Correlation between aqueous flare and chorioretinal neovascularization in age-related macular degeneration following intravitreal bevacizumab injections.

PURPOSE: Prospective evaluation of aqueous flare following intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) injections in eyes with choroidal neovascularization due to age-related macular degeneration. PATIENTS AND METHODS: Sixteen eyes of eight patients were recruited. Aqueous humor flare was determined by laser flare meter every month after one intravitreal injection of 1.25mg of bevacizumab at baseline followed by a second injection at month3 (day 100±21days). Four patients received an injection at month6 (±10days), and one patient received an injection at month7. RESULTS: Two months after the first intravitreal bevacizumab injection, flare values decreased from 10±5.57 (mean±standard deviation) to 5.2±1.69photon count/ms (P=0.0207) and from 8.3±3.59 to 5.4±0photon counts/ms, 2months after the second injection (P=0.02). CONCLUSION: Significantly decreased aqueous humor flare levels were noted after repeated injections of bevacizumab.

RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.

Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50µl, 5µg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases.

[A relevant choice for corticoid eye drops: solution or suspension?]. / Quel choix pour un collyre de corticoïdes : solution ou suspension ?

INTRODUCTION: The various forms of ophthalmic pharmaceutical presentation of steroids is proliferating on the market: solutions, gels, and suspensions. Suspensions are characterized by particles in solution and require agitation before instillation. This trial studied the impact of agitation on the corticoid concentration of eye drop solutions, gels, and suspensions. METHODS: Corticosteroid levels in a drop of a dexamethasone solution or suspension or betamethasone suspension or gel were compared using liquid chromatography. These levels were measured after shaking for 5, 10, 30s, and 1 min using a vortex or without shaking. RESULTS: The results of this study show that, whatever shaking time was used, the suspension form seems less suited to instillation of corticosteroids. The suspension did not deliver consistent levels of corticosteroids (mean between 23 and 99%) compared to solutions and gels, which released about 100% of the corticosteroid content in each drop. CONCLUSION: Physicians, ophthalmologists, and pharmacists should remind the patient of the proper use of these suspensions before instillation. In cases of treatment failure, it is necessary to check the instillation method before questioning patient compliance.

[Preservatives in eye drops: toward awareness of their toxicity]. / Les conservateurs des collyres : vers une prise de conscience de leur toxicité.

Preservatives are present in numerous multidose eyedrops and provide the sterility of the solution against bacteria and fungi. However, numerous studies have shown their toxicity for the ocular surface, particularly in long-term treatments. The most widely used preservative in eyedrops is benzalkonium chloride. This quaternary ammonium acts as a detergent, antiseptic, disinfectant, fungicide, bactericide, and spermicide. Its use on the ocular surface therefore has significant consequences. Indeed, the preservatives are pro-apoptotic, pro-inflammatory and they cause the dissolution of the lachrymal film. The prolonged administration of one or several eye drops containing preservatives induces changes in the superficial structures (conjunctiva, cornea) as well as in deeper structures (trabecula, lens). The least severe symptoms are irritation and discomfort, including sensation of a foreign body, itching, or burning sensations. However, more severe side effects have been described, such as chronic inflammation of variable intensity or the progressive development of fibrosis with higher risk of failure after glaucoma filtering surgery. Ideally, preservative-free eyedrops should be recommended, or at least a reduction of the number of instilled preserved eyedrops should be considered. All these strategies could increase patient comfort, quality of life, and compliance, with better outcome at the time of filtering surgery.

Severe ocular infections with contact lens: role of multipurpose solutions.

PURPOSE: To determine whether multipurpose solutions, widely used for contact lens disinfections, could be at the origin of ocular pathologies (contact lens intolerance and ocular infections). METHODS: An observational cohort study (questionnaire analysis) was carried out to estimate the number of contact lens wearers, type of infection, and type of lens care regimen used by patients. Besides, multipurpose solutions cytotoxicity (necrosis and apoptosis) was evaluated on a conjunctival cell line using cytofluorometry. RESULTS: In the general population, 59% of contact lens wearers use multipurpose solutions whereas 35% use oxidative products. Of the questioned contact lens wearers with ocular infections, 80% used multipurpose solutions. Multipurpose solutions are therefore not efficient enough against microorganisms, and cannot be considered as disinfectant solutions but only as preservatives. However, preservatives are known to be toxic to ocular surface, so apoptosis induced by multipurpose solutions could lead to ocular surface diseases. Our cytofluorometry study allowed us to demonstrate that contact lens multipurpose solutions containing preservatives are cytotoxic through caspase 3 induction, chromatin condensation and P2X7 cell-death receptor activation, in contrast with unpreserved sterile saline solutions that were found inert. CONCLUSIONS: Multipurpose solutions seem to be preservative but not disinfecting solutions. They are not adapted to the final rinse of contact lenses because of apoptosis induction. It could explain part of lens intolerance.

