Prospective pilot study: efficacy of intravitreal dexamethasone and bevacizumab injections in the treatment of macular oedema associated with branch retinal vein occlusion.

BACKGROUND/AIMS: To compare the efficacy of intravitreal injections of dexamethasone implants (IVD) with those of bevacizumab (IVB) for the treatment of macular oedema associated with branch retinal vein occlusion. METHODS: A total of 19 patients (19 eyes) were included in this prospective pilot study. Initially, 8 eyes received three IVBs (group 1) and 11 received one IVD (group 2). All the patients underwent a 1-, 3-, 4- and 6-month follow-up visit. A repeated IVB (group 1) or IVD (group 2) was proposed at 4 months when necessary. RESULTS: The mean visual acuity was significantly better 1 month after treatment in group 2, while the mean central macular thickness was also significantly lower in group 2. However, there was no longer any difference between the two groups at 3, 4 and 6 months, neither in terms of visual acuity nor in terms of retinal thickness. More than three IVBs were needed in 3 of 10 patients in group 1 while two IVDs were required in 10 of 11 patients in group 2. CONCLUSION: There was no significant difference between the two treatment regimens at the 6-month follow-up visit. A more rapid functional and anatomical efficacy was noted with IVD during the first month; however, reinjection at 4 months seemed more frequent with IVD than with IVB treatment.

[Ocular surface and outdoor air pollution: A systematic review]. / Surface oculaire et pollution environnementale extérieure : revue systématisée de la littérature.

INTRODUCTION: Air pollution has steadily increased for several decades, with widely studied effects on human health, including increased mortality, incidence of stroke, respiratory and allergic disease. However, the effects of pollution on the ocular surface, in direct contact with the outside world, have been less precisely studied. MATERIALS AND METHODS: We conducted a literature review of articles on the subject published from 1966 to October 2020. Among the 661 articles identified, 33 were retained. Ocular surface disease associated with pollution included non-specific conjunctivitis, dry eye disease, blepharitis, and allergic conjunctivitis. The studied pollutants were particulate matter less than 2.5µm and 10µm (PM2.5, PM10), ozone (O3), nitrogen dioxide (NO2), carbon monoxide (CO) and sulfur dioxide (SO2). Certain air quality parameters such as temperature and relative humidity were also studied. RESULTS: Among the markers of air pollution possibly associated with ophthalmic disease, NO2 and SO2 appear to be the most frequent and highly correlated. High temperatures and low humidity levels also appear to be aggravating factors for the ocular surface. However, due to the heterogeneity of the studies, the results must be interpreted with caution. Indeed, the methodology and the results of the various studies are sometimes contradictory. The inclusion of patients, the analysis of environmental data, and the correlation between these two elements indeed raise numerous methodological questions. CONCLUSION: Air pollution control would appear essential, as well as the development of new studies based on reliable methods of studying the environmental and its clinical effects.

[Digital eye strain. Functional symptoms and binocular balance analysis in intensive digital users]. / Stress oculaire induit par les écrans. Analyses des symptômes fonctionnels et de l'équilibre binoculaire chez des utilisateurs intensifs.

INTRODUCTION: In almost 50 % of cases, acute or chronic screen exposure is accompanied by symptoms of dry eye or binocular imbalance, known as digital eye strain. This phenomenon is described relatively little in the literature. The goal of this study is to determinate the effects of screen exposure on subjective comfort and binocular balance. PATIENTS AND METHODS: This is a cross-sectional, prospective, monocentric pilot study conducted from August to October 2019. The first part of the study focused on disturbances induced by short-term screen exposure (comparison between morning and evening examinations) between a control group (less than 5hours a day) and an exposed group (more than 5hours a day). The second part investigates the consequences of chronic exposure (screen exposure greater than 5hours a day, 5 days a week for one year) excluding pre-presbyopic and presbyopic patients (over 35 years of age). The study parameters consisted of an ocular discomfort questionnaire and binocular function tests (refraction, phoria, near point of accommodation and convergence, fusional vergence (FV), and binocular amplitude facility (BAF)). RESULTS: Short exposure : 52 participants were included. No significant difference was found between the control group (n=24, mean exposure=2.6 hr) and the exposed group (n=28, mean exposure=6.1 hr) for any of the objective parameters. The ocular discomfort score was highest in the exposed group for the following parameters: near (p=0.04) and intermediate (p=0.02) blurred vision and light sensitivity (p=0.04). Chronic exposure: 35 participants were included. The exposed group (n=12, mean exposure=6.7 hr) showed a decrease in FV (p=0.045) and BAF (p=0.038) compared to the control group (n=23, mean exposure=2.1 hr). DISCUSSION: Binocular balance is disturbed by intensive and chronic use of screens. Special attention must therefore be paid to these patients.

