Effectiveness and Safety of Weekly Adalimumab for Non-Infectious Chronic Anterior Uveitis in Children.

PURPOSE: Non-infectious chronic anterior uveitis (CAU) remains a therapeutic challenge. The purpose of this study was to analyze the effectiveness and safety of weekly dosing of adalimumab in children with non-infectious refractory CAU. Methods: Demographic and clinical data of children followed by non-infectious CAU treated with adalimumab were retrospectively reviewed. RESULTS: Of the 42 children with CAU, 27/42 (64.3%) were treated with adalimumab. Escalation to weekly dosing of adalimumab was necessary for 11/27 children (40.7%). After 3 and 6 months, 7/11 children (63.6%) met the composite endpoint of inflammation control improvement. Children requiring weekly adalimumab had initially more severe uveitis: anterior chamber cells (p = 0.02), aqueous flare (p = 0.02), and presence of macular edema (p = 0.007). No children had serious systemic side effects. CONCLUSION: Weekly adalimumab in children with refractory CAU appears to be an effective and safe treatment for inflammation control and corticosteroid sparing, and an alternative before biologic switching. Controlled studies are needed.

Efficacious switching from subcutaneous to intravenous tocilizumab in patients with non-infectious non-anterior uveitis.

PURPOSE: The efficacy of tocilizumab in refractory chronic noninfectious uveitis has been previously reported, but no data comparing intravenous and subcutaneous tocilizumab in uveitis are available. RESULTS: We report a case series of patients with chronic noninfectious uveitis with incomplete efficacy of subcutaneous tocilizumab, improved after switching to intravenous routes. Improvement of visual acuity was observed with intravenous tocilizumab for all patients. Half of the patients could stop corticosteroids. Rapid efficacy of intravenous tocilizumab was observed, between 2 and 3 months. CONCLUSION: In uveitis, tocilizumab administration could be optimized by a switching from a subcutaneous to an intravenous administration route.

Ocular sequelae of epidermal necrolysis: French national audit of practices, literature review and proposed management.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known as epidermal necrolysis (EN). They are characterized by more or less extensive epidermal detachment, associated with mucous membrane involvement, and may be complicated during the acute phase by fatal multiorgan failure. SJS and TEN can lead to severe ophthalmologic sequelae. There are no recommendations for ocular management during the chronic phase. We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. Ophthalmologists and dermatologists from the French reference center for epidermal necrolysis were asked to complete a questionnaire on management practices in the chronic phase of SJS/TEN. The survey focused on the presence of a referent ophthalmologist at the center, the use of local treatments (artificial tears, corticosteroid eye drops, antibiotic-corticosteroids, antiseptics, vitamin A ointment (VA), cyclosporine, tacrolimus), the management of trichiatic eyelashes, meibomian dysfunction, symblepharons, and corneal neovascularization, as well as the contactologic solutions implemented. Eleven ophthalmologists and 9 dermatologists from 9 of the 11 centers responded to the questionnaire. Based on questionnaire results, 10/11 ophthalmologists systematically prescribed preservative-free artificial tears, and 11/11 administered VA. Antiseptic or antibiotic eye drops or antibiotic-corticosteroid eye drops were recommended as needed by 8/11 and 7/11 ophthalmologists, respectively. In case of chronic inflammation, topical cyclosporine was consistently proposed by 11/11 ophthalmologists. The removal of trichiatic eyelashes was mainly performed by 10/11 ophthalmologists. Patients were referred to a reference center for fitting of scleral lenses (10/10,100%). Based on this practice audit and literature review, we propose an evaluation form to facilitate ophthalmic data collection in the chronic phase of EN and we also propose an algorithm for the ophthalmologic management of ocular sequelae.

Multicenter prospective observational study of dupilumab-induced ocular events in atopic dermatitis patients.

BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.

Saprochaete clavata Chorioretinitis in a Post-chemotherapy Immunocompromised 9-Year-Old Child.

