Depth-resolved Corneal Biomechanical Changes Measured Via Optical Coherence Elastography Following Corneal Crosslinking.

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.

Depth-Dependent Corneal Biomechanical Properties in Normal and Keratoconic Subjects by Optical Coherence Elastography.

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.

Analysis of planning strategies in primary eyes gaining a line or more of visual acuity after topography-guided laser in situ keratomileusis.

PURPOSE: To analyze planning strategies for eyes that gained 1 or more lines of corrected distance visual acuity (CDVA) after topography-guided custom treatment (TCAT). SETTING: Refractive Surgery Clinic, Cleveland Clinic, Ohio, USA. DESIGN: Retrospective case series. METHODS: Eyes having TCAT by the same surgeon between February 2016 and June 2017 were enrolled. The corneal shape was captured with the Wavelight Allegretto Topolyzer diagnostic device coupled with refraction, generating an ablation profile. The cylinder magnitude and axis of laser entry were decided by the surgeon based on the manifest and measured values, assisted by additional data from the Pentacam Scheimpflug tomographer and Ladarwave ocular wavefront aberrometer. RESULTS: The study comprised 256 eyes. At 3 months, uncorrected distance visual acuity was 20/20 or better in 95.7% and 20/15 or better in 81.4%; 25.6% gained 1 or more lines of CDVA. The measured and manifest axes differed by less than 15 degrees in 59%, between 15 degrees and 30 degrees in 18%, and by more than 30 degrees in 23%. When it differed by at least 5 degrees, the measured axis was treated in 79%, 75%, and 73% of eyes, respectively. In eyes with higher measured cylinder, 75% were treated between the manifest and measured values, with 7% at full measured value. When the manifest value was greater, 60% were treated at the total measured value and 40% in between. Whole-eye aberrometry showed a small increase in coma, spherical aberration and the total root mean square (all P < .001). CONCLUSIONS: The TCAT procedure achieved visual acuity better than the preoperative CDVA in more than 25.0% of eyes. Tomography and wavefront aberrometry assisted in the selection process to achieve optimum visual outcomes.

Noninvasive Assessment of Corneal Crosslinking With Phase-Decorrelation Optical Coherence Tomography.

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.

Live human assessment of depth-dependent corneal displacements with swept-source optical coherence elastography.

PURPOSE: To assess depth-dependent corneal displacements in live normal subjects using optical coherence elastography (OCE). METHODS: A 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. RESULTS: Seventeen 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. CONCLUSION: OCE 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.

Custom air puff-derived biomechanical variables in a refractive surgery screening setting: Study from 2 centers.

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 R2 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.

Comparison of Patient-Specific Computational Modeling Predictions and Clinical Outcomes of LASIK for Myopia.

Purpose: To assess the predictive accuracy of simulation-based LASIK outcomes. Methods: Preoperative and 3-month post-LASIK tomographic data from 20 eyes of 12 patients who underwent wavefront-optimized LASIK for myopia were obtained retrospectively. Patient-specific finite element models were created and case-specific treatment settings were simulated. Simulated keratometry (SimK) values and the mean tangential curvature of the central 3 mm (Kmean) were obtained from the anterior surfaces of the clinical tomographies, and computational models were compared. Correlations between Kmean prediction error and patient age, preoperative corneal hysteresis (CH), and corneal resistance factor (CRF) were assessed. Results: The mean difference for Kmean between simulated and actual post-LASIK cases was not statistically significant (-0.13 ± 0.36 diopters [D], P = 0.1). The mean difference between the surgically induced clinical change in Kmean and the model-predicted change was -0.11 ± 0.34 D (P = 0.2). Kmean prediction error was correlated to CH, CRF, and patient age (r = 0.63, 0.53, and 0.5, respectively, P < 0.02), and incorporation of CH values into predictions as a linear offset increased their accuracy. Simulated changes in Kmean accounted for 97% of the variance in actual spherical equivalent refractive change. Conclusions: Clinically feasible computational simulations predicted corneal curvature and manifest refraction outcomes with a level of accuracy in myopic LASIK cases that approached the limits of measurement error. Readily available preoperative biomechanical measures enhanced simulation accuracy. Patient-specific simulation may be a useful tool for clinical guidance in de novo LASIK cases.

Effect of needle type and injection technique on pain level and vitreal reflux in intravitreal injection.

