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REVIEW 4 major objections 4 minor 3 references

Evaluation of In Vivo Subject-Specific Mechanical Modeling of the Optic Nerve Head for Robust Assessment of Ocular Mechanics

T0 review · 4 major / 4 minor · reviewed 2026-08-16 · deepseek-v4-flash

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Pith's one-line read Finite element modeling of two healthy eyes shows scleral stiffness dominates optic nerve head mechanics and Bruch's membrane can be omitted.

desk verdict A careful sensitivity study whose main practical claim—drop Bruch's membrane—is plausible but only tested at one pressure condition, so the abstract overstates the evidence. read the letter →

arxiv 2504.21765 v1 pith:VNNJPNF3 submitted 2025-04-30 physics.med-ph physics.bio-phphysics.comp-ph

Soumaya Ouhsousou , Lucy Q. Shen , Chhavi Saini , Amin Pourasghar , Mengyu Wang , John C. Brigham This is my paper · ORCID
classification physics.med-phphysics.bio-phphysics.comp-ph
keywords opticnerveheadbiomechanicsfiniteelementmodelingsubject-specificeyemodellaminacribrosastrainintraocularpressureintracranialsclerastiffnessBruch'smembrane
verification ladder T0 review T1 audit T2 compute T3 formal

The pith

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The reading

This paper asks which tissue regions must be present in a subject-specific computer model of the optic nerve head to faithfully predict how the lamina cribrosa, retina, and optic nerve deform under pressure. Using two healthy eyes imaged in vivo and finite element analysis with literature-based properties for tissues that are not visible on imaging, it finds that the stiffness of the sclera has the largest influence on the strain response of all three regions, while Bruch's membrane has a negligible effect. The authors conclude that accurate optic nerve head mechanics can be obtained by including only the tissue regions identified as necessary, and they show that the resulting reduced model produces the behavior expected from earlier studies: lamina cribrosa strain increases with both intraocular and intracranial pressure and is highest in the inferior and temporal sectors. The practical consequence would be simpler and more consistent finite element models for studying pressure-related optic nerve head loading in glaucoma.

What carries the argument

The central object is a three-dimensional, subject-specific finite element model of the optic nerve head reconstructed from six radial swept-source OCT slices, embedded in a spherical eye globe sized from each subject's spherical equivalent. Tissues are modeled as homogeneous, isotropic, nearly incompressible materials, with the sclera, lamina cribrosa, pia mater, dura mater, and annular ring treated as Neo-Hookean and the remaining tissues as linear elastic. Two probes carry the argument: a local sensitivity analysis that raises and lowers each tissue's Young's modulus by 25 percent, and binary tests that remove or replace the lowest-impact tissues one at a time. Outcomes are judged by average and peak principal tensile and compressive strains in the four subregions of the lamina cribrosa, in the retina, and in the optic nerve, with peak strains defined as 95th and 5th percentiles to avoid mesh artifacts.

What would settle it

Measure lamina cribrosa strain quantitatively in human eyes in vivo or ex vivo (for example, with OCT-based displacement tracking or marker-based loading) and compare the magnitude and the inferior/temporal pattern with the model's predictions; if the measured strains differ substantially from the predicted values, the tissue-necessity ranking would need revision. Alternatively, repeat the sensitivity and removal tests using subject-specific measured scleral stiffness and measured Bruch's membrane thickness; if sclera stiffness no longer dominates or removing Bruch's membrane changes lamina cribrosa strain well beyond the reported 1.2 percent, the central claim would fail.

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Extended reading notes

Core claim

The central claim is that a finite element model of the optic nerve head built from in vivo imaging of two healthy subjects, with each major ocular tissue assigned a distinct material property, can determine which tissue regions are mechanically necessary. In these models, varying the sclera's Young's modulus by 25 percent produced the largest change in the principal strains of the lamina cribrosa, retina, and optic nerve; removing Bruch's membrane changed lamina cribrosa strains by only about 1.2 percent on average. The paper therefore asserts that accurate ONH mechanical representation can be obtained by including only the tissues identified as necessary, with Bruch's membrane excluded. It supports this by showing that the reduced model reproduces literature-consistent trends: strain in the lamina cribrosa rises when intraocular pressure or intracranial pressure increases, and the highest strains appear in the inferior and temporal subregions.

