Validation of a fornix depth measurer: a putative tool for the assessment of progressive cicatrising conjunctivitis

Background/aims Documentation of conjunctival forniceal foreshortening in cases of progressive cicatrising conjunctivitis (PCC) is important in ascertaining disease stage and progression. Lower fornix shortening is often documented subjectively or semi-objectively, whereas upper forniceal obliteration is seldom quantified. Although tools such as fornix depth measurers (FDMs) have been described, their designs limit upper fornix measurement. The purpose of this study was to custom-design a FDM to evaluate the upper fornix and to assess variability in gauging fornix depth. \ud \ud Methods A polymethylmethacrylate FDM was constructed using industry-standard jewellery computer software and machinery. Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland–Altman plots. \ud \ud Results Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (±2SD) of −15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, ±1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between −2 and + 3 mm. \ud \ud Conclusions This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring

A qualitative exploration of physical, mental and ocular fatigue in patients with primary Sjögren's Syndrome

Introduction Primary Sjögren's Syndrome (pSS) affects exocrine glands such as those producing the tear film, leading to dry and painful eyes, but is also associated with fatigue. The experience of fatigue in pSS, and its relationship with sicca symptoms, is poorly understood. Methods Twenty people diagnosed with pSS were recruited to participate in a semi-structured qualitative interview about their symptoms experience. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Results People with pSS described physical tiredness, mental fatigue and ocular fatigue. Mental fatigue was characterised by difficulties in attention, particularly, the ability to follow conversations and short-term memory problems. Participants linked their experience of fatigue to feeling of depression, frustration, irritation and anxiety, and therefore, fatigue was suggested to have had a large impact on their psychological well-being. People with pSS also described a range of ocular symptoms including pain, dryness, and itching, which were compounded by fatigue. For some, eye fatigue was pervasive, and daily activities involving the eyes such as reading, using the computer and driving were impaired. In some cases, the level of ocular discomfort was so severe it prevented sleep, which in turn impacted on general fatigue levels. Conclusions People with pSS experience fatigue in a range of ways; physical, mental and ocular fatigue were described. Fatigue was suggested to exacerbate other ocular symptoms, posed serious physical limitations and caused psychological distress. Further research into the nature of fatigue and ocular symptoms in pSS is required

Elevation of conjunctival epithelial CD45INTCD11b⁺CD16⁺CD14⁻ neutrophils in ocular Stevens-Johnson syndrome and toxic epidermal necrolysis

PURPOSE. Ocular complications related to Stevens-Johnson Syndrome (SJS)–Toxic Epidermal Necrolysis (TEN) may persist and progress after resolution of systemic disease. This is thought to be related in part to persistent ocular innate-immune signaling. In this study, our aim was to characterize infiltrative conjunctival cellular profiles during acute (<12 months) and chronic (>12 months) disease. METHODS. Consecutive patients presenting with SJS-TEN over a 12-month period were followed for 1 year. Detailed clinical examination and conjunctival impression cell recovery was analyzed by flow cytometry for the presence of intraepithelial leukocytes and compared with healthy controls (n = 21). RESULTS. Ten patients were recruited of whom six had acute disease and five were classified as TEN (SCORTEN = 1, n = 4). Conjunctival inflammation was graded as absent/mild in a total of nine patients; but despite this, evidence of fornix shrinkage was observed in nine subjects. This inversely correlated with disease duration (P < 0.05). A reduction in percentage of CD8αβ(+) T cells compared with controls (80% vs. 57%; P < 0.01) was associated with a corresponding increase in the number/percentage of CD45(INT)CD11b(+)CD16(+)CD14(−) neutrophils (186 vs. 3.4, P < 0.01, 31% vs. 0.8%, P < 0.001). Neutrophils inversely correlated with disease duration (r = −0.71, P = 0.03), yet there was no absolute change in the CD8αβ(+) or neutrophil populations during the study period (P = 1.0). CONCLUSIONS. These data highlight that a neutrophilic infiltrate is present in mildly inflamed or clinically quiescent conjunctival mucosa in patients with ocular SJS-TEN, where neutrophil numbers inversely correlate with disease duration. Neutrophil persistence endorses the hypothesis of an unresolved innate-inflammatory process that might account for disease progression

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

Cytokine production and antigen recognition by human mucosal homing conjunctival effector memory CD8+ T cells