PURPOSE: To evaluate the amount of reflux and degree of pain with intravitreal injection (IVT) using 6 different types of syringes/needles and 5 techniques of scleral incision, including 3 modifications of a beveled scleral incision. METHODS: This was a study conducted in 205 eyes of 205 patients. IVT of bevacizumab for retinal pharmacotherapy with 6 types of needles and 5 techniques of scleral incision. The severity of subjectively evaluated pain (0-10) and the width of the subconjunctival bleb arising from the vitreal reflux. Secondary outcomes were increase in intraocular pressure and complication rate. RESULTS: The straight technique caused greater vitreal reflux than the beveled approaches, when compared individually or as a group (P < 0.01). No difference in the severity of pain was found among all 5 types of incisions (P > 0.05). There was greater reflux with 26- and 27-gauge needles in comparison to 29- and 30-gauge needles (P < 0.001); however, the width of the needle significantly affected the degree of reflux only when using the nonbeveled incision (P < 0.001). The patients injected with the 26- or 27-gauge needle experienced more pain matched to the 29- and 30-gauge needles (P < 0.001). No difference was found between the incision technique or width of subconjunctival reflux and the increase in intraocular pressure (P > 0.05). Postinjection events included transient mild uveitis, disease-related vitreous hemorrhage, foreign body sensation, conjunctival hemorrhage, and mild punctuate keratitis. CONCLUSIONS: The beveled scleral incision showed benefit in performing IVTs. The 29- and 30-gauge needles caused less pain.

Experimental investigation of needles, syringes and techniques for intravitreal injections.

BACKGROUND: To assess the techniques and materials used in intravitreal injections. DESIGN: Descriptive study realized at the Vision Institute of the Federal University of São Paulo, Brazil. SAMPLES: Different brands of needles and syringes, as well as enucleated porcine eyeballs. METHODS: The ultra-structures of commonly used needles were analysed by scanning electron microscope, and they were compared using different criteria, such as irregularities and debris from the lubrication process. The scleral incision was also assessed using needles of different brands and sizes. Accuracies in drug administration were studied by comparing the residual and delivered volume of needles and also by the analysis of reflux after intravitreal injections. MAIN OUTCOME MEASURES: Efficiency and quality of materials used in intravitreal injections. RESULTS: Ultra-structure analyses showed that all needles had different types of irregularities. Some photographs showed debris from the lubrication process, especially in BD needles. Scleral incision analysis showed a tendency of reducing the ocular damage with increasing gauge (P=0.024). The investigation of delivery accuracy showed that almost all needles underdosed the amount injected (P<0.05), and that the reflux could be minimized by tunnelled injections with thinner needles. CONCLUSION: Needles used in intravitreal injections possess many irregularities in their structures, which may cause different injection outcomes. Analyses of scleral incisions showed that the larger the needle gauge, the lesser the scleral damage and the risk of complications. Moreover, drug administration inaccuracies might be one of the causes for some unsuccessful attempts of treatment.

Interchangeability between Placido disc and Scheimpflug system: quantitative and qualitative analysis.

PURPOSE: Many systems try to replace Placido disc-based topographers, such as those based in Scheimpflug principles. The purpose of this study is to check if they are interchangeable. METHODS: Quantitative analysis evaluated data obtained from EyeSys and Pentacam, i.e. simulated keratometric values, in addition to flattest and steepest keratometric values. Sixty-three maps from each device (EyeSys scale=0.5 D; Pentacam scale= 0.25 D) were used for the comparison. Qualitative analysis selected 10 EyeSys and 15 Pentacam topographies used in the quantitative evaluation. Aspheric, keratoconus suspects (KS) and established keratoconus corneas were included. Four groups (children [CH], non-physicians adults [AD], residents in ophthalmology [OP] and refractive surgeons [RS]) were asked to match the topographies belonging to the same eye. RESULTS: Analysis showed that the parameters are correlated; however they are not clinically similar. In the qualitative analysis, the percent of correct matches increased when KS was removed. CH group was statistically different from every group in these comparisons. When only KS was considered, CH vs. OP, CH vs. RS and AD vs. RS remained statistically different. AD vs. OP showed no relevant difference in any comparison. CONCLUSIONS: The systems are not fully interchangeable, yet they are correlated. Practitioners who are adapting to Pentacam should use the 0.25 D scale maps and transform formulas that use EyeSys parameters. Only with persistent training may the topographies be properly matched; KS corneas are more difficult to be correctly paired.

Interchangeability between Placido disc and Scheimpflug system: quantitative and qualitative analysis / Permutabilidade entre o disco de Plácido e o sistema Scheimpflug: análise quantitativa e qualitativa

