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The aim of this study was to evaluate docosahexaenoic acid (DHA) as a potential antifibrotic agent after glaucoma filtration surgery (GFS) in rats.A total of 36 10-week-old Brown Norway rats underwent GFS. Animals were equally divided into three groups: a control group, a DHA group and a mitomycin C (MMC) group. Intraocular pressure (IOP) was measured using a dynamic rebound tonometer, and a photograph of the surgical site was taken on days 1, 3, 7, 10, 14 and 17. The incorporation of DHA into fibroblasts was evaluated by gas chromatography. The expression of alfa-smooth muscle actin (α-SMA) and Smad proteins was assessed by Western blotting.IOP decreased after surgery in animals from the three groups on day 1 after surgery. Over time, IOP remained lower in the DHA and MMC groups than in the control group (median [interquartile range] 8.0 [7.0-8.0] and 8.0 [7.3-8.0] mmHg vs. 9.0 [8.0-9.0] mmHg, respectively; p 0.001). Bleb area in the DHA and MMC groups remained larger than that of the control group from day 7 to day 14 (3.9 [2.9-5.2] and 3.5 [2.3-4.4] mmThe impact of DHA on IOP and bleb area was similar to that of MMC. The mechanisms of action of DHA in rat eye fibroblasts deserve further investigation.

International audience; PURPOSE: To describe the glaucoma surgery offer in France in 2016. METHODS: We used the French National Health Care System database to identify all medical procedures carried out in 2016. The study investigated the entire population aged 30 years and older that had undergone glaucoma surgery, alone or combined with another surgery. We calculated the incidence of surgeries per 100 000 inhabitants 30 years of age and older performed by ophthalmologists carrying out at least 50 procedures annually, the number of surgeons doing these surgeries, the mean age of these practitioners, and the number of surgeons older than 55 years. RESULTS: In 2016, 16 854 glaucoma surgeries were performed in patients aged 30 years and older, for an incidence of 40.8 per 100 000 inhabitants aged 30 years and older. The most frequent procedure performed was trabeculectomy followed by non-penetrating deep sclerectomy (16.7 and 11.7, respectively, per 100 000 inhabitants 30 years of age and older). Private practice glaucoma surgery accounted for 47% of the activity of surgeons performing at least 50 surgeries per year and 60% of the total surgical activity. Of the private practice ophthalmologists performing at least 50 glaucoma surgery procedures per year, 58.5% were over 55 years of age, and 23.5% of public hospital ophthalmologists were over 55 years of age. CONCLUSIONS: This study demonstrates that surgeons performing glaucoma surgeries are often older. It is necessary to take note of the country's educational capacity to ensure that the number of ophthalmological surgeons remains adapted to demand.

International audience

National audience; Purpose Excessive scarring of the conjunctiva is the major cause of failure of the surgical treatment for glaucoma. The activation of human Tenon's fibroblast (HTFs) is supposed to be responsible for wound healing and scar formation. Antimetabolites are used to inhibit subconjunctival fibrosis but these molecules may lead to serious complication. Previous studies have shown that omega‐3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) have anti‐inflammatory, anti‐proliferative and anti‐angiogenic properties. The aims of this study were to evaluate DHA as a potential inhibitor of human Tenon's fibroblasts. Methods Primary HTF cells were obtained from patients during glaucoma surgery and were cultured in DMEM medium. After stimulation with TGF‐β2, HTFs were treated with MMC (0.01 mg/mL) and different concentrations of DHA (50, 100 and 200 μM) for 48 hours. Lipid profile of HTFs was determined by gas chromatography, cell proliferation by Ki67 assay, cell migration was evaluated by videomicroscopy and cell toxicity by MTT assay. The expression α‐SMactin and MAPK p38, ERK, JNK in their non‐phosphorylated and phosphorylated forms was determined by western blotting. Results MMC reduced proliferation, migration compared to control but showed important toxicity suggested by the increased respiratory rate of mitochondrie in cytotoxicity assay and confirmed by a G2 arrest in cell cycle. DHA had no significant impact on cellular viability. DHA at 200 μM showed an efficacity similar to MMC. A reduction of the ability of cells to migrate was observed with DHA in a dose‐dependent manner. DHA efficiently dicreased α‐SMactin expression of myofibroblasts. Proteins from the Smad signaling pathway could not be observed. Conclusions These findings indicate that DHA inhibits migration and differentiation of HTFs to myofibroblats.