[Oxidative stress modulation using polyphenol-rich blueberries: application on a human retinal cell model]. / Modulation du stress oxydant par la myrtille riche en polyphénols sur un modèle de cellules humaines de rétine.

INTRODUCTION: The retina is located in a highly oxygenated environment and is therefore particularly susceptible to oxidative damage. Blueberries have a high antioxidant potential since they are rich in anthocyans. The aim of this study was to investigate the cytoprotective role of blueberries on human retinal cells. MATERIALS AND METHODS: Blueberry extract was incubated at 0.05% and 0.1% for 15 minutes or 24 hours on a human retinal cell line. Then oxidative stress was induced by 150 microM tert-butylhydroperoxide (tBHP) for 1 hour. Intracellular metabolism, reactive oxygen species, superoxide anion, and mitochondrial apoptosis were evaluated using Alamar blue, DCFDA, dihydroethidium, and nonylacridine orange dyes, respectively. Tests were performed using cytofluorometry adapted to microplates. RESULTS: Blueberry protected cells against tBHP-induced cytotoxicity. It increased cell viability, decreased oxidative stress and mitochondrial apoptosis. After a 24-hour preincubation time, blueberry totally inhibited tBHP-induced cytotoxicity. CONCLUSION: Blueberry seems to be a potent antioxidant and could be easily added to food complements to prevent or limit ocular pathologies induced by oxidative stress.

[Pilot study of a new matrix therapy agent (RGTA OTR4120) in treatment-resistant corneal ulcers and corneal dystrophy]. / Etude pilote d'un nouvel agent de thérapie matricielle (RGTA OTR4120) dans les ulcères de cornée et les dystrophies cornéennes rebelles.

AIMS: This study's objective was to evaluate the tolerance and safety of a new ophthalmic solution based on ReGeneraTing agent (RGTA) technology in a pilot noncontrolled exploration on compassion use for corneal ulcers and severe chronic dystrophies resistant to the usual treatments. RATIONALE: RGTAs are large biopolymers engineered to replace heparan sulfates specifically bound to matrix proteins and growth factors destroyed after a lesion has occurred. The RGTA-bound proteins are protected from proteolysis and this allows the extracellular matrix microenvironment to restore its original proper organization. The initial endogenous signals needed for tissues to regenerate are back on the restored matrix. They are expected to trigger the natural onset of events, signaling cells to migrate and multiply with the cascades and equilibrium found in tissue homeostasis. RGTA-induced matrix therapy is a possible alternative to cell or gene therapy in regenerative medicine. In a rabbit preclinical model of alkali-induced severe corneal ulcers, a single instillation of RGTA ophthalmic solution was found sufficient to enhance speed and quality of healing, restoring an almost normal corneal histology after only 1 week. These data prompted us to initiate this study. PATIENTS AND METHODS: Eleven eyes from ten patients were included in this study. All patients had severe dystrophic cornea or painful corneal ulcers rated over 50 on the VAS pain scale ranging from 0 to 100 and had undergone unsuccessful treatments. The RGTA ophthalmic solution was administered by the investigator during each weekly consultation as a single drop over 1 month. Tolerance and efficacy were judged on subjective criteria based on pain evaluation and functional inconvenience as well as on objective clinical criteria through a complete ophthalmic examination at days 3, 7, 14, 21, 28 and after 2 and 3 months from the beginning of the treatment. RESULTS: The study was conducted to completion for all patients included at the beginning. Tolerance was excellent both locally and generally: no uneasiness during instillation, no worsening of the initial pathology, no occurrence of ocular inflammation or increase in ocular pressure, and no general side effects were observed. In addition, we observed a noticeable analgesic effect, increasing with time and instillations, but pain reappeared in the majority of cases as treatment ended. The mean visual analog scale pain score was 72.73 +/- 7.86, it decreased significantly with the first drops of treatment. After 1 month, the mean visual analog scale pain score was 32+/-15.49, then it increased after the end of the treatment, confirming the link between the effects observed and the treatment. Efficacy on keratitis was moderate but with an overall tendency toward improvement. The initial Oxford Score was 3.37 +/- 1.06. After 1 month, it decreased significantly to 1.57 +/- 0.97 and then it rose again after the end of the treatment. As for corneal ulcers, of the five cases included, four healed during the protocol. Two reversed when the treatment stopped, two healed without reversion at the last follow-up visit. The last case was characterized by stem cell deficiency and no improvement was noted. It is important to keep in mind that these ulcers were all resistant to usual therapies. CONCLUSION: This RGTA ophthalmic solution is the first matrix therapy product in ophthalmology. The RGTA OTR4120 was used in treating chronic and severe corneal dystrophies as well as corneal ulcers resistant to usual treatments. It was very well tolerated with no side effects. It significantly reduced pain and favored corneal healing in almost all corneal ulcers. Weekly instillation of a single drop seems insufficient and these very promising data need to be confirmed on a larger population in a controlled trial with more adapted dosages. Based on these preliminary data, a RGTA-based matrix therapy product may be a very innovative solution to unresolved pain and corneal surface healing problems.

