Early elastic and viscoelastic corneal biomechanical changes after photorefractive keratectomy and small incision lenticule extraction.

PURPOSE: To compare early changes in the corneal biomechanical parameters after photorefractive keratectomy (PRK) and small incision lenticule extraction (SMILE) and their correlations with corneal shape parameters. METHODS: One hundred twenty four eyes received myopic PRK and SMILE for similar amounts of myopia. Corneal tomography with Pentacam HR, biomechanical parameters using Corvis ST, and Ocular Response Analyzer (ORA) were evaluated before and 2 weeks after surgery. The change in each parameter was compared between groups, while the difference in central corneal thickness and cornea-compensated intraocular pressure measured before and after surgery were considered as covariates. RESULTS: A significant reduction was seen in the corneal stiffness parameter at first applanation, and an increase in deformation amplitude ratio (DAR), and integrated inverse radius (IIR) in both groups after surgery (p < 0.001) Changes in DAR, and IIR were significantly greater in the SMILE than in the PRK group (p < 0.001) Corneal hysteresis (CH) and corneal resistance factor (CRF) decreased in both SMILE and PRK groups after surgery, (p < 0.001) with no statistically significant difference between groups (p > 0.05) Among new Corvis ST parameters, DAR showed a significant correlation with changes in Ambrosio relational thickness in both groups (p < 0.05). CONCLUSIONS: Both techniques caused significant changes in corneal biomechanics in the early postoperative period, with greater elastic changes in the SMILE group compared to the PRK group, likely due to lower tension in the SMILE cap and thinner residual stromal bed in SMILE. There were no differences in viscoelastic changes between them, so the lower CH may reflect the volume of tissue removed.

Comparison of corneal biomechanical parameters in healthy corneas with symmetric and asymmetric bow-tie topographic pattern with inferior and superior steepening.

PURPOSE: To compare the corneal biomechanical parameters in healthy corneas with symmetric and asymmetric bow-tie topographic patterns. METHODS: In this cross-sectional study, 144 eyes were divided based on inferior-superior asymmetry value (I-S) into symmetric (zero I-S: - 0.50 to + 0.50 D) and asymmetric bow-tie topographic patterns with inferior (positive I-S: + 0.51 to + 1.4 D) or superior (negative I-S: - 2.5 to - 0.51 D) steepening. The biomechanical assessment was performed using Corvis ST and ocular response analyzer (ORA). A general linear model univariate analysis was used to compare the parameters, while the central corneal thickness, intraocular pressure, and age were considered covariates. RESULTS: Only the peak distance (PD) at the highest concavity phase (P = 0.007) and tomographic biomechanical index (TBI, P = 0.001) showed statistically significant differences between the three groups. For TBI, this difference was statistically significant between the positive I-S group separately with the zero I-S group (P < 0.001), and with the negative I-S group (P = 0.022). For PD, the significant difference was between the negative I-S group separately with zero I-S (P = 0.019), and positive I-S groups (P = 0.018). There was a statistically significant correlation between the I-S value with PD (r = 0.281, P = 0.001) and TBI (r = 0.170, P = 0.044). CONCLUSIONS: Most corneal biomechanical parameters are not statistically significant compared to the zero I-S group. However, superior steepening is associated with a stiffer response based solely on the shorter PD values seen in this group, and the group with the inferior steepening shows the highest or more suspicious values based on TBI.

Intereye Differences in the Clinical Assessment of Intraocular Pressure and Ocular Biomechanics.

