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Optical coherence elastography (OCE) has recently been used to characterize the natural frequencies of delicate tissues (e.g., the in vivo human cornea) with sub-micron tissue oscillation magnitudes. Here, we investigate broadband spectrum sample stimulation using a contact-based piezoelectric transducer (PZT) chirp excitation and compare its performance with a non-contact, air-pulse excitation for OCE measurements on 1.0-7.5% agar phantoms and an ex vivo porcine cornea under intraocular pressures (IOPs) of 5-40 mmHg. The 3-ms duration air-pulse generated a ∼0-840 Hz excitation spectrum, effectively quantifying the first-order natural frequencies in softer samples (e.g., 1.0%-4.0% agar: 239-782 Hz, 198 Hz/%; porcine cornea: 68-414 Hz, 18 Hz/mmHg, IOP: 5-25 mmHg), but displayed limitations in measuring natural frequencies for stiffer samples (e.g., 4.5%-7.5% agar, porcine cornea: IOP ≥ 30 mmHg) or higher order natural frequency components. In contrast, the chirp excitation produced a much wider spectrum (e.g., 0-5000 Hz), enabling the quantification of both first-order natural frequencies (1.0%-7.5% agar: 253-1429 Hz, 181 Hz/%; porcine cornea: 76-1240 Hz, 32 Hz/mmHg, IOP: 5-40 mmHg) and higher order natural frequencies. A modified Bland-Altman analysis (mean versus relative difference in natural frequency) showed a bias of 20.4%, attributed to the additional mass and frequency introduced by the contact nature of the PZT probe. These findings, especially the advantages and limitations of both excitation methods, can be utilized to validate the potential application of natural frequency OCE, paving the way for the ongoing development of biomechanical characterization methods utilizing sub-micron tissue oscillation features., Competing Interests: GL, JX and YH: Weiren Meditech Co., Ltd. (C); JQ. and LA: Weiren Meditech Co., Ltd. (E)., (© 2024 Optica Publishing Group.)

Microliter air-pulse optical coherence elastography (OCE) has recently been proposed for the characterization of soft-tissue biomechanics using transient, sub-nanometer to micrometer-scale natural frequency oscillations. However, previous studies have not been able to provide real-time air-pulse monitoring during OCE natural frequency measurement, which could lead to inaccurate measurement results due to the unknown excitation spectrum. To address this issue, we introduce a dual-channel air-pulse OCE method, with one channel stimulating the sample and the other being simultaneously measured with a pressure sensor. This allows for more accurate natural frequency characterization using the frequency response function, as proven by a comprehensive comparison under different conditions with a diverse range of excitation spectra (from broad to narrow, clean to noisy) as well as a diverse set of sample response spectra. We also demonstrate the capability of the frequency-response analysis in distinguishing samples with different stiffness levels: the dominant natural frequencies increased with agar concentrations (181-359 Hz, concentrations: 1-2%, and maximum displacements: 0.12-0.47 µm) and intraocular pressures (IOPs) for the silicone cornea (333-412 Hz, IOP: 5-40 mmHg, and maximum displacements: 0.41-0.52 µm) under a 200 Pa stimulation pressure. These frequencies remained consistent across different air-pulse durations (3 ms to 35 ms). The dual-channel OCE approach that uses transient, low-pressure stimulation and high-resolution imaging holds the potential to advance our understanding of sample frequency responses, especially when investigating delicate tissues such as the human cornea in vivo ., Competing Interests: GL, JX and YH: Weiren Meditech Co., Ltd. (C); JQ. and LA: Weiren Meditech Co., Ltd. (E)., (© 2024 Optica Publishing Group.)

