The Epidemiology of Stargardt Disease in the United Kingdom

The authors thank the British Ophthalmological Surveillance Unit (BOSU) for the support received, as well as Mr Barnaby Foot, research coordinator for BOSU, for his help and advice on this project. The authors thank the following ophthalmologists who assisted with data collection for this study: N. Acharya, S. Anwar, V. Bansal, P.N. Bishop, D. Byles, J.S. Chawla, A. Churchill, M. Clarke, B. Dhillon, M. Ekstein, S. George, J. Gillian, J.T. Gillow, D. Gilmour, R. Gray, P.T.S. Gregory, R. Gupta, S.P. Kelly, I.C. Lloyd, A. Lotery, M. McKibbin, R. MacLaren, G. Menon, A.T. Moore, A. Mulvihill, Y. Osoba, R. Pilling, H. Porooshani, A. Raghu Ram, T. Rimmer, I. Russell-Eggitt, M. Sarhan, R. Savides, S. Shafquat, A. Smith, A. Tekriwal, P. Tesha, P. Watts.Peer reviewedPublisher PD

Patients views on a new surveillance pathway involving allied non-medical staff for people with treated diabetic macular oedema and proliferative diabetic retinopathy

Background/Objective To explore acceptability by patients and health care professionals of a new surveillance pathway for people with previously treated and stable diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR). Subject/Methods Structured discussions in 10 focus groups with patients; two with ophthalmic photographers/graders, and one with ophthalmologists, held across the UK as part of a large diagnostic accuracy study (EMERALD). Results The most prominent issues raised by patients concerned (i) expertise of the various professionals within clinic, (ii) quality of interactions with clinic professionals, especially the flow of information from professionals to patients, and (iii) wish to be treated holistically. Ophthalmologists suggested such issues could be best dealt with via a programme of patient education and tended to overlook deeper implications of patient concerns for the organisation of services. Conclusion For patients, the clinical service should not only include the identification and treatment of disease but also exchange of information, reassurance, and mitigation of anxiety. Alterations in the standard care pathway need to take account of such concerns and their implications, in addition to any assessments of ‘efficiency’ that may flow from changes in diagnostic technology, or the division of professional labour

Treatments for dry age-related macular degeneration and Stargardt disease : a systematic review

Background Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. Objective To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Design Systematic review. Methods We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. Results The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or government

Surveillance of people with previously successfully treated diabetic macular oedema and proliferative diabetic retinopathy by trained ophthalmic graders : cost analysis from the EMERALD study

Background/aims: Surveillance of people with previously successfully treated diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) adds pressure on ophthalmology services. This study evaluated a new surveillance pathway entailing multimodal imaging reviewed by trained ophthalmic graders and compared it with the current standard care (face-to-face evaluation by an ophthalmologist). Methods: Cost analysis of the new ophthalmic grader pathway, compared with the standard of care, from the perspective of the UK National Health Service, based on evidence from the Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy study. Resource use data were prospectively obtained including times to undertake each procedure. Effectiveness was assessed in terms of sensitivity and specificity of referral decisions in the grader pathway. Costs (SDs) were analysed per 100 patients separately for DMO and PDR at 2018/2019 costs. Results: For DMO, where sensitivity was very high (97%), the cost difference (savings) for the grader’s pathway would be £1390 per 100 patients. For PDR, the cost would be reduced by £461 for seven-field Early Treatment for Diabetic Retinopathy Study (ETDRS) images and by £1889 for ultrawide field images, per 100 patients. Ultrawide images required less time to be obtained and read than seven-field ETDRS. The real savings would be in ophthalmologist time, which could be then redirected to the evaluation of people at high risk of visual loss. Conclusions: Surveillance of people with previously successfully treated DMO and PDR by trained ophthalmic graders can achieve satisfactory results and release ophthalmologist time. Trial registration numbers: NCT03490318, ISRCTN10856638

Polarized retinal pigment epithelium generates electrical signals that diminish with age and regulate retinal pathology

Fight for Sight. Grant Numbers: 1712/13, 1361/1362 NHS Grampian Endowments, Friends of ANCHOR, Action Medical Research. Grant Number: GN2299Peer reviewedPublisher PD

Testing the performance of risk prediction models to determine progression to referable diabetic retinopathy in an Irish type 2 diabetes cohort

Background /aims: To evaluate the performance of existing prediction models to determine risk of progression to referable diabetic retinopathy (RDR) using data from a prospective Irish cohort of people with type 2 diabetes (T2D). Methods: A cohort of 939 people with T2D followed prospectively was used to test the performance of risk prediction models developed in Gloucester, UK, and Iceland. Observed risk of progression to RDR in the Irish cohort was compared with that derived from each of the prediction models evaluated. Receiver operating characteristic curves assessed models' performance. Results: The cohort was followed for a total of 2929 person years during which 2906 screening episodes occurred. Among 939 individuals followed, there were 40 referrals (4%) for diabetic maculopathy, pre-proliferative DR and proliferative DR. The original Gloucester model, which includes results of two consecutive retinal screenings; a model incorporating, in addition, systemic biomarkers (HbA1c and serum cholesterol); and a model including results of one retinopathy screening, HbA1c, total cholesterol and duration of diabetes, had acceptable discriminatory power (area under the curve (AUC) of 0.69, 0.76 and 0.77, respectively). The Icelandic model, which combined retinopathy grading, duration and type of diabetes, HbA1c and systolic blood pressure, performed very similarly (AUC of 0.74). Conclusion: In an Irish cohort of people with T2D, the prediction models tested had an acceptable performance identifying those at risk of progression to RDR. These risk models would be useful in establishing more personalised screening intervals for people with T2D

