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Martin Buist

Publications and source records attributed to Martin Buist.

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Myelin Distribution at the Optic Nerve Myelination Transition Zone Influences Axonal Biomechanics

Purpose: The lamina cribrosa (LC) is considered the initial site of glaucomatous retinal ganglion cell (RGC) injury, and is also the region where unmyelinated RGC axons become myelinated. Here we sought to use finite element (FE) modeling to investigate how the configuration of the myelination transition zone (MTZ) influences the mechanical insult to RGC axons. Methods: A multiscale FE framework was developed to investigate the biomechanical effect of myelin distribution on IOP-induced axonal stress and strain at the MTZ. An anatomically based macro-scale FE eye model was used to compute LC deformations under 15 and 45 mmHg IOP. These deformations were then applied to micro-scale models of the posterior LC, consisting of axons, myelin sheaths, and surrounding matrix. Four distinct MTZ boundary configurations were simulated: one flat and three with random posterior offsets of 3, 6, or 9 μm, representing potential physiological variations. IOP-induced effective axonal strains and stresses were quantified across the different MTZ configurations. Results: Under IOP loading, axons exhibited longitudinal compression and transverse stretch, with marked effective stress and strain discontinuities at the myelin boundary. Across all models, the unmyelinated region exhibited higher effective stress and strain than the myelinated region, and this mechanical discontinuity increased with larger MTZ offsets. Conclusions: Glaucoma-associated demyelination has been previously suggested to precede RNFL thinning. Here we have shown that the MTZ configuration directly influences RGC axonal mechanics. Whether different MTZ profiles can initiate glaucomatous injury, whether demyelination accelerates disease progression, or whether both mechanisms contribute, remains to be determined.

cs.CE

AI to Identify Strain-sensitive Regions of the Optic Nerve Head Linked to Functional Loss in Glaucoma

Objective: (1) To assess whether ONH biomechanics improves prediction of three progressive visual field loss patterns in glaucoma; (2) to use explainable AI to identify strain-sensitive ONH regions contributing to these predictions. Methods: We recruited 237 glaucoma subjects. The ONH of one eye was imaged under two conditions: (1) primary gaze and (2) primary gaze with IOP elevated to ~35 mmHg via ophthalmo-dynamometry. Glaucoma experts classified the subjects into four categories based on the presence of specific visual field defects: (1) superior nasal step (N=26), (2) superior partial arcuate (N=62), (3) full superior hemifield defect (N=25), and (4) other/non-specific defects (N=124). Automatic ONH tissue segmentation and digital volume correlation were used to compute IOP-induced neural tissue and lamina cribrosa (LC) strains. Biomechanical and structural features were input to a Geometric Deep Learning model. Three classification tasks were performed to detect: (1) superior nasal step, (2) superior partial arcuate, (3) full superior hemifield defect. For each task, the data were split into 80% training and 20% testing sets. Area under the curve (AUC) was used to assess performance. Explainable AI techniques were employed to highlight the ONH regions most critical to each classification. Results: Models achieved high AUCs of 0.77-0.88, showing that ONH strain improved VF loss prediction beyond morphology alone. The inferior and inferotemporal rim were identified as key strain-sensitive regions, contributing most to visual field loss prediction and showing progressive expansion with increasing disease severity. Conclusion and Relevance: ONH strain enhances prediction of glaucomatous VF loss patterns. Neuroretinal rim, rather than the LC, was the most critical region contributing to model predictions.

cs.LG

Impact of Optic Nerve Tortuosity, Globe Proptosis, and Size on Retinal Ganglion Cell Thickness Across General, Glaucoma, and Myopic Populations: Insights from the UK Biobank

