BackgroundAge-related macular degeneration (AMD) in its late stages is a leading cause of sight loss in developed countries. Some previous studies have suggested that metformin may be associated with a reduced risk of developing AMD, but the evidence is inconclusive.AimsTo explore the relationship between metformin use and development of AMD among patients with type 2 diabetes in the UK.MethodsA large, population-based retrospective open cohort study with a time-dependent exposure design was carried out using IQVIA Medical Research Data, 1995–2019. Patients aged ≥40 with diagnosed type 2 diabetes were included.The exposed group was those prescribed metformin (with or without any other antidiabetic medications); the comparator (unexposed) group was those prescribed other antidiabetic medications only. The exposure status was treated as time varying, collected at 3-monthly time intervals.Extended Cox proportional hazards regression was used to calculate the adjusted HRs for development of the outcome, newly diagnosed AMD.ResultsA total of 173 689 patients, 57% men, mean (SD) age 62.8 (11.6) years, with incident type 2 diabetes and a record of one or more antidiabetic medications were included in the study. Median follow-up was 4.8 (IQR 2.3–8.3, range 0.5–23.8) years. 3111 (1.8%) patients developed AMD. The adjusted HR for diagnosis of AMD was 1.02 (95% CI 0.92 to 1.12) in patients prescribed metformin (with or without other antidiabetic medications) compared with those prescribed any other antidiabetic medication only.ConclusionWe found no evidence that metformin was associated with risk of AMD in primary care patients requiring treatment for type 2 diabetes.

IntroductionRecent years have witnessed an upsurge of demand in eye care services in the UK. With a large proportion of patients referred to Hospital Eye Services (HES) for diagnostics and disease management, the referral process results in unnecessary referrals from erroneous diagnoses and delays in access to appropriate treatment. A potential solution is a teleophthalmology digital referral pathway linking community optometry and HES.Methods and analysisThe HERMES study (Teleophthalmology-enabled and artificial intelligence-ready referral pathway for community optometry referrals of retinal disease: a cluster randomised superiority trial with a linked diagnostic accuracy study) is a cluster randomised clinical trial for evaluating the effectiveness of a teleophthalmology referral pathway between community optometry and HES for retinal diseases. Nested within HERMES is a diagnostic accuracy study, which assesses the accuracy of an artificial intelligence (AI) decision support system (DSS) for automated diagnosis and referral recommendation. A postimplementation, observational substudy, a within-trial economic evaluation and discrete choice experiment will assess the feasibility of implementation of both digital technologies within a real-life setting. Patients with a suspicion of retinal disease, undergoing eye examination and optical coherence tomography (OCT) scans, will be recruited across 24 optometry practices in the UK. Optometry practices will be randomised to standard care or teleophthalmology. The primary outcome is the proportion of false-positive referrals (unnecessary HES visits) in the current referral pathway compared with the teleophthalmology referral pathway. OCT scans will be interpreted by the AI DSS, which provides a diagnosis and referral decision and the primary outcome for the AI diagnostic study is diagnostic accuracy of the referral decision made by the Moorfields-DeepMind AI system. Secondary outcomes relate to inappropriate referral rate, cost-effectiveness analyses and human–computer interaction (HCI) analyses.Ethics and disseminationEthical approval was obtained from the London—Bromley Research Ethics Committee (REC 20/LO/1299). Findings will be reported through academic journals in ophthalmology, health services research and HCI.Trial registration numberISRCTN18106677 (protocol V.1.1).

Aims Several observational studies have examined the potential protective effect of angiotensin‐converting enzyme inhibitor (ACE‐I) use on the risk of age‐related macular degeneration (AMD) and have reported contradictory results owing to confounding and time‐related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE‐I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. Methods In this study, 53 832 and 43 106 new users of ACE‐I and CCB were included between 1995 and 2019, respectively. In an on‐treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow‐up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE‐I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. Results During a median follow‐up of 2 years (interquartile range 1–5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2–2.6) and 2.2 (2.0–2.4) per 1000 person‐years among the weighted new users of ACE‐I and CCB, respectively. There was no association of ACE‐I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on‐treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90–1.27] and 0.87 [0.71–1.07], respectively). Conclusion We found no evidence that the use of ACE‐I is associated with risk of AMD in patients with hypertension.

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