Stephen James Talks

Background: Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. Methods: A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a ‘good–moderate–poor’ rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. Results: A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. Conclusions: The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.

In the UK, macular laser is the treatment of choice for people with diabetic macular oedema with central retinal subfield thickness (CST) < 400 μm, as per National Institute for Health and Care Excellence guidelines. It remains unclear whether subthreshold micropulse laser is superior and should replace standard threshold laser for the treatment of eligible patients. DIAMONDS is a pragmatic, multicentre, allocation-concealed, randomised, equivalence, double-masked clinical trial that aims to determine the clinical effectiveness and cost-effectiveness of subthreshold micropulse laser compared with standard threshold laser, for the treatment of diabetic macular oedema with CST < 400 μm. The primary outcome is the mean change in best-corrected visual acuity in the study eye from baseline to month 24 post treatment. Secondary outcomes (at 24 months) include change in binocular best corrected visual acuity; CST; mean deviation of the Humphrey 10–2 visual field; change in percentage of people meeting driving standards; European Quality of Life-5 Dimensions, National Eye Institute Visual Functioning Questionnaire-25 and VisQoL scores; incremental cost per quality-adjusted life year gained; side effects; number of laser treatments and use of additional therapies. The primary statistical analysis will be per protocol rather than intention-to-treat analysis because the latter increases type I error in non-inferiority or equivalence trials. The difference between lasers for change in best-corrected visual acuity (using 95% CI) will be compared to the permitted maximum difference of five Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Linear and logistic regression models will be used to compare outcomes between treatment groups. A Markov-model-based cost-utility analysis will extend beyond the trial period to estimate longer-term cost-effectiveness. This trial will determine the clinical effectiveness and cost-effectiveness of subthreshold micropulse laser, when compared with standard threshold laser, for the treatment of diabetic macular oedema, the main cause of sight loss in people with diabetes mellitus. International Standard Randomised Controlled Trials, ISRCTN17742985 . Registered on 19 May 2017 (retrospectively registered).

Background Diabetic macular oedema (DMO) is effectively treated with ranibizumab but multiple injections are required. Where there is also peripheral ischaemia, it has been promoted that targeted panretinal photocoagulation (PRP) may reduce the number of injections. Method Patients with optical coherence tomography confirmed DMO and Ultra-widefield Fundus Fluorescein Angiography confirmed peripheral retinal ischaemia were randomised to PRP plus ranibizumab or ranibizumab monotherapy. After three injections, repeat injections were given until the visual acuity was stable and the macula was dry. Re-treatment was given if there was a drop of visual acuity and/or a recurrence of intra-retinal fluid. The primary outcome was the number of repeat injections required after the first 6 months up until 1 year. Results There were 49 patients, 25 in the ranibizumab only group and 24 in the ranibizumab + PRP group recruited at seven UK sites. The average number of injections in the ranibizumab-only arm was 6.84 over 1 year and 2.52 between months 6 and 12. The average number of injections in the combined arm was 6.67, with the number of injections in the second 6 months 1.92. For the primary outcome, comparing the number of 6- to 12-month injections, the result was not statistically significant (p = 0.33). Conclusion The addition of targeted PRP to areas of non-perfusion in a patient with DMO does not reduce the number of injections required in the first year. It seems most likely that local VEGF at the macula is the main cause of DMO.

Expanding the role of medical retina virtual clinics using multimodal ultra-widefield and optical coherence tomography imaging Jing Xian Lee,1 Vina Manjunath,2 S James Talks2 1Faculty of Medicine, Newcastle University, Newcastle upon Tyne, UK; 2Newcastle Eye Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK Background: An increasingly elderly population with a corresponding increase in ophthalmic conditions has led to increased pressure on hospital eye services (HES). In this study, we evaluated the use of a medical retina virtual clinic (MRVC), which has expanded into assessing all new medical retina referrals, where the need for urgent treatment was not clear. Methods: Retrospective analysis of all new patients who were seen in the MRVC between April 2016 and May 2018. Pro forma sheets were used in the MRVC to record the patient history, visual acuity, and type of imaging required. Two consultants reviewed the completed pro formas and images and provided a final diagnosis and management plan. These results and reasons for face-to-face (F2F) clinic appointment requests were analyzed. Results: Six hundred ten new referrals were enrolled in the virtual clinic. The most common diagnosis was diabetic eye disease (59.9%). In the virtual clinic 44.1% were followed up, 28.1% were discharged, and 27.8% were booked an F2F clinic appointment (urgent/routine). The main reason for F2F clinic was to offer treatment. Urgent F2F appointments took place on average 11.9 days after virtual clinic attendance. In only two cases was the image quality felt to be inadequate to assess the retina. Conclusions: MRVC is an effective way of triaging medical retina referrals to allow those patients needing treatment to be seen promptly in the medical retinal service. The use of multimodal ultra-widefield and optical coherence tomography imaging allows assessment of a wide range of retinal pathologies and is a promising solution to alleviate the burden on HES. Keywords: virtual clinic, optical coherence tomography, macular degeneration, choroidal naevus, diabetic retinopathy, teleophthalmology

Introduction: Widefield and ultra-widefield (uwf) retinal imaging of diabetic retinopathy can provide information outside that obtained by standard retinal imaging and has the potential to improve the clinical management of diabetic retinopathy. Areas covered: The evidence for clinical benefit of ultra-widefield imaging has been reviewed and put into context in relation to other retinal imaging systems. A medline search was performed using the relevant key words. Several variants of the term ‘ultra widefield’ were searched in relation to diabetic retinopathy imaging as no standard term has been used over time. Expert commentary: Uwf colour and fluorescein angiography combined with optical coherence tomography images, read by a reading centre, provide the most accurate way of assessing the retina. Widefield optical coherence tomography angiography is also becoming available. The use of these technologies can provide better screening, referral refinement, more efficient and accurate clinic assessments and alter management by making it less likely that pathology is missed. Potentially they can lead to alternative treatment approaches, such as retina sparing peripheral laser, but this is yet to be proved. Automated reading of such images is in development.

Introduction Wide-field retinal imaging (Optomap), used for detecting diabetic retinopathy (DR), has been shown to compare well with seven-field early treatment diabetic retinopathy study (ETDRS) photographs. An Optomap 200° image covers 80% of the retinal surface, compared with the standard seven-field, 30° images, covering 30% of the retinal surface. In England, DR screening is performed by grading two, 45° images per eye, by the DR screening service (DRSS). Purpose To assess how often retinal new vessels (NVs) are observed on Optomap imaging, outside the DRSS two fields and standard seven-field photography, in a cohort of patients referred by the DRSS. Method A consecutive series of treatment naïve patients with DR, referred from DRSS with pre-proliferative or proliferative DR or diabetic maculopathy, were imaged with Optomap colour images, within 3 months of DRSS referral. The incidence and distribution of NVs were recorded in relation to two-field and seven-field areas. Results NVs were found in 102 of 1562 treatment naïve eyes (6.5%) of 781 patients. Of these, 72 were referred from DRSS as having NVs, but an additional 30 eyes (29% of NVs detected) from 25 patients were referred with a lesser degree of DR. In 25 of the 30 eyes without NVs reported on referral, NVs were located outside the standard two fields taken at DRSS, and in 12, NVs were outside the area covered on seven-field imaging (11.7% of eyes with NVs). Conclusions Wide-field imaging with Optomap detected approximately 30% more NVs than standard two-field imaging in patients referred from a UK DRSS.