National audience; Purpose To assess retinal sensitivity by means of microperimetry and to evaluate the intersession fluctuation using the MAIA microperimeter in healthy volunteers. Methods Prospective, monocentre study. Fifty‐six healthy volunteers (age range, 20–80 years), underwent an automatic, full‐threshold microperimetry of the central field (custom grid, area of 10° in diameter, 37 stimulated points), with the MAIA microperimeter (CenterVue, Padova, Italy). A subgroup of 24 subjects was retested after 1 h (test 2) and 1 week (test 3) to determine the repeatability of the technique. A subgroup of 22 subjects was also tested on the OPKO microperimeter (Optos, Dunfermline, Scotland) (area of 10° in diameter, 28 stimulated points). Results Median age was 30 years [25.3–47.8]. The overall mean sensitivity for test 1 was 29.4 ± 1.4 dB, 29.8 ± 1.0 dB for test 2 and 29.9 ± 1.1 dB for test 3, respectively. Linear regression analysis showed a significant 0.5 dB sensitivity loss for each decade of life (r² = 0.27). In a subset of 24 subjects, the repeatability of the test performed at 3 separate visits showed a statistically significant difference between test 1 and 3 (p < 0.004). Test 2 and 3 showed consistent values over time (p = 0.160). Furthermore, the MAIA showed higher threshold values than the OPKO for all test locations. Linear regression of the perimetric results showed significant correlation between the 2 machines (r = 0.44; p < 0.001). Conclusions This study found an age‐related macular sensitivity loss. These findings are in agreement with previous data obtained with the MP1 and the OPKO microperimeters. The increase in sensitivity between test 1 and test 2 and 3 should be taken into account in clinical practice. Automatic fundus perimetry with the MAIA microperimeter allows for accurate, repeatable examination, if a training session is performed.

National audience; Purpose The aim of this study was to identify retinal vascular network patterns using semi‐automated software in an elderly population over 75 years in a population‐based study, the MONTRACHET (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) study. Methods In 2009–2011, participants from the 3 Cities Study living in Dijon, were proposed to take part in the MONTRACHET study with a complete eye examination. During these exams, color retinal photographs were performed (centered on the optic disc). Semi‐automated software (Singapore Institute Vessel Assessment: SIVA) was used in order to describe the retinal vascular network of subjects with a photograph of sufficient quality. All subjects with epiretinal membranes and vascular pathology were excluded. Fifty‐four geometric features such as fractal dimension, diameter, tortuosity and branching angle were systematically collected. A principal component analysis (PCA) was used to identify independent patterns. Results Overall, 1,067 photographs were reviewed with SIVA software among the 1,153 participants of the MONTRACHET study. The mean age was 79.8 ± 3.8 years and 62.7% were female. After PCA processing, we extracted 3 vascular patterns summarizing 41% of the retinal vascular network information. The first pattern corresponded to a lower density in the vascular network as well as a higher variability in the vascular width (29% of the total variability). The second pattern was highly correlated to large vessels diameters and width. The third pattern matched to an increased tortuosity. Conclusions In this preliminary study, three vascular patterns were identified: decreased vascular density and heterogeneous network, increased vessels diameter and tortuosity. The next step of this study is to identify associations between these patterns and cardiovascular diseases in this population‐based study.

National audience; Summary The Montrachet Study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) is a population‐based derived from the 3C Study performed in Dijon. In 2009–2011, 1153 participants from the 3 Cities Study, aged 75 years or more, had an initial eye examination. Apart from the old age of this population, the main interest is that information on cardiovascular and neurologic diseases and a large comprehensive database (blood samples, genetic testing, cognitive tests, MRI) were available. Our first results showed us that despite the high prevalence of self‐reported eye diseases in this elderly population, visual impairment was low and increased with age. These results can improve our knowledge on the characteristics of ocular data in the elderly as well as the relations between eye and age‐related vascular and neurologic diseases.