Assessing corneal biomechanics in vivo has long been a challenge in the field of ophthalmology. Despite recent advances in optical coherence tomography (OCT)-based elastography (OCE) methods, controversy remains regarding the effect of intraocular pressure (IOP) on mechanical wave propagation speed in the cornea. This could be attributed to the complexity of corneal biomechanics and the difficulties associated with conducting in vivo corneal shear-wave OCE measurements. We constructed a simplified artificial eye model with a silicone cornea and controllable IOPs and performed surface wave OCE measurements in radial directions (54-324°) of the silicone cornea at different IOP levels (10-40 mmHg). The results demonstrated increases in wave propagation speeds (mean ± STD) from 6.55 ± 0.09 m/s (10 mmHg) to 9.82 ± 0.19 m/s (40 mmHg), leading to an estimate of Young's modulus, which increased from 145.23 ± 4.43 kPa to 326.44 ± 13.30 kPa. Our implementation of an artificial eye model highlighted that the impact of IOP on Young's modulus (ΔE = 165.59 kPa, IOP: 10-40 mmHg) was more significant than the effect of stretching of the silicone cornea (ΔE = 15.79 kPa, relative elongation: 0.98-6.49%). Our study sheds light on the potential advantages of using an artificial eye model to represent the response of the human cornea during OCE measurement and provides valuable insights into the impact of IOP on wave-based OCE measurement for future in vivo corneal biomechanics studies.

Clinical measurement of corneal biomechanics can aid in the early diagnosis, progression tracking, and treatment evaluation of ocular diseases. Over the past two decades, interdisciplinary collaborations between investigators in optical engineering, analytical biomechanical modeling, and clinical research has expanded our knowledge of corneal biomechanics. These advances have led to innovations in testing methods ( ex vivo , and recently, in vivo) across multiple spatial and strain scales. However, in vivo measurement of corneal biomechanics remains a long-standing challenge and is currently an active area of research. Here, we review the existing and emerging approaches for in vivo corneal biomechanics evaluation, which include corneal applanation methods, such as ocular response analyzer (ORA) and corneal visualization Scheimpflug technology (Corvis ST), Brillouin microscopy, and elastography methods, and the emerging field of optical coherence elastography (OCE). We describe the fundamental concepts, analytical methods, and current clinical status for each of these methods. Finally, we discuss open questions for the current state of in vivo biomechanics assessment techniques and requirements for wider use that will further broaden our understanding of corneal biomechanics for the detection and management of ocular diseases, and improve the safety and efficacy of future clinical practice., Competing Interests: GL, YH, and JX are consultants at Weiren Meditech Co., Ltd. JQ and LA are currently working at Weiren Meditech Co., Ltd. Remaining authors have no disclosures., (© 2023 The Authors.)

The localized application of the riboflavin/UV-A collagen cross-linking (UV-CXL) corneal treatment has been proposed to concentrate the stiffening process only in the compromised regions of the cornea by limiting the epithelium removal and irradiation area. However, current clinical screening devices dedicated to measuring corneal biomechanics cannot provide maps nor spatial-dependent changes of elasticity in corneas when treated locally with UV-CXL. In this study, we leverage our previously reported confocal air-coupled ultrasonic optical coherence elastography (ACUS-OCE) probe to study local changes of corneal elasticity in three cases: untreated, half-CXL-treated, and full-CXL-treated in vivo rabbit corneas (n = 8). We found a significant increase of the shear modulus in the half-treated (>450%) and full-treated (>650%) corneal regions when compared to the non-treated cases. Therefore, the ACUS-OCE technology possesses a great potential in detecting spatially-dependent mechanical properties of the cornea at multiple meridians and generating elastography maps that are clinically relevant for patient-specific treatment planning and monitoring of UV-CXL procedures., Competing Interests: The authors declare no conflicts of interest., (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes., Competing Interests: Authors GL, YH, LA, JX, and JQ were employed by Weiren Meditech Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lan, Shi, Wang, Ma, Cai, Feng, Huang, Gu, An, Xu, Qin and Twa.)