PURPOSE. Conjunctival epithelial T cells are dominated by CD3(+)CD56-TCRαβ(+)CD8αβ(+) lymphocytes. In this study we explored the antigen experience status, mucosal homing phenotype, cytokine expression, and viral antigen recognition of conjunctival epithelial CD8(+) T cells from healthy individuals. METHODS. Following ocular surface impression cytology, conjunctival cells were recovered by gentle agitation and analyzed by flow cytometry for cell surface markers, cytokine production (stimulated by phorbol 12-myristate 13-acetate [PMA]/ionomycin), and Epstein-Barr virus (EBV)/cytomegalovirus (CMV) immunodominant epitope recognition using major histocompatibility complex (MHC) class I peptide tetramers. RESULTS. In contrast to peripheral blood, conjunctival epithelial CD8(+) T cells were dominantly CD45RA(−)CCR7(−) effector memory cells, and the vast majority expressed the mucosal homing integrin αEβ7. Conjunctival memory CD8(+) T cells maintained effector functions with the ability to secrete IFN-γ and expression of Granzyme B, although they expressed significantly reduced amounts per cell compared to peripheral blood T cells. Interestingly, herpetic virus-specific CD8(+) T cells recognizing epitopes derived from EBV and CMV could be detected in the conjunctival cells of healthy virus carriers, although they were generally at lower frequencies than in the peripheral blood of the same donor. Virus-specific conjunctival CD8(+) T cells were dominated by CD45RA(−)CCR7(−) effector memory cells that expressed αEβ7. CONCLUSIONS. These data demonstrate that the majority of conjunctival epithelial CD8(+) T cells are mucosal homing αEβ7(+) effector memory T cells, which can recognize viral epitopes and are capable of secreting Granzyme B and IFN-γ

Efficacy of sub-Tenon's block using an equal volume of local anaesthetic administered either as a single or as divided doses. A randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Sub-Tenon's anaesthetic is effective and reliable in producing both akinesia and anaesthesia for cataract surgery. Our clinical experience indicates that it is sometimes necessary when absolute akinesia is required during surgery to augment the block with 1–2 ml of local anaesthetic. Hypothesis was that after first injection some of the volume injected may spill out and before second injection the effect of hyaluronidase has taken place and second volume injectate will have desired effect.</p> <p>Methods</p> <p>A prospective, randomised, control trial in which patients were randomly allocated to one of two groups. In group 1, single injection of 5 ml of local anaesthetic was injected. In group 2, 3 ml of the same anaesthetic solution was injected followed by application of gentle orbital pressure for 2 minutes. A further 2 ml of the same anaesthetic solution was injected through the same conjunctival incision. Measurement of movement in four quadrants of eye was done by the surgeon at 3 and 6 minutes. Intraocular pressure, chemosis, and subconjuctival haemorrhage were also measured.</p> <p>Results</p> <p>Significant differences at 3 minutes between groups for overall movement, medial, superior, and lateral quadrants occurred. At 6 minutes no significant group differences emerged for the overall movement or for any of four quadrants.</p> <p>Conclusion</p> <p>Single injection of local anaesthesia for sub-Tenon's block with mixture of lignocaine with adrenaline, bupivacaine and hyaluronidase was found to be superior to provide akinesia of ocular muscles compared to divided dose given by two injections. No difference in groups in terms of haemorrhage, chemosis, patient's satisfaction and intraocular pressure was found.</p> <p>Trial registration</p> <p>Trial registration no-ISRCTN73431052</p

The TRACTISS protocol: a randomised double blind placebo controlled clinical trial of anti-B-cell therapy in patients with primary Sjögren's Syndrome.

Background: Primary Sjögren's Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 - 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes. Methods/design: TRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition. Discussion: The TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity. Trial registration: UKCRN Portfolio ID: 9809 ISRCTN65360827

Implementation of a suite of components for Software Defined Radio using an SCA-compliant framework

The aim of this work is to introduce Software Defined Radio (SDR) technology, present an open source SCA-compliant framework whose name is Redhawk, which derives from the OSSIE project and describes an implementation example of some processing instances. Since in SDR applications it is necessary to run the same software on different hardware, portability becomes the main important aspect in the development of software radio applica- tions. The use of a SCA-compliant framework solves this issue making hardware transparent to the programmer and reducing time and costs of code development. This aspect can be exploited for prototyping applications quickly without the need of a spe- cific hardware or testing new standards and protocols. We will introduce some basic concepts of SDR, of the SCA architecture, based on CORBA, and Redhawk. We will then talk about of the implementation of a suite of components, writ- ten by using Redhawk IDE and C++ programming language. These will be tied together to form an application called waveform. We will also present the results obtained by enforcing a certain level of parallelism in our algorithm to speed up computation in Redhawk components and boost performances against a more simpler non concurrent implementation of the same algorithms