PURPOSE: To describe the management of bilateral chorioretinitis with Saprochaete clavata in a post-chemotherapy immunocompromised young patient. METHOD: A retrospective case report. RESULT: A 9-year-old boy treated with chemotherapy for type 2 acute myeloid leukaemia was diagnosed with Saprochaete clavata (formerly called Geotrichum clavatum) fungaemia. Systematic ocular examination revealed chorioretinitis of the left eye becoming bilateral within the next 3 days. Therapy was based on systemic administration of voriconazole, amphotericin B and flucytosine associated with granulocytic stimulation without stabilizing the ophthalmological situation. Bilateral intravitreal injections of amphotericin B were administered. Voriconazole residual blood concentration was monitored to adjust daily dose. Final best corrected visual acuity in the right eye was 20/50 and 20/20 in the left eye. CONCLUSION: This is the first report of chorioretinitis with Saprochaete clavata. Because of its unpredictable pharmacokinetics, especially in pediatric population, therapeutic drug monitoring of voriconazole is essential to control fungal infection.

Lower Relapses Rate With Infliximab Versus Adalimumab in Sight-Threatening Uveitis: A Multicenter Study of 330 Patients.

PURPOSE: To compare the relapse rate of sight-threatening noninfectious uveitis (NIU) in patients treated with infliximab (IFX) or adalimumab (ADA). DESIGN: Observational retrospective multicenter study. METHODS: A total of 330 patients (median age, 36 years; interquartile range, 27-54), 45.2% men) with sight-threatening NIU (ie, retinal vasculitis and/or macular edema) treated with anti-tumor necrosis factor [TNF]-α agents (IFX intravenously at 5 mg/kg at weeks 0, 2, 6, and every 4 to 6 weeks or ADA subcutaneously at 80 mg, then 40 mg every 2 weeks). Data were obtained retrospectively from patients' medical records. Main outcome measures were relapse rate, complete response of NIU, corticosteroid sparing effect, and safety. RESULTS: Main etiologies of uveitis included Behçet disease (27%), idiopathic juvenile arthritis (5.8%), and sarcoidosis (5.5%). The estimated relapse rate at 6 months after introduction of biological agents was 13% (95% CI = 0.009-0.16). IFX was associated with less relapse risk than ADA (hazard ratio [HR] = 0.52, 95% CI = 0.36- 0.77, P = .001). ADA and IFX were comparable in terms of complete response rate of NIU as well as corticosteroid-sparing effect. Behçet disease was associated with higher odds of complete response (HR = 2.04, 95% CI = 1.16 -3.60, P = .01] and lower relapse rate (HR = 0.53, 95% CI = 0.33-0.85, P = .009) than other causes of NIU with anti-TNF-α agents. CONCLUSIONS: In sight-threatening NIU, IFX seems to be associated with a lower relapse rate than ADA.

Acyclovir-Resistant Herpes Simplex Virus 1 Keratitis: A Concerning and Emerging Clinical Challenge.

PURPOSE: To describe the clinical and virological profiles of patients with herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) strains of herpes simplex virus 1 (HSV-1). DESIGN: Multicenter retrospective case series. METHODS: HSV-1 resistance to ACV was confirmed using sequencing of genes encoding HSV-1 thymidine kinase (TK) and DNA polymerase (DNA pol). Data were collected on the number of HSK episodes before and after the diagnosis of resistance, ocular findings including the type of HSK, immune status of patients, antiviral treatments, and HSV-1 genotypic resistance profiles. RESULTS: This study evaluated 18 HSK patients (13 male and 5 female, aged 66.8 ± 4.7 years) with ACVR HSV-1-positive ocular samples. Genotypic resistance testing was performed because of frequent recurrences despite adequate antiviral prophylaxis (AVP) (n = 13, 72%), or poor response to suppressive antiviral therapy (n = 5, 28%). Resistance mutations were found in the TK (n = 15, 83%) or in the DNA pol gene (n = 3, 17%). Prior to the diagnosis of resistance, the duration of disease was 29.8 ± 20.4 years, with more than 10 HSK recurrences in 15 patients (83%). The number of recurrences between the first episode and the diagnosis of resistance was significantly lower in immunocompromised patients (n = 6, 33%) than in immunocompetent patients (n = 12; 67%) (11.5 ± 4.9 vs 16.4 ± 1.9, P = .05). CONCLUSION: HSV-1 resistance to ACV must be suspected in HSK patients with recurrences despite AVP and/or in cases that respond poorly to a suppressive antiviral regimen. Immunocompromised patients and/or those with longstanding disease may be particularly at risk for developing resistance.