SIGNIFICANCE: Clinicians and researchers will have evidence whether intereye differences confound clinical measurements of intraocular pressure or of ocular biomechanical parameters. PURPOSE: The purpose of this study was to determine whether intraocular pressure and biomechanical parameters, as measured by the Ocular Response Analyzer (ORA) and by Cornea Visualization with Scheimpflug Technology (CorVis ST), are different between the first and second eye measured. METHODS: Intraocular pressure and biomechanical parameters were collected from both eyes of healthy participants (N = 139). The ORA measured corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, and corneal hysteresis. The CorVis ST measured biomechanically corrected intraocular pressure, stiffness parameter at first applanation, and stiffness parameter at highest concavity. For each measurement, a paired t test compared the value of the first eye measured against that of the second eye measured. RESULTS: For the ORA, Goldmann-correlated intraocular pressure was significantly higher ( P = .001) in the first eye (14.8 [3.45] mmHg) than in the second eye (14.3 [3.63] mmHg). For the CorVis ST, biomechanically corrected intraocular pressure was significantly higher ( P < .001) in the second eye (14.7 [2.14] mmHg) than in the first eye (14.3 [2.11] mmHg). Stiffness parameter at first applanation (intereye difference, 6.85 [9.54] mmHg/mm) was significantly ( P < .001) higher in the first eye than in the second eye. Stiffness parameter at highest concavity was significantly higher ( P = .01) in the second eye (14.3 [3.18] mmHg/mm) than in the first eye (14.0 [3.13] mmHg/mm). CONCLUSIONS: Although there were statistically significant intereye differences in intraocular pressure and in biomechanical parameters for both devices, the variations were small and thus unlikely to affect clinical outcomes.

Novel High-Resolution Imaging Using ANTERION Optical Coherence Tomography to Assess Fluid Reservoir Change in Scleral Lens Periphery.

OBJECTIVES: To assess scleral lens fluid reservoir (FR) change simultaneously in four quadrants with single acquisition using novel ANTERION anterior segment swept-source optical coherence tomography (SS-OCT). METHODS: A prospective, observational, clinical study of 18 subjects (30 eyes) was performed on adults fitted with a scleral lens for ocular surface disease (n=8), irregular cornea/scar (n=7), and corneal ectasia (n=15). ANTERION anterior segment SS-OCT imaging was obtained at the initial visit and at the follow-up to determine pre and post scleral lens settling, measured in microns, centrally and peripherally. Peripheral measurements were grouped into four quadrants. Repeated-measures ANOVA was performed comparing vault post minus pre differences by quadrant, and TTests comparing difference in FR by lens design were performed with a significant threshold at P <0.05. RESULTS: The mean central scleral lens settling was significant at -48.3±41.7 µm. The change in FR by quadrant was superior (S): -47.8±67.3 µm, inferior (I): -68.0±102.2 µm, nasal (N) -46.3±63.4 µm, and temporal (T): -56.7±49.3 µm. There were no significant differences in lens settling between the quadrants. Within the three categories, the irregular cornea group experienced significantly greater lens settling. There was no significant difference in central FR when comparing lens design or lens diameter. CONCLUSIONS: The ANTERION SS-OCT allows for high-resolution central and peripheral assessment of FR in scleral lens wear. With increased technology available for scleral lens customization, this imaging modality can assist in more detailed assessment in quadrant-specific scleral lens designs.

Effect of penetration enhancer with novel corneal cross-linking using recombinant human decoron in porcine eyes.

The aim of the study was to investigate the effectiveness of exogenous recombinant human decoron and an accompanying penetration-enhancing solution in stiffening ex-vivo porcine corneas both transepithelially and after de-epithelialization. Eight porcine paired eyes were treated transepithelially: one eye with a pre-treatment solution (Pre-Tx), penetration enhancing solution (PE), and decoron while the fellow eye was treated by the same protocol but without decoron. A second group included 4 de-epithelialized pairs treated identically. The final group included 4 de-epithelialized pairs with one eye treated with Pre-Tx, PE, and decoron while the fellow eye was treated without PE. Uniaxial tensile testing was used to compare the corneal stiffness between the different treatment conditions. Residual tissue underwent immunohistochemistry analysis to evaluate the depth of penetration of decoron into the corneal stroma. There was no stiffening effect exhibited among corneas treated transepithelially with decoron compared to control (P > 0.05) and poor stromal penetration was exhibited on tissue analysis. Among de-epithelialized corneas, there was a significant stiffening effect seen in those treated with decoron at 3%, 4%, 5%, & 6% strain (P < 0.05) compared to control. Among de-epithelialized corneas there was also a significant stiffening effect seen in those treated with the PE and decoron at 4%, 5%, & 6% strain (P < 0.05) with improved stromal penetration confirmed by immunohistochemistry, versus without PE. De-epithelialization is necessary for effective stromal penetration of decoron. Depth of penetration and subsequent corneal stiffening may be improved with a penetration enhancing solution. Compared to riboflavin, decoron requires shorter treatment time and spares UV light exposure.

KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for hemodialysis vascular access since 1996. Since the last update in 2006, there has been a great accumulation of new evidence and sophistication in the guidelines process. The 2019 update to the KDOQI Clinical Practice Guideline for Vascular Access is a comprehensive document intended to assist multidisciplinary practitioners care for chronic kidney disease patients and their vascular access. New topics include the end-stage kidney disease "Life-Plan" and related concepts, guidance on vascular access choice, new targets for arteriovenous access (fistulas and grafts) and central venous catheters, management of specific complications, and renewed approaches to some older topics. Appraisal of the quality of the evidence was independently conducted by using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and interpretation and application followed the GRADE Evidence to Decision frameworks. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.

Biomechanical contribution of the sclera to dynamic corneal response in air-puff induced deformation in human donor eyes.

This study was conducted to evaluate the impact of varying scleral material properties on the biomechanical response of the cornea under air-puff induced deformation. Twenty pairs of human donor eyes were obtained for this study. One eye from each pair had its sclera stiffened using 4% glutaraldehyde, while the fellow eye served as control for uniaxial strip testing. The whole globes were mounted in a rigid holder and intraocular pressure (IOP) was set using a saline column. Dynamic corneal response parameters were measured before and after scleral stiffening using the CorVis ST, a dynamic Scheimpflug analyzer. IOP was set to 10, 20, 30, and 40 mmHg, with at least 3 examinations performed at each pressure step. Uniaxial tensile testing data were fit to a neo-Hookean model to estimate the Young's modulus of treated and untreated sclera. Scleral Young's modulus was found to be significantly correlated with several response parameters, including Highest Concavity Deformation Amplitude, Peak Distance, Highest Concavity Radius, and Stiffness Parameter-Highest Concavity (SP-HC). There were significant increases in SP-HC after scleral stiffening at multiple levels of IOP, while no significant difference was observed in the corneal Stiffness Parameter - Applanation 1 (SP-A1) at any level of IOP. Scleral mechanical properties significantly influenced the corneal deformation response to an air-puff. The stiffer the sclera, the greater the constraining effect on corneal deformation resulting in lower displaced amplitude. This may have important clinical implications and suggests that both corneal and scleral material properties contribute to the observed corneal response in air-puff induced deformation.

Fundus-simulating phantom for calibration of retinal vessel oximetry devices.

Retinal vessel oxygen supply is important for retinal tissue metabolism. Commonly used retinal vessel oximetry devices are based on dual-wavelength spectral measurement of oxyhemoglobin and deoxyhemoglobin. However, there is no traceable standard for reliable calibration of these devices. In this study, we developed a fundus-simulating phantom that closely mimicked the optical properties of human fundus tissues. Microchannels of precisely controlled topological structures were produced by soft lithography to simulate the retinal vasculature. Optical properties of the phantom were adjusted by adding scattering and absorption agents to simulate different concentrations of fundus pigments. The developed phantom was used to calibrate the linear correlation between oxygen saturation (SO2) level and optical density ratio in a dual-wavelength oximetry device. The obtained calibration factors were used to calculate the retinal vessel SO2 in both eyes of five volunteers aged between 24 and 27 years old. The test results showed that the mean arterial and venous SO2 levels after phantom calibration were coincident with those after empirical value calibration, indicating the potential clinical utility of the produced phantom as a calibration standard.

Ex-vivo experimental validation of biomechanically-corrected intraocular pressure measurements on human eyes using the CorVis ST.

