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Biomedical subjects

C Creuzot-Garcher

Publications and source records attributed to C Creuzot-Garcher.

At least 19 recordsLinked to original sources

Measurement of inflammatory cytokines by multicytokine assay in tears of patients with glaucoma topically treated with chronic drugs.

AIM: To investigate the ocular surface inflammatory response to chronic topical treatments in patients with glaucoma by measuring the cytokine level in tears using multiplex bead analysis. METHODS: Tear samples were collected from 21 patients with glaucoma and 12 healthy volunteers. Tears were analysed for the presence of 17 cytokines: interleukin (IL)1beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, granulocyte-colony stimulating factor, granulocyte-macrophage stimulating factor, interferon (INF)gamma, monocyte chemotactic protein (MCP)1, macrophage inflammatory protein 1beta and tumour necrosis factor (TNF)alpha. The cytokines in each sample of tears were measured using multiplex bead analysis with microspheres as solid support for immunoassays. RESULTS: In the tears of treated patients, proinflammatory cytokines (IL1beta, IL6, IL12, TNFalpha) were significantly increased compared with controls. T helper (Th)1 (INFgamma, IL2) and Th2 (IL5, IL10, IL4) type cytokines were also significantly higher (p<0.05); however, the most marked increase was observed with Th1 cytokines. The expression of chemokine IL8 and MCP1 was also increased in the treated group. CONCLUSION: This study shows that pro-inflammatory cytokine secretion by conjunctival cells is increased in response to topical treatments for glaucoma. The characterisation of cytokines in tears was previously limited by the small volume attainable, a limitation that has been overcome by multiplex analysis.

Administration, Topical↗

Trefoil factor family 1, MUC5AC and human leucocyte antigen-DR expression by conjunctival cells in patients with glaucoma treated with chronic drugs: could these markers predict the success of glaucoma surgery?

AIMS: To evaluate conjunctival expression of trefoil factor family (TFF)1, MUC5AC and human leucocyte antigen (HLA)-DR in patients with glaucoma treated with topical drugs, and to determine whether these parameters can predict the outcome of glaucoma surgery. METHODS: 77 conjunctival impression cytology specimens were collected from 77 patients with glaucoma (66 receiving drops with preservative and 11 treated with preservative-free drops) and 43 controls. TFF1, MUC5AC and HLA-DR expression was analysed using flow cytometry. Trabeculectomy was performed in 56 patients; success was defined as an intraocular pressure (IOP) < or =15 mm Hg without any IOP-lowering drug at 6 months. RESULTS: The expression of TFF1, MUC5AC and HLA-DR was significantly higher in patients than in controls (p = 0.01, 0.05 and 0.004, respectively). A higher expression of MUC5AC was found in patients treated with preserved drops than in those receiving unpreserved drops (p = 0.04). A higher MUC5AC expression and a lower HLA-DR expression was observed in successful glaucoma surgeries than in failures. CONCLUSIONS: TFF1 and MUC5AC secretions are probably a response to mild ocular surface changes caused by long-term use of topical treatment. Their increased expression could be a predicting factor of further successful glaucoma surgery.

Adrenergic beta-Antagonists↗

[How to perform intravitreal injections].

Drugs to treat retinal diseases are often injected intravitreally. This procedure can cause severe complications. We present ways to minimize the risk for complications. Rigorous preoperative antisepsis with povidone iodine, a sterile environment (using gloves and a mask for the injector, a lid speculum, and a drape on the eye to be injected), and immediate follow-up after injection are key issues of the injection technique.

Humans↗

[Activation of TH1/TH2 pathways detected through the expression of CCR4 and CCR5 on the ocular surface of glaucomatous patients treated over the long term].