[Management of ocular toxoplasmosis in France: Results of a modified Delphi study]. / Prise en charge de la toxoplasmose oculaire en France : résultats d'une étude Delphi modifiée.

OBJECTIVE: To evaluate diagnostic and therapeutic practices and then establish a consensus on the management of ocular toxoplasmosis in France through a Delphi study. MATERIALS AND METHODS: Twenty-three French experts in ocular toxoplasmosis were invited to respond to a modified Delphi study conducted online, in the form of two questionnaires, in an attempt to establish a consensus on the diagnosis and management of this pathology. The threshold for identical responses to reach consensus was set at 70 %. RESULTS: The responses of 19 experts out of the 23 selected were obtained on the first questionnaire and 16 experts on the second. The main elements agreed upon by the experts were to treat patients with a decrease in visual acuity or an infectious focus within the posterior pole, to treat peripheral lesions only in the presence of significant inflammation, the prescription of first-line treatment with pyrimethamine-azithromycin, the use of corticosteroid therapy after a period of 24 to 48hours, the prophylaxis of frequent recurrences (more than 2 episodes per year) with trimethoprim-sulfamethoxazole as well as the implementation of prophylactic treatment of recurrences in immunocompromised patients. On the other hand, no consensus emerged with regard to the examinations to be carried out for the etiological diagnosis (anterior chamber paracentesis, fluorescein angiography, serology, etc.), second-line treatment (in the case of failure of first-line treatment), or treatment of peripheral foci. CONCLUSION: This study lays the foundations for possible randomized scientific studies to be conducted to clarify the management of ocular toxoplasmosis, on the one hand to confirm consensual clinical practices and on the other hand to guide practices for which no formal consensus has been demonstrated.

[Digital eye strain. Symptoms, prevalence, pathophysiology, and management]. / Perturbations oculaires secondaires à l'utilisation de supports numériques. Symptômes, prévalence, physiopathologie et prise en charge.

The digital revolution, which has been underway since the 1980's, is disrupting our daily routines with an exponential increase in the use of screens, which has not been without consequence to our visual system. Digital eye strain (DES), or computer vision syndrome (CVS), includes all the visual symptoms secondary to the use of digital devices. DES is present in at least 50% of regular users of digital media and is defined by blurred vision, difficulty focusing, ocular irritation or burning, dry eye, visual fatigue, headaches and increased sensitivity to light. Exposure time, age, female gender, and work environment are the main factors increasing its prevalence. Its pathophysiology, still poorly understood, is felt to be multifactorial and includes disturbances in the accommodative-convergence balance and changes in the ocular surface. Regarding accommodation and convergence, the studies are mostly old and their results heterogeneous. Conversely, many studies have shown an increase in the prevalence of dry eye in screen users. Although the retinal toxicity of blue light has been proven in in vitro models, the low level of evidence in the available studies does not allow it to be clearly correlated with the symptoms of DES. The objective of this review is to condense the knowledge available in the literature on the symptoms, prevalence, pathophysiology and management of DES.

[Vision screening for children: Recommended practices from AFSOP]. / Le dépistage visuel chez l'enfant : les recommandations de l'Association Francophone de Strabologie et d'Ophtalmologie Pédiatrique (AFSOP).