The purpose of this study was to assess the validity of the Corvis ST (Oculus; Wetzlar, Germany) biomechanical correction algorithm (bIOP) in determining intraocular pressure (IOP) using experiments on ex-vivo human eyes. Five ex-vivo human ocular globes (age 69 ±â€¯3 years) were obtained and tested within 3-5 days post mortem. Using a custom-built inflation rig, the internal pressure of the eyes was controlled mechanically and measured using the CorVis ST (CVS-IOP). The CVS-IOP measurements were then corrected to produce bIOP, which was developed for being less affected by variations in corneal biomechanical parameters, including tissue thickness and material properties. True IOP (IOPt) was defined as the pressure inside of the globe as monitored using a fixed pressure transducer. Statistical analyses were performed to assess the accuracy of both CVS-IOP and bIOP, and their correlation with corneal thickness. While no significant differences were found between bIOP and IOPt (0.3 ±â€¯1.6 mmHg, P = 0.989) using ANOVA and Bonferroni Post-Hoc test, the differences between CVS-IOP and IOPt were significant (7.5 ±â€¯3.2 mmHg, P < 0.001). Similarly, bIOP exhibited no significant correlation with central corneal thickness (p = 0.756), whereas CVS-IOP was significantly correlated with the thickness (p < 0.001). The bIOP correction has been successful in providing close estimates of true IOP in ex-vivo tests conducted on human donor eye globes, and in reducing association with the cornea's thickness.

Neurorestorative Responses to Delayed Human Mesenchymal Stromal Cells Treatment of Stroke in Type 2 Diabetic Rats.

BACKGROUND AND PURPOSE: Comorbidity of diabetes mellitus and stroke results in worse functional outcome, poor long-term recovery, and extensive vascular damage. We investigated the neurorestorative effects and mechanisms of stroke treatment with human bone marrow-derived mesenchymal stromal cells (hMSCs) in type 2 diabetes mellitus (T2DM) rats. METHODS: Adult male Wistar rats were induced with T2DM, subjected to 2 hours of middle cerebral artery occlusion (MCAo) and treated via tail-vein injection with (1) PBS (n=8) and (2) hMSCs (n=10; 5×106) at 3 days after MCAo. RESULTS: In T2DM rats, hMSCs administered at 3 days after MCAo significantly improves neurological function without affecting blood glucose, infarct volume, and incidence of brain hemorrhage in comparison to T2DM-MCAo PBS-treated rats. Delayed hMSC treatment of T2DM stroke significantly improves blood-brain barrier integrity, increases vascular and arterial density and cerebral vascular perfusion, and promotes neuroblast cell migration and white matter remodeling as indicated by increased doublecortin, axon, myelin, and neurofilament density, respectively. Delayed hMSC treatment significantly increases platelet-derived growth factor expression in the ischemic brain, decreases proinflammatory M1 macrophage and increases anti-inflammatory M2 macrophage compared to PBS-treated T2DM-MCAo rats. In vitro data show that hMSCs increase subventricular zone explant cell migration and primary cortical neuron neurite outgrowth, whereas inhibition of platelet-derived growth factor decreases hMSC-induced subventricular zone cell migration and axonal outgrowth. CONCLUSIONS: In T2DM stroke rats, delayed hMSC treatment significantly improves neurological functional outcome and increases neurorestorative effects and M2 macrophage polarization. Increasing brain platelet-derived growth factor expression may contribute to hMSC-induced neurorestoration.

Importance of accurately assessing biomechanics of the cornea.

PURPOSE OF REVIEW: This article summarizes the state-of-the-art in clinical corneal biomechanics, including procedures in which biomechanics play a role, and the clinical consequences in terms of error in estimating intraocular pressure (IOP). RECENT FINDINGS: Corneal biomechanical response to refractive surgery can be categorized into either stable alteration of surface shape and thus visual outcome, or unstable biomechanical decompensation. The stable response is characterized by central flattening and peripheral steepening that is potentiated in a stiffer cornea. Two clinical devices for assessing corneal biomechanics do not yet measure classic biomechanical properties, but rather provide assessment of corneal deformation response. Biomechanical parameters are a function of IOP, and both the cornea and sclera become stiffer as IOP increases. Any assessment of biomechanical parameters must include IOP, and one value of stiffness does not adequately characterize a cornea. SUMMARY: Corneal biomechanics plays a role in the outcomes of any procedure in which lamellae are transected. Once the corneal structure has been altered in a manner that includes central thinning, IOP measurements with applanation tonometry are likely not valid, and other technologies should be used.

Stroke Induces Nuclear Shuttling of Histone Deacetylase 4.

