Iris Stromal Structural Resilience Following Selective Melanin Modulation: A Conceptual Framework

Iris pigmentation and stromal architecture are biologically related but distinct tissue characteristics. This preprint introduces I-STROMAL, a hypothesis-generating framework for examining whether baseline iris stromal architecture provides additional information about longitudinal structural outcomes following selective melanin modulation beyond that explained by apparent pigmentation, baseline morphology, and relevant clinical characteristics. The framework distinguishes architectural preservation, adaptive morphological change, and pathological structural alteration as possible observational outcomes, without assuming an obligatory biological sequence. Its primary hypothesis addresses the incremental explanatory or predictive contribution of predefined, non-redundant architectural descriptors. Secondary and exploratory hypotheses address pigmentary–structural dissociation and differences in temporal response. Proposed methods include standardized iris photography, anterior segment optical coherence tomography, prespecified anatomical endpoints, assessment of segmentation and pupillary variability, and comparisons of appropriately validated statistical models. No original clinical outcome dataset is analyzed, and no structural-resilience score, tissue-remodeling mechanism, treatment threshold, or safety guarantee is claimed. I-STROMAL is a conceptual research proposal requiring prospective and independent validation, not a peer-reviewed clinical study.