[Real life retrospective study of 98 eyes treated with intravitreal dexamethasone or anti-VEGF injections for macular edema due to diabetes or retinal vein occlusion]. / Étude rétrospective de vraie vie de patients traités par injections intra-vitréennes de dexaméthasone ou d'anti-VEGF pour œdèmes maculaires diabétiques ou secondaires à une occlusion veineuse rétinienne : à propos de 98 yeux.

PURPOSE: To evaluate long term outcomes of patients presenting with diabetic macular edema (DME) or edema secondary to a retinal vein occlusion (RVO). METHODS: This is a real world, retrospective, single-center study of 65 eyes of 47 patients treated for DME and 33 eyes of 33 patients with macular edema secondary to RVO between July 2012 and October 2018. The patients treated were treatment-naive and were followed for at least one year. We collected data such as visual acuity, central macular thickness, intravitreal injections (number/year, injection schedule, number of switches), number of visits and cases of vision loss. RESULTS: DME: the mean age at inclusion was 65.9years with 60.4% women, and the mean follow-up was 28.5months. The mean gain in visual acuity after 1year of follow-up was 6.4 ETDRS letters for patients treated with anti-VEGF and 2.6 letters for patients treated with dexamethasone. The average number of intravitreal injections of anti-VEGF was 5.6/year, compared to 2.9/year for dexamethasone. Fourteen patients initially treated with anti-VEGF were switched to dexamethasone. RVO: the mean age at inclusion was 68.8years with 54.5% women and a mean follow-up of 31.1months. The mean gain in visual acuity after 1year of follow-up was 26.7 ETDRS letters for patients treated with anti-VEGF and 7.0 letters for patients treated with dexamethasone. The average number of intravitreal injections of anti-VEGF was 5.8/year, compared to 2.4/year for dexamethasone. Five patients initially treated with anti-VEGF were switched to dexamethasone in the first year of follow-up. CONCLUSION: In this real-life retrospective study, we found good anatomical and functional results similar to those reported in other studies, remaining stable over time, for patients with DME or macular edema secondary to RVO.

[Treatment of exudative age-related macular degeneration: Consensus of French experts for first-line treatment selection and the importance of long-term risk/benefit ratio]. / Consensus d'experts français sur les critères de choix d'un traitement de 1re intention dans la DMLA néovasculaire et importance du ratio bénéfice/risque à long terme.

Choosing a first-line treatment to optimize long-term outcomes is a major challenge for treating patients with neovascular age-related macular degeneration (AMD). The development of several new molecules makes it critical to identify the relevant factors to consider so as to provide an optimal risk-benefit ratio when initiating a treatment in naïve patients with neovascular AMD. This paper proposes a consensus established with the Delphi method (which includes a gradation in a consensus based on an analysis of the convergence rate of answers) to provide criteria that guide the ophthalmologist's decision for treatment initiation and follow-up in neovascular AMD patients. Fourteen questions were submitted to 93 French retina experts. Thirteen (93%) of the questions reached a consensus (≥50% of answers consensual). The criteria recommended to take into account were both efficacy and onset of action of the molecules, their safety, and the ability to decrease injection frequency. The primary criterion of expected efficacy of a molecule is a combination of the gain in visual acuity and resorption of retinal fluid. With regard to safety, experts recommend tighter follow-up for molecules currently in development, and at every scheduled visit, patients should be screened to identify early any potential adverse effects such as intraocular inflammation, retinal vasculitis or vascular occlusion. Experts also emphasize the importance of the packaging of the biological, with a preference toward prefilled syringes. Injection frequency is a key factor, and the authors recommended aiming for a maximal injection interval of 12 to 16 weeks. The stability of that maximum interval is also an important factor to consider in treatment selection.

[Neovascular recurrences in 42 treatment-naive eyes with neovascular age-related macular degeneration (AMD) followed for over 2 years]. / Étude des récidives exsudatives chez 42 yeux naïfs atteints de dégénérescence maculaire liée à l'âge suivis plus de 2 ans.

