Comparison of waveform-derived corneal stiffness and stress-strain extensometry-derived corneal stiffness using different cross-linking irradiances: an experimental study with air-puff applanation of ex vivo porcine eyes.

PURPOSE: To assess corneal stiffening of standard (S-CXL) and accelerated (A-CXL) cross-linking protocols by dynamic corneal response parameters and corneal bending stiffness (Kc[mean/linear]) derived from Corvis (CVS) Scheimpflug-based tonometry. These investigations were validated by corneal tensile stiffness (K[ts]), derived from stress-strain extensometry in ex vivo porcine eyes. METHODS: Seventy-two fresh-enucleated and de-epithelized porcine eyes were soaked in 0.1% riboflavin solution including 10% dextran for 10 min. The eyes were separated into four groups: controls (n = 18), S-CXL (intensity in mW/cm2*time in min; 3*30) (n = 18), A-CXL (9*10) (n = 18), and A-CXL (18*5) (n = 18), respectively. CXL was performed using CCL Vario. CVS measurements were performed on all eyes. Subsequently, corneal strips were extracted by a double-bladed scalpel and used for stress-strain measurements. K[ts] was calculated from a force-displacement curve. Mean corneal stiffness (Kc[mean]) and constant corneal stiffness (Kc[linear]) were calculated from raw CVS data. RESULTS: In CVS, biomechanical effects of cross-linking were shown to have a significantly decreased deflection amplitude as well as integrated radius, an increased IOP, and SP A1 (P < 0.05). Kc[mean]/Kc[linear] were significantly increased after CXL (P < 0.05). In the range from 2 to 6% strain, K[ts] was significantly higher in S-CXL (3*30) compared to A-CXL (9*10), A-CXL (18*5), and controls (P < 0.05). At 8% to 10% strain, all protocols induced a higher stiffness than controls (P < 0.05). CONCLUSION: Several CVS parameters and Kc[mean] as well as Kc[linear] verify corneal stiffening effect after CXL on porcine eyes. S-CXL seems to have a higher tendency of stiffening than A-CXL protocols have, which was demonstrated by Scheimpflug-based tonometry and stress-strain extensometry.

Attenuation of lysyl oxidase and collagen gene expression in keratoconus patient corneal epithelium corresponds to disease severity.

PURPOSE: Keratoconus (KC) is characterized by progressive vision loss due to corneal thinning and structural abnormalities. It is hypothesized that KC is caused by deregulated collagen levels and collagen fibril-maturating enzyme lysyl oxidase (LOX). Further, it is currently not understood whether the gene expression deregulated by the corneal epithelium influences KC pathogenesis. We studied (i) the expressions of the LOX, collagen I (COL IA1), collagen IV (COL IVA1), MMP9, and IL6 genes in KC corneal epithelia, (ii) validated their expression levels in patient tissues, and (iii) correlated expression levels with KC disease severity. The primary goal of this study was to evaluate the importance of these genes in the progression of KC. METHODS: We analyzed the gene expression levels of the key proteins LOX, collagens (COL IA1 and COL IVA1), MMP9, and IL6 in debrided corneal epithelia from a large cohort of KC patients (90 eyes) and compared them to control patients (52 eyes) without KC. We measured the total LOX activity in the tears of KC patients compared to controls. We also correlated the protein expression levels of LOX and collagens by immunohistochemistry (IHC) in primary tissues from KC patients (27 eyes) undergoing keratoplasty compared to healthy donor corneas (15 eyes). RESULTS: We observed a significant reduction in LOX transcript levels in KC corneal epithelia, and LOX activity in KC tears correlated with disease severity. Collagen transcripts were also reduced in KC while MMP9 transcript levels were upregulated and correlated with disease severity. IL6 was moderately increased in KC patients. IHC demonstrated a reduction in the protein expression levels of LOX in the epithelium and collagen IV in the basement membrane of KC patients compared to healthy donor corneas. CONCLUSIONS: The data demonstrates that the structural deformity of the KC cornea may be dependent on reduced expressions of collagens and LOX, as well as on MMP9 elevated by the corneal epithelium.

