Central serous chorioretinopathy (CSCR) is a major cause of vision threat among middle-aged male individuals. Multimodal imaging led to the description of a wide range of CSCR manifestations, and highlighted the contribution of the choroid and pigment epithelium in CSCR pathogenesis. However, the exact molecular mechanisms of CSCR have remained uncertain. The aim of this review is to recapitulate the clinical understanding of CSCR, with an emphasis on the most recent findings on epidemiology, risk factors, clinical and imaging diagnosis, and treatments options. It also gives an overview of the novel mineralocorticoid pathway hypothesis, from animal data to clinical evidences of the biological efficacy of oral mineralocorticoid antagonists in acute and chronic CSCR patients. In rodents, activation of the mineralocorticoid pathway in ocular cells either by intravitreous injection of its specific ligand, aldosterone, or by over-expression of the receptor specifically in the vascular endothelium, induced ocular phenotypes carrying many features of acute CSCR. Molecular mechanisms include expression of the calcium-dependent potassium channel (KCa2.3) in the endothelium of choroidal vessels, inducing subsequent vasodilation. Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.

Macular edema consists of intra- or subretinal fluid accumulation in the macular region. It occurs during the course of numerous retinal disorders and can cause severe impairment of central vision. Major causes of macular edema include diabetes, branch and central retinal vein occlusion, choroidal neovascularization, posterior uveitis, postoperative inflammation and central serous chorioretinopathy. The healthy retina is maintained in a relatively dehydrated, transparent state compatible with optimal light transmission by multiple active and passive systems. Fluid accumulation results from an imbalance between processes governing fluid entry and exit, and is driven by Starling equation when inner or outer blood-retinal barriers are disrupted. The multiple and intricate mechanisms involved in retinal hydro-ionic homeostasis, their molecular and cellular basis, and how their deregulation lead to retinal edema, are addressed in this review. Analyzing the distribution of junction proteins and water channels in the human macula, several hypotheses are raised to explain why edema forms specifically in the macular region. "Pure" clinical phenotypes of macular edema, that result presumably from a single causative mechanism, are detailed. Finally, diabetic macular edema is investigated, as a complex multifactorial pathogenic example. This comprehensive review on the current understanding of macular edema and its mechanisms opens perspectives to identify new preventive and therapeutic strategies for this sight-threatening condition.

In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals.

The present review draws together wide-ranging studies performed over the last decades that catalogue the effects of artificial-light-at-night (ALAN) upon living species and their environment. We provide an overview of the tremendous variety of light-detection strategies which have evolved in living organisms - unicellular, plants and animals, covering chloroplasts (plants), and the plethora of ocular and extra-ocular organs (animals). We describe the visual pigments which permit photo-detection, paying attention to their spectral characteristics, which extend from the ultraviolet into infrared. We discuss how organisms use light information in a way crucial for their development, growth and survival: phototropism, phototaxis, photoperiodism, and synchronization of circadian clocks. These aspects are treated in depth, as their perturbation underlies much of the disruptive effects of ALAN. The review goes into detail on circadian networks in living organisms, since these fundamental features are of critical importance in regulating the interface between environment and body. Especially, hormonal synthesis and secretion are often under circadian and circannual control, hence perturbation of the clock will lead to hormonal imbalance. The review addresses how the ubiquitous introduction of light-emitting diode technology may exacerbate, or in some cases reduce, the generalized ever-increasing light pollution. Numerous examples are given of how widespread exposure to ALAN is perturbing many aspects of plant and animal behaviour and survival: foraging, orientation, migration, seasonal reproduction, colonization and more. We examine the potential problems at the level of individual species and populations and extend the debate to the consequences for ecosystems. We stress, through a few examples, the synergistic harmful effects resulting from the impacts of ALAN combined with other anthropogenic pressures, which often impact the neuroendocrine loops in vertebrates. The article concludes by debating how these anthropogenic changes could be mitigated by more reasonable use of available technology – for example by restricting illumination to more essential areas and hours, directing lighting to avoid wasteful radiation and selecting spectral emissions, to reduce impact on circadian clocks. We end by discussing how society should take into account the potentially major consequences that ALAN has on the natural world and the repercussions for ongoing human health and welfare.

In chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR. This randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18-60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed. Between Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI -1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]). Eplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice. Efficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.