Summary Background The number of individuals with vision impairment worldwide is increasing because of an ageing population. We aimed to systematically identify studies describing the association between vision impairment and mortality, and to assess the association between vision impairment and all-cause mortality. Methods For this systematic review and meta-analysis, we searched MEDLINE (Ovid), Embase, and Global Health database on Feb 1, 2020, for studies published in English between database inception and Feb 1, 2020. We included prospective and retrospective cohort studies that measured the association between vision impairment and all-cause mortality in people aged 40 years or older who were followed up for 1 year or more. In a protocol amendment, we also included randomised controlled trials that met the same criteria as for cohort studies, in which the association between visual impairment and mortality was independent of the study intervention. Studies that did not report age-adjusted mortality data, or that focused only on populations with specific health conditions were excluded. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. We graded the overall certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations framework. We did a random-effects meta-analysis to calculate pooled maximally adjusted hazard ratios (HRs) for all-cause mortality for individuals with a visual acuity of <6/12 versus those with ≥6/12; <6/18 versus those with ≥6/18; <6/60 versus those with ≥6/18; and <6/60 versus those with ≥6/60. Findings Our searches identified 3845 articles, of which 28 studies, representing 30 cohorts (446 088 participants) from 12 countries, were included in the systematic review. The meta-analysis included 17 studies, representing 18 cohorts (47 998 participants). There was variability in the methods used to assess and report vision impairment. Pooled HRs for all-cause mortality were 1·29 (95% CI 1·20–1·39) for visual acuity <6/12 versus ≥6/12, with low heterogeneity between studies (n=15; τ 2 =0·01, I 2 =31·46%); 1·43 (1·22–1·68) for visual acuity <6/18 versus ≥6/18, with low heterogeneity between studies (n=2; τ 2 =0·0, I 2 =0·0%); 1·89 (1·45–2·47) for visual acuity <6/60 versus ≥6/18 (n=1); and 1·02 (0·79–1·32) for visual acuity <6/60 versus ≥6/60 (n=2; τ 2 =0·02, I 2 =25·04%). Three studies received an assessment of low risk of bias across all six domains, and six studies had a high risk of bias in one or more domains. Effect sizes were greater for studies that used best-corrected visual acuity compared with those that used presenting visual acuity as the vision assessment method (p=0·0055), but the effect sizes did no...

Background Neovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options. Methods TIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 μg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms. Discussion The best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy. Trial registration ClinicalTrials.govNCT04663750; EudraCT: 2020-004917-10.

The World Health Organization (WHO) is developing a Package of Eye Care Interventions (PECI) to facilitate the integration of eye care into Universal Health Coverage. This paper presents the results of a systematic review of clinical practice guidelines for cataract in adults, to help inform PECI development. We searched academic and guideline databases, and websites of professional associations, for guidelines published between January 2010 and April 2020. Guidelines were excluded if there was commercial funding or unmanaged conflicts of interest. Quality appraisal was conducted using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool. We identified 3778 reports, 35 related to cataract guidelines, four of which met the inclusion criteria (United Kingdom: 2, United States: 1, Iran: 1). The recommendations across the four guidelines covered pre-operative (43%), intra-operative (37%), and post-operative interventions (20%). Most ‘strong’ recommendations were supported by good quality evidence. Differences in recommendations across guidelines may be attributable to time of publication or regional differences in surgical practice. Few guidelines met the quality criteria, and only three countries were represented. The results of this step of the PECI development process will inform subsequent phases for development of the WHO’s package of evidence-based eye care interventions for cataract.