Anti-Tumor Necrosis Factor α versus Tocilizumab in the Treatment of Refractory Uveitic Macular Edema: A Multicenter Study from the French Uveitis Network.

PURPOSE: To analyze the factors associated with response (control of ocular inflammation and corticosteroid-sparing effect) to biologics (anti-tumor necrosis factor [TNF]-α agents and tocilizumab) in patients with refractory uveitic macular edema (ME). DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Adult patients with uveitic ME refractory to systemic corticosteroids, disease-modifying antirheumatic drugs, or both. METHODS: Patients received anti-TNF-α agents (infliximab 5 mg/kg at week 0, 2, 6, and every 4-6 weeks [n = 69] and adalimumab 40 mg/2 weeks [n = 80]) and tocilizumab (8 mg/kg every 4 weeks intravenously [n = 39] and 162 mg/week subcutaneously [n = 16]). MAIN OUTCOME MEASURES: Analysis of complete and partial response rates, relapse rate, low vision (visual acuity in at least 1 eye of ≥ 1 logarithm of the minimum angle of resolution), corticosteroid-sparing effect, and adverse events at 6 months. RESULTS: Two hundred four patients (median age, 40 years [interquartile range, 28-58 years]; 42.2% men) were included. Main causes of uveitis included Behçet's disease (17.2%), birdshot chorioretinopathy (11.3%), and sarcoidosis (7.4%). The overall response rate at 6 months was 46.2% (21.8% of complete response) with anti-TNF-α agents and 58.5% (35.8% of complete response) with tocilizumab. In multivariate analysis, treatment with tocilizumab (odds ratio, 2.10; 95% confidence interval [CI], 1.06-4.06; P = 0.03) was associated independently with complete response of uveitic ME compared with anti-TNF-α agents. Anti-TNF-α agents and tocilizumab did not differ significantly in terms of relapse rate (hazard ratio, 1.00; 95% CI, 0.31-3.18; P = 0.99) or occurrence of low vision (odds ratio, 1.02; 95% CI, 0.51-2.07; P = 0.95) or corticosteroid-sparing effect (P = 0.29). Adverse events were reported in 20.6% of patients, including serious adverse events reported in 10.8% of patients. CONCLUSIONS: Tocilizumab seems to improve complete response of uveitic ME compared with anti-TNF-α agents.

Perspectives for immunotherapy in noninfectious immune mediated uveitis.

Introduction: Noninfectious uveitis (NIU) is one of the leading causes of blindness worldwide. In adult patients, anterior NIU is usually managed with topical corticosteroids. In intermediate, posterior uveitis. and panuveitis, systemic corticosteroids are used especially in case of bilaterality or association with systemic disease. Biotherapies are recommended in case of inefficacy or intolerance to corticosteroids or conventional immunosuppressive drugs. Anti-TNF-α agents are by far the most widely used biotherapies. In case of failure or poor tolerance to anti-TNF-α, new targeted therapies can be proposed.Areas covered: We present and discuss an updated overview on biologics and biotherapies in NIU.Expert opinion: In case of dependency to systemic or intravitreal steroids, sight-threatening disease, and/or failure of conventional immunosuppressive drugs, anti-TNF-α are used as first-line biologics to achieve quiescence of inflammation. Anti-interleukin-6 is another option that may be proposed as first-line biologic or in case of poor efficacy of anti-TNF-α. Interferon can be directly proposed in specific indications (e.g. refractory macular edema, sight-threatening Behçet's uveitis). In the rare cases that remain unresponsive to traditional biotherapies, novel molecules, such as Janus-associated-kinase and anti-phosphodiesterase-4-inhibitors can be used. Therapeutic response must always be evaluated by clinical and appropriate ancillary investigations.

Old and New Challenges in Uveitis Associated with Behçet's Disease.

