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center dot PURPOSE: To optimize artificial intelligence (AI) algo-rithms to integrate Scheimpflug-based corneal tomogra-phy and biomechanics to enhance ectasia detection.center dot DESIGN: Multicenter cross-sectional case-control ret-rospective study.center dot METHODS: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Op-tikgerate GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy.center dot RESULTS: The area under the receiver operating char-acteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sen-sitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), devel-oped with 18 features in 156 trees using 10-fold cross -validation, had a significantly higher AUC (0.945; De -Long, P < .0001) for detecting VAE-NT (84.4% sen-sitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001).center dot CONCLUSIONS: AI optimization to integrate Scheimpflug-based corneal tomography and biome-chanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning consider-ing additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will con-tinuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society. (Am J Ophthalmol 2023;251: 126-142. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))

To determine the impact of corneal epithelial thickness maps on screening for refractive surgery candidacy in a single refractive surgical practice.Comparison of screening methods.A total of 100 consecutive patients who presented for refractive surgery screening were evaluated. For each patient, screening based on Scheimpflug tomography, clinical data, and patient history was performed and a decision on eligibility for laser in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), and small incision lenticule extraction (SMILE)was independently made by 2 masked examiners. Examiners were then shown patients' epithelial thickness maps derived from optical coherence tomography (OCT). The percentage of screenings that changed after evaluating the epithelial thickness maps, with regard to candidacy for surgery, and ranking of surgical procedures from most to least favorable was determined.Candidacy for corneal refractive surgery changed in 16% of patients after evaluation of the epithelial thickness maps, with 10% of patients screened in and 6% screened out. Surgery of choice changed for 16% of patients, and the ranking of surgical procedures from most to least favorable changed for 25% of patients. A total of 11% of patients gained eligibility for LASIK, whereas 8% lost eligibility for LASIK. No significant difference was found between the evaluations of the 2 examiners.Epithelial thickness mapping derived from optical coherence tomography imaging of the cornea altered candidacy for corneal refractive surgery, as well as choice of surgery, in a substantial percentage of patients in our practice, and was thus a valuable tool for screening evaluations. Overall, the use of epithelial thickness maps resulted in screening in a slightly larger percentage of patients for corneal refractive surgery.

PURPOSE To compare the results of intrastromal corneal ring segment (ICRS) alone or combined with same-day corneal crosslinking (CXL) and investigate the relationship of preoperative corneal biomechanics data on the outcomes. SETTING Department of Ophthalmology of Federal University of Parana. DESIGN Prospective nonrandomized interventional comparative study. METHODS Forty-nine eyes of 44 keratoconus patients underwent ICRS only (n = 27, Group 1) or same day ICRS+CXL (n = 22, Group 2) and were followed up for at least 24 months. Visual acuity and preoperative and postoperative tomographic variables were compared between groups. Tomographic data were obtained with a dual Scheimpflug analyzer, and eye-specific finite-element models were used to derive 3 variables related to preoperative biomechanical strain (maximum principal strain [MPS]): mean MPS (mMPS), highest local MPS (hMPS), and position of the hMPS (hMPSx and hMPSy). The relationship between preoperative strain data and the change (∆, difference between postoperative and preoperative data) in tomographic parameters was also investigated. RESULTS Steepest (K2) and maximum keratometry (Kmax), inferior-superior (I-S) index, coma, and cone location magnitude index (CLMI) significantly improved in both groups. Corrected distance visual acuity was significantly better after ICRS alone (P = .03), whereas corneal asymmetry measured through the I-S index was better after CXL+ICRS (P = .04). In Group 1, hMPSy significantly correlated with K2, tomographical cylinder, mean keratometry, and ∆spherical aberration, whereas mMPS significantly correlated with ∆eccentricity. In Group 2, hMPS significantly correlated with K2, Kmax, I-S index, and ∆coma, and hMPSy significantly correlated with I-S index and ∆coma. The mMPS significantly correlated with ∆CLMI. CONCLUSIONS ICRS alone seems to be the most suitable option to improve visual acuity, whereas combined ICRS+CXL provided better corneal regularizing results. Preoperative peak strain (hMPS) was predictive of the extent of regularization and flattening after ICRS+CXL.

