Several important diseases and treatments of the cornea present primarily on a micromechanical level. Here, a technique called temporal phase decorrelation OCT is used to observe micromechanical weakening in the cornea after refractive surgery. This technique uses conventional OCT systems without hardware additions and may be readily adopted to enable earlier detection of disease and optimization of treatments.
Both disease and treatment of the cornea alter its microstructural and biomechanical properties. Previous work showed that dynamic light scattering (DLS) reflects changes in the cornea with respect to crosslinking treatment and post-surgical healing in vivo. However, due to the complex structure of the corneal stroma, the exact mechanisms which give rise to the DLS signal are unclear. This work attempts to determine the cause of DLS in the cornea by comparing the scattering signal under different conditions. The conclusions drawn from these studies inform the use of OCT-based dynamic light scattering measurements for corneal assessment.
While previously published work demonstrated the overall sensitivity of phase decorrelation optical coherence tomography (PhD-OCT) to crosslinking (CXL) in the cornea, it did not capitalize on the depth-resolving capability of PhD-OCT. Here, PhD-OCT was used to observe the depth-dependent differences in accelerated crosslinking efficiency with and without supplemental oxygen. Traditional crosslinking showed good crosslink formation in the anterior stroma. For accelerated CXL with supplemental oxygen, a significant stiffening effect was seen throughout the stroma. No stiffening was observed in accelerated CXL without supplemental oxygen or sham treatment. Thus, PhD-OCT may observe depth-dependent, protocol-specific changes in corneal tissue due to crosslinking.
The structure and composition of the corneal nerves in health and disease have been extensively studied, however, study of corneal nerve function in living systems has been challenging and limited. Here, we demonstrate non-contact, longitudinal imaging of in vivo murine corneal nerve signaling and in vivo stimulus-response. These developments have the potential to allow for new studies of changes to corneal nerve function in disease and damage, and for better assessment of therapies to treat dysfunction and diminished nerve function.
Corneal biomechanical properties are of great importance in the structural homeostasis of the cornea, the principle focusing element of the eye. Because of the exquisite relationship between corneal geometry and optical performance, alterations in these properties have direct consequences for human visual function. The precision and safety of corneal refractive surgery procedures are highly influenced by inter-individual differences in these properties, and focal corneal weakness is a key feature of corneal ectatic diseases such as keratoconus. This presentation will highlight clinical applications of corneal elasticity imaging and advances in the implementation of an applanation-based approach to optical coherence elastography.
The morphology and histology of the corneal nerves in health and disease has been extensively studied, however, the function of these nerves has only been studied in a limited fashion with electrophysiology of the ciliary nerves or calcium reporter dyes in ex vivo corneas. Here, we present non-contact methods for imaging the genetically encoded calcium indicator GCaMP6f in murine corneal nerves both in situ in ex vivo globes and in vivo. These tools have great potential to improve understanding of diseases of the corneal nerves and the development of therapies for diminished neural function.
Changes in the protein aggregation within the ocular lens may be responsible for both presbyopia and cataracts. Treatments for these conditions are under development, but are likely to be most effective when administered early in the disease. Therefore, a technique compatible with in vivo use which could detect early changes in aggregations is desired. Here, we assess if phase-decorrelation OCT may be sensitive to cold-induced protein aggregation in ex vivo porcine lenses. A major challenge of this approach is the relatively weak scattering signal obtained from the lens nucleus while the lens is in situ. We observed a substantial increase in decorrelation time as the cold cataract reversed. Backscatter intensity also decreased as the cold cataract reversed, as expected. However, compared to backscatter intensity, decorrelation is better correlated with cataract reversal.
Nearly all benchtop studies of corneal biomechanics have relied on protocols which stiffen the cornea, such as riboflavin-UV crosslinking, as a way of providing contrast and validation of biomechanical measurements. However, there are strong clinical motivations to detect softening of the cornea. In this work, we present the evidence that phase-decorrelation OCT (PhD-OCT) is able to detect a small degree of corneal softening due to enzymatic digestion. This benchtop study supports the idea that PhD-OCT may detect keratoconus and early ectasia clinically.
Purpose: To measure the spatially resolved compressive stiffness properties under in vivo conditions to evaluate the effects of clinical corneal crosslinking (CXL) on patients with keratoconus.
Methods: Patients with keratoconus who were scheduled to undergo CXL were imaged before (<1 week) and after (3 to 6 months) treatment. The study was approved under the Cleveland Clinic Institutional Review Board (IRB #13-213). The imaging procedure consists of a continuous compression with a flat glass plate while imaging with swept-source OCT. The frame-to-frame displacements were measured using speckle tracking. Maps of the first order fit of applied force vs cumulative axial displacement were created. Spatially averaged central anterior and posterior regions were defined to generate a relative stiffness value (k) expressing anterior properties relative to posterior stromal properties. Data previously collected from normal patients were also used for group comparison purposes.
Results: Qualitative comparison of the color map representation showed significant differences in the distribution of compressive mechanical properties between all three patient types. Mean k-value were 1.129 ± 0.067 in normal eyes (n=12), 0.988 ± 0.089 in keratoconus eyes (n=8), and 1.27 ± 0.16 in keratoconus eyes after CXL (n=6, p<0.05 for all groups using Mann-Whitney U test).