BACKGROUND AND PURPOSE: Histone deacetylases (HDACs) 4 and 5 are abundantly expressed in the brain and have been implicated in the regulation of neurodegeneration. Under physiological conditions, HDACs 4 and 5 are expressed in the cytoplasm of brain cells where they cannot directly access chromatin. In response to external stimuli, they can shuttle to the nucleus and regulate gene expression. However, the effect of stroke on nuclear shuttling of HDACs 4 and 5 remains unknown. METHODS: Using a rat model of middle cerebral artery occlusion, we examined the subcellular localization of HDACs 4 and 5 in the peri-infarct cortex during brain repair after stroke. RESULTS: Stroke significantly increased nuclear HDAC4 immunoreactivity in neurons, but not in astrocytes or in oligodendrocytes, of the peri-infarct cortex at 2, 7, and 14 days after middle cerebral artery occlusion. Neurons with nuclear HDAC4 immunoreactivity distributed across all layers of the peri-infarct cortex and were Ctip2+ excitatory and parvalbumin+ inhibitory neurons. These neurons were not TUNEL or BrdU positive. Furthermore, nuclear HDAC4 immunoreactivity was positively and significantly correlated with increased dendritic, axonal, and myelin densities as determined by microtubule-associated protein 2, phosphorylated neurofilament heavy chain, and myelin basic protein, respectively. Unlike HDAC4, stroke did not alter nuclear localization of HDAC5. CONCLUSIONS: Our data show that stroke induces nuclear shuttling of HDAC4 in neurons in the peri-infarct cortex, and that increased nuclear HDAC4 is strongly associated with neuronal remodeling but not with neuronal cell death, suggesting a role for nuclear HDAC4 in promoting neuronal recovery after ischemic injury.

Neurorestorative Therapy of Stroke in Type 2 Diabetes Mellitus Rats Treated With Human Umbilical Cord Blood Cells.

BACKGROUND AND PURPOSE: Diabetes mellitus is a high-risk factor for ischemic stroke. Diabetic stroke patients suffer worse outcomes, poor long-term recovery, risk of recurrent strokes, and extensive vascular damage. We investigated the neurorestorative effects and the underlying mechanisms of stroke treatment with human umbilical cord blood cells (HUCBCs) in type 2 diabetes mellitus (T2DM) rats. METHODS: Adult male T2DM rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo). Three days after MCAo, rats were treated via tail-vein injection with (1) PBS and (2) HUCBCs (5×10(6)), n=10 per group. RESULTS: HUCBC stroke treatment initiated 3 days after MCAo in T2DM rats did not significantly decrease blood-brain barrier leakage (P=0.1) and lesion volume (P=0.078), but significantly improved long-term functional outcome and decreased brain hemorrhage (P<0.05) when compared with the PBS-treated T2DM MCAo control group. HUCBC treatment significantly promoted white matter remodeling as indicated by increased expression of Bielschowsky silver (axons marker), Luxol fast blue (myelin marker), SMI-31 (neurofilament), and Synaptophysin in the ischemic border zone. HUCBC promoted vascular remodeling and significantly increased arterial and vascular density. HUCBC treatment of stroke in T2DM rats significantly increased M2 macrophage polarization (increased M2 macrophage, CD163and CD 206; decreased M1 macrophage, ED1 and inducible nitric oxide synthase expression) in the ischemic brain compared with PBS-treated T2DM MCAo controls (P<0.05). HUCBC also significantly decreased proinflammatory factors, that is, matrix metalloproteinase 9, receptor for advanced glycation end products and toll-like receptor 4 expression in the ischemic brain. CONCLUSIONS: HUCBC treatment initiated 3 days after stroke significantly increased white matter and vascular remodeling in the ischemic brain as well as decreased neuroinflammatory factor expression in the ischemic brain in T2DM rats and promoted M2 macrophage polarization. HUCBC reduction of neuroinflammation and increased vascular and white matter axonal remodeling may contribute to the HUCBC-induced beneficial effects in T2DM stroke rats.

Biomechanical Modeling of Femtosecond Laser Keyhole endokeratophakia Surgery.

