Childhood uveitis not associated with juvenile idiopathic arthritis: a national survey of incidence, management and visual outcomes.

AIMS: To estimate the incidence of childhood uveitis not associated with juvenile idiopathic arthritis (JIA) in the United Kingdom. METHODS: Children under 16 years who presented with a new diagnosis of uveitis from November 2014 to October 2015 were identified prospectively through the British and Scottish Ophthalmological Surveillance Unit reporting card system. Incident questionnaires were sent to reporting ophthalmologists at presentation and 12 months. RESULTS: From 1st November 2014 to 31st October 2015, 119 cases were reported. Thirty-nine cases were excluded. The estimated minimum annual incidence of non-JIA uveitis in children younger than 16 years is 0.66 per 100,000 (95% CI 0.52-0.82). Median age at presentation was 10 years. 73% had bilateral uveitis. Median (IQR) BCVA in the worse eye was 0.3 (IQR 0.1-0.66) logMAR. The location of uveitis was: anterior 36%, intermediate 24%, posterior 6.8% and panuveitis 30%. 70% of cases were idiopathic. Most children were started on topical corticosteroids at presentation (86%, n = 51). At presentation, 31% (n = 19) were on started on systemic corticosteroids. At 1 year only 13% (n = 7) remained on corticosteroids, with the majority transitioned to steroid-sparing agents: methotrexate (30.8%, n = 16), mycophenolate (5.8%) and anti-TNF agents 5 (9.6%). At 1 year, 46% had ongoing intraocular inflammation despite treatment. The most common ocular adverse event was raised intraocular pressure (13.5%, n = 7). CONCLUSION: Our study provides the first national population-based data of non-JIA childhood uveitis. Most children remain on treatment at 1 year, but visual acuity improves and none were eligible for sight-impairment registration.

Long-term visual and treatment outcomes of whole-population pre-school visual screening (PSVS) in children: a longitudinal, retrospective, population-based cohort study.

BACKGROUND: This study reports the long-term visual and treatment outcomes in a whole-population, orthoptic-delivered pre-school visual screening (PSVS) programme in Scotland and further examines their associations with socioeconomic backgrounds and home circumstances. METHODS: Retrospective case review was conducted on 430 children who failed PSVS. Outcome measures included best corrected visual acuity (BCVA), severity of amblyopia (mild, moderate and severe), binocular vision (BV) (normal, poor and none), ophthalmic diagnosis and treatment modalities. Parameters at discharge were compared to those at baseline and were measured against the Scottish index of multiple deprivation (SIMD) and Health plan indicator (HPI), which are indices of deprivation and status of home circumstances. RESULTS: The proportion of children with amblyopia reduced from 92.3% (373/404) at baseline to 29.1% (106/364) at discharge (p < 0.001). Eighty percent (291/364) had good BV at discharge compared to 29.2% (118/404) at baseline (p < 0.001). Children from more socioeconomically deprived areas (OR 2.19, 95% CI 1.01-4.30, p = 0.003) or adverse family backgrounds (OR 3.94, 95% CI 1.99-7.74, p = 0.002) were more likely to attend poorly and/or become lost to follow-up. Children from worse home circumstances were five times more likely to have residual amblyopia (OR 5.37, 95% CI 3.29-10.07, p < 0.001) and three times more likely to have poor/no BV (OR 3.41, 95% CI 2.49-4.66, p < 0.001) than those from better home circumstances. CONCLUSIONS: Orthoptic-delivered PSVS is successful at screening and managing amblyopia. Children from homes requiring social care input are less likely to attend and are more likely to have poorer visual outcomes.

The UK Paediatric Ocular Trauma Study 3 (POTS3): clinical features and initial management of injuries.

