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.

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. (C) 2011 Published by Elsevier Masson SAS.

Recombinant interferon alpha (IFN2B) is a proposed therapy for corneal intraepithelial neoplasia (CIN). Clinical response to this treatment is frequently challenging due to the delay between initiation of the IFN2B topical application and the beginning of CCIN regression. We present the case of a successful IFN2B treatment with prospective in vivo confocal microscopy imaging. A 50-year-old man was referred to our department for a recurrence of a conjunctival–corneal intraepithelial neoplasia (CCIN) in his right eye. A 2-month course of topical 0.02% mitomycin C (MMC) therapy was withdrawn a month earlier due to lid allergy. The lesion extended nasally from conjunctiva to peripheral cornea. Despite a surgical excision with cryotherapy, the intraepithelial neoplasia recurred 1 month later in the peripheral cornea (figs 1, 2). Since the large limbal resection and MMC treatment presented the risk of corneal epithelial stem cell deficiency, IFN2B was chosen as a subsequent therapeutic procedure.1 The follow-up included slit lamp and in vivo confocal microscopy examination on a monthly basis during 6 months. Under this regimen, healing was observed within …

CACICOL20 (R) is a new ophthalmic device, derived from RGTA (R) based matrix therapy. RGTA (R) are biodegradable nanobiopolymers engineered to mimic heparan sulfates and used after injury to restore extracellular matrix microenvironment back to its original architecture. A pilot study was performed on eleven eyes from ten patients with severe keratitis or painful corneal ulcers rating over 50 on the visual analog pain scale (VAS). All had undergone unsuccessful treatments with a mean lasting over 8 years. CACICOL20 (R) was instilled once a week over 1 month. General and local tolerance were excellent. Mean VAS dropped from 72.73 +/- 7.86. to 32+/-15.49, and increased after the end of the treatment, Mean severity of keratitis measured by initial Oxford Score was 3.37 +/- 1.06, decreased significantly to 1.57 +/- 0.97 and rose again after the end of the treatment. Four from the five included ulcers healed during the protocol, two reversed after. CACICOL20 (R) is available in Europe and provides an innovative solution for unresolved pain and corneal surface healing problems.

C. Khammari Chebbi, K. Kichenin, N. Amar, H. Nourry, J.M. Warnet, D. Barritault, C. Baudouin

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.

Devant la multiplicité des présentations de corticoïdes à usage ophtalmique, associés ou non à un antibiotique, et le développement des génériques, le service Pharmacie du CHNO des XV-XX a souhaité analyser l’impact de la formulation galénique sur la teneur en principe actif d’une goutte instillée. Dans cette étude, deux corticoïdes ont été choisis sous différentes formes galéniques : la dexaméthasone en suspension et en solution et la bétaméthasone en suspension et en gel. L’analyse de la teneur d’une goutte de chaque formulation a été réalisée par chromatographie, soit sans agitation préalable, soit après une agitation de 5 secondes à 1 minute. Les résultats montrent un taux de recouvrement de 100 % de la teneur en corticoïde pour la solution de dexaméthasone et pour le gel de betaméthasone. En revanche, pour les suspensions de dexaméthasone et de betaméthasone, le taux de recouvrement est de l’ordre de 60 % quelle que soit la durée d’agitation. Si les solutions et gels oculaires de corticoïdes sont plus homogènes que les suspensions, le choix d’un corticoïde ne doit pas reposer uniquement sur cet argument car les suspensions permettent d’instiller des molécules lipophiles qui ont une meilleure pénétration cornéenne. Aussi, face à un échec thérapeutique avec un collyre à base de corticoïde, le médecin doit vérifier impérativement la forme galénique dispensée et revoir avec le patient le bon usage des collyres, notamment en suspension, cette dernière forme ne délivrant pas forcément 100 % de la teneur attendue.

We report the first case of endophthalmitis caused by Phoma glomerata. A 32-year-old man 62 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 1 mu g/ml, for caspofungin was 2 mu g/ml, and for itraconazole was 8 mu g/ml or more. The MIC for voriconazole was up to 8 mu g/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.