Discriminant value of custom ocular response analyzer waveform derivatives in keratoconus.

PURPOSE: 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. DESIGN: Retrospective case series. PARTICIPANTS: Fifty-four eyes of 27 unaffected patients and 49 eyes of 25 KC patients from the Instituto de Olhos, Rio de Janeiro, Brazil. METHODS: 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. MAIN OUTCOME MEASURES: Discriminant value of standard and derived ORA variables as measured by AUC. RESULTS: 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. CONCLUSIONS: 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.

Using adaptive optics to optimize the spherical aberration of eyes implanted with EDOF and enhanced monofocal intraocular lenses.

PURPOSE: To assess the effect of change in ocular spherical aberration (SA) with adaptive optics on visual acuity (VA) at different defocus after implantation of extended depth-of-focus (EDOF) and enhanced monofocal intraocular lenses (IOLs). SETTINGS: Narayana Nethralaya Eye Hospital, Bangalore, India. DESIGN: Prospective, longitudinal, observational. METHODS: 80 eyes (40 patients) that had cataract surgery were included in the study. 40 eyes were implanted with Eyhance EDOF IOLs and the remaining with Vivity EDOF IOLs. Baseline ocular aberrations were measured with a visual adaptive optics aberrometer, then the optimal SA was determined by increasing it in steps of -0.01 µm up to -0.1 µm until the maximum improvement in near distance VA was observed for a given eye. Then the defocus curve for each eye was measured after modifying the ocular SA by magnitude equal to optimal SA. RESULTS: Most of the eyes accepted a negative induced SA of -0.05 µm (Eyhance group: 67.6%; Vivity group, 45.2%). In the Eyhance group (dominant eyes), VA improved at -2 diopters (D) ( P < .02) only and degraded at 0 D, +0.5 D, and +1 D defocus ( P < .05). In the Vivity group, the VA remained unchanged at all defocus ( P > .05). In the Eyhance group (nondominant eyes), VA improved at -3.5 D defocus only and degraded at +1.5 D and +2 D defocus ( P < .05). In the Vivity group, VA improved at -2.5 D defocus ( P < .05) only. CONCLUSIONS: A negative induced SA of -0.05 µm in implanted eyes was optimal for a slight improvement in distance-corrected near and intermediate VA without any significant decrease in baseline distance-corrected VA.

Inverse computational analysis of in vivo corneal elastic modulus change after collagen crosslinking for keratoconus.

Corneal collagen crosslinking with riboflavin photosensitization and ultraviolet irradiation is a novel approach to limiting the progression of keratoconus in patients by increasing the elastic modulus of the degenerate cornea. Beneficial reductions in corneal steepness and aberrations after crosslinking also frequently occur. In a previous study, we described a computational modeling approach to simulating topographic progression in keratoconus and regression of disease with corneal collagen crosslinking. In the current study, this model has been expanded and applied to the inverse problem of estimating longitudinal time-dependent changes in the corneal elastic modulus after crosslinking using in vivo measurements from 16 human eyes. Topography measured before crosslinking was used to construct a patient-specific finite element model with assumed hyperelastic properties. Then the properties of the cornea were altered using an inverse optimization method to minimize the difference between the model-predicted and in vivo corneal shape after crosslinking. Effects of assumptions regarding sclera-to-cornea elastic modulus ratio and spatial attenuation of treatment effect due to ultraviolet beam characteristics on the predicted change in elastic modulus were also investigated. Corneal property changes computed by inverse finite element analysis provided excellent geometric agreement with clinical topography measurements in patient eyes post-crosslinking. Over all post-treatment time points, the estimated increase in corneal elastic modulus was 110.8 ± 48.1%, and slightly less stiffening was required to produce the same amount of corneal topographic regression of disease when the sclera-to-cornea modulus ratio was increased. Including the effect of beam attenuation resulted in greater estimates of stiffening in the anterior cornea. Corneal shape responses to crosslinking varied considerably and emphasize the importance of a patient-specific approach.

