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Introduction: Randomised controlled trials provide evidence that a treatment works. Real world evidence is required to assess if proven treatments are effective in practice., Method: Retrospective data collection on patients given aflibercept for diabetic macular oedema over 3 years from 21 UK hospitals: visual acuity (VA); Index of multiple deprivation score (IMD); injection numbers; protocols used, compared as a cohort and between sites., Results: Complete data: 1742 patients (from 2196 eligible) at 1 year, 860 (from 1270) at 2, 305 (from 506) at 3 years. The median VA improved from 65 to 71, 70, 70 (ETDRS letters) at 1, 2 and 3 years with 6, 9 and 12 injections, respectively. Loss to follow-up: 10% 1 year, 28.8% at 3. Centres varied: baseline: mean age 61-71 years (p < 0.0001); mean IMD score 15-37 (p < 0.0001); mean VA 49-68 (p < 0.0001). Only four centres provided a loading course of five injections at monthly intervals and one 6. This did not alter VA outcome at 1 year. Higher IMD was associated with younger age (p = 0.0023) and worse VA at baseline (p < 0.0001) not total number of injections or change in VA. Lower starting VA, higher IMD and older age were associated with lower adherence (p = 0.0010)., Conclusions: The data showed significant variation between treatment centres for starting age, VA and IMD which influenced adherence and chances of good VA. Once treatment was started IMD did not alter likelihood of improvement. Loading dose intensity did not alter outcome at one year., (© 2021. The Author(s).)

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.

Importance: Threshold of retinal nonperfusion for the development of proliferative diabetic retinopathy (PDR) is unclear., Objectives: To identify a threshold of retinal nonperfusion for the presence of retinal neovascularization and the distribution and area of retinal nonperfusion in eyes with severe nonproliferative diabetic retinopathy (NPDR), PDR, neovascularization of the optic disc (NVD), and retinal neovascularization elsewhere (NVE)., Design, Setting, and Participants: This cross-sectional image analysis study was performed between September 24, 2018, and October 24, 2018, at a multicenter national study in the United Kingdom. Baseline images were obtained from 2 completed randomized clinical trials (Ranibizumab for Diabetic Macular Edema Panretinal Photocoagulation [RDP] study and Clinical Efficacy of Intravitreal Aflibercept vs Panretinal Photocoagulation for Best Corrected Visual Acuity in Patients With Proliferative Diabetic Retinopathy at 52 Weeks [CLARITY] study). The RDP study recruited eyes with severe NPDR between April 1, 2014, and December 31, 2015, and the CLARITY study recruited eyes with PDR between August 22, 2014, and November 20, 2015. Ultra-widefield angiography images of eyes with no prior panretinal photocoagulation treatment were included., Main Outcomes and Measures: The total area of retinal nonperfusion, the area of posterior pole retinal nonperfusion, and the area of peripheral retinal nonperfusion were measured., Results: A total of 92 patients (92 eyes) were included in the study: 59 in the PDR group (mean [SD] age, 42 [15] years; 20 female [33.9%]) and 33 in the NPDR group (mean [SD] age, 63 [10] years; 3 female [9.1%]). Forty eyes had NVE and 19 had NVD with or without NVE. We identified a retinal nonperfusion threshold of 118.3 disc areas (DA) with a specificity of 84.9% (95% CI, 68.1% to 94.9%) for PDR. The median area of retinal nonperfusion was 67.8 DA (95% CI, 44.2 to 107.3 DA) in the NPDR eyes and 147.9 DA (95% CI, 127.4 to 173.5 DA) for eyes with proliferative changes, with a difference of 69.0 DA (95% CI, 42.2 to 97.7 DA; P < .001). No difference was found in the median area of posterior nonperfusion between NPDR and PDR, with a difference of 0 DA (95% CI, -6.7 to 5.2 DA; P = .56). As for peripheral nonperfusion, NPDR eyes measured 64.1 DA and PDR eyes measured 130.6 DA, with a difference of 70.8 DA (95% CI, 48.4 to 94.9 DA; P < .001). Eyes with NVD had the largest total area of retinal nonperfusion, with a difference of 65.1 DA (95% CI, 28.6 to 95.8 DA; P < .001) compared with eyes with only NVE., Conclusions and Relevance: These findings suggest eyes with at least 107.3 DA of nonperfusion are at risk of proliferative disease, and eyes with NVD have the largest area of retinal nonperfusion.

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., (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/)

Purpose: To assess the short-term effects of argon laser on retinal thickening as demonstrated by optical coherence tomography (OCT)., Methods: A prospectively collected consecutive series of patients undergoing routine focal argon laser treatment for sight-threatening diabetic maculopathy had bilateral OCT performed before laser treatment and 1 hour, 24 hours, and 2 weeks after treatment. The main outcome measure was change in retinal thickness in the region of laser treatment., Results: Forty-six eyes were analyzed. There was a small increase in retinal thickness in the treated area 1 hour after laser treatment, with a mean change from before laser treatment of +2.6 microm (95% confidence interval [CI], +0.2 to + 5.0). However, there was a larger change 24 hours after treatment of +39.0 microm (95% CI, +31.6 to + 46.4) and a significant decrease 2 weeks after treatment of -14.6 microm (95% CI, -21.6 to -7.7) from before laser treatment values., Conclusion: Focal argon laser treatment remains the first-line treatment for sight-threatening diabetic maculopathy. This study shows that in the short-term, areas of retinal thickening worsen before settling in response to argon laser treatment as demonstrated by OCT.