematically searched 11 literature databases on 18 May 2022 for studies on the prevalence of PCV among a consecutive and representative group of patients with suspected neovascular age-related macular degeneration (AMD). Prevalence of PCV in patients with suspected neovascular AMD was summarized and included in a prevalence meta-analysis. We then used current population data and population forecasts by Eurostat and the Office for National Statistics to determine current and future number of patients with neovascular AMD in Europe. Then, we calculated the number of patients with PCV with our calculated estimate of the prevalence of PCV among Europeans suspected with neovascular AMD. A total of five eligible studies were identified which included a total of 1359 patients. All these studies used the gold standard of indocyanine green angiography as a routine part of their diagnostic approach. Among patients undergoing detailed retinal examination for suspected neovascular AMD, our meta-analysis calculated the prevalence of PCV to be 8.3% (95% confidence interval: 6.8-9.8%). Our population estimates find that a total of 217,404 patients with PCV exist in Europe in the year 2022, which constitutes 0.04% of the entire population of Europe. This number is estimated to increase to 287,517 patients in the year 2040. Our estimates are important for different healthcare stakeholders, especially when planning and allocating expensive resources.

Cushing's syndrome is a rare disease with an endogenous cause of excess cortisol secretion. More evidence substantially links cortisol levels to the pachychoroid spectrum diseases. In this systematic review and meta-analysis, we summarize available evidence on pachychoroid spectrum diseases in patients with Cushing's syndrome. We performed a systematic literature search in 11 databases on 21 May 2022. Studies were considered eligible if they performed retinal examination of a consecutive group of patients with Cushing's syndrome using optical coherence tomography (OCT) scans. We extracted data on subfoveal choroidal thickness in patients with Cushing's syndrome compared to matched controls. We also extracted data on the prevalence of pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and polypoidal choroidal vasculopathy (PCV). We identified six eligible studies with a total of 159 patients with Cushing's syndrome. On average, patients with Cushing's syndrome have 49.5 µm thicker subfoveal choroidal thickness compared to matched healthy individuals. Pachychoroid spectrum diseases were relatively common in these patients: PPE in 20.8%, CSC in 7.7%, and PCV in 2.8%. We conclude that there should be low threshold to recommend ophthalmic examination to patients with Cushing's syndrome, and that a macular OCT is recommended during this examination.

Purpose: Comparing the effect of half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment on retinal pigment epithelial detachments (PEDs) in chronic central serous chorioretinopathy., Methods: This study included data from the PLACE trial, a prospective randomized controlled trial comparing half-dose photodynamic therapy and high-density subthreshold micropulse laser treatment in chronic central serous chorioretinopathy. Main outcome measurements were changes in both the foveal PED and the highest PED within the macula at baseline compared with first and final evaluation visit., Results: At baseline, a macular PED was detected in 76.9% of patients (123/160), and a PED within 1,500 µm from the foveal center in 37.5% of patients (60/160). In the half-dose photodynamic therapy arm (61 patients), there was a significantly larger decrease in the highest macular PED compared with the high-density subthreshold micropulse laser treatment arm (62 patients) at both first and final evaluation visits (P < 0.001 and P = 0.012, respectively). The decrease of highest foveal PED was significant at first visit (P = 0.025)., Conclusion: Half-dose photodynamic therapy is superior to high-density subthreshold micropulse laser treatment with regard to a statistically significant reduction in the height of macular PEDs in active chronic central serous chorioretinopathy. These findings may also have implications for other diseases within the pachychoroid disease spectrum that can present with PEDs.

Background: To investigate the anatomical and functional results in eyes with peripapillary pachychoroid syndrome (PPS) undergoing photodynamic therapy (PDT)., Methods: A total of 25 eyes from 23 patients with PPS treated with PDT were retrospectively evaluated in this multicentric study. Main outcome measure was the proportion of eyes that achieved treatment success, defined as a decrease in both subretinal fluid (SRF) height and central subfield thickness (CST), at 3 months after PDT compared to baseline. Secondary outcomes were the change in CST, SRF, and best-corrected visual acuity (BCVA) 3 months after treatment and predictive factors for treatment success. When available, data between 3 and 12 months were also reviewed., Results: Treatment success was achieved in 16 eyes (64%). In the total cohort, CST decreased significantly from 356 ± 118 µm at baseline to 282 ± 90 µm and 270 ± 91 µm at 1 and 3 months, respectively (p < 0.001). Maximal SRF height decreased significantly from 102 ± 83 µm at baseline to 38 ± 46 µm and 32 ± 42 µm at 1 and 3 months, respectively (p < 0.001), and remained stable at month 6 (29 ± 44 µm) and month 12 (23 ± 35 µm). BCVA improved significantly from baseline to month 3 (p = 0.021)., Conclusions: PDT can be considered an efficacious treatment option in patients with PPS. Prospective data with longer follow-up in a bigger cohort are needed in order to determine the optimal treatment algorithm in this relatively novel disease., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)