INTRODUCTION: The objective of this study was to analyze the reproducibility or variability of the time period to exudative recurrences in patients who were treated with intravitreal injections (IVT) of anti-VEGF (ranibizumab, aflibercept) for exudative age-related macular degeneration (AMD). The data studied included the number of recurrences per year, the time between the last IVT and the recurrence, fluctuation over time in the same patient, and changes in the therapeutic management of these exudative recurrences with regard to repeat induction therapy of three IVT, changes in monitoring protocols, and switches in anti-VEGF molecules. MATERIALS AND METHODS: We conducted a retrospective, single center, "real-life" study at the Nantes University Hospital, including 33 patients (42 eyes) between March 2012 and March 2017. These were IVT-naive patients, in whom anti-VEGF IVT treatment was initiated for management of exudative AMD, with a follow-up period of at least two consecutive years. The main outcome was the fluctuation in recurrences times for the same patient. RESULTS: Of the 33 patients included, 9 had bilateral involvement, for a total of 42 eyes. Twenty were women (60.6 %), the median age at inclusion was 78.5 years with a follow-up period of 3.7 years. The average time to recurrence was 11.6 weeks after the last IVT. The first recurrence occurred within 9.8 weeks after the last IVT. 12.3% of the eyes had consisent recurrence times, with fluctuations of less than 2 weeks between the various relapses over the two years of follow-up. a total of 7.1% of the eyes had no exudative recurrences during follow-up. The first exudative recurrence occurred at a mean of 38.2 weeks after diagnosis of the disease, or 37.2 weeks after the first IVT. 14.3% of the recurrences led to the administration of a repeat induction of three intravitreal anti-VEGF injections, 8.6% led to a change in anti-VEGF molecule, and 7.1% to a modification of the treatment protocol. DISCUSSION: The goal of this study was to analyze the variability of the time to exudative recurrence in patients treated with anti-VEGF IVT in the context of exudative AMD, because, since the advent of anti-VEGF IVT in 2007, few data have been available on long-term follow-up and fluctuations in recurrence times in patients who will receive treatment for several years. CONCLUSION: Recurrences times are not reproducible over follow-up, particularly in patients experience their first exudative recurrence beyond 8 weeks and in patients with multiple exudative recurrences.

[Anatomic-functional correlations in birdshot chorioretinopathy: An observational single-center prospective study]. / Corrélations anatomo-fonctionnelles dans la choriorétinopathie de Birdshot : étude prospective monocentrique observationnelle.

INTRODUCTION: The purpose of this study was to identify anatomic-functional correlations in patients with Birdshot chorioretinopathy in order to better understand the mechanisms of visual loss. MATERIALS AND METHODS: We conducted a single-center observational prospective study at the Nantes University Medical Center including all patients followed for Birdshot chorioretinopathy between January 2019 and July 2019. The parameters studied were visual acuity, microperimetry, standard automated perimetry, SD-OCT, EDI-OCT, OCT-A, RNFL-OCT, wide-field fundus photographs, and fluorescein and ICG angiography. RESULTS: Forty-four eyes were studied. A significant correlation was found between visual acuity and retinal thickness (P=0.002, r=0.44), but not choroidal thickness (P=0.16). A significant correlation was also observed between retinal sensitivity and total macular thickness (P<0.001, r=0.68) as well as inner retinal thickness (P<0.001, r=0.65), while the correlation was weaker with choroidal thickness (P=0.03, r=0.32). There was a weak correlation between retinal sensitivity and superficial capillary density (P=0.02, r=0.42) as well as deep capillary density (P=0.02, r=0.41). The peripheral hypo-autofluorescent zones correspond to the visual field defects, but these defects are larger than the hypo-autofluorescent zones. Patients with paracentral or peripheral field defects had a history of vasculitis more often than hypo-ICG spots. DISCUSSION: We found significant correlations between functional parameters such as visual acuity and retinal sensitivity and retinal anatomic parameters, particularly the inner retina, while there was no correlation shown with choroidal anatomic parameters. CONCLUSION: The main results of our study suggest a retinal rather than choroidal origin of the degradation of visual function in birdshot chorioretinopathy.

