Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: An LOC network study.

The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011 and 2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 42/59 (71%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

Prevention of hypothermia in trauma victims - the HYPOTRAUM 2 study.

INTRODUCTION: Hypothermia is common in trauma patients. It contributes to increasing mortality rate. Hypothermia is multifactorial, favoured by exposure to cold, severity of the patient's state and interventions such as infusion of fluids at room temperature. AIM: To demonstrate that specific management of hypothermia (or of the risk of hypothermia) increases the number of trauma patients arriving at the hospital with a temperature >35°C. DESIGN: This is a prospective, multicentre, open-label, pragmatic, cluster randomized clinical trial of an expected 1,200 trauma patients included by 12 out-of-hospital mobile intensive care units (MICU). Trauma patients are included in a prehospital setting if they present at least one of the following criteria known to be associated with an increased incidence of hypothermia: ambient temperature <18°C, Glasgow coma scale <15, systolic arterial blood pressure <100 mm Hg or body temperature <35°C. Patients are randomized, by cluster, to receive a conventional management or 'interventional' nursing management associating: continuous epitympanic temperature monitoring, early installation in the heated ambulance (temperature target >30°C controlled by infrared thermometer), protection by a survival blanket, and use of heated solutes (temperature objective >35°C controlled by infrared thermometer). The primary end point is the prevalence of hypothermia on arrival at the hospital. The hypothesis tested is a reduction from 20% to 13% in the prevalence of hypothermia. Secondary end points are to evaluate the interaction between the effectiveness of the measures taken and: (1) the severity of the patients assessed by the Revised Trauma Score; (2) the meteorological conditions when they are managed; (3) the time of care; and (4) therapeutic interventions. DISCUSSION: This trial will assess the effectiveness of an invasive, out-of-hospital, temperature management on the onset of hypothermia in moderate to severe trauma patients. IMPACT: Specific management of hypothermia is expected to decrease hypothermia in trauma patients.

Evaluating the cost-consequence of a standardized strategy for the etiological diagnosis of uveitis (ULISSE study).

MAIN OBJECTIVE: To prospectively assess the cost-consequence of a standardized diagnostic strategy as to compared to an open one for the etiological diagnosis of uveitis. DESIGN: This was a prospective, non-inferiority, multicentre, randomized controlled trial. METHODS: We included all consecutive patients with uveitis who had visited at least one of the Departments of Ophthalmology. In the standardized group, patients had a minimal work-up regardless of the type of uveitis (including evaluation of the CBC, ESR, C-reactive protein, tuberculin skin test, syphilis serology and chest X-ray). Depending on ophthalmological findings, further investigations could be performed. In the open strategy, ophthalmologists were free to order any kind of investigation. The main outcome was the mean cost per patient of each strategy. RESULTS: 903 uveitis patients were included from January, 2010 to May, 2013. The mean cost per patient of the standardized strategy was 182.97 euros [CI 95% (173.14; 192.80)], and the mean cost per patient of the open strategy was 251.75 euros [CI 95% (229.24; 274.25)]. Therefore, the mean cost per patient of the standardized strategy was significantly lower than the mean cost per patient of the open strategy (p<0.001). There were significantly fewer visits (p<0.001), fewer radiological procedures (p<0.004) and fewer laboratory investigations (p<0.001) in the standardized group. CONCLUSION: A standardized strategy is a cost-saving approach for the etiological diagnosis of uveitis.

Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis).

