| AI in Clinical Medicine, ISSN 2819-7437 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, AI Clin Med and Elmer Press Inc |
| Journal website https://aicm.elmerpub.com |
Original Article
Volume 2, January 2026, e38
Fidelity, Robustness, and Plausibility of Post-Hoc Explanations for Diabetic Retinopathy Grading: An Empirical Application of the Clinical-Explainable Artificial Intelligence Evaluation Framework
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Tables
| Split | Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Total |
|---|---|---|---|---|---|---|
| Training | 486 | 128 | 206 | 194 | 66 | 1,080 |
| Validation | 54 | 12 | 28 | 20 | 6 | 120 |
| Test | 174 | 46 | 92 | 68 | 20 | 400 |
| Parameter | Value |
|---|---|
| CNN: convolutional neural network; LR: learning rate; QWK: quadratic weighted kappa; ReLU: rectified linear unit; ResNet: residual network. | |
| Primary architecture | 4-block CNN (32→64→128→256 channels); each block 3 × 3 convolution, batch normalization, ReLU, 2 × 2 max pooling; 390,661 parameters |
| Input and normalization | 64 × 64 × 3; intensities scaled to 0–1; channel-wise standardization implemented as the first network layer |
| Pretrained weights | None (trained from scratch) |
| Pooling/classifier head | Global average pooling → dropout (P = 0.4) → linear (256→5) |
| Loss function | Class-weighted cross-entropy (weights inversely proportional to class frequency) |
| Optimizer | Adam (initial LR 10−3, weight decay 10−4); batch size 64 |
| LR schedule | ReduceLROnPlateau (factor 0.5, patience 8 epochs, monitored on validation loss) |
| Data augmentation | Horizontal flip (P = 0.5); rotation by 90°, 180°, or 270° (P = 0.3) |
| Max epochs/early stopping | 150 max; patience 25 epochs on validation QWK |
| Random seeds | 42 (primary); 7, 123, 2024, and 31337 (replicates) |
| Epochs actually trained | 49 for seed 42 (best checkpoint at epoch 24); 48–64 across the five seeds |
| Comparator architecture | ResNet-18 trained from scratch; first convolution 3 × 3 with stride 2, no initial max pooling (4 × 4 final feature map); 11.2 million parameters; seeds 42, 7, and 123; identical training procedure; 33–46 epochs trained |
| Item | Setting |
|---|---|
| AUC: area under the curve; CI: confidence interval; CNN: convolutional neural network; CPUs: central processing units; Grad-CAM: Gradient-weighted Class Activation Mapping; LIME: Local Interpretable Model-agnostic Explanations; ReLU: rectified linear unit; ResNet: residual network; SHAP: SHapley Additive exPlanations. | |
| Grad-CAM | Captum LayerGradCam on the output of the final convolutional block (CNN: block 4, 4 × 4 × 256; ResNet-18: layer 4, 4 × 4 × 512); ReLU applied to the weighted activation map; bilinear upsampling to 64 × 64. Resolution ablation: penultimate block (8 × 8). |
| LIME | lime_image LimeImageExplainer; quickshift segmentation (kernel size 2, maximum distance 6, ratio 0.5, seed 0; median 28 superpixels); hidden superpixels replaced by their mean color; 1,000 perturbation samples; explainer seed 0 (seed 1 for the explainer-seed floor); pixel value = surrogate weight of its superpixel for the target class. |
| SHAP | GradientExplainer (expected gradients); fixed background of 32 training images; 200 samples; seed 0 (seed 1 for the explainer-seed floor); attributions summed over color channels. |
| Explained class | Class predicted for the clean image; held fixed for noisy-input and randomized-model explanations. |
