Histologic validation of optical coherence tomography-based three-dimensional morphometric measurements of the human optic nerve head: Methodology and preliminary results

Fazio, Massimo A.; Gardiner, Stuart Keith; Bruno, Luigi; Hubbard, Meredith; Bianco, Gianfranco; Karuppanan, Udayakumar; Kim, Jihee; Hamdaoui, Mustapha El; Grytz, Rafael; Downs, J Crawford C; Girkin, Christopher A.

doi:10.1016/j.exer.2021.108475

Cited by 14 publications

(8 citation statements)

References 43 publications

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“…Another possible explanation for the differences in rotation angle is that there is an error in our automated OCT measurement of rotation angle. To investigate this issue, the rotation angle was calculated using an independent automated and histologically validated OCT method (41). Similar results were observed suggesting strongly that the rotation angle is not larger in eyes of the high myopic group compared to eyes in the mild and no myopia group (data not shown, personal communication with Massimo Fazio-June 2020).…”

Section: Discussionmentioning

confidence: 55%

Comparison of Optic Disc Ovality Index and Rotation Angle Measurements in Myopic Eyes Using Photography and OCT Based Techniques

Rezapour

Tran²,

Bowd³

et al. 2022

Front. Med.

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PurposeTo compare optic nerve head (ONH) ovality index and rotation angle measurements based on semi-automated delineation of the clinical ONH margin derived from photographs and automated BMO configuration derived from optical coherence tomography (OCT) images in healthy and glaucomatous eyes with high-, mild- and no axial myopia.MethodsOne hundred seventy-five healthy and glaucomatous eyes of 146 study participants enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optic disc photographs and Spectralis OCT ONH scans acquired on the same day were stratified by level of axial myopia (non-myopic [n = 56, axial length (AL) <24 mm], mild-myopic [n = 58, AL 24–26 mm] and high-myopic [n = 32, AL >26 mm]. The clinical disc margin of each photograph was manually annotated, and semi-automated measurements were recorded of the ovality index and rotation angle based on a best-fit ellipse generated using ImageJ software. These semi-automated photograph-based measurements were compared to ovality index and rotation angle generated from custom automated BMO-based analysis using segmented OCT ONH volumes. R2 values from linear mixed effects models were used to describe the associations between semi-automated, photograph-based and automated OCT-based measurements.ResultsAverage (95% CI) axial length was 23.3 (23.0, 23.3) mm, 24.8 (24.7, 25.0) mm and 26.8 (26.6, 27.0) mm in non-myopic, mild-myopic and high-myopic eyes, respectively (ANOVA, p ≤ 0.001 for all). The R2 association (95% CI) between semi-automated photograph-based and automated OCT-based assessment of ONH OI for all eyes was [0.26 (0.16, 0.36); p < 0.001]. This association was weakest in non-myopic eyes [0.09 (0.01, 0.26); p = 0.02], followed by mild-myopic eyes [0.13 (0.02, 0.29); p = 0.004] and strongest in high-myopic eyes [0.40 (0.19, 0.60); p < 0.001]. No significant associations were found between photography- and OCT-based assessment of rotation angle with R2 values ranging from 0.00 (0.00, 0.08) in non-myopic eyes to 0.03 (0.00, 0.21) in high-myopic eyes (all associations p ≥ 0.33).ConclusionsAgreement between photograph-based and automated OCT-based ONH morphology measurements is limited, suggesting that these methods cannot be used interchangeably for characterizing myopic changes in the ONH.

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Section: Discussionmentioning

confidence: 55%

Comparison of Optic Disc Ovality Index and Rotation Angle Measurements in Myopic Eyes Using Photography and OCT Based Techniques

Rezapour

Tran²,

Bowd³

et al. 2022

Front. Med.

