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Purpose The analysis of circulating tumor DNA (ctDNA), a fraction of total cell-free DNA (cfDNA), might be of special interest in retinoblastoma patients. Because the accessibility to tumor tissue is very limited in these patients, either for histopathological diagnosis of suspicious intraocular masses (biopsies are proscribed) or for somatic RB1 studies and genetic counseling (due to current successful conservative approaches), we aim to validate the detection of ctDNA in plasma of non-hereditary retinoblastoma patients by molecular analysis of RB1 gene. Experimental design In a cohort of 19 intraocular unilateral non-hereditary retinoblastoma patients for whom a plasma sample was available at diagnosis, we performed high-deep next-generation sequencing (NGS) of RB1 in cfDNA. Two different bioinformatics/statistics approaches were applied depending on whether the somatic RB1 status was available or not. Results Median plasma sample volume was 600 μL [100–1000]; median cfDNA plasma concentration was 119 [38–1980] and 27 [11–653] ng/mL at diagnosis and after complete remission, respectively. In the subgroup of patients with known somatic RB1 alterations (n = 11), seven of nine somatic mutations were detected (median allele fraction: 6.7%). In patients without identified somatic RB1 alterations (n = 8), six candidate variants were identified for seven patients. Conclusions Despite small tumor size, blood-ocular barrier, poor ctDNA blood release and limited plasma sample volumes, we confirm that it is possible to detect ctDNA with high-deep NGS in plasma from patients with intraocular non-hereditary retinoblastoma. This may aid in diagnosis of suspicious cases, family genetic counseling or follow-up of residual intraocular disease.

PurposeObjective structured clinical examinations (OSCE) evaluate clinical reasoning, communication skills, and interpersonal behavior during medical education. In France, clinical training has long relied on bedside clinical practice in academic hospitals. The need for a simulated teaching environment has recently emerged, due to the increasing number of students admitted to medical schools, and the necessity of objectively evaluating practical skills. This study aimed at investigating the relationships between OSCE grades and current evaluation modalities.MethodsThree-hundred seventy-nine 4th-year students of University-of-Paris Medical School participated to the first large-scale OSCE at this institution, consisting in three OSCE stations (OSCE#1-3). OSCE#1 and #2 focused on cardiovascular clinical skills and competence, whereas OSCE#3 focused on relational skills while providing explanations before planned cholecystectomy. We investigated correlations of OSCE grades with multiple choice (MCQ)-based written examinations and evaluations of clinical skills and behavior (during hospital traineeships); OSCE grade distribution; and the impact of integrating OSCE grades into the current evaluation in terms of student ranking.ResultsThe competence-oriented OSCE#1 and OSCE#2 grades correlated only with MCQ grades (r = 0.19, P0.75). Conversely, the behavior-oriented OSCE#3 grades correlated with traineeship skill and behavior grades (r = 0.19, PConclusionThis large-scale French experience showed that OSCE designed to assess a combination of clinical competence and behavioral skills, increases the discriminatory capacity of current evaluations modalities in French medical schools.