Load-bearing premise

The ranking of which tissues are necessary assumes that the literature-based material properties and estimated dimensions of the non-visible tissues (posterior lamina cribrosa boundary, pia mater, dura mater, Bruch's membrane, border tissue, annular ring) are representative for the two subjects' eyes; if those inputs are not representative, the sensitivity and removal rankings, and the recommendation to drop Bruch's membrane, could change.

Editorial extensions

If this is right

  • Optic nerve head models can omit Bruch's membrane without materially changing predicted lamina cribrosa, retina, or optic nerve strains, simplifying segmentation while preserving accuracy.
  • Scleral stiffness is the input that matters most: errors in the scleral modulus will propagate into the largest errors in predicted lamina cribrosa strain, so subject-specific characterization of the sclera should be prioritized.
  • For the pia mater, border tissue, and annular ring, geometric presence matters more than precise stiffness values, because their removal changes strains substantially even though their modulus variations do not.
  • The reduced model reproduces the reported increase of lamina cribrosa strain with elevated intraocular and intracranial pressure and the inferior/temporal localization of peak strain, supporting its use in pressure-response studies.
  • A consistent tissue-inclusion standard of this kind could reduce the disagreements among eye models that currently differ in which tissue regions they represent.

Reading between the lines

Editorial extensions of the paper, not claims the author makes directly.

  • Because the paper attributes Bruch's membrane's negligible effect to its thinness and distance from the lamina cribrosa, a parametric sweep of its thickness and stiffness would map the range where that conclusion holds and where it would break.
  • The two-subject demonstration suggests population stability is untested; repeating the removal and sensitivity tests across eyes with varied axial length, age, and lamina cribrosa thickness would show whether the tissue-necessity ranking is general.
  • If scleral stiffness truly dominates the lamina cribrosa response, then non-invasive estimates of peripapillary scleral stiffness could become a clinically useful input for patient-specific glaucoma risk models, a step the paper does not take.
  • The pattern that thin stiff membranes matter less than their geometry would suggest that other models of the eye can safely use literature geometry for such tissues while concentrating measurement effort on the sclera.
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Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, and a circularity audit.

Referee Report

4 major / 4 minor

Summary. The paper builds subject-specific finite element models of the optic nerve head from SS-OCT imaging of two healthy subjects, assigning distinct, literature-based material properties to all major ocular tissues, including several non-visible regions whose geometry is estimated from published data. The authors perform local sensitivity analyses (±25% modulus variations) and binary tissue-removal tests to rank the influence of each tissue on strains in the lamina cribrosa, retina, and optic nerve. They report that scleral stiffness has the largest overall impact and that Bruch's membrane has a negligible effect, then construct a reduced model without Bruch's membrane and evaluate LC strains under an IOP/ICP grid (IOP 10-30 mmHg, ICP 5-15 mmHg), comparing the resulting trends qualitatively with literature. The central claim is that accurate ONH mechanical representation can be obtained by including only the tissues identified as necessary, with scleral stiffness as the most influential input.

Significance. If the claim is established, the paper offers practical guidance for ONH modeling: future in vivo subject-specific models could omit Bruch's membrane and prioritize accurate scleral properties without materially changing predicted LC strains. The study is clearly described, uses clinically plausible imaging data, and does not fit any parameter to the target strain outcomes, avoiding circularity in the sensitivity ranking. The pressure-response trends are consistent with several published studies. However, the significance is tempered by the small sample (two subjects, one shown), the reliance on literature-based geometry and material properties for non-visible tissues, the qualitative nature of the validation, and the fact that the key binary-removal test for Bruch's membrane is performed at a single loading condition.