PURPOSE: To apply a finite element model to endokeratophakia and evaluate anterior and posterior corneal surface changes. METHODS: Spatial elevation data (Pentacam HR; Oculus, Wetzlar, Germany) were obtained for the front and back corneal surfaces of an eye prior to undergoing an endokeratophakia procedure. These were used to warp a spherical template finite element model of the cornea to create a patient-specific finite element mesh and the initial stress distribution was computed with an iterative approach. The finite element model (Optimeyes; Integrated Scientific Services, Biel, Switzerland) included non-linear elastic characteristics of the stroma. The endokeratophakia procedure was recreated in the model: a donor lenticule (-10.50 diopters [D], 5.75-mm zone, 127-µm thick) was inserted into a lamellar pocket (180-µm deep, 6.25-mm diameter) and two 2-mm small incisions were made at 150° and 330°. Anterior and posterior surfaces, computed by the finite element model, were compared to clinical data to assess accuracy and reliability of finite element modeling. RESULTS: The postoperative axial curvature produced by the model closely resembled the patient data; average curvature was 48.01 D clinically and 48.23 D in the simulation, and corneal astigmatism was 3.01 D clinically and 2.88 D in the simulation. The posterior best-fit sphere elevation map also matched the patient data, replicating inward bulging of the posterior surface by approximately 40 µm. Stress distribution modeling predicted a stress increase by 159.94% ± 73% in the cap and a stress decrease by 32.41% ± 21% in the stromal bed. CONCLUSIONS: Finite element modeling of the cornea reproduced the clinically observed anterior and posterior corneal surface changes following an endokeratophakia procedure. This case sets the stage for further study to refine and yield predictive finite element modeling for the evaluation of corneal refractive surgical procedures.

Beneficial effects of gfap/vimentin reactive astrocytes for axonal remodeling and motor behavioral recovery in mice after stroke.

The functional role of reactive astrocytes after stroke is controversial. To elucidate whether reactive astrocytes contribute to neurological recovery, we compared behavioral outcome, axonal remodeling of the corticospinal tract (CST), and the spatio-temporal change of chondroitin sulfate proteoglycan (CSPG) expression between wild-type (WT) and glial fibrillary acidic protein/vimentin double knockout (GFAP(-/-) Vim(-/-) ) mice subjected to Rose Bengal induced cerebral cortical photothrombotic stroke in the right forelimb motor area. A foot-fault test and a single pellet reaching test were performed prior to and on day 3 after stroke, and weekly thereafter to monitor functional deficit and recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the CST axons. Compared with WT mice, the motor functional recovery and BDA-positive CST axonal length in the denervated side of the cervical gray matter were significantly reduced in GFAP(-/-) Vim(-/-) mice (n = 10/group, P < 0.01). Immunohistological data showed that in GFAP(-/-) Vim(-/-) mice, in which astrocytic reactivity is attenuated, CSPG expression was significantly increased in the lesion remote areas in both hemispheres, but decreased in the ischemic lesion boundary zone, compared with WT mice (n = 12/group, P < 0.001). Our data suggest that attenuated astrocytic reactivity impairs or delays neurological recovery by reducing CST axonal remodeling in the denervated spinal cord. Thus, manipulation of astrocytic reactivity post stroke may represent a therapeutic target for neurorestorative strategies.

Ocular biomechanical metrics by CorVis ST in healthy Brazilian patients.