Universal architecture of corneal segmental tomography biomarkers for artificial intelligence-driven diagnosis of early keratoconus.

AIMS: To develop a comprehensive three-dimensional analyses of segmental tomography (placido and optical coherence tomography) using artificial intelligence (AI). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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'.

Simultaneous Topography-guided Custom Ablation With Corneal Cross-linking for Keratoconus: 10-Year Prospective Outcomes.

PURPOSE: To assess 10-year visual and tomographic outcomes of topography-guided custom ablation (T-CAT) with corneal cross-linking (CXL) in eyes with keratoconus. METHODS: T-CAT with CXL was performed in 600 eyes (522 patients). Based on the T-CAT ablation plan, the theoretical maximum ablation depth was 50 µm after epithelium removal. After ablation, accelerated corneal cross-linking (CXL) was performed in the central 8-mm zone (9 mW/cm2 for 10 minutes in "epi-off" mode). The visual acuity and tomography were assessed. RESULTS: There was significant improvement in uncorrected (P = .001) and corrected (P = .001) distance visual acuity after the procedure. Keratometry, root mean square lower order aberrations and higher order aberrations, defocus, coma 90°, and spherical aberration reduced significantly after surgery at 10 years of follow-up (P < .005). All Pentacam (Oculus Optikgerate GmbH) tomographic variables showed significant changes indicating regularization after T-CAT (P < .005). Flattening of greater than 5.00 diopters in maximum keratometry was noted in 6 eyes (1%). Two of 600 eyes progressed postoperatively and required repeat CXL. CONCLUSIONS: T-CAT plus CXL is a safe and effective technique even in the long term for regularizing the anterior corneal surface with significant visual improvement and reduction in higher order corneal aberrations. [J Refract Surg. 2023;39(11):759-766.].

Minimum Corneal Diameter and Anterior Steep Axis Curvature Share the Same Meridian: A Novel Finding.

PURPOSE: To define the external scleral sulcus (ESS) on a Scheimpflug image and use it for a morphometric analysis of corneal diameter (CD). DESIGN: Retrospective, cross-sectional study of pediatric Asian-Indian eyes. METHODS: One random eye of 353 subjects between 5 and 18 years underwent 25-scan Pentacam HR imaging. For all scans, densitometry values along the anterior corneal edge were recorded and differentiated. The peaks on the differentiated curve were chosen as the ESS points, and this distance between them was called CD. Vertical (vCD), maximum (maxCD), minimum (minCD) CD and their meridians were defined. Multiple regression models (MRMs) with CD and other Pentacam parameters were built to predict astigmatism and its axis, mean keratometry (Kmean), and Belin/Ambrósio enhanced ectasia display deviation (BAD-D). MRMs were validated using intraclass correlation coefficient (ICC). Estimated horizontal CD (hCD) was validated against digital caliper measurement using ICC. RESULTS: The ICC (95% CI) between caliper and hCD was 0.96 (0.93, 0.97). MRM predictions (P < .001) used CD parameters, anterior chamber depth, corneal volume and distance from the corneal thinnest location to apex. These predictions achieved an ICC of 0.34 (0.18, 0.46), 0.82 (0.78, 0.86), 0.87 (0.84, 0.89), and 0.81 (0.76, 0.84), respectively. The astigmatism axis prediction depended on the minCD and maxCD meridians. Its within-subject SD (4.97°) was less than 2 consecutive Pentacam scan angles (7.2°). CONCLUSIONS: The CD metric strongly correlated with the astigmatism axis, keratometry, and BAD-D. Its spatial description may be significant in corneal treatment planning and disease diagnoses.

Phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive OCT.