PURPOSE: Worldwide, as many as 6 million children annually sustain ocular trauma, with up to a quarter of a million children requiring hospitalization. Management of pediatric ocular trauma differs from that in adults, both in terms of initial assessment and acute intervention, with significant variation in practice between different centers. Patterns of healing and long-term outcomes are also very different for children compared to adults. In order to develop effective protocols for management, it is first necessary to understand current trends in presentation and treatment. METHODS: We conducted a prospective, observational study of pediatric ocular trauma presenting to UK-based ophthalmologists over a one-year period; reporting cards were distributed by the British Ophthalmic Surveillance Unit, and clinicians were asked to report cases of acute orbital and ocular trauma in children aged 16 years or less requiring inpatient or day-case admission. A validated, standardized questionnaire was sent to reporting ophthalmologists to collect data on clinical features and initial management of injury. RESULTS: Eighty-six episodes of pediatric ocular trauma were reported. Trauma involving the globe was reported in 66/86 patients (76.7%), of which 40/66 (60.1%) were open-globe. Trauma to the anterior segment was reported in 57/86 (66.3%), and posterior segment in 23/86 patients (26.7%). Twenty-five of 86 (29.1%) patients sustained severe trauma defined as having best-corrected visual acuity worse than 6/60 Snellen (incidence 0.19 per 100,000 population). CONCLUSIONS: There has been no improvement in the incidence or severity of pediatric ocular injury rates over the past 25 years. Eye-care providers must be able to provide the necessary services for assessment and management of severe pediatric ocular trauma in the emergency setting.

The UK Paediatric Ocular Trauma Study 2 (POTS2): demographics and mechanisms of injuries.

PURPOSE: Pediatric ocular trauma is an important cause of visual morbidity worldwide, accounting for up to one-third of all ocular trauma admissions. It has long-term implications for those affected and significant economic consequences for healthcare providers. It has been estimated that 90% of all ocular trauma is preventable. Targeted strategies are required to reduce the incidence and the severity of pediatric ocular trauma; this requires an understanding of the epidemiology and characteristics of these injuries and the children involved. METHODS: Prospective, observational study of pediatric ocular trauma cases presenting to UK-based ophthalmologists over a 1-year period; reporting cards were distributed by the British Ophthalmological Surveillance Unit, and clinicians were asked to report incidents of acute orbital and ocular trauma in children aged ≤16 years requiring inpatient or day-case admission. A validated, standardized questionnaire was sent to reporting ophthalmologists to collect data on the demographics and circumstances of injury. RESULTS: Median age at presentation was 7.7 years, with boys more than twice as likely to be affected than girls (M:F =2.1:1.0). Almost 50% of injuries occurred at home, with 25% occurring in school or nursery. A total of 67% of injuries occurred during play, and 31% involved a sharp implement. CONCLUSION: Pediatric ocular trauma remains an important public health problem. At least three-quarters of all injuries are preventable through measures, including education of children and responsible adults, restricting access to sharp implements, improving adult supervision, and appropriate use of eye protection.

Socioeconomic deprivation and serious ocular trauma in Scotland: a national prospective study.

OBJECTIVE: To identify the population at risk of serious ocular trauma by exploring relationships with socioeconomic factors. DESIGN: National, prospective, population-based, cross-sectional and follow-up study. PARTICIPANTS: Patients with serious ocular trauma requiring hospital admission in Scotland. METHODS: Case definition and ascertainment-cases of serious ocular trauma necessitating admission to hospital under the care of a consultant ophthalmologist were identified using the British Ophthalmological Surveillance Unit reporting scheme. Using the postcode of residence, we assigned a Scottish Index of Multiple Deprivation (SIMD) score, SIMD quintile ( 0%-20% most deprived; 20%-40%, 40%-60%, 60%-80%, 80%-100% least deprived areas), geographical access score as well as the estimated travel time to the nearest general practitioner (GP) practice using either car or public transport for each patient. Population estimates were obtained from the General Register Office for Scotland. MAIN OUTCOME MEASURE: Serious ocular trauma requiring hospital admission. RESULTS: A total of 104 patients (85.6% male) were reported as being admitted with ocular trauma with a median age of 32 years (IQR 24-54). There was a trend for increasing incidence of serious ocular injury with increasing socioeconomic deprivation (p=0.034). Patients from the most deprived areas (SIMD: 0%-20%) were twice as likely to sustain ocular injury compared with those from the least deprived (SIMD: 80%-100%) areas (relative risk: 2.19, 95% CI 1.02 to 4.81). There was no significant difference in the drive/public transport time to GP practices across the SIMD quintiles. CONCLUSIONS: Increasing socioeconomic deprivation was associated with a higher incidence of serious ocular injury. Targeted interventions are needed to address inequality in eye healthcare in deprived areas.

