William J. Dupps

Effect of Acute Biomechanical Changes on Corneal Curvature After Photokeratectomy

PURPOSE Unintended hyperopic shift is a common yet poorly understood complication of phototherapeutic keratectomy (PTK) that raises fundamental questions about the etiology of corneal curvature change in PRK and LASIK. We investigated the relative contributions of ablation profile and peripheral stromal thickening to intraoperative PTK-induced central flattening, and propose a biomechanical model of the acute corneal response to central ablation. METHODS Fourteen de-epithelialized eye bank globes from seven donors underwent either broadbeam ablation (approximately 100-microm depth, no programmed dioptric change) or sham photoablation in paired-control fashion. Peripheral stromal thickness changes and the pattern of thickness loss across each ablation zone were evaluated by optical section image analysis as predictors of acute corneal flattening. RESULTS Relative to sham ablation, keratectomy caused significant anterior corneal flattening (-6.3+/-3.2 D, P = .002). Concomitant peripheral stromal thickening (+57+/-43 microm, P = .01) was a significant predictor of acute hyperopic shift (r = 0.68, P = .047). Ablation pattern bias did not consistently favor hyperopia and was a poor lone predictor of hyperopic shift. CONCLUSIONS Unintended keratectomy-induced hyperopic shift is replicable in a human donor model and is associated with significant thickening of the unablated peripheral stroma. This biomechanical response may have a considerable impact on early refractive outcomes in PTK, PRK, and LASIK.

Femtosecond Laser and Microkeratome Corneal Flaps: Comparison of Stromal Wound Healing and Inflammation

PURPOSE To examine early postoperative wound healing in rabbit corneas that had LASIK flaps formed with three different models (15 KHz, 30 KhZ, and 60 KHz) of a femtosecond laser compared with flaps formed with a microkeratome. METHODS Thirty-nine rabbit eyes were randomized to receive either no surgery or corneal flaps formed with one of the lasers or the microkeratome. Sixteen eyes also had lamellar cuts with no side cuts with the 30 KHz laser. Animals were sacrificed and corneas processed as frozen sections or fixed for transmission electron microscopy. Frozen sections were evaluated with the TUNEL assay to detect apoptosis, immunocytochemistry for Ki67 to detect cell mitosis, and immunocytochemistry for CD11b to detect mononuclear cells. RESULTS Rabbit corneas that had flaps formed with the 15 KHz laser had significantly more stromal cell death, greater stromal cell proliferation, and greater monocyte influx in the central and peripheral comea at 24 hours after surgery than corneas that had flaps formed with the 30 KHz or 60 KHz laser or the microkeratome. Results of the 60 KHz laser and microkeratome were not significantly different for any of the parameters at 24 hours, except for mitotic stromal cells at the flap margin. Transmission electron microscopy revealed that the primary mode of stromal cell death at 24 hours after laser ablation was necrosis. CONCLUSIONS Stromal cell necrosis associated with femtosecond laser flap formation likely contributes to greater inflammation after LASIK performed with the femtosecond laser, especially with higher energy levels that result in greater keratocyte cell death.

Method for optical coherence elastography of the cornea

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 Poissons ratio that may be relevant in the early diagnosis of corneal ectatic disease.

Comparison of biomechanical effects of small-incision lenticule extraction and laser in situ keratomileusis: Finite-element analysis

Purpose To theoretically compare the corneal stress distribution of laser in situ keratomileusis (LASIK) with the stress distribution of small‐incision lenticule extraction. Setting Cleveland Clinic Cole Institute, Cleveland, and The Ohio State University, Columbus, Ohio, USA. Design Computational modeling study. Methods 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. Results 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. Conclusions 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. Financial Disclosures Proprietary or commercial disclosures are listed after the references.

Biomechanics of corneal ectasia and biomechanical treatments

UNLABELLED Many algorithms exist for the topographic/tomographic detection of corneas at risk for post-refractive surgery ectasia. It is proposed that the reason for the difficulty in finding a universal screening tool based on corneal morphologic features is that curvature, elevation, and pachymetric changes are all secondary signs of keratoconus and post-refractive surgery ectasia and that the primary abnormality is in the biomechanical properties. It is further proposed that the biomechanical modification is focal in nature, rather than a uniform generalized weakening, and that the focal reduction in elastic modulus precipitates a cycle of biomechanical decompensation that is driven by asymmetry in the biomechanical properties. This initiates a repeating cycle of increased strain, stress redistribution, and subsequent focal steepening and thinning. Various interventions are described in terms of how this cycle of biomechanical decompensation is interrupted, such as intrastromal corneal ring segments, which redistribute the corneal stress, and collagen crosslinking, which modifies the basic structural properties. FINANCIAL DISCLOSURES Proprietary or commercial disclosures are listed after the references.

Standardized graphs and terms for refractive surgery results.

A critical element of peer-reviewed publication is clear communication to the reader and the ophthalmic and medical community. Refractive surgery has the luxury of multiple procedures with multiple outcome parameters that are relevant to clinicians, researchers, and, of course, patients. This diversity introduces complexity for the reader in evaluating and comparing various procedures as they are applied to various patient populations. For over a decade, the editors of the Journal of Refractive Surgery (JRS) and the Journal of Cataract & Refractive Surgery (JCRS) have advocated a minimally acceptable level of standardization in reporting results of refractive surgical procedures.1,2 This has culminated in a set of criteria that include basic elements that must be reported in every manuscript. To further this goal of clear reporting, the editors of JCRS, JRS, and Cornea would like to announce their collaboration in standardizing two aspects of data reporting in refractive surgery.