PURPOSE: To assess phase retardation and corneal sublayer thickness repeatability using ultrahigh-resolution polarization-sensitive optical coherence tomography (PS-OCT). SETTING: Narayana Nethralaya Eye Hospital, Bangalore. DESIGN: Observational. METHODS: In this study, all eyes were imaged using a custom-built ultrahigh-resolution PS-OCT and high-resolution hybrid OCT (MS-39). The repeatability of phase retardation en face maps and corneal sublayer thickness profiles was evaluated. The reflectivity and phase retardation were calculated from the 2 orthogonal polarization channels to generate en face maps of phase retardation and corneal sublayer thicknesses. 3 consecutive measurements of all participants were acquired for each eye. For each measurement, the participant was asked to sit back and was realigned again. The repeatability was assessed using the intraclass correlation coefficient (ICC). RESULTS: The study included 20 healthy eyes of 20 participants. The phase retardation en face maps showed preferential arrangement of collagen fibrils with least retardation in the apex and maximum retardation in the periphery. The phase retardation showed excellent repeatability (ICC >0.95) in all zones. The Bowman layer and stromal layer thicknesses were measured with excellent repeatability (ICC >0.93 and >0.99, respectively). Significant differences ( P < .05) in stromal layer thickness were observed between MS-39 and PS-OCT. The repeatability of epithelial thickness measurements was better with PS-OCT than MS-39. CONCLUSIONS: The combinational assessment of corneal birefringence and sublayer thicknesses shows the advanced potential of ultrahigh-resolution PS-OCT in routine clinical practice over current OCT devices.

Tear biomarkers in dry eye disease: Progress in the last decade.

Dry eye disease (DED) is a commonly occurring, multifactorial disease characterized by reduced tear film stability and hyperosmolarity at the ocular surface, leading to discomfort and visual compromise. DED is driven by chronic inflammation and its pathogenesis involves multiple ocular surface structures such as the cornea, conjunctiva, lacrimal glands, and meibomian glands. The tear film secretion and its composition are regulated by the ocular surface in orchestration with the environment and bodily cues. Thus, any dysregulation in ocular surface homeostasis causes an increase in tear break-up time (TBUT), osmolarity changes, and reduction in tear film volume, all of which are indicators of DED. Tear film abnormalities are perpetuated by underlying inflammatory signaling and secretion of inflammatory factors, leading to the recruitment of immune cells and clinical pathology. Tear-soluble factors such as cytokines and chemokines are the best surrogate markers of disease severity and can also drive the altered profile of ocular surface cells contributing to the disease. Soluble factors can thus help in disease classification and planning treatment strategies. Our analysis suggests increased levels of cytokines namely interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-9, IL-12, IL-17A, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α); chemokines (CCL2, CCL3, CCL4, CXCL8); MMP-9, FGF, VEGF-A; soluble receptors (sICAM-1, sTNFR1), neurotrophic factors (NGF, substance P, serotonin) and IL1RA and reduced levels of IL-7, IL-17F, CXCL1, CXCL10, EGF and lactoferrin in DED. Due to the non-invasive sample collection and ease of quantitively measuring soluble factors, tears are one of the best-studied biological samples to molecularly stratify DED patients and monitor their response to therapy. In this review, we evaluate and summarize the soluble factors profiles in DED patients from the studies conducted over the past decade and across various patient groups and etiologies. The use of biomarker testing in clinical settings will aid in the advancement of personalized medicine and represents the next step in managing DED.

New simulation software to predict postoperative corneal stiffness before laser vision correction.

PURPOSE: To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kc mean ) after laser vision correction (LVC) surgery. SETTING: Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy. DESIGN: Retrospective observational case series. METHODS: 529 eyes from 529 patients from 3 eye centers and 10 post-small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kc mean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters. RESULTS: In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kc mean were not statistically different ( P = .96). Although no statistically significant differences in these values were observed between the stable and ectasia groups ( P ≥ .14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0. CONCLUSIONS: The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required.

Corneal biomechanics and biomaterials.

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.

Mapping of corneal birefringence in thin and asymmetric keratoconus corneas with ultrahigh-resolution polarization-sensitive OCT.

