A Noninvasive Clinical Method to Measure in Vivo Mechanical Strains of the Lamina Cribrosa by OCT.

Objective: To measure mechanical strain of the lamina cribrosa (LC) after intraocular pressure (IOP) change produced 1 week after a change in glaucoma medication. Design: Cohort study. Participants: Adult glaucoma patients (23 eyes, 15 patients) prescribed a change in IOP-lowering medication. Intervention: Noninvasive OCT imaging of the eye. Main Outcome Measures: Deformation calculated by digital volume correlation of OCT scans of the LC before and after IOP lowering by medication. Results: Among 23 eyes, 17 eyes of 12 persons had IOP lowering ≥ 3 mmHg (reduced IOP group) with tensile anterior-posterior Ezz strain = 1.0% ± 1.1% (P = 0.003) and compressive radial strain (Err) = -0.3% ± 0.5% (P = 0.012; random effects models accounting inclusion of both eyes in some persons). Maximum in-plane principal (tensile) strain and maximum shear strain in the reduced-IOP group were as follows: Emax = 1.7% ± 1.0% and Γmax = 1.4% ± 0.7%, respectively (both P < 0.0001 vs. zero). Reduced-IOP group strains Emax and Γmax were significantly larger with greater % IOP decrease (P < 0.0001 and P < 0.0001, respectively). The compliances of the Ezz, Emax, and Γmax strain responses, defined as strain normalized by the IOP decrease, were larger with more abnormal perimetric mean deviation or visual field index values (all P ≤ 0.02). Strains were unrelated to age (all P ≥ 0.088). In reduced-IOP eyes, mean LC anterior border posterior movement was only 2.05 µm posteriorly (P = 0.052) and not related to % IOP change (P = 0.94, random effects models). Only Err was significantly related to anterior lamina depth change, becoming more negative with greater posterior LC border change (P = 0.015). Conclusions: Lamina cribrosa mechanical strains can be effectively measured by changes in eye drop medication using OCT and are related to degree of visual function loss in glaucoma. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Long-term Remodeling Response in the Lamina Cribrosa Years after Intraocular Pressure Lowering by Suturelysis after Trabeculectomy.

OBJECTIVE: To measure the remodeling of the lamina cribrosa (LC) years after intraocular pressure (IOP) lowering by suturelysis. DESIGN: Cohort study. PARTICIPANTS: Glaucoma patients were imaged 20 minutes after laser suturelysis after trabeculectomy surgery and at their follow-up appointment 1 to 4 years later (16 image pairs; 15 persons). INTERVENTION: Noninvasive OCT imaging of the eye. MAIN OUTCOME MEASURES: Deformation calculated by correlating OCT scans of the LC immediately after IOP lowering by suturelysis and those acquired years later (defined as remodeling strain). RESULTS: The LC anterior border moved 60.9 ± 54.6 µm into the eye (P = 0.0007), and the LC exhibited regions of large local stretch in the anterior-posterior direction on long-term, maintained IOP lowering, resulting in a mean anterior-posterior remodeling strain of 14.0% ± 21.3% (P = 0.02). This strain and the LC border movement was 14 times and 124 times larger, respectively, than the direct response to IOP lowering by suturelysis. A larger anterior LC border movement was associated with greater mean anterior-posterior remodeling strain (P = 0.004). A thinner retinal nerve fiber layer at suturelysis was also associated with greater mean anterior-posterior remodeling strain at follow-up (P = 0.05). Worsening visual field indexes during follow-up were associated with a greater mean circumferential remodeling strain (P = 0.02), due to regions of large local circumferential stretch of the LC. Eyes with a more compliant LC torsional shear strain response at lysis were associated with worse mean deviation at follow-up (P = 0.03). CONCLUSIONS: Strains and LC border position changes measured years after IOP lowering are far larger than the immediate response to IOP lowering and indicate dramatic remodeling of the LC anatomical structure caused by IOP lowering and glaucoma progression. The remodeling strains indicate substantial local stretch in the anterior-posterior direction and are associated with movement of the LC anterior border into the eye. Eyes with greater direct strain response to IOP lowering, greater glaucoma damage at suturelysis, and greater worsening of visual field at follow-up experienced greater remodeling. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03267849. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A noninvasive clinical method to measure in vivo mechanical strains of the lamina cribrosa by optical coherence tomography.

