To theoretically compare the corneal stress distribution of laser in situ keratomileusis (LASIK) with the stress distribution of small-incision lenticule extraction.
Cleveland Clinic Cole Institute, ...Cleveland, and The Ohio State University, Columbus, Ohio, USA.
Computational modeling study.
A finite-element anisotropic collagen fiber-dependent model of myopic surgery using patient-specific corneal geometry was constructed for LASIK, small-incision lenticule extraction, and a geometry analog model with unaltered material properties from preoperative but with postoperative geometry including thickness. Surgical parameters, magnitude of myopic correction, LASIK flap thickness, and lenticule depth in small-incision lenticule extraction were varied. Two sets of models, 1 with uniform and 1 with depth-dependent material properties, were constructed.
Stress distribution between small-incision lenticule extraction simulations and the geometry analog model were similar. In contrast, LASIK consistently reduced stress in the flap and increased stress in the residual stromal bed (RSB) compared with the geometry analog model. An increase in flap thickness or lenticule depth resulted in a greater increase in RSB stress in the LASIK model than in the small-incision lenticule extraction model.
Small-incision lenticule extraction may present less biomechanical risk to the residual bed of susceptible corneas than comparable corrections involving LASIK flaps. Deeper corrections in the stroma may be possible in small-incision lenticule extraction without added risk for ectasia.
Proprietary or commercial disclosures are listed after the references.
To develop a comprehensive three-dimensional analyses of segmental tomography (placido and optical coherence tomography) using artificial intelligence (AI).
Preoperative imaging data (MS-39, CSO, ...Italy) of refractive surgery patients with stable outcomes and diagnosed with asymmetric or bilateral keratoconus (KC) were used. The curvature, wavefront aberrations and thickness distributions were analysed with Zernike polynomials (ZP) and a random forest (RF) AI model. For training and cross-validation, there were groups of healthy (n=527), very asymmetric ectasia (VAE; n=144) and KC (n=454). The VAE eyes were the fellow eyes of KC patients but no further manual segregation of these eyes into subclinical or forme-fruste was performed.
The AI achieved an excellent area under the curve (0.994), accuracy (95.6%), recall (98.5%) and precision (92.7%) for the healthy eyes. For the KC eyes, the same were 0.997, 99.1%, 98.7% and 99.1%, respectively. For the VAE eyes, the same were 0.976, 95.5%, 71.5% and 91.2%, respectively. Interestingly, the AI reclassified 36 (subclinical) of the VAE eyes as healthy though these eyes were distinct from healthy eyes. Most of the remaining VAE (n=104; forme fruste) eyes retained their classification, and were distinct from both KC and healthy eyes. Further, the posterior surface features were not among the highest ranked variables by the AI model.
A universal architecture of combining segmental tomography with ZP and AI was developed. It achieved an excellent classification of healthy and KC eyes. The AI efficiently classified the VAE eyes as 'subclinical' and 'forme-fruste'.
To evaluate a fully automated local fractal dimension method to quantify vessel density and foveal avascular zone (FAZ) area in optical coherence tomography angiography (OCTA) images.
Fifty-two ...healthy Asian Indian eyes underwent imaging prospectively with OCTA system. Superficial and deep retinal vascular plexus was imaged. Local fractal analysis was applied to the OCTA images. A scan area of 3 × 3 mm was selected in the superficial and deep retinal layers. Foveal avascular zone area and vessel density were quantified in circular and sectoral zones around the fovea. A unique contour map of vessel density and dropout zones was developed to perform regional comparisons.
Foveal avascular zone of superficial (0.35 ± 0.013 mm2) and deep (0.49 ± 0.012 mm2) retinal vascular plexus was segmented. The agreement between the manually segmented and local fractal dimension segmented FAZ area was 0.97 (95% confidence interval CI: 0.94-0.98) and did not change significantly with age (P = 0.94 and 0.21, respectively). The vessel density was greater in the deep than the superficial retinal vascular plexus (P < 0.0001). When the image was subdivided into sectors around the FAZ, inferior sector had greater vessel density than the others (temporal, superior, and nasal) in both superficial and deep retinal vascular plexus (P < 0.05). These observations were similar to recent studies on animal retinal vasculature map.