PURPOSE: ULISSE is the only study that prospectively assessed the efficiency of a standardized strategy, compared to an open strategy for the etiologic diagnosis of uveitis. Our aim was to evaluate the diagnostic yield of the tests prescribed in the ULISSE study to clarify their relevance. METHODS: ULISSE is a non-inferiority, prospective, multicenter and cluster randomized study. The standardized strategy is a two-steps strategy: in the first step, common standard tests were performed, and in the second step, tests were guided by the clinical and anatomic type of uveitis. We reported the relevance of the diagnostic tests used in the standardized strategy, as well as the profitability of the tests that were prescribed to more than twenty patients in each group. Based on diagnostic criteria, either an ophthalmologist, or an internist, established the profitability of a test by considering whether the test lead to a diagnosis or not. RESULTS: Among the 676 patients included (standardized 303; open 373), a diagnosis was made for 152 (50.4%) in the standardized group and 203 (54.4%) in the open group. The most common entities were HLA-B27 associated uveitis (22%), spondyloarthritis (11%), sarcoidosis (18%), tuberculosis (10.7%) and herpes virus infections (8.5%). Among the first step's systematic tests, tuberculin skin test was the most contributive investigation (17.1%), followed by chest X-ray (8.4%), C reactive protein and ESR (6.6% and 5.1%), complete blood count (2.2%) and VDRL (2.0%). The second step's most often contributive tests were: HLA B27 (56.3%), chest-CT (30.3%) and angiotensin converting enzyme (ACE) (16.5%). HLA B27 and ACE were significantly more contributive in the standardized group than in the open group. Immunological tests were never contributive. Among the free investigations, or among the investigations guided by clinical or paraclinical findings, the most often contributive tests were: Quantiferon® (24%), electrophoresis of serum protein (7.8%) and sacroiliac imagery (46.4%). Intracellular serologies (1.7%), serum calcium (2.1%) and hepatic tests (3.3%) were exceptionally contributive. Among the third intention tests, labial salivary gland biopsies were contributive in 17.9% of cases, but the profitability of other invasive investigations (anterior chamber tap, vitrectomy, bronchoscopy and lumbar puncture) or specialized imagery (18F-FDG PET, Brain MRI) could not be determined since these test were rarely performed. CONCLUSION: Only a few diagnostic tests are useful for the etiological assessment of uveitis. They are often cheap, simple, more often guided by the clinical findings, and lead to an etiological diagnosis in most patients. On the other hand, some tests are never or exceptionally contributive, such as immunological tests or intracellular serologies. Further studies are required to evaluate the profitability of third intention imagery and invasive investigations.

Clinical and biometric determinants of actual lens position after cataract surgery.

PURPOSE: To evaluate the preoperative clinical and biometric determinants associated with the actual lens position after cataract surgery. SETTING: Department of Ophthalmology, University Hospital of Montpellier, France. DESIGN: Prospective longitudinal cohort study. METHODS: The data collected included clinical factors (age, sex, history of vitrectomy) and biometry factors (axial length [AL], anterior chamber depth [ACD], lens thickness, white-to-white [WTW] distance) that might affect actual lens position. Each patient had optical low-coherence reflectometry biometry (Lenstar) preoperatively and 1 month postoperatively. The actual lens position was measured as the postoperative position of the center of the intraocular lens (IOL). Patients were stratified into 3 groups by type of IOL: Acrysof SN60WF or SN6AT (Group 1), Tecnis ZCB00 or ZCT (Group 2), and Asphina 409 MV (Group 3). RESULTS: The study comprised 168 eyes (mean age 73.3 years ± 9.8 [SD]). The mean actual lens position was 4.88 ± 0.29 mm, 5.01 ± 0.29 mm, and 5.05 ± 0.32 mm in Group 1 (n = 67 eyes), Group 2 (n = 52 eyes), and Group 3 (n = 49 eyes), respectively. In the overall population, AL, ACD, anterior segment depth, and WTW distance were correlated with actual lens position (r = 0.48, P < .0001; r = 0.64, P < .001; r = 0.58, P < .0001; r = 0.39, P < .001, respectively). CONCLUSIONS: The AL, ACD, anterior segment depth, and WTW distance correlated with actual lens position after cataract surgery. The integration of these data in IOL formulas could help improve refractive outcomes after the surgery.

Randomized Controlled Trial Evaluating a Standardized Strategy for Uveitis Etiologic Diagnosis (ULISSE).

PURPOSE: To prospectively assess the efficiency of a standardized diagnostic approach, compared to an open strategy, for the etiologic diagnosis of uveitis. DESIGN: Noninferiority, prospective, multicenter, clustered randomized controlled trial. METHODS: Consecutive patients with uveitis, who visited 1 of the participating departments of ophthalmology, were included. In the standardized group, all patients had a minimal evaluation regardless of the type of uveitis (complete blood count, erythrocyte sedimentation rate, C-reactive protein, tuberculin skin test, syphilis serology, and chest radiograph) followed by more complex investigations according to ophthalmologic findings. In the open group, the ophthalmologist could order any type of investigation. Main outcome was the percentage of etiologic diagnoses at 6 months. RESULTS: Nine hundred and three patients with uveitis were included from January 2010 to May 2013 and the per-protocol population comprised 676 patients (open 373; standardized 303). Mean age at diagnosis was 46 years. Anatomic distribution of uveitis was as follows: anterior (60.8% and 72.3%, P = .0017), intermediate (11.7% and 12.3%, P = .8028), posterior (17.8% and 8.2%, P = .0004), and panuveitis (15.3% and 15.2%, P = .9596). An etiologic diagnosis was established in 54.4% of cases in the open group and 49.5% in the standardized group (P = .2029). The difference between both strategies (standardized minus open) was -4.9% (95% CI [-12.5%; 2.6%]). There were more investigations in the open group than in the standardized group (5371 vs 3759, P < .0001). CONCLUSION: The standardized strategy appears to be an efficient diagnostic approach for the etiologic diagnosis of uveitis, although its noninferiority cannot be proved.