PURPOSE: The aim of this work was to study, using flow cytometry, the expression of two chemokine receptors, CCR4 and CCR5, known to be related to the TH2 and TH1 systems, respectively, and the expression of HLA-DR, a hallmark of inflammation, on conjunctival impression cytology specimens (ICS) of glaucomatous patients treated over the long term. PATIENTS AND METHODS: In this case-control study, ICS were taken in a series of 35 glaucomatous patients treated with topical antiglaucoma drugs for more than 1 year (seven with beta-blockers, ten with prostaglandins, and 18 receiving multiple treatments), and 20 normal subjects. Conjunctival cells were collected and incubated with specific monoclonal antibodies directed against CCR4, CCR5, and HLA-DR, in order to measure, in a masked manner using flow cytometry, the percentage of cells positive to each marker in the conjunctival epithelium. RESULTS: Compared to normal subjects, HLA DR expression was significantly elevated in glaucomatous patients, with a tendency toward higher levels in the multitreatment group and lower levels in patients treated with prostaglandins, which did not differ significantly from control values. Both CCR4 and CCR5 significantly increased in glaucoma patients on multitreatment or monotherapy compared with normal subjects. CONCLUSION: This study demonstrates the overexpression of these two chemokine receptors in the conjunctival epithelium of patients treated for more than 1 year. Our results showing the simultaneous overexpression of CCR4 and CCR5 thus suggest that the chronic use of topical treatments may concurrently stimulate the TH1 and TH2 systems. These results evoke inflammatory mechanisms, combining allergy and toxicity, and confirm the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.

Case-Control Studies↗

[Analogies between atherosclerosis and age-related maculopathy: expected roles of oxysterols].

The pathogenesis of age-related macular degeneration (ARMD) is not clearly understood. Like other age-related diseases, it is associated with abnormal deposits called drusen. These drusens are localized in Bruch's membrane. Recent investigations have shown a link between drusen formation and inflammatory and immunologic reactions. The involvement of oxidative stress is supported by available data as an important contributing factor in the developement of ARMD. The data regarding the nature and the source of the deposits suggest that ARMD may share similar pathways with atherosclerosis. The role of oxydized products of cholesterol, the oxysterols, in the pathogenesis of atherosclerosis is well known. As cholesterol is a constituent of drusens, oxysterols could be involved in retinal pigment epithelium and photoreceptor lesions occurring in ARMD owing to their cytotoxic, pro-inflammatory, and pro-oxydant properties.

Atherosclerosis↗

[Conjunctival provocation test: recommendations].

The diagnosis of ocular allergy, which has become a real public health problem occurring in 25% of the general population and continues to rise, requires allergic testing. Skin and blood tests combined with interviewing the patient demonstrate sensitivity to one or more antigens. However, while allergic testing and interviews generally reveal the cause of the symptoms, only the conjunctival provocation test (CPT) provides clear evidence of a functional relation between the conjunctival pathology and exposure to the antigen. Since there is still no validated consensus regarding the criteria for positivity of the CPT in routine practice, the working group attempted to establish the major guidelines for conducting the test, to standardize approaches and pinpoint areas of uncertainty. The group established a consensus regarding the conditions for using the test (patient selection, allergens to be tested, usable concentrations, the test protocol, the signs and symptoms to be assessed, interpretation of results, follow-up) and identified two distinct patient groups (outpatients and hospitalized patients) in whom test-taking conditions are different. The outpatient group includes patients suffering from benign forms of conjunctivitis (acute, seasonal, or chronic) and those sensitive to the usual allergens (mainly domestic and airborne). In these cases, the test is given in a medical setting with an allergologist or an ophthalmologist who instills the drops relatively rapidly. The criterion for positivity is the extent of the pruritus. On the other hand, in the hospital population, which is composed of patients suffering from vernal conjunctivitis, the attempt to establish the triggering factor requires a more elaborate protocol carried out in an ophthalmologic setting and based on the association of a range of clinical and biological factors. The deliberations of the working group should lead to the standardization of the CPT procedure for diagnostic purposes.

Allergens↗

[Lacrimal film and the ocular surface].

Abnormalities of the ocular surface affect a large proportion of the general population. Symptoms depend on whether the lids, the corneoconjunctival surface, or the lacrimal layer are involved. The latter results from the balance of a fragile mixture of water, lipids, and mucus. Different circumstances can lead to the disruption of the lacrimal layer associated with dry-eye symptoms, eventually leading to inflammation. Alterations observed during dry-eye disease, meibomian dysfunction, allergic conjunctivitis, contact lens wear infectious conjunctivitis, or after refractive surgery are reviewed. Patient relief depends on a reliable analysis of the mechanism involved in the ocular surface disease.