Significance: Both consumers and eye care practitioners need to know how well online optical vendors conform with the accepted standards for quality and safety. We found that almost 1 in 10 prescriptions failed to meet national standards, which is a significant improvement over previous studies., Purpose: The purpose of this study was to assess the accuracy and repeatability of spectacle lens prescriptions ordered from a sample of online vendors., Methods: Spectacle lens prescriptions were ordered by paid participants with no optical training who were masked to the study objectives. The prescription powers ordered (sphere, cylinder, and axis) were statistically sampled from 1000 previously filled prescriptions. A total of 100 orders were placed with each of three online vendors that included a range of high- and low-powered single vision lenses and progressive addition lenses, and duplicate orders to assess repeatability. An independent certified testing laboratory was contracted to assess conformance with voluntary consensus standards (ANSI Z80.1-2015) and Food and Drug Administration drop-ball safety testing. Lenses not meeting these standards were counted as failures., Results: The overall failure rates for the three vendors were 11.2 ± 3.2% (vendor A), 8.0 ± 2.7% (vendor B), and 8.2 ± 2.8% (vendor C). The repeatability for 20 prescriptions ordered five times from each vendor was high, with correlation coefficients greater than 90%. There were no observed lens impact failures., Conclusions: Almost 1 in 10 spectacle lens prescriptions ordered from three online vendors failed to meet national standards for optical quality. Additional studies are needed to assess eyewear ordered online for other important patient-specific variables that can influence visual performance and ultimate acceptability of prescription eyewear, such as lens placement relative to the visual axis, frame fit, and cosmetic acceptability., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Significance: Patients with glaucoma and providers recognized perceived treatment efficacy, patient-provider relationship, psychological stress, instillation skill, good quality of life, and forgetfulness as key determinants of glaucoma adherence. This shared insight could help shape the development of clinical and behavioral interventions for addressing treatment barriers and improving adherence., Purpose: Despite their impact on adherence in glaucoma, sociobehavioral factors may not be adequately explored during clinical consultations. We aimed to elicit consensus between patients and providers around key determinants of adherence and hypothesized that patients would place greater emphasis on sociobehavioral factors compared with providers., Methods: A two-round Delphi survey was used to assess treatment beliefs, barriers, facilitators, motivators, and needs among 18 patients with glaucoma and providers. In round 1, agreement with 46 statements was scored on a 5-point Likert scale (strongly disagree to strongly agree). Statements with which 80% or more of panelists agreed reached consensus and advanced to round 2, where participants were asked to prioritize them based on their importance to treatment., Results: There was consensus regarding the influence of perceived treatment efficacy, good provider relationship, good quality of life, psychological stress, glaucoma knowledge, instillation skill, and forgetfulness on glaucoma adherence. For statements that failed to reach consensus, the Bonferroni-corrected Mann-Whitney U test revealed that the greatest differences between patients and providers pertained to regimen complexity (provider median, 4 [interquartile range {IQR}, 1]; patient median, 1.5 [IQR, 1]; P = .002), instillation skill (providers, 4 [IQR, 0.5]; patients, 2 [IQR, 1]; P = .001), and low motivation (providers, 3 [IQR, 2.25]; patients, 1 [IQR, 0]; P = .003)., Conclusions: Although patients and providers prioritized sociobehavioral factors as key determinants of adherence, disagreement between these groups was observed in other areas. Continued juxtaposition of patient and provider perspectives could spotlight underexplored areas and guide the development of successful interventions for improving adherence., Competing Interests: Conflict of Interest Disclosure: The authors listed (LR) have reported a financial conflict of interest. The sponsor provided financial support but had no role in study design, conduct, analysis and interpretation, or writing. Each of the authors had full access to the study data and takes full responsibility for the presentation in this article., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