National audience; Purpose To compare the central retinal thickness (CRT) 9 months after a pan retinal photocoagulation (PRP) with a multi‐spot semi‐automated pattern‐scanning laser (PASCAL) in one sitting (1S‐PRP) vs. four monthly sitting (4S‐PRP) for diabetic retinopathy. Methods Prospective multicenter randomized study carried out between October 2011 and November 2015, including patients with a mild proliferative diabetic retinopathy or a pre‐proliferative diabetic retinopathy (DR). Patients with best‐corrected visual acuity (BCVA) under 54 letters ETDRS (Early Treatment Diabetic Retinopathy Study) and CRT ≥ 350 mm were excluded. DR was treated by PRP with at least 3,000 burns given with a PASCAL laser either in one session or in four monthly sessions. Each patient underwent a complete ophthalmologic exam including an assessment of BCVA, a 9 fields retinophotography and a Spectral‐Domain Optical Coherence Tomography (SD‐OCT) macular imaging at baseline and at one, two, three, six and nine months after inclusion. Results Eighty one eyes of 81 patients were included with a median age of 56 years [IQR : 47.0; 66.0]. The mean CRT and median BCVA did not significantly differ between both groups during all the follow‐up and especially at 9 months (285 mm [273.5; 304.0] in 1S‐PRP vs. 291 mm [275.5; 313.0] in 4S‐PRP, p = 0.27/82 letters [76.8; 87.3] vs. 82 letters [75.3; 87.0], p = 0.76). A positive effect on DR at 9 months was observed in 32 (84.2%) of eyes in the 1S‐PRP group vs. 27 (75.0%) of eyes in the 4S‐PRP group (p = 0.39). The 1S‐PRP strategy was nearly 2 times shorter and less expensive (22 min [17.5; 30.5], 471€/patient) compared with the 4S‐PRP strategy (43 min [37.0; 59.5], p < 0.001, 775€/patient). Conclusions Our study showed the non‐inferiority of the PRP in 1 sitting versus 4 monthly sittings in term of CRT and the medico‐economic interest of a single session PRP.

Hen's egg lysozyme (HEL) activity was measured in vitro with gentamicin and norfloxacin by a turbidimetric technique. Gentamicin at the concentration of 10(-3) M inhibited HEL activity by 39%, while 10(-3) M norfloxacin did not affect HEL activity. However, an in vivo study in healthy persons did not show any significant statistical difference in tear lysozyme activity when 0.3% gentamicin or 0.3% norfloxacin were topically applied.

Purpose: Collagen fibrils and proteoglycans are the main components of the corneal extracellular matrix and corneal transparency depends crucially on their proper arrangement. In the present study, we investigated the formation of collagen fibrils and proteoglycans in the developing cornea of the zebrafish, a model organism used to study vertebrate embryonic development and genetic disease. Methods: We employed thin-section electron microscopy to investigate the ultrastructure of the zebrafish cornea at different developmental stages. Results: The layering of the zebrafish cornea into an epithelium, a Bowman’s layer, stroma and endothelium was observed starting at 72 hr post-fertilization. At this stage, the stroma contained orthogonally arranged collagen fibrils and small proteoglycans. The density of proteoglycans increased gradually throughout subsequent development of the cornea. In the stroma of 2-week-old larvae, the collagen fibrils were organized into thin lamellae and were separated by very large, randomly distributed proteoglycans. At 4 weeks, a regular arrangement of proteoglycans in relation to the collagen fibrils was observed for the first time and the lamellae were also thickened. Conclusion: The present study, for the first time, provides ultrastructural details of collagen fibril and proteoglycan development in the zebrafish cornea. Furthermore, it directly correlates the collagen fibril and proteoglycan composition of the zebrafish cornea with that of the human cornea. The similarities between the two species suggest that the zebrafish could serve as a model for investigating the genetics of human corneal development and diseases.

National audience; The aim of our study was to compare macular pigment optical density between pkakic and pseudophakic eyes in a population‐based study in the elderly. Methods The hree city study (3C) included 9294 participants aged 65 years or more from three cities (Bordeaux, Dijon and Montpellier) in 1999. After a 10‐year follow‐up, Dijon's cohort had a complete ophthalmic examination in the MONTRACHET study; 1153 participants older than 75 years were included. Every participant had fundus photographs, macular pigment optical density measured by two‐wavelength autofluorescence. We retained only one eye for each subject, the one with the best image quality. An experimented investigator recorded macular pigment optical density at 0.5, 1, 2, and 6° eccentricity and classified images into one of the three patterns: no ring, ringlike or intermediate. Subjects with age‐related macular degeneration were excluded. Results We included 534 participants with good image quality. The age was 82.3 ± 3.7 years. There were 247 (46.3%) phakic and 287 (53.7%) pseudophakic. Mean macular pigment optical density was significantly higher in pseudophakic eyes at 0.5° (0.66 ± 0.25 vs 0.44 ± 0.23 density units) at 1° (0.56 ± 0.21 vs 0.39 ± 0.19 density units) at 2° (0.35 ± 0.14 vs 0.25 ± 0.13 density units) and at 6° (0.08 ± 0.04 vs 0.06 ± 0.04 density units), p < 0,0001. There were no significant differences of macular pigment pattern between whatever the lens status (p = 0.64). Conclusions Macular pigment optical density measurement by two‐wavelength autofluorescence is dependent on the lens status so that it should be taken into account when used in elderly where cataractarct surgery is common.