| Images | 40 test images (eight per true grade) selected at random with a fixed seed; identical for all methods, models, and seeds. |
| Input perturbation | Additive Gaussian noise, σ = 0.05 on the 0–1 scale, per pixel and channel, clipped to [0, 1]; three fixed realizations per image, identical for all methods, models, and seeds. |
| Deletion/insertion | 64 steps of 64 pixels; replacement image = Gaussian blur (σ = 4 pixels) of the same image; target-class softmax probability; trapezoidal AUC over the fraction of pixels (0–1). Reference rankings: random (mean of 3) and center-prior. |
| Sanity check | Re-initialization of (a) the final convolutional block and classification layer, or (b) all layers; Spearman correlation of absolute-value maps. |
| Background-attention mask | Channel-mean intensity > 15/255; morphological opening (3 × 3, one iteration); hole filling. |
| Statistics | Image as unit; 95% percentile bootstrap CIs (5,000 resamples); two-sided Wilcoxon signed-rank tests with Holm adjustment within each family of three tests. |
| Software | Python 3.13.16; PyTorch 2.14.1; torchvision 0.29.1; Captum 0.9.0; LIME 0.2.0.1; SHAP 0.53.0; scikit-image 0.26.0; scikit-learn 1.9.1; SciPy 1.18.1; NumPy 2.5.3. All computation on CPUs. |
| Dimension | Tested in this study? | Protocol used/reason not tested |
|---|---|---|
| AUC: area under the curve; XAI: explainable artificial intelligence. | ||
| 1. Fidelity | Yes | Deletion/insertion AUC compared with random and center-prior rankings; model-randomization sanity check for all three methods |
| 2. Robustness | Yes | Spearman stability under Gaussian noise (σ = 0.05; three matched realizations) at native and 4 × 4-pooled resolution |
| 3. Plausibility | Partially (background-attention check only) | Share of attribution inside the fundus disk compared with the disk-area share; does not assess lesion localization, which requires lesion annotations or a reader study |
| 4. Actionability | No | Requires measuring change in clinician behavior or patient outcome under real/simulated deployment |
| 5. Equity | No | RetinaMNIST provides no demographic or device subgroup metadata (e.g., sex, age, ethnicity, imaging device) |
| 6. Regulatory readiness | No | Requires assessment against a specific jurisdiction’s documentation and oversight requirements; outside the scope of this technical analysis |
| Severity grade | Precision | Recall | F1-score | Support (n) |
|---|---|---|---|---|
| CNN: convolutional neural network; DR: diabetic retinopathy. | ||||
| Grade 0 (no DR) | 0.836 | 0.730 | 0.779 | 174 |
| Grade 1 (mild) | 0.238 | 0.326 | 0.275 | 46 |
| Grade 2 (moderate) | 0.380 | 0.413 | 0.396 | 92 |
| Grade 3 (severe) | 0.390 | 0.338 | 0.362 | 68 |
| Grade 4 (proliferative) | 0.192 | 0.250 | 0.217 | 20 |
| Macro average | 0.407 | 0.411 | 0.406 | 400 |
| Weighted average | 0.554 | 0.520 | 0.534 | 400 |
| Dimension/metric | Grad-CAM | LIME | SHAP |
|---|---|---|---|
| Values are means with 95% bootstrap confidence intervals over n = 40 images (primary CNN, seed 42) unless stated; P values are Holm-adjusted Wilcoxon signed-rank tests. Reference rankings: random 0.500 (0.499, 0.501), center-prior 0.513 (0.499, 0.527) (combined fidelity score). Penultimate-layer (8 × 8) Grad-CAM: fidelity 0.556 (0.543, 0.572), robustness (native) 0.687 (0.608, 0.760), pooled 0.701 (0.612, 0.779). Sanity-check n < 40 for Grad-CAM because randomized models produced all-zero maps for the remaining images. Mean disk-area share 0.700. AUC: area under the curve; CNN: convolutional neural network; Grad-CAM: Gradient-weighted Class Activation Mapping; LIME: Local Interpretable Model-agnostic Explanations; SHAP: SHapley Additive exPlanations; ρ: Spearman rank correlation. | |||