e21601 Background: MBD4 encodes a glycosylase implicated in repair of lesions induced by DNA deamination and its inactivation in tumors is associated with a hypermutated phenotype. Uveal melanoma (UM) is a rare but aggressive form of melanoma carrying an extremely low mutation burden. Although metastatic UM (mUM) are usually resistant to immune checkpoint inhibitors (ICI), the first reported MBD4-mutated (MBD4m) patient responded to ICI, suggesting that MBD4 mutation may predict response to ICI. Since then, other MBD4-inactivated UMs, acute myeloid leukemias, colorectal adenocarcinomas, gliomas and spiradenocarcinoma cases have been reported. Methods: Retrospective cohort of mUM patients treated with ICI. MBD4 was sequenced in a subset of these patients. Results: Three hundred mUM patients were analyzed. Median follow-up was 17.3 months. Ten objective responses and 20 stable disease for > 12 months were observed, corresponding to an objective response rate of 3.3% and a clinical benefit (CB; i.e. responder patients and stable disease) rate of 10%. Median progression-free survivals (PFS) in patients without and with CB were 3.1 and 16.3 months, respectively (p < 0.0001). Of the 134 tumors sequenced for MBD4, five (3.7%) were mutated. MBD4 inactivation was associated with higher mutation burden (179 to 643 variants versus a median of 16 in MBD4 wild-type), better objective response rate as 60% of MBD4m versus 4% of MBD4-wild type patients responded (Fisher’s exact p-test = 0.0009). Median PFS was 4.0 months in MBD4-wild type and 22.3 months in MBD4m patients (HR = 0.22; p = 0.01). Median overall survival was 16.6 months in MBD4-wild type and unreached in MBD4m patients (HR = 0.11; p = 0.004). Conclusions: In mUM patients, MBD4 mutation is highly predictive for response to ICI, PFS and overall survival benefit. MBD4 could be a tissue-agnostic biomarker and should be sequenced in mUM and other tumor types where MBD4 mutations are reported.

Macular edema is an increase in volume of the central area of the retina, responsible for visual acuity. Visual symptoms handicap the lives of millions of patients with macular edema secondary to chronic and sometimes acute retinal disease. Proteins that neutralize the vascular endothelial growth factor (VEGF) pathway or glucocorticoids, at the cost of repeated intraocular injections over years, limit visual symptoms. A better understanding of why and how edema forms and how therapeutic molecules exert an anti-edematous effect will help prevent this disabling and blinding retinal complication from occurring.Les œdèmes maculaires - Mieux comprendre leurs mécanismes pour mieux les traiter.L’œdème maculaire est une augmentation de volume de la macula, zone centrale de la rétine, responsable de l’acuité visuelle. Des symptômes visuels handicapent la vie de millions de patients atteints d’œdème maculaire secondaire à une maladie chronique et parfois aiguë de la rétine. Les protéines qui neutralisent la voie du facteur de croissance de l’endothélium vasculaire (VEGF) ou les glucocorticoïdes, au prix d’injections intraoculaires répétées pendant des années, limitent les symptômes visuels. Mieux comprendre pourquoi et comment l’œdème se forme et comment les molécules thérapeutiques exercent un effet anti-œdémateux permettra de mieux prévenir la survenue de cette complication rétinienne handicapante et cécitante.

International audience; L’œdème maculaire est une augmentation de volume de la macula, zone centrale de la rétine, responsable de l’acuité visuelle. Des symptômes visuels handicapent la vie de millions de patients atteints d’œdème maculaire secondaire à une maladie chronique et parfois aiguë de la rétine. Les protéines qui neutralisent la voie du facteur de croissance de l’endothélium vasculaire (VEGF) ou les glucocorticoïdes, au prix d’injections intraoculaires répétées pendant des années, limitent les symptômes visuels. Mieux comprendre pourquoi et comment l’œdème se forme et comment les molécules thérapeutiques exercent un effet anti-œdémateux permettra de mieux prévenir la survenue de cette complication rétinienne handicapante et cécitante.

International audience; L’œdème maculaire est une augmentation de volume de la macula, zone centrale de la rétine, responsable de l’acuité visuelle. Des symptômes visuels handicapent la vie de millions de patients atteints d’œdème maculaire secondaire à une maladie chronique et parfois aiguë de la rétine. Les protéines qui neutralisent la voie du facteur de croissance de l’endothélium vasculaire (VEGF) ou les glucocorticoïdes, au prix d’injections intraoculaires répétées pendant des années, limitent les symptômes visuels. Mieux comprendre pourquoi et comment l’œdème se forme et comment les molécules thérapeutiques exercent un effet anti-œdémateux permettra de mieux prévenir la survenue de cette complication rétinienne handicapante et cécitante.