Conclusions: The spatial biomechanical effects of CXL are measurable with in vivo compressive OCE. The normal anterior to posterior stromal force/displacement ratio appears to be reduced in keratoconus and is increased to or even beyond normal levels after CXL due to selective stiffening of the anterior stroma.
Corneal collagen crosslinking (CXL) is a treatment used for corneal ectasia, a major cause of impaired vision in the United States and a leading indication for corneal transplantation. Existing methods of measuring the mechanical properties of normal and ectatic corneas still face a number of hurdles, including low spatial resolution, patient motion, measurement speed, patient comfort, and intraocular-pressure dependence. We have recently developed a phase-decorrelation OCT (PhD-OCT) method which avoids these drawbacks. PhD-OCT is sensitive to the endogenous random motion within the cornea. This nanometer-level motion can be detected with 5ms (M-scan) measurements using spectral-domain OCT. The random motion is reduced in crosslinked regions of the cornea, which provides contrast to enable mapping of corneal properties during CXL. These maps agree well with the current understanding of the CXL process, showing a distinct region of increased stiffness in the anterior portion of the cornea which corresponds to the demarcation line sometimes visible in conventional OCT. The PhD-OCT method uses conventional OCT and does not involve perturbing the cornea. This method may be useful clinically for pre-surgical screening, ectasia diagnosis, and treatment monitoring and customization.
Deep anterior lamellar keratoplasty (DALK) is an alternative to full-thickness corneal transplant and has advantages including the absence of allograft rejection; shortened duration of topical corticosteroid treatment and reduced associated risk of glaucoma, cataract, or infection; and enables use of grafts with poor endothelial quality. DALK begins by performing a trephination of approximately 80% stromal thickness, as measured by pachymetry. After removal of the anterior stoma, a needle is inserted into the residual stroma to inject air or viscoelastic to dissect Descemet’s membrane. These procedures are inherently difficult and intraoperative rates of Descemet’s membrane perforation between 4-39% have been reported. Optical coherence tomography (OCT) provides high-resolution images of tissue microstructures in the cornea, including Descemet’s membrane, and allows quantitation of corneal layer thicknesses. Here, we use crosssectional intraoperative OCT (iOCT) measurements of corneal thickness during surgery and a novel micrometeradjustable biopsy punch to precision-cut the stroma down to Descemet’s membrane. Our prototype cutting tool allows us to establish a dissection plane at the corneal endothelium interface, mitigates variability in cut-depths as a result of tremor, reduces procedure complexity, and reduces complication rates. iOCT-guided modified DALK procedures were performed on 47 cadaveric porcine eyes by non-experts and achieved a perforation rate of ~5% with a mean corneal dissection time <18 minutes. The procedure was also successful performed on a human donor eye without perforation. Our data shows the potential for iOCT-guided precision anterior segment surgery without variability as a result of tremor and improvements to standard clinical care.
KEYWORDS: Cornea, Optical coherence tomography, Elastography, Tissues, Signal to noise ratio, Tissue optics, Coherence (optics), Surgery, Detection and tracking algorithms, In vivo imaging
The material properties of the cornea are important determinants of corneal shape and refractive power. Corneal ectatic diseases, such as keratoconus, are characterized by material property abnormalities, are associated with progressive thinning and distortion of the cornea, and represent a leading indication for corneal transplantation. We describe a corneal elastography technique based on optical coherence tomography (OCT) imaging, in which displacement of intracorneal optical features is tracked with a 2-D cross-correlation algorithm as a step toward nondestructive estimation of local and directional corneal material properties. Phantom experiments are performed to measure the effects of image noise and out-of-plane displacement on effectiveness of displacement tracking and demonstrated accuracy within the tolerance of a micromechanical translation stage. Tissue experiments demonstrate the ability to produce 2-D maps of heterogeneous intracorneal displacement with OCT. The ability of a nondestructive optical method to assess tissue under in situ mechanical conditions with physiologic-range stress levels provides a framework for in vivo quantification of 3-D corneal elastic and viscoelastic resistance, including analogs of shear deformation and Poisson's ratio that may be relevant in the early diagnosis of corneal ectatic disease.
The viscoelastic properties of the cornea are important determinants of the corneal response to surgery and disease. The purpose of this work is to develop an OCT-based technique for non-contact, high-resolution pan-corneal strain mapping using clinically-achievable pressure changes as a stressor. Porcine corneas were excised and mounted on an artificial anterior chamber that facilitated maintenance of a simulated intraocular pressure (IOP). Pressure was controlled and monitored continuously by saline infusion with an in-line transducer and digital monitor. Mounted specimens were positioned under a laboratory-based high-speed OCT system and imaged in three dimensions at various IOP levels. Matlab and C++ routines were written to perform 2-D bitmap cross-correlation analyses on corresponding images at different pressure levels. Resulting correlations produced a likelihood estimate of the 2-D vector displacement of corneal optical features. Strain maps from cross-correlation analyses revealed local areas of highly consistent displacements interspersed with inter-regional variability. Displacements occurred predominantly along axial vectors. Our analysis produces results consistent with expected and observed displacement of the cornea with varying IOP. Cross-correlation analysis of optical feature flow in the corneal stroma can provide high-resolution strain maps capable of distinguishing spatial heterogeneity in the corneal response to pressure change. A non-destructive, non-contact technique for corneal strain mapping offers numerous potential advantages over tensile testing of excised tissue strips for inferring viscoelastic behavior, and the membrane inflation model employed here could potentially be extended to clinical biomechanical characterizations.
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