Purpose Holly et al. (1984) showed that the wetting length of the Schirmer strip is influenced by evaporation and may be affected by ambient humidity. This could explain poor reproducibility in different environmental conditions. We therefore studied how preventing evaporation affected wetting length in different conditions of relative humidity. Methods A closed-eye Schirmer test was performed bilaterally in 8 subjects with normal eyes (3 male; mean age 35.5 years SD ± 25), in a Weiss-Gallenkamp controlled environmental chamber, at a temperature of 23°C and with a laminar airflow of 0.08 m/s. Tests were conducted at relative humidities (RH) of 25%, 15% and 5%, with a 10 min break between each test. Eyes received either a standard Schirmer paper (Whatman No. 41 – Biotech®), or a Schirmer paper clad in a waterproof sheath, on a random basis. Sheaths were constructed from a double layer of laminating plastic (Fellowes® ImageLast – outer layer: polyethylene terephthalate; inner layer: ethylene-vinyl acetate), heat-sealed to form a lightweight pouch. Papers were inserted, first on the right eye and then on the left. Wetting length was measured at 5 minutes. If full wetting occurred before this time, the time was noted. Results The wetting length was greater on the sheathed side in 23/24 tests. At 25% RH the mean difference in wetting length was 39.3% SD ± 14.7 (n = 8), at 15% RH the mean difference was 44.3% SD ± 17.8 (n = 8) and at 5% RH the mean difference was 56.3% SD ± 17.7 (n = 7). However, no significant difference was found in % means at different RH, P (0.287) > α ± (0.05) using a repeated measures ANOVA test. Conclusions Sheathing of the Schirmer strip frees the test from a dependence on ambient conditions that can vary seasonally, geographically and locally from clinic to clinic. Such standardisation would improve the performance and utility of the test.

Purpose To evaluate the efficacy and safety of the ultrasonic circular cyclocoagulation procedure in patients with open-angle glaucoma naive of previous filtering surgery. Methods Prospective non-comparative interventional clinical study conducted in five French University Hospitals. Thirty eyes of 30 patients with open-angle glaucoma, intra-ocular pressure (IOP) > 21 mmHg and with no previous filtering glaucoma surgeries were sonicated with a probe comprising six piezoelectric transducers. The six transducers were activated with a 6-s exposure time. Complete ophthalmic examinations were performed before the procedure and at 1 day, 1 week, 1, 2, 3, 6 and 12 months after the procedure. Primary outcomes were qualified surgical success (defined as IOP reduction from baseline ≥20% and IOP > 5 mmHg with possible re-intervention and without hypotensive medication adjunction) and complete surgical success (defined as IOP reduction from baseline ≥20%, IOP > 5 mmHg and IOP

Purpose To evaluate the efficacy and safety of the Ultrasonic Circular Cyclo Coagulation (UC3) procedure in patients naive of previous filtering glaucoma surgery. Methods Prospective non comparative interventional clinical study performed in 5 French glaucoma centers. Thirty eyes of 30 patients (24 primary open-angle glaucoma and 6 secondary glaucoma), with intraocular pressure (IOP) > 21 mmHg, naive of previous filtering glaucoma surgeries, were insonified with a therapy probe comprising 6 piezoelectric transducers. The 6 transducers were activated with a 6 seconds exposure time. Complete ophthalmic examinations were performed before the procedure, and at 1 day, 1 week, 1, 2, 3, 6 and 12 months after. Primary outcomes were surgical success (defined as IOP reduction from baseline ≥ 20% and IOP > 5mmHg) at the last follow-up visit, and vision-threatening complications. Secondary outcomes were mean IOP at each follow-up visits compared to baseline, medication use, and complications. Results IOP was significantly reduced (p 20%) was achieved in 63% of eyes at 6 months after one HIFU procedure, with a mean IOP decrease of 39%. No major intra- or post-operative complications occurred. Conclusion Ultrasonic Circular Cyclo Coagulation seems to be an effective and well tolerated method to reduce intraocular pressure in glaucoma patients naive of previous glaucoma surgery. Commercial interest

