Bristol Eye Hospital

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

PURPOSE: To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors. DESIGN: Retrospective database study of electronic medical records (EMRs). PARTICIPANTS: A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites. METHODS: Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded. MAIN OUTCOME MEASURE: Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery. RESULTS: Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57-4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45-9.07), uveitis (RR, 2.88; 95% CI, 1.50-5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56-5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60-5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36-2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12-7.58) and rose proportionately with increasing severity of DR. CONCLUSIONS: Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs.

AIMS: To describe the outcomes of cataract surgery in the United Kingdom. METHODS: Anonymised data on 180 114 eyes from 127 685 patients undergoing cataract surgery between August 2006 and November 2010 were collected prospectively from 28 sites. Outcome measures included intraoperative and postoperative complication rates, and preoperative and postoperative visual acuities. RESULTS: Median age at first eye surgery was 77.1 years, 36.9% cases had ocular co-pathology and 41.0% patients underwent cataract surgery on both eyes. Preoperative visual acuity was 0.30 logMAR or better in 32.0% first eyes and 47.7% second eyes. Postoperative best-measured visual acuity was 0.00 and 0.30 logMAR or better in 50.8 and 94.6% eyes without ocular co-pathology, and 32.5 and 79.9% in eyes with co-pathology. For eyes without co-pathology, postoperative uncorrected distance visual acuity was 0.00 and 0.30 logMAR or better in 27.3 and 80.9% eyes. Posterior capsule rupture or vitreous loss or both occurred in 1.95% cases, and was associated with a 42 times higher risk of retinal detachment surgery within 3 months and an eight times higher risk of endophthalmitis. CONCLUSION: These results provide updated data for the benchmarking of cataract surgery. Visual outcomes, and the rate of posterior capsule rupture or vitreous loss or both appear stable over the past decade.

Vascular endothelial growth factor A (VEGFA; hereafter referred to as VEGF) is a key regulator of physiological and pathological angiogenesis. Two families of VEGF isoforms are generated by alternate splice-site selection in the terminal exon. Proximal splice-site selection (PSS) in exon 8 results in pro-angiogenic VEGFxxx isoforms (xxx is the number of amino acids), whereas distal splice-site selection (DSS) results in anti-angiogenic VEGFxxxb isoforms. To investigate control of PSS and DSS, we investigated the regulation of isoform expression by extracellular growth factor administration and intracellular splicing factors. In primary epithelial cells VEGFxxxb formed the majority of VEGF isoforms (74%). IGF1, and TNFalpha treatment favoured PSS (increasing VEGFxxx) whereas TGFbeta1 favoured DSS, increasing VEGFxxxb levels. TGFbeta1 induced DSS selection was prevented by inhibition of p38 MAPK and the Clk/sty (CDC-like kinase, CLK1) splicing factor kinase family, but not ERK1/2. Clk phosphorylates SR protein splicing factors ASF/SF2, SRp40 and SRp55. To determine whether SR splicing factors alter VEGF splicing, they were overexpressed in epithelial cells, and VEGF isoform production assessed. ASF/SF2, and SRp40 both favoured PSS, whereas SRp55 upregulated VEGFxxxb (DSS) isoforms relative to VEGFxxx. SRp55 knockdown reduced expression of VEGF165b. Moreover, SRp55 bound to a 35 nucleotide region of the 3'UTR immediately downstream of the stop codon in exon 8b. These results identify regulation of splicing by growth and splice factors as a key event in determining the relative pro-versus anti-angiogenic expression of VEGF isoforms, and suggest that p38 MAPK-Clk/sty kinases are responsible for the TGFbeta1-induced DSS selection, and identify SRp55 as a key regulatory splice factor.

PURPOSE: To assess how intraocular lens (IOL) formula choice affects refractive outcomes after cataract surgery using IOLMaster biometry. SETTING: Department of Ophthalmology, Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, United Kingdom. DESIGN: Database study. METHODS: Hypothetical prediction errors were retrospectively calculated on prospectively collected data from electronic medical records using optimized Hoffer Q, Holladay 1, and SRK/T formulas (Sofport AO and Akreos Fit IOLs) across a range of 0.5 mm or 1.0 mm axial length (AL) subgroups. RESULTS: In short eyes, the Hoffer Q had the lowest mean absolute error (MAE) for ALs from 20.00 to 20.99 mm. The Hoffer Q and Holladay 1 had a lower MAE than the SRK/T for ALs from 21.00 to 21.49 mm. There were no statistically significant differences in MAE for ALs from 21.50 to 21.99 mm. In medium eyes, there were no statistically significant differences in MAE for any IOL formula for ALs from 22.00 to 23.49 mm. For ALs from 23.50 to 25.99 mm, there was a trend toward lower MAEs for the Holladay 1, with statistically significant differences in 2 subgroups. In long eyes, the SRK/T had the lowest MAE, with statistically significant differences for ALs of 27.00 mm or longer. CONCLUSIONS: The Hoffer Q performed best for ALs from 20.00 to 20.99 mm, the Hoffer Q and Holladay 1 for ALs from 21.00 to 21.49 mm, and the SRK/T for ALs of 27.00 mm or longer. Using optimized constants, refractive outcomes of 40%, 75%, and 95% within ±0.25 diopter (D), ±0.50 D, and ±1.00 D, respectively, were achievable. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Additional disclosure is found in the footnotes.

