Mechanistic Evaluation of Panretinal Photocoagulation Versus Aflibercept in Proliferative Diabetic Retinopathy: CLARITY Substudy

PURPOSE: The purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy. //METHODS: This is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA). // RESULTS: The AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, −0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45). // CONCLUSIONS: Intravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks

Comparison of subjective and objective methods to determine the retinal arterio-venous ratio using fundus photography

Purpose: To assess the inter and intra observer variability of subjective grading of the retinal arterio-venous ratio (AVR) using a visual grading and to compare the subjectively derived grades to an objective method using a semi-automated computer program. Methods: Following intraocular pressure and blood pressure measurements all subjects underwent dilated fundus photography. 86 monochromatic retinal images with the optic nerve head centred (52 healthy volunteers) were obtained using a Zeiss FF450+ fundus camera. Arterio-venous ratios (AVR), central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were calculated on three separate occasions by one single observer semi-automatically using the software VesselMap (ImedosSystems, Jena, Germany). Following the automated grading, three examiners graded the AVR visually on three separate occasions in order to assess their agreement. Results: Reproducibility of the semi-automatic parameters was excellent (ICCs: 0.97 (CRAE); 0.985 (CRVE) and 0.952 (AVR)). However, visual grading of AVR showed inter grader differences as well as discrepancies between subjectively derived and objectively calculated AVR (all p < 0.000001). Conclusion: Grader education and experience leads to inter-grader differences but more importantly, subjective grading is not capable to pick up subtle differences across healthy individuals and does not represent true AVR when compared with an objective assessment method. Technology advancements mean we no longer rely on opthalmoscopic evaluation but can capture and store fundus images with retinal cameras, enabling us to measure vessel calibre more accurately compared to visual estimation; hence it should be integrated in optometric practise for improved accuracy and reliability of clinical assessments of retinal vessel calibres

Identifying important questions for Cochrane systematic reviews in Eyes and Vision: Report of a priority setting exercise

Introduction Systematic reviews are important to inform decision-making for evidence-based health care and patient choice. Deciding which reviews should be prioritized is a key issue for decision-makers and researchers. Cochrane Eyes and Vision conducted a priority setting exercise for systematic reviews in eye health care. Methods We established a steering group including practitioners, patient organizations, and researchers. To identify potential systematic review questions, we searched global policy reports, research prioritization exercises, guidelines, systematic review databases, and the Cochrane Library (CENTRAL). We grouped questions into separate condition lists and conducted a two-round online modified Delphi survey, including a ranking request. Participants in the survey were recruited through social media and the networks of the steering group. Results In Round 1, 343 people ranked one or more of the condition lists. Participants were eye care practitioners (69%), researchers (37%), patients or carers (24%), research providers/funders (5%), or noneye health care practitioners (4%) and from all World Health Organization regions. Two hundred twenty-six people expressed interest in completing Round 2 and 160 of these (71%) completed the Round 2 survey. Reviews on cataract and refractive error, reviews relevant to children, and reviews on rehabilitation were considered to have an important impact on the magnitude of disease and equity. Narrative comments emphasized the need for reviews on access to eye health care, particularly for underserved groups, including people with intellectual disabilities. Conclusion A global group of stakeholders prioritized questions on the effective and equitable delivery of services for eye health care. When considering the impact of systematic reviews in terms of reducing the burden of eye conditions, equity is clearly an important criterion to consider in priority-setting exercises

Identifying priority review questions for Cochrane Eyes and Vision: protocol for a priority setting exercise

INTRODUCTION: Cochrane Eyes and Vision (CEV) is an international network of individuals working to prepare, maintain and promote access to systematic reviews of interventions to treat, prevent or diagnose eye diseases or vision impairment. CEV plans to undertake a priority setting exercise to identify systematically research questions relevant to our scope, and to formally incorporate input from a wide range of stakeholders to set priorities for new and updated reviews. METHODS AND ANALYSIS: The scope of CEV is broad and our reviews include conditions that are common and have a high global disease burden, for example, cataract and dry eye disease, and conditions that are rare but have a high impact on quality of life and high individual cost such as eye cancer. We plan to focus on conditions prioritised by WHO during the development of the Package of Eye Care Interventions. These conditions were selected based on a combination of data on disease magnitude, healthcare use and expert opinion. We will identify priority review questions systematically by summarising relevant data on research in Eyes and Vision from a range of sources, and compiling a list of 10-15 potential review questions (new and/or updates) for each condition group. We will seek the views of external and internal stakeholders on this list by conducting an online survey. Equity will be a specific consideration. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee of the London School of Hygiene & Tropical Medicine. We will disseminate the findings through Cochrane channels and prepare a summary of the work for publication in a peer-reviewed journal

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

Background: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. Methods: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. Findings: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). Interpretation: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. Funding: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership

A systematic review of the association of diabetic retinopathy and cognitive impairment in people with Type 2 diabetes

A systematic review of studies reporting data on the relationship between diabetic eye disease and cognitive impairment in Type 2 diabetes was conducted. The increase in cognitive impairment has mirrored the global increase in diabetes. The aim of the systematic review was to determine the level of association between diabetic retinopathy and cognitive impairment. Item selection, data extraction and critical appraisal were undertaken using standard procedures and independently verified by two researchers. 3 out of 10 potentially relevant studies were included. All studies showed a level of association between diabetic retinopathy and cognitive impairment, suggesting a near threefold increased risk of cognitive impairment in patients with diabetic retinopathy compared to those without. An association of cognitive impairment and severity of diabetic retinopathy was found in males. Diabetic retinopathy was more strongly linked to impairment in the cognitive domains of verbal learning and recent memory. An increased risk of cognitive impairment in patients with diabetic retinopathy was found in the reviewed studies. However, the relationship of severity of diabetic retinopathy and cognitive impairment has not been established. Further studies with standardized measurements for cognitive impairment and diabetic retinopathy are required to delineate this relationship and the role of other factors in this relationship