In light of the international literature, a workgroup of experts from the AFSOP met in February 2019 to formulate updated recommendations for visual screening in children. An ophthalmologic examination during the first month of life is recommended for children at risk of developing infantile organic amblyopia. An ophthalmologic examination including cycloplegic refraction between 12 and 15 months of age is recommended for children at risk of developing functional amblyopia. At any age, a prompt ophthalmologic examination is recommended for a child suspected of functional or organic ocular pathology. In children without risk factors or warning signs, a systematic orthoptic screening examination is recommended during the third year of life, including a monocular visual acuity test, a cover-test and a refraction by photoscreener. The child is referred to the ophthalmologist only in the case of an abnormal screening result, according to the following criteria: visual acuity <5/10, or >1 difference between eyes, abnormal cover test, photodetection refraction values <-3D or>+2.5D for the sphere,>1.5D for astigmatism and>1D for anisometropia. Finally, we review normal childhood refractive errors as a function of age as well as the correct use of photo screening devices.

[Clinical and epidemiological features in Neuromyelitis Optica Spectrum Disorder]. / Comparaison clinico-épidémiologique des pathologies du spectre des neuromyélites optiques.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMO-SD) has been recognized for the past decade. Biomarkers such as anti-Aquaporin 4 antibodies (AQP4) and anti-Myelin Oligodendrocyte Glycoprotein (MOG) have been able to classify NMO-SD into several groups. METHODS: A retrospective study was performed in the Strasbourg University Medical Center among patients with AQP4+, MOG+ and double-seronegative NMO to compare their clinical, epidemiological and paraclinical features. RESULTS: Thirty-two patients with NMO were included. The AQP4+ NMO patients had a median of age of 45 years, with associated myelitis in 62.5% of cases and other autoantibodies in 37.5% of cases. The mean number of relapses by clinical history was 3. The mean initial visual acuity during an exacerbation was 0.3 LogMAR, and the visual acuity after an exacerbation was 0.1 LogMAR. MOG+NMO patients had a median age of 23 years, with severely impaired initial visual acuity (0.6 LogMAR) but better recovery (0 LogMAR); optic disc edema was present in 80% of cases; the mean number of relapses on clinical history was 1. AQP4-/MOG- NMO's were more common in women (70%) and were bilateral in 40% of cases. CONCLUSION: The diagnostic characteristics of NMO-SD are becoming increasingly differentiated, with a positive impact on functional prognosis and long-term progression. Other biomarkers have yet to be identified to improve the diagnosis and treatment of these disorders.

[Interest of environmental exposure chambers in the evaluation of allergic conjunctivitis]. / Intérêt des chambres d'exposition environnementale dans l'évaluation des conjonctivites allergiques.

Allergic conjunctivitis affects 15 to 20% of the general population. It is currently evaluated by the Conjunctival Provocation Test (CPT), which is considered as the gold standard. In the investigation of allergic rhinitis and asthma, environmental exposure chambers (EEC) are increasingly utilised. For allergic conjunctivitis, EEC might be a valid alternative to the CPT. However, evaluation of the allergen response in individual provocation tests or in EECs is still in discussion due to the multiplicity of symptom scores. Indeed, there are many scores used to evaluate allergic conjunctivitis. The main criteria used were described by Abelson in 1990 and include redness, itching, tearing, and swelling. In clinical studies, the specifically ocular score most used is the Total Ocular Symptom Score (TOSS). Few treatments have been evaluated by EEC, including cold compresses, epinastine and N-acetyl aspartyl glutamic acid. Moreover, early data shows good correlation between ocular symptoms induced in an EEC and those assessed during natural exposure. EEC might be a valid alternative to CPT and correlate with natural seasonal allergen exposure. Finally, EEC might be useful in other fields as well, such as in the study of dry eye disease.

Biomimetic doxorubicin loaded polymersomes from hyaluronan-block-poly(gamma-benzyl glutamate) copolymers.

