IMPORTANCE The best treatment option for primary vitreoretinal lymphoma (PVRL) without signs of central nervous system lymphoma (CNSL) involvement determined on magnetic resonance imaging or in cerebrospinal fluid is unknown. OBJECTIVE To evaluate the outcomes of treatment regimens used for PVRL in the prevention of subsequent CNSL. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted at 17 referral ophthalmologic centers in Europe. We reviewed clinical, laboratory, and imaging data on 78 patients with PVRL who did not have CNSL on presentation between January 1, 1991, and December 31, 2012, with a focus on the incidence of CNS manifestations during the follow-up period. INTERVENTIONS The term extensive treatment was used for various combinations of systemic and intrathecal chemotherapy, whole-brain radiotherapy, and peripheral blood stem cell transplantation. Therapy to prevent CNSL included ocular radiotherapy and/or ocular chemotherapy (group A, 31 patients), extensive systemic treatment (group B, 21 patients), and a combination of ocular and extensive treatment (group C, 23 patients); 3 patients did not receive treatment. A total of 40 patients received systemic chemotherapy. MAIN OUTCOMES AND MEASURES Development of CNSL following the diagnosis of PVRL relative to the use or nonuse of systemic chemotherapy and other treatment regimens. RESULTS Overall, CNSL developed in 28 of 78 patients (36%) at a median follow-up of 49 months. Specifically, CNSL developed in 10 of 31 (32%) in group A, 9 of 21 (43%) in group B, and 9 of 23 (39%) in group C. The 5-year cumulative survival rate was lower in patients with CNSL (35% [95% CI, 50% to 86%]) than in patients without CNSL (68% [95% CI, 19% to 51%]; P = .003) and was similar among all treatment groups (P = .10). Adverse systemic effects occurred in 9 of 40 (23%) patients receiving systemic chemotherapy; the most common of these effects was acute renal failure. CONCLUSIONS AND RELEVANCE In the present series of patients with isolated PVRL, the use of systemic chemotherapy was not proven to prevent CNSL and was associated with more severe adverse effects compared with local treatment.

The majority of sarcoidosis patients with persistent disabling symptoms, even those with radiological stage IV, had PET positive findings with remarkably 80% extrathoracic lesions. In 20% PET was positive without signs of serological inflammatory activity. PET appeared to be of additional value to assess inflammatory activity in patients with persistent symptoms in the absence of signs of serological inflammatory activity and to detect extrathoracic lesions.

IntroductionAdalimumab, a humanized monoclonal antibody targeted against TNF-α, has proved to be successful in the treatment of uveitis. Another anti-TNF-α agent, i.e., infliximab, has been reported of benefit in the treatment of refractory sarcoidosis. The aim of this prospective case series was to evaluate the effect of adalimumab on intraocular inflammatory signs and other relevant clinical manifestations (lung function, serological inflammatory parameters, and fatigue) of sarcoidosis.MethodsSarcoidosis patients with refractory posterior uveitis (n = 26, 17 females, 41 eyes in total) were systematically followed for 12 months after initiation of adalimumab 40 mg sc once a week. Inclusion criteria were non-responsiveness to prednisone and methotrexate (MTX) or intolerance to these drugs. Adjunctive therapy with prednisone and MTX was tapered during treatment with adalimumab. Localization and improvement, stabilization or deterioration of intraocular inflammatory signs was scored. Pulmonary function- and laboratory testing were performed and Fatigue Assessment Scale was completed. Results at baseline, 6 months, and 12 months were compared.ResultsChoroidal involvement resolved in 10/15 patients, five had partial improvement; vasculitis resolved in 1/1 patient; papillitis resolved in 7/8 patients, one had partial response; macular edema resolved in 5/8 patients, three had partial response; vitreous cleared completely in 5/5 patients. Overall outcome regarding intraocular inflammatory signs showed improvement in 22 patients (85%) and stabilization in four patients (15%). At 12 months, no recurrences were reported in those successfully treated. Laboratory parameters of inflammatory activity (C-reactive protein; serum angiotensin-converting enzyme and soluble interleukin-2 Receptor) improved (p < 0.01). Moreover, fatigue improved in 14/21 (67%) of the patients suffering from fatigue and the diffusion capacity for carbon monoxide (DLCO) improved in 7/8 (88%) of patients with a decreased DLCO (p < 0.01). The dosage of both prednisone and MTX could be tapered down significantly (p < 0.01 and p < 0.05, respectively).ConclusionsAdalimumab appeared successful in sarcoidosis patients with refractory chronic non-infectious uveitis showing improvement in intraocular inflammatory signs as well as in other relevant clinical indicators of disease activity. Future randomized studies are needed to determine the optimal dosage, dose interval and duration of therapy in refractory multisystemic sarcoidosis.