[Usefulness of voriconazole in treatment of Phoma glomerata after penetrating injury]. / Endophtalmie à Phoma glomerata après plaie du globe et efficacité du traitement par voriconazole en intravitréen.

We report the first case of endophthalmitis caused by Phoma glomerata. A 32-year-old man who underwent retinal detachment surgery consecutive to a penetrating globe injury presented with endophthalmitis 7 days after surgery. Anterior chamber tap and intravitreal injection of antibiotics (ceftazidime and vancomycin) were performed systematically. Fungus was observed at microscopic examination of the aqueous humor and treatment with intravitreal injection of amphotericin B was decided. The patient failed to improve with intravitreal amphotericin B but responded clinically to intravitreal voriconazole. The fungus was identified after culture as Phoma glomerata. The MIC for amphotericin B was 1microg/ml, for caspofungin was 2microg/ml, and for itraconazole was 8microg/ml or more. The MIC for voriconazole was up to 8microg/ml. The clinical response after intravitreal injection may be related to the high concentrations reached in the vitreous. Because of severity and ominous prognosis of intraocular fungal infections and posttraumatic Phoma ocular infections, aggressive management is required by intravitreal voriconazole administration.

Reduction of quaternary ammonium-induced ocular surface toxicity by emulsions: an in vivo study in rabbits.

PURPOSE: To evaluate and compare the toxicological profiles of two quaternary ammonium compounds (QAC), benzalkonium chloride (BAK), and cetalkonium chloride (CKC), in standard solution or cationic emulsion formulations in rabbit eyes using newly developed in vivo and ex vivo experimental approaches. METHODS: Seventy eyes of 35 adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 microl of phosphate-buffered saline (PBS), PBS containing 0.02% BAK or 0.002% CKC (BAK Sol and CKC Sol, respectively), and emulsion containing 0.02% BAK or 0.002% CKC (BAK Em and CKC Em, respectively) were applied to rabbit eyes 15 times at 5-min intervals. The ocular surface changes induced by these eye drops were investigated using slit-lamp examination, flow cytometry (FCM), impression cytology (IC) on conjunctiva, and corneal in vivo confocal microscopy (IVCM). Standard immunohistology in cryosections was also examined for cluster of differentiation (CD) 45+ infiltrating and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL)+ apoptotic cells. RESULTS: Clinical observations and IVCM showed that the highest toxicity was induced by BAK Sol, characterized by damaged corneal epithelium and a high level of inflammatory infiltration. BAK Em and CKC Sol presented moderate effects, and CKC Em showed the lowest toxicity with results similar to those of PBS. Conjunctival imprints analyzed by FCM showed a higher expression of RLA-DR and TNFR1 markers in BAK Sol-instilled eyes than in all other groups, especially at 4 h. Immunohistology was correlated with in vivo and ex vivo findings and confirmed this toxicity profile. A high level of infiltration of CD45+ inflammatory cells and TUNEL+ apoptotic cells was observed in limbus and conjunctiva, especially in QAC solution-receiving eyes compared to QAC emulsion-instilled eyes. CONCLUSIONS: The acute administration of 15 instillations at 5 min intervals was a rapid and efficient model to assess quaternary ammonium toxicity profiles. This model showed the highest toxicity, induced by the BAK solution, and the lowest level of toxicity, induced by the CKC emulsion. These in vivo and ex vivo experimental approaches demonstrated that ocular surface toxicity was reduced by using an emulsion instead of a traditional solution and that a CKC emulsion was safe for future ocular administration.