OBJECTIVE: To estimate the distribution and predictors of some common visual problems (strabismus, amblyopia, hypermetropia) within a population-based cohort of children at the age of 7 years. METHODS: Children participating in a birth cohort study were examined by orthoptists who carried out cover/uncover, alternate cover, visual acuity and non-cycloplegic refraction tests. Prospectively collected data on potential risk factors were available from the study. RESULTS: Data were available for 7825 seven-year-old children. 2.3% (95% CI 2.0% to 2.7%) had manifest strabismus, 3.6% (95% CI 3.3% to 4.1%) had past/present amblyopia, and 4.8% (95% CI 4.4% to 5.3%) were hypermetropic. Children from the lowest occupational social class background were 1.82 (95% CI 1.03% to 3.23%) times more likely to be hypermetropic than children from the highest social class. Amblyopia (p = 0.089) and convergent strabismus (p = 0.066) also tended to increase as social class decreased. CONCLUSIONS: Although strabismus has decreased in the UK, it and amblyopia remain common problems. Children from less advantaged backgrounds were more at risk of hypermetropia and to a lesser extent of amblyopia and convergent strabismus. Children's eye-care services may need to take account of this socio-economic gradient in prevalence to avoid inequity in access to care.

TOPIC: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. CLINICAL RELEVANCE: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. METHODS: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic review of the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE, CINAHL, SCOPUS, BIOSIS, and Web of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review. A total of 44 globally representative group members met in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. RESULTS: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. CONCLUSIONS: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents.

BACKGROUND/AIMS: Tuberous sclerosis complex (TSC) has retinal and non-retinal ophthalmic manifestations. This study was designed to determine the prevalence of the ophthalmic manifestations and of refractive errors in a population of patients with TSC. METHODS: 179 patients identified were in a prevalence study of TSC in the south of England and 107 of these agreed to full ophthalmic examination which was successful in 100. Ophthalmic examination included examination of the eyelids, cover test, examination of the irides, dilation funduscopy using both direct and indirect ophthalmoscopy, and refraction using retinoscopy. Myopia was defined as a spherical equivalent <-0.5D and hyperopia as a spherical equivalent >+0.5D. RESULTS: Retinal hamartomas were seen in 44 of the 100 patients. The commonest morphological type of hamartoma seen was the flat, translucent lesion in 31 of the 44 patients (70%). The multinodular "mulberry" lesion was seen in 24 of the 44 patients (55%) and the transitional type lesion was seen in four of the 44 patients (9%). Punched out areas of retinal depigmentation were seen in 39 of the 100 patients but only six of 100 controls. 27% of eyes were myopic, 22% were hyperopic, and 27% had astigmatism >0.75D. Of the non-retinal findings, 39 patients had angiofibromas of the eyelids, five had non-paralytic strabismus, and three had colobomas. CONCLUSION: Apart from the higher prevalence of flat retinal hamartomas, the findings of this study compare closely with previous large clinic based series of TSC patients. Refractive findings were similar to previous studies of a similarly aged non-TSC population. This is the first series to document the statistically significant association of punched out chorioretinal depigmentation with TSC and the authors believe that it should be looked for as an aid to diagnosis.

Currently, there is an increasing interest for setting up medical systems that can screen a large number of people for sight threatening diseases, such as diabetic retinopathy. This paper presents a method for automated identification of exudate pathologies in retinopathy images based on computational intelligence techniques. The color retinal images are segmented using fuzzy c-means clustering following some preprocessing steps, i.e., color normalization and contrast enhancement. The entire segmented images establish a dataset of regions. To classify these segmented regions into exudates and nonexudates, a set of initial features such as color, size, edge strength, and texture are extracted. A genetic-based algorithm is used to rank the features and identify the subset that gives the best classification results. The selected feature vectors are then classified using a multilayer neural network classifier. The algorithm was implemented using a large image dataset consisting of 300 manually labeled retinal images, and could identify affected retinal images with 96.0% sensitivity while it recognized 94.6% of the normal images, i.e., the specificity. Moreover, the proposed scheme illustrated an accuracy including 93.5% sensitivity and 92.1% predictivity for identification of retinal exudates at the pixel level.