The UK Paediatric Ocular Trauma Study 1 (POTS1): development of a global standardized protocol for prospective data collection in pediatric ocular trauma.

BACKGROUND: Ocular trauma is an important cause of visual morbidity in children worldwide. Pediatric ocular trauma accounts for up to one third of all ocular trauma admissions, with significant economic implications for health care providers. It is estimated that 90% of all ocular trauma is preventable. Development of strategies to reduce the incidence and severity of pediatric ocular trauma requires an understanding of the epidemiology of these injuries and their characteristics. This will enable appropriate targeting of resources toward prevention and allow effective service planning. At present, there is no standardized methodology for the collection of global cross-sectional data in pediatric ocular trauma, and the ability to undertake detailed epidemiological and health-economic analyses is limited. Furthermore, it is difficult to draw international comparisons in incidence, etiology, and outcomes of pediatric ocular trauma due to the range of published reporting criteria. This study describes two novel questionnaires for standardized data collection in pediatric ocular trauma, which can be adopted across a range of health care settings internationally. METHODS: Two standardized data collection questionnaires have been developed from previously reported templates. The first enables collection of demographic and incident data on serious pediatric ocular trauma requiring hospitalization, and the second enables follow-up outcome data collection. Both the questionnaires are designed to collect primarily categorical data in order to increase ease of completion and facilitate quantitative analysis. These questionnaires enable acquisition of standardized data on the incidence, etiology, and outcomes of pediatric ocular trauma. DISCUSSION: These questionnaires enable collection of standardized data and are designed for global use across all health care settings. Through prospective data collection, epidemiological trends can be determined, allowing health care providers to develop collaborative global preventive strategies. Furthermore, the same questionnaires may be used in future studies to draw comparisons with baseline data, allowing assessment of the efficacy of targeted preventative interventions.

Endonasal versus external dacryocystorhinostomy for nasolacrimal duct obstruction.