Comparative study on the cytotoxic effects of benzalkonium chloride on the Wong-Kilbourne derivative of Chang conjunctival and IOBA-NHC cell lines.

PURPOSE: The Wong-Kilbourne derivative of Chang conjunctiva-derived cell line has been widely used for toxicological and functional in vitro studies on the ocular surface. The common reserve to this cell line is the reported contamination with HeLa cells. Thus, the IOBA-NHC spontaneously immortalized conjunctival epithelial cell line has been recently developed and did not show other cell type contamination. Our purpose was to determine whether both cell lines would be equally suitable for in vitro toxicological studies. Therefore, we compared in these two cell types the toxic effects of the preservative, benzalkonium chloride (BAC); its toxicity has been often reported on conjunctival in vivo and in vitro models. METHODS: The necrotic, apoptotic, and oxidative effects of BAC were evaluated on Chang and IOBA-NHC cell lines using microplate cytofluorometry tests (neutral red, 2,7- dichlorofluorescein diacetate dye [H(2)DCF-DA], hydroethidine, and Yopro-1), flow cytometry (Annexin V/7-AAD and DNA content tests), and standard immunofluorescence stainings. Cells were exposed to five concentrations of BAC (10(-2)%, 5.10(-3)%, 10(-3)%, 10(-4)%, and 10(-5)%) for two incubation times: 15 min of treatment and 15 min of treatment followed by 24 h of cell recovery in complete medium. RESULTS: All parameters of toxicity increased in a BAC dose-dependent manner on both cell lines. CONCLUSIONS: The comparison of BAC toxicity on both cell lines supported the use of IOBA-NHC and Chang cells for toxicological in vitro studies. Drawbacks of both cell lines have to be known and considered in studies performed on these cell lines.

Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

Modulated expression of cell surface molecules and in vivo outgrowth of modified melanoma cells.

Modulation of cell surface molecules involved in immune recognition and cellular interactions (class I major histocompatibility complex or MHC-I, B7.1 or CD80, integrin alpha4 or CD49d, tetraspanins CD9, CD81) was examined in modified B16 melanoma cells displaying either inhibited IGF-I expression or transfected OVA encoding gene. It was shown that inhibiting IGF-I expression or inserting OVA encoding gene did not lead to modification relevant to the presence of MHC-I or B7.1. However downregulation of tetraspanin CD9 was observed in modified IGF-I but not in OVA encoding gene inserted melanoma cells. Expression of tetraspanin CD81 and integrin alpha4/CD49d remained unchanged. Inoculated into syngeneic recipients, the modified melanoma cells exhibited significant delayed outgrowth with a reduction in the percentage of lethal tumors observed essentially in hosts injected with inhibited IGF-I expression cells.

[Role of conditioning medium cytotoxicity. An example with an intraocular lens preloaded in injector]. / Rôle de la cytotoxicité du milieu de transport d'implants: cas de lentilles intraoculaires conditionnées en injecteur.

INTRODUCTION: Following material vigilance cases encountered with the hydrophilic acrylic intraocular lens, ACR6D SE preloaded in the Premier shooter, we studied the cytotoxicity of the intraocular lens and its conditioning to identify the cytotoxic element. We proposed medical device modification to improve its biocompatibility. MATERIALS AND METHODS: Biocompatibility-cytotoxicity assays were carried out according to ISO 10993-5 recommendations. Tests were performed on the SRA 01/04 human lens epithelial cell line. Neutral red, Hoechst 33342, and YO-PRO-1 fluorescent probes were used to assess membrane integrity, total DNA, and membrane fluidity, respectively. Materials samples were prepared in culture medium according to the ISO 10993-5 elution procedure. Pure saline solutions and conditioning liquids were tested directly on cells. RESULTS: The intraocular lens and injector were not cytotoxic. Conditioning liquids induced membrane fluidity perturbation characteristic of apoptosis. Tests performed on new versions of the medical device identified a better adapted conditioning liquid. CONCLUSION: The results suggest that the cytotoxicity of the conditioning liquid could explain the postoperative complication rate. When we changed the conditioning liquid with sterile irrigating solution (i.e., rich divalent cation marine solution), we eliminated cellular stress. Fluorescent probes are well adapted to assess medical device biocompatibility-cytotoxicity.