In optical coherence elastography (OCE), air-pulse stimulation has been widely used to produce propagation of mechanical waves for elastic characterization of tissues. In this paper, we propose the use of spatial deformation spreading (SDS) on the surface of samples produced by air-pulse stimulation for the OCE of transverse isotropic tissues. Experiments in isotropic tissue-mimicking phantoms and anisotropic chicken tibialis muscle were conducted using a spectral-domain optical coherence tomography system synchronized with a confocal air-pulse stimulation. SDS measurements were compared with wave speeds values calculated at different propagation angles. We found an approximately linear relationship between shear wave speed and SDS in isotropic phantoms, which was confirmed with predictions made by the numerical integration of a wave propagation model. Experimental measurements in chicken muscle show a good agreement between SDS and surface wave speed taken along and across the axis of symmetry of the tissues, also called degree of anisotropy. In summary, these results demonstrated the capabilities of SDS produced by the air-pulse technique in measuring the shear elastic anisotropy of transverse isotropic tissues.

Reliable and quantitative assessment of corneal biomechanics is important for the detection and treatment of corneal disease. The present study evaluates the repeatability and reproducibility of a novel optical coherence tomography (OCT)-based elastography (OCE) method for in vivo quantification of corneal natural frequency in 20 normal human eyes. Sub-micron corneal oscillations were induced by repeated low-force (13 Pa) microliter air pulses at the corneal apex and were observed by common-path phase-sensitive OCT imaging adjacent to a measurement region of 1-6.25 mm 2 . Corneal natural frequencies were quantified using a single degree of freedom model based on the corneal oscillations. Corneal natural frequencies ranged from 234 to 277 Hz (coefficient of variation: 3.2%; n = 286 for a 2.5 × 2.5 mm 2 area; time: 28.6 s). The same natural frequencies can be acquired using a smaller sampling size (n = 9 for 1 mm 2 ) and a shorter time (0.9 s). Spatial distribution and local changes in natural frequencies can be distinguished using denser sampling (e.g., 26 × 41 points for 2.5 × 5 mm 2 ). This novel optical method demonstrates highly repeatable and reliable in vivo measurements of human corneal natural frequencies. While further studies are required to fully characterize anatomical and structural dependencies, this method may be complementary to the current OCE methods used to estimate Young's modulus from strain- or shear-wave-based measurements for the quantitative determination of corneal biomechanics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Significance: A novel imaging technology, dynamic optical coherence elastography (OCE), was adapted for clinical noninvasive measurements of corneal biomechanics., Purpose: Determining corneal biomechanical properties is a long-standing challenge. Elasticity imaging methods have recently been developed and applied for clinical evaluation of soft tissues in cancer detection, atherosclerotic plaque evaluation, surgical guidance, and more. Here, we describe the use of dynamic OCE to characterize mechanical wave propagation in the human cornea in vivo, thus providing a method for clinical determination of corneal biomechanical properties., Methods: High-resolution phase-sensitive optical coherence tomography imaging was combined with microliter air-pulse tissue stimulation to perform dynamic elasticity measurements in 18 eyes of nine participants. Low-pressure (0.1 mmHg), spatiotemporally discreet (150 μm, 800 μs) tissue stimulation produced submicron-scale tissue deformations that were measured at multiple positions over a 1-mm2 area. Surface wave velocity was measured and used to determine tissue stiffness. Elastic wave propagation velocity was measured and evaluated as a function of IOP and central corneal thickness., Results: Submicron corneal surface displacement amplitude (range, 0.005 to 0.5 μm) responses were measured with high sensitivity (0.24 nm). Corneal elastic wave velocity ranged from 2.4 to 4.2 m/s (mean, 3.5; 95% confidence interval, 3.2 to 3.8 m/s) and was correlated with central corneal thickness (r = 0.64, P < .001) and IOP (r = 0.52, P = .02)., Conclusions: Phase-sensitive optical coherence tomography imaging combined with microliter air-pulse mechanical tissue stimulation has sufficient detection sensitivity to observe submicron elastic wave propagation in corneal tissue. These measurements enable in vivo corneal stiffness determinations that will be further studied for use with disease detection and for monitoring clinical interventions., Competing Interests: Conflict of Interest Disclosure: The authors have existing and pending patents related to the subject matter of this work., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