PURPOSE: To assess the incidence and long-term persistence of both subjective (rainbow glare phenomenon) and objective metrics of light scattering (stray light measurement) in femtosecond laser-assisted in situ keratomileusis (FS-LASIK). SETTINGS: Cleveland Clinic Foundation, Cole Eye Institute DESIGN: Prospective, contralateral eye study in which 54 myopic eyes of 27 patients underwent LASIK using the ALLEGRETTO® Eye-Q excimer laser. Flap creation was created by IntraLASE FS60 (IL) in one eye and Wave Light FS200 (FS) in the contralateral eye. Rainbow glare and stray light measurements (C-Quant, Oculus Inc, Lynnwood, WA) were obtained preoperatively, and at 1 week, 1, 3, and 9 months postoperatively. Manifest and wavefront refractions were performed at each postoperative visit. RESULTS: Stray light measurements in both IL and FS groups peaked at 1 week postoperatively (log 1.28 ± 0.16, p = 0.02 and log 1.26 ± 0.12, p = 0.039, respectively) with statistically significant improvement at 3 months (log 1.12 ± 0.35, p = 0.007 and log 1.20 ± 0.15, p = 0.04) and 9 months (log 1.11 ± 0.17, p = 0.008 and log 1.15 ± 0.14, p = 0.011). No statistically significant differences were found between IL and FS eyes at all time points. 11 patients reported postoperative rainbow glare at 1 week (42%), which decreased to 6 patients at 9 months (33%) in the IL treated eye. 14 patients reported postoperative rainbow glare at 1 week (54%), which decreased to 7 patients at 9 months (39%) in the FS treated eye. CONCLUSION: Both rainbow glare and objective light scatter were greatest at 1 week and were significantly reduced by 1 to 3 months postoperatively. Rainbow glare is a mild optical side effect of femtosecond laser LASIK that improves with time.

The question of whether the epithelium should be removed in corneal cross-linking (CXL) in the treatment of keratoconus and other corneal ectatic disorders remains controversial. The motivation for epithelium-on CXL methods, which are not yet FDA approved and vary greatly in methodology, is to reduce the risk of vision-threatening complications related to debridement. However, as discussed in this counterpoint piece, most high-level evidence suggests that removal of the epithelium facilitates greater crosslinking effectiveness as measured by primary clinical outcome metrics such as topographic flattening and stabilization of disease. Furthermore, quality evidence is still lacking for a significant reduction in rates of infectious keratitis or loss of vision that can be attributed to debridement-related complications. In the absence of comparative effectiveness trials or long-term follow-up studies that show otherwise, the FDA-approved epi-off protocol is still the standard-bearer for safe and effective stabilization of corneal ectatic disease.

Purpose To evaluate depth-resolved changes of corneal biomechanical properties in eyes with corneal ectasia after corneal crosslinking (CXL) using optical coherence elastography. Methods In a prospective pilot series of eyes with corneal ectasia, a custom high-speed swept source optical coherence tomography system was used to image the cornea before and 3 months after CXL during a low-speed applanating deformation while monitoring applanation force. Cross-correlation was applied to track frame-by-frame two-dimensional optical coherence tomography speckle displacements, and the slope of force versus local axial displacement behavior during the deformation was used to produce a two-dimensional array of axial stiffness (k). These values were averaged for anterior (ka) and posterior (kp) stromal regions and expressed as a ratio (ka/kp) to assess depth-dependent differences in stiffness. CXL was performed according to the Dresden protocol with a system approved by the U.S. Food and Drug Administration. Results Four eyes from four patients with keratoconus (n = 3) or post-LASIK ectasia (n = 1) underwent optical coherence elastography before and 3 months after CXL. The mean ka/kp was 1.03 ± 0.07 before CXL compared with 1.34 ± 0.17 after the CXL procedure. All four eyes demonstrated at least a 20% increase in the ka/kp. Conclusions Preferential stiffening of the anterior stroma with the standard CXL protocol was demonstrated with optical coherence elastography in live human subjects. Translational Relevance Although ex vivo studies have demonstrated anterior stiffening effects after CXL using various destructive and nondestructive methods, this report presents the first evidence of such changes in serial live human measurements.