Conjunctiva↗

Evolving European guidance on the medical management of neovascular age related macular degeneration.

BACKGROUND: Until recently, only two options were available for the treatment of choroidal neovascularisation (CNV) associated with age related macular degeneration (AMD)-thermal laser photocoagulation and photodynamic therapy with verteporfin (PDT-V). However, new treatments for CNV are in development, and data from phase III clinical trials of some of these pharmacological interventions are now available. In light of these new data, expert guidance is required to enable retina specialists with expertise in the management of AMD to select and use the most appropriate therapies for the treatment of neovascular AMD. METHODS: Consensus from a round table of European retina specialists was obtained based on best available scientific data. Data rated at evidence levels 1 and 2 were evaluated for laser photocoagulation, PDT-V, pegaptanib sodium, and ranibizumab. Other treatments discussed are anecortave acetate, triamcinolone acetonide, bevacizumab, rostaporfin (SnET2), squalamine, and transpupillary thermotherapy. RESULTS: PDT-V is currently recommended for subfoveal lesions with predominantly classic CNV, or with occult with no classic CNV with evidence of recent disease progression and a lesion size <or=4 Macular Photocoagulation Study (MPS) disc areas (DA). The new classes of anti-angiogenic agents-namely, pegaptanib sodium and ranibizumab (the latter when peer reviewed phase III data become available) are recommended for subfoveal lesions with any proportion of classic CNV or occult with no classic CNV. For juxtafoveal classic CNV, PDT-V or anti-angiogenic therapy should be considered if the new vessels are so close to the fovea that laser photocoagulation would almost certainly extend under the centre of the foveal avascular zone. For all other well demarcated juxtafoveal lesions and for extrafoveal classic lesions, laser photocoagulation remains the standard treatment. Therapy should be undertaken within 1 week of the fluorescein angiogram on which the clinical decision to treat is based. At each follow up, fluorescein angiography should be performed and best corrected visual acuity measured as a minimum requirement. CONCLUSIONS: These recommendations provide evidence based guidance for the choice and use of non-surgical therapies for the management of neovascular AMD. Revisions of the recommendations may be required as new data become available.

Antibodies, Monoclonal↗

[Ocular proprioception and developmental dyslexia. Sixty clinical observations].

PURPOSE: The objective of this study is to assess proprioception anomalies in postural deficiency syndrome in a group of children suffering from reading impairment. MATERIAL AND METHODS: Sixty male patients with an average age of 11 years and 9 months were included in the study. Initially, they were given a standardized neuropsychological examination, which confirmed the diagnosis of reading impairment. Then after filling out a questionnaire seeking a proprioceptive anomaly, the patients were subjected to a clinical ocular and postural examination consisting of nine precisely described steps. RESULTS: All of the patients recruited for the study presented clinical signs confirming a proprioception disorder found as a part of postural deficiency syndrome. CONCLUSION: This study opens a new direction for research concerning the origin and treatment of at least some reading-impaired children.

Adolescent↗

[Postoperative acute endophthalmitis: a prospective study. Clinical presentation, management and prognostic factors].

AIMS: To assess the characteristics and visual outcome of patients with acute postoperative endophthalmitis hospitalized in a referral center. MATERIALS AND METHODS: All patients suspected of having infectious endophthalmitis were included in this study. All patients were treated with the same protocol including at least intravitreal injection of antibiotics and instillation of fortified antibiotics. Symptoms, visual acuity, and slit lamp examination were recorded before treatment, at the end of hospitalization and during clinical follow-up. Treatments and biological results were also reported. For patients developing infectious endophthalmitis after cataract surgery, intraoperative management such as location of the incision, suture or sutureless incision, and material of the intraocular lens were also noted. RESULTS: Forty-one patients were included in the study over 32 months (33 patients after cataract surgery). Intraocular inflammation and a decrease in subjective visual acuity were the most frequently reported findings (90% and 94%, respectively). Ocular pain and conjunctiva injection were less frequently reported (47% and 48%, respectively). Symptoms occurred 5 days after the surgery (median); 56% of patients needed a second intravitreal injection of antibiotics. There was a significant increase in visual acuity during and after hospitalization; median final visual acuity was 4.6/10 (0.34 log MAR = 20/43); 30% of patients had less than 20/200, but 44% more than 20/40. In endophthalmitis following cataract surgery, incisions were corneal in all cases and sutured in 62% of cases. Incisions were temporal in 55% of patients. DISCUSSION: Our results are similar to those previously published for acute endophthalmitis following ocular surgery. Intravitreal antibiotic injection remains the gold standard on the management of acute postoperative endophthalmitis.