[Retinal detachment surgery: Evaluation of the anatomical success and functional outcomes in a consecutive series of patients operated between 2011 and 2014 at Nantes University Medical Center]. / Chirurgie des décollements de rétine : évaluation du succès anatomique et du devenir fonctionnel sur une série consécutive de patients opérés entre 2011 et 2014 au CHU de Nantes.

OBJECTIVE: Evaluate the anatomical and functional outcomes of retinal detachment (RD) surgery from January 2011 to November 2014. MATERIALS AND METHODS: We conducted a retrospective study of 182 eyes of 175 patients with a minimum follow-up of 6 months, operated for RD at Nantes University Medical Center. It consists of 56 simple RDs and 126 complex RDs treated in first intention by Scleral Buckling (SB), vitrectomy or combined surgery. The analysis is based on anatomic reattachment at the end of a follow-up of at least 6 months after the first surgery and the progression of the best corrected visual acuity (BCVA). RESULTS: One hundred and seventy-two vitrectomies, 15 SB and 5 combined surgeries (vitrectomy+SB) were performed. The overall anatomical success rate after a single operation was 131 eyes (72 %). It increased to 163 eyes (90 %) at the end of the follow-up. Depending on the type of RD, anatomic success at 6 months after surgery was achieved for 47 simple RDs (84 %) and 84 complex RDs (67 %). At the end of the follow-up, after one or more operations, these rates increased to 53 simple RDs (95 %) and 110 complex RDs (87 %). For all RDs with an anatomically successful result, we observed a visual improvement≥2 lines in 45 % of cases and a postoperative BCVA≥5/10 in 40 % of cases. CONCLUSION: This study confirms the evolution toward vitrectomy surgery for retinal detachment. It finds anatomical and functional results consistent with the literature, with a percentage of approximately 5 % of RDs still not reattached in spite of several operations.

[Management of wet AMD in France in 2015]. / Prise en charge de la DMLA exsudative en France en 2015.

PURPOSE AND CONTEXT: Intravitreal administration of anti-VEGF agents, available in France since 2007, allows stabilization and improvement in visual acuity in wet age-related macular degeneration (AMD). In the past few years, the management of this disease has evolved in terms of both diagnostic methods and treatment schedules, which have been adapted to the pathophysiology of AMD. The goal of this survey, performed in a representative sample of French ophthalmologists, was to describe the evolution of medical practices one year after a similar survey (Massé et al., J Fr Ophtalmol 2016; 39: 40-7). METHOD: The survey was performed from December, 2014 to March, 2015 in 191 ophthalmologists (53 general ophthalmologists and 98 retina specialists) with an on-line questionnaire. This questionnaire was designed by a committee of ophthalmologists to describe practices concerning screening, diagnosis, treatment and follow-up of wet AMD. RESULTS: An initial intravitreal injection of an anti-VEGF agent was usually performed within 10 days after the diagnosis of wet AMD by 98% of ophthalmologists and within 5 days by 63%. The treatment protocols favored by retina specialists were pro re nata (PRN) for 58%, Observe and Plan for 25% and Treat and Extend for 17%. Bilateral intravitreal injections were performed on the same day by 46% of retina specialists, mostly for the convenience of the patient and because of the low infectious risk. The initial protocol was maintained by one third of retina specialists throughout the course of treatment, while two thirds of them reported that they reassessed the protocol on average after 5 months. CONCLUSION: This survey on the practices of the ophthalmologists in wet AMD highlights an improvement in the time course of patient management and an evolution of treatment schedules toward individualized protocols.

