Directional drift in biologically meaningful vector planes: A proposed geometric framework for early detection of subthreshold disease

BACKGROUND: Most conventional diagnostic systems rely on fixed thresholds to differentiate disease states from normal. However, early pathological changes may begin before these thresholds are crossed. Therefore, a system that works in this pre-threshold state can potentially lead to earlier diagnosis. OBJECTIVE: To propose and evaluate a geometric framework that models early disease as a directional drift from a physiological plane to a pathological plane, allowing for pre-threshold detection using biologically interpretable variables. METHODS: In this modeling study on synthetic data derived from published clinical trends, two clinically meaningful variables were used to define a 2D feature space. The model was applied to a synthetic dataset of 4000 eyes divided into four phenotypes: normal stable (NS), early disease stable (ED_S), early disease progressive (ED_P), and pre-threshold progressive (PT_P). A physiological plane was constructed using range-normalized values from the NS group. A canonical disease vector was derived from the ED_P group. Each subject's follow-up data was transformed into a subject-specific drift vector, and the Composite Drift Score (CDS) was calculated as the product of directional alignment (Directional Emphasis Multiplier, DEM) and a Magnitude-to-Noise Ratio (MNR). RESULTS: CDS increased significantly over follow-ups in both ED_P and PT_P, distinguishing them from the two stable cohorts (p < 0.001). DEM and MNR components showed consistent trends, with progressive cases exhibiting higher alignment with the disease vector and supra-noise magnitude of change. Visual and statistical analyses confirmed early drift detection even within numerically normal ranges. CONCLUSION: In this early modeling study based on simulation data, we could quantify the directional drift with a unitless, interpretable metric (CDS) and its derivatives. It showed similar trends in pre-threshold groups as early disease groups, showing potential for further evaluation.