Using "click chemistry" as an easy and versatile synthetic strategy to combine hyaluronan and polyglutamate blocks, we have prepared nanovesicles (polymersomes) that present a controlled size, excellent colloidal stability, and a high loading capacity for hydrophilic and hydrophobic drugs. The unique feature of our concept is the use of hyaluronan, a polysaccharide with known capacity for targeting cancer-related protein receptors, as the hydrophilic portion of a block copolymer system. The cytotoxicity and internalization mechanism of doxorubicin-loaded polymersomes have been evaluated in C6 glioma tumor cell lines. The dual purpose served by hyaluronan, as both a hydrophilic block critical to vesicle formation and a binding agent for biological targets, breaks new ground in terms of multifunctional nanomaterial design for drug delivery.

[Vision screening in children: Review of the literature]. / Dépistage visuel de l'enfant : revue de la littérature.

In children, refractive errors and amblyopia are the two most common causes of avoidable visual impairment. Screening for these is essential, especially since there is a so-called "sensitive" period during which the maturation of the visual pathways is not complete. The child's visual prognosis will therefore depend on his or her age, the duration of the visual deprivation and the timing of management. Visual screening is part of a public health approach, but there are significant regional disparities regarding its organization and the means used. We conducted a review of the literature in order to establish an inventory of available resources and improve practices.

[Clinical and epidemiological profile of pediatric uveitis, course of inflammatory uveitis treated with anti-TNF alpha]. / Profil clinique et épidémiologique des uvéites pédiatriques, évolution des uvéites inflammatoires sous anti-TNF alpha.

INTRODUCTION: Uveitis is the leading cause of acquired childhood blindness with a prevalence of 30 cases per 100,000 inhabitants. There are multiple causes ; nevertheless, there is no standardized etiological assessment. The goal of our study is to define an epidemiological and clinical profile of uveitis diagnosed in a university hospital and their course when treated with anti-tumor necrosis factor (TNF) α. PATIENTS AND METHODS: All cases of uveitis under 18 years old, from 1994 to 2016, were included. Post-traumatic, post-surgical, pseudo-uveitis and retinopathy of prematurity were excluded. Demographic data, patient history, initial ophthalmological status, etiologic assessment data and treatments already underway were collected. RESULTS: Ninety cases of pediatric uveitis were included, among which were 16.7 % infectious uveitis, 38.9 % inflammatory uveitis and 44.4 % idiopathic uveitis. Etiologic investigations were considered incomplete in 45 % of idiopathic uveitis cases. Treatment with anti-TNFα was selected for 15.5 % of patients. In total, 33 % of patients treated with etanercept required other anti-TNFα drugs due to a lack of control of inflammation. Infliximab and adalimumab successfully managed to control inflammation in 28.6 % of cases each. DISCUSSION: Diagnostic criteria based adult systemic disease are sometimes inappropriate for children. The advent of anti-TNFα appears to improve the visual prognosis of inflammatory uveitis resistant to conventional immunosuppressant therapy, but we still need to perfect protocols for their use. CONCLUSION: There are neither standardized etiological assessment nor clear diagnostic and therapeutic protocols for children. TNFα inhibitors are more effective in controlling inflammation in severe pediatric uveitis.

Phase I trial of recombinant adenovirus gene transfer in lung cancer. Longitudinal study of the immune responses to transgene and viral products.

Animal studies indicate that the use of replication-deficient adenovirus for human gene therapy is limited by host antivector immune responses that result in transient recombinant protein expression and blocking of gene transfer when rechallenged. Therefore, we have examined immune responses to an adenoviral vector and to the beta-galactosidase protein in four patients with lung cancer given a single intratumor injection of 10(9) plaque-forming units of recombinant adenovirus. The beta-galactosidase protein was expressed in day-8 tumor biopsies from all patients at variable levels. Recombinant virus DNA was detected by PCR in day-30 and day-60 tumor biopsies from all patients except patient 1. A high level of neutralizing antiadenovirus antibodies was detected in patient 1 before Ad-beta-gal injection whereas it was low (patient 3) or undetectable in the other two patients. All patients developed potent CD4 type 1 helper T cell (Th1) responses to adenoviral particles which increased gradually over time after injection. Antiadenovirus cytotoxic T lymphocyte responses were consistently boosted in the two patients examined (patients 3 and 4). Sustained production of anti-beta-galactosidase IgG was observed in all patients except patient 1. Consistent with anti-beta-gal antibody production, all patients except patient 1 developed intense, dose-dependent Th1 responses to soluble beta-galactosidase which increased over time. Strong beta-galactosidase-specific cytotoxic T lymphocyte responses were detected in patients 2, 3, and 4. Our results clearly show that despite the intensity of antiadenovirus responses, transgene protein expression was sufficient to induce strong and prolonged immunity in three patients. Recombinant adenovirus injected directly into the tumor is a highly efficient vector for immunizing patients against the transgene protein.

