Does your dermatology classifier know what it doesn't know? Detecting the long-tail of unseen conditions.

Supervised deep learning models have proven to be highly effective in classification of dermatological conditions. These models rely on the availability of abundant labeled training examples. However, in the real-world, many dermatological conditions are individually too infrequent for per-condition classification with supervised learning. Although individually infrequent, these conditions may collectively be common and therefore are clinically significant in aggregate. To prevent models from generating erroneous outputs on such examples, there remains a considerable unmet need for deep learning systems that can better detect such infrequent conditions. These infrequent 'outlier' conditions are seen very rarely (or not at all) during training. In this paper, we frame this task as an out-of-distribution (OOD) detection problem. We set up a benchmark ensuring that outlier conditions are disjoint between the model training, validation, and test sets. Unlike traditional OOD detection benchmarks where the task is to detect dataset distribution shift, we aim at the more challenging task of detecting subtle differences resulting from a different pathology or condition. We propose a novel hierarchical outlier detection (HOD) loss, which assigns multiple abstention classes corresponding to each training outlier class and jointly performs a coarse classification of inliers vs. outliers, along with fine-grained classification of the individual classes. We demonstrate that the proposed HOD loss based approach outperforms leading methods that leverage outlier data during training. Further, performance is significantly boosted by using recent representation learning methods (BiT, SimCLR, MICLe). Further, we explore ensembling strategies for OOD detection and propose a diverse ensemble selection process for the best result. We also perform a subgroup analysis over conditions of varying risk levels and different skin types to investigate how OOD performance changes over each subgroup and demonstrate the gains of our framework in comparison to baseline. Furthermore, we go beyond traditional performance metrics and introduce a cost matrix for model trust analysis to approximate downstream clinical impact. We use this cost matrix to compare the proposed method against the baseline, thereby making a stronger case for its effectiveness in real-world scenarios.

Validation and Clinical Applicability of Whole-Volume Automated Segmentation of Optical Coherence Tomography in Retinal Disease Using Deep Learning.

IMPORTANCE: Quantitative volumetric measures of retinal disease in optical coherence tomography (OCT) scans are infeasible to perform owing to the time required for manual grading. Expert-level deep learning systems for automatic OCT segmentation have recently been developed. However, the potential clinical applicability of these systems is largely unknown. OBJECTIVE: To evaluate a deep learning model for whole-volume segmentation of 4 clinically important pathological features and assess clinical applicability. DESIGN, SETTING, PARTICIPANTS: This diagnostic study used OCT data from 173 patients with a total of 15 558 B-scans, treated at Moorfields Eye Hospital. The data set included 2 common OCT devices and 2 macular conditions: wet age-related macular degeneration (107 scans) and diabetic macular edema (66 scans), covering the full range of severity, and from 3 points during treatment. Two expert graders performed pixel-level segmentations of intraretinal fluid, subretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment, including all B-scans in each OCT volume, taking as long as 50 hours per scan. Quantitative evaluation of whole-volume model segmentations was performed. Qualitative evaluation of clinical applicability by 3 retinal experts was also conducted. Data were collected from June 1, 2012, to January 31, 2017, for set 1 and from January 1 to December 31, 2017, for set 2; graded between November 2018 and January 2020; and analyzed from February 2020 to November 2020. MAIN OUTCOMES AND MEASURES: Rating and stack ranking for clinical applicability by retinal specialists, model-grader agreement for voxelwise segmentations, and total volume evaluated using Dice similarity coefficients, Bland-Altman plots, and intraclass correlation coefficients. RESULTS: Among the 173 patients included in the analysis (92 [53%] women), qualitative assessment found that automated whole-volume segmentation ranked better than or comparable to at least 1 expert grader in 127 scans (73%; 95% CI, 66%-79%). A neutral or positive rating was given to 135 model segmentations (78%; 95% CI, 71%-84%) and 309 expert gradings (2 per scan) (89%; 95% CI, 86%-92%). The model was rated neutrally or positively in 86% to 92% of diabetic macular edema scans and 53% to 87% of age-related macular degeneration scans. Intraclass correlations ranged from 0.33 (95% CI, 0.08-0.96) to 0.96 (95% CI, 0.90-0.99). Dice similarity coefficients ranged from 0.43 (95% CI, 0.29-0.66) to 0.78 (95% CI, 0.57-0.85). CONCLUSIONS AND RELEVANCE: This deep learning-based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research.