Behçet's disease (BD) is a systemic vasculitis disease of unknown origin occurring in young people, which can be venous, arterial or both, classically occlusive. Ocular involvement is particularly frequent and severe; vascular occlusion secondary to retinal vasculitis may lead to rapid and severe loss of vision. Biologics have transformed the management of intraocular inflammation. However, the diagnosis of BD is still a major challenge. In the absence of a reliable biological marker, diagnosis is based on clinical diagnostic criteria and may be delayed after the appearance of the onset sign. However, therapeutic management of BD needs to be introduced early in order to control inflammation, to preserve visual function and to limit irreversible structural damage. The aim of this review is to provide current data on how innovations in clinical evaluation, investigations and treatments were able to improve the prognosis of uveitis associated with BD.

Rheumatoid Arthritis Associated Episcleritis and Scleritis: An Update on Treatment Perspectives.

Episcleritis and scleritis are the most common ocular inflammatory manifestation of rheumatoid arthritis. Rheumatoid arthritis (RA) accounts for 8% to 15% of the cases of scleritis, and 2% of patients with RA will develop scleritis. These patients are more likely to present with diffuse or necrotizing forms of scleritis and have an increased risk of ocular complications and refractory scleral inflammation. In this review we provide an overview of diagnosis and management of rheumatoid arthritis-associated episcleritis and scleritis with a focus on recent treatment perspectives. Episcleritis is usually benign and treated with oral non-steroidal anti- inflammatory drugs (NSAIDs) and/or topical steroids. Treatment of scleritis will classically include oral NSAIDs and steroids but may require disease-modifying anti-rheumatic drugs (DMARDs). In refractory cases, treatment with anti TNF biologic agents (infliximab, and adalimumab) is now recommended. Evidence suggests that rituximab may be an effective option, and further studies are needed to investigate the potential role of gevokizumab, tocilizumab, abatacept, tofacitinib, or ACTH gel. A close cooperation is needed between the rheumatology or internal medicine specialist and the ophthalmologist, especially when scleritis may be the first indicator of an underlying rheumatoid vasculitis.

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis.

OBJECTIVE: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis. METHODS: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria. RESULTS: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06). CONCLUSION: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency.

Corneal Pharmacokinetics of Voriconazole and Posaconazole following Intrastromal Injection and Posaconazole Eye Drops Instillation in Rats.

Purpose/Aims: Infectious keratitis is a major cause of visual impairment and blindness worldwide. Common difficulties in treating fungal keratitis prompt new therapeutic possibilities. In this study, intrastromal voriconazole and posaconazole, and topical posaconazole were tested for their potential to obtain therapeutic cornea concentrations. Materials and Methods: Pharmacokinetics of triazole intracorneal/eye drop administration was studied in rats. Sixty-two rats were treated either by voriconazole or posaconazole. Twenty-nine and 33 rats received intrastromal injection of voriconazole solution (1 µl, 10 mg/ml) and posaconazole solution (1 µl, 18 mg/ml), respectively, administered under microscopic examination with a 32 gauge needle in the left cornea. Posaconazole (1.8% solution) eye drops were used. Cornea and plasma concentrations were determined using 2D HPLC separation and tandem MS, at 30 min, 3 h, 6 h, 24 h, 48 h, 72 h, and 144 h (6 days) post-intrastromal injection. The entire rat cornea was used for chromatography analyses. Results: In anesthetized rats, single intracorneal injection resulted, after 30 min, in respectively, >300 ng/mg and >260 ng/mg cornea concentrations, dropping to low levels within hours, while staying low in plasma. The effect of hourly posaconazole eye drops resulted in >10 ng/mg cornea concentration, which was maintained with instillations every 2 and then every 4 h. Conclusion: Our results show that there is little interest of intrastromal triazole administration due to the short duration of high cornea concentrations obtained after intracorneal injection. Posaconazole eye drops maintain therapeutic cornea concentrations in rats and could be used to treat severe infectious keratitis.

Mapping of proteomic profile and effect of the spongy layer in the human amniotic membrane.

