3D Growth and Remodeling Theory Explains Posterior Staphyloma Formation from Local Scleral Weakening under Normal Intraocular Pressure

Core Concepts

Local scleral weakening is sufficient to trigger the development of posterior staphylomas under normal intraocular pressure, as predicted by 3D growth and remodeling theory.

Abstract

The study used a finite element model of the posterior pole of the eye and a growth and remodeling (G&R) framework to investigate the potential mechanism behind the development of posterior staphylomas. The key findings are:

A local weakening of the ground substance matrix within the peripapillary sclera was a sufficient trigger to elicit either stable or unstable eye growth, resulting in the formation of posterior staphylomas.

The final shape of the simulated posterior staphyloma closely resembled a Type-III staphyloma, also known as a peripapillary staphyloma, with notable features including ectatic outpouching of the peripapillary sclera, a characteristic change in scleral curvature at the staphyloma ridge, and drastic thinning of the sclera within the staphyloma region.

An increase in the growth parameter (governing the rate of mass turnover) led to less pronounced deformations and a more stable posterior staphyloma, suggesting the importance of determining patient-specific growth parameters for predicting staphyloma formation and progression.

The study explored two distinct types of growth - volumetric growth and mass density growth. Mass density growth resulted in a thinner peripapillary sclera compared to volumetric growth, indicating the potential importance of understanding the predominant mode of growth in staphyloma formation.

Overall, the study provides a computational framework based on 3D growth and remodeling theory that could help enhance our understanding of the pathophysiology of posterior staphylomas and guide the development of novel treatment strategies.

Stats

The study reported the following key metrics and figures:
"We found a notable change in scleral curvature, a shift in collagen fiber distribution from a ratio of 90:10 of circumferential to meridional fibers to 75:10, and a thinning of the PPS from 0.50 mm to an average of 0.08 mm (an 84% reduction in thickness)."
"In scenario 2 and 3 where the growth parameter was increased from kσ = 2 ∙10⁻⁴ days⁻¹ to kσ = 2 ∙10⁻³ days⁻¹, we observed that following an initial rise in collagen fiber stress/growth stimulus in the PPS region due to the reduction of the shear stiffness of the ground matrix, the collagen fiber stress in both, the meridional and circumferential directions, gradually returned to their homeostatic level, resulting in growth stimuli close to zero."
"Mass density growth (scenario 3) resulted in a thinner PPS region (58% reduction from 0.50 mm to 0.21 mm) compared to a 30% reduction in average PPS thickness from 0.50 mm to 0.35 mm in the case of transmural volumetric growth (scenario 2)."

Quotes

"A local scleral defect could be the sole driving factor for the formation and development of posterior staphylomas."
"An increase in growth parameter kσ from 2 ∙10⁻⁴ days⁻¹ (in scenario 1) to 2 ∙10⁻³ days⁻¹ (in scenario 2 and 3) resulted in less pronounced deformations of the posterior pole of the eye, leading to a smaller posterior staphyloma after 13.7 years of G&R."
"Mass density growth resulted in a thinner PPS region (58% reduction from 0.50 mm to 0.21 mm) compared to a 30% reduction in average PPS thickness from 0.50 mm to 0.35 mm in the case of transmural volumetric growth."

Key Insights Distilled From

3D Growth and Remodeling Theory Supports the Hypothesis of Staphyloma Formation from Local Scleral Weakening under Normal Intraocular Pressure

by Fabi... at arxiv.org 04-05-2024

https://arxiv.org/pdf/2404.03330.pdf

Deeper Inquiries

What other factors, such as the choroid or Bruch's membrane, could potentially contribute to the development of posterior staphylomas, and how could they be incorporated into the computational framework?

In addition to scleral weakening, factors like the choroid and Bruch's membrane could play a role in the development of posterior staphylomas. The choroid provides oxygen and nutrients to the sclera and could influence its structural integrity. Thinning of the choroid, as seen in staphylomas, could lead to local scleral thinning and decreased resistance to intraocular pressure (IOP). On the other hand, Bruch's membrane, if excessively growing, could compress the choroid against the sclera, causing thinning of the choroid and pushing the sclera posteriorly in areas of weakness.
To incorporate these factors into the computational framework, the model could be expanded to include the mechanical properties and interactions of the choroid and Bruch's membrane with the sclera. This would involve developing constitutive equations and biomechanical properties specific to these tissues, considering their contributions to the overall biomechanics of the eye. By integrating these components into the model, researchers can simulate the combined effects of scleral weakening, choroidal thinning, and Bruch's membrane alterations on the development of staphylomas.

How could the proposed computational model be validated and refined using longitudinal clinical data, such as changes in the shape of the posterior pole observed through optical coherence tomography (OCT) scans?

To validate and refine the computational model using longitudinal clinical data from OCT scans, researchers could follow these steps:

Data Collection: Obtain longitudinal OCT scans of patients with varying degrees of myopia and staphylomas to track changes in the shape of the posterior pole over time.

Image Processing: Process the OCT images to extract relevant geometric data, such as scleral thickness, curvature, and staphyloma morphology.

Model Calibration: Use the longitudinal data to calibrate the computational model by adjusting parameters to match the observed changes in the posterior pole shape.

Model Validation: Compare the model predictions with the longitudinal clinical data to assess the model's accuracy in capturing the progression of staphylomas over time.

Refinement: Refine the model by incorporating feedback from the validation process, adjusting parameters, and improving the model's predictive capabilities.

By iteratively comparing model predictions with clinical data, researchers can enhance the model's fidelity and predictive power, leading to a more accurate representation of staphyloma development.

Could the insights gained from this study on the role of scleral weakening in staphyloma formation inspire the development of novel treatment strategies, such as targeted scleral reinforcement or collagen crosslinking, to prevent or slow the progression of this condition?

The insights from this study on the role of scleral weakening in staphyloma formation could indeed inspire the development of novel treatment strategies. Targeted scleral reinforcement, where a piece of donor sclera is attached to the recipient sclera to provide additional support, could be explored as a potential treatment option. This reinforcement could help stabilize the weakened scleral region and prevent further staphyloma progression.
Collagen crosslinking, a technique that strengthens collagen fibers in the sclera, could also be considered. By enhancing the structural integrity of the sclera through crosslinking, the progression of staphylomas may be slowed or halted. This approach could potentially reduce the risk of complications associated with staphylomas, such as myopic traction maculopathy.
Overall, the study's findings could pave the way for personalized treatment strategies that target the underlying mechanisms of staphyloma formation, offering new avenues for managing and potentially preventing the development of this vision-threatening condition.