Objective: To measure mechanical strain of the lamina cribrosa (LC) after intraocular pressure (IOP) change produced one week after a change in glaucoma medication. Design: Cohort study. Participants: Adult glaucoma patients (23 eyes, 15 patients) prescribed a change in IOP-lowering medication. Intervention: Non-invasive optical coherence tomography (OCT) imaging of the eye. Main Outcomes: Deformation calculated by digital volume correlation of OCT scans of the LC before and after IOP lowering by medication. Results: Among 23 eyes, 17 eyes of 12 persons had IOP lowering ≥ 3 mmHg (reduced IOP group) with tensile anterior-posterior E zz strain = 1.0% ± 1.1% (p = 0.003) and compressive radial strain ( E rr ) = -0.3% ± 0.5% (p=0.012; random effects models accounting inclusion of both eyes in some persons). Maximum in-plane principal (tensile) strain and maximum shear strain in the reduced IOP group were: E max = 1.7% ± 1.0% and Γ max = 1.4% ± 0.7%, respectively (both p<0.0001 versus zero). Reduced IOP group strains E max and Γ max were significantly larger with greater %IOP decrease (<0.0001, <0.0001). The compliance of the E zz , E max , and Γ max strain response, defined as strain normalized by the IOP decrease, were larger with more abnormal perimetric mean deviation or visual field index values (all p≥0.02). Strains were unrelated to age (all p≥0.088). In reduced IOP eyes, mean LC anterior border posterior movement was only 2.05 µm posteriorly (p=0.052) and not related to % IOP change (p=0.94, random effects models). Only E rr was significantly related to ALD change, becoming more negative with greater posterior LC border change (p=0.015). Conclusion: LC mechanical strains can be effectively measured by changes in eye drop medication using OCT and are related to degree of visual function loss in glaucoma. Trial Registration: ClinicalTrials.gov Identifier: NCT03267849.

The Curvature, Collagen Network Structure, and Their Relationship to the Pressure-Induced Strain Response of the Human Lamina Cribrosa in Normal and Glaucoma Eyes.

The lamina cribrosa (LC) is a connective tissue in the optic nerve head (ONH). The objective of this study was to measure the curvature and collagen microstructure of the human LC, compare the effects of glaucoma and glaucoma optic nerve damage, and investigate the relationship between the structure and pressure-induced strain response of the LC in glaucoma eyes. Previously, the posterior scleral cups of 10 normal eyes and 16 diagnosed glaucoma eyes were subjected to inflation testing with second harmonic generation (SHG) imaging of the LC and digital volume correlation (DVC) to calculate the strain field. In this study, we applied a custom microstructural analysis algorithm to the maximum intensity projection of SHG images to measure features of the LC beam and pore network. We also estimated the LC curvatures from the anterior surface of the DVC-correlated LC volume. Results showed that the LC in glaucoma eyes had larger curvatures p≤0.03), a smaller average pore area (p = 0.001), greater beam tortuosity (p < 0.0001), and more isotropic beam structure (p = 0.01) than in normal eyes. The difference measured between glaucoma and normal eyes may indicate remodeling of the LC with glaucoma or baseline differences that contribute to the development of glaucomatous axonal damage.

The Strain Response to Intraocular Pressure Decrease in the Lamina Cribrosa of Patients with Glaucoma.

OBJECTIVE: To measure biomechanical strains in the lamina cribrosa (LC) of living human eyes with intraocular pressure (IOP) lowering. DESIGN: Cohort study. PARTICIPANTS: Patients with glaucoma underwent imaging before and after laser suturelysis after trabeculectomy surgery (29 image pairs; 26 persons). INTERVENTION: Noninvasive imaging of the eye. MAIN OUTCOME MEASURES: Strains in optic nerve head tissue and changes in depths of the anterior border of the LC. RESULTS: Intraocular pressure decreases caused the LC to expand in thickness in the anterior-posterior strain (Ezz = 0.94 ± 1.2%; P = 0.00020) and contract in radius in the radial strain (Err = - 0.19 ± 0.33%; P = 0.0043). The mean LC depth did not significantly change with IOP lowering (1.33 ± 6.26 µm; P = 0.26). A larger IOP decrease produced a larger, more tensile Ezz (P < 0.0001), greater maximum principal strain (Emax; P < 0.0001), and greater maximum shear strain (Γmax; P < 0.0001). The average LC depth change was associated with the Γmax and radial-circumferential shear strain (Erθ; P < 0.02) but was not significantly related to tensile or compressive strains. An analysis by clock hour showed that in temporal clock hours 3 to 6, a more anterior LC movement was associated with a more positive Emax, and in clock hours 3, 5, and 6, it was associated with a more positive Γmax. At 10 o'clock, a more posterior LC movement was related to a more positive Emax (P < 0.004). Greater compliance (strain/ΔIOP) of Emax (P = 0.044), Γmax (P = 0.052), and Erθ (P = 0.018) was associated with a thinner retinal nerve fiber layer. Greater compliance of Emax (P = 0.041), Γmax (P = 0.021), Erθ (P = 0.024), and in-plane shear strain (Erz; P = 0.0069) was associated with more negative mean deviations. Greater compliance of Γmax (P = 0.055), Erθ (P = 0.040), and Erz (P = 0.015) was associated with lower visual field indices. CONCLUSIONS: With IOP lowering, the LC moves either into or out of the eye but, on average, expands in thickness and contracts in radius. Shear strains are nearly as substantial as in-plane strains. Biomechanical strains are more compliant in eyes with greater glaucoma damage. This work was registered at ClinicalTrials.gov as NCT03267849.