Purpose was to create an in vitro model of human retinal detachment (RD) to study the mechanisms of photoreceptor death. Methods Human retinas were obtained through eye globe donations for research purposes and cultivated as explants. Cell death was investigated in retinas with (control) and without retinal pigment epithelium (RPE) cells to mimic RD. Tissues were studied at different time points and immunohistological analyses for TUNEL, Cleaved caspase3, AIF, CDK4 and the epigenetic mark H3K27me3 were performed. Human and monkey eye globes with retinal detachment served as controls. Results The number of TUNEL-positive cells, compared between 1 and 7 days, increased with time in both retinas with RPE (from 1.2 ± 0.46 to 8 ± 0.89, n = 4) and without RPE (from 2.6 ± 0.73 to 16.3 ± 1.27, p < 0.014). In the group without RPE, cell death peaked at day 3 (p = 0.014) and was high until day 7. Almost no Cleaved-Caspase3 signal was observed, whereas a transient augmentation at day 3 of AIF-positive cells was observed to be about 10-fold in comparison to the control group (n = 2). Few CDK4-positive cells were found in both groups, but significantly more in the RD group at day 7 (1.8 ± 0.24 vs. 4.7 ± 0.58, p = 0.014). The H3K27me3 mark increased by 7-fold after 5 days in the RD group (p = 0.014) and slightly decreased at day 7 and was also observed to be markedly increased in human and monkey detached retina samples. Conclusion AIF expression coincides with the first peak of cell death, whereas the H3K27me3 mark increases during the cell death plateau, suggesting that photoreceptor death is induced by different successive pathways after RD. This in vitro model should permit the identification of neuroprotective drugs with clinical relevance.

Objectives Simulation-based training (SBT) is increasingly used to teach clinical patient-doctor communication skills (CS) to medical students. However, the long-lasting impact of this training has been poorly studied. Methods In this observational study we included all fourth-year undergraduate medical students from a French medical school who undertook a CS objective structured clinical examination (OSCE) and who answered a post-examination survey. OSCE scores and students’ feedback were compared by whether students had received a specific CS-SBT or not 12 months prior to the OSCE. Results A total of 173 students were included in the study. Of them, 97 (56%) had followed the CS-SBT before the OSCE. Students who had undergone CS-SBT had significantly higher CS-OSCE scores in the multivariate analysis compared to untrained students (mean score 7.5/10 ±1.1 vs. 7.0/10 ±1.6, respectively, Cohen’s d = 0.4, p

Purpose To investigate choroidal blood flow changes after isometric exercise in patients with chronic central serous chorioretinopathy nontreated or treated with mineralocorticoid receptor antagonists (MRA). Methods Foveolar choroidal laser Doppler flowmetry parameters - velocity (ChVel), volume (ChVol) and blood flow (ChBF) - of 22 eyes of 22 treated patients, 16 eyes of 16 untreated patients and 19 healthy controls were measured during a squatting test. Treatment consisted in MRA administration (eplerenone 50 mg/day or spironolactone 50 mg/day). The experiment comprised three successive periods: 30 seconds of rest, 2 min of continuous squatting exercise, and 150 seconds of recovery. Significance levels were calculated using a generalized estimating equation. Results During the squatting period, nontreated CSCR eyes had a similar change in ChVel (p = 0.8), ChVol (p = 0.8), ChBF (p = 0.5) and resistance to healthy eyes. Treated CSCR eyes exhibited significantly smaller changes in ChVel (-0.1 ± 11%, p = 0.04) than healthy eyes (6 ± 8%). No significant difference was found for ChVol and ChBF between the groups. The increase in ChVol from baseline in the nontreated CSCR group (4.4 ± 9%) was lower than that of treated group (6.7%±11%; p = 0.01). Finally, ChBF and ChVel changes in the CSCR groups were not significantly different. Conclusions No abnormalities were detected in the changes in ChBF parameters during increased ocular perfusion pressure in nontreated CSCR patients compared with controls. MRA treatment in CSCR patients induced a significant reduction in ChBVel and an increase in ChBVol in response to isometric exercise, suggesting that MRA exerts effects on choroidal vascular changes.

