Impact of new lamellar techniques of keratoplasty on eye bank activity

Abstract Background Deep anterior lamellar keratoplasty (DALK) has become an increasingly popular alternative to penetrating keratoplasty in patients with stromal corneal pathologies. The main advantages of DALK are: prevention of long-term endothelial loss, elimination of allograft reaction and short topical steroid treatment with lower risks of glaucoma, cataract and infection. Because this technique enables surgeons to use corneal grafts with low endothelial density, the aim of this paper was to determine whether this type of innovation has had a significant impact on eye bank activity. Methods We reviewed our corneal graft activity over a 40-month period and assessed the proportion of deep lamellar and penetrating keratoplasties. During the same period, we also evaluated our eye bank activity and recorded the utilisation of grafts with endothelium abnormalities, which were only suitable for lamellar techniques. Results Deep lamellar keratoplasty represented 29.8% (85 out of 285) of corneal transplantations. Forty-eight percent of all corneas stored at the local eye bank were unsuitable for penetrating keratoplasty; 36.6% of those were not suitable for endothelial deficiencies. Among these, 72.7% were used for DALK and 27.3% were rejected. This permitted a 24.5% increase in corneal grafting activity. In contrast, Descemet's membrane was removed at the time of surgery in 12% of corneas with healthy endothelium, which was used for deep lamellar keratoplasty. Conclusions Deep anterior lamellar keratoplasty development and close collaboration between eye banks and surgeons can induce a significant increase in corneal grafting. This could be a partial solution in countries confronted with corneal graft shortages

Incidence of postoperative nosocomial endophthalmitis: results of an eight-year prospective surveillance programme in a university hospital in France

International audienc

Biologic Therapy for HLA-B27-associated Ocular Disorders

The treatment of articular and extra-articular manifestations associated with HLA-B27 has undergone dramatic changes over the past two decades, mainly as a consequence of the introduction of biologic agents and in particular anti-tumor necrosis factor α (anti-TNFα) agents. Uveitis is known to be the most frequent extra-articular feature in HLA-B27-associated spondyloarthritides. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment. However, biologic therapy may be effective in the management of refractory or recurrent forms of uveitis. This review gives an update on the management of HLA-B27-associated ocular disorders with biologics, including anti-TNFα agents and non-anti-TNFα biologic modifier drugs. There is an emerging role for newer biologics targeting interleukin-12/23 and interleukin-17 for the treatment of spondyloarthritides but data on their efficacy on anterior uveitis are sparse

Evaluation of voriconazole anti-Acanthamoeba polyphaga in vitro activity, rat cornea penetration and efficacy against experimental rat Acanthamoeba keratitis

International audienceBackground: Acanthamoeba keratitis (AK) is a sight-threatening infectious disease. Its effective and safe medical therapy remains highly debated. Recently, voriconazole, a monotriazole with noted in vitro activity against a large variety of fungi, has been successfully used both topically and systemically to treat human AK cases.Objectives: To measure anti-Acanthamoeba polyphaga in vitro activity, anti-rat AK efficiency and rat cornea penetration of eye-drop and oral voriconazole.Methods: A. polyphaga was maintained in axenic cultures. In vitro, amoebicidal and cysticidal activities of voriconazole were measured using an XTT assay. AK lesions of Sprague Dawley rats were scored from grade 0 to grade 3. For 21 days, from day 7 post-infection, voriconazole (1% solution) eye drops were instilled or voriconazole was administered by gavage (60 mg/kg/day). After killing, superficial corneal epithelium scrapings were cultured and analysed by PCR, and eye-globe histology was performed. Cornea and plasma concentrations were determined using 2D HPLC separation and tandem MS.Results: In vitro, voriconazole inhibited trophozoite proliferation with an IC50 value of 0.02 mg/L and an IC90 value of 2.86 mg/L; no cysticidal effect was found. In AK rats, eye drops reduced clinical worsening from day 7 to day 14 post-infection and oral voriconazole was not effective. Voriconazole cornea concentrations were directly dependent on the frequency of eye-drop instillations, which resulted in lower plasma concentrations, whilst oral voriconazole resulted in lower cornea concentrations.Conclusions: Present data underline the need for high-frequency eye-drop instillation regimens for efficient AK therapy

Toxic Epidermal Necrolysis with Ocular Involvement Following Vaccination for Hemorrhagic Fever with Renal Syndrome

