Optical coherence tomography imaging biomarkers associated with neovascular age-related macular degeneration: a systematic review

Abstract

The aim of this systematic literature review is twofold, (1) detail the impact of retinal biomarkers identifiable via optical coherence tomography (OCT) on disease progression and response to treatment in neovascular age-related macular degeneration (nAMD) and (2) establish which biomarkers are currently identifiable by artificial intelligence (AI) models and the utilisation of this technology. Following the PRISMA guidelines, PubMed was searched for peer-reviewed publications dated between January 2016 and January 2022. Population: Patients diagnosed with nAMD with OCT imaging. Settings: Comparable settings to NHS hospitals. Study designs: Randomised controlled trials, prospective/retrospective cohort studies and review articles. From 228 articles, 130 were full-text reviewed, 50 were removed for falling outside the scope of this review with 10 added from the author’s inventory, resulting in the inclusion of 90 articles. From 9 biomarkers identified; intraretinal fluid (IRF), subretinal fluid, pigment epithelial detachment, subretinal hyperreflective material (SHRM), retinal pigmental epithelial (RPE) atrophy, drusen, outer retinal tabulation (ORT), hyperreflective foci (HF) and retinal thickness, 5 are considered pertinent to nAMD disease progression; IRF, SHRM, drusen, ORT and HF. A number of these biomarkers can be classified using current AI models. Significant retinal biomarkers pertinent to disease activity and progression in nAMD are identifiable via OCT; IRF being the most important in terms of the significant impact on visual outcome. Incorporating AI into ophthalmology practice is a promising advancement towards automated and reproducible analyses of OCT data with the ability to diagnose disease and predict future disease conversion.Systematic Review Registration: This review has been registered with PROSPERO (registration ID: CRD42021233200).

Treatment of age‐related macular degeneration with aflibercept using a treat, extend and fixed protocol; A 4‐year study of treatment outcomes, durability, safety and quality of life (An extension to the MATE randomised controlled trial)

“…At the discretion of the investigator, extension of the retreatment interval was allowed if stability of signs, such as sub retinal fluid was suspected. The presence of disease activity at outset of treatment is associated with a poor outcome but some biomarkers such as sub retinal fluid if present during the disease journey, may be tolerated, if stable, with no apparent adverse outcomes at least in the medium term (Hanson et al, 2022). Explanations for this burden of treatment include how the MATE‐EX study may have been influenced by the COVID‐19 pandemic so that further extensions of a retreatment interval in some were not tried, or the retreatment criteria being too intolerant of potential markers of disease activity (when activity was not present) or an unusual participant population.…”

Systematic Review of Neovascular Age-Related Macular Degeneration Disease Activity Criteria Use to Shorten, Maintain or Extend Treatment Intervals with Anti-VEGF in Clinical Trials: Implications for Clinical Practice

“…Nine of the 12 clinical trials used a change in macular fluid as a disease activity criterion. Qualitative interpretation of structural OCT images for nAMD disease biomarkers is well established in clinical practice as a way of determining improvement, stability or worsening of nAMD disease activity [ 23 ]. However, a recent review identified 11 features or biomarkers, some with more robust evidence base to support their use over other less well-established biomarkers where consensus is still lacking [ 23 ].…”

“…Qualitative interpretation of structural OCT images for nAMD disease biomarkers is well established in clinical practice as a way of determining improvement, stability or worsening of nAMD disease activity [ 23 ]. However, a recent review identified 11 features or biomarkers, some with more robust evidence base to support their use over other less well-established biomarkers where consensus is still lacking [ 23 ]. Even when considering intraretinal fluid as an imaging biomarker of nAMD disease activity, clinicians need to attempt to distinguish IRF associated with atrophy and tubulation from IRF associated with worsening exudative, nAMD.…”

Correlation of Aqueous, Vitreous, and Serum Protein Levels in Patients With Retinal Diseases

“…Biomarkers have emerged as valuable tools in ophthalmology, providing measurable indicators of disease processes and treatment responses. 1 Although imaging is widely used in the study of retinal diseases, 2 – 5 it is not suitable for detecting the molecular changes associated with ocular pathophysiology. By complementing imaging investigations, molecular factors (including proteins, lipids, metabolites, miRNAs, and extracellular DNA, for example) in aqueous humor (AH) and vitreous humor (VH) have the potential to offer insights into the pathophysiology of retinal disorders.…”