The graft of human amniotic membrane (HAM) contributes to the healing of corneal perforating ulcers and so to save a large number of eyes suffering of severe chemical burns. This biological material is used for the treatment of ocular surface diseases because of its capacity to reduce inflammation and promote a quicker wound healing. For clinical use, the HAM is denuded from its spongy layer, but this layer can be an important source of growth factors which promote re-epithelialization. The aim of our study is to provide a general view of protein expression of the HAM and the spongy layer and therefore to determine if the spongy layer and/or a specific part of HAM have a beneficial role in the process of wound healing in patients with corneal ulcers. For this study, human placentas were obtained from healthy women after vaginal delivery or caesarean section after signing the consent form. Mapping of protein expression is done by dividing the placenta in 2 equal parts, one with spongy layer and another without (conventional HAM). Each part is also divided in 3 zones depending on the distance from the umbilical cord. The proteomic analysis was done by ELISA, targeting growth factors (EGF, HGF, KGF, NGF and TGF-beta1) and pro inflammatory cytokine TNF-α in the HAM without spongy layer and in the spongy layer. In this study we observed significant difference in the total amount of protein extract between the different donors. We do not observe a significant difference in the growth factor level between the conventional HAM and the spongy layer. No variation was observed in the expression of HGF, KGF and NGF in different zone of HAM and neither between conventional HAM and spongy layer in each zone. (*p value < 0.05, **p value<0.01,***p value < 0.001). We do detect very low dose of TNF-α and no correlation with the amount of growth factors. In our study we demonstrated that keeping the spongy layer in conventional method of handling HAM can add more GF, and so probably have a positive affect the wound healing process. Variation in some growth factors expression has been observed between the placentas and therefore this may explain the variation in clinical results. No indicator for the selection of placentas with a higher rate of growth factor was found.

Contact Lenses and Infectious Keratitis: From a Case-Control Study to a Computation of the Risk for Wearers.

PURPOSE: Contact lens (CL)-related microbial keratitis (MK) has major public health implications, with about 300 million wearers worldwide, and certain potentially modifiable risk factors. This study aimed to identify the risk factors of CL-related MK. METHODS: A multicenter case-control study was conducted between 2014 and 2017. Cases presenting with CL-related MK were submitted to an anonymous 52-item questionnaire, which was also completed by healthy controls. Univariate followed by multivariate logistic regression analysis was performed. Risk factors for CL-related MK were given as odds ratio (OR) with 95% confidence interval and P-value. RESULTS: The study included a total of 2267 patients (1198 cases and 1069 controls). The MK risk factors for the daily disposable lenses group were exceeding the lens renewal period (OR = 9.16, P = 0.008) and occasionally wearing CL when sleeping (OR = 15.83, P = 0.035). The most important risk factors in the nondaily disposable lenses group were lens cleaning solution distributed by eye care brands (OR = 3.50, P < 0.001) and failure to renew lens cases (OR = 3.39, P = 0.001). Statistically and clinically significant variables were used to establish the MK risk equation for CL wearers, allowing an individual calculation of the risk of MK under lenses. CONCLUSIONS: The MK risk equation is a valuable tool for educating patients about the risks associated with wearing CL. It allows the patient to be informed about their overall risk of infection while detailing the precipitating elements of the infectious risk with the aim of modifying risk behavior.

Face-to-face phacoemulsification using a slitlamp in patients who are unable to lie flat.

Phacoemulsification can be challenging in patients who are unable to lie flat or sit in a reclined position that exceeds 30 degrees to 45 degrees during surgery. We describe a new technique that we have used on 4 eyes of two patients. Both were operated on while sitting in a strictly upright position, resting their chin in front of a mobile slitlamp in the same manner as during a standard ophthalmologic examination. The surgeon sits on the other side of the slitlamp, facing the patient, and operates via a temporal corneal incision. The described operating conditions were deemed perfectly adequate by the experienced surgeon. Both patients recovered a corrected distance visual acuity of 20/20 in both eyes and said they would recommend this surgery to anyone who cannot lie flat. Surgeons should consider this technique when standard surgical positioning is not possible.

Chronic and recurrent non-infectious paediatric-onset uveitis: a French cohort.