A novel implementation of local fractal dimension to calculate vessel density and FAZ area was demonstrated. Age did not impact vessel density but sectoral analyses showed greater vessel density in the inferior zone.
To correlate retinal vascular features with severity and systemic indicators of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).
A total of 209 eyes of 122 type 2 ...diabetes mellitus patients with DR and 60 eyes of 31 normal Indian subjects underwent OCTA imaging. The diabetic retinopathy patients were graded as having either nonproliferative diabetic retinopathy (NPDR: mild, moderate, and severe NPDR using Early Treatment Diabetic Retinopathy Study classification) or proliferative diabetic retinopathy (PDR). Local fractal analysis was applied to the superficial and deep retinal OCTA images. Foveal avascular zone area (FAZ in mm2); vessel density (%); spacing between large vessels (%); and spacing between small vessels (%) were analyzed. Sensitivity and specificity of vascular parameters were assessed with receiver operating characteristics (ROC) curve.
Normal eyes had a significantly lower FAZ area, higher vessel density, and lower spacing between large and small vessels compared with DR grades (P < 0.001). In the superficial layer, PDR and severe NPDR had higher spacing between large vessels than mild and moderate NPDR (P = 0.04). However, mild NPDR had higher spacing between the small vessels (P < 0.001). Spacing between the large vessels in the superficial retinal layer correlated positively with HbA1c (r = 0.25, P = 0.03); fasting (r = 0.23, P = 0.02); and postprandial (r = 0.26, P = 0.03) blood sugar. The same spacing in the deep retinal vascular plexus had the highest area under the ROC curve (0.99 ± 0.01) and was uniformly elevated in all diabetic eyes (P > 0.05).
Spacing between the large vessels in the superficial and deep retinal layers had superior diagnostic performance than overall vessel density.
To evaluate the performance of corneal hysteresis (CH), corneal resistance factor, and 16 investigator-derived Ocular Response Analyzer (ORA) variables in distinguishing keratoconus (KC) from the ...nondiseased state.
Retrospective case series.
Fifty-four eyes of 27 unaffected patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de Janeiro, Brazil.
Sixteen candidate variables were derived from exported ORA signals to characterize putative indicators of biomechanical behavior. Area under the receiver operating characteristic curve (AUC) and the Z statistic were used to compare diagnostic performance.
Discriminant value of standard and derived ORA variables as measured by AUC.
Fifteen of 16 candidate variables performed significantly better than chance (AUC, >0.5) at discriminating KC. Diagnostic performance was greatest for a custom variable related to the depth of deformation as defined by the minimum applanation signal intensity during corneal deformation (concavity(min); mean AUC ± standard error, 0.985 ± 0.002) and a new measure incorporating the pressure-deformation relationship of the entire response cycle (hysteresis loop area, 0.967 ± 0.002). Z statistics assessing the discriminative value of each of the top 5 variables demonstrated superiority to CH (AUC, 0.862 ± 0.002). Concavity(min) had the best overall predictive accuracy (cutoff value, 50.37; 94.9% sensitivity, 91.7% specificity, and 93.2% test accuracy), and the top 4 variables demonstrated the most consistent relationships to KC severity.
Investigator-derived ORA variables related to the depth of deformation and the pressure-deformation relationship demonstrated very high test accuracy for detecting the presence of KC. Beyond their diagnostic value, the candidate variables described in this report provide mechanistic insight into the nature of the ORA signal and the characteristic changes in corneal dynamics associated with KC.
To model keratoconus (KC) progression and investigate the differential responses of central and eccentric cones to standard and alternative collagen cross-linking (CXL) patterns.
Three-dimensional ...finite element models (FEMs) were generated with clinical tomography and IOP measurements. Graded reductions in regional corneal hyperelastic properties and thickness were imposed separately in the less affected eye of a KC patient. Topographic results, including maximum curvature and first-surface, higher-order aberrations (HOAs), were compared to those of the more affected contralateral eye. In two eyes with central and eccentric cones, a standard broad-beam CXL protocol was simulated with 200- and 300-μm treatment depths and compared to spatially graded broad-beam and cone-centered CXL simulations.