Different lasers and techniques for proliferative diabetic retinopathy

BACKGROUND: Diabetic retinopathy (DR) is a chronic progressive disease of the retinal microvasculature associated with prolonged hyperglycaemia. Proliferative DR (PDR) is a sight-threatening complication of DR and is characterised by the development of abnormal new vessels in the retina, optic nerve head or anterior segment of the eye. Argon laser photocoagulation has been the gold standard for the treatment of PDR for many years, using regimens evaluated by the Early Treatment of Diabetic Retinopathy Study (ETDRS). Over the years, there have been modifications of the technique and introduction of new laser technologies. OBJECTIVES: To assess the effects of different types of laser, other than argon laser, and different laser protocols, other than those established by the ETDRS, for the treatment of PDR. We compared different wavelengths; power and pulse duration; pattern, number and location of burns versus standard argon laser undertaken as specified by the ETDRS. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 8 June 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of pan-retinal photocoagulation (PRP) using standard argon laser for treatment of PDR compared with any other laser modality. We excluded studies of lasers that are not in common use, such as the xenon arc, ruby or Krypton laser. DATA COLLECTION AND ANALYSIS: We followed Cochrane guidelines and graded the certainty of evidence using the GRADE approach. MAIN RESULTS: We identified 11 studies from Europe (6), the USA (2), the Middle East (1) and Asia (2). Five studies compared different types of laser to argon: Nd:YAG (2 studies) or diode (3 studies). Other studies compared modifications to the standard argon laser PRP technique. The studies were poorly reported and we judged all to be at high risk of bias in at least one domain. The sample size varied from 20 to 270 eyes but the majority included 50 participants or fewer.Nd:YAG versus argon laser (2 studies): very low-certainty evidence on vision loss, vision gain, progression and regression of PDR, pain during laser treatment and adverse effects.Diode versus argon laser (3 studies): very-low certainty evidence on vision loss, vision gain, progression and regression of PDR and adverse effects; moderate-certainty evidence that diode laser was more painful (risk ratio (RR) troublesome pain during laser treatment (RR 3.12, 95% CI 2.16 to 4.51; eyes = 202; studies = 3; I2 = 0%).0.5 second versus 0.1 second exposure (1 study): low-certainty evidence of lower chance of vision loss with 0.5 second compared with 0.1 second exposure but estimates were imprecise and compatible with no difference or an increased chance of vision loss (RR 0.42, 95% CI 0.08 to 2.04, 44 eyes, 1 RCT); low-certainty evidence that people treated with 0.5 second exposure were more likely to gain vision (RR 2.22, 95% CI 0.68 to 7.28, 44 eyes, 1 RCT) but again the estimates were imprecise . People given 0.5 second exposure were more likely to have regression of PDR compared with 0.1 second laser PRP again with imprecise estimate (RR 1.17, 95% CI 0.92 to 1.48, 32 eyes, 1 RCT). There was very low-certainty evidence on progression of PDR and adverse effects.'Light intensity' PRP versus classic PRP (1 study): vision loss or gain was not reported but the mean difference in logMAR acuity at 1 year was -0.09 logMAR (95% CI -0.22 to 0.04, 65 eyes, 1 RCT); and low-certainty evidence that fewer patients had pain during light PRP compared with classic PRP with an imprecise estimate compatible with increased or decreased pain (RR 0.23, 95% CI 0.03 to 1.93, 65 eyes, 1 RCT).'Mild scatter' (laser pattern limited to 400 to 600 laser burns in one sitting) PRP versus standard 'full' scatter PRP (1 study): very low-certainty evidence on vision and visual field loss. No information on adverse effects.'Central' (a more central PRP in addition to mid-peripheral PRP) versus 'peripheral' standard PRP (1 study): low-certainty evidence that people treated with central PRP were more likely to lose 15 or more letters of BCVA compared with peripheral laser PRP (RR 3.00, 95% CI 0.67 to 13.46, 50 eyes, 1 RCT); and less likely to gain 15 or more letters (RR 0.25, 95% CI 0.03 to 2.08) with imprecise estimates compatible with increased or decreased risk.'Centre sparing' PRP (argon laser distribution limited to 3 disc diameters from the upper temporal and lower margin of the fovea) versus standard 'full scatter' PRP (1 study): low-certainty evidence that people treated with 'centre sparing' PRP were less likely to lose 15 or more ETDRS letters of BCVA compared with 'full scatter' PRP (RR 0.67, 95% CI 0.30 to 1.50, 53 eyes). Low-certainty evidence of similar risk of regression of PDR between groups (RR 0.96, 95% CI 0.73 to 1.27, 53 eyes). Adverse events were not reported.'Extended targeted' PRP (to include the equator and any capillary non-perfusion areas between the vascular arcades) versus standard PRP (1 study): low-certainty evidence that people in the extended group had similar or slightly reduced chance of loss of 15 or more letters of BCVA compared with the standard PRP group (RR 0.94, 95% CI 0.70 to 1.28, 270 eyes). Low-certainty evidence that people in the extended group had a similar or slightly increased chance of regression of PDR compared with the standard PRP group (RR 1.11, 95% CI 0.95 to 1.31, 270 eyes). Very low-certainty information on adverse effects. AUTHORS' CONCLUSIONS: Modern laser techniques and modalities have been developed to treat PDR. However there is limited evidence available with respect to the efficacy and safety of alternative laser systems or strategies compared with the standard argon laser as described in ETDRS

Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial : FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Fullthickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2–3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity ≤ 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery. Trial registration: This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.Chief Scientist Office, Scotland (project ref no CZH/4/235), NHS GrampianPeer reviewedPublisher PD