Purpose: To investigate the impact of optic nerve tortuosity (ONT), and the interaction of globe proptosis and globe size on retinal ganglion cell (RGC) thickness, using Retinal Nerve Fiber Layer (RNFL) thickness, across general, glaucoma, and myopic populations. Methods: We analyzed 17,940 eyes from the UKBiobank cohort (ID 76442), including 72 glaucoma and 2475 myopic eyes. AI models segmented structures from 3D optical coherence tomography (OCT) scans and magnetic resonance images (MRI). RNFL thickness was derived from OCT scans and corrected for ocular magnification, was derived from OCT. From MRIs, we extracted: ONT, globe proptosis, axial length, and a novel interzygomatic line-to-posterior pole (ILPP) distance, a composite marker of globe proptosis and size. GEE models assessed associations between orbital and retinal features across all populations. Results: Segmentation models achieved Dice coefficients over 0.94 for both MRI and OCT. RNFL thickness was positively correlated with both ONT and ILPP distance (r = 0.065, p < 0.001, and r = 0.206, p < 0.001 respectively). The same was true for glaucoma (r = 0.040, p = 0.74, and r = 0.224, p = 0.059), and for myopia (r = 0.069, p < 0.001, and r = 0.100, p < 0.0001). GEE models revealed straighter optic nerves and shorter ILPP distance as predictive of thinner RNFL in all populations. Conclusions: This study emphasizes the impact of ONT, globe size, and proptosis on retinal health, suggesting RNFL thinning may arise from biomechanical stress due to straighter optic nerves or reduced ILPP distance, particularly in glaucoma or myopia. The novel ILPP metric, integrating globe size and position, shows potential as a biomarker for axonal health. These findings highlight the role of orbit structures in RGC axonal health and warrant further exploration of the biomechanical relationship between the orbit and optic nerve.

physics.med-ph

Introducing the Biomechanics-Function Relationship in Glaucoma: Improved Visual Field Loss Predictions from intraocular pressure-induced Neural Tissue Strains

Objective. (1) To assess whether neural tissue structure and biomechanics could predict functional loss in glaucoma; (2) To evaluate the importance of biomechanics in making such predictions. Design, Setting and Participants. We recruited 238 glaucoma subjects. For one eye of each subject, we imaged the optic nerve head (ONH) using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation. Main Outcomes: We utilized automatic segmentation of optic nerve head (ONH) tissues and digital volume correlation (DVC) analysis to compute intraocular pressure (IOP)-induced neural tissue strains. A robust geometric deep learning approach, known as Point-Net, was employed to predict the full Humphrey 24-2 pattern standard deviation (PSD) maps from ONH structural and biomechanical information. For each point in each PSD map, we predicted whether it exhibited no defect or a PSD value of less than 5%. Predictive performance was evaluated using 5-fold cross-validation and the F1-score. We compared the model's performance with and without the inclusion of IOP-induced strains to assess the impact of biomechanics on prediction accuracy. Results: Integrating biomechanical (IOP-induced neural tissue strains) and structural (tissue morphology and neural tissues thickness) information yielded a significantly better predictive model (F1-score: 0.76+-0.02) across validation subjects, as opposed to relying only on structural information, which resulted in a significantly lower F1-score of 0.71+-0.02 (p < 0.05). Conclusion: Our study has shown that the integration of biomechanical data can significantly improve the accuracy of visual field loss predictions. This highlights the importance of the biomechanics-function relationship in glaucoma, and suggests that biomechanics may serve as a crucial indicator for the development and progression of glaucoma.

eess.IV

Are Macula or Optic Nerve Head Structures better at Diagnosing Glaucoma? An Answer using AI and Wide-Field Optical Coherence Tomography

Purpose: (1) To develop a deep learning algorithm to automatically segment structures of the optic nerve head (ONH) and macula in 3D wide-field optical coherence tomography (OCT) scans; (2) To assess whether 3D macula or ONH structures (or the combination of both) provide the best diagnostic power for glaucoma. Methods: A cross-sectional comparative study was performed which included wide-field swept-source OCT scans from 319 glaucoma subjects and 298 non-glaucoma subjects. All scans were compensated to improve deep-tissue visibility. We developed a deep learning algorithm to automatically label all major ONH tissue structures by using 270 manually annotated B-scans for training. The performance of our algorithm was assessed using the Dice coefficient (DC). A glaucoma classification algorithm (3D CNN) was then designed using a combination of 500 OCT volumes and their corresponding automatically segmented masks. This algorithm was trained and tested on 3 datasets: OCT scans cropped to contain the macular tissues only, those to contain the ONH tissues only, and the full wide-field OCT scans. The classification performance for each dataset was reported using the AUC. Results: Our segmentation algorithm was able to segment ONH and macular tissues with a DC of 0.94 $\pm$ 0.003. The classification algorithm was best able to diagnose glaucoma using wide-field 3D-OCT volumes with an AUC of 0.99 $\pm$ 0.01, followed by ONH volumes with an AUC of 0.93 $\pm$ 0.06, and finally macular volumes with an AUC of 0.91 $\pm$ 0.11. Conclusions: this study showed that using wide-field OCT as compared to the typical OCT images containing just the ONH or macular may allow for a significantly improved glaucoma diagnosis. This may encourage the mainstream adoption of 3D wide-field OCT scans. For clinical AI studies that use traditional machines, we would recommend the use of ONH scans as opposed to macula scans.

eess.IV