Objective: To evaluate the demographics, aetiologies, complications, treatments and visual prognoses of chronic and recurrent non-infectious paediatric-onset uveitis in France. Methods: Descriptive, retrospective and bicentric study in patients whose disease started before 17 and who were followed up in two centres from January 2010 to May 2017. Results: We included 147 patients with 268 affected eyes. Eighty-two had juvenile idiopathic arthritis-associated chronic uveitis, 58 were antinuclear antibody (ANA) positive and 24 were ANA negative, 36 had idiopathic uveitis, 9 had enthesitis-related arthritis-associated uveitis, 9 had sarcoidosis-associated uveitis and 11 had other inflammatory aetiologies. These patients cumulated 161 complications: ocular hypertension, cataract, band keratopathy, macular oedema, optic disk oedema and decreased visual acuity, including permanent visual loss for 31 patients. The most used treatments were corticosteroid (CS) eye drops (82%), systemic CSs (34%), methotrexate (58%) and biologics (38%). At the latest follow-up, 45 patients had achieved remission of uveitis without any treatment, 56 had inactive uveitis on topical steroids and 48 still had active uveitis. Conclusion: Paediatric-onset uveitis are associated with a high rate of complications. However, following the introduction of biologics and particularly antitumour necrosis factor alpha antibodies, a significant proportion of uveitis became inactive on or even off treatment.

Therapeutic advances in juvenile idiopathic arthritis - associated uveitis.

PURPOSE OF REVIEW: The aim of this review is to highlight recent changes in the treatment of juvenile idiopathic arthritis (JIA) - associated uveitis in the era of biologics. RECENT FINDINGS: Early introduction of steroid-sparing therapies is paramount for appropriate management. Biologic therapies have improved the therapeutic management of JIA-uveitis and adalimumab is currently approved for pediatric-onset noninfectious chronic anterior uveitis with an inadequate response to topical steroids and methotrexate. Recent studies suggest that ocular complications in JIA-uveitis are less frequent compared with previous publications. However, patients with JIA-uveitis seem to be particularly dependent on classical immunosuppressive drugs or biologics. Indications for primary lens implantation have expanded considerably with the evolution of materials and better control of inflammation with biologics. The rate of serious adverse events related to new therapeutic approaches seem acceptable, however longer term follow-up is necessary. SUMMARY: Improvement in the initial screening and improved inflammation control with biologics has considerably reduced the potentially sight-threatening prognosis of JIA-uveitis.

Endothelial quality of eye bank-prestripped DMEK prepared form organ-cultured corneas with the Muraine technique.

Our aim was to measure the endothelial quality of prestripped Descemet membrane endothelial keratoplasty (DMEK) 48 h after preparation in an eye bank with the Muraine technique and shipping in a distant center. Ten pairs of human corneas with similar eye bank endothelial cell density (ebECD) were stored in organ-culture (OC) for 25 days (20, 28) [median (10-90 percentiles)]. One cornea was then randomized to DMEK preparation using the Moria Muraine trephine, the other served as control. The grafts were left attached to the center of the cornea, immersed in the OC medium (without Dextran) and shipped to a distant center. After 48 h, the viable ECD (vECD) was assessed by image analysis after staining with Hoechst/Ethidium/Calcein-AM. In addition, immunostaining was performed on flat mounted tissues for structural (ZO-1, NCAM, CD166) and functional (Na+/K+ ATPase) proteins of ECs, and for collagen I. Just before stripping, ebECD was 2428 (2268-2669) cells/mm2 for DMEK and 2471 (2135-2714) for controls (P = 1). Forty-eight hours after stripping, vECD was 2057 (1829-2463) cells/mm2 for DMEK and 2119 (1496-2525) for controls (P = 0.508). The expression patterns of the 5 proteins were similar in ECs of both groups. Notably, the deep posterior folds observed in OC controls almost disappeared in prestripped DMEK due to the lack of a link between Descemet membrane and stroma. As a consequence of the elimination of mechanical stress in these zones, EC evenly covered the whole graft. In conclusion, DMEK prestripping with the Muraine technique and shipping away can be used safely by eye banks.