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“… 43 However, the differences between live and postmortem tissue in thickness and composition suggest the need for testing of living ONH. 84 We and others have developed a method to estimate LC strains in living eyes using OCT and digital volume correlation analysis of radial ONH images after suture lysis or trabeculectomy. 85 , 86 This research suggests that glaucoma eyes are not uniformly stiffer in LC strain response to IOP than non-glaucoma eyes.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Guan

Pease

Quillen

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose To measure quantitatively changes in lamina cribrosa (LC) cell and connective tissue structure in human glaucoma eyes. Methods We studied 27 glaucoma and 19 age-matched non-glaucoma postmortem eyes. In 25 eyes, LC cross-sections were examined by confocal and multiphoton microscopy to quantify structures identified by anti-glial fibrillary acidic protein (GFAP), phalloidin-labeled F-actin, nuclear 4′,6-diamidino-2-phenylindole (DAPI), and by second harmonic generation imaging of LC beams. Additional light and transmission electron microscopy were performed in 21 eyes to confirm features of LC remodeling, including immunolabeling by anti-SOX9 and anti-collagen IV. All glaucoma eyes had detailed clinical histories of open-angle glaucoma status, and degree of axon loss was quantified in retrolaminar optic nerve cross-sections. Results Within LC pores, the proportionate area of both GFAP and F-actin processes was significantly lower in glaucoma eyes than in controls ( P = 0.01). Nuclei were rounder (lower median aspect ratio) in glaucoma specimens ( P = 0.02). In models assessing degree of glaucoma damage, F-actin process width was significantly wider in glaucoma eyes with more damage ( P = 0.024), average LC beam width decreased with worse glaucoma damage ( P = 0.042), and nuclear count per square millimeter rose with worse damage ( P = 0.019). The greater cell count in LC pores represented 92.3% astrocytes by SOX9 labeling. The results are consistent with replacement of axons in LC pores by basement membrane labeled by anti-collagen IV and in-migrating astrocytes. Conclusions Alteration in LC structure in glaucoma involves migration of astrocytes into axonal bundles, change in astrocyte orientation and processes, production of basement membrane material, and thinning of connective tissue beams.

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“…Second, although the 3D reconstruction methodology that forms the morphological basis for the LC microstructure, sclera, and pia geometries is consistent with the tissue morphology in vivo, 105 there is some artifact due to tissue processing, fixation, and embedding for histologic reconstruction. 105 …”

Section: Discussionmentioning

confidence: 99%

Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues

Karimi

Razaghi

Rahmati

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose The laminar region of the optic nerve head (ONH), thought to be the site of damage to the retinal ganglion cell axons in glaucoma, is continuously loaded on its anterior and posterior surfaces by dynamic intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSFP), respectively. Thus, translaminar pressure (TLP; TLP = IOP-CSFP) has been proposed as a glaucoma risk factor. Methods Three eye-specific finite element models of the posterior human eye were constructed, including full 3D microstructures of the load-bearing lamina cribrosa (LC) with interspersed laminar neural tissues (NTs), and heterogeneous, anisotropic, hyperelastic material formulations for the surrounding peripapillary sclera and adjacent pia. ONH biomechanical responses were simulated using three combinations of IOP and CSFP loadings consistent with posture change from sitting to supine. Results Results show that tensile, compressive, and shear stresses and strains in the ONH were higher in the supine position compared to the sitting position ( P < 0.05). In addition, LC beams bear three to five times more TLP-driven stress than interspersed laminar NT, whereas laminar NT exhibit three to five times greater strain than supporting LC ( P < 0.05). Compared with CSFP, IOP drove approximately four times greater stress and strain in the LC, NT, and peripapillary sclera, normalized per mm Hg pressure change. In addition, IOP drove approximately three-fold greater scleral canal expansion and anterior-posterior laminar deformation than CSFP per mm Hg ( P < 0.05). Conclusions Whereas TLP has been hypothesized to play a prominent role in ONH biomechanics, the IOP and CSFP effects are not equivalent, as IOP-driven stress, strain, and deformation play a more dominant role than CSFP effects.

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Histologic validation of optical coherence tomography-based three-dimensional morphometric measurements of the human optic nerve head: Methodology and preliminary results

Cited by 14 publications

References 43 publications

Comparison of Optic Disc Ovality Index and Rotation Angle Measurements in Myopic Eyes Using Photography and OCT Based Techniques

Comparison of Optic Disc Ovality Index and Rotation Angle Measurements in Myopic Eyes Using Photography and OCT Based Techniques

Quantitative Microstructural Analysis of Cellular and Tissue Remodeling in Human Glaucoma Optic Nerve Head

Relative Contributions of Intraocular and Cerebrospinal Fluid Pressures to the Biomechanics of the Lamina Cribrosa and Laminar Neural Tissues

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