Raman spectroscopy is a highly specific technique for the identification of molecules by way of the associated characteristic spectra. The aim of this feasibility study is to assess the combination of the multivariate calibration technique of Partial Least-Squares with Raman spectroscopy for the estimation of glucose, lactic acid, and urea concentrations in the presence of each other in a water substrate. The instrument is a CCD-based Raman spectrometer utilizing the 514.5 nm argon laser line. The estimates for the analyte concentrations yielded a standard deviation of concentration residuals of 20.71 mg/dL for glucose, 12.92 mg/dL for lactic acid, and 19.07 mg/dL for urea.

Responsiveness to tumour necrosis factor (TNF) inhibitors has been associated with the TNF-a G-308A polymorphism in rheumatoid arthritis. The aim of this study was to examine the association between the presence of this polymorphism and the response to TNF inhibitors in patients with refractory sarcoidosis.Patients (n5111) who started TNF-inhibitor treatment (76 infliximab, 35 adalimumab) were followed for at least 1 year. The main symptoms in these patients were fatigue (n5100, 90.1%), small fibre neuropathy (n591, 82.0%), pulmonary involvement (n569, 62.2%), and/or uveitis (n531, 27.9%). Patients were additionally genotyped for the presence of the TNF-a G-308A polymorphism. Treatment response was assessed using clinical outcome measures and questionnaires.Three-quarters (n583, 74.8%) of the patients responded well. Of the patients without the variant A-allele 93.6% (73 out of 78, p,0.001) improved, while 30.3% (10 out of 33) of variant A-allele carriers responded favourably to TNF inhibitors. For patients with the GG-genotype, the probability of improving compared with remaining stable or deteriorating was three times higher (risk ratio 3.09, 95% CI 1. 84-5.20).Sarcoidosis patients without the TNF-a -308A variant allele (GG-genotype) had a three-fold higher response to TNF inhibitors (adalimumab or infliximab). Further research is needed to evaluate the value of genotyping for the TNF-a G-308A polymorphism in order to tailor TNF-inhibitor treatment. @ERSpublications TNF-a G-308A polymorphism predicts TNF-inhibitor response in refractory sarcoidosis: a step to personalised medicine?

Raman spectroscopy is a qualitative and quantitative optical technique for determining the molecular composition of matter. Improvements in spectroscopic instruments, especially the modality to detect low light level signals extended the Raman technique to biomedical applications, even in delicate structures like the eye. The purpose of this paper was to make an inventory of performed applications of Raman spectroscopy in biomedical science and especially in ophthalmology. A literature search was done using Medline, Current Contents, a patent server on the Internet, and references found in articles and patents. This search revealed a variety of Raman techniques and applications in biomedical research, and an increasing flow of articles starting in the late 1970s on Raman spectroscopy in ophthalmology. This increase in literature about Raman spectroscopy in ophthalmology feeds the expectation that this valuable technique will be introduced in the future into clinical practice.

Individual concentrations of glucose, lactic acid, and urea down to 0.1 wt % have been investigated in aqueous solutions by the Raman scattering technique. These measurements have been conducted with three different laser excitation wavelengths at 514.5, 632.8, and 751.8 nm in conjunction with a single-grating spectrometer and a liquid nitrogen-cooled charge-coupled device (CCD). Rabbit and human aqueous humor specimens have also been studied by this method. In addition to a water background, the large fluorescence structure in the Raman spectra resulting from these aqueous humor specimens has been subtracted out by being fitted to a first-degree polynomial. Raman peaks similar to the stretching vibrations of methylene and methyl groups associated with glucose and lactate, respectively, were observed in the human specimens within the region from 2800 to 3050 cm−1. Similar structure was observed from the rabbit specimens. In addition, a Raman peak, indicative of the carbon-nitrogen stretching mode of urea and various amino acids, was observed at 1006 cm−1 in all aqueous humor specimens. However, some of the Raman peaks in the rabbit specimens may have resulted from the euthanasia process.

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