| Fidelity: combined deletion/insertion score | 0.545 (0.534, 0.558) | 0.504 (0.497, 0.510) | 0.538 (0.528, 0.550) |
| Fidelity: deletion AUC (lower = better) | 0.433 (0.374, 0.496) | 0.479 (0.415, 0.544) | 0.456 (0.392, 0.523) |
| Fidelity: insertion AUC (higher = better) | 0.523 (0.458, 0.590) | 0.486 (0.421, 0.554) | 0.532 (0.466, 0.600) |
| Fidelity minus random ranking (paired) | 0.045 (0.033, 0.058) P < 0.001 | 0.003 (−0.004, 0.010) P = 0.36 | 0.038 (0.028, 0.050) P < 0.001 |
| Fidelity minus center-prior ranking (paired) | 0.032 (0.020, 0.045) | −0.009 (−0.027, 0.007) | 0.025 (0.008, 0.043) |
| Sanity check: ρ, trained vs. top-randomized model | −0.120 (−0.221, −0.013) (n = 35) | 0.335 (0.255, 0.411) | 0.386 (0.366, 0.406) |
| Sanity check: ρ, trained vs. fully randomized model | 0.269 (0.140, 0.386) (n = 22) | 0.357 (0.271, 0.437) | 0.311 (0.291, 0.331) |
| Explainer-seed floor: ρ, two seeds, clean image | 1 (deterministic) | 0.991 (0.986, 0.994) | 0.935 (0.928, 0.941) |
| Robustness: ρ, clean vs. noisy, native 64 × 64 | 0.786 (0.726, 0.840) | 0.097 (0.048, 0.149) | 0.254 (0.235, 0.274) |
| Robustness: ρ, clean vs. noisy, pooled to 4 × 4 | 0.767 (0.704, 0.823) | 0.171 (0.084, 0.254) | 0.739 (0.670, 0.797) |
| Robustness (native), prediction unchanged (n = 18) | 0.871 (0.812, 0.924) | 0.092 (−0.001, 0.185) | 0.296 (0.266, 0.326) |
| Robustness (native), prediction changed (n = 22) | 0.716 (0.629, 0.797) | 0.102 (0.048, 0.156) | 0.219 (0.205, 0.235) |
| Background attention: share of attribution in fundus disk | 0.786 (0.764, 0.806) | 0.846 (0.815, 0.874) | 0.888 (0.865, 0.909) |
| Background attention: in-disk share minus disk-area share (paired) | 0.086 (0.069, 0.103) P < 0.001 | 0.146 (0.115, 0.175) P < 0.001 | 0.188 (0.174, 0.200) P < 0.001 |
| Images with positive paired difference (of 40) | 36 | 35 | 40 |
| Metric | Model | Grad-CAM | LIME | SHAP |
|---|---|---|---|---|
| CNN values are the mean ± standard deviation, across the five seeds (42, 7, 123, 2024, 31337), of each model’s 40-image mean; each model was evaluated on the same 40 images with the same noise realizations. CNN: convolutional neural network; ResNet: residual network; SD: standard deviation; ρ: Spearman rank correlation; AUC: area under the curve; CNN: convolutional neural network; Grad-CAM: Gradient-weighted Class Activation Mapping; LIME: Local Interpretable Model-agnostic Explanations; SHAP: SHapley Additive exPlanations; ρ: Spearman rank correlation. | ||||
| Fidelity: combined score | CNN, 2 seeds (mean ± SD) | 0.543 ± 0.003 | 0.502 ± 0.003 | 0.536 ± 0.003 |
| Fidelity minus random ranking | CNN, 2 seeds (mean ± SD) | 0.043 ± 0.002 | 0.002 ± 0.002 | 0.036 ± 0.002 |
| Sanity check: ρ vs. top-randomized model | CNN, 2 seeds (mean ± SD) | −0.097 ± 0.033 | 0.355 ± 0.028 | 0.393 ± 0.010 |
| Robustness: ρ, native resolution | CNN, 2 seeds (mean ± SD) | 0.725 ± 0.087 | 0.043 ± 0.076 | 0.254 ± 0.000 |
| Robustness: ρ, pooled to 4 × 4 | CNN, 2 seeds (mean ± SD) | 0.704 ± 0.088 | 0.088 ± 0.117 | 0.707 ± 0.045 |
| In-disk share minus disk-area share | CNN, 2 seeds (mean ± SD) | 0.087 ± 0.001 | 0.129 ± 0.024 | 0.190 ± 0.003 |