PURPOSE: To evaluate ocular biomechanical metrics given by the CorVis ST (Oculus, Inc., Berlin, Germany) in a population of healthy Brazilian patients. METHODS: An observational and cross-sectional study involving 1 eye randomly selected from 90 healthy patients. Studied parameters (including deformation amplitude, first applanation time, highest concavity time, second applanation time, first applanation length, second applanation length, curvature radius highest concavity, curvature radius normal, velocity in, and velocity out) derived from the CorVis ST were correlated to central corneal thickness from the Pentacam (Oculus, Inc.). Differences between data on the basis of gender were evaluated. RESULTS: Mean patient age was 35.80 ± 12.83 years (range: 21.07 to 78.84 years). Mean central corneal thickness was 547.50 ± 32.00 µm (range: 490 to 647 µm) and mean spherical equivalent refraction was -3.29 ± 3.69 diopters (range: -9.50 to +10.37 diopters). Mean deformation amplitude was 1.05 ± 0.08 mm (range: 0.91 to 1.26 mm). Highest concavity time was 18.38 ± 0.93 ms (range: 16.95 to 21.07 ms). Intraocular pressure was 16.43 ± 2.15 mm Hg (range: 11.50 to 21.0 mm Hg). First applanation time was 8.32 ± 0.33 ms (range: 7.53 to 9.12 ms) and second applanation time was 23.80 ± 0.44 ms (range: 22.76 to 24.95 ms). First applanation length (max) was 2.07 ± 0.38 mm (range: 1.20 to 3.10 mm) and second applanation length (max) was 2.37 ± 0.47 mm (range: 1.33 to 4.12 mm). Curvature radius highest concavity was 11.09 ± 2.06 mm (range: 7.58 to 15.98 mm) and curvature radius normal was 7.59 ± 0.67 mm (range: 6.82 to 11.02 mm). Velocity in was 0.21 ± 0.05 m/s (range: 0.16 to 0.72 m/s) and velocity out was -0.33 ± 0.07 m/s (range: -0.72 to -0.20 m/s). Studied parameters were not associated with gender. CONCLUSIONS: Eight of 11 ocular biomechanical metrics given by the CorVis ST were associated with central corneal thickness, but the influence of central corneal thickness on these measurements was low.

Corneal curvature gradient map: a new corneal topography map to predict the corneal healing process.

PURPOSE: To evaluate a new curvature gradient topography map to predict postoperative corneal remodeling. METHODS: In this retrospective study, 32 eyes of 16 patients with myopia underwent excimer ablation surgery with a postoperative high curvature gradient. The new curvature gradient map (acquired immediately postoperatively) shows the difference between the curvatures of two points over the distance between them; it was compared to the tangential curvature difference map between 1 and 12 months postoperatively to determine their relationship. Corneas were divided into 12 regions for analysis: four 90°-wide sectors centered on 0°, 90°, 180°, and 270°. There were three subdivisions in each sector: central (radius: 0 to 2.75 mm), paracentral (radius: 2.75 to 3.25 mm), and peripheral (radius: 3.25 to 4.5 mm). Linear regression analysis was performed by region. RESULTS: The following regions had significant relationships between the initial curvature gradient and curvature difference between 1 and 12 months postoperatively: the paracentral zone of the 90° sector (P = .0145; R(2) = 0.1832) and both the central (P = .0034; R(2) = 0.2522) and paracentral (P = .0452; R(2) = 0.1271) zones of the 270° sector. The greatest average initial tangential curvature was in the 270° sector. CONCLUSIONS: The initial curvature gradient after surgery predicted change in tangential curvature over the subsequent 12 months in areas where initial tangential curvature was greatest. When the curvature gradient was high, the surface curvature modification remained in progress months after surgery.

Air puff induced corneal vibrations: theoretical simulations and clinical observations.

PURPOSE: To investigate air puff induced corneal vibrations and their relationship to the intraocular pressure (IOP), viscoelasticity, mass, and elasticity of the cornea based on theoretical simulations and preliminary clinical observations. METHODS: To simulate the corneal movement during air puff deformation, a kinematic viscoelastic corneal model was developed involving the factors of corneal mass, damping coefficient, elasticity, and IOP. Different parameter values were taken to investigate how factors would affect the corneal movements. Two clinical ocular instruments, CorVis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) and the Ocular Response Analyzer (ORA; Reichert, Inc., Buffalo, NY), were employed to observe the corneal dynamical behaviors. RESULTS: Numerical results showed that during the air puff deformation, there would be vibrations along with the corneal deformation, and the damping viscoelastic response of the cornea had the potential to reduce the vibration amplitude. With consistent IOP, the overall vibration amplitude and inward motion depths were smaller with a stiffer cornea. CONCLUSIONS: A kinematic viscoelastic model of the cornea is presented to illustrate how the vibrations are associated with factors such as corneal mass, viscoelasticity, and IOP. Also, the predicted corneal vibrations during air puff deformation were confirmed by clinical observation.