Le poste in gioco europee e gli affetti che suscitano sono solo il sintomo del disagio che sfascia i legami sociali molto al di là dell’Europa economica e geografica. Sono prese in un mondo in cui il capitalismo liberale non ha più le alternative che aveva invece nel corso del xx secolo grazie alle speranze sollevate dalla Rivoluzione nell’Unione Sovietica e in Cina. Gli affetti d’amore e d’odio che per secoli dilaniarono i paesi dell’Europa accompagnavano la volontà egemonica degli uni e deg...

Il Forum europeo tenutosi a Milano sul tema “Amore e odio per l’Europa” è stato un evento maggiore che ha riunito numerosi psicoanalisti provenienti dalle Scuole europee e mondiali del Campo freudiano, mettendoli a confronto con specialisti di diverse discipline, economisti, politologi, filosofi, storici, giuristi. La posta in gioco di questo straordinario dibattito era una riflessione, ormai urgente, sullo spazio europeo. Con questo si intende ovviamente non solo lo spazio geografico – tuttavia importante da definire concretamente nella prospettiva della globalizzazione – ma soprattutto lo spazio politico, di pensiero, di scambi che non possono limitarsi al mercato, se non vogliamo che l’Europa cada nell’indifferenza dei popoli che la abitano. In un’epoca in cui le tensioni ideali non sono più un motore vivo della storia, bisogna puntare a far nascere il desiderio per altre vie. Il capitalismo ha scelto il diluvio d’oggetti, quel che siamo soliti chiamare consumismo e che mostra la corda nei vicoli ciechi in cui ci ha condotti il neoliberismo. Con la psicoanalisi possiamo trovare nuove strade, possiamo aprire a un’erotizzazione del pensiero, un amore che resta attualmente soffocato dietro le forme di odio cui spesso abbiamo assistito negli ultimi tempi. L’insegnamento freudiano però non ci lascia ignari del fatto che né l’odio né l’amore sono mai puri, ed è con questo intreccio complesso che, in molti modi, i testi del libro cercano di confrontarsi.

Despite significant recent advances in the local treatment of ocular diseases, the use of systemic treatments is still required to cure and control refractory ocular cancers and metastatic relapse, particularly in retinoblastoma, and other intra-ocular cancers. To achieve effective anticancer drug activity, drug distribution from the blood into the tumor site remains a critical pharmacokinetic process. Release and penetration of many anticancer drugs into the retinal parenchyma are often sub-optimal due to specific anatomical and biochemical features of the retina, regulated through blood-retinal barriers molecular exchanges with the blood compartment. This chapter reviews clinical and therapeutic aspects of retinoblastoma and choroidal melanoma, the main retinal and choroidal cancers, as well as anatomy, histology and biochemical aspects of the blood-retinal barriers focusing on drug-metabolizing enzymes and drug transporters, with respect to ocular chemotherapy.

Our comprehensive cohort of 1100 unrelated achromatopsia (ACHM) patients comprises a considerable number of cases (~5%) harboring only a single pathogenic variant in the major ACHM gene CNGB3. We sequenced the entire CNGB3 locus in 33 of these patients to find a second variant which eventually explained the patients' phenotype. Forty-seven intronic CNGB3 variants were identified in 28 subjects after a filtering step based on frequency and the exclusion of variants found in cis with pathogenic alleles. In a second step, in silico prediction tools were used to filter out those variants with little odds of being deleterious. This left three variants that were analyzed using heterologous splicing assays. Variant c.1663-1205G>A, found in 14 subjects, and variant c.1663-2137C>T, found in two subjects, were indeed shown to exert a splicing defect by causing pseudoexon insertion into the transcript. Subsequent screening of further unsolved CNGB3 subjects identified four additional cases harboring the c.1663-1205G>A variant which makes it the eighth most frequent CNGB3 variant in our cohort. Compound heterozygosity could be validated in ten cases. Our study demonstrates that whole gene sequencing can be a powerful approach to identify the second pathogenic allele in patients apparently harboring only one disease-causing variant.

