Unraveling the deep learning gearbox in optical coherence tomography image segmentation towards explainable artificial intelligence.

Machine learning has greatly facilitated the analysis of medical data, while the internal operations usually remain intransparent. To better comprehend these opaque procedures, a convolutional neural network for optical coherence tomography image segmentation was enhanced with a Traceable Relevance Explainability (T-REX) technique. The proposed application was based on three components: ground truth generation by multiple graders, calculation of Hamming distances among graders and the machine learning algorithm, as well as a smart data visualization ('neural recording'). An overall average variability of 1.75% between the human graders and the algorithm was found, slightly minor to 2.02% among human graders. The ambiguity in ground truth had noteworthy impact on machine learning results, which could be visualized. The convolutional neural network balanced between graders and allowed for modifiable predictions dependent on the compartment. Using the proposed T-REX setup, machine learning processes could be rendered more transparent and understandable, possibly leading to optimized applications.

Challenging a Myth and Misconception: Red-Light Vision in Rats.

Due to the lack of L-cones in the rodent retina, it is generally assumed that red light is invisible to rodents. Thus, red lights and red filter foils are widely used in rodent husbandry and experimentation allowing researchers to observe animals in an environment that is thought to appear dark to the animals. To better understand red-light vision in rodents, we assessed retinal sensitivity of pigmented and albino rats to far-red light by electroretinogram. We examined the sensitivity to red light not only on the light- but also dark-adapted retina, as red observation lights in husbandry are used during the dark phase of the light cycle. Intriguingly, both rods and cones of pigmented as well as albino rats show a retinal response to red light, with a high sensitivity of the dark-adapted retina and large electroretinogram responses in the mesopic range. Our results challenge the misconception of rodents being red-light blind. Researchers and housing facilities should rethink the use of red observation lights at night.

A 3D model to evaluate retinal nerve fiber layer thickness deviations caused by the displacement of optical coherence tomography circular scans in cynomolgus monkeys (Macaca fascicularis).

The main objective of the study was to analyze deviations in retinal nerve fiber layer (RNFL) thickness measurements caused by the displacement of circular optic disc optical coherence tomography scans. High-density radial scans of the optic nerve heads of cynomolgus monkeys were acquired. The retinal nerve fiber layer was manually segmented, and a surface plot of the discrete coordinates was generated. From this plot, the RNFL thicknesses were calculated and compared between accurately centered and intentionally displaced circle scans. Circle scan displacement caused circumpapillary retinal nerve fiber layer thickness deviations of increasing magnitude with increasing center offset. As opposed to the human eye, horizontal displacement resulted in larger RNFL thickness deviations than vertical displacement in cynomolgus monkeys. Acquisition of high-density radial scans allowed for the mathematical reconstruction and modelling of the nerve fiber layer and extrapolation of its thickness. Accurate and strictly repeatable circle scan placement is critical to obtain reproducible values, which is essential for longitudinal studies.

Retinal Features in Cynomolgus Macaques (Macaca fascicularis) Assessed by Using Scanning Laser Ophthalmoscopy and Spectral Domain Optical Coherence Tomography.

Cynomolgus macaques are an important and commonly used species in preclinical toxicology studies, but structural reports of in vivo retinal findings are rare in this species. The purpose of this study was to diminish this gap and document optical coherence tomography and scanning laser ophthalmoscopy imaging data in the healthy posterior pole of cynomolgus monkeys' eyes at predose examinations. The current study is a retrospective assessment of baseline spectral domain OCT data obtained from the 768 eyes of 384 cynomolgus monkeys (192 males and 192 females) of Mauritian origin. The data set was obtained from studies conducted over a 4-y period in the context of ocular safety evaluations of various compounds under preclinical development. The most prevalent findings were the presence of Bergmeister papilla and intravitreal hyperreflective spots. Less common findings included disorganization of retinal zones, abnormalities of the retinal vasculature, partial posterior vitreous detachment, and abnormally shaped foveal pits. Thoughtful consideration of these physiologic findings will aid in distinguishing normal features from toxic outcomes in future preclinical ophthalmic studies.

Macular thickness measurements of healthy, naïve cynomolgus monkeys assessed with spectral-domain optical coherence tomography (SD-OCT).

The purpose of this study was to measure central macular thickness in an unprecedented number of cynomolgus monkeys. Macular thickness was measured with Heidelberg spectral-domain OCT in 320 eyes of healthy and treatment-naïve cynomolgus monkeys (80 males and 80 females). The macula was successfully measured in all 320 eyes. Macular thickness was not significantly different between the sexes. The mean central macular thickness was 244 µm (+/- 21 µm). Macular thicknesses in the quadrants were 327 +/-17 µm (temporal inner), 339 +/- 17 µm (inferior inner), 341 +/- 14 µm (superior inner), 341 +/-18 µm (nasal inner), and 299 +/- 20 µm (temporal outer), 320 +/- 16 µm (superior outer), 332 +/-23 µm (inferior outer), and 337 +/-18 µm (nasal outer). Highly significant differences between the nasal and temporal quadrants were detected. This study successfully demonstrated the feasibility of retinal thickness measurements in healthy cynomolgus monkeys. The present findings indicate that the macula is thicker in cynomolgus monkeys than in humans and provide important normative data for future studies.