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.

Purpose: To investigate the possibility of an adverse effect of infracyanine-guided internal limiting membrane (ILM) removal on functional results of macular hole surgery.Patients and methods: A retrospective study of two consecutive groups of patients operated for macular hole between January 1998 and December 2001. In group 1 (21 patients), no attempt was made to remove the internal limiting membrane. In group 2 (21 patients), the ILM was peeled using infracyanine green (ICG).Results: In group 1, 17 of 21 (81%) macular holes were closed by one surgery and 20 of 21 (95%) in group 2; however, this was not statistically significant. Mean preoperative visual acuity was close to 1 on the Logmar scale in both groups. Postoperative visual acuity was 0.6 in group 1 and 0.5 in group 2: four Snellen lines of improvement in group 1 and five lines in group 2. Postoperative visual acuity was the same or better in 16 of 21 patients in group 1 and in 18 of 21 in group 2. These differences were not statistically significant. Late reopening of the hole was statistically less frequent in group 2. Three cases of atrophic patterns at the level of foveal pigment epithelium were noted in each group as was one case of phototraumatism in group 1. These results were stable after more than 18 months of follow-up. All eyes became pseudophakic.Conclusion: In this study, infracyanine-guided removal of the internal limiting membrane did not significantly improve the results of macular hole surgery. No adverse effect of infracyanine on visual function or retinal toxicity was found and late reopening was less frequent.

Avec l’apparition des anti-VEGF, le traitement de la dégénérescence maculaire lié à l’âge a été amélioré. Aussi, le service Pharmacie des XV-XX a dû trouver les moyens techniques et financiers de mettre à disposition des ophtalmologistes ces nouvelles molécules. Le but de cette présentation est de faire le point, en France, sur les thérapeutiques actuellement disponibles ainsi que leur statut et les possibilités pour les ophtalmologistes de les prescrire tout en respectant la réglementation. Depuis quelques années, deux molécules sont utilisées pour le traitement de la dégénérescence maculaire lié à l’âge, la verteporfine pour le traitement des néovaisseaux choroïdiens rétrofovéolaires et la triamcinolone en injection intravitréenne utilisée en dehors de son autorisation de mise sur le marché (AMM). En janvier 2006, le premier anti-VEGF, le pegaptanib, a eu l’AMM. Depuis peu, un deuxième anti-VEGF, le ranizumab, est disponible sous autorisation temporaire d’utilisation nécessitant une demande d’importation auprès de l’AFSSAPS. Devant certains échecs de ces traitements, et les difficultés d’approvisionnement, les ophtalmologistes ont voulu disposer du bevacizumab qui est utilisée en oncologie mais ne dispose pas d’AMM, ni de présentation adaptée à l’ophtalmologie. Aussi, la Pharmacie des XV-XX propose des seringues stériles pré remplies à 0,12 ml de bevacizumab permettant d’injecter 1,25 mg. Son utilisation a nécessité la mise en place d’un protocole (critères d’inclusion, indications) validé par la COMEDIMS (Commission du Médicament et des Dispositifs Médicaux Stériles), d’un consentement et d’une ordonnance nominative spécifique. L’utilisation des anti-VEGF pose le problème à la fois de leur statut réglementaire, de leur approvisionnement ou encore de leur financement, d’autant plus crucial pour les hôpitaux qui sont dans l’impossibilité de les rétrocéder avec alors un financement entièrement à leur charge. L’AFSSAPS ayant pris officiellement connaissance du problème devrait prochainement clarifier la situation. Le plus urgent, est la prise de conscience des tutelles, des moyens financiers à accorder aux hôpitaux, permettant ainsi au praticien de s’affranchir des paramètres réglementaires et financiers.