Crosslinking involves the formation of bonds between polymer chains, such as proteins. In biological tissues, these bonds tend to stiffen the tissue, making it more resistant to mechanical degradation and deformation. In ophthalmology, the crosslinking phenomenon is being increasingly harnessed and explored as a treatment strategy for treating corneal ectasias, keratitis, degenerative myopia, and glaucoma. This review surveys the multitude of exogenous crosslinking strategies reported in the literature, both "light" (involving light energy) and "dark" (involving non-photic chemical processes), and explores their mechanisms, cytotoxicity, and stage of translational development. The spectrum of ophthalmic applications described in the literature is then discussed, with particular attention to proposed therapeutic mechanisms in the cornea and sclera. The mechanical effects of crosslinking are then discussed in the context of their proposed site and scale of action. Biomechanical characterization of the crosslinking effect is needed to more thoroughly address knowledge gaps in this area, and a review of reported methods for biomechanical characterization is presented with an attempt to assess the sensitivity of each method to crosslinking-mediated changes using data from the experimental and clinical literature. Biomechanical measurement methods differ in spatial resolution, mechanical sensitivity, suitability for detecting crosslinking subtypes, and translational readiness and are central to the effort to understand the mechanistic link between crosslinking methods and clinical outcomes of candidate therapies. Data on differences in the biomechanical effect of different crosslinking protocols and their correspondence to clinical outcomes are reviewed, and strategies for leveraging measurement advances predicting clinical outcomes of crosslinking procedures are discussed. Advancing the understanding of ophthalmic crosslinking, its biomechanical underpinnings, and its applications supports the development of next-generation crosslinking procedures that optimize therapeutic effect while reducing complications.

Purpose There is strong evidence that abnormalities in corneal biomechanical play a causal role in corneal ectasias, such as keratoconus. Additionally, corneal crosslinking (CXL) treatment, which halts progression of keratoconus, directly appeals to corneal biomechanics. However, existing methods of corneal biomechanical assessment have various drawbacks: dependence on IOP, long acquisition times, or limited resolution. Here, we present a method that may avoid these limitations by using optical coherence tomography (OCT) to detect the endogenous random motion within the cornea, which can be associated with stromal crosslinking. Methods Phase-decorrelation OCT (PhD-OCT), based in the theory of dynamic light scattering, is a method to spatially resolve endogenous random motion by calculating the decorrelation rate, Γ, of the temporally evolving complex-valued OCT signal. PhD-OCT images of ex vivo porcine globes were recorded during CXL and control protocols. In addition, human patients were imaged with PhD-OCT using a clinical OCT system. Results In both the porcine cornea and the human cornea, crosslinking results in a reduction of Γ (P < 0.0001), indicating more crosslinks. This effect was repeatable in ex vivo porcine corneas (change in average Γ = -41.55 ± 9.64%, n = 5) and not seen after sham treatments (change in average Γ = 2.83 ± 12.56%, n = 5). No dependence of PhD-OCT on IOP was found, and correctable effects were caused by variations in signal-to-noise ratio, hydration, and motion. Conclusions PhD-OCT may be a useful and readily translatable tool for investigating biomechanical properties of the cornea and for enhancing the diagnosis and treatment of patients.

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.

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 characterization of corneal biomechanical properties has important implications for the management of ocular disease and prediction of surgical responses. Corneal refractive surgery outcomes, progression or stabilization of ectatic disease, and intraocular pressure determination are just examples of the many key clinical problems that depend highly upon corneal biomechanical characteristics. However, to date there is no gold standard measurement technique. Since the advent of a 1-dimensional (1D) air-puff based technique for measuring the corneal surface response in 2005, advances in clinical imaging technology have yielded increasingly sophisticated approaches to characterizing the biomechanical properties of the cornea. Novel analyses of 1D responses are expanding the clinical utility of commercially-available air-puff-based instruments, and other imaging modalities-including optical coherence elastography (OCE), Brillouin microscopy and phase-decorrelation ocular coherence tomography (PhD-OCT)-offer new opportunities for probing local biomechanical behavior in 3-dimensional space and drawing new inferences about the relationships between corneal structure, mechanical behavior, and corneal refractive function. These advances are likely to drive greater clinical adoption of in vivo biomechanical analysis and to support more personalized medical and surgical decision-making.