Contains fulltext : 229749.pdf (Publisher’s version ) (Open Access) No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Lipocalin 2 (LCN2 or NGAL), alone or complexed with MMP-9 (NGAL/MMP-9), is increased in several retinal disorders. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched healthy controls (n = 130). Samples with CRP > 5 mg/L, creatinine > 100 µmol/L, and/or urea > 7.5 mmol/L were excluded. Serum LCN2 was lower in CSCR patients than controls (81.4 ± 48.7 vs 107.3 ± 44.5 ng/ml, p

Our comprehensive cohort of 1100 unrelated achromatopsia (ACHM) patients comprises a considerable number of cases (~5%) harboring only a single pathogenic variant in the major ACHM gene CNGB3. We sequenced the entire CNGB3 locus in 33 of these patients to find a second variant which eventually explained the patients’ phenotype. Forty-seven intronic CNGB3 variants were identified in 28 subjects after a filtering step based on frequency and the exclusion of variants found in cis with pathogenic alleles. In a second step, in silico prediction tools were used to filter out those variants with little odds of being deleterious. This left three variants that were analyzed using heterologous splicing assays. Variant c.1663–1205G>A, found in 14 subjects, and variant c.1663-2137C>T, found in two subjects, were indeed shown to exert a splicing defect by causing pseudoexon insertion into the transcript. Subsequent screening of further unsolved CNGB3 subjects identified four additional cases harboring the c.1663–1205G>A variant which makes it the eighth most frequent CNGB3 variant in our cohort. Compound heterozygosity could be validated in ten cases. Our study demonstrates that whole gene sequencing can be a powerful approach to identify the second pathogenic allele in patients apparently harboring only one disease-causing variant. © 2019 Wiley Periodicals, Inc.

Purpose: To report a case of iris implantation cysts occurring 24 years after penetrating keratoplasty and its management. Observations: A 60-year-old man was referred for diagnosis and management of white iris masses of the right eye. He had undergone bilateral penetrating keratoplasty 24 years before without complication. The clinical findings were suggestive of iris implantation cysts and Ultrasound Biomicroscopy (UBM) and anterior-segment optical coherence tomography confirmed the diagnosis. The patient did not develop any ocular complications from the cysts after one-year follow-up from the diagnosis of iris implantation cysts. Conclusions and importance: Iris implantation cysts are rare benign tumors that develop after the ectopic implantation of epithelial cells within the iris stroma. They can be congenital or secondary to penetrating trauma or surgery. Their diagnosis relies on clinical examination and UBM. In case of intraocular complications, treatment may be required, otherwise observational follow-up is appropriate.

The eye is an exemplarily challenging organ to treat when considering ocular tumors. It is at the crossroads of several major aims in oncology: tumor control, organ preservation, and functional outcomes including vision and quality of life. The proximity between the tumor and organs that are susceptible to radiation damage explain these challenges. Given a high enough dose of radiation, virtually any cancer will be destroyed with radiotherapy. Yet, the doses inevitably absorbed by normal tissues may lead to complications, the likelihood of which increases with the radiation dose and volume of normal tissues irradiated. Precision radiotherapy allows personalized decision-making algorithms based on patient and tumor characteristics by exploiting the full knowledge of the physics, radiobiology, and the modifications made to the radiotherapy equipment to adapt to the various ocular tumors. Anticipation of the spectrum and severity of radiation-induced complications is crucial to the decision of which technique to use for a given tumor. Radiation can damage the lacrimal gland, eyelashes/eyelids, cornea, lens, macula/retina, optic nerves and chiasma, each having specific dose–response characteristics. The present review is a report of non-cancer effects that may occur following ionizing irradiation involving the eye and orbit and their specific patterns of toxicity for a given radiotherapy modality.

