Search

Introduction: The diagnosis of neovascular age-related macular degeneration (nAMD), the leading cause of visual impairment in the developed world, relies on the interpretation of various imaging tests of the retina. These include invasive angiographic methods, such as Fundus Fluorescein Angiography (FFA) and, on occasion, Indocyanine-Green Angiography (ICGA). Newer, non-invasive imaging modalities, predominately Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), have drastically transformed the diagnostic approach to nAMD. The aim of this study is to undertake a comprehensive diagnostic accuracy assessment of the various imaging modalities used in clinical practice for the diagnosis of nAMD (OCT, OCTA, FFA and, when a variant of nAMD called Polypoidal Choroidal Vasculopathy is suspected, ICGA) both alone and in various combinations., Methods and Analysis: This is a non-inferiority, prospective, randomised diagnostic accuracy study of 1067 participants. Participants are patients with clinical features consistent with nAMD who present to a National Health Service secondary care ophthalmology unit in the UK. Patients will undergo OCT as per standard practice and those with suspicious features of nAMD on OCT will be approached for participation in the study. Patients who agree to take part will also undergo both OCTA and FFA (and ICGA if indicated). Interpretation of the imaging tests will be undertaken by clinicians at recruitment sites. A randomised design was selected to avoid bias from consecutive review of all imaging tests by the same clinician. The primary outcome of the study will be the difference in sensitivity and specificity between OCT+OCTA and OCT+FFA (±ICGA) for nAMD detection as interpreted by clinicians at recruitment sites., Ethics and Dissemination: The study has been approved by the South Central-Oxford B Research Ethics Committee with reference number 21/SC/0412.Dissemination of study results will involve peer-review publications, presentations at major national and international scientific conferences., Trial Registration Number: ISRCTN18313457., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack)., Design: Diagnostic Test Accuracy study., Setting: Six UK hospitals., Methods: The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges., Results: Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers., Conclusions: Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose., Trial Registration Number: ISRCTN79058224., Competing Interests: Competing interests: REH reports attendance at Roche Digital Health Advisory Meeting July 2019. She also received partial PhD Studentship funding from Okko Health 2021 for home monitoring of Diabetic Retinopathy. SS reports grants from Boehringer Ingleheim, receiving consulting fees from Boehringer Ingleheim, Novartis, Apellis, Bayer, Oculis, Oxurion, Roche, and Biogen. She also received payment or honoraria from Boehringer Ingleheim and Bayer, support for attending meetings from Bayer and participation in an advisory board with Bayer. She is also a Macular Society Trustee (unpaid). TP reports grants from Boehringer Ingelheim and Novartis; receiving consulting fees from Boehringer Ingelheim, Novartis, Apellis, Bayer, Oxurion, Roche, and Sandoz. She also received payment or honoraria (speakers fee/and/or advisory board) from Boehringer Ingelheim, Bayer, Roche, Apellis, Sandoz, Heidelberg, Zeiss, Optos. PCK reports software support from Vital Art and Science who produced the My Vision Track App. AL reports receiving consulting fees from and owning stock or stock options of Gyroscope Therapeutics. RW, SRO'C, EAG, EW, CT, BJLB, CAR and BCR have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Adalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care., Methods and Analysis: The ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted., Ethics and Dissemination: The trial received Research Ethics Committee (REC) approval from South Central - Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available., Trial Registration: ISRCTN31474800. Registered 14 April 2020., Competing Interests: Competing interests: CAR received support from the National Institute for Health and Care Research (NIHR) for the project associated with this manuscript, which was paid to the University of Bristol. KP, MH, LC, MPYL, SB and BCR received support from the NIHR for the project associated with this manuscript, which contributed to their salary. SW, TP, SMS, NAVB and AD received support from the NIHR for the project associated with this manuscript, which was paid to their institution. SMS is the chair of the NIHR Uveitis Clinical Study Group. PAK receives support from UK Research and Innovation and Moorfields Eye Charity. PAK reports payment for consulting for Novartis, Boehringer-Ingleheim, Apellis, Abbvie, Roche and Adecco. PAK reports payment or honoraria for educational events for Novartis, Gyroscope, Bayer, Thea, Boehringer-Ingleheim, Apellis, Abbvie and Alimera. PAK participates on an advisory board for RetinAI, Novartis, Boehringer-Ingleheim, Roche and Abbvie. PAK reports patents for Google US10198832B2 (issued) and Google US20220301152A1 (pending). PAK reports stock with Big Picture Medical (stocks) and Bitfount (stock options). NAVB receives support from Wellcome Trust and recently receives support from