Inam Ullah

Inam Ullah, Imran Razzak, Shoaib Jameel

Learning causal models from fragmented biomedical data is challenging because clinical, molecular, and imaging variables are often incomplete or not jointly observed. We propose RetiSEM, a domain-constrained structural equation modelling (SEM) framework for causal graph recovery and mediation analysis under limited multimodal resources. This proposed work organises variables into biologically informed blocks, applies forbidden-edge constraints, and decomposes pathway-level effects into TE, NDE, and NIE components. We evaluate RetiSEM across ten synthetic benchmark scenarios that vary in dimensionality, nonlinearity, causal depth, and pathway structure, together with a fragmented real-world setting that combines NHANES clinical variables with externally derived retinal representations. This approach achieves lower structural error and higher causal accuracy than unconstrained baselines across the synthetic benchmarks. In the real-data analysis, retinal variables behave mainly as downstream biomarker-like indicators, with smaller but detectable indirect effects. These findings support our strategy as an interpretable framework for testing structured causal hypotheses in limited-resource biomedical AI. The code and resources for this work are publicly available at: https://github.com/Inamullah-Colab/ReitSEM.

Inam Ullah, Imran Razzak, Shoaib Jameel

Automated diabetic retinopathy (DR) grading from colour fundus photographs can achieve strong predictive performance, but clinical interpretation requires more than an image-level label. It requires understanding how lesion evidence is distributed around retinal vessels and how this evidence relates to quantitative vascular biomarkers. We present a dual-edge spatial-Jacobian image graph for interpretable DR grading. Each fundus image is represented as a graph node with four aligned evidence streams: AutoMorph vessel information ($X_1$), DR-XAI-style lesion evidence maps ($X_2$), a 128-dimensional lesion-based contrastive image embedding ($X_3$), and AutoMorph morphometric biomarkers ($X_4$). The spatial edge branch ($X_{12}$) encodes vessel-lesion geometry, while the Jacobian branch ($X_{34}$) models embedding-biomarker sensitivity. Lightweight two-token attention fuses both edge families into a final image graph. On 2,910 matched non-augmented APTOS images, the full graph achieves 0.8076 accuracy, 0.8312 quadratic weighted kappa, 0.5915 macro-F1, and 0.9330 adjacent-grade accuracy; referable DR reaches 0.9055 accuracy and 0.9711 AUROC. The framework is positioned as an explainable representation-learning tool for lesion-biomarker hypothesis generation, rather than as a deployment-ready clinical classifier. The code is available at https://github.com/Inamullah-Colab/dual-edge-dr-graph-xai.

Inam Ullah, Imran Razzak, Shoaib Jameel

Diabetic retinopathy (DR) is a local retinal lesion process and a visible manifestation of systemic microvascular injury. Modern retinal AI can grade images accurately, but often leaves unanswered how local lesion evidence, retinal vascular structure, and systemic disease pathways are connected. This paper introduces \emph{Causal-RetiGraph}, a compact biomedical informatics framework that links retinal graph phenotypes with NHANES-anchored pathway modelling. The retinal-image fold constructs an interpretable $X1234$ phenotype from vessel maps, lesion evidence, image embeddings, and AutoMorph biomarkers through spatial $X_{12}$ and Jacobian $X_{34}$ branches. The NHANES fold models systemic exposures, covariates, a same-subject retinal mediator family $R^*$, and downstream outcome families. $X1234$ is used for retinal support and pathway prioritisation, while $R^*$ is used for participant-level pathway summaries. On the retinal fold, $X1234$ achieves 0.9055 binary DR accuracy and 0.9711 AUROC, with graded DR QWK of 0.8312. The results show that lesion and biomarker streams improve contextual retinal representation under scarce and imbalanced data. In NHANES, HbA1c, urine albumin, pulse pressure, fasting glucose, and systolic blood pressure are the strongest binary DR anchors. Participant-level pathway analysis identifies glycaemic--renal and glycaemic--haemodynamic pathways as the clearest mediator-style signals. These results suggest that retinal graph phenotypes can help prioritise systemic pathways in DR while preserving the distinction between image-derived support and same-subject mediation.

Inamullah, Ernesto Elias Vidal Rosas, Imran Razzak et al.

Cardiovascular disease (CVD) remains the leading global cause of mortality, yet current risk stratification methods often fail to detect early, subclinical changes. Previous studies have generally not integrated retinal microvasculature characteristics with comprehensive serum lipidomic profiles as potential indicators of CVD risk. In this study, an innovative imaging omics framework was introduced, combining retinal microvascular traits derived through deep learning based image processing with serum lipidomic data to highlight asymptomatic biomarkers of cardiovascular risk beyond the conventional lipid panel. This represents the first large scale, covariate adjusted and stratified correlation analysis conducted in a healthy population, which is essential for identifying early indicators of disease. Retinal phenotypes were quantified using automated image analysis tools, while serum lipid profiling was performed by Ultra High Performance Liquid Chromatography Electrospray ionization High resolution mass spectrometry (UHPLC ESI HRMS). Strong, age- and sex-independent correlations were established, particularly between average artery width, vessel density, and lipid subclasses such as triacylglycerols (TAGs), diacylglycerols (DAGs), and ceramides (Cers). These associations suggest a converging mechanism of microvascular remodeling under metabolic stress. By linking detailed vascular structural phenotypes to specific lipid species, this study fills a critical gap in the understanding of early CVD pathogenesis. This integration not only offers a novel perspective on microvascular metabolic associations but also presents a significant opportunity for the identification of robust, non-invasive biomarkers. Ultimately, these findings may support improved early detection, targeted prevention, and personalized approaches in cardiovascular healthcare.

Inamullah, Imran Razzak, Shoaib Jameel

The unique vascularized anatomy of the human eye, encased in the retina, provides an opportunity to act as a window for human health. The retinal structure assists in assessing the early detection, monitoring of disease progression and intervention for both ocular and non-ocular diseases. The advancement in imaging technology leveraging Artificial Intelligence has seized this opportunity to bridge the gap between the eye and human health. This track paves the way for unveiling systemic health insight from the ocular system and surrogating non-invasive markers for timely intervention and identification. The new frontiers of oculomics in ophthalmology cover both ocular and systemic diseases, and getting more attention to explore them. In this survey paper, we explore the evolution of retinal imaging techniques, the dire need for the integration of AI-driven analysis, and the shift of retinal imaging from classical techniques to oculomics. We also discuss some hurdles that may be faced in the progression of oculomics, highlighting the research gaps and future directions.