Specific protein binding to the simian virus 40 enhancer in vitro.

HeLa cell nuclear extracts and wild-type or mutated simian virus 40 enhancer DNA were used in DNase I footprinting experiments to study the interaction of putative trans-acting factors with the multiple enhancer motifs. We show that these nuclear extracts contain proteins that bind to these motifs. Because point mutations which are detrimental to the activity of a particular enhancer motif in vivo specifically prevent protection of that motif against DNase I digestion in vivo, we suggest that the bound proteins correspond to trans-acting factors involved in enhancement of transcription. Using mutants in which the two domains A and B of the simian virus 40 enhancer are either separated by insertion of DNA fragments or inverted with respect to their natural orientation, we also demonstrate that the trans-acting factors bind independently to the two domains.

Detection of MET mRNA in gastric cancer in situ. Comparison with immunohistochemistry and sandwich immunoassays.

Determination of predictive biomarkers by immunohistochemistry (IHC) relies on antibodies with high selectivity. RNA in situ hybridization (RNA ISH) may be used to confirm IHC and may potentially replace it if suitable antibodies are not available or are insufficiently selective to discriminate closely related protein isoforms. We validated RNA ISH as specificity control for IHC and as a potential alternative method for selecting patients for treatment with MET inhibitors. MET, the HGF receptor, is encoded by the MET proto-oncogene that may be activated by mutation or amplification. MET expression and activity were tested in a panel of control cell lines. MET could be detected in formalin fixed paraffin, embedded (FFPE) samples by IHC and RNA ISH, and this was confirmed by sandwich immunoassays of fresh frozen samples. Gastric cancer cell lines with high MET expression and phosphorylation of tyrosine-1349 respond to the MET inhibitor, BAY-853474. High expression and phosphorylation of MET is a predictive biomarker for response to MET inhibitors. We then analyzed MET expression and activity in a matched set of FFPE vs. fresh frozen tumor samples consisting of 20 cases of gastric cancer. Two of 20 clinical samples investigated exhibited high MET expression with RNA ISH and IHC. Both cases were shown by sandwich immunoassays to exhibits strong functional activity. Expression levels and functional activity in these two cases were in a range that predicted response to treatment. Our findings indicate that owing to its high selectivity, RNA ISH can be used to confirm findings obtained by IHC and potentially may replace IHC for certain targets if no suitable antibodies are available. RNA ISH is a valid platform for testing predictive biomarkers for patient selection.

Phase I study of a recombinant adenovirus-mediated gene transfer in lung cancer patients.