Keratoconus cone location influences ocular biomechanical parameters measured by the Ocular Response Analyzer.

BACKGROUND: Keratoconus is characterized by asymmetry in the biomechanical properties of the cornea, with focal weakness in the area of cone formation. We tested the hypothesis that centrally-measured biomechanical parameters differ between corneas with peripheral cones and corneas with central cones. METHODS: Fifty participants with keratoconus were prospectively recruited. The mean ± standard deviation age was 38 ± 13 years. Axial and tangential corneal topography were analyzed in both eyes, if eligible. Cones in the central 3 mm of the cornea were considered central, and cones outside the central 3 mm were considered peripheral. Each eye was then measured with the Ocular Response Analyzer (ORA) tonometer. T-tests compared differences in ORA-generated waveform parameters between cohorts. RESULTS: Seventy-eight eyes were analyzed. According to the axial topography maps, 37 eyes had central cones and 41 eyes had peripheral cones. According to the tangential topography maps, 53 eyes had central cones, and 25 eyes had peripheral cones. For the axial-topography algorithm, wave score (WS) was significantly higher in peripheral cones than central cones (inter-cohort difference = 1.27 ± 1.87). Peripheral cones had a significantly higher area of first peak, p1area (1047 ± 1346), area of second peak, p2area (1130 ± 1478), height of first peak, h1 (102 ± 147), and height of second peak, h2 (102 ± 127), than central cones. Corneal hysteresis (CH), width of the first peak, w1, and width of the second peak, w2, did not significantly differ between cohorts. There were similar results for the tangential-topography algorithm, with a significant difference between the cohorts for p1area (855 ± 1389), p2area (860 ± 1531), h1 (81.7 ± 151), and h2 (92.1 ± 131). CONCLUSIONS: Cone location affects the biomechanical response parameters measured under central loading of the cornea. The ORA delivers its air puff to the central cornea, so the fact that h1 and h2 and that p1area and p2area were smaller in the central cone cohort than in the peripheral cone cohort suggests that corneas with central cones are softer or more compliant centrally than corneas with peripheral cones, which is consistent with the location of the pathology. This result is evidence that corneal weakening in keratoconus is focal in nature and is consistent with localized disruption of lamellar orientation.

A New Biomechanical Deformation Response Parameter: Change in Central Corneal Thickness During Air Puff Induced Corneal Deformation.

PURPOSE: To investigate the percent change in central corneal thickness (%ΔCCT) during air-puff-induced deformation as an indicator of corneal biomechanical response. METHODS: Forty ex vivo human eyes from forty donors were imaged using the CorVis ST at experimentally controlled intraocular pressure (IOP) of 10, 20, 30, and 40 mmHg, followed by uniaxial strip testing to calculate tensile modulus. The CorVis ST research software tracked the anterior and posterior cornea edges and determined the dynamic corneal response (DCR) parameters. Eyes were excluded if image quality or posterior tracking issues were present. Custom algorithms were used to calculate CCT during deformation using a ray-tracing method to correct for Scheimpflug and optical distortion within each image. Correlation and stepwise regression analyses between the shape-related DCR parameters and %ΔCCT were conducted. A mixed model analysis was performed to test the effect of IOP and the strongest significant predictors of the stepwise regression on %ΔCCT. The significance threshold was set to p < 0.05. RESULTS: Thirty eyes were ultimately analyzed and CCT increased significantly from the pre-deformation state to the highest concavity state at each IOP level (p < 0.001). IOP and multiple shape DCRs were found to be significantly related to %ΔCCT (p < 0.0001). The strongest predictor of %ΔCCT was integrated inverse radius (IIR) (p < 0.0001; partial R2 = 0.4772) with no other parameter having a partial R2 value greater than 0.04. The mixed model analysis showed that IIR was the sole predictor (p = 0.0098) and IOP was no longer significant as a single predictor. However, the interaction of IIR with IOP (p = 0.0023) had a significant effect on %ΔCCT. CONCLUSION: Percent change in CCT is influenced by corneal stiffness as indicated by the significant relationship with IIR. The %ΔCCT may be a potential biomarker for determining differences in corneal deformation response with corneal diseases.