Surface wave elastometry of the cornea in porcine and human donor eyes.

PURPOSE To introduce a nondestructive technique for characterization of corneal stiffness, determine measurement precision, and investigate comparative stiffness values along central, radial, and circumferential vectors in porcine corneas. The effects of epithelial debridement, relaxing incisions, and crosslink-mediated stiffening on surface wave velocity are also studied. METHODS A handheld prototype system was used to measure ultrasound surface wave propagation time between two fixed-distance transducers along a ten-position map. Repeatability was assessed with replicate measurements in 6 porcine corneas. In 12 porcine globes with controlled intraocular pressure (IOP), serial measurements were performed before and after epithelial removal, then after 250- and 750-microm-deep relaxing incisions. In human globes with constant intravitreal pressure, central wave velocity and transcorneal IOP measurements were compared before and after collagen cross-linking. RESULTS Measurement repeatability across all regions was between 2.2% and 8.1%. Epithelial removal resulted in increases in measured stiffness in 67% of eyes, but statistical power was insufficient to detect a systematic change. Wave velocity across a central incision decreased significantly after 250-microm keratotomy (P < .001), but did not undergo a significant further decrease with deeper keratotomy. Meridional stiffness changes consistent with coupling effects were detected after keratotomy. Surface wave velocity and transcorneal IOP measurements increased markedly after collagen cross-linking despite maintenance of a constant IOP. CONCLUSIONS Handheld corneal elastometry provides a repeatable measure of regional stiffness changes after relaxing incisions and collagen cross-linking in in vitro experiments. Surface wave elastometry allows focal assessment of corneal biomechanical properties that are relevant in refractive surgery, ectatic disease, and glaucoma.

Patient-Specific Computational Modeling of Keratoconus Progression and Differential Responses to Collagen Cross-linking

PURPOSE To model keratoconus (KC) progression and investigate the differential responses of central and eccentric cones to standard and alternative collagen cross-linking (CXL) patterns. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Effects of Altered Corneal Stiffness on Native and Postoperative LASIK Corneal Biomechanical Behavior: A Whole-Eye Finite Element Analysis

PURPOSE To investigate the impact of corneal elasticity on corneal shape changes before and after simulated LASIK with and without consideration of whole-eye biomechanics. METHODS A finite element whole-eye model of a human eye was constructed. The cornea was modeled as hyperelastic and incompressible using experimental data representing a range of corneal stiffness. The corneal response to intraocular pressure loading and LASIK for 2.00, 4.00, and 6.00 diopters of spherical myopia was analyzed as a function of corneal stiffness and limbal boundary conditions. RESULTS Myopic LASIK produced different degrees of central flattening and postoperative ametropia in low-stiffness and high-stiffness corneas. Although a cornea-only model demonstrated maximum stresses and displacements in the central cornea and predicted residual myopia, a whole-eye model with equivalent corneal stiffness predicted greater paracentral displacements and less myopic undercorrection. In a whole-eye model with a stiffer cornea, maximum displacements shifted further toward the limbus, favoring additional mechanically mediated central flattening and refractive overcorrection (hyperopia). In postoperative LASIK models thinned by high myopic corrections, corneal stiffening caused central cornea flattening. CONCLUSIONS Differences in the corneoscleral stiffness relationship affect simulated refractive outcomes after LASIK and may be a source of individual variation in refractive surgery outcomes. A whole-eye model allowing limbal motion illustrates a stiffness-dependent biomechanical balance between central corneal flattening and pre-ectatic weakening of the corneal apex not demonstrated in previous computational models and provides insight into under- and overcorrection in myopic LASIK and the previously unexplained phenomenon of corneal flattening after therapeutic collagen cross-linking for keratoconus.

Patient-specific modeling of corneal refractive surgery outcomes and inverse estimation of elastic property changes

The purpose of this study is to develop a 3D patient-specific finite element model (FEM) of the cornea and sclera to compare predicted and in vivo refractive outcomes and to estimate the corneal elastic property changes associated with each procedure. Both eyes of a patient who underwent laser-assisted in situ keratomileusis (LASIK) for myopic astigmatism were modeled. Pre- and postoperative Scheimpflug anterior and posterior corneal elevation maps were imported into a 3D corneo-scleral FEM with an unrestrained limbus. Preoperative corneal hyperelastic properties were chosen to account for meridional anisotropy. Inverse FEM was used to determine the undeformed corneal state that produced <0.1% error in anterior elevation between simulated and in vivo preoperative geometries. Case-specific 3D aspheric ablation profiles were simulated, and corneal topography and spherical aberration were compared at clinical intraocular pressure. The magnitude of elastic weakening of the residual corneal bed required to maximize the agreement with clinical axial power was calculated and compared with the changes in ocular response analyzer (ORA) measurements. The models produced curvature maps and spherical aberrations equivalent to in vivo measurements. For the preoperative property values used in this study, predicted elastic weakening with LASIK was as high as 55% for a radially uniform model of residual corneal weakening and 65% at the point of maximum ablation in a spatially varying model of weakening. Reductions in ORA variables were also observed. A patient-specific FEM of corneal refractive surgery is presented, which allows the estimation of surgically induced changes in corneal elastic properties. Significant elastic weakening after LASIK was required to replicate clinical topographic outcomes in this two-eye pilot study.