BACKGROUND: A dacryocystorhinostomy (DCR) procedure aims to restore drainage of tears by bypassing a blockage in the nasolacrimal duct, through the creation of a bony ostium that allows communication between the lacrimal sac and the nasal cavity. It can be performed using endonasal or external approaches. The comparative success rates of these two approaches have not yet been established and this review aims to evaluate the relevant up-to-date research. OBJECTIVES: The primary aim of this review is to compare the success rates of endonasal DCR with that of external DCR. The secondary aim is to compare the complication rates between the two procedures. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2016, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to 22 August 2016), Embase (January 1980 to 22 August 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to 22 August 2016), Web of Science Conference Proceedings Citation Index- Science (CPCI-S) (January 1990 to 22 August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 22 August 2016. We requested or examined relevant conference proceedings for appropriate trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing endonasal and external DCRs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility and extracted data on reported outcomes. We attempted to contact investigators to clarify the methodological quality of the studies. We graded the certainty of the evidence using GRADE. MAIN RESULTS: We included two trials in this review. One trial from Finland compared laser-assisted endonasal DCR with external DCR, and one trial from India compared mechanical endonasal DCR (using punch forceps) with external DCR. The trials were poorly reported and it was difficult to judge the extent to which bias had been avoided.Anatomic success was defined as the demonstration of a patent lacrimal passage on syringing, or endoscopic visualisation of fluorescein dye at the nasal opening of the anastomoses after a period of at least six months following surgery. Subjective success was defined as the resolution of symptoms of watering following surgery after a period of at least six months. Both included trials used anatomic patency demonstrated by irrigation as a measure of anatomic success. Different effects were seen in these two trials (I2 = 76%). People receiving laser-assisted endonasal DCR were less likely to have a successful operation compared with external DCR (63% versus 91%; risk ratio (RR) 0.69, 95% confidence intervals (CI) 0.52 to 0.92; 64 participants). There was little or no difference in success comparing mechanical endonasal DCR and external DCR (90% in both groups; RR 1.00, CI 0.81 to 1.23; 40 participants). We judged this evidence on success to be very low-certainty, downgrading for risk of bias, imprecision and inconsistency. The trial from Finland also assessed subjective improvement in symptoms following surgery. Resolution of symptoms of watering in outdoor conditions was reported by 84% of the participants in the external DCR group and 59% of those in the laser-assisted endonasal DCR group (RR 0.70, CI 0.51 to 0.97; 64 participants, low-certainty evidence).There were no cases of intraoperative bleeding in any participant in the trial that compared laser-assisted endonasal DCR to external DCR. This was in contrast to the trial comparing mechanical endonasal DCR to external DCR in which 45% of participants in both groups experienced intraoperative bleeding (RR 1.00, 95% CI 0.50 to 1.98; 40 participants). We judged this evidence on intraoperative bleeding to be very low-certainty, downgrading for risk of bias, imprecision and inconsistency.There were only two cases of postoperative bleeding, both in the external DCR group (RR 0.33, 95% CI 0.04 to 3.10; participants = 104; studies = 2). There were only two cases of wound infection/gaping, again both in the external DCR group (RR 0.20, CI 0.01 to 3.92; participants = 40; studies = 1). We judged this evidence on complications to be very low-certainty, downgrading one level for risk of bias and two levels for imprecision due to the very low number of cases. AUTHORS' CONCLUSIONS: There is uncertainty as to the relative effects of endonasal and external DCR. Differences in effect seen in the two trials included in this review may be due to variations in the endonasal technique, but may also be due to other differences between the trials. Future larger RCTs are required to further assess the success and complication rates of endonasal and external DCR. Different techniques of endonasal DCR should also be assessed, as the choice of endonasal technique can influence the outcome. Strict outcome criteria should be adopted to assess functional and anatomical outcomes with a minimal follow-up of six months.

Management of patients with Graves' orbitopathy: initial assessment, management outside specialised centres and referral pathways.

Graves' orbitopathy (GO) is uncommon, but responsible for considerable morbidity. A coordinated approach between healthcare professionals is required in order to meet the needs of patients. Early diagnosis can be achieved by a simple clinical assessment. Low-cost effective interventions can be initiated by generalists, which may improve outcomes. Moderate-to-severe GO should be referred to specialised centres. Recommendations for clinical diagnosis, initial management and referral pathways are highlighted.

Impact of socioeconomic deprivation on the development of diabetic retinopathy: a population-based, cross-sectional and longitudinal study over 12 years.

OBJECTIVE: To study the association between socioeconomic deprivation and prevalence of diabetic retinopathy (DR). DESIGN: Population-based, cross-sectional observational study and retrospective longitudinal analysis over 12 years. SETTING: Primary care, East of Scotland. METHODS: Outcome data from DR screening examinations (digital retinal photography) were collected from the Scottish regional diabetes electronic record from inception of database to December 2012. The overall Scottish Index of Multiple Deprivation (SIMD) 2012 score for each patient was obtained using their residential postcode. Multiple binary logistic regression was used to analyse the relationship between overall SIMD score and prevalence of DR, adjusting for other variables: age, gender, glycated haemoglobin, cholesterol levels and duration of disease. PRIMARY OUTCOME: Any retinopathy (R1 and above) in either eye. RESULTS: A total of 1861 patients with type 1 diabetes mellitus (DM) and 18,197 patients with type 2 DM were included in the study. Prevalence of DR in type 1 and type 2 DM were 56.3% and 25.5%, respectively. Increased prevalence of DR in type 1 DM was associated with higher overall SIMD score (p=0.002), with an OR for the most deprived relative to the least deprived of 2.40 (95% CI 1.36 to 4.27). In type 2 DM, the overall SIMD score was not significantly associated with increased prevalence of DR, with an OR for the most deprived relative to the least deprived of 0.85 (95% CI 0.71 to 1.02, p=0.07). CONCLUSIONS: Socioeconomic deprivation is associated with increased prevalence of DR in patients with type 1 DM and this occurs earlier. This highlights the need for targeted interventions to address inequalities in eye healthcare.