Indonesian Endowment Fund for Education paid to their institution. NAVB reports payments for consulting for Roche. NAVB reports payment or honoria for educational events for Alimera Sciences. NAVB is a member of the Scientific Committee of the Royal College of Ophthalmologists. AD receives support from NIHR Biomedical Research Centre, Janssen Pharmaceuticals, Macular Society, MRC Cluster Consortium Awards and Arthritis Research UK, which is paid to his institution. AD receives royalties from The Eye Basic Science in Practice (Elsevier). AD reports payment for consulting for Hovartis, Hubble Htz, Active Bio and Gilead. AD participates on an advisory board for Co-THEIA Randomised Controlled Trial in Spain. AD is a non-executive director at Moorfields NHS Foundation Trust. No other conflicts were reported., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

SARS-CoV-2 binds to ACE2 receptors and enters cells. The symptoms are cough, breathlessness, loss of taste/smell and X-ray evidence of infiltrates on chest imaging initially caused by oedema, and subsequently by a lymphocytic pneumonitis. Coagulopathy, thrombosis and hypotension occur. Worse disease occurs with age, obesity, ischaemic heart disease, hypertension and diabetes.These features may be due to abnormal activation of the contact system. This triggers coagulation and the kallikrein-kinin system, leading to accumulation of bradykinin and its derivatives, which act on receptors B1R and B2R. Receptor activation causes cough, hypotension, oedema and release of the cytokine interleukin-6 (IL-6) which recruits lymphocytes. These effects are core features seen in early SARS CoV-2 infection., Methods and Analysis: In this study, hypoxic patients with COVID-19 with symptom onset ≤7 days will be randomised to either a bradykinin inhibitor (icatibant) or placebo. Patients and investigators will be blinded. The primary outcome will be blood oxygenation, measured by arterial blood sampling. The secondary outcome will be cardiovascular status. Retinal imaging will be performed to assess vessel size. Blood samples will be taken for measurement of inflammatory analyses including IL-6. As a separate substudy, we will also take comparator blood inflammatory samples from a COVID-19-negative cohort., Ethics and Dissemination: The study has received the following approvals: West Midlands-Edgbaston Research Ethics Committee. Medicines and Healthcare products Regulatory Agency has issued a clinical trial authorisation. Belfast Health and Social Care Trust is the study sponsor. Results will be made available to participants upon request and findings will be presented and published., Trial Registration Number: NCT05407597., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To test an online training course for non-ophthalmic diabetic retinopathy (DR) graders for recognition of glaucomatous optic nerves in Vietnam., Methods: This was an uncontrolled, experimental, before-and-after study in which 43 non-ophthalmic DR graders underwent baseline testing on a standard image set, completed a self-paced, online training course and were retested using the same photographs presented randomly. Twenty-nine local ophthalmologists completed the same test without the training course. DR graders then underwent additional one-to-one training by a glaucoma specialist and were retested. Test performance (% correct, compared with consensus grades from four fellowship-trained glaucoma experts), sensitivity, specificity, positive and negative predictive value, and area under the receiver operating (AUC) curve, were computed., Results: Mean age of DR graders (32.6±5.5 years) did not differ from ophthalmologists (32.3±7.3 years, p=0.13). Online training required a mean of 297.9 (SD 144.6) minutes. Graders' mean baseline score (33.3%±14.3%) improved significantly after training (55.8%±12.6%, p<0.001), and post-training score did not differ from ophthalmologists (58.7±15.4%, p=0.384). Although grader sensitivity reduced before [85.5% (95% CI 83.5% to 87.3%)] versus after [80.4% (78.3% to 82.4%)] training, specificity improved significantly [47.8 (44.9 to 50.7) vs 79.8 (77.3 to 82.0), p<0.001]. Grader AUC also improved after training [66.6 (64.9 to 68.3)] to [80.1 (78.5 to 81.6), p<0.001]. Additional one-to-one grader training by a glaucoma specialist did not further improve grader scores., Conclusion: Non-ophthalmic DR graders can be trained to recognise glaucoma using a short online course in this setting, with no additional benefit from more expensive one-to-one training. After 5-hour online training in recognising glaucomatous optic nerve head, scores of non-ophthalmic DR graders doubled, and did not differ from local ophthalmologists. Intensive one-to-one training did not further improve performance., Competing Interests: Competing interests: Congdon serves as a paid consultant for Belkin Vision, a company selling devices for the treatment of glaucoma. Kahook has an equity interest in SpyGlass Pharma and receives royalties from New World Medical and Alcon. Olusola Olawoye is a Consortium for Advanced Research and Training in Africa (CARTA) Fellow., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To compare the accuracy of trained level 1 diabetic retinopathy (DR) graders (nurses, endocrinologists and one general practitioner), level 2 