Les kératomycoses et les infections fongiques endo-oculaires sont difficiles à traiter et de mauvais pronostic ; ce dernier va dépendre de la rapidité du diagnostic et de la mise en route d’un traitement efficace. Le traitement des lésions cornéennes fait appel à des collyres antibiotiques à spectre large, amphotéricine B, natamycin, ou plus spécifiques, des levures fluconazole, flucytosine. Dans les cas graves, en échec thérapeutique, le voriconazole et la caspofungine ont pu être utilisés sous la forme collyre, en dernier recours, sous surveillance car il n’existe pas de recul quant à leur tolérance en usage local. Les infections profondes et les endophtalmies nécessitent un traitement par voie générale ; ces dernières années, l’utilisation du voriconazole et de la caspofungine a permis d’améliorer considérablement le traitement de ces infections.

Nous rapportons un cas d’endophtalmie à Fusarium chez un patient 10 mois après une plaie du globe. Il s’agit d’un patient âgé de 32 ans, qui a présenté une endophtalmie dans les suites d’un traumatisme avec plaie du globe par corps étranger de verre. La plaie avait été initialement suturée en urgence. Le patient avait été opéré de décollement de rétine 9 mois plus tard par chirurgie endo-oculaire avec un prélèvement réalisé pendant l’intervention, négatif bactériologiquement. Deux semaines après l’intervention le patient présentait une photophobie accompagnée de douleur oculaire, une cornée blanche et un aspect d’hypopion total faisant porter le diagnostic d’endophtalmie. Les cultures réalisées à partir du prélèvement vitréen retrouvaient un Fusarium. Avant le résultat du prélèvement, le patient avait reçu une injection intravitréenne de ceftazidime et de vancomycine, puis d’amphotéricine B devant la découverte de filaments mycéliens à l’examen direct. L’état clinique du patient s’améliora après l’injection intra-vitréenne de voriconazole. Le résultat de l’antifongigramme plusieurs jours après le prélèvement révèle une résistance de la souche de Fusarium en cause à tous les traitements anti-fongiques disponibles, y compris le voriconazole. Les récents cas rapportés dans la littérature montrent l’efficacité du voriconazole dans les endophtalmies fongiques à Fusarium et Aspergillus après échec des traitements classiques habituellement recommandés dans cette indication. Il n’existe pour combattre ce type d’infections que peu d’alternatives thérapeutiques disponibles par voie intra-vitréenne ou générale. Ce cas a permis d’observer l’efficacité certaine du voriconazole dans certains cas d’endophtalmies fongiques. Pour certaines espèces comme le Fusarium dont la concentration minimale inhibitrice est plus élevée que les concentrations intravitréennes atteintes par administration systémique, les injections intra-vitréennes de voriconazole sont efficaces.

PURPOSE:To investigate the possibility of an adverse effect of infracyanine-guided internal limiting membrane (ILM) removal on functional results of macular hole surgery.PATIENTS AND METHODS:A retrospective study of two consecutive groups of patients operated for macular hole between January 1998 and December 2001. In group 1 (21 patients), no attempt was made to remove the internal limiting membrane. In group 2 (21 patients), the ILM was peeled using infracyanine green (ICG).RESULTS:In group 1, 17 of 21 (81%) macular holes were closed by one surgery and 20 of 21 (95%) in group 2; however, this was not statistically significant. Mean preoperative visual acuity was close to 1 on the Logmar scale in both groups. Postoperative visual acuity was 0.6 in group 1 and 0.5 in group 2: four Snellen lines of improvement in group 1 and five lines in group 2. Postoperative visual acuity was the same or better in 16 of 21 patients in group 1 and in 18 of 21 in group 2. These differences were not statistically significant. Late reopening of the hole was statistically less frequent in group 2. Three cases of atrophic patterns at the level of foveal pigment epithelium were noted in each group as was one case of phototraumatism in group 1. These results were stable after more than 18 months of follow-up. All eyes became pseudophakic.CONCLUSION:In this study, infracyanine-guided removal of the internal limiting membrane did not significantly improve the results of macular hole surgery. No adverse effect of infracyanine on visual function or retinal toxicity was found and late reopening was less frequent.