Acute Disease↗

[Study of ocular surface involvement in diabetic patients].

INTRODUCTION: Diabetes mellitus leads to microvascular complications and altered basement membranes, which are partly responsible for ocular complications. Corneal nerve impairment is involved in ocular surface disease as well. We examined the possible relation between ocular surface signs and retinal or neuronal degenerative complications due to diabetes. PATIENTS AND METHODS: Diabetics and control subjects were compared for corneal sensitivity and tear function parameters such as the Schirmer test, tear film break-up time (BUT), and fluorescein and lissamine green stainings. The relation of the duration of the disease, the stage of retinopathy, metabolic control (HbA1c), and diabetic peripheral neuropathy with ocular surface disorders were noted. RESULTS: Twelve healthy patients were compared to 48 diabetics. The Schirmer test value, BUT, and fluorescein and lissamine green impregnations were significantly modified in diabetics compared to controls (p<0.0001), with no relation to the duration of the disease or metabolic control. The mean corneal sensitivity was significantly lower in diabetic patients (p<0.01), diabetics with peripheral neuropathy (p=0.00008), and diabetics with preproliferative retinopathy (p=0.0003). Tear function parameters were more frequently altered in patients presenting preproliferative retinopathy and peripheral neuropathy (p<0.001). CONCLUSIONS: Diabetes can lead to ocular surface impairments with qualitative and quantitative tear disorders, all of which seem to evolve in close relation with retinopathy and peripheral neuropathy. These lacrymal and corneoconjunctival abnormalities, even if not currently mentioned by diabetic patients, can result in severe neurotrophic complications.

Basement Membrane↗

[A screening questionnaire for determining risk of Creuzfeldt-Jacob disease transmission during ophthalmic examination].

INTRODUCTION: The risk of prion transmission during an ophthalmic examination concerns all ophthalmologists screening patients at risk, a procedure normally based on collecting past history and clinical data. PATIENTS AND METHODS: The authors proposed a shortened version of a questionnaire where the patient provides only the past history by answering three questions, which are then validated by the ophthalmologist. RESULTS: This procedure was proposed to 500 patients. Only five patients answered one of the questions positively, and the ophthalmologist did not use any contact device during their examination. Of these five patients, none was confirmed to be at risk for prion transmission. CONCLUSION: This questionnaire seems to be a suitable way to compensate the lack of time and reduced staff in ophthalmology, whatever the ophthalmic practice may be.

Creutzfeldt-Jakob Syndrome↗

[Treating severe dry eye syndromes with autologous serum].

BACKGROUND: Dry eye syndrome with tear deficiency can be improved with artificial tears, which can be associated with topical anti-inflammatory agents. Autologous serum can provide the ocular surface with beneficial growth factors and vitamins. PATIENTS AND METHODS: Twenty-one patients suffering from severe dry eye due to Sjögren's syndrome were treated with 20% autologous serum for 2 Months. The Schirmer I test, break-up time, and fluorescein and lissamine green stainings were performed before and after treatment. Subjective complaints such as burning, foreign body sensation, dryness and photophobia were assessed by a questionnaire as well as a face score reflecting the current condition of patients' eyes. RESULTS: Lissamine green and fluorescein scores improved significantly as well as subjective symptoms of burning, foreign body sensation and dryness (p<0.05). The face score was significantly improved. Bacterial culture of serum delivered to the patients all remained negative. DISCUSSION: Autologous serum provides growth factors and vitamins that are useful for an altered ocular surface due to Sjögren's disease. However, some problems still remain: risk of contamination, arbitrary dilution of autologous serum, and a current lack of regulations for use of autologous serum. A close collaboration between ophthalmologists and the Etablissement Français du Sang (French Blood Bank) is mandatory because autologous serum should be considered as a useful tool to treat severe ocular surface disorders. CONCLUSION: The use of autologous serum improved symptoms and objective signs caused by severe Sjögren's syndrome. Currently, a lack of clear regulations prevents its widespread use in severe ocular surface disorders.