graders (midlevel ophthalmologists) and level 3 graders (senior ophthalmologists) in Vietnam against a reference standard from the UK and assess the impact of supplementary targeted grader training., Design: Diagnostic test accuracy study., Setting: Secondary care hospitals in Southern Vietnam., Participants: DR training was delivered to Vietnamese graders in February 2018 by National Health Service (NHS) UK graders. Two-field retinal images (412 patient images) were graded by 14 trained graders in Vietnam between August and October 2018 and then regraded retrospectively by an NHS-certified reference standard UK optometrist (phase I). Further DR training based on phase I results was delivered to graders in November 2019. After training, a randomised subset of images from January to October 2020 (115 patient images) was graded by six of the original cohort (phase II). The reference grader regraded all images from phase I and II retrospectively in masked fashion., Primary and Secondary Outcome Measures: Sensitivity was calculated at the two different time points, and χ 2 was used to test significance., Results: In phase I, the sensitivity for detecting any DR for all grader groups in Vietnam was low (41.8-42.2%) and improved in phase II after additional training was delivered (51.3-87.2%). The greatest improvement was seen among level 1 graders (p<0.001), and the lowest improvement was observed among level 3 graders (p=0.326). There was a statistically significant improvement in sensitivity for detecting referable DR and referable diabetic macular oedema between all grader levels. The post-training values ranged from 40.0 to 61.5% (including ungradable images) and 55.6%-90.0% (excluding ungradable images)., Conclusions: This study demonstrates that targeted training interventions can improve accuracy of DR grading. These findings have important implications for improving service delivery in DR screening programmes in low-resource settings., Competing Interests: Competing interests: NC is employed as a Research Director by Orbis International., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Globally, diabetic retinopathy (DR) is the leading cause of blindness in working-aged adults. Early detection and treatment of DR is essential for preventing sight loss. Services must be available, accessible and acceptable to patients if we are to ensure they seek such care., Objectives: To understand patients' knowledge and attitudes towards laser versus antivascular endothelial growth factor (VEGF) injections to treat DR in Vietnam, and to identify factors Vietnamese ophthalmologists consider when making treatment decisions., Methods: This is a descriptive qualitative study based on semi-structured interviews with 18 patients (12 from Ho Chi Minh City and 6 from Hanoi) plus individual interviews with 24 ophthalmologists working in eye clinics in these cities. Thematic analysis was used to analyse the data., Results: In total, 10/24 (41.7%) ophthalmologists were female, and their median age was 41 years (range 29-69 years). The median age of patients was 56.5 years (range 28-72 years), and 7/18 (38.9%) were female. Briefly, factors that influence DR treatment decisions for ophthalmologists are medical considerations (ie, severity of disease, benefits and risks), availability (ie, treatment and resources) and patient-related factors (ie, costs and adherence). Patient's perceived barriers and facilitators to treatments were based on patient and family related factors (ie, treatment and transportation costs) and previous treatment experiences (ie, positive and negative). Recommendations by all participants included ensuring that both laser and anti-VEGF injections are widely available across the country and controlling costs for patients and the healthcare system., Conclusions: Reducing DR treatment costs, optimising treatments options, and expanding the network of clinics offering treatment outside metropolitan areas were the main issues raised by participants. These findings can help inform policy changes in Vietnam and may be generalisable to other low-resource settings., Competing Interests: Competing interests: NC is employed as a Research Director by Orbis International., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We examined the hypothesis that baseline retinal vascular geometry in patients with proliferative diabetic retinopathy (PDR) predicts disease activity 6 months after panretinal photocoagulation (PRP)., Methods and Analysis: We included 47 eyes from 40 patients with treatment-naïve PDR in a 6-month prospective study. Diagnosis of PDR and disease activity was evaluated by wide-field fluorescein angiography (Optomap, Optos, Dunfermline, Scotland, UK). At baseline and 6-month follow-up, the retinal vessel geometry was measured on optic disc centred images using semiautomated software Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE, Dundee, Scotland)., Results: At baseline, mean age and duration of diabetes was 51.6 and 21.4 years, and 62.5% were men. Seventeen eyes (36.2%) had progression of PDR during follow-up. At baseline, we found higher retinal arteriolar calibre (31.3±0.8 vs 28.8±0.8 pixels, p=0.02) and venous fractal dimension (F D ) (1.257±0.011 vs 1.222±0.011, p=0.02) in eyes with progression of PDR as compared with eyes with non-progression. In