[Treatment of macular edema: Comparison of efficacy and tolerability of subconjunctival triamcinolone injections, sub-tenon's triamcinolone injections and intravitreal dexamethasone implant]. / Traitement des œdèmes maculaires : comparaison de l'efficacité et de la tolérance des injections sous-conjonctivales de triamcinolone, des injections sous-ténoniennes de triamcinolone et des injections intra-vitréennes de l'implant de dexaméthasone.

The area of uveitis is related to numerous pathological entities. One of the main causes of decreased visual acuity in these patients is macular edema. One aspect of the treatment includes cortosteroids used peri- and intra-ocularly. MATERIALS AND METHODS: The goal of our work was to estimate the criteria of efficacy (on improvement in visual acuity and macular edema, as well as time to recurrence) and safety (on intraocular pressure and cataract) of these various routes of administration of corticosteroid after a single injection. We compared patients treated with Ozurdex® versus subconjonctival triamcinolone versus sub-tenon's triamcinolone. This is a retrospective study conducted in 2 tertiary centers, the university medical center of Nantes and La Pitié-Salpêtrière hospital from November, 2011 to November, 2013. RESULTS: At presentation, 25 % of the patients displayed VA better than 5/10. During follow-up, this proportion increased to 45 % at M1, 50 % at M3, 49 % at M6 and 48 % at the end of follow-up. There was no significant difference between the groups with respect to VA gain. The reductions in mean CMT compared with D0 were all statistically significant (improvement of one line in log-OCT). We observed an improvement in macular thickness of 88 % at M1, 86 % at M3, 61 % at M6 and 60 % at the end of follow-up, significant at each time, with no significant difference between the three groups. A comparison of time to anatomic vs. functional recurrence was performed, showing no difference. The largest increase in IOP was observed at M1, statistically different from the other time points. DISCUSSION: Intra- and periocular injections should be considered as an adjuvant therapy, since the majority of the conditions in question require systemic treatment. They allow for increased intravitreal concentrations with fewer systemic effects. CONCLUSION: We demonstrated neither any true superiority of any of the 3 treatments nor any difference in tolerability between the 3 groups.

[Overview of medical practices in wet AMD in France]. / Vue d'ensemble des pratiques médicales dans la DMLA exsudative en France.

BACKGROUND AND OBJECTIVES: Wet AMD is characterized by the formation of choroidal neovascularization, mediated by vascular endothelial growth factor (VEGF) and responsible for a decrease in visual acuity and metamorphopsia of sudden onset. Intravitreal anti-VEGF can stabilize or even improve visual acuity. Although there is a consensus among ophthalmologists about the induction phase injection of anti-VEGF, there appear to be differences in practice regarding therapeutic treatment modalities. The goal of this work was to explore this hypothesis and to better understand real life practices. METHOD: The Ipsos institute conducted a qualitative survey of 16 retinal specialists and 9 general ophthalmologists in September and October 2013, using a questionnaire developed by a scientific committee of experts. Fifteen telephone interviews and 4 face-to-face meetings with a retina specialist and an ophthalmologist were conducted. This qualitative study allowed the development of a quantitative survey of 200 retina specialists and general ophthalmologists, conducted between November 2013 and January 2014, to describe practices in diagnosis, treatment and follow-up of wet AMD. RESULTS: A distribution of roles between the ophthalmologist making the initial diagnosis and the retinal specialists responsible for treatment and follow-up was noted. Treatment was initiated within 10 days of diagnosis as recommended by the HAS in only one third of patients. After the induction phase of treatment, i.e. three monthly injections of anti-VEGF, treatment and monitoring practices were heterogeneous with 74% of physicians using a PRN treatment protocol, 22% a bimonthly protocol (with monthly monitoring in 19.4% of cases) and 4% a "treat and extend" protocol. There was little change in the protocol chosen in the case of recurrence. CONCLUSION: Three quarters of ophthalmologists report using a PRN protocol, and over 90% report seeing their patients monthly, either for injection or for a check-up. This apparent uniformity is in reality more complex: for the large majority, they prefer to closely follow the patient so as to treat the slightest recurrence, but with great variability in practices with regard to individualization of treatment.