Purpose Diurnal variation in intraocular pressure (IOP) is well recognized, yet important decisions in glaucoma management are frequently made after 1 or 2 IOP measurements. Twenty-four-hour monitoring of IOP may identify IOP variation and spikes. This study determined the value of 24-hour IOP monitoring in routine clinical practice. Methods Data were acquired retrospectively from case notes of 29 glaucoma patients sequentially admitted for 24-hour IOP monitoring while taking their established antiglaucoma therapy. Results While there was no difference between the mean clinic (office) and mean 24-hour IOP measurements, the peak IOP during 24-hour monitoring was on average 4.9 mm Hg higher than the peak clinic IOP (P <0.0001). In 4 (13.8%) patients, the peak IOP over 24 hours was at least 12 mm Hg higher than the clinic peak. Peak IOP values occurred outside normal office hours in 51.7% of patients. Twenty-four-hour IOP monitoring resulted in a change of clinical management in 23 (79.3%) patients, including 13 (44.8%) who were offered trabeculectomy. Conclusion Twenty-four-hour monitoring of IOP frequently led to a change of glaucoma management by identifying IOP fluctuations and spikes. High IOP and wide diurnal IOP variation are considered major risk factors for glaucoma progression, and standard clinic follow-up evaluations failed to identify these phenomena.

Remarkable improvements in optical coherence tomography (OCT) technology have resulted in highly sophisticated, noninvasive machines allowing detailed and advanced morphological evaluation of all retinal and choroidal layers. Postproduction semiautomated imaging analysis with dedicated public-domain software allows precise quantitative analysis of binarized OCT images. In this regard, the choroidal vascularity index (CVI) is emerging as a new imaging tool for the measurement and analysis of the choroidal vascular system by quantifying both luminal and stromal choroidal components. Numerous reports have been published so far regarding CVI and its potential applications in healthy eyes as well as in the evaluation and management of several chorioretinal diseases. Current literature suggests that CVI has a lesser variability and is influenced by fewer physiologic factors as compared to choroidal thickness. It can be considered a relatively stable parameter for evaluating the changes in the choroidal vasculature. In this review, the principles and the applications of this advanced imaging modality for studying and understanding the contributing role of choroid in retinal and optic nerve diseases are discussed. Potential advances that may allow the widespread adoption of this tool in the routine clinical practice are also presented.

OBJECTIVES: To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration. DESIGN: Prospective, double masked, multicentre, randomised controlled trial. SETTING: Three ophthalmology centres in the United Kingdom. PARTICIPANTS: 131 patients (mean age 81) with wet age related macular degeneration randomised 1:1 to intervention or control. INTERVENTIONS: Intravitreous bevacizumab (1.25 mg, three loading injections at six week intervals followed by further treatment if required at six week intervals) or standard treatment available at the start of the trial (photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration, or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration). PRIMARY OUTCOME: proportion of patients gaining >or=15 letters of visual acuity at one year (54 weeks). SECONDARY OUTCOMES: proportion of patients with stable vision and mean change in visual acuity. RESULTS: Of the 131 patients enrolled in the trial, five patients did not complete the study because of adverse events, loss to follow-up, or death. In the bevacizumab group, 21 (32%) patients gained 15 or more letters from baseline visual acuity compared with two (3%) in the standard care group (P<0.001); the estimated adjusted odds ratio was 18.1 (95% confidence interval 3.6 to 91.2) and the number needed to treat was 4 (3 to 6). In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91% (59) v 67% (44) in standard care group; P<0.001). Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the standard care group (P<0.001), and the initial improvement at week 18 (plus 6.6 letters) was sustained to week 54. Among 65 patients treated with bevacizumab, there were no cases of endophthalmitis or serious uveitis related to the intervention. All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over standard care. CONCLUSIONS: Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to standard care (pegaptanib sodium, verteporfin, sham), with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 54 weeks. Trial registration number Current controlled trials ISRCTN83325075.