BACKGROUND: Despite vigorous efforts at curbing tobacco consumption and aggressive combined-modality treatment programs, both the incidence of and the mortality from lung cancer have remained virtually unchanged in the last 10 years. More effective innovative therapies are clearly needed. The direct transfer into tumor cells of tumor suppressor genes or toxic gene products that specifically promote tumor cell death and spare nonmalignant cells is a potentially novel anticancer treatment approach that should be investigated. PURPOSE: On the basis of compelling preclinical data, we initiated a phase I study involving six patients with inoperable lung cancer and an endobronchial lesion accessible by bronchoscopy. Our purpose was to evaluate the feasibility, tolerance, and clinical, biologic, and immunologic effects of the intratumoral administration of a recombinant, replication-deficient adenovirus (rAd.RSV beta-gal), using the Rous sarcoma virus promoter to drive transcription of the Escherichia coli lacZ marker gene that encodes for the bacterial enzyme beta-galactosidase (beta-gal). METHODS: From June 1994 through April 1995, six patients (five males and one female) were enrolled in the trial. A single dose of recombinant virus suspension containing 10(7) or 10(8) plaque-forming units (PFU) was injected intratumorally into two successive cohorts of three patients. Eligible patients received concomitant chemotherapy. Patients were kept under isolation conditions from 3 days before the injection was given until virus excretion was undetectable. Biopsy specimens of the tumor and surrounding mucosa were collected on the 8th day and at 1, 2, and 3 months after injection. They were analyzed by cell culture, polymerase chain reaction (PCR), and beta-gal expression for the presence of recombinant adenovirus. So that the risk of virus recombination or complementation could be minimized, wildtype adenovirus carriers among the hospital staff (identified by PCR) were excluded from contact with patients who were potentially excreting recombinant virus. RESULTS: beta-gal was expressed in tumor biopsy specimens of three patients (one who received the 10(7) PFU dose level and two who received 10(8)). Bronchoalveolar lavage specimens collected immediately after injection were positive for recombinant adenovirus when analyzed in culture and by PCR. All biologic fluids were negative for recombinant virus as judged by PCR after day 12, with the exception of bronchoalveolar lavage specimens (positive PCR up to 90 days in two of three patients treated with 10(8) PFU). The blood samples obtained from the three patients treated with 10(8) PFU showed positive PCR results immediately after virus injection. Patients were kept in isolation for a median of 17 days. The most common toxic effects were moderate bleeding (occurring in two patients) during bronchoscopy and fever (seen in four patients). Endoscopic and clinically objective antitumor responses were seen in four patients, including one patient who showed a complete response by pathologic evaluation. The median survival for the patients was 12.5 months (range, 3-16+ months). Throughout the study, hospital staff remained negative for recombinant adenovirus infection. CONCLUSIONS: This ongoing phase I study has demonstrated that a recombinant adenovirus-mediated marker gene, such as rAd.RSV beta-gal, can be safely introduced into humans and that the gene product is expressed by lung tumor cells of the host.

Diuretic effects on cardiac hypertrophy in the stroke prone spontaneously hypertensive rat.

OBJECTIVE: The aim was to compare the effects of two diuretics, indapamide and hydrochlorothiazide, on cardiac hypertrophy in stroke prone spontaneously hypertensive rats (SHR-SP). METHODS: Six week old SHR-SP, on a 1% sodium chloride water intake, were treated with oral indapamide (3 mg.kg-1 x d-1) or hydrochlorothiazide (20 mg.kg-1 x d-1) over a 44 d period. The hypertrophic process was evaluated by classical indices and by the morphological analysis of myocyte cross sectional area, coronary artery thickness, and immunohistochemical analysis of interstitial fibrosis. RESULTS: In the untreated SHR-SP on 1% sodium chloride, all animals developed severe hypertension and cardiac hypertrophy when compared to normotensive salt loaded WKY by 13 weeks of age. In salt loaded SHR-SP treated with indapamide or hydrochlorothiazide, systolic blood pressure was moderately decreased by the end of the treatment when compared with untreated SHR-SP, at 259(7) and 245(7) mm Hg respectively, v 300(11) mm Hg, p < or = 0.05. Myocyte enlargement appears to be the main feature involved in the development of cardiac hypertrophy in the SHR-SP. By the end of treatment both indapamide and hydrochlorothiazide prevented the development of cardiac hypertrophy evaluated by heart weight to body weight ratio [4.69(0.07) and 4.61(0.08) respectively, v 5.39(0.13), p < or = 0.001] and myocyte hypertrophy (-33% and -21% of the SHR-SP values, p < or = 0.001). Myocardial interstitial fibrosis and perivascular fibrosis were practically absent in the two treated groups. CONCLUSIONS: Our results allow the characterisation of SHR-SP cardiac hypertrophy and indicate that the two types of chronic diuretic treatment prevent SHR-SP cardiac hypertrophy with a drug specific efficiency.