PURPOSE: To evaluate phase retardation (PR) across healthy eyes and eyes with thin corneas (<500 µm) and with asymmetric and bilateral keratoconus (KC). SETTING: Narayana Nethralaya Eye Hospital, Bangalore, India. DESIGN: Observational cross-sectional. METHODS: There were 4 eye groups: healthy eyes (Group 1; n = 10 eyes), eyes with thin corneas and no clinical disease (Group 2; n = 10 eyes), eyes with asymmetric KC (Group 3; n = 5 eyes), and eyes with clinical KC (Group 4; n = 15 eyes). All eyes were imaged with polarization-sensitive optical coherence tomography (PS-OCT), MS-39, and Corvis-ST. Using PS-OCT, PR was analyzed in annular regions. The anterior (A-E) and Bowman (E-B) wavefront aberrations, epithelial Zernike indices (EZI), total corneal thickness, Corvis biomechanical index (CBI), total biomechanical index (TBI), and Belin-Ambrósio overall deviation index (BAD-D) were analyzed. RESULTS: Only CBI, TBI, BAD-D, A-E and E-B aberrations, EZI, and total corneal thickness distributions of Groups 1 (n =10), 2 (n =10), and 3 (n =5) were similar ( P > .05) but not CCT ( P < .05). PR distributions clearly showed that the eyes in Groups 1, 2, and 3 had a normal corneal birefringence unlike Group 4 (n = 10) eyes ( P < .05). The PR map was similar to the preferred orientations of collagen fibers seen in X-ray diffraction ex vivo studies of corneal stroma. CONCLUSIONS: PR distributions may eliminate the uncertainty associated with the stromal status of thin and asymmetric KC corneas. Group 2 and 3 eyes appeared as healthy because of normal corneal birefringence at the time of imaging, but a longitudinal follow-up of these eyes with PS-OCT may assist in early detection of onset of disease.

Corneal wound healing after ultraviolet-A/riboflavin collagen cross-linking: a rabbit study.

PURPOSE: To investigate corneal wound healing following ultraviolet-A (UVA)/riboflavin corneal collagen cross-linking (CXL) in rabbit corneas. METHODS: Thirty-six rabbits were enrolled in the study. Animals were divided into three treatment groups and corneas were analyzed at 24 hours and 4 weeks postoperatively. Thus, each group had 6 rabbits at each time point. Treatment groups were: 1) standard UVA+riboflavin CXL, 2) UVA alone, and 3) riboflavin alone. One eye of each rabbit served as an untreated control eye. TUNEL assay was performed to detect stromal cell apoptosis. Immunocytochemistry was performed to detect the inflammatory marker CD11b expressed in monocytes and the alpha-smooth muscle actin (SMA) marker expressed in myofibroblasts. RESULTS: At 24 hours, corneas from the UVA+riboflavin CXL group had significantly more apoptosis than the UVA alone and riboflavin alone groups. Eyes from all three groups had significantly more inflammatory cell influx into the cornea than unwounded controls. Four weeks after the procedure, many corneas in the UVA+riboflavin CXL group had mild haze, but very few SMA-positive myofibroblasts could be detected in the central cornea. CONCLUSIONS: Riboflavin+UVA CXL triggers more anterior keratocyte apoptosis than corneal scrape with UVA alone or riboflavin alone. Inflammation monitored by the monocyte marker CD11b was present, but not statistically different among the three groups. Very little myofibroblast generation could be detected after UVA+riboflavin CXL, indicating that the mild stromal haze associated with this procedure is normally related to transient corneal fibroblast generation rather than more persistent haze due to generation of myofibroblasts.

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.

Repeatability of biometry measured by three devices and its impact on predicted intraocular lens power.

PURPOSE: To compare the repeatability of ocular biometry measured with the LENSTAR LS 900, IOLMaster 700, and Anterion and its impact on predicted intraocular lens (IOL) power. SETTING: Tertiary eye-care facility in South India. DESIGN: Prospective, observational, cross-sectional study. METHODS: Eyes diagnosed with cataract had 3 consecutive scans on each biometers. The repeatability was assessed using the within-subject standard deviation (Sw), test-retest repeatability, and coefficient of variation (CoV). The agreement was evaluated with the intraclass correlation (ICC). The IOL power was calculated with the Barrett Universal II formula. RESULTS: The study comprised 127 eyes of 76 patients. The repeatability of all parameters for a given device were excellent (ICC >0.9, low CoV and Sw). The agreement of the parameters between the biometers was very good (range from 0.93 to 0.99). The predicted IOL power differed statistically between the devices (P < .05), but the difference was clinically insignificant between the 3 biometers (ICC >0.99 for repeat calculation of IOL power). CONCLUSIONS: All the biometers included in the study had good to excellent repeatability of biometry parameters. The agreement of the predicted IOL power was excellent between the 3 optical biometers.