Age-dependent effects on redox status, oxidative stress, mitochondrial activity and toxicity induced by fluoroquinolones on primary cultures of rabbit tendon cells.

The age-related difference in fluoroquinolone-induced tendon toxicity was investigated. In vitro tendon cells from juvenile and young adult rabbits, respectively, were incubated with quinolone (nalidixic acid, NA) or fluoroquinolone (ofloxacin, OFX or pefloxacin, PEF) at 0.01 microM to 1 mM for 72 h. Redox status, glutathione (GSH), reactive oxygen species (ROS), and mitochondrial activity were assessed using intracellular fluorescent probes. Fluorescence signal was detected on living adherent tenocytes in microplates using cold-light cytofluorometry. Tendon toxicity differed significantly between the two cell groups and the difference was greatest with highest dose (1 mM). For 72 h, significant (p < 0.001) differences between immature and young adult primary tenocytes were observed for redox status decrease, GSH decrease, and ROS production increase. Mitochondrial activity remained unaltered in immature tenocytes. We confirm two groups of intrinsic tendon toxicity (OFX/NA vs. PEF) associated to oxidative stress (GSH decrease). Our in vitro experimental model confirms the clinical observations of age dependent tenotoxicity. First group (NA, OFX) showed greater intrinsic tenotoxicity for young adult than immature tenocytes, second group (PEF) was highly toxic for immature and young adult cells. The three quinolones do not altered mitochondrial activity in immature tenocytes whereas alteration was observed in young adult tenocytes.

[Cytotoxicity evaluation of different eyes drops with cyclosporine oral solution (Sandimmun)]. / Etude de la cytotoxicité de différents collyres à base de ciclosporine A buvable (Sandimmun).

INTRODUCTION: Cyclosporine is a molecule used in ophthalmology for the prevention of corneal graft rejection. The systemic use of this product can lead to serious adverse side effects that can be avoided using the topical formulation of cyclosporine. However, cyclosporine application can induce ocular irritation. MATERIAL AND METHODS: The aim of this study is to evaluate the cytotoxicity of four formulations of 2% cyclosporine eye drops: Sandimmum intravenous solution diluted with NaCl 0.9%, Sandimmun oral solution diluted in castor oil or corn oil after ethanol evaporation, and Sandimmun oral solution diluted in castor oil without previous ethanol evaporation. Two tests--the Draize test and the evaluation of cytotoxicity of adherent alive cells with cold light cytofluorimetry on microplates--were used in this study. RESULTS: These tests demonstrated that the aqueous solution shows more toxicity than the other formulations, and the type of oil and ethanol concentration influence cell viability. CONCLUSION: These results helped the Pharmacy unit choose the vehicles for a safe cyclosporine eye drop formulation and thus decrease the side effects of cyclosporine eye drop instillation with a decrease in ethanol concentration compared to published formulations.

[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]. / Activation des voies TH1/TH2 détectée par l'expression de CCR4 et CCR5 sur la surface oculaire de patients glaucomateux traités au long cours.

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.

[Heavy silicone oil as internal tamponade for retinal detachment: efficacy and tolerance]. / Efficacité et tolérance de l'huile de silicone lourde dans la chirurgie du décollement de rétine.