We present an air-coupled ultrasonic radiation force probe co-focused with a phase-sensitive optical coherence tomography (OCT) system for quantitative wave-based elastography. A custom-made 1 MHz spherically focused piezoelectric transducer with a concentric 10 mm wide circular opening allowed for confocal micro-excitation of waves and phase-sensitive OCT imaging. Phantom studies demonstrated the capabilities of this probe to produce quasi-harmonic excitation up to 4 kHz for generation of elastic waves. Experimental results in ocular tissues showed highly detailed 2D and 3D elasticity mapping using this approach with great potential for clinical translation.

Purpose: Currently, the biomechanical properties of the corneo-scleral limbus when the eye-globe deforms are largely unknown. The purpose of this study is to evaluate changes in elasticity of the cornea, sclera, and limbus when subjected to different intraocular pressures (IOP) using wave-based optical coherence elastography (OCE). Special attention was given to the elasticity changes of the limbal region with respect to the elasticity variations in the neighboring corneal and scleral regions., Methods: Continuous harmonic elastic waves (800 Hz) were mechanically induced in the sclera near the corneo-sclera limbus of in situ porcine eye-globes (n = 8). Wave propagation was imaged using a phase-sensitive optical coherence tomography system (PhS-OCT). The eyes were subjected to five different IOP-levels (10, 15, 20, 30, and 40 mm Hg), and spatially distributed propagation velocities were calculated along corneal, limbal, and scleral regions. Finite element analysis (FEA) of the same regions under the same excitation conditions were conducted for further validation of results., Results: FEA demonstrated that the stiffness of the heterogeneous cornea-limbus-sclera transition can be characterized by phase velocity measurements of the elastic waves produced at 800 Hz in the anterior eye. Experimental results revealed that the wave speed in the limbus (cL = 6.5 m/s) is between the cornea (cc = 2.9 m/s) and sclera (cs = 10.0 m/s) at a physiological IOP level (15 mm Hg) and rapidly increases as the IOP level is increased, even surpassing the wave speed in the sclera. Finally, the change in elastic wave speed in the limbus (ΔcL∼18.5 m/s) was greater than in the cornea (Δcc ∼12.6 m/s) and sclera (Δcs∼8.1 m/s) for the same change in IOP., Conclusions: We demonstrated that wave-based OCE can be utilized to assess limbus biomechanical properties. Moreover, experimental evidence showed that the corneo-scleral limbus is highly nonlinear compared to the cornea and sclera when the eye-globe is deformed by an increase of IOP. This may suggest that the limbus has enough structural flexibility to stabilize anterior eye shape during IOP changes.

We demonstrate the use of OCT-based elastography for soft-tissue characterization using natural frequency oscillations. Sub-micrometer to sub-nanometer oscillations were induced in tissue phantoms and human cornea in vivo by perpendicular air-pulse stimulation and observed by common-path OCT imaging (sensitivity: 0.24 nm). Natural frequency and damping ratio were acquired in temporal and frequency domains using a single degree of freedom method. The dominant natural frequency was constant for different stimulation pressures (4-32 Pa) and measured distances (0.3-5.3 mm), and decreased as the sample thickness increased. The dominant natural frequencies of 0.75-2% agar phantoms were 127-774 Hz (mean coefficient of variation [CV]: 0.9%), and correlated with the square root of Young's moduli (16.5-117.8 kPa, mean CV: 5.8%). These preliminary studies show repeatable in vivo corneal natural frequency measurements (259 Hz, CV: 1.9%). This novel OCE approach can distinguish tissues and materials with different mechanical properties using the small-amplitude tissue oscillation features, and is suitable for characterizing delicate tissues in vivo such as the eye., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)