We report a case of toxic epidermal necrolysis with ocular involvement following vaccination for hemorrhagic fever with renal syndrome. A healthy 20-year-old male soldier presented with confluent purpuric and erythematous dusky red macules evolving to flaccid blister and epidermal detachment on the whole body with conjunctival injection. The patient had no antecedent medical or surgical conditions except for two doses of hemorrhagic fever with renal syndrome vaccination. With supportive care, skin lesions were improved. Ophthalmic examinations revealed conjunctival injection with epithelial defects in both eyes. Ocular complications were resolved after amniotic membrane transplantation. Toxic epidermal necrolysis may be considered as a possible complication of hemorrhagic fever with renal syndrome vaccination

AAV2-Mediated Combined Subretinal Delivery of IFN-α and IL-4 Reduces the Severity of Experimental Autoimmune Uveoretinitis

We previously showed that adeno-associated virus 2 (AAV2) mediated subretinal delivery of human interferon-alpha (IFN-α) could effectively inhibit experimental autoimmune uveoretinitis (EAU). In this study we investigated whether subretinal injection of both AVV2.IFN-α and AAV2.IL-4 had a stronger inhibition on EAU activity. B10RIII mice were subretinally injected with AAV2.IFN-α alone (1.5×107 vg), AAV2.IL-4 alone (3.55×107 vg), and AAV2.IFN-α combined with AAV2.IL-4. PBS, AAV2 vector encoding green fluorescent protein (AAV2.GFP) (5×107 vg) was subretinally injected as a control. IFN-α and IL-4 were effectively expressed in the eyes from three weeks to three months following subretinal injection of AAV2 vectors either alone or following combined administration and significantly attenuated EAU activity clinically and histopathologically. AAV2.IL-4 showed a better therapeutic effect as compared to AAV2.IFN-α. The combination of AAV2.IL-4 and AAV2.IFN-α was not significantly different as compared to AAV2.IL-4 alone. There was no difference concerning DTH (delayed-type hypersensitivity) reaction, lymphocyte proliferation and IL-17 production among the investigated treatment groups, suggesting that local retinal gene delivery did not affect the systemic immune response

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis : an international, multidisciplinary Delphi-based consensus

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.Peer reviewe

Contribution à l'étude de nouveaux agents antiamibiens dans un modèle expérimental de kératite à Acanthamoeba chez le rat

Acanthamoeba keratitis (AK) is a rare and severe form of infectious keratitis,which is potentially sight-threatening. The infection is caused by Acanthamoeba spp.a common protozoan present in soil, air and water. Up to 85% of AK cases areassociated with contact lens wearing, more rarely after corneal injury.Currently, there are no agents approved for the treatment of AK in theEuropean Union or in the United States of America. In recent years, combinations ofunlicensed anti-amoebic agents such as biguanides and diamidines have been usedas the reference treatment. Treatment regimens and concentrations of active agentsare based on empirical data. Recently, voriconazole, a mono-triazole, wassuccessfully used to treat cases of human AK. Despite this, the ophthalmologicalcommunity is most often faced with severe forms of the disease with severemanagement difficulties and sometimes with a situation of therapeutic impasse. Thefunctional and anatomical loss of an eye can occur.Several agents and routes of administration have been tested in a rat model ofAK. First, as part of the European ODAK project (Orphan drug for AcanthamoebaKeratitis), our work suggested that a concentration of PHMB eye drops greater thanor equal to 0.04% should be preferred. Second, we were able to show the superiorityof voriconazole in eye drops compared to the oral route. Finally, our study on thepharmacokinetics of voriconazole and posaconazole after intrastromal injections,demonstrates their low utility in human because of the need for frequent reinjection.Nevertheless, additional analyses are necessary to confirm the interest ofposaconazole eye drops. All of this work could make it possible to adapt thetherapeutic protocols of AK.La kératite à Acanthamoeba (KA) est une kératite infectieuse rare et grave,potentiellement cécitante. L'infection est causée par Acanthamoeba spp., unprotozoaire ubiquitaire présent dans le sol, l'air et l'eau. Jusqu'à 85% des cas de KAsont associés au port de lentilles cornéennes, et plus rarement suite à untraumatisme.Actuellement, aucune molécule n’a d’autorisation de mise sur le marché danscette indication dans l'Union européenne et aux États-Unis. Ces dernières années,des combinaisons d'agents anti-amibiens tels que les biguanides et les diamidinesont été utilisées comme traitement de référence. Cependant, les schémasthérapeutiques et les concentrations d'agents actifs reposent sur des donnéesempiriques. Récemment, le voriconazole, antifongique triazolé, a été utilisé avecsuccès pour traiter des KA humaines. Malgré cela, la communauté ophtalmologiquese heurte le plus souvent dans les formes sévères à de grandes difficultés de prise encharge et se retrouve parfois en situation d’impasse thérapeutique. La pertefonctionnelle et anatomique de l’oeil est encore possible.A partir d’un modèle de KA chez le rat, plusieurs molécules et voiesd’administration ont été testées. Dans une première partie, en lien avec projeteuropéen ODAK (Orphan drug for Acanthamoeba Keratitis), nos travaux ont suggéréqu’une concentration de collyre PHMB supérieure ou égale à 0,04% devait êtrepréférée. Dans une deuxième partie, nous avons pu montrer la supériorité duvoriconazole en collyre par rapport à la voie orale. Enfin, l’étude de lapharmacocinétique du voriconazole et du posaconazole après injections directesintracornéennes, démontre leur faible utilité en clinique humaine du fait de lafréquence nécessaire de réinjection, bien que des analyses complémentairesconcernant le posaconazole en collyre pour confirmer son intérêt soient nécessaires.L'ensemble de ces travaux pourrait permettre d’adapter les protocolesthérapeutiques de la KA