Purpose Compare depth-resolved biomechanical properties in normal and keratoconic corneas in live human subjects using optical coherence elastography (OCE). Methods In a prospective series of normal and keratoconus (KC) eyes, a corneal perturbation was applied by a custom swept-source OCE system using a transparent flat lens coupled to force transducers. Cross-correlation was applied to track frame-by-frame OCT speckle displacement. Regional displacements for the anterior and posterior stroma were plotted in force versus displacement (k) graphs. A spatial biomechanical property ratio (ka/kp ) was defined by dividing the maximum total displacement by the maximum force for the anterior (ka ) and posterior cornea (kp) and was compared between normal and KC groups with the Mann-Whitney U test. Area under the receiver operating characteristics curve (AUROC) for differentiating normal and KC eyes was calculated for ka/kp , kmax, and thinnest point of corneal thickness (TPCT). Results Thirty-six eyes were analyzed (21 eyes of 12 normal subjects and 15 KC eyes of 12 subjects). The ka/kp for the normal group was 1.135 ± 0.07 (mean ± standard deviation) and 1.02 ± 0.08 for the KC group (P < 0.001), indicating a relative deficit in anterior stromal stiffness in KC eyes. AUROC was 0.91 for ka /kp , 0.95 for kmax, and 1 for TPCT. Conclusions Significant differences in depth-dependent corneal biomechanical properties were observed between normal and KC subjects. Translational Relevance OCE was applied for the first time to human KC subjects and revealed alterations in the normal anterior-to-posterior stromal stiffness gradient, a novel and clinically accessible disease biomarker.

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.

Corneal ectasias, such as keratoconus, are modeled ex vivo by the application of enzymes found to be upregulated in ectasia. Phase-decorrelation OCT is shown to non-invasively detect a small degree of enzymatically-induced weakening.

Purpose To report the 3-year assessment of feasibility and usefulness of microscope-integrated intraoperative OCT (iOCT) during ophthalmic surgery. Design Prospective, consecutive case series. Participants Adult participants undergoing incisional ophthalmic surgery with iOCT imaging who consented to be enrolled in the Determination of Feasibility of Intraoperative Spectral-Domain Microscope Combined/Integrated OCT Visualization during En Face Retinal and Ophthalmic Surgery (DISCOVER) study. Methods The DISCOVER study is a single-site, multisurgeon, institutional review board-approved investigational device prospective study. Participants included patients undergoing anterior or posterior segment surgery who underwent iOCT imaging with 1 of 3 prototype microscope-integrated iOCT systems (i.e., Zeiss Rescan 700, Leica EnFocus, or Cole Eye iOCT systems). Clinical characteristics were documented, iOCT was directed by the operating surgeon at predetermined surgical time points, and each surgeon completed a questionnaire after surgery to evaluate the usefulness of iOCT during surgery. Main Outcome Measures Feasibility of iOCT based ability to obtain an OCT image during surgery and usefulness of iOCT based on surgeon reporting during surgery. Results Eight hundred thirty-seven eyes (244 anterior segment cases and 593 posterior segment cases) were enrolled in the DISCOVER study. Intraoperative OCT demonstrated feasibility with successful image acquisition in 820 eyes (98.0%; 95% confidence interval [CI], 96.8%–98.8%). In 106 anterior segment cases (43.4%; 95% CI, 37.1%–49.9%), the surgeons indicated that the iOCT information impacted their surgical decision making and altered the procedure. In posterior segment procedures, surgeons reported that iOCT enabled altered surgical decision making during the procedure in 173 cases (29.2%; 95% CI, 25.5%–33.0%). Conclusions The DISCOVER iOCT study demonstrated both generalized feasibility and usefulness based on the surgeon-reported impact on surgical decision making. This large-scale study confirmed similar findings from other studies on the potential value and impact of iOCT on ophthalmic surgery.

PURPOSE: To assess the ability of air puff-derived biomechanical variables to predict surgeon-perceived candidacy for laser in situ keratomileusis (LASIK). SETTING: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, and Emory Eye Institute, Emory University, Atlanta, Georgia, USA. DESIGN: Retrospective case series. METHODS: Data were collected from refractive surgery screening examinations by 2 surgeons at 2 centers. Disqualified cases (19 eyes and 28 eyes from each surgeon) were judged not to be candidates based on available data including standard variables from the Ocular Response Analyzer. Controls consisted of LASIK candidates (n = 26 and 23). Three custom biomechanical variables not available during screening were calculated and compared by group and surgeon. RESULTS: The hysteresis loop area was significantly different between disqualified cases and controls for both surgeons (Surgeon 1: controls, 121.50 ± 25.38 [SD], disqualified, 107.62 ± 18.50, P = .04; Surgeon 2: controls, 135.89 ± 22.47, disqualified, 106.11 ± 16.40, P < .001). The area under the curves of the receiver operating characteristics and the cutoff values were statistically significant for the concavity minimum and hysteresis loop area for Surgeon 1 and for all variables except concavity minimum for Surgeon 2. The hysteresis loop area had the highest odds ratio (Surgeon 1, 4.48, Surgeon 2, 20.00). Adjusted R(2) in best-subsets regressions were 40.2% for Surgeon 1 and 62.9% for Surgeon 2. CONCLUSIONS: The hysteresis loop area was predictive of which patients were disqualified for LASIK at different sites. Certain measures of the corneal dynamic response to an air puff might serve as correlates to clinically perceived ectasia risk.

