I.M.N. IANCU

https://www.doi.org/10.59277/RJB.2026.3.02

Independent Researcher, Research alias: TEKTOR, Romania,ORCID: 0009-0008-9519-3146

Abstract. The response of inherited retinal degeneration to gene or genome-editing therapy depends not only on correction of the primary molecular defect but also on the biological state of the retina when treatment is delivered. I propose dynamic retinal competence (DRC) as an operational framework for testing whether a measurable change in retinal response to a standardized perturbation can provide information about later therapeutic rescue beyond conventional baseline measurements. The framework separates therapeutic accessibility, tissue recoverability, treatment interaction, and measurement uncertainty rather than treating a favorable final outcome as evidence for a single mechanism. To make the proposal falsifiable, I also report RETINA-DRC-00R, an exploratory secondary computational reconstruction from exact patient- or eye-level values published in three independent retinal pigment epithelium-specific 65 kDa protein (RPE65)/voretigene neparvovec cohorts, comprising 18 study-local patients and 32 eye-level records across the three source studies. Models were evaluated by leave-one-patient-out validation, keeping both eyes of each participant in the same fold; no missing values were imputed. A multidimensional baseline model did not robustly outperform the best single baseline predictor across the reconstructed cohorts. One eye-level Oxford sensitivity analysis favored the multidimensional model after exclusion of a one-month follow-up case, but the advantage disappeared after patient-level aggregation. These results do not validate DRC as a clinical predictor; instead, they delimit the conditions that a future confirmatory study must satisfy. The principal claim is therefore narrow: dynamic pre-therapeutic state is a testable candidate source of incremental predictive information, not an established causal mediator or validated clinical biomarker.

Key words: Inherited retinal degeneration, dynamic retinal competence, RPE65, voretigene neparvovec, optoretinography, gene therapy, identifiability, patient-grouped validation

Corresponding author’s e-mail: iancu.mircea.nicolae@gmail.com