Recent trends in glaucoma surgery in Scotland, England and Wales.

OBJECTIVE: To evaluate national trends of trabeculectomy, aqueous shunts and cycloablation performed in Scotland, England and Wales from 1993 to 2012. METHODS: The annual numbers of trabeculectomies and aqueous shunts carried out between 1993 and 2012 were obtained from national Scottish, English and Welsh National Health Service databases. The annual rates of trabeculectomy, aqueous shunts and cycloablation were calculated per 100,000 of the population and analysed in the following age groups: 0-14 years, 15-59 years, over 60 years. RESULTS: The highest annual rate of trabecuelctomy was in 1995, this was followed by a sharp decline and subsequent stable rates since 2000. The total annual rates of aqueous shunts have increased more than sixfold from 2003 to 2012. In the 0-14 years age group from 2003 to 2012 the ratio of trabeculectomy to aqueous shunts has reversed; trabeculectomy rates have decreased while rates of aqueous shunts have increased. From 2003 to 2012, rates of cyclocryotherapy have reduced while rates of photocoagulation to the ciliary body have doubled. CONCLUSIONS: Trabeculectomy is the most commonly performed glaucoma operation. Aqueous shunts are rapidly increasing in the surgical management of glaucoma. During the study period, the ratio of trabeculectomy to aqueous shunts has reversed in the younger age group (0-14 years). Rates of cyclocyrotherapy to the ciliary body have dramatically declined while laser photocoagulation to the ciliary body is gaining wider acceptability.

Diagnosis of Graves' orbitopathy (DiaGO): results of a pilot study to assess the utility of an office tool for practicing endocrinologists.

CONTEXT: In active Graves' orbitopathy (GO), treatment can improve the final cosmetic and visual outcome. Diagnostic delay results in significant morbidity and increases patient dissatisfaction. However, it can be challenging for endocrinologists to recognize GO and decide who should be referred for ophthalmic care. OBJECTIVE: DiaGO, a clinical assessment tool, was developed for use in patients with Graves' disease (GD). The tool is designed to alert clinicians to the possibility of GO and prompt early ophthalmic assessment. DESIGN AND SETTING: A 20-point assessment tool was devised and tested on 104 GD patients: 27 "positive controls" with GO and 77 people with GD attending endocrine clinics over 17 months. Those scoring positively in endocrine clinics were referred for ophthalmic assessment. Both the appropriateness of the referral and subsequent treatment were assessed. RESULTS: Eighty-eight of the 104 patients (85%) were female (mean age, 48.5 y; range, 18-76 y). All 27 "controls" scored positively. Of the 77 people evaluated with GD, 27 (35%) scored above the threshold for referral and GO was confirmed in 24/26 (92%) who attended for specialist ophthalmic assessment. Twelve of these 24 (50%) were offered specific treatment following ophthalmology review. CONCLUSIONS: The timely diagnosis of GO is important because early intervention in active disease can improve prognosis. DiaGO alerts clinicians to the possibility of GO and prompts referral to specialist ophthalmic care. It is quick and easy to use and does not require specialist ophthalmic skills. Overall, half of those referred after use of DiaGO were offered specific treatment, suggesting its use might significantly improve the management of patients.

siRNA silencing of the mutant keratin 12 allele in corneal limbal epithelial cells grown from patients with Meesmann's epithelial corneal dystrophy.