PURPOSE: Computational analyses were performed to quantify and directly compare the biomechanical impact of flapless and flap-based procedures in a series of patients undergoing small incision lenticule extraction (SMILE) in one eye and flap-based femtosecond lenticule extraction in the other. METHODS: Tomographic data from 10 eyes of 5 patients undergoing femtosecond laser refractive lenticule extraction for myopic astigmatism with or without a stromal flap (femtosecond lenticule extraction in one eye, SMILE in the contralateral eye) were used to generate computational models. Inverse finite element analyses were performed at physiologic intraocular pressure followed by forward analyses at elevated intraocular pressure to assess corneal displacement and stress under differential loading. Case-specific treatment settings were incorporated. Preoperative material constants were obtained through inverse finite element analyses, and the surgically induced change in fiber stiffness within each flap was determined by minimization of the error between the simulated and actual 6-month topographic outcomes. RESULTS: Flap-based procedures produced a 49% (range: 2% to 87%) greater mean reduction in effective stromal collagen fiber stiffness within the flap region than contralateral SMILE cases. Lower stresses and deformations were observed within the residual stromal bed in SMILE cases than in flap-based cases. Stromal bed displacements and stresses were more affected by a loading increase in flap-based eyes than flapless eyes. CONCLUSIONS: Intrastromal flapless procedures had less impact on anterior stromal collagen mechanics and resulted in lower stromal bed displacements and stresses than flap-based procedures in contralateral eyes. However, biomechanical impact varied widely between individuals and this reinforces the need for individualized assessment of ectasia risk. [ J Refract Surg. 2017;33(7):444–453].

Biomechanics is the science concerned with the origin and effects of forces that act on living organisms. The cornea is a complex composite whose behavior depends on its structural subcomponents and their organizational motifs. A better understanding of its biomechanical features is essential to understand the consequences of procedures such excimer laser refractive surgery and corneal collagen crosslinking and to improve the detection and management of ectatic corneal diseases. Devices such as the Ocular Response Analyzer and the Corvis STL use an air-puff to perturb the cornea and assess biomechanical responses. Although both devices use similar approaches, data produced by them cannot be used interchangeably. Moreover, current commercial technologies lack capabilities for regional property discrimination, which is of paramount importance for comprehensive biomechanical analysis. To address this gap, other methodologies such as optical coherence elastography and Brillouin microscopy are being developed and early in vivo studies show promising results. Finally, another important tool for studying complex structures is computational modeling using the finite element method. The cornea can be represented as a mesh of smaller geometric elements with specific material properties. Advances in this area have the potential to enhance diagnosis, enable personalized risk assessment, and optimize treatment design toward the goal of improving safety and outcomes for corneal and refractive surgery patients.

The use of computational mechanics for assessing the structural and optical consequences of corneal refractive procedures is increasing. In practice, surgeons who elect to perform PRK rather than LASIK must often reduce the programmed refractive treatment magnitude to avoid overcorrection of myopia. Building on a recent clinical validation study of finite element analysis (FEA)-based predictions of LASIK outcomes, this study compares predicted responses in the validated LASIK cases to theoretical PRK treatments for the same refractive error. Simulations in 20 eyes demonstrated that PRK resulted in a mean overcorrection of 0.17 &plusmn, 0.10 D relative to LASIK and that the magnitude of overcorrection increased as a function of attempted correction. This difference in correction closely matched (within 0.06 &plusmn, 0.03 D) observed differences in PRK and LASIK from a historical nomogram incorporating thousands of cases. The surgically induced corneal strain was higher in LASIK than PRK and resulted in more forward displacement of the central stroma and, consequently, less relative flattening in LASIK. This FE model provides structural confirmation of a mechanism of action for the difference in refractive outcomes of these two keratorefractive techniques, and the results were in agreement with empirical clinical data.