Simultaneous Topography-Guided PRK/CXL Versus Topography-Assisted PTK/CXL: 1-Year Prospective Outcomes in Keratoconic Eyes.

PURPOSE: To compare 1-year visual and tomographic outcomes of topography-guided photorefractive keratectomy (TGPRK) and topography-assisted phototherapeutic keratectomy (TPTK) with corneal cross-linking (CXL). METHODS: TGPRK and TPTK were performed in 72 eyes (68 patients) and 74 eyes (71 patients), respectively. Based on the TGPRK ablation plan, the eyes underwent TPTK where the theoretical minimum corneal thickness (MCT) after surgery was less than 400 µm. In the TGPRK group, the theoretical maximum ablation depth was 50 µm after epithelium removal. In TPTK, a decentered single-step PTK was performed only in the steepest anterior curvature zone and the stromal ablation depth was limited to 25 µm. After ablation, accelerated CXL was performed in the central 8-mm zone (9 mW/cm2 for 10 minutes in "epithelium-off" mode) in both TGPRK and TPTK. The visual acuity and tomography were assessed. RESULTS: Improvement in uncorrected (P = .73) and corrected (P = .66) distance visual acuity was similar between the two groups. However, TGPRK eyes had a greater decrease in keratometry, anterior defocus, and spherical aberration (P < .001) at the cost of greater ablation of tissue (P < .001). The median MCT decreased by 27 and 52.5 µm in the TPTK and TGPRK eyes, respectively. Both groups had similar decreases in anterior root mean square of lower (P = .10) and higher (P = .12) order aberrations. CONCLUSIONS: Both TGPRK and TPTK improved visual acuity in the keratoconic eyes at 1 year of follow-up. However, TPTK removed less volume of tissue. Further, it could be an alternative to TGPRK if the theoretical stromal ablation exceeds 50 µm in thin keratoconic corneas. [J Refract Surg. 2021;37(8):562-569.].

Artificial Intelligence Efficiently Identifies Regional Differences in the Progression of Tomographic Parameters of Keratoconic Corneas.

PURPOSE: To develop an artificial intelligence (AI) model to effectively assess local versus global progression of keratoconus using multiple tomographic parameters. METHODS: This was a retrospective review of medical records of patients diagnosed as having keratoconus. A total of 1,884 Pentacam (Oculus Optikgeräte GmbH) scans of 366 eyes (296 patients) were analyzed. Based on an increase in maximum anterior curvature (Kmax), the eyes were classified as actual "progression" and "no progression." The corresponding changes in other Pentacam parameters were incorporated to train and cross-validate (five-fold) the AI models. Three AI models were trained (an increase in Kmax by A = 0.75 diopters [D], B = 1.00 D, and C = 1.25 D). The area under the curve (AUC), sensitivity, specificity, and classification accuracy, along with other metrics, were evaluated. RESULTS: The AUC, sensitivity, specificity, and classification accuracy were 0.90, 85%, 82%, and 83%, respectively, for Model A; 0.91, 86%, 82%, and 88%, respectively, for Model B; and 0.93, 89%, 81%, and 91%, respectively, for Model C. All models also predicted that 60% to 62% of the actual progression eyes had concomitant progression-associated changes in the other Pentacam parameters (global progression). However, there was discordance between increase in Kmax and concomitant associated changes in the other parameters in 38.8% to 40% of the eyes (local progression). CONCLUSIONS: The AI models identified the eyes where the increase in Kmax and corresponding progression-associated changes in the other parameters were in agreement. These eyes may require corneal cross-linking earlier than the rest. [J Refract Surg. 2021;37(4):240-248.].