F. Becquet

Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies.

OBJECTIVES To investigate conjunctival and trabecular specimens from patients with glaucoma according to the duration and number of drugs received before filtration surgery, and to confirm, in a complementary experimental model, the role of preservative by comparing the effects of preserved and nonpreserved timolol. STUDY DESIGN Experimental animal and human tissue study. PARTICIPANTS Paired specimens of conjunctiva and trabeculum were taken from 61 patients undergoing trabeculectomy. Twenty-six patients were treated with 2 or more drugs for at least 1 year; 30 had received a beta-blocker for more than 1 year and 5 underwent primary surgery. A second study was performed in 25 rats receiving topical solutions in both eyes for 1 month. INTERVENTION Immunohistochemistry was performed in all biopsy specimens using 12 different monoclonal antibodies. Ocular structures from rats treated for 1 month with preserved 0.5% timolol, nonpreserved 0.5% timolol, or 0.01% benzalkonium chloride were similarly investigated in an experimental study. MAIN OUTCOME MEASURES Inflammatory cell infiltrates and fibroblasts were evaluated in biopsies, as well as in animal specimens, together with histologic changes induced by the drugs applied. RESULTS Twenty-four of 26 conjunctivae and 21 of 24 trabecular pieces from multitreated patients were found to be abnormally infiltrated by cells expressing inflammatory or fibroblastic markers or both. Nineteen of 30 conjunctivae and 9 of 22 trabeculums in the monotherapy group and only 1 of 5 specimens from the primary surgery group were abnormal. In rats, preserved timolol and benzalkonium similarly showed infiltrates together with toxic histopathologic changes as compared to the nonpreserved timolol and control groups. CONCLUSIONS These two combined studies confirmed histopathologic effects of antiglaucomatous drugs on the conjunctiva and showed similar effects in the trabecular meshwork. The experimental study showed that benzalkonium chloride is at least, to a large part, responsible for these toxic or immunoinflammatory effects or both on the ocular structures.

Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface

PURPOSE Long term use of topical drugs has clearly been shown to induce toxic immunopathological changes in the ocular surface. However, little is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAC) is the most used preservative and its cytotoxicity is well known, but other preservatives have not yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by applications of various preservatives, with special attention to inflammatory infiltrates. METHODS A total of 35 brown Norway rats were divided into seven groups of five each. They received, for one month, in both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or phosphate-buffered saline (PBS), the last group remaining untreated. Then, animals were sacrificed and eyes were processed for histological and immunological procedures with monoclonal antibodies to rat immunocompetent cells. RESULTS When compared to controls, all preservative-treated eyes consistently showed corneal and conjunctival damage, including epithelial alterations, various degrees of keratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium. No difference was found between the five tested drugs. CONCLUSIONS This study confirms that most preservatives used in ophthalmic eyedrops may similarly induce strong histopathological and inflammatory changes in the ocular surface after short term use. Although obtained in animal model, these results confirm strong toxic side effects in patients with preexisting ocular surface disorders and/or receiving topical drugs for long periods.

Does 23-gauge sutureless vitrectomy modify the risk of postoperative retinal detachment after macular surgery? A comparison with 20-gauge vitrectomy.

Purpose: To compare the cumulative risk of retinal detachment (RD) after macular surgery with 23-gauge sutureless vitrectomy and with 20-gauge vitrectomy. Methods: A single-center retrospective comparative study was conducted, comparing eyes operated for epiretinal membrane, macular hole, vitreomacular traction, and internal limiting membrane peeling. The 23-gauge group included 349 eyes operated consecutively between June 2007 and December 2008. The 20-gauge group included 346 eyes operated between October 2003 and September 2007. Results: After a 6-month follow-up, the cumulative probability of RD was 1.1% in the 23-gauge group and 3.5% in the 20-gauge group (P = 0.04). With a median follow-up of 14 months (range, 6-30 months) in the 23-gauge group and 30 months (range, 6-72 months) in the 20-gauge group, the cumulative probability of RD was, respectively, 1.1% and 4.9% (P = 0.04; log-rank test). Overall, RD was observed in 7 of 96 cases after macular hole surgery (7.3%), in 11 of 478 cases after epiretinal membrane surgery (2.3%), and in 3 of 70 cases after vitreomacular traction surgery (4.3%) (P = 0.14; log-rank test). Conclusion: After a short-term follow-up, a lower rate of postoperative RD was observed in the 23-gauge group. Sutureless 23-gauge vitrectomy appears safe when considering the risk of postoperative RD. Prospective and long-term studies are still needed to confirm these results.

Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical

Abstract · Background: A study was carried out to investigate the effect of two antioxidants –Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD) – in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. · Methods: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 µl of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n=8) did not receive any treatment and served as a positive control. Groups 2 (n=8) and 3 (n=8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n=4) was treated by three intramuscular injections of 15 000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. · Results: Intravitreal injection of xanthine–xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2–4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. · Conclusion: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Juxtapapillary subretinal pigment epithelial polypoid pseudocysts associated with unilateral tilted optic disc: Case report with clinicopathologic correlation

OBJECTIVE To describe the unique preoperative appearance, successful postoperative clinical course, and histopathologic features of a cluster of progressively enlarging pseudocysts that arose at the temporal margin of a unilateral tilted optic disc. STUDY DESIGN Case report. METHODS Clinical observation, color fundus photography, fluorescein angiography, and optical coherence tomography, as well as routine histologic and immunohistochemical studies of tissue removed by subretinal surgery. RESULTS Subretinal surgical excision of the lesions resulted in retinal reattachment with improved postoperative visual acuity. Histologic examination disclosed a cluster of fluid-filled polypoid pseudocysts lined by small vessels of choroidal origin lying beneath the basement membrane of the overlying retinal pigment epithelium (RPE). CONCLUSIONS We postulate that buds of small vessels of choroidal origin grew through or around the edge of Bruchs membrane at the temporal margin of the tilted optic disc and then passed under the juxtapapillary RPE. Ensuing leakage of proteinaceous fluid from these vessels eventuated in formation of a cluster of polypoid pseudocysts and subsequent localized papillomacular retinal separation with visual loss. The lesions were amenable to subretinal surgical removal with restoration of visual acuity.