[Management of macular edema secondary to retinal vein occlusion]. / Prise en charge de l'œdème maculaire secondaire à une occlusion veineuse rétinienne.

BACKGROUND: In recent years, intravitreal injections have added to the treatment modalities available for macular edema (ME) secondary to retinal vein occlusion (RVO). This article aims to provide an update regarding the management of ME secondary to RVO. METHODS: A work group met in order to analyze the literature available on Embase/PubMed, regarding treatments for venous occlusion that have received market approval and are reimbursed in France. In total, 33 articles were selected. Consensus within the group for recommendations was based on this data from the literature review and clinical experience and was reported in this article. RESULTS: The management of ME secondary to branch retinal vein occlusion (BRVO) or central vein occlusion of the retina (CRVO) differs on a number of points. Methods of best practice were discussed separately for BRVO and CRVO, taking into account various ocular and associated parameters. DISCUSSION: Ranibizumab and dexamethasone implant are the first-line treatments for visual impairment due to ME secondary to RVO. The choice of either of these drugs may take into account various ocular and extraocular parameters. A change of treatment to one or the other or to laser may also be considered during follow-up.

[Anterior chamber migration of intravitreal dexamethasone implant (Ozurdex®) in pseudophakic eyes: report of three cases]. / Migration en chambre antérieure de l'implant intravitréen de dexaméthasone Ozurdex® chez le pseudophake: à propos de trois cas.

INTRODUCTION: Intravitreal implantation of Ozurdex(®) (Allergan Inc., Irvine, CA, USA) is being used widely for the treatment of macular edema secondary to retinal vein occlusion and in the setting of non-infectious posterior uveitis. We describe a complication little reported in the literature until now: migration of the dexamethasone implant into the anterior chamber. PATIENTS AND METHODS: We report three cases of migration in two pseudophakic patients with iris claw lenses (on the anterior and posterior aspects of the iris) and in one pseudophakic patient with a posterior chamber IOL and zonular rupture. DISCUSSION: The risk of anterior chamber migration of the Ozurdex(®) implant is increased in cases of prior vitrectomy (three cases), prone positioning and dilation of the pupil (mydriasis). Clinical tolerability of the implant in the anterior chamber is poor in all cases, with diffuse corneal edema. Endothelial cell loss occurs, as demonstrated by specular microscopy performed in two of our patients. Removal or repositioning of the Ozurdex(®) implant into the posterior segment must be performed without delay because of the risk of endothelial toxicity. CONCLUSION: Patients without perfect zonular/posterior capsular integrity present a high risk of anterior chamber migration of the Ozurdex(®) implant. In such cases, anti-VEGF therapies should be discussed as an alternative.

[The myopic vitreous. Why is its examination so difficult?]. / Le vitré du myope fort. Pourquoi son examen est-il si difficile ?

The examination of a high myopic vitreous is difficult for several reasons, including optic phenomena and vitreous liquefaction. The diagnosis of a posterior vitreous detachment may be problematic and confused with the observation of a large lacuna posterior margin.

[Neuraminidase inhibitors and risk of H5N1 influenza]. / Les inhibiteurs de neuraminidase face au risque de grippe aviaire.

