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.

Nous rapportons le cas d'un homme de 27 ans qui a consulté par télémédecine lors de la pandémie de Coronavirus Disease 2019 (COVID-19), pour une sensation de corps étranger et une rougeur à l'oeil gauche. L'examen a révélé un oedème palpébral unilatéral et une hyperémie conjonctivale diffuse modérée. Quelques heures plus tard, le patient a présenté des céphalées intenses, de la fièvre, de la toux et une dyspnée sévère, et une PCR nasopharyngée est revenue positive au SARS-CoV-2, posant le diagnostic de COVID-19. Ce cas démontre la possibilité d'une conjonctivite inaugurale lors de l'infection COVID-19. Il illustre l'intérêt de la télémédecine en ophtalmologie lors de la pandémie, une hyperémie conjonctivale modérée pouvant être le premier signe d'une détresse respiratoire sévère. Abstract We report here the case of a 27-year-old man who consulted by telemedicine during the Coronavirus Disease 2019 (COVID-19) pandemic, due to foreign body sensation and left eye redness. Examination revealed unilateral eyelid edema and moderate conjunctival hyperemia. A few hours later the patient experienced intense headache and developed fever, cough and severe dyspnea. A nasopharyngeal swab proved positive for SARS-CoV-2. This case demonstrates that conjunctivitis can be the inaugural manifestation of the COVID-19 infection. It illustrates the interest of telemedicine in ophthalmology during the COVID-19 pandemic, since moderate conjunctival hyperemia can be the first sign of a severe respiratory distress. Page 4 of 7 J o u r n a l P r e -p r o o f Legend Figure 1: Smartphone photograph of a left eye conjunctivitis as first presentation of Coronavirus Disease 2019 during teleophthalmology consultation. A. Left eyelid edema. B. Moderate temporal conjunctival hyperemia of the left eye. C. Inferior bulbar conjunctival hyperemia of the left eye.

Multiple factors influence the risk of central serous chorioretinopathy recurrence. These findings may contribute to identify patients at higher risk, who could benefit from earlier or more intensive treatment.

The investigation of clinical and multimodal imaging factors influencing the duration of first, acute, and treatment-naive CSCR episodes by survival analysis showed that higher subfoveal choroidal thickness, higher pigment epithelial detachment or bump at leakage sites, and older age were independent predictors of longer episodes.

PurposeTo evaluate the efficacy and safety of oral mineralocorticoid-receptor antagonist (MRa) therapy in three clinical presentations of nonresolving central serous chorioretinopathy (CSCR) with chronic epitheliopathy.MethodsRetrospective case series of consecutive patients with nonresolving CSCR treated with oral eplerenone or spironolactone. Treatment criteria were: persistent CSCR with subretinal fluid (SRF) lasting longer than 4 months; recurrent CSCR with SRF lasting longer than 2 months; persistent CSCR (SRF ≥ 4 months) with fundus autofluorescence gravitational tracks. Outcomes at 1, 3, and 6 months were: foveal SRF height, central macular thickness (CMT), subfoveal choroidal thickness (SFCT), best-corrected visual acuity (BCVA), and occurrence of side effects.ResultsAmong 54 eyes from 42 patients (mean age: 53 years), mean foveal SRF, CMT, and SFCT decreased significantly at 1, 3, and 6 months after treatment initiation. Mean BCVA improved significantly at 6 months. In the subgroup analysis, mean foveal SRF, CMT, and SFCT decreased significantly at 3 and 6 months in the persistent and recurrent groups. In persistent cases with tracks, a significant diminution of mean CMT and SFCT was achieved at 6 months. Treatment-related side effects were observed in 6 patients, prompting treatment discontinuation in one case.ConclusionResponse to treatment was observed in the three subgroups. In persistent CSCR with tracks the response was delayed compared with persistent and recurrent cases, suggesting that longer treatment durations would be beneficial in patients with gravitational tracks of RPE alteration.Translational RelevanceThe clinical response to oral MRa is consistent with the involvement of the mineralocorticoid pathway in CSCR pathogenesis.

Choriocapillaris flow voids colocalize with choriocapillaris thinning and deep choroidal vessel dilation in CSCR eyes. Age and CSCR severity influence choriocapillaris flow, a key contributor to CSCR pathophysiology and clinical expression.

PURPOSE. To analyze microvascular and structural changes in radiation maculopathy and their influence on visual acuity (VA), using optical coherence tomography (OCT) and OCT angiography (OCTA).METHODS. This was a retrospective analysis of consecutive patients with radiation maculopathy, 12 months or more after proton-beam irradiation for uveal melanoma, imaged with fluorescein angiography, OCT, and OCTA. Clinical parameters potentially affecting VA were recorded, including OCTA-derived metrics: foveal avascular zone (FAZ) area, vascular density, and local fractal dimension of the superficial (SCP) and deep capillary plexuses (DCP). Nonirradiated fellow eyes served as controls. RESULTS.Ninety-three patients were included. FAZ was larger, while SCP/DCP capillary density and local fractal dimension were lower in the 35 irradiated than in the 35 fellow eyes (P < 0.0001). Microvascular alterations graded on fluorescein angiography (minimally damaged/ disrupted/disorganized) were correlated to FAZ area and SCP/DCP density on OCTA (P < 0.01). By univariate analysis, worse VA was associated to macular detachment at presentation (P ¼ 0.024), total macular irradiation (P ¼ 0.0008), higher central macular thickness (CMT) (P ¼ 0.019), higher absolute CMT variation (P < 0.0001), cystoid edema (P ¼ 0.030), ellipsoid zone disruption (P ¼ 0.002), larger FAZ (P < 0.0001), lower SCP (P ¼ 0.001) and DCP capillary density (P < 0.0001), and lower SCP (P ¼ 0.009) and DCP local fractal dimension (P < 0.0001). Two multivariate models with either capillary density or fractal dimension as covariate showed that younger age (P ¼ 0.014/0.017), ellipsoid zone disruption (P ¼ 0.034/0.019), larger FAZ (P ¼ 0.0006/0.002), and lower DCP density (P ¼ 0.008) or DCP fractal dimension (P ¼ 0.012), respectively, were associated with worse VA.CONCLUSIONS. VA of eyes with radiation maculopathy is influenced by structural and microvascular factors identified with OCTA, including FAZ area and DCP integrity.