Blood Transfusion, Autologous↗

[Ocular tolerance of a new formulation of nonpreserved diclofenac].

AIM: To compare the ocular tolerance of nonpreserved diclofenac versus thiomersal-preserved diclofenac in healthy volunteers. MATERIALS AND METHODS: Forty healthy volunteers instilled Dicloabak in the randomised eye and thiomersal-preserved diclofenac in the other eye, according to a strictly identical dosing regimen, for 28 days. Each volunteer thus served as his or her own control. The dose regimen was five drops/day for 7 days followed by three drops/day for 20 days. Ocular tolerance was assessed by the discomfort upon instillation (measured on a visual analogue scale [VAS]), subjective ocular symptoms following instillation (irritation/burning/stinging, eye dryness and foreign body sensation) and finally by an objective examination of the ocular surface. These criteria were evaluated on days 0, 14, 21 and 28. RESULTS: The subjective ocular symptoms following instillation were significantly lower in the nonpreserved group at Day 7 and nearly significantly lower until the end of the study. The biomicroscopy exam confirmed that there was better tolerance without thiomersal. There was less follicular-papillary conjunctivitis and a significantly better lissamine green score in the Dicloabak group. CONCLUSION: The results of this study demonstrate that the nonpreserved formulation of diclofenac is better tolerated by the ocular surface and thus constitutes a therapeutic benefit.

Adult↗

[Hormonal regulatory influence in tear film].

Tear film quality depends on fine regulatory mechanisms affected by neuronal and hormonal influences. Indeed, receptors for androgens, estrogens, progesterone and prolactin have been identified in several ocular tissues in the rat, rabbit and in humans. The eye is thus a target organ for sex hormones, particularly the androgens. These hormones regulate the immune system, the morphology and secretory functions of lacrimal glands and the functioning of Meibomian glands. The influence of hormone replacement therapy in menopausal women remains unclear, as some authors support the idea that they improve the quality and the volume of tear film, whereas others have shown that they increase the risk of dry eye. Finally, knowledge of the interactions between the hormones that influence the lacrimal glands is essential for the understanding of the regulation of lacrimal gland function. However, the data presently available strongly suggest that optimal bioavailable androgen levels are essential for normal lacrimal gland function and that prolactin and estrogens also play important roles in providing a hormonal milieu that contributes to normal lacrimal gland function.

Animals↗

Blood group related antigens in ocular cicatricial pemphigoid.

AIM: To study the MUC5AC and the blood group related antigen expression in ocular cicatricial pemphigoid (OCP) according to the distribution of Lewis and secretor phenotypes in OCP patients compared to normal subjects. METHODS: Immunostaining was performed on conjunctival biopsy specimens from 22 consecutive patients suffering from OCP, using monoclonal antibodies (Mabs) directed against the peptidic core MUC5AC mucin (anti-M1/MUC5AC Mabs) and against the saccharide moieties (anti-blood group related antigens). These latter included anti-Le(a), anti-Le(b), anti-sialyl Le(a), and H type 2 Mabs, which immunoreact with Lewis positive and non-secretor (Le(a)), Lewis positive and secretor (Le(b)), Lewis positive (sialyl Le(a)), and secretor (H type 2) phenotypes respectively. Serological tests were also performed to confirm the phenotype of each patient. The immunohistopathological patterns and the distribution of Lewis and secretor phenotypes were compared with the results of a previous study in normal individuals. RESULTS: (1) In OCP patients compared to the normal population, anti-M1 immunoreactivity of goblet cells was unchanged, whereas anti-Le(a), anti-Le(b), and anti-sialyl Le(a) immunoreactivities of epithelial and/or goblet cells were markedly decreased. (2) 41% of OCP patients had a non-secretor phenotype, which is statistically significantly more than the estimated incidence of the same phenotype in the French population (20%) (p approximately 0.04). CONCLUSIONS: Mucins in OCP patients showed a decreased expression of blood group related antigens whereas the MUC5AC peptidic core detected by anti-M1 Mab remained unchanged. These results also seem to indicate that OCP may be associated with a non-secretor phenotype.