INTRODUCTION: To evaluate the tolerance and efficacy of heavy silicone oil as internal tamponade for retinal detachment surgery. PATIENTS AND METHODS: Sixty-six eyes requiring heavy silicone oil for retinal detachment, with at least 1 month follow-up, were retrospectively studied. Preoperative status, surgical technique, tolerance, and anatomical and functional results were analyzed from the patient's file. Indications for heavy silicone injection were inferior retinotomy or inferior retraction in 65% of cases. PVR grade C was present in at least 63% of cases. Retinotomy was performed in 45% of cases. An exchange procedure was performed versus DKline in 65% of cases. Mean follow-up was 7 +/- 4 months. RESULTS: At the end of follow-up, 59% of eyes had a completely reattached retina, 32% without internal tamponade. Another surgery was necessary in 54% of cases. During follow-up, mean intraocular pressure was normal, and there was a significant intraocular inflammation in three cases (4.5%). In seven cases of the 44 ablations of heavy silicone oil, an adherence of residual bubbles was present. Redetachment occurred after ablation for anatomical success in 41% of cases. BCVA was better than 0.05 (20/400) in 54% of cases at the end of follow-up. CONCLUSION: Heavy silicone was well tolerated and seems not to be pro-inflammatory in our study. It is a good alternative to standard silicone for inferior retinotomy and inferior breaks without PVR. It is not a treatment of inferior retraction, and is not a long-term internal tamponade. During the ablation of heavy silicone oil, adherence of residual bubbles is possible, in which case a coaxial light or an endoillumination could be needed during ablation.

[Postoperative endophthalmitis: 2000-2002 results in the XV-XX National Ophthalmologic Hospital]. / Infections nosocomiales endoculaires au CHNO des XV-XX de 2000 à 2002.

PURPOSE: Prevention of nosocomial infection is a priority for the Infection Control Committee (ICC). Following their recommendations, the XV-XX National Ophthalmologic Hospital's ICC conducted a survey on cases of infection and we report these results for the 2000-2002 period. METHODS: During the 2000-2002 period, 21,384 programmed intraocular surgeries were done. Every day, a hygiene coordinator was informed of each bacterial or fungal laboratory test on intraocular samples and for all patients who were hospitalized for endophthalmitis. After data analysis with a referent ICC physician, resulting infection was declared postoperative nosocomial endophthalmitis. For these patients, prophylactic antibiotic use, the surgery report, and bacterial laboratory test results were reviewed. RESULTS: The overall 3-year incidence of suspected postoperative endophthalmitis after intraocular surgery was 2.0 per 1000 (42 cases). Confirmed microbiological growth was demonstrated in 19 cases (45%). For cataract surgery, the incidence was 1.0 per 1000 for acute-onset culture-proven postoperative endophthalmitis, 0.1 per 1000 for delayed culture-proven postoperative endophthalmitis, 2.1 per 1000 for acute-onset suspected postoperative endophthalmitis and 0.5 per 1000 for delayed suspected postoperative endophthalmitis. Gram-positive cocci were isolated in 77%. Twenty-one patients received systemic prophylactic antibiotics. Bacterial growth was positive in five of these 21 cases. For two cases, organisms were resistant to the prophylactic antibiotics used. CONCLUSION: Monitoring postoperative nosocomial infection is mandatory to detect incidence variation and evaluate infection control management. Prophylactic antibiotic efficacy remains to be evaluated.

[Anethole dithiolethione: an antioxidant agent against tenotoxicity induced by fluoroquinolones]. / L'anethole dithiolethione: un agent cytoprotecteur contre la ténotoxicité induite par les fluoroquinolones.

Tendinopathy and tendon rupture are the adverse effects observed with fluoroquinolone antibiotics in old patients. The aim of this study was to investigate the effect of anethole dithiolethione (5-[p-methoxyphenyl]3H-1,2-dithiole-3-thione) on the oxidative stress induced by three fluoroquinolones (pefloxacin, ofloxacin, ciprofloxacin) incubated with rabbit tenocyte cell line. Anethole dithiolethione is a well known antioxidant and glutathione inducer. Anethole dithiolethione is widely used in human therapy for its choleretic, sialogogic properties and recently proposed as cytoprotective agent in lung precancerous lesions prevention in smokers. In this purpose, protection against oxidative stress induced by fluoroquinolones has been assessed using cytofluorimetric probes to quantify cytotoxicity and reactive oxygen species production. Fluorescence signal was quantified in 96-well microplates, using cold light cytofluorometer. Significant reactive oxygen species production was detected after 45 minutes for all fluoroquinolones tested. Anethole dithiolethione has been evaluated on this parameter. Anethole dithiolethione significantly (*: P<0.05) reduces and normalizes reactive oxygen species induced by fluoroquinolones. So, anethole dithiolethione (Sulfarlem), well known for its antioxidant and glutathione inducing properties, good tissue diffusion and good tolerance in humans, could be beneficially associated to fluoroquinolones, and be proposed as a therapeutic adjuvant to prevent oxidative stress and tendinous adverse effects induced by xenobiotics and more precisely by fluoroquinolones.