Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis.

INTRODUCTION: Adalimumab, 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. METHODS: Sarcoidosis 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. RESULTS: Choroidal 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). CONCLUSIONS: Adalimumab 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.

Inflammatory activity assessment by F18 FDG-PET/CT in persistent symptomatic sarcoidosis.

BACKGROUND: Establishing inflammatory activity in sarcoidosis patients with persistent disabling symptoms is important. Whole body F(18)-FDG PET/CT (PET) appeared to be a sensitive method to detect inflammatory activity in newly diagnosed symptomatic sarcoidosis. The aim was to assess the presence of inflammatory activity using PET in sarcoidosis patients with unexplained persistent disabling symptoms and the association between PET findings and serological inflammatory markers. METHODS: Sarcoidosis patients who underwent a PET between June 2005 and June 2010 (n = 89), were retrospectively included. All PET scans were examined and positive findings were classified as thoracic and/or extrathoracic. As serological markers of inflammatory activity angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), and neopterin were considered. RESULTS: In 65/89 (73%) of the studied patients PET was positive, 52 of them (80%) had serological signs of inflammatory activity. In 14/15 patients with a Chest X-ray stage IV PET was positive. In 80% of the PET positive patients extrathoracic inflammatory activity was found. Sensitivity of combined serological inflammatory markers for the presence of inflammatory activity as detected by PET was 80%, specificity 100%, positive predictive value 100%, negative predictive value 65%. CONCLUSIONS: 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.

Raman spectroscopy in ophthalmology: from experimental tool to applications in vivo.

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.

Noninvasive Raman spectroscopic identification of intraocular lens material in the living human eye.

PURPOSE: To develop a safe noninvasive technique for identifying the material of intraocular lenses (IOLs) implanted in patients. SETTING: Center for Biomedical Engineering and the Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas, USA. METHODS: Raman spectroscopy was used to noninvasively identify the type of IOL implanted after previous cataract surgery in 9 eyes of 6 patients who were legally blind as a result of eye disease. Three IOLs were characterized: poly(methyl methacrylate) (PMMA) (n = 5), acrylic (n = 3), and silicone (n = 1). Confocal Raman spectroscopy was used with a laser power of 95 microW and exposure time of 1 second. RESULTS: Distinct spectral peaks associated with each type of IOL were obtained. These included spectra peaks at 2840 cm(-1), 2946 cm(-1), and 3000 cm(-1) for PMMA; 2917 cm(-1), 2939 cm(-1), and 3055 cm(-1) for acrylic; and 2900 cm(-1), 2961 cm(-1), and 3048 cm(-1) for silicone. The procedure was well accepted by patients, and there were no complications. CONCLUSIONS: The specific Raman spectra of the IOLs allowed for noninvasive determination of IOL material with the use of a safe light dose and an exposure time of 1 second.

Identification of intraocular lens materials using confocal Raman spectroscopy.

PURPOSE: To develop and test a noninvasive method to identify intraocular lens (IOL) materials in vitro. SETTING: Center for Biomedical Engineering and the Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, USA. METHODS: A laser confocal Raman spectroscopy system (Conforam) was used for the noninvasive assessment of Raman spectra in the lower and the higher spectral regions (299.1 to 1833.7 cm-1 and 2633.8 to 3819.6 cm-1, respectively) of 4 IOL materials: silicone, poly(methyl methacrylate) (PMMA), acrylic, and hydrogel. RESULTS: Each lens material showed a distinctive spectrum in both the higher and the lower spectral regions. Most materials had unique peaks and a distinct profile using 1 mW of laser power and a 1 second exposure time. All materials still had a unique spectrum in both the higher and the lower region that allowed 1 material to be distinguished from the others. CONCLUSIONS: A Conforam differentiated silicone, PMMA, acrylic, and hydrogel lenses in vitro. Raman spectroscopy using the Conforam may provide a fast, safe, and reliable noninvasive method to gain information about the material of an implanted IOL and the stability of lens materials and their coatings.