PURPOSE: Many systems try to replace Placido disc-based topographers, such as those based in Scheimpflug principles. The purpose of this study is to check if they are interchangeable. METHODS: Quantitative analysis evaluated data obtained from EyeSys and Pentacam, i.e. simulated keratometric values, in addition to flattest and steepest keratometric values. Sixty-three maps from each device (EyeSys scale=0.5 D; Pentacam scale= 0.25 D) were used for the comparison. Qualitative analysis selected 10 EyeSys and 15 Pentacam topographies used in the quantitative evaluation. Aspheric, keratoconus suspects (KS) and established keratoconus corneas were included. Four groups (children [CH], non-physicians adults [AD], residents in ophthalmology [OP] and refractive surgeons [RS]) were asked to match the topographies belonging to the same eye. RESULTS: Analysis showed that the parameters are correlated; however they are not clinically similar. In the qualitative analysis, the percent of correct matches increased when KS was removed. CH group was statistically different from every group in these comparisons. When only KS was considered, CH vs. OP, CH vs. RS and AD vs. RS remained statistically different. AD vs. OP showed no relevant difference in any comparison. CONCLUSIONS: The systems are not fully interchangeable, yet they are correlated. Practitioners who are adapting to Pentacam should use the 0.25 D scale maps and transform formulas that use EyeSys parameters. Only with persistent training may the topographies be properly matched; KS corneas are more difficult to be correctly paired.

OBJETIVO: Muitos sistemas tentam substituir os topógrafos baseados no disco de Plácido, como aqueles baseados nos princípios de Scheimpflug. O objetivo deste estudo é verificar se eles são intercambiáveis. MÉTODOS: A análise quantitativa avaliou dados obtidos através do EyeSys e do Pentacam, os valores de ceratometria simulada, além dos menores e maiores valores ceratométricos observados. Sessenta e três mapas de cada dispositivo (escala do EyeSys=0,5D; escala do Pentacam=0,25D) foram utilizados na comparação. Para a análise qualitativa, foram selecionadas 10 topografias do Pentacam e 15 do EyeSys. Córneas asféricas, suspeitas de ceratocone (KS) e com diagnóstico de ceratocone foram incluídas. Quatro grupos (crianças [CH], os adultos não-médicos [AD], residentes em oftalmologia [OP] e cirurgiões refrativos [RS]) foram convidados a corresponder as topografias pertencentes ao mesmo olho. RESULTADOS: As análises mostraram que os parâmetros estão correlacionados, no entanto, não são clinicamente similares. Na análise qualitativa, o porcentual de acertos aumentou quando KS foram removidas. O grupo CH foi estatisticamente diferente de qualquer outro grupo, nestas comparações. Quando somente KS foram consideradas, CH vs. OP, CH vs. RS e AD vs. RS manteve-se estatisticamente diferente. AD vs. OP não mostrou nenhuma diferença relevante em qualquer comparação. CONCLUSÕES: Os sistemas não são totalmente intercambiáveis, porém são correlacionados. Os profissionais que estão se adaptando ao Pentacam devem utilizar os mapas de escala 0,25 D e transformar fórmulas que usem parâmetros do EyeSys. Somente com treinamento persistente as topografias podem ser devidamente relacionadas; córneas KS são mais difíceis de ser pareadas corretamente.

Ability of new vital dyes to stain intraocular membranes and tissues in ocular surgery.

PURPOSE: To evaluate the ability of novel dyes to stain lens capsule (LC), internal limiting membrane (ILM), epiretinal membrane (ERM), and vitreous. DESIGN: Experimental study in animal and human donor eyes. METHODS: Thirteen dyes, methyl violet, crystal violet, eosin Y, sudan black B, methylene blue, toluidine blue, light green, indigo carmine, fast green, congo red, evans blue, brilliant blue, and bromophenol blue, were injected onto the LC and ILM of enucleated porcine eyes. The vitreous was stained with 2 mL of dyes for 1 minute. Six dyes (indigo carmine, evans blue, fast green, light green, bromophenol blue, and brilliant blue) were selected for experiments in human donor eyes and freshly removed ERM. RESULTS: In the porcine eyes, ILM staining with methylene blue, toluidine blue, indigo carmine, evans blue, bromophenol blue, and fast green was moderate, and methyl violet, crystal violet, brilliant blue, or sudan black resulted in strong staining. Methyl violet, crystal violet, sudan black, toluidine blue, and methylene blue caused histologic damage in porcine retinas. Vitreous examination revealed moderate staining with congo red, crystal violet, fast green, eosin Y, methylene blue, toluidine blue, brilliant blue, bromophenol blue, and methyl violet and strong staining with light green and evans blue. ERMs showed strong staining with 0.5% evans blue and moderate staining with 0.5% light green, fast green, brilliant blue, and bromophenol blue. Evaluation of donor eyes disclosed moderate staining with evans blue, light green, and bromophenol blue and strong staining with 0.5% brilliant blue. Moderate or strong staining of the vitreous occurred with most dyes. LC evaluation showed moderate staining with 0.5% evans blue, fast green, and brilliant blue, whereas 0.5% light green produced strong LC staining. CONCLUSIONS: Brilliant blue shows the best ILM staining, whereas bromophenol blue, evans blue, and light green also stain ILM. Most dyes bind well to LC, vitreous, and ERM.