major comments (4)
  1. [Section 'Effect of Materials on Lamina Cribrosa Mechanics' (Figure 6) and Section 4] The binary removal test for Bruch's membrane is performed only at the baseline loading condition (IOP=20 mmHg, ICP=10 mmHg), where it changes average LC strains by about 1.2%. Section 4 then uses the reduced model over IOP 10-30 mmHg and ICP 5-15 mmHg without re-testing the effect of omitting Bruch's membrane at those pressures. Because the mechanical role of a thin shell may vary with the pressure differential across the eye, the claim that accurate ONH representation omits Bruch's membrane is not supported outside the baseline state. The authors should run the binary removal test across the IOP/ICP grid and report the range of strain change, or explicitly restrict the conclusion to the tested condition.
  2. [Section 4 (Effect of Pressure Variations on Lamina Cribrosa Mechanics)] The validation compares only qualitative trends (strain increases with IOP and ICP, highest strains in inferior and temporal subregions) against literature studies with different loading protocols and species; there is no quantitative comparison and no comparison of the reduced model against the full model on the same pressure grid. The phrase 'accurate ONH mechanical representation' is therefore stronger than the evidence: a full-model/reduced-model comparison would directly quantify the error introduced by omitting Bruch's membrane and would support the central claim.
  3. [Methods, Data Acquisition and first paragraph of Results] The necessity ranking is based on two subjects' eyes, and results from only one subject are shown. The statement that 'all significant observations were consistent for both subjects' is asserted but not documented. Please report the second subject's sensitivity and binary-removal results, for example in supplementary material, or prominently state this limitation in the abstract and conclusions; as written, the generalizability of the tissue-necessity ranking is not verifiable.
  4. [Methods Section 2 and Table 1] The posterior LC boundary and the geometry of the pia mater, dura mater, Bruch's membrane, border tissue, and annular ring are estimated from literature rather than measured for the subjects, and no sensitivity analysis is performed on these geometric parameters. Since the main recommendation (omitting Bruch's membrane) depends on the assumed thickness and position of a non-visible tissue, the robustness of the ranking to the assumed geometry should be tested (e.g., thickness variations) or explicitly acknowledged as a limitation in the abstract and conclusions.
minor comments (4)
  1. [Equation 1] Equation 1 uses an empirical formula for axial length derived from spherical equivalent; please state whether the resulting axial length was compared with any available biometric data for the two subjects, or note that it is an estimate.
  2. [Table in Figure 3] The table in Figure 3 reports strain values as percentages, but the units are not explicitly stated in the table caption; please add a clear statement that all strain values are in percent.
  3. [References (Feola et al., 2016a and 2016b)] The references list Feola et al. 2016a and 2016b with nearly identical titles and journal information; please verify whether these are the same paper cited twice, and if so, consolidate the citations.
  4. [Figure 6 description] Figure 6 plots a single average of the relative change in compressive and tensile strains, but some removed tissues affect these strain components differently; please report the tensile and compressive changes separately or explicitly state that the panel shows their average.

Circularity Check

0 steps flagged · score 2.0 of 10

No load-bearing circularity: the sensitivity and binary-removal rankings are direct forward finite-element outputs with literature-based inputs, and the pressure-response validation is external. The only self-citation is a data-provenance citation, and the 2% threshold is an arbitrary decision rule rather than a circular reduction.

full rationale

The derivation chain is self-contained in the sense required here: tissue mechanical properties (Table 1) are taken from prior independent publications, geometries are segmented from OCT with literature-based dimensions for non-visible tissues, and the sensitivity/binary-removal rankings are direct outputs of forward finite-element simulations at a fixed IOP/ICP. No parameter is fitted to the target strain outcomes, and no 'prediction' is a renamed fit. The pressure-response section compares LC strain trends against external experimental and computational studies (Feola et al. 2017; Midgett et al. 2017; Beotra et al. 2018), so the validation is external rather than circular. The only self-citation is to Li et al. 2017, used solely to document the source of the two subjects' OCT data; this citation is not load-bearing for any mechanical conclusion. The hand-chosen 2% threshold used to label tissues as having 'least effect' or as unnecessary is arbitrary, and the abstract's statement that 'accurate ONH mechanical representation can be obtained by only including those tissue regions identified as necessary' is close to a restatement of that threshold. However, this is a decision-rule/validity limitation rather than a circular reduction, because the threshold is not fitted from the outcomes and the sensitivity ranking itself is an independent simulation result. A genuine validity gap is that the reduced model's exclusion of Bruch's membrane is tested only at the baseline 20/10 mmHg condition (Results Section 1, Figure 6) and is not re-checked across the IOP/ICP grid used for validation in Section 4; this weakens the generalization of the claim but does not make the derivation circular.

