Demographic and Clinical Factors that Influence the Visual Response to Anti-Vascular Endothelial Growth Factor Therapy in Patients with Neovascular Age-Related Macular Degeneration: A Systematic Review

BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of blind registrations in the developed world. Standard therapy includes the use of anti-vascular endothelial growth factor (anti-VEGF) drugs, and whilst the clinical efficacy is well established, there is variability in the clinical effect of visual outcome. The purpose of this systematic review is to identify whether there is evidence for the influence of demographic and clinical factors on the effectiveness of anti-VEGF therapy in patients with nAMD, in settings comparable to the National Health Service (NHS). METHODS: This systematic review followed the PRISMA guidelines for systematic reviews. Electronic databases Medline, EMBASE, Web of Science, CINAHL and the Cochrane Library were searched for studies dated from 2005 onwards. Studies were appraised using the Newcastle–Ottawa Score, and a narrative synthesis was used. ELIGIBILITY CRITERIA: Population: Patients with nAMD being treated with anti-VEGF therapy. Comparator: Presence or absence of potential predictive demographic and clinical factors. Settings: Comparable settings to NHS hospitals. Outcomes: Predicting demographic and clinical factors. Study designs: Randomised controlled trials, prospective cohort studies, retrospective cohort studies and case series dated from 2005. RESULTS: Thirty papers were identified in this review. The evidence suggests that the number of anti-VEGF injections that patients receive, age and lesion size at baseline are factors that influence how effective anti-VEGF therapy is in the short and long term. There was also evidence that suggested that baseline visual acuity influenced the effectiveness of anti-VEGF therapy at longer time points of more than 2 years. Due to a lack of standardised statistical reporting among the included studies, it was not possible to undertake a meaningful statistical synthesis or meta-analysis. CONCLUSIONS: This review has demonstrated that there is some evidence of clinical and demographic factors that affect the effectiveness of anti-VEGF therapy and hence variation in visual acuity (VA) outcome. However, this review was unable to identify as wide a range of factors as was hoped. The findings of this review are important because some of the factors, such as VA and lesion size at diagnosis and the number of injections, are potentially modifiable through improvements in early diagnosis and service provision. Future work also needs to focus on the importance of this variation, such as the effect on patients’ quality of life, and how variation can be minimised. SYSTEMATIC REVIEW REGISTRATION: This review has been registered with PROSPERO (Registration number CRD42018094191). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40123-020-00288-0) contains supplementary material, which is available to authorized users.