Purpose: To report a case of locally recurrent spindle-cell iris amelanotic melanoma 16 years after proton-beam therapy. Observations: In 2001, a 45-year-old man presented with an amelanotic iris melanoma, extending from the 5 to 10 o'clock positions on his left eye. High-frequency ultrasonography showed extension of melanoma into the ciliary body. He was initially managed with proton-beam therapy (60 Gy delivered in four fractions over four consecutive days) and underwent ocular and systemic examination at regular intervals over the following years. Local tumor control was achieved, and the patient did not develop metastasis during sixteen consecutive years. In 2017, 16 years after he received proton-beam therapy, the patient developed a focal amelanotic lesion strongly suggestive of a local recurrence of iris melanoma, although it extended from the 1 to 6 o'clock positions. He also presented with treatment-resistant glaucoma with an intraocular pressure (IOP) of 37 mmHg, despite maximal topical IOP-lowering therapy. Since a second irradiation of the anterior segment was contraindicated, the eye was enucleated. Pathological analysis confirmed the diagnosis of iris melanoma and demonstrated iridocorneal angle invasion extending from the initial site to the recurrent tumor location. Conclusions and importance: Regular ophthalmological surveillance for life with gonioscopy and high-frequency ultrasonography is recommended in patients with iris melanoma, due to the possibility of delayed local recurrence more than a decade after the initial treatment. Keywords: Ciliary body, Iris, Melanoma, Radiotherapy, Irido-corneal angle, Proton-beam therapy

PURPOSE To determine the age distribution of children with Coats disease and the impact of age at diagnosis on the visual prognosis. METHODS Consecutive Coats disease cases aged 18 years or younger at diagnosis were retrospectively included. Clinical and imaging parameters were analyzed by comparative, correlation, survival, univariate, and multivariate statistics. RESULTS Ninety-eight patients were included. At diagnosis, mean age was 5.4 years ± 4.3 years (1 month-18 years). Younger age at diagnosis was correlated with more severe disease stage (P < 0.0001, r = -0.52), which was confirmed by survival analysis (P < 0.0001). Comparative analysis was performed between patients younger and older than 4 years at diagnosis. Leukocoria or strabismus was more frequent at presentation in patients younger than 4 years (P < 0.0001). Areas of peripheral nonperfusion and peripheral telangiectasia were more extensive at presentation in younger than older patients (P = 0.0003 and P = 0.039). Foveal sparing at diagnosis was less frequent in younger than older patients (2% vs. 23%, P = 0.002). The incidence of structural complications or enucleation during follow-up (mean duration: 5.9 years ± 4.5 years) was higher, and last-recorded visual acuity was lower in younger than older patients (P = 0.001 and P = 0.0009). Final logarithm of the minimal angle of resolution visual acuity was negatively correlated with age at diagnosis (P = 0.001, Spearman r = -0.42). Multivariate analysis indicated that disease stage (P < 0.0001), but not age at diagnosis (P = 0.07), independently influenced the last-recorded visual acuity. CONCLUSION Onset of Coats disease in children of younger age is associated with more severe manifestations, more advanced stage, and worse visual outcome. Age, correlated with disease stage, should be considered a prognostic marker in Coats disease.

