Biologic agents in the management of inflammatory eye diseases

Biologics are a new class of drugs that comprise recombinant cytokines and monoclonal antibodies directed against selected cell-surface markers. They include the tumor necrosis factor-α inhibitors infliximab, etanercept, and adalimumab; the antilymphocyte drugs rituximab and alemtuzumab; the interleukin-2 receptor blocker daclizumab; and recombinant interferon-α. This article reviews the rationale and current evidence for their use in uveitis, scleritis, and orbital inflammation.     

Orbital inflammatory disease

OBJECTIVES: To familiarize rheumatologists and internists with the signs, symptoms, and management of orbital inflammatory disease (OID). METHODS: A comprehensive literature review related to OID was performed and reported from the perspectives of rheumatology, ophthalmology, and radiology. RESULTS: OID is a general term encompassing inflammatory diseases that affect some or all of the structures contained within the orbit external to the globe. Orbital involvement as a part of the initial symptom complex is not uncommon for systemic diseases such as Graves' disease, Wegener's granulomatosis, and sarcoidosis. The management of these and other causes of OID, such as idiopathic orbital inflammation (formerly known as "orbital pseudotumor"), orbital myositis, and Tolosa-Hunt syndrome frequently involves systemic immunosuppression. Before immunosuppression is considered, however, infectious and malignant causes of inflammation must be ruled out. DISCUSSION: Rheumatologists should be familiar with the differential diagnosis of OID and often need to assist colleagues in ophthalmology and internal medicine with the management of this group of diseases.     

Inflammatory complications of CGRP monoclonal antibodies: a case series

BackgroundCalcitonin gene-related peptide (CGRP) is expressed throughout the body and is a known mediator of migraine, exerting this biological effect through activation of trigeminovascular, meningeal and associated neuronal pathways located in close proximity to the central nervous system. Monoclonal antibodies (mAb) targeting the CGRP pathway are an effective new preventive treatment for migraine, with a generally favourable adverse event profile. Pre-clinical evidence supports an anti-inflammatory/immunoregulatory role for CGRP in other organ systems, and therefore inhibition of the normal action of this peptide may promote a pro-inflammatory response.CasesWe present a case series of eight patients with new or significantly worsened inflammatory pathology in close temporal association with the commencement of CGRP mAb therapy.ConclusionThis case series provides novel insights on the potential molecular mechanisms and side-effects of CGRP antagonism in migraine and supports clinical vigilance in patient care going forward.     

Impact of cataract surgery on quality of life in patients with early age-related macular degeneration.

PURPOSE: To investigate if cataract surgery improves overall and specific areas of quality of life (QoL) in patients with early age-related macular degeneration (AMD) using the impact of vision impairment (IVI) questionnaire. METHODS: Patients with visually significant cataract and early AMD, who were being considered for cataract surgery in the study eye, were recruited. Eligible patients were randomized to either "early surgery" or "standard surgery" (standard cataract surgery waiting time of 6 months) groups. The IVI, sociodemographic, and clinical data were collected. Rasch analysis was used to estimate QoL person measures at baseline and follow-up. The data were analyzed using repeated measures ANOVA. Effect sizes were calculated using Cohen's d coefficient. RESULTS: Fifty six patients (mean age = 78.5 years and visual acuity = 6/15) had one eye randomly allocated to either the early surgery (n = 29) or standard surgery (n = 27) groups. At follow-up, significant interaction effects were found for the overall IVI score [F(1,54) = 17.7; p < 0.001], the emotional well-being [F(1,54) = 13.4; p = 0.001], mobility and independence [F(1,54) = 13.4; p = 0.001], and reading and accessing information subscales [F(1,54) = 13.1; p = 0.001]. The standard surgery group systematically recorded worse scores at 6 months on all QoL measures whereas the early surgery group recorded significant gains (p < 0.001; Cohen's d = 0.66 to 0.91) on all of them. Visual acuity in the study eye significantly improved in the early surgery group only (Cohen's d = 1.1; p < 0.05) and improvement in log MAR lines read was identified as the single independent predictor of enhanced QoL explaining between 26 and 34% of the variance in the IVI scores. CONCLUSIONS: Cataract surgery is justified in patients with early AMD. It brings significant improvements in visual acuity, aspects of daily living, and overall QoL.     

Changes in F-actin organization induced by hard metal particle exposure in rat pulmonary epithelial cells using laser scanning confocal microscopy

Chronic inhalation of hard metal (WC-Co) particles causes alveolitis and the eventual development of pulmonary fibrosis. The initial inflammatory response includes a change in the alveolar epithelial cell-capillary barrier, which has been shown to be regulated by the state of assembly and organization of the actin cytoskeletal network. The objective of this study was to evaluate the effect WC-Co particles have on F-actin organization of lung epithelial cells in an in vitro culture system. Rat lung epithelial (L2) cells were exposed to 5, 25, and 100 microg/mL of WC-Co particles, as well as the individual components (Co and WC) of the hard metal mixture particles for 24 h. The effect on F-actin organization was visualized by laser scanning confocal microscopy (LSCM) following Bodipy-Phallacidin staining. Minimal changes in the F-actin microfilaments of L2 cells were observed by LSCM after exposure to WC and WC-Co at 5 and 25 microg/mL, while at 100 microg/mL, there was a noticeable disruption in the uniform distribution of L2 cell F-actin microfilaments. After exposure to Co, a dose-dependent change in the F-actin organization of the L2 cells was observed. Little change in F-actin assembly was observed after treatment with 5 microg/mL of Co (the concentration equivalent to the 5% amount of Co commonly present in 100 microg/mL of the WC-Co sample mixture). However, at 100 microg/mL of Co, the microfilaments aggregated into homogeneous masses within the cells, and a significant loss in the organization of L2 F-actin was observed. These dramatic alterations in F-actin organization seen after exposure to the higher doses of Co were attributed to an increase in L2 cell injury as measured by lactate dehydrogenase and trypan blue exclusion. We conclude the pulmonary response evoked in the lung by inhalation of high levels of WC-Co particles is unlikely due to alterations in the F-actin microfilaments of lung-epithelial cells.