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.

L’analyse de la littérature a permis d’identifier un certain nombre d’actions dont l’impact clinique, pharmacologique, écologique et économique a pu être évalué, et de les hiérarchiser en fonction de leur utilité, de la simplicité de leur mise en œuvre, et de leur coût. À l’échelle de l’établissement, l'élément pivot des stratégies gagnantes de la politique d’utilisation des antibiotiques est le couple pharmacien–infectiologue, associant maîtrise de la dispensation et expertise clinique, au sein d’une équipe multidisciplinaire. En ne retenant que les mesures utiles, et dans un compromis entre priorité et faisabilité, les actions à mettre en place dans les établissements de soins peuvent être hiérarchisées de la façon suivante : 1) création sans délai d’une commission des antibiotiques ; 2) et mise en place d’une équipe pluridisciplinaire opérationnelle en infectiologie composée de temps de pharmacien, de bactériologiste, et de clinicien référent ; 3) rédaction des référentiels de prescriptions (antibioprophylaxie, antibiothérapie curative pour 80 % des situations) ; 4) puis mise en place des ordonnances spécifiques nominatives justifiées, uniquement si les référentiels existent, et du contrôle de prescription ciblé pour les situations difficiles ; 5) informatisation progressive de la prescription, dont l’absence initiale ne doit pas freiner la mise en place des premières mesures de contrôle ; 6) à tout moment utilisation de l’outil d’audit pour évaluer les situations existantes et l’impact des mesures prises ; 7) information et formation des prescripteurs.The clinical outcome, pharmacological and bacteriological impact, as well as patient safety and economic issues of different measures were evaluated according to the literature. They were sorted by usefulness and cost-effectiveness. A partnership between the pharmacist and the infectious diseases physician within a multidisciplinary task force is the main issue of the hospital antibiotic policy. Measures to be developed in hospitals could be classified as follows: 1) immediate creation of an antibiotic committee; 2) implementation of a multidisciplinary transversal action involving a pharmacist, a microbiologist, and antibiotic experts; 3) elaboration of antibiotic clinical practice guidelines covering 80% of clinical situations (including antibioprophylaxis); 4) use of antibiotic order forms, only if prescription guidelines are already used, and of targeted prescription control in complex clinical situations; 5) progressive implementation of computer decision support for antibiotic selection and prescription; 6) use of the audit technique to evaluate present situations and the impact of previous measures; 7) information and training of prescribers.

PURPOSE:Fluoroquinolones are mainly used in ophthalmic antibiotic prophylaxis because of their broad spectrum activity and good ocular diffusion. But a single oral dose of fluoroquinolones can result in a serious source of tendinopathy and tendon rupture, especially in patients 60 years and older. It seems very important to investigate tendon toxicity of fluoroquinolones to improve the risk-benefit ratio in ophthalmologic antibiotic prophylaxis.MATERIAL:and methods: The intrinsic tenotoxic potential of four fluoroquinolones (pefloxacin, ofloxacin, ciprofloxacin, levofloxacin) was directly evaluated on living adherent tendon cells in microplates. Cell viability and reactive oxygen species production was evaluated using neutral red, alamar blue, and dichlorofluorescin diacetate tests.RESULTS:Results showed a loss of viability associated with free radical production depending on fluoroquinolone molecules. Pefloxacin appeared more tenotoxic but no study has confirmed its efficacy in surgical antibiotic prophylaxis and its use in the patient who is 60 years and older could be disputed. Ciprofloxacin is highly toxic with a low ocular diffusion and seems to be inappropriate for antibiotic prophylaxis. Ofloxacin and levofloxacin are less cytotoxic, associated with good ocular diffusion and a broad antibacterial spectrum.CONCLUSION:Ofloxacin and levofloxacin seem to be good alternatives for improving the risk-benefit ratio in surgical antibiotic prophylaxis in patients 60 years and older.