Oseltamivir and zanamivir are highly potent inhibitors of influenza A and B neuraminidase and operate by inhibiting viral replication, and more specifically, the release and the movement of the virus through mucus. Neuraminidase inhibitors reduce the severity and duration of symptoms, and prevent clinical influenza as post-exposure and seasonal prophylaxis. Both have similar efficacy; oseltamivir has a more convenient route of administration, and zanamivir a more favourable resistance profile. Pending availability of effective vaccines, neuraminidase inhibitors are the only specific antiviral drugs which might be opposed to a possible pandemic that could emerge from the current highly pathogenic H5N1 virus. Although the effectiveness of oseltamivir and zanamivir for the therapy of clinical H5N1 influenza is questionable, simulation models suggest that a combination of targeted antiviral prophylaxis and quarantine might be able to contain an emerging influenza strain at the source. As a consequence, after an initial lack of commercial success probably related to the mild intensity of seasonal influenza during the last winters, neuraminidase inhibitors are now stockpiled by many countries to prepare for an outbreak.

What is the arcuate eminence?

A study was made of 100 homogeneous CT scans of the petrous part of the temporal bone to determine whether or not the arcuate eminence (AE) is a good landmark for the superior semicircular canal (SSCC) in the suprapetrous approach to the internal acoustic meatus which is used in the extirpation of acoustic neuromas. Direct measurements were made on consecutive coronal sections, 1 mm thick. The AE was absent from the petrous surface in 15% of cases. It corresponded to the relief of the SSCC in 37% of cases; laterally, however, it was separated from the petrous cortex by bone whose thickness varied from 0.5 to 5 mm. Finally, in 48% of cases, the AE was not a good landmark for the canal although nonetheless it participated in the development of this bulge in 46% of cases, always lying towards the medial border of the pneumatized eminence. In addition, study of the coronal sections with MRI allowed us to confirm that the AE does not routinely correspond to the imprint of a temporal sulcus. The AE, whose presence on the petrous surface is due to the combined effects of the SSCC, the air cells of the petrous part of the temporal bone and the temporal sulci, is only a good guide to the SSCC in 37% of cases and should not be considered as a reliable surgical landmark.

Single-chain lipopeptide vaccines for the induction of virus-specific cytotoxic T cell responses in randomly selected populations.

Effective vaccine development is now taking advantage of the rapidly accumulating information concerning the molecular basis of a protective immune response. Analysts and medicinal chemists have joined forces with immunologists and taken up the clear challenge of identifying immunologically active structural elements and synthesizing them in pure, reproducible forms. Current literature reveals the growing interest for extremely reductionist approaches aiming at producing totally synthetic vaccines that would be fully defined at the molecular level and particularly safe. The sequential information contained in these formulations tends to be minimized to those epitopes which elicit neutralizing antibodies, or cell-mediated responses. In the following review, we describe some of our results in developing fully synthetic, clinically acceptable lipopeptide vaccines for inducing cytotoxic T lymphocytes (CTL) responses in randomly selected populations.

Lipopeptide presentation pathway in dendritic cells.

Lipopeptides are currently being evaluated as candidate vaccines in human volunteers. They elicit cytotoxic responses from CD8(+) T lymphocytes, whereas peptides without a lipidic moiety usually do not. The exact processing and presentation pathways leading to association with MHC class I molecules has not yet been defined. This is of particular interest in dendritic cells, which are required for primary T cell stimulation. We have tracked lipopeptides derived from an HLA-A2.1-restricted HIV-1 Reverse Transcriptase epitope, by N-terminal addition of an N-epsilon-palmitoyl-lysine. Entry of the lipopeptides into human monocyte-derived dendritic cells (MDC) was mediated by endocytosis, as assessed by colocalization using analogs labelled with rhodamine, and by confocal microscopy. This internalization in DC induced functional stimulation of CD8(+) T lymphocytes specific for the epitopes, quantified by Interferon-gamma ELISPOT assays. The peptide alone was not visualized inside the DC and was only presented through direct surface association to HLA-A*0201. Therefore, lipopeptides provide a model system to define precisely the cross-presentation pathways that lead exogenous proteins to associate with class I MHC molecules within dendritic cells. Using this approach, cross-presentation pathways can be better defined and vaccine lipopeptides can be further optimized for MHC class I association in human dendritic cells.

Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.