Retinal cell membranes are known to be rich in ether-linked phospholipids also termed as “plasmalogens”. Although their functions remain enigmatic, plasmalogens are considered as reservoirs of polyunsaturated fatty acids (PUFAs). These PUFAs were shown to be released from plasmalogens by specific enzymes under specific conditions in order to play several key functions within cells. Data from our laboratory suggest that the metabolism of plasmalogens and PUFAs may be implicated in the pathophysiology of glaucoma, the leading cause of blindness worldwide. Through several experiments on human patients and rodent models of ocular hypertony, we have shown that the metabolism of plasmalogens and PUFAs is affected in patients with primary open-angle glaucoma (POAG) in a stage-dependent manner, that the modifications in plasmalogen metabolism may start years prior the first clinical symptoms of POAG, and that several combinations of dietary PUFAs could be efficient in preventing retinal glaucomatous damage in rodents.

National audience; Purpose: To determine anatomical and functional retinal modifications in patients with idiopathic epiretinal membrane (ERM) without objective symptoms. Methods: This prospective monocentric study included 28 eyes of 28 patients with ERM having a best corrected visual acuity greater than 20/25. All patients underwent a complete ophthalmic examination, including the measurement of the visual acuity on the ETDRS scale, a macular SD‐OCT and a microperimetry at 0, 6 and 12 months. We assessed macular abnormalities on SD‐OCT namely: retinal folds, retrofoveolar deposits, cystoid cavities and external retinal layers alterations. Results: At baseline the mean visual acuity was 85±4 letters, the mean macular sensitivity was 14.3±1.3 decibels, the mean macular thickness was 357±32 micrometers and the score of the SD‐OCT retinal abnormalities per patient was 2.5±0.8. At one year, the score of the SD‐OCT retinal abnormalities per patient was significantly higher: 3.3±1.3 (p=0.007). At one year, the mean visual acuity, the mean macular sensitivity and the mean macular thickness were stable at 84±5 letters (p=0.8), 14.4±1.7 decibels (p=0.8) and 356±43 micrometers (p=0.3), respectively. Conclusion: This study showed an increased number of retinal lesions observed on SD‐OCT with a stable visual acuity and a stable retinal sensitivity measured with the microperimetry after one year of follow‐up.

Purpose To assess what is driving the decision to perform a filtering procedure in a patient suffering from glaucoma. Methods Retrospective study in one single University centre with one glaucoma specialist. All the indications for filtering glaucoma surgeries (alone or combined with cataract extraction) undertaken during 2013 with the same surgeon were reviewed. The indications were as follows: clinical evaluation of the optic disc, visual field progression, progression on imaging (OCT and HRT), poor tolerance to medical treatment, non controlled intraocular pressure (IOP) and cataract. Results Retrospective study in one single University centre with one glaucoma specialist. All the indications for filtering glaucoma surgeries (alone or combined with cataract extraction) undertaken during 2013 with the same surgeon were reviewed. The indications were as follows: clinical evaluation of the optic disc, visual field progression, progression on imaging (OCT and HRT), poor tolerance to medical treatment, non controlled intraocular pressure (IOP) and cataract. Conclusion The indications for glaucoma surgery may be highly variable according to the country, the practice and the surgeon. A multicentre study should be useful to better define what is driving the indications for glaucoma surgery.

National audience; Sufficient oxygen and nutrient supplies to the retina are dependent on a correct development of blood vessels. Polyunsaturated fatty acids (PUFAs) were shown to modulate factors involved in tissue vascularization. A congenital deficiency in ether‐linked phospholipids also termed as “plasmalogens” was shown to lead to abnormal ocular vascularization. Because plasmalogens are considered as reservoirs of PUFAs, we investigated whether they may influence retinal vascular development through the release of fatty acids by a specific phospholipase A2 (PLA2). Studies on mouse models of plasmalogen deficiency and of retinal PLA2 inhibition have shown that plasmalogens regulate retinal angiogenesis during early phases of retinal vascular development by influencing glial activity and primary astrocyte template formation. Subsequent modifications in the expression of genes involved in retinal angiogenesis impacted endothelial cell proliferation and retinal vessel outgrowth. These early defects in retinal vascular development led to a disorganized and dysfunctional retinal vascular network at adult age. These data suggest a crucial role of plasmalogens in retinal vascularization processes through a signalization involving PUFAs and PLA2.