Adult↗

[Creating a specific diagnostic and quality-of-life questionnaire for patients with ocular surface disease].

INTRODUCTION: Ocular surface diseases (OSD) affect about 15% of the population over 65 years of age. Nevertheless, OSD knowledge in the scientific community remains poor, and the healthcare system does not adequately recognize this disorder. However, many patients with OSD suffering from chronic pain experience substantial alteration in their quality of life (QoL). PURPOSE: Our work aimed at developing a patient self-evaluation questionnaire specific to OSD. This questionnaire could thus become a useful diagnostic tool that ophthalmologists could employ in daily practice in order to better understand patients'complaints and thereby correctly treat their disease. It also may serve as an evaluation tool in medical research. This article describes the phases of item generation, validation by experts, and identification of dimensions in the QoL section. METHODS: The questionnaire was developed in French by a group of experts including clinicians and methodologists. It comprised two parts: one on diagnostic aid, and the other on subjective perception of the disease (symptoms, perception of treatment, quality of life). The questionnaire was tested on five patients. It was then modified according to the patients' suggestions and tested again on 20 patients. After a second review by the scientific committee, a pilot questionnaire suitable for systematic use in quantitative studies was prepared. A cross-sectional observational study then identified the statistical dimensions of the QoL section, which led to a reduction in the total number of items. RESULTS: The resulting operational version of the questionnaire included four sections CONCLUSION: The next study will test the reproducibility of the operational version of the OSD questionnaire obtained after the item reduction phase.

Adult↗

[Flow cytometric analysis of HLA-DR, IL-6 and IL-8 expression by conjunctival epithelial cells from patients with prolonged topical antiglaucoma treatments].

AIM OF THE STUDY: To investigate the expression of three inflammation markers, HLA-DR, IL-6, and IL-8, by conjunctival epithelial cells obtained using impression cytology (IC) samples from long-term treated glaucoma patients. PATIENTS AND METHODS: IC samples were obtained from the 60 following individuals: 45 patients suffering from primary open-angle glaucoma and receiving topical treatments for at least 1 year and 15 subjects with no ophthalmological disease (controls). Membrane expression of HLA-DR and intracellular expression of IL-6 and IL-8 were quantified, respectively, by indirect and direct immunofluorescence techniques. Fluorescence levels were quantified using calibrated fluorescent beads. RESULTS: The percentage of HLA-DR-positive cells was significantly higher on IC samples from multitreated glaucoma patients and from patients treated by either preserved betablocker or preserved prostaglandin analogue than on IC samples from control individuals. Interestingly, the percentage of HLA-DR-positive cells was not significantly increased upon treatment with unpreserved betablocker. However, the percentage of IL-6- and IL-8-positive cells as well as IL-6 and IL-8 expression levels was significantly higher in patients than in controls, regardless of the treatment type and the presence of preservative. A significant positive correlation was found between HLA-DR and cytoplasmic IL-6 expression, between HLA-DR and cytoplasmic IL-8 as well as between IL-6 and IL-8 cytoplasmic expressions. CONCLUSION: The present study confirms that there is an increased expression of HLA-DR in treated glaucoma patients compared to controls and demonstrates that antiglaucoma treatments lead to increased IL-6 and IL-8 expressions. It also indicates that benzalkonium-preserved eyedrops and preserved multitherapy may induce stronger inflammatory responses than do unpreserved eyedrops, although further studies are needed to determine the respective inflammatory role of preservative and therapeutic molecules. In this study, flow cytometry was used to detect the intracellular pro-inflammatory cytokines in conjunctival cells obtained by impression cytology. This standardized and reliable technique was a useful tool to assess inflammatory and allergic ocular surface disorders.

Adrenergic beta-Antagonists↗