In a model of KC progression, maximum curvature and HOA increased as regional corneal hyperelastic properties were decreased. A topographic cone could be generated without a reduction in corneal thickness. Simulation of standard 9-mm-diameter CXL produced decreases in corneal curvature comparable to clinical reports and affected cone location. A 100-μm increase in CXL depth enhanced flattening by 24% to 34% and decreased HOA by 22% to 31%. Topographic effects were greatest with cone-centered CXL simulations.
Progressive hyperelastic weakening of a cornea with subclinical KC produced topographic features of manifest KC. The clinical phenomenon of topographic flattening after CXL was replicated. The magnitude and higher-order optics of this response depended on IOP and the spatial distribution of stiffening relative to the cone location. Smaller diameter simulated treatments centered on the cone provided greater reductions in curvature and HOA than a standard broad-beam CXL pattern.
The ability to clearly observe one's environment in the visible spectrum provides a tremendous evolutionary advantage in most of the world's habitats. The complex optical processing system that has ...evolved in higher vertebrate animals gathers, focuses, detects, transduces, and interprets incoming visible light. The cornea resides at the front end of this imaging system, where it provides a clear optical aperture, substantial refractive power, and the structural stability required to protect the fragile intraocular components. Nature has resolved these simultaneous design requirements through an exceedingly clever manipulation of common extracellular-matrix structural materials (e.g., collagen and proteoglycans). In this review, we (a) examine the biophysical and optical roles of the cornea, (b) discuss increasingly popular approaches to altering its natural refractive properties with an emphasis on biomechanics, and (c) investigate the fast-rising science of corneal replacement via synthetic biomaterials. We close by considering relevant open problems that would benefit from the increased attention of bioengineers.
To determine the discriminant function of optical coherence tomography angiography (OCTA) by disease severity in glaucoma.
In this prospective, observational cross-sectional study, all subjects ...underwent visual fields, retinal nerve fiber layer (RNFL) measurements, and OCTA imaging. Local fractal analysis was applied to OCTA images (radial peripapillary capillaries RPC layer). Vessel density en face and inside the disc and spacing between large and small vessels were quantified. Stepwise logistic regression was performed and a glaucoma severity score (range, 0-1: 0, normal; 1, severe glaucoma) was developed by using global and regional (superotemporal ST, inferotemporal IT, temporal, superonasal SN, inferonasal, and nasal) vascular parameters. Glaucoma severity score was compared with visual field and RNFL indices.
One hundred ninety-nine eyes (112 subjects) with glaucoma (28 eyes preperimetric; 83 early, 43 moderate, and 45 severe glaucoma) and 74 normal (54 subjects) eyes were enrolled. Preperimetric and glaucomatous eyes had significantly altered (P < 0.001) global vascular parameters as compared to normal; regionally, ST, then SN and IT sectors (in that order) showed more change in glaucomatous eyes. Vascular parameters showed better discriminant ability (area under the curve AUC, sensitivity, and specificity of 0.70, 69.2%, and 72.9%, respectively) than structural parameters between normal and preperimetric glaucomatous eyes. Vascular parameters had comparable AUC (P > 0.05) to visual fields for perimetric glaucoma. Glaucoma severity score identified preperimetric glaucoma and early glaucoma better than did visual fields.
Vascular parameters could be a useful adjunct tool to evaluate/diagnose glaucoma. Longitudinal studies are needed to determine their use in early detection and prognostication.
With the advent of newer techniques to correct refraction such as flapless laser procedure and collagen crosslinking, in vivo estimation of corneal biomechanical properties has gained importance. In ...this study, a new 3-D patient specific inverse finite element method of estimating corneal biomechanical properties from air-puff applanation was developed. The highlight of the model was inclusion of patient-specific corneal tomography, fiber dependent hyperelastic model, cross links between collagen lamellae and epithelium layer. A lumped mass, spring and dashpot model was included to model the resistance to motion and deformation of the eye globe caused by air-puff applanation. 10 normal eyes of 10 human subjects were used for the study. 3-D finite element models were constructed and custom routines were scripted for performing the inverse calculations. The model for each eye was perturbed to estimate the effect of measured intraocular pressure on the estimated biomechanical variables. The study demonstrated that the inverse method was effective in quantification of material properties and was sensitive to intraocular pressure alterations. Specifically, in vivo fiber dependent hyperelastic biomechanical properties of human corneas were estimated for the first time.
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