Assumptions & free parameters 1 free parameters · 6 assumptions · 0 invented entities

The central claim depends on standard modeling simplifications and on transferring literature values to the two subjects. No new physical entities are introduced, and the only hand-chosen decision criterion is the 2% 'negligible effect' threshold. The material parameters and geometry estimates from prior studies are treated as given inputs rather than fitted outputs.

free parameters (1)
  • Necessity impact threshold = 2% total averaged strain change
    The authors classify tissues with less than 2% total averaged impact on principal strains as having 'least effect' and potentially unnecessary (Sections 1-3). Choosing a different threshold would alter the recommendation to exclude Bruch's membrane, so this hand-chosen value affects the central conclusion.
assumptions (6)
  • domain assumption All ocular tissues are homogeneous and isotropic within each region.
    Methods Section 3 assumes each tissue is homogeneous, isotropic, and nearly incompressible (partially compressible for retina and optic nerve). A preliminary anisotropic test is said to have no significant effect, but results are not shown.
  • domain assumption Baseline material properties from Table 1 (from Wang 2016, Feola 2016, Jin 2018, etc.) are representative for the two subjects.
    The models use literature-based moduli and Poisson's ratios without subject-specific measurement; errors here would directly affect the sensitivity rankings.
  • domain assumption Dimensions of non-visible tissue regions are accurate for the subjects.
    Methods Section 2: posterior LC boundary is not visible in OCT, and pia, dura, Bruch's membrane, border tissue, and annular ring dimensions are set from prior literature; the empirical axial length formula (Equation 1) is used for eye size.
  • domain assumption The constitutive models and boundary conditions (quasi-static, fully bonded interfaces, equatorial supports) capture the mechanics of the ONH under IOP and ICP.
    Methods Section 3 applies standard FE modeling choices; if these are invalid, the computed strain fields and subsequent rankings could change.
  • domain assumption Two healthy subjects are sufficient to generalize the tissue-necessity findings.
    The study draws broad conclusions from n=2 subjects and shows results for only one subject; the consistency claim is not supported by detailed quantitative comparison.
  • domain assumption OCT segmentation of visible tissues is accurate.
    The 3D geometry is built from manual segmentation of six radial OCT slices supervised by ophthalmologists; segmentation errors would propagate into geometry and strains.

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Cite this review

Pith. "Pith review of Evaluation of In Vivo Subject-Specific Mechanical Modeling of the Optic Nerve Head for Robust Assessment of Ocular Mechanics." pith.science (2026). https://pith.science/paper/VNNJPNF3

@misc{pith2026250421765,
  author       = {Pith},
  title        = {Pith review of: Evaluation of In Vivo Subject-Specific Mechanical Modeling of the Optic Nerve Head for Robust Assessment of Ocular Mechanics},
  year         = {2026},
  howpublished = {\url{https://pith.science/paper/VNNJPNF3}},
  note         = {Machine review of arXiv:2504.21765}
}
read the original abstract

To establish the tissue regions necessary to accurately represent the mechanics of the optic nerve head (ONH), imaging data of the ONH from 2 healthy subjects were used to create in vivo subject-specific eye mechanical models considering distinct properties for all major ocular tissues. Tests were performed to evaluate the effect of the material properties and the inclusion of these tissues on the mechanics of the lamina cribrosa (LC), retina, and optic nerve. Then, the LC mechanical response due to variations in intraocular and intracranial pressures was evaluated to validate the modeling approach. The sclera stiffness has the largest impact on the mechanics of the LC, retina, and optic nerve, while Bruchs membrane has a negligible effect on these tissues response. The validation tests showed increased LC strain with increased pressure and highest strains in the inferior and temporal subregion, as seen in literature studies. Consequently, accurate ONH mechanical representation can be obtained by only including those tissue regions identified as necessary.

Figures

Figures reproduced from arXiv: 2504.21765 by the authors.

Figure 1
Figure 1. Example slice from the SS-OCT scan of the optic nerve head with the segmentation shown for all tissue regions evaluated for one of the subjects. After each 2D image was segmented, an arc in the circumferential direction was created defining the interface between the ONH and the eye globe. Closed surfaces bounding each tissue region were then created by linearly interpolating each segmented slice edge in the anterior… view at source ↗
Figure 2
Figure 2. Reconstructed 3D subject-specific eye geometry 3. Eye Mechanical Analysis Assuming all applied forces and other boundary conditions were sufficiently constant to neglect any dynamic effects, standard static finite element analysis was applied to estimate the subject-specific mechanical response (i.e., displacement, stress, and strain) of the eyes due to variations in IOP and ICP. All tissue regions detailed in the p… view at source ↗

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Works this paper leans on

3 extracted references · 2 canonical work pages

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