PURPOSE: To compare the accuracy of new/updated methods of intraocular lens (IOL) power calculation (Kane, Hill-RBF 2.0, and Holladay 2 with new axial length adjustment) with that of established methods (Barrett Universal II, Olsen, Haigis, Holladay 1, Hoffer Q, and SRK/T). SETTING: Bristol Eye Hospital, University Hospitals Bristol National Health Service, Foundation Trust, Bristol, UK. DESIGN: Retrospective consecutive case series. METHODS: Data from patients having uneventful cataract surgery with the insertion of 1 of 4 IOL types were included. Optimized IOL constants were used to calculate the predicted refraction of each formula for each patient. This was compared with the actual refractive outcome to give the prediction error. A subgroup analysis occurred based on the axial length and IOL type. RESULTS: The study included 10 930 eyes of 10 930 patients with the Kane formula having the lowest mean absolute prediction error (MAE), which was statistically significant (P < .001 in all cases) followed by the Hill 2.0, Olsen, Holladay 2, Barrett Universal 2, Holladay 1, SRK/T, Haigis, and Hoffer Q formula. The percentage of eyes predicted within ±0.5 D was Kane, 72%; Hill 2.0, 71.2%; Olsen, 70.6%; Holladay 2, 71%; Barrett 2, 70.7%; SRK/T, 69.1%; Haigis, 69%; and Hoffer Q, 68.1%. The Kane formula had the lowest MAE for short, medium, and long axial length subgroups and for each IOL type assessed. The updated versions of the Holladay 2 and Hill 2.0 formulas have resulted in improved accuracy. CONCLUSIONS: Overall and in each axial length subgroup, the Kane formula was more accurate than the other formulas.

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.

BACKGROUND: Few papers have addressed the psychological impact of strabismus in adults, with none comparing preoperative and postoperative data using standardised questionnaires relating surgical results and psychosocial outcomes. METHODS: 46 participants were seen at their 6 week preoperative and 3 month postoperative appointments. Standardised measures of anxiety and depression (Hospital Anxiety and Depression Scale), social anxiety (Derriford Appearance Scale), and quality of life (WHOQoLBref) were completed. RESULTS: Preoperatively, levels of depression were comparable to relevant population norms; however, levels of general anxiety were slightly raised and levels of social anxiety and social avoidance were significantly poorer than population norms. Surgery resulted in significant improvements in psychosocial adjustment with improvements on all study variables for the participant group as a whole. The non-diplopic group made more significant gains than the diplopic group. Approximately one third of study measures were significantly correlated with the objective measure of eye misalignment preoperatively dropping to only one variable postoperatively. Calculations involving the subjective measure of eye misalignment and study variables showed the opposite pattern with five variables achieving significance postoperatively. There were no clear sex or age effects apparent in the data. CONCLUSION: Strabismus surgery offers significant improvements to psychological and physical functioning.

Sexual violence against children represents a major public health and social welfare problem within UK society affecting 16% of under 16s to 2m children and young people. It is under identified and under reported. Better understanding of the impact on individuals and families by commissioners, health and social care providers only goes part way to resolving the current problems. It is only by recognising the range of presentations, symptoms and the variety of settings in which the presence and impact of sexual violence might reveal itself that statutory and voluntary services can hope to respond appropriately to the needs of individuals. It is the responsibility of individual professionals and local services to ensure that the individual needs of people are met at the right time, by the right people, in the most sensitive way. This paper uses recent evidence relating to prevalence, incidence and the impact of sexual violence against children. In particular it identifies the ways in which the NHS can effectively respond to the physical and psychological needs of children young people and their families to ensure that health services are age appropriate, timely, provided in an environment which is supportive and by knowledgeable staff.

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders.

AIM: On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism. METHODS: Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991. RESULTS: Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection. CONCLUSIONS: While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.

PURPOSE: To investigate whether wearing glasses, having manifest strabismus, or having a history of wearing an eye patch predisposes preadolescent children to being victimized more frequently at school and whether the impact may be different on boys than on girls. METHODS: Data were examined on 6536 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) based in the United Kingdom. At 7.5 years, the children undertook a detailed eye examination by orthoptists, including a cover test and visual acuity assessment. At 8.5 years, trained psychologists assessed the children's bullying involvement as either victim or perpetrator for overt and relational bullying, in a standard interview. RESULTS: Children currently wearing glasses or with a history of wearing eye patches were 35% to 37% more likely to be victims of physical or verbal bullying, even after adjustment for social class and maternal education. No interactions were found between sex and visual problems in the prediction of bullying. CONCLUSIONS: For those children who require glasses, opticians should be aware of the risks of bullying, and strategies should be developed and discussed that help reduce their vulnerability.