Vitrectomie assistée par triamcinolone dans le traitement des récidives de décollement de rétine par trou maculaire du myope fort

But Decrire les avantages de la vitrectomie assistee par triamcinolone pour identifier les causes d’echec de la vitrectomie de premiere intention dans le traitement du decollement de retine par trou maculaire du myope fort. Observations Nous rapportons les cas de trois patients myopes forts ayant presente une recidive de decollement de retine par trou maculaire apres avoir ete traites initialement par vitrectomie avec creation du decollement posterieur du vitre, pelage de la surface retinienne et injection de SF6. Lors de la recidive, aucune traction residuelle ni dehiscence autre que le trou maculaire n’etait visualisee. La reprise chirurgicale avec injection de triamcinolone au cours de la vitrectomie a mis en evidence la persistance de reliquat de hyaloide posterieure ou de membrane friable et fortement adherente a la retine qui ont pu etre disseques dans tous les cas. Ces trois reinterventions ont conduit a un succes anatomique. Conclusion L’injection de triamcinolone ameliore la qualite de la vitrectomie dans le traitement des decollements de retine chez les myopes forts. La vitrectomie assistee par triamcinolone permet la visualisation de reliquats de hyaloide ou de membrane epiretinienne pouvant etre source de traction sur la retine et expliquer les echecs de la vitrectomie. Le pelage de ces structures transparentes a permis le succes de l’intervention.

125 Effet du clopidogrel sur les hémorragies dans la chirurgie vitréo-rétinienne

Introduction Le but de cette etude est de presenter le devenir des patients beneficiant d’un traitement anti-aggregant plaquettaire et operes de chirurgie vitreo-retinienne. Materiels et Methodes Une etude retrospective a ete realisee. Les dossiers de 37 patients (41 interventions) operes entre janvier 2006 et octobre 2007 ont ete etudies. Les elements suivants ont ete pris en compte : arret du clopidogrel ou non avant l’intervention, prise concomitante d’aspirine, presence d’une hypertension arterielle ou d’un diabete, indication operatoire, type d’intervention realisee, survenue d’une hemorragie per operatoire ou postoperatoire, devenir de l’œil opere. Resultats Trois cas (8 %) d’hemorragies postoperatoires ont ete observes. Dans tous ces cas le clopidogrel n’avait pas ete stoppe avant l’intervention. Dans deux cas, il s’agissait d’une hemorragie supra choroidienne qui a recidive malgre une ou plusieurs interventions supplementaires ce qui a conduit a la perte de la vision. Discussion Aucun cas d’hemorragie per ou post-operatoire n’a ete observe lorsque le clopidogrel a pu etre arrete avant l’intervention de chirurgie vitreo-retinienne. Conclusion La survenue d’une hemorragie dans les suites d’une chirurgie vitreo retinienne chez un patient sous clopidogrel n’est pas frequente mais semble de mauvais pronostic lorsque ce traitement ne peut etre arrete.

300 Absence d’amélioration un mois après injection intravitréenne de bevacizumab dans le traitement de la DMLA néovasculaire : facteurs de risque et devenir

Introduction Plusieurs etudes ont suggere l’interet de l’injection intravitreenne de bevacizumab dans le traitement de la DMLA neovasculaire. Le but de cette etude est : - d’etudier le devenir des patients dont l’examen clinique et angiographique 4 semaines apres l’injection ne met en evidence aucune amelioration ; - de degager des facteurs permettant de predire l’absence d’amelioration a cette date. Materiels et Methodes Etude retrospective multicentrique analysant les dossiers des patients ayant beneficie d’une injection intravitreenne de 0,05 mg de bevacizumab pour une DMLA neovasculaire apres consentement eclaire. Tous les patients ont beneficie d’un examen clinique, angiographique et OCT avant et 4 semaines apres l’injection. Resultats L’etude comprend 127 yeux de 121 patients (âge moyen 77 ans). Vingtneuf yeux (23 %) n’ont pas ete ameliores sur l’OCT et l’angiographie a la fluoresceine a la quatrieme semaine. Le suivi median apres l’injection etait de 18 semaines. Onze yeux ont ete ensuite traites par une nouvelle injection qui a permis une amelioration anatomique dans 7 cas. Trois cas de dechirure de l’epithelium pigmente et 3 cas d’hematome maculaire ont ete notes. Les patients non repondeurs a 4 semaines avaient une plus mauvaise acuite visuelle avant injection (P = 0,03). Discussion L’absence d’amelioration anatomique 4 semaines apres injection de bevacizumab n’est pas rare. Les patients non repondeurs a 4 semaines avaient une acuite visuelle significativement plus mauvaise avant injection. Conclusion L’absence d’amelioration anatomique 4 semaines apres injection de bevacizumab n’est pas rare. Une nouvelle injection a permis une amelioration dans les deux tiers des cas avec un suivi court. Les patients non repondeurs a 4 semaines avaient une acuite visuelle significativement plus mauvaise avant injection.