An exploratory study evaluating the effects of macular carotenoid supplementation in various retinal diseases

Roxanne Crosby-Nwaobi, Philip Hykin, Tunde Peto, Sobha Sivaprasad NIHR Clinical Research Facility, NIHR&nbsp;Moorfields Biomedical Research Centre, London, UK Purpose: The aim of this study was to assess the impact of daily oral supplementation with Macushield (10&nbsp;mg/d meso-zeaxanthin, 10&nbsp;mg/d lutein, and 2&nbsp;mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. Methods: Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6&nbsp;months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. Results: A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P&lt;0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3&nbsp;months and 6&nbsp;months. Ceiling effects confounded other visual function tests and quality of life changes. Conclusion: Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases. Keywords: macular pigment optical density, diabetes, central serous retinopathy, age-related macular degeneratio

Photodynamic therapy for central serous chorioretinopathy

Central serous chorioretinopathy (CSCR) is an idiopathic disorder characterised by detachment of the neurosensory retina due to serous fluid accumulation between the photoreceptor outer segments and the retinal pigment epithelium. There are currently no set guidelines or protocols on its treatment. This study was undertaken to assess the current literature on the efficacy and safety of photodynamic therapy (PDT) as a treatment option for CSCR.MethodsSeven databases (PubMed, CENTRAL, MEDLINE, Web of Science, Embase, Scopus, and The Cochrane Database of Systematic Reviews) were searched without restrictions on time or location. We followed PRISMA guidelines and evaluated quality according to STROBE criteria. In total, 117 citations were identified and 31 studies describing 787 eyes were included for review. Data on indications for PDT in CSCR, dosing regimens of verteprofin PDT (which includes treatment dose of vertoporfin, treatment time, fluence, and spot size), number of treatment sessions, response to treatment, mean length of follow-up, and complications were extracted and analysed.ResultsSince the introduction of PDT for the treatment of CSCR in 2003, there have been three randomised controlled trials (RCTs), one for acute and two chronic CSCR and 28 further studies that met the STROBE criteria that compared the use of PDT with other treatment options. All studies showed short-term efficacy of PDT in CSCR. The studies were of small sample size and lacked sufficient follow-up to draw conclusions on long-term efficacy and safety.ConclusionsThere is sufficient scientific evidence to suggest that PDT may be a useful treatment option for chronic CSCR in the short-term. The review identifies a need for robust RCTs with longer follow-up to ascertain the role of PDT as a useful treatment option for CSCR

The relationship between diabetic retinopathy and cognitive impairment

OBJECTIVE: Recent studies have shown an increased risk for cognitive impairment and dementia in patients with diabetes. An association between diabetic retinopathy (DR) and retinal microvasculature disease and cognitive impairment has been reported as potential evidence for a microvascular component to the cognitive impairment. It was hypothesized that severity of DR would be associated with cognitive impairment in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Three hundred eighty patients with type 2 diabetes were recruited from a population-based eye screening program and grouped by severity of DR as follows: no/mild DR (n=252) and proliferative diabetic retinopathy (PDR) (n=128). Each participant underwent psychosocial assessment; depression screening; ophthalmic and physical examination, including blood assays; and cognitive assessment with the Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), and the Mini-Cog. General linear modeling was used to examine severity of DR and cognitive impairment, adjusting for confounders. RESULTS: Severity of DR demonstrated an inverse relationship with cognitive impairment (fully adjusted R2=0.415, P<0.001). Ethnicity contributed most to the variance observed (16%) followed by education (7.3%) and retinopathy status (6.8%). The no/mild DR group had lower cognitive impairment scores on ACE-R (adjusted mean±SE 77.0±1.9) compared with the PDR group (82.5±2.2, P<0.001). The MMSE cutoff scores showed that 12% of the no/mild DR group (n=31) had positive screening results for dementia or significant cognitive impairment compared with 5% in the PDR group (n=6). CONCLUSIONS: Patients with minimal DR demonstrated more cognitive impairment than those with advanced DR. Therefore, the increased prevalence of cognitive impairment in diabetes may be associated with factors other than evident retinal microvascular disease

Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

Rishma Gohil,1,2 Roxanne Crosby-Nwaobi,1,2 Angus Forbes,2 Ben J Burton,3 Philip Hykin,1 Sobha Sivaprasad1,4 1National Institute for Health Research Moorfields Biomedical Research Centre, London, 2Diabetes Nursing, King&rsquo;s College London, London, 3Ophthalmology Department, James Paget University Hospital, Great Yarmouth, 4Laser and Retinal Research Unit, King&rsquo;s College Hospital, London, UK Context: Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD) remains unclear.Aims: The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting.Settings and design: A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact.Materials and methods: A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8) and the patients&rsquo; demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined.Results: The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8), health-related quality of life (EQ-5D-3L), and duration of AMD. Visual acuity changes were rated as less important than one would have expected.Conclusion: The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment. Keyword: macular treatment satisfaction questionnaire, patient related outcome measure, treatment history, quality of life&nbsp