a multiple logistic regression model, both higher retinal arteriolar calibre (OR 1.34, 95% CI, 1.09 to 1.64, p<0.01) and venular F D (OR 1.15, 95% CI, 1.04 to 1.27, p<0.01) predicted progression of PDR. Venular calibre was seen to increase from baseline to month six regardless of disease progression (non-progression 45.0±0.7 vs 52.7±1.8 pixels, p<0.01; progression 46.2±0.8 vs 51.0±1.7 pixels, p<0.01)., Conclusion: Our prospective study showed that arteriolar calibre and venular F D at baseline were predictive of disease activity 6 months after PRP treatment in patients with treatment-naïve PDR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There is contrasting evidence on the relationship between socioeconomic status (SES) and age-related macular degeneration (AMD), the most common cause of visual impairment (VI) in developed countries. This study examines the relationship between SES, cardiovascular risk factors and self-reported AMD., Methods and Analysis: Over 500000 people participated in the UK Biobank study from 2006 to 2019, with sociodemographic data and clinical measurements collected using standardised procedures. Visual acuity was measured in 117907 participants with VI defined as LogMAR ≤0.3. We used logistic regression to examine the cross-sectional associations between SES and self-reported AMD., Results: Self-reported AMD was available for 133339 participants aged 50 and older. People reporting AMD had higher academic qualifications, lower income, were unable to work due to disability, have higher BMI, diabetes and vascular heart disease after adjusting for age and sex. In a multivariable analysis, higher income was protective of AMD and economic inactivity due to disability increased the odds of AMD (2.02, 95% CI 1.13 to 3.61). Both associations were independent of cardiovascular factors, but was no longer significant after adjusting for VI., Conclusions: The association between education, employment and household income with AMD was independent of cardiovascular risk factors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Introduction: The diabetes mellitus (DM) epidemic is a major public health concern globally, with the highest-burden in low-income and middle-income countries (LMICs). Diabetic retinopathy (DR) is a microvascular complication of diabetes, and if left untreated can lead to visual impairment and blindness. Epidemiological studies suggest that the incidence of sight-threatening DR is decreasing in high-income countries due to improved treatments and management of DM; however, these trends are not replicated in LMICs. In this paper, we outline a scoping review protocol that aims to identify which LMICs have included DR in their national DM, non-communicable disease or prevention of blindness plans. The scoping review also aims to assess gaps when implementing national DR screening programmes in LMICs., Methods and Analysis: This scoping review will follow the Arksey and O'Malley (2005) methodology and the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Review guidelines. A comprehensive search of peer-reviewed and grey literature will be conducted from October 1989 (St. Vincent Declaration) to February 2020. Studies will be identified from electronic databases; Medline, Embase and CENTRAL (Cochrane Library). To identify further relevant articles, a hand search will be conducted using the reference lists of included studies. Two reviewers will independently screen records for relevant data and disagreements about eligibility will be resolved through consensus or arbitration by a third reviewer. A quantitative analysis will be performed to highlight key findings and thematic analysis will be used to identify emerging themes and subthemes from included studies. The key themes will highlight countries progress in terms of national-level DR service planning and screening implementation., Ethics and Dissemination: No ethical approval is required because the scoping review methodology aims to synthesise information from publicly available resources. The results will be disseminated through conference presentations and peer-reviewed publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Given the increasing burden of repetitive intravitreal injections in diabetic macular oedema (DMO) treatment, non-invasive markers of treatment outcome are needed. Hence, we aimed to examine retinal oximetry parameters as markers of need for intravitreal aflibercept in patients with DMO., Methods: This study was based on data from a 12-month clinical trial including 35 eyes of 25 patients with centre involving DMO. Retinal oximetry, visual acuity (VA) and central retinal thickness (CRT) were performed at baseline (BL). Patients then received 3 monthly injections of aflibercept followed by focal/grid laser photocoagulation. From month 4 (M4) through 12 (M12), patients were followed monthly and additional injections were given pro re nata if criteria of retreatment were met. We evaluated the difference in need for intravitreal aflibercept in groups of eyes with the highest and lowest retinal arteriolar and venular oxygen saturations, respectively., Results: From BL-M12, overall VA letter score improved by 8.7 (7.2-10.2). Likewise CRT reduced by 100.7 (68.2-133.3) µm and the mean number of injections was 4.3 (3.8-4.8). Overall retinal