AimsTo evaluate the long-term oral mineralocorticoid receptor antagonist (MRa) treatment in chronic central serous chorioretinopathy (CSC).MethodsPatients with chronic non-resolving CSC (defined as foveal subretinal fluid (SRF) lasting >4 months with retinal pigment epithelium (RPE) alterations) treated with MRa only (eplerenone or spironolactone) for at least 6 months were retrospectively included. Clinical and imaging characteristics were recorded during visits at baseline, 6, 12, 18 and 24 months.ResultsSixteen eyes of 16 patients were included (mean age 53±11 years; 14 men, 2 women). Mean duration of SRF before treatment initiation was 11.2±19.7 months. MRa treatment was administered during 21.0±5.1 months (range, 10–24 months). There was a progressive improvement of visual acuity (p=0.05), a decrease of foveal SRF height (p=0.011), central macular thickness (p=0.004) and subfoveal choroidal thickness (p=0.002) over 24 months. Changes in SRF were correlated with subfoveal choroidal thickness at 24 months (p=0.006, Spearman r=065). The mean time to complete foveal SRF resolution was 10.5±8.0 months after treatment initiation. At 24 months, foveal SRF resolution was achieved in 13 eyes (81%). Minor side effects occurred in five patients (31%) and resolved after switching between MRa.ConclusionThe visual and anatomical benefit of MRa treatment prolonged for 6 months or more in chronic, non-resolving CSC appeared to be maintained over a 24-month period. These results suggest that MRa can be proposed as an alternative therapy in severe CSC with advanced RPE alterations.

Multimodal imaging provides insights into phenotype and disease progression in inherited retinal disorders. Congenital achromatopsia (ACHM), a cone dysfunction syndrome, has been long considered a stable condition, but recent evidence suggests structural progression. With gene replacement strategies under development for ACHM, there is a critical need for imaging biomarkers to define progression patterns and follow therapy. Using semiquantitative plots, near-infrared (NIR-AF) and short-wavelength autofluorescence (SW-AF) were explored and correlated with clinical characteristics and retinal structure on optical coherence tomography (OCT). In sixteen ACHM patients with genetic confirmation (CNGA3, n = 8; CNGB3, n = 7; PDE6C, n = 1), semiquantitative plots allowed the detailed analysis of autofluorescence patterns, even in poorly fixating eyes. Twelve eyes showed perifoveal hyperautofluorescent rings on SW-AF, and 7 eyes had central hypoautofluorescent areas on NIR-AF, without association between these alterations (P = 0.57). Patients with central NIR-AF hypoautofluorescence were older (P = 0.004) and showed more advanced retinal alterations on OCT than those with normal NIR-AF (P = 0.051). NIR-AF hypoautofluorescence diameter was correlated to patient age (r = 0.63, P = 0.009), size of ellipsoid zone defect on OCT (r = 0.67, P = 0.005), but not to the size of SW-AF hyperautofluorescence (P = 0.27). These results demonstrate the interest of NIR-AF as imaging biomarker in ACHM, suggesting a relationship with age and disease progression.

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.

To describe the clinical features of cataract during the course of Coats disease and to determine its risk factors and effects on the long-term visual outcome.The medical records of consecutive patients with Coats disease followed for at least 2 years were analyzed retrospectively. Ophthalmological examination, ancillary tests, and treatment modalities were reviewed. The time of cataract diagnosis and its management were recorded. Parameters influencing cataract development and final visual outcome were investigated using uni- and multivariate analysis.A total of 57 patients (mean age, 5.0 ± 4.0 years; 51 males) were included; cataract formation was observed in 16 (28%) during a mean follow-up of 7.1 ± 3.7 years. The mean time from diagnosis of Coats disease to cataract detection was 25 ± 22 months. Total white cataract developed in 12 patients (75%); posterior subcapsular cataract, in 4 (25%). Cataracts were surgically removed in 10 patients to improve fundus visualization and clinical follow-up. Presence of exudative retinal detachment at diagnosis was an independent risk factor for cataract formation (P = 0.031). Cataract development was associated with more advanced disease stages (P 0.001). History of cataract was a significant predictor for worse final visual outcome (P 0.001), independent of disease stage (P = 0.003) and presence of macular complication, such as atrophy, fibrosis, or tractional retinal detachment (P 0.001, adjusted RCataract development is frequent in children with Coats disease and aggravates the visual prognosis. Exudative retinal detachment at diagnosis, present in more advanced disease stages, is an independent risk factor for cataract formation.