Clinical, histopathologic, and ultrastructural characteristics of BIGH3(TGFBI) amyloid corneal dystrophies are supportive of the existence of a new type of LCD: the LCDi.

PURPOSE: To assess the morphologic differences of three types of lattice corneal dystrophies (LCDs) from histologic, immunohistochemical, and ultrastructural studies. METHODS: Corneas from three patients, one LCD1, one His626Arg-LCD, and one LCD3A were processed for Congo red, betaig-h3(541-564) antibodies immunostaining, and electron transmission microscopy studies. Control tissues were submitted to identical analyses and consisted of one cornea from a patient not having LCD and one skin biopsy from the patient suffering from LCD1. RESULTS: The three corneas displayed birefringent congophilic deposits under polarized light, confirming their amyloid nature. The deposits differed regarding their shape and location in each of the corneas. A strong immunoreactivity for betaig-h3 was shown in the LCD1 and His626Arg-LCD deposits, which was faint for the LCD3A deposits. Ultrastructural analysis confirmed the dissimilarity of the deposits among the different types of LCD. No amyloid deposits were observed in the skin from the LCD1 patient, whereas immunostaining showed the presence of high amounts of betaig-h3. CONCLUSION: Our results show that betaig-h3 is involved in amyloid deposition in all the LCDs included in the study (LCD1, His626Arg-LCD, and LCD3A). These three forms of LCD, clinically different, were also distinguishable histologically, confirming that they belong to distinctive groups of LCDs. The absence of amyloid deposition in skin from the LCD1 patient supports cornea-specific amyloid formation. In light of the present clinical, histologic, and ultrastructural data, His626Arg and related LCDs constitute a separate group of LCD that could be considered as of intermediate type on clinical grounds.

Visual acuity outcome and predictive factors after bevacizumab for central retinal vein occlusion.

PURPOSE: To evaluate the 12-month outcome and predictive factors of visual acuity (VA) changes following bevacizumab therapy for central retinal vein occlusion (CRVO). METHODS: A total of 50 eyes from 50 patients with CRVO were consecutively included in this prospective study. Predictive factors were assessed by comparing baseline characteristics of patients classified into 3 groups: those showing a decrease in VA; those displaying a change in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score between 0 and 15; and those in whom an increase in VA =15 letters was achieved. Baseline variables considered in the analyses of predictive factors were demographic and clinical characteristics. RESULTS: Mean baseline ETDRS letter score was 20±12 and mean macular thickness was 575.1±152.7 µm. Mean final ETDRS letter score improved significantly, reaching 27±20, p=0.04, while mean macular thickness decreased significantly to 391.1±229.6 µm, p<0.001. The predictive factors associated with an increase in VA =15 ETDRS letters were younger age (p=0.002), shorter duration of symptoms before treatment initiation (p=0.001), and a higher visual acuity pretreatment (p=0.004). The frequency of ischemic CRVO and low vision at baseline was higher among nonresponsive patients (p=0.005). CONCLUSIONS: Intravitreal bevacizumab seems to be an effective primary treatment option for macular edema due to CRVO. Its main drawback is that multiple injections are often necessary to maintain visual improvement. Early injections of bevacizumab in young patients in whom VA is relatively preserved leads to a significant improvement in VA. Ischaemic CRVO and poor baseline VA are associated with nonresponse to such therapy.

Ipsilateral uveitis and optic neuritis in multiple sclerosis.

Background. Uveitis is 20 times more frequent in multiple sclerosis (MS) patients than in the general population. Methods. A retrospective study of local multiple sclerosis (n = 700) and uveitis cohorts (n = 450) described the ophthalmological and neurological characteristics of patients with multiple sclerosis and uveitis. Results. Uveitis and multiple sclerosis were associated in seven patients. The time intervals between diagnoses of MS and uveitis ranged from 6 months to 15 years. Analysis of the patients' characteristics revealed that multiple sclerosis was associated with an older age of onset than usually expected, that is, 39 years. Uveitis was bilateral in three cases and mainly posterior (5/10). Five patients presented with acute optic neuritis (two in one eye and three in both eyes). All eyes presenting with acute optic neuritis were also affected by uveitis (P = 0.02), though not simultaneously. Conclusion. The ipsilateral association between optic neuritis and uveitis in this series of patients with multiple sclerosis may suggest a reciprocal potentiation between optic neuritis and uveitis in multiple sclerosis.