Contribution to the study of new antiamoebic agents in an experimental model of Acanthamoeba keratitis in rats

La kératite à Acanthamoeba (KA) est une kératite infectieuse rare et grave,potentiellement cécitante. L'infection est causée par Acanthamoeba spp., unprotozoaire ubiquitaire présent dans le sol, l'air et l'eau. Jusqu'à 85% des cas de KAsont associés au port de lentilles cornéennes, et plus rarement suite à untraumatisme.Actuellement, aucune molécule n’a d’autorisation de mise sur le marché danscette indication dans l'Union européenne et aux États-Unis. Ces dernières années,des combinaisons d'agents anti-amibiens tels que les biguanides et les diamidinesont été utilisées comme traitement de référence. Cependant, les schémasthérapeutiques et les concentrations d'agents actifs reposent sur des donnéesempiriques. Récemment, le voriconazole, antifongique triazolé, a été utilisé avecsuccès pour traiter des KA humaines. Malgré cela, la communauté ophtalmologiquese heurte le plus souvent dans les formes sévères à de grandes difficultés de prise encharge et se retrouve parfois en situation d’impasse thérapeutique. La pertefonctionnelle et anatomique de l’oeil est encore possible.A partir d’un modèle de KA chez le rat, plusieurs molécules et voiesd’administration ont été testées. Dans une première partie, en lien avec projeteuropéen ODAK (Orphan drug for Acanthamoeba Keratitis), nos travaux ont suggéréqu’une concentration de collyre PHMB supérieure ou égale à 0,04% devait êtrepréférée. Dans une deuxième partie, nous avons pu montrer la supériorité duvoriconazole en collyre par rapport à la voie orale. Enfin, l’étude de lapharmacocinétique du voriconazole et du posaconazole après injections directesintracornéennes, démontre leur faible utilité en clinique humaine du fait de lafréquence nécessaire de réinjection, bien que des analyses complémentairesconcernant le posaconazole en collyre pour confirmer son intérêt soient nécessaires.L'ensemble de ces travaux pourrait permettre d’adapter les protocolesthérapeutiques de la KA.Acanthamoeba keratitis (AK) is a rare and severe form of infectious keratitis,which is potentially sight-threatening. The infection is caused by Acanthamoeba spp.a common protozoan present in soil, air and water. Up to 85% of AK cases areassociated with contact lens wearing, more rarely after corneal injury.Currently, there are no agents approved for the treatment of AK in theEuropean Union or in the United States of America. In recent years, combinations ofunlicensed anti-amoebic agents such as biguanides and diamidines have been usedas the reference treatment. Treatment regimens and concentrations of active agentsare based on empirical data. Recently, voriconazole, a mono-triazole, wassuccessfully used to treat cases of human AK. Despite this, the ophthalmologicalcommunity is most often faced with severe forms of the disease with severemanagement difficulties and sometimes with a situation of therapeutic impasse. Thefunctional and anatomical loss of an eye can occur.Several agents and routes of administration have been tested in a rat model ofAK. First, as part of the European ODAK project (Orphan drug for AcanthamoebaKeratitis), our work suggested that a concentration of PHMB eye drops greater thanor equal to 0.04% should be preferred. Second, we were able to show the superiorityof voriconazole in eye drops compared to the oral route. Finally, our study on thepharmacokinetics of voriconazole and posaconazole after intrastromal injections,demonstrates their low utility in human because of the need for frequent reinjection.Nevertheless, additional analyses are necessary to confirm the interest ofposaconazole eye drops. All of this work could make it possible to adapt thetherapeutic protocols of AK