PURPOSE: The aim of this study is to further assess our previously reported keratin 12 (K12)-Leu132Pro specific siRNA in silencing the mutant allele in Meesmann's Epithelial Corneal Dystrophy (MECD) in experimental systems more akin to the in vivo situation through simultaneous expression of both wild-type and mutant alleles. METHODS: Using KRT12 exogenous expression constructs transfected into cells, mutant allele specific knockdown was quantified using pyrosequencing and infrared Western blot analysis, while the silencing mechanism was assessed by a modified rapid amplification of cDNA ends (5'RACE) method. Corneal limbal biopsies taken from patients suffering from MECD were used to establish cultures of MECD corneal limbal epithelial stem cells and the ability of the siRNA to silence the endogenous mutant KRT12 allele was assessed by a combination of pyrosequencing, qPCR, ELISA, and quantitative-fluorescent immunohistochemistry (Q-FIHC). RESULTS: The siRNA displayed a potent and specific knockdown of K12-Leu132Pro at both the mRNA and protein levels with exogenous expression constructs. Analysis by the 5'RACE method confirmed siRNA-mediated cleavage. In the MECD cells, an allele-specific knockdown of 63% of the endogenous mutant allele was observed without effect on wild-type allele expression. CONCLUSIONS: Combined with an effective delivery vehicle this siRNA approach represents a viable treatment option for prevention of the MECD pathology observed in K12-Leu132Pro heterozygous individuals.

Development of allele-specific gene-silencing siRNAs for TGFBI Arg124Cys in lattice corneal dystrophy type I.

PURPOSE: This study aimed to investigate the potency and specificity of short-interfering RNA (siRNA) treatment for TGFBI-Arg124Cys lattice corneal dystrophy type I (LCDI) using exogenous expression constructs in model systems and endogenous gene targeting in an ex vivo model using corneal epithelial cell cultures. METHODS: A panel of 19 TGFBI-Arg124Cys-specific siRNAs were assessed by a dual-luciferase reporter assay. Further assessment using pyrosequencing and qPCR was used to identify the lead siRNA; suppression of mutant TGFBIp expression was confirmed by Western blot and Congo red aggregation assays. An ex vivo model of LCDI was established using limbal biopsies from corneal dystrophy patients harboring the Arg124Cys mutation. Treatment efficiency of the siRNA was assessed for the inhibition of the mutant allele in the primary patient's corneal epithelial cells using pyrosequencing, quantitative PCR (qPCR), and an ELISA. RESULTS: A lead siRNA was identified, and demonstrated to be potent and specific in inhibiting the TGFBI-Arg124Cys mutant allele at the mRNA and protein levels. Besides high allele specificity, siRNA treatment achieved a 44% reduction of the endogenous Arg124Cys allele in an ex vivo model of LCDI. CONCLUSIONS: We have identified a lead siRNA specific to the TGFBI-Arg124Cys mutant allele associated with LCDI. Silencing of exogenous TGFBI was observed at mRNA and protein levels, and in an ex vivo model of LCDI with an efficient suppression of the endogenous mutant allele. This result indicates the potential of siRNA treatment as a personalized medicine approach for the management of heritable TGFBI-associated corneal dystrophies.

Acute-onset diplopia.

PURPOSE: To investigate the clinical features of all patients with acute-onset diplopia presenting to the ophthalmology department. METHODS: The notes of every patient who presented with acute onset (<4-week duration) diplopia to the ophthalmology clinic over a 2-year period were reviewed. Data regarding clinical features, underlying aetiology, past medical history, investigations and outcomes were extracted. RESULTS: One hundred and forty-nine patients presented with 53.7% having an isolated third, fourth or sixth nerve palsy, 10.7% a mechanical cause, 10.1% a dysfunction of higher control, 8.1% decompensation of a pre-existing heterophoria, 6.7% idiopathic, 5.4% causes of monocular diplopia and 5.3% another diagnosis. Neuroradiological investigation identified that <5% of patients had a serious underlying pathology, which required immediate management; 80.5% had a diagnosis and underlying aetiology, which were obvious at presentation based only on clinical information and evaluation. CONCLUSIONS: Acute onset diplopia is an uncommon and challenging presentation for the ophthalmologist to manage. These results demonstrate that the aetiology is commonly identifiable at the first presentation based on clinical evaluation, only a small percentage require urgent radiological investigation and a small minority of cases are likely to have serious emergent pathology.