arteriolar and venular oxygen saturations were 95.7 (93.0-98.4)% and 62.7 (59.4-65.9)% at BL. Eyes with the highest retinal arteriolar oxygen saturations had significantly more injections between BL and M12 compared with eyes with the lowest retinal arteriolar oxygen saturations (5.0 (4.2-5.8) vs 3.6 (3.1-4.0), p=0.002)., Conclusion: Higher retinal arteriolar oxygen saturation independently predicted the need for more intravitreal aflibercept during the first year of DMO treatment and may serve as a valuable adjunctive to established procedures for retinal imaging in terms of individualised treatment plans., Trial Registration Number: NCT02554747., Competing Interests: Competing interests: SLB reports no competing interests. TP reports personal fees from Novartis, personal fees from Bayer, personal fees from OPTOS, personal fees from Heidelberg, outside the submitted work. JG reports personal fees from Bayer, personal fees from Novartis, outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To determine the performance of combinations of structural and functional screening tests in detecting sight-threatening eye disease in a cohort of elderly subjects recruited from primary care., Methods: 505 subjects aged ≥60 years underwent frequency doubling technology (FDT) perimetry, iVue optical coherence tomography (iWellness and peripapillary retinal nerve fibre layer (RNFL) scans) and intraocular pressure with the Ocular Response Analyzer, all performed by an ophthalmic technician. The reference standard was a full ophthalmic examination by an experienced clinician who was masked to the index test results. Subjects were classified as presence or absence of sight-threatening eye disease (clinically significant cataract, primary open-angle glaucoma, intermediate or advanced age-related macular degeneration and significant diabetic retinopathy). Univariate and multivariate logistic regression analyses were used to determine the association between abnormal screening test results and the presence of sight-threatening eye disease., Results: 171 subjects (33.8%) had one or more sight-threatening eye diseases. The multivariate analysis found significant associations with any of the target conditions for visual acuity of <6/12, an abnormal FDT and peripapillary RNFL thickness outside the 99% normal limit. The sensitivity of this optimised screening panel was 61.3% (95% CI 53.5 to 68.7), with a specificity of 78.8% (95% CI 74.0 to 83.1), a positive predictive value of 59.5% (95% CI 53.7 to 65.2) and an overall diagnostic accuracy of 72.9% (95% CI 68.8 to 76.8)., Conclusions: A subset of screening tests may provide an accurate and efficient means of population screening for significant eye disease in the elderly. This study provides useful preliminary data to inform the development of further larger, multicentre screening studies to validate this screening panel., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank., Participants: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun., Findings to Date: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process., Future Plans: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life., Competing Interests: Competing interests: This analysis was supported by the Eranda Foundation via the International Glaucoma Association in the design and conduct of the study. The UCL ORS and GRS programmes provided scholarship support for ZM, PTK, PJF, and PP and SYLC received salary support from the NIHR BRC at Moorfields Eye Hospital. PJF received support from the Richard Desmond Charitable Trust, via Fight for Sight, London. PJF reports personal fees from Allergan, Carl Zeiss, Google/DeepMind and Santen, a grant from Alcon, outside the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: High-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access., Design: Longitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations., Setting: National Health Service (NHS) care in England., Population: Patients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders., Interventions: Higher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders., Main Outcome Measures: National procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing., Results: Injection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to £447 million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a 'high use' CCG were 9.08 times higher than in a 'low use' CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9)., Conclusions: The high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals., Design: A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design., Setting: A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics., Participants: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes., Interventions: The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions., Main Outcome Measures: Correct classification of whether further treatment is needed, compared with a reference standard., Results: The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%)., Conclusions: In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms., Trial Registration Number: ISRCTN07479761; Pre-results., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery., Design: Prospective cohort study (1 week) and analysis of linked electronic health records (3 years)., Setting: UK tertiary care centre., Participants: All patients admitted sequentially to the acute medical service under an infectious diseases acute physician (IDP) and other medical teams during 1 week in 2013 (n=297), and 3 years 2012-2014 (n=47 585)., Primary Outcome Measure: Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case mix., Secondary Outcome Measures: 30-day all-cause mortality, treatment failure and length of stay., Results: Antibiotic use was 173 vs 282 DOT/100 admissions in the IDP versus non-IDP group. Using case mix-adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07 to 0.84), p=0.03) and received shorter courses (adjusted rate ratio (RR)=0.71 (95% CI 0.54 to 0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% vs 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p>0.5; also in the 3-year data set), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24 to 10.03), p=0.03) and have longer length of stay (adjusted RR=1.19 (95% CI 1.05 to 1.36), p=0.007)., Conclusions: The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will increase or decrease risk of antibiotic-resistant infections., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To compare the ability of ophthalmologists versus optometrists to correctly classify retinal lesions due to neovascular age-related macular degeneration (nAMD)., Design: Randomised balanced incomplete block trial. Optometrists in the community and ophthalmologists in the Hospital Eye Service classified lesions from vignettes comprising clinical information, colour fundus photographs and optical coherence tomographic images. Participants' classifications were validated against experts' classifications (reference standard)., Setting: Internet-based application., Participants: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care., Interventions: The trial emulated a conventional trial comparing optometrists' and ophthalmologists' decision-making, but vignettes, not patients, were assessed. Therefore, there were no interventions and the trial was virtual. Participants received training before assessing vignettes., Main Outcome Measures: Primary outcome-correct classification of the activity status of a lesion based on a vignette, compared with a reference standard. Secondary outcomes-potentially sight-threatening errors, judgements about specific lesion components and participants' confidence in their decisions., Results: In total, 155 participants registered for the trial; 96 (48 in each group) completed all assessments and formed the analysis population. Optometrists and ophthalmologists achieved 1702/2016 (84.4%) and 1722/2016 (85.4%) correct classifications, respectively (OR 0.91, 95% CI 0.66 to 1.25; p=0.543). Optometrists' decision-making was non-inferior to ophthalmologists' with respect to the prespecified limit of 10% absolute difference (0.298 on the odds scale). Optometrists and ophthalmologists made similar numbers of sight-threatening errors (57/994 (5.7%) vs 62/994 (6.2%), OR 0.93, 95% CI 0.55 to 1.57; p=0.789). Ophthalmologists assessed lesion components as present less often than optometrists and were more confident about their classifications than optometrists., Conclusions: Optometrists' ability to make nAMD retreatment decisions from vignettes is not inferior to ophthalmologists' ability. Shared care with optometrists monitoring quiescent nAMD lesions has the potential to reduce workload in hospitals., Trial Registration Number: ISRCTN07479761; pre-results registration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To describe the prevalence and phenotypic characteristics of small eyes in the European Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study., Design: Community cross-sectional study., Setting: East England population (Norwich, Norfolk and surrounding area)., Participants: 8033 participants aged 48-92 years old from the EPIC-Norfolk Eye Study, Norfolk, UK with axial length measurements. Participants underwent a standardised ocular examination including visual acuity (LogMAR), ocular biometry, non-contact tonometry, autorefraction and fundal photography. A small eye phenotype was defined as a participant with one or both eyes with axial length of <21 mm., Outcome Measures: Prevalence of small eyes, proportion with visual impairment, demographic and biometric factors., Results: Ninety-six participants (1.20%, 95% CI 0.98% to 1.46%) had an eye with axial length less than 21 mm, of which 74 (77%) were women. Prevalence values for shorter axial lengths were <20 mm: 0.27% (0.18% to 0.41%); <19 mm: 0.17% (0.11% to 0.29%); <18 mm: 0.14% (0.08% to 0.25%). Two participants (2.1%) had low vision (presenting visual acuity >0.48 LogMAR) and one participant was blind (>1.3 LogMAR). The prevalence of unilateral visual impairment was higher in participants with a small eye. Multiple logistic regression modelling showed presence of a small eye to be significantly associated with shorter height, lower body mass index, higher systolic blood pressure and lower intraocular pressure., Conclusions: The prevalence of people with small eyes is higher than previously thought. While small eyes were more common in women, this appears to be related to shorter height and lower body mass index. Participants with small eyes were more likely to be blind or to have unilateral visual impairment.