PURPOSE: To develop a computational approach to corneal biomechanical risk analysis in refractive surgery and to investigate its utility in an enigmatic case of unilateral ectasia after bilateral LASIK. METHODS: Preoperative corneal elevation datasets from both eyes of a patient who developed unilateral post-LASIK ectasia were used to construct geometrically patient-specific, microstructurally motivated finite element models. Models were assessed before and after implementation of case-specific treatment parameters for interocular differences in corneal geometry and strain behavior under physiological loading conditions. RESULTS: Standard clinical predictors of post-LASIK ectasia risk were similar for the affected and contralateral eyes, and no risk factor asymmetry was identified in tomographic screening that included posterior corneal elevation analysis. However, differences in the magnitude and distribution of strain and stress were observed that are consistent with greater predisposition to biomechanical instability in the affected eye. Load testing with simulated intraocular pressure increases provoked opposite trends in curvature change in the preoperative models representing affected and unaffected eyes, with steepening in the ectatic eye and flattening in the clinically stable eye. CONCLUSIONS: Patient-specific computational analyses revealed differences in intrinsic biomechanical behaviors that may predispose a cornea to instability after refractive surgery. Strain and stress analyses elucidated differential risk not ascertained with current refractive surgery screening paradigms. This pilot study illustrates a risk analysis approach that implicitly considers the entire corneal three-dimensional geometry and can be performed a priori in a screening setting. [ J Refract Surg. 2016;32(12):811–820.]

Purpose Millions of people suffer from diseases that involve corneal nerve dysfunction, caused by various conditions, including dry eye syndrome, neurotrophic keratopathy, diabetes, herpes simplex, glaucoma, and Alzheimer's disease. The morphology of corneal nerves has been studied extensively. However, corneal nerve function has only been studied in a limited fashion owing to a lack of tools. Here, we present a new system for studying corneal nerve function. Methods Optical imaging was performed on the cornea of excised murine globes taken from a model animal expressing a genetically encoded calcium indicator, GCaMP6f, to record calcium transients. A custom perfusion and imaging chamber for ex vivo murine globes was designed to maintain and stabilize the cornea, while allowing the introduction of chemical stimulation during imaging. Results Imaging of calcium signals in the ex vivo murine cornea was demonstrated. Strong calcium signals with minimal photobleaching were observed in experiments lasting up to 10 minutes. Concentrated potassium and lidocaine solutions both modulated corneal nerve activity. Similar responses were observed in the same neurons across multiple chemical stimulations, suggesting the feasibility of using chemical stimulations to test the response of the corneal nerves. Conclusions Our studies suggest that this tool will be of great use for studying functional changes to corneal nerves in response to disease and ocular procedures. This process will enable preclinical testing of new ocular procedures to minimize damage to corneal innervation and therapies for diminished neural function.

PurposeTo assess depth-dependent corneal displacements in live normal subjects using optical coherence elastography (OCE).MethodsA corneal elastography method based on swept-source optical coherence tomography (OCT) was implemented in a clinical prototype. Low amplitude corneal deformation was produced during OCT imaging with a linear actuator-driven lens coupled to force transducers. A cross-correlation algorithm was applied to track frame-by-frame speckle displacement across horizontal meridian scans. Intra-measurement force and displacement data series were plotted against each other to produce local axial stiffness approximations, k, defined by the slope of a linear fit to the force/displacement data (ignoring non-axial contributions from corneal bending). Elastographic maps displaying local k values across the cornea were generated, and the ratio of mean axial stiffness approximations for adjacent anterior and posterior stromal regions, ka/kp, was calculated. Intraclass correlation coefficients (ICC) were used to estimate repeatability.ResultsSeventeen eyes (ten subjects) were included in this prospective first-in-humans translational study. The ICC was 0.84. Graphs of force vs. displacement demonstrated that, for simultaneously acquired measurements involving the same applied force, anterior stromal displacements were lower (suggesting stiffer behavior) than posterior stromal displacements. Mean ka was 0.016±0.004 g/mm and mean kp was 0.014±0.004 g/mm, giving a mean ka/kp ratio of 1.123±0.062.ConclusionOCE is a clinically feasible, non-invasive corneal biomechanical characterization method capable of resolving depth-dependent differences in corneal deformation behavior. The anterior stroma demonstrated responses consistent with stiffer properties in compression than the posterior stroma, but to a degree that varied across normal eyes. The clinical capability